bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alanine substitutions in the GXXXG motif alter C99 cleavage by γ‐secretase but not its dimerization
Authors: Higashide Hidekazu , Ishihara Seiko , Nobuhara Mika , Ihara Yasuo , Funamoto Satoru 
Published: December 2016

AbstractThe amyloid β (Aβ) protein is a major component of senile plaques, one of the neuropathological hallmarks of Alzheimer's disease. Amyloidogenic processing of amyloid precursor protein (APP) by β‐ and γ‐secretases leads to production of Aβ. APP contains tandem triple repeats of the GXXXG motif in its extracellular juxtamembrane and transmembrane regions. It is reported that the GXXXG motif is related to protein–protein interactions, but it remains controversial whether the GXXXG motif in APP is involved in substrate dimerization and whether dimerization affects γ‐secretase‐dependent cleavage. Therefore, the relationship between the GXXXG motifs, substrate dimerization, and γ‐secretase‐dependent cleavage sites remains unclear. Here, we applied blue native poly acrylamide gel electrophoresis to examine the effect of alanine substitutions within the GXXXG motifs of APP carboxyl terminal fragment (C99) on its dimerization and Aβ production. Surprisingly, alanine substitutions in the motif failed to alter C99 dimerization in detergent soluble state. Cell‐based and solubilized γ‐secretase assays demonstrated that increasing alanine substitutions in the motif tended to decrease long Aβ species such as Aβ42 and Aβ43 and to increase in short Aβ species concomitantly. Our data suggest that the GXXXG motif is crucial for Aβ production, but not for C99 dimerization.
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Stereological analysis of size and density of hepatocytes in the porcine liver
Authors: Junatas Khan L. , Tonar Zbyněk , Kubíková Tereza , Liška Václav , Pálek Richard , Mik Patrik , Králíčková Milena , Witter Kirsti 
Published: December 2016

AbstractThe porcine liver is frequently used as a large animal model for verification of surgical techniques, as well as experimental therapies. Often, a histological evaluation is required that include measurements of the size, nuclearity or density of hepatocytes. Our aims were to assess the mean number‐weighted volume of hepatocytes, the numerical density of hepatocytes, and the fraction of binuclear hepatocytes (BnHEP) in the porcine liver, and compare the distribution of these parameters among hepatic lobes and macroscopic regions of interest (ROIs) with different positions related to the liver vasculature. Using disector and nucleator as design‐based stereological methods, the morphometry of hepatocytes was quantified in seven healthy piglets. The samples were obtained from all six hepatic lobes and three ROIs (peripheral, paracaval and paraportal) within each lobe. Histological sections (thickness 16 μm) of formalin‐fixed paraffin‐embedded material were stained with the periodic acid‐Schiff reaction to indicate the cell outlines and were assessed in a series of 3‐μm‐thick optical sections. The mean number‐weighted volume of mononuclear hepatocytes (MnHEP) in all samples was 3670 ± 805 μm3 (mean ± SD). The mean number‐weighted volume of BnHEP was 7050 ± 2550 μm3. The fraction of BnHEP was 4 ± 2%. The numerical density of all hepatocytes was 146 997 ± 15 738 cells mm−3 of liver parenchyma. The porcine hepatic lobes contained hepatocytes of a comparable size, nuclearity and density. No significant differences were identified between the lobes. The peripheral ROIs of the hepatic lobes contained the largest MnHEP with the smallest numerical density. The distribution of a larger MnHEP was correlated with a larger volume of BnHEP and a smaller numerical density of all hepatocytes. Practical recommendations for designing studies that involve stereological evaluations of the size, nuclearity and density of hepatocytes in porcine liver are provided.
Multisource feedback to graduate nurses: a multimethod study
Authors: McPhee Samantha , Phillips Nicole M , Ockerby Cherene , Hutchinson Alison M 
Published: December 2016

