155 research outputs found

    PHAR 553.01: Therapeutics III

    Get PDF

    PHAR 595.01: Therapeutics III

    Get PDF

    PHAR 552.01: Therapeutics III

    Get PDF

    SLR Station Recovery, Center of Frame Motion, and Time Varying Gravity

    Get PDF
    Weekly station position estimates, beginning with 1993, are derived from the ITRF2008-based SLR processing of up to four satellites: Lageos 1, Lageos2, Starlette, and Stella. Helmert parameters obtained from c omparison of weekly SLR station positions and the a-priori SLRF2008 station complement are evaluated for geocenter motion and scale. Two me thods for modeling time varying gravity are employed in the SLR satel lite POD processing, with GGM03S serving as the static gravity field. Both methods forward model atmosphere gravity derived from 6-hour ECM WF pressure data. The standard approach applies an annual 20x20 field estimated from 4 years of GRACE data, and the IERS2003 recommended linear rates for C20, C30, C40, C21, and S21. The alternate approach us es a new set of low-order/degree 4x4 coefficients estimated weekly fr om SLR & DORIS processing to 10 satellites from 1993-2012. This exper imental tvg4x4 model has been shown to improve the TOPEX, Jason-1, and Jason-2 altimeter satellite orbits,. In this paper we apply the more detailed time-variable gravity modeling to the SLR satellite POD pro cessing and subsequent reference frame analyses. For this study we will evaluate the orbit differences (periodic and secular) for the satel lites concerned, characterize the impact on the station coordinate solutions, and the impact on reference frame parameters (geocenter and s cale)

    A mouse model for MERS coronavirus-induced acute respiratory distress syndrome

    Get PDF
    Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel virus that emerged in 2012, causing acute respiratory distress syndrome (ARDS), severe pneumonia-like symptoms, and multi-organ failure, with a case fatality rate of ~36%. Limited clinical studies indicate that humans infected with MERS-CoV exhibited pathology consistent with late stages of ARDS, which is reminiscent of disease observed in patients infected with SARS coronavirus. Models of MERS-CoV-induced severe respiratory disease have been difficult to achieve, and small animal models traditionally used to investigate viral pathogenesis (mouse, hamster, guinea pig, and ferret) are naturally resistant to MERS-CoV. Therefore, we used CRISPR/Cas9 to modify the mouse genome to encode two human amino acids (288 and 330) in the dipeptidyl peptidase 4 receptor, making mice susceptible to MERS-CoV replication. Serial MERS-CoV passage in these engineered mice was then used to generate a mouse-adapted virus that replicated efficiently within the lungs, and evoked symptoms indicative of severe acute respiratory distress syndrome (ARDS), including decreased survival, extreme weight loss, decreased pulmonary function, pulmonary hemorrhage, and pathological signs indicative of end stage lung disease. Importantly, therapeutic countermeasures comprising MERS-CoV neutralizing antibody treatment or a MERS-CoV spike protein vaccine protected engineered mice against MERS-CoV-induced ARDS

    Thoughts on Poverty from a South Asian Rubbish Dump:

    Get PDF
    Summaries The author reflects on the interlocking circuits of accumulation and consumption that characterise the management of household solid waste or garbage in two South Asian cities. She examines the multiple axes of inequality and interdependence that characterise the social relations of residential waste work. Interactions are explored among household members, and between them and paid waste workers such as domestic workers, sweepers and pickers. The article challenges gender stereotypes of women having a special affinity with the environment, at least in the context of the urban environment and solid waste management. It also rejects any essentialist linking of particular social groups to waste and dirty work, arguing that in the case of both gender and caste relations, association with waste is socially constructed. It is argued that women's responsibility for waste management in the household gender division of labour is mediated by both wealth and poverty. Equally, that particular groups of waste workers have occupational niches in different areas of waste work is mediated by gender and caste?like relations. A case is made for recognising the micro?politics of household and residential solid waste management in policy formulation and planning. The article proposes that this has implications both for effective waste management and for policies concerned to integrate anti?poverty strategies in efforts to improve the managment of urban services

    Vertebral Augmentation: Is It Time to Get Past the Pain? A Consensus Statement from the Sardinia Spine and Stroke Congress

    Get PDF
    Vertebral augmentation has been used to treat painful vertebral compression fractures and metastatic lesions in millions of patients around the world. An international group of subject matter experts have considered the evidence, including but not limited to mortality. These considerations led them to ask whether it is appropriate to allow the subjective measure of pain to so dominate the clinical decision of whether to proceed with augmentation. The discussions that ensued are related below

    MERS-CoV Accessory ORFs Play Key Role for Infection and Pathogenesis

    Get PDF
    ABSTRACT While dispensable for viral replication, coronavirus (CoV) accessory open reading frame (ORF) proteins often play critical roles during infection and pathogenesis. Utilizing a previously generated mutant, we demonstrate that the absence of all four Middle East respiratory syndrome CoV (MERS-CoV) accessory ORFs (deletion of ORF3, -4a, -4b, and -5 [dORF3-5]) has major implications for viral replication and pathogenesis. Importantly, attenuation of the dORF3-5 mutant is primarily driven by dysregulated host responses, including disrupted cell processes, augmented interferon (IFN) pathway activation, and robust inflammation. In vitro replication attenuation also extends to in vivo models, allowing use of dORF3-5 as a live attenuated vaccine platform. Finally, examination of ORF5 implicates a partial role in modulation of NF-κB-mediated inflammation. Together, the results demonstrate the importance of MERS-CoV accessory ORFs for pathogenesis and highlight them as potential targets for surveillance and therapeutic treatments moving forward. IMPORTANCE The initial emergence and periodic outbreaks of MERS-CoV highlight a continuing threat posed by zoonotic pathogens to global public health. In these studies, mutant virus generation demonstrates the necessity of accessory ORFs in regard to MERS-CoV infection and pathogenesis. With this in mind, accessory ORF functions can be targeted for both therapeutic and vaccine treatments in response to MERS-CoV and related group 2C coronaviruses. In addition, disruption of accessory ORFs in parallel may offer a rapid response platform to attenuation of future emergent strains based on both SARS- and MERS-CoV accessory ORF mutants
    • …
    corecore