bluuebunny/crossref_metadata_2025_split huggingface dataset:
CRISPRdigger: detecting CRISPRs with better direct repeat annotations
Authors: Ge Ruiquan , Mai Guoqin , Wang Pu , Zhou Manli , Luo Youxi , Cai Yunpeng , Zhou Fengfeng 
Published: September 2016

AbstractClustered regularly interspaced short palindromic repeats (CRISPRs) are important genetic elements in many bacterial and archaeal genomes, and play a key role in prokaryote immune systems’ fight against invasive foreign elements. The CRISPR system has also been engineered to facilitate target gene editing in eukaryotic genomes. Using the common features of mis-annotated CRISPRs in prokaryotic genomes, this study proposed an accurate de novo CRISPR annotation program CRISPRdigger, which can take a partially assembled genome as its input. A comprehensive comparison with the three existing programs demonstrated that CRISPRdigger can recover more Direct Repeats (DRs) for CRISPRs and achieve a higher accuracy for a query genome. The program was implemented by Perl and all the parameters had default values, so that a user could annotate CRISPRs in a query genome by supplying only a genome sequence in the FASTA format. All the supplementary data are available at http://www.healthinformaticslab.org/supp/.
The Surface Polarized Graphene Oxide Quantum Dot Films for Flexible Nanogenerators
Authors: Liu Liangbin , Cheng Yafei , Zhu Lili , Lee Shuit-Tong , Liao Fan , Shao Mingwang 
Published: September 2016

AbstractAbundant disorderly-distributed surface functional groups, such as hydroxyl, carboxyl, ether and amino groups, endow an isolated graphene oxide quantum dot (GOQD) the polar property due to the symmetry breaking, although the aggregated counterparts present no polarization owing to the random orientation. Here, flexible polarized films were fabricated using aggregated GOQDs with the assistance of external electric fields and their polarization was confirmed with the electrostatic force microscopy and polarization-electric field hysteresis loop. Such polarized GOQD films may induce charges under externally applied deformation. Here, we fabricated nanogenerators based on the films, which gave out an average current value of 0.12 μA and an average voltage value of 12 V under a mechanical force of 60 N. This work has proposed a convenient electric-field-assisted method to give the nanomaterials new functions, which can be generalized to other materials and found applications in various fields.
Docetaxel plus cetuximab biweekly is an active regimen for the first-line treatment of patients with recurrent/metastatic head and neck cancer
Authors: Posch Doris , Fuchs Hannah , Kornek Gabriela , Grah Anja , Pammer Johannes , Aretin Marie-Bernadette , Fuereder Thorsten 
Published: September 2016

AbstractFor patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (SCCHN) limited therapeutic options exist. Only a subset of patients is suitable for combination chemotherapy regimens. Biweekly docetaxel plus cetuximab might be an alternative option. Thus, we performed this retrospective analysis in unselected patients in order to investigate the efficacy and safety of this regimen. Thirty-one patients receiving off protocol docetaxel (50 mg/m2) plus cetuximab (500 mg/m2) biweekly were included. Data collection included baseline demographic, response rate (ORR), disease control rate (DCR), overall survival (OS), progression free survival (PFS) as well as toxicity. OS and PFS were 8.3 months (95% CI 4.8–11.8) and 4.0 months (95% CI 1.0–7.0), respectively. Three (9.7%) patients achieved a complete response and one patient (3.2%) a partial response. The DCR was 41.9% and we observed an ORR of 12.9%. The one-year survival rate was 25.8%. The therapy was well tolerated and the most common grade 3/4 adverse events were neutropenia (19.4%), hypomagnesaemia (12.9%) and acne-like rash (9.7%). Biweekly cetuximab/docetaxel is an effective regimen and well tolerated in R/M SCCHN patients not suitable for platinum doublet treatment. Further evaluation of this regimen in prospective clinical trials is warranted.
Sterilizing immunity to influenza virus infection requires local antigen-specific T cell response in the lungs
Authors: Dutta Avijit , Huang Ching-Tai , Lin Chun-Yen , Chen Tse-Ching , Lin Yung-Chang , Chang Chia-Shiang , He Yueh-Chia 
Published: September 2016

