bluuebunny/crossref_metadata_2025_split huggingface dataset:
APPROPRIATE CAUSAL MODELS AND THE STABILITY OF CAUSATION
Authors: HALPERN JOSEPH Y. 
Published: January 2016

AbstractCausal models defined in terms of structural equations have proved to be quite a powerful way of representing knowledge regarding causality. However, a number of authors have given examples that seem to show that the Halpern–Pearl (HP) definition of causality (Halpern & Pearl, 2005) gives intuitively unreasonable answers. Here it is shown that, for each of these examples, we can give two stories consistent with the description in the example, such that intuitions regarding causality are quite different for each story. By adding additional variables, we can disambiguate the stories. Moreover, in the resulting causal models, the HP definition of causality gives the intuitively correct answer. It is also shown that, by adding extra variables, a modification to the original HP definition made to deal with an example of Hopkins & Pearl (2003) may not be necessary. Given how much can be done by adding extra variables, there might be a concern that the notion of causality is somewhat unstable. Can adding extra variables in a “conservative” way (i.e., maintaining all the relations between the variables in the original model) cause the answer to the question “Is X = x a cause of Y = y?” to alternate between “yes” and “no”? It is shown that we can have such alternation infinitely often, but if we take normality into consideration, we cannot. Indeed, under appropriate normality assumptions. Adding an extra variable can change the answer from “yes’ to “no”, but after that, it cannot change back to “yes”.
Peter J. Webster Receives 2015 International Award
Authors:   AGU
Published: January 2016

Peter J. Webster received the 2015 International Award at the American Geophysical Union Fall Meeting Honors Ceremony, held on 16 December 2015 in San Francisco, Calif. The award honors "an individual scientist, group, or a small team for making an outstanding contribution to furthering the Earth and space sciences and using science for the benefit of society in developing nations."
Autophosphorylation at Thr279 of Entamoeba histolytica atypical kinase EhAK1 is required for activity and regulation of erythrophagocytosis
Authors: Mansuri M Shahid , Babuta Mrigya , Ali Mohammad Sabir , Bharadwaj Ravi , jhingan Gagan Deep , Gourinath Samudrala , Bhattacharya Sudha , Bhattacharya Alok 
Published: January 2016

AbstractPhagocytosis plays a key role in survival and pathogenicity of Entamoeba histolytica. We have recently demonstrated that an atypical kinase EhAK1 is involved in phagocytosis in this parasite. It is recruited to the phagocytic cups through interaction with EhCaBP1. EhAK1 manipulates actin dynamics by multiple mechanisms including phosphorylation of G-actin. Biochemical analysis showed that EhAK1 is a serine/threonine kinase with broad ion specificity and undergoes multiple trans-autophosphorylation. Three autophosphorylation sites were identified by mass spectrometry. Out of these Thr279 appears to be involved in both autophosphorylation as well as substrate phosphorylation. Over expression of the mutant Thr279A inhibited erythrophagocytosis showing dominant negative phenotype. Multiple alignments of different kinases including alpha kinases displayed conserved binding sites that are thought to be important for function of the protein. Mutation studies demonstrated the importance of some of these binding sites in kinase activity. Binding studies with fluorescent-ATP analogs supported our prediction regarding ATP binding site based on sequence alignment. In conclusion, EhAK1 has multiple regulatory features and enrichment of EhAK1 at the site of phagocytosis stimulates trans-autophosphorylation reaction that increases kinase activity resulting in enhanced actin dynamics and phagocytosis. Some of the properties of EhAK1 are similar to that seen in alpha kinases.
Ozone-induced IL-17A and neutrophilic airway inflammation is orchestrated by the caspase-1-IL-1 cascade
Authors: Che Luanqing , Jin Yan , Zhang Chao , Lai Tianwen , Zhou Hongbin , Xia Lixia , Tian Baoping , Zhao Yun , Liu Juan , Wu Yinfang , Wu Yanping , Du Jie , Li Wen , Ying Songmin , Chen Zhihua , Shen Huahao 
Published: January 2016

