In this paper, I examine whether John Stuart Mill’s account of free speech can survive three main challenges posed by social media. First, I consider the problem of social media failing to distinguish between emotive and factual language. Second, I look at the problem of algorithms creating moralism. I then turn to a potential objection to my first two challenges. The objection elucidates the benefits of social media’s emotional and algorithmic character, amplifying arguments and increasing public engagement. However, I take (...) issue with this objection on consequentialist terms. I finally return to the third challenge, where I focus on how anonymity removes the consequences to our words; I contend that this final failure is the ultimate reason why Mill’s account cannot persist in the modern age. In conclusion, I argue that Mill’s account cannot withstand the problems posed by social media. (shrink)

Arthur Pap worked in analytic philosophy while maintaining a strong Kantian or neo-Kantian element throughout his career, stemming from his studying with Ernst Cassirer. I present these elements in the different periods of Pap’s works, showing him to be a consistent critic of logical empiricism, which Pap shows to be incapable of superseding the Kantian framework. Nevertheless, Pap’s work is definitely analytic philosophy, both in terms of the content and the style. According to Pap, the central topics of analytic (...) philosophy concern meaning, modality, and analysis. Pap was also influenced by pragmatism, especially in his dissertation, although he does not fully embrace it in either its classical or its Quinean form. (shrink)

Within the context of the Quine–Putnam indispensability argument, one discussion about the status of mathematics is concerned with the ‘Enhanced Indispensability Argument’, which makes explicit in what way mathematics is supposed to be indispensable in science, namely explanatory. If there are genuine mathematical explanations of empirical phenomena, an argument for mathematical platonism could be extracted by using inference to the best explanation. The best explanation of the primeness of the life cycles of Periodical Cicadas is genuinely mathematical, according to Baker (...) :223–238, 2005; Br J Philos Sci 60:611–633, 2009). Furthermore, the result is then also used to strengthen the platonist position :779–793, 2017a). We pick up the circularity problem brought up by Leng Mathematical reasoning, heuristics and the development of mathematics, King’s College Publications, London, pp 167–189, 2005) and Bangu :13–20, 2008). We will argue that Baker’s attempt to solve this problem fails, if Hume’s Principle is analytic. We will also provide the opponent of the Enhanced Indispensability Argument with the so-called ‘interpretability strategy’, which can be used to come up with alternative explanations in case Hume’s Principle is non-analytic. (shrink)

This book presents Robert S. Hartman’s formal theory of value and critically examines many other twentieth century value theorists in its light, including A.J. Ayer, Kurt Baier, Brand Blanshard, Paul Edwards, Albert Einstein, William K. Frankena, R.M. Hare, Nicolai Hartmann, Martin Heidegger, G.E. Moore, P.H. Nowell-Smith, Jose Ortega y Gasset, Charles Stevenson, Paul W. Taylor, Stephen E. Toulmin, and J.O. Urmson.

Kit Fine has proposed a new solution to what he calls ‘a familiar puzzle’ concerning modality and existence. The puzzle concerns the argument from the alleged truths ‘It is necessary that Socrates is a man’ and ‘It is possible that Socrates does not exist’ to the apparent falsehood ‘It is possible that Socrates is a man and does not exist’. We discuss in detail Fine’s setting up of the ‘puzzle’ and his rejection, with which we concur, of two mooted solutions (...) to it. (One of these uses standard, Kripkean, notions, and the other rests on work done by Arthur Prior.) We set out, and reject, the philosophy of modality underlying Fine’s new solution, and we defend an alternative response to the alleged puzzle. Our solution follows the work of David Wiggins in distinguishing between the sentential operator ‘It is necessary that’ and the predicate modifier ‘necessarily’. We briefly provide this distinction with a possible- world semantics on which it is neither a necessary truth, in some sense, that Socrates exists nor true, in some sense, that Socrates necessarily exists. (shrink)

There is a widespread, popular view—and one I basically endorse—that Nietzsche is, in one sense of the word, a nihilist. As Arthur Danto put it some time ago, according to Nietzsche, “there is nothing in [the world] which might sensibly be supposed to have value.” As interpreters of Nietzsche, though, we cannot simply stop here. Nietzsche's higher men, Übermenschen, “genuine philosophers”, free spirits—the types Nietzsche wants to bring forth from the human, all-too-human herds he sees around him with the (...) fish hooks, as he says, of his books—seem to engage in what looks like valuing. These free spirits are supposed to revalue the old values—revaluing, as is clear from the texts, is not simply to remove the old values from circulation (Nietzsche uses “umwerten” and not “entwerten”)—and they are supposed to create new values. And, of course, Nietzsche himself, free spirit that he is, takes on the task of revaluing all values and seems to assert many a strident evaluation. So we need to say more here. What are Nietzsche and his free spirits up to when they engage in what looks, for all the world, like a practice of valuing? What is the practice of valuing Nietzsche is recommending for his free spirits? I argue for two claims: (i) First, we end up facing an interpretive puzzle when we attempt to explain how Nietzsche's free spirits are supposed to engage in a practice of valuing. (ii) Second, we can solve the interpretive puzzle by taking Nietzsche's free spirits to be engaged in a fictionalist simulacrum of valuing. (shrink)

Se presenta la traducción de los capítulos 1 y 2 del libro Spinoza and Time del filósofo judío Samuel Alexander, el que deriva de la Cuarta Conferencia en Memoria de Arthur Davis, dictada ante la Jewish Historical Society de Inglaterra, el domingo 1 de mayo, 1921/23 de Nisan, 5681. La traducción responde a la necesidad de contar con un acercamiento en castellano al corpus alexandriano, ya que no existe al día de hoy una traducción total de sus libros. A (...) su vez el traductor encuentra motivación en el redescubrimiento de autores judíos que aborden el tema de la temporalidad. (shrink)

If artworks and their aesthetic properties stand in constitutive relationships to historical context and circumstances, so that some understanding of relevant facts is involved in responding to a work, what becomes of the intuitive view that we see artworks and at least some of their aesthetic properties? This question is raised by arguments in both aesthetics and art history for the historical nature of works of art. The paper argues that the answer needs to take philosophy of perception into account. (...) The principal development that has shaped philosophy of perception in the last thirty years—explaining perceptual experience in terms of contents that represent that such-and-such is the case—is directly relevant to key arguments for the historical nature of art because contents can represent complex kinds and properties. Conceptual realism is especially well-suited for explaining perception of artworks and aesthetic properties because it emphasizes that forms of understanding—in the sense of capacities, abilities and techniques—are involved in perceptual engagement with individual objects and instances of properties. To make this case, the paper examines influential arguments for the historical nature of art and aesthetic properties by Arthur C. Danto and Kendall L. Walton; and examines art-historical discussions by Michael Baxandall, Linda Nochlin and T. J. Clark. The paper argues that the aesthetic properties of an artwork depend on human intentional uses of properties, colours and contours among them, and such uses may themselves be aesthetic. The Wittgensteinian notion of use is contextual and historical, and uses are perceptible. (shrink)

Short article on the history of the Otago Department.

I advance a novel argument for an infallibilist theory of knowledge, according to which we know all and only those propositions that are certain for us. I argue that this theory lets us reconcile major extant theories of knowledge, in the following sense: for any of these theories, if we require that its central condition (evidential support, reliability, safety, etc.) obtains to a maximal degree, we get a theory of knowledge extensionally equivalent to infallibilism. As such, the infallibilist can affirm (...) that, when their conditions are suitably interpreted, most post-Gettier theories of knowledge offer necessary and sufficient conditions for knowledge. The infallibilist can thus reconcile major theories of knowledge, and is in a better position to explain the intuitive appeal of these theories than the fallibilist who only accepts one of them, and rejects the rest. (shrink)

I argue that when we use ‘probability’ language in epistemic contexts—e.g., when we ask how probable some hypothesis is, given the evidence available to us—we are talking about degrees of support, rather than degrees of belief. The epistemic probability of A given B is the mind-independent degree to which B supports A, not the degree to which someone with B as their evidence believes A, or the degree to which someone would or should believe A if they had B as (...) their evidence. My central argument is that the degree-of-support interpretation lets us better model good reasoning in certain cases involving old evidence. Degree-of-belief interpretations make the wrong predictions not only about whether old evidence confirms new hypotheses, but about the values of the probabilities that enter into Bayes’ Theorem when we calculate the probability of hypotheses conditional on old evidence and new background information. (shrink)

