bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantification of Somatic Chromosomal Rearrangements in Circulating Cell-Free DNA from Ovarian Cancers
Authors: Harris Faye R. , Kovtun Irina V. , Smadbeck James , Multinu Francesco , Jatoi Aminah , Kosari Farhad , Kalli Kimberly R. , Murphy Stephen J. , Halling Geoffrey C. , Johnson Sarah H. , Liu Minetta C. , Mariani Andrea , Vasmatzis George 
Published: July 2016

AbstractRecently, the use of a liquid biopsy has shown promise in monitoring tumor burden. While point mutations have been extensively studied, chromosomal rearrangements have demonstrated greater tumor specificity. Such rearrangements can be identified in the tumor and subsequently detected in the plasma of patients using quantitative PCR (qPCR). In this study we used a whole-genome mate-pair protocol to characterize a landscape of genomic rearrangements in the primary tumors of ten ovarian cancer patients. Individualized tumor-specific primer panels of aberrant chromosomal junctions were identified for each case and detected by qPCR within the cell-free DNA. Selected chromosomal junctions were detected in pre-surgically drawn blood in eight of the ten patients. Of these eight, three demonstrated the continued presence of circulating tumor DNA (ctDNA) post-surgery, consistent with their documented presence of disease, and in five ctDNA was undetectable in the post-surgical blood collection, consistent with their lack of detectable disease. The ctDNA fraction was calculated using a novel algorithm designed for the unique challenges of quantifying ctDNA using qPCR to allow observations of real-time tumor dynamics. In summary, a panel of individualized junctions derived from tumor DNA could be an effective way to monitor cancer patients for relapse and therapeutic efficacy using cfDNA.
The abrupt onset of the modern South Asian Monsoon winds
Authors: Betzler Christian , Eberli Gregor P. , Kroon Dick , Wright James D. , Swart Peter K. , Nath Bejugam Nagender , Alvarez-Zarikian Carlos A. , Alonso-García Montserrat , Bialik Or M. , Blättler Clara L. , Guo Junhua Adam , Haffen Sébastien , Horozal Senay , Inoue Mayuri , Jovane Luigi , Lanci Luca , Laya Juan Carlos , Mee Anna Ling Hui , Lüdmann Thomas , Nakakuni Masatoshi , Niino Kaoru , Petruny Loren M. , Pratiwi Santi D. , Reijmer John J. G. , Reolid Jesús , Slagle Angela L. , Sloss Craig R. , Su Xiang , Yao Zhengquan , Young Jeremy R. 
Published: July 2016

AbstractThe South Asian Monson (SAM) is one of the most intense climatic elements yet its initiation and variations are not well established. Dating the deposits of SAM wind-driven currents in IODP cores from the Maldives yields an age of 12. 9 Ma indicating an abrupt SAM onset, over a short period of 300 kyrs. This coincided with the Indian Ocean Oxygen Minimum Zone expansion as revealed by geochemical tracers and the onset of upwelling reflected by the sediment’s content of particulate organic matter. A weaker ‘proto-monsoon’ existed between 12.9 and 25 Ma, as mirrored by the sedimentary signature of dust influx. Abrupt SAM initiation favors a strong influence of climate in addition to the tectonic control, and we propose that the post Miocene Climate Optimum cooling, together with increased continentalization and establishment of the bipolar ocean circulation, i.e. the beginning of the modern world, shifted the monsoon over a threshold towards the modern system.
Pollination and seed dispersal are the most threatened processes of plant regeneration
Authors: Neuschulz Eike Lena , Mueller Thomas , Schleuning Matthias , Böhning-Gaese Katrin 
Published: July 2016

AbstractPlant regeneration is essential for maintaining forest biodiversity and ecosystem functioning, which are globally threatened by human disturbance. Here we present the first integrative meta-analysis on how forest disturbance affects multiple ecological processes of plant regeneration including pollination, seed dispersal, seed predation, recruitment and herbivory. We analysed 408 pairwise comparisons of these processes between near-natural and disturbed forests. Human impacts overall reduced plant regeneration. Importantly, only processes early in the regeneration cycle that often depend on plant-animal interactions, i.e. pollination and seed dispersal, were negatively affected. Later processes, i.e. seed predation, recruitment and herbivory, showed overall no significant response to human disturbance. Conserving pollination and seed dispersal, including the animals that provide these services to plants, should become a priority in forest conservation efforts globally.
SOX9 directly Regulates CTGF/CCN2 Transcription in Growth Plate Chondrocytes and in Nucleus Pulposus Cells of Intervertebral Disc
Authors: Oh Chun-do , Yasuda Hideyo , Zhao Weiwei , Henry Stephen P. , Zhang Zhaoping , Xue Ming , de Crombrugghe Benoit , Chen Di 
Published: July 2016

