bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nanovesicles Based on Mixtures of a Biantennary Glycolipid with Ionic Co‐Surfactants
Authors: Mak Oi Wei , Seman Nursyafikah , Harun Nor Hamizah , Hussen Rusnah Syahila Duali , Rodzi Nasrulzamani Mohd , Heidelberg Thorsten 
Published: October 2015

AbstractA biantennary surfactant based on a synthetic C16‐maltoside was chosen to prepare vesicles for a potential vesicular drug delivery system. The synthesis comprised of three stages: Initial synthesis of β‐d‐maltose octaacetate was followed by glycosidation of 2‐hexyl‐decanol and final glycolipid deacetylation. Both α‐ and β‐anomers were prepared and their anomeric purity was evaluated by 1H NMR. Owing to the low water solubility of the glycolipid, addition of ionic co‐surfactants was believed to promote the surfactant distribution, thus leading to smaller and more uniform vesicles. The assembly behavior of the surfactant systems was studied by contact penetration under an optical polarizing microscope, while interfacial properties were determined by surface tension measurements. Vesicles were prepared by injection of an ethanolic solution into bulk water and investigated by dynamic light scattering and field emission scanning electron microscopy. Contact of the surfactant mixtures with water indicated a high tendency to exhibit the lamellar phase and confirmed the expected low molecular solubility. These findings suggest a potential of the surfactant to form stable vesicles. Injection of an ethanolic surfactant solution into bulk water gave sub‐micrometer sized vesicles with a narrow size distribution. Application of ionic co‐surfactants reduced the vesicle size. In particular ∼20 % of anionic SDS proved highly effective, lowering the vesicle size by nearly one decade, thus accessing nano‐sized vesicles. Encapsulation of a water‐soluble drug was achieved in a 76 ± 10 % efficiency.
Maternal age and outcome of preterm infants at discharge from the neonatal intensive care unit
Authors: Eventov‐Friedman Smadar , Zisk‐Rony Rachel Y. , Nosko Sophia , Bar‐Oz Benjamin 
Published: October 2015

AbstractObjectiveTo assess the effect of maternal age on preterm neonates' survival free from major morbidity at discharge from two neonatal intensive care units in Jerusalem, Israel.MethodsA retrospective chart review of two hospitals from 2009–2010 was performed. Eligible neonates were born at less than 35 weeks of gestation and survived to discharge. Major morbidity included at least one of the following: chronic lung disease, at least grade 3 intraventricular hemorrhage, periventricular leukomalacia, at least stage 3 retinopathy of prematurity, at least stage 2 necrotizing enterocolitis, or sepsis.ResultsThe analysis was performed on 380 neonates of 294 mothers. Mean maternal age was 30.5 years (range, 17–52), mean gestational age was 31.5 weeks (range, 24–34), and mean birth weight was 1705.5 g (range, 460–3150). Of the neonates, 90 (23.7%) had major morbidity, which was associated with lower mean gestational age (29.5 weeks vs 32.3 weeks, P < 0.001), birth weight (1326.5 g vs 1822.2 g, P < 0.001), and the need for resuscitation at birth (P < 0.001) in comparison with neonates without major morbidity. A comparison of maternal age between the two outcome groups yielded a nonsignificant result. A logistic regression model revealed that maternal age does not contribute significantly to poor neonatal outcomes.ConclusionAdvanced maternal age was not associated with major morbidity of preterm neonates at discharge from the neonatal intensive care units.
Chk1 phosphorylated at serine345 is a predictor of early local recurrence and radio‐resistance in breast cancer
Authors: Alsubhi Nouf , Middleton Fiona , Abdel-Fatah Tarek M.A. , Stephens Peter , Doherty Rachel , Arora Arvind , Moseley Paul M. , Chan Stephen Y.T. , Aleskandarany Mohammed A. , Green Andrew R. , Rakha Emad A. , Ellis Ian O. , Martin Stewart G. , Curtin Nicola J. , Madhusudan Srinivasan 
Published: October 2015