Can new technology enhance purpose-driven, democratic dialogue in groups, governments, and societies? Online Deliberation: Design, Research, and Practice is the first book that attempts to sample the full range of work on online deliberation, forging new connections between academic research, technology designers, and practitioners. Since some of the most exciting innovations have occurred outside of traditional institutions, and those involved have often worked in relative isolation from each other, work in this growing field has often failed to reflect the full (...) set of perspectives on online deliberation. This volume is aimed at those working at the crossroads of information/communication technology and social science, and documents early findings in, and perspectives on, this new field by many of its pioneers. -/- CONTENTS: -/- Introduction: The Blossoming Field of Online Deliberation (Todd Davies, pp. 1-19) -/- Part I - Prospects for Online Civic Engagement -/- Chapter 1: Virtual Public Consultation: Prospects for Internet Deliberative Democracy (James S. Fishkin, pp. 23-35) -/- Chapter 2: Citizens Deliberating Online: Theory and Some Evidence (Vincent Price, pp. 37-58) -/- Chapter 3: Can Online Deliberation Improve Politics? Scientific Foundations for Success (Arthur Lupia, pp. 59-69) -/- Chapter 4: Deliberative Democracy, Online Discussion, and Project PICOLA (Public Informed Citizen Online Assembly) (Robert Cavalier with Miso Kim and Zachary Sam Zaiss, pp. 71-79) -/- Part II - Online Dialogue in the Wild -/- Chapter 5: Friends, Foes, and Fringe: Norms and Structure in Political Discussion Networks (John Kelly, Danyel Fisher, and Marc Smith, pp. 83-93) -/- Chapter 6: Searching the Net for Differences of Opinion (Warren Sack, John Kelly, and Michael Dale, pp. 95-104) -/- Chapter 7: Happy Accidents: Deliberation and Online Exposure to Opposing Views (Azi Lev-On and Bernard Manin, pp. 105-122) -/- Chapter 8: Rethinking Local Conversations on the Web (Sameer Ahuja, Manuel Pérez-Quiñones, and Andrea Kavanaugh, pp. 123-129) -/- Part III - Online Public Consultation -/- Chapter 9: Deliberation in E-Rulemaking? The Problem of Mass Participation (David Schlosberg, Steve Zavestoski, and Stuart Shulman, pp. 133-148) -/- Chapter 10: Turning GOLD into EPG: Lessons from Low-Tech Democratic Experimentalism for Electronic Rulemaking and Other Ventures in Cyberdemocracy (Peter M. Shane, pp. 149-162) -/- Chapter 11: Baudrillard and the Virtual Cow: Simulation Games and Citizen Participation (Hélène Michel and Dominique Kreziak, pp. 163-166) -/- Chapter 12: Using Web-Based Group Support Systems to Enhance Procedural Fairness in Administrative Decision Making in South Africa (Hossana Twinomurinzi and Jackie Phahlamohlaka, pp. 167-169) -/- Chapter 13: Citizen Participation Is Critical: An Example from Sweden (Tomas Ohlin, pp. 171-173) -/- Part IV - Online Deliberation in Organizations -/- Chapter 14: Online Deliberation in the Government of Canada: Organizing the Back Office (Elisabeth Richard, pp. 177-191) -/- Chapter 15: Political Action and Organization Building: An Internet-Based Engagement Model (Mark Cooper, pp. 193-202) -/- Chapter 16: Wiki Collaboration Within Political Parties: Benefits and Challenges (Kate Raynes-Goldie and David Fono, pp. 203-205) -/- Chapter 17: Debian’s Democracy (Gunnar Ristroph, pp. 207-211) -/- Chapter 18: Software Support for Face-to-Face Parliamentary Procedure (Dana Dahlstrom and Bayle Shanks, pp. 213-220) -/- Part V - Online Facilitation -/- Chapter 19: Deliberation on the Net: Lessons from a Field Experiment (June Woong Rhee and Eun-mee Kim, pp. 223-232) -/- Chapter 20: The Role of the Moderator: Problems and Possibilities for Government-Run Online Discussion Forums (Scott Wright, pp. 233-242) -/- Chapter 21: Silencing the Clatter: Removing Anonymity from a Corporate Online Community (Gilly Leshed, pp. 243-251) -/- Chapter 22: Facilitation and Inclusive Deliberation (Matthias Trénel, pp. 253-257) -/- Chapter 23: Rethinking the ‘Informed’ Participant: Precautions and Recommendations for the Design of Online Deliberation (Kevin S. Ramsey and Matthew W. Wilson, pp. 259-267) -/- Chapter 24: PerlNomic: Rule Making and Enforcement in Digital Shared Spaces (Mark E. Phair and Adam Bliss, pp. 269-271) -/- Part VI - Design of Deliberation Tools -/- Chapter 25: An Online Environment for Democratic Deliberation: Motivations, Principles, and Design (Todd Davies, Brendan O’Connor, Alex Cochran, Jonathan J. Effrat, Andrew Parker, Benjamin Newman, and Aaron Tam, pp. 275-292) -/- Chapter 26: Online Civic Deliberation with E-Liberate (Douglas Schuler, pp. 293-302) -/- Chapter 27: Parliament: A Module for Parliamentary Procedure Software (Bayle Shanks and Dana Dahlstrom, pp. 303-307) -/- Chapter 28: Decision Structure: A New Approach to Three Problems in Deliberation (Raymond J. Pingree, pp. 309-316) -/- Chapter 29: Design Requirements of Argument Mapping Software for Teaching Deliberation (Matthew W. Easterday, Jordan S. Kanarek, and Maralee Harrell, pp. 317-323) -/- Chapter 30: Email-Embedded Voting with eVote/Clerk (Marilyn Davis, pp. 325-327) -/- Epilogue: Understanding Diversity in the Field of Online Deliberation (Seeta Peña Gangadharan, pp. 329-358). -/- For individual chapter downloads, go to odbook.stanford.edu. (shrink)

Defenders of Inference to the Best Explanation claim that explanatory factors should play an important role in empirical inference. They disagree, however, about how exactly to formulate this role. In particular, they disagree about whether to formulate IBE as an inference rule for full beliefs or for degrees of belief, as well as how a rule for degrees of belief should relate to Bayesianism. In this essay I advance a new argument against non-Bayesian versions of IBE. My argument focuses on (...) cases in which we are concerned with multiple levels of explanation of some phenomenon. I show that in many such cases, following IBE as an inference rule for full beliefs leads to deductively inconsistent beliefs, and following IBE as a non-Bayesian updating rule for degrees of belief leads to probabilistically incoherent degrees of belief. (shrink)

Where E is the proposition that [If H and O were true, H would explain O], William Roche and Elliot Sober have argued that P(H|O&E) = P(H|O). In this paper I argue that not only is this equality not generally true, it is false in the very kinds of cases that Roche and Sober focus on, involving frequency data. In fact, in such cases O raises the probability of H only given that there is an explanatory connection between them.

A common argument for atheism runs as follows: God would not create a world worse than other worlds he could have created instead. However, if God exists, he could have created a better world than this one. Therefore, God does not exist. In this paper I challenge the second premise of this argument. I argue that if God exists, our world will continue without end, with God continuing to create value-bearers, and sustaining and perfecting the value-bearers he has already created. (...) Given this, if God exists, our world—considered on the whole—is infinitely valuable. I further contend that this theistic picture makes our world's value unsurpassable. In support of this contention, I consider proposals for how infinitely valuable worlds might be improved upon, focusing on two main ways—adding value-bearers and increasing the value in present value-bearers. I argue that neither of these can improve our world. Depending on how each method is understood, either it would not improve our world, or our world is unsurpassable with respect to it. I conclude by considering the implications of my argument for the problem of evil more generally conceived. (shrink)

The cucumber is a creeping vine that roots in the ground and grows up trellises or other supporting frames, wrapping around supports with thin, spiraling tendrils. The plant may also root in a soilless medium, whereby it will sprawl along the ground in lieu of a supporting structure. The vine has large leaves that form a canopy over the fruits. Among these common diseases, we single out the diseases that affect the cucumber, which is affected by about 22 diseases, with (...) different symptoms for each disease. Today, technology is facilitating human life in all areas of life, and among these facilities are expert systems that have become an integral part of human life as they contain several systems and areas, for example: Artificial Intelligence (AI), which refers to systems or devices that simulate Human intelligence to perform tasks that can improve itself based on some human information, and other areas, and with reference to expert systems and their importance to humans, an integrated expert system has been created in the agricultural field that diagnoses cucumber diseases using CLIPS Expert System language Delphi language. The system was used to design and implement the proposed expert system. The system facilitates the diagnosis of cucumber-related diseases. There is no doubt that this expert system will help farmers and those involved in the agricultural field to diagnose cucumber-related diseases. Objectives: is to help farmers diagnose pear diseases in the correct way and how to treat these diseases. Method: The system contains a program that diagnoses 22 diseases that affect cucumber. Results: The expert system was evaluated by farmers and praised for helping them with it. Conclusion: The expert system for diagnosing cucumber diseases is effective and usable. (shrink)

Abstract— This study aimed to identify the degree of use of the capabilities of decision-support systems in Palestinian institutions higher education, Aqsa University in Gaza - a case study. The study used a analytical descriptive approach, and the researchers used the of questionnaire tool to collect the data, the researchers using stratified random sample distributed (150) questioners to the study population and (126) was obtained back with rate of 84%. The study showed that the most important results are: that senior (...) management supports the existence of decision support systems and that there is approval by the respondents on the paragraphs of the use of the capabilities of decision support systems in general. And that there are no significant differences between the averages of the answers of respondents differences about the degree of use of decision support systems capabilities attributed to personal data. The study also concluded a series of recommendations including: increasing the adoption of the senior management decision support in their decision-making systems. And increased regulatory attention to the potential available to decision support systems directly to the senior management in the Palestinian universities in the Gaza Strip. There is an increased interest in the physical and technical possibilities available for the use of decision support systems. There is an increased interest in human potential available for the use of decision support systems. Investment of information available to universities in building the capacities of integration techniques and other information technology capabilities. The empowerment of human resources in universities and participating in making decisions concerning the construction of the capabilities of information technology. (shrink)

