ABSTRACT Why did the popping of the housing bubble bring the financial system—rather than just the housing sector of the economy—to its knees? The answer lies in two methods by which banks had evaded regulatory capital requirements. First, they had temporarily placed assets—such as securitized mortgages—in off‐balance‐sheet entities, so that they did not have to hold significant capital buffers against them. Second, the capital regulations also allowed banks to reduce the amount of capital they held against assets that remained on (...) their balance sheets—if those assets took the form of AAA‐rated tranches of securitized mortgages. Thus, by repackaging mortgages into mortgage‐backed securities, whether held on or off their balance sheets, banks reduced the amount of capital required against their loans, increasing their ability to make loans many‐fold. The principal effect of this regulatory arbitrage, however, was to concentrate the risk of mortgage defaults in the banks and render them insolvent when the housing bubble popped. (shrink)

The morbidity of tick‐borne encephalitis (TBE) varies yearly by as much as 10‐fold among the people of Western Siberia. This long‐term variation is dependent on many factors such as the density of the tick populations, the prevalence of TBE virus (TBEV) among sub‐adult ticks, the yearly virulence of the TBEV, and prophylactic measures. Here we highlight the role of small mammal hosts in the circulation of TBEV through the ecosystem. Refining classical models of non‐viremic horizontal transmission, we emphasize the recently (...) understood fact that the physiological and immunological status of the small mammal hosts affects the tick and virus‐host interactions. In addition to its theoretical interest, our approach may lead to some practical improvements in the precision of epidemiological forecasts and perhaps in forestalling the severity of outbreaks of TBE, or, at least, in forewarning medical authorities and the general public of impending TBE outbreaks. (shrink)

The concept of human gene therapy came on the heels of fundamental discoveries on the nature and working of the gene. However, realistic prospects to correct the underlying cause of recessive genetic disorders through the transfer of wild‐type alleles of defective genes had to wait for the arrival of recombinant DNA technology. These techniques permitted the isolation and insertion of genes into the first recombinant delivery systems. The realization that viruses are natural gene carriers provided inspiration for gene therapy and, (...) as engineered vectors, viruses became prominent gene delivery vehicles. Nonetheless, when put in the context of human and non‐human primate studies, all vectors fell short of success regardless of their viral or non‐viral origin. Recognition of issues such as inefficient gene transfer and short‐lived or scant expression in the relevant cell type(s) prompted researchers to refine and develop several gene delivery systems, in particular those based on retroviruses, adeno‐associated viruses and adenoviruses. Concomitantly, available technology was deployed to tackle disorders that require few genetically corrected cells to attain therapy. BioEssays 27: 506–517, 2005. © 2005 Wiley periodicals, Inc. (shrink)

The COVID-19 pandemic has resulted in more than 524 million cases and 6 million deaths worldwide. Various drug interventions targeting multiple stages of COVID-19 pathogenesis can significantly reduce infection-related mortality. The current within-host mathematical modeling study addresses the optimal drug regimen and efficacy of combination therapies in the treatment of COVID-19. The drugs/interventions considered include Arbidol, Remdesivir, Interferon and Lopinavir/ritonavir. It is concluded that these drugs, when administered singly or in combination, reduce the number of infected cells and viral (...) load. Four scenarios dealing with the administration of a single drug, two drugs, three drugs and all four are discussed. In all these scenarios, the optimal drug regimen is proposed based on two methods. In the first method, these medical interventions are modeled as control interventions and a corresponding objective function and optimal control problem are formulated. In this framework, the optimal drug regimen is derived. Later, using the comparative effectiveness method, the optimal drug regimen is derived based on the basic reproduction number and viral load. The average number of infected cells and viral load decreased the most when all four drugs were used together. On the other hand, the average number of susceptible cells decreased the most when Arbidol was administered alone. The basic reproduction number and viral load decreased the most when all four interventions were used together, confirming the previously obtained finding of the optimal control problem. The results of this study can help physicians make decisions about the treatment of the life-threatening COVID-19 infection. (shrink)

The versatile clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system has emerged as a promising technology for therapy and molecular diagnosis. It is especially suited for overcoming viral infections outbreaks, since their effective control relies on an efficient treatment, but also on a fast diagnosis to prevent disease dissemination. The CRISPR toolbox offers DNA‐ and RNA‐targeting nucleases that constitute dual weapons against viruses. They allow both the manipulation of viral and host genomes for therapeutic purposes and the detection (...) of viral nucleic acids in “Point of Care” sensor devices. Here, we thoroughly review recent advances in the use of the CRISPR/Cas system for the treatment and diagnosis of viral deleterious infections such as HIV or SARS‐CoV‐2, examining their strengths and limitations. We describe the main points to consider when designing CRISPR antiviral strategies and the scientific efforts to develop more sensitive CRISPR‐based viral detectors. Finally, we discuss future prospects to improve both applications. Also see the video abstract here: https://www.youtube.com/watch?v=C0z1dLpJWl4. (shrink)

