bluuebunny/crossref_metadata_2025_split huggingface dataset:
Small RNA combination therapy for lung cancer
Authors: Xue Wen , Dahlman James E. , Tammela Tuomas , Khan Omar F. , Sood Sabina , Dave Apeksha , Cai Wenxin , Chirino Leilani M. , Yang Gillian R. , Bronson Roderick , Crowley Denise G. , Sahay Gaurav , Schroeder Avi , Langer Robert , Anderson Daniel G. , Jacks Tyler 
Published: August 2014

Significance
Small RNAs can potently and precisely regulate gene expression; as a result, they have tremendous clinical potential. However, effective delivery of small RNAs to solid tumors has remained challenging. Here we report that a lipid/polymer nanoparticle can deliver small RNAs to treat autochthonous tumors in the so-called “KP” mouse model of lung cancer. Nanoparticles formulated with mimics of the p53-regulated miRNA miR-34a downregulated target genes and delayed tumor progression, while nanoparticles formulated with siRNA targeting Kirsten rat sarcoma viral oncogene homolog (siKras) slowed tumor growth and increased apoptosis. Notably, concurrent delivery of miR-34a and siKras increased anti-tumor effects, and led to tumor regression. These results demonstrate that small RNA therapies can impact solid lung tumor growth, and that targeted RNA combination therapies may be used to improve therapeutic response.
Quasi-resonant circulation regimes and hemispheric synchronization of extreme weather in boreal summer
Authors: Coumou Dim , Petoukhov Vladimir , Rahmstorf Stefan , Petri Stefan , Schellnhuber Hans Joachim 
Published: August 2014

SignificanceThe recent decade has seen an exceptional number of boreal summer weather extremes, some causing massive damage to society. There is a strong scientific debate about the underlying causes of these events. We show that high-amplitude quasi-stationary Rossby waves, associated with resonance circulation regimes, lead to persistent surface weather conditions and therefore to midlatitude synchronization of extreme heat and rainfall events. Since the onset of rapid Arctic amplification around 2000, a cluster of resonance circulation regimes is observed involving wave numbers 7 and 8. This has resulted in a statistically significant increase in the frequency of high-amplitude quasi-stationary waves with these wave numbers. Our findings provide important insights regarding the link between Arctic changes and midlatitude extremes.
Mapping of SUMO sites and analysis of SUMOylation changes induced by external stimuli
Authors: Impens Francis , Radoshevich Lilliana , Cossart Pascale , Ribet David 
Published: August 2014

Significance
Small ubiquitin-related modifier (SUMO) is a posttranslational modification essential for many functions in eukaryotic cells. A better understanding of the role of this ubiquitin-like modification, identification of proteins modified by SUMO, and knowledge of the exact sites of SUMO conjugation are critical but remain experimentally challenging. We have developed an innovative proteomic strategy allowing proteome-wide identification of SUMOylation sites and quantification of cell SUMOylation changes in response to diverse stimuli. Identification of yet unknown SUMO targets and characterization of SUMOylome alterations in response to environmental stresses, drugs, toxins, or bacterial and viral infections will help decipher previously unidentified roles of SUMOylation in cell physiology and disease.
Do Family Policies Matter for Educational Outcomes?
Authors: Crettaz Eric , Jacot Cédric 
Published: August 2014

ABSTRACT
The aim of this article is to shed some light on the impact of family policies on educational mobility; this link has been often debated, but rarely measured. Another aim of this contribution is to build a bridge between social mobility research and social policy analysis. We investigate whether the level of expenditure on family services in the 1980s and 1990s has had a positive impact on educational achievements and mobility in 11 European countries, by closely looking at a cohort of young adults aged 25–35. To this end, multilevel logistic regression models that control for other policies that have an impact on educational mobility are presented; fixed effects models are also provided. Our results suggest that, in terms of the likelihood of going to university, these policies seem to have reduced the gap between individuals whose parents are well educated, and those who have a more modest background.
Hydration of protein–RNA recognition sites
Authors: Barik Amita , Bahadur Ranjit Prasad 
Published: August 2014