The research aims to identify the learning organizations and their role in achieving organizational excellence in the Palestinian universities in Gaza Strip. The researchers used descriptive analytical approach and used the questionnaire as a tool for information gathering. The questionnaires were distributed to senior management in the Palestinian universities. The study population reached (344) employees in senior management is dispersed over (3) Palestinian universities. A stratified random sample of (182) workers from the Palestinian universities was selected and the recovery rate (...) was (69.2%). Statistical analysis (SPSS) program was used for analysis and processing the data. The research found the following results: there is a fair degree of approval on "cognitive dimension", there is a high approval about the importance of "organizational dimension", there is moderately consent of the importance of "Community dimension", there is a large degree of consent about the importance of axis of the "leadership excellence", there is a large degree of consent about the importance of axis of the "service-excellence", there is a fair degree approval about the importance of the axis of "cognitive excellence", and there is a moderately consent of the importance of "Organizational Excellence". The research found a group of recommendations including: the need to develop appropriate strategies for the University, employ modern technology in information systems, in addition to provide appropriate environment that achieve learning organizations, develop technological infrastructure, adopt universities for knowledge management in the academic and administrative departments because knowledge is the core of the work of these departments, create technological incubators in universities to adopt excellence academic research projects, and protected them, support them, and market them. Establishing of centers of excellence for scientific research in the university.The need for cooperation and coordination between local, Arab and international universities for the exchange of knowledge, information, and participation programs and training courses, as it provides an opportunity to develop the capabilities and skills of personnel and expertise. (shrink)

This study aims to look at the role of the practice of excellence strategies in education in achieving sustainable competitive advantage for the Higher educational institutions of the faculty of Engineering and Information Technology at Al-Azhar University in Gaza, a model, and the study considered the competitive advantage of educational institutions stems from the impact on the level of each student, employee, and the institution. The study was based on the premise that the development of strategies for excellence in education, (...) and its implementation is a vital important prerequisite to achieve sustainable competitive advantage in higher educational institutions. The study followed a systematic exploratory descriptive methodology through review of the theoretical literature, and the adoption of the experience of the Faculty of Engineering and Information Technology at Al-Azhar University in Gaza as a model for its unique experience in the field of excellence in education. The study results showed that the most important are: There is a strong correlation between the level of exercising excellence strategies in education and the achievement of higher educational institutions to the sustainable competitive advantage. The results include a general required number of important sub results on the subject of the model - Faculty of Engineering and Information Technology at Al-Azhar University in Gaza as follows: - The student considered the academic focus of the operation in the development process of the workers’ skills, particularly academics at the university helps to distinguish students and increase the employment rate after graduation. - The existence of consistency in development efforts and quality improvement for all three levels (student, employee, and the university), and this contributes to the Faculty excellence. - The Faculty has been able to achieve competitive advantages by offering excellent services without harming the efficiency, and this alone is a great success because improving service properties requires great investments, which negatively affect the continued institutional development. The study also reached a set of recommendations as follows: - The need to exercise excellence strategies in education, excellence reward at the national level, and those higher educational institutions follow the criteria for measuring the competitive advantages of its institutions always. - There is a need to increase efforts to implement programs of excellence, the allocation of adequate time, reward outstanding efforts as well. There is a necessity for each faculty to achieve competitive advantage and sustainability, using the general philosophies of competitive advantage, but with a different strategically content from what is in the private commercial sector, it reflects the Faculties mission and objectives, depending on making improvements and excellence in processes that ensure the safety of its outputs. As well as the need to find a balance between the work of teaching and research work of the faculty members, this has important implications regarding the criteria used in the process of excellence evaluation. The study recommended the adoption of strategies for excellence in education on a national public policy level mainly in the processes of change in higher education institutions. The need to support the existence of a common understanding of the efforts of excellence to create a general culture that appreciates excellence in faculties and universities. This underlines the need for transparent, fair rewards systems, to encourage innovation in education. The need to conduct a comprehensive surveys on the graduates of faculties and universities including the areas of employment and skills, because that will give accurate indications of the graduates and will help to establish a link to a more precise about the relationship of excellence strategies with the competitive advantages. (shrink)

