201 research outputs found

    Alien Registration- Inman, George H. (Mapleton, Aroostook County)

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    https://digitalmaine.com/alien_docs/34134/thumbnail.jp

    The Effectiveness of the Response and Follow Up Processes to the Learndirect ‘Gremlins’ Campaign in the Nottingham Area

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    In the late 1990s the Government concluded that poor adult literacy and numeracy were having an effect on the United Kingdom’s competitiveness. Consequently, in 1999, Claus Moser was asked to undertake a review and make recommendations as to how greater numbers of disadvantaged adults might be encouraged to seek advice and start learning. Moser’s findings stimulated the Government to develop and launch the Skills for Life Strategy out of which came the Learndirect ‘Gremlins’ Campaign, a flagship awareness raising programme. The researcher set out to develop a body of knowledge related to participation in learning, to find out more about callers to the Learndirect Helpline, and to draw conclusions about the effectiveness of the publicly funded support services such as the Information, Advice & Guidance Service and providers of learning. Out of a cohort of 360 callers, 165 agreed to take part in a telephone interview, and 52 said they had taken up a learning opportunity; however, only 27 were found to have taken up Learning & Skills Council ( LSC ) funded programmes leaving the researcher to conclude that the remaining 25 had either taken up programmes funded by Jobcentre Plus, started to learn informally, or were uncomfortable in admitting that they hadn’t started learning. Perhaps the most striking finding from the research was that the majority of respondents who chose not to take up learning were keen to stay involved. Also it was found that adults living in disadvantaged communities were significantly less likely to take up LSC funded learning opportunities; but, with additional support, learners from those communities had the potential to perform better than those from other areas. Of those who went into learning a lower percentage than the Nottinghamshire average was employed full - time, a higher percentage was employed part - time and a higher percentage was economically inactive. More were in lower order occupations, with a bias towards personal service occupations. The Government responded to Moser’s findings by setting challenging targets; however, although the targets have been exceeded, there is a significant difference in performance between 16 to 19 year olds re – taking GCSEs in English and Mathematics, and adults, aged 20 +, taking literacy and / or numeracy qualifications. During the 2004 academic year 46% of the former achieved their learning aim, but only 20% of the latter, suggesting that a renewed focus is needed on adults, especially the hard to reach living in disadvantaged communities. It is recommended, therefore, that there should be a drive for greater consistency in the quality of information, advice & guidance and learning provision, and a more coherent network of high quality community based provision with enhanced levels of support provided by Information, Advice & Guidance Partnerships

    Perfused multiwell plate for 3D liver tissue engineering

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    In vitro models that capture the complexity of in vivo tissue and organ behaviors in a scalable and easy-to-use format are desirable for drug discovery. To address this, we have developed a bioreactor that fosters maintenance of 3D tissue cultures under constant perfusion and we have integrated multiple bioreactors into an array in a multiwell plate format. All bioreactors are fluidically isolated from each other. Each bioreactor in the array contains a scaffold that supports formation of hundreds of 3D microscale tissue units. The tissue units are perfused with cell culture medium circulated within the bioreactor by integrated pneumatic diaphragm micropumps. Electronic controls for the pumps are kept outside the incubator and connected to the perfused multiwell by pneumatic lines. The docking design and open-well bioreactor layout make handling perfused multiwell plates similar to using standard multiwell tissue culture plates. A model of oxygen consumption and transport in the circulating culture medium was used to predict appropriate operating parameters for primary liver cultures. Oxygen concentrations at key locations in the system were then measured as a function of flow rate and time after initiation of culture to determine oxygen consumption rates. After seven days of culture, tissue formed from cells seeded in the perfused multiwell reactor remained functionally viable as assessed by immunostaining for hepatocyte and liver sinusoidal endothelial cell (LSEC) phenotypic markers.National Institute of Environmental Health Sciences (grant number 5P30ES002109-30)National Institutes of Health (U.S.) (NIH grant number 5R01ES015241)DuPont MIT AlliancePfizer Inc.National Science Foundation (U.S.) (NSF grant number EEC-9843342

    Sarilumab for the treatment of ankylosing spondylitis: results of a Phase II, randomised, double-blind, placebo-controlled study (ALIGN)

