648 research outputs found

    A self-determination perspective of strengths use at work: Examining its determinant and performance implications

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    We investigate the role of strengths use in the workplace by drawing on self-determination theory (SDT) to propose that strengths use at work can yield performance benefits in terms of task performance and discretionary helping, and that the social context, in the form of leader autonomy support, can promote employees’ strengths use. Further, consistent with an interactional psychology perspective, we contend that the relationship between autonomy support and strengths use will be stronger among individuals with strong independent self-construal. We tested the model using matched data from 194 employees and their supervisors and found evidence for the relevance of strengths use at work, even after accounting for the role of intrinsic motivation. In addition to providing practical implications on developing employee strengths use and how to do so, this study advances theory and research on workplace strength use, SDT, and positive organizational behavior

    Prefrontal Pathways Provide Top-Down Control of Memory for Sequences of Events

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    We remember our lives as sequences of events, but it is unclear how these memories are controlled during retrieval. In rats, the medial prefrontal cortex (mPFC) is positioned to influence sequence memory through extensive top-down inputs to regions heavily interconnected with the hippocampus, notably the nucleus reuniens of the thalamus (RE) and perirhinal cortex (PER). Here, we used an hM4Di synaptic-silencing approach to test our hypothesis that specific mPFC→RE and mPFC→PER projections regulate sequence memory retrieval. First, we found non-overlapping populations of mPFC cells project to RE and PER. Second, suppressing mPFC activity impaired sequence memory. Third, inhibiting mPFC→RE and mPFC→PER pathways effectively abolished sequence memory. Finally, a sequential lag analysis showed that the mPFC→RE pathway contributes to a working memory retrieval strategy, whereas the mPFC→PER pathway supports a temporal context memory retrieval strategy. These findings demonstrate that mPFC→RE and mPFC→PER pathways serve as top-down mechanisms that control distinct sequence memory retrieval strategies

    Characterization of potential biomarkers of reactogenicity of licensed antiviral vaccines: randomized controlled clinical trials conducted by the BIOVACSAFE consortium

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    Funding text The authors are grateful for the vital contributions of the participating study volunteers, clinicians, nurses, and laboratory technicians at the Surrey study site. The work by Roberto Leone, laboratory technician at Humanitas Clinical and Research Center, is gratefully acknowledged. Finally, they thank Ellen Oe (GSK) for scientific writing assistance. The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement n°115308, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007–2013) and EFPIA companies’ in-kind contribution. The contribution of the European Commission to the Advanced Immunization Technologies (ADITEC) project (grant agreement n° 280873) is also gratefully acknowledged. Publisher Copyright: © 2019, The Author(s).Biomarkers predictive of inflammatory events post-vaccination could accelerate vaccine development. Within the BIOVACSAFE framework, we conducted three identically designed, placebo-controlled inpatient/outpatient clinical studies (NCT01765413/NCT01771354/NCT01771367). Six antiviral vaccination strategies were evaluated to generate training data-sets of pre-/post-vaccination vital signs, blood changes and whole-blood gene transcripts, and to identify putative biomarkers of early inflammation/reactogenicity that could guide the design of subsequent focused confirmatory studies. Healthy adults (N = 123; 20–21/group) received one immunization at Day (D)0. Alum-adjuvanted hepatitis B vaccine elicited vital signs and inflammatory (CRP/innate cells) responses that were similar between primed/naive vaccinees, and low-level gene responses. MF59-adjuvanted trivalent influenza vaccine (ATIV) induced distinct physiological (temperature/heart rate/reactogenicity) response-patterns not seen with non-adjuvanted TIV or with the other vaccines. ATIV also elicited robust early (D1) activation of IFN-related genes (associated with serum IP-10 levels) and innate-cell-related genes, and changes in monocyte/neutrophil/lymphocyte counts, while TIV elicited similar but lower responses. Due to viral replication kinetics, innate gene activation by live yellow-fever or varicella-zoster virus (YFV/VZV) vaccines was more suspended, with early IFN-associated responses in naïve YFV-vaccine recipients but not in primed VZV-vaccine recipients. Inflammatory responses (physiological/serum markers, innate-signaling transcripts) are therefore a function of the vaccine type/composition and presence/absence of immune memory. The data reported here have guided the design of confirmatory Phase IV trials using ATIV to provide tools to identify inflammatory or reactogenicity biomarkers.Peer reviewe

    The helicase HAGE prevents interferon-a-induced PML expression in ABCB5+ malignant melanoma-initiating cells by promoting the expression of SOCS1

