205 research outputs found

    A Strategic Approach to Public Health Workforce Development and Capacity Building

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    In February 2010, CDC’s National Center for HIV/AIDS, Viral Hepatitis, Sexually Transmitted Disease (STD), and Tuberculosis (TB) Prevention (NCHHSTP) formally institutionalized workforce development and capacity building (WDCB) as one of six overarching goals in its 2010–2015 Strategic Plan. Annually, workforce team members finalize an action plan that lays the foundation for programs to be implemented for NCHHSTP’s workforce that year. This paper describes selected WDCB programs implemented by NCHHSTP during the last 4 years in the three strategic goal areas: (1) attracting, recruiting, and retaining a diverse and sustainable workforce; (2) providing staff with development opportunities to ensure the effective and innovative delivery of NCHHSTP programs; and (3) continuously recognizing performance and achievements of staff and creating an atmosphere that promotes a healthy work–life balance. Programs have included but are not limited to an Ambassador Program for new hires, career development training for all staff, leadership and coaching for mid-level managers, and a Laboratory Workforce Development Initiative for laboratory scientists. Additionally, the paper discusses three overarching areas—employee communication, evaluation and continuous review to guide program development, and the implementation of key organizational and leadership structures to ensure accountability and continuity of programs. Since 2010, many lessons have been learned regarding strategic approaches to scaling up organization-wide public health workforce development and capacity building. Perhaps the most important is the value of ensuring the high-level strategic prioritization of this issue, demonstrating to staff and partners the importance of this imperative in achieving NCHHSTP’s mission

    The Effectiveness of Coenzyme Q1 and Q10 in Mitigating Myocardial Reperfusion/Ischemia (MI/R) Injury

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    Mitochondria may be a principle source of oxidative stress causing MI/R injury. Coenzyme Q10 (CoQ10) is essential for electron transport in normal mitochondria, has antioxidant properties but its bioavailability is likely reduced due to oxidative stress during MI/R. Coenzyme Q1 (CoQ1) is a derivative of CoQ10, but is a more potent antioxidant than CoQ10 due to a shorter isoprene chain. We hypothesize that CoQ1 will exhibit better cardioprotective effects during MI/R. CoQ1 (MW=250 g/mol; 20 ΌM, n=5) and CoQ10 (MW=863 g/mol; 20 ΌM, n=5) were given at reperfusion in isolated rat hearts subjected to I (30 min)/R (45 min). We found that MI/R hearts (n=7) and MI/R+DMSO hearts (n=4) (0.2% DMSO was used to solubilize CoQ1 and CoQ10) exhibited significantly compromised cardiac contractile/diastolic pressures and coronary flow during reperfusion compared to those of sham hearts (n=5). By contrast, the final left ventricular developed pressure was significantly improved by CoQ1 treatment (56.0±5.3 mmHg), but not CoQ10 treatment (38.4±8.6 mmHg), when compared to that in MI/R hearts (33.6±6.2 mmHg) and MI/R+DMSO hearts (36.4±9.7 mmHg) (p\u3c0.05). Similarly, the final peak of the firstderivative of left ventricular pressure was significantly higher in CoQ1 treatment (1294.2±104.6mmHg/s), but not CoQ10 treatment (770.6±120.1 mmHg/s), when compared to that in MI/R hearts (700.6±134.7 mmHg/s) and MI/R+DMSO hearts (and 741.5±168.6 mmHg/s) (p\u3c0.05). CoQ1 and CoQ10 treated hearts showed no improvement on diastolic pressure and coronary flow compared to the controls. Moreover, infarct size was reduced by CoQ1 treatment (25±3%) and CoQ10 treatment (29±4%) compared to that in untreated MI/R (44±6%) and MI/R+DMSO (35±3%). In summary, our preliminary results indicate that CoQ1 was more effective than CoQ10 in restoring post-reperfused cardiac contractile function, but not infarct size during MI/R

    Yellow fever virus capsid protein is a potent suppressor of RNA silencing that binds double-stranded RNA

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    Mosquito-borne flaviviruses, including yellow fever virus (YFV), Zika virus (ZIKV), and West Nile virus (WNV), profoundly affect human health. The successful transmission of these viruses to a human host depends on the pathogen’s ability to overcome a potentially sterilizing immune response in the vector mosquito. Similar to other invertebrate animals and plants, the mosquito’s RNA silencing pathway comprises its primary antiviral defense. Although a diverse range of plant and insect viruses has been found to encode suppressors of RNA silencing, the mechanisms by which flaviviruses antagonize antiviral small RNA pathways in disease vectors are unknown. Here we describe a viral suppressor of RNA silencing (VSR) encoded by the prototype flavivirus, YFV. We show that the YFV capsid (YFC) protein inhibits RNA silencing in the mosquito Aedes aegypti by interfering with Dicer. This VSR activity appears to be broadly conserved in the C proteins of other medically important flaviviruses, including that of ZIKV. These results suggest that a molecular “arms race” between vector and pathogen underlies the continued existence of flaviviruses in nature

    Synergistic effect of pro-inflammatory TNFα and IL-17 in periostin mediated collagen deposition: Potential role in liver fibrosis

