The human immune system can directly lyse invading micro‐organisms and aberrant host cells by generating pores in the cell envelope, called membrane attack complexes (MACs). Recent studies using single‐particle cryoelectron microscopy have revealed that the MAC is an asymmetric, flexible pore and have provided a structural basis on how the MAC ruptures single lipid membranes. Despite these insights, it remains unclear how the MAC ruptures the composite cell envelope of Gram‐negative bacteria. Recent functional studies on Gram‐negative bacteria elucidate that local (...) assembly of MAC pores by surface‐bound C5 convertase enzymes is essential to stably insert these pores into the bacterial outer membrane (OM). These convertase‐generated MAC pores can subsequently efficiently damage the bacterial inner membrane (IM), which is essential for bacterial killing. This review summarizes these recent insights of MAC assembly and discusses how MAC pores kill Gram‐negative bacteria. Furthermore, this review elaborates on how MAC‐dependent OM damage could lead to IM destabilization, which is currently not well understood. A better understanding on how MAC pores kill bacteria could facilitate the future development of novel strategies to treat infections with Gram‐negative bacteria. (shrink)

There can be no doubt that discrimination based on sex, race, ethnicity, religion or beliefs should not be tolerated in academia. Surprisingly, however, in recent years, policies of Diversity, Inclusion and Equity (DIE), officially introduced to counteract discrimination, have increasingly led to quite the opposite result: the exclusion of individuals who do not share a radical 'woke' ideology on identity politics (feminism, other gender activisms, critical race theory, etc.), and to the suppression of the academic freedom to discuss such dogmas. (...) This subversion of academia — disguised Trojan-horse style as universal human rights advocacy — is unacceptable because academia must be politically neutral and protect freedom of speech, a cornerstone of professional scholarly activity without which universities as we know them will slowly but surely suffocate. Our purpose here is to put together some particularly illustrative cases of such repression in a single book, testifying to a ubiquitous trend within western culture, irreducible to a few isolated complaints. The essays contained here illustrate the abuse of power, censorship and witch-hunts at many universities and research centres in the name of DIE. List of coauthors in alphabetical order: Dorian Abbot, Tomonori Agoh, Gerhard Amendt, Ivar Arpi, David Benatar, Peter Boghossian, Civitas Research Team, David Díaz Pardo de Vera, Pedro Domingos, Janice Fiamengo, Étienne Forest, Jorge Gibert Galassi, Norman Goldstuck, José L. González Quirós, Lawrence M. Krauss, Patrick LaBelle, Martín López Corredoira, Heather Mac Donald, Martin Malmgren, Jordan Peterson, Constantin Polychronakos, Erik. J. Olsson, Philip C. Salzman, Alessandro Strumia, Tom Todd, Andrei Yafaev. (shrink)

David Lewis's modal realism claims that nothing can exist in more than one world or time, and that statements about how something would have been are to be analysed in terms of its counterpart. I first explain why the counterpart relation depends on de re modal statements in an intensional language, so that intuitive properties of similarity relations cannot be used to show that the counterpart relation is not an equivalence relation. I then look at test sentences in (the intensional) (...) natural language, and show that none of them provide compelling evidence that a counterpart semantics is needed. (shrink)

An additional compartment of vaccinated individuals is considered in a SIS stochastic epidemic model with infection reintroduction. The quantification of the spread of the disease is modeled by a continuous time Markov chain. A well-known measure of the initial transmission potential is the basic reproduction number $$R_0$$, which determines the herd immunity threshold or the critical proportion of immune individuals required to stop the spread of a disease when a vaccine offers a complete protection. Due to repeated contacts between the (...) typical infective and previously infected individuals, $$R_0$$ overestimates the average number of secondary infections and leads to, perhaps unnecessary, high immunization coverage. Assuming that the vaccine is imperfect, alternative measures to $$R_0$$ are defined in order to study the influence of the initial coverage and vaccine efficacy on the transmission of the epidemic. (shrink)

