bluuebunny/crossref_metadata_2025_split huggingface dataset:
The power of coarse graining in biomolecular simulations
Authors: Ingólfsson Helgi I. , Lopez Cesar A. , Uusitalo Jaakko J. , de Jong Djurre H. , Gopal Srinivasa M. , Periole Xavier , Marrink Siewert J. 
Published: August 2013

Computational modeling of biological systems is challenging because of the multitude of spatial and temporal scales involved. Replacing atomistic detail with lower resolution, coarse grained (CG), beads has opened the way to simulate large‐scale biomolecular processes on time scales inaccessible to all‐atom models. We provide an overview of some of the more popular CG models used in biomolecular applications to date, focusing on models that retain chemical specificity. A few state‐of‐the‐art examples of protein folding, membrane protein gating and self‐assembly, DNA hybridization, and modeling of carbohydrate fibers are used to illustrate the power and diversity of current CG modeling.This article is categorized under:

Molecular and Statistical Mechanics > Molecular Dynamics and Monte-Carlo Methods
Prediction of pathological mutations in proteins: the challenge of integrating sequence conservation and structure stability principles
Authors: Riera Casandra , Lois Sergio , de la Cruz Xavier 
Published: August 2013

The recent drop in genome sequencing costs has created a promising horizon for the development of genomic medicine. Within the biomedical environment, sequencing data are increasingly used for disease diagnosis and prognosis, treatment development, counseling, and so on. Many of these applications rely on the identification of disease causing variants. This is a particularly challenging problem because of the large number and wide variety of sequence variants identified in sequencing projects, and also because we only have a limited understanding of the physicochemical/biochemical properties that differentiate neutral from pathologic variants. Nonetheless, these last years have witnessed important methodological advances for one class of variants, those corresponding to changes in the amino‐acid sequence of proteins. Proteins are a main constituent of living systems. We know that although their biological properties are essentially determined by the amino‐acid sequence, not all the changes in this sequence have the same impact. Some are neutral, but others affect protein function and lead to disease. A large body of evidence shows that whether one or the other is the case that depends on properties such as mutation location in the protein structure, interspecies conservation, and so on. Mutation prediction methods based on these features have good success rates, in the 70–90% range, although representation over time suggests there is a performance plateau that would limit their applicability. In light of the most recent advances in the field, and after reviewing the foundations of prediction methods, we discuss the existence of this performance threshold and how it can be overcomed.This article is categorized under:Computer and Information Science > Databases and Expert Systems
Hepatic Artery Reconstruction in Living Donor Liver Transplantation: Risk Factor Analysis of Complication and a Role of MDCT Scan for Detecting Anastomotic Stricture
Authors: Marubashi Shigeru , Kobayashi Shogo , Wada Hiroshi , Kawamoto Koichi , Eguchi Hidetoshi , Doki Yuichiro , Mori Masaki , Nagano Hiroaki 
Published: August 2013

AbstractBackgroundIn partial liver transplantation, reconstruction of the hepatic artery is technically highly demanding and the incidence of arterial complications is high. We attempted to identify the risk factors for anastomotic complications after hepatic artery reconstruction and examined the role of multidetector‐row computed tomography (MDCT) in the evaluation of the reconstructed hepatic artery in liver transplant recipients.MethodsA total of 109 adult‐to‐adult living donor liver transplantations (LDLT) were performed at our institute between 1999 and July 2011. Hepatic artery reconstruction was performed under a surgical microscope (MS group, n = 84), until we began to adopt surgical loupes (4.5×) for arterial reconstructions in all cases after January 2009 (SL group, n = 25). A dynamic MDCT study was prospectively carried out on postoperative days 7, 14, and 28, and at postoperative month 3, 6, and 12 after April 2005 (n = 60).ResultsThere were no cases of hepatic artery thrombosis and six cases (5.5 %) of interventional radiology‐confirmed hepatic artery stenosis (HAS). Risk factor analysis for HAS showed that ABO‐incompatible LDLT was associated with HAS. Use of surgical loupes provided superior results as compared to anastomosis under a surgical microscope, and it also provided the advantage of reduced operative time. The MDCT procedure was useful for detecting HAS; however, the false positive rate was relatively high until 3 months after the LDLT (100 % sensitivity and 72.8 % specificity at 3 months).ConclusionsHepatic arterial anastomosis using surgical loupes tended to be time‐saving and to yield similar or better results than traditional microscope‐anastomosis. The use of MDCT aided the diagnosis of HAS, although the substantial false positive rate should be borne in mind in clinical practice.
Airtight Tracheocutaneostomy After Window Resection of the Trachea for Invasive Papillary Thyroid Carcinoma: Experience of 109 Cases
Authors: Ito Yasuhiro , Miyauchi Akira , Kihara Minoru , Higashiyama Takuya , Kobayashi Kaoru , Miya Akihiro 
Published: August 2013

