Upon separation of the protein from the nucleic acid component of tobacco mosaic virus by phenol, using a fast and gentle procedure, the nucleic acid is infective in assays on tobacco leaves. A series of qualitative and quantitative control experiments demonstrates that the biological activity cannot depend on residual proteins in the preparation, but is a property of isolated nucleic acid which is thus the genetic material of the virus.

The present study examines the physiological alterations in prolactin (PRL) messenger ribonucleic acid (mRNA) and serum PRL levels during the rat estrous cycle and the effed of naloxone, an endogenous opioid peptide receptor antagonist, on PRL gene expression during the rat estrous cycle. Adult female rats exhibiting at least two consecutive 4-day estrous cycles were used in this study. A single injection of naloxone (2mg/kg b.w.) or saline was given sc 30 mm prior to decapitation. Animals were sacrificed (...) at 10:00 h of each stage of the estrous cycle, and at 2-h intervals from 10:00 h to 20:00 h during the proestrus. PRL mRNA and serum PRL levels were determined by an RNA-blot hybridization with the rat PRL cDNA probe and by a PRL radioimmunoassay, respectively. PRL mRNA and serum PRL levels were not dramatically altered in the morning of each stage of diestrus I, II, and proestrus, and naloxone failed to modify the two parameters. During estrus naloxone clearly suppressed serum PRL levels, but it was unable to modify PRL mRNA levels. A more detailed examination of the proestrus stage revealed that PRL mRNA and serum PRL levels fluctuated as a function of time: PRL mRNA levels reached a maximum level at 12:00 h and gradually decreased until 18:00 h. PRL mRNA levels then rose at 20:00 h. No difference in PRL mRNA levels between the control and naloxone-treated groups was observed. Changes in serum PRL level during proestrus were conversely related to changes in PRL mRNA: serum PRL levels were low from 10:00 h to 14:00 h, then increased and reached a maximum level at 16:00-18:00 h. Following then, serum PRL levels were decreased. Naloxone was effective in suppressing the characteristic afternoon surge of PRL from 16:00 h to 20:00 h. These data clearly showed that alterations in PRL mRNA levels were conversely correlated with changes in serum PRL levels on proestrus, indicating differential regulation of PRL gene expression and secretion. (shrink)

Within the sedimentation diagram of infective RNA preparations isolated from Tobacco Mosaic Virus, undegraded molecules form a sharp peak with a molecular weight corresponding to the total RNA content of the virus particle. Degradation kinetics by ribonuclease is of the linear, single-target type, indicating that the RNA is single-stranded. The intact RNA of a virus particle thus forms one big single-stranded molecule. Quantitative evaluation of the effect degradation by RNA-ase on the infectivity of the RNA shows that the integrity of (...) the entire molecule is required for its biological activity. (shrink)

Uric acid has increasingly been associated with insulin resistance, hyperinsulinemia, and type 2 diabetes mellitus. Diabetic patients who are hyperuricemic have a risk of developing diabetic complications. Pathogenesis of uric acid may decrease nitric oxide bioavailability in vascular smooth muscle, endothelial cells and direct scavenging of nitric oxide by uric acid. A decrease in endothelial nitric oxide production by uric acid has also been associated with endothelial dysfunction and insulin resistance. This study aims to determine the (...) relationship between uric acid and glucose levels in patients with type 2 diabetes mellitus. The study included 161 Libyan patients (67 males and 94 females) diagnosed with type 2 diabetes mellitus. Both levels of serum uric acid and hemoglobin A1c (HbA1c) were determined. The patients were divided into two groups. The controllable diabetic group with HbA1c of less than 06.0% and the uncontrollable diabetic group with HbA1c of more than 06.0%. Patients who are suffering from type 2 diabetes mellitus without complications were included whereas patients with smoking, alcoholism, nephrotic disease, malignancy, hepatitis, and renal failure or kidney disease were excluded. The mean and standard deviation of uric acid, HbA1c and Pearson correlation coefficient test were considered. In the controllable diabetic group, serum uric acid mean was found to be 4.807±1.39 and HbA1c was found to be 5.032±1.39. In the uncontrollable diabetic group, serum uric acid was 4.897±1.66 and HbA1c was 8.396±1.65. Uric acid level has significantly been correlated with HBA1C in controlled and uncontrolled diabetic patients (p<0.05). In addition, the uric acid level was found to be higher in the uncontrolled diabetic group than that in the controlled group (p<0.05). A possible relationship between serum uric acid and the incidence of type 2 diabetes mellitus was noted. Thus, uric acid can be used as a potential biomarker to indicate impaired glucose metabolism. (shrink)

Ascorbic acid (vitamin C) is a water-soluble vitamin; it is present in the highest concentration in the brain. Ascorbic acid in high doses acts as a potential treatment for various neuropathological and psychiatric conditions. Flumazenil is a benzodiazepine antagonist; it competitively inhibits the activity of benzodiazepine and non-benzodiazepine substances that interact with benzodiazepine receptors site on the GABA/benzodiazepine receptor complex. This study aims to investigate the effect of flumazenil on the anxiolytic action of ascorbic acid using an (...) elevated plus maze model of anxiety in rats. Male Albino Wistar rats weighing between 250 and 320 grams were used. Rats were divided into four equal groups of seven rats each and treated as follows: Group I, the control group received a single dose of 1.0% tween 80; Group II treated with a single dose of 125 mg/kg ascorbic acid; Group III was injected by a single dose of 1.0 mg/kg flumazenil; Group IV received a combination treatment of 125 mg/kg ascorbic acid and 1.0 mg/kg flumazenil. Behavioural measurements using a plus maze were scored 30 min after the administration. The parameters scored are the time spent on the open and closed arms, the lines and number of entries into open and closed arms, and the anxiety measure. Ascorbic acid decreased anxiety measure and increased the total lines and total number of entries; this effect was abolished by the administration of flumazenil with ascorbic acid. Thus, ascorbic acid produces an anxiolytic-like effect in rats; this effect was abolished by flumazenil administration with ascorbic acid. This may indicate that the GABA/benzodiazepine receptor complex has to be stimulated to produce the anxiolytic effect. (shrink)

For a period of several years the philosopher of science Hasok Chang has promoted various inter-related views including pluralism, pragmatism, and an associated view of natural kinds. He has also argued for what he calls the persistence of everyday terms in the scientific view. Chang claims that terms like phlogiston were never truly abandoned but became transformed into different concepts that remain useful. On the other hand, Chang argues that some scientific terms such as acidity have suffered a form of (...) “rupture”, especially in the case of the modern Lewis definition of acids. Chang also complains that the degree of acidity of a Lewis acid cannot be measured using a pH meter and seems to regard this as a serious problem. The present paper examines some of these views, especially what Chang claims to be a rupture in the definition of acidity. It is suggested that there has been no such rupture but a genuine generalization, on moving from the Brønsted-Lowry theory to the Lewis theory of acidity. It will be shown how the quantification and measurement of Lewis acidity can easily be realized through the use of equilibrium theory and the use of stability constants. (shrink)

Physicians in Islamic countries might be requested to participate in the Islamic legal code of qiṣāṣ, in which the victim or family has the right to an eye-for-an-eye retaliation. Qiṣāṣ is only used as a punishment in the case of murder or intentional physical injury. In situations such as throwing acid, the national legal system of some Islamic countries asks for assistance from physicians, because the punishment should be identical to the crime. The perpetrator could not be punished without (...) a physician’s participation, because there is no way to guarantee that the sentence would be carried out without inflicting more injury than the initial victim had suffered. By examining two cases of acid throwing, this paper discusses issues related to physicians’ participation in qiṣāṣ from the perspective of medical ethics and Islamic Shari’a law. From the standpoint of medical ethics, physicians’ participation in qiṣāṣ is not appropriate. First, qiṣāṣ is in sharp contrast to the Hippocratic Oath and other codes of medical ethics. Second, by physicians’ participation in qiṣāṣ, medical practices are being used improperly to carry out government mandates. Third, physician participation in activities that cause intentional harm to people destroys the trust between patients and physicians and may adversely affect the patient–physician relationship more generally. From the standpoint of Shari’a, there is no consensus among Muslim scholars whether qiṣāṣ should be performed on every occasion. We argue that disallowing physician involvement in qiṣāṣ is necessary from the perspectives of both medical ethics and Shari’a law. (shrink)

The neurotransmitters GABA and glutamate have been suggested to play a role in Major Depressive Disorder (MDD) through an imbalance between cortical inhibition and excitation. This effect has been highlighted in higher brain areas, such as the prefrontal cortex, but has also been posited in basic sensory cortices. Based on this, magnetic resonance spectroscopy (MRS) was used to investigate potential changes to GABA+ and glutamate+glutamine (Glx) concentrations within the occipital cortex in MDD patients (n = 25) and healthy controls (n (...) = 25). No difference in occipital GABA+ or Glx concentrations, nor in the GABA+/Glx ratio, was found between groups. An analysis of an extended MDD patient and unmatched control dataset (n = 90) found no correlation between metabolite concentrations and depressive symptoms. These results were integrated with prior studies through metabolite-specific meta-analyses, revealing no difference in occipital GABA and Glx concentrations between patients and controls. An effect of publication year on GABA group differences was found, suggesting that previously reported results may have been artifacts of measurement accuracy. Taken together, our results suggest that, contrary to some prior reports, MRS measurements of occipital GABA and Glx do not differ between MDD patients and controls. (shrink)

The aim of this article is to explore the impact of Darwinism in metaethics and dispel some of the confusion surrounding it. While the prospects for a Darwinian metaethics appear to be improving, some underlying epistemological issues remain unclear. We will focus on the so-called Evolutionary Debunking Arguments (EDAs) which, when applied in metaethics, are defined as arguments that appeal to the evolutionary origins of moral beliefs so as to undermine their epistemic justification. The point is that an epistemic disanalogy (...) can be identified in the debate on EDAs between moral beliefs and other kinds of beliefs, insofar as only the former are regarded as vulnerable to EDAs. First, we will analyze some significant debunking positions in metaethics in order to show that they do not provide adequate justification for such an epistemic disanalogy. Then, we will assess whether they can avoid the accusation of being epistemically incoherent by adopting the same evolutionary account for all kinds of beliefs. In other words, once it is argued that Darwinism has a corrosive impact on metaethics, what if its universal acid cannot be contained? (shrink)

The generation of viral mutants in vitro was demonstrated by treatment of the isolated RNA of Tobacco Mosaic Virus by nitrous acid. This agent causes deaminations converting cytosine into uracil, and adenine into hypoxanthine. Our assay for mutagenesis was the production of local lesions on a tobacco variety on which the untreated strain produces systemic infections only. A variety of different mutants are generated in this way. Quantitative analysis of the kinetics of mutagenesis leads to the conclusion that alteration (...) of a single out of the 6000 nucleotides of the viral RNA is sufficient for causing a mutation. (shrink)

Abstract: 1,3-dichloro-5,5-dimethylhydantoin (DCDMH) hydrolysed of this compounds leads to the formation of active positive halogen species like HOCl and H2O+Cl. The H2O+Cl in non-polar or less polar media, extensively used as a chlorinating and oxidizing agents in organic substrate. The rate of reaction is enhanced by the increasing [H+] and percentage of acetic acid. The main product of the oxidation is corresponding aldehydes. The thermodynamic parameters for the oxidation have been computed in the show step mechanism. The observed rate (...) law was in good conformity with the mechanism. (shrink)