Gerhard Ebeling on faith. Gerhard Ebeling (1912–2001), not only the foremost Luther researcher of the previous century but also one of the most prominent contributors to protestant theology during that period, wrote extensively about faith throughout his long and productive life as a professional theologian. He learnt from Luther that discerning judgement in the differentiation of related matters forms the basis of all sound theology. Applying this insight to his own thought, he reflects on the development of the phenomenon of (...) faith in the Old Testament community and early Christianity and the formalisation of the concept for use in the domain of religious studies. He defends the argument that Christian faith is not only faith in Jesus as the Christ and Lord but also that Jesus, and He only, is the founder and perfecter of faith. The concept of faith is also explored by Ebeling in relation to love, life and reason. The article concludes with a critical evaluation of Ebeling’s contribution in guiding us to witness authentically about our own faith in Jesus Christ within our own situation and against the background of the problems it poses for believing in Christ. (shrink)

In the recent past, several papers have pointed to the possibility that tumour removal generates a permissive environment in which tumour growth is potentiated. This phenomenon has been coined “perioperative tumour growth” and whilst it represents a departure in terms of our attitude to the surgical process, this concept was first hinted at by Paget1Sir James Paget (1814–1899) was a surgeon and physiologist who is widely held (along with Rudolph Virchow) to be the father of the science of pathology. Paget (...) described Paget's disease of the nipple as well as Paget's disease of bone. himself. Despite this, the time interval immediately before and after cancer surgery (i.e. the perioperative period) remains an underutilised interval during which chemotherapeutic regimens are rarely implemented. Herein, we present a summarised review of the literature that supports the concept that tumour removal may potentiate the growth of residual neoplastic disease. We also outline current knowledge regarding underlying mechanisms and in this manner highlight potential therapeutic entry points. Finally, we emphasise the urgent need for trials of agents that could protect patients against the harmful host–tumour interactions that may occur during the perioperative period. BioEssays 28: 433–437, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Morgan has argued that attitudes to the medicalisation of sports are historically conditioned.While the history of doping offers contested versions of when the sports world turned againstconservative forces, Morgan has argued that these attitudes are out of step with prevailingnorms and that the World Anti Doping Agency's policy needs to be modified to better reflectthis. As an advocate of critical democracies in sports, he argues that anti-doping policy mustacknowledge and reflect these shifts in order to secure their legitimacy. In response, (...) wecritically present the World Anti-Doping Agency's policy that incorporates the Prohibited Listof Substances and Methods for athletes. We evaluate the validity of the therapy-enhancementdistinction in relation to its role in both justifying and sustaining the operation of theProhibited List. In particular, we focus on the case of thyroxine, which has been the subjectof controversy in athletic doping. While thyroxine is not currently banned, critics haveclaimed that its use in the absence of a relevant pathology is tantamount to doping. Wechallenge Morgan's claim that a conventionalist defence of the therapy-enhancementdistinction is the best available, and his conclusion that this properly supports a morepermissive stance towards performance-enhancing drug use. Furthermore, we reject hisconventionalist support for democratic line drawing in relation to doping and in particular thestatus of thyroxine with regard to the prohibited list. We offer a modified defence of the statusquo, a qualified, naturalist account of health and disease, where athletes may be prescribeddrugs that are genuine responses to medical necessity that do not, or do not typically, threatenthe goods of athletic excellence. (shrink)

Individuals make decisions under uncertainty every day based on incomplete information concerning the potential outcome of the choice or chance levels. The choices individuals make often deviate from the rational or mathematically objective solution. Accordingly, the dynamics of human decision-making are difficult to capture using conventional, linear mathematical models. Here, we present data from a two-choice task with variable risk between sure loss and risky loss to illustrate how a simple nonlinear dynamical system can be employed to capture the dynamics (...) of human decision-making under uncertainty (i.e., multi-stability, bifurcations). We test the feasibility of this model quantitatively and demonstrate how the model can account for up to 86% of the observed choice behavior. The implications of using dynamical models for explaining the nonlinear complexities of human decision-making are discussed, as well as the degree to which nonlinear dynamical systems theory might offer an alternative framework for understanding human decision-making processes. (shrink)

