bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two-Step Delivery: Exploiting the Partition Coefficient Concept to Increase Intratumoral Paclitaxel Concentrations In vivo Using Responsive Nanoparticles
Authors: Colby Aaron H. , Liu Rong , Schulz Morgan D. , Padera Robert F. , Colson Yolonda L. , Grinstaff Mark W. 
Published: January 2016

AbstractDrug dose, high local target tissue concentration and prolonged duration of exposure are essential criteria in achieving optimal drug performance. However, systemically delivered drugs often fail to effectively address these factors with only fractions of the injected dose reaching the target tissue. This is especially evident in the treatment of peritoneal cancers, including mesothelioma, ovarian and pancreatic cancer, which regularly employ regimens of intravenous and/or intraperitoneal chemotherapy (e.g., gemcitabine, cisplatin, pemetrexed and paclitaxel) with limited results. Here, we show that a “two-step” nanoparticle (NP) delivery system may address this limitation. This two-step approach involves the separate administration of NP and drug where, first, the NP localizes to tumor. Second, subsequent administration of drug then rapidly concentrates into the NP already stationed within the target tissue. This two-step method results in a greater than 5-fold increase in intratumoral drug concentrations compared to conventional “drug-alone” administration. These results suggest that this unique two-step delivery may provide a novel method for increasing drug concentrations in target tissues.
An authenticity survey of herbal medicines from markets in China using DNA barcoding
Authors: Han Jianping , Pang Xiaohui , Liao Baosheng , Yao Hui , Song Jingyuan , Chen Shilin 
Published: January 2016

AbstractAdulterant herbal materials are a threat to consumer safety. In this study, we used DNA barcoding to investigate the proportions and varieties of adulterant species in traditional Chinese medicine (TCM) markets. We used a DNA barcode database of TCM (TCMD) that was established by our group to investigate 1436 samples representing 295 medicinal species from 7 primary TCM markets in China. The results indicate that ITS2 barcodes could be generated for most of the samples (87.7%) using a standard protocol. Of the 1260 samples, approximately 4.2% were identified as adulterants. The adulterant focused on medicinal species such as Ginseng Radix et Rhizoma (Renshen), Radix Rubi Parvifolii (Maomeigen), Dalbergiae odoriferae Lignum (Jiangxiang), Acori Tatarinowii Rhizoma (Shichangpu), Inulae Flos (Xuanfuhua), Lonicerae Japonicae Flos (Jinyinhua), Acanthopanacis Cortex (Wujiapi) and Bupleuri Radix (Chaihu). The survey revealed that adulterant species are present in the Chinese market and these adulterants pose a risk to consumer health. Thus, regulatory measures should be adopted immediately. We suggest that a traceable platform based on DNA barcode sequences be established for TCM market supervision.
Antigenic mapping of an H9N2 avian influenza virus reveals two discrete antigenic sites and a novel mechanism of immune escape
Authors: Peacock Thomas , Reddy Kolli , James Joe , Adamiak Beata , Barclay Wendy , Shelton Holly , Iqbal Munir 
Published: January 2016

AbstractH9N2 avian influenza virus is a major cause of poultry production loss across Asia leading to the wide use of vaccines. Efficacy of vaccines is often compromised due to the rapid emergence of antigenic variants. To improve the effectiveness of vaccines in the field, a better understanding of the antigenic epitopes of the major antigen, hemagglutinin, is required. To address this, a panel of nine monoclonal antibodies were generated against a contemporary Pakistani H9N2 isolate, which represents a major Asian H9N2 viral lineage. Antibodies were characterized in detail and used to select a total of 26 unique ‘escape’ mutants with substitutions across nine different amino acid residues in hemagglutinin including seven that have not been described as antigenic determinants for H9N2 viruses before. Competition assays and structural mapping revealed two novel, discrete antigenic sites “H9-A” and “H9-B”. Additionally, a second subset of escape mutants contained amino acid deletions within the hemagglutinin receptor binding site. This constitutes a novel method of escape for group 1 hemagglutinins and could represent an alternative means for H9N2 viruses to overcome vaccine induced immunity. These results will guide surveillance efforts for arising antigenic variants as well as evidence based vaccine seed selection and vaccine design.
Fatigue-induced Orosomucoid 1 Acts on C-C Chemokine Receptor Type 5 to Enhance Muscle Endurance
Authors: Lei Hong , Sun Yang , Luo Zhumin , Yourek Gregory , Gui Huan , Yang Yili , Su Ding-Feng , Liu Xia 
Published: January 2016

