157 research outputs found

    Livelyhoods Partnership Evaluation Toolkit

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    These partnership evaluations provide LivelyHoods with an assessment of its current partnerships throughout Tanzania and Uganda. These assessments include a SWOT analysis of business and impact models to determine potential synergies and opportunities in LivelyHoods’ current and future partners

    As a Matter of Impact: Scaling Livelyhoods

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    This scaling toolkit analyzes critical success factors for LivelyHoods’ expansion both domestically and internationally. These factors are analyzed in tandem with a menu of business strategies LivelyHoods can implement to facilitate the scaling of the enterprise. The business strategy menu will include a matrix and explanations to optimize revenue streams and reduce costs of LivelyHoods’ operations

    The excitation cascade of Limulus ventral photoreceptors: guanylate cyclase as the link between InsP(3)-mediated Ca(2+ )release and the opening of cGMP-gated channels

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    BACKGROUND: Early stages in the excitation cascade of Limulus photoreceptors are mediated by activation of G(q )by rhodopsin, generation of inositol-1,4,5-trisphosphate by phospholipase-C and the release of Ca(2+). At the end of the cascade, cGMP-gated channels open and generate the depolarizing receptor potential. A major unresolved issue is the intermediate process by which Ca(2+ )elevation leads to channel opening. RESULTS: To explore the role of guanylate cyclase (GC) as a potential intermediate, we used the GC inhibitor guanosine 5'-tetraphosphate (GtetP). Its specificity in vivo was supported by its ability to reduce the depolarization produced by the phosphodiesterase inhibitor IBMX. To determine if GC acts subsequent to InsP(3 )production in the cascade, we examined the effect of intracellular injection of GtetP on the excitation caused by InsP(3 )injection. This form of excitation and the response to light were both greatly reduced by GtetP, and they recovered in parallel. Similarly, GtetP reduced the excitation caused by intracellular injection of Ca(2+). In contrast, this GC inhibitor did not affect the excitation produced by injection of a cGMP analog. CONCLUSION: We conclude that GC is downstream of InsP3-induced Ca2+ release and is the final enzymatic step of the excitation cascade. This is the first invertebrate rhabdomeric photoreceptor for which transduction can be traced from rhodopsin photoisomerization to ion channel opening

    BAY 81-8973, a full-length recombinant factor VIII: Human heat shock protein 70 improves the manufacturing process without affecting clinical safety

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    AbstractBAY 81-8973 is a full-length, unmodified recombinant human factor VIII (FVIII) approved for the treatment of hemophilia A. BAY 81-8973 has the same amino acid sequence as the currently marketed sucrose-formulated recombinant FVIII (rFVIII-FS) product and is produced using additional advanced manufacturing technologies. One of the key manufacturing advances for BAY 81-8973 is introduction of the gene for human heat shock protein 70 (HSP70) into the rFVIII-FS cell line. HSP70 facilitates proper folding of proteins, enhances cell survival by inhibiting apoptosis, and potentially impacts rFVIII glycosylation. HSP70 expression in the BAY 81-8973 cell line along with other manufacturing advances resulted in a higher-producing cell line and improvements in the pharmacokinetics of the final product as determined in clinical studies. HSP70 protein is not detected in the harvest or in the final BAY 81-8973 product. However, because this is a new process, clinical trial safety assessments included monitoring for anti-HSP70 antibodies. Most patients, across all age groups, had low levels of anti-HSP70 antibodies before exposure to the investigational product. During BAY 81-8973 treatment, 5% of patients had sporadic increases in anti-HSP70 antibody levels above a predefined threshold (cutoff value, 239 ng/mL). No clinical symptoms related to anti-HSP70 antibody development occurred. In conclusion, addition of HSP70 to the BAY 81-8973 cell line is an innovative technology for manufacturing rFVIII aimed at improving protein folding and expression. Improved pharmacokinetics and no effect on safety of BAY 81-8973 were observed in clinical trials in patients with hemophilia A

    The time variation of dose rate artificially increased by the Fukushima nuclear crisis

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    A car-borne survey for dose rate in air was carried out in March and April 2011 along an expressway passing northwest of the Fukushima Dai-ichi Nuclear Power Station which released radionuclides starting after the Great East Japan Earthquake on March 11, 2011, and in an area closer to the Fukushima NPS which is known to have been strongly affected. Dose rates along the expressway, i.e. relatively far from the power station were higher after than before March 11, in some places by several orders of magnitude, implying that there were some additional releases from Fukushima NPS. The maximum dose rate in air within the high level contamination area was 36 μGy h−1, and the estimated maximum cumulative external dose for evacuees who came from Namie Town to evacuation sites (e.g. Fukushima, Koriyama and Nihonmatsu Cities) was 68 mSv. The evacuation is justified from the viewpoint of radiation protection

    Assessment of aerosol radiation environment in short-range region of ChNPP during building of the new safe confinement

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    Variability of ¹³⁷Cs volume activity in a subsurface layer of the atmosphere of a short-range region of the object "Shelter" (object "Ukryttya") during the works on building of a new safety confinement in 2016 was investigated. Influence of the type and location of works, weather conditions, and sampling points was shown. Excess of medial permissible concentrations of ¹³⁷Cs in the air was not fixed during the observations. However, due to the averaging of the measured values of the volume activity for the exposure time of the filter and use of the stationary aerosol samplers, it cannot ensure the absence of excess of the permissible concentrations at the locations of works and on the propagation path of the local emission plumes. In 2016, as well as in 2013 - 2015, high levels of ¹³⁷Cs volume activity in the air were preferentially localized near to the machine hall of the 4th block and near to the places of ground works at the industrial site [ 1]. Concurrently the levels of volume activity essentially grew (practically by the order of magnitude) due to the intense works on the machine hall transformation. The conservative estimation of volume activity of isotopes of the plutonium, executed in the assumption of fuel composition of hot particles, showed the presence of substantial excess of permissible limits even for