bluuebunny/crossref_metadata_2025_split huggingface dataset:
The SIRAH force field 2.0: Altius, Fortius, Citius
Authors: Machado Matías R. , Barrera Exequiel E. , Klein Florencia , Sóñora Martín , Silva Steffano , Pantano Sergio 
Published: October 2018

ABSTRACTA new version of the coarse-grained (CG) SIRAH force field for proteins has been developed. Modifications to bonded and non-bonded interactions on the existing molecular topologies significantly ameliorate the structural description and flexibility of a non-redundant set of proteins. The SIRAH 2.0 force field has also been ported to the popular simulation package AMBER, which along with the former implementation in GROMACS expands significantly the potential range of users and performance of this CG force field on CPU/GPU codes.As a non-trivial example of application, we undertook the structural and dynamical analysis of the most abundant and conserved calcium-binding protein, namely, Calmodulin (CaM). CaM is constituted by two calcium-binding motifs called EF-hands, which in presence of Calcium specifically recognize a cognate peptide by embracing it. CG simulations of CaM bound to four Calcium ions in the presence or absence of a binding peptide (holo and apo forms, respectively), resulted in good and stable ion coordination. The simulation of the holo form starting from an experimental structure sampled near-native conformations, retrieving quasi-atomistic precision. Removing the binding peptide enabled the EF-hands to perform large reciprocal movements, comparable to those observed in NMR structures. On the other hand, the isolated peptide starting from the helical conformation experienced spontaneous unfolding, in agreement with previous experimental data. However, repositioning the peptide in the neighborhood of one EF-hand not only prevented the peptide unfolding but also drove CaM to a fully bound conformation with both EF-hands embracing the cognate peptide, resembling the experimental holo structure.Therefore, SIRAH 2.0 showed the capacity to handle a number of structurally and dynamically challenging situations including metal ion coordination, unbiased conformational sampling, and specific protein-peptide recognition.
TOC.
Down syndrome fibroblasts exhibit diminished autophagic clearance and endosomal dysfunction after serum starvation
Authors: Aivazidis Stefanos , Jain Abhilasha , Anderson Colin C. , Orlicky David J. , Rauniyar Abhishek K. , Fritz Kristofer S. , Harris Peter S. , Siegel David , Maclean Kenneth N. , Roede James R. 
Published: October 2018

AbstractDown syndrome (DS) is a genetic disorder caused by trisomy of chromosome 21 (Tri21). This unbalanced karyotype has the ability to produce proteotoxic stress and dysfunction of the proteostasis network (PN), which are mechanistically associated with several comorbidities found in the DS phenotype. Autophagy is the cellular process responsible for bulk protein degradation and its impairment could negatively impact protein quality control. Based on our previous observations of PN disruption in DS, we investigated possible dysfunction of the autophagic machinery in human DS fibroblasts. Both euploid (CTL) and DS fibroblasts induced autophagy successfully through serum starvation (SS), as evidenced by increased LC3-II abundance in CTL and DS. However, DS cells displayed evidence of autophagolysosome (AL) accumulation and impaired clearance of autophagosome cargo, e.g. accumulation of p62 and NBR1. Similar observations were also present in DS cells from multiple differentiation stages, implicating impeded autophagic degradation as a possible early pathologic mechanism in DS. Lysosomal pH and cathepsin B proteolytic activity were found to not differ in CTL and DS fibroblasts after SS, indicating that lysosomal dysfunction did not appear to contribute to unsuccessful autophagic clearance. Based on these results, we hypothesized that possible interference of the endosomal system with autophagy results in autophagosome fusion with endosomal vesicles and negatively impacts degradation. Consistent with this hypothesis, we observed increased abundance of the recycling endosome marker, Rab11, after SS in DS fibroblasts. Further, colocalization of autophagosome markers with resident proteins of early endosomes, late endosomes and recycling endosomes (Rab11) further support our hypothesis. In summary, our work is consistent with impairment of autophagic flux and general PN dysfunction as candidate mechanisms for pathology in DS.
Evolved phenological cueing strategies show variable responses to climate change
Authors: Edwards Collin B. , Yang Louie 
Published: October 2018

