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)

This long-awaited book replaces Hughes and Cresswell's two classic studies of modal logic: _An Introduction to Modal Logic_ and _A Companion to Modal Logic_. _A New Introduction to Modal Logic_ is an entirely new work, completely re-written by the authors. They have incorporated all the new developments that have taken place since 1968 in both modal propositional logic and modal predicate logic, without sacrificing tha clarity of exposition and approachability that were essential features of their earlier works. The book takes (...) readers from the most basic systems of modal propositional logic right up to systems of modal predicate with identity. It covers both technical developments such as completeness and incompleteness, and finite and infinite models, and their philosophical applications, especially in the area of modal predicate logic. (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)

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)

Semantic Indexicality shows how a simple syntax can be combined with a propositional language at the level of logical analysis. It is the adoption of such a base language which has not been attempted before, and it is this which constitutes the originality of the book. Cresswell's simple and direct style makes this book accessible to a wider audience than the somewhat specialized subject matter might initially suggest.

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)

In the _Proslogion_, St. Anselm presents a philosophical argument for the existence of God. Anselm's proof, known since the time of Kant as the ontological argument for the existence of God, has played an important role in the history of philosophy and has been incorporated in various forms into the systems of Descartes, Leibniz, Hegel, and others. Included in this edition of the_ Proslogion _are Gaunilo's "A Reply on Behalf of the Fool" and St. Anselm's "The Author's Reply to Gaunilo." (...) All three works are in the original Latin with English translation on facing pages. Professor Charlesworth's introduction provides a helpful discussion of the context of the _Proslogion_ in the theological tradition and in Anselm's own thought and writing. (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)

We distinguish two types of cases that have potential to generate quasi-cyclical preferences: self-involving choices where an agent oscillates between first- and third-person perspectives that conflict regarding their life-changing implications, and self-serving choices where frame-based reasoning can be “first-personally rational” yet “third-personally irrational.” We argue that the distinction between these types of cases deserves more attention in Bermúdez's account.

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)