bluuebunny/crossref_metadata_2025_split huggingface dataset:
CH···O Interactions Are Not the Cause of Trends in Reactivity and Secondary Kinetic Isotope Effects for Enzymatic SN2 Methyl Transfer Reactions
Authors: Zhang Jianyu , Klinman Judith P. 
Published: September 2016

AbstractCompaction mattersSN2 substitution represents an important class of reaction for both chemical and biological systems. The ability to assess enzymatic transition state structure within this class of reaction remains a major experimental challenge. Here, we comment on and compare the relative impact of compaction along the axis of reaction to the impact of an orthogonal CH···O hydrogen bonding interaction. The latter is concluded to play a limited role in determining relative reaction rates and secondary KIEs derived from experimental structure-activity correlations.
Consistency of EEG source localization and connectivity estimates
Authors: Mahjoory Keyvan , Nikulin Vadim V. , Botrel Loïc , Linkenkaer-Hansen Klaus , Fato Marco M. , Haufe Stefan 
Published: September 2016

AbstractAs the EEG inverse problem does not have a unique solution, the sources reconstructed from EEG and their connectivity properties depend on forward and inverse modeling parameters such as the choice of an anatomical template and electrical model, prior assumptions on the sources, and further implementational details. In order to use source connectivity analysis as a reliable research tool, there is a need for stability across a wider range of standard estimation routines. Using resting state EEG recordings of N=65 participants acquired within two studies, we present the first comprehensive assessment of the consistency of EEG source localization and functional/effective connectivity metrics across two anatomical templates (ICBM152 and Colin27), three electrical models (BEM, FEM and spherical harmonics expansions), three inverse methods (WMNE, eLORETA and LCMV), and three software implementations (Brainstorm, Fieldtrip and our own toolbox). Source localizations were found to be more stable across reconstruction pipelines than subsequent estimations of functional connectivity, while effective connectivity estimates where the least consistent. All results were relatively unaffected by the choice of the electrical head model, while the choice of the inverse method and source imaging package induced a considerable variability. In particular, a relatively strong difference was found between LCMV beamformer solutions on one hand and eLORETA/WMNE distributed inverse solutions on the other hand. We also observed a gradual decrease of consistency when results are compared between studies, within individual participants, and between individual participants. In order to provide reliable findings in the face of the observed variability, additional simulations involving interacting brain sources are required. Meanwhile, we encourage verification of the obtained results using more than one source imaging procedure.
Genomic signature of kin selection in an ant with obligately sterile workers
Authors: Warner Michael R. , Mikheyev Alexander S. , Linksvayer Timothy A. 
Published: September 2016

AbstractKin selection is thought to drive the evolution of cooperation and conflict, but the specific genes and genome-wide patterns shaped by kin selection are unknown. We identified thousands of genes associated with the sterile ant worker caste, the archetype of an altruistic phenotype shaped by kin selection, and then used population and comparative genomic approaches to study patterns of molecular evolution at these genes. Consistent with population genetic theoretical predictions, worker-upregulated genes showed relaxed adaptive evolution compared to genes upregulated in reproductive castes. Worker-upregulated genes included more taxonomically-restricted genes, indicating that the worker caste has recruited more novel genes, yet these genes also showed relaxed selection. Our study identifies a putative genomic signature of kin selection and helps to integrate emerging sociogenomic data with longstanding social evolution theory.
A novel ENU-induced ankyrin-1 mutation impairs parasite invasion and increases erythrocyte clearance during malaria infection in mice
Authors: Huang Hong Ming , Bauer Denis C. , Lelliott Patrick M. , Greth Andreas , McMorran Brendan J. , Foote Simon J. , Burgio Gaetan 
Published: September 2016