An alliance of established experts on critical care, Front Line COVID-19 Critical Care Alliance (FLCCC), has published two protocols for treatment of COVID-19. The first one, methylprednisolone, ascorbic acid, thiamine, and heparin (MATH+), is intended for hospital and intensive care unit treatment of pulmonary phases of the disease. It is based on affordable, commonly available components: anti-inflammatory corticosteroids (methylprednisolone, "M"), high-dose vitamin C infusion (ascorbic acid, "A"), vitamin B1 (thiamine, "T"), anticoagulant heparin ("H"), antiparasitic agent ivermectin, and supplemental (...) components ("+") including melatonin, vitamin D, elemental zinc, and magnesium. -/- The MATH+ protocol has received scarce attention due to the World Health Organization (WHO) advising against the use of corticosteroids in the beginning of the pandemic. In addition, randomized controlled clinical trials were required as a condition for adoption of the protocol. As the hospital mortality rate of MATH+ treated patients was approximately a quarter of the rate of patients receiving a standard of care, the authors of the protocol considered performing such trials unethical. Other parties have later performed clinical trials with corticosteroids and anticoagulants, which has led to a more widespread adoption of these components. -/- In October 2020, ivermectin was upgraded from an optional component to an essential component of the protocol. According to the authors, ivermectin is considered the first agent effective for both prophylaxis (prevention) of COVID-19 and for treatment of all phases of COVID-19 including outpatient treatment of the early symptomatic phase. Therefore, at the end of October 2020, a separate ivermectin-based I-MASK+ protocol for prophylaxis and early outpatient treatment of COVID-19 was published. (shrink)

Starting with 1985, we discovered the possible existence of electrons with net helicity in biomolecules as amino acids and their possibility to discern between the two quantum spin states. It is well known that the question of a possible fundamental role of quantum mechanics in biological matter constitutes still a long debate. In the last ten years we have given a rather complete quantum mechanical elaboration entirely based on Clifford algebra whose basic entities are isomorphic to the well known spin (...) Pauli matrices. A number of our recent results indicate the possible logical origin of quantum mechanics and the direct admission of quantum mechanics in the field of cognitive sciences. In February 2011 the authors Gölder et al., published their important discovery on Science about Spin Selectivity in Electron Transmission Through Self-Assembled Monolayers of Double-Stranded DNA confirming in such manner that the principles of quantum mechanics apply to biological systems. (shrink)

The type-level abstraction is a formal way to represent molecular structures in biological practice. Graphical representations of molecular structures of biological objects are also used to identify functional processes of things. This paper will reveal that category theory is a formal mathematical language not only to visualize molecular structures of biological objects as type-level abstraction formally but also to understand how to infer biological functions from the molecular structures of biological objects. Category theory is a toolkit to understand biological knowledge (...) at the type-level formally, not individual token-level, as well as typical heuristic strategies in molecular biology. (shrink)

3, 5 dinitro benzoic acid hydrazide was prepared by the hydrazinolysis of the corresponding ethyl ester. Condensation of this hydrazide with different aromatic acids in presence of POCl3 gave 2-3, 5 dinitropheny1-5-substituted pheny1 1, 3, 4-oxadiazoles. All the final compounds were tested against Ranikhet Disease Virus (RDV). However no compound showed antiviral activity against RDV.

Scientific realists don’t standardly discriminate between, say, biology and fundamental physics when deciding whether the evidence and explanatory power warrant the inclusion of new entities in our ontology. As such, scientific realists are committed to a lush rainforest of special science kinds (Ross, 2000). Viruses certainly inhabit this rainforest – their explanatory power is overwhelming – but viruses’ properties can be explained from the bottom up: reductive explanations involving amino acids are generally available. However, reduction has often been taken to (...) lead to a metaphysical downgrading, so how can viruses keep their place in the rainforest? In this paper, we show how the inhabitants of the rainforest can be inoculated against the eliminative threat of reduction: by demonstrating that they are emergent. According to our account, emergence involves a screening off condition as well as novelty. We go on to demonstrate that this account of emergence, which is compatible with theoretical reducibility, satisfies common intuitions concerning what should and shouldn’t count as real: viruses are emergent, as are trout and turkeys, but philosophically gerrymandered objects like trout-turkeys do not qualify. (shrink)

The current COVID-19 pandemic and the previous SARS/MERS outbreaks of 2003 and 2012 have resulted in a series of major global public health crises. We argue that in the interest of developing effective and safe vaccines and drugs and to better understand coronaviruses and associated disease mechenisms it is necessary to integrate the large and exponentially growing body of heterogeneous coronavirus data. Ontologies play an important role in standard-based knowledge and data representation, integration, sharing, and analysis. Accordingly, we initiated the (...) development of the community-based Coronavirus Infectious Disease Ontology in early 2020. -/- As an Open Biomedical Ontology (OBO) library ontology, CIDO is open source and interoperable with other existing OBO ontologies. CIDO is aligned with the Basic Formal Ontology and Viral Infectious Disease Ontology. CIDO has imported terms from over 30 OBO ontologies. For example, CIDO imports all SARS-CoV-2 protein terms from the Protein Ontology, COVID-19-related phenotype terms from the Human Phenotype Ontology, and over 100 COVID-19 terms for vaccines (both authorized and in clinical trial) from the Vaccine Ontology. CIDO systematically represents variants of SARS-CoV-2 viruses and over 300 amino acid substitutions therein, along with over 300 diagnostic kits and methods. CIDO also describes hundreds of host-coronavirus protein-protein interactions (PPIs) and the drugs that target proteins in these PPIs. CIDO has been used to model COVID-19 related phenomena in areas such as epidemiology. The scope of CIDO was evaluated by visual analysis supported by a summarization network method. CIDO has been used in various applications such as term standardization, inference, natural language processing (NLP) and clinical data integration. We have applied the amino acid variant knowledge present in CIDO to analyze differences between SARS-CoV-2 Delta and Omicron variants. CIDO's integrative host-coronavirus PPIs and drug-target knowledge has also been used to support drug repurposing for COVID-19 treatment. -/- CIDO represents entities and relations in the domain of coronavirus diseases with a special focus on COVID-19. It supports shared knowledge representation, data and metadata standardization and integration, and has been used in a range of applications. (shrink)

I present a reconstruction of F.H.C. Crick's two 1957 hypotheses "Sequence Hypothesis" and "Central Dogma" in terms of a contemporary philosophical theory of causation. Analyzing in particular the experimental evidence that Crick cited, I argue that these hypotheses can be understood as claims about the actual difference-making cause in protein synthesis. As these hypotheses are only true if restricted to certain nucleic acids in certain organisms, I then examine the concept of causal specificity and its potential to counter claims about (...) causal parity of DNA and other cellular components. I first show that causal specificity is a special kind of invariance under interventions, namely invariance of generalizations that range over finite sets of discrete variables. Then, I show that this notion allows the articulation of a middle ground in the debate over causal parity. (shrink)

It is a platitude that when we reason, we often take things for granted, sometimes even justifiably so. The chemist might reason from the fact that a substance turns litmus paper red to that substance being an acid. In so doing, they take for granted, reasonably enough, that this test for acidity is valid. We ordinarily reason from things looking a certain way to their being that way. We take for granted, reasonably enough, that things are as they look (...) Although it is a platitude that we often take things for granted when we reason—whether justifiably or not—one might think that we do not have to. In fact, it is a natural expectation that were we not pressed by time, lack of energy or focus, we could always in principle make explicit in the form of premises every single presupposition we make in the course of our reasoning. In other words, it is natural to expect it to be true that presuppositionless reasoning is possible. In this essay, I argue that it is false: presuppositionless reasoning is impossible. Indeed, I think this is one of the lessons of a long-standing paradox about inference and reasoning known as Lewis Carroll’s (1985) regress of the premises. Many philosophers agree that Carroll’s regress teaches us something foundational about reasoning. I part ways about what it is that it teaches us. What it teaches us is that the structure of reasoning is constitutively presuppositional. (shrink)

Modeling mechanisms is central to the biological sciences – for purposes of explanation, prediction, extrapolation, and manipulation. A closer look at the philosophical literature reveals that mechanisms are predominantly modeled in a purely qualitative way. That is, mechanistic models are conceived of as representing how certain entities and activities are spatially and temporally organized so that they bring about the behavior of the mechanism in question. Although this adequately characterizes how mechanisms are represented in biology textbooks, contemporary biological research practice (...) shows the need for quantitative, probabilistic models of mechanisms, too. In this paper we argue that the formal framework of causal graph theory is well-suited to provide us with models of biological mechanisms that incorporate quantitative and probabilistic information. On the ba-sis of an example from contemporary biological practice, namely feedback regulation of fatty acid biosynthesis in Brassica napus, we show that causal graph theoretical models can account for feedback as well as for the multi-level character of mechanisms. However, we do not claim that causal graph theoretical representations of mechanisms are advantageous in all respects and should replace common qualitative models. Rather, we endorse the more balanced view that causal graph theoretical models of mechanisms are useful for some purposes, while being insufficient for others. (shrink)

Saturated free fatty acids-induced hepatocyte lipoapoptosis plays a pivotal role in non-alcoholic steatohepatitis. Theactivation of endoplasmic reticulum (ER) stress isinvolved in hepatocyte lipoapoptosis induced by thesaturated free fatty acidpalmitate (PA). However, the underlying mechanismsof the role of ER stress in hepatocyte lipoapoptosis remain largely unclear.In this study, we showed that PA and tunicamycin (Tun), a classic ER stress inducer, resulted in differential activation of ERstress pathways. Our data revealed that PA inducedchronic and persistent ER stress response, but Tuninduced acute and (...) transientER stress response. Compared with Tun treatment, PAinduced much lower glucose-regulated protein 78 (GRP78), a centralregulator of ER homeostasis, accumulation. It is noteworthy that GRP78 over-expression not only inhibited PA-induced ERstress but also decreased PA-induced apoptosis. Taken together, our data suggest that the differentialactivation of ER stresssignal plays an important role in PA-induced hepatocyte lipoapoptosis. More detailed studies on the mechanisms of PA inrepressing the accumulation of GRP78 will contribute to the understanding of molecular mechanisms of lipoapoptosis. (shrink)

Inflammation is said to be a healthy component of the body's immune system's reaction. Inflammation is characterised by four key symptoms: pain, redness, heat or warmth and swelling. As secondary metabolites, plants may produce a wide range of phytochemical compounds, which possess anti-inflammatory characteristics. Herbal remedies are important therapies for a wide range of ailments all over the world. There are around 7,500 species of medicinal plants, including representatives from over 17,000 flowering plant species. Even though synthetic chemistry has developed (...) its expectations, the use of natural ingredients in the manufacture of drugs used in contemporary medicine is unparalleled. By interfering with the biology of inflammation, anti-inflammatory medications may assist to minimising tissue damage and increase patient comfort. Because of the bulky figure of species reachable for study, the effective development of novel naturally taking place anti-inflammatory drugs is mostly dependent on a multidisciplinary approach to discovering new chemicals. Despite the statistic that many review papers have been produced in this field, the conventional of them simply examined the issue from an area perspective. Several non-steroidal anti-inflammatory drugs have been shown to reduce inflammation and pain by decreasing the isoform of the cyclooxygenase enzyme's digestion of arachidonic acid, hence lowering prostaglandin production. Non-steroidal anti-inflammatory drugs have a host of harmful effects. There are, however, medicinal herbs with anti-inflammatory pharmacological properties that have few or no negative effects. (shrink)

