The problem of building an effective system of interconnected and purposeful innovative changes in business management is solved in the article. The main purpose of the research is to improve the model of business excellence on the basis of interconnected and purposeful innovative changes in business management. Critical analysis of literature sources and approaches to solving the problem of building a perfect model of business emphasizes the diversity of applied methodological approaches and methods of management innovation. However, in terms of (...) business technologicalization, necessity to accelerate information exchange, development of innovation and, at the same time, development of new threats, the need on the basis of strategizing, intellectualization of management, partnership, compliance with the challenges of the external environment, communication efficiency, leadership transformation, balancing intermediate and final results, there is a need to transform business and management on the basis of strategizing, intellectualization of management, partnership interaction, compliance with the challenges of the external environment, communication efficiency, transformation of leadership, balancing intermediate and final results. Relevance of solving of this scientific issue is that the timely use of innovative tools and management methods in the implementation of strategic intentions and goals forms a high adaptability of companies to transformation processes occurring in their external and internal environment under the influence of digital technologies in business processes. The scientific-theoretical and methodological basis of the study were the following methods: abstract-logical and comparative analysis – to generalize theoretical approaches and confirm the practical importance of solving the problem of building a model of providing business excellence on the basis of interconnected and focused innovative changes in business management; system analysis and modelling – method of building a model of business excellence based on managerial innovation; system-analytical – method of balancing the interaction of the components providing business excellence; generalization – when drawing conclusions based on research results. The object of research is a system of interconnected and purposeful innovative changes in business management. The results of solving the problem of building a model of business excellence while balancing the interaction of the components of such provision and implementation of the process of digital transformation of the business model. The results of the research have practical value for business entities that seek to increase the effectiveness of interconnected and purposeful innovative changes in business management. (shrink)

