bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of lesion subtypes in biopsies of ductal carcinoma in situ of the breast using biomarker ratio imaging microscopy
Authors: Clark Andrea J. , Petty Howard R. 
Published: June 2016

AbstractAlthough epidemiological studies propose aggressive and non-aggressive forms of ductal carcinoma in situ (DCIS), they cannot be identified with conventional histopathology. We now report a retrospective study of human biopsy samples using biomarker ratio imaging microscopy (BRIM). Using BRIM, micrographs of biomarkers whose expression correlates with breast cancer aggressiveness are divided by micrographs of biomarkers whose expression negatively correlates with aggressiveness to create computed micrographs reflecting aggressiveness. The biomarker pairs CD44/CD24, N-cadherin/E-cadherin and CD74/CD59 stratified DCIS samples. BRIM identified subpopulations of DCIS lesions with ratiometric properties resembling either benign fibroadenoma or invasive carcinoma samples. Our work confirms the existence of distinct subpopulations of DCIS lesions, which will likely have utility in breast cancer research and clinical practice.
Superior bit error rate and jitter due to improved switching field distribution in exchange spring magnetic recording media
Authors: Suess D. , Fuger M. , Abert C. , Bruckner F. , Vogler C. 
Published: June 2016

AbstractWe report two effects that lead to a significant reduction of the switching field distribution in exchange spring media. The first effect relies on a subtle mechanism of the interplay between exchange coupling between soft and hard layers and anisotropy that allows significant reduction of the switching field distribution in exchange spring media. This effect reduces the switching field distribution by about 30% compared to single-phase media. A second effect is that due to the improved thermal stability of exchange spring media over single-phase media, the jitter due to thermal fluctuation is significantly smaller for exchange spring media than for single-phase media. The influence of this overall improved switching field distribution on the transition jitter in granular recording and the bit error rate in bit-patterned magnetic recording is discussed. The transition jitter in granular recording for a distribution of Khard values of 3% in the hard layer, taking into account thermal fluctuations during recording, is estimated to be a = 0.78 nm, which is similar to the best reported calculated jitter in optimized heat-assisted recording media.
Non integrative strategy decreases chromosome instability and improves endogenous pluripotency genes reactivation in porcine induced pluripotent-like stem cells
Authors: Congras Annabelle , Barasc Harmonie , Canale-Tabet Kamila , Plisson-Petit Florence , Delcros Chantal , Feraud Olivier , Oudrhiri Noufissa , Hadadi Eva , Griscelli Franck , Bennaceur-Griscelli Annelise , Turhan Ali , Afanassieff Marielle , Ferchaud Stéphane , Pinton Alain , Yerle-Bouissou Martine , Acloque Hervé 
Published: June 2016

AbstractThe pig is an emerging animal model, complementary to rodents for basic research and for biomedical and agronomical purposes. However despite the progress made on mouse and rat models to produce genuine pluripotent cells, it remains impossible to produce porcine pluripotent cell lines with germline transmission. Reprogramming of pig somatic cells using conventional integrative strategies remains also unsatisfactory. In the present study, we compared the outcome of both integrative and non-integrative reprogramming strategies on pluripotency and chromosome stability during pig somatic cell reprogramming. The porcine cell lines produced with integrative strategies express several pluripotency genes but they do not silence the integrated exogenes and present a high genomic instability upon passaging. In contrast, pig induced pluripotent-like stem cells produced with non-integrative reprogramming system (NI-iPSLCs) exhibit a normal karyotype after more than 12 months in culture and reactivate endogenous pluripotency markers. Despite the persistent expression of exogenous OCT4 and MYC, these cells can differentiate into derivatives expressing markers of the three embryonic germ layers and we propose that these NI-iPSLCs can be used as a model to bring new insights into the molecular factors controlling and maintaining pluripotency in the pig and other non-rodent mammalians.
The origin of the cooperativity in the streptavidin-biotin system: A computational investigation through molecular dynamics simulations
Authors: Liu Fengjiao , Zhang John Z. H. , Mei Ye 
Published: June 2016