Saturated free fatty acids-induced hepatocyte lipoapoptosis plays a pivotal role in non-alcoholic steatohepatitis. Theactivation of endoplasmic reticulum (ER) stress isinvolved in hepatocyte lipoapoptosis induced by thesaturated free fatty acidpalmitate (PA). However, the underlying mechanismsof the role of ER stress in hepatocyte lipoapoptosis remain largely unclear.In this study, we showed that PA and tunicamycin (Tun), a classic ER stress inducer, resulted in differential activation of ERstress pathways. Our data revealed that PA inducedchronic and persistent ER stress response, but Tuninduced acute and (...) transientER stress response. (shrink)

In a recent paper, Max Deutsch argues that there is no “qua problem” for purely causal theories of reference, according to which the extensions of some expressions are grounded in causal relations to members of their extensions during dubbing acts. The qua problem is the difficulty in specifying the facts in virtue of which the reference of “elephant” is grounded by causal contact with something _qua_ elephant and not _qua_ its other properties. If no such specification can be given, reference (...) remains unacceptably indeterminate. This has led many to abandon purely causal reference grounding. Deutsch’s argument for the dissolution of the problem goes as follows: we usually agree that an event can cause its effect _qua_ some of its properties and not _qua_ others. For example, a hot acidic solution causes a glass beaker to break due to its heat and not due to its acidity. Given this assumption, we can simply say that an event caused a dubbing act _qua_ the causally relevant property and not _qua_ the causally irrelevant properties, thus grounding the reference of the term; the qua problem has vanished. I will argue that causal mechanisms, and in particular the facts about causal relevance appealed to by Deutsch, are insufficient to dissolve the qua problem. It is not generally the case that a _unique_ property is causally relevant in purely physical cases of causation; but this is precisely what is required to avoid the referential indeterminacy highlighted by the qua problem. I will demonstrate that if we rely on causal relevance to dissolve the qua problem, there is no way to respect the uniqueness requirement: there are too many properties that are causally relevant to the occurrence of any single dubbing act, including the intentional states of the dubber. (shrink)

The chemical characterization of the substance responsible for the phenomenon of “transformation” of pneumococci was presented in the now famous 1944 paper by Avery, MacLeod, and McCarty. Reception of this work was mixed. Although interpreting their results as evidence that deoxyribonucleic acid (DNA) is the molecule responsible for genetic changes was, at the time, controversial, this paper has been retrospectively celebrated as providing such evidence. The mixed and changing assessment of the evidence presented in the paper was due to (...) the work’s interpretive flexibility – the evidence was interpreted in various ways, and such interpretations were justified given the neophytic state of molecular biology and methodological limitations of Avery’s transformation studies. I argue that the changing context in which the evidence presented by Avery’s group was interpreted partly explains the vicissitudes of the assessments of the evidence. Two less compelling explanations of the reception are a myth-making account and an appeal to the wartime historical context of its publication. (shrink)

The Protein Ontology (PRO; http://proconsortium.org) formally defines protein entities and explicitly represents their major forms and interrelations. Protein entities represented in PRO corresponding to single amino acid chains are categorized by level of specificity into family, gene, sequence and modification metaclasses, and there is a separate metaclass for protein complexes. All metaclasses also have organism-specific derivatives. PRO complements established sequence databases such as UniProtKB, and interoperates with other biomedical and biological ontologies such as the Gene Ontology (GO). PRO relates (...) to UniProtKB in that PRO’s organism-specific classes of proteins encoded by a specific gene correspond to entities documented in UniProtKB entries. PRO relates to the GO in that PRO’s representations of organism-specific protein complexes are subclasses of the organism-agnostic protein complex terms in the GO Cellular Component Ontology. The past few years have seen growth and changes to the PRO, as well as new points of access to the data and new applications of PRO in immunology and proteomics. Here we describe some of these developments. (shrink)

Midazolam, a benzodiazepine medication, is used for sedation during diagnostic and therapeutic medical procedures. Insufficient doses of sedatives, including midazolam, can result in patient anxiety and awareness during the procedure. Several brands of midazolam are available in the Libyan market. This study aims to identify and estimate the medication content of intravenous midazolam in various marketed products using different analytical methods. Product identity was confirmed using Infrared methods (IR) and retention times of High-Performance Liquid Chromatographic methods (HPLC). Quantification was performed (...) using a rapid reverse-phase HPLC method. Chromatographic analysis was conducted on a C18 column (250 mm×3.3 mm I.D., 5.0 μm particle size) with a mobile phase comprising acetonitrile, methanol, and 0.065 M ammonium acetate buffer (50: 20: 30, v/v/v), adjusted to a pH of 5.5±0.02 with orthophosphoric acid, at a flow rate of 1.0 ml/min. Ultraviolet (UV) detection was set at 220 nm. The identification results met British Pharmacopeia (BP) standards. However, the midazolam content in the Tunisian brand was shallow compared to the products from Germany and Switzerland. Thus, post-marketing testing is essential to assess the quality of critical drugs like midazolam, and further investigations, including clinical evaluations and regulatory follow-up, are necessary. (shrink)