AbstractSeveral lines of evidence indicate that connective tissue growth factor (CTGF/CCN2) stimulates chondrocyte proliferation and maturation. Given the fact that SOX9 is essential for several steps of the chondrocyte differentiation pathway, we asked whetherCtgf(Ccn2) is the direct target gene of SOX9. We found thatCtgfmRNA was down-regulated in primary sternal chondrocytes fromSox9flox/floxmice infected with Ad-CMV-Cre.We performed ChIP-on-chip assay using anti-SOX9 antibody, covering theCtgfgene from 15 kb upstream of its 5′-end to 10 kb downstream of its 3′-end to determine SOX9 interaction site. One high-affinity interaction site was identified in theCtgfproximal promoter by ChIP-on-chip assay. An important SOX9 regulatory element was found to be located in −70/−64 region of theCtgfpromoter. We found the same site for SOX9 binding to theCtgfpromoter in nucleus pulposus (NP) cells. The loss ofSox9in growth plate chondrocytes in knee joint and in NP cells in intervertebral disc led to the decrease in CTGF expression. We suggest thatCtgfis the direct target gene of SOX9 in chondrocytes and NP cells. Our study establishes a strong link between two regulatory molecules that have a major role in cartilaginous tissues.
Methylomes of renal cell lines and tumors or metastases differ significantly with impact on pharmacogenes
Authors: Winter Stefan , Fisel Pascale , Büttner Florian , Rausch Steffen , D’Amico Debora , Hennenlotter Jörg , Kruck Stephan , Nies Anne T. , Stenzl Arnulf , Junker Kerstin , Scharpf Marcus , Hofmann Ute , van der Kuip Heiko , Fend Falko , Ott German , Agaimy Abbas , Hartmann Arndt , Bedke Jens , Schwab Matthias , Schaeffeler Elke 
Published: July 2016

AbstractCurrent therapies for metastatic clear cell renal cell carcinoma (ccRCC) show limited efficacy. Drug efficacy, typically investigated in preclinical cell line models during drug development, is influenced by pharmacogenes involved in targeting and disposition of drugs. Here we show through genome-wide DNA methylation profiling, that methylation patterns are concordant between primary ccRCC and macro-metastases irrespective of metastatic sites (rs ≥ 0.92). However, 195,038 (41%) of all investigated CpG sites, including sites within pharmacogenes, were differentially methylated (adjusted P < 0.05) in five established RCC cell lines compared to primary tumors, resulting in altered transcriptional expression. Exemplarily, gene-specific analyses of DNA methylation, mRNA and protein expression demonstrate lack of expression of the clinically important drug transporter OCT2 (encoded by SLC22A2) in cell lines due to hypermethylation compared to tumors or metastases. Our findings provide evidence that RCC cell lines are of limited benefit for prediction of drug effects due to epigenetic alterations. Similar epigenetic landscape of ccRCC-metastases and tumors opens new avenue for future therapeutic strategies.
Interaction of ARF-1.1 and neuronal calcium sensor-1 in the control of the temperature-dependency of locomotion in Caenorhabditis elegans
Authors: Todd Paul A. C. , McCue Hannah V. , Haynes Lee P. , Barclay Jeff W. , Burgoyne Robert D. 
Published: July 2016

AbstractNeuronal calcium sensor-1 (NCS-1) mediates changes in cellular function by regulating various target proteins. Many potential targets have been identified but the physiological significance of only a few has been established. Upon temperature elevation, Caenorhabditis elegans exhibits reversible paralysis. In the absence of NCS-1, worms show delayed onset and a shorter duration of paralysis. This phenotype can be rescued by re-expression of ncs-1 in AIY neurons. Mutants with defects in four potential NCS-1 targets (arf-1.1, pifk-1, trp-1 and trp-2) showed qualitatively similar phenotypes to ncs-1 null worms, although the effect of pifk-1 mutation on time to paralysis was considerably delayed. Inhibition of pifk-1 also resulted in a locomotion phenotype. Analysis of double mutants showed no additive effects between mutations in ncs-1 and trp-1 or trp-2. In contrast, double mutants of arf-1.1 and ncs-1 had an intermediate phenotype, consistent with NCS-1 and ARF-1.1 acting in the same pathway. Over-expression of arf-1.1 in the AIY neurons was sufficient to rescue partially the phenotype of both the arf-1.1 and the ncs-1 null worms. These findings suggest that ARF-1.1 interacts with NCS-1 in AIY neurons and potentially pifk-1 in the Ca2+ signaling pathway that leads to inhibited locomotion at an elevated temperature.
Plasma matrix metalloproteinase 1 improves the detection and survival prediction of esophageal squamous cell carcinoma
Authors: Chen Yu-Kuei , Tung Chun-Wei , Lee Jui-Ying , Hung Yi-Chun , Lee Chien-Hung , Chou Shah-Hwa , Lin Hung-Shun , Wu Ming-Tsang , Wu I-Chen 
Published: July 2016