AbstractSterilizing immunity is a unique immune status, which prevents effective virus infection into the host. It is different from the immunity that allows infection but with subsequent successful eradication of the virus. Pre-infection induces sterilizing immunity to homologous influenza virus challenge in ferret. In our antigen-specific experimental system, mice pre-infected with PR8 influenza virus through nasal route are likewise resistant to reinfection of the same strain of virus. The virus is cleared before establishment of effective infection. Intramuscular influenza virus injection confers protection against re-infection with facilitated virus clearance but not sterilizing immunity. Pre-infection and intramuscular injection generates comparable innate immunity and antibody response, but only pre-infection induces virus receptor reduction and efficient antigen-specific T cell response in the lungs. Pre-infection with nH1N1 influenza virus induces virus receptor reduction but not PR8-specific T cell immune response in the lungs and cannot prevent infection of PR8 influenza virus. Pre-infection with PR8 virus induced PR8-specific T cell response in the lungs but cannot prevent infection of nH1N1 virus either. These results reveal that antigen-specific T cell immunity is required for sterilizing immunity.
Solitons in PT-symmetric periodic systems with the logarithmically saturable nonlinearity
Authors: Zhan Kaiyun , Tian Hao , Li Xin , Xu Xianfeng , Jiao Zhiyong , Jia Yulei 
Published: September 2016

AbstractWe report on the formation and stability of induced solitons in parity-time (PT) symmetric periodic systems with the logarithmically saturable nonlinearity. Both on-site and off-site lattice solitons exist for the self-focusing nonlinearity. The most intriguing result is that the above solitons can also be realized inside the several higher-order bands of the band structure, due to the change of nonlinear type with the soliton power. Stability analysis shows that on-site solitons are linearly stably, and off-site solitons are unstable in their existence domain.
Endothelial damage in major depression patients is modulated by SSRI treatment, as demonstrated by circulating biomarkers and an in vitro cell model
Authors: Lopez-Vilchez I , Diaz-Ricart M , Navarro V , Torramade S , Zamorano-Leon J , Lopez-Farre A , Galan A M , Gasto C , Escolar G 
Published: September 2016

AbstractThere is a link between depression, cardiovascular events and inflammation. We have explored this connection through endothelial dysfunction, using in vivo and in vitro approaches. We evaluated circulating biomarkers of endothelial dysfunction in patients with major depression at their diagnosis (MD-0) and during antidepressant treatment with the selective serotonin reuptake inhibitor escitalopram, for 8 and 24 weeks (MD-8 and MD-24). Results were always compared with matched healthy controls (CON). We measured in vivo circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) in blood samples, and assessed plasma levels of soluble von Willebrand factor (VWF) and vascular cell adhesion molecule-1 (VCAM-1). CEC counts, soluble VWF and VCAM-1 were statistically elevated in MD-0 (P<0.01 versus CON) and gradually decreased during treatment. Conversely, EPC levels were lower in MD-0, tending to increase throughout treatment. In vitro studies were performed in human endothelial cells cultured in the presence of sera from each study group. Elevated expression of the inflammation marker intercellular adhesion molecule-1 and oxidative stress, with lower presence of endothelial nitric oxide synthase and higher reactive oxygen species production, were found in cells exposed to MD-0 sera (P<0.05 versus CON). These results were normalized in cells exposed to MD-24 sera. Thrombogenicity of extracellular matrices generated by these cells, measured as expression of VWF, tissue factor and platelet reactivity, showed non-significant differences. We provide a model of cultured endothelial cells reproducing endothelial dysfunction in naive patients with major depression, demonstrating endothelial damage and inflammation at diagnosis, and recovering with selective serotonin reuptake inhibitor treatment for 24 weeks.
Systemischer Lupus erythematodes
Authors: Aringer M. , Schneider M. 
Published: September 2016

