Depletion of mitochondrial endo/exonuclease G‐like (EXOG) in cultured neonatal cardiomyocytes stimulates mitochondrial oxygen consumption rate (OCR) and induces hypertrophy via reactive oxygen species (ROS). Here, we show that neurohormonal stress triggers cell death in endo/exonuclease G‐like‐depleted cells, and this is marked by a decrease in mitochondrial reserve capacity. Neurohormonal stimulation with phenylephrine (PE) did not have an additive effect on the hypertrophic response induced by endo/exonuclease G‐like depletion. Interestingly, PE‐induced atrial natriuretic peptide (ANP) gene expression was completely abolished in endo/exonuclease (...) G‐like‐depleted cells, suggesting a reverse signaling function of endo/exonuclease G‐like. Endo/exonuclease G‐like depletion initially resulted in increased mitochondrial OCR, but this declined upon PE stimulation. In particular, the reserve capacity of the mitochondrial respiratory chain and maximal respiration were the first indicators of perturbations in mitochondrial respiration, and these marked the subsequent decline in mitochondrial function. Although pathological stimulation accelerated these processes, prolonged EXOG depletion also resulted in a decline in mitochondrial function. At early stages of endo/exonuclease G‐like depletion, mitochondrial ROS production was increased, but this did not affect mitochondrial DNA (mtDNA) integrity. After prolonged depletion, ROS levels returned to control values, despite hyperpolarization of the mitochondrial membrane. The mitochondrial dysfunction finally resulted in cell death, which appears to be mainly a form of necrosis. In conclusion, endo/exonuclease G‐like plays an essential role in cardiomyocyte physiology. Loss of endo/exonuclease G‐like results in diminished adaptation to pathological stress. The decline in maximal respiration and reserve capacity is the first sign of mitochondrial dysfunction that determines subsequent cell death. (shrink)

The author argues that Luther 's two-kingdoms doctrine rests upon a limited conception of law: "criminal" law, to use the terminology of British legal philosopher H. L. A. Hart. In contrast, "contract" law is the potent means through which networks of political, economic, and social relations have been built up since Luther 's day. Using the 1523 Leisnig experiment in social governance as an example, the author suggests that Lutheran ethicists need to pay more attention to "cooperative self- obligation " (...) as the basic device through which social covenants are established and sustained. The essay concludes with four emphases that Lutheran ethicists might bring to such a rethinking of law as an ethical concept. (shrink)

The Database on Ethics Related Legislation and Guidelines was launched in March 2007 as the fourth database of the UNESCO Global Ethics Observatory system of databases in ethics of science and technology. The database offers a collection of legal instruments searchable by region, country, bioethical themes, legal categories and applicability to specific articles of the UNESCO Universal Declaration on Bioethics and Human Rights and International Declaration on Human Genetic Data. This paper discusses the background and rationale for the database and (...) its role as a consultative and comparative resource hub for the study of ethics related legal instruments across the world, with the purpose of informing and inspiring relevant stakeholders on the implementation of the principles contained within the UNESCO declarations on bioethics. (shrink)

The US neutrino community gathered at the Workshop on the Intermediate Neutrino Program at Brookhaven National Laboratory February 4-6, 2015 to explore opportunities in neutrino physics over the next five to ten years. Scientists from particle, astroparticle and nuclear physics participated in the workshop. The workshop examined promising opportunities for neutrino physics in the intermediate term, including possible new small to mid-scale experiments, US contributions to large experiments, upgrades to existing experiments, R&D plans and theory. The workshop was organized into (...) two sets of parallel working group sessions, divided by physics topics and technology. Physics working groups covered topics on Sterile Neutrinos, Neutrino Mixing, Neutrino Interactions, Neutrino Properties and Astrophysical Neutrinos. Technology sessions were organized into Theory, Short-Baseline Accelerator Neutrinos, Reactor Neutrinos, Detector R&D and Source, Cyclotron and Meson Decay at Rest sessions.This report summarizes discussion and conclusions from the workshop. (shrink)