AbstractPrevious experimental study measuring the binding affinities of biotin to the wild type streptavidin (WT) and three mutants (S45A, D128A and S45A/D128A double mutant) has shown that the loss of binding affinity from the double mutation is larger than the direct sum of those from two single mutations. The origin of this cooperativity has been investigated in this work through molecular dynamics simulations and the end-state free energy method using the polarized protein-specific charge. The results show that this cooperativity comes from both the enthalpy and entropy contributions. The former contribution mainly comes from the alternations of solvation free energy. Decomposition analysis shows that the mutated residues nearly have no contributions to the cooperativity. Instead, N49 and S88, which are located at the entry of the binding pocket and interact with the carboxyl group of biotin, make the dominant contribution among all the residues in the first binding shell around biotin.
HIF-1α and HIF-2α induced angiogenesis in gastrointestinal vascular malformation and reversed by thalidomide
Authors: Feng Nan , Chen Haiying , Fu Sengwang , Bian Zhaolian , Lin Xiaolu , Yang Li , Gao Yunjie , Fang Jingyuan , Ge Zhizheng 
Published: June 2016

AbstractThalidomide is used in clinical practice to treat gastrointestinal vascular malformation (GIVM), but the pathogenesis of GIVM is not clear. Hypoxia inducible factor 1 alpha (HIF-1α) and 2 alpha (HIF-2α/EPAS1) are in the same family and act as master regulators of the adaptive response to hypoxia. HIF-1α and HIF-2α are up-regulated in vascular malformations in intestinal tissues from GIVM patients, but not in adjacent normal vessels. Therefore, we investigated the role of HIF-1α and HIF-2α during angiogenesis and the mechanism of thalidomide action. In vitro experiments confirmed that vascular endothelial growth factor (VEGF) was a direct target of HIF-2α and that HIF-1α and HIF-2α regulated NOTCH1, Ang2 and DLL4, which enhanced vessel-forming of endothelial cells. Thalidomide down-regulated the expression of HIF-1α and HIF-2α and inhibited angiogenesis. In vivo zebrafish experiments suggested that HIF-2α overexpression was associated with abnormal subintestinal vascular (SIV) sprouting, which was reversed by thalidomide. This result indicated that thalidomide regulated angiogenesis via the inhibition of HIF-1α and HIF-2α expression, which further regulated downstream factors, including VEGF, NOTCH1, DLL4 and Ang2. The abnormally high expression of HIF-1α and HIF-2α may contribute to GIVM.
New GroEL-like chaperonin of bacteriophage OBP Pseudomonas fluorescens suppresses thermal protein aggregation in an ATP-dependent manner
Authors: Semenyuk Pavel I. , Orlov Victor N. , Sokolova Olga S. , Kurochkina Lidia P. 
Published: June 2016

Recently, we discovered and studied the first virus-encoded chaperonin of bacteriophage EL Pseudomonas aeruginosa, gene product (gp) 146. In the present study, we performed bioinformatics analysis of currently predicted GroEL-like proteins encoded by phage genomes in comparison with cellular and mitochondrial chaperonins. Putative phage chaperonins share a low similarity and do not form a monophyletic group; nevertheless, they are closer to bacterial chaperonins in the phylogenetic tree. Experimental investigation of putative GroEL-like chaperonin proteins has been continued by physicochemical and functional characterization of gp246 encoded by the genome of Pseudomonas fluorescens bacteriophage OBP. Unlike the more usual double-ring architecture of chaperonins, including the EL gp146, the recombinant gp246 produced by Escherichia coli cells has been purified as a single heptameric ring. It possesses ATPase activity and does not require a co-chaperonin for its function. In vitro experiments demonstrated that gp246 is able to suppress the thermal protein inactivation and aggregation in an ATP-dependent manner, thus indicating chaperonin function. Single-particle electron microscopy analysis revealed the different conformational states of OBP chaperonin, depending on the bound nucleotide.
Decoupled evolution of soft and hard substrate communities during the Cambrian Explosion and Great Ordovician Biodiversification Event
Authors: Buatois Luis A. , Mángano Maria G. , Olea Ricardo A. , Wilson Mark A. 
Published: June 2016