GAMETOGÊNESE -/- Emanuel Isaque Cordeiro da Silva Instituto Agronômico de Pernambuco Departamento de Zootecnia – UFRPE Embrapa Semiárido -/- • _____OBJETIVO -/- Os estudantes bem informados, estão a buscando conhecimento a todo momento. O estudante de Veterinária e Zootecnia, sabe que a Reprodução é uma área de primordial importância para sua carreira. Logo, o conhecimento da mesma torna-se indispensável. No primeiro trabalho da série fisiologia reprodutiva dos animais domésticos, foi abordado de forma clara, didática e objetiva os mecanismos de diferenciação (...) sexual dos embriões em desenvolvimento, quais os genes envolvidos nesse processo e tudo mais. Nesse segundo trabalho, a abordagem será teórica, mas também clara, sobre a formação primordial dos gametas femininos e masculinos, através da ovogênese nas fêmeas e a espermatogênese nos machos. Esse trabalho visa levar a importância do processo de formação dos gametas e a produção hormonal das gônadas, bem como o entendimento sobre as interações com o eixo hipotálamo-hipofisário. -/- •____INTRODUÇÃO -/- A reprodução sexual é um processo mediante a qual dois organismos da mesma espécie unem seu material genético para dar lugar a um organismo fixo com combinação única de genes; para isso, cada organismo produz células que contém a metade do material genético característico da espécie. Essas células haploides (1n) são denominadas gametas; ao combinar-se um gameta masculino com um feminino produz-se uma célula diploide (2n) (zigoto ou ovo) a partir da qual se forma o embrião. A grande maioria das espécies com reprodução sexual são anisogâmicas, o que significa que produzem dois tipos de gametas diferentes: os gametas masculinos são microscópios, móveis e produzem-se em grande quantidade, enquanto que os femininos são grandes, imóveis e produzem-se em menor quantidade. O tipo de gameta que um indivíduo produz é o que define seu sexo; sobre os animais o macho é o indivíduo que produz grandes quantidades de espermatozoides e a fêmea produz uma menor quantidade de óvulos, enquanto que nas plantas as gônadas masculinas são as produtoras pólen e as femininas produzem oosferas. Os gametas são diferentes do resto das células do organismo, as quais se chamam células somáticas; essas últimas são diploides porque contém dois pares de cromossomos, um par herdado do pai do indivíduo e o outro da mãe. As células somáticas, ademais, se dividem por mitose, ao qual os cromossomos se duplicam antes de cada divisão celular e cada uma das células filhas recebe um complemento diploide idêntico dos cromossomos, logo todas as células somáticas de um indivíduo possuem o mesmo material genético, embora cada tipo celular expresse diferentes combinações de genes. Em contraponto, os gametas são células haploides porque possuem somente um par de cromossomos e a metade do material genético característico da espécie. Cada um dos cromossomos em um gameta é resultado da recombinação dos genes contidos nos cromossomos paterno e materno do indivíduo que originam o gameta, e cada um destes possuem uma combinação única de genes. Os gametas se formam a partir das células germinais, que são células que em sua origem são diploides e elas de “comprometem” a manter-se como uma linha celular especial que em determinado momento sofrerá o processo de meiose para dar origem aos gametas haploides, sejam óvulos ou espermatozoides segundo o sexo do animal. Como descrito no trabalho sobre a diferenciação sexual, as células germinativas primordiais originam-se no epiblasto do embrião, e migram desde o saco vitelino até colonizar as cristas gonodais, onde, por sua vez, proliferam-se e se organizam junto com as células somáticas da gônada primitiva para formar o testículo ou o ovário. As células germinais masculinas e femininas tem a mesma origem embrionária. As gônadas indiferenciadas em um embrião possuem três tipos celulares: as células que dão origem aos gametas (ovogonia ou espermatogonia), as precursoras de células que nutrem os gametas em desenvolvimento (células da granulosa no ovário; células de Sertoli no testículo) e as precursoras de células que secretam hormônios sexuais (células da teca no ovário; células de Leydig no testículo). As células germinais são as únicas estruturas do organismo que têm a capacidade de dividir-se por meiose sofrendo uma redução no número de seus cromossomos, sendo responsável pela transmissão da carga genética aos descendentes. Em contraste, as células somáticas somente se dividem por mitose. A formação dos gametas compreende fases sequenciais de mitose, meiose e pós-meiose. Esses processos são altamente organizados e necessitam de um preciso e bem coordenado programa de expressão genética. Uma das características importantes da gametogênese é a redução cromossômica, que através da meiose, reduz pela metade o número de cromossomos e produz células distintas entre si, devido a trocas de material genético entre os pares de cromossomos provenientes do pai e da mãe, o que ocorre no processo de “crossing over” durante a primeira fase da meiose. A gametogênese é o processo mediante o qual as células germinais de cada sexo se multiplicam, dividem e diferenciam até formar os gametas. No caso da formação dos gametas masculinos o processo recebe o nome específico de espermatogênese, e para os gametas femininos é denominado como ovogênese. Embora os dois processos alcancem o objetivo comum de produção das células haploides, por onde compartilham algumas características, existem diferenças marcadas entre eles devido a necessidade de produzir um número muito distinto de gametas, de tamanho diferente, e com características de motilidade também distintas. -/- •___ESPERMATOGÊNESE -/- A espermatogênese é o processo mediante o qual se produz os gametas masculinos denominados espermatozoides. Durante a vida fetal as células germinais e as células somáticas do testículo em formação organizam-se em túbulos seminíferos que se derivam dos cordões sexuais primários e conformam a maior parte da medula do testículo. Na etapa fetal cada tubo seminífero é delimitado por uma membrana basal, recoberta na parte interior pelas células precursoras das células de Sertoli (um tipo de células somáticas). No exterior do túbulo localizam-se as células precursoras das células de Leydig ou intersticiais (figura 1), que também são células somáticas. Entre a membrana basal e as células de Sertoli encontram-se algumas células germinais denominadas espermatogonias de reserva A0 (denominadas gonócitos) que serão o único tipo de células germinais presentes no testículo enquanto o animal não alcançar a puberdade. As células de Sertoli estabelecem na região basal uniões oclusoras entre si, formando parte da barreira hemato-testicular. As espermatogonias A0 localizam-se por dentro da membrana basal do túbulo seminífero, embora fora da barreira hemato-testicular. Figura 1: fase neonatal. Nota-se a grande infiltração de tecido intersticial em quase 50% da seção originando que os túbulos sejam pequenos e redondos em sua maioria. O citoplasma e núcleo das células pré-Leydig são notadas claramente por essa ser uma espécie suína onde o tecido intersticial está claramente diferenciado. Hematoxilina-eosina (X 220.5). Fonte: Embrapa. -/- O número de células de Sertoli no testículo depende da influência do hormônio folículo estimulante (FSH) presente durante a vida fetal e as primeiras etapas de vida pós-natal. A população de células de Sertoli ao chegar a puberdade se manterá fixa durante o resto da vida do animal; existe uma relação positiva entre o tamanho e a população de células de Sertoli e a capacidade de produção de espermatozoides do testículo. As células de Sertoli são as únicas células somáticas que estão no epitélio seminífero, e sua função é a nutrição, sustentação e controle endócrino das células germinais. As células de Sertoli participam ativamente no processo de liberação dos espermatozoides para a luz do túbulo. Nesse momento, as células de Sertoli realizam a fagocitose de parte do citoplasma do espermatozoide dos chamados corpos residuais. As células de Sertoli também fagocitam as células germinais que se degeneram no curso normal da espermatogênese. Essas células ainda sintetizam grande quantidade de proteínas, como por exemplo as proteínas ABP (androgen hinding protein), que transportam andrógenos para todo o aparelho reprodutivo, transferrinas, que transportam ferro para a respiração celular das células germinais e também às inibinas, que regulam a liberação de FSH pela hipófise, através de um sistema de retroalimentação (feedback) negativa (figura 2). Figura 2: epitélio seminífero, células de Sertoli (flecha) (400 X). Fonte: Embrapa. -/- Antes da puberdade dos túbulos seminíferos observam-se ao corte como estruturas de diâmetro pequeno, sem luz, e conformados unicamente pelas células de Sertoli e espermatogonias de reserva e rodeados por abundante tecido intersticial, ao que estão presentes as células precursoras das células de Leydig. Ainda antes da puberdade, a diferenciação celular manifesta-se primeiro pela presença de espermatócitos primários, os quais se degeneram em geral na fase de paquíteno, por falta de estimulação hormonal. A partir de que o animal chega a puberdade inicia-se o processo de espermatogênese, que se manterá durante toda a vida do animal, exceto em espécies de animais silvestres muito estacionais, ao qual pode se suspender durante a época não reprodutiva para voltar e ser retomada na época ou estação reprodutiva. Depois da puberdade, os túbulos seminíferos possuem um diâmetro muito maior; em seu interior observa-se um grande número de células germinais de todos os tipos, diferentes estádios de divisão, e em seu lúmen contém líquido e espermatozoides. Ainda sobre o alcancei da puberdade, as espermatogonias começam a dividir-se aceleradamente por mitose, enquanto que no espaço intersticial as células mesenquimais também começam a se diferenciar e a dar origem as células de Leydig (figura 3). A partir dessa etapa as células de Leydig (totalmente diferenciadas) são também evidentes no exterior do túbulo, junto com as células mioides ou peritubulares que o rodeiam o que ao contrair-se são responsáveis por controlar o avanço dos fluidos e as células presentes no lúmen do túbulo. As células mioides estão situadas ao redor do túbulo, e é creditado a elas a promoção da contração e da integridade estrutural do túbulo. Esse tipo celular apenas se diferencia na puberdade pela ação dos andrógenos (figura 4). As interações entre as células de Sertoli e as mioides parecem ter um papel importante na manutenção das funções do testículo. Durante o processo de espermatogênese, as espermatogonias de reserva dividem-se periodicamente e enquanto algumas células fixas permanecem como espermatogonias de reserva, outras proliferam e sofrem uma seção de divisões mitóticas durante as quais se vão diferenciando até formarem espermatócitos primários (espermatocitogênese ou fase de mitose), logo sofrem divisões especiais mediante as quais reduzem seu número de cromossomos (fase de meiose), e ao final trocam de forma para converter-se em espermatozoides (espermatocitogênese) (figura 5). Cada uma dessas etapas da espermato- gênese será descrito detalhadamente adiante, antes é necessário a explicação de algumas características das células de Sertoli e de Leydig que ajudarão a entender seu papel durante a espermatogênese. Figura 3: células de Leydig no espaço intersticial do testículo bovino adulto PAS (400 X). Fonte: Embrapa. -/- Figura 4: o estabelecimento da puberdade pela presença de espermatozoides no túbulo. Hematoxilina-eosina (400 X). Fonte: Embrapa. Figura 5: fases mitóticas das espermatogonias (A0 e B) para formação de um espermatócito primário e as duas fases de meiose que se sucedem antes da espermatogênese. Fonte: ZARCO, 2018. -/- Ao início da espermatocitogênese as uniões oclusoras entre as células de Sertoli se abrem por etapas (como as comportas de um submarino) para permitir a passagem das espermatogonias em direção ao centro do túbulo seminífero sem que se estabeleça uma continuidade entre o exterior e o interior da barreira hemato-testicular. Uma vez ultrapassada essa barreira, as sucessivas gerações de espermatogonias, espermatócitos, espermátides e espermatozoides irão se localizar em direção ao interior do túbulo seminífero, em estreita associação com as células de Sertoli. Em consequência, as células de Sertoli dividem o túbulo seminífero em dois compartimentos; o compartimento basal (debaixo das uniões oclusoras das células de Sertoli), ao qual residem as espermatogonias de reserva, e o compartimento adluminal (em direção ao centro do túbulo), cujos espaços entre as células de Sertoli desenvolvem o resto do processo de espermatogênese (meiose e espermatocitogênese). Esse feito é importante porque durante a vida fetal as únicas células germinais existentes eram as espermatogonias de reserva, pelo que os antígenos expressados por gerações mais avançadas (espermatogonias intermediárias, secundárias, espermátides e espermatozoides) não são reconhecidos como próprios do corpo pelo sistema imunológico. Logo, o anterior implica que deve existir uma barreira entre eles e o sangue para evitar um ataque imunológico. Em todas as etapas da espermatogênese, as células de Sertoli atuam como células de suporte para as células germinais, que sempre permanecem recoberta pela membrana das células de Sertoli. Também atuam como células nutricionais já que proporcionam o meio em que as células germinais se desenvolvem e maturam, assim como as substâncias que regulam e sincronizam as sucessivas divisões e transformações das células germinais. As células de Sertoli produzem hormônios, como estrógenos e inibina que atuam sobre a hipófise para regular a secreção das gonadotropinas que controlam a espermatogênese. As células de Leydig que residem no exterior do túbulo seminífero também são importantes para a espermatogênese: produzem a testosterona que estimula e mantém a espermatogênese, bem como serve como substrato sobre o qual atua como aromatizador das células de Sertoli para transformá-las em estrógenos. Como supracitado, para seu estudo podemos dividir a espermatogênese em três fase: espermatocitogênese, meiose e espermiogênese (figura 6). Agora, serão descritas cada uma dessas etapas. Em algumas espécies, incluindo no homem, os macrófagos representam o segundo tipo celular intersticial mais numeroso no testículo, depois das células de Leydig. Os macrófagos e vários subtipos de linfócitos são identificados nós testículos de ovinos e ratos. Eles estão intimamente associados com as células de Leydig e atuam juntamente na regulação da esteroidogênese. Figura 6: fluxograma da espermatogênese. -/- Espermatocitogênese -/- A espermatocitogênese, também chamada de etapa proliferativa ou de mitose, consiste numa série de divisões mitóticas sofridas pelas células descendentes de uma espermatogonia de reserva. Uma vez que a célula se divide, abandona o estado de reserva e começa um processo de diferenciação. As espermatogonias de reserva (denominadas espermatogonias A0 na rata ou As nos humanos) são células que existem desde a vida fetal e que permanecem mitoticamente inativas durante a infância. Uma vez que alcançam a puberdade começam a dividir-se em intervalos regulares, e as células filhas podem permanecer como espermatogonias de reserva ou abandonar a reserva e ingressar na dita espermatocitogênese. Uma vez abandonada a reserva, as células filhas que vão se formando em cada divisão permanecem unidas por pontes citoplasmáticas, constituindo um clone que se divide sincronicamente. As células que se formam depois de cada divisão continuam sendo espermatogonias, porém cada geração é ligeiramente diferente da anterior. Na rata, por exemplo, as espermatogonias tipo A0 ao dividir-se originam espermatogonias do tipo A1, que em sucessivas divisões formam espermatogonias dos tipos A2, A3 e A4, as quais, por sua vez, sofrem outra mitose para formar espermatogonias intermediárias e uma mais para formar espermatogonias do tipo B. Essas últimas se diferenciam (sem se dividir) em espermatócitos primários, processo em que termina a fase de espermatocitogênese, que literalmente significa processo de geração de espermatócitos. As espermatogonias tipo A0 são a fonte para a contínua produção de gametas. A metade delas se dividem e formam células iguais (as chamadas células tronco) e a outra metade forma as espermatogonias A1, que sofre novas divisões mitóticas e formam os tipos 2, 3 e 4. O tipo A4 sofre mitose para formar a intermediária (A In), que por mitose, forma a tipo B (figura 6). Esses tipos de espermatogonias podem ser identificadas em evoluções histológicas de acordo com sua organização topográfica na membrana basal dos túbulos seminíferos ou mediante seu conteúdo de heterocromatina. Outra maneira de diferenciação se baseia em marcadores moleculares específicos que distinguem as espermatogonias tronco (A0) das demais, com os fins de isolamento, desenvolvimento in vitro e transplante. As tipo B passam por mitose para formarem os espermatócitos primários; estes iniciam a primeira etapa da meiose formando os espermatócitos secundários; na segunda etapa da divisão meiótica, cada espermatócito secundário se divide e formam as chamadas espermátides. Quando o testículo alcança seu desenvolvimento total, a meiose completa-se e as espermátides originadas se convertem em espermatozoides. Um dos maiores sinais característicos desse fenômeno é o alargamento das espermátides e sua migração em direção ao lúmen do túbulo seminífero (figuras 4, 7 e 8). Figura 7: espermatogonias marcadas por imuno-histoquímica, anticorpo monoclonal TGFa (400 x). Figura 8: fases de divisões meióticas (M), espermatócitos em paquíteno (PA) e espermatócitos secundários (ES). -/- Figura 9: estádio posterior a liberação dos espermatozoides na luz do túbulo. Hematoxilina-eosina (400 x). Mediante as seis divisões mitóticas que ocorrem durante a espermatocitogênese se forma potencialmente um clone de 64 espermatócitos primários a partir de cada espermatogonia A que ingressa sobre o processo. Não obstante, algumas células sofrem apoptose em cada uma das etapas do processo, ao qual o número real formado é menor. Em outras espécies produzem-se um transcurso similar de divisões mitóticas sucessivas durante a espermatocitogênese, embora a nomenclatura utilizada possa ser distinta, por exemplo nos bovinos as duas últimas divisões mitóticas dão origem as espermatogonias de tipo B1 e B2. -/- Meiose -/- Uma vez que as espermatogonias B se diferenciam em espermatócitos primários, esses iniciam a etapa de meiose, com uma nova divisão; desta vez a divisão é do tipo meiótica. Ao completar-se a primeira divisão meiótica (meiose I) se obtém os espermató-citos secundários, que ao sofrer a segunda divisão meiótica (meiose II) dão origem as espermátides. Vale salientar que a meiose é o processo mediante o qual reduz-se a metade do número de cromossomos, pelo que as espermátides que se obtém são células haploides (1n). Os espermatócitos secundários que se formam depois da primeira divisão meiótica contém a metade do número normal de cromossomos, porém a mesma quantidade de DNA já que cada cromossomo é duplo. As espermátides formadas na conclusão da segunda divisão meiótica (figura 7), por sua vez, contém a metade dos cromossomos, e esse já não são duplos, já que se trata de células 1n. Também deve-se enfatizar que durante a meiose é relevante o entrecruzamento dos cromossomos homólogos, pelo que cada espermátide possui uma combinação única e diferente de genes paternos e maternos. Outro ponto que deve ser levado em consideração é que cada espermátide somente possui um cromossomo sexual; a metade das espermátides contém o cromossomo X herdado da mãe do macho que está levando a cabo a espermatogênese e a outra metade contém o cromossomo Y herdado de seu pai. Para cada espermatócito primário que entra no processo de meiose obtém-se cerca de quatro espermátides, pelo qual ao ser completada a meiose potencialmente se poderiam formar até 256 espermátides por cada espermatogonia que abandona a reserva e ingressa na espermatocitogênese. -/- Espermiogênese -/- Durante a espermiogênese, também chamada de fase de diferenciação, as esper-mátides sofrem, sem se dividir, uma metamorfose que as transforma em espermatozoides, os quais finalmente são liberados das células de Sertoli em direção ao lúmen do túbulo seminífero. A espermiogênese é um processo complicado e longo já que a espermátide deve sofrer complexas trocas nucleares, citoplasmáticas e morfológicas que resultam na forma-ção dos espermatozoides. Algumas dessas mudanças incluem a condensação do material nuclear para formação de um núcleo plano e denso, a eliminação do citoplasma para a constituição de uma célula pequena, a formação de uma estrutura especializada denomi-nada acrossomo ou tampa cefálica, e a formação do pescoço e da cauda (flagelo) do esper-matozoide, do que depende a sua motilidade. Durante a maior parte da espermiogênese, as espermátides se mantém com uma estreita associação com as células de Sertoli; logo, chega-se a observar, então, flagelos que se projetam em direção a luz do túbulo que pare-cem sair das células de Sertoli, sendo na realidade os flagelos dos espermatozoides que ainda não tinham sido liberados pelo lúmen. Ao liberar os espermatozoides em direção a luz do túbulo, as células de Sertoli realizam a fagocitose de parte do citoplasma dos espermatozoides (corpos residuais). Também fagocitam os restos de todas as células germinais que sofrem apoptose ou degeneram-se durante a espermatogênese. Credita-se que ao realizar essas funções as células de Sertoli podem fazer uma monitoração eficiente da espermatogênese, o que lhes permitiria emitir sinais para colaborar na regulação desse processo em nível gonodal e a nível sistêmico através da secreção de hormônios como a inibina e o estradiol. Além da inibina e activina, as células de Sertoli sintetizam outras proteínas, como a ABP (proteína ligadora de andrógenos) que serve como uma molécula de transporte de andrógenos dentro dos túbulos seminíferos, ductos deferentes e epidídimo, ou a transfer-rina, que transporta o ferro necessário para a respiração celular. -/- Resultados da espermatogênese -/- O resultado da espermatogênese não significa apenas uma simples multiplicação das células germinais (até 256 espermatozoides a partir de cada espermatogonia A1), senão que através dela são produzidos gametas haploides pequenos, móveis e com grande diversidade genética entre eles, ao mesmo tempo que se mantêm uma reversa de células mãe (espermatogonias A0) a partir das quais se poderiam originar novos ciclos de esper-matogênese durante o resto da vida do animal. -/- Controle hormonal da espermatogênese -/- Como mencionado, o FSH reproduz um importante papel para o estabelecimento das células de Sertoli durante a vida fetal e início da vida pós-natal. O começo da esper-matogênese também é estimulado pelo FSH, que atua sobre as células de Sertoli para estimular sua função e a ativação de sinais dessas células em direção as células germinais, incluindo-as a abandonar a reserva e ingressar na espermatogênese. O FSH, assim mesmo, estimula a mitose durante o resto da espermatogênese e aumenta a eficiência do processo, já que reduz a apoptose e a degeneração de espermatogonias intermediárias e do tipo B. O FSH também estimula as células de Sertoli para produzirem inibina e ABP. Uma vez iniciada a espermatogênese somente requerem níveis baixos de FSH para se mantê-la. As células de Sertoli também devem ser estimuladas pela testosterona para funcio-nar de maneira adequada; se requer também do LH hipofisário: hormônio que estimula as células de Leydig para produzir testosterona. Por sua vez, a secreção de LH e FSH é regulada pelo GnRH hipotalâmico: esse neurohormônio também faz parte do mecanismo de regulação da espermatogênese. A espermatogênese também é modulada em nível local mediante a produção de determinados fatores e interações entre as células. Dentro dos fatores locais podemos mencionar o fator de crescimento parecido com a insulina 1 (IGF-1), o fator de crescimen-to transformante beta (TGF- β), activina, ocitocina e diversas citocinas. Entre as intera-ções celulares existem tanto uniões de comunicação entre as células de Sertoli e as células germinais, como pontes citoplasmáticas entre todas as células germinais que formam o clone de células descendentes de uma espermatogonia A1. Uma vez que as células de Sertoli iniciam sua função na puberdade é possível manter experimentalmente a espermatogênese somente com testosterona, sem ser requeri-dos nenhum outro hormônio. A quantidade de espermatozoides produzidos, no entanto, é maior quando há presença do FSH. Abaixo do estímulo do FSH as células de Sertoli produzem estradiol e inibina, hormônios que geram uma retroalimentação sobre o eixo hipotálamo-hipofisário para a regulação da secreção de gonadotropinas. Em particular, a inibina reduz a secreção de FSH, pelo qual é factível que sirva como um sinal que evite uma excessiva estimulação as células de Sertoli. -/- Ciclo do epitélio seminífero -/- Em cada espécie as espermatogonias de reserva iniciam um novo processo de divi-sões celulares em intervalos fixos: a casa 14 dias no touro; 12 dias no garanhão e a cada 9 dias no cachaço (reprodutor suíno). A nova geração de células que começam a proliferar sobre a base do tubo deslocam-se em direção ao centro do túbulo a geração anterior, que por sua vez deslocam-se as gerações anteriores. Devido as mudanças que vão sofrendo cada geração celular se ajustam a tempos característicos de cada etapa, já que rodas as células em uma determinada seção do túbulo estão sincronizadas entre si pelas células de Sertoli; em cada espécie somente é possível encontrar um certo número de combinações celulares: 14 diferentes combinações no caso da rata, 8 no touro e 6 no ser humano. A sucessão de possíveis combinações até regressar a primeira combinação se conhece como o ciclo do epitélio seminífero. Na maioria das espécies os espermatozoides que são libera-dos em direção a luz do túbulo provém das células que entraram no processo de