AbstractThis study aimed to identify noninvasive protein markers capable of detecting the presence and prognosis of esophageal squamous-cell carcinoma (ESCC). Analyzing microarray expression data collected from 17-pair ESCC specimens, we identified one protein, matrix metalloproteinase-1 (MMP1), as a possibly useful marker. Plasma MMP1 was then measured by enzyme-linked immunosorbent assay (ELISA) in 210 ESCC patients and 197 healthy controls. ESCC patients had higher mean levels of MMP1 than controls (8.7 ± 7.5 vs. 6.7 ± 4.9 ng/mL, p < 0.0001). Using the highest quartile level (9.67 ng/mL) as cut-off, we found a 9.0-fold risk of ESCC in those with higher plasma MMP1 after adjusting for covariates (95% confidence interval = 2.2, 36.0). Heavy smokers and heavy drinkers with higher plasma MMP1 had 61.4- and 31.0 times the risk, respectively, than non-users with lower MMP1. In the survival analysis, compared to those with MMP1 ≤ 9.67 ng/mL, ESCC patients with MMP1 > 9.67 ng/mL had a 48% increase in the risk of ESCC death (adjusted hazard ratio = 1.48; 95% CI = 1.04–2.10). In conclusion, plasma MMP1 may serve as a noninvasive marker of detecting the presence and predicting the survival of ESCC.
Switching of magnetic easy-axis using crystal orientation for large perpendicular coercivity in CoFe2O4 thin film
Authors: Shirsath Sagar E. , Liu Xiaoxi , Yasukawa Yukiko , Li Sean , Morisako Akimitsu 
Published: July 2016

AbstractPerpendicular magnetization and precise control over the magnetic easy axis in magnetic thin film is necessary for a variety of applications, particularly in magnetic recording media. A strong (111) orientation is successfully achieved in the CoFe2O4 (CFO) thin film at relatively low substrate temperature of 100 °C, whereas the (311)-preferred randomly oriented CFO is prepared at room temperature by the DC magnetron sputtering technique. The oxygen-deficient porous CFO film after post-annealing gives rise to compressive strain perpendicular to the film surface, which induces large perpendicular coercivity. We observe the coercivity of 11.3 kOe in the 40-nm CFO thin film, which is the highest perpendicular coercivity ever achieved on an amorphous SiO2/Si substrate. The present approach can guide the systematic tuning of the magnetic easy axis and coercivity in the desired direction with respect to crystal orientation in the nanoscale regime. Importantly, this can be achieved on virtually any type of substrate.
Narrowband random lasing in a Bismuth-doped active fiber
Authors: Lobach Ivan A. , Kablukov Sergey I. , Skvortsov Mikhail I. , Podivilov Evgeniy V. , Melkumov Mikhail A. , Babin Sergey A. , Dianov Evgeny M. 
Published: July 2016

AbstractRandom fiber lasers operating via the Rayleigh scattering (RS) feedback attract now a great deal of attention as they generate a high-quality unidirectional laser beam with the efficiency and performance comparable and even exceeding those of fiber lasers with conventional cavities. Similar to other random lasers, both amplification and random scattering are distributed here along the laser medium being usually represented by a kilometers-long passive fiber with Raman gain. However, it is hardly possible to utilize normal gain in conventional active fibers as they are usually short and RS is negligible. Here we report on the first demonstration of the RS-based random lasing in an active fiber. This became possible due to the implementation of a new Bi-doped fiber with an increased amplification length and RS coefficient. The realized Bi-fiber random laser generates in a specific spectral region (1.42 μm) exhibiting unique features, in particular, a much narrower linewidth than that in conventional cavity of the same length, in agreement with the developed theory. Lasers of this type have a great potential for applications as Bi-doped fibers with different host compositions enable laser operation in an extremely broad range of wavelengths, 1.15–1.78 μm.
Neurogenic differentiation factor NeuroD confers protection against radiation-induced intestinal injury in mice
Authors: Li Ming , Du Aonan , Xu Jing , Ma Yanchao , Cao Han , Yang Chao , Yang Xiao-Dong , Xing Chun-Gen , Chen Ming , Zhu Wei , Zhang Shuyu , Cao Jianping 
Published: July 2016