Significance
The majority of body plans were established during the Cambrian Explosion (CE), whereas the significant taxonomic increases during the Great Ordovician Biodiversification Event (GOBE) were manifest at lower taxonomic levels. Data on the diversity and disparity of bioturbation and bioerosion indicate that soft and hard substrate communities experienced decoupled evolution. Ichnofossil data indicate that rapid diversification of bioturbation occurred during the early early Cambrian (Fortunian) rather than during the late early Cambrian as indicated by shelly fossils. The first rapid increase in bioerosion took place during the GOBE approximately 80 My after the CE in bioturbation.
Credit assignment in movement-dependent reinforcement learning
Authors: McDougle Samuel D. , Boggess Matthew J. , Crossley Matthew J. , Parvin Darius , Ivry Richard B. , Taylor Jordan A. 
Published: June 2016

Significance
Thorndike's Law of Effect states that when an action leads to a desirable outcome, that action is likely to be repeated. However, when an action is not rewarded, the brain must solve a credit assignment problem: Was the lack of reward attributable to a bad decision or poor action execution? In a series of experiments, we find that salient motor error signals modulate biases in a simple decision-making task. This effect is independent of the participant’s sense of control, suggesting that the error information impacts behavior in an implicit and automatic manner. We describe computational models of reinforcement learning in which execution error signals influence, or gate, the updating of value representations, providing a novel solution to the credit assignment problem.
Highly variable individual donor cell fates characterize robust horizontal gene transfer of an integrative and conjugative element
Authors: Delavat François , Mitri Sara , Pelet Serge , van der Meer Jan Roelof 
Published: June 2016

Significance
DNA conjugation is a fascinating process that bestows the prokaryotic world with the ability to exchange hundreds of genes in a single event. What has long been puzzling is the low rate of horizontal gene transfer at the population level. Here, we develop a fluorescent tool to study the dynamic fate of a chromosomally located conjugative DNA. We find that donor cells becoming transfer proficient undergo highly variable cell fates, likely as a result of the conjugative element wreaking havoc in the cell. Modeling of the partnership between the cell and integrative and conjugative element (ICE) suggests that ICE fitness is optimal at low activation rates, explaining why gene transfer in bacterial populations occurs at low frequencies despite its ecological importance for adaptation.
Multidimensional structure-function relationships in human β-cardiac myosin from population-scale genetic variation
Authors: Homburger Julian R. , Green Eric M. , Caleshu Colleen , Sunitha Margaret S. , Taylor Rebecca E. , Ruppel Kathleen M. , Metpally Raghu Prasad Rao , Colan Steven D. , Michels Michelle , Day Sharlene M. , Olivotto Iacopo , Bustamante Carlos D. , Dewey Frederick E. , Ho Carolyn Y. , Spudich James A. , Ashley Euan A. 
Published: June 2016

Significance
Genetic variants in human β-cardiac myosin, which causes muscle contraction in the heart, can lead to hypertrophic cardiomyopathy (HCM), an inherited heart disease that can cause sudden death. New technologies have generated sequence data for large numbers of patients with HCM and unaffected individuals. In this study, we compare the protein structural locations of genetic variants of patients with HCM and the general population to identify spatial regions of the myosin that have a higher than expected proportion of genetic variants associated with HCM and earlier age at diagnosis. In addition, we develop new methods to interrogate the localization of genetic changes in protein structures. Our study demonstrates the power of combining clinical, genetic, and structural data to gain insight into Mendelian disease.
Descartes on Sensation
Authors: Vendler Zeno 
Published: June 2016

Contemporary readers of Descartes can hardly fail to notice that the author uses the word pensée, or cogitatio, in a much broader sense than French speakers use pensée nowadays, or we use the closest English word, thought. He consistently maintains that feelings, sensations, as well as the products of one's fancy, are one and all modes of thought.Yet, clearly, according to the normal use of the word, sensations of light, of sound, of hunger, and so forth, are not regarded as part of one's thinking, nor do we so regard the spontaneous flight of the imagination one might experience in daydreams or real dreams, or while thinking about unrelated matters. Some of these sensations, notably aches, pains, pangs of hunger, blinding light, and strong noise, are not only not counted among our thoughts, but they are apt to interfere with our thinking, and, in extreme cases, might stop it altogether. In a similar way, the lascivious play of St. Antony's imagination did not embellish his meditations on the holy mysteries; he had to overcome or ignore it to be able to pursue the train of his thought.
Lewis and Quine on Private Meanings and Subjectivism
Authors: Wilder Hugh T. 
Published: June 2016