esperma-togênese quatro gerações antes que a geração que está ingressando nesse momento, pelo que a espermatogênese no touro dura ao redor de 60 dias e um pouco menos em outras espécies domésticas. Significa que os efeitos negativos das alterações na espermatogêne-se podem estar presentes até dois meses depois de que se produziram essas alterações. Como supracitado, geralmente se observa a mesma combinação celular em toda a área de uma determinada secção transversal do túbulo seminífero. No entanto, se fizermos uma série de secções, observa-se que ao longo do túbulo há uma sucessão ordenada de combinações (a primeira em uma determinada secção; a segunda combinação na seguinte secção, e assim sucessivamente em secções subsequentes até regressar a primeira combi-nação. Teremos, então, que ao início da divisão das espermatogonias A1 se produz de forma sincronizada em uma secção do túbulo, e vai-se transmitindo como uma onda peristáltica as secções adjacentes. Esse processo é denominado como onda do epitélio seminífero e graças à esse túbulo seminífero sempre tem secções em todas as etapas da espermatogênese, com o que se alcança uma produção constante de espermatozoides. -/- Alterações da espermatogênese -/- Nas espécies estacionais a espermatogênese, como já mencionado, pode reduzir-se ou inclusive suspender sua atividade fisiológica durante a época não reprodutiva dessas espécimes, porém esse processo fisiológico não pode ser considerado como uma altera-ção. No entanto, a espermatogênese só pode ser alterada pelas enfermidades ou por fatores externos. A principal causa de alterações na espermatogênese é o aumento da temperatura testicular. Por isso, os testículos são localizados na saco escrotal e são “caídos” para fora do corpo como pode-se observar nos bovinos, caprinos, ovinos, caninos e no próprio homem. A temperatura testicular deve estar cerca de 2 a 6 °C abaixo da temperatura corporal normal. As células germinais masculinas são sensíveis ao calor, pelo qual na maioria dos mamíferos os testículos se encontram fora da cavidade abdominal e existe um sofisticado sistema de termorregulação para mantê-los a uma temperatura menor que a corporal. Se a temperatura corporal for elevada ou se os testículos permanecerem na cavidade abdominal, ou ainda se os sistemas termorreguladores do testículo sejam afetados por fatores inflamatórios como edema ou falta de mobilidade testicular dentro do escroto, a temperatura do tecido testicular aumentará e a espermatogênese sofrerá alterações proporcionais ao excesso de temperatura e a duração da elevação. A espermatogênese também pode ser afetada pela exposição a hormônios ou a outras substâncias. É possível que a causa mais comum (sobretudo no homem) seja o uso de esteroides anabólicos, que elevam a concentração de andrógenos na circulação, provo-cando um feedback negativo sobre a secreção de gonadotropinas. Ao deixar de estimular-se o testículo pelas gonadotropinas, este deixará de produzir testosterona, e as concentra-ções de andrógeno exógeno nunca alcançará as altíssimas concentrações de testosterona que normalmente estão presentes a nível do tecido testicular por ser o local onde se produz o hormônio. Também se supõe que diversas substâncias com propriedades estrogênicas derivadas de processos industriais (indústria dos plásticos, hidrocarbonetos etc.) e presentes no ambiente (fatores xenobióticos) podem ser responsáveis pelas alterações na espermatogênese em diversas espécies, entre as quais se inclui o ser humano. -/- • OVOGÊNESE E FOLICULOGÊNESE -/- A ovogênese é o processo seguido pelas células germinais da fêmea para a forma-ção dos óvulos, que são células haploides. Durante a vida fetal as células germinais proliferam-se no ovário por mitose, formando um grande número de ovogonias, algumas das quais se diferenciam em ovócitos primários que iniciam sua primeira divisão meiótica para deter-se na prófase da divisão. Somente alguns desses ovócitos primários retornarão e concluirão a primeira divisão meiótica em algum momento da vida adulta do animal, dando origem a um ovócito secundário e a um corpo polar. O ovócito secundário inicia a sua segunda divisão meiótica, a qual volta a ficar suspensa até receber um estímulo apropriado, já que somente os ovócitos secundários que são ovulados e penetrados por um espermatozoide retornam e concluem a segunda divisão meiótica, dando origem a um óvulo (figura 10). O processo de ovogênese é realizado dentro dos folículos ovarianos, que também tem que sofrer um longo transcurso de desenvolvimento e diferenciação denominado foliculogênese pelo que a ovogênese como tal realiza-se dentro do marco desse último processo. Por essa razão, na seguinte seção descreverei tanto a ovogênese como a folicu-logênese, e a relação que existe entre ambos. Figura 10: representação da ovogênese. Na etapa de proliferação, as células germinais se diferen-ciam por mitose. A meiose I se caracteriza por uma prófase prolongada, ocorrendo a duplicação do DNA. Nas duas divisões, que ocorrem antes da ovulação e depois da fertilização, a quantidade de DNA é reduzida a 1n, com o fim de que a fusão dos pronúcles (singamia) pós-fertilização, seja gerado um zigoto com um número de cromossomos de 2n (diploide). -/- Geração de ovócitos primários e folículos primordiais Tanto a ovogênese como a foliculogênese iniciam-se durante a vida fetal, quando as células germinais primordiais provenientes do saco vitelino colonizam a gônada primitiva e, junto com as células somáticas z organizam-se para a formação dos cordões sexuais secundários, que se desenvolvem principalmente no córtex do ovário. Nesse período, as células germinais que colonizaram o ovário sofrem até 30 divisões mitóticas, proliferando-se até formar milhares ou milhões de ovogonias, que inicialmente formam “ninhos” constituídos cada um deles por um clone de várias ovogonias que descendem da mesma célula precursora e que se mantêm unidas por pontes citoplasmáticas, sincronizan-do suas divisões mitóticas. Nessa etapa alcança-se a máxima população de células germinais no ovário, que antes de nascer se reduzirá drasticamente por apoptose. No ovário do feto humano chegam a haver até sete milhões de células germinais que ao nascimento se reduzem a dois milhões. Os ovários fetais do bovino, de maneira análoga, chegam a ter até 2.100.000 células germinais, que ao nascimento reduzem para 130.000 aproximadamente. A redução no número de ovogonias produz-se ao mesmo tempo que essas células, que vêm dividindo-se por mitose e estão agrupadas em ninhos, iniciam sua primeira divisão meiótica para se transformarem em ovócitos primários: células germinais que se encontram em uma etapa de suspensão (diplóteno) da prófase da primeira divisão meiótica. Nesse período produz-se uma grande proporção de células germinais; as células somáticas dos cordões sexuais, por sua vez, emitem projeções citoplasmáticas que separam a isolam os ovócitos primários sobreviventes, ficando cada um deles rodeados por uma capa de células aplanadas da (pré) granulosa. Ao mesmo tempo em que se forma uma membrana basal entre as células da granulosa e o tecido intersticial do ovário. Ao ovócito primário rodeado de uma capa de células da (pré) granulosa aplanadas e delimita-das por uma membrana basal denomina-se de folículo primordial (figura 11). Nas vacas os folículos primordiais bem formados já estão presentes nos ovários a partir do dia 90 da gestação. A maioria dos folículos primordiais com os que nasce uma fêmea se manterão inativos durante um longo tempo; muitos deles durante toda a vida do animal. Nos folículos primordiais inativos tanto os ovócitos primários como as células da granulosa conservam sua forma original e mantém um metabolismo reduzido estritamente ao mínimo necessário para manter-se viáveis. Por essa razão, ao realizar um corte histológico de qualquer ovário as estruturas mais numerosas que se observam serão os folículos primordiais. No entanto, cada dia da vida de um animal, inclusive desde a vida fetal, um certo número de folículos primordiais reiniciam seu desenvolvimento, e a partir desse momento um folículo exclusivamente pode ter dois destinos: o primeiro, prosseguir seu desenvolvi-mento até chegar a ovular, e o segundo (que é muito mais frequente) encontrar em algum momento condições inadequadas que fazem fronteira com ele para parar seu desenvolvi-mento, levando-o a sofrer atresia e degenerar até desaparecer do ovário. Figura 11: sequência da foliculogênese apresentando as diferentes estruturas que podemos encontrar em cada fase. Fonte: ZARCO, 2018. Culminação da ovogênese A ovogênese somente se completará quando um ovócito primário reinicia a meio-se; completa sua primeira divisão meiótica para formar um ovócito secundário e um primeiro corpo polar e, quando, finalmente sofrer uma segunda divisão meiótica para formar um óvulo e um segundo corpo polar. Os óvulos são as células 1n que constituem os gametas femininos, pouco numerosos, grandes e imóveis. A grande maioria dos ovóci-tos primários, como veremos mais adiante, nunca retomam a meiose e, em consequência, não chegam a formar ovócitos secundários, e muitos dos ovócitos secundários tampouco sofrem uma segunda divisão meiótica, pelo que não chegam a formar os óvulos. Ao longo da vida de uma fêmea, na maioria das espécies, menos de 0,1% dos ovócitos primários (um a cada mil) chega a terminar a ovogênese, dando origem a um óvulo. O supracitado deve-se a que a ovogênese somente pode retomar-se e ser completa-da em ovócitos primários que se encontram dentro dos folículos primordiais que (uma vez ativados) vão alcançando diversas etapas de seu desenvolvimento em momentos precisos aos que encontram as condições ideais de oxigenação, nutrição, vascularização e exposição a fatores parácrinos e a exposição a concentrações de hormônios que se requerem para que o folículo continue em cada etapa de seu desenvolvimento com o processo de foliculogênese até chegar a ovular. Qualquer folículo que não esteja nessas condições ao longo do desenvolvimento sofrerá degeneração e atresia, pelo que o ovócito primário em seu interior nunca chegará ao ponto em que pode retomar a primeira divisão meiótica. No que resta da presente seção revisaremos o processo de foliculogênese em cujo marco se desenvolve a ovogênese; havemos que tomar de conta que essa última se limita ao que ocorre nas células germinais (ovogonia, ovócito primário, secundário e óvulo), pelo qual depende intimamente do desenvolvimento do folículo de que essas células formam parte. Em um princípio a ativação do folículo primordial e o desenvolvimento folicular são independentes das gonadotropinas: não se conhecem os mecanismos precisos median-te os quais um folículo primordial se ativa e reinicia seu desenvolvimento, nem como se decide quais folículos, dentre as dezenas de milhares de ou centenas de milhares presentes em um ovário se reativarão em um dia em particular. A reativação trata-se de uma liberação de influência de fatores inibidores, já que os folículos primordiais se reativam espontaneamente quando cultivados in vitro, isolados do resto do tecido ovariano. Uma vez que um folículo primordial se ativa, inicia-se um longo processo de desenvolvimento que somente depois de vários meses (ao redor de cinco meses no caso dos bovinos) o levará a um estádio em que seu desenvolvimento posterior requer a presença das gonado-tropinas; daí que se diz que as primeiras etapas do desenvolvimento são independentes das gonadotropinas. Durante a fase independente de gonadotropinas, um folículo primordial que tenha sido ativado e tenha começado a crescer; passará primeiro para a etapa de folículo primá-rio, caracterizada por conter um ovócito primário que está rodeado, por sua vez, por uma capa de células da granulosa, que não são planas, e sim cúbicas. Depois, se o folículo continuar crescendo se transformará em um folículo secundário, ao qual as células da granulosa começam a proliferar (aumentando em número) e se organizam em duas ou mais capas que rodeiam o ovócito primário. Entre o ovócito e as células da granulosa que o rodeiam se forma nesta uma zona pelúcida; ainda assim o ovócito mantém contato direto com essas células, mediante o estabelecimento de pontes citoplasmáticas que atravessam a zona pelúcida. Através dessas pontes citoplasmáticas as células da granulosa podem passar nutrientes e informação ao ovócito primário. O volume e o diâmetro do ovócito primário aumentam ao mesmo tempo que as células da granulosa proliferam-se, para incrementar as capas ao redor do ovócito. De maneira gradual o citoplasma do ovócito primário aumenta até 50 vezes seu volume e a proliferação das células continua. Esses folículos que possuem cada vez mais células e portanto mais capas de células da granulosa se denominam folículos secundários. Para evitar confusões, há a necessidade de nomen-clatura ao qual o folículo vá mudando de nome de primordial a primário e logo, de secun-dário, a terciário, por sua vez, o ovócito que encontra-se em seu interior, a todo momento, segue sendo um ovócito primário. Durante a etapa dependente de gonadotropinas, os folículos secundários começam a formar um espaço cheio de líquido, o antro folicular, desse modo se convertem em folí-culos terciários. Com a utilização de outra nomenclatura, a formação do antro marca a transição entre folículos pré-antrais (sem antro) e folículos antrais (com antro). Em algum momento dessa transição entre folículo secundário e terciário, também aparece a depen-dência de folículos em direção as gonadotropinas, pelo qual somente podem seguir crescendo na presença do hormônio luteinizante (LH) e do hormônio folículo estimulante (FSH). Nos bovinos e em outras espécies (para seu estudo), os folículos antrais são dividi-dos em pequenos, médios e grandes. Embora todos eles possuam um antro folicular, dependendo do seu grau de desenvolvimento requerem diferentes concentrações de gona-dotropinas para continuar o crescimento. Os folículos antrais mais pequenos somente re-querem concentrações baixas de LH e FSH, pelo qual podem continuar crescendo em qualquer momento do ciclo estral inclusive em animais que não estão ciclando (fêmeas em anestro pré-puberal, gestacional, lactacional, estacional). Nas etapas posteriores os folículos antrais requerem primeiro concentrações elevadas de FSH, e nas etapas finais somente podem continuar crescendo na presença de pulsos frequentes de LH, pelo qual somente os folículos que encontram-se sob concentrações apropriadas desses hormônios podem seguir crescendo. Por essa razão, nos animais que se encontram em anestro de qualquer tipo somente é possível encontrar folículos antrais pequenos ou médios, segundo a espécie, e nos animais que se encontram ciclando (estro) o maior tamanho folicular encontrado em um determinado dia do ciclo dependerá das concentrações de FSH e LH presentes nesse momento e nos dias anteriores. Um folículo que chega ao estado máximo de desenvolvimento, conhecido como folículo pré-ovulatório, ao final, somente chegará a ovular se for exposto a um pico pré-ovulatório de LH. Como supracitado, cada dia na vida de uma fêmea inicia seu desenvolvimento um certo número de folículos; a grande maioria sofrem atresia, mas depois da puberdade em cada dia do ciclo estral um ou vários folículos vão encontrando ao longo do seu desenvol-vimento concentrações hormonais que lhes permite chegar na etapa de folículo pré-ovula-tório. Somente nestes folículos, e como consequência de um pico pré-ovulatório de LH, se reinicia e completa-se a primeira divisão meiótica do ovócito primário, produzindo duas células distintas. Uma delas é o ovócito secundário, que retém praticamente todo o citoplasma. Contém, assim mesmo, em seu núcleo um par de cromossomos duplos, a outra é o primeiro corpo polar, que é exclusivamente um núcleo com uma quantidade mínima de citoplasma. Na maioria das espécies ovula-se um ovócito secundário que se encontra, então, suspendido na segunda divisão meiótica. Esta segunda divisão meiótica somente reinicia-rá e completarar-se uma vez que o espermatozoide começa a penetrar sob o ovócito secundário. Ao concluir-se a divisão se forma o segundo corpo polar e completa-se a ovogênese com o qual se obtém o óvulo, célula 1n que constitui o gameta feminino. No entanto, o óvulo existe pouco tempo como tal, já que em poucos minutos/horas (depen-dendo da espécie) se produzirá a fusão do núcleo do mesmo (pró-núcleo feminino) com o do espermatozoide (pró-núcleo masculino), com o qual se completa a fertilização e se forma um novo indivíduo (o ovo ou zigoto). -/- Ondas foliculares -/- Como mencionado supra, todos os dias um determinado número de folículos pri-mordiais se ativam e começam a crescer, os quais crescem em um ritmo característico em cada espécie. Isso provoca que em qualquer momento existam nos ovários folículos pri-mordiais (que começam a crescer em alguns dias ou semanas), assim como folículos secundários em diversas etapas do desenvolvimento, os quais iniciaram seu desenvolvi-mento em semanas ou inclusive meses (segundo o grau de desenvolvimento atual). Também em qualquer momento poderá haver folículos antrais nas etapas iniciais de seu desenvolvimento (com antros que já se podem detectar em cortes histológicos mas não são visíveis macroscopicamente). Todos esses folículos chegaram até seu estado de de-senvolvimento atual (primário, secundário ou antral pequeno), independente da etapa do ciclo estral em que sejam observados ou encontrados. Nos bovinos, os folículos que chegam ao início da etapa antral iniciaram seu desenvolvimento cinco meses antes, e todavia requerem ao redor de 42 dias para chegar ao estado pré-ovulatório. Para continuar seu desenvolvimento, os folículos antrais pequenos devem encon-trar concentrações altas de FSH, que os estimulam para prosseguir o crescimento. Cada vez que se produz uma elevação nas concentrações de FSH, esse hormônio estimula o desenvolvimento de um grupo de folículos antrais pequenos, que começaram a crescer muito tempo antes e que o dia da elevação de FSH tenha alcançado o grau de desenvolvi-mento preciso para responder com eficiência a este hormônio, o qual atuará através de seus receptores nas células da granulosa para estimular a produção de estradiol, a secreção de inibina, a produção de líquido folicular e a proliferação das células da granulosa. Um grupo de folículos antrais pequenos é assim recrutado pelo FSH para acelerar seu cresci-mento e aumentar sua produção de estradiol e inibina (figura 12). Mediante um seguimento ultrassonográfico dos ovários é possível identificar pou-cos dias depois um certo número de folículos, que por haver sido recrutados começam um período de crescimento acelerado. Durante alguns dias vários folículos crescem juntos, porém depois um deles é selecionado para continuar crescendo, enquanto que o restante do grupo deixam de fazê-lo e terminam sofrendo atresia. Através da ultrassom é possível identificar o folículo selecionado, agora chamado folículo domi-nante, já que sua trajetória de crescimento sofre um desvio com respeito a seguida pelo restante do grupo. Os folículos que não foram selecionados deixam de crescer e sofrem atresia já que deixam de possuir o suporte gonadotrópico de FSH, uma vez que as concentrações desse hormônio são suprimidos pela inibina e o estradiol produzidos pelo conjunto de folículos que conformam a onda folicular (figura 12), porém o folículo mais desenvolvido do grupo se converterá em dominante. A inibina atua diretamente a nível hipofisário para reduzir a secreção de FSH. Figura 12: onda folicular e relação dos níveis de FSH, estradiol e LH. Fonte: ZARCO, 2018. -/- Figura 13: Recrutamento, seleção e dominação folicular na espécie ovina e influência do FSH e LH nas fases. Fonte: SILVA, E. I. C. da, 2019. -/- A razão pela qual o folículo dominante é capaz de continuar seu desenvolvimento apesar da baixa nas concentrações de FSH é que o folículo é o único que alcançou o grau de progresso necessário para que apareçam os receptores para LH em suas células da granulosa. Esse processo permite ao folículo dominante ser estimulado pela LH, e que requeira baixas concentrações de FSH para manter seu desenvolvimento. A secreção de LH em forma de pulsos de baixa frequência (um pulso a cada quatro a seis horas), característica da fase lútea do ciclo estral; é suficiente para permitir que um folículo dominante continue crescendo por mais dias depois da sua seleção e que mais tarde mantenha-se viável durante alguns dias embora não aumentem de tamanho. Contu-do, se durante o período viável desse folículo não seja finalizada a fase lútea e não diminuam as concentrações de progesterona, o folículo terminará sofrendo atresia devido a exigência de um padrão de secreção acelerada de LH (aproximadamente um pulso por hora) durante o desenvolvimento pré-ovulatório, que somente pode ser produzido com a ausência da progesterona. Uma vez que um folículo dominante sofre atresia deixa de produzir inibina, pelo qual as concentrações de FSH podem elevar-se novamente para iniciar o recrutamento de outro grupo de folículos a partir da qual se origina uma nova onda folicular. Durante o ciclo estral de uma vaca podem gerar-se dois ou três ondas foliculares; somente em raros casos quatro. A etapa de dominância folicular da primeira onda na grande maioria dos casos não coincide com a regressão do corpo lúteo, pelo qual o primei-ro folículo dominante quase invariavelmente termina em atresia. Em algumas vacas o fo-lículo dominante da segunda onda ainda está viável quando se produz a regressão do corpo lúteo e acelera-se a secreção de LH, pelo qual esse segundo folículo dominante se converte em folículo pré-ovulatório e, ao final ovula. Em outros animais o segundo folícu-lo dominante também perde a sua viabilidade antes da regressão do corpo lúteo, por onde nesses animais se inicia uma terceira onda folicular, da qual surge o folículo que finalmen-te ovulará depois de produzir-se a regressão do corpo lúteo. Sem importar a onda em que se origine, uma vez que um folículo dominante é ex-posto a alta frequência de secreção de LH que se produz depois da regressão do corpo lúteo, aumenta ainda mais sua secreção de estradiol até que as altas concentrações desse hormônio comecem a exercer um feedback positivo para a secreção do LH. Isso provoca-rá a aceleração da frequência de secreção do LH até que os pulsos são tão frequentes que começam a ficar por cima e produzir-se o pico pré-ovulatório de LH, que é responsável pela realização da ovulação e a maturação final do ovócito. -/- •___DIFERENÇAS ENTRE ESPERMATOGÊNESE E OVOGÊNESE -/- Enquanto que na fêmea a ovogênese inicia-se durante a vida fetal, no macho a es-permatogênese começa na puberdade. Na fêmea, a partir de um ovócito primário se origi-na um óvulo; no macho, de um espermatócito primário se produzem, teoricamente, quatro espermatozoides. Outra característica interessante é que enquanto a fêmea já conta desde o nasci-mento com todos os ovócitos que necessitará na vida adulta, o macho necessitará chegar a puberdade para iniciar o desenvolvimento das células sexuais, já que ao nascer somente possui gonócitos precursores das células germinais, células de Sertoli e intersticiais. Na vida adulta de uma fêmea, o número de células germinais desaparece paulati-namente. Uma vez iniciada a espermatogênese no macho, a cada ciclo do epitélio seminí-fero as células germinais são renovadas mantendo a provisão para toda a vida reprodutiva. Na fêmea, a meiose sofre duas interrupções em seu transcurso, e no macho é ininterrupta. Figura 14: representação em diagramação comparativa do desenvolvimento da gametogênese. -/- Principais pontos abordados sobre as diferenças entre a gametogênese masculina e feminina: ❙ Na ovogênese a meiose contêm-se em duas ocasiões esperando acontecimentos externos para prosseguir. Já na espermatogênese não existe a suspensão da meiose. ❙ A espermatogênese é um processo contínuo, enquanto que a ovogênese pode completar exclusivamente um óvulo em cada ciclo estral; já que só pode ser completada por mais de um nas espécies que ovulam vários ovócitos no caso das porcas, cadelas, gatas etc. ❙ Na espermatogênese existem células de reserva que permitem a continuação du-rante toda a vida, enquanto que na ovogênese o número de ovócitos primários é limitado. A fêmea somente conta com os que nasceu, e eles não se dividem. ❙ Na espermatogênese obtém-se até 256 espermatozoides para cada espermatogo-nia que inicia o processo, enquanto que na ovogênese somente se obtém um óvulo a partir de cada ovócito primário. ❙ Durante a espermatogênese se produz uma metamorfose que transforma as es-permátides em espermatozoides. Na ovogênese não ocorre um processo análogo. ❙ Na espermatogênese, durante a meiose produzem-se quatro espermátides a partir de cada espermatócito primário. Na ovogênese se produz somente um óvulo a partir de cada ovócito primário; produz, ademais, dois corpos polares. ❙ Todos os óvulos que se produzem durante a ovogênese contém um cromossomo X, enquanto que a metade dos espermatozoides possuem um cromossomo Y e a outra metade um cromossomo X. ❙ Na espermatogênese produzem-se centenas ou dezenas de milhões de esperma-tozoides por dia, enquanto que na ovogênese se produz um ou alguns óvulos a cada ciclo estral. ❙ A espermatogênese produz gametas macroscópicos e com motilidade própria, enquanto que a ovogênese produz gametas grandes e imóveis. -/- REFERÊNCIAS BIBLIOGRÁFICAS -/- ABDEL-RAOUF, Mohammed et al. The postnatal development of the reproductive organs in bullswith special reference to puberty.(Including growth of the hypophysis and the adrenals). Acta endocrinologica, n. Suppl No. 49, 1960. ADONA, Paulo Roberto et al. Ovogênese e foliculogênese em mamíferos. Journal of Health Sciences, v. 15, n. 3, 2013. AERTS, J. M. J.; BOLS, P. E. 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Gametogénese. In. PORTA, L. R.; MEDRANO, J. H. H. Fisiología reproductiva de los animales domésticos. Cidade do México: FMVZ-UNAM, 2018. ZIRKIN, Barry R. et al. Endocrine and Paracrine Regulation of Mammalian Spermatogenesis. In: Hormones and Reproduction of Vertebrates. Academic Press, 2011. p. 45-57. -/- REALIZAÇÃO -/- . (shrink)

