bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual ALK and CDK4/6 Inhibition Demonstrates Synergy against Neuroblastoma
Authors: Wood Andrew C. , Krytska Kateryna , Ryles Hannah T. , Infarinato Nicole R. , Sano Renata , Hansel Theodore D. , Hart Lori S. , King Frederick J. , Smith Timothy R. , Ainscow Edward , Grandinetti Kathryn B. , Tuntland Tove , Kim Sunkyu , Caponigro Giordano , He You Qun , Krupa Shiva , Li Nanxin , Harris Jennifer L. , Mossé Yaël P. 
Published: December 2016

Abstract
Purpose: Anaplastic lymphoma kinase (ALK) is the most frequently mutated oncogene in the pediatric cancer neuroblastoma. We performed an in vitro screen for synergistic drug combinations that target neuroblastomas with mutations in ALK to determine whether drug combinations could enhance antitumor efficacy.
Experimental Design: We screened combinations of eight molecularly targeted agents against 17 comprehensively characterized human neuroblastoma-derived cell lines. We investigated the combination of ceritinib and ribociclib on in vitro proliferation, cell cycle, viability, caspase activation, and the cyclin D/CDK4/CDK6/RB and pALK signaling networks in cell lines with representative ALK status. We performed in vivo trials in CB17 SCID mice bearing conventional and patient-derived xenograft models comparing ceritinib alone, ribociclib alone, and the combination, with plasma pharmacokinetics to evaluate for drug–drug interactions.
Results: The combination of ribociclib, a dual inhibitor of cyclin-dependent kinase (CDK) 4 and 6, and the ALK inhibitor ceritinib demonstrated higher cytotoxicity (P = 0.008) and synergy scores (P = 0.006) in cell lines with ALK mutations as compared with cell lines lacking mutations or alterations in ALK. Compared with either drug alone, combination therapy enhanced growth inhibition, cell-cycle arrest, and caspase-independent cell death. Combination therapy achieved complete regressions in neuroblastoma xenografts with ALK-F1174L and F1245C de novo resistance mutations and prevented the emergence of resistance. Murine ribociclib and ceritinib plasma concentrations were unaltered by combination therapy.
Conclusions: This preclinical combination drug screen with in vivo validation has provided the rationale for a first-in-children trial of combination ceritinib and ribociclib in a molecularly selected pediatric population. Clin Cancer Res; 23(11); 2856–68. ©2016 AACR.
Cyanate‐Impaired Angiogenesis: Association With Poor Coronary Collateral Growth in Patients With Stable Angina and Chronic Total Occlusion
Authors: Sun Jia Teng , Yang Ke , Mao Jing Yan , Shen Wei Feng , Lu Lin , Wu Qi Hong , Wang Yan Ping , Wu Li Ping , Zhang Rui Yan 
Published: December 2016

Background
Cyanate has recently gained attention for its role in the pathogenesis of vascular injury. Nonetheless, the effect of cyanate on angiogenesis remains unclear.

Methods and Results

In this study, we demonstrated that oral administration of cyanate impaired blood perfusion recovery in a mouse hind‐limb ischemia model. A reduction in blood perfusion recovery at day 21 was observed in the ischemic tissue of cyanate‐treated mice. Likewise, there were fewer capillaries in the ischemic hind‐limb tissue of cyanate‐exposed mice. Our in vitro study showed that cyanate, together with its carbamylated products, inhibited the migration, proliferation, and tube‐formation abilities of endothelial cells. Further research revealed that cyanate regulated angiogenesis partly by interrupting the vascular endothelial growth factor receptor 2/phosphatidylinositol 3‐kinase/Akt pathway. The serum concentrations of homocitrulline, a marker of cyanate exposure, were determined in 117 patients with stable angina and chronic total occlusion. Consistent with the antiangiogenic role of cyanate, homocitrulline levels were increased in patients with poor coronary collateralization (n=58) compared with those with high collateralization (n=59; 21.09±13.08 versus 15.54±9.02 ng/mL,
P
=0.009). In addition, elevated homocitrulline concentration was a strong predictor of poor coronary collateral growth.