James V. Neel, one of the leading human geneticists of the 21st Century, has long been concerned about the consequences of human overpopulation and the accompanying destruction of the earth's ecosystem. His point of view, summarized in this paper, is contrasted with some recent optimistic projections presented by demographers and population biologists who believe the population bomb has been defused by evidence of a decrease in worldwide fertility along with a significant increase in food production. The authors of this paper (...) are not so optimistic and see a continuing need for concern rather than complacency based on ever increasing human wants and aspirations together with the minimal results of recent environmental summits. The case of HIV/aids is used to illustrate the evolutionary implications of the interaction between population dynamics and genetic change based on the concepts of population bottlenecks, genetic drift and founder effects. What becomes evident from this illustration is that epidemics by viral and other pathogens in the 21st Century can affect the size of human populations and thereby the course of the species' evolutionary makeup. The potential of evolutionary medicine and in particular molecular biology to improve our prediction capabilities and modulate some of the possible consequences is discussed. (shrink)

Ductin is the highest conserved membrane protein yet found in eukaryotes. It is multifunctional, being the subunit c or proteolipid component of the vacuolar H+‐ATPase and at the same time the protein component of a form of gap junction in metazoan animals. Analysis of its structure shows it to be a tandem repeat of two 8‐kDa domains derived from the subunit c of the F0 proton pore from the F1F0 ATPase. Each domain contains two transmembrane α‐helices, which together may form (...) a four‐helix bundle. In both the V‐ATPase and gap junction channel, ductin is probably arranged as a hexamer of subunits forming a central channel of gap junction‐like proportions. The two functions appear to be seggregated by ductin having two orientations in the bilayer. Ductin is also the major component of the mediatophore, a protein complex which may aid in the release of neurotransmitters across the pre‐synaptic membrane. It is also a target for a class of poorly understood viral polypeptides. These polypeptides are small and highly hydrophobic and some have oncogenic activity. Ductin thus appears to be at the crossroads of a number of biological processes. (shrink)

Purpose. The article is aimed to substantiate the view on the phenomenon of laughter as a subject of semiotic analysis, which leads to the following tasks: to reveal the possibilities of semiotics application in the study of laughter nature; to analyze the phenomenon of laughter as a cultural and natural phenomenon, as a sign and as an attribute; to consider the place of laughter in culture, which is understood as a sign system. Theoretical basis. The semiotic approach proceeds from the (...) fact that human lives in the world of signs, all the surrounding reality can be interpreted as a sign system. The basic concept of semiotics is the concept of a sign. The theoretical basis of the article is understanding the culture as a sign-symbolic system. Laughter is considered as a phenomenon ontologically rooted in human culture. At the same time, laughter is on the edge of culture. The research is based on the work of semiotic authors, cultural researchers, and the researchers of laughter. Originality. The originality lies in the application of the semiotic method to the research of laughter phenomenon, consideration of the dialectics of natural and cultural, signedness and non-signedness, manifested in the phenomenon of laughter. Conclusions. Laughter is considered as a psychophysiological phenomenon and as a cultural phenomenon. Laughter acts as an emotional manifestation, a physiological reaction, but socially and culturally mediated. In any case, laughter indicates an emotional or cognitive state of a human. Laughter acts as a process and result of the interpretation of a sign, a reaction to a sign. Laughter is a form and a means of communication. Being a natural phenomenon, in the process of social evolution, laughter acquires signedness, is integrated by culture as a sign system, and, at the same time, maintains a connection with nature. Thus, laughter occupies an ambivalent position between nature and culture. In the phenomenon of laughter, the dual state of human is revealed. In laughter, boundaries are blurred, the unity and opposition of natural and cultural, biological and social, soul and body, thought and feeling, sign and attribute are manifested. (shrink)