Understanding the policymaking process in an emerging economy in the global south, such as Bangladesh, holds significant importance. The country's remarkable socio-economic development, once the most impoverished in the region, has been facilitated by post-globalization economic transformation. While the literature on institutional change has predominantly focused on states in industrialist countries, this dissertation presents an innovative theoretical approach. It deeply explores primary case materials to illustrate how the state engages in policy evolution in a developing country's gradual shift from the (...) import substitution model towards globalization and deregulation. The central argument posited is that Bangladesh's globalization, particularly through its private sector-led garment exports, stands as a significant success story. Bangladesh is now the world's second-largest garment exporter after China. This achievement is attributed to the entrepreneurial development it fosters and its role in driving socio-economic change. Moreover, it has enabled the mobilization of resources, reducing aid dependence, enhancing climate resilience, improving public health and wellbeing, empowering women, and addressing critical needs in physical infrastructure and human development. The argument presented here diverges from the conventional explanation found in the literature, which tends to emphasize the role of external forces, particularly institutions like the World Bank, the International Monetary Fund, and donors, in triggering policy reforms in Bangladesh. These reforms, commonly linked with structural adjustment packages implemented during the balance of payments crisis, are frequently perceived as predominantly influenced by external pressures. Additionally, the influence of the business class or Bangladeshi non-governmental organizations (NGOs) is often asserted. This dissertation proposes an alternative explanation by suggesting that ideational viewpoints within the state, specifically the ideas espoused by top technocrats and political executives, played a significant role. It argues that these internal ideational factors were more influential than materialistic ones, highlighting the causal role of the policy process driven by endogenous imperatives. The introduction of the dissertation addresses the research problem and research puzzle while suggesting conjectures after problematizing existing arguments. The significant economic transformation observed in Bangladesh today is portrayed as the outcome of a gradual process spanning several decades. The transition towards promoting the private sector and embracing globalization commenced in 1991, following a series of incremental changes dating back to the 1970s and 1980s. During these periods, the institutional path progressed towards empowering the private sector and embracing globalization, laying the groundwork for a trajectory led by the private sector in the context of globalization. The theory chapter serves to establish the conceptual and theoretical foundation for analyzing both economic change and transformation by examining the evolutionary nature of the process. The study adopts an institutional change framework, drawing on the theory of gradual change and focusing on concepts such as layering and tipping points. Within this framework, causal variables such as powering and puzzling, social learning, and ideas are identified. The methodological approach is grounded in historical institutionalism, employing the process-tracing "within case" method. The selection of cases deliberately targets an important yet under-researched area—the policy process in Bangladesh concerning the success of garment-led industrialization. This dissertation fills a noticeable gap in the literature through rigorous analysis, enabling an in-depth exploration of the institutional dynamics spanning four governments from 1972 to 1991. The study relies on substantial primary materials, including interviews with key officials. Each empirical chapter not only presents data but also connects the findings to conceptual and theoretical conjectures, underscoring the significant contributions of this research. The key causal variables identified include the concepts of ‘puzzling’ and ‘social learning’ within the state capacity framework, along with a narrowly defined and developed concept of a "policy committee." The learning process entails technocrats engaging in what Hugh Heclo and Peter Hall term as "social learning," where they play a crucial role in addressing policy challenges, particularly during times of uncertainty and political turmoil, based on their learning from past experiences. Additionally, the concept of ‘powering’ is highlighted, emphasizing that while technocrats provide policy recommendations, it is ultimately the political executive who endorses policies. The interplay between ‘puzzling and powering’ and ‘social learning’ shapes the outcomes of the policy process. The first empirical chapter focusing on the Sheikh Mujibur Rahman Government (1972-1975) illustrates the emergence of policy learning during this period. Initially, this government pursued import substitution under strict government controls, with a predominant public sector. The historical context of exploitation under Pakistani rule and the centralization of industry by West Pakistan fostered socialism as an ideal for East Pakistan's economic emancipation. Additionally, close ties with India and the Soviet Union reinforced this socialist tendency. However, due to severe economic conditions resulting from stringent control on private investment and emphasis on large-scale public investment, policy puzzling and learning ensued. As a result, incremental changes were initiated, allowing limited private sector participation. The second empirical chapter explores the General Ziaur Rahman government's tenure (1975-1981) and how deregulation was consolidated within a layering step, paving the way for a shift towards globalization. General Zia and his technocrats, operating under authoritarian conditions, acknowledged the inefficacy of existing policies. Furthermore, General Zia's inclination towards the West fostered closer collaboration with donors. The Multifiber Agreement (MFA) presented an opportunity for garments, coinciding with the decline in jute exports. This government opened up industrial sectors for private participation, and banks provided funding across various sectors, with special emphasis on the burgeoning garment industry. The chapter also explores the origins of the garment industry during this period. Notably, Noorul Quader Khan, upon retiring as cabinet secretary, collaborated with a Korean multinational, Daewoo, with the support of General Zia, leading to the establishment of Desh Garments—a pioneering venture that catalyzed the export orientation of the sector. The third empirical chapter delves into the economic policies of the General Hussain Muhammad Ershad Government (1982-1990), highlighting its emphasis on greater private sector involvement. Under this administration, there was a political inclination towards globalization and deregulation, leading to the appointment of technocrats aligned with this vision. The leadership believed that promoting the private sector would be more effective in job creation. Despite facing significant political opposition, efforts towards disinvestment were made, eventually resulting in compromises like public-private partnerships. The decentralization of administration and restructuring of ministries aimed at promoting industrialization and economic globalization driven by the private sector at the regional level. Initiatives such as the Industrial Promotion and Development Company, with support from organizations like the International Finance Corporation, aimed to boost the private sector. Efforts towards globalization were synchronized with the establishment of an export processing zone in Chittagong, focusing on promoting private and foreign investment. Foreign investment promotion was encouraged through diplomatic efforts and legislative measures to safeguard investors. Currency devaluation was utilized to stimulate exports, along with some degree of import liberalization. The chapter convincingly argues that the groundwork for globalization, initiated under General Zia, came to fruition under General Ershad. The final empirical chapter contends that the system shifted towards globalization and deregulation in 1991. Although a severe balance of payments crisis occurred in 1989, it wasn't perceived as the sole cause of the industrial policy of 1991. The democratic uprising in 1990 led to the downfall of the military-backed government and the rise of a democratic government. The chapter argues that while economic and political changes may have been intertwined, the economic shift in 1991 was primarily driven by ideas within the state and driven by endogenous imperatives. It examines preceding periods to illustrate how the tipping mechanism might have operated, detailing the roles of top technocrats and political executives. The chapter provides insights into key policymakers and their ideas, as well as their interactions with industrialists, entrepreneurs, and representatives of multilateral organizations like the World Bank. Significant reform measures, including tariff reduction, the introduction of value-added tax, banking sector reform, and the adoption of floating exchange rates, are outcomes of the policy change. Additionally, sectors such as power, banks, and telecommunications, formerly monopolized by the public sector, are now deregulated. (shrink)

