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)

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)

Although research into the biosemiotic mechanisms underlying the purposeful behavior of brainless living systems is extensive, researchers have not adequately described biosemiosis among neurons. As the conscious use of signs is well-covered by the various fields of semiotics, we focus on subconscious sign action. Subconscious semiotic habits, both functional and dysfunctional, may be created and reinforced in the brain not necessarily in a logical manner and not necessarily through repeated reinforcement. We review literature that suggests hypnosis may be effective in (...) changing subconscious dysfunctional habits, and we offer a biosemiotic framework for understanding these results. If it has been difficult to evaluate any psychological approach, including hypnosis, this may be because contemporary neuroscience lacks a theory of the sign. We argue that understanding the fluid nature of representation in biological organisms is prerequisite to understanding the nature of the subconscious and may lead to more effective of treatments for dysfunctional habits developed through personal experience or culture. (shrink)

V. C. Chappell; IV*—Stuff and Things, Proceedings of the Aristotelian Society, Volume 71, Issue 1, 1 June 1971, Pages 61–76, https://doi.org/10.1093/aristotelia.

Is it possible to invoke the use of moral responsibility as part of the selection criteria in the allocation of livers for transplant? Criticism has been applied to the difficulties inherent in including such a criterion and also the effect that employing such a judgement might have upon the relationship between the physician and patient. However, these criticisms rely on speculation and conjecture and do not relate to all the arguments put forward in favour of applying moral responsibility. None of (...) the present arguments against using moral responsibility in the allocation of livers for transplant are good enough to warrant its dismissal. (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)

Aristotle's views on the fundamental nature of reality are usually taken to be inconsistent. The two main sources for these views are the Categories and the central books of the Metaphysics, particularly book Zeta. In the early theory of the Categories the basic entities of the world are concrete objects such as Socrates: Aristotle calls them 'primary substances'. But the later theory awards this title to the forms of concrete objects. Michael Wedin proposes a compatibilist solution to this long-standing puzzle, (...) arguing that Aristotle is engaged in quite different projects in the two works. The theory of Metaphysics Zeta is meant to explain central features of the standing doctrine of the Categories, and so presupposes the essential truth of the early theory. The Categories offers a theory of underlying ontological configurations, while book Zeta gives form the status of primary substance because it is primarily the form of a concrete object that explains its nature, and this form is the substance of the object. So when the late theory identifies primary substance with form, it appeals to an explanatory primacy that is quite distinct from the ontological primacy that dominates the Categories. Wedin's new interpretation thus allows us to see the two treatises as complementing each other: they are parts of a unified history of substance. (shrink)

In an article which appeared a few years ago, entitled ‘God's Death’ , A.D. Smith launched one of the most interesting of recent attacks on the traditional doctrine of the Incarnation. Focusing on the death of Christ, he claimed to demonstrate the logical impossibility of Jesus having been both human and divine. Each of the premises of his argument was said to be a commitment of orthodox theology. He thus presented his reasoning as displaying an internal incoherence in that way (...) of thinking about divinity, humanity, and the person of Christ. The argument was basically quite simple: According to Christian theology and in concurrence with general thought on the matter, we must hold that human death involves the possibility of annihilation. As a man, Jesus of Nazareth faced and underwent a human death. He thus faced the possibility of annihilation. But orthodox theologians hold God to be of such an ontological status that no divine being could even possibly be annihilated. So no divine person could die a human death. From this follows the impossibility of the traditional claim that the Second Person of the divine Trinity became a man, lived a human life, and died a human death for us and our salvation. The qualitative difference between God and man is such as to render incarnational christology an incoherent theological stance. (shrink)

Aristotle's views on the fundamental nature of reality are usually taken to be inconsistent. The two main sources for these views are the Categories and the central books of the Metaphysics, particularly book Zeta. In the early theory of the Categories the basic entities of the world are concrete objects such as Socrates: Aristotle calls them 'primary substances'. But the later theory awards this title to the forms of concrete objects. Michael Wedin proposes a compatibilist solution to this long-standing puzzle, (...) arguing that Aristotle is engaged in quite different projects in the two works. The theory of Metaphysics Zeta is meant to explain central features of the standing doctrine of the Categories, and so presupposes the essential truth of the early theory. The Categories offers a theory of underlying ontological configurations, while book Zeta gives form the status of primary substance because it is primarily the form of a concrete object that explains its nature, and this form is the substance of the object. So when the late theory identifies primary substance with form, it appeals to an explanatory primacy that is quite distinct from the ontological primacy that dominates the Categories. Wedin's new interpretation thus allows us to see the two treatises as complementing each other: they are parts of a unified history of substance. (shrink)

After learning about the concept of determinism, a natural tendency is to conclude that if anyone actually believed in the determinism of human nature, then all future human actions are "set out for us" or "cut and dried" and, in some sense, utterly unavoidable. Another way of referring to such inevitability is that human action appears to be..