Conclusions
Impaired angiogenesis induced by cyanate might contribute to poor coronary collateral growth.
Objectivity and the First Law of History Writing
Authors: Assis Arthur Alfaix 
Published: December 2016

Abstract
Cicero once stressed as the first law of history that “the historian must not dare to tell any falsehood.” This precept entails a minimal ethical requirement that remains unscathed by the whirlpools of epistemic relativism that have called many other aspects of professional historians’ practice into question in the last century or so. No commendable scholar seems willing to invalidate Cicero’s first law, and dependable scholarship—whether relying on objectivity-friendly or objectivity-hostile theoretical assumptions—follows shared standards of integrity and accuracy with which someone from Cicero’s time, for instance, would never be able to comply. In this essay, I suggest that those two circumstances should dispose us more favorably toward a refreshed notion of historical objectivity pointing not only to epistemology but also to professional ethics. I address the condemnation of lying and, more generally, historians’ commitment to sincerity as a way to highlight the ethical dimension of history writing. By focusing on the deep but underexplored moral roots of objectivity, I argue that this concept is still very useful as both an analytical tool and a normative ideal. Objectivity, in the sense I underline here, does not stand in opposition to subjectivity—on the contrary, it is actually tied up with subjective dispositions, virtues, and skills that help shape responsible historiography.
Historical Experience as a Mode of Comprehension
Authors: Díaz-Maldonado Rodrigo 
Published: December 2016

Abstract
In the past two and a half decades, Frank Ankersmit has developed a complex notion of historical experience. Despite its many virtues it has at least one major difficulty: it implies a sharp separation between experience and language. This essay aims to bridge this gap, while preserving the positive aspects of Ankersmit’s theory. To do this, I will first present the ontological and epistemological implications of Ankersmit’s notion of historical experience. Next, I will present my objections to his idea. Finally, I will propose two modifications to his notion of historical experience: first, in the epistemological sense by considering historical experience as a form of Louis Mink’s configurational comprehension and, second, in the ontological sense by relating historical experience with the vitalist ontology of José Ortega y Gasset.
Negation
Authors: Napoli Ernesto 
Published: December 2016

The paper is concerned with negation in artificial and natural languages. "Negation" is an ambiguous word. It can mean three different things: An operation(negating), an operator (a sign of negation), the result of an operation. The threethings, however, are intimately linked. An operation such as negation, is realizedthrough an operator of negation, i.e. consists in adding a symbol of negation to an entity to obtain an entity of the same type; and which operation it is dependson what it applies to and on what results from its application.
I argue that negation is not an operation on linguistic acts but rather anoperation on the objects of linguistic acts, namely sentences. And I assume that the negation of a sentence is a sentence that contradicts it. If so, the negation of a sentence may be obtained, in case the sentence is molecular, by applying the operation of negation not to the sentence itself but to a constituent sentence. To put it in a succinct and paradoxically sounding way we could say that in order to negate a sentence it is sufficient but not necessary to negate it.
However that negation applies to sentences is true only for artificial languages, in which the sign of negation is a monadic sentential connective. In natural language, negation applies to expressions other than sentences, namely word sand non-sentential phrases. Still words and not sentential phrases are interesting and valuable only as ultimate or immediate constituents of sentences, as a means of saying (something that can be true or false) and the concern with negation is ultimately the concern with the negation of sentences. So the problem is what sub-sentential and non sentential expressions negation should apply to in order to obtain the negation of the containing sentence. The standard answer is that the negation of a natural language sentence is equivalent to the negation of its predicate. Yet, I argue, predicate negation is necessary but not sufficient, due to the existence of molecular sentences.
Finally I notice that if to apply negation to an artificial sentence is to put the negation sign in front of it, to negate the predicate of a natural language sentencemay or may not be to put the negation sign in front of it.
Features of Concrete Deep Foundations Integrity Ultrasonic Testing in Russia
Authors: Харитонов  , Kharitonov Aleksandr 
Published: December 2016