DIFERENCIAÇÃO SEXUAL -/- Emanuel Isaque Cordeiro da Silva Instituto Agronômico de Pernambuco Embrapa Semiárido -/- • _____OBJETIVO -/- Os estudantes de Veterinária e de Zootecnia estão ligados à disciplina Reprodução Animal, um pelos mecanismos fisiológicos para evitar e tratar as possíveis patologias do trato reprodutivo dos animais domésticos, e outro para o entendimento dos processos fisiológicos visando o manejo reprodutivo e a procriação para a formação de um plantel geneticamente melhorado. Sendo assim, a finalidade do presente trabalho é apresentar os (...) mecanismos que regulam as diferenças sobre o desenvolvimento embrionário relativos à diferenciação e determinação sexual de machos e fêmeas, que também incluem o desenvolvimento dos órgãos envolvidos na reprodução e a origem das diferenças entre ambos os sexos. -/- •____INTRODUÇÃO -/- Os organismos que se reproduzem sexualmente são descendentes de organismos ao qual não existia a diferenciação sexual. Em algum momento da evolução surgiu a reprodução sexual como um mecanismo para incrementar a diversidade genética e facilitar a troca de informações genéticas mediante o material genético da fêmea com o do macho. Devido sua origem comum, na maioria das espécies, tanto os machos como as fêmeas possuem todos os genes necessários para desenvolverem-se em qualquer dos sexos. O que efetivamente faz diferença entre os sexos é a forma e a ordem ao qual se expressam os genes durante o processo de desenvolvimento. A diferenciação sexual é regulada principalmente por mecanismos epigenéticos, mais do que as diferenças genéticas de grande magnitude entre os sexos. Todo o controle epigenético de qualquer processo de desenvolvimento depende basicamente de uma série de expressões gênicas, através da qual a expressão de certa combinação de genes resulta na presença de determinadas proteínas, conhecidas como os fatores de transcrição, que induzem ou reprimem a expressão de outro(os) gene(es), a partir dos quais se produzem novas proteínas, que em certos casos também atuam como fatores de transcrição para outros genes, e assim sucessivamente. Logo, a expressão ou falta de expressão de um gene ao início da série pode resultar em um ladrão totalmente diferente da expressão de outros genes subsequentes, o que pode ocasionar profundas mudanças no processo de desenvolvimento e até a mutações indesejáveis. O padrão predeterminado de expressões gênica relativo a diferenciação sexual na maioria das espécies tanto domésticas quanto selvagens, leva ao desenvolvimento de um dos sexos (o padrão predeterminado dos mamíferos é o sexo feminino). Em consequência, a diferenciação faz com que um indivíduo do sexo oposto exija a expressão de um gene de determinação sexual que desvie a subsequente série de expressões gênica em direção ao dito sexo. Nos mamíferos, a expressão do gene SRY, localizado no cromossomo Y (e portanto ausente nas fêmeas), redige o padrão de diferenciação sexual de sua via pré-estabelecida feminina em direção ao padrão masculino. A existência de uma única diferença genética (presença do gene SRY nos machos e ausentes nas fêmeas), vai se amplificando e termina resultando no desenvolvimento de indivíduos diferentes entre si. Esse é um mecanismo de diferenciação sexual cromossômica. O primeiro passo de uma série de diferenciação sexual, em sentido estrito, não depende nem requer necessariamente a presença de um gene diferente em algum dos sexos. O gene “disparador” da diferenciação sexual pode estar presente em todos os embriões, porém pode expressar-se somente em algum deles, devido a fatores ambientais que formam parte da sua regulação epigenética, isto é, uma determinação sexual ambiental. Em algumas espécies de tartarugas ou de lagartos a expressão ou falta de expressão do gene “disparador”, por exemplo, depende da temperatura existente durante a incubação dos ovos, pelo qual alguns embriões desenvolvem-se como machos e outros como fêmeas, apesar de não existir diferença genética entre eles, simplesmente como consequência da temperatura: a determinação sexual depende da temperatura a que cada um deles foi submetido durante a incubação. Em certas espécies as temperaturas mais elevadas facilitam o desenvolvimento de fêmeas e outras de machos, enquanto que em outras espécies as temperaturas amenas (intermediárias) resultam em machos, e as inferiores como as superiores induzem o desenvolvimento de fêmeas. A existência dessa diversidade indica que a temperatura por si mesma não é a que induz ou a que provoca o desenvolvimento do macho e da fêmea, senão a que atua somente como um regulador inicial da diferenciação sexual. Em outras espécies o fator ambiental que regula a determinação sexual pode ser distinto. A densidade populacional, por exemplo, pode atuar como um regulador. Podemos concluir que a determinação sexual dependente da temperatura ou de outros fatores ambientais estabelece-se antes da determinação sexual cromossômica, a qual evoluiu depois como um método que oferece maior certeza e resultado, já que a proporção de machos e fêmeas não é afetada por mudanças ambientais ou de hábitat. -/- •___FORMAÇÃO INICIAL DA GÔNADA -/- Basicamente em todos os embriões, inicialmente se formam as chamadas gônadas indiferenciadas (com o potencial de desenvolver-se em ovários ou testículos) a partir da invasão das cristas genitais pelas células germinais primordiais, que migram desde seu local de origem no epiblasto, perto do lugar onde o saco vitelino se une com o intestino primitivo e que chegam até às cristas genitais que são engrossamentos de tecido situados na região mesonéfrica do embrião. A migração das células germinais primordiais ocorre muito cedo sobre o processo de desenvolvimento do embrião (dia 26 nos bovinos). Ao chegas as cristas genitais, as células germinativas proliferam-se e se organizam com as células somáticas já existentes nas cristas para ir formando a gônada (figura 1). Para regular essa remodelação e conformação adequada da gônada vários genes se expressam, como o OCT-4 (que aparentemente mantém a totipotencialidade da gônada), assim como o SF-1 (Fator esteroidogênico 1) e o WT-1 (gene associado ao tumor de Wilms). Esses dois últimos genes estimulam a proliferação celular e estabelecimento dos cordões sexuais. Nessa etapa inicial do desenvolvimento todos esses genes se expressam sem distinção de sexo, pelo que a gônada em formação mantém a capacidade de se diferenciar em testículo ou em ovário. -/- Figura 1: migração das células germinais primordiais em direção a crista gonodal. Diferenciação das gônadas femininas e masculinas. Fonte: ZARCO, 2018. -/- •___SEXO CROMOSSÔMICO -/- Têm-se observado que nos mamíferos a determinação sexual depende diretamente dos cromossomos. As fêmeas possuem dois cromossomos sexuais X (um contribuído do óvulo e o outro por um espermatozoide “X”). Os machos, por sua vez, possuem um cromossomo sexual X(proveniente do óvulo) e um cromossomo sexual Y, que provém de um espermatozoide “Y” (figura 2). A metade dos espermatozoides produzidos por um macho são X e a metade Y, isso porque durante a espermatogênese a divisão meiótica provoca que a partir de cada espermatócito primário, célula diploide que por pertencer a um indivíduo macho tem um cromossomo X e um Y, se originem das espermátides haploides a cada um das que eles tocam cromossomos X, e outras espermátides haploides as que eles tocam os cromossomos Y. Dessa forma, de acordo com o tipo do espermatozoide que fertilize o ovócito, se originará um indivíduo com cariótipo feminino “XX” ou um cariótipo masculino “XY” (figura 2). Esse processo é conhecido como sexo cromossômico, ao qual se determina o momento da fertilização. Figura 2: nos mamíferos todos os óvulos produzidos pelas fêmeas possuem um cromossomo sexual X. A metade dos espermatozoides produzidos pelos machos possuem um cromossomo X e a outra metade possui um cromossomo Y. Dependendo do cromossomo presente no espermatozoide que fertilize o óvulo pode-se gerar um indivíduo XX (fêmea) ou um XY (macho). Fonte: ZARCO, 2018. -/- O cromossomo “Y” é uma “invenção” relativamente recente na história da evolução das espécies e do estudo da genética. Surgiu a partir de uma mutação de um cromossomo “X”, que resultou na perda de um de seus braços, que é por onde se originou a morfologia do cromossomo Y. A maioria dos genes presentes no cromossomo Y também existem no cromossomo X; assim mesmo somente alguns genes do cromossomo Y foram evoluídos até ser diferentes dos genes do cromossomo X. Embora os machos possuam um cromossomo que não está presente nas fêmeas, esse mesmo cromossomo não aporta toda a informação genética original. Todos os genes existentes nas fêmeas estão também presentes nos dos machos, já que eles também possuem um cromossomo X. Uma particularidade do cromossomo Y, ao existir somente uma cópia nos machos, é que ele sofre um entrecruzamento com um cromossomo análogo durante o processo de meiose, pelo que o cromossomo Y de um macho é idêntico ao de seu progenitor e ao de seus descendentes, exceto no caso em que ocorra uma mutação espontânea. Em contraste, os cromossomos X das fêmeas (um proveniente do pai e outro da mãe) se entrecruzam durante a meiose, por onde cada óvulo produzido pela fêmea terá uma combinação de alelos distinta em seu cromossomo X. Ao estudar as diferenças presentes na sequência de DNA do cromossomo Y, é possível identificar a distância filogenética entre os indivíduos (quanto mais diferenças existirem entre os cromossomos significa que seu ancestral comum está mais longe). Algo análogo ocorre com o DNA das mitocôndrias, que sempre são aportados pela mãe e nunca sofrem recombinação genética. Gene SRY -/- Um dos poucos genes do cromossomo Y que não possuem correspondência com o cromossomo X é o gene SRY (Sex-determining Region of the Y chromossome – região do cromossomo Y determinante do sexo). Esse gene se expressa somente na gônada em formação nos embriões machos, em particular em células precursoras das células de Sertoli; ele codifica uma proteína da família SOX (SRY-like Box) que é uma família formada por proteínas que possuem um domínio de união ao DNA e que atuam como fatores de transcrição. Ao produzir-se a proteína SRY nas células precursoras das células de Sertoli estimula-se a expressão (transcrição) de outro gene análogo, denominado SOX-9 que, por sua vez, atua como um fator de transcrição que ativa a expressão de outros genes, como o FGF-9 (Fibroblast Growth Factor-9), ou seja ele é o estimulante de ativação dos demais. Os produtos dos genes SOX-9 e FGF-9 iniciam uma cascata de expressões que provocam a diferenciação das células de suporte da gônada indiferenciada (crista genital) em células de Sertoli. Em seguida, essas células dirigem a diferenciação das células intersticiais da crista genital em células de Leydig, o que finalmente resulta na formação de um testículo. Outro dos efeitos da proteína codificada por SOX-9 é um estímulo maior da expressão de seu próprio gene, pelo qual é produzido um ciclo de retroalimentação positiva que favorece a continuidade do processo de formação testicular. Como nos embriões da fêmea não existe o gene SRY, a gônada indiferenciada não é estimulada para expressar os genes SOX-9 nem o FGF-9 nas células de suporte (que nesse caso serão precursoras de células da granulosa). A gônada, em mudança, expressa em forma constitutiva, isto é, sem a necessidade de estimulação, outra cascata de genes que incluem o WNT4 (Wingless-integration Factor 4) e o RAPO1 (Respondina-1), que por sua vez iniciam uma cascata de expressão gênica, a qual provoca a diferenciação das células somáticas da gônada indiferenciada para formação das células da granulosa e células da teca, esse feito conduz, por sua vez, a formação de um ovário. No embrião macho a proteína SOX-9 inibe a expressão dos genes WNT4 e RSPO-1, pelo que a presença do gene SRY, e portanto de SOX-9, inibem a formação de um ovário ao mesmo tempo que estimulam a formação do testículo (figura 3). Em suma, se o embrião possui genótipo XY (um embrião macho), o gene SRY começa a expressar-se sobre as células precursoras da gônada imediatamente depois da formação da mesma, quando os cordões sexuais primários estão se desenvolvendo na medula. A expressão do gene, assim como a presença subsequente das proteínas SOX-9 e FGF-9 estimula a distinção das células de Sertoli e que se organizem os tubos seminíferos a partir dos cordões sexuais primários. Em contrapartida, em um embrião com genótipo XX (fêmea) não existe o gene SRY, pelo qual é impossível que se elevem os níveis das proteínas SOX-9 e FGF-9 e as células precursoras não se diferenciam em células de Sertoli, e portanto os cordões sexuais primários sofrem regressão. Depois de alguns dias, começam a organizar-se os cordões sexuais secundários e as células precursoras iniciam a expressão do gene WNT4, o que leva as mesmas a diferenciar-se em células da granulosa, que serão a base para a conformação dos folículos ovarianos. Se em um embrião XY, macho, a expressão do gene SRY demora, é formada um ovo-testículo devido a que algumas das células somáticas das cristas gonodais começam a expressar o gene WNT4, e a diferenciar-se em células da granulosa, enquanto que em outras a proteína SRY chega a tempo para dirigir a diferenciação para formação das células de Sertoli. No ovário em formação é expressado um gene denominado DAX-1 (Dosage-sensitive Sex Reversal). Esse gene, localizado no cromossomo X, codifica uma proteína que é um membro da família dos receptores nucleares ao que lhe falta o domínio de união ao DNA, pelo que parece atuar no bloqueio de diversos fatores de transcrição, entre os que se encontra o SRY. Como a proteína DAX-1 impede a ação da proteína SRY, um excesso de expressão do gene DAX-1 pode provocar a feminilização gonodal de indivíduos XY, macho, embora tenham SRY. Em condições normais, a expressão adequada do gene DAX-1 não é capaz de evitar a masculinização gonodal de embriões com o gene SRY, daqui o nome de reversão sexual dependente da dose. Figura 3: série de expressão gênica para a determinação gonodal. SRY (Região do cromossomo Y determinante do sexo), SOX-9 (SRY-like Box-9), FGF-9 (Fator de crescimento de fibroblastos-9), WNT4 (Wingless-integration Factor-4), RSPO-1 (Respondina-1). Uma vez que o SRY induz a expressão de SOX-9 na gônada masculina, inicia-se um processo de feedback positivo mediante o qual os níveis de expressão de SOX-9 e FGF-9 vão aumentando, ao mesmo tempo que inibem a expressão de WNT-4 e RSPO-1. Na gônada feminina não se expressam SRY, SOX-9 e nem FGF-9, o que permite que se expressem os genes WNT-4 e