bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac GPCR–Mediated EGFR Transactivation: Impact and Therapeutic Implications
Authors: Grisanti Laurel A. , Guo Shuchi , Tilley Douglas G. 
Published: January 2017

Abstract:
G protein–coupled receptors (GPCRs) remain primary therapeutic targets for numerous cardiovascular disorders, including heart failure (HF), because of their influence on cardiac remodeling in response to elevated neurohormone signaling. GPCR blockers have proven to be beneficial in the treatment of HF by reducing chronic G protein activation and cardiac remodeling, thereby extending the lifespan of patients with HF. Unfortunately, this effect does not persist indefinitely, thus next-generation therapeutics aim to selectively block harmful GPCR-mediated pathways while simultaneously promoting beneficial signaling. Transactivation of epidermal growth factor receptor (EGFR) has been shown to be mediated by an expanding repertoire of GPCRs in the heart, and promotes cardiomyocyte survival, thus may offer a new avenue of HF therapeutics. However, GPCR-dependent EGFR transactivation has also been shown to regulate cardiac hypertrophy and fibrosis by different GPCRs and through distinct molecular mechanisms. Here, we discuss the mechanisms and impact of GPCR-mediated EGFR transactivation in the heart, focusing on angiotensin II, urotensin II, and β-adrenergic receptor systems, and highlight areas of research that will help us to determine whether this pathway can be engaged as future therapeutic strategy.
Dalbavancin Pharmacokinetics and Safety in Children 3 Months to 11 Years of Age
Authors: Gonzalez Daniel , Bradley John S. , Blumer Jeffrey , Yogev Ram , Watt Kevin M. , James Laura P. , Palazzi Debra L. , Bhatt-Mehta Varsha , Sullivan Janice E. , Zhang Li , Murphy Jennifer , Ussery Xilla T. , Puttagunta Sailaja , Dunne Michael W. , Cohen-Wolkowiez Michael 
Published: January 2017

Background:
Dalbavancin is a novel lipoglycopeptide antibiotic that has potent in vitro activity against Gram-positive microorganisms.

Methods:
We performed a phase 1, open-label, multicenter study to investigate the pharmacokinetics (PK) and safety of a single dose of intravenous dalbavancin in hospitalized pediatric subjects 3 months to 11 years of age. We combined these data with previously collected adolescent PK data and performed a population PK analysis.

Results:
Model development was performed using 311 dalbavancin plasma concentrations from 43 subjects. The median age was 5.9 years (range: 0.3–16.9). A 3-compartment, linear PK model was developed. Based on simulations, the following age-dependent dosing regimen was found to achieve similar dalbavancin exposure to that in adults administered a 2-dose regimen: children 6 to <18 years of age, 12 mg/kg (1000 mg maximum) on day 1 and 6 mg/kg (500 mg maximum) on day 8 and children 3 months to <6 years of age, 15 mg/kg (1000 mg maximum) on day 1 and 7.5 mg/kg (500 mg maximum) on day 8. Similarly, the following age-dependent regimen was found to match adult exposure after a single-dose (1500 mg): 6 to <18 years of age, 18 mg/kg (1500 mg maximum) on day 1 and 3 months to <6 years of age, 22.5 mg/kg (1500 mg maximum) on day 1. Nineteen subjects experienced 36 treatment-emergent adverse events. Five of 36 adverse events were assessed as possibly or probably related to treatment.

Conclusions:
Dalbavancin pediatric dosing that matched adult exposure was identified. Overall, dalbavancin was well tolerated in our study population.
Valproic Acid: Special Considerations and Targeted Monitoring
Authors: Collins-Yoder Angela , Lowell Jordan 
Published: January 2017

ABSTRACT
Valproic acid (VPA) is a medication used to treat multiple neuroscience conditions. It is an inexpensive and useful medication, with a low incidence of adverse drug events. Nonetheless, optimal clinical outcomes require that a series of screening and laboratory steps be followed before the initiation of VPA therapy. An additional aspect of pharmacovigilance is to recognize clinical patterns signaling genetic traits that preclude VPA, background of the black box warnings, targeted assessments, and laboratory monitoring indicated while on VPA. The intention of this article is to provide a focused summary of published information clinically relevant to prescribing and monitoring these patients.
FastProject: A Tool for Low-Dimensional Analysis of Single-Cell RNA-Seq Data
Authors: DeTomaso David , Yosef Nir 
Published: January 2017