Aims and objectives(1) To explore graduate nurses’ perceptions of the influence of multisource feedback on their performance and (2) to explore perceptions of Clinical Nurse Educators involved in providing feedback regarding feasibility and benefit of the approach.BackgroundGraduate registered nurses are expected to provide high‐quality care for patients in demanding and unpredictable clinical environments. Receiving feedback is essential to their development. Performance appraisals are a common method used to provide feedback and typically involve a single source of feedback. Alternatively, multisource feedback allows the learner to gain insight into performance from a variety of perspectives. This study explores multisource feedback in an Australian setting within the graduate nurse context.DesignMultimethod study.MethodsEleven graduates were given structured performance feedback from four raters: Nurse Unit Manager, Clinical Nurse Educator, preceptor and a self‐appraisal. Thirteen graduates received standard single‐rater appraisals. Data regarding perceptions of feedback for both groups were obtained using a questionnaire. Semistructured interviews were conducted with nurses who received multisource feedback and the educators.ResultsIn total, 94% (n = 15) of survey respondents perceived feedback was important during the graduate year. Four themes emerged from interviews: informal feedback, appropriateness of raters, elements of delivery and creating an appraisal process that is ‘more real’. Multisource feedback was perceived as more beneficial compared to single‐rater feedback. Educators saw value in multisource feedback; however, perceived barriers were engaging raters and collating feedback.ConclusionsSome evidence exists to indicate that feedback from multiple sources is valued by graduates. Further research in a larger sample and with more experienced nurses is required.Relevance to clinical practiceEvidence resulting from this study indicates that multisource feedback is valued by both graduates and educators and informs graduates’ development and transition into the role. Thus, a multisource approach to feedback for graduate nurses should be considered.
In Pursuit of Time: Business Plan Sequencing, Duration and Intraentrainment Effects on New Venture Viability
Authors: Hopp Christian , Greene Francis J. 
Published: December 2016

AbstractIn this study, we examine three under‐explored dimensions of the temporal relationship between formal written business plans and the achievement of new venture viability. First, we theorize and investigate the effects of plan sequencing; arguing that a business plan written early on in new venture development increases the prospects of venture viability. Second, we examine plan duration effects, and argue that there is a curvilinear relationship between spending time on a plan and achieving venture viability. Finally, we investigate plan intraentrainment effects (synchronization with other gestation activities). We theorize that if plans are synchronized with other gestation activities, venture viability is more likely. Using longitudinal data and controlling for truncation and endogeneity issues, we find that it is beneficial to plan early but that this is contingent on how long a founder spent on a plan and whether or not a plan is intraentrained with other gestation activities.
Boundary Capabilities in MNCs: Knowledge Transformation for Creative Solution Development
Authors: Tippmann Esther , Sharkey Scott Pamela , Parker Andrew 
Published: December 2016

AbstractThe management of knowledge across country units is critical to multinational corporations (MNCs). Building on the argument that boundary spanning leads to the development of creative problem solving outcomes, this study advances the concept of MNC knowledge transformation and examines its relationship with solution creativity. Using questionnaire data on 67 problem solving projects, we find that opportunity formation is an underlying mechanism linking MNC knowledge transformation to the development of creative solutions. These insights contribute to our understanding of boundary spanning in global organizations by substantiating MNC knowledge transformation and elaborating the relationship between boundary spanning and creative solution development. If successful at knowledge transformation, collaborators from across the MNC can construct previously unimagined opportunities for the generation of creative outcomes.
Toward a Framework of Leader Character in Organizations
Authors: Crossan Mary M. , Byrne Alyson , Seijts Gerard H. , Reno Mark , Monzani Lucas , Gandz Jeffrey 
Published: December 2016

AbstractWhile the construct of character is well grounded in philosophy, ethics, and more recently psychology, it lags in acceptance and legitimacy within management research and mainstream practice. Our research seeks to remedy this through four contributions. First, we offer a framework of leader character that provides rigor through a three‐phase, multi‐method approach involving 1817 leaders, and relevance by using an engaged scholarship epistemology to validate the framework with practicing leaders. This framework highlights the theoretical underpinnings of the leader character model and articulates the character dimensions and elements that operate in concert to promote effective leadership. Second, we bring leader character into mainstream management research, extending the traditional competency and interpersonal focus on leadership to embrace the foundational component of leader character. In doing this, we articulate how leader character complements and strengthens several existing theories of leadership. Third, we extend the virtues‐based approach to ethical decision making to the broader domain of judgement and decision making in support of pursuing individual and organization effectiveness. Finally, we offer promising directions for future research on leader character that will also serve the larger domain of leadership research.
Antibody‐dependent and antibody‐independent uptake of HBsAg across human leucocyte subsets is similar between individuals with chronic hepatitis B virus infection and healthy donors
Authors: Tharinger H. , Rebbapragada I. , Samuel D. , Novikov N. , Nguyen M. H. , Jordan R. , Frey C. R. , Pflanz S. 
Published: December 2016