Radiation‐induced DNA damage activates the DNA damage response (DDR). DDR up‐regulation may predict radio‐resistance and increase the risk of early local recurrence despite radiotherapy in early stage breast cancers. In 1755 early stage breast cancers, DDR signalling [ATM, ATR, total Ckh1, Chk1 phosphorylated at serine345 (pChk1), Chk2, p53], base excision repair [PARP1, POLβ, XRCC1, FEN1, SMUG1], non‐homologous end joining (Ku70/Ku80, DNA‐PKcs) and homologous recombination [RAD51, BRCA1, γH2AX, BLM, WRN, RECQL5, PTEN] protein expression was correlated to time to early local recurrence. Pre‐clinically, radio‐sensitization by inhibition of Chk1 activation by ATR inhibitor (VE‐821) and inhibition of Chk1 (V158411) were investigated in MDA‐MB‐231 (p53 mutant) and MCF‐7 (p53 wild‐type) breast cancer cells. In the whole cohort, 208/1755 patients (11.9%) developed local recurrence of which 126 (61%) developed local recurrence within 5 years of initiation of primary therapy. Of the 20 markers tested, only pChk1 and p53 significantly associated with early local recurrence (p value = 0.015 and 0.010, respectively). When analysed together, high cytoplasmic pChk1‐nuclear pChk1 (p = 0.039), high cytoplasmic pChk1‐p53 (p = 0.004) and high nuclear pChk1‐p53 (p = 0.029) co‐expression remain significantly linked to early local recurrence. In multivariate analysis, cytoplasmic pChk1 level independently predicted early local recurrence (p = 0.025). In patients who received adjuvant local radiotherapy (n = 949), p53 (p = 0.014) and high cytoplasmic pChk1‐p53 (p = 0.017) remain associated with early local recurrence. Pre‐clinically, radio‐sensitisation by VE‐821 or V158411 was observed in both MCF‐7 and MDA‐MB‐231 cells and was more pronounced in MCF‐7 cells. We conclude that pChk1 is a predictive biomarker of radiotherapy resistance and early local recurrence.
Is a pure TIPS strategy truly risk free?
Authors: Haensly Paul J. 
Published: October 2015

AbstractA Treasury Inflation‐Protected Security (TIPS) is virtually risk free. As an obligation of the U.S. Treasury, it is mostly free of default risk. As an inflation‐indexed security held to maturity, it is risk free in terms of purchasing power. However, investing in a TIPS‐only portfolio for retirement is not risk free. This paper presents the results of a simulation analysis designed to evaluate the performance of a portfolio of inflation‐indexed Treasury coupon bonds. This study demonstrates that significant shortfall risk exists for TIPS‐only portfolios across a range of savings plans and the securities selection rules.
Properties, laws, and worlds
Authors: Smith Deborah C. 
Published: October 2015

AbstractJonathan Schaffer argues against a necessary connection between properties and laws. He takes this to be a question of what possible worlds we ought to countenance in our best theories of modality, counterfactuals, etc. In doing so, he unfairly rigs the game in favor of contingentism. I argue that the necessitarian can resist Schaffer’s conclusion while accepting his key premise that our best theories of modality, counterfactuals, etc. require a very wide range of things called ‘possible worlds’. However, the necessitarian can and should insist that, in many cases, these worlds are not metaphysically possible. I will further argue that, having taken such a stance, the necessitarian has additional resources to respond to Schaffer’s other arguments against the view.
Brief Intervention for Daily Marijuana Users Identified by Screening in Primary Care: A Subgroup Analysis of the ASPIRE Randomized Clinical Trial
Authors: Fuster Daniel , Cheng Debbie M. , Wang Na , Bernstein Judith A. , Palfai Tibor P. , Alford Daniel P. , Samet Jeffrey H. , Saitz Richard 
Published: October 2015

Background The use of brief intervention for decreasing frequent marijuana use holds potential, but its efficacy in primary care is not known. Methods Objective: To assess the impact of 2 brief interventions on marijuana use among daily/or almost daily marijuana users. Design: Subgroup analysis of a 3-arm randomized clinical trial of 2 brief counseling interventions compared with no brief intervention on daily marijuana use in a primary care setting (ASPIRE). Participants: ASPIRE study participants who both reported 21–30 days of marijuana use during the past month and identified marijuana as their drug of most concern. Interventions: (1) brief negotiated interview (BNI), a 10–15-minute structured interview, and (2) an adaptation of motivational interviewing (MOTIV), a 30–45-minute intervention. Control group participants received only a list of substance use treatment resources. Main measures: The primary outcome was number of days of marijuana use in the past 30 days at the 6-month follow-up. Secondary outcomes were (1) number of days of marijuana use at 6-week follow-up and (2) drug problems (Short Inventory of Problems—Drugs, SIP-D) at 6-week and 6-month follow-ups. Differences between intervention groups were analyzed using negative binomial regression models. Results Among the 167 eligible participants, we did not find any significant impact of either of the 2 interventions on past 30 days of marijuana use at 6 months (adjusted incidence rate ratio [aIRR]: 0.95, 95% confidence interval [CI]: 0.75–1.15, P = .82 for BNI vs. control; aIRR: 1.02, 95% CI: 0.85–1.23, P = .82 for MOTIV vs. control). There was no significant impact on drug-related problems at 6-month follow-up (aIRR: 1.12, 95% CI: 0.69–1.82, P = .66 and aIRR: 1.46, 95% CI: 0.89–2.38, P = .27 for BNI vs. control and MOTIV vs. control, respectively). Results were similar at 6 weeks. Conclusions Brief intervention has no apparent impact on marijuana use or drug-related problems among primary care patients with frequent marijuana use identified by screening.
Structural optimization of 10-methyl-aplog-1, a simplified analog of debromoaplysiatoxin, as an anticancer lead
Authors: Kikumori Masayuki , Yanagita Ryo C , Tokuda Harukuni , Suenaga Kiyotake , Nagai Hiroshi , Irie Kazuhiro 
Published: October 2015