AbstractBackgroundA key challenge in the emerging field of single-cell RNA-Seq is to characterize phenotypic diversity between cells and visualize this information in an informative manner. A common technique when dealing with high-dimensional data is to project the data to 2 or 3 dimensions for visualization. However, there are a variety of methods to achieve this result and once projected, it can be difficult to ascribe biological significance to the observed features. Additionally, when analyzing single-cell data, the relationship between cells can be obscured by technical confounders such as variable gene capture rates.ResultsTo aid in the analysis and interpretation of single-cell RNA-Seq data, we have developed FastProject, a software tool which analyzes a gene expression matrix and produces a dynamic output report in which two-dimensional projections of the data can be explored. Annotated gene sets (referred to as gene ‘signatures’) are incorporated so that features in the projections can be understood in relation to the biological processes they might represent. FastProject provides a novel method of scoring each cell against a gene signature so as to minimize the effect of missed transcripts as well as a method to rank signature-projection pairings so that meaningful associations can be quickly identified. Additionally, FastProject is written with a modular architecture and designed to serve as a platform for incorporating and comparing new projection methods and gene selection algorithms.ConclusionsHere we present FastProject, a software package for two-dimensional visualization of single cell data, which utilizes a plethora of projection methods and provides a way to systematically investigate the biological relevance of these low dimensional representations by incorporating domain knowledge.
Switching of metabolic programs in response to light availability is an essential function of the cyanobacterial circadian clock
Authors: Puszynska Anna M. , O’Shea Erin K. 
Published: January 2017

AbstractThe transcription factor RpaA is the master regulator of circadian transcription in cyanobacteria, driving genome-wide oscillations in mRNA abundance. Deletion ofrpaAhas no effect on viability in constant light conditions, but renders cells inviable in cycling conditions when light and dark periods alternate. We investigated the mechanisms underlying this viability defect, and demonstrate that therpaA-strain cannot maintain appropriate energy status at night, does not accumulate carbon reserves during the day, and is defective in transcription of genes crucial for utilization of carbohydrate stores at night. Reconstruction of carbon utilization pathways combined with provision of an external carbon source restores energy charge and viability of therpaA-strain in light/dark cycling conditions. Our observations highlight how a circadian program controls and temporally coordinates essential pathways in carbon metabolism to maximize fitness of cells facing periodic energy limitations.
Individual movement variability magnitudes are predicted by cortical neural variability
Authors: Haar Shlomi , Donchin Opher , Dinstein Ilan 
Published: January 2017

ABSTRACTHumans exhibit considerable motor variability even across trivial reaching movements. This variability can be separated into specific kinematic components such as extent and direction, which are thought to be governed by distinct neural processes. Here, we report that individual subjects exhibit different magnitudes of kinematic variability, which are consistent (within individual) across movements to different targets and regardless of which arm (right or left) was used to perform the movements. Simultaneous fMRI recordings revealed that the same subjects also exhibited different magnitudes of fMRI variability across movements in a variety of motor system areas. These fMRI variability magnitudes were also consistent across movements to different targets when performed with either arm. Cortical fMRI variability in the posterior-parietal cortex of individual subjects predicted their movement-extent variability. This relationship was apparent only in posterior-parietal cortex and not in other motor system areas, thereby suggesting that individuals with more variable movement preparation exhibit larger kinematic variability. We, therefore, propose that neural and kinematic variability are reliable and interrelated individual characteristics that may predispose individual subjects to exhibit distinct motor capabilities.
The contribution of striatal pseudo-reward prediction errors to value-based decision-making
Authors: Mas-Herrero Ernest , Sescousse Guillaume , Cools Roshan , Marco-Pallarés Josep 
Published: January 2017

AbstractMost studies that have investigated the brain mechanisms underlying learning have focused on the ability to learn simple stimulus-response associations. However, in everyday life, outcomes are often obtained through complex behavioral patterns involving a series of actions. In such scenarios, parallel learning systems are important to reduce the complexity of the learning problem, as proposed in the framework of hierarchical reinforcement learning (HRL). One of the key features of HRL is the computation of pseudo-reward prediction errors (PRPEs) which allow the reinforcement of actions that led to a sub-goal before the final goal itself is achieved. Here we wanted to test the hypothesis that, despite not carrying any rewarding valueper se, pseudo-rewards might generate a bias in choice behavior when reward contingencies are not well-known or uncertain. Second, we also hypothesized that this bias might be related to the strength of PRPE striatal representations. In order to test these ideas, we developed a novel decision-making paradigm to assess reward prediction errors (RPEs) and PRPEs in two studies (fMRI study: n = 20; behavioural study: n = 19). Our results show that overall participants developed a preference for the most pseudo-rewarding option throughout the task, even though it did not lead to more monetary rewards. fMRI analyses revealed that this preference was predicted by individual differences in the relative striatal sensitivity to PRPEs vs RPEs. Together, our results indicate that pseudo-rewards generate learning signals in the striatum and subsequently bias choice behavior despite their lack of association with actual reward.
How context alters value: Price information recruits the brain’s valuation and affective regulation system for shaping experienced taste pleasantness
Authors: Schmidt Liane , Skvortsova Vasilisa , Kullen Claus , Weber Bernd , Plassmann Hilke 
Published: January 2017