AbstractUnderstanding and managing fatigue is a significant challenge in clinic and society. In attempting to explore how the body responds to and regulates fatigue, we found in rodent fatigue models that orosomucoid 1 (ORM1) was significantly increased in multiple tissues, including blood and muscle. Interestingly, administration of exogenous ORM1 increased muscle glycogen and enhanced muscle endurance, whereas ORM1 deficiency resulted in a significant decrease of muscle endurance both in vivo and in vitro, which could largely be restored by exogenous ORM1. Further studies demonstrated that ORM1 can bind to C-C chemokine receptor type 5 (CCR5) on muscle cells and deletion of the receptor abolished the effect of ORM1. Thus, fatigue upregulates the level of ORM1, which in turn functions as an anti-fatigue protein to enhance muscle endurance via the CCR5 pathway. Modulation of the level of ORM1 and CCR5 signaling could be a novel strategy for the management of fatigue.
A comprehensive characterization of simple sequence repeats in pepper genomes provides valuable resources for marker development in Capsicum
Authors: Cheng Jiaowen , Zhao Zicheng , Li Bo , Qin Cheng , Wu Zhiming , Trejo-Saavedra Diana L. , Luo Xirong , Cui Junjie , Rivera-Bustamante Rafael F. , Li Shuaicheng , Hu Kailin 
Published: January 2016

AbstractThe sequences of the full set of pepper genomes including nuclear, mitochondrial and chloroplast are now available for use. However, the overall of simple sequence repeats (SSR) distribution in these genomes and their practical implications for molecular marker development in Capsicum have not yet been described. Here, an average of 868,047.50, 45.50 and 30.00 SSR loci were identified in the nuclear, mitochondrial and chloroplast genomes of pepper, respectively. Subsequently, systematic comparisons of various species, genome types, motif lengths, repeat numbers and classified types were executed and discussed. In addition, a local database composed of 113,500 in silico unique SSR primer pairs was built using a homemade bioinformatics workflow. As a pilot study, 65 polymorphic markers were validated among a wide collection of 21 Capsicum genotypes with allele number and polymorphic information content value per marker raging from 2 to 6 and 0.05 to 0.64, respectively. Finally, a comparison of the clustering results with those of a previous study indicated the usability of the newly developed SSR markers. In summary, this first report on the comprehensive characterization of SSR motifs in pepper genomes and the very large set of SSR primer pairs will benefit various genetic studies in Capsicum.
Oxidative Dimerization of PHD2 is Responsible for its Inactivation and Contributes to Metabolic Reprogramming via HIF-1α Activation
Authors: Lee Gibok , Won Hyung-Sik , Lee Yoon-Mi , Choi Jae-Wan , Oh Taek-In , Jang Jeong-Hwa , Choi Dong-Kug , Lim Beong-Ou , Kim Young Jun , Park Jong-Wan , Puigserver Pere , Lim Ji-Hong 
Published: January 2016

AbstractProlyl hydroxylase domain protein 2 (PHD2) belongs to an evolutionarily conserved superfamily of 2-oxoglutarate and Fe(II)-dependent dioxygenases that mediates homeostatic responses to oxygen deprivation by mediating hypoxia-inducible factor-1α (HIF-1α) hydroxylation and degradation. Although oxidative stress contributes to the inactivation of PHD2, the precise molecular mechanism of PHD2 inactivation independent of the levels of co-factors is not understood. Here, we identified disulfide bond-mediated PHD2 homo-dimer formation in response to oxidative stress caused by oxidizing agents and oncogenic H-rasV12 signalling. Cysteine residues in the double-stranded β-helix fold that constitutes the catalytic site of PHD isoforms appeared responsible for the oxidative dimerization. Furthermore, we demonstrated that disulfide bond-mediated PHD2 dimerization is associated with the stabilization and activation of HIF-1α under oxidative stress. Oncogenic H-rasV12 signalling facilitates the accumulation of HIF-1α in the nucleus and promotes aerobic glycolysis and lactate production. Moreover, oncogenic H-rasV12 does not trigger aerobic glycolysis in antioxidant-treated or PHD2 knocked-down cells, suggesting the participation of the ROS-mediated PHD2 inactivation in the oncogenic H-rasV12-mediated metabolic reprogramming. We provide here a better understanding of the mechanism by which disulfide bond-mediated PHD2 dimerization and inactivation result in the activation of HIF-1α and aerobic glycolysis in response to oxidative stress.
Genome-wide identification of DNA methylation provides insights into the association of gene expression in rice exposed to pesticide atrazine
Authors: Lu Yi Chen , Feng Sheng Jun , Zhang Jing Jing , Luo Fang , Zhang Shuang , Yang Hong 
Published: January 2016