AbstractWe investigate the role of water molecules in 89 protein–RNA complexes taken from the Protein Data Bank. Those with tRNA and single-stranded RNA are less hydrated than with duplex or ribosomal proteins. Protein–RNA interfaces are hydrated less than protein–DNA interfaces, but more than protein–protein interfaces. Majority of the waters at protein–RNA interfaces makes multiple H-bonds; however, a fraction do not make any. Those making H-bonds have preferences for the polar groups of RNA than its partner protein. The spatial distribution of waters makes interfaces with ribosomal proteins and single-stranded RNA relatively ‘dry’ than interfaces with tRNA and duplex RNA. In contrast to protein–DNA interfaces, mainly due to the presence of the 2′OH, the ribose in protein–RNA interfaces is hydrated more than the phosphate or the bases. The minor groove in protein–RNA interfaces is hydrated more than the major groove, while in protein–DNA interfaces it is reverse. The strands make the highest number of water-mediated H-bonds per unit interface area followed by the helices and the non-regular structures. The preserved waters at protein–RNA interfaces make higher number of H-bonds than the other waters. Preserved waters contribute toward the affinity in protein–RNA recognition and should be carefully treated while engineering protein–RNA interfaces.
Quantitative models for accelerated protein dissociation from nucleosomal DNA
Authors: Chen Cai , Bundschuh Ralf 
Published: August 2014

Abstract
Binding of transcription factors to their binding sites in promoter regions is the fundamental event in transcriptional gene regulation. When a transcription factor binding site is located within a nucleosome, the DNA has to partially unwrap from the nucleosome to allow transcription factor binding. This reduces the rate of transcription factor binding and is a known mechanism for regulation of gene expression via chromatin structure. Recently a second mechanism has been reported where transcription factor off-rates are dramatically increased when binding to target sites within the nucleosome. There are two possible explanations for such an increase in off-rate short of an active role of the nucleosome in pushing the transcription factor off the DNA: (i) for dimeric transcription factors the nucleosome can change the equilibrium between monomeric and dimeric binding or (ii) the nucleosome can change the equilibrium between specific and non-specific binding to the DNA. We explicitly model both scenarios and find that dimeric binding can explain a large increase in off-rate while the non-specific binding model cannot be reconciled with the large, experimentally observed increase. Our results suggest a general mechanism how nucleosomes increase transcription factor dissociation to promote exchange of transcription factors and regulate gene expression.
Molecular basis for the differential interaction of plant mitochondrial VDAC proteins with tRNAs
Authors: Salinas Thalia , El Farouk-Ameqrane Samira , Ubrig Elodie , Sauter Claude , Duchêne Anne-Marie , Maréchal-Drouard Laurence 
Published: August 2014

AbstractIn plants, the voltage-dependent anion-selective channel (VDAC) is a major component of a pathway involved in transfer RNA (tRNA) translocation through the mitochondrial outer membrane. However, the way in which VDAC proteins interact with tRNAs is still unknown. Potato mitochondria contain two major mitochondrial VDAC proteins, VDAC34 and VDAC36. These two proteins, composed of a N-terminal α-helix and of 19 β-strands forming a β-barrel structure, share 75% sequence identity. Here, using both northwestern and gel shift experiments, we report that these two proteins interact differentially with nucleic acids. VDAC34 binds more efficiently with tRNAs or other nucleic acids than VDAC36. To further identify specific features and critical amino acids required for tRNA binding, 21 VDAC34 mutants were constructed and analyzed by northwestern. This allowed us to show that the β-barrel structure of VDAC34 and the first 50 amino acids that contain the α-helix are essential for RNA binding. Altogether the work shows that during evolution, plant mitochondrial VDAC proteins have diverged so as to interact differentially with nucleic acids, and this may reflect their involvement in various specialized biological functions.
Drivers and Trajectories of Resistance to New First-Line Drug Regimens for Tuberculosis
Authors: Shrestha Sourya , Knight Gwenan M. , Fofana Mariam , Cohen Ted , White Richard G. , Cobelens Frank , Dowdy David W. 
Published: August 2014