ZusammenfassungDie heutigen Therapieoptionen und -konzepte haben die Chancen von SLE-Patientinnen und -Patienten auf ein langes und gutes Leben mit Lupus deutlich verbessert. Gerade deshalb stellt die Erkrankung weiter eine relevante ärztliche Herausforderung dar. Die Breite der möglichen Organbeteiligung fordert den „Vollblut“-Internisten in jedem Rheumatologen heraus. Schübe, Infektionen und vaskuläre Ereignisse können kaum je längerfristig ausgeschlossen werden und benötigen von Patienten wie Ärzten ein hohes Maß an Aufmerksamkeit. Zusätzlich haben psychische Faktoren oft deutlichen Einfluss auf das Gesamtbild. Dennoch lassen sich für die meisten häufigen Situationen ähnlich wie bei der rheumatoiden Arthritis (RA) klare, einfache Regeln aufstellen. Diese sollen in der vorliegenden Übersicht skizziert werden.
“Do not call them bastards”: Shakespeare as an invasive species
Authors: Saenger Michael 
Published: September 2016

AbstractThis essay assesses two dominant modes of understanding William Shakespeare’s effect on world cultures. Those two modes are anchored on the ideas of tradition and commerce. Each offers valuable insight but also carries with it inherent limitations. This essay borrows from recent interdisciplinary work on ecosystems to offer a third way of approaching the life of Shakespeare’s work in the centuries after his death. We suggest that this third mode, which can be called “naturecultural”, offers fresh ethical perspectives on Shakespeare’s life in contemporary culture. This article is published as part of a collection to commemorate the 400th anniversary of Shakespeare’s death.
Order restricted inference for oscillatory systems for detecting rhythmic signals
Authors: Larriba Yolanda , Rueda Cristina , Fernández Miguel A , Peddada Shyamal D 
Published: September 2016

AbstractMotivationMany biological processes, such as cell cycle, circadian clock, menstrual cycles, are governed by oscillatory systems consisting of numerous components that exhibit rhythmic patterns over time. It is not always easy to identify such rhythmic components. For example, it is a challenging problem to identify circadian genes in a given tissue using time-course gene expression data. There is a great potential for misclassifying non-rhythmic as rhythmic genes and vice versa. This has been a problem of considerable interest in recent years. In this article we develop a constrained inference based methodology called Order Restricted Inference for Oscillatory Systems (ORIOS) to detect rhythmic signals. Instead of using mathematical functions (e.g. sinusoidal) to describe shape of rhythmic signals, ORIOS uses mathematical inequalities. Consequently, it is robust and not limited by the biologist's choice of the mathematical model. We studied the performance of ORIOS using simulated as well as real data obtained from mouse liver, pituitary gland and data from NIH3T3, U2OS cell lines. Our results suggest that, for a broad collection of patterns of gene expression, ORIOS has substantially higher power to detect true rhythmic genes in comparison to some popular methods, while also declaring substantially fewer non-rhythmic genes as rhythmic.Availability and ImplementationA user friendly code implemented in R language can be downloaded from http://www.niehs.nih.gov/research/atniehs/labs/bb/staff/peddada/index.cfm.Contactpeddada@niehs.nih.gov
Topographic viscous fingering: fluid–fluid displacement in a channel of non-uniform gap width
Authors: Woods Andrew W. , Mingotti Nicola 
Published: September 2016