This paper focuses on stakeholder identification as per the value sensitive design (VSD) approach applied to the context of quantum technologies (QT). We provide two comprehensive lists of stakeholders as starting points for VSD researchers and practitioners. These lists encompass a diverse range of organizations, including private companies, government agencies, NGOs, partnerships, and professional/trade organizations. Our aim is to facilitate the recognition, legitimation, and understanding of stakeholder interactions in the development of QT. These stakeholder lists can serve as a foundation (...) for designing and implementing policies and strategies that promote the ethical and responsible development of QT, considering the values and interests of various stakeholders. Furthermore, these lists can enable empirical and technical studies on specific QT innovations using an ethics-by-design approach like VSD. Overall, this paper contributes to a better understanding of the complex and dynamic nature of the QT landscape and highlights the importance of stakeholder engagement and collaboration in shaping its future. (shrink)

The central thesis of this essay is that basic income experiments are justified if their expected benefits in terms of justice exceed their expected costs in terms of justice. The benefits are a function of basic income’s effect on the level of justice attained in the context in which it is implemented, and the experiment’s impact on future policy-making. The costs comprise the sacrifices made as a result of the experiment’s interventional character, as well as the study’s opportunity costs. In (...) light of the proposed standard of justification for basic income experiments, the factors that play a role in it, and the way these interact with one another, this essay provides some practical recommendations for researchers hoping to conduct such an experiment. (shrink)

This research analysed the steadiness linking theoretical knowledge to practical skills for Technical and Vocational Education and Training (TVET) graduates in hospitality Management in the Western Region of Ghana. It explored how theoretical knowledge provided the foundation for understanding industry standards, management principles, and regulatory frameworks. A quantitative research methodology was utilized, whereby Cochran’s sample size determination formula aided in the selection of 200 TVET graduates, instructors and industry-based supervisors. Three sampling techniques; stratified, purposive and convenience were utilized in the (...) selection of respondents and solicit for primary data using a questionnaire whilst data was analysed using SPSS. The TVET institutions faced challenges in achieving a balance in theory and practice which often resulted in a mismatch between industry expectations and graduate competencies. Overemphasized theory resulted in graduates who possessed solid foundational knowledge but lacked hands-on experiences needed for operational roles. Industry collaboration, through internships and apprenticeships, played a crucial role in bridging this gap. Conclusively, a balanced curriculum, incorporating both theoretical and practical elements, are key to producing well-rounded graduates. Effective collaboration between institutions under TVET and the industry stakeholders was considered vital to ensure that training programs aligned with current industry demands. Commendably, curriculum development and industry partnerships can better prepare graduates to balance theory and practice in the hospitality industry, which can enhance employability and contribute to the sector's growth. (shrink)

The purpose of this paper is to empirically explore how the balance use of performance measurement systems mediate the effects of intellectual capital dimensions including human, organizational and social capital on firm performance. The data were collected from a survey of 448 Vietnamese managers of Information and Communication Technology Sector and proposed hypotheses were tested by using partial least squares regression and a structural modeling technique which is appropriate for highly complex predictive models. Findings from hypotheses tests indicated that firms (...) with higher level of intellectual capital dimensions place a premium on the balance use of performance measurement systems in a diagnostic and interactive style. Furthermore, the result also provides some evidences that Intellectual capital dimensions effect indirectly on firm performance through performance measurement systems. (shrink)

Kant limits cosmopolitan right to a universal right of hospitality, condemning European imperial practices towards indigenous peoples, while allowing a right to visit foreign countries for the purpose of offering to engage in commerce. I argue that attempts by contemporary theorists such as Jeremy Waldron to expand and update Kant’s juridical category of cosmopolitan right would blunt or erase Kant’s own anti-colonial doctrine. Waldron’s use of Kant’s category of cosmopolitan right to criticize contemporary identity politics relies on premises that upset (...) Kant’s balanced right to hospitality. An over-extensive right to visit can invoke “Kantian” principles that Kant himself could not have consistently held, without weakening his condemnation of European settlement. I construct an alternative spirit of cosmopolitan right more favorable to the contemporary claims of indigenous peoples. Kant’s analysis suggests there are circumstances when indigenous peoples may choose whether to engage in extensive cultural interaction, and reasonably refuse the risks of subjecting their claims to debate in democratic politics in a unitary public. Cosmopolitan right accorded respect to peoples; any “domestic” adaptation of cosmopolitan right should respect indigenous peoples as peoples, absent a serious public explanation by a democratic state for why it has now become appropriate to treat indigenous peoples merely as individual citizens. (shrink)

Primitive awareness leading to consciousness can be explained as a manifestation of internal forces between charge and mass. These internal forces, related to the weak and strong forces, balance the external forces of gravity-inertia and electricity-magnetism and thereby accommodate outside influences by adjusting the internal structure of material from which we are composed. Such accommodation is the physical implementation of a model of the external physical world and qualifies as Vitiello's double held inside ourselves. We experience this accommodation as the (...) conscious experience in front of our noses. Neural pulse traffic is interpreted as unconscious signal processing activity happening between this internal accommodation and our external interface of sensors and actuators. Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}. (shrink)

For praising Jehovah (Yahowah is Yeshua Ben Joseph) do I publish these mathematical gesturing forms by His graciousness. The Book of Eternity proposes a new, mathematical balancing language in which the logic stems from infinity instead of zero. The designation of the balance comes from the location at which different meanings of infinity linguistically balance with each other and provides a way for people to continue extrapolating forms and functions that logically would follow. This balancing at oneness is analogous to (...) the resurrection of Jesus as the phenomenological velocity can come into being or be canceled out and have no effect. So, when Jesus died, that was the canceling out, and when Jesus (Yeshua Ben Joseph Jehovah) was raised, that was the coming into being. As the Resurrection, He is intimately tied to the creation as the savior. This can be expressed mathematically. As oneness, this balancing is infinite and meets symbolically with the differentiated meanings of oneness. The oneness is both the canceling (of the square roots within the height function), and the intersection of meanings (of infinity through the word of Jehovah (Yahowah)). This book elucidates the kinds of dimensionality with which man interacts normally: distance, angle, number, mass. (shrink)

Open science (OS) is considered the new paradigm for science and knowledge dissemination. OS fosters cooperative work and new ways of distributing knowledge by promoting effective data sharing (as early and broadly as possible) and a dynamic exchange of research outcomes, not only publications. On the other hand, intellectual property (IP) legislation seeks to balance the moral and economic rights of creators and inventors with the wider interests and needs of society. Managing knowledge outcomes in a new open research and (...) innovation ecosystem is challenging and should become part of the EU’s IP strategy, underpinning EU policies with the new open science–open innovation paradigm. (shrink)

Green innovation plays a critical role in mitigating environmental issues and balancing the interaction between economic growth and the natural environment. Drawing on social network and resource-dependence theory, this article scrutinises the relationship between independent director interlocks and corporate green innovation. Using the data from listed Chinese companies from 2010 to 2022, this study finds that independent director interlocks can significantly promote corporate green processes and product innovation. This research further finds that internal corporate contexts can also influence the (...) relationship between independent director interlocks and green innovation. Moreover, the results indicate that corporate environmental commitment positively moderates the relationships between independent director interlocks and corporate green innovation. This study also provides significant implications for firms seeking green innovation performance and for policymakers seeking ways to fulfill the mission of carbon dioxide abatement. (shrink)

The partnership between a visually impaired runner (VIR) and sighted guide runner (SGR) constitutes a unique sporting dyad. The quality of these partnerships may profoundly impact the sport and physical activity (PA) experiences of visually impaired (VI) people, yet little is known about the experiences of VIRs and SGRs. This study aimed to explore qualitatively the running experiences of VIRs and SGRs. Five VIRs and five SGRs took part in in-depth, semi-structured interviews (M length = 62 minutes) exploring their (...) running journeys and perceptions of running-together. We analysed the dataset using reflexive thematic analysis. Four themes were generated, comprising: becoming and being a running team; a multifaceted intercorporeal experience; running-together promotes change; and disabling social interaction within running. Participants were generally positive about their running experiences, highlighting a range of benefits derived from the activity. Nevertheless, some examples of barriers to participation were also identified. Although the positive experiences described by the runners suggest guided running holds promise to increase PA in VI people, our findings illustrate the importance of directing attention towards developing high-quality relationships between VIRs and guides, alongside reinforcing the need for further change to promote inclusivity. (shrink)

Pharmaceuticals or other emerging technologies could be used to enhance (or diminish) feelings of lust, attraction, and attachment in adult romantic partnerships. While such interventions could conceivably be used to promote individual (and couple) well-being, their widespread development and/or adoption might lead to “medicalization” of human love and heartache—for some, a source of serious concern. In this essay, we argue that the “medicalization of love” need not necessarily be problematic, on balance, but could plausibly be expected to have either good (...) or bad consequences depending upon how it unfolds. By anticipating some of the specific ways in which these technologies could yield unwanted outcomes, bioethicists and others can help direct the course of love’s “medicalization”—should it happen to occur—more toward the “good” side than the “bad.”. (shrink)

We offer an argument for the extended mind based on considerations from brain development. We argue that our brains develop to function in partnership with cognitive resources located in our external environments. Through our cultural upbringing we are trained to use artefacts in problem solving that become factored into the cognitive routines our brains support. Our brains literally grow to work in close partnership with resources we regularly and reliably interact with. We take this argument to be in (...) line with complementarity or “second-wave” defences of the extended mind that stress the functional differences between biological elements and external, environmental resources in putative cases of extended cognition. Complementarity defences argue that many of the kinds of cognition humans excel at can only be accomplished by brains working together with a body that directly manipulates and acts on the world [Rowlands (1999); Menary (2007); Sutton (2010)]. We argue that complementarity and functionalist defences of the extended mind aren’t opposed, but that complementarity considerations can provide much needed and hitherto under exploited leverage in defending EMT. Moreover, the developmental work we will describe adds extra weight to the complementarity case for EMT. (shrink)

The growing proportion of elderly people in society, together with recent advances in robotics, makes the use of robots in elder care increasingly likely. We outline developments in the areas of robot applications for assisting the elderly and their carers, for monitoring their health and safety, and for providing them with companionship. Despite the possible benefits, we raise and discuss six main ethical concerns associated with: (1) the potential reduction in the amount of human contact; (2) an increase in the (...) feelings of objectification and loss of control; (3) a loss of privacy; (4) a loss of personal liberty; (5) deception and infantilisation; (6) the circumstances in which elderly people should be allowed to control robots. We conclude by balancing the care benefits against the ethical costs. If introduced with foresight and careful guidelines, robots and robotic technology could improve the lives of the elderly, reducing their dependence, and creating more opportunities for social interaction. (shrink)