In the early chapters of Mind and the World Order, Lewis develops a theory of meaning which has interesting points of similarity with that mentalistic or propositional theory of meaning which has been rejected by Quine, in Word and Object and elsewhere. There are also interesting similarities, however, between Lewis’ theory and Quine's own naturalistic theory. In this paper, I shall concentrate on one such similarity: namely, the analogy, noticed by Quine, between the predicament formulated in his own thesis of the indeterminacy of translation, and the “predicament of private worlds” in which Lewis’ theory of meaning is involved.These analogous predicaments have a bearing on the problems of the commensurability of scientific theories and of objectivity in science in general; in fact, my primary motivation in attempting to explicate the analogy between Quine's theory of meaning and Lewis’ theory is to clear the way for an assessment of Quine's position on the problem of the objectivity of theories in science.
Bodily Motions and Religious Feelings
Authors: Matthews Gareth B. 
Published: June 2016

For when men pray they do with the members of their bodies what befits suppliants—when they bend their knees and stretch out their hands, or even prostrate themselves, and whatever else they do visibly, although their invisible will and the intention of their heart is known to God. Nor does He need these signs for the human mind to be laid bare to Him. But in this way a man excites himself to pray more and to groan more humbly and more fervently. I do not know how it is that, although these motions of the body cannot come to be without a motion of the mind preceding them, when they have been made, visibly and externally, that invisible inner motion which caused them is itself strengthened. And in this manner the disposition of the heart which preceded them in order that they might be made, grows stronger because they are made. Of course if someone is constrained or even bound, so that he cannot do these things with his limbs, it does not follow that, when he is stricken with remorse, the inner man does not pray and prostrate himself before the eyes of God in his most secret chamber.(Augustine: De cura pro mortuis 5.7)One smiles and tells the expert chef how good the sauce béarnaise is, not so much to inform him about the sauce (he knows better than we do how good it is) as to assure him that we are enjoying it and that we appreciate his efforts. But when a man kneels in his pew and repeats a litany of thanksgiving it is not, it seems, that he means to be informing God of anything—not even of his thankfulness. For God, unlike the chef, has no need of information.
Retributive Justice
Authors: Ezorsky Gertrude 
Published: June 2016

Retributivists who proclaim our moral obligation to punish criminals have displayed, on their own behalf, a type of argumant which I shall call Moral Balance. There are three versions of Moral Balance. According to Moral Balance I, retaliatory punishment restores the equality disturbed by the criminal. Moral Balance II philosophers admire the proportion between morality and welfare which punishment can yield. Those who hold with Moral Balance Ill are fascinated by the equilibrium of social benefits and burdens set by punishment. All three versions are flawed as follows: they imply that crime is morally justified.Moral Balance 1: EqualityHegel informs us that:his (the criminal's action) is the action of a rational being and this implies that it is something universal and that by doing it the criminal has laid down a law which he has explicitly recognized in his action and under which in consequence he should be brought as under his right.
lfs and Cans -II
Authors: Pears D. F. 
Published: June 2016

The dispositional analysis of sentences ascribing powers and abilities to things and people runs into many difficulties. The situation is especially complex and confusing when such ascriptions are brought to bear on particular occasions, and carry some implication about the opportunities available on those occasions. Some of these difficulties are produced by superficial confusions, but I shall concentrate on those that beset any version of the dispositional analysis. Three difficulties will be examined, one presented by Lehrer, and two by Austin.Lehrer presents his difficulty as a refutation of Moore's dispositional analysis of “X could have acted otherwise”, which was “If X had chosen, he would have acted otherwise”. I shall introduce his objection by relating it to the distinctions drawn in Part I.· Expressed in my terminology, his point is that Moore's analysis presupposes that choosing is not an S-factor, and yet it might conceivably be an S-factor.
Presuppositions, Conditions, and Consequences
Authors: Govier Trudy 
Published: June 2016