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    OBJECTIVES: The ALIGN study (NCT01061723) evaluated the efficacy and safety of sarilumab, the first fully human monoclonal antibody against interleukin-6 receptor-alpha (IL-6Ralpha), in patients with ankylosing spondylitis (AS). METHODS: Patients with active AS despite conventional treatment were randomised to placebo, or one of five subcutaneous dose regimens of sarilumab (100, 150 or 200 mg every other week, or 100 or 150 mg every week), for 12 weeks. The primary efficacy end point was the percentage of patients achieving the Axial SpondyloArthritis international Society (ASAS) 20 response criteria at week 12. Secondary endpoints included ASAS40 response, ASAS partial remission, AS Disease Activity Score, high-sensitivity C-reactive protein (hs-CRP) value, and safety. RESULTS: Baseline demographic and disease characteristics of the 301 patients enrolled were similar across treatment groups. At week 12, there was no statistically significant difference in ASAS20 response rate between placebo (ASAS20 = 24.0%) and any sarilumab dose group. A significantly greater reduction in hs-CRP value was achieved with the higher sarilumab doses versus placebo. No other statistically significant differences were evident for secondary efficacy endpoints.The most common treatment-emergent adverse events reported for sarilumab included infections (non-serious), neutropenia, and increase in alanine aminotransferase. No cases of tuberculosis, opportunistic, or fungal infections, or bowel perforations were reported. Seven patients experienced a treatment-emergent serious adverse event (all in sarilumab treatment groups). No deaths occurred. CONCLUSIONS: The ALIGN study shows that IL-6Ralpha blockade with sarilumab was not an effective treatment for AS. Sarilumab was generally well tolerated with a manageable safety profile

    Aberrant axial mineralization precedes spinal ankylosis: a molecular imaging study in ank/ank mice

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    Abstract Introduction The diagnosis of ankylosing spondylitis is made from a combination of clinical features and the presence of radiographic evidence that may be detected only after many years of inflammatory back pain. It is not uncommon to have a diagnosis confirmed 5 to 10 years after the initial onset of symptoms. Development of a more-sensitive molecular imaging technology to detect structural changes in the joints would lead to earlier diagnosis and quantitative tracking of ankylosis progression. Progressive ankylosis (ank/ank) mice have a loss of function in the Ank gene, which codes for a regulator of PPi transport. In this study, we used these ank/ank mutant mice to assess a noninvasive, quantitative measure of joint ankylosis with near-infrared (NIR) molecular imaging in vivo. Methods Three age groups (8, 12, and 18 weeks) of ank/ank (15 mice) and wild-type littermates (12 +/+ mice) were assessed histologically and radiographically. Before imaging, OsteoSense 750 (bisphosphonate pamidronate) was injected i.v. Whole-body images were analyzed by using the multispectral Maestro imaging system. Results OsteoSense 750 signals in the paw joints were higher in ank/ank mice in all three age groups compared with controls. In the spine, significantly higher OsteoSense 750 signals were detected early, in 8-week-old ank/ank mice compared with controls, although minimal radiographic differences were noted at this time point. The molecular imaging changes in the ank/ank spine (8 weeks) were supported by histologic changes, including calcium apatite crystals at the edge of the vertebral bodies and new syndesmophyte formation. Conclusions Changes in joint pathology of ank/ank mice, as evaluated by histologic and radiographic means, are qualitative, but only semiquantitative. In contrast, molecular imaging provides a quantitative assessment. Ankylosis in ank/ank mice developed simultaneously in distal and axial joints, contrary to the previous notion that it is a centripetal process. NIR imaging might be feasible for early disease diagnosis and for monitoring disease progression in ankylosing spondylitis

    Transplanting cells from old but not young donors causes physical dysfunction in older recipients.

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    Adipose-derived mesenchymal stem cell (ADSC)-based regenerative therapies have shown potential for use in many chronic diseases. Aging diminishes stem cell regenerative potential, yet it is unknown whether stem cells from aged donors cause adverse effects in recipients. ADSCs can be obtained using minimally invasive approaches and possess low immunogenicity. Nevertheless, we found that transplanting ADSCs from old donors, but not those from young donors, induces physical dysfunction in older recipient mice. Using single-cell transcriptomic analysis, we identified a naturally occurring senescent cell-like population in ADSCs primarily from old donors that resembles in vitro-generated senescent cells with regard to a number of key pathways. Our study reveals a previously unrecognized health concern due to ADSCs from old donors and lays the foundation for a new avenue of research to devise interventions to reduce harmful effects of ADSCs from old donors

    Transforming growth factor- directly induces p53-up-regulated modulator of apoptosis (PUMA) during the rapid induction of apoptosis in myc-driven B-cell lymphomas

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    Background: TGF-β induces apoptosis in Burkitt's lymphoma cells. Results: PUMA is a direct target gene of TGF-β signaling and is required for rapid apoptosis. Conclusion: TGF-β-mediated direct induction of PUMA contributes to apoptosis in human and murine c-Myc-driven lymphomas. Significance: These studies link TGF-β signaling and transcriptional activation of PUMA, two factors with critical roles in regulating B-cell survival

    Tetranuclear Zn/4f coordination clusters as highly efficient catalysts for Friedel-Crafts alkylation

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    A series of custom-designed, high yield, isoskeletal tetranuclear Zn/4f coordination clusters showing high efficiency as catalysts with low catalytic loadings in Friedel-Crafts alkylation are described for the first time. The possibility of altering the 4f centers in these catalysts without altering the core topology allows us to further confirm their stability via EPR and NMR, as well to gain insights into the plausible reaction mechanism, showcasing the usefulness of these bimetallic systems as catalysts
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