Abstract
Aplog-1 is a simplified analog of debromoaplysiatoxin (DAT) with potent tumor-promoting and proinflammatory activities. Aplog-1 and DAT exhibited anti-proliferative activities against several human cancer cell lines, whereas aplog-1 did not have tumor-promoting nor proinflammatory activities. We have recently found 10-methyl-aplog-1 (1) to have strong anti-proliferative activity compared with aplog-1. To further investigate the structural factors involved in the tumor-promoting, proinflammatory, and anti-proliferative activities, two dimethyl derivatives of aplog-1 (2, 3) were synthesized, where two methyl groups were installed at positions 4 and 10 or 10 and 12. 10,12-Dimethyl-aplog-1 (2) had stronger inhibitory effects on the growth of several human cancer cell lines than 1 and DAT, but exhibited no tumor-promoting and proinflammatory activities. In contrast, 4,10-dimethyl-aplog-1 (3) displayed weak tumor-promoting and proinflammatory activities along with anti-proliferative activity similar to that of 1 and DAT. Compound 2 would be the optimized seed for anticancer drugs among the simplified analogs of DAT.
Relationship between physical activity, physical fitness and multiple metabolic risk in youths from Muzambinho's study
Authors: Barbosa João Paulo Dos Anjos Souza , Basso Luciano , Seabra André , Prista Antonio , Tani Go , Maia José António Ribeiro , Forjaz Cláudia Lúcia De Moraes 
Published: October 2015

AbstractNegative associations between physical activity (PA), physical fitness and multiple metabolic risk factors (MMRF) in youths from populations with low PA are reported. The persistence of this association in moderately‐to highly active populations is not, however, well established. The aim of the present study was to investigate this association in a Brazilian city with high frequency of active youths. We assessed 122 subjects (9.9 ± 1.3 years) from Muzambinho city. Body mass index, waist circumference, glycaemia, cholesterolaemia, systolic and diastolic blood pressures were measured. Maximal handgrip strength and one‐mile walk/run test were used. Leisure time PA was assessed by interview. Poisson regression was used in the analysis. The model explained 11% of the total variance. Only relative muscular strength and one‐mile walk/run were statistically significant (p < .05). Those who needed more time to cover the one‐mile walk/run test had an increased in metabolic risk of 11%, and those with greater strength reduced the risk by about 82%. In conclusion, children and youths from an active population who need less time to cover the one‐mile walk/run test or who had greater muscular strength showed a reduced metabolic risk. These results suggest that even in children and youths with high leisure time PA, a greater aerobic fitness and strength might help to further reduce their MMRF.
Observations of 6.7 GHz methanol masers with East-Asian VLBI Network. II. Internal proper motion measurement in G006.79−00.25
Authors: Sugiyama Koichiro , Fujisawa Kenta , Hachisuka Kazuya , Yonekura Yoshinori , Motogi Kazuhito , Sawada-Satoh Satoko , Matsumoto Naoko , Hirano Daiki , Hayashi Kyonosuke , Kobayashi Hideyuki , Kawaguchi Noriyuki , Shibata Katsunori M. , Honma Mareki , Hirota Tomoya , Murata Yasuhiro , Doi Akihiro , Ogawa Hideo , Kimura Kimihiro , Niinuma Kotaro , Chen Xi , Xia Bo , Li Bin , Sorai Kazuo , Momose Munetake , Saito Yu , Takaba Hiroshi , Omodaka Toshihiro , Kim Kee-Tae , Shen Zhiqiang 
Published: October 2015