An analysis of necessary condition and presupposition reveals that, as logical relations, these notions are basically similar to each other and different from the notion of entailment or other ‘if-then’ relations of logical consequence. Both necessary condition and presupposition seem to be two-directional in a rather peculiar way. Appreciating this is helpful in interpreting philosophers such as Kant and Strawson who have relied extensively on these relations in constructing the philosophical arguments often referred to as transcendental arguments. It also suggests some fundamental shortcomings in Strawson's account of presupposition and in the logician's way of presenting necessary condition using ‘⊂'.In the discussion which follows I shall exhibit some of the differences between necessary condition and presupposition on the one hand and entailment on the other. I shall then go on to offer an explanation of these differences in conjunction with an analysis of necessary condition and presupposition which diverges from other contemporaty accounts. Once these distinctions and explanations have been stated, I shall make some suggestions about their relevance to the interpretation and assessment of philosophical texts and arguments.
Mind-Brain Analogies
Authors: White Alan R. 
Published: June 2016

In the history of thought the relation between the mind and the body has been discussed in terms of various analogies. Plato, for example, examined the analogy of a man and his clothes and of the music of an instrument and the instrument itself; Aristotle advocated the analogy of an instrument's capacity and the instrument itself; Descartes alluded to that of a pilot and his ship; and Ryle derided that of a ghost and a machine.What I wish to discuss, however, are the analogies used by contemporary philosophers to explain their theory that the mind is the brain, that the mind's states, capacities and qualities are the brain's states, capacities and qualities, that our thoughts and our thinking are brain elements and brain movements and that our mental experiences, such as having images or sensations, are brain processes. Various analogies have been advanced to explain the sense in which one of the former is one of the latter.
Freedom And Plastic Control
Authors: Hannay Alastair 
Published: June 2016

In his Arthur Holly Compton Memorial Lecture Sir Karl Popper tackles a problem raised by Compton himself in an earlier lecture. The problem is to understand how such abstract things as aims, purposes, rules, or agreements can influence or control the movements of men, and perhaps also of animals (p. 15). To illustrate the problem Compton had remarked on the amazing faith and confidence shown by his audience and the lecture's organizer that he should arrive on the agreed date to give the lecture, considering ‘the great physical improbability that their confidence was justified’. ForIn the meanwhile my work called me to the Rocky Mountains and across the ocean to sunny Italy. A phototropic organism [such as I happen to be, would not easily] . . . tear himself away from there to go to chilly New Haven. Considered as a physical event, the probability of meeting my engagement would have been fantastically small.
True and False Speech in Plato's CRATYLUS 385 B-C
Authors: Pfeiffer W. M. 
Published: June 2016

In 385B-C of the Cratylus, Plato appears to be formulating a version of the correspondence theory of truth, in such a way that it applies not only to discourse, but to individual names as well. However commentators who have remarked on this passage, either take exception to the reasoning, or find it necessary to interpret the conclusion with qualifications that Plato never could have intended. Richard Robinson, for example, on p.328 of “A Criticism of Plato’s Cratylus”, sums up the argument thus:. . . since statements have a truthvalue, their parts, including names, must have a truthvalue too. Therefore names are true or false.and criticises it for involving a fallacy of division. Lorenz and Mittelstrasse, by contrast, construe the argument as validly proceeding from the true-false distinction of sentences to a corresponding true-false distinction of their parts.
What Follows from ‘I Promise ...’?
Authors: Martin Robert M. 
Published: June 2016

Searle’s famous attempt at what might loosely be called deriving ought from is has received much critical attention; but the main lines of attack on his attempt have been (as Searle himself has shown) irrelevant, mistaken, or otherwise defective. I shall here offer an account of what, I feel, really centrally has gone wrong with his attempt. I shall use the version of the derivation attempt which is found in Searle’s book, Speech Acts.The attempted derivation has, as its important steps, the following statements:S uttered the words, “I hereby promise to perform A for you, H.”S promised to perform A for H.S placed himself under a (prima facie) obligation to perform A for H.S is under a (prima facie) obligation to perform A for H.S ought (prima facie) to do A for H.