SummaryMaintaining detectable levels of antibodies to hepatitis B surface antigen (HBsAg) in serum after HBsAg sero‐conversion is the key clinical endpoint indicative of recovery from infection with hepatitis B virus (HBV). As HBV‐infected hepatocytes secrete HBsAg subviral particles in vast excess over HBV virions, detectable hepatitis B surface antibody (anti‐HBs) titres imply complete elimination of HBV virions as well as HBsAg particles. Although intrahepatic phagocytes, for example Kupffer cells, are thought to mediate clearance of HBsAg via antibody (Ab)‐dependent and Ab‐independent mechanisms, the relative contributions of circulating phagocytic cell types to HBsAg elimination are poorly characterized. Understanding the role of various immune cell subsets in the clearance of HBsAg is important because Ab‐dependent or Ab‐independent phagocytic HBsAg uptake may modulate presentation of HBsAg‐derived epitopes to antigen‐specific T cells and hence plays a critical role in adaptive immunity against HBV. This study aims to characterize phagocytic leucocyte subsets capable of internalizing HBsAg immune complexes (HBsAg:IC) or un‐complexed HBsAg particles in whole blood directly ex vivo. The data show that uptake of HBsAg:IC occurs most prominently in monocytes, B cells, dendritic cells and in neutrophils. In contrast, B cells, and to a lesser degree also monocytes, seem to be effective phagocytes for un‐complexed HBsAg. Importantly, a similar pattern of phagocytic HBsAg uptake was observed in blood from chronic hepatitis B (CHB) patients compared to healthy controls, suggesting that phagocytosis‐related cellular functions are not altered in the context of CHB.
Deep learning for sentiment analysis
Authors: Rojas‐Barahona Lina Maria 
Published: December 2016

AbstractResearch and industry are becoming more and more interested in finding automatically thepolarised opinionof the general public regarding a specific subject. The advent ofsocial networkshas opened the possibility of having access tomassive blogs,recommendations, andreviews. The challenge is to extract thepolarityfrom these data, which is a task ofopinion miningorsentiment analysis. The specific difficulties inherent in this task include issues related tosubjectiveinterpretation andlinguistic phenomenathat affect the polarity of words. Recently,deep learninghas become a popular method of addressing this task. However, different approaches have been proposed in the literature. This article provides an overview of deep learning for sentiment analysis in order to place these approaches in context.
Comparative Efficacy and Tolerability of Antimuscarinic Agents and the Selective β3‐Adrenoceptor Agonist, Mirabegron, for the Treatment of Overactive Bladder: Which is More Preferable as an Initial Treatment?
Authors: KOBAYASHI Minoru , NUKUI Akinori , KAMAI Takao 
Published: December 2016