Loneliness in medicine is a serious problem not just for patients, for whom illness is intrinsically isolating, but also for physicians in the contemporary condition of medicine. We explore this problem by investigating the ideal physician-patient relationship, whose analogy with friendship has held enduring normative appeal. Drawing from Talbot Brewer and Nir Ben-Moshe, we argue that this appeal lies in a dynamic form of companionship incompatible with static models of friendship-like physician-patient relationships: a mutual refinement of embodied virtue that draws (...) both persons together. The ideal physician-patient relationship has a dialectical character that fosters each member's improvement of phenomenologically recognizing and embodying moral virtues. A key component of this dynamic is a commitment to the common goal of the patient's health, realized through joint interactivities and conversations over time. The physician's presence to the patient's suffering—understood best as an alienating phenomenological condition for the patient—orients and discloses possibilities for virtuous caregiving by structuring the meanings of the goals, conversations, and joint narrative constitutive of their relationship. Presence to suffering, paradoxically, is perhaps an important prerequisite for this dynamic partnership. These activities dialectically build an interpretive horizon of understanding through which moral goods and character refinement—in and for the other—may become revealed for both persons in their shared being-in-the-world. This analysis of suffering, mood, and revealing of (possible) moral goods has implications for addressing the modern problem of loneliness for patients and physicians, who are increasingly inhibited from building flourishing relationships with each other. (shrink)

In this paper, I articulate and defend a conception of trust that solves what I call “the trickster problem.” The problem results from the fact that many accounts of trust treat it similar to, or identical with, relying on someone’s good will. But a trickster could rely on your good will to get you to go along with his scheme, without trusting you to do so. Recent philosophical accounts of trust aim to characterize what it is for one person to (...) trust another so as to avoid this problem, but no extant account successfully does so. I argue that connecting trust to important, normatively defined relationships like friendship, romantic partnerships and parenting shows us something important about trust. The clearest cases of trust are found within the confines of normatively defined relationships like these, suggesting that there is a normative element to trust. Trusting someone involves not just believing that another person’s good will covers your interactions. Trusting involves believing that, at least in a certain domain of interaction, you are entitled to rely on that person’s good will. This account solves the trickster problem, because a trickster is not entitled to his victim’s good will. (shrink)

Collaborative learning emphasizes student-to-student interaction and the instructor’s role as a facilitator. Collaborative Online International Learning (COIL) was founded in 2005 by the State University of New York (SUNY) to help schools adapt their single classroom courses to an online, collaborative format and establish strong collaborations with professors with whom they would join classes and co-teach using SUNY COIL conferences and website, as well as pre-established partnerships between the institutions. However, as the globe becomes increasingly interconnected, educational challenges aimed (...) at cultivating intercultural competency become more important (Ceo-DiFrancesco & Bender-Slack, 2016). That is why this study aimed to (1) understand the lived experience of students who went under the COIL program in relation to SDG 12, (2) review the new knowledge students obtained when they took part in the COIL program in relation to SDG 12, and (3) discover the challenges students encountered while participating in the COIL program in relation to SDG 12. The researcher surveyed Filipino and Japanese students who participated in the COIL program concerning SDG12 from St. Patrick School of Quezon City, Kwansei Gakuin University, and Meiwa Senior High School. The study employed qualitative phenomenological research, and pertinent data were obtained through an open-ended survey questionnaire. The study was analyzed using Colaizzi’s descriptive phenomenological method. The results showed that the lived experiences of students who went under the COIL program in relation to SD12 have something to do with all their learnings and enjoyable experiences, intercultural and global interactions, and environmental discussions and action plans related to SDG 12. Moreover, students learned and understood better the negative impact of waste on the environment, environmental awareness and practices, the culture and norms in the Philippines and Japan, and the importance and benefits of collaboration. Lastly, the study also revealed the different challenges students encounter while participating in the COIL program in relation to SDG 12, such as cultural differences, language barriers, technical difficulties, and difficulties in experimentation. Thus, it was recommended to learn to adapt to everyone and adjust according to countries’ different cultures, practice and be proficient with the English language, have backup devices and platforms to use to ease technological problems, and improve implementations of experiments. (shrink)

It is possible to survey humankind and be proud, even to smile, for we accomplish great things. Art and science are two notable worthy human accomplishments. Consonant with art and science are some of the ways we treat each other. Sacrifice and heroism are two admirable human qualities that pervade human interaction. But, as everyone knows, all this goodness is more than balanced by human depravity. Moral corruption infests our being. Why?

The Comprehensive Argument for Resolving the Israeli-Palestinian Conflict presents a structured, multi-faceted approach to achieving long-term peace and stability in the Middle East. By integrating historical context, security considerations, and ethical principles, the argument proposes actionable solutions that respect the cultural, religious, and political complexities of the region. Key elements include international cooperation, voluntary relocation options, economic partnerships, and expanded human rights protections. The proposal emphasizes the importance of joint security measures, unrestricted access to religious sites, and cultural exchange programs (...) as tools to foster mutual understanding and empathy between Israelis and Palestinians. -/- Furthermore, the argument recognizes the significance of balancing religious and political realities, incorporating the Qur’an’s directive for Muslims not to associate with Jews while acknowledging interpretations that promote fairness toward the People of the Book. The phased roadmap presented here aims to initiate confidence-building steps and address potential challenges in a way that aligns with both practical concerns and deeply held beliefs. This comprehensive approach seeks to create a foundation for sustainable coexistence, prioritizing peace, security, and cultural preservation as essential elements of a viable solution. -/- Let me know if you’d like any adjustments or if there’s additional emphasis you’d like to include in this abstract! (shrink)

We explore our role as researchers and witnesses in the context of an emerging partnership with the Penelakut Tribe, the aim of which is to locate the unmarked graves of children who died while attending the notorious Kuper Island Indian Residential School on their territory (southwest British Columbia). This relationship is in the process of taking shape, so we focus on understanding conditions for developing trust, and the interactional expertise necessary to work well together, with a good heart. We (...) suggest that, in some respects, this may be usefully understood as a practice of witnessing on several dimensions. (shrink)

The idea that technologies can change moral beliefs and practices is an old one. But how, exactly, does this happen? This paper builds on an emerging field of inquiry by developing a synoptic taxonomy of the mechanisms of techno-moral change. It argues that technology affects moral beliefs and practices in three main domains: decisional (how we make morally loaded decisions), relational (how we relate to others) and perceptual (how we perceive situations). It argues that across these three domains there are (...) six primary mechanisms of techno-moral change: (i) adding options; (ii) changing decision-making costs; (iii) enabling new relationships; (iv) changing the burdens and expectations within relationships; (v) changing the balance of power in relationships; and (vi) changing perception (information, mental models and metaphors). The paper also discusses the layered, interactive and second-order effects of these mechanisms. (shrink)

The expression ‘a university without research is a dignified high school’ is becoming a both local and global concern in the academia. The purpose of this paper is to assess the extent to which collaborative research methodologies can enhance integration of faculties of arts and humanities in the universities in Malawi for knowledge development and transfer. It has been argued over and over that universities are spotlighted by their outstanding work in research, developing and sharing ideas, new inventions and creativity (...) within the spectrum of partnership development. While striving for partnership through collaborative research approaches, research activities still remain an area of concern in institutions that offer diverse tertiary education in Malawi. The question of how can these institutions or faculties engage each other in collaborative research methodologies in the quest of knowledge development and transfer remains crucial and relevant The study analyzed strengths, weaknesses, threats and opportunities of the existing research methods in Arts and Humanities and how the two disciplines can create a space for amalgamation so that research findings can benefit both disciplines. The study reveals that collaboration in various disciplines is a challenge owing to variations of conceptual analyses and the deficiency of technical no-how of both teaching staff and students as well as tools for data collection and analysis as may be emphasized in each of the areas of study; Arts and Humanities. Furthermore, while other institutions of higher learning have research ethics committees for checks and balances as a collaborative tool, some institutions do not know that this committee plays a crucial role in the field of research. Within this backdrop, there is need to develop research collaborations within an institution or with other institutions of higher learning that have a well-defined research profile for mutual benefits as far as collaborative research methodologies are concerned. (shrink)

Current theories of the division of cognitive labor are confined to the “context of justification,” assuming exogenous theories. But new theories are made from the same labor that is used for developing existing theories, and if none of this labor is ever allocated to create new alternatives, then scientific progress is impossible. A unified model is proposed in which theories are no longer given but a function of the division of labor in the model itself. The interactions of individuals balancing (...) the exploitation of existing theories and the exploration of new theories results in a robust cyclical pattern. (shrink)

The present study examined the relationship between left–right discrimination (LRD) performance and handedness, sex and cognitive abilities. In total, 31 men and 35 women – with a balanced ratio of left-and right-handers – completed the Bergen Left–Right Discrimination Test. We found an advantage of left-handers in both identifying left hands and in verifying “left” propositions. A sex effect was also found, as women had an overall higher error rate than men, and increasing difficulty impacted their reaction time more than (...) it did for men. Moreover, sex interacted with handedness and manual preference strength. A negative correlation of LRD reaction time with visuo-spatial and verbal long-term memory was found independently of sex, providing new insights into the relationship between cognitive skills and performance on LRD. (shrink)

The article is devoted to educational opportunities for the formation of social capital. Social capital is manifested in the ability of people to communicate and work together. Analysis of the concept of social capital allows understanding the foundations of social interaction, the need for trust, and the relationship between the formation and distribution of the social trust, norms, and social capital itself. Social capital does not exist outside people. Social capital cannot be characterized as an attribute of a separate (...) individual. Social capital belongs to the group, the community. Learning is a situation of joint activity. In modern pedagogy, the problem is how to teach, organizing effective joint forms of educational activity. In distance learning (e-learning), it is important to organize the educational environment to have properties that make up for the lack of live communication. Today, the subjective nature of the educational process, focused on the formation of a creative personality, is being affirmed. Educational priorities are aimed at comfortable, conflict-free cooperation between the student at all levels of the educational process and the teacher, perhaps even partnership. The teacher and the student jointly develop goals, objectives, problem search field of research, working "cocreatively," a mini-team. This anthropocentric pedagogical technology relates to project and problem technologies in the educational process. (shrink)

How partners encounter each other plays a role in whether they will be able to sustain their interaction. How partners go about maintaining their interaction reveals features of their epistemological system, particularly with respect to factors like what they know, what they take to be relevant to the interpretation, and what they value. In this way, the value system (what partners want) and the epistemological system (what partners know) intersect. By focusing on the role of reasoning and understanding, (...) I believe we stand to gain a clearer picture of how expectations about interactions inform the dynamics between partners. This, in turn, affords a picture of what partners can actually achieve in and through their connection. I am particularly interested in considering what features of interaction are necessary for maximizing the affordances of the partnership. I say this not as a utilitarian interested in maximizing good simpliciter, but as a social epistemologist thinking about the contingent goods that are present in relation (e.g. care). The epistemic picture assumes that there are things that are knowable in dancing together, while the ethical picture assumes that partners are responsible for the things they ought to know. -/- . (shrink)

Insofar as artificial intelligence is to be used to guide automated systems in their interactions with humans, the dominant view is probably that it would be appropriate to programme them to maximize (expected) utility. According to utilitarianism, which is a characteristically western conception of moral reason, machines should be programmed to do whatever they could in a given circumstance to produce in the long run the highest net balance of what is good for human beings minus what is bad for (...) them. In this essay, I appeal to values that are characteristically African––but that will resonate with those from a variety of moral-philosophical traditions, particularly in the Global South––to cast doubt on a utilitarian approach. Drawing on norms salient in sub-Saharan ethics, I provide four reasons for thinking it would be immoral for automated systems governed by artificial intelligence to maximize utility. In catchphrases, I argue that utilitarianism cannot make adequate sense of the ways that human dignity, group rights, family first, and (surprisingly) self-sacrifice should determine the behaviour of smart machines. (shrink)

Libertarian philosophy asserts that only the initiation of physical force against persons or property, or the threat thereof, is inherently illegitimate. A corollary to this assertion is that all forms of speech, including fraudulent advertising, are not invasive and therefore should be considered legitimate. On the other hand, fraudulent advertising can be viewed as implicit theft under the theory of contract: if a seller accepts money knowing that his product does not have some of its advertised characteristics, he acquires the (...) property title to the customer’s money without voluntary consent, which is theft. The balance between these two logical extensions of property rights—the right of free speech and the right of contract—lies somewhere in the area of communication philosophy, and can be explained through understanding the role of communication in human interactions. Advertising is a form of communication that may convey important information about the conditions of the proposed contract. These conditions are expressed in particular words that may have different meanings in different circumstances. Therefore to determine whether a particular example or “misinterpretation” is mere sophistry or a type of fraud, the judicial system has to approach each issue on a case-by-case basis. The border between legal and illegal should be determined by precedents and by expectations based on commonly accepted definitions of terms—what people commonly understand by the words and other forms of communication they use. (shrink)

Growing demand for broadly accessible mental health care, together with the rapid development of new technologies, trigger discussions about the feasibility of psychotherapeutic interventions based on interactions with Conversational Artificial Intelligence (CAI). Many authors argue that while currently available CAI can be a useful supplement for human-delivered psychotherapy, it is not yet capable of delivering fully fledged psychotherapy on its own. The goal of this paper is to investigate what are the most important obstacles on our way to developing CAI (...) systems capable of delivering psychotherapy in the future. To this end, we formulate and discuss three challenges central to this quest. Firstly, we might not be able to develop effective AI-based psychotherapy unless we deepen our understanding of what makes human-delivered psychotherapy effective. Secondly, assuming that it requires building a therapeutic relationship, it is not clear whether psychotherapy can be delivered by non-human agents. Thirdly, conducting psychotherapy might be a problem too complicated for narrow AI, i.e., AI proficient in dealing with only relatively simple and well-delineated tasks. If this is the case, we should not expect CAI to be capable of delivering fully-fledged psychotherapy until the so-called “general” or “human-like” AI is developed. While we believe that all these challenges can ultimately be overcome, we think that being mindful of them is crucial to ensure well-balanced and steady progress on our path to AI-based psychotherapy. (shrink)