RSPO-1, que iniciam uma cascata de sinalização que dirige a formação de um ovário. Fonte: ZARCO, 2018. -/- • ___DIFERENCIAÇÃO SEXUAL DOS GENITAIS -/- Uma vez que se formam os testículos, todo o desenvolvimento subsequente dos órgãos e as características “masculinas” em lugar das femininas é em consequência dos hormônios produzidos pelos testículos em formação, incluindo os andrógenos e o hormônio inibidor dos ductos de Müller. Mediante a ausência de testículos todo o desenvolvimento dos órgãos genitais internos e externos segue um padrão feminino, sem levar em conta se estão presentes os ovários; o que significa a ausência de hormônios gonodais determina que o embrião se desenvolva como fêmea, uma vez que não requerem hormônios ovarianos para desencadear o padrão feminino. Por sua vez, as gônadas masculinas (os testículos), produzem substâncias que desviam o desenvolvimento em direção ao padrão masculino. Sob etapas relativamente rápidas da diferenciação todos os embriões possuem dois pares de dutos sexuais, os dutos de Wolff ou mesonéfricos e os dutos de Müller ou paramesonéfricos (figura 4). A testosterona secretada pelos testículos do feto macho em desenvolvimento atua sobre os dutos de Wolff, o que induz a formação posterior dos dutos deferentes, do epidídimo e das glândulas seminais (figura 4). Figura 4: formação dos órgãos genitais internos a partir dos dutos de Wolff no macho e dos dutos de Müller na fêmea. Fonte: ZARCO, 2018. -/- Os testículos produzem ao mesmo tempo, uma glicoproteína chamada Hormônio Inibidor dos Dutos de Müller (Müllerian Inhibiting Hormone, MIH, também chamado de Anti-Müllerian Hormone, AMH); como o seu nome indica, inibe o desenvolvimento dos dutos de Müller ou paramesonéfricos, provocando sua regressão, que impede a formação dos órgãos genitais característicos da fêmea como os ovidutos, o útero, a cérvix e a porção cranial da vagina (figura 4). O MIH é uma glicoproteína da família dos fatores de crescimento transformativo β (TGFβ). O gene MIH possui locais de união para os produtos dos genes SOX-9 e SF-1, pelo que a presença simultânea de ambos fatores de transcrição é necessária para a secreção do MIH e leva a cabo sua função de iniciação dos dutos de Müller sobre o embrião macho (vale lembrar que nessa etapa tanto a gônada de embriões machos como de embriões fêmeas expressam o gene SF-1, mas somente o macho expressa o SOX-9, para que unicamente esse último produza MIH). O certo é que na gônada do embrião fêmea não se produzem quantidades importantes da proteína SOX-9, além de que se produz a proteína DAX-1, mesma que antagoniza tanto a SOX-9 como a SF-1, todo o qual impede a produção de MIH e resulta no desenvolvimento dos dutos de Müller até a formação dos ovidutos, útero, cérvix e a porção cranial da vagina (figura 4). Assim, na fêmea, ao não haver testículos não circulam concentrações elevadas de andrógenos, o que impedirá o desenvolvimento dos dutos de Wolff, enquanto que os dutos de Müller se desenvolvem já que não haverá a presença do MIH para impedi-lo. O desenvolvimento dos genitais internos e externos femininos não requerem a presença de nenhum hormônio ovariano o que levará a cabo de maneira predeterminada (ou pré-estabelecida) na ausência de testículos. Outra estrutura interna que também se desenvolve de forma distinta nos machos e nas fêmeas é o seio urogenital, que no embrião macho é estimulado pela testosterona para formação da próstata, das glândulas bulbouretrais e da uretra peniana, enquanto que na fêmea forma a porção caudal da vagina. A respeito dos órgãos genitais externos (figura 5), nos embriões de ambos os sexos existem estruturas precursoras chamadas de tubérculo genital e pregas vestibulares. Na fêmea o tubérculo genital da origem ao clitóris e as pregas vestibulares dão origem aos lábios vulvares sem a necessidade da atuação de hormônios ovarianos, já que o padrão “por via pré-estabelecida” é feminino. Em contrapartida, no macho, tanto o tubérculo genital quanto as pregas vestibulares respondem ao hormônio 5α-dehidro-testosterona (DHT), ao qual se formam as células da pele da zona genital a partir da testosterona que é secretada pelos testículos. Para isso existem nas células a enzima 5α-reductasa, que transforma a testosterona em DHT. Uma vez formada, a DHT atua sobre as pregas vestibulares do embrião macho para que se fusionem e formem o escroto (em lugar dos lábios vulvares), e sobre o tubérculo genital para formar o pênis (em lugar do clitóris). Figura 5: estruturas que se desenvolvem nos embriões de cada sexo a partir do seio urogenital, o tubérculo genital e as pregas vestibulares. A cor do né de cada estrutura final corresponde com a cor do nome da estrutura a partir da qual se originou. Fonte: ZARCO, 2018. -/- • ___DIFERENCIAÇÃO SEXUAL DO SISTEMA NERVOSO -/- Existem inúmeras diferenças funcionais entre o sistema nervoso da fêmeas e o do machos, em humanos podem incluir diferenças tão complexas como a maior capacidade de verbal da mulher ou a maior capacidade de orientação espacial do homem. Nessa parte será abordada aquelas diferenças que influenciam diretamente sobre a função reprodutiva, como as diferenças na regulação da secreção de gonadotropinas ou as diferenças na capacidade de comportamento sexual masculino ou feminino. É necessário lembrar que, apesar de que essas diferenças se originem durante um período crítico da vida fetal ou neonatal (dependendo da espécie), geralmente se fazem presentes até que o animal chegue a vida adulta e demonstre obter ou não a capacidade para se comportar como macho ou como fêmea uma vez que é exposto aos hormônios sexuais que são secretada depois da puberdade. Igualmente aos processos acima citados, podemos afirmar que nos mamíferos o padrão pré-estabelecido de comportamento sexual e de secreção de gonadotropinas é o feminino. Se durante os primeiros dias de vida neonatal uma rata fêmea não é exposta a nenhum hormônio gonodal, ao chegar a vida adulta ela terá a capacidade de se comportar como fêmea na presença de estrógenos, assim como de secretar um pico pré-ovulatório de GnRH/LH em resposta aos mesmos (figura 6). Essa rata, portanto, não poderá se comportar como macho embora que em sua vida adulta seja exposta a testosterona. O sistema nervoso do rato macho recém-nascido que é exposto aos andrógenos produzidos pelos testículos, em detrimento, faz com que adquiram o potencial para se comportar como machos em sua vida adulta e que perdem o potencial para ter conduta de fêmeas na presença e/ou administração de estrógenos (processo conhecido como desfeminização do SNC). Se por meios de experimentos injetamos testosterona em uma rata fêmea recém-nascida, essa rata não poderá se comportar como fêmea em sua vida adulta, e passará a se comportar como macho. A castração neonatal de um rato (visando evitar a exposição de seu SNC a andrógenos testiculares), assim mesmo, resultará em sua vida adulta um padrão feminino (SNC feminizado e não masculinizado). O hipotálamo das ratas adultas possui uma área em que o número, características e densidade dos corpos neurais difere em machos e fêmeas, essa área é denominada como “núcleo sexualmente dimórfico do hipotálamo”, e tem demonstrado que quando as ratas são tratadas com testosterona na vida neonatal, a morfologia de seu núcleo sexualmente dimórfico será masculinizado em sua vida adulta, enquanto que a castração neonatal de ratos resulta em um núcleo sexualmente dimórfico feminizado em sua vida adulta. Isso significa que a exposição ou não a testosterona na vida neonatal é o que determina que tipo de núcleo sexualmente dimórfico se desenvolverá, o que por sua vez está relacionado com o tipo de conduta que o animal poderá expressar em sua vida adulta. Não deixa de ser um paradoxo que ao injetar uma dose elevada de estrógenos nos primeiros dias de vida de uma rata, os núcleos sexualmente dimórficos da mesma se desenvolverão como macho e em sua vida adulta seu potencial de conduta estará masculinizado e desfeminizado. O hormônio “feminino” conhecido como estradiol, masculiniza o hipotálamo e a conduta do animal. Logo, se a rata neonatal for exposta a injeção de andrógeno não-aromatizado (que não pode ser transformado em estrógenos pelas células) ela não se masculiniza. A masculinização e desfeminização dos ratos ou das ratas tratados com testosterona, na realidade, não são provocados pela própria testosterona, senão pelos estrógenos que se formam dentro dos neurônios quando absorvem a testosterona do sangue e a aromatizam para transformá-la em estrógenos (figura 6). Figura 6: desfeminização e masculinização do sistema nervoso central por meio da testosterona, que quando não absorvida pela α-fetoproteína pode entrar nos neurônios, onde se aromatizam para serem transformados em estrógenos, hormônio que é responsável pela desfeminização. Fonte: ZARCO, 2018. Por que as ratas, que possuem ovários funcionalmente produtores de estrógenos, não se masculinizam? A resposta está em uma proteína denominada α-fetoproteína que circula em altas concentrações nos fetos e nos recém-nascidos. Essa proteína possui a capacidade de unir-se aos estrógenos, ao qual impede seu entrada nas células. Os ratos, em desenvolvimento, produzem testosterona, no entanto não possui afinidade pela α-fetoproteína, o que permite com que ela circule livremente. Ao chegar ao SNC, a testosterona (que não foi absorvida) pode entrar nos neurônios e dentro deles se aromatizam e transformam-se em estrógenos, que finalmente masculinizam o SNC. A diferenciação sexual do hipotálamo depende, em síntese, da presença ou ausência dos testículos, o que permite que se produza ou não o hormônio testosterona que pode não ser absorvida por parte da α-fetoproteína, transformar-se em estrógenos e masculinizar o SNC. -/- •___CONCLUSÃO -/- Nos mamíferos todo o processo que se requerem para o desenvolvimento de um macho depende da existência de somente um gene do cromossomo Y, o gene SRY; a ausência desse gene resulta no desenvolvimento de uma fêmea. A presença ou ausência do gene SRY determina, então, a cadeia de eventos morfogênicos que ocorrerá em sua expressão ou não, para desenvolver todos os órgãos e características de um macho ou de uma fêmea. Por essa razão, os indivíduos com uma monossomia XOA (síndrome de Turner) são fêmeas (por não possuir o cromossomo Y nem o gene SRY), enquanto que os indivíduos triploides XXY (síndrome de Kleinefelter) são machos embora possuam dois cromossomos X. Em algumas espécies, no entanto, têm-se identificado machos que são cromossomicamente XX; nesses casos é determinado invariavelmente que por ser um erro durante a meiose a região do cromossomo Y em que reside o gene SRY tem sido transloucada ao cromossomo X. Da mesma forma, em alguns casos tem sido encontrado fêmeas com cariótipo XY; que nelas se identifica uma mutação inabilitante do gene SRY. Isso demonstra experimentalmente que por meio da engenharia genética é possível produzir machos com cariótipo XY mas com o gene SRY eliminado (knockout). Como é de se esperar, esses machos desenvolvem ovários e todos seus órgãos genitais, tanto internos quanto externos, e se desenvolvem como fêmeas. Os machos cromossomicamente XX transgênicos aos que se insertam uma cópia do gene SRY, desenvolvem testículos e um fenótipo masculino, embora sejam estéreis por causa da ausência de alguns genes do cromossomo Y que são necessários para a realização de uma espermatogênese normal. As falhas nos mecanismos de diferenciação sexual podem, diretamente, ocasionar anormalidades como as observadas nas bezerras Freemartin, que são bezerras originadas de uma gestação gemelar em que seu gêmeo era macho. O que sucede é que na espécie bovina, quando há uma gestação gemelar, é produzido um certo grau de anastomose entre as placentas dos fetos, o que permite a troca de sangue e de células entre ambos. Os produtos recebem, então, algumas células de seu gêmeos, que encontram seu lugar no órgão correspondente e se integram a ele. No caso particular das gônadas, quando o ovário primitivo de um embrião fêmea é colonizado por algumas células gonodais de seu gêmeo macho, essas células expressam o gene SRY, o que fará com que essa região da gônada se diferencie como testículo. Como resultado, se desenvolve um ovo-testículo (com maior ou menor proporção de tecido testicular dependendo do grau de colonização da gônada em formação por células provenientes do gêmeo macho). Ademais, ao haver certa quantidade de tecido testicular produtor de MIH, circularão sobre o feto fêmea níveis desse hormônio que, embora baixos, afetarão o desenvolvimento normal dos dutos de Müller, fazendo com que as bezerras Freemartin possuam genitálias internas ausentes ou pouco desenvolvidas. Os andrógenos produzidos pelas zonas de tecido testicular, por fim, são suficientes para causar um certo grau de masculinização, que se manifesta como um clitóris mais grande que o normal ou um desenvolvimento corporal masculinizado. -/- REFERÊNCIAS BIBLIOGRÁFICAS -/- ARNOLD, Arthur P.; CHEN, Xuqi; ITOH, Yuichiro. What a difference an X or Y makes: sex chromosomes, gene dose, and epigenetics in sexual differentiation. In: Sex and gender differences in pharmacology. Springer, Berlin, Heidelberg, 2013. p. 67-88. CUNNINGHAM, James. Tratado de fisiologia veterinária. Elsevier Health Sciences, 2011. DERIVAUX, Jules; BARNABÉ, Renato Campanarut. Reprodução dos animais domésticos. Zaragoza: Acribia, 1980. DA SILVA, Emanuel Isaque Cordeiro. Desenvolvimento Embrionário e Diferenciação Sexual nos Animais Domésticos. Disponível em:. Acesso em: Julho de 2020. HAFEZ, Elsayed Saad Eldin; HAFEZ, Bahaa. Reprodução animal. São Paulo: Manole, 2004. HIDALGO, C. Galina et al. Reproducción de animales domésticos. México: Limusa, 2008. MACLAUGHLIN, David T.; DONAHOE, Patricia K. Sex determination and differentiation. New England Journal of Medicine, v. 350, n. 4, p. 367-378, 2004. MCCARTHY, Margaret M.; ARNOLD, Arthur P. Reframing sexual differentiation of the brain. Nature neuroscience, v. 14, n. 6, p. 677, 2011. PLANT, Tony M.; ZELEZNIK, Anthony J. (Ed.). Knobil and Neill's physiology of reproduction. Academic Press, 2014. REY, Rodolfo. Diferenciación sexual embrio-fetal: De las moléculas a la anatomía. Revista chilena de anatomía, v. 19, n. 1, p. 75-82, 2001. SENGER, P. L. Embryogenesis of the pituitary gland and male or female reproductive system. In. Pathways to Pregnancy and Parturition. Current Conception Inc, v. 1, p. 8-76, 1997. ZARCO, L. Diferenciación sexual. In. PORTA, L. R.; MEDRANO, J. H. H. Fisiología reproductiva de los animales domésticos. Cidade do México: FMVZ-UNAM, 2018. -/- REALIZAÇÃO -/- . (shrink)