AbstractThe gastrointestinal tract, especially the small intestine, is particularly sensitive to radiation and is prone to radiation-induced injury as a result. Neurogenic differentiation factor (NeuroD) is an evolutionarily-conserved basic helix-loop-helix (bHLH) transcription factor. NeuroD contains a protein transduction domain (PTD), which allows it to be exogenously delivered across the membrane of mammalian cells, whereupon its transcription activity can be unleashed. Whether NeuroD has therapeutic effects for radiation-induced injury remains unclear. In the present study, we prepared a NeuroD-EGFP recombinant protein and explored its protective effects on the survival and intestinal damage induced by ionizing radiation. Our results showed that NeuroD-EGFP could be transduced into small intestine epithelial cells and tissues. NeuroD-EGFP administration significantly increased overall survival of mice exposed to lethal total body irradiation (TBI). This recombinant NeuroD also reduced radiation-induced intestinal mucosal injury and apoptosis and improved crypt survival. Expression profiling of NeuroD-EGFP-treated mice revealed upregulation of tissue inhibitor of metalloproteinase 1 (TIMP-1), a known inhibitor of apoptosis in mammalian cells. In conclusion, NeuroD confers protection against radiation-induced intestinal injury and provides a novel therapeutic clinical option for the prevention of intestinal side effects of radiotherapy and the treatment of victims of incidental exposure.
Direct targeting of membrane fusion by SNARE mimicry: Convergent evolution ofLegionellaeffectors
Authors: Shi Xingqi , Halder Partho , Yavuz Halenur , Jahn Reinhard , Shuman Howard A. 
Published: July 2016

SignificanceLegionellapneumophila, the bacterium causing Legionnaires’ disease, invades lung cells by creating intracellular vacuoles where it is protected and where it can multiply. For expansion, the vacuoles must hijack intracellular vesicles while avoiding destruction by lysosomes. To achieve these goals,Legionellaexports effector proteins into the cytoplasm and into the membrane of the vacuole. Here we report that certainLegionellaeffectors mimic intracellular fusion proteins of the SNARE family, allowing them to selectively fuse with specific intracellular transport vesicles, thus providing more space for the dividing bacteria. In contrast to SNAREs, however, theLegionellaproteins can be used only once, thus allowing the bacteria to control the amount of hijacked vesicles.
Selectivity of ORC binding sites and the relation to replication timing, fragile sites, and deletions in cancers
Authors: Miotto Benoit , Ji Zhe , Struhl Kevin 
Published: July 2016

Significance
The origin recognition complex (ORC) binds sites from which DNA replication is initiated. By mapping binding sites in human cells, we show that ORC binds selectively to open (DNase I-hypersensitive) regions containing active chromatin marks. There are far more ORC sites in early replicating regions of the genome, and computational simulation based on ORC binding indicates that replication timing is due primarily to ORC density and stochastic initiation of DNA replication from origins. Large genomic regions with a paucity of ORC sites are strongly associated with common fragile sites and recurrent deletions in cancers. Thus, replication origins, replication timing, and replication-dependent chromosome breaks are determined ultimately by the genomic distribution of activator proteins at enhancers and promoters.
A Simulation Assessment of Model-Assisted Estimation of Steelhead Redd Abundance
Authors: McCormick Joshua L. , Ruzycki James R. 
Published: July 2016

Abstract
Redd abundance for steelhead Oncorhynchus mykiss is frequently estimated using design-based redd surveys. Redd abundance estimates may be biased low because redds may not be distinguishable prior to or in between sampling events (i.e., removal bias). Removal bias is typically mitigated by increasing temporal sampling intensity, thereby potentially reducing the level of spatial replication. In this study a model-assisted estimation technique to correct for removal bias was described and evaluated. Parametric survival time models were fit to redd data to estimate redd longevity and parameterize a simulation to evaluate the model-assisted estimation approach. The simulation showed increasing negative bias in redd counts not adjusted for removal bias as redd longevity decreased and as sampling intervals increased. Average bias among simulated datasets was as high as 43% using raw counts when redd longevity was relatively short at a 25-d sampling interval. Average bias was reduced to as low 1.3% using the model-assisted approach. Relative benefits of the model-assisted approach compared with traditional estimates decreased as redd longevity increased, and the accuracy of model-assisted estimates were sensitive to the function used to estimate redd longevity. The results of this study suggest that commonly used sampling intervals can potentially be increased with no appreciable increase in bias when using model-assisted estimation techniques.
Received October 7, 2015; accepted March 21, 2016 Published online July 20, 2016
Injuries during football tournaments in 45,000 children and adolescents
Authors: Kolstrup Line Agger , Koopmann Kristian Ugelvig , Nygaard Uffe Harboe , Nygaard Rie Harboe , Agger Peter 
Published: July 2016