ObjectivesThe objective of the present study was to evaluate comparative efficacy and tolerability of antimuscarinics and mirabegron as primary and salvage therapy in patients with overactive bladder (OAB).MethodsPatients ≥50 years with OAB symptoms were enrolled. Patients were initially treated with antimuscrinics or mirabegron for 8 weeks. When patients were refractory or intolerant to an initial treatment, drugs were switched to the other. The initial and second‐line efficacy was assessed at baseline, 4 and 8 weeks after the treatment having the following parameters of the International Prostatic Symptom Score (IPSS), quality of life (QOL) index, Overactive Bladder Symptom Score (OABSS) and post‐void residual (PVR) urine volume. Dry mouth and constipation were evaluated using dry mouth scale and constipation assessment scale, respectively.ResultsA total of 117 patients were enrolled. As an initial treatment, 60 patients were given antimuscarinics and 57 patients received mirabegron. Similar initial treatment efficacy was observed between the two drugs in the whole patients. However, mirabegron was more efficacious to men with OAB unresponsive to prior α1‐blocker. Dry mouth and constipation were less burdensome in patients treated with mirabegron. Such differences in efficacy and tolerability were associated with significantly greater persistence of mirabegron. As a second‐line setting, both drugs appear to be equally effective at least to relieve urgency symptoms remaining after an initial therapy.ConclusionThe present study suggests that mirabegron seems to have priority as an initial therapy with a distinct efficacy/tolerability balance. Mirabegron also represents a reasonable alternative to antimuscarinics for patients who had insufficient efficacy and poor tolerability.
Temporal dynamics of microbial communities in microcosms in response to pollutants
Authors: Jiao Shuo , Zhang Zhengqing , Yang Fan , Lin Yanbing , Chen Weimin , Wei Gehong 
Published: December 2016

AbstractElucidating the mechanisms underlying microbial succession is a major goal of microbial ecology research. Given the increasing human pressure on the environment and natural resources, responses to the repeated introduction of organic and inorganic pollutants are of particular interest. To investigate the temporal dynamics of microbial communities in response to pollutants, we analysed the microbial community structure in batch microcosms that were inoculated with soil bacteria following exposure to individual or combined pollutants (phenanthrene, n‐octadecane, phenanthrene + n‐octadecane and phenanthrene + n‐octadecane + CdCl2). Subculturing was performed at 10‐day intervals, followed by high‐throughput sequencing of 16S rRNA genes. The dynamics of microbial communities in response to different pollutants alone and in combination displayed similar patterns during enrichment. Specifically, the repression and induction of microbial taxa were dominant, and the fluctuation was not significant. The rate of appearance for new taxa and the temporal turnover within microbial communities were higher than the rates reported in other studies of microbial communities in air, water and soil samples. In addition, conditionally rare taxa that were specific to the treatments exhibited higher betweenness centrality values in the co‐occurrence network, indicating a strong influence on other interactions in the community. These results suggest that the repeated introduction of pollutants could accelerate microbial succession in microcosms, resulting in the rapid re‐equilibration of microbial communities.
Transcriptomic imprints of adaptation to fresh water: parallel evolution of osmoregulatory gene expression in the Alewife
Authors: Velotta Jonathan P. , Wegrzyn Jill L. , Ginzburg Samuel , Kang Lin , Czesny Sergiusz , O'Neill Rachel J. , McCormick Stephen D. , Michalak Pawel , Schultz Eric T. 
Published: December 2016

AbstractComparative approaches in physiological genomics offer an opportunity to understand the functional importance of genes involved in niche exploitation. We used populations of Alewife (Alosa pseudoharengus) to explore the transcriptional mechanisms that underlie adaptation to fresh water. Ancestrally anadromous Alewives have recently formed multiple, independently derived, landlocked populations, which exhibit reduced tolerance of saltwater and enhanced tolerance of fresh water. Using RNA‐seq, we compared transcriptional responses of an anadromous Alewife population to two landlocked populations after acclimation to fresh (0 ppt) and saltwater (35 ppt). Our results suggest that the gill transcriptome has evolved in primarily discordant ways between independent landlocked populations and their anadromous ancestor. By contrast, evolved shifts in the transcription of a small suite of well‐characterized osmoregulatory genes exhibited a strong degree of parallelism. In particular, transcription of genes that regulate gill ion exchange has diverged in accordance with functional predictions: freshwater ion‐uptake genes (most notably, the ‘freshwater paralog’ of Na+/K+‐ATPase α‐subunit) were more highly expressed in landlocked forms, whereas genes that regulate saltwater ion secretion (e.g. the ‘saltwater paralog’ of NKAα) exhibited a blunted response to saltwater. Parallel divergence of ion transport gene expression is associated with shifts in salinity tolerance limits among landlocked forms, suggesting that changes to the gill's transcriptional response to salinity facilitate freshwater adaptation.
Distal and proximal promoters co‐regulate pqsR expression in Pseudomonas aeruginosa
Authors: Farrow John M. , Pesci Everett C. 
Published: December 2016

