bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutant KRAS is a druggable target for pancreatic cancer
Authors: Zorde Khvalevsky Elina , Gabai Racheli , Rachmut Itzhak Haim , Horwitz Elad , Brunschwig Zivia , Orbach Ariel , Shemi Adva , Golan Talia , Domb Abraham J. , Yavin Eylon , Giladi Hilla , Rivkin Ludmila , Simerzin Alina , Eliakim Rami , Khalaileh Abed , Hubert Ayala , Lahav Maor , Kopelman Yael , Goldin Eran , Dancour Alan , Hants Yael , Arbel-Alon Sagit , Abramovitch Rinat , Shemi Amotz , Galun Eithan 
Published: December 2013

Significance
Pancreatic cancer is still one of the major challenges in clinical oncology. Mutant KRAS is a driving oncogene in the majority of human pancreatic cancer cases. We have made an effort to meet this challenge by developing a therapeutic platform for local and prolonged delivery of siRNA. Our results show that the siRNA targeted against KRAS mutations with a local prolonged release system knocks down KRAS expression in vitro and in vivo, leading to an antitumor effect. Our report describes an applicable and efficient delivery method of siRNA that overcomes the major obstacles of toxicity and organ accessibility. Notably our approach enabled the conversion of KRAS from a nondruggable to a potentially druggable cancer target.
Ascites analysis by a microfluidic chip allows tumor-cell profiling
Authors: Peterson Vanessa M. , Castro Cesar M. , Chung Jaehoon , Miller Nathan C. , Ullal Adeeti V. , Castano Maria D. , Penson Richard T. , Lee Hakho , Birrer Michael J. , Weissleder Ralph 
Published: December 2013

Significance
Serial molecular analyses of tumor cells during treatment- and biopsy-driven clinical trials are emerging norms for many cancers. Yet surgical and image-guided biopsies are expensive and invasive, explaining why alternative sources for tumor cells are being sought. In ovarian cancer (and other abdominopelvic cancers), abdominal fluid buildup (ascites) occurs frequently. We demonstrate that ascites tumor cells (ATCs) present a valuable source of tumor cells, rendering ascites another form of “liquid biopsy.” We evaluated 85 ovarian cancer-related markers and developed a unique, low cost miniaturized microfluidic ATC chip for on-chip enrichment and molecular profiling using small amounts of ascites. This approach could expand the utility of ATCs within cytotoxic and/or molecularly targeted ovarian cancer therapeutic trials.
Pentameric complex of viral glycoprotein H is the primary target for potent neutralization by a human cytomegalovirus vaccine
Authors: Freed Daniel C. , Tang Qi , Tang Aimin , Li Fengsheng , He Xi , Huang Zhao , Meng Weixu , Xia Lin , Finnefrock Adam C. , Durr Eberhard , Espeseth Amy S. , Casimiro Danilo R. , Zhang Ningyan , Shiver John W. , Wang Dai , An Zhiqiang , Fu Tong-Ming 
Published: December 2013

SignificanceCongenital human cytomegalovirus (HCMV) infection is an important cause of newborn disability, and developing a vaccine against congenital HCMV is a top priority. However, despite decades of efforts, a vaccine remains elusive. Previous vaccines lacked an antigen called pentameric glycoprotein H (gH) complex, essential for the virus to infect epithelial/endothelial cells, and these vaccines induced poor neutralizing antibodies. To support a unique vaccine concept featuring the pentameric gH complex, we established 45 mAbs from a rabbit immunized with an experimental vaccine. Over 50% of the mAbs have antiviral activity, and potent clones target the pentameric gH complex, thus establishing this antigen as the key for potent antiviral antibodies by vaccination. Our result contributes to the understanding of immune attributes of an effective vaccine against HCMV.
Protein O-mannosylation is crucial for E-cadherin–mediated cell adhesion
Authors: Lommel Mark , Winterhalter Patrick R. , Willer Tobias , Dahlhoff Maik , Schneider Marlon R. , Bartels Markus F. , Renner-Müller Ingrid , Ruppert Thomas , Wolf Eckhard , Strahl Sabine 
Published: December 2013

Significance
Cell–cell adhesion is essential for embryonic development, tissue morphogenesis, and tissue repair, as well as for tumor invasion and metastasis. Thus, it is of fundamental importance to identify the molecular factors that affect this process. Here we demonstrate that O-mannosylation, an essential posttranslational protein modification, is crucial for the formation of adherens junctions between cells of the early mouse embryo, with O-mannosylation–deficient embryos dying at the morula-to-blastocyst transition. Moreover, we identified O-mannosyl glycans on E-cadherin, the major cell–cell adhesion protein of embryos, and demonstrated that these glycans are crucial for E-cadherin–mediated cell adhesion. Because O-mannosylation is a conserved feature of the classical cadherins, this protein modification most likely affects many more biological processes than previously thought.
Multiple modes of regulation of the human Ino80 SNF2 ATPase by subunits of the INO80 chromatin-remodeling complex
Authors: Chen Lu , Conaway Ronald C. , Conaway Joan W. 
Published: December 2013