We consider the displacement of one fluid by a second immiscible fluid through a long, thin permeable channel whose thickness and permeability decrease away from the axis of the channel. We build a model that illustrates how the shape of the fluid–fluid interface evolves in time. We find that if the injected fluid is of the same viscosity as the original fluid, then the cross-channel variations in permeability and thickness tend to focus the flow along the centre of the channel. If the viscosity of the injected fluid is smaller than the original fluid, then this flow focusing intensifies, leading to very poor sweep of the original fluid in the system, with the injected fluid bypassing much of the channel. We also show that if the viscosity ratio of the injected fluid to the original fluid is sufficiently large, then a blunt nose may develop at the leading edge of the injected fluid, whereas the remainder of the fluid–fluid interface becomes stretched out along the edges of the channel. This leads to a much more efficient sweep of the original fluid from the channel. We generalize the model to illustrate how buoyancy forces and capillary pressure affect the evolution of the system and compare our model predictions with some simple laboratory experiments. This partial stabilization of a fluid interface in a channel of non-uniform width represents a generalization of the classical Saffman–Taylor instability, and our nonlinear solutions for the evolution of the interface highlight the importance of cross-channel variations in permeability and thickness in modelling flow in channelled reservoirs.This article is part of the themed issue ‘Energy and the subsurface’.
Effects of rock mineralogy and pore structure on stress-dependent permeability of shale samples
Authors: Al Ismail Maytham I. , Zoback Mark D. 
Published: September 2016

We conducted pulse-decay permeability experiments on Utica and Permian shale samples to investigate the effect of rock mineralogy and pore structure on the transport mechanisms using a non-adsorbing gas (argon). The mineralogy of the shale samples varied from clay rich to calcite rich (i.e. clay poor). Our permeability measurements and scanning electron microscopy images revealed that the permeability of the shale samples whose pores resided in the kerogen positively correlated with organic content. Our results showed that the absolute value of permeability was not affected by the mineral composition of the shale samples. Additionally, our results indicated that clay content played a significant role in the stress-dependent permeability. For clay-rich samples, we observed higher pore throat compressibility, which led to higher permeability reduction at increasing effective stress than with calcite-rich samples. Our findings highlight the importance of considering permeability to be stress dependent to achieve more accurate reservoir simulations especially for clay-rich shale reservoirs.
This article is part of the themed issue ‘Energy and the subsurface’.
Ultrasensitive detection of TCR hypervariable region in solid-tissue RNA-seq data
Authors: Li Bo , Li Taiwen , Wang Binbin , Dou Ruoxu , Pignon Jean-Chrisophe , Choueiri Toni K. , Signoretti Sabina , Liu Jun S , Liu Xiaole Shirley 
Published: September 2016

AbstractCharacterization of tissue-infiltrating T cell repertoire is critical to understanding tumor-immune interactions and autoimmune disease etiology. We present TRUST, an open source algorithm for calling the TCR transcript hypervariable CDR3 regions using unselected RNA-seq data profiled from solid tissues. TRUST achieved high sensitivity in CDR3 calling even for samples with low sequencing depth and has demonstrated utilities in its application to large tumor cohorts.
Improving the temporal accuracy of functional Magnetic Resonance Imaging
Authors: Janssen Niels , Hernández-Cabrera Juan A. , Ezama Foronda Laura 
Published: September 2016

AbstractA major drawback of functional Magnetic Resonance Imaging (fMRI) concerns the lack of temporal accuracy of the measured signal. Although this limitation stems in part from the neuro-vascular nature of the fMRI signal, it also reflects particular methodological decisions in the fMRI data analysis pathway. Here we show that the temporal accuracy of fMRI is affected by the specific way in which whole-brain volumes are created from individually acquired brain slices. Specifically, we show how the current volume creation method leads to whole-brain volumes that contain within-volume temporal distortions and that are available at a low temporal resolution. To address these limitations, we propose a new framework for fMRI data analysis. The new framework creates whole-brain volumes from individual brain slices that are all acquired at the same point in time relative to a presented stimulus. These whole-brain volumes contain no temporal distortions, and are available at a high temporal resolution. Statistical signal extraction occurs on the basis of a novel time point-by-time point approach. We evaluated the temporal characteristics of the extracted signal in the standard and new framework with simulated and real-world fMRI data. The new slice-based data-analytic framework yields greatly improved temporal accuracy of fMRI signals.
Improved assemblies and comparison of two ancientYersinia pestisgenomes
Authors: Luhmann Nina , Doerr Daniel , Chauve Cedric 
Published: September 2016