AbstractBackgroundThere are some tracheal surgeries for invasive papillary thyroid carcinoma (PTC) requiring tracheal resection. We create an airtight tracheocutaneostomy (TCS) by suturing the tracheal hole to the skin when window resection of the trachea is required. Here, we present the outcomes of PTC patients who underwent surgery with airtight TCS.MethodsWe enrolled 109 patients (18 males and 91 females) who underwent initial surgery for PTC and TCS after partial window resection of the trachea between 1987 and 2010. The average patient age was 61 and the average follow‐up was 99 months. The TCS was closed using a local skin flap 3–6 months after surgery in 78 patients, and it closed spontaneously in 13 patients. The TCS of the remaining 18 patients was not closed for various reasons, such as a poor general condition, permanent bilateral vocal cord paralysis, and loss to follow‐up.ResultsNone of the 109 patients showed any serious complications of TCS. Minor wound infection, partial skin necrosis, granulation, and air leakage were observed in 12 (11 %), 2 (2 %), 7 (6 %), and 4 (4 %) patients, respectively. Infection was more likely to occur in patients whose cricoid cartilage was resected (p = 0.0456). Although macroscopically curative surgery was performed for all patients, 38 patients (35 %) had a suspiciously positive margin in the resected tracheal mucosa. Five margin‐positive (13 %) and five margin‐negative (7 %) patients showed excision site recurrence, but the margin status did not directly affect the prognosis. External beam radiation therapy (EBRT) (50–60 Gy) was administered to nine patients, none of whom showed excision site recurrence, although eight were microscopically margin‐positive. Among various clinicopathological features, tumor size > 4 cm and age ≥ 60 years were significant (p = 0.0281) and marginal (p = 0.0771) predictors of excision site recurrence on univariate analysis. On multivariate analysis, age ≥ 60 years (p = 0.0484) and tumor size > 4 cm (p = 0.0763) were independent and marginal predictors of excision site recurrence, respectively. To date, 14 and 17 patients have shown lymph node and distant recurrence, respectively, and nine have died of PTC.ConclusionsTracheocutaneostomy is a safe surgical technique after partial window resection of the trachea, although we have to be careful of infection when resecting the cricoid cartilage. Large tumor size and old age are risk factors for excision site recurrence. EBRT may be useful to prevent excision site recurrence, especially in patients with a suspected positive margin.
Dissection of the BCR-ABL signaling network using highly specific monobody inhibitors to the SHP2 SH2 domains
Authors: Sha Fern , Gencer Emel Basak , Georgeon Sandrine , Koide Akiko , Yasui Norihisa , Koide Shohei , Hantschel Oliver 
Published: August 2013