This special issue, Withholding artificial nutrition and hydration, comprises several papers, commentaries and responses centred largely around the issues raised by the 2011 decision of the English Court of Protection in W v M.i In that case, the mother of an adult patient applied for the withdrawal of life-sustaining treatment . In 2003, the patient, M, had contracted viral encephalitis and suffered irreparable brain damage as a result. She fell into a coma, and when she emerged appeared to be (...) in a vegetative state and for 8 years was entirely dependent on life-sustaining care.Following her mother's application, M was held to lack capacity and hence in accordance with section 4 of the Mental Capacity Act 2005 , the matter turned on whether it was in her best interests for the treatment to be withdrawn. It was made clear in the 1993 decision of Airedale NHS Trust v Bland that life-sustaining treatment could be withdrawn from a patient in a permanent vegetative state if, on balance, it was not in his or her interest to continue treatment.ii The MCA also allows for withdrawal of treatment, although the approach to best interests is slightly different. However, the case of W v M is importantly different from the Bland case, because M was found not to be in a PVS, but instead was minimally conscious . Much evidence was presented of her capacity to respond to stimuli, seemingly express emotion and occasionally speak.In the first of his papers in this issue , Julian Sheather provides an overview of the case, particularly illuminating the discussions of M's interests and the views of her …. (shrink)

Currently, any dentist in the UK who is HIV-seropositive must stop treating patients. This is despite the fact that hepatitis B-infected dentists with a low viral load can continue to practise, and the fact that HIV is 100 times less infectious than hepatitis B. Dentists are obliged to treat HIV-positive patients, but are obliged not to treat any patients if they themselves are HIV-positive. Furthermore, prospective dental students are now screened for hepatitis B and C and HIV, and are (...) not allowed to enrol on Bachelor of Dental Surgery degrees if they are infectious carriers of these diseases. -/- This paper will argue that: (i) the current restriction on HIV-positive dentists is unethical, and unfair; (ii) dentists are more likely to contract HIV from patients than vice versa, and this is not reflected by the current system; (iii) the screening of dental students for HIV is also unethical; (iv) the fact that dentists can continue to practise despite hepatitis B infection, but infected prospective students are denied matriculation, is unethical; and (v) that the current Department of Health protocols, as well as being intrinsically unfair, have further unethical effects, such as the waste of valuable resources on ‘lookback’ exercises and the even more damaging loss of present and future dentists. Regulation in this area seems to have been driven by institutional fear of public fear of infection, rather than any scientific evidence or ethical reasoning. (shrink)

Purpose. The purpose of this paper is to investigate the anthropological and socio-philosophical dimensions of human existence of the older age group given the challenges of pandemic threats caused by COVID-19. To this end, it is planned to solve a number of tasks, among which one should distinguish the following: 1) to investigate the manifestations of age discrimination in the context of the social and labor areas of human existence; 2) to focus on the asymmetry of the behavior of society (...) and the state relative to persons of the older age group in the field of healthcare in the context of a pandemic crisis; 3) to represent the anthropological features of changes in the socialization and activity of older people under the current conditions of globalization-pandemic challenges. Theoretical basis. Despite such a broad representation of the age-related issue in public relations, there are still no practical guarantees that would apply to discriminatory aspects of older age groups in various areas of their manifestation. The synergistic evolution of social reality requires substantive analysis of the issue under the current conditions for the transformation of social life, which is affected by globalization crises caused by the pandemic threats of COVID-19. Originality. The stereotypical assumptions underlying legal policy and established social relations are based solely on the application of chronological age. The novelty is in justifying an individual approach to the elderly through the personification of the personal characteristics of a person. The study of anthropological and socio-philosophical dimensions of the existence of a person of the older age group in the face of the challenges of pandemic threats caused by COVID-19 has made it possible to analyze the destructive nature of age discrimination in the context of the social and labor areas of human existence. As well as focus on the asymmetry of the behavior of society and the state in relation to these persons in the field of health care, and emphasize the anthropological features of changes in the socialization and human activity under the current conditions of globalization-pandemic challenges. Conclusions. External threats to human existence call for special attention to the implementation and protection of human rights, freedoms, individual freedoms, and identity. Pandemic threats have transformed all dimensions of human existence, especially for those groups of society that are less socially protected. The pandemic crisis has created additional grounds for discrimination against older people in various areas of human existence. Equalization of persons by age without personifying the personal characteristics of an individual is discrimination on an age basis, which violates the principles of democracy and humanism in the society, leads to stigmatization of the person, is the cause of the anthropological crisis of a person. (shrink)

This article explores the uptake and circulation of ‘transgender’ in academic and philanthropic institutions, as a way of taking seriously Robyn Wiegman’s call for a divergentist approach. In so doing, the article aims to demonstrate the intimate entanglements between non-profit and academic spheres and identity knowledges therein. Taken together, both contexts reveal the messiness and complexities of institutionality, not only as a lived reality for individuals such as philanthropy professionals and academics, but also as an object of study itself.

The tutorial is an expanded and revised English version of the Ukrainian edition. (Filosofiya nauky: navch. posib OM Kuzʹ, VF Cheshko - Kharkiv: KHNEU im. S. Kuznetsya, 2017.). -/- .