110 research outputs found

    Shale Public Finance: Local government revenues and costs associated with oil and gas development

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    Oil and gas development associated with shale resources has increased substantially in the United States, with important implications for local governments. These governments tend to experience increased revenue from a variety of sources, such as severance taxes distributed by the state government, local property taxes and sales taxes, direct payments from oil and gas companies, and in-kind contributions from those companies. Local governments also tend to face increased demand for services such as road repairs due to heavy truck traffic and from population growth associated with the oil and gas sector. This paper describes the major oil- and gas related revenues and service demands (i.e., costs) that county and municipal governments have experienced in Arkansas, Colorado, Louisiana, Montana, North Dakota, Pennsylvania, Texas, and Wyoming. Based on extensive interviews with officials in the most heavily affected parts of these states, along with analysis of financial data, it appears that most county and municipal governments have experienced net financial benefits, though some in western North Dakota and eastern Montana appear to have experienced net negative fiscal impacts. Some municipalities in rural Colorado and Wyoming also struggled to manage fiscal impacts during recent oil and gas booms, though these challenges faded as drilling activity slowed

    HIV clinical stage progression of patients at 241 outpatient clinics in Democratic Republic of Congo: Disparities by gender, TB status and rurality

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    Background: HIV clinical care programs are increasingly cognizant of the importance of customizing services according to patients’ clinical stage progression (WHO\u27s four-tiered staging) and other risk assessments. Understanding factors associated with Persons Living with HIV (PLHIV) patients’ progression through the treatment cascade and clinical stages is essential for programs to provide patient-centered, evidence-based services. Methods and materials: To analyze patient characteristics associated with disease progression stages for PLHIV on antiretroviral therapy (ART), this quantitative study used data, from January 2014–June 2019, from 49,460 PLHIV on ART from 241 HIV/AIDS outpatient clinics in 23 health zones in Haut-Katanga and Kinshasa provinces, Democratic Republic of Congo. To assess bivariate and multivariate associations, we performed Chi-square and multinomial logistic regression. Results: Among PLHIV receiving ART, 4.4% were at stage 4, and 30.7% at stage 3. Those at the less severe stages 2 and 1 constituted 22.9% and 41.9%. After controlling for covariates, patients with no TB were significantly more likely than those with TB (p\u3c = .05) to be at stage 1, rather than 3 or 4 (adjusted odds ratio or AOR, 5.73; confidence interval or CI, 4.98–6.59). Other characteristics significantly associated with higher odds of being at stage 1 included being female (AOR, 1.35; CI, 1.29–1.42), and shorter duration on ART (vs. \u3e 40.37 months); for ART duration less than 3.23 months the AOR was 2.47, for 3.23–14.52 months duration the AOR was 2.60, and for 14.53–40.37 months duration the AOR was 1.77 (quartile cut points used). Compared to patients in urban health zones, those in rural (AOR, 0.32) and semi-rural health zones (AOR, 0.79) were less likely to be at stage 1. Conclusion: Significant and substantial variation in HIV clinical progression stage by geographic location and demographic characteristics existed, indicative of the need for targeted efforts to improve the effectiveness of HIV care. Patients with TB coinfection compared to those without coinfection had a much greater risk of being at stage 3 or 4, implying a need for customized approaches and clinical regimens for this high-risk population

    Older people's priorities in health and social care research and practice: a public engagement workshop

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    As the world’s population ages, there is an increasing need for research that addresses the priorities of older people. A public engagement workshop focusing on the priorities of older people for research and practice in health and social care was attended by seventy-five people aged 70 years and above in London, United Kingdom (UK). The workshop aimed to identify and prioritise issues important to older people that would benefit from further research and act as a platform to promote sharing of ideas and problems related to these important issues. Key priorities emerged including loneliness and isolation, support and training for professional and family carers, post-surgical care, negative perceptions of older people and inequalities related to public services and healthcare. Participants further suggested older people should be actively involved in all stages of the research process

    Making nonwoven fibrous poly(epsilon-caprolactone) constructs for antimicrobial and tissue engineering applications by pressurized melt gyration

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    A pressurized melt gyration process has been used for the first time to generate poly(ε-caprolactone) (PCL) fibers. Gyration speed, working pressure, and melt temperature are varied and these parameters influence the fiber diameter and the temperature enabled changing the surface morphology of the fibers. Two types of nonwoven PCL fiber constructs are prepared. First, Ag-doped PCL is studied for antibacterial activity using Gram-negative Escherichia coli and Pseudomonas aeruginosa microorganisms. The melt temperature used to make these constructs significantly influences antibacterial activity. Neat PCL nonwoven scaffolds are also prepared and their potential for application in muscular tissue engineering is studied with myoblast cells. Results show significant cell attachment, growth, and proliferation of cells on the scaffolds