The construct of “choking under pressure” is concerned with the phenomenon of unexpected, sudden, and significant declines in individual athletes’ performances in important situations and has received empirical attention in the field of sport psychology. Although a number of theories about the reasons for the occurrence of choking under pressure exist and several intervention approaches have been developed, underlying mechanisms of choking are still under debate and the effectiveness of existing interventions remains contested. These sudden performance declines also occur in (...) team sport. “Collective sport team collapse,” which describes the situation when an entire sport team underperforms significantly within an important competitive situation, has received less empirical attention, in comparison to individual choking research. While there are a few studies that have investigated causes of collective team collapse, understandably, there has been limited empirical investigation of preventative and intervention strategies. Although the two constructs appear to share several similar characteristics and mechanisms, research has not yet examined the conceptual, theoretical, empirical, and practical links between choking under pressure and collective sport team collapse. In this review article, we seek to examine these similarities and differences and identify new ways of thinking about future interventions. Furthermore, current empirical understandings in the field of choking under pressure and collective sport team collapse are presented and the most effective intervention approaches for both constructs are introduced. On the basis of this examination, we modestly make some initial recommendations for sport psychological practitioners and future research. (shrink)

Of course you know the movie, just by cultural assimilation if not by having seen it. There’s this young elephant, Dumbo, who has laughably big ears and has been pitiably separated from his mom. He’s aided by a friendly talking mouse[ii] into translating those otherwise hapless ears into the power of flight, which he eventually uses to rescue his mom and live happily ever after. The way the wily mouse gets Dumbo to believe that he could fly is to give (...) him a “magic feather” which, held in his trunk, demonstrably imparts the gift of flight. Naturally the mouse believes throughout all this that Dumbo can fly anyway, but he also knows that Dumbo needs the feather as a confidence-builder to do so. At the critical juncture of the tale Dumbo loses the feather after being pushed off a precipice, and he thus plummets perilously towards earth—only to find at the last moment that he can indeed fly on his own. (shrink)

All right, first off I need to disappoint some people who despise reading the fine print on things or just plain love to speed-read only large fonts: this is not only not my last lecture, I m not even retiring anytime soon. So sorry to those of you poised to shout Good riddance to bad rubbish! at the end of this soliloquy. You re going to have to be patient a while longer.

Of course you know the movie, just by cultural assimilation if not by having seen it. There’s this young elephant, Dumbo, who has laughably big ears and has been pitiably separated from his mom. He’s aided by a friendly talking mouse2 into translating those otherwise hapless ears into the power of flight, which he eventually uses to rescue his mom and live happily ever after. The way the wily mouse gets Dumbo to believe that he could fly is to give (...) him a “magic feather” which, held in his trunk, demonstrably imparts the gift of flight. Naturally the mouse believes throughout all this that Dumbo can fly anyway, but he also knows that Dumbo needs the feather as a confidence-builder to do so. At the critical juncture of the tale Dumbo loses the feather after being pushed off a precipice, and he thus plummets perilously towards earth—only to find at the last moment that he can indeed fly on his own. (shrink)

“Men can never be free, because they’re weak, corrupt, worthless and restless. The people believe in authority; they’ve grown tired of waiting for miracle or mystery. Science is their religion; no greater explanation exists for them.” (Cigarette Smoking Man, "Talitha Cumi" The X-Files 3X24).

Harry Frankfurt's famous examples of overdetermined moral agents who are nevertheless responsible for their actions and omissions have long been hailed as proofs that the ability and/or opportunity to do otherwise is not a necessary condition for moral responsibility. In this paper I use recent clarifications of some of these examples by Frankfurt himself to show that their force relies in part on tacit ceteris paribus assumptions concealing a reliance on PAP that concerns matters of fairness in assessing moral responsibility.

Analysis shows that statements of ability are disguised conditionals. More exactly, the correct analysis of 'X could have done A' is 'If X h decided (chosen, willed ...) to do A, X would have done A'. Therefore having acted freely--having been able to act otherwise than one fact did--is compatible with determinism (with the causal determination of one's acts).

Hud Hudson has argued that with a few assumptions one can prove that superluminal objects exist. I argue that even if the assumptions are true that his argument, if sound, leads to a proliferation of movers packing given spaces. I further argue that his argument as it stands cannot in fact entail that objects moving at any speed exist.

The author examines the single topic approach to the construction of introductory philosophy courses. The author considers the single topic approach to be an alternative to more historically- and topically-based approaches. The traditional approach to philosophy is often broad and difficult for students to engage with in classroom discussion. A narrow and detailed treatment of a standard area or topic facilitates classroom discussion and allows students to transfer insights and skills in areas of their own disciplines. The author outlines a (...) methodology that treats philosophical texts in an interdisciplinary context, which emphasizes to students that philosophy is not a detached field of study. (shrink)

In this paper we present an executable approach to model interactions between agents that involve sensitive, privacy-related information. The approach is formal and based on deontic, epistemic and action logic. It is conceptually related to the Belief-Desire-Intention model of Bratman. Our approach uses the concept of sphere as developed by Waltzer to capture the notion that information is provided mostly with restrictions regarding its application. We use software agent technology to create an executable approach. Our agents hold beliefs about the (...) world, have goals and commitment to the goals. They have the capacity to reason about different courses of action, and communicate with one another. The main new ingredient of our approach is the idea to model information itself as an intentional agent whose main goal it is to preserve the integrity of the information and regulate its dissemination. We demonstrate our approach by applying it to an important process in the insurance industry: applying for a life insurance. In this paper we will: (1) describe the challenge organizational complexity poses in moral reasoning about informational relationships; (2) propose an executable approach, using software agents with reasoning capacities grounded in modal logic, in which moral constraints on informational relatio nships can be modeled and investigated; (3) describe the details of our approach, in which information itself is modeled as an intentional agent in its own right; (4) test and validate it by applying it to a concrete ‘hard case’ from the insurance industry; and (5) conclude that our approach upholds and offers potential for both research and practical application. (shrink)