continent. 1.1 : 3-13. / 0/ – Introduction I want to propose, as a trajectory into the philosophically weird, an absurd theoretical claim and pursue it, or perhaps more accurately, construct it as I point to it, collecting the ground work behind me like the Perpetual Train from China Mieville's Iron Council which puts down track as it moves reclaiming it along the way. The strange trajectory is the following: Kant's critical philosophy and much of continental philosophy which has followed, (...) has been a defense against horror and madness. Kant's prohibition on speculative metaphysics such as dogmatic metaphysics and transcendental realism, on thinking beyond the imposition of transcendental and moral constraints, has been challenged by numerous figures proceeding him. One of the more interesting critiques of Kant comes from the mad black Deleuzianism of Nick Land stating, “Kant’s critical philosophy is the most elaborate fit of panic in the history of the Earth.” And while Alain Badiou would certainly be opposed to the libidinal investments of Land's Deleuzo-Guattarian thought, he is likewise critical of Kant's normative thought-bureaucracies: Kant is the one author for whom I cannot feel any kinship. Everything in him exasperates me, above all his legalism—always asking Quid Juris? Or ‘Haven’t you crossed the limit?’—combined, as in today’s United States, with a religiosity that is all the more dismal in that it is both omnipresent and vague. The critical machinery he set up has enduringly poisoned philosophy, while giving great succour to the academy, which loves nothing more than to rap the knuckles of the overambitious [….] That is how I understand the truth of Monique David-Menard’s reflections on the properly psychotic origins of Kantianism. I am persuaded that the whole of the critical enterprise is set up to to shield against the tempting symptom represented by the seer Swedenborg, or against ‘diseases of the head’, as Kant puts it. An entire nexus of the limits of reason and philosophy are set up here, namely that the critical philosophy not only defends thought from madness, philosophy from madness, and philosophy from itself, but that philosophy following the advent of the critical enterprise philosophy becomes auto-vampiric; feeding on itself to support the academy. Following Francois Laruelle's non-philosophical indictment of philosophy, we could go one step further and say that philosophy operates on the material of what is philosophizable and not the material of the external world. [1] Beyond this, the Kantian scheme of nestling human thinking between our limited empirical powers and transcendental guarantees of categorical coherence, forms of thinking which stretch beyond either appear illegitimate, thereby liquefying both pre-critical metaphysics and the ravings of the mad in the same critical acid. In rejecting the Kantian apparatus we are left with two entities – an unsure relation of thought to reality where thought is susceptible to internal and external breakdown and a reality with an uncertain sense of stability. These two strands will be pursued, against the sane-seal of post-Kantian philosophy by engaging the work of weird fiction authors H.P. Lovecraft and Thomas Ligotti. The absolute inhumanism of the formers universe will be used to describe a Shoggothic Materialism while the dream worlds of the latter will articulate the mad speculation of a Ventriloquil Idealism. But first we must address the relation of philosophy to madness as well as philosophy to weird fiction. /1/ – Philosophy and Madness There is nothing that the madness of men invents which is not either nature made manifest or nature restored. Michel Foucault. Madness and Civilization. The moment I doubt whether an event that I recall actually took place, I bring the suspicion of madness upon myself: unless I am uncertain as to whether it was not a mere dream. Arthur Schopenhauer. The World as Will and Idea, Vol. 3. Madness is commonly thought of as moving through several well known cultural-historical shifts from madness as a demonic or otherwise theological force, to rationalization, to medicalization psychiatric and otherwise. Foucault's Madness and Civilization is well known for orientating madness as a form of exclusionary social control which operated by demarcating madness from reason. Yet Foucault points to the possibility of madness as the necessity of nature at least prior to the crushing weight of the church. Kant’s philosophy as a response to madness is grounded by his humanizing of madness itself. As Adrian Johnston points out in the early pages of Time Driven pre-Kantian madness meant humans were seized by demonic or angelic forces whereas Kantian madness became one of being too human. Madness becomes internalized, the external demonic forces become flaws of the individual mind. Foucault argues that, while madness is de-demonized it is also dehumanized during the Renaissance, as madmen become creatures neither diabolic nor totally human reduced to the zero degree of humanity. It is immediately clear why for Kant, speculative metaphysics must be curbed – with the problem of internal madness and without the external safeguards of transcendental conditions, there is nothing to formally separate the speculative capacities for metaphysical diagnosis from the mad ramblings of the insane mind – both equally fall outside the realm of practicality and quotidian experience. David-Menard's work is particularly useful in diagnosing the relation of thought and madness in Kant's texts. David-Menard argues that in Kant's relatively unknown “An Essay on the Maladies of the Mind” as well as his later discussion of the Seer of Swedenborg, that Kant formulates madness primarily in terms of sensory upheaval or other hallucinatory theaters. She writes: “madness is an organization of thought. It is made possible by the ambiguity of the normal relation between the imaginary and the perceived, whether this pertains to the order of sensation or to the relations between our ideas” Kant's fascination with the Seer forces Kant between the pincers of “aesthetic reconciliation” – namely melancholic withdrawal – and “a philosophical invention” – namely the critical project. Deleuze and Guattari's schizoanalysis is a combination and reversal of Kant's split, where an aesthetic over engagement with the world entails prolific conceptual invention. Their embrace of madness, however, is of course itself conceptual despite all their rhizomatic maneuvers. Though they move with the energy of madness, Deleuze and Guattari save the capacity of thought from the fangs of insanity by imbuing materiality itself with the capacity for thought. Or, as Ray Brassier puts it, “Deleuze insists, it is necessary to absolutize the immanence of this world in such a way as to dissolve the transcendent disjunction between things as we know them and as they are in themselves”. That is, whereas Kant relied on the faculty of judgment to divide representation from objectivity Deleuze attempts to flatten the whole economy beneath the juggernaut of ontological univocity. Speculation, as a particularly useful form of madness, might fall close to Deleuze and Guattari’s shaping of philosophy into a concept producing machine but is different in that it is potentially self destructive – less reliant on the stability of its own concepts and more adherent to exposing a particular horrifying swath of reality. Speculative madness is always a potential disaster in that it acknowledges little more than its own speculative power with the hope that the gibbering of at least a handful of hysterical brains will be useful. Pre-critical metaphysics amounts to madness, though this may be because the world itself is mad while new attempts at speculative metaphysics, at post-Kantian pre-critical metaphysics, are well aware of our own madness. Without the sobriety of the principle of sufficient reason we have a world of neon madness: “we would have to conceive what our life would be if all the movements of the earth, all the noises of the earth, all the smells, the tastes, all the light – of the earth and elsewhere, came to us in a moment, in an instant – like an atrocious screaming tumult of things”. Speculative thought may be participatory in the screaming tumult of the world or, worse yet, may produce its spectral double. Against theology or reason or simply commonsense, the speculative becomes heretical. Speculation, as the cognitive extension of the horrorific sublime should be met with melancholic detachment. Whereas Kant's theoretical invention, or productivity of thought, is self -sabotaging, since the advent of the critical project is a productivity of thought which then delimits the engine of thought at large either in dogmatic gestures or non-systematizable empirical wondrousness. The former is celebrated by the fiction of Thomas Ligotti whereas the latter is espoused by the tales of H.P. Lovecraft. /2/ – Weird Fiction and Philosophy. Supernatural horror, in all its eerie constructions, enables a reader to taste treats inconsistent with his personal welfare. Thomas Ligotti Songs of a Dead Dreamer. I choose weird stories because they suit my inclination best—one of my strongest and most persistent wishes being to achieve,momentarily, the illusion of some strange suspension or violation of the galling limitations of time, space, and natural law which forever imprison us and frustrate our curiosity about the infinite cosmic spaces beyond the radius of our sight and analysis H.P. Lovecraft. “Notes on Writing Weird Fiction” Lovecraft states that his creation of a story is to suspend natural law yet, at the same time, he indexes the tenuousness of such laws, suggesting the vast possibilities of the cosmic. The tension that Lovecraft sets up between his own fictions and the universe or nature is reproduced within his fictions in the common theme of the unreliable narrator; unreliable precisely because they are either mad or what they have witnessed questions the bounds of material reality. In “The Call of Cthulhu” Lovecraft writes: The most merciful thing in the world, I think, is the inability of the human mind to correlate all its contents. We live on a placid island of ignorance in the midst of black seas of infinity, and it was not meant that we should voyage far. The sciences, each straining in its own direction, have hitherto harmed us little; but some day the piecing together of dissociated knowledge will open up such terrifying vistas of reality, and of our frightful position therein, that we shall either go mad from the revelation or flee from the deadly light into the peace and safety of a new dark age. Despite Lovecraft's invocations of illusion, he is not claiming that his fantastic creations such as the Old Ones are supernatural but, following Joshi, are only ever supernormal. One can immediately see that instead of nullifying realism Lovecraft in fact opens up the real to an unbearable degree. In various letters and non-fictional statements Lovecraft espoused strictly materialist tenets, ones which he borrowed from Hugh Elliot namely the uniformity of law, the denial of teleology and the denial of non-material existence. Lovecraft seeks to explore the possibilities of such a universe by piling horror upon horror until the fragile brain which attempts to grasp it fractures. This may be why philosophy has largely ignored weird fiction – while Deleuze and Guattari mark the turn towards weird fiction and Lovecraft in particular, with the precursors to speculative realism as well as contemporary related thinkers have begun to view Lovecraft as making philosophical contributions. Lovecraft's own relation to philosophy is largely critical while celebrating Nietzsche and Schopenhauer. This relationship of Lovecraft to philosophy and philosophy to Lovecraft is coupled with Lovecraft's habit of mercilessly destroying the philosopher and the figure of the academic more generally in his work, a destruction which is both an epistemological destruction and an ontological destruction. Thomas Ligotti's weird fiction which he has designated as a kind of “confrontational escapism” might be best described in the following quote from one of his shortstories, “The human phenomenon is but the sum of densely coiled layers of illusion each of which winds itself on the supreme insanity. That there are persons of any kind when all there can be is mindless mirrors laughing and screaming as they parade about in an endless dream”. Whereas Lovecraft's weirdness draws predominantly from the abyssal depths of the uncharted universe, Ligotti's existential horror focuses on the awful proliferation of meaningless surfaces that is, the banal and every day function of representation. In an interview, Ligotti states: We don't even know what the world is like except through our sense organs, which are provably inadequate. It's no less the case with our brains. Our whole lives are motored along by forces we cannot know and perceptions that are faulty. We sometimes hear people say that they're not feeling themselves. Well, who or what do they feel like then? This is not to say that Ligotti sees nothing beneath the surface but that there is only darkness or blackness behind it, whether that surface is on the cosmological level or the personal. By addressing the implicit and explicit philosophical issues in Ligotti's work we will see that his nightmarish take on reality is a form of malevolent idealism, an idealism which is grounded in a real, albeit dark and obscure materiality. If Ligotti's horrors ultimately circle around mad perceptions which degrade the subject, it takes aim at the vast majority of the focus of continental philosophy. While Lovecraft's acidic materialism clearly assaults any romantic concept of being from the outside, Ligotti attacks consciousness from the inside: Just a little doubt slipped into the mind, a little trickle of suspicion in the bloodstream, and all those eyes of ours, one by one, open up to the world and see its horror [...] Not even the solar brilliance of a summer day will harbor you from horror. For horror eats the light and digests it into darkness. Clearly, the weird fiction of Lovecraft and Ligotti amount to a anti-anthrocentric onslaught against the ramparts of correlationist continental philosophy. /3/ – Shoggothic Materialism or the Formless Formless protoplasm able to mock and reflect all forms and organs and processes—viscous agglutinations of bubbling cells—rubbery fifteen-foot spheroids infinitely plastic and ductile—slaves of suggestion, builders of cities—more and more sullen, more and more intelligent, more and more amphibious, more and more imitative—Great God! What madness made even those blasphemous Old Ones willing to use and to carve such things? H.P. Lovecraft. “At the Mountains of Madness” On the other hand, affirming that the universe resembles nothing and is only formless amounts to saying that the universe is something like a spider or spit. Georges Bataille. “Formless”. The Shoggoths feature most prominently in H.P. Lovecraft's shortstory “At the Mountains of Madness” where they are described in the following manner: It was a terrible, indescribable thing vaster than any subway train – a shapeless congeries of protoplasmic bubbles, faintly self -luminous, and with myriads of temporary eyes forming and un-forming as pustules of greenish light all over the tunnel-filling front that bore down upon us, crushing the frantic penguins and slithering over the glistening floor that it and its kind had swept so evilly free of all litter. The term is a litmus test for materialism itself as the Shoggoth is an amorphous creature. The Shoggoths were living digging machines bio engineered by the Elder Things, and their protoplasmic bodies being formed into various tools by their hypnotic powers. The Shoggoths eventually became self aware and rose up against their masters in an ultimately failed rebellion. After the Elder Ones retreated into the oceans leaving the Shoggoths to roam the frozen wastes of the Antarctic. The onto-genesis of the Shoggoths and their gross materiality, index the horrifyingly deep time of the earth a concept near and dear to Lovecraft's formulation of horror as well as the fear of intelligences far beyond, and far before, the ascent of humankind on earth and elsewhere. The sickly amorphous nature of the Shoggoths invade materialism at large, where while materiality is unmistakably real ie not discursive, psychological, or otherwise overly subjectivist, it questions the relation of materialism to life. As Eugene Thacker writes: The Shoggoths or Elder Things do not even share the same reality with the human beings who encounter them—and yet this encounter takes place, though in a strange no-place that is neither quite that of the phenomenal world of the human subject or the noumenal world of an external reality. Amorphous yet definitively material beings are a constant in Lovecraft's tales. In his tale “The Dream-Quest of Unknown Kadatth” Lovecraft describes Azathoth as, “that shocking final peril which gibbers unmentionably outside the ordered universe,” that, “last amorphous blight of nethermost confusion which blashphemes and bubbles at the centre of all infinity,” who, “gnaws hungrily in inconceivable, unlighted chambers beyond time”. Azathoth's name may have multiple origins but the most striking is the alchemy term azoth which is both a cohesive agent and a acidic creation pointing back to the generative and the decayed. The indistinction of generation and degradation materially mirrors the blur between the natural and the unnatural as well as life and non-life. Lovecraft speaks of the tension between the natural and the unnatural is his short story “The Unnameable.” He writes, “if the psychic emanations of human creatures be grotesque distortions, what coherent representation could express or portray so gibbous and infamous a nebulousity as the spectre of a malign, chaotic perversion, itself a morbid blasphemy against Nature?”. Lovecraft explores exactly the tension outlined at the beginning of this chapter, between life and thought. At the end of his short tale Lovecraft compounds the problem as the unnameable is described as “a gelatin—a slime—yet it had shapes, a thousand shapes of horror beyond all memory”. Deleuze suggests that becoming-animal is operative throughout Lovecraft's work, where narrators feel themselves reeling at their becoming non-human or of being the anomalous or of becoming atomized. Following Eugene Thacker however, it may be far more accurate to say that Lovecraft's tales exhibit not a becoming-animal but a becoming-creature. Where the monstrous breaks the purportedly fixed laws of nature, the creature is far more ontologically ambiguous. The nameless thing is an altogether different horizon for thought. The creature is either less than animal or more than animal – its becoming is too strange for animal categories and indexes the slow march of thought towards the bizarre. This strangeness is, as aways, some indefinite swirling in the category of immanence and becoming. Bataille begins “The Labyrinth” with the assertion that being, to continue to be, is becoming. More becoming means more being hence the assertion that Bataille's barking dog is more than the sponge. This would mean that the Shoggotth is altogether too much being, too much material in the materialism. Bataille suggests that there is an immanence between the eater and the eaten, across the species and never within them. That is, despite the chaotic storm of immanence there must remain some capacity to distinguish the gradients of becoming without reliance upon, or at least total dependence upon, the powers of intellection to parse the universe into recognizable bits, properly digestible factoids. That is, if we undo Deleuze's aforementioned valorization of sense which, for his variation of materialism, performed the work of the transcendental, but refuse to reinstate Kant's transcendental disjunction between thing and appearance, then it must be a quality of becoming-as-being itself which can account for the discernible nature of things by sense. In an interview with Peter Gratton, Jane Bennett formulates the problem thusly: What is this strange systematicity proper to a world of Becoming? What, for example, initiates this congealing that will undo itself? Is it possible to identify phases within this formativity, plateaus of differentiation? If so, do the phases/plateaus follow a temporal sequence? Or, does the process of formation inside Becoming require us to theorize a non-chronological kind of time? I think that your student’s question: “How can we account for something like iterable structures in an assemblage theory?” is exactly the right question. Philosophy has erred too far on the side of the subject in the subject-object relation and has furthermore, lost the very weirdness of the non-human. Beyond this, the madness of thought need not override. /4/ - Ventriloquial Idealism or the Externality of Thought My aim is the opposite of Lovecraft's. He had an appreciation for natural scenery on earth and wanted to reach beyond the visible in the universe. I have no appreciation for natural scenery and want the objective universe to be a reflection of a character. Thomas Ligotti. “Devotees of Decay and Desolation.” Unless life is a dream, nothing makes sense. For as a reality, it is a rank failure [….] Horror is more real than we are. Thomas Ligotti. “Professor Nobody's Little Lectures on Supernatural Horror”. Thomas Ligotti's tales are rife with mannequins, puppets, and other brainless entities which of replace the valorized subject of philosophy – that of the free thinking human being. His tales such as “The Dream of the Manikin” aim to destroy the rootedness of consciousness. James Trafford has connected the anti-egoism of Ligotti to Thomas Metzinger – where the self is at best an illusion and we plead desperately for someone else to acknowledge that we are real. Trafford has stated it thus, “Life is played out as an inescapable puppet show, an endless dream in which the puppets are generally unaware that they are trapped within a mesmeric dance of whose mechanisms they know nothing and over which they have no control”. An absolute materialism, for Ligotti, implies an alienation of the idea which leads to a ventriloquil idealism. As Ligotti notes in an interview, “the fiasco and nightmare of existence, the particular fiasco and nightmare of human existence, the sense that people are puppets of powers they cannot comprehend, etc.” And then further elaborates that,“[a]ssuming that anything has to exist, my perfect world would be one in which everyone has experienced the annulment of his or her ego. That is, our consciousness of ourselves as unique individuals would entirely disappear”. The externality of the idea leads to the unfortunate consequence of consciousness eating at itself through horror which, for Ligotti, is more real than reality and goes beyond horror-as-affect. Beyond this, taking together with the unreality of life and the ventriloquizing of subjectivity, Ligotti's thought becomes an idealism in which thought itself is alien and ultimately horrifying. The role of human thought and the relation of non-relation of horror to thought is not completely clear in Ligotti's The Conspiracy Against the Human Race. Ligotti argues in his The Conspiracy Against the Human Race,that the advent of thought is a mistake of nature and that horror is being in the sense that horror results from knowing too much. Yet, at the same time, Ligotti seems to suggest that thought separates us from nature whereas, for Lovecraft, thought is far less privileged – mind is just another manifestation of the vital principal, it is just another materialization of energy. In his brilliant “Prospects for Post-Copernican Dogmatism” Iain Grant rallies against the negative definition of dogmatism and the transcendental, and suggests that negatively defining both over-focuses on conditions of access and subjectivism at the expense of the real or nature. With Schelling, who is Grant's champion against the subjectivist bastions of both Fichte and Kant, Ligotti's idealism could be taken as a transcendental realism following from an ontological realism. Yet the transcendental status of Ligotti's thought move towards a treatment of the transcendental which may threaten to leave beyond its realist ground. Ligotti states: Belief in the supernatural is only superstition. That said, a sense of the supernatural, as Conrad evidenced in Heart of Darkness, must be admitted if one's inclination is to go to the limits of horror. It is the sense of what should not be- the sense of being ravaged by the impossible. Phenomenally speaking, the super-natural may be regarded as the metaphysical counterpart of insanity, a transcendental correlative of a mind that has been driven mad. Again, Ligotti equates madness with thought, qualifying both as supernatural while remaining less emphatic about the metaphysical dimensions of horror. The question becomes one of how exactly the hallucinatory realm of the ideal relates to the black churning matter of Lovecraft's chaos of elementary particles. In his tale “I Have a Special Plan for This World” Ligotti formulates thus: A: There is no grand scheme of things. B: If there were a grand scheme of things, the fact – the fact – that we are not equipped to perceive it, either by natural or supernatural means, is a nightmarish obscenity. C: The very notion of a grand scheme of things is a nightmarish obscenity. Here Ligotti is not discounting metaphysics but implying that if it does exist the fact that we are phenomenologically ill-equipped to perceive that it is nightmarish. For Ligotti, nightmare and horror occur within the circuit of consciousness whereas for Lovecraft the relation between reality and mind is less productive on the side of mind. It is easier to ascertain how the Kantian philosophy is a defense against the diseases of the head as Kant armors his critical enterprise from too much of the world and too much of the mind. The weird fiction of both Lovecraft and Ligotti demonstrates that there is too much of both feeding into one another in a way that corrodes the Kantian schema throughly, breaking it down into a dead but still ontologically potentiated nigredo. The haunting, terrifying fact of Ligotti's idealism is that the transcendental motion which brought thought to matter, while throughly material and naturalized, brings with it the horror that thought cannot be undone without ending the material that bears it either locally or completely. Thought comes from an elsewhere and an elsewhen being-in-thought. The unthinkable outside thought is as maddening as the unthought engine of thought itself within thought which doesn't exist except for the mind, the rotting décor of the brain. /5/ - Hyperstitional Transcendental Paranoia or Self -Expelled Thought Weird fiction has been given some direct treatment in philosophy in the mad black Deleuzianism of Nick Land. Nick Land along with others in the 1990s created the Cyber Culture Research Unit as well as the research group Hyperstition. The now defunct hyperstitional website, an outgrowth of the Cyber Culture Research Unit, defined hyperstition in the following fourfold: 1-Element of effective culture that makes itself real. 2-Fictional quantity functional as a time-traveling device. 3-Coincidence intensifier. 4-Call to the Old Ones. The distinctively Lovecraftian character of hyperstition is hard to miss as is its Deleuzo-Guattarian roots. In the opening pages of A Thousand Plateaus Deleuze and Guattari write, “We have been criticized for over-quoting literary authors. But when one writes, the only question is which other machine the literary machine can be plugged into”. The indisinction of literature and philosophy mirrors the mess of being and knowing as post-correlationist philosophy, where philosophy tries to make itself real where literature, especially the weird, aims itself at the brain-circuit of horror. The texts of both Lovecraft and Ligotti work through horror as epistemological plasticity meeting with proximity as well as the deep time of Lovecraft and the glacially slow time of paranoia in Ligotti. Against Deleuze, and following Brassier, we cannot allow the time of consciousness, the Bergsonian time of the duree, to override natural time, but instead acknowledge that it is an unfortunate fact of existence as a thinking being. Horror-time, the time of consciousness, with all its punctuated moments and drawn out terrors, cannot compare to the deep time of non-existence both in the unreachable past and the unknown future. The crystalline cogs of Kant's account of experience as the leading light for the possibility of metaphysics must be throughly obliterated. His gloss of experience in Prolegomena to any Future Metaphysics could not be more sterile: Experience consists of intuitions, which belong to the sensibility, and of judgments, which are entirely a work of the understanding. But the judgments which the understanding makes entirely out of sensuous intuitions are far from being judgments of experience. For in the one case the judgment connects only the perceptions as they are given in sensuous intuition [....] Experience consists in the synthetic connection of appearances in consciousness, so far as this connection is necessary. Here it is difficult to dismiss the queasiness that Kant's legalism induces upon sight for both Badiou and David-Menard. Kant's thought becomes, as Foucault says when reflecting on Sade's text in relation to nature, “the savage abolition of itself”. For Badiou, Kant's philosophy simply closes off too much of the outside, freezing the world of thought in an all too limited formalism. Critical philosophy is simply the systematized quarantine on future thinking, on thinking which would threaten the formalism which artificially grants thought its own coherency in the face of madness. Even the becoming-mad of Deleuze, while escaping the rumbling ground, makes grounds for itself, mad grounds but grounds which are thinkable in their affect. The field of effects allows for Deleuze's aesthetic and radical empiricism, in which effects and/or occasions make up the material of the world to be thought as a chaosmosis of simulacra. Given a critique of an empiricism of aesthetics, of the image, it may be difficult to justify an attack on Kantian formalism with the madness of literature, which does not aim to make itself real but which we may attempt to make real. That is, how do Lovecraft's and Ligotti's materials, as materials for philosophy to work on, differ from either the operative formalisms of Kant or the implicitly formalized images of Deleuzian empiricism? It is simply that such texts do not aim to make themselves real, and make claims to the real which are more alien to us than familiar, which is why their horror is immediately more trustworthy. This is the madness which Blanchot discusses in The Infinite Conversation through Cervantes and his knight – the madness of book-life, of the perverse unity of literature and life a discussion which culminates in the discussion of one of the weird's masters, that of Kafka. The text is the knowing of madness, since madness, in its moment of becoming-more-mad, cannot be frozen in place but by the solidifications of externalizing production. This is why Foucault ends his famous study with works of art. Furthermore extilligence, the ability to export the products of our maligned brains, is the companion of the attempts to export, or discover the possibility of intelligences outside of our heads, in order for philosophy to survive the solar catastrophe. To borrow again from Deleuze, writing is inseparable from becoming. The mistake is to believe that madness is reabsorbed by extilligence, by great works, or that it could be exorcised by the expelling of thought into the inorganic or differently organic. Going out of our heads does not guarantee we will no longer mean we cannot still go out of our minds. This is simply because of the outside, of matter, or force, or energy, or thing-in-itself, or Schopenhauerian Will. In Lovecraft’s “The Music of Erich Zahn” an “impoverished student of metaphysics” becomes intrigued by strange viol music coming from above his room. After meeting the musician the student discovers that each night he plays frantic music at a window in order to keep some horridness at bay, some “impenetrable darkness with chaos and pandemonium”. The aesthetic defenses provided by the well trained brain can bear the hex of matter for so long, the specter of unalterability within it which too many minds obliterate, collapsing everything before the thought of thought as thinkable or at least noetically mutable on our own terms. Transcendental paranoia is the concurrent nightmare and promise of Paul Humphrey's work, of being literally out of our minds. It is the gothic counterpart of thinking non-conceptually but also of thinking never belonging to any instance of purportedly solid being. As Bataille stated, “At the boundary of that which escapes cohesion, he who reflects within cohesion realizes there is no longer any room for him” Thought is immaterial only to the degree that it is inhuman, it is a power that tries, always with failure, to ascertain its own genesis. Philosophy, if it can truly return to the great outdoors, if it can leave behind the dead loop of the human skull, must recognize not only the non-priority of human thought, but that thought never belongs to the brain that thinks it, thought comes from somewhere else. To return to the train image from the beginning “a locomotive rolling on the surface of the earth is the image of continuous metamorphosis” this is the problem of thought, and of thinking thought, of being no longer able to isolate thought, with only a thought-formed structure. [1] One of the central tenets of Francois Laruelle's non-philosophy is that philosophy has traditionally operated on material already presupposed as thinkable instead of trying to think the real in itself. Philosophy, according to Laruelle, remains fixated on transcendental synthesis which shatters immanence into an empirical datum and an a prori factum which are then fused by a third thing such as the ego. For a critical account of Laruelle's non-philosophy see Ray Brassier's Nihil Unbound. (shrink)