The growth of knowledge and its effects on the practice of medicine have been issues of philosophical and ethical interest for several decades and will remain so for many years to come. The outline of the present volume was conceived nearly three years ago. In 1987, a conference on this theme was held in Maastricht, the Netherlands, on the occasion of the founding of the European Society for Philosophy of Medicine and Health Care (ESPMH). Most of the chapters of this (...) book are derived from papers presented at that meeting, and for the purpose of editing the book Stuart Spicker, Ph. D., joined two founding members of ESPMH, Henk ten Have and Gerrit Kimsma. The three of them successfully brought together a number of interesting contribu tions to the theme, and ESPMH is grateful and proud to have initiated the production of this volume. The Society intends that annual meetings be held in different European countries on a rotating basis and to publish volumes related to these meetings whenever feasible. In 1988, the second conference was held in Aarhus, Denmark on "Values in Medical Decision Making and Resource Allocation in Health Care". In 1989, a meeting was held in Czestochowa, Poland, on "European Traditions in Philosophy of Medicine. From Brentano to Bieganski". It is hoped that these conferences and the books to be derived from them, will initiate a new European tradition, lasting well into the 21 st century! P. J. (shrink)

In list-method directed forgetting, reexposure to forgotten List 1 items has been shown to reduce directed forgetting. proposed that reexposure to a few List 1 items only during a direct test of memory reinstates the entire List 1 episode. In the present experiments, part-list reexposure in the context of indirect as well as direct memory tests reduced directed forgetting. Directed forgetting was reduced when 50% or more of the items were reexposed, and was intact when only 25% were reexposed. Furthermore, (...) part-list reexposure appeared to reinstate only reexposed items-not the entire List 1 episode. (shrink)

An orthodox review of work on kant from 1955 to 1965 concentrating on (1) the continental school, Holding kant's interest to be in founding a practical-Dogmatic metaphysics, With its main work being done on the early period, Things in themselves, And the categories; (2) questions about the fischer-Trendelenburg controversy on the relation of "transcendentally ideal" to "transcendentally real"; (3) english work throwing light on the aesthetic and on the analytic, With the still obsessive concern for the second analogy; (4) the (...) continuing debate on whether the categorical imperative is a moral criterion, And its relation to the golden rule; and (5) the important work on the concepts of freedom and the highest good. (shrink)

Africa’s current socio-economic predicament is often solely attributed to political and economic mismanagement. However, such an analysis is far from comprehensive, as it fails to account for the historical, sociological and psychological causes of the current unsatisfactory social conditions in the continent. Consequently, using the critical and prescriptive techniques of philosophic reflection, this paper examines four apparent mental impediments to desirable social transformation in contemporaryAfrica, namely, conservatism, feeble social consciousness, blind acceptance of the white-black dichotomy, and a fixation with foreign (...) paradigms of managing public affairs. The paper calls for an interdisciplinary approach to the verifying, mitigating and/or eliminating of these impediments. (shrink)

While H. Odera Oruka is best known for his views on sage philosophy, he spent a considerable portion of his philosophical career agonizing over the question of human rights. The present paper argues that there is need for further philosophical reflection on Oruka’s account of the foundation of human rights with a view to refining it.

Scientific tradition holds that it is essential to permit individual researchers almost complete freedom in their selection of research projects. As a result, structured research planning has not played a major role in determining the course of the sciences. By “structural research planning” we mean the methodical establishment of goals, and the identification of research routines which apparently accord priority to highest value goals, while minimizing the cost and time of their attainment. With increasing competition for limited fiscal and intellectual (...) resources this kind of planning may become more necessary. Let us cite three specific examples: First, the individual researcher is often faced with the question of how best to spend his time in pursuing a particular line of investigation. He must allocate his personal resources of time and talent to work which appears to hold the promise of highest pay-off. Second, on a larger scale, the competition for resources also raises the question of priority among alternative government-sponsored research projects. Individuals proposing equally alluring projects sometimes seek the same funds; government planners need some sort of objective criteria in order to judge the proposals. Furthermore, government planners face the problem of justifying their request for “big science” resources; a planning strategy which defines the use and expected output of the requested resources can help in the design and promotion of their concept. Finally, there is a growing sentiment that at least some research should be directed toward the solution of current and anticipated societal problems, to find means of circumventing or minimizing the impact of potentially dangerous problems of civilization. These needs : the choice of individual research, allocation of national resources among competing projects, and selecting research of societal importance, suggest that structured research planning might be valuable. (shrink)