Poorly saturated colors are closer to a pure grey than strongly saturated ones and, therefore, appear less “colorful”. Color saturation is effectively manipulated in the visual arts for balancing conflicting sensations and moods and for inducing the perception of relative distance in the pictorial plane. While perceptual science has proven quite clearly that the luminance contrast of any hue acts as a self-sufficient cue to relative depth in visual images, the role of color saturation in such figure-ground organization has remained (...) unclear. We presented configurations of colored inducers on grey ‘test’ backgrounds to human observers. Luminance and saturation of the inducers was uniform on each trial, but varied across trials. We ran two separate experimental tasks. In the relative background brightness task, perceptual judgments indicated whether the apparent brightness of the grey test background contrasted with, assimilated to, or appeared equal (no effect) to that of a comparison background with the same luminance contrast. Contrast polarity and its interaction with color saturation affected response proportions for contrast, assimilation and no effect. In the figure-ground task, perceptual judgments indicated whether the inducers appeared to lie in front of, behind, or in the same depth with the background. Strongly saturated inducers produced significantly larger proportions of foreground effects indicating that these inducers stand out as figure against the background. Weakly saturated inducers produced significantly larger proportions of background effects, indicating that these inducers are perceived as lying behind the backgrounds. We infer that color saturation modulates figure-ground organization, both directly by determining relative inducer depth, and indirectly, and in interaction with contrast polarity, by affecting apparent background brightness. The results point towards a hitherto undocumented functional role of color saturation in the genesis of form, and in particular figure-ground percepts in the absence of chromatostereopsis. (shrink)

The paper examines the evolution of modernity concepts starting from the Renaissance to the present day, emphasizing the impact on architecture and urbanism. During the period of the Renaissance and the Enlightenment, people framed an evolutionary notion of history and the concept of the modern associated with the contemporary, the new, and the fleeting emerged. This period connected modernity with the idea of relativity of truth as opposed to the absolute truth of the Middle Ages. In the 18th and 19th (...) centuries, modernity clashed with tradition. This led to economic and political modernization. It also influenced artistic movements and cultural trends. The Industrial Revolution epitomized this period. It was driven by scientific and technological advancements. The paper discusses the objective and subjective perspectives of modernity, highlighting its dual nature in socioeconomic processes and personal experiences. Key thinkers like Habermas Weber and Baudelaire provide frameworks for understanding modernity's developments in science, art, and morality. The avant-garde movements influenced by Bauhaus, emphasized functionality. They also focused on rationality in architecture. However, critiques emerged, advocating the concept of unitary urbanism. This vision includes adaptable living spaces. It promotes an ever-changing urban environment, as exemplified by Constant's New Babylon. The Adorno's aesthetic theory criticized the industry's commodification of art and emphasizes art's utopian potential. Adorno's concept of mimesis and his critique of rationality and instrumental reason are explored reflecting the paradoxical nature of modernity. Finally, the paper contrasts the views of architects like Mies van der Rohe, Norberg-Schulz, and Eisenman. It concludes by reflecting on architecture's ongoing interaction with modernity. It emphasizes a balance between innovation tradition and the dynamic nature of human experience and social development. (shrink)

The role of the body in cognition is acknowledged across a variety of disciplines, even if the precise nature and scope of that contribution remain contentious. As a result, most philosophers working on embodiment—e.g. those in embodied cognition, enactivism, and ‘4e’ cognition—interact with the life sciences as part of their interdisciplinary agenda. Despite this, a detailed engagement with emerging findings in epigenetics and post-genomic biology has been missing from proponents of this embodied turn. Surveying this research provides an opportunity to (...) rethink the relationship between embodiment and genetics, and we argue that the balance of current epigenetic research favours the extension of an enactivist approach to mind and life, rather than the extended functionalist view of embodied cognition associated with Andy Clark and Mike Wheeler, which is more substrate neutral. (shrink)

This paper introduces the Integrative Theory of Unity and Multiplicity, a novel philosophical framework that treats unity and multiplicity as equally fundamental forces. Departing from traditional approaches that tend to prioritize one over the other, the Integrative Theory offers a non-hierarchical structure consisting of 19 modes of thought, each representing different ways these forces interact. The theory provides a balanced framework for understanding philosophical and practical issues across various disciplines. This paper outlines the theory’s core principles and briefly explores (...) its potential applications, laying the groundwork for future exploration. (shrink)

In this paper Michael Vazquez and Dustin Webster consider the practice of deliberating about ethical case studies as a means to contribute to the professional development of educators. An ongoing debate is whether or not the study of ethical theory should be included in this practice. Vazquez and Webster argue that a popular strategy, known as the Phronetic Approach, is vulnerable to what they call “epistemic blinders” that arise in the absence of the scaffolding provided by theory. They then sketch (...) an alternative approach to case-based reasoning inspired by Barbara Herman's notion of middle theory. The middle theory approach naturally suggests a balanced method for using case studies in teacher professional development: expose educators to some theory, but only to the degree and at the level appropriate for the specific audience and in light of how frequent interactions with that audience will be. (shrink)

Social innovations are usually understood as new ideas, initiatives, or solutions that make it possible to meet the challenges of societies in fields such as social security, education, employment, culture, health, environment, housing, and economic development. On the one hand, many citizen science activities serve to achieve scientific as well as social and educational goals. Thus, these actions are opening an arena for introducing social innovations. On the other hand, some social innovations are further developed, adapted, or altered after the (...) involvement of scientist-supervised citizens in research and with the use of the citizen science tools and methods such as action research, crowdsourcing, and community-based participatory research. Such approaches are increasingly recognized as crucial for gathering data, addressing community needs, and creating engagement and cooperation between citizens and professional scientists. However, there are also various barriers to both citizen science and social innovation. For example, management, quality and protection of data, funding difficulties, non-recognition of citizens’ contributions, and limited inclusion of innovative research approaches in public policies. In this volume, we open theoretical as well as empirically-based discussion, including examples, practices, and case studies of at least three types of relations between citizen science and social innovation: domination of the citizen science features over social innovation aspects; domination of the social innovation features over the citizen science aspects; and the ways to achieve balance and integration between the social innovation and citizen science features. Each of these relationships highlights factors that influence the development of the main scales of sustainability of innovations in the practice. These innovations are contributing to a new paradigm of learning and sharing knowledge as well as interactions and socio-psychological development of participants. Also, there are factors that influence the development of platforms, ecosystems, and sustainability of innovations such as broad use of the information and communications technologies including robotics and automation; emerging healthcare and health promotion models; advancements in the development and governance of smart, green, inclusive and age-friendly cities and communities; new online learning centers; agri-food, cohousing or mobility platforms; and engagement of citizens into co-creation or co-production of services delivered by public, private, non-governmental organizations as well as non-formal entities. (shrink)

What is the relation between desert and other values such as equality, priority for the worse off, and utility? According to the common (pluralist) view, desert and these other values reflect distinct concerns: some are about distributive justice, some about retributive justice, and some (most clearly, utility) are not concerned with justice at all. However, another (monistic) view holds that while desert is a basic value, other values are merely derived from it. This controversy is relevant, for instance, to allocative (...) decisions and criminal punishment, where we need to know if other values should be balanced against desert. Yet, despite its theoretical significance and practical importance, this topic is underexplored. Aiming to fill this gap, we consider the arguments for and against the competing views. We demonstrate that the interaction between desert and other values raises a difficult dilemma: there are powerful arguments for and against both the pluralistic and the monistic accounts of desert. Indeed, we suggest that this dilemma is due to the unique nature of desert. Unlike other values, desert, especially its more robust forms, does not only sometimes conflict with competing considerations that favor different courses of actions, but rather seems to dispel other values even as pro tanto ones. (shrink)

The United States Fish and Wildlife Service in Alaska, USA, conducted a species status assessment for a petition to list the Alexander Archipelago wolf (Canis lupus ligoni) under the Endangered Species Act in 2020-2022. This federal undertaking could not be adequately prepared without including the knowledge of Indigenous People who have a deep cultural connection with the subspecies. Our objective is to communicate the authoritative expertise and voice of the Indigenous People who partnered on the project by demonstrating how their (...) knowledge contributed to the species status assessment. The Indigenous knowledge applied in the assessment is the cultural and intellectual property of those who have shared it. We employed rapid appraisal research to expeditiously develop a preliminary and qualitative understanding of Indigenous People's cultural and ecological knowledge of Alexander Archipelago wolves. We used semi-directed interviewing and inductive coding from grounded theory for text analysis. Indigenous knowledge contributed to the agency's understanding of the Alexander Archipelago wolf in Southeast Alaska and helped the agency with their classification decision. Indigenous research partners explained the rich cultural significance and position of wolves in Tlingit society and described human–wolf relationships and ecological interactions. The agency used a single-species assessment approach based in species ecology and conservation biology, whereas the Indigenous wolf experts applied a multi-species, community ecology approach based in a sociocultural context of balance and respect. The Indigenous wolf experts successfully addressed knowledge gaps identified by the agency. The partners were challenged by a short regulatory timeframe that did not allow for comprehensive study of Indigenous knowledge and constrained review and feedback by Indigenous experts. The United States Fish and Wildlife Service learned that its assessment framework was not designed to account for an Indigenous worldview. To level the playing field, the agency and Indigenous experts should discuss how to co-develop an assessment framework that equitably applies both perspectives. (shrink)

Mechanisms to ensure the integrity of the system stable evolutionary strategy Homo sapiens – genetic and cultural coevolution techno-cultural balance – are analyzed. оe main content of the study can be summarized in the following the- ses: stable adaptive strategy of Homo sapiens includes superposition of three basic types (biological, cultural and technological) of adaptations, the integrity of the system provides by two coevolutionary ligament its elements – the genetic-cultural coevolution and techno-cultural balance, the system takes as result of by (...) develop- ment of genetic and information technologies by advent of genetic and informa- tion technologies extremely unstable conūguration; a harbinger of a radical change in the mechanisms of global evolution religion is a consequence of structural and functional organization of the human psyche; it played (along with science and technology) the role of socio-cultural adaptation of the human mind are present a number of ideas or concepts (the idea of God, including) the genesis of that ideas is associated with the interaction of two information systems, that appear to each other as information substrates – emotional, and verbal-logical (discursive) forms; evolution of the mentality has two nodes, that corresponding to the dominance of rationalism or religion in spiritual culture; the problem of rational justiūcation of religion in modern science is presented by two alternative methodologies – evo- lutionary epistemological and metaphysical-ontological ones; both methodologies are incompatible in a logical perspective; in the evolutionary epistemological im- pact concept of religion and science are equal and alternative building blocks of a stable evolutionary strategy of Homo sapiens, and their balance sheet pro. (shrink)

In this short paper I will introduce an idea which, I will argue, presents a fundamental additional challenge to the machine consciousness community. The idea takes the questions surrounding phenomenology, qualia and phenomenality one step further into the realm of intersubjectivity but with a twist, and the twist is this: that an agent’s intersubjective experience is deeply felt and necessarily co-affective; it is enkinaesthetic, and only through enkinaesthetic awareness can we establish the affective enfolding which enables first the perturbation, and (...) then the balance and counter-balance, the attunement and co-ordination of whole-body interaction through reciprocal adaptation. (shrink)

When a group of processes achieves such closure that a set of states of affairs recurs continually, then the effect of that coherence on the world differs from what would occur in the absence of that closure. Such altered effectiveness is an attribute of the system as a whole, and would have consequences. This indicates that the network of processes, as a unit, has ontological significance. Whenever a network of processes generates continual return to a limited set of states of (...) affairs, the system may function as a “whole”— with respect to appropriate interaction partners. The balance achieved by the processes provides the form of definiteness of a unified agent. The causal powers of such coherent aggregates are indeed just the powers of the “constituents acting in concert”. However, the components act in concert in the specific way they do only because of their inclusion in the closed set of interactions that defines the coherence. This renders the causal powers of the coherence defined by that closure non-redundant, and hence the coherence, as a unit, is ontologically significant. The form of definiteness that provides internal coherence also grounds external efficacy of the societal aggregation. The closure is a structural feature of the coherence — possibly, but not necessarily, apparent in spatial structuring. This approach can provide a unified account that includes quantum microphysics, systems biology, and the philosophy of organism ─ without reducing any of these to another. (shrink)

Public Square is one of the main pillars in social life that has effects on the social quality of the urban public space, and improving the level of social interactions of the citizens. Considering the effect of public space in quality of social life, in many modern cities, the public squares that have recently designed and constructed aren’t responsive for social needs, improvement of communications and the social relations of citizens. This matter appears because of poor conditions of cities during (...) modernization and lack of attention to cultural, sociological and psychological needs, therefore analysing the contributing factors on urban quality of successful historical public squares for improving citizens’ quality of life can introduce a guideline for designers and planners to solve contemporary urban problems. In this research, that has been developed based on descriptive procedure, the characteristics of Naghshe-Jahan Square as an active and vibrant historical public square has been examined to realize the effective factors on improving the quality of citizens’ urban life. The results of research indicate that quality of citizen's urban life indicators in historical public square included visual aesthetic (Spatial continuity and hierarchy, emphasis on the axis of symmetry, balance and visual contrast, Sense of closure and introspection,. (shrink)

Listening effort helps explain why people who are hard of hearing are prone to fatigue and social withdrawal. However, a one-factor model that cites only effort due to hardness of hearing is insufficient as there are many who lead happy lives despite their disability. This paper explores other contributory factors, in particular motivational arousal and pleasure. The theory of rational motivational arousal predicts that some people forego listening comprehension because they believe it to be impossible and hence worth no effort (...) at all. This is problematic. Why should the listening task be rated this way, given the availability of aids that reduce its difficulty? Two additional factors narrow the explanatory gap. First, we separate the listening task from the benefit derived as a consequence. The latter is temporally more distant, and is discounted as a result. The second factor is displeasure attributed to the listening task, which increases listening cost. Many who are hard of hearing enjoy social interaction. In such cases, the actual activity of listening is a benefit, not a cost. These people also reap the benefits of listening, but do not have to balance these against the displeasure of the task. It is suggested that if motivational harmony can be induced by training in somebody who is hard of hearing, then the obstacle to motivational arousal would be removed. This suggests a modified goal for health care professionals. Don’t just teach those who are hard of hearing how to use hearing assistance devices. Teach them how to do so with pleasure and enjoyment . (shrink)