Abstract
We detected internal proper motions of the methanol maser features at 6.7 GHz in a high-mass star-forming region G006.79−00.25 with the East-Asian VLBI Network. The spatial distribution of the maser features shows an elliptical morphology. The internal proper motions of 17 methanol maser features relative to the barycenter of the features were measured. The amplitude of the internal motions ranged from 1.30 to 10.25 km s−1. Most of the internal proper motions of the maser features seem to point counterclockwise along the elliptical morphology of the maser features. We applied the disk model, which includes both rotating and expanding components, to the observed positions, l.o.s. velocities, and proper motions. The derived rotation, expansion, and systemic velocities are $+3^{+2}_{-2}$, $+6^{+2}_{-2}$, and $+21^{+2}_{-2}\:$km s−1, respectively, at the radius of 1260 au on the disk with a position angle of the semi-major axis of − 140° and an inclination of 60°. The derived rotating motion suggests that the methanol maser emissions showing the elliptical spatial morphology possibly trace the rotating disk. The derived expanding motion might be caused by the magnetic-centrifugal wind on the disk, which was estimated on the basis of the typical magnetic field strength at emitting zones of a methanol maser.
Absence of left atrial stunning after cardioversion of recent-onset atrial fibrillation in patients at low-stroke risk
Authors: Antonielli Emanuele , Pizzuti Alfredo , Dogliani Sarah , Stasi Michele , Bassignana Antonia , Doronzo Baldassarre 
Published: October 2015

Objective
The aim of the present study was to evaluate the presence and degree of spontaneous echo contrast (SEC) in the left atrium and of left atrial appendage (LAA) contractility before and after cardioversion (CV) in patients with recent-onset atrial fibrillation (AF).

Methods
Our study included 56 patients divided into two groups: group 1, comprising 32 clinically stable patients who were admitted to the Emergency Department with less than or equal to 48 h duration AF, and who underwent transoesophageal echocardiography (TEE)-guided CV; and the control group (group 2), comprising 24 patients admitted to the Cardiological Department for elective TEE-guided CV of greater than 48 h AF. All patients underwent repeat TEE within 1 h after successful CV.

Results
Patients with recent-onset AF (group 1) showed no thrombogenic milieu at baseline without any evidence of atrial stunning after successful CV. SEC mean grade (0–3 grading) was 0.09±0.3 versus 0.12±0.4 after CV (P=0.98), and LAA flow velocity was 60.7±19.4 versus 56.7±20.5 cm/s after CV (P=0.07). Group 2 patients showed a significantly higher degree of SEC compared with those in group 1 (0.09±0.3 vs. 0.66±0.7, P=0.0093) and significantly lower LAA flow velocities (60.7±19.4 vs. 32.5±12.4, P<0.0001), with significant worsening after successful CV (SEC degree: 0.66±0.9 vs. 1.37±0.9, P=0.0093; LAA flow velocity: 32.5±12.4 vs. 20.4±12.7 cm/s, P<0.0001).

Conclusion
The absence of thrombogenic milieu and of left atrial stunning after CV in patients with recent-onset AF favours early CV without anticoagulation, at least in patients with a low thromboembolic risk profile. These patients could be discharged earlier from urgent care.
Cell-cell interactions and evolution using evolutionary game theory
Authors: Basanta David 
Published: October 2015

AbstractCancers arise from genetic abberations but also consistently display high levels of intra-tumor heterogeneity and evolve according to Darwinian dynamics. This makes evolutionary game theory an ideal tool in which to mathematically capture these cell-cell interactions and in which to investigate how they impact evolutionary dynamics. In this chapter we present some examples of how evolutionary game theory can elucidate cancer evolution.
Heterogeneity of Transcription Factor binding specificity models within and across cell lines
Authors: Sharmin Mahfuza , Corrada Bravo Héctor , Hannenhalli Sridhar 
Published: October 2015