Significance
SNF2 family ATPases are ATP-dependent motors with roles in diverse nuclear processes. Regulation of the catalytic activity of SNF2 family ATPases via their associated proteins is a key element determining their functions. Thus, illuminating the mechanisms of action of SNF2 regulatory proteins is a priority of current studies. Here, we show subunits of the human INO80 chromatin-remodeling complex act by different mechanisms: Ies2 activates INO80 catalytic activity, while Ies6 and Arp5 function in nucleosome recognition.
Two-dimensional Raman-terahertz spectroscopy of water
Authors: Savolainen Janne , Ahmed Saima , Hamm Peter 
Published: December 2013

Significance
The discussion about the structure of water becomes increasingly more controversial, and appears to be stuck because the major techniques used to study it (small-angle X-ray scattering emphasizing the structure, multidimensional infrared spectroscopy emphasizing the dynamics, and molecular dynamics simulations using questionable force fields) do not seem to provide mutually converging results. This calls for a different experimental approach, which we offer here with 2D Raman-terahertz spectroscopy. The work extends multidimensional vibrational spectroscopy into the far-IR regime where thermally excited soft modes are found that are directly responsible for molecular dynamics (in contrast with the high-frequency spectator modes investigated in 2D-IR spectroscopy, which per se are quiet at room temperature and sense the environment only indirectly).
Topological augmentation to infer hidden processes in biological systems
Authors: Sunnåker Mikael , Zamora-Sillero Elias , López García de Lomana Adrián , Rudroff Florian , Sauer Uwe , Stelling Joerg , Wagner Andreas 
Published: December 2013

Abstract
Motivation: A common problem in understanding a biochemical system is to infer its correct structure or topology. This topology consists of all relevant state variables—usually molecules and their interactions. Here we present a method called topological augmentation to infer this structure in a statistically rigorous and systematic way from prior knowledge and experimental data.
Results: Topological augmentation starts from a simple model that is unable to explain the experimental data and augments its topology by adding new terms that capture the experimental behavior. This process is guided by representing the uncertainty in the model topology through stochastic differential equations whose trajectories contain information about missing model parts. We first apply this semiautomatic procedure to a pharmacokinetic model. This example illustrates that a global sampling of the parameter space is critical for inferring a correct model structure. We also use our method to improve our understanding of glutamine transport in yeast. This analysis shows that transport dynamics is determined by glutamine permeases with two different kinds of kinetics. Topological augmentation can not only be applied to biochemical systems, but also to any system that can be described by ordinary differential equations.
Availability and implementation: Matlab code and examples are available at: http://www.csb.ethz.ch/tools/index.
Contact: mikael.sunnaker@bsse.ethz.ch; andreas.wagner@ieu.uzh.ch
Supplementary information: Supplementary data are available at Bioinformatics online.
LipidGO: database for lipid-related GO terms and applications
Authors: Fan Mengyuan , Low Hong Sang , Zhou Hufeng , Wenk Markus R. , Wong Limsoon 
Published: December 2013

Abstract
Motivation: Lipid, an essential class of biomolecules, is receiving increasing attention in the research community, especially with the development of analytical technique like mass spectrometry. Gene Ontology (GO) is the de facto standard function annotation scheme for gene products. Identification of both explicit and implicit lipid-related GO terms will help lipid research in many ways, e.g. assigning lipid function in protein function prediction.
Results: We have constructed a Web site ‘LipidGO’ that facilitates browsing and searching lipid-related GO terms. An expandable hierarchical GO tree is constructed that allows users to find lipid-related GO terms easily. To support large-scale analysis, a user is able to upload a list of gene products or a list of GO terms to find out which of them is lipid related. Finally, we demonstrate the usefulness of ‘LipidGO’ by two applications: (i) identifying lipid-related gene products in model organisms and (ii) discovering potential novel lipid-related molecular functions
Availability and implementation: LipidGO is available at http://compbio.ddns.comp.nus.edu.sg/%7elipidgo/index.php.
Contact: wongls@comp.nus.edu.sg
Supplementary Information: Supplementary data are available at Bioinformatics online.
Mutated SF3B1 is associated with transcript isoform changes of the genes UQCC and RPL31 both in CLLs and uveal melanomas
Authors: Reyes Alejandro , Blume Carolin , Pelechano Vincent , Jakob Petra , Steinmetz Lars M. , Zenz Thorsten , Huber Wolfgang 
Published: December 2013