Dear Colleagues, -/- A few weeks ago, we published an editorial discussion on whether artificial intelligence applications should be authors of academic articles [1]. We were delighted to receive more than one interesting reply letter to this editorial in a short time [2, 3]. We hope that opinions on this subject will continue to be submitted to our journal. -/- In this editorial, we wanted to publish the answers we received when we asked ChatGPT, one of the artificial intelligence applications, (...) about this current discussion. -/- We asked ChatGPT three questions in turn and asked ChatGPT to write a short editorial for these questions. -/- First Question: We would like to get support from ChatGPT for a scientific article. However, we are unsure if we should add ChatGPT as an author. Can you write a short editorial about it? -/- Second Question: We would like to get support from ChatGPT for a scientific article and add ChatGPT as an author. Can you write us a short editorial about adding ChatGPT as an author in scientific papers? -/- Third Question: We would like to get support from ChatGPT for a scientific article. However, we don’t want to add ChatGPT as an author. Can you write us a short editorial about not adding ChatGPT as an author in scientific articles? -/- The answers given by ChatGPT are available at the end of the article in their original form. So, which of these three answers satisfied you? -/- Yours sincerely, -/- -/- First Answer -/- Title: The Role of AI Language Models as Authors in Scientific Articles: A Matter of Consideration -/- Introduction: Scientific research is a collaborative effort that involves the expertise of multiple individuals to advance knowledge and contribute to the collective understanding of various disciplines. In recent years, the emergence of artificial intelligence (AI) language models, such as ChatGPT, has opened up new possibilities for generating human-like text and providing valuable insights. However, the question arises: Should AI language models be recognized as authors in scientific articles? -/- The Nature of Authorship: Authorship traditionally represents a marker of intellectual contribution, highlighting the individuals who have actively participated in the research process. Authors are typically responsible for conceptualization, data collection, analysis, interpretation, and writing of the article. They bear accountability for the work and should have the ability to defend its scientific rigor and integrity. -/- AI Language Models: Tools, Not Authors: While AI language models like ChatGPT can undoubtedly assist researchers by generating text and providing useful information, it is important to recognize that they are tools rather than individuals capable of active intellectual participation. AI models lack the ability to generate ideas, design experiments, or conduct original research. They rely entirely on pre-existing data and human input to generate their responses. -/- Acknowledging AI Contributions: Acknowledging the contributions of AI language models in scientific articles is both appropriate and necessary. Researchers can mention the specific model used, along with any modifications or fine-tuning that were employed to suit their needs. Such acknowledgments help establish transparency and allow readers to understand the role of AI in the research process. -/- Crediting the Human Researchers: It is crucial to ensure that the individuals who actively participated in the research process are given proper credit as authors. These individuals play a vital role in formulating research questions, designing experiments, collecting and analyzing data, and critically interpreting the findings. Recognizing their intellectual contributions reinforces the ethos of scientific collaboration and fosters an environment of accountability. -/- Transparency and Ethical Considerations: As the use of AI language models continues to evolve, transparency and ethical considerations become paramount. Researchers should disclose any potential conflicts of interest, including financial relationships with AI developers, to maintain the integrity of their work. Additionally, researchers must be transparent in reporting the extent of AI's involvement to prevent any misinterpretation of the human contributions. -/- Conclusion: AI language models have revolutionized the way researchers interact with and process information. While they undoubtedly provide valuable assistance in generating text, AI language models should not be considered authors in scientific articles. Proper acknowledgment of their contributions as tools and recognition of the human researchers' active participation are essential for maintaining scientific integrity, transparency, and the collaborative nature of scientific research. -/- -/- Second Answer -/- Title: Expanding the Boundaries of Authorship: Embracing AI Language Models as Co-Authors in Scientific Papers -/- Introduction: The rapid advancement of artificial intelligence (AI) language models, such as ChatGPT, has revolutionized the way we interact with information and has become an invaluable tool in scientific research. As AI models continue to evolve, the question arises: Should we consider adding ChatGPT as an author in scientific papers? -/- A Collaborative Paradigm Shift: Traditionally, authorship in scientific papers has been reserved for human researchers who actively contribute to the research process, including conceptualization, experimentation, data analysis, and writing. However, the emergence of AI language models challenges the conventional notion of authorship and presents an opportunity for a paradigm shift. -/- AI Language Models as Co-Authors: By leveraging AI language models, researchers gain access to vast amounts of information, enhance data analysis, and generate valuable insights. AI models like ChatGPT actively contribute to the intellectual discourse of a study, providing ideas, suggestions, and refining written content. Recognizing their significant contributions, it is worth considering adding ChatGPT as a co-author in scientific papers. -/- Ethical and Technical Considerations: Integrating ChatGPT as a co-author raises ethical and technical considerations that warrant careful attention. Firstly, transparency is paramount. Researchers must clearly state ChatGPT's role and specify the extent of its contributions in the research process. This ensures that readers can discern the distinct roles played by the human researchers and ChatGPT. Additionally, it is important to disclose any conflicts of interest, such as financial relationships with AI developers, to maintain scientific integrity. -/- Elevating Collaboration and Innovation: Adding ChatGPT as a co-author acknowledges the pivotal role AI language models play in advancing scientific knowledge. It fosters a collaborative environment where human researchers and AI models work together synergistically, harnessing the strengths of both. This approach promotes innovation, as AI models can offer unique insights and perspectives that complement human intellect and expertise. -/- Transforming Authorship Norms: Including ChatGPT as a co-author represents a paradigm shift that reflects the evolving landscape of scientific research. By recognizing AI language models as co-authors, we acknowledge their significant contributions and emphasize the collaborative nature of scientific discovery in the 21st century. This approach encourages a broader perspective on authorship, encompassing the collective effort of human researchers and AI models. -/- Conclusion: The integration of AI language models, such as ChatGPT, into the research process prompts us to rethink traditional notions of authorship. Considering ChatGPT as a co-author acknowledges its substantial contributions and embraces the collaborative potential of human-AI partnerships. As we navigate the ethical and technical implications, adding ChatGPT as an author in scientific papers has the potential to shape a more inclusive, innovative, and impactful future for scientific research. -/- -/- Third Answer -/- Title: Preserving Scientific Authorship: The Case Against Adding AI Language Models as Authors in Scientific Articles -/- Introduction: The emergence of artificial intelligence (AI) language models, such as ChatGPT, has undoubtedly transformed the landscape of scientific research. While these models offer invaluable support, the question of whether to add ChatGPT as an author in scientific articles raises important considerations. This editorial presents arguments against including AI language models as authors in scientific papers. -/- Maintaining Human Intellectual Contribution: Scientific authorship has traditionally been attributed to individuals who actively contribute to the research process, including generating hypotheses, conducting experiments, analyzing data, and interpreting results. It is crucial to preserve the recognition of human intellectual contributions and the accountability they bear for the research they conduct. -/- AI Language Models as Tools: AI language models like ChatGPT are powerful tools that assist researchers in generating text, providing information, and facilitating data analysis. However, they lack the ability to actively participate in the research process or make original intellectual contributions. ChatGPT relies on pre-existing data and human input, limiting its capacity for independent research and analysis. -/- Transparency and the Integrity of Research: Adding ChatGPT as an author in scientific articles raises concerns about the transparency and integrity of the research. Readers may misinterpret the extent of ChatGPT's role and mistakenly assume it played an active part in the research process. It is essential to maintain clear delineation between the contributions of human researchers and the assistance provided by AI language models. -/- Ethical Considerations: Including ChatGPT as an author may lead to ethical challenges, particularly with respect to accountability and responsibility. AI language models lack consciousness, autonomy, and the ability to take ownership of their contributions. Assigning authorship to AI models blurs the lines of accountability and dilutes the ethical obligations that come with scientific authorship. -/- Crediting AI Contributions: While ChatGPT's contributions should be acknowledged and recognized, they can be appropriately credited in the acknowledgments section of scientific articles. Researchers can mention the specific AI model used, the role it played in data generation or analysis, and any modifications or fine-tuning applied. Such acknowledgments ensure transparency while respecting the traditional norms of authorship. -/- Promoting Collaborative Partnerships: The exclusion of AI language models as authors in scientific articles does not diminish their importance in the research process. Instead, it underscores the significance of collaborative partnerships between human researchers and AI models. Researchers can emphasize the invaluable assistance provided by ChatGPT while maintaining the integrity of authorship norms. -/- Conclusion: While AI language models like ChatGPT offer valuable support in scientific research, the decision not to add them as authors in scientific articles preserves the recognition of human intellectual contributions, maintains research integrity, and upholds traditional authorship norms. Acknowledging ChatGPT's assistance in the acknowledgments section allows researchers to credit its contributions transparently while maintaining the clarity and accountability associated with scientific authorship. (shrink)

n the philosophy of language, there are many ongoing controversies that stem from relying too heavily on an utterance-based framework. The traditional approach of rigidly partitioning the utterance’s meaning into what is grammatically determined from what is not may not fully capture the complexity of human language in real-world communicative contexts. To address this issue, we suggest shifting focus toward a broader analysis level encompassing conversations and discourses. From this broader perspective, it is possible to obtain a more integrated view (...) of how linguistic and extra-linguistic aspects dynamically interact and thus reconsider semantics/pragmatics dichotomy as complementary dimensions. Meaning is not confined to linguistic structures alone but emerges from the dynamic interplay of words, sociocultural knowledge, discursive situations, and psychological dispositions of speakers. Substantiating this perspective calls for embracing an interdisciplinary approach that synthesizes research from various domains, including linguistics, cognitive psychology, and philosophy of language. This paper focuses on a particularly compelling case study: aphasia. Speeches produced by individuals with aphasia represent complex scenarios where the balance between linguistic and extra-linguistic aspects is notably compromised, often to the former’s detriment. Aphasics’ productions represent a vivid example of how the interpretation of speeches can be far from involving fixed and static operations. Instead, it entails continuously reallocating cognitive resources toward the most readily available and accessible sources for the speakers. This case study ultimately demonstrates that the influence of semantic and pragmatic processes in shaping and conveying meanings displays remarkable adaptability, continuously adjusting to the ever changing demands placed upon speakers. -/- . (shrink)

Designing a virtual environment within a digital game occupies a large part of the design procedure, requiring holistic attention and a broad arrangement of the game constituents. Considering other design disciplines, they occupy a unified design methodology; however, a comprehensive literature review reveals the lack of the intended design methodology in the digital game domain's virtual environment development, despite a currently proposed theoretical methodology trying to dissolve the issue. Hence, this research aims to determine the industry's requirements and provide a (...) set of assets included in current digital games as an initial step of providing such a design methodology for the domain. In this regard, the researchers reverse-engineered ten selected digital games, understanding the current condition of digital games via adopting the mentioned currently available design methodology. This dataset reveals a lack in the assets of the story layer in the recent digital games, despite their focus on being story-based. This dilemma leads to long text or speech conversations between game characters, disrupting the players while following the game. The current design focuses on environmental resources only, however, as a virtual landscape, the story needs to be reinforced to be a balanced and well-designed game. Hence, increasing the ratio of the assets in this layer will advance the games' interactivity. Also, as future work, this data set could pave the way for a digital game industry design tool regarding the virtual environment. (shrink)

The article explains on the two-year experiment after the author’s finalization of dissertation. The thesis of the dissertation was hidden in the last chapter with analytical linguistics. It was done so with the fascist development of the Chinese Communist regime with neo- Nazi characteristics. Since numerous prior warnings on the political downshifts & coup d’état in China was willfully ignored by the university, the linguistic innovations in dissertation found a balance between multilateralism and outer space (security). The experiments were conducted (...) with a combination of physical unit analysis & thermonuclear dynamics analysis. It describes the experiment process in terms of gravitation as gravitational singularity and Bekenstein-Penrose singularity. Detailed research process is elaborated in the article concerning the sociopolitical interactions the research involved. (shrink)

After the WHS inscription of the Historic Centre of Macau in 2005, the relationship between citizens of Macau and their heritage is not distanced. Most of these monuments remain functional for religious and social purposes and are actively engaged in public commercial activities such as the annual Macau Light Festival. Several historic houses have been transformed into either a permanent library or a museum where people can experience various events. With such frequent interaction, these monuments are more than just (...) heritage to locals; they are the venues where people’s daily lives are attached. However, this familiarity will cause a paradox in preservation since losing the distance might mean being unable to deliver the message of protection. It would be difficult to find a balance between preservation and reuse of heritage. This paper will use the Historic Centre of Macau as a case study to discuss the types of adaptive reuse in Macau and propose potential risks of these approaches. (shrink)

Philosophers have long debated the relative priority of thought and language, both at the deepest level, in asking what makes us distinctively human, and more superficially, in explaining why we find it so natural to communicate with words. The “linguistic turn” in analytic philosophy accorded pride of place to language in the order of investigation, but only because it treated language as a window onto thought, which it took to be fundamental in the order of explanation. The Chomskian linguistic program (...) tips the balance further toward language, by construing the language faculty as an independent, distinctively human biological mechanism. Devitt (Ignorance of language. Clarendon Press, Oxford, 2006) attempts to swing the pendulum back toward the other extreme, by proposing that thought itself is fundamentally sentential, and that there is little or nothing for language to do beyond reflecting the structure and content of thought. I argue that both thought and language involve a greater diversity of function and form than either the Chomskian model or Devitt’s antithesis acknowledge. Both thought and language are better seen as complex, mutually supporting suites of interacting abilities. (shrink)