Abstract
Background.  New first-line drug regimens for treatment of tuberculosis (TB) are in clinical trials: emergence of resistance is a key concern. Because population-level data on resistance cannot be collected in advance, epidemiological models are important tools for understanding the drivers and dynamics of resistance before novel drug regimens are launched.
Methods.  We developed a transmission model of TB after launch of a new drug regimen, defining drug-resistant TB (DR-TB) as resistance to the new regimen. The model is characterized by (1) the probability of acquiring resistance during treatment, (2) the transmission fitness of DR-TB relative to drug-susceptible TB (DS-TB), and (3) the probability of treatment success for DR-TB versus DS-TB. We evaluate the effect of each factor on future DR-TB prevalence, defined as the proportion of incident TB that is drug-resistant.
Results.  Probability of acquired resistance was the strongest predictor of the DR-TB proportion in the first 5 years after the launch of a new drug regimen. Over a longer term, however, the DR-TB proportion was driven by the resistant population's transmission fitness and treatment success rates. Regardless of uncertainty in acquisition probability and transmission fitness, high levels (&gt;10%) of drug resistance were unlikely to emerge within 50 years if, among all cases of TB that were detected, 85% of those with DR-TB could be appropriately diagnosed as such and then successfully treated.
Conclusions.  Short-term surveillance cannot predict long-term drug resistance trends after launch of novel first-line TB regimens. Ensuring high treatment success of drug-resistant TB through early diagnosis and appropriate second-line therapy can mitigate many epidemiological uncertainties and may substantially slow the emergence of drug-resistant TB.
Efficacy of Recombinant Human Interleukin 7 in a Patient With Severe Lymphopenia-Related Progressive Multifocal Leukoencephalopathy
Authors: Gasnault Jacques , de Goër de Herve Marie-Ghislaine , Michot Jean-Marie , Hendel-Chavez Houria , Seta Vannina , Mazet Anne-Aurélie , Croughs Thérèse , Stankoff Bruno , Bourhis Jean-Henri , Lambotte Olivier , Delfraissy Jean-François , Taoufik Yassine 
Published: August 2014

Abstract
In this study, we report the case of a patient with profound lymphopenia after allogenic bone marrow transplantation who developed severe progressive multifocal leukoencephalopathy. Single-agent recombinant human interleukin-7 therapy was associated with restoration of anti-John Cunningham polyomavirus (JCV) T-cell responses, JCV clearance from cerebrospinal fluid, and a dramatic clinical improvement.
The Distinctiveness of Soviet Culture
Authors: Brooks Jeffrey , Zhuk Sergei I. 
Published: August 2014

Abstract
The quintessentially Soviet element of cultural development in the USSR between 1932 and 1991 was Socialist Realism. The period prior to the 1930s was its preface and that from the mid-1950s a long post-script. By the mid-1980s, Soviet publics had moved irreversibly beyond Socialist Realism in all the arts, and no viable new contender could assume the particularist mantle. The best official offerings to compete with new Western movements after 1945 were too little and too late. In the absence of a viable particularist contender and with institutions of isolationism eroding, Soviet culture inexorably drew closer to its counterparts abroad. By 1991 it had been gone so long that its formal passing was hardly noticed.
Arithmetic Word Problem Solving and Mental Representations
Authors: Thevenot Catherine , Barrouillet Pierre 
Published: August 2014

Abstract
Arithmetic word problem solving is considered as a testing ground of mathematical achievement, but remains the area of mathematics in which students experience the greatest difficulties. In this chapter, we review recent theoretical and empirical work that could shed light on these difficulties. We first describe the most frequently used classifications of word problems and assess their psychological relevance. Then, we present the main hypotheses concerning the nature of the representations involved in word problems. Some theories assume that problem solving relies on the instantiation of schemas abstracted from recurrently encountered problems of the same relational structure, whereas other theories propose that ad hoc transient mental representations are constructed for each problem encountered. A third part is devoted to the impact of individual differences in calculation, reading comprehension, and more general factors, such as working memory capacity. Finally, we address the issue of enhancing performance in word problem solving.
Historical Perspectives of Sport-Related Concussion
Authors: De Marco Anthony P. , Barth Jeffrey T. 
Published: August 2014