Provision of the deep foundations quality is quite a challenge. Cross-hole pile integrity ultrasonic testing developed since 1970s’ is currently the most efficient and precise method to provide deep foundations quality monitoring. In the meantime, various standards, norms and regulations were created to control the application of this method.
This paper contains a comparative analysis of the current international standards referring to the pile integrity ultrasonic testing including the following aspects: preparation of and procedures for such testing, devices specifications, and the first-event time calculations. Various strong and weak approaches accepted in the standards of different countries have been analyzed.
Since all standards, norms and regulations are updated regularly, the analysis presented in the paper can be used as a reference to develop a local standard for the company authorized to carry out such tests.
Generations Sharing the Holocaust Experience
Authors: Hautzig Esther 
Published: December 2016

The author's feelings and experiences in sharing the Holocaust with her own children and the children she addresses regularly in schools are discussed in this paper. From her talks and exchanges with young people, it has been the author's experience that stories of how we lived, not perished, make the greatest impact on young and old listeners. Unless we know the people's lives and what the Jewish people, as well as society at large, lost through the deaths of countless brilliant, educated, compassionate people, as well as children whose futures will always remain unknown and unrealized, we cannot fully mourn their deaths. To really know what the world lost through the Nazi terror, we must share stories of family members and of people we knew and admired with those to whom Holocaust victims are becoming statistics and numbers, not individuals with vibrant lives and futures that were cut down.
Children particularly need to hear life stories of those who perished, not only the facts of how their lives ended. The author reports on sharing the Holocaust experience, not only with Jewish children, but with children of all religions, colors, ages and backgrounds-not only in person, but through correspondence, conference calls/ visits and classroom exchanges as a volunteer for the New York City School Volunteers Program in which she takes part.
Evaluation Of Exchange Reaction In Soil In Sediments Of A Region Affected By Anthropogenic Activity In Relation To The Time And To The Selected Potentially Toxic Elements
Authors: Urminská Jana , Václav Boris , Ondrišík Peter 
Published: December 2016

Abstract
The aim of this study was to analyse sediments of the selected water reservoirs of Piargs group. Secondly, our purpose was to determine values of exchange reactions in soil of these sediments during the period from 2001 to 2010 and to evaluate environmental hazards caused by the selected potentially toxic elements affected by pH. Based on the results gained by analysis we aim to determine the correlation and statistical significance of dependencies of the analysed environmental parameters. Two different methods, the flow electrochemical method and the atomic absorption spectrometric method have been used to analyse the content of potentially toxic chemical elements in leachate. The analysis of leachate samples, in order to find out the values of exchange reactions in soil, was carried out by potentiometry. Ascertained values of exchange reactions in soil ranged from 5.6 to 7.2. According to the calculated indices of dependencies, the development of pH/KCl values can be evaluated as moderately dynamic. The calculated indices of the Spearman‘s correlation coefficient for exchange reactions in soil demonstrate statistically significant dependence, especially for zinc and cadmium.
The Evaluation Of The Concentration Of Chlorides And Sulphates In Surface Water Of The National Nature Reserve Čičov Oxbow
Authors: Noskovič Jaroslav , Babošová Mária , Ivanič Porhajašová Jana , Čeryová Terézia 
Published: December 2016

Abstract
In the years 2013–2014 we evaluated changes in concentrations of chlorides and sulphates in waters of the National Nature Reserve Čičov oxbow depending on the time and place of sampling. Collections of samples were realized regularly at monthly intervals, always in the half of a month. Sampling sites were determined in order to assess the impact of natural and anthropogenic source of surface water quality. In order to evaluate the quality of surface water in the sampling sites by individual indicators, we used the values of the 90th percentile (P90), which was calculated from the measured values and then compared with their matching set of limit values referred to the Regulation of the Government of the Slovak Republic No. 269/2010 Coll. According to that Regulation, the recommended value for chlorides is 200 mg dm;; and for sulphates 250 mg dm−3. Based on the calculated values of 90th percentile (P90) of these indicators, we found out that the calculated characteristic values are lower.
The role of relative membrane capacitance and time delay in cerebellar Purkinje cells
Authors: Wang Jing , Liu Shenquan , Lu Bo , Zeng Yanjun 
Published: December 2016