Justicia carnea, a plant rich in bioactive compounds, has traditionally been used as a haemoglobin booster by herbal practitioners in rural areas of Edo State of Nigeria. In this study, the methanol leaves extract of Justicia carnea was investigated for its antisickling potential in hemoglobin SS (HbSS) in-vitro by sodium metabisulphite assay and characterized by Gas Chromatography-Mass Spectrometry (GC-MS) and High-Performance Liquid Chromatography (HPLC). Terpenoids, saponins, glycosides, phenolics, flavonoids and alkaloids were present except tannins. Photomicrograph examinations revealed a reduction of (...) sickle cells with a percentage decrease from 37.50%, and 22.22% down to 3.85% with 100 mg/mL crude extract of Justicia carnea at three durations, respectively. Detected compounds from Gas Chromatography-Mass Spectrometry included hexadecanoic acid methyl ester (Retention time (Rt): 21.46, 05.99%) and 9,12-octadecadienoic acid, methyl ester (Rt: 23.567, 02.59%) while the major constituent was phytol (Rt: 23.741, 67.28%). While kaempferol (Rt: 17.23, 16.72%) was the major component from High-Performance Liquid Chromatography quantification among resveratrol (Rt: 3.7, 13.85%), gallic acid (Rt: 5.88, 3.55%), Justicinol (Rt: 11.85, 01.34%) and phytic acid (Rt 5.06, 01.43 %). These compounds have been cited as physiological agents that reduce inflammation, and oxidative stress and potentially prolong the lifespan of cells across species. The antisickling results from this study corroborate and support the traditional use of the plant in treating patients with sickle cell anemia. (shrink)