SummaryThe ubiquitous bacterium Pseudomonas aeruginosa is an opportunistic pathogen that can cause serious infections in immunocompromised individuals. P. aeruginosa virulence is controlled partly by intercellular communication, and the transcription factor PqsR is a necessary component in the P. aeruginosa cell‐to‐cell signaling network. PqsR acts as the receptor for the Pseudomonas quinolone signal, and it controls the production of 2‐alkyl‐4‐quinolone molecules which are important for pathogenicity. Previous studies showed that the expression of pqsR is positively controlled by the quorum‐sensing regulator LasR, but it was unclear how LasR is able to induce pqsR transcription. In this report, we further investigated the control of pqsR, and discovered two separate promoter sites that contribute to pqsR expression. LasR‐mediated activation occurs at the distal promoter site, but this activation can be antagonized by the regulator CysB. The proximal promoter site also contributes to pqsR transcription, but initiation at this site is inhibited by a negative regulatory sequence element, and potentially by the H‐NS family members MvaT and MvaU. We propose a model where positive and negative regulatory influences at each promoter site are integrated to modify pqsR expression. This arrangement could allow for information from both environmental signals and cell‐to‐cell communication to influence PqsR levels.
Stereotypes, Prejudice, and the Taxonomy of the Implicit Social Mind1
Authors: Madva Alex , Brownstein Michael 
Published: December 2016

AbstractHow do cognition and affect interact to produce action? Research in intergroup psychology illuminates this question by investigating the relationship between stereotypes and prejudices about social groups. Yet it is now clear that many social attitudes are implicit (roughly, nonconscious or involuntary). This raises the question: how does the distinction between cognition and affect apply to implicit mental states? An influential view—roughly analogous to a Humean theory of action—is that “implicit stereotypes” and “implicit prejudices” constitute two separate constructs, reflecting different mental processes and neural systems. On this basis, some have also argued that interventions to reduce discrimination should combat implicit stereotypes and prejudices separately. We propose an alternative (anti‐Humean) framework. We argue that all putative implicit stereotypes are affect‐laden and all putative implicit prejudices are “semantic,” that is, they stand in co‐activating associations with concepts and beliefs. Implicit biases, therefore, consist in “clusters” of semantic‐affective associations, which differ in degree, rather than kind. This framework captures the psychological structure of implicit bias, promises to improve the power of indirect measures to predict behavior, and points toward the design of more effective interventions to combat discrimination.
Contract theories and partnership in health care. A philosophical inquiry to the philosophy of John Rawls and Seyla Benhabib
Authors: Määttä Sylvia , Lützén Kim , Öresland Stina 
Published: December 2016

AbstractOver the last 20 years, a paternalistic view in health care has been losing ground. The question about less asymmetrical positions in the healthcare professional–patient relationship is, for example, being addressed by the increased emphasis on person‐centred care, promoted in disciplines such as medicine and nursing. Partnership is considered as a key component in person‐centred care. Although the previous studies have addressed the attributes inherent in partnership, there is still potential for further discussion on how the various interpretations of partnership influence their use in healthcare literature. A vague understanding might also affect education and evaluation. As we see it, the philosophical underpinnings of the idea of partnership have not been sufficiently explored and discussed. The study reveals that partnership originates in the term “partener” defined as a relationship between individuals or groups characterized by cooperation and responsibility. Etymologically speaking, partnership is hence bound by a contract, which in this study is discussed in the frame of Rawls’ contract theory, which in turn intersects with Benhabib and her distinction between “the abstract” and “the concrete Other.” Further, the expression “equal partnership,” which often appears in the context of person‐centredness, is explored in relation to the philosophies of Rawls and Benhabib. The opportunity for partnership, as well as the risk of partnership becoming a tempting magnet with a vague and imprecise meaning, is discussed. Without exploration, reflection and discussion of the philosophical underpinnings, partnership carries a substantial risk of becoming an indistinct idea used in health care.