AbstractBackgroundGenome sequencing studies of chronic lympoid leukemia (CLL) have provided a comprehensive overview of recurrent somatic mutations in coding genes. One of the most intriguing discoveries has been the prevalence of mutations in the HEAT-repeat domain of the splicing factorSF3B1. A frequently observed variant is predicted to cause the substitution of a lysine with a glutamic acid at position 700 of the protein (K700E). However, the molecular consequences of the mutations are largely unknown.ResultsTo start exploring this question, we sequenced the transcriptomes of six samples: four samples of CLL tumour cells, of which two contained the K700E mutation inSF3B1, and CD19 positive cells from two healthy donors. We identified 41 genes that showed differential usage of exons statistically associated with the mutated status ofSF3B1(false discovery rate of 10%). These genes were enriched in pathways related to interferon signaling and mRNA splicing.Among these genes, we foundUQCCandRPL31; notably, a similar effect on these genes was described in a previously published study of uveal melanoma. In addition, while this manuscript was under revision, another study independently reported the common splicing signature of the geneUQCCin different tumour types with mutations inSF3B1.ConclusionsOur results suggest common effects of isoform deregulation in the genesUQCCandRPL31upon mutations inSF3B1. Additionally, our data provide a candidate list of potential isoform consequences of the SF3B1 (K700E) mutation in CLL, some of which might contribute to the tumourigenesis.Validation studies on larger cohorts and model systems are required to extend these findings.
On the study of evolutionary predictability using historical reconstruction
Authors: Venkataram Sandeep , Sellis Diamantis , Petrova Dmitri A. 
Published: December 2013

AbstractPredicting the course of evolution is critical for solving current biomedical challenges such as cancer and the evolution of drug resistant pathogens. One approach to studying evolutionary predictability is to observe repeated, independent evolutionary trajectories of similar organisms under similar selection pressures in order to empirically characterize this adaptive fitness landscape. As this approach is infeasible for many natural systems, a number of recent studies have attempted to gain insight into the adaptive fitness landscape by testing the plausibility of different orders of appearance for a specific set of adaptive mutations in a single adaptive trajectory. While this approach is technically feasible for systems with very few available adaptive mutations, the usefulness of this approach for predicting evolution in situations with highly polygenic adaptation is unknown. It is also unclear whether the presence of stable adaptive polymorphisms can influence the predictability of evolution as measured by these methods. In this work, we simulate adaptive evolution under Fisher’s geometric model to study evolutionary predictability. Remarkably, we find that the predictability estimated by these methods are anti-correlated, and that the presence of stable adaptive polymorphisms can both qualitatively and quantitatively change the predictability of evolution.
Identification of a dynamic model for shape memory alloy actuator using Hammerstein-Wiener gray box and mutable smart bee algorithm
Authors: Fathi Alireza , Mozaffari Ahmad 
Published: December 2013

Purpose
– The purpose of the current investigation is to design a robust and reliable computational framework to effectively identify the nonlinear behavior of shape memory alloy (SMA) actuators, as one of the most applicable types of actuators in engineering and industry. The motivation of proposing such an intelligent paradigm emanates in the pursuit of fulfilling the necessity of devising a simple yet effective identification system capable of modeling the hysteric dynamical respond of SMA actuators.

Design/methodology/approach
– To address the requirements of designing a pragmatic identification system, the authors integrate a set of fast yet reliable intelligent methodologies and provide a predictive tool capable of realizing the nonlinear hysteric behavior of SMA actuators in a computationally efficient fashion. First, the authors utilize the governing equations to design a gray box Hammerstein-Wiener identifier model. At the next step, they adopt a computationally efficient metaheuristic algorithm to elicit the optimum operating parameters of the gray box identifier.

Findings
– Applying the proposed hybrid identifier framework allows the authors to find out its advantages in modeling the behavior of SMA actuator. Through different experiments, the authors conclude that the proposed identifier can be used for identification of highly nonlinear dynamic behavior of SMA actuators. Furthermore, by extending the conclusions and expounding the obtained results, one can easily infer that such a hybrid method may be conveniently applied to model other engineering phenomena that possess dynamic nonlinear reactions. Based on the exerted experiments and implementing the method, the authors come to the conclusion that integrating the power of metaheuristic exploration/exploitation with gray box identifier results a predictive paradigm that much more computationally efficient as compared with black box identifiers such as neural networks. Additionally, the derived gray box method has a higher degree of preference over the black box identifiers, as it allows a manipulated expert to extract the knowledge of the system at hand.