This paper addresses two related topics: 1. The disanalogies between elective cosmetic practices and sex reassignment surgery. Why does it seem necessary for me – an aging professional woman – to ignore the blandishments of hairdressers wielding dyes and dermatologists wielding acids and scalpels? Why does it not seem equally necessary for a transgendered person to repudiate sex reassignment procedures? 2. The role of the body in identity and agency. How do phenomenological insights regarding the constitution of selfhood in relation (...) to the interplay between the body image and corporeal know-how contribute to an account of the agency of transgendered individuals? Studying several paintings by contemporary feminist artist Jenny Saville has advanced my thinking on these topics. Saville’s imagery is an invaluable aid to reflection on these issues because she uses her painterly technique, which critics often dub “virtuoso,” to represent lived human bodies. In her work, viewers encounter representations of subjectivized, agentic corporeity, as distinct from inert, objectified flesh. Moreover, her sympathetic engagement with nonconformist, devalued bodies helps to reconfigure the standard gestalts of the human body that viewers typically carry with them and thus to convert fear and/or disgust into appreciation and understanding. In this paper, I consider three of Saville’s paintings. Plan, Saville’s self-portrait as a nude female whose body has been prepped for liposuction, conveys the pathos of this procedure. Matrix is a nude portrait of self-described “gender variant visual artist” Del LaGrace Volcano. In the words of one critic Saville’s depiction of Volcano’s nude intersexed body “restores beauty to the primitive [female] genital organ.” Passage, another nude portrait of an intersexed individual, is an image of vibrant sexuality despite the presumptively jarring juxtaposition of breasts and a penis. I argue that conceiving the agentic subject as a rational deliberative capability that uses a conjoined body as the instrument of its will makes it impossible to theorize the agency of transgendered people. In contrast, when agentic subjects are understood as embodied subjects and embodiment is understood as a dimension of practical intelligence, the agency of transgendered individuals is intelligible. (shrink)

The present thesis explores some metaphysical issues concerning biochemical kinds and the relations between chemical and biological properties and phenomena. The main result of this thesis is that there is something sui generis about biochemical kinds. This result is motivated by two theoretical steps. The first is characterising biochemical functions as weakly emergent from the chemical structure [Chapter 3, Chapter 6]. The second is via an account for which biochemical kinds are natural categories [Chapter 4, Chapter 7]. The thesis comprises (...) four parts. Part I [Chapter 1, Chapter 2] aims to offer the methodological and conceptual tools that underpin this research. Chapter 1 presents the debate on the unity of science and the motivation of the research. Chapter 2 presents the account of natural kinds that will be used throughout the thesis. Part II [Chapter 3, Chapter 4] offers a detailed metaphysical analysis of the molecular gene. Chapter 3 argues that molecular genes are weakly emergent from nucleic acids. Chapter 4 argues that the category "molecular gene" can be deemed a natural kind, following the account presented in Chapter 2. Part III [Chapter 5, Chapter 6, Chapter 7] explores some of the themes related to biochemical kinds and generalises some of the results from Part II. Chapter 5 considers biochemical functions and how functional attribution should be interpreted for biochemical molecules. Chapter 6 considers the relation between biochemical functions and structure, spelt in terms of weak emergence and explores unity in biochemistry. Chapter 7 considers the topic of biochemical kinds per se and argues that biochemical kinds are natural categories. Part IV [Chapter 8] elucidates the main outcome and the implications that this research can have for future discussion in the philosophy and metaphysics of biochemistry and the unity of science. (shrink)

Intermediary metabolism molecules are orchestrated into logical pathways stemming from history (L-amino acids, D-sugars) and dynamic constraints (hydrolysis of pyrophosphate or amide groups is the driving force of anabolism). Beside essential metabolites, numerous variants derive from programmed or accidental changes. Broken down, variants enter standard pathways, producing further variants. Macromolecule modification alters enzyme reactions specificity. Metabolism conform thermodynamic laws, precluding strict accuracy. Hence, for each regular pathway, a wealth of variants inputs and produces metabolites that are similar to but not (...) the exact replicas of core metabolites. As corollary, a shadow, paralogous metabolism, is associated to standard metabolism. We focus on a logic of paralogous metabolism based on diversion of the core metabolic mimics into pathways where they are modified to minimize their input in the core pathways where they create havoc. We propose that a significant proportion of paralogues of well-characterized enzymes have evolved as the natural way to cope with paralogous metabolites. A second type of denouement uses a process where protecting/deprotecting unwanted metabolites - conceptually similar to the procedure used in the laboratory of an organic chemist - is used to enter a completely new catabolic pathway. (shrink)

R E S U M O Diante do grande consumo de carne a nível mundial, bem como a ascensão do vegetarianismo e veganismo, os consumidores de carne, especialmente de carne de grandes animais, estão cada vez mais exigentes quantos aos aspectos sensoriais e características organolépticas e de bem-estar animal cabendo, com isso, ao mercado abastecer o mercado cárneo com produtos de alta qualidade. Deve-se assegurar a qualidade para satisfazer o consumidor. A qualidade da carcaça, assim como a da carne podem (...) ser influenciadas por diversos fatores, entre eles a raça e o tipo ou sistema de alimentação podem possuir maior influência, dependendo do sistema de produção ao qual os animais estão submetidos. A qualidade dos produtos tem adquirido relevância durante as últimas décadas, sendo considerada de distinta forma pelos integrantes da cadeia agroalimentar. Os consumidores, produtores e a indústria possuem distinta importância sobre os parâmetros de qualidade da carne e da carcaça; todavia, todos os integrantes da cadeia cárnea devem assegurar qualidade para um correto e idôneo funcionamento e melhorar sua competitividade. A raça pode influenciar os pesos, rendimentos e conformação da carcaça, entre outras variáveis, como também o pH e a composição de ácidos graxos da carne. Enquanto o manejo nutricional afeta a conformação da carcaça, as características de maciez, cor, composição química e de ácidos graxos. É por esses motivos que nos diferentes sistemas de produção de ovinos os efeitos da raça e da alimentação devem ser considerados para a obtenção de um produto de qualidade que satisfaça as demandas dos consumidores. Palavras-Chaves: Raça, Alimentação, Qualidade, Carne, Ovinos. Effects of breed and the nutritional management about the characteristics of quality carcass and the meat in sheeps A B S T R A C T Given the high consumption of meat at a global level, as well as the rise of vegetarianism and veganism, meat consumers, especially of large animals, are becoming increasingly demanding in terms of sensory aspects, organoleptic characteristics, and animal welfare, requiring the market to supply the meat market with high-quality products. Quality must be ensured to satisfy the consumer. The quality of the carcass, as well as the meat, can be influenced by various factors, including breed and the type or system of feeding, which may have a greater influence depending on the production system to which the animals are subjected. The quality of products has gained importance in recent decades and is considered in different ways by participants in the agri-food chain. Consumers, producers, and the industry each hold distinct importance regarding the parameters of meat and carcass quality; however, all participants in the meat chain must ensure quality for proper and reputable functioning and to enhance competitiveness. The breed can influence carcass weight, yield, and conformation, among other variables, as well as the pH and composition of fatty acids in the meat. While the nutritional management affects carcass conformation, tenderness, color, chemical composition, and fatty acid characteristics. It is for these reasons that in different sheep production systems, the effects of breed and feed must be considered to obtain a quality product that meets consumer demands. Keywords: Breed, Feeding, Quality, Meat, Sheeps. (shrink)

In Jylkkä's (Philosophy and Psychedelics: Frameworks for Exceptional Experience, Bloomsbury Academic, New York, 2022) Mary on Acid: Experiences of unity and the epistemic gap, the author contends that psychedelic experience, by inducing unitary—nondual—experiences of subject–object dissolution, brings to light the epistemic gap between unitary knowledge, constituted by experience, and relational knowledge, distinct from experience. Jylkkä draws a connection between the nondual experience as occasioned through psychedelic usage, and Buddhist contemplative practices. While Jylkkä's attempt to establish a dialogue between analytic (...) philosophy, Buddhism and the science of psychedelics is laudable, we contend that more rigorous attention is required to characterizing nondual experience, the forms of experience occasioned by psychedelic use, and whether they truly constitute parallel to states cultivated through Buddhist practice traditions. While such parallelism may speak to a deeper unification, such a claim requires substantiation to avoid the perennialist eliding of the varied and rich engagement with nonduality across completive traditions. This article highlights the internal tensions that exist surrounding the nature of the nondual as elucidated across Indo-Tibetan traditions, dangers of decontextualizing states induced through culturally embedded contemplative practices including the underrecognized epistemic function of ceremonial ethnomedicine usage in generating Indigenous metaphysics; and the under acknowledged potential of psychedelic substances for attenuating introspective bias in first-person phenomenological inquiry. (shrink)

It is widely understood that protein functions can be exhaustively described in terms of no single parameter, whether this be amino acid sequence or the three-dimensional structure of the underlying protein molecule. This means that a number of different attributes must be used to create an ontology of protein functions. Certainly much of the required information is already stored in databases such as Swiss-Prot, Protein Data Bank, SCOP and MIPS. But the latter have been developed for different purposes and (...) the separate data-structures which they employ are not conducive to the needed data integration. When we attempt to classify the entities in the domain of proteins, we find ourselves faced with a number of cross-cutting principles of classification. Our question here is: how can we bring together these separate taxonomies in order to describe protein functions? Our proposed answer is: via a careful top-level ontological analysis of the relevant principles of classification, combined with a new framework for the simultaneous manipulation of classifications constructed for different purposes. (shrink)

Significant associations have been found between specific human leukocyte antigen (HLA) alleles and organ transplant rejection, autoimmune disease development, and the response to infection. Traditional searches for disease associations have conventionally measured risk associated with the presence of individual HLA alleles. However, given the high level of HLA polymorphism, the pattern of amino acid variability, and the fact that most of the HLA variation occurs at functionally important sites, it may be that a combination of variable amino acid (...) sites shared by several alleles (shared epitopes) are better descriptors of the actual causative genetic variants. Here we describe a novel approach to genetic association analysis in which genes/proteins are broken down into smaller sequence features and then variant types defined for each feature, allowing for independent analysis of disease association with each sequence feature variant type. We have used this approach to analyze a cohort of systemic sclerosis patients and show that a sequence feature composed of specific amino acid residues in peptide binding pockets 4 and 7 of HLA-DRB1 explains much of the molecular determinant of risk for systemic sclerosis. (shrink)

Background: Food-borne outbreaks have been associated with sourcing unsafe food. Therefore, the first preventative strategy should be to source safe food. Even if the sourced food is safe, measures need to be put in place to ensure that it remains safe during the transfer, storage, preparation and serving activities that follow. An understanding of the ship food supply and transfer chain will help to illustrate the points at which the food can become contaminated en route to the point of consumption. (...) Objectives: The study was conducted in selected sea port in the core Niger Delta to assessed the microbiological quality of food served at different ship galley to crew and passengers and compared it to standard. Methods: Samples of food were taken from three (Port Harcourt Area one (PHSP), Warri (WSP) and Koko (KSP)) seaports within the South-South zone for laboratory analysis to uncover food spoilage microorganisms capable of causing disease outbreak among ship which could result to Transborder diseases. Eleven samples of different ready to eat food were collected from the locations, which included cooked rice; fried fish, irish potato porridge, vegetable soup, griki, pepper soup, fried irish potato, salad and bread were collected randomly. The samples were prepared and analyzed using standard procedures. Mean viable counts of aerobic and anaerobic bacteria were determined, ranging from (13×103cfu/g to 78×104 cfu/g) for ready to eat food. Results: Based on the finding KSP I, KSP J and KSP K food samples had the highest bacterial contamination on food while WSP F, WSP G and WSP H food samples had the least with the following isolates Salmonella spp, Nocardia spp, Shigella spp, Listeria spp, Bacillus cereus, Leuconostoc spp, Acinetobacter spp, Acetobacter spp, campylobacter spp, Clostridium spp and Vibrio spp which revealed that the isolates were susceptible to any of these antibiotics Septrin, Chloramphenicol, Gentamycin, Tarvid, Streptomycin, Reflacin, Augumetin, Ceporex, Nalidixic acid, Ampicillin, Ciproflox, Penicillin and Erythromycin. Conclusion: Thus, ships operators and regulatory body are expected to take all practicable measures to ensure that they do not receive unsafe or unsuitable food and maintain adequate food temperature at all time. (shrink)