Abstract
The membrane capacitance of a neuron can influence the synaptic efficacy and the speed of electrical signal propagation. Exploring the role of membrane capacitance will help facilitate a deeper understanding of the electrical properties of neurons. Thus, in this paper, we investigated the neuronal firing behaviors of a two-compartment model in Purkinje cells. We evaluated the influence of membrane capacitance under two different circumstances: in the absence of time delay and in the presence of time delay. Firstly, we separately studied the influence of somatic membrane capacitance Cs
and dendritic membrane capacitance Cd
on neuronal firing patterns. Through numerical simulation, we observed that they had two different types of period-adding scenarios, i.e. with and without chaotic bursting. Secondly, our results indicated that when the time delay was included in the model, periodic motions were more inclined to be destroyed, while at the same time, corresponding new chaotic motions were induced. These findings suggested that membrane capacitance and time delay play a pivotal functional role in modulating dynamical firing properties of neurons, especially aspects which lead to behaviors which result in changes to bursting patterns.
Physiologic changes of urinary proteome by caffeine and excessive water intake
Authors: Peerapen Paleerath , Ausakunpipat Nardtaya , Sutthimethakorn Suchitra , Aluksanasuwan Siripat , Vinaiphat Arada , Thongboonkerd Visith 
Published: December 2016

AbstractBackground:Diurnal variations and physiologic changes of urinary proteome have been suggested in the urinary proteomics field. However, no clear evidence has been demonstrated. The present study thus aimed to define changes in urinary proteome by physiological stimuli, i.e. caffeine intake and excessive water drinking, both of which cause physiologic diuresis.Methods:Urine samples were collected from 30 healthy individuals under three different conditions: (i) morning void as the control; (ii) after drinking a cup of coffee; and (iii) after drinking 1 L of water within 20 min. Thereafter, differentially excreted proteins were analyzed by 2-DE proteomics approach and validated by Western blotting and ELISA.Results:Spot matching, quantitative intensity analysis, and ANOVA followed by Tukey’s post-hoc multiple comparisons and the Bonferroni correction revealed significant differences in levels of five protein spots among three different conditions. These proteins were identified by quadrupole time-of-flight mass spectrometry (Q-TOF MS) and/or MS/MS analyses as kininogen 1 isoform 3, β-actin, prostaglandin D synthase (PGDS), fibrinogen α-chain and immunoglobulin light chain. Among these, the decreased level of immunoglobulin was successfully validated by Western blotting and ELISA.Conclusions:These data indicated that caffeine intake and excessive water drinking could affect urinary excretion of some proteins and may affect urinary proteome analysis.
The impact of admission neutrophil-to-platelet ratio on in-hospital and long-term mortality in patients with infective endocarditis
Authors: Wei Xue-biao , Liu Yuan-hui , He Peng-cheng , Yu Dan-qing , Tan Ning , Zhou Ying-ling , Chen Ji-yan 
Published: December 2016

Abstract

Background:
Infective endocarditis (IE) is associated with increased neutrophil and reduced platelet counts. We assessed the relationship between the neutrophil-to-platelet ratio (NPR) on admission and adverse outcomes in patients with IE.

Methods:
Patients diagnosed with IE between January 2009 and July 2015 (n=1293) were enrolled, and 1046 were finally entered into the study. Study subjects were categorized into four groups according to NPR quartiles: Q1<18.9 (n=260); Q2: 18.9–27.7 (n=258); Q3: 27.7–43.3 (n=266); and Q4>43.3 (n=262). Cox proportional hazards regression was performed to identify risk factors for long-term mortality; the optimal cut-off was evaluated by receiver operating characteristic curves.

