398 research outputs found

    Bcl3 prevents acute inflammatory lung injury in mice by restraining emergency granulopoiesis

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    Granulocytes are pivotal regulators of tissue injury. However, the transcriptional mechanisms that regulate granulopoiesis under inflammatory conditions are poorly understood. Here we show that the transcriptional coregulator B cell leukemia/lymphoma 3 (Bcl3) limits granulopoiesis under emergency (i.e., inflammatory) conditions, but not homeostatic conditions. Treatment of mouse myeloid progenitors with G-CSF — serum concentrations of which rise under inflammatory conditions — rapidly increased Bcl3 transcript accumulation in a STAT3-dependent manner. Bcl3-deficient myeloid progenitors demonstrated an enhanced capacity to proliferate and differentiate into granulocytes following G-CSF stimulation, whereas the accumulation of Bcl3 protein attenuated granulopoiesis in an NF-κB p50–dependent manner. In a clinically relevant model of transplant-mediated lung ischemia reperfusion injury, expression of Bcl3 in recipients inhibited emergency granulopoiesis and limited acute graft damage. These data demonstrate a critical role for Bcl3 in regulating emergency granulopoiesis and suggest that targeting the differentiation of myeloid progenitors may be a therapeutic strategy for preventing inflammatory lung injury

    Oscillations in the bispectrum

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    There exist several models of inflation that produce primordial bispectra that contain a large number of oscillations. In this paper we discuss these models, and aim at finding a method of detecting such bispectra in the data. We explain how the recently proposed method of mode expansion of bispectra might be able to reconstruct these spectra from separable basis functions. Extracting these basis functions from the data might then lead to observational constraints on these models.Comment: 6 pages, 2 figures, submitted to JOP: Conference Series, PASCOS 201

    How Software Practitioners Use Informal Local Meetups to Share Software Engineering Knowledge

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    Informal technology "meetups" have become an important aspect of the software development community, engaging many thousands of practitioners on a regular basis. However, although local technology meetups are well-attended by developers, little is known about their motivations for participating, the type or usefulness of information that they acquire, and how local meetups might differ from and complement other available communication channels for software engineering information. We interviewed the leaders of technology-oriented Meetup groups, and collected quantitative information via a survey distributed to participants in technology-oriented groups. Our findings suggest that participants in these groups are primarily experienced software practitioners, who use Meetup for staying abreast of new developments, building local networks and achieving transfer of rich tacit knowledge with peers to improve their practice. We also suggest that face to face meetings are useful forums for exchanging tacit knowledge and contextual information needed for software engineering practice

    On D3-brane Potentials in Compactifications with Fluxes and Wrapped D-branes

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    We study the potential governing D3-brane motion in a warped throat region of a string compactification with internal fluxes and wrapped D-branes. If the Kahler moduli of the compact space are stabilized by nonperturbative effects, a D3-brane experiences a force due to its interaction with D-branes wrapping certain four-cycles. We compute this interaction, as a correction to the warped four-cycle volume, using explicit throat backgrounds in supergravity. This amounts to a closed-string channel computation of the loop corrections to the nonperturbative superpotential that stabilizes the volume. We demonstrate for warped conical spaces that the superpotential correction is given by the embedding equation specifying the wrapped four-cycle, in agreement with the general form proposed by Ganor. Our approach automatically provides a solution to the problem of defining a holomorphic gauge coupling on wrapped D7-branes in a background with D3-branes. Finally, our results have applications to cosmological inflation models in which the inflaton is modeled by a D3-brane moving in a warped throat.Comment: 45 pages, 1 figure; v2: added reference, clarified notatio

    Role of advanced neuroimaging, fluid biomarkers and genetic testing in the assessment of sport-related concussion: a systematic review

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    Objective To conduct a systematic review of published literature on advanced neuroimaging, fluid biomarkers and genetic testing in the assessment of sport-related concussion (SRC). Data sources Computerised searches of Medline, PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, Scopus and Cochrane Library from 1 January 2000 to 31 December 2016 were done. There were 3222 articles identified. Study selection In addition to medical subject heading terms, a study was included if (1) published in English, (2) represented original research, (3) involved human research, (4) pertained to SRC and (5) involved data from neuroimaging, fluid biomarkers or genetic testing collected within 6 months of injury. Ninety-eight studies qualified for review (76 neuroimaging, 16 biomarkers and 6 genetic testing). Data extraction Separate reviews were conducted for neuroimaging, biomarkers and genetic testing. A standardised data extraction tool was used to document study design, population, tests employed and key findings. Reviewers used a modified quality assessment of studies of diagnostic accuracy studies (QUADAS-2) tool to rate the risk of bias, and a modified Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to rate the overall level of evidence for each search. Data synthesis Results from the three respective reviews are compiled in separate tables and an interpretive summary of the findings is provided. Conclusions Advanced neuroimaging, fluid biomarkers and genetic testing are important research tools, but require further validation to determine their ultimate clinical utility in the evaluation of SRC. Future research efforts should address current gaps that limit clinical translation. Ultimately, research on neurobiological and genetic aspects of SRC is predicted to have major translational significance to evidence-based approaches to clinical management of SRC, much like applied clinical research has had over the past 20 years