AbstractOzone is a common environmental air pollutant leading to respiratory illness. The mechanisms regulating ozone-induced airway inflammation remain poorly understood. We hypothesize that ozone-triggered inflammasome activation and interleukin (IL)-1 production regulate neutrophilic airway inflammation through IL-17A. Pulmonary neutrophilic inflammation was induced by extended (72 h) low-dose (0.7 ppm) exposure to ozone. IL-1 receptor 1 (Il1r1)−/−, Il17a−/− mice and the caspase-1 inhibitor acetyl-YVAD-chloromethylketone (Ac-YVAD-cmk) were used for in vivo studies. Cellular inflammation and protein levels in bronchial alveolar lavage fluid (BALF), cytokines and IL-17A-producing γδT-cells, as well as mitochondrial reactive oxygen species (ROS), mitochondrial DNA (mtDNA) release and inflammasome activation in lung macrophages were analyzed. Ozone-induced neutrophilic airway inflammation, accompanied an increased production of IL-1β, IL-18, IL-17A, Granulocyte-colony stimulating factor (G-CSF), Interferon-γ inducible protein 10 (IP-10) and BALF protein in the lung. Ozone-induced IL-17A production was predominantly in γδT-cells and Il17a-knockout mice exhibited reduced airway inflammation. Lung macrophages from ozone-exposed mice exhibited higher levels of mitochondrial ROS, enhanced cytosolic mtDNA, increased caspase-1 activation and higher production of IL-1β. Il1r1-knockout mice or treatment with Ac-YVAD-cmk decreased the IL-17A production and subsequent airway inflammation. Taken together, we demonstrate that ozone-induced IL-17A and neutrophilic airway inflammation is orchestrated by the caspase-1-IL-1 cascade.
Irisin promotes osteoblast proliferation and differentiation via activating the MAP kinase signaling pathways
Authors: Qiao Xiaoyong , Nie Ying , Ma Yaxian , Chen Yan , Cheng Ran , Yin Weiyao , Hu Ying , Xu Wenming , Xu Liangzhi 
Published: January 2016

AbstractPhysical exercise is able to improve skeletal health. However, the mechanisms are poorly known. Irisin, a novel exercise-induced myokine, secreted by skeletal muscle in response to exercise, have been shown to mediate beneficial effects of exercise in many disorders. In the current study, we demonstrated that irisin promotes osteoblast proliferation and increases the expression of osteoblastic transcription regulators, such as Runt-related transcription factor-2, osterix/sp7; and osteoblast differentiation markers, including alkaline phosphatase, collagen type 1 alpha-1, osteocalcin and osteopontin in vitro. Irisin also increase ALP activity and calcium deposition in cultured osteoblast. These osteogenic effects were mediated by activating the p38 mitogen-activated protein kinase (p-p38 MAPK) and extracellular signal-regulated kinase (ERK). Inhibition of p38 MAPK by SB203580 or pERK by U0126 abolished the proliferation and up-regulatory effects of irisin on Runx2 expression and ALP activity. Together our observation suggest that irisin directly targets osteoblast, promoting osteoblast proliferation and differentiation via activating P38/ERK MAP kinase signaling cascades in vitro. Whether irisin can be utilized as the therapeutic agents for osteopenia and osteoporosis is worth to be further pursued
Crystal structures of Mycobacterium tuberculosis HspAT and ArAT reveal structural basis of their distinct substrate specificities
Authors: Nasir Nazia , Anant Avishek , Vyas Rajan , Biswal Bichitra Kumar 
Published: January 2016

AbstractAminotransferases of subfamily Iβ, which include histidinol phosphate aminotransferases (HspATs) and aromatic amino acid aminotransferases (ArATs), are structurally similar but possess distinct substrate specificities. This study, encompassing structural and biochemical characterisation of HspAT and ArAT from Mycobacterium tuberculosis demonstrates that the residues lining the substrate binding pocket and N-terminal lid are the primary determinants of their substrate specificities. In mHspAT, hydrophilic residues in the substrate binding pocket and N-terminal lid allow the entry and binding of its preferential substrate, Hsp. On the other hand, the hydrophobic nature of both the substrate binding pocket and the N-terminal lid of mArAT is responsible for the discrimination of a polar substrate such as Hsp, while facilitating the binding of Phe and other aromatic residues such as Tyr and Trp. In addition, the present study delineates the ligand induced conformational rearrangements, providing insights into the plasticity of aminotransferases. Furthermore, the study also demonstrates that the adventitiously bound ligand 2-(N-morpholino)ethanesulfonic acid (MES) is indeed a specific inhibitor of HspAT. These results suggest that previously untapped morpholine-ring scaffold compounds could be explored for the design of new anti-TB agents.
Mathematical modelling of transcriptional heterogeneity identifies novel markers and subpopulations in complex tissues
Authors: Wang Niya , Hoffman Eric P. , Chen Lulu , Chen Li , Zhang Zhen , Liu Chunyu , Yu Guoqiang , Herrington David M. , Clarke Robert , Wang Yue 
Published: January 2016