AbstractGenetic defects in various red blood cell (RBC) cytoskeletal proteins have been long associated with changes in susceptibility towards malaria infection. In particular, while ankyrin (Ank-1) mutations account for approximately 50% of hereditary spherocytosis (HS) cases, an association with malaria is not well-established, and conflicting evidence has been reported. We describe a novel N-ethyl-N-nitrosourea (ENU)-induced ankyrin mutation MRI61689 that gives rise to two different ankyrin transcripts: one with an introduced splice acceptor site resulting a frameshift, the other with a skipped exon.Ank-1(MRI61689/+)mice exhibit an HS-like phenotype including reduction in mean corpuscular volume (MCV), increased osmotic fragility and reduced RBC deformability. They were also found to be resistant to rodent malariaPlasmodium chabaudiinfection. Parasites inAnk-1(MRI61689/+)erythrocytes grew normally, but red cells showed resistance to merozoite invasion. UninfectedAnk-1(MRI61689/+)erythrocytes were also more likely to be cleared from circulation during infection; the “bystander effect”. This increased clearance is a novel resistance mechanism which was not observed in previous ankyrin mouse models. We propose that this bystander effect is due to reduced deformability ofAnk-1(MRI61689/+)erythrocytes. This paper highlights the complex roles ankyrin plays in mediating malaria resistance.
Containing Emerging Epidemics: a Quantitative Comparison of Quarantine and Symptom Monitoring
Authors: Peak Corey M , Childs Lauren M , Grad Yonatan H , Buckee Caroline O 
Published: September 2016

ABSTRACTStrategies for containing an emerging infectious disease outbreak must be non-pharmaceutical when drugs or vaccines for the pathogen do not yet exist or are unavailable. The success of these non-pharmaceutical strategies will depend not only on the effectiveness of quarantine or other isolation measures but also on the epidemiological characteristics of the infection. However, there is currently no systematic framework to assess the relationship between different containment strategies and the natural history and epidemiological dynamics of the pathogen. Here, we compare the effectiveness of quarantine and symptom monitoring, implemented via contact tracing, in controlling epidemics using an agent-based branching model. We examine the relationship between epidemic containment and the disease dynamics of symptoms and infectiousness for seven case study diseases with diverse natural histories including Ebola, Influenza A, and Severe Acute Respiratory Syndrome (SARS). We show that the comparative effectiveness of symptom monitoring and quarantine depends critically on the natural history of the infectious disease, its inherent transmissibility, and the intervention feasibility in the particular healthcare setting. The benefit of quarantine over symptom monitoring is generally maximized for fast-course diseases, but we show the conditions under which symptom monitoring alone can control certain outbreaks. This quantitative framework can guide policy-makers on how best to use non-pharmaceutical interventions to contain emerging outbreaks and prioritize research during an outbreak of a novel pathogen.SIGNIFICANCEQuarantine and symptom monitoring of contacts with suspected exposure to an infectious disease are key interventions for the control of emerging epidemics; however, there does not yet exist a quantitative framework for comparing the control performance of each. Here, we use a mathematical model of seven case study diseases to show how the choice of intervention is influenced by the natural history of the infectious disease, its inherent transmissibility, and the intervention feasibility in the particular healthcare setting. We use this information to identify the most important characteristics of the disease and setting that need to be characterized for an emerging pathogen in order to make an informed decision between quarantine and symptom monitoring.
Behavioral tagging and the penumbra of learning
Authors: Gershman Samuel J. 
Published: September 2016

AbstractIn noisy, dynamic environments, organisms must distinguish genuine change (e.g., the movement of prey) from noise (e.g., the rustling of leaves). Expectations should be updated only when the organism believes genuine change has occurred. Although individual variables can be highly unreliable, organisms can take advantage of the fact that changes tend to be correlated (e.g., movement of prey will tend to produce changes in both visual and olfactory modalities). Thus, observing a change in one variable provides information about the rate of change for other variables. We call this thepenumbra of learning.At the neural level, the penumbra of learning may offer an explanation for why strong plasticity in one synapse can rescue weak plasticity at another (synaptic tagging and capture). At the behavioral level, it has been observed that weak learning of one task can be rescued by novelty exposure before or after the learning task. Here, using a simple number prediction task, we provide direct behavioral support for the penumbra of learning in humans, and show that it can be accounted for by a normative computational theory of learning.
Eukaryotic translation initiation factor 3 plays distinct roles at the mRNA entry and exit channels of the ribosomal preinitiation complex
Authors: Aitken Colin Echeverría , Beznosková Petra , Vlčkova Vladislava , Chiu Wen-Ling , Zhou Fujun , Valášek Leoš , Hinnebusch Alan G. , Lorsch Jon R. 
Published: September 2016