    Mechanism of human PINK1 activation at the TOM complex in a reconstituted system

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    Loss-of-function mutations in PTEN-induced kinase 1 (PINK1) are a frequent cause of early-onset Parkinson's disease (PD). Stabilization of PINK1 at the translocase of outer membrane (TOM) complex of damaged mitochondria is critical for its activation. The mechanism of how PINK1 is activated in the TOM complex is unclear. Here, we report that co-expression of human PINK1 and all seven TOM subunits in Saccharomyces cerevisiae is sufficient for PINK1 activation. We use this reconstitution system to systematically assess the role of each TOM subunit toward PINK1 activation. We unambiguously demonstrate that the TOM20 and TOM70 receptor subunits are required for optimal PINK1 activation and map their sites of interaction with PINK1 using AlphaFold structural modeling and mutagenesis. We also demonstrate an essential role of the pore-containing subunit TOM40 and its structurally associated subunits TOM7 and TOM22 for PINK1 activation. These findings will aid in the development of small-molecule activators of PINK1 as a therapeutic strategy for PD.</p

    Mechanism of human PINK1 activation at the TOM complex in a reconstituted system

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    Loss-of-function mutations in PTEN-induced kinase 1 (PINK1) are a frequent cause of early-onset Parkinson's disease (PD). Stabilization of PINK1 at the translocase of outer membrane (TOM) complex of damaged mitochondria is critical for its activation. The mechanism of how PINK1 is activated in the TOM complex is unclear. Here, we report that co-expression of human PINK1 and all seven TOM subunits in Saccharomyces cerevisiae is sufficient for PINK1 activation. We use this reconstitution system to systematically assess the role of each TOM subunit toward PINK1 activation. We unambiguously demonstrate that the TOM20 and TOM70 receptor subunits are required for optimal PINK1 activation and map their sites of interaction with PINK1 using AlphaFold structural modeling and mutagenesis. We also demonstrate an essential role of the pore-containing subunit TOM40 and its structurally associated subunits TOM7 and TOM22 for PINK1 activation. These findings will aid in the development of small-molecule activators of PINK1 as a therapeutic strategy for PD.</p

    Mechanism of human PINK1 activation at the TOM complex by reconstitution

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    Loss of function mutations in PTEN-induced kinase 1 (PINK1) are a frequent cause of earlyonset Parkinson’s disease (PD). Stabilisation of PINK1 at the Translocase of Outer Membrane (TOM) complex of damaged mitochondria is a critical step for its activation. To date the mechanism of how PINK1 is activated in the TOM complex is unclear. Herein we report coexpression of human PINK1 and all seven TOM subunits in Saccharomyces cerevisiae is sufficient for PINK1 activation. We use this reconstitution system to systematically assess the role of each TOM subunit towards PINK1 activation. We unambiguously demonstrate that the TOM20 and TOM70 receptor subunits are required for optimal PINK1 activation and map their sites of interaction with PINK1 using AlphaFold structural modelling and mutagenesis. We also demonstrate an essential role of the pore-containing subunit TOM40 and its structurally associated subunits TOM7 and TOM22 for PINK1 activation. These molecular findings will aid in the development of small molecule activators of PINK1 as a therapeutic strategy for PD

    Mechanism of human PINK1 activation at the TOM complex by reconstitution

    Get PDF
    Loss of function mutations in PTEN-induced kinase 1 (PINK1) are a frequent cause of earlyonset Parkinson’s disease (PD). Stabilisation of PINK1 at the Translocase of Outer Membrane (TOM) complex of damaged mitochondria is a critical step for its activation. To date the mechanism of how PINK1 is activated in the TOM complex is unclear. Herein we report coexpression of human PINK1 and all seven TOM subunits in Saccharomyces cerevisiae is sufficient for PINK1 activation. We use this reconstitution system to systematically assess the role of each TOM subunit towards PINK1 activation. We unambiguously demonstrate that the TOM20 and TOM70 receptor subunits are required for optimal PINK1 activation and map their sites of interaction with PINK1 using AlphaFold structural modelling and mutagenesis. We also demonstrate an essential role of the pore-containing subunit TOM40 and its structurally associated subunits TOM7 and TOM22 for PINK1 activation. These molecular findings will aid in the development of small molecule activators of PINK1 as a therapeutic strategy for PD
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