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    Background The pro-inflammatory cytokines, tumor necrosis factor (TNF)-α, and interleukin (IL)-17, have been implicated in the pathogenesis of liver fibrosis. In this study, we investigated the role of TNFα and IL-17 toward induction of profibrotic factor, periostin. Methods HepG2 cells were cultured and treated with inflammatory cytokines, TNFα and IL-17. Computational promoter sequence analysis of the periostin promoter was performed to define the putative binding sites for transcription factors. Transcription factors were analyzed by Western blot and Chromatin Immunoprecipitation. Periostin and transcription factor expression analysis was performed by RT-PCR, Western blot, and fluorescence microscopy. Type I collagen expression from fibroblast cultures was analyzed by Western blot and Sircol soluble collagen assay. Results Activation of HepG2 Cells with TNFα and IL-17 enhanced the expression of periostin (3.5 and 4.4 fold, respectively p \u3c 0.05) compared to untreated cells. However, combined treatment with both TNFα and IL-17 at similar concentration demonstrated a 13.3 fold increase in periostin (p \u3c 0.01), thus suggesting a synergistic role of these cytokines. Periostin promoter analysis and specific siRNA knock-down revealed that TNFα induces periostin through cJun, while IL-17 induced periostin via STAT-3 signaling mechanisms. Treatment of the supernatant from the cytokine activated HepG2 cells on fibroblast cultures induced enhanced expression of type I collagen (\u3e9.1 fold, p \u3c 0.01), indicative of a direct fibrogenic effect of TNFα and IL-17. Conclusion TNFα and IL-17 induced fibrogenesis through cJun and STAT-3 mediated expression of profibrotic biomarker, periostin. Therefore, periostin might serve as a novel biomarker in early diagnosis of liver fibrosis

    TOP2A and EZH2 Provide Early Detection of an Aggressive Prostate Cancer Subgroup.

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    Purpose: Current clinical parameters do not stratify indolent from aggressive prostate cancer. Aggressive prostate cancer, defined by the progression from localized disease to metastasis, is responsible for the majority of prostate cancer–associated mortality. Recent gene expression profiling has proven successful in predicting the outcome of prostate cancer patients; however, they have yet to provide targeted therapy approaches that could inhibit a patient\u27s progression to metastatic disease. Experimental Design: We have interrogated a total of seven primary prostate cancer cohorts (n = 1,900), two metastatic castration-resistant prostate cancer datasets (n = 293), and one prospective cohort (n = 1,385) to assess the impact of TOP2A and EZH2 expression on prostate cancer cellular program and patient outcomes. We also performed IHC staining for TOP2A and EZH2 in a cohort of primary prostate cancer patients (n = 89) with known outcome. Finally, we explored the therapeutic potential of a combination therapy targeting both TOP2A and EZH2 using novel prostate cancer–derived murine cell lines. Results: We demonstrate by genome-wide analysis of independent primary and metastatic prostate cancer datasets that concurrent TOP2A and EZH2 mRNA and protein upregulation selected for a subgroup of primary and metastatic patients with more aggressive disease and notable overlap of genes involved in mitotic regulation. Importantly, TOP2A and EZH2 in prostate cancer cells act as key driving oncogenes, a fact highlighted by sensitivity to combination-targeted therapy. Conclusions: Overall, our data support further assessment of TOP2A and EZH2 as biomarkers for early identification of patients with increased metastatic potential that may benefit from adjuvant or neoadjuvant targeted therapy approaches. ©2017 AACR

    Sub-0.6 eV Inverted Metamorphic GaInAs Cells Grown on InP and GaAs Substrates for Thermophotovoltaics and Laser Power Conversion

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    We present inverted metamorphic Ga0.3In0.7As photovoltaic converters with sub-0.60 eV bandgaps grown on InP and GaAs substrates. The compositionally graded buffers in these devices have threading dislocation densities of 1.3x10^6 cm^-2 and 8.9x10^6 cm^-2 on InP and GaAs, respectively. The devices generate open-circuit voltages of 0.386 V and 0.383 V, respectively, at a current density of ~10 A/cm^2, yielding bandgap-voltage offsets of 0.20 and 0.21 V. We measured their broadband reflectance and used it to estimate thermophotovoltaic efficiency. The InP-based cell is estimated to yield 1.09 W/cm^2 at 1100 degrees C vs. 0.92 W/cm^2 for the GaAs-based cell, with efficiencies of 16.8 vs. 9.2%. The efficiencies of both devices are limited by sub-bandgap absorption, with power weighted sub-bandgap reflectances of 81% and 58%, respectively, which we assess largely occurs in the graded buffers. We estimate that the thermophotovoltaic efficiencies would peak at ~1100 degrees C at 24.0% and 20.7% in structures with the graded buffer removed, if previously demonstrated reflectance is achieved. These devices also have application to laser power conversion in the 2.0-2.3 micron atmospheric window. We estimate peak LPC efficiencies of 36.8% and 32.5% under 2.0 micron irradiances of 1.86 W/cm^2 and 2.81 W/cm^2, respectively.Comment: 14 pages, 6 figure

    Miniature exoplanet radial velocity array I: design, commissioning, and early photometric results

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    The MINiature Exoplanet Radial Velocity Array (MINERVA) is a US-based observational facility dedicated to the discovery and characterization of exoplanets around a nearby sample of bright stars. MINERVA employs a robotic array of four 0.7 m telescopes outfitted for both high-resolution spec- troscopy and photometry, and is designed for completely autonomous operation. The primary science program is a dedicated radial velocity survey and the secondary science objective is to obtain high precision transit light curves. The modular design of the facility and the flexibility of our hardware allows for both science programs to be pursued simultaneously, while the robotic control software provides a robust and efficient means to carry out nightly observations. In this article, we describe the design of MINERVA including major hardware components, software, and science goals. The telescopes and photometry cameras are characterized at our test facility on the Caltech campus in Pasadena, CA, and their on-sky performance is validated. New observations from our test facility demonstrate sub-mmag photometric precision of one of our radial velocity survey targets, and we present new transit observations and fits of WASP-52b—a known hot-Jupiter with an inflated radius and misaligned orbit. The process of relocating the MINERVA hardware to its final destination at the Fred Lawrence Whipple Observatory in southern Arizona has begun, and science operations are expected to commence within 2015
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