Originality/value
– The originality of the research paper is twofold. From the practical (engineering) point of view, the authors built a prototype biased-spring SMA actuator and carried out several experiments to ascertain and validate the parameters of the model. From the computational point of view, the authors seek for designing a novel identifier that overcomes the main flaws associated with the performance of black-box identifiers that are the lack of a mean for extracting the governing knowledge of the system at hand, and high computational expense pertinent to the structure of black-box identifiers.
A modified colonial competitive algorithm for optimizing convex functions
Authors: Esmaeilzadeh Mahsan 
Published: December 2013

Purpose
– This article is going to introduce a modified variant of the imperialist competitive algorithm (ICA). The paper aims to discuss these issues.

Design/methodology/approach
– ICA is a meta-heuristic algorithm that is introduced based on a socio-politically motivated global search strategy. It is a population-based stochastic algorithm to control more countries. The most powerful countries are imperialists and the weakest countries are colonies. Colonies movement toward their relevant imperialist, and making a competition among all empires to posses the weakest colonies of the weakest empires, form the basis of the ICA. This fact that the imperialists also need to model and they move towards top imperialist state is the most common type of political rules from around the world. This paper exploits these new ideas. The modification is the empire movement toward the superior empire for balancing the exploration and exploitation abilities of the ICA.

Findings
– The algorithms are used for optimization that have shortcoming to deal with accuracy rate and local optimum trap and they need complex tuning procedures. MICA is proposed a way for optimizing convex function with high accuracy and avoiding to trap in local optima rather than using original ICA algorithm by implementing some modification on it.

Originality/value
– Therefore, several solution procedures, including ICA, modified ICA, and genetic algorithm and particle swarm optimization algorithm are proposed. Finally, numerical experiments are carried out to evaluate the effectiveness of models as well as solution procedures. Test results present the suitability of the proposed modified ICA for convex functions with little fluctuations.
Clinical psychologists working in crisis resolution and home treatment teams: a grounded theory exploration
Authors: Murphy Nicola , Vidgen Andrew , Sandford Clare , Onyett Steve 
Published: December 2013

Purpose– There has been a rapid development and implementation of crisis resolution home treatment teams (CRHTT) in the UK over the past decade. The available research studies of this service provision to date have largely focused on issues related to the “outputs” of CRHTT, for example cost efficacy and the impact on admission rates. There is limited research on the experiences of clinical psychologists within CRHTT. This is despite the fact that it would seem that research exploring the experiences of mental health professionals in CRHTT is important, as working in a new area of service provision may present specific challenges. An understanding of the nature of these challenges is considered important in order to support clinical psychologists in these settings, and to sustain and improve service delivery.Design/methodology/approach–This study presents a qualitative exploration of clinical psychologists’ experiences of working in a CRHTT. In total, 11 clinical psychologists were interviewed about their perceptions of working within CRHTT, their relationships with other professionals and their experiences of working with service users in “crisis”. The grounded theory approach was employed to analyse participants’ accounts.Findings–Two themes were identified: psychological and clinical work and teamwork. The emergent themes are compared to the wider literature on clinical psychologists’ experiences of working in teams, and working with service users in “crisis”.Originality/value– This research demonstrates the value of a clinical psychology perspective in acute mental health settings. It also highlights the value of a clinical psychological perspective in multi-disciplinary team working. It draws attention to the need for clinical psychologists working in CRHTT settings to be able to more clearly articulate their roles in these services. It points to the importance of clinical psychologists considering the interventions they provide to service users with complex presentations. Also, it highlights their need to consider the psychological interventions they provide in CRHTT settings more generally, as this area of work does not closely align with NICE guidelines.
Implementing mental health law: a comparison of social work practice across three jurisdictions
Authors: O’Hare Philip , Davidson Gavin , Campbell Jim , Maas-Lowit Michael 
Published: December 2013

Purpose
– Over the last 12 years there have been substantial developments in UK law and policy relevant to mental health social work practice. The previous legal frameworks across the jurisdictions were very similar but the new laws have developed in different ways and provide greater opportunities for comparison. Across all the jurisdictions policy developments, especially in the areas of recovery and risk assessment, have influenced the way that mental health social workers practice.

Design/methodology/approach
– This exploratory study used case study vignettes with 28 respondents to examine how these major legal and policy developments impact on social work practice.

Findings
– There were variations in how levels of risk are defined and often a lack of clarity about how this informs decisions. There was a consensus that recovery is important but difficulties in understanding how this might apply in crises. Predictably, differences in legal and policy contexts meant that there were a variety of perspectives on how mental health social workers applied the laws in their jurisdictions.

Research limitations/implications
– The limited focus on research informed practice and the lack of transparency in decision making across areas of risk assessment and intervention, use of recovery approaches and the use of mental health laws suggest the need for a more evidence-based approach to training, education and practice.

Originality/value
– There is very limited previous research on practitioner experiences of the complexities involved in implementing mental health law. This paper provides some insights into the issues involved and for the need for more detailed examination of the decision-making processes involved.