AbstractAtrazine (ATR) is a pesticide widely used for controlling weeds for crop production. Crop contamination with ATR negatively affects crop growth and development. This study presents the first genome-wide single-base-resolution maps of DNA methylation in ATR-exposed rice. Widespread differences were identified in CG and non-CG methylation marks between the ATR-exposed and ATR-free (control) rice. Most of DNA methyltransferases, histone methyltransferases and DNA demethylase were differentially regulated by ATR. We found more genes hypermethylated than those hypomethylated in the regions of upstream, genebody and downstream under ATR exposure. A stringent group of 674 genes (p < 0.05, two-fold change) with a strong preference of differential expression in ATR-exposed rice was identified. Some of the genes were identified in a subset of loss of function mutants defective in DNA methylation/demethylation. Provision of 5-azacytidine (AZA, inhibitor of DNA methylation) promoted the rice growth and reduced ATR content. By UPLC/Q-TOF-MS/MS, 8 degraded products and 9 conjugates of ATR in AZA-treated rice were characterized. Two of them has been newly identified in this study. Our data show that ATR-induced changes in DNA methylation marks are possibly involved in an epigenetic mechanism associated with activation of specific genes responsible for ATR degradation and detoxification.
Efficient OPSL-pumped mode-locked Yb:Lu2O3 laser with 67% optical-to-optical efficiency
Authors: Heuer Alexander M. , Saraceno Clara J. , Beil Kolja , Huber Günter , Kränkel Christian 
Published: January 2016

AbstractWe present a mode-locked Yb:Lu2O3 laser with up to 67% of optical-to-optical efficiency. By utilizing a high brightness optically pumped semiconductor laser (OPSL) as a pump source and using a semiconductor saturable absorber mirror (SESAM) we obtained self-starting mode locking. A pulse duration of 571 fs at 4.73 W of average output power with an optical-to-optical efficiency of 67% was achieved. In a slightly different cavity configuration the pulse duration was reduced to 313 fs at 2.16 W of average output power. In both cases the pulse duration was longer than the Fourier limit and the spectrum supports significantly shorter pulse durations. The laser wavelength is centered at 1034 nm and the repetition rate is 100.76 MHz in both cases. In continuous wave fundamental mode operation the optical-to-optical efficiency was as high as 78% with output powers exceeding 5 W.
Mycotoxins: cytotoxicity and biotransformation in animal cells
Authors: Wen Jikai , Mu Peiqiang , Deng Yiqun 
Published: January 2016

Abstract
Mycotoxins are secondary metabolites produced by many microfungi. Hitherto, over 300 mycotoxins with diverse structures have been identified. They contaminate most cereals and feedstuffs, which threaten human and animal health by exerting acute, sub-acute and chronic toxicological effects, with some considered as carcinogens. Many mycotoxins at low concentrations are able to induce the expression of cytochrome P450 and other enzymes implicated in the biotransformation and metabolization of mycotoxins in vivo and in vitro. Mycotoxins and their metabolites elicit different cellular disorders and adverse effects such as oxidative stress, inhibition of translation, DNA damage and apoptosis in host cells, thus causing various kinds of cytotoxicities. In this review, we summarize the biotransformation of mycotoxins in animal cells by CYP450 isoforms and other enzymes, their altered expression under mycotoxin exposure, and recent progress in mycotoxin cytotoxicity in different cell lines. Furthermore, we try to generalize the molecular mechanisms of mycotoxin effects in human and animal cells.
Capacities and Natures: An Exercise in Ontology
Authors: McMullin Ernan 
Published: January 2016