Significance
Protein–protein interactions are essential for cellular regulation, but how changes in individual interactions influence cellular physiology or cause disease remains poorly characterized. Although selective and potent inhibitors of protein–protein interactions are powerful tools, developing such reagents is challenging. This is because signaling networks are composed of members of highly conserved protein domain families, with the Src-homology 2 (SH2) domain as an archetype. To address this challenge, we used protein design to successfully generate a set of reagents, termed monobodies, directed to the SH2 domains of SH2 domain-containing phosphatase 2 (SHP2), for which no specific inhibitors had been identified. These monobodies selectively and potently inhibit SHP2 function and demonstrate utility in dissecting the signaling networks of cancer cells.
Integration of responses within and acrossArabidopsisnatural accessions uncovers loci controlling root systems architecture
Authors: Rosas Ulises , Cibrian-Jaramillo Angelica , Ristova Daniela , Banta Joshua A. , Gifford Miriam L. , Fan Angela Huihui , Zhou Royce W. , Kim Grace Jaeyoon , Krouk Gabriel , Birnbaum Kenneth D. , Purugganan Michael D. , Coruzzi Gloria M. 
Published: August 2013

SignificanceSpecies display a range of plastic phenotypes that presumably have evolved as a result of adaptation to heterogeneous environments. We asked whether the genetic mechanisms that underlie adaptation across populations also determine the response of an individual plant to environmental cues inArabidopsis. Using an integrative root phenotyping approach, genes that underlie natural variation in root architecture across populations were shown to control plasticity responses within an individual. Together, our results uncover a genetic mechanism underlying the phenotypic plasticity of an individual and phenotypic diversity across natural variants.
Tuning the redox activity of encapsulated metal clusters via the metallic and semiconducting character of carbon nanotubes
Authors: Zhang Fan , Pan Xiulian , Hu Yongfeng , Yu Liang , Chen Xiaoqi , Jiang Peng , Zhang Hongbo , Deng Shibin , Zhang Jin , Bolin Trudy B. , Zhang Shuo , Huang Yuying , Bao Xinhe 
Published: August 2013

Significance
The unique property of carbon nanotube channels has triggered wide research interest in different fields. An increasing number of studies show that confinement of metal or metal oxide nanoparticles inside these channels often leads to significantly modified catalytic activity with respect to the same bare metal nanoparticles or those dispersed on the outer walls. We demonstrate here that reactions can be further modulated by the electronic nature (metallic vs. semiconducting character) of nanotubes by taking encapsulated rhenium nanocatalysts as a probe. Particularly, the chemical state of the encapsulated rhenium is tuned due to host–guest electronic interaction. This is of significance for catalytic reactions sensitive to the chemical state of active metals, because it may change the reaction pathways.
Cellular capsules as a tool for multicellular spheroid production and for investigating the mechanics of tumor progression in vitro
Authors: Alessandri Kévin , Sarangi Bibhu Ranjan , Gurchenkov Vasily Valérïévitch , Sinha Bidisha , Kießling Tobias Reinhold , Fetler Luc , Rico Felix , Scheuring Simon , Lamaze Christophe , Simon Anthony , Geraldo Sara , Vignjević Danijela , Doméjean Hugo , Rolland Leslie , Funfak Anette , Bibette Jérôme , Bremond Nicolas , Nassoy Pierre 
Published: August 2013

Significance
Tumor growth intrinsically generates pressure onto the surrounding tissues, which conversely compress the tumor. These mechanical forces have been suggested to contribute to tumor growth regulation. We developed a microfluidic technique to produce 3D cell-based assays and to interrogate the interplay between tumor growth and mechanics in vitro. Multicellular spheroids are grown in permeable elastic capsules. Capsule deformation provides a direct measure of the exerted pressure. By simultaneously imaging the spheroid by confocal microscopy, we show that confinement induces a drastic cellular reorganization, including increased motility of peripheral cells. We propose that compressive stress has a beneficial impact on slowing down tumor evolution but may have a detrimental effect by triggering cell invasion and metastasis.
Ether lipid generating enzyme AGPS alters the balance of structural and signaling lipids to fuel cancer pathogenicity
Authors: Benjamin Daniel I. , Cozzo Alyssa , Ji Xiaodan , Roberts Lindsay S. , Louie Sharon M. , Mulvihill Melinda M. , Luo Kunxin , Nomura Daniel K. 
Published: August 2013