AbstractSeveral studies have documented a global pattern of phenological advancement that is consistent with ongoing climate change. However, the magnitude of these phenological shifts is highly variable across taxa and locations. This variability of phenological responses has been difficult to explain mechanistically. To examine how the evolution of multi-trait cueing strategies could produce variable responses to climate change, we constructed a model in which organisms evolve strategies that integrate multiple environmental cues to inform anticipatory phenological decisions. We simulated the evolution of phenological cueing strategies in multiple environments, using historic climate data from 78 locations in North America and Hawaii to capture features of climatic correlation structures in the real world. Organisms in our model evolved diverse strategies that were spatially autocorrelated across locations on a continental scale, showing that similar strategies tend to evolve in similar climates. Within locations, organisms often evolved a wide range of strategies that showed similar response phenotypes and fitness outcomes under historical conditions. However, these strategies responded differently to novel climatic conditions, with variable fitness consequences. Our model shows how the evolution of phenological cueing strategies can explain observed variation in phenological shifts and unexpected responses to climate change.
WITER: A powerful method for the estimation of cancer-driver genes using a weighted iterative regression accurately modelling background mutation rate
Authors: Jiang Lin , Zheng Jingjing , Him Kwan Johnny Sheung , Dai Sheng , Li Cong , Li Mulin Jun , Yu Bolan , TO Ka Fai , Sham Pak Chung , Zhu Yonghong , Li Miaoxin 
Published: October 2018

AbstractGenomic identification of driver mutations and genes in cancer cells are critical for precision medicine. Due to difficulty in modeling distribution of background mutations, existing statistical methods are often underpowered to discriminate driver genes from passenger genes. Here we propose a novel statistical approach, weighted iterative zero-truncated negative-binomial regression (WITER), to detect cancer-driver genes showing an excess of somatic mutations. By solving the problem of inaccurately modeling background mutations, this approach works even in small or moderate samples. Compared to alternative methods, it detected more significant and cancer-consensus genes in all tested cancers. Applying this approach, we estimated 178 driver genes in 26 different cancers types. In silico validation confirmed 90.5% of predicted genes as likely known drivers and 7 genes unique for individual cancers as likely new drivers. The technical advances of WITER enable the detection of driver genes in TCGA datasets as small as 30 subjects, rescuing more genes missed by alternative tools.
Integrative Network and Brain Expression Analysis reveals Mechanistic Modules in Ataxia
Authors: Eidhof Ilse , Warrenburg Bart P van de , Schenck Annette 
Published: October 2018

AbstractBackgroundGenetic forms of ataxia are a heterogenous group of degenerative diseases of the cerebellum. Many causative genes have been identified, but a systematic investigation of these genes to understand ataxia pathophysiology has not been performed.MethodsA manually curated catalogue of 71 genes involved in disorders with progressive ataxias as a major clinical feature was subjected to an integrated gene ontology (GO), protein network, and brain gene expression profiling analysis.ResultsWe found that ataxia genes operate in networks with significantly enriched protein connectivity, demonstrating coherence on a global level, independent of inheritance mode. Moreover, elevated expression specifically in the cerebellum predisposes to ataxia. Genes expressed in this pattern are significantly overrepresented among ataxia genes and are enriched for ion homeostasis/synaptic functions. The majority of ataxia genes, however, does not show elevated cerebellar expression that could account for region-specific degeneration. For these, we identified defective cellular stress responses as a major common biological theme, suggesting that the defense pathways against stress are more critical to maintain cerebellar integrity than integrity of other brain regions. Approximately half of the ataxia genes, mostly part of the stress module, show higher expression at embryonic stages, which argues for a developmental predisposition.ConclusionGenetic defects in ataxia predominantly affect neuronal homeostasis, to which the cerebellum appears to be excessively susceptible. Based on the identified modules, it is conceivable to propose common therapeutic interventions that target deregulated calcium and ROS levels, or mechanisms that can decrease the harmful downstream effects of these deleterious insults.
Optimised DNA extraction and library preparation for minute arthropods: application to target enrichment in chalcid wasps used for biocontrol
Authors: Cruaud Astrid , Nidelet Sabine , Arnal Pierre , Weber Audrey , Fusu Lucian , Gumovsky Alex , Huber John , Polaszek Andrew , Rasplus Jean-Yves 
Published: October 2018

AbstractEnriching subsets of the genome prior to sequencing allows focusing effort on regions that are relevant to answer specific questions. As experimental design can be adapted to sequence many samples simultaneously, using such approach also contributes to reduce cost. In the field of ecology and evolution, target enrichment is increasingly used for genotyping of plant and animal species or to better understand the evolutionary history of important lineages through the inference of statistically robust phylogenies. Limitations to routine target enrichment by research laboratories are both the complexity of current protocols and low input DNA quantity. Thus, working with tiny organisms such as micro-arthropods can be challenging. Here, we propose easy to set up optimisations for DNA extraction and library preparation prior to target enrichment. Prepared libraries were used to capture 1432 Ultra-Conserved Elements (UCEs) from microhymenoptera (Chalcidoidea), which are among the tiniest insects on Earth and the most commercialized worldwide for biological control purposes. Results show no correlation between input DNA quantities (1.8-250ng, 0.4 ng with an extra whole genome amplification step) and the number of sequenced UCEs. Phylogenetic inferences highlight the potential of UCEs to solve relationships within the families of chalcid wasps, which has not been achieved so far. The protocol (library preparation + target enrichment), allows processing 96 specimens in five working days, by a single person, without requiring the use of expensive robotic molecular biology platforms, which could help to generalize the use of target enrichment for minute specimens.
Cerebral blood flow measured with diffusing wave spectroscopy during anesthesia
Authors: Belau Markus , Scheffer Wolfgang , Maret Georg 
Published: October 2018