AbstractTissue heterogeneity is both a major confounding factor and an underexploited information source. While a handful of reports have demonstrated the potential of supervised computational methods to deconvolute tissue heterogeneity, these approaches require a priori information on the marker genes or composition of known subpopulations. To address the critical problem of the absence of validated marker genes for many (including novel) subpopulations, we describe convex analysis of mixtures (CAM), a fully unsupervised in silico method, for identifying subpopulation marker genes directly from the original mixed gene expressions in scatter space that can improve molecular analyses in many biological contexts. Validated with predesigned mixtures, CAM on the gene expression data from peripheral leukocytes, brain tissue and yeast cell cycle, revealed novel marker genes that were otherwise undetectable using existing methods. Importantly, CAM requires no a priori information on the number, identity, or composition of the subpopulations present in mixed samples and does not require the presence of pure subpopulations in sample space. This advantage is significant in that CAM can achieve all of its goals using only a small number of heterogeneous samples and is more powerful to distinguish between phenotypically similar subpopulations.
Probing Intersubunit Interfaces in AMPA-subtype Ionotropic Glutamate Receptors
Authors: Yelshanskaya Maria V. , Saotome Kei , Singh Appu K. , Sobolevsky Alexander I. 
Published: January 2016

AbstractAMPA subtype ionotropic glutamate receptors (iGluRs) mediate the majority of fast neurotransmission across excitatory synapses in the central nervous system. Each AMPA receptor is composed of four multi-domain subunits that are organized into layers of two amino-terminal domain (ATD) dimers, two ligand-binding domain (LBD) dimers, transmembrane domains and carboxy-terminal domains. We introduced cysteine substitutions at the intersubunit interfaces of AMPA receptor subunit GluA2 and confirmed substituted cysteine crosslink formation by SDS-PAGE. The functional consequence of intersubunit crosslinks was assessed by recording GluA2-mediated currents in reducing and non-reducing conditions. Strong redox-dependent changes in GluA2-mediated currents were observed for cysteine substitutions at the LBD dimer-dimer interface but not at the ATD dimer-dimer interface. We conclude that during gating, LBD dimers undergo significant relative displacement, while ATD dimers either maintain their relative positioning, or their relative displacement has no appreciable effect on AMPA receptor function.
Remarks on Explanatory Power
Authors: Jeffrey Richard C. 
Published: January 2016

The idea of using information-theoretical concepts to quantify the notion of explanatory power of theories is an attractive one. Where the theory is adequately represented by a probability measure p on Boolean algebra A of propositions, it is natural to think of measuring explanatory power by some function of H(A), the entropy or uncertainty of p. But recently, Greeno and others have been exploring measures of explanatory power which are suggested by more detailed representations of theories - representations which are themselves suggested by communication-theoretical analogies.To avoid inessential complications, suppose that the Boolean algebra A is finite, and let ‘a’ range over the atoms of A, viz., the strongest propositions in A which are not logically false. (Any two atoms are logically incompatible, and any proposition in A is expressible as a disjunction of atoms.) Then we havewhere we set p(a) logp(a)=0 in case p(a)=0.
Tachyons, Backwards Causation, and Freedom
Authors: Fitzgerald Paul 
Published: January 2016