SUMMARYInformational cues such as the price of a wine can trigger expectations about its taste quality and thereby modulate the sensory experience on a reported and neural level. Yet it is unclear how the brain translates such expectations into sensory pleasantness. We used multilevel mediation analysis of neural and behavioral data obtained in participants who tasted identical wines cued with different prices. We found that the brain's valuation system (BVS) in concert with the anterior prefrontal cortex explained the effect of price cues on taste pleasantness ratings. The sensitivity of the BVS to rewards outside the taste domain moderated the strength of these effects. Moreover, brain mediators of price cue effects overlapped with brain regions previously found to be involved in placebo analgesia. These findings provide novel evidence for the fundamental role that neural pathways linked to motivation and affective regulation play for the effect of informational cues on sensory experiences.
Using pseudoalignment and base quality to accurately quantify microbial community composition
Authors: Reppell M. , Novembre J. 
Published: January 2017

AbstractPooled DNA from multiple unknown organisms arises in a variety of contexts, for example microbial samples from ecological or human health research. Determining the composition of pooled samples can be difficult, especially at the scale of modern sequencing data and reference databases. Here we propose the novel pooled DNA classification method Karp. Karp combines the speed and low-memory requirements of k-mer based pseudoalignment with a likelihood framework that uses base quality information to better resolve multiply mapped reads. In this text we apply Karp to the problem of classifying 16S rRNA reads, commonly used in microbiome research. Using simulations, we show Karp is accurate across a variety of read lengths and when samples contain reads originating from organisms absent from the reference. We also assess performance in real 16S data, and show that relative to other widely used classification methods Karp can reveal stronger statistical association signals and should empower future discoveries.
Tracking the Subtle Mutations Thriving Host Sensing by the Plant PathogenStreptomyces scabies
Authors: Jourdan Samuel , Francis Isolde M. , Deflandre Benoit , Loria Rosemary , Rigali Sébastien 
Published: January 2017

AbstractThe acquisition of genetic material conferring the arsenal necessary for host virulence is a prerequisite on the path to become a plant pathogen. More subtle mutations are also required for perception of cues witnessing the presence of the target host and optimal conditions for colonization. The decision to activate the pathogenic lifestyle is not ‘taken lightly’ and involves efficient systems monitoring environmental conditions. But how can a pathogen timely trigger the expression of virulence genes if the main signal inducing its pathogenic behavior originates from cellulose, the most abundant polysaccharide on earth? This situation is encountered byStreptomyces scabiesresponsible for common scab disease on tuber and root crops. We here propose a series of hypotheses of howS. scabiescould optimally distinguish whether cello-oligosaccharides originate from decomposing lignocellulose (nutrient sources) or, instead, emanate from living and expanding plant tissue (virulence signals), and accordingly adapt its physiological response.
Automatic target recognition system for unmanned aerial vehicle via backpropagation artificial neural network
Authors: Jia Jiaqi , Duan Haibin 
Published: January 2017

Purpose
The purpose of this paper is to propose a novel target automatic recognition method for unmanned aerial vehicle (UAV), which is based on backpropagation – artificial neural network (BP-ANN) algorithm, with the objective of optimizing the structure of backpropagation network, to increase the efficiency and decrease the recognition time. A hardware-in-the-loop system for UAV target automatic recognition is also developed.

Design/methodology/approach
The hybrid model of BP-ANN structure is established for aircraft automatic target recognition. This proposed method identifies controller parameters and reduces the computational complexity. Approaching speed of the network is faster and recognition accuracy is higher. This kind of network combines or better fuses the advantages of backpropagation artificial neural algorithm and Hu moment. with advantages of two networks and improves the speed and accuracy of identification. Finally, a hardware-in-the-loop system for UAV target automatic recognition is also developed.

Findings
The double hidden level backpropagation artificial neural can easily increase the speed of recognition process and get a good performance for recognition accuracy.

Research limitations/implications
The proposed backpropagation artificial neural algorithm can be ANN easily applied to practice and can help the design of the aircraft automatic target recognition system. The standard backpropagation algorithm has some obvious drawbacks, namely, converging slowly and falling into the local minimum point easily. In this paper, an improved algorithm based on the standard backpropagation algorithm is constructed to make the aircraft target recognition more practicable.

Originality/value
A double hidden levels backpropagation artificial neural algorithm is presented for automatic target recognition system of UAV.
Customisable framework for project risk management
Authors: Firmenich Jennifer 
Published: January 2017

Purpose
The purpose of this paper is to emphasise on the need for efficient and effective project risk management practices and to support project managers in increasing the cost certainty of projects by proposing a new framework for project risk management.

Design/methodology/approach
The author adopts a “constructivist” methodology, drawing on practices common in construction management sciences and new institutional economics.