My task in writing a paper to accompany Milton Fisk's complex and provocative one is unusually difficult. His argument is so condensed and at such a high level of abstraction that I could easily devote my entire discussion to a single paragraph of his, to his very first one for example. Instead of doing this, I thought it would be more helpful to say something about the historical background from which his essay derives, and then go on to raise some difficulties regarding his central claim that nature is something over and above part and property. I will end with some suggestions on my own part as to how the categories of capacity and nature might best be related.But first it is worth asking: to whom is this paper addressed? Its language and general approach are not those to which readers of the philosophy of science are accustomed.
Notes on Lakatos
Authors: Kuhn Thomas S. 
Published: January 2016

The invitation which has brought me here to comment on Professor Lakatos’ paper has given me much pleasure, for I have long been an admirer of his work, particularly of his early four-part paper, ‘Proofs and Refutations’. That does not mean, of course, that we have often agreed, but I have enjoyed the arguments that resulted and looked forward to this one. My pleasure, furthermore, was considerably enhanced when I discovered that Lakatos was going to be able to confound all precedent, his own and others, by getting this paper to me well in advance. It is a privilege few commentators are given, and I am correspondingly grateful.All that I could have said before opening Lakatos’ manuscript — in fact, I did so in letters to both Lakatos and Roger Buck. Reading it has only increased my satisfaction, but in an unanticipated way.
On the Radical Incompleteness of the Manifest Image
Authors: van Fraassen Bas C. 
Published: January 2016

In my discussion of Sellars I have said as little as possible about my own position. But I think I should just mention that the descriptions of instrumentalists by Professors Sellars and Cornman do not fit me. That is why I would prefer the term “anti-realist”.To my mind, theoretical entities are fictions. To explain this, let me draw an analogy. Suppose someone writes a short story about a quarrel between a man and a cat. There may be or have been in the world, somewhere, a man and a cat who quarrelled, and who are by and large just like the characters in the story. This possibility is quite irrelevant to what the author is doing, and to our evaluation of the story. Of course, it keeps us from saying categorically that all short stories are false; but this too is quite irrelevant.
How Complex are Complex Systems?
Authors: Simon Herbert A. 
Published: January 2016

As it has turned out—and not, I think, by conscious design—this symposium has a truly Hegelian structure. The thesis and antithesis are provided by the themes of complexity and simplicity, respectively. Professor Nelson pleads the case for complexity, and I for simplicity; and we both count on Professor Suppes to propose the synthesis.Methods of characterizing the simplicity or complexity of systems are many. Let me mention some of them:(1) Systems that have many components may be considered complex relative to systems that have few. Hence the cardinality of a set may be taken as one measure of its complexity.(2) Systems in which there is much interdependence among the components are generally regarded as more complex than systems with less interdependence among components.(3) Systems that are undecidable may be regarded as complex in comparison with those that are decidable.
The Plurality of Science
Authors: Suppes Patrick 
Published: January 2016

What I have to say falls under four headings: What is unity of science, unity and reductionism, the search for certainty, and the search for completeness.To answer this initial question, I turned to the introductory essay by Otto Neurath for Volume 1, Part 1, of the International Encyclopedia of Unified Science. He begins this way:Unified science became historically the subject of this Encyclopedia as a result of the efforts of the unity of science movement, which includes scientists and persons interested in science who are conscious of the importance of a universal scientific attitude.The new version of the idea of unified science is created by the confluence of divergent intellectual currents. Empirical work of scientists was often antagonistic to the logical constructions of a priori rationalism bred by philosophico-religious systems; therefore, “empiricalizatlon” and “logicalization” were considered mostly to be in opposition—the two have now become synthesized for the first time in history (p. I).
The Formal and the Informal
Authors: Berkson William 
Published: January 2016

I became acquainted with Lakatos’s work in 1965 when I started studying at London School of Economics—where Lakatos taught. As his work was developed over the succeeding years until his death in 1974, one thing always puzzled me: his work seemed to contain such conflicting tendencies. He would continue developing his ideas along a progressive line, and suddenly would insert an element which appeared to me quite reactionary. By ‘reactionary’, I should hasten to add, I mean imbued with the spirit of Positivism—a person of different bias might reverse the labels!When I was given this opportunity to reflect again on Lakatos’s work I did not try to resolve the puzzle by looking into Lakatos’s intellectual history1; rather I attempted to separate clearly those aspects of Lakatos’s work which seemed to me driving in the right and the wrong directions. Both aspects concern the research program which has dominated both philosophy of science and philosophy of mathematics in the twentieth century.
Two Theories of Probability
Authors: Shafer Glenn 
Published: January 2016