AbstractThe adequate perfusion of the brain is of utmost importance where already short periods of hypoperfusion may lead to permanent damage. In order to increase patient safety the cerebral blood flow should be monitored in clinical settings during situations, such as anesthesia, where the perfusion might be disturbed. The cerebral blood flow is however not monitored on a routine basis during anesthesia. Diffusing wave spectroscopy is a relative novel optical method that non-invasively measures changes in cerebral blood flow. Here we report changes in cerebral blood flow associated with a delayed cardiac output, a change in isoflurane concentration and body temperature observed during general anesthesia with isoflurane in pigeons.
Robust Algorithms for Capturing Population Dynamics and Transport in Oceanic Variables along Drifter Trajectories using Linear Dynamical Systems with Latent Variables
Authors: Yan Yan , Jebara Tony , Abernathey Ryan , Goes Joaquim , Gomes Helga 
Published: October 2018

AbstractThe blooms ofNoctilucain the Gulf of Oman and the Arabian Sea have been intensifying in recent years posing a threat to regional fisheries and the long-term health of an ecosystem supporting a coastal population of nearly 120 million people. We present the results of a microscopic data analysis to investigate the onset and patterns of theNoctiluca(mixotrophic dinoflagellateNoctiluca scintillans) blooms, which form annually during the winter monsoon in the Gulf of Oman and in the Arabian Sea. Our approach combines methods in physical and biological oceanography with machine learning techniques. In particular, we present a robust algorithm, the variable-length Linear Dynamic Systems (vLDS) model, that extracts the causal factors and latent dynamics at the microscopic population-level along each individual drifter trajectory, and demonstrate its effectiveness by using it to test and confirm previously benchmarked macroscopic scientific hypotheses. The test results provide microscopic statistical evidence to support and recheck the macroscopic physical and biological Oceanography hypotheses on theNoctilucablooms; it also helps identify complementary microscopic dynamics that might not be visible or discoverable at the macroscopic scale. The vLDS model also exhibits a generalization capability (inherited from a machine learning methodology) to investigate important causal factors and hidden dynamics associated with ocean biogeochemical processes and phenomena at the population-level.
Topological Scoring of Protein Interaction Networks
Authors: Sardiu Mihaela E. , Gilmore Joshua M. , Groppe Brad D. , Dutta Arnob , Florens Laurence , Washburn Michael P. 
Published: October 2018

AbstractIt remains a significant challenge to define individual protein associations within networks where an individual protein can directly interact with other proteins and/or be part of large complexes, which contain functional modules. Here we demonstrate the topological scoring (TopS) algorithm for the analysis of quantitative proteomic analyses of affinity purifications. Data is analyzed in a parallel fashion where a bait protein is scored in an individual affinity purification by aggregating information from the entire dataset. A broad range of scores is obtained which indicate the enrichment of an individual protein in every bait protein analyzed. TopS was applied to interaction networks derived from human DNA repair proteins and yeast chromatin remodeling complexes. TopS captured direct protein interactions and modules within complexes. TopS is a rapid method for the efficient and informative computational analysis of datasets, is complementary to existing analysis pipelines, and provides new insights into protein interaction networks.
Nonlinear time-optimal trajectory planning for varying-rope-length overhead cranes
Authors: Wu Yiming , Sun Ning , Chen He , Zhang Jianyi , Fang Yongchun 
Published: October 2018

Purpose
From practical perspectives and to improve the working efficiency, trolley transportation and payload hoisting/lowering should be simultaneously controlled. Moreover, in practical crane applications, the transportation time is an important criterion for improving transportation efficiency. Based on these requirements, this paper aims to solve positioning and antiswing control problems and shorten the transportation time for underactuated varying-rope-length overhead cranes.

Design/methodology/approach
By choosing trolley acceleration and varying-rope-length acceleration as system inputs, the crane system dynamic model is converted into an equivalent model without linearizing/approximating. Then, based on the converted model and system state constraints, a time-optimal problem is formulated. Further, the original problem is converted into an optimization problem with algebraic constraints which can be conveniently solved. Finally, by solving the optimization problem, the optimal trajectories of system states, including displacements, velocities and accelerations, are obtained.

Findings
This paper first provides a nonlinear time-optimal trajectory planner for varying-rope-length overhead cranes, which achieves accurate and fast trolley positioning and eliminates payload residual swings. Meanwhile, all system states satisfy the given constraints during the entire process. Hardware experimental results show that the proposed time-optimal planner is effective and has better performance compared with existing methods.