Findings
The author presents a holistic and customisable project risk management framework that is grounded in both practice and academia. The framework is holistic because, amongst others, all steps of the typical risk management process are addressed. The framework is customisable, because it allows for alternative ways of implementing the project risk management steps depending on the project-specific circumstances.

Research limitations/implications
The framework does not address the potential unwillingness of the project players to set up a project risk management process, at all. The proposed framework has not yet been tested empirically. Future research will seek to validate the framework.

Originality/value
The framework is designed to account for the difficult circumstances of a complex construction project. It is intended to support decision makers in customising a practical yet comprehensive project risk management concept to the characteristics of the unique project. Although many other project risk management concepts are designed based on the assumption that actors are perfectly rational and informed, this framework’s design is based on the opposite assumption. The framework is dynamic and should adapt over time.
Business process management – a construction case study
Authors: Dave Bhargav 
Published: January 2017

Purpose
This paper aims to demonstrate the need for a structured business process improvement effort needed while restructuring organisational processes within a construction company. Through the longitudinal study, the study also highlights the importance of a continuous improvement initiative to sustain such an improvement effort.

Design/methodology/approach
The research followed an action research and the case study approach using semi-structured interviews and group workshops within the case organisation. Overall, six departments were analysed, 35 interviews with senior and middle managers were conducted, existing business process documents were studied and processes were documented. The data were compiled using a process modelling software and Business Process Markup Notation methodology. Additionally, a longitudinal analysis following the completion of process modelling exercise was carried out over a period of eight years.

Findings
The overall study highlights the importance of business process management (BPM) for construction organisations. The case study also demonstrated that even smaller business units and its processes affected the overall value chain in a major way and the importance to analyse the process interdependencies between organisational units.

Research limitations/implications
The main limitation of the research was that it is based on a single-case-study company based in the UK. More research is needed with other organisations with different work practices and culture and geographic location.

Practical implications
Primarily, the research outlines specific steps taken during a structured process improvement exercise in a construction company, including procedures for collecting data, developing process maps and analysis of data. The longitudinal study highlights the challenges in sustaining such an initiative. For practitioners, strengths and weaknesses of various process improvement methods and a detailed description of a BPM implementation can be used as a guideline for future projects. From a research point of view, the paper highlights the need for deeper and long-term analysis of such initiatives and the importance of immersion of researchers within the environment.

Originality/value
The paper provides deeper insights into the structured process improvement exercise within a construction company. Second and more importantly, the longitudinal study is one of its kind in the construction industry to shed light on the factors affecting sustainability of such initiatives.
Diffusion of a systemic innovation
Authors: Lindgren John , Emmitt Stephen 
Published: January 2017

PurposeThe purpose of this paper is to identify factors that influence the diffusion of a systemic innovation in the Swedish construction sector. The focus is on high-rise multi-storey timber housing; the development of which was enabled by a change in building regulations. This allowed building higher than two stories in timber.Design/methodology/approachA longitudinal case study was used with multiple data collection methods to study the development and diffusion of a multi-storey timber house system by a case study organisation.FindingsThe findings contribute to understanding for a number of interacting factors influencing the diffusion of a systemic innovation related to the case study organisation.Originality/valueThe research provides a holistic view of interacting factors influencing the diffusion of a systemic innovation. The results have value to the Swedish construction sector and to the global community of construction researchers, as it provides empirical findings that further increase the understanding for diffusion of systemic innovations in a specific context.
Demographic factors, personality and entrepreneurial inclination
Authors: Chaudhary Richa 
Published: January 2017

PurposeThe purpose of this paper is to investigate the influence of demographic, social and personal dispositional factors on determining the entrepreneurial inclination. Specifically, the author examined the role of gender, age, stream of study, family business background and six psychological traits of locus of control, tolerance for ambiguity, propensity to take risk, self-confidence and innovation in differentiating entrepreneurs from non-entrepreneurs.Design/methodology/approachAs university students constitute pool of potential entrepreneurs, participants for the study consisted of 274 students from two new and upcoming universities in an emerging economy of India. The sample included students from both business and non-business schools. Data were reported and analysed using descriptive statistics, frequency distribution,t-test and stepwise logistic regressionFindingsThe study results suggest that the traits of locus of control, tolerance for ambiguity, self-confidence and innovativeness were significant in differentiating entrepreneurs from non-entrepreneurs. At the same time it was also observed that need for achievement and risk-taking propensity were not found to be significantly different for these two groups which was contradictory to the expectations. In addition to these six psychological traits, the study results also underlined the role of family background and school in predicting entrepreneurial inclination.Practical implicationsThe study carries huge public policy implications for education system in India which largely prepares the students for jobs in public and private sectors rather than entrepreneurship.Originality/valueThe study discusses some of the missing links in the entrepreneurship research by providing new insights from India.