Abstract
Evaluation and management of sport-related concussion have received much deserved attention in the wake of recent state legislation and congressional hearings centered on concussion management; however, neuropsychology as a field has been interested in the sequelae of concussive injuries for more than three decades. To provide the historical perspective of sport-related concussion, this chapter begins by exploring the shifts in concussion terminology. While clinically driven, societal and medicolegal influences have clearly exerted a force in shaping the clinical vernacular associated with brain injuries. After reviewing some of the more commonly referenced definitions of concussion proffered over the years, this chapter will examine the history of concussion evaluation and management from a sports neuropsychology perspective.
Computer Instrumentation Issues in Sport-Related Concussion Assessment
Authors: Schatz Philip 
Published: August 2014

Abstract
The clinical utility and psychometric properties of computer-based neuropsychological assessment measures have been widely discussed in the literature. Regardless of the outcomes of scholarly debates regarding these issues, computerized baseline testing of athletes has become a hallmark (if not “de rigeur”) component of concussion management programs. The current chapter discusses issues related to the equivalency of computer-based and paper-based neurocognitive assessment, methodological issues related to the use of computer-based neurocognitive assessments, and hardware and software issues related to the use of computer-based neurocognitive assessments.
The Five Percenters
Authors: Knight Michael Muhammad 
Published: August 2014

Abstract
This article focuses on the Five Percenters, also known as the Five Percent Nation or Nation of Gods and Earths (NGE), and how this movement has become a controversial movement with respect to its own relationship to Islam as well as Islam’s relationship to blackness. It first looks at the history of the Five Percenters, tracing its roots to 1960s New York and its link to the theology and theodicy of the Nation of Islam (NOI) and its radical reinterpretation of the NOI’s concept of godhood. It then examines the Five Percenters’ complex construction of Islam, which is often contested both in polemics with Muslims and within the movement itself. the chapter also discusses the movement’s exponential growth, first throughout New York City’s five boroughs and then in major cities throughout the country and even internationally. In addition, it considers the Five Percenters’ constructions of race, gender, and godhood. The article analyzes two distinct documents that are central to the movement, Supreme Mathematics and Supreme Alphabets, before concluding with an assessment of its contribution to hip-hop and rap music.
Transformation in Post-Tonal Music
Authors: Roeder John 
Published: August 2014

Abstract
Post-tonal music (loosely, most Western art-music compositions since the turn of the 20th century) manifests many organizational techniques but not the processes of harmony and counterpoint that direct and articulate time in tonal music. Of the diverse theories for explaining this music, the theory of musical transformations is especially productive. Not only does its notion of a transformational graph offer a powerful, hierarchical view of musical relationships, but it also embraces a processive attitude toward musical form that has broad applicability. This article identifies four specifically temporal aspects of transformational theory that have been neglected in the recent literature and demonstrates how they can inform understanding of a variety of post-tonal music much more recent than the modernist works to which the theory has mostly been applied. The demonstrations proceed through detailed analytical consideration of compositions by Kurtág, Adams, Adès, Sheng, Haas, and Saariaho.
Juvenile Justice in Poland
Authors: Krajewski Krzysztof 
Published: August 2014

AbstractThe juvenile justice system in Poland is an example of a paternalistic and welfare approach to juvenile justice. Special, nonpenal responsibility for juveniles applies for those between 13 and 17 years. For younger juveniles, special measures of exclusively educational and care character are possible. Indeterminate measures are child welfare oriented without any justice considerations. This includes the correctional center imposed in cases of most serious misbehavior. Waiver of juvenile jurisdiction is never automatic or mandatory and happens very seldom. Jurisdiction over all juvenile cases have special courts, and juvenile judges enjoy broad discretionary powers. Procedure used in juvenile cases constitutes a mix of criminal and civil procedure. One of the most hotly debated issues constitutes lack of sufficient procedural safeguards enjoyed by adult offenders. Despite this, recent amendments retain basic features of the system, although they also attempt to regulate better procedural guarantees of juveniles.
Branching and oscillations in the epigenetic landscape of cell-fate determination
Authors: Rabajante Jomar Fajardo , Babierra Ariel Lagdameo 
Published: August 2014

