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)

Issledovanie ėtapov zhizni, nauchnykh stateĭ professora Kievskoĭ Dukhovnoĭ Akademii I.P. Chetverikova -- Obzor genezisa termina "lichnostʹ" v ego rossiĭskom filosofsko-literaturnom kontekste do nachala XX veka.

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)

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)

We consider structural completeness in modal logics. The main result is the necessary and sufficient condition for modal logics over K4 to be hereditarily structurally complete: a modal logic λ is hereditarily structurally complete $\operatorname{iff} \lambda$ is not included in any logic from the list of twenty special tabular logics. Hence there are exactly twenty maximal structurally incomplete modal logics above K4 and they are all tabular.

While specifications and verifications of concurrent systems employ Linear Temporal Logic , it is increasingly likely that logical consequence in image will be used in the description of computations and parallel reasoning. Our paper considers logical consequence in the standard image with temporal operations image and image . The prime result is an algorithm recognizing consecutions admissible in image, so we prove that image is decidable w.r.t. admissible inference rules. As a consequence we obtain algorithms verifying the validity of consecutions (...) in image and solving the satisfiability problem. We start by a simple reduction of logical consecutions of image to equivalent ones in the reduced normal form . Then we apply a semantic technique based on image-Kripke structures with formula definable subsets. This yields necessary and sufficient conditions for a consecution to be not admissible in image. These conditions lead to an algorithm which recognizes consecutions admissible in image by verifying the validity of consecutions in special finite Kripke structures of size square polynomial in reduced normal forms of the consecutions. As a consequence, this also solves the satisfiability problem for image. (shrink)

In this book, the extend to which we can equip artificial agents with moral reasoning capacity is investigated. Attempting to create artificial agents with moral reasoning capabilities challenges our understanding of morality and moral reasoning to its utmost. It also helps philosophers dealing with the inherent complexity of modern organizations. Modern society with large multi-national organizations and extensive information infrastructures provides a backdrop for moral theories that is hard to encompass through mere theorising. Computerized support for theorising is needed to (...) be able to fully grasp and address the inherent complexity. Using moral reasoning capacity will help us addressing the challenges that technological artefacts pose. They do not only contain information about us, they start to act on our behalves.With the increasing autonomy comes an increased need to ensure that their behaviour is in line with what we expect from them. To investigate and address these issues a laboratoy for philosophy is outlined: SophoLab. It consists of a methodology; a framework of modal logic, DEAL; and multi-agent software systems. SophoLab provides the basis for an experimental, computational philosophy. Its viability and usefulness are demonstrated through several experiments. (shrink)

In this paper, I argue that scholars such as John Braithwaite and Lode Walgrave rely on fictions when presenting their utopian vision of restorative justice. Three claims in particular are shown to be fictitious. Proponents of restorative justice maintain, first, that the offender and the victim voluntarily attend the restorative conference. Second, that the restorative conference enables the offender and the victim to take on active responsibility. Third, that the reparatory tasks on which the parties agree should not be understood (...) in terms of the intentional infliction of harm. These fictions, so I argue, are not merely a mistake, but instead serve an important function: the various parties need to believe that they adequately capture the reality of the restorative conference as they are more likely to acquiesce if they believe the fictions to be true. I conclude that the fictions are the driving force within the restorative endeavour. (shrink)

The urgency of the study of the interaction of man, culture and education in the information society is gaining momentum, as the information society needs to deepen this interaction. This problem arises because people are beginning to rethink the problem of the context of the interaction of culture and education, which affect the person as a creature. The purpose of the study is to conceptualize the interaction of man, culture and education in an information society that requires conditions under which (...) effective interaction is effected that influences the deployment of essential forces in these areas. Formation of the aims of the article: studying the problems of human interaction, culture and education in the conditions of the information society; Identification of the concept of "educational and informational culture" as the coexistence of educational and information culture; an analysis of the interaction of man, culture and education as a value-mutually determined phenomena of human existence, which saturate, enrich and complement each other. An analysis of recent researches and publications from which the solution to this problem was initiated: the use of articles by the authors of V.Andruschenko, T.Andruschenko, O.Bazaluk, A. Boyko, V.Vashkevich, V.Voronkova, L.Gorbunova, O.Kivlyuk, S. Klepko, A. Kravchenko, S. Kutsepal, O. Punchchenko, I. Radionova, N. Skotnoy. Among the Belarusian scientists, we distinguish works by P. Vodopianov, A. Zelenkov, A. Lazarevich, V. Starginsky, V. Tsepkalo. Among the foreign ones are works by Carol Dvec, Richard Florida, Mary Furst and Jurgen Trinks, Eric Brignolfsson and Andrew Macafi, and others. Research methodology is a method of cultural creativity, which contributes to the construction of a model of cultural and innovative education and polity as the main drivers of sustainable development. Scientific novelty - identification of problems of interaction of man, culture and education in the conditions of the information society, contributing to the formation of a new cultural and educational policy as a policy of sustainable development. The results of the research: the interaction of man, culture and education - it is a valuable inter-deterministic phenomena of human existence, which saturate, enrich and complement each other. Therefore, the emergence of the concept of educational culture, and sometimes there is a scientific and educational culture, or educational and information culture, is not accidental in the information age. It is also complemented by the concept of "cultural and educational policy". Conclusion - we formed the concept of interaction of man, culture and education in the information society, based on a new cultural and educational policy that contributes to the formation of a policy of sustainable development. (shrink)

Purpose: To develop a realistic view that integrates the idea that knowledge is a constructive process. Problem: In the controversy between realism and constructivism, both sides have often misunderstood each other. Many realists still consider constructivism as a kind of idealism. And constructivists often assume that realists believe they have direct access to things as they really are. It seems necessary to clarify the statements of either side, to rule out some misunderstandings, and then to discuss anew the central epistemological (...) problems. Solution: A version of realism is proposed that takes into account constructivist ideas and objections. Realism as presented here is not opposed to the idea that cognition is a constructive process. According to this view, reality is something we presuppose in any attempt to attain knowledge though we can never be certain how things really are. Having knowledge amounts to the preliminary judgment that some hypotheses seem to correspond to reality better than others. In addition, it is demonstrated that a constructivist position that reduces the claim to knowledge even further does not solve the problems better but creates new ones. Finally, Mitterer's non-dualizing view of descriptions is discussed. It is argued that description necessarily presupposes something different from language. (shrink)