Cyclin-dependent kinase 5 has been implicated in Alzheimer's disease pathogenesis. Here, we demonstrate that overexpression of p25, an activator of cdk5, led to increased levels of BACE1 mRNA and protein in vitro and in vivo. A p25/cdk5 responsive region containing multiple sites for signal transducer and activator of transcription was identified in the BACE1 promoter. STAT3 interacts with the BACE1 promoter, and p25-overexpressing mice had elevated levels of pSTAT3 and BACE1, whereas cdk5-deficient mice had reduced levels. Furthermore, mice with a (...) targeted mutation in the STAT3 cdk5 responsive site had lower levels of BACE1. Increased BACE levels in p25 overexpressing mice correlated with enhanced amyloidogenic processing that could be reversed by a cdk5 inhibitor. These data demonstrate a pathway by which p25/cdk5 increases the amyloidogenic processing of APP through STAT3-mediated transcriptional control of BACE1 that could have implications for AD pathogenesis. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:BOOK REVIEWS 249 larger sections of the work will be translated-preferably not from the Latin, but from the Arabic original. JOSEPHL. B~u Columbia University Commentary on the Metaphysics of Aristotle. By St. Thomas Aquinas. Trans. by John P. Rowan. (Chicago, Illinois: Henry Regnery Company, 1961. Pp. xxiii + 955.2 vols., boxed, $25.00.) Generally speaking, the two Summae of St. Thomas, long available in English translation, contain all that is (...) most personal and most profound in his philosophical thought. Nonetheless, it is quite impossible to get a fully adequate conception of St. Thomas' place in the history of western thought from a consideration of his theological writings alone. Hence, by translating St. Thomas' Commentary on the Metaphysics of Aristotle into English, Professor J. P. Rowan has provided the non-Latin reading student of the history of philosophy an invaluable service. For it is in his r61e as Aristotelian commentator that we see St. Thomas creating for the Schoolmen a version of Aristotle which served to render the Stagirite's thought into terms which became fundamental to the philosophical defense of Christianity. Further, by keeping in mind the fully-developed notions of St. Thomas on the existence of God and the nature of being as these are given us to understand in the Summae, the reader becomes better enabled, by a critical reading of Thomas' Commentary, to grasp the sense in which the Saint's theological writings are said by his enthusiasts to represent a "completing" and "perfecting" of Aristotle's thought. Professor Rowan's translation is based upon the Turin, 1950, edition of R. M. Spiazzi. This edition is itself fundamentally the older edition of M. R. Cathala, containing but few emendations. Although the translator was obliged to check Spiazzi occasionally against the Parma and Viv6s editions of Thomas' Opera Omnia, the usefulness of such consultation was, as Professor Rowan himself states, "limited inasmuch as both the editions of Viv~s and that of Cathala use Parma as their basic text" (p. vii). Further, since the edition from which he worked was not critical, Professor Rowan found it necessary in some instances to himself emend the reading of the Spiazzi text. However, where such alterations were made, and where indeed they were not obviously required, Professor Rowan indicated his iustification for the change in a footnote. It is unfortunate that no critical edition of Thomas' work was available to his translator; still, although a final evaluation of his emendations must, of course, attend the future appearance of a critical edition of Thomas' work, so far as we were able to judge, Professor Rowan's 250 HISTORY OF PHILOSOPHY changes were in all instances quite reasonable and well ]ustified. Professor Rowan has wisely included a translation of that version of the Aristotelian text upon which St. Thomas (in all probability) based his commentary. As this Latin version frequently departs from such currently available English translations as those of W. D. Ross, H. Tredennik, and others which are based upon Greek sources, a good deal of confusion as to Thomas' actual point of departure would have been introduced had this inclusion not been made. The general value and utility of Professor Rowan's work is further increased by his footnoted indications of the more important variations obtaining between the Greek text (as given in Bekker), and the Latin version employed by St. Thomas. For the reader who wishes to compare the Latin version, the Greek text, and the English translations, Professor Rowan has provided the standard Bekker reference numbers at the beginning of each of Thomas' Lectiones. To further simplify the whole matter of reference and cross-reference, Professor Rowan has used the letter C, followed by a numeral, to designate sections of Thomas' Commentary. These sections are the same as those established originally by Cathala. Numbers not preceded by C designate the appropriate sections of the Latin version of Aristotle's text, and correspond with those given by Spiazzi in his revision of the Cathala edition. Thus, as example, in such a reference as (241:C345), the first number designates the section of the version of Aristotle employed by St. Thomas, and the second, the section of St. Thomas... (shrink)