Significance
Ether lipid levels are higher in tumors, but their specific function in cancer has remained unclear. We show here that the metabolic enzyme alkylglyceronephosphate synthase (AGPS), a critical step in the synthesis of ether lipids, is up-regulated across multiple types of aggressive human cancer cells and primary tumors. Inactivation of AGPS leads to significant impairments in cancer pathogenicity through not only lowering the levels of cellular ether lipids, but also by altering fatty acid, eicosanoid, and glycerophospholipid metabolism, resulting in an overall reduction in the levels of several oncogenic signaling lipids.
Converting stem cells to dendritic cells by agonist antibodies from unbiased morphogenic selections
Authors: Yea Kyungmoo , Zhang Hongkai , Xie Jia , Jones Teresa M. , Yang Guang , Song Byeong Doo , Lerner Richard A. 
Published: August 2013

SignificanceIn this paper we describe a unique method for selection of agonist antibodies that regulate stem cell fate. Unbiased combinatorial libraries (not preselected by phage panning) were used and, thus, no constraints were placed on the discovery process. Remarkably, we found that a single agonist antibody against the alpha chains of integrins can induce human stem cells to become dendritic cells. These studies are important because they help deconvolute an otherwise complex developmental process. This approach is analogous to forward genetics and should be widely used to identify previously undescribed proteins involved in important cellular pathways.
Group B Streptococcus meningitis.
Authors: Nizet V. , Doran K. S. 
Published: August 2013

Abstract

This chapter reviews the current understanding of the physiopathology of group B streptococcal (GBS) meningitis, highlighting important bacterial virulence factors and host interactions that promote disease progression. The relationship between bacteraemia and the development of GBS meningitis, and the mechanisms of GBS immune evasion, GBS invasion of the blood-brain barrier (BBB), and GBS activation of the central nervous system's inflammatory response are discussed.
Identification of transcription factor binding sites from ChIP-seq data at high resolution
Authors: Bardet Anaïs F. , Steinmann Jonas , Bafna Sangeeta , Knoblich Juergen A. , Zeitlinger Julia , Stark Alexander 
Published: August 2013

Abstract
Motivation: Chromatin immunoprecipitation coupled to next-generation sequencing (ChIP-seq) is widely used to study the in vivo binding sites of transcription factors (TFs) and their regulatory targets. Recent improvements to ChIP-seq, such as increased resolution, promise deeper insights into transcriptional regulation, yet require novel computational tools to fully leverage their advantages.
Results: To this aim, we have developed peakzilla, which can identify closely spaced TF binding sites at high resolution (i.e. resolves individual binding sites even if spaced closely), as we demonstrate using semisynthetic datasets, performing ChIP-seq for the TF Twist in Drosophila embryos with different experimental fragment sizes, and analyzing ChIP-exo datasets. We show that the increased resolution reached by peakzilla is highly relevant, as closely spaced Twist binding sites are strongly enriched in transcriptional enhancers, suggesting a signature to discriminate functional from abundant non-functional or neutral TF binding. Peakzilla is easy to use, as it estimates all the necessary parameters from the data and is freely available.
Availability and implementation: The peakzilla program is available from https://github.com/steinmann/peakzilla or http://www.starklab.org/data/peakzilla/.
Contact: stark@starklab.org
Supplementary information: Supplementary data are available at Bioinformatics online.
Modelling larval fish navigation: the way forward
Authors: Staaterman Erica , Paris Claire B. 
Published: August 2013