Originality/value
This paper proposes a time-optimal trajectory planner for overhead crane systems with hoisting/lowering motion. The proposed planner achieves fast trolley positioning and eliminates payload residual swing with all the system states being constrained within given scopes. The planner is presented based on the original nonlinear system dynamics without linearization/approximation.
Flight path optimization with application to in-flight replanning to changing destinations
Authors: Babel Luitpold 
Published: October 2018

PurposeThe purpose of this paper is to present a new approach for finding a minimum-length trajectory for an autonomous unmanned air vehicle or a long-range missile from a release point with specified release conditions to a destination with specified approach conditions. The trajectory has to avoid obstacles and no-fly zones and must take into account the kinematic constraints of the air vehicle.Design/methodology/approachA discrete routing model is proposed that represents the airspace by a sophisticated network. The problem is then solved by applying standard shortest-path algorithms.FindingsIn contrast to the most widely used grids, the generated networks allow arbitrary flight directions and turn angles, as well as maneuvers of different strengths, thus fully exploiting the flight capabilities of the aircraft. Moreover, the networks are resolution-independent and provide high flexibility by the option to adapt density.Practical implicationsAs an application, a concept for in-flight replanning of flight paths to changing destinations is proposed. All computationally intensive tasks are performed in a pre-flight planning prior to the launch of the mission. The in-flight planning is based entirely on precalculated data, which are stored in the onboard computer of the air vehicle. In particular, no path finding algorithms with high or unpredictable running time and uncertain outcome have to be applied during flight.Originality/valueThe paper presents a new network-based algorithm for flight path optimization that overcomes weaknesses of grid-based approaches and allows high-quality solutions. The method can be applied for quick in-flight replanning of flight paths.
Paradigms in business process management specifications: a critical overview
Authors: Chountalas Panos T. , Lagodimos Athanasios G. 
Published: October 2018

Purpose
Despite its popularity, business process management (BPM) is not unequivocally defined, but obtains different forms with varying specifications. This paper presents a critical overview of BPM, as it appears within four dominant management paradigms: total quality management, standardized management systems, business process reengineering and Six Sigma. The purpose of this paper is to explore BPM specifications and compare the BPM implementation potential under each paradigm.

Design/methodology/approach
This is based on the analysis of a large number of highly cited scholarly publications. In order to identify the nature of BPM within each paradigm, a common framework for comparison is first established and then, for each paradigm, BPM is analyzed according to the main parameters of this framework.

Findings
Many differences among various BPM forms are paradigm driven. So, the approach adopted by each paradigm (i.e. individual-process or systemic approach) affects the scope and role of BPM. The principles of each paradigm directly affect the attributes assigned to BPM. Despite of important differences, the structure of BPM within all paradigms conforms to the stages of the classical BPM lifecycle. However, each paradigm assigns different weights to each stage and also displays different levels of BPM implementability.

Originality/value
The paper presents a first systematic comparison of BPM specifications for the dominant management paradigms primarily deployed. It thus explains why many attributes originating from the paradigms have crept into the general BPM specifications. This work can be considered as a step toward defining the core attributes of a paradigm-independent BPM model, thus enhancing its application scope as an invaluable management tool.
Manufacturing strategy, organizational slack, and the formation of interfirm linkages
Authors: Lu Lin-Hua , Huang Yi-Fen 
Published: October 2018

PurposeThis study aims to examine what types of interfirm linkages a firm enters in relation to its manufacturing strategy. The authors further aim to determine whether heterogeneous resources have different moderating effects on the relationship between a firm’s manufacturing strategy and interfirm linkages.Design/methodology/approachThe sample consists of survey and archival data on 80 publicly listed electronics firms from the semiconductor and optoelectronics industries in Taiwan. Because the dependent variable, interfirm linkage, is a binary term, the authors apply logistic regression in our study.FindingsThis paper provides empirical insight into how a firm’s manufacturing strategy affects its probability to engage in specific types of interfirm linkages. The authors find that when a firm pursues an efficiency (flexibility) strategy, it will tend to engage in marketing (technical) interfirm linkages. In addition, absorbed slack strengthens the fit between manufacturing strategy and interfirm linkage type more than unabsorbed slack does.Research limitations/implicationsBecause the sample is drawn from the Taiwanese semiconductor and optoelectronic industries, the authors encourage scholars to examine the generalizability of the findings. Future studies can furthermore adopt in-depth interviews to facilitate a better understanding of decision-makers’ considerations when entering interfirm linkages.Originality/valueThis study extends resource dependence theory across a firm’s boundary and applies the resource-based view to resource heterogeneity. The findings advance the understanding of the relationships between strategic orientation, slack resources and interfirm linkage choices. The authors show that it is important that firms consider strategic fit when they create linkages outside their existing boundaries.