AbstractThe well-known Waddington’s epigenetic landscape of cell-fate determination is not static but varies because of the dynamic gene regulation during development. However, existing mathematical models with few state variables and fixed parameters are inadequate in characterizing the temporal transformation of the landscape. Here we simulate a decision-switch model of gene regulation with more than two state variables and with time-varying repression among regulatory factors. We are able to demonstrate multi-lineage differentiation at different timescales that portrays the branching canals in Waddington’s illustration. We also present a repressilator-type system that activates suppressed genes via sustained oscillations in a flattened landscape, hence providing an alternative scheme for cellular reprogramming. The time-dependent parameters governed by gradient-based dynamics regulate cell differentiation, dedifferentiation and transdifferentiation. Our prediction integrates the theories of branching and structural oscillations in cell-fate determination, which reveals key temporal patterns of cell differentiation and associated diseases, such as cancer.
A versatile two-step CRISPR- and RMCE-based strategy for efficient genome engineering inDrosophila
Authors: Zhang Xu , Koolhaas Wouter , Schnorrer Frank 
Published: August 2014

AbstractThe development of CRISPR/Cas9 technologies promises a quantum leap in genome-engineering of model organisms. However, CRISPR-mediated gene targeting reports inDrosophilaare still restricted to a few genes, use variable experimental conditions and vary in efficiency, questioning the universal applicability of the method. Here, we developed an efficient, two-step strategy to flexibly engineer the fly genome by combining CRISPR with recombinase-mediated cassette exchange (RMCE). In the first step, two sgRNAs, whose activity had been tested in cell culture, were co-injected together with a donor plasmid into transgenicAct5C-Cas9, Ligase4mutant embryos and the homologous integration events were identified by eye fluorescence. In the second step, the eye marker was replaced with DNA sequences of choice using RMCE enabling flexible gene modification. We applied this strategy to engineer four different loci, including a gene on the fourth chromosome, at comparably high efficiencies, suggesting that any fly lab can engineer their favourite gene for a broad range of applications within about three months.
Homocysteine and nitrite levels are modulated by MTHFR 677C>T polymorphism in obese women treated with simvastatin
Authors: Villela Maria P , Andrade Vanessa L , Eccard Bryelle , Jordão Alceu A , Sertório Jonas T , Tanus‐Santos Jose E , Silva Ieda FO , Silveira Josianne N , Sandrim Valéria C 
Published: August 2014

SummaryHigher homocysteine (Hcy) levels are associated with cardiovascular risk. The aim of the present study was to evaluate the effect of simvastatin treatment on circulating Hcy levels in obese women without hypertension, diabetes or dyslipidaemia; and to determine whether the 677C>T polymorphism located in methylenetetrahydrofolate reductase (NAD(P)H) (MTHFR) gene modulates the effects of this treatment on Hcy and nitrite (as a biomarker of nitric oxide (NO) bioavailability). Twenty‐five obese women (body mass index ≥ 30 kg/m2) who had received 20 mg/day simvastatin for 6 weeks were enrolled in the study. Venous blood samples were collected to measure plasma biomarkers and gene polymorphisms. Simvastatin treatment significantly reduced total cholesterol, low‐density lipoprotein–cholesterol, thiobarbituric acid‐reactive substances, high‐sensitivity C‐reactive protein and Hcy, whereas nitrite levels were increased. The reduction in Hcy levels in carriers of the T allele was −20.3% compared with –9.4% in patients with the CC genotype. Importantly, before treatment, nitrite levels were significantly higher in patients with the CC genotype compared with T allele carriers, whereas after treatment these levels were similar between groups. Our findings demonstrate that obese women without comorbidities and carrying the T variant of the 677C>T polymorphism of MTHFR exhibit benefits with simvastatin treatment, mainly in terms of increased NO levels.