It is often said to-day that mathematics is nothing but an extension or development of logic; indeed, the identity of logic and pure mathematics is alleged so confidently by persons whose mathematical attainments entitle them to consideration when they talk about the subject-matter of mathematics, as to be in danger of being ranked with the truths that an educated man should accept on the authority of the specialist. Yet a little reflection might at least make one hesitate. For whatever else (...) may be said about logic, it is generally allowed to study thinking. Some would say merely that it studies inference; but inference is thinking. Now the mathematician thinks and infers, but he does not study the activity of thinking and inferring; and a study of that activity would never make the discoveries credited to the mathematicians. (shrink)

Is 'n transendentale kritiek religieus bepaald? deur V. Brümmer. -- Constitution and creativity in the philosophy of Edmund Husserl, by A. L. Conradie. -- Studium Generale, deur H. J. De Vleeschauwer. -- Sociology of law and its philosophical foundtions, by H. Dooyeweerd. -- Beginvrae en antwoorde in der Wysbegeerte, deur P. G. W. Du Plesis. -- Max Scheler's concern with the highest perfection, by S. I. M. Du Plessis. -- Christelike wetenskap, highest perfection, by S. I. M. Deu Plessis. -- (...) Christelike wetenskap, deur B. Duvenage. -- Malan's critical study, by H. Hart. -- Raakpunte vir 'n dialoog met 'n Christelike Wysbegeerte, deur A. M. T. Meyer. -- Nuwe gedagtes oor die begrip Natuurwet, deur A. H. Murray. -- Die voorwaardes vir die uitbou van 'n wysgerige antropologie, deur C. K. Oberholzer. -- De structuur van feit-en-betekenis, deur K. J. Popma. -- The relation of the arts to the presentation of the truth, by C. G. Seerveld. -- Gezag en vrijheid in het licht van Gods Woord, deur J. Stellingwerff. -- Voorveronderstellings vir 'n filosogie van die opvoeding, deur J. A. L. Taljaard. -- Objektiwiteit, sekularisasie en geskiedenis, deur N. T. Van der Merwe. -- Etiek: wetenskap van relasies, deur S. P. Van der Walt. -- Wetten en feiten, deur C. A. Van Peursen. -- Enige opmerkingen over entiteiten, deur H. Van Riessen. -- Richard Kroner on Herman Dooyeweerd, by C. Van Til. -- De mens in de taalkunde, deur P. A. Verburg, -- Enkele motieven van het anti-militair pacifisme, deur S, U. Zuidema. -- Publications of prof. dr. H. G. Stoker. Publikasies van prof. dr. H. G. Stoker (p. 303-311). (shrink)

Caplan & Waters's neuropsychological evidence for two types of verbal working memory rests entirely on a very restricted definition of “syntactic complexity,” one in terms of word order. This opens the possibility that the dissociation they observe relates to the differential use of word-order strategies rather than to the structure of verbal working memory.

Grodzinsky's theory of agrammatic sentence processing fails to account for crucial empirical facts. In contrast to his predictions, the data show that there are (1) degrees of severity and (2) problems with sentences that do not require movement, and that (3) under the right task circumstances, full-fledged syntactic trees are constructed.

First published in 1938. The aim of this book is to expound Kant’s _Critique of Judgement _by interpreting all the details in the light of what Kant himself declares to be his fundamental problem. _A Commentary on Kant’s Critique of Judgement _provides an excellent introduction to Kant’s third critique, and will be of interest to students of philosophy.

An English language translation accompanies the original Greek text of Aristotle's book about the nature of the state, constitutions, revolutions, democracy, and oligarchy.

First published in 2002. Routledge is an imprint of Taylor & Francis, an informa company.

'Uncertainty and chance' is a subject with a broad span, in that there is no academic discipline or walk of life that is not beset by uncertainty and chance. In this book a range of approaches is represented by authors from varied disciplines: natural sciences, mathematics, social sciences and medical sciences. At one extreme, this volume is concerned with the foundations of probability. At the other extreme, we have scholars who acknowledge the concept of chance and uncertainty but do not (...) cope with it by means of systematic measurement or quantative analysis. (shrink)