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    The tumour suppressor PML (promyelocytic leukaemia protein) regulates several cellular pathways involving cell growth, apoptosis, differentiation and senescence. PML also has an important role in the regulation of stem cell proliferation and differentiation. Here, we show the involvement of the helicase HAGE in the transcriptional repression of PML expression in ABCB5 + malignant melanoma-initiating cells (ABCB5 + MMICs), a population of cancer stem cells which are responsible for melanoma growth, progression and resistance to drug-based therapy. HAGE prevents PML gene expression by inhibiting the activation of the JAK-STAT (janus kinase-signal transducers and activators of transcription) pathway in a mechanism which implicates the suppressor of cytokine signalling 1 (SOCS1). Knockdown of HAGE led to a significant decrease in SOCS1 protein expression, activation of the JAK-STAT signalling cascade and a consequent increase of PML expression. To confirm that the reduction in SOCS1 expression was dependent on the HAGE helicase activity, we showed that SOCS1, effectively silenced by small interfering RNA, could be rescued by re-introduction of HAGE into cells lacking HAGE. Furthermore, we provide a mechanism by which HAGE promotes SOCS1 mRNA unwinding and protein expression in vitro

    ‘More willing to carry on in the face of adversity’: how beginner teachers facing challenging circumstances experience positive psychology coaching. An interpretative phenomenological analysis

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    Positive psychology coaching (PPC) is defined as activating positive psychology (PP) in an applied and systematic way through coaching (Passmore, J., & Oades, P. (2014). Positive psychology coaching – A model for coaching practice. The Coaching Psychologist, 10(2), 68–70). Currently studies looking at how PPC is experienced by coachees are limited. While there has been some early success cited in using a PPC approach in professional development in education with adults (Zwart, R. C., Korthagen, F. A. J., & Attema-Noordewier, S. (2014). A strength-based approach to teacher professional development. Professional Development in Education, 41(3), 579–596. https://doi.org/10.1080/19415257.2014.919341) it is not yet known how teachers experience PPC. The purpose of this paper was to gain an understanding of how PPC is experienced by beginner teachers undergoing challenging circumstances. This initial explorative study adopted a qualitative approach using Interpretative Phenomenological Analysis (IPA) (Smith, J., Flowers, P., & Larkin, M. (2009). Interpretative phenomenological analysis: Theory, method and research. Sage). Four superordinate themes emerged: ‘perfectly normal to feel this way’; making sense and ‘joining the dots’; increased positive emotion; and, time to think ‘in an easy-going environment’. Further studies of the application of PPC in educational settings are needed

    The Case for RackOut: Scalable Data Serving Using Rack-Scale Systems

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    To provide low latency and high throughput guarantees, most large key-value stores keep the data in the memory of many servers. Despite the natural parallelism across lookups, the load imbalance, introduced by heavy skew in the popularity distribution of keys, limits performance. To avoid violating tail latency service-level objectives, systems tend to keep server utilization low and organize the data in micro-shards, which provides units of migration and replication for the purpose of load balancing. These techniques reduce the skew, but incur additional monitoring, data replication and consistency maintenance overheads. In this work, we introduce RackOut, a memory pooling technique that leverages the one-sided remote read primitive of emerging rack-scale systems to mitigate load imbalance while respecting service-level objectives. In RackOut, the data is aggregated at rack-scale granularity, with all of the participating servers in the rack jointly servicing all of the rack’s micro-shards. We develop a queuing model to evaluate the impact of RackOut at the datacenter scale. In addition, we implement a RackOut proof-of-concept key-value store, evaluate it on two experimental platforms based on RDMA and Scale-Out NUMA, and use these results to validate the model. Our results show that RackOut can increase throughput up to 6× for RDMA and 8.6× for Scale-Out NUMA compared to a scale-out deployment, while respecting tight tail latency service-level objectives

    HAGE (DDX43) is a biomarker for poor prognosis and a predictor of chemotherapy response in breast cancer

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    Background: HAGE protein is a known immunogenic cancer-specific antigen. Methods: The biological, prognostic and predictive values of HAGE expression was studied using immunohistochemistry in three cohorts of patients with BC (n=2147): early primary (EP-BC; n=1676); primary oestrogen receptor-negative (PER-BC; n=275) treated with adjuvant anthracycline-combination therapies (Adjuvant-ACT); and primary locally advanced disease (PLA-BC) who received neo-adjuvant anthracycline-combination therapies (Neo-adjuvant-ACT; n=196). The relationship between HAGE expression and the tumour-infiltrating lymphocytes (TILs) in matched prechemotherapy and postchemotherapy samples were investigated. Results: Eight percent of patients with EP-BC exhibited high HAGE expression (HAGEþ) and was associated with aggressive clinico-pathological features (Ps<0.01). Furthermore, HAGEþexpression was associated with poor prognosis in both univariate and multivariate analysis (Ps<0.001). Patients with HAGE+ did not benefit from hormonal therapy in high-risk ER-positive disease. HAGE+ and TILs were found to be independent predictors for pathological complete response to neoadjuvant-ACT; P<0.001. A statistically significant loss of HAGE expression following neoadjuvant-ACT was found (P=0.000001), and progression-free survival was worse in those patients who had HAGE+ residual disease (P=0.0003). Conclusions: This is the first report to show HAGE to be a potential prognostic marker and a predictor of response to ACT in patients with BC
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