In a recent monograph, I advocated a new theory—the theory of belief functions—as an alternative to the Bayesian theory of epistemic probability. In this paper I compare the two theories in the context of a simple but authentic example of assessing evidence.The Bayesian theory is ostensibly the theory that assessment of evidence should proceed by conditioning additive probability distributions; this theory dates from the work of Bayes and Laplace in the second half of the eighteenth century. It is indisputably the dominant theory of epistemic probability today.The theory of belief functions differs from the Bayesian theory in that it uses certain non-additive set functions in the place of additive probability distributions and in that it generalizes the rule of conditioning to a general rule for combining evidence. As a mathematical theory its apparent origin is rather recent and abrupt; it first appears in work of A. P. Dempster, published in the 1960’s.
The Philosophy of Progress…
Authors: Laudan Larry 
Published: January 2016

Philosophical dialogue is a curious activity. Arguments are expected to be rigorous, but no demand is made that there must be evidence for the premisses. Terminology is expected to be precise, but its appropriateness to the subject matter under discussion can be left unexplored. Officially, nothing is conceded; but, in fact, a great deal is taken for granted. Ad argumentum mingles indiscriminately with ad hominem; and, above all, the evidential warrant for one’s philosophical claims is, like the topics of sex and religion to the less enlightened, one of those delicate issues never to be discussed in mixed company.Such conventions as these that are associated with contemporary philosophical exchange make it difficult to have a balanced discussion about Progress and Its Problems. That work is, in the first instance, a descriptive model of theory change in science. It purports to establish what sorts of factors have in fact influenced scientific decision-making.
On the Reality of Chance
Authors: Vickers John M. 
Published: January 2016

In this paper I consider the question of the reality of chance. This is not what divides contemporary probabilists into the objective and subjective schools. That division is accomplished by the question whether there are objective grounds for the correctness of probability judgments. The subjectivists say that there need not be such grounds, and that probability judgments thus need not be empirically meaningful in the verificationist sense, or perhaps that they are not judgments at all, but rather expressions of attitude. (See [11], pp. 156-198). The objectivists say that the truth conditions for probability judgments are such as the frequencies of traits in populations or the existence of propensities. Objectivists and subjectivists are, however, agreed that there are no objective chances. (See [2], pp. 141, 142; and [12], §16).There is a Humean argument against the reality of chance which depends mainly upon the premise that we have no experience of it.
A Formal Statement of Schrödinger's Cat Paradox
Authors: McGrath James H. 
Published: January 2016

Schrödinger's argument about a “cat penned up in a steel chamber” is a timely challenge to those concerned with the philosophy of quantum theory; the argument prompts difficult decisions about correlated quantum mechanical systems, locality, reality and completeness. Here Schrödinger's own text is reproduced and, in view of the text, several plausible axioms and formal rules are chosen. Then, beginning with the axioms and using the rules, a contradiction is derived. This result establishes that Schrödinger's argument can be viewed as a paradox, a derivation of a contradiction from plausible assumptions. A final section of the paper refines the paradox and treats two possible resolutions as representative of a watershed issue in the foundations of quantum mechanics.Comments concerning the method of formalization were provided when I applied the method to the Einstein-Podolsky-Rosen argument (1978).
On Einstein's Invention of Special Relativity
Authors: Miller Arthur I. 
Published: January 2016

Albert Einstein distinguished sharply between the context of discovery and the context of invention. For example, in a letter of 6 January 1948 to Michele Besso, Einstein wrote:Mach's weakness, as I see it , lies in the fact that he believed more or less strongly, that science consists merely of putting experimental results in order; that is, he did not recognize the free constructive element in the creation of a concept. He thought that somehow theories arise by means of discovery [durch Entdeckung] and not by means of invention [nicht durch Erfindung]. (1972, p. 391, italics in original).By “invention” Einstein meant the mind's ability to leap across what he took to be the essential abyss between perceptions and data on the one side in order to create concepts and axioms on the other. Although sometimes Einstein interchanged the terms discovery and invention, he deemed invention to be the route of creative scientific thinking.