Over the years, ethylene-diamine-tetra-acetate (EDTA) has been widely used for many purposes. However, there are inadequate phytoassessment studies conducted using EDTA in Vetiver grass. Hence, this study evaluates the phytoassessment (growth performance, accumulation trends, and proficiency of metal uptake) of Vetiver grass, Vetiveria zizanioides (Linn.) Nash in both single and mixed heavy metal (Cd, Pb, Cu, and Zn)—disodium EDTA-enhanced contaminated soil. The plant growth, metal accumulation, and overall efficiency of metal uptake by different plant parts (lower root, upper root, lower (...) tiller, and upper tiller) were thoroughly examined. The relative growth performance, metal tolerance, and phytoassessment of heavy metal in roots and tillers of Vetiver grass were examined. Metals in plants were measured using the flame atomic absorption spectrometry (F-AAS) after acid digestion. The root-tiller (R/T) ratio, biological concentration factor (BCF), biological accumulation coefficient (BAC), tolerance index (TI), translocation factor (TF), and metal uptake efficacy were used to estimate the potential of metal accumulation and translocation in Vetiver grass. All accumulation of heavy metals were significantly higher (p < 0.05) in both lower and upper roots and tillers of Vetiver grass for Cd + Pb + Cu + Zn + EDTA treatments as compared with the control. The single Zn + EDTA treatment accumulated the highest overall total amount of Zn (8068 ± 407 mg/kg) while the highest accumulation for Cu (1977 ± 293 mg/kg) and Pb (1096 ± 75 mg/kg) were recorded in the mixed Cd + Pb + Cu + Zn + EDTA treatment, respectively. Generally, the overall heavy metal accumulation trends of Vetiver grass were in the order of Zn >>> Cu > Pb >> Cd for all treatments. Furthermore, both upper roots and tillers of Vetiver grass recorded high tendency of accumulation for appreciably greater amounts of all heavy metals, regardless of single and/or mixed metal treatments. Thus, Vetiver grass can be recommended as a potential phytoextractor for all types of heavy metals, whereby its tillers will act as the sink for heavy metal accumulation in the presence of EDTA for all treatments. (shrink)

Applying mild methods of preparation, part of the ribosomes of rabbit reticulocytes are found in aggregates (later called polyribosomes) of up to six ribosomal units. Upon treatment with RNA-ase, they desintegrate into single ribosomes. The fast-sedimenting aggregates are found to be more active in protein synthesis in terms of incorporation of radioactive amino acids, whereas the single ribosomes are more receptive to stimulation by the artificial messenger RNA poly-U. The findings indicate that the linkage of ribosomes into aggregates is due (...) to the messenger RNA. They support a tape-reading mechanism of protein synthesis whereby growth of the peptide chain is accompanied by shifting the active site of the ribosome from one coding group of nucleotides of the messenger RNA to the next. (shrink)

Gregor Mendel (1822-1884) was the first to explain that certain 'traits' were inherited in plants from one generation to the next. These would later become known as genes. Frederich Miescher in 1869 analyzed a substance from the nucleus of cells, which he therefore called nuclein. Further study of nuclein revealed that it contained elements like hydrogen, oxygen, nitrogen and phosphorous, with a specific ratio of nitrogen to phosphorous. Then in 1878 Albrecht Kossel determined that nuclein contained nucleic acid, from (...) which he isolated five nucleobases (nitrogen compounds now referred to by the letters C, G, A, T, U representing cytosine, guanine, adenine, thymine, and uracil). It was also discovered that ribose, a sugar was present in the nuclein compound. What Miescher had isolated from the cell nucleus was actually what would latter be identified as DNA (Deoxyribonucleic acid). C. H. Waddington (1905 - 1975) first proposed the term “epigenetics” in 1942 to describe the region between the gene and the whole organism (phenotype) [3]. Today, what is called the epigenome refers to all the chromosomal modifications, DNA modifications, chromatin protein modifications and their complexes. It is the epigenome that determines both the expression of the genes and their inheritance. R. A. Jorgenson reports [4], "Many of these modifications appear to be “programmable” and to be “read out” to influence chromosomal functions." Nobel laureate Barbara McClintock stated this revolutionary proposal more clearly in her Nobel lecture [5], “to determine the extent of knowledge the cell has of itself, and how it utilizes this knowledge in a ‘thoughtful’ manner when challenged.” In 1960 R. A. Brinks suggested that chromosomes possess a paragenetic function in addition to their genetic function [7]. The physical nature of the paragenetic function is characterized by the variety of forms or states of chromatin that can reside at any genetic locus. While the genetic function is stable, the paragenetic function is labile and programmable in ontogeny. It is this latter function that allows organisms to transfer informational macromolecules (RNA and proteins) in a systematic and regulated manner over what is known as the “RNA information superhighway.” Given this capacity, organisms may be able to store information at numerous genetic loci in the form of paragenetic chromatin states, which can be reprogrammed during ontogeny or environmental stress [8]. This reprogrammable system could operate over the whole organism as a storage device, allowing it to make informed ‘decisions' during growth and development, or in response to the environment. Such processing capacity could be considered a form of ‘intelligence,' which also could be passed on to future generations. The study of the flow of information within and between cells and organisms represents the cutting edge of modern biological research. While physical correlates of cognitive behavior in living organisms are being discovered, it does not spell reduction to such correlates. The electronic activity within the physical components of a radio, for example, may be minutely determined, but ultimately it is not merely the electrical activity that produces the intelligent speech that is heard. Only the intelligent person whose voice is being broadcast through the radio can explain that. Without the broadcaster, the radio would sit silently even though fully functional. An organism without its living agency also appears to be devoid of metabolic activity although all the chemical components are fully present. How to connect life to matter will be the ultimate challenge that has to be met. This will prove to be a philosophical problem we hope to address in the near future. (shrink)

When this article was first planned, writing was going to be exclusively about two things - the origin of life and human evolution. But it turned out to be out of the question for the author to restrict himself to these biological and anthropological topics. A proper understanding of them required answering questions like “What is the nature of the universe – the home of life – and how did it originate?”, “How can time travel be removed from fantasy and (...) science fiction, to be made scientific and practical?”, and “How can the proposed young age of genus Homo be made to actually be reasonable – when simply stating it would be solid ground for instant rejection and dismissal?” The result is that the article also talks about subjects like Artificial Intelligence, General Relativity, and cosmology. -/- From where did life originate? God? Evolution? Panspermia? If the tendency of humans and scientists to regard undiscovered science as pseudoscience can be overcome, Einstein gave another alternative to consider when he introduced General Relativity. Time isn’t linear – progressing in a straight line from past to present to future. That assumption ignores Relativity which states that space AND TIME are curved. Where did life and the genetic code come from? Can the answer build AI? -/- The first question can be answered by the section of this article titled SETI, Evolution, and Time which says life (possibly multicellular and intelligent) and the genetic code came from humans acquiring knowledge of these things over the centuries, then applying that knowledge – via terraforming, accumulation of raw materials like amino acids and nucleic acids, genetic engineering - to a time in the past when life didn’t exist. From that origin, life evolved through innumerable mutations and adaptations, with humans once again acquiring knowledge of it in cyclic (nonlinear) time. -/- The second question is answered by saying artificial intelligence (AI) as the product of life is only half of the equation. The other half refers to Relativity’s curved space-time and violation of the notion that time always travels from past to future. We have always lived in an artificially intelligent, non-probabilistic universe where everything in time and space is connected into one thing by quantum entanglement – making the brain and genes products of binary-digit activity or artificial intelligence (life is not merely dependent on biology’s “lock and key” mechanisms but also possesses AI). -/- The earliest documented representative of the genus Homo is Homo habilis, which evolved around 2.8 million years ago. Scientists used to believe there was a straight line from H. habilis to us, Homo sapiens. This article will use the “advanced” waves loved by Physics Nobel laureate Richard Feynman, view the history of science through the lens of Conic Sections applied to Relativity’s curved space-time, and incorporate the necessity of so-called imaginary time * – popularized by Prof. Stephen Hawking. While the evolutionary proposals are more in agreement with this early straight line than with modern theories, Albert Einstein’s General Relativity is used to transform the straight line into a curved line, ultimately concluding that Homo habilis (H. habilis) originated only (and unbelievably, as far as today’s science and technology is concerned) ~250,000 years ago. Other branches and dead ends of Homo – e.g. Neanderthals – are the result of mutations and adaptations, with the resultant modifications to anatomy and physiology. The surprisingly young age of H. habilis allows nearly 200,000 years for habilis, or one of its descendants, to reach Australia … if this country’s indigenous Aboriginal population did, as claimed, reach this “island continent” 60,000 years ago. -/- * The ultraviolet catastrophe, also called the Rayleigh–Jeans catastrophe, is a failure of classical physics to predict observed phenomena: it can be shown that a blackbody - a hypothetical perfect absorber and radiator of energy - would release an infinite amount of energy, contradicting the principles of conservation of energy and indicating that a new model for the behaviour of blackbodies was needed. At the start of the 20th century, physicist Max Planck derived the correct solution by making some strange (for the time) assumptions. In particular, Planck assumed that electromagnetic radiation can only be emitted or absorbed in discrete packets, called quanta. Albert Einstein postulated that Planck's quanta were real physical particles (what we now call photons), not just a mathematical fiction. From there, Einstein developed his explanation of the photoelectric effect (when quanta or photons of light shine on certain metals, electrons are released and can form an electric current). So it appears entirely possible that another supposed mathematical trickery (imaginary time and the y-axis of Wick rotation) will find practical application in the future. -/- The article includes mathematical references to cosmology (spoiler alert – you’ll read about things like Vector-Tensor-Scalar Geometry, topology, the “eternal present”, Einstein’s Unified Field, the inverse-square law, and there being no Big Bang and no multiverse - but there will also be no equations). -/- The other subheadings in this essay are – -/- NONLINEAR TIME AND ELECTRICAL ENGINEERING (about a 2009 electrical engineering experiment at America’s Yale University, and cosmic wormholes) -/- BITS AND TOPOLOGY (base-2 maths aka Binary digiTS, Mobius strips, and figure-8 Klein bottles) -/- WICK ROTATION, CAUSALITY, AND UNITING TIME (do past, present and future co-exist in an “eternal present”?) -/- DIGITAL BRAIN, DIGITAL UNIVERSE (if the brain and the universe are ultimately composed of binary digits, we'll someday be able to do the same things with the brain and universe that we now do with computers) -/- PROPOSAL: HUMAN AND ANIMAL INSTINCTS ARE THE RESULT OF THE UNIVERSE BEING UNIFIED BY BINARY DIGITS (AND TOPOLOGY) (If everything in the universe is ultimately composed of electronic BITS, then the universe must possess Artificial Intelligence - some prefer the term Cosmic Consciousness) -/- INFORMATION THEORY CONQUERS A RED GIANT (preserving Earth by keeping the Sun near today’s level of activity forever). 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nanological gates, in order to design nano-scale computers with dual-scale capabilities. All living biological systems function due to the molecular interactions of different subsystems. Molecular components (proteins and nucleic acids, lipids and carbohydrates, DNA and RNA) can be used as an inspirational strategy on how to design high-performance NEMS and MEMS that have the required features and characteristics. Considered. In addition, analytical and numerical methods are available for dynamic analysis and three-dimensional geometry, bonding and other properties of atoms and molecules. (...) Thus, electromagnetic and mechanical, and other physical and chemical properties can be studied. Nanostructures and nanosystems can be widely used in medicine and health. Possible applications of nanotechnology include: drug synthesis and drug delivery (therapeutic potential is greatly increased due to the effective direct delivery of new types of drugs to specific sites in the body), nanosurgery and nanotherapy Synthesis and detection of genomes, nano-scale stimuli and sensors (diagnosis and prevention of disease), design and implantation of non-rejection artificial organs and design of high performance nanomaterials. It is important that these technologies change the manufacture of materials, devices and systems. (shrink)