AbstractFour percent of the world's population, or 265 million people, play football, and many players are injured every year. The present study investigated more than 1800 injuries in over 45,000 youth players participating in three consecutive international football tournaments in Denmark in 2012–2014. The aim was to investigate the injury types and locations in children and adolescent football players and the differences between genders and age groups (11–15 and 16–19 years of age). An overall injury rate of 15.3 per 1000 player hours was found. The most common injury location was lower extremities (66.7%), and the most common injury type was contusion (24.4%). Girls had a relative risk of injury of 1.5 compared with boys, p < .001, and they had a higher proportion of injuries to knee and lower leg, 23.8%, than boys, 19.0%, p < .01. Boys had a higher proportion of fracture, 6.8%, as opposed to 3.3% among girls, p < .001. In conclusion, we found the youngest girls to have a higher incidence of almost all injury categories than any other group. In general, the incidence of injury decreased with age. The study provides a detailed insight into the injuries that may be expected at a large youth football tournament. These findings are of great value for organizations and healthcare professionals planning similar events and for planning injury prevention strategies, which would be of special interest in the youngest female players in general.
Validation studies of gyrokinetic ITG and TEM turbulence simulations in a JT-60U tokamak using multiple flux matching
Authors: Nakata Motoki , Honda Mitsuru , Yoshida Maiko , Urano Hajime , Nunami Masanori , Maeyama Shinya , Watanabe Tomo-Hiko , Sugama Hideo 
Published: July 2016

Abstract
Quantitative validation studies of flux-tube gyrokinetic Vlasov simulations on ion and electron heat transport are carried out for the JT-60U tokamak experiment. The ion temperature gradient (ITG) and/or trapped electron modes (TEM) driven turbulent transport and zonal flow generations are investigated for an L-mode plasma in the local turbulence limit with a sufficiently small normalized ion thermal gyroradius and weak mean radial electric fields. Nonlinear turbulence simulations by the GKV code successfully reproduce radial profiles of the ion and electron energy fluxes in the core region. The numerical results show that the TEM-driven zonal flow generation in the outer region is more significant than that in the core region with ITG- and ITG–TEM-dominated turbulence, leading to moderate transport shortfall of the ion energy flux. Error levels in the prediction of the ion and electron temperature gradient profiles in the core region are estimated as less than

±

30
%

, based on a multiple flux matching technique, where the simulated ion and electron energy fluxes are simultaneously matched to the experimental values.
Variance adaptive shrinkage (vash): flexible empirical Bayes estimation of variances
Authors: Lu Mengyin , Stephens Matthew 
Published: July 2016

Motivation: Genomic studies often involve estimation of variances of thousands of genes (or other genomic units) from just a few measurements on each. For example, variance estimation is an important step in gene expression analyses aimed at identifying differentially expressed genes. A common approach to this problem is to use an Empirical Bayes (EB) method that assumes the variances among genes follow an inverse-gamma distribution. This distributional assumption is relatively inflexible; for example, it may not capture ‘outlying’ genes whose variances are considerably bigger than usual. Here we describe a more flexible EB method, capable of capturing a much wider range of distributions. Indeed, the main assumption is that the distribution of the variances is unimodal (or, as an alternative, that the distribution of the precisions is unimodal). We argue that the unimodal assumption provides an attractive compromise between flexibility, computational tractability and statistical efficiency.Results: We show that this more flexible approach provides competitive performance with existing methods when the variances truly come from an inverse-gamma distribution, and can outperform them when the distribution of the variances is more complex. In analyses of several human gene expression datasets from the Genotype Tissues Expression consortium, we find that our more flexible model often fits the data appreciably better than the single inverse gamma distribution. At the same time we find that in these data this improved model fit leads to only small improvements in variance estimates and detection of differentially expressed genes.Availability and Implementation: Our methods are implemented in an R package vashr available from http://github.com/mengyin/vashr.Contact: mstephens@uchicago.eduSupplementary information: Supplementary data are available at Bioinformatics online.