    Association of Blood Biomarkers With Acute Sport-Related Concussion in Collegiate Athletes: Findings From the NCAA and Department of Defense CARE Consortium

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    Importance: There is potential scientific and clinical value in validation of objective biomarkers for sport-related concussion (SRC). Objective: To investigate the association of acute-phase blood biomarker levels with SRC in collegiate athletes. Design, Setting, and Participants: This multicenter, prospective, case-control study was conducted by the National Collegiate Athletic Association (NCAA) and the US Department of Defense Concussion Assessment, Research, and Education (CARE) Consortium from February 20, 2015, to May 31, 2018, at 6 CARE Advanced Research Core sites. A total of 504 collegiate athletes with concussion, contact sport control athletes, and non-contact sport control athletes completed clinical testing and blood collection at preseason baseline, the acute postinjury period, 24 to 48 hours after injury, the point of reporting being asymptomatic, and 7 days after return to play. Data analysis was conducted from March 1 to November 30, 2019. Main Outcomes and Measures: Glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neurofilament light chain, and tau were quantified using the Quanterix Simoa multiplex assay. Clinical outcome measures included the Sport Concussion Assessment Tool-Third Edition (SCAT-3) symptom evaluation, Standardized Assessment of Concussion, Balance Error Scoring System, and Brief Symptom Inventory 18. Results: A total of 264 athletes with concussion (mean [SD] age, 19.08 [1.24] years; 211 [79.9%] male), 138 contact sport controls (mean [SD] age, 19.03 [1.27] years; 107 [77.5%] male), and 102 non-contact sport controls (mean [SD] age, 19.39 [1.25] years; 82 [80.4%] male) were included in the study. Athletes with concussion had significant elevation in GFAP (mean difference, 0.430 pg/mL; 95% CI, 0.339-0.521 pg/mL; P < .001), UCH-L1 (mean difference, 0.449 pg/mL; 95% CI, 0.167-0.732 pg/mL; P < .001), and tau levels (mean difference, 0.221 pg/mL; 95% CI, 0.046-0.396 pg/mL; P = .004) at the acute postinjury time point compared with preseason baseline. Longitudinally, a significant interaction (group × visit) was found for GFAP (F7,1507.36 = 16.18, P < .001), UCH-L1 (F7,1153.09 = 5.71, P < .001), and tau (F7,1480.55 = 6.81, P < .001); the interaction for neurofilament light chain was not significant (F7,1506.90 = 1.33, P = .23). The area under the curve for the combination of GFAP and UCH-L1 in differentiating athletes with concussion from contact sport controls at the acute postinjury period was 0.71 (95% CI, 0.64-0.78; P < .001); the acute postinjury area under the curve for all 4 biomarkers combined was 0.72 (95% CI, 0.65-0.79; P < .001). Beyond SCAT-3 symptom score, GFAP at the acute postinjury time point was associated with the classification of athletes with concussion from contact controls (β = 12.298; 95% CI, 2.776-54.481; P = .001) and non-contact sport controls (β = 5.438; 95% CI, 1.676-17.645; P = .005). Athletes with concussion with loss of consciousness or posttraumatic amnesia had significantly higher levels of GFAP than athletes with concussion with neither loss of consciousness nor posttraumatic amnesia at the acute postinjury time point (mean difference, 0.583 pg/mL; 95% CI, 0.369-0.797 pg/mL; P < .001). Conclusions and Relevance: The results suggest that blood biomarkers can be used as research tools to inform the underlying pathophysiological mechanism of concussion and provide additional support for future studies to optimize and validate biomarkers for potential clinical use in SRC

    Towards an Explicit Model of D-brane Inflation

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    We present a detailed analysis of an explicit model of warped D-brane inflation, incorporating the effects of moduli stabilization. We consider the potential for D3-brane motion in a warped conifold background that includes fluxes and holomorphically-embedded D7-branes involved in moduli stabilization. Although the D7-branes significantly modify the inflaton potential, they do not correct the quadratic term in the potential, and hence do not cause a uniform change in the slow-roll parameter eta. Nevertheless, we present a simple example based on the Kuperstein embedding of D7-branes, z_1=constant, in which the potential can be fine-tuned to be sufficiently flat for inflation. To derive this result, it is essential to incorporate the fact that the compactification volume changes slightly as the D3-brane moves. We stress that the compactification geometry dictates certain relationships among the parameters in the inflaton Lagrangian, and these microscopic constraints impose severe restrictions on the space of possible models. We note that the shape of the final inflaton potential differs from projections given in earlier studies: in configurations where inflation occurs, it does so near an inflection point. Finally, we comment on the difficulty of making precise cosmological predictions in this scenario. This is the companion paper to arXiv:0705.3837.Comment: 68 pages, 6 figures; v2: fixed typos, added refs and clarifications; v3: expanded discussion of inflection point inflatio
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