AbstractEukaryotic translation initiation factor 3 (eIF3) is a central player in recruitment of the pre-initiation complex (PIC) to mRNA. We probed the effects on mRNA recruitment of a library ofS. cerevisiaeeIF3 functional variants spanning its 5 essential subunits using an in vitro-reconstituted system. Mutations throughout eIF3 disrupt its interaction with the PIC and diminish its ability to accelerate recruitment to a native yeast mRNA. Alterations to the eIF3a CTD and eIF3b/i/g significantly slow mRNA recruitment, and mutations within eIF3b/i/g destabilize eIF2·GTP·Met-tRNAibinding to the PIC. Using model mRNAs lacking contacts with the 40S entry or exit channels, we uncover a critical role for eIF3 requiring the eIF3a NTD, in stabilizing mRNA interactions at the exit channel, and an ancillary role at the entry channel requiring residues of the eIF3a CTD. These functions are redundant: defects at each channel can be rescued by filling the other channel with mRNA.
Thewhitegene controls copulation success inDrosophila melanogaster
Authors: Xiao Chengfeng , Qiu Shuang , Robertson R Meldrum 
Published: September 2016

ABSTRACTCharacteristics of male courtship behavior inDrosophila melanogasterhave been well-described, but the genetic basis of male-female copulation is largely unknown. Here we show that thewhite(w) gene, a classical gene for eye color, is associated with copulation success. 82.5% of wild-type Canton-S flies copulated within 60 minutes in circular arenas, whereas few white-eyed mutants mated successfully. Thew+allele exchanged to the X chromosome or duplicated to the Y chromosome in the white-eyed genetic background rescued the defect of copulation success. Thew+-associated copulation success was independent of eye color phenotype. Addition of the mini-white(mw+) gene to the white-eyed mutant rescued the defect of copulation success in a manner that was mw+copy number-dependent. Lastly, male-female sexual experience mimicked the effects ofw+/mw+in improving successful copulation. These data suggest that thew+gene controls copulation success inDrosophila melanogaster.
Wide-ranging and unexpected consequences of altered Pol II catalytic activity in vivo
Authors: Malik Indranil , Qiu Chenxi , Snavely Thomas , Kaplan Craig D. 
Published: September 2016

AbstractHere we employ a set of RNA Polymerase II (Pol II) activity mutants to determine the consequences of increased or decreased Pol II catalysis on gene expression inSaccharomycescerevisiae. We find that alteration of Pol II catalytic rate, either fast or slow, leads to decreased Pol II occupancy and apparent reduction in elongation ratein vivo. However, we also find that determination of elongation ratein vivoby chromatin IP can be confounded by the kinetics and conditions of transcriptional shutoff in the assay. We identify promoter and template-specific effects on severity of gene expression defects for both fast and slow Pol II mutants. We show that mRNA half-lives for a reporter gene are increased in both fast and slow Pol II mutant strains and the magnitude of half-life changes correlate both with mutants’ growth and reporter expression defects. Finally, we tested a model that altered Pol II activity sensitizes cells to nucleotide depletion. In contrast to model predictions, mutated Pol II retains normal sensitivity to altered nucleotide levels. Our experiments establish a framework for understanding the diversity of transcription defects derived from altered Pol II activity mutants, essential for their use as probes of transcription mechanisms.
Regulation of cancer epigenomes with a histone-binding synthetic transcription factor
Authors: Nyer David B. , Vargas Daniel , Hom Caroline , Haynes Karmella A. 
Published: September 2016