This paper discusses the uniqueness thesis, a core thesis in the epistemology of disagreement. After presenting uniqueness and clarifying relevant terms, a novel counterexample to the thesis will be introduced. This counterexample involves logical disagreement. Several objections to the counterexample are then considered, and it is argued that the best responses to the counterexample all undermine the initial motivation for uniqueness.

The research aims to identify the reality of modern methods applied in the process of performance assessments of employees in the municipalities of Gaza-strip, Complete Census method of community study was used, (571) questionnaires were distributed to all members of the community study, (524) questionnaires were recovery with rate of (91.76%). The most important findings of the study: There were statistically significant relationship differences between the applications of modern methods in the performance assessments of employees in the municipalities of Gaza-strip. (...) There was statistically significant relationship between the evaluation criteria that fit the required performance and the application of standards evaluations on performance of employees in the municipalities of Gaza-strip. There was statistically significant relationship between the use of methods, models for the evaluation of appropriate functions and the application of the performance assessments of employees in the municipalities of Gaza-strip. There was statistically significant relationship between the feedback and the application of performance assessments of employees in the municipalities of Gaza-strip. There was statistically significant relationship between the efficient, professional assessors and the application of the performance assessments of employees in the municipalities of Gaza-strip. There was statistically significant relationship between the extent of awareness of subordinates, participation in the evaluation of their performance and the application of the performance assessments of employees in the municipalities of Gaza-strip. The research also concluded a series of recommendations, including: that the design of evaluation models must be done with the participation of the employees and inform them of it, and that a date must be set to provide feedback and discuss the results with them, that they should be allowed grievance in front of an ad hoc committee in accordance with the known system. Direct manager must inform employees of their performance assessment date, discuss the results of the evaluation with them, and others should be involved with the direct manager of employees in their performance evaluation. The application of modern methods of performance evaluation through the good and purposeful planning should be used, analyzing and employing the results in administrative decisions regarding the employees, and the application of modern methods must be used in an effective and efficient performance evaluation. (shrink)

Among Bayesian confirmation theorists, several quantitative measures of the degree to which an evidential proposition E confirms a hypothesis H have been proposed. According to one popular recent measure, s, the degree to which E confirms H is a function of the equation P(H|E) − P(H|~E). A consequence of s is that when we have two evidential propositions, E1 and E2, such that P(H|E1) = P(H|E2), and P(H|~E1) ≠ P(H|~E2), the confirmation afforded to H by E1 does not equal the (...) confirmation afforded to H by E2. I present several examples that demonstrate the unacceptability of this result, and conclude that we should reject s (and other measures that share this feature) as a measure of confirmation. (shrink)

In order to improve our understanding of the components that reflect functionally important processes during reward anticipation and consumption, we used principle components analyses (PCA) to separate and quantify averaged ERP data obtained from each stage of a modified monetary incentive delay (MID) task. Although a small number of recent ERP studies have reported that reward and loss cues potentiate ERPs during anticipation, action preparation, and consummatory stages of reward processing, these findings are inconsistent due to temporal and spatial overlap (...) between the relevant electrophysiological components. Our results show three components following cue presentation are sensitive to incentive cues (N1, P3a, P3b). In contrast to previous research, reward‐related enhancement occurred only in the P3b, with earlier components more sensitive to break‐even and loss cues. During feedback anticipation, we observed a lateralized centroparietal negativity that was sensitive to response hand but not cue type. We also show that use of PCA on ERPs reflecting reward consumption successfully separates the reward positivity from the independently modulated feedback‐P3. Last, we observe for the first time a new reward consumption component: a late negativity distributed over the left frontal pole. This component appears to be sensitive to response hand, especially in the context of monetary gain. These results illustrate that the time course and sensitivities of electrophysiological activity that follows incentive cues do not follow a simple heuristic in which reward incentive cues produce enhanced activity at all stages and substages. (shrink)