‘Tachyons’ are hypothetical faster-than-light particles. Their existence has been suspected and sought, on the ground that they appear to be compatible with the laws of nature, particularly with Special Relativity, and so there is at least some likelihood that they exist. That last mad inferential leap is justified by the experience of particle physicists, summed up in ‘Gell-Mann's totalitarian principle’ that “whatever is not forbidden is compulsory.” Experimental searches made so far have failed to find them.The classical reason for ruling out faster-than-light particles has been that according to Special Relativity an infinite force would be required to accelerate a particle up to and beyond the speed of light. For if the particle's rest mass mo is greater than zero, then its relativistic mass, given by the formulaapproaches infinity as the particle's velocity v approaches c, the speed of light.
The Structure, Growth and Application of Scientific Knowledge: Reflections on Relevance and the Future of Philosophy of Science
Authors: Giere Ronald N. 
Published: January 2016

I would like to make it clear at the outset that this paper is not about a problem in the philosophy of science; it is about the philosophy of science itself. Furthermore, the discussion will not be confined to developments internal to philosophy of science but will include considerations of external factors and their possible relations to the philosophy of science. The justification for this departure from standard practice is simply that the issues to be discussed seem to be enough on many peoples’ minds to justify bringing them out into the public arena.There is no need to dwell on the all too familiar external factors labeled by well-known catch phrases such as ‘over-population’, ‘pollution’, ‘violence’, ‘runaway technology’, ‘social disintegration’, etc., etc. Although one may debate their precise nature and speculate on their eventual relative significance, the seriousness of these problems, especially in conjunction, can hardly be doubted.
Two Kinds of Theory in the Social Sciences
Authors: Morrison Paul G. 
Published: January 2016

In one sense, not every science of social phenomena qualifies as a social science, but only one which investigates the structure of one or more entire societies or cultures. It is within this context, perhaps, that historical linguistics, despite its central concern with an important variety of socially transmitted behavior and its largely deductive character, is less often classified with the social sciences than with the humanities.From a broader standpoint, however, one may construe as a social science any science which investigates a complex of human behavior, attitude and belief that is transmitted, maintained, modified or discontinued through interpersonal influence. If the social sciences are understood in this broad sense, it is possible to distinguish two kinds of theory at work in them. On one hand, we may discern theories of social phenomena which function in deductive-nomothetic explanation. A typical example is the theory of the evolution of the Indo-European languages.
Elsasser, Generalized Complementarity, and Finite Classes: A Critique of his Anti-Reductionism
Authors: Kauffman Stuart 
Published: January 2016

Serious students of cellular and developmental biology confront what may well be the gravest epistemological problems ever faced by scientists. These are direct consequences of the immense, ordered biochemical complexity of organisms.One of the most extensive discussions of the epistemological problems confronting cell biologists has been supplied by Elsasser, whose views have had a rather wide audience [1, 2]. Elsasser is greatly to be admired for his insistence that biologists confront the epistemological problems of their science, and for his efforts to analyze those problems, which he feels center in our incapacity to know the quantum microstate of an organism. While I am sympathetic with his effort, I feel he misconstrues the epistemological consequences of our failure to know completely the organism's quantum microstates.
Randomness
Authors: Kyburg Henry E. 
Published: January 2016

Mr. Coffa's admirable and lucid exposition of the history of mathematical randomness, leaves, to my mind, nothing to be desired. I am not sure whether, or how, its end result is of use to the theoretically minded statistician, but it is certainly interesting enough in its own right to need no excuse.I tend also to agree wholeheartedly with Mr. Coffa's treatment of physical randomness, or at least with his conclusion. I can easily imagine that he will not have succeeded in convincing those who are sure that epistemology is built into physics - say in quantum mechanics - but he has certainly given even these people some food for thought. I can even swallow the peroration of his last paragraph whole, and agree that one might hope and expect that physics can make its claims without a reference to knowledge or to randomness.
Kant, the Dynamical Tradition, and the Role of Matter in Explanation
Authors: Buroker Jill Vance 
Published: January 2016