This book (in German) on "Physics, life and mind" is on the physical foundations of modern biology. The basic features of living systems, reproduction, mutation and metabolism, can be explained in terms of molecular processes involving nucleic acids as genetic material, and proteins as catalysts. The generation of structure and form in each generation results from spatiotemporal gene regulation in conjunction with the de novo formation of spatial order in which interplays of activation and inhibition play a crucial part. Brain (...) functions can be understood in terms of information processing in neural networks. Fundamental limitations of explanations of biological phenomena on the basis of physics are expected for the relation between neural and mental states, which may not be fully decodable by finite procedures. A complete algorithmic theory of the human mind encompassing all, including self-referential, aspects appears to be impossible even in principle, not only in practice. The range and limitations of explanations of life on the basis of physical laws and processes reflect the scope and limits of science in general. In contrast to the notions in circulation in the 19th century, modern science is open at the metatheoretical level to different philosophical, cultural and religious interpretations of man and the universe. -/- . (shrink)

The relations between life and cogntion have been addressed through different perspectives [Stewart 1996, Boden 2001, Bourgine and Stewart 2004, van Duijn & all 2006, Di Paolo 2009]. We would like here to address that subject by relating life to cognition through a process of meaning generation. Life emerged on earth as a far from thermodynamic equilibrium performance that had to maintain herself. Life is charactertized by a ‘stay alive’ constraint that has to be satisfied (such constraint can be included (...) in the constraint of being able to maintain far from equilibrium thermodynamic conditions [Bickhard 2011]). The local ‘stay alive‘ constraint has to be satisfied in an environment containing elements potentially supportive or harmfull. A key activity for the living entity is to characterize these elements in terms of meaningfulness relatively to the ‘stay alive’ constraint. This process can be modeled with an existing tool where a system submitted to an internal constraint generates meaningful information characterizing elements of the environment: the Meaning Generator System (MGS) [Menant, 2003, 2014 a]. In a few words: when a system submitted to an internal constraint receives from the environment an information that has a connection with the constraint it generates a meaning usable for the implementation of an action satisfying the constraint.The generated meaning is the connection existing between the received information and the constraint. The MGS models this process and interfaces to the action implementation for constraint satisfaction The meaning is generated by and for the system. The MGS grounds meaning generation in constraint satisfaction and links the living entity to her environment in a relational process. A simple example is with a paramecium close to a drop of acid. The paramecium which is submitted to a ‘stay alive’ constraint will move away from the acid area. The received information ‘presence of acid’ generates the meaning ‘acid not compatible with the ‘stay alive’ constraint‘ which triggers the moving away action (that example is close to Varela’s bacteria swimming up a sugar gradient. What the MGS brings in addition is a modeling of the significance of the chemical gradient for the organism). The action implemented to satisfy the constraint modifies the environment and the received information, establishing an interactive process linking the living entity to her environment. During its evolution animal life has elaborated new constraints (like ‘live group life’) and new functions enriching meaning generation and action scenarios. As a result the build up of meaningful representations has improved the constraint satisfaction processes of animals, embedding them in their environments in relational and interactive terms [Menant, 2011]. Cognition can be defined by proposing that ‘a system is cognitive if and only if sensory inputs serve to trigger actions in a specific way, so as to satisfy a viability constraint’ [Bourgine, Stewart 2004]. Cognition can also be considered as exemplifying a ‘vital criterion of responsiveness’ [Boden, 2001 ]. Consequently the MGS can be positioned as an elementary and generic version of animal cognition. For animal life, meaning generation for internal constraint satisfaction links life and cognition in a relational and interactive process. Cognition for human life is more complex as new performances have to be taken into account like self-consciousness and free-will. Meaning generation at human level is a challenging subject as human constraints are not clearly understood [Menant, 2011]. Many research activities are in process looking for some understanding of human mind [Philpapers]. One area of investigation is an evolutionary approach to self-consciousness using meaning generation where anxiety limitation comes up as a generic human constraint [Menant, 2014 b]. Assuming that we can have clear enough an understanding of some human constraints, we can look at the MGS for partly extending to humans the link between life and cognition that has been established for animals. So overall, we can consider that the MGS approach makes available an evolutionary link between life and cognition for animals, and partly for humans. A characteristic of the proposed system approach to meaning generation is the possibility to use it for any type of agent, be it organic (with intrinsic constraints ) or artificial (with derived constraints). Such characterization of agents through meaning generation can be used to discriminate artificial itelligence from human intelligence (see the MGS usage to support Searle’s chinese room argument [Menant, 2013]). On a more general basis, the proposed system approach can positions the MGS as a simple model for an internal source of normativity. It’s usage as a simple building block allows a bottom-up modeling for normativity in the sensorimotor approach. The ‘stay alive’ constraint could also be taken as a starting point for an evolutionary grounding of sensorimotor norms ‘in the biological normativity of the agent as a whole’ [Di Paolo & all 2014]. The proposed presentation will develop the points summarized here above and position them relatively to the autopoietic and enactive approaches. Several possible continuations will also be highlighted. (shrink)

This article was motivated by the avalanche of finance spent annually on addressing the harm caused by corrosion on household wares and buildings, industrial machines and facilities, hospital equipment and many other establishment of man in the universe. Corrosion is a universal phenomenon referred to as the deterioration of metallic material. Metal alloys like stainless steel and aluminium are extensively used in household utensils for their durability, affordability and corrosion resistance. However, these materials can leach heavy metals such as chromium, (...) nickel, iron, and aluminium into food, posing serious health challenges. Stainless steel, despite its corrosion resistance, releases harmful metals when exposed to acidic foods, while aluminium utensils corrode and release harmful elements under certain conditions too. Hence, this article was aimed at examining the historical background of corrosion, the causes of corrosion in household wares and utensils, its impact especially on human health and economy, and the potential remedies. The findings indicated that acidic foods and prolonged storage increase metal leaching. Health concerns included increased risks of anemia, dementia, and osteomalacia due to excessive metal accumulation in the body. Mitigation strategies included using anodized aluminium, minimizing storage time of acidic foods in metal containers, and increasing public awareness about the potential health risks. Proper maintenance and selection of utensils could significantly reduce the hazards associated with metal leaching. (shrink)

Historically, hypotheses failed in most cases to correctly forecast the workings of complex biological systems. Francis Crick’s adaptor hypothesis, however, stands out as an exceptional case of a confirmed abstract prediction. This hypothesis presciently anticipated the existence of RNA adaptors that function as bridges between amino acids and the chemically different nucleic acid template for proteins. Crick conjectured that the adaptors are enzymatically charged with cognate amino acids, they bind to complementary protein-coding nucleic acid, and their liberated amino (...) acids are incorporated into growing protein chains. Independently from and concomitantly with Crick’s hypothesis, Mahlon Hoagland and Paul Zamecnik conducted experiments with no guiding theory that culminated in discoveries of the actual adaptors, transfer RNA (tRNA) molecules, and their amino acids charging enzymes. This paper traces the parallel histories of Crick’s adaptor hypothesis and of the experimental discovery of tRNA and compares their relative impacts on the scientific community. Remarkably, despite the brilliance of Crick’s confirmed prognostication, it had marginal impact on practicing scientists. Conversely, Hoagland and Zamecnik’s experimental discoveries and their evidence-based model of protein synthesis had immediate and enduring impact. I discuss possible explanations for the different impacts of the theoretical prediction and experimental identifications of the same entities. (shrink)

The study developed and determined instant melon (Citrulluscolocynthis) soup powder’s shelf life for working-class mothers in Lagos, Nigeria. The study adopted research and development design. The population for the study was 2,077. The sample size for the study was 341. This consisted of three groups made up of 25 lecturers, 192 mothers working in banks and 124 mothers working. Seven sets of instruments were used for data collection. Data was analyzed using mean and standard deviation for the research questions. Findings (...) of the study indicated that the shelf life determinants included free fatty acid (FFA), moisture content and total viable count measured over a period of 22 weeks. From the analysis, FFA content slightly appreciated over the weeks; from 0.60 at the start to 0.7 5 at 4weeks; 0.86 at 8weeks; 0.95 at 12 weeks; 1.70 at 16 weeks and 4.06 at 22 weeks. The analysis showed that the moisture content of the developed melon soup powder slightly decreased over the weeks; from 9.41 at the start to 9.30 at 4 weeks; 9.00 at 8 weeks; 8.82 at 12 weeks; 8.60 at 16 weeks and 8.30 at 22 weeks. The total viable count (TVC) of the developed melon soup powder increased over the weeks. At the start of the experiment, the TVC of the developed melon soup powder was 8; TVC increased to 10 at 4 weeks; 14 at 8 weeks; 15 at 12 weeks; 18 at 16 weeks and 29 at 22 weeks. (shrink)

Financial analysis is a combined effort of knowledge and experience to obtain relevant ratios and elaborate on the results. The study is an application of financial analysis on Istanbul Public Transportation Company. As seen in the literature review section of the study public transportation companies require high subsidies by governments which is a factor to consider in the research. The research period is 2014- 2016. It is a comparative study with the inclusion of Izmir – ESHOT and Ankara – EGO (...) public transportation companies. The results are therefore compared with industry averages computed by the average of public transportation companies of three big cities in Turkey. The research is based on 7 selected ratios, 3 for measuring liquidity and the remaining 4 for measuring solvency. The ratios used in this paper are current ratio, acid test ratio, cash ratio, total debt ratio, debt equity ratio, equity multiplier, and long term debt ratio. According to the results, the companies have a very low current ratio which means they operate with low liquidity. Solvency analysis also reveal that, there are high degrees of leverage and negative shareholders’ equity. The research shows that companies might struggle to repay debts without government support. (shrink)

Financial analysis is a combined effort of knowledge and experience to obtain relevant ratios and elaborate on the results. The study is an application of financial analysis on Istanbul Public Transportation Company. As seen in the literature review section of the study public transportation companies require high subsidies by governments which is a factor to consider in the research. The research period is 2014- 2016. It is a comparative study with the inclusion of Izmir – ESHOT and Ankara – EGO (...) public transportation companies. The results are therefore compared with industry averages computed by the average of public transportation companies of three big cities in Turkey. The research is based on 7 selected ratios, 3 for measuring liquidity and the remaining 4 for measuring solvency. The ratios used in this paper are current ratio, acid test ratio, cash ratio, total debt ratio, debt equity ratio, equity multiplier, and long term debt ratio. According to the results, the companies have a very low current ratio which means they operate with low liquidity. Solvency analysis also reveal that, there are high degrees of leverage and negative shareholders’ equity. The research shows that companies might struggle to repay debts without government support. (shrink)

Milk contains a prominently beneficial nutritional value. Amino acids, fats, carbohydrates, vitamins, and also minerals can be found in it. Therefore, consuming it has an important role in children’s diet. Calcium is one of its most significant components, which is indispensable for bones and teeth, and for normal activity of muscle and nervous system, and also for controlling clotting processes. This manuscript reviews the key nutritional values of milk, and then determines some consumption recommendations for milk and dairy products, which (...) might support creating children’s proper diet, and also maintain their growth and calcium balance. (shrink)