Abstract
Recent advances in high-resolution ocean circulation models, coupled with a greater understanding of larval behaviour, have increased the sophistication of individual-based, biophysical models used to study the dispersal of larvae in the sea. Fish larvae, in particular, have the ability to swim directionally and increasingly fast during ontogeny, indicating that they may not only disperse, but also migrate using environmental signals. How and when larvae use local and large-scale cues remains a mystery. Including three-dimensional swimming schemes into biophysical models is becoming essential to address these questions. Here, we highlight state-of-the-art modelling of vertical and horizontal migrations of fish larvae, as well as current challenges in moving towards more realistic larval movements in response to cues. Improved understanding of causes for orientation will provide insight into the evolutionary drivers of dispersal strategies for fish and marine organisms in general.
Implementing ecosystem-based fisheries management: from single-species to integrated ecosystem assessment and advice for Baltic Sea fish stocks
Authors: Möllmann Christian , Lindegren Martin , Blenckner Thorsten , Bergström Lena , Casini Michele , Diekmann Rabea , Flinkman Juha , Müller-Karulis Bärbel , Neuenfeldt Stefan , Schmidt Jörn O. , Tomczak Maciej , Voss Rüdiger , Gårdmark Anna 
Published: August 2013

Abstract
Theory behind ecosystem-based management (EBM) and ecosystem-based fisheries management (EBFM) is now well developed. However, the implementation of EBFM exemplified by fisheries management in Europe is still largely based on single-species assessments and ignores the wider ecosystem context and impact. The reason for the lack or slow implementation of EBM and specifically EBFM is a lack of a coherent strategy. Such a strategy is offered by recently developed integrated ecosystem assessments (IEAs), a formal synthesis tool to quantitatively analyse information on relevant natural and socio-economic factors, in relation to specified management objectives. Here, we focus on implementing the IEA approach for Baltic Sea fish stocks. We combine both tactical and strategic management aspects into a single strategy that supports the present Baltic Sea fish stock advice, conducted by the International Council for the Exploration of the Sea (ICES). We first review the state of the art in the development of IEA within the current management framework. We then outline and discuss an approach that integrates fish stock advice and IEAs for the Baltic Sea. We intentionally focus on the central Baltic Sea and its three major fish stocks cod (Gadus morhua), herring (Clupea harengus), and sprat (Sprattus sprattus), but emphasize that our approach may be applied to other parts and stocks of the Baltic, as well as other ocean areas.
Cosmological structure formation with augmented Lagrangian perturbation theory
Authors: Kitaura Francisco-Shu , Heß Steffen 
Published: August 2013

AbstractWe present a new fast and efficient approach to model structure formation with augmented Lagrangian perturbation theory (ALPT). Our method is based on splitting the displacement field into a long- and a short-range component. The long-range component is computed by second-order LPT (2LPT). This approximation contains a tidal non-local and non-linear term. Unfortunately, 2LPT fails on small scales due to severe shell crossing and a crude quadratic behaviour in the low-density regime. The spherical collapse (SC) approximation has been recently reported to correct for both effects by adding an ideal collapse truncation. However, this approach fails to reproduce the structures on large scales where it is significantly less correlated with the N-body result than 2LPT or linear LPT (the Zel'dovich approximation). We propose to combine both approximations using for the short-range displacement field the SC solution. A Gaussian filter with a smoothing radius rS is used to separate between both regimes. We use the result of 25 dark-matter-only N-body simulations to benchmark at z = 0 the different approximations: first-, second-, third-order LPT, SC and our novel combined ALPT model. This comparison demonstrates that our method improves previous approximations at all scales showing ∼25 and ∼75 per cent higher correlation than 2LPT with the N-body solution at k = 1 and 2 h Mpc−1, respectively. We conduct a parameter study to determine the optimal range of smoothing radii and find that the maximum correlation is achieved with rS = 4–5 h−1 Mpc. This structure formation approach could be used for various purposes, such as setting-up initial conditions for N-body simulations, generating mock galaxy catalogues, cosmic web analysis or for reconstructions of the primordial density fluctuations.