AbstractComplex gene expression patterns are mediated by binding of transcription factors (TF) to specific genomic loci. Thein vivooccupancy of a TF is, in large part, determined by the TF’s DNA binding interaction partners, motivating genomic context based models of TF occupancy. However, the approaches thus far have assumed a uniform binding model to explain genome wide bound sites for a TF in a cell-type and as such heterogeneity of TF occupancy models, and the extent to which binding rules underlying a TF’s occupancy are shared across cell types, has not been investigated. Here, we develop an ensemble based approach (TRISECT) to identify heterogeneous binding rules of cell-type specific TF occupancy and analyze the inter-cell-type sharing of such rules. Comprehensive analysis of 23 TFs, each with ChIP-Seq data in 4-12 cell-types, shows that by explicitly capturing the heterogeneity of binding rules,TRISECTaccurately identifiesin vivoTF occupancy (93%) substantially improving upon previous methods. Importantly, many of the binding rules derived from individual cell-types are shared across cell-types and reveal distinct yet functionally coherent putative target genes in different cell-types. Closer inspection of the predicted cell-type-specific interaction partners provides insights into context-specific functional landscape of a TF. Together, our novel ensemble-based approach reveals, for the first time, a widespread heterogeneity of binding rules, comprising interaction partners within a cell-type, many of which nevertheless transcend cell-types. Notably, the putative targets of shared binding rules in different cell-types, while distinct, exhibit significant functional coherence.
The evolutionary advantage of heritable phenotypic heterogeneity
Authors: Carja Oana , Plotkin Joshua B. 
Published: October 2015

AbstractPhenotypic plasticity is an evolutionary driving force in diverse biological processes, including the adaptive immune system, the development of neoplasms, and the bacterial acquisition of drug resistance. It is essential, therefore, to understand the evolutionary advantage of an allele that confers cells the ability to express a range of phenotypes. Of particular importance is to understand how this advantage of phenotypic plasticity depends on the degree of heritability of non-genetically encoded phenotypes between generations, which can induce irreversible evolutionary changes in the population. Here, we study the fate of a new mutation that allows the expression of multiple phenotypic states, introduced into a finite population otherwise composed of individuals who can express only a single phenotype. We analyze the fixation probability of such an allele as a function of the strength of inter-generational phenotypic heritability, called memory, the variance of expressible phenotypes, the rate of environmental changes, and the population size. We find that the fate of a phenotypically plastic allele depends fundamentally on the environmental regime. In a constant environment, the fixation probability of a plastic allele always increases with the degree of phenotypic memory. In periodically fluctuating environments, by contrast, there is an optimum phenotypic memory that maximizes the probability of the plastic allele’s fixation. This same optimum value of phenotypic memory also maximizes geometric mean fitness, in steady state. We interpret these results in the context of previous studies in an infinite-population framework. We also discuss the implications of our results for the design of therapies that can overcome resistance, in a variety of diseases.
Distinct genomic and epigenomic features demarcate hypomethylated blocks in colon cancer
Authors: Sharmin Mahfuza , Corrada Bravo Héctor , Hannenhalli Sridhar 
Published: October 2015

AbstractBackground.Large mega base-pair genomic regions show robust alterations in DNA methylation levels in multiple cancers, a vast majority of which are hypo-methylated in cancers. These regions are generally bounded by CpG islands, overlap withLamin Associated DomainsandLarge organized chromatin lysine modifications,and are associated with stochastic variability in gene expression. Given the size and consistency ofhypo-methylated blocks (HMB)across cancer types, their immediate causes are likely to be encoded in the genomic region near HMB boundaries, in terms of specific genomic or epigenomic signatures. However, a detailed characterization of the HMB boundaries has not been reported.Method.Here, we focused on ~13k HMBs, encompassing approximately half the genome, identified in colon cancer. We analyzed a number of distinguishing features at the HMB boundaries including transcription factor (TF) binding motifs, various epigenomic marks, and chromatin structural features.Result.We found that the classical promoter epigenomic mark – H3K4me3, is highly enriched at HMB boundaries, as are CTCF bound sites. HMB boundaries harbor distinct combinations of TF motifs. Our Random Forest model based on TF motifs can accurately distinguish boundaries not only from regions inside and outside HMBs, but surprisingly, from active promoters as well. Interestingly, the distinguishing TFs and their interacting proteins are involved in chromatin modification. Finally, HMB boundaries significantly coincide with the boundaries ofTopologically Associating Domainsof the chromatin.Conclusion.Our analyses suggest that the overall architecture of HMBs is guided by pre-existing chromatin architecture, and are associated with aberrant activity of promoter-like sequences at the boundary.
Characterization of inner membrane protein YciB in Escherichia coli: YciB interacts with cell elongation and division proteins
Authors: Li Gaochi , Badaluddin Noor Afiza , Kitakawa Madoka 
Published: October 2015

ABSTRACTThe function of inner membrane protein YciB in Escherichia coli has not been identified. In this study, the membrane topology of the protein that contains five transmembrane domains was clarified. YciB was found to interact with various proteins involved in cell elongation and cell division using a bacterial two‐hybrid system. It was also found that the deletion mutant of yciB is susceptible to the low osmolarity. These observations together with previous reports indicate that YciB is involved in synthesis of the cell envelope by interacting with cell elongation and cell division complexes.