ABSTRACTChromatin proteins have expanded the mammalian synthetic biology toolbox by enabling control of active and silenced states at endogenous genes. Others have reported synthetic proteins that bind DNA and regulate genes by altering chromatin marks, such as histone modifications. Previously we reported the first synthetic transcriptional activator, the "Polycomb-based transcription factor" (PcTF), that reads histone modifications through a protein-protein interaction between the PCD motif and trimethylated lysine 27 of histone H3 (H3K27me3). Here, we describe the genome-wide behavior of PcTF. Transcriptome and chromatin profiling revealed PcTF-sensitive promoter regions marked by proximal PcTF and distal H3K27me3 binding. These results illuminate a mechanism in which PcTF interactions bridge epigenetic marks with the transcription initiation complex. In three cancer-derived human cell lines tested here, many PcTF-sensitive genes encode developmental regulators and tumor suppressors. Thus, PcTF represents a powerful new fusion-protein-based method for cancer research and treatment where silencing marks are translated into direct gene activation.
Rethinking researching project management
Authors: Lloyd-Walker Beverley , French Erica , Crawford Lynn 
Published: September 2016

Purpose
The purpose of this paper is to identify issues in the long-term development of project workers, their career paths, their contribution to organizational success and their need for equity of opportunity. The long-term development of project workers, their career paths and their contribution to organizational success is explored.

Design/methodology/approach
A qualitative research design using semi-structured interviews was employed to gain an understanding of social and human issues related to careers in project management (PM). By researching the lived experiences and feelings of those pursuing a career in PM the aim was to gain insight into the career journeys and experiences of practicing project managers.

Findings
Those who choose to pursue a career in PM have the personal characteristics and sufficiently high levels of self-efficacy to deal effectively with the uncertainty inherent in the nature of projects and of project-based employment.

Research limitations/implications
Participants were drawn from current project practitioners. As a result, the views of those who have worked on projects and chosen not to continue their career in the area have not been gathered.

Practical implications
Predictions are that there will be a continuing demand for project managers with the capabilities required to deliver successful projects. The challenge for organizations is to create an environment that will encourage greater numbers of people to embrace the uncertainty of project. The findings reported provide insight into how organizations might attract, develop and retain the project expertise they require for success.

Originality/value
This research provides further understanding into the lived experience of project managers, with a focus on those who have unexpectedly found themselves pursuing a career in PM.
The Danish agenda for rethinking project management
Authors: Svejvig Per , Grex Sara 
Published: September 2016

PurposeThe purpose of this paper is to analyze the similarities and differences between the Danish rethinking project management (RPM) initiative named Project Half Double (PHD) and the RPM research stream. The paper furthermore discusses how PHD and RPM can inspire each other in research and practice.Design/methodology/approachThis is an empirical paper based on collaborative research between industry and researchers. PHD has developed principles and practices driven by industry consisting of ten leading stars and the impact, leadership and flow (ILF) method. The ten leading stars and ILF method are compared to RPM research. The comparative analysis is then used in a broader discussion about how the research-driven RPM initiative can enrich the industry-driven PHD initiative and vice versa depicted in a theoretical understanding of translations between global ideas and local implementations.FindingsRPM and PHD share a focus on value creation, social processes, learning and complexity while PHD also focusses on lean thinking, agile thinking, front-end loading and leadership, which are largely topics beyond the RPM research stream.Originality/valueThe paper presents how stakeholders from Danish industry interpret the actuality in projects and how they want to move forward with a radically different project paradigm. This is expressed in the ten leading stars and ILF method, which is compared and contrasted to the existing RPM literature providing a foundation for further development of both RPM and PHD.
Mechanical properties of a carbon fabric-reinforced epoxy composite with carbon nanotubes and a flame retardant
Authors: Kadlec Martin , Hron Robin , Guadagno Liberata 
Published: September 2016

Purpose
The purpose of this paper is to present the mechanical and morphological characterization of new multifunctional carbon fibre-reinforced composites (CFRCs) that are able to overcome two of the main drawbacks of aeronautical composite materials: reduced electrical conductivity and poor flame resistance. Multiwall carbon nanotubes and glycidyl POSS (GPOSS) were used to simultaneously enhance electrical conductivity and flame resistance. The effect of these two combined components on the mechanical and morphological properties of the manufactured CFRCs was analysed.