ABSTRACTYersinia pestisis the causative agent of the bubonic plague, a disease responsible for several dramatic historical pandemics. Progress in ancient DNA (aDNA) sequencing rendered possible the sequencing of whole genomes of important human pathogens, including the ancientYersinia pestisstrains responsible for outbreaks of the bubonic plague in London in the 14th century and in Marseille in the 18th century among others. However, aDNA sequencing data are still characterized by short reads and non-uniform coverage, so assembling ancient pathogen genomes remains challenging and prevents in many cases a detailed study of genome rearrangements. It has recently been shown that comparative scaffolding approaches can improve the assembly of ancient Yersinia pestis genomes at a chromosome level. In the present work, we address the last step of genome assembly, the gap-filling stage. We describe an optimization-based method AGapEs (Ancestral Gap Estimation) to fill in inter-contig gaps using a combination of a template obtained from related extant genomes and aDNA reads. We show how this approach can be used to refine comparative scaffolding by selecting contig adjacencies supported by a mix of unassembled aDNA reads and comparative signal. We apply our method to two data sets from the London and Marseilles outbreaks of the bubonic plague. We obtain highly improved genome assemblies for both the London strain and Marseille strain genomes, comprised of respectively five and six scaffolds, with 95% of the assemblies supported by ancient reads. We analyze the genome evolution between both ancient genomes in terms of genome rearrangements, and observe a high level of synteny conservation between these two strains.
Precise label-free quantitative proteomes in high-throughput by microLC and data-independent SWATH acquisition
Authors: Vowinckel Jakob , Zelezniak Aleksej , Kibler Artur , Bruderer Roland , Muelleder Michael , Reiter Lukas , Ralser Markus 
Published: September 2016

AbstractWhile quantitative proteomics is a key technology in biological research, the routine industry and diagnostics application is so far still limited by a moderate throughput, data consistency and robustness. In part, the restrictions emerge in the proteomics dependency on nanolitre/minute flow rate chromatography that enables a high sensitivity, but is difficult to handle on large sample series, and on the stochastic nature in data-dependent acquisition strategies. We here establish and benchmark a label-free, quantitative proteomics platform that uses microlitre/minute flow rate chromatography in combination with data-independent SWATH acquisition. Being able to largely compensate for the loss of sensitivity by exploiting the analytical capacities of microflow chromatography, we show that microLC-SWATH-MS is able to precisely quantify up to 4000 proteins in an hour or less, enables the consistent processing of sample series in high-throughput, and gains quantification precisions comparable to targeted proteomic assays. MicroLC-SWATH-MS can hence routinely process hundreds to thousands of samples to systematically create precise, label free quantitative proteomes.
Intrinsic brain connectivity after partial sleep deprivation in young and older adults: results from the Stockholm Sleepy Brain study
Authors: Nilsonne Gustav , Tamm Sandra , Schwarz Johanna , Almeida Rita , Fischer Håkan , Kecklund Göran , Lekander Mats , Fransson Peter , Åkerstedt Torbjörn 
Published: September 2016

AbstractSleep deprivation has been reported to affect intrinsic brain connectivity, notably reducing connectivity in the default mode network. Studies to date have however shown inconsistent effects, in many cases lacked monitoring of wakefulness, and largely included young participants. We investigated effects of sleep deprivation on intrinsic brain connectivity in young and older participants. Participants aged 20–30 (n=30) and 65–75 (n=23) years underwent partial sleep deprivation (3h sleep) in a cross-over design, with two 8-minutes eyes-open resting state functional magnetic resonance imaging (fMRI) runs in each session, monitored by eye-tracking. We assessed intrinsic brain connectivity using independent components analysis (ICA) as well as seed-region analyses of functional connectivity, and also analysed global signal variability, regional homogeneity, and the amplitude of low-frequency fluctuations. Sleep deprivation caused increased global signal variability. In our study, changes in investigated resting state networks and in regional homogeneity were not statistically significant. Younger participants had higher connectivity in most examined networks, as well as higher regional homogeneity in areas including anterior and posterior cingulate cortex. In conclusion, we found that sleep deprivation caused increased global signal variability. We speculate that this may be caused by wake-state instability.