The epistemic probability of A given B is the degree to which B evidentially supports A, or makes A plausible. This paper is a first step in answering the question of what determines the values of epistemic probabilities. I break this question into two parts: the structural question and the substantive question. Just as an object’s weight is determined by its mass and gravitational acceleration, some probabilities are determined by other, more basic ones. The structural question asks what probabilities are (...) not determined in this way—these are the basic probabilities which determine values for all other probabilities. The substantive question asks how the values of these basic probabilities are determined. I defend an answer to the structural question on which basic probabilities are the probabilities of atomic propositions conditional on potential direct explanations. I defend this against the view, implicit in orthodox mathematical treatments of probability, that basic probabilities are the unconditional probabilities of complete worlds. I then apply my answer to the structural question to clear up common confusions in expositions of Bayesianism and shed light on the “problem of the priors.”. (shrink)

I present a cumulative case for the thesis that we only know propositions that are certain for us. I argue that this thesis can easily explain the truth of eight plausible claims about knowledge: -/- (1) There is a qualitative difference between knowledge and non-knowledge. (2) Knowledge is valuable in a way that non-knowledge is not. (3) Subjects in Gettier cases do not have knowledge. (4) If S knows that P, P is part of S’s evidence. (5) If S knows (...) that P, ~P is epistemically impossible for S. (6) If S knows that P, S can rationally act as if P. (7) If S knows that P, S can rationally stop inquiring whether P. (8) If S knows each of {P1, P2, … Pn}, and competently deduces Q from these propositions, S knows that Q. -/- I then argue that the skeptical costs of this thesis are outweighed by its explanatory power. (shrink)

We present a model of the distribution of labour in science. Such models tend to rely on the mechanism of the invisible hand . Our analysis starts from the necessity of standards in distributed processes and the possibility of multiple standards in science. Invisible hand models turn out to have only limited scope because they are restricted to describing the atypical single-standard case. Our model is a generalisation of these models to J standards; single-standard models such as Kitcher are a (...) limiting case. We introduce and formalise this model, demonstrate its dynamics and conclude that the conclusions commonly derived from invisible hand models about the distribution of labour in science are not robust against changes in the number of standards. (shrink)

Molinists hold that there are contingently true counterfactuals about what agents would do if put in specific circumstances, that God knows these prior to creation, and that God uses this knowledge in choosing how to create. In this essay we critique Molinism, arguing that if these theses were true, agents would not be free. Consider Eve’s sinning upon being tempted by a serpent. We argue that if Molinism is true, then there is some set of facts that fully explains both (...) Eve’s action and everything else Eve does that influences that action; and that if this is the case, Eve does not act freely. The first premise of this argument follows from the explanatory relations the Molinist is committed to, and the second premise follows from libertarian intuitions about free will. (shrink)

This chapter presents a typology of the different kinds of inductive inferences we can draw from our evidence, based on the explanatory relationship between evidence and conclusion. Drawing on the literature on graphical models of explanation, I divide inductive inferences into (a) downwards inferences, which proceed from cause to effect, (b) upwards inferences, which proceed from effect to cause, and (c) sideways inferences, which proceed first from effect to cause and then from that cause to an additional effect. I further (...) distinguish between direct and indirect forms of downwards and upwards inferences. I then show how we can subsume canonical forms of inductive inference mentioned in the literature, such as inference to the best explanation, enumerative induction, and analogical inference, under this typology. Along the way, I explore connections with probability and confirmation, epistemic defeat, the relation between abduction and enumerative induction, the compatibility of IBE and Bayesianism, and theories of epistemic justification. (shrink)

This study aims to identify the digital reputation at the University of Palestine: an analytical perspective of the employees ’point of view, where the researchers used the descriptive and analytical approach, through a questionnaire distributed to a sample of employees at the University of Palestine, where the size of the study population is (234) employees, and the size of The sample is (117) employees, of whom (90) employees responded. The study provided a theoretical framework for what the writers and researchers (...) presented about the study variables, as well as a practical analytical framework for the opinions of employees at the University of Palestine. The digital reputation was expressed as an independent variable through its four indicators (feeling about the organization (satisfaction), admiration and respect, and trust, and social responsibility). The study found a set of results, the most important of which are: the existence of a high degree of digital reputation at the University of Palestine from the viewpoint of employees, and the absence of differences in the opinions of the study sample about digital reputation according to demographic variables. The study presented a set of recommendations, the most important of which are: The need for universities to enhance their digital reputation and raise its level. (shrink)

This publication is the translation of the first fragment of F. W. J Schelling's Presentation of Philosophical Empiricism accompanied by the analytical translator's preface. In his treatise, Schelling assesses the history of modern philosophy. Namely, he treats it as history of experiments, the goal of which was in the search for the primary fact in the world. In Schelling's opinion, this fact is in the growing over-weight of the subjective over the objective. Only his philosophy of nature was able to (...) find this fact. However, it is not genuine fact but only pure fact, because it does not content in itself any ground for the over-weighting of the subjective over the objective. For resolve this problem, Schelling starts to use the concepts formed by Ancient philosophers, namely by Pythagoras and Plato. The concepts of the limitless and the limit are belonging to the series of the mentioned concepts. Accordantly, Schelling associates the notion of the objective with the one of the limitless being and the notion of the subjective with the one of the limit or limiting instance. His inquiry into the correlation between the limitless being and the limit, i.e. between the objective and the subjective leads him to the declaration of the existence of the free efficient cause, which determinates their interplay and the rise of that-what-should-be from that-what-should-not-be. Since the limitless is the objective and the limit is the subjective in accordance with Schelling, such efficient cause is also the cause of the progressive over-weighting of the subjective over the objective as well. It can explain the fact, which the Schelling's philosophy of nature has only found but not explained. The in his preface, the translator puts the question of the possibility as well as of a relevance of the Schelling's late philosophy to the phenomenological thought. In this context, he emphasizes few moments, by which the later Schelling' philosophy could be of interests for phenomenologists, namely the following ones: the concept of philosophical empiricism itself, the Schelling's division between the pure fact and the genuine fact, his treatment of history of philosophy as history of experiments. Moreover, he speaks about main difficulties connected with the translation of Schelling's text into Russian and gives a German-Russian glossary for utility of Russian readers. The translator gives also the commentaries by Arthur Drews, who reedited the Schelling's treatise in 1902, in their Russian translation. (shrink)

According to a simple Bayesian argument from evil, the evil we observe is less likely given theism than given atheism, and therefore lowers the probability of theism. I consider the most common skeptical theist response to this argument, according to which our cognitive limitations make the probability of evil given theism inscrutable. I argue that if skeptical theists are right about this, then the probability of theism given evil is itself largely inscrutable, and that if this is so, we ought (...) to be agnostic about whether God exists. (shrink)

Den filosofiske position konsekventialisme er ofte genstand for debat i filosofikredse, men alt for hyppigt opstår der misforståelser blandt de involverede, fordi de ikke er eksplicitte, hvad grundantagelser og væsentlige distinktioner angår. Denne korte artikel vil give en approksimation af, hvad der forstås ved konsekventialisme på et generisk niveau. Målet med artiklen er at klargøre nogle af de grundantagelser og distinktioner, som konsekventialister ofte benytter i deres teoridannelse, og som bør holdes for øje i ønsket om en frugtbar debat.

The classical Confucian philosopher Xunzi proposed a naturalistic virtue ethics account of ritual: rituals are practices that channel human emotion and desire so that one develops virtues. In this paper I show that William of Auxerre’s Summa de Officiis Ecclesiasticis can be understood as presenting a similar account of ritual. William places great emphasis on the emotional power of the liturgy, which makes participants like the blessed in heaven by developing virtue. In other words, he has a virtue ethics of (...) ritual closely aligned with that of Xunzi. Xunzi’s writings on ritual illuminate and enrich one’s reading of the Summa de Officiis. But unlike Xunzi, William is not a naturalist with regard to ritual: although much of William’s language about the causal power of liturgy can be explained in Xunzian terms, Christian liturgy has an irreducible supernatural element. (shrink)

ABSTRACT: Recent work in moral theory includes an intriguing new argument that the vagueness of moral properties, together with two well-known and well-received metaethical principles, entails the incredible conclusion that it is impossible to be moral. I show that the argument equivocates between “it is true that A and B are morally indistinguishable” and “it is not false that A and B are morally indistinguishable.” As expected the argument is interesting but unsound. It is therefore not impossible to be moral.RÉSUMÉ: (...) Les travaux récents en théorie morale comprennent un nouvel argument intrigant voulant que le caractère vague des propriétés morales, joint à deux principes métaéthiques bien connus et généralement admis, entraîne une conclusion incroyable, soit qu’il est impossible d’être moral. Je montre que cet argument entretient l’équivoque entre «il est vrai que A et B sont moralement impossibles à distinguer» et «il n’est pas faux que A et B soient moralement impossibles à distinguer». Comme on s’y attendait, l’argument est intéressant mais mal fondé. Il n’est donc pas impossible d’être moral. (shrink)