Design/methodology/approach
This paper describes the mechanical test results obtained for interlaminar shear strength, three-point bending, and tensile and fracture toughness in mode I tests. Carbon fibre-reinforced epoxy resin plates were manufactured in two series with blank resin and CNT+flame retardant GPOSS-enhanced resin.

Findings
The mechanical properties were decreased by no more than 10 per cent by combined influence of CNTs and GPOSS. Agglomerates of CNTs were observed using scanning electron microscopy. The agglomerates were large enough to be visible to the naked eye as black spots on the delaminated fracture surface. The decrease of the mechanical properties could be caused by these agglomerates or by a changed fibre volume content that was affected by the difficult infusion procedure due to high resin viscosity.

Originality/value
If we consider the benefit of CNTs as a nanofiller to increase electrical conductivity and the GPOSS as a component to increase the flame resistance of the resin, the decrease of strength seems to be insignificant.
IPO performance at announcement and in the aftermarket
Authors: Abraham Rebecca , Harris Judith , Auerbach Joel 
Published: September 2016

Purpose
The purpose of this paper is to investigate IPO performance. At announcement, the impact of purchases by informed traders on stock returns and uninformed traders on volatility were assessed. In the post-IPO period, returns were expected to be driven by firms with high returns on equity and the implementation of growth strategies. Return on equity was evaluated further in terms of whether it had a direct effect or was instrumented by volatility, cash flow, profit margin or revenue growth.

Design/methodology/approach
All IPOs announced in 2009-2014 were used. Measures were created to demarcate growth firms from risk-averse firms and firms with highly volatile cash flows from their counterparts with cash flows of lesser volatility. Event studies were used to measure abnormal return and abnormal volume, while multiple regressions tested the influence of predictors on abnormal returns, volatility and holding period return. Instruments of return on equity were also assessed.

Findings
The offer volume of informed traders significantly explained announcement-day returns, while the offer volume of uninformed traders explained the increase in volatility of IPO stock. The ability to capitalize on growth opportunities and increase shareholder wealth through higher return on equity significantly predicted holding period returns. Return on equity, was explained by volatility, cash flow to assets and profit margin.

Originality/value
The data are highly current with 2014 IPOs being used. The paper clearly distinguishes between fleeting announcement-day returns driven by informed traders and long-term holding period returns in a departure from the prevailing practice of measuring long-term post-IPO performance with abnormal returns. Finally, the paper creates subjective measures of volatility and growth strategies.
Economic fluctuations and crime: temporary and persistent effects
Authors: Bender Keith , Theodossiou Ioannis 
Published: September 2016

PurposeSince the literature on the effect of the unemployment rate as reflection of economic fluctuations on crime shows an empirically ambiguous effect, the purpose of this paper is to argue that a new way of modeling the dynamics of unemployment and crime by focussing on the transitory and persistent effect of unemployment on crime helps resolve this ambiguity.Design/methodology/approachPanel data for US states from 1965 to 2006 are examined using the Mundlak (1978) methodology to incorporate the dynamic interactions between crime and unemployment into the estimation.FindingsAfter decomposing the unemployment effect on crime into a transitory and persistent effect, evidence of a strong positive correlation between unemployment and almost all types of crime rates is unearthed. This evidence is robust to endogeneity and the controlling for cross-panel correlation and indicators for state imprisonment.Originality/valueThe paper is the first to examine the dynamics of the interaction of crime and economic fluctuations using the temporary and persistent effects framework of Mundlak (1978). In one set of estimates, one can evaluation both the short- and long-run effects of changes of unemployment on crime.