Results:
Risk of in-hospital death increased progressively with NPR group number (1.9 vs. 5.0 vs. 9.8 vs. 14.1%, p<0.001). The follow-up period was a median of 28.8 months, during which 144 subjects (14.3%) died. Long-term mortality increased from the lowest to the highest NPR quartiles (7.6, 11.8, 17.4, and 26.2%, respectively, p<0.001). Multivariate Cox proportional hazard analysis revealed that lgNPR (HR=2.22) was an independent predictor of long-term mortality. Kaplan-Meier survival curves showed that subjects in Q4 had an increased long-term mortality compared with the other groups.

Conclusions:
Increased NPR was associated with in-hospital and long-term mortality in patients with IE. As a simple and inexpensive index, NPR may be a useful and rapid screening tool to identify IE patients at high risk of mortality.
microRNAs in lipoprotein and lipid metabolism: from biological function to clinical application
Authors: Desgagné Véronique , Bouchard Luigi , Guérin Renée 
Published: December 2016

AbstractmicroRNAs (miRNAs) are short (~22 nucleotides), non-coding, single-stranded RNA molecules that regulate the expression of target genes by partial sequence-specific base-pairing to the targeted mRNA 3′UTR, blocking its translation, and promoting its degradation or its sequestration into processing bodies. miRNAs are important regulators of several physiological processes including developmental and metabolic functions, but their concentration in circulation has also been reported to be altered in many pathological conditions such as familial hypercholesterolemia, cardiovascular diseases, obesity, type 2 diabetes, and cancers. In this review, we focus on the role of miRNAs in lipoprotein and lipid metabolism, with special attention to the well-characterized miR-33a/b, and on the huge potential of miRNAs for clinical application as biomarkers and therapeutics in the context of cardiometabolic diseases.
A Study on Chinese Students’ Acquisition of English Articles and Interlanguage Syntactic Impairment
Authors: Qihao Xu , Yunzhang Shi , Neal Snape 
Published: December 2016

Abstract
This study investigated the resetting process of the articles’ parameters by Chinese English learners with a Forced Choice Elicitation Task on the basis of the Article Choice Parameter and Fluctuation Hypothesis proposed by Ionin, Ko and Wexler (2004). It was found that Chinese English learners fluctuate between definiteness and specificity, the two parameter-settings of articles. Our findings are consistent with the Fluctuation Hypothesis. Their performance can be accounted for under the theoretical framework of Distributed Morphology. The difficulty in article acquisition lies in the fact that Chinese English learners can not easily identify the correct features in the specification of syntactic terminal nodes as well as the vocabulary items, but they possess the syntactic knowledge and they can access the definiteness parameter setting with enough L2 input. Chinese English learners’ interlanguage syntax is not impaired and UG full access is supported.
Using schema theory to support a whole-word approach to phonological acquisition
Authors: Sowers-Wills Sara 
Published: December 2016

AbstractEarly child phonological acquisition data typically contain exceptional phonetic forms that defy segment-based rules and have long challenged traditional theoretical frameworks. The templatic approach to phonological acquisition claims that whole-word phonotactic patterns emerge as the first primary units of representation, later giving way to segmental knowledge. This approach places importance on the relationships among a child’s forms in addition to those between child forms and their corresponding adult targets. Inscribed within dynamic systems theory, the templatic approach assumes a developing phonological system to be self-organizing and driven by general cognitive processes in response to patterns in the ambient language. This paper analyzes data from a diary study of one monolingual child acquiring American English. Data collected during the first six months of word production were put to templatic analysis, then examined for evidence of schematic structure. Incorporating the chronology of utterances the child produced, analysis revealed varying degrees of abstraction as early patterns integrated with newer patterns. The results reveal schema theory to be an informative supplementary framework for templatic analysis. Schema theory provides a structured way to trace the emergence and interaction of whole-word patterns a child uses to facilitate the production of first words.
The development of the right of self-realisation in the Netherlands
Authors: Groen Lisanne 
Published: December 2016

AbstractThe term “self-realisation” is not defined in any Dutch legal provision, but has emerged from case law based on the Expropriation Act. This article describes the development of the right of self-realisation in the Netherlands. In addressing this subject, the article presents a brief historical overview of the Dutch land policy and land policy instruments. In addition, Royal Decrees and case law about the right of self-realisation are discussed.