Ted Sider’s Proportionality of Justice condition requires that any two moral agents instantiating nearly the same moral state be treated in nearly the same way. I provide a countermodel in supervaluation semantics to the proportionality of justice condition. It is possible that moral agents S and S' are in nearly the same moral state, S' is beyond all redemption and S is not. It is consistent with perfect justice then that moral agents that are not beyond redemption go determinately to (...) heaven and moral agents that are beyond all redemption go determinately to hell. I conclude that moral agents that are in nearly the same moral state may be treated in very unequal ways. (shrink)

"Correlation is not causation" is one of the mantras of the sciences—a cautionary warning especially to fields like epidemiology and pharmacology where the seduction of compelling correlations naturally leads to causal hypotheses. The standard view from the epistemology of causation is that to tell whether one correlated variable is causing the other, one needs to intervene on the system—the best sort of intervention being a trial that is both randomized and controlled. In this paper, we argue that some purely correlational (...) data contains information that allows us to draw causal inferences: statistical noise. Methods for extracting causal knowledge from noise provide us with an alternative to randomized controlled trials that allows us to reach causal conclusions from purely correlational data. (shrink)

Empirical evidence shows that people have multiple time-biases. One is near-bias; another is future-bias. Philosophical theorising about these biases often proceeds on two assumptions. First, that the two biases are _independent_: that they are explained by different factors (the independence assumption). Second, that there is a normative asymmetry between the two biases: one is rationally impermissible (near-bias) and the other rationally permissible (future-bias). The former assumption at least partly feeds into the latter: if the two biases were not explained by (...) different factors, then it would be less plausible that their normative statuses differ. This paper investigates the independence assumption and finds it unwarranted. In light of this, we argue, there is reason to question the normative asymmetry assumption. (shrink)

:The study aimed to identify the level of enhancing the competitive advantage of training institutions in Palestine. The study used the descriptive analytical approach. A structured questionnaire was used to collect data that contribute to achieving the objectives of the study. The study population consists of workers in training institutions operating in the southern Palestinian governorates. The random sample for data collection, where (90) applicable questionnaires were retrieved. The results of the study showed that the general estimate for the competitive (...) advantage axis came with a high degree and a relative weight (90.67%). The results also showed that there were no statistically significant differences in enhancing the competitive advantage according to the variables (gender, governorate). As well as the existence of statistically significant differences in enhancing the competitive advantage according to the variables (Educational Qualification, Age Group, Number Of Years of Service). The study presented a set of recommendations, the most important of which are: the need for centers to develop their training systems in line with modern technology, in addition to the need for centers to target new areas in their service by opening other branches in diffe rent geographical locations. (shrink)

It has become customary to conceptualize the living cell as an intricate piece of machinery, different to a man-made machine only in terms of its superior complexity. This familiar understanding grounds the conviction that a cell's organization can be explained reductionistically, as well as the idea that its molecular pathways can be construed as deterministic circuits. The machine conception of the cell owes a great deal of its success to the methods traditionally used in molecular biology. However, the recent introduction (...) of novel experimental techniques capable of tracking individual molecules within cells in real time is leading to the rapid accumulation of data that are inconsistent with an engineering view of the cell. This paper examines four major domains of current research in which the challenges to the machine conception of the cell are particularly pronounced: cellular architecture, protein complexes, intracellular transport, and cellular behaviour. It argues that a new theoretical understanding of the cell is emerging from the study of these phenomena which emphasizes the dynamic, self-organizing nature of its constitution, the fluidity and plasticity of its components, and the stochasticity and non-linearity of its underlying processes. (shrink)

Philosophy of biology is often said to have emerged in the last third of the twentieth century. Prior to this time, it has been alleged that the only authors who engaged philosophically with the life sciences were either logical empiricists who sought to impose the explanatory ideals of the physical sciences onto biology, or vitalists who invoked mystical agencies in an attempt to ward off the threat of physicochemical reduction. These schools paid little attention to actual biological science, and as (...) a result philosophy of biology languished in a state of futility for much of the twentieth century. The situation, we are told, only began to change in the late 1960s and early 1970s, when a new generation of researchers began to focus on problems internal to biology, leading to the consolidation of the discipline. In this paper we challenge this widely accepted narrative of the history of philosophy of biology. We do so by arguing that the most important tradition within early twentieth-century philosophy of biology was neither logical empiricism nor vitalism, but the organicist movement that flourished between the First and Second World Wars. We show that the organicist corpus is thematically and methodologically continuous with the contemporary literature in order to discredit the view that early work in the philosophy of biology was unproductive, and we emphasize the desirability of integrating the historical and contemporary conversations into a single, unified discourse. (shrink)

A central tenet of truthmaker theory is that necessitation is necessary for truthmaking (NEC). This paper defends NEC in a novel, piecemeal way, namely by responding to a potential counterexample involving a changing past. If Carter won a race at t1 but is later disqualified at t2, then Carter no longer won at t1. A wholly past event seems to have changed in the future. The event makes ‘Carter won the race at t1’ (RACE) true between t1‐2 but fails to (...) make it true at t2. So, we have a potential counterexample to necessitation: a truthmaker of RACE fails in another context to make the same truthbearer RACE true. I argue that the best solution to this challenge is not that there are different truthbearers at t1‐2 and t2 (the semantic response), or that RACE was never true because of the future disqualification or will always be true despite the future disqualification. The best solution is to accept that the past can change: past events can change based on what happens in the future (e.g., via their effects). This paper's novel defence of necessitation will illustrate the importance of utilising explicitly ontological and commonsensical tools in accounting for truth. (shrink)

Data involving epistemic modals suggest that some classically valid argument forms, such as _reductio_, are invalid in natural language reasoning as they lead to modal collapses. We adduce further data showing that the classical argument forms governing the existential quantifier are similarly defective, as they lead to a _de re–de dicto_ collapse. We observe a similar problem for disjunction. But if the classical argument forms for negation, disjunction and existential quantification are invalid, what are the correct forms that govern the (...) use of these items? Our diagnosis is that epistemic modals interfere with hypothetical reasoning. We present a modal first-order logic and model theory that characterizes hypothetical reasoning with epistemic modals in a principled manner. One upshot is a sound and complete natural deduction system for reasoning with epistemic modals in first-order logic. (shrink)

Different authors offer subtly different characterizations of naïve realism. We disentangle the main ones and argue that illusions provide the best proving ground for naïve realism and its main rival, representationalism. According to naïve realism, illusions never involve per- ceptual error. We assess two leading attempts to explain apparent perceptual error away, from William Fish and Bill Brewer, and conclude that they fail. Another lead- ing attempt is assessed in a companion paper, which also sketches an alternative representational account.

Open Access: What if it doesn’t get better? Against more hopeful and optimistic views that it is not just ideal but possible to put an end to what John Rawls calls “the great evils of human history,” I aver that when it comes to evils caused by human beings, the situation is hopeless. We are better off with the heavy knowledge that evils recur than we are with idealizations of progress, perfection, and completeness; an appropriate ethic for living with such (...) heavy knowledge, which I call an ‘Imperfectionist Ethic,’ could include resisting evils, improving the lives of victims, and even enjoying ourselves. Better conceptions of the objects of hope, and the good life, inform a praxis-centered, nonideal ethic, supportive of sustained moral motivation, resilience, and even cheer. I connect elements of stoic and pessimistic philosophy in order to outline some normative recommendations for living with evils. A praxis-centered ethic would helpfully adjust our expectations from changing an uncontrollable future, to developing better skills for living in a world that exceeds our control. (shrink)

A dialogue in which Freya nan Max are determined to argue abut free will.

This paper explores the role of moral uncertainty in explaining the morally disruptive character of new technologies. We argue that existing accounts of technomoral change do not fully explain its disruptiveness. This explanatory gap can be bridged by examining the epistemic dimensions of technomoral change, focusing on moral uncertainty and inquiry. To develop this account, we examine three historical cases: the introduction of the early pregnancy test, the contraception pill, and brain death. The resulting account highlights what we call “differential (...) disruption” and provides a resource for fields such as technology assessment, ethics of technology, and responsible innovation. (shrink)

The article studies the impact of Fintech on entrepreneurship in Arabic region by using Crowdfunding platforms as the field of study. The article focuses on Arabic Crowdfunding platforms. The population of (12) platforms consist of: individuals, entrepreneurs, investors, employees at Crowdfunding platforms. Descriptive and quantitative approach used in this article, and a questionnaire used as a tool to collect primary data. The results indicate an impact for Fintech on entrepreneurship in general and obvious obstacles to use it widely in Arabic (...) region cause of legislations or e-payments. The article recommended more awareness for innovative products and services such as Fintech, Crowdfunding and adopting the culture of e-business models. Also the article promoting the process of developing regulations that organize e-business models, especially Fintech and Crowdfunding, the use of modern communication technology to serve the development of society, more interest to innovation and creativity as a key factor for entrepreneurial success. (shrink)

There is no doubt that tomato diseases are one of the important reasons that destroy the tomato plant and its crops. This leads to clear damage to these plants and they become inedible. Discovering these diseases after a good step for proper and correct treatment. Determining the treatment with high accuracy depends on the method used in the diagnosis. Correctly, expert systems can greatly help to avoid damage to these plants. The expert system diagnoses tomato disease correctly to facilitate farmers (...) to find the correct treatment based on the appropriate diagnosis. Objectives: An expert system has been established based on CLIPS to diagnose tomato plant disease. (shrink)