Both the history of science and the history of philosophy demonstrate that different explanations of nature are motivated by different assumptions about what types of things need to be explained and what types of things are capable of explaining them. The view that diversity must be explained, for example, decrees that what is most fundamental is the immutable, and that diverse features of nature arise from essentially unchanging elements. This sort of view is best illustrated in atomistic theories where the characteristics of objects of our experience are ultimately accounted for in terms of the varying configurations and motions of indestructible atoms.When we examine physical theories in order to determine what assumptions lead philosophers to value some aspects of nature as more fundamental than others, we will find that the focal point for these underlying assumptions is the concept of matter expounded in the theory.
The Operation Called Verstehen: Towards a Redefinition of the Problem
Authors: McCarthy Thomas 
Published: January 2016

One of the more constant elements in the ‘legacy of logical positivism’ has been a rather low estimate of the importance of the concept of Verstehen for a logic of the social sciences. To be sure, it has been the accepted practice among philosophers under the influence of this movement that any extended treatment of the logic of the social sciences include an analysis of the role of Verstehen. But these analyses have almost invariably taken the form of a whittling down to size of an outsized concept with, it is often noted, rather suspicious origins in German metaphysical thought.Apart from the philosophical arguments advanced, there are a number of historical considerations which throw some light on the sceptical attitude of the logical positivists and of their descendants towards the idea of a procedure peculiar to the social sciences.
Bressan and Suppes on Modality
Authors: Van Fraassen Bas C. 
Published: January 2016

Professors Bressan and Suppes have both argued that modality is of great importance to the philosophy of science. I shall not dispute this, but I shall raise some problems of interpretation, which arise if one considers the possibility of a philosophical retrenchment with respect to the use of modal concepts.Professor Bressan uses the discussion initiated by Mach's attempted definition of mass as a paradigm example of the use of modal concepts in foundational work in physics. He mentions the modal terms used in informal axiomatizations of mechanics which followed Mach, and explains how mass is defined in his own formalized axiomatic mechanics.On the other hand, in his book Introduction to Logic, Professor Suppes had said unequivocally that he knew of no problem in philosophy of science to which modality is relevant.
Explanation and Subsumption
Authors: Cummins Robert 
Published: January 2016

Quine once claimed that modal logic derived from a use-mention mistake (p. 196). In this paper, I will peddle an, equally outrageous claim: the thesis that subsumption is an essential goal of fundamental explanatory theorizing rests on a failure to distinguish explaining what made x happen from explaining why we believe what we do about what made x happen. I don't mean to suggest that the distinction wasn't noticed (except perhaps by Hume); only that it wasn't vigorously enforced. There have always been philosophers who assimilated a belief to its justification with malice aforethought.Everyone knows that subsumption is not sufficient for explanation: the length of a pendulum is not explained by appeal to its period and the pendulum law, and emission spectra are not explained by Balmer's formula. But the spirit of the deductive-nomological account of explanation lives on in the belief that subsumption is an essential feature of an explanatory theory.
Grades of Organization and the Units of Selection Controversy
Authors: Richardson Robert C. 
Published: January 2016

R. C. Lewontin (1970) proposed three criteria as jointly sufficient for a unit of evolutionary change and immediately went on to argue that selection could operate simultaneously at a variety of levels of organization. For natural selection to operate on a unit, there must be variation in the objects in question: natural selection “chooses” between alternatives, so there must be different alternatives. This variation must affect fitness: the variation available must create different probabilities of reproductive success. Third, this variation in fitness must be heritable: there must be a correlation between parents and offspring for the traits yielding variation in fitness. In brief, for there to be evolution by natural selection, there must be heritable variation in fitness.Among the concerns that might be raised over Lewontin's formula, one is particularly important. It was clearly brought out by Williams (1966) and is emphasized by Elliott Sober (1981).
Models, High-Energy Theoretical Physics and Realism
Authors: Cushing James T. 
Published: January 2016

Let me say at the outset that the following exercise is an attempt to make some sense out of what I have seen my colleagues (and indeed at times myself) doing in science - more particularly in theoretical high-energy physics. I do not claim that my conclusions are final or permanent. In fact, it appears to me that Professor MacKinnon's new book, Scientific Explanation and Atomic Physics, may; present a suitable framework within which to discuss the issues raised here. In any event, since most of this paper consists of a story to be told, it may be of interest to philosophers of science.Today I shall use developments In the field of theoretical high-energy physics to examine three issues of interest to the philosophy of science. First will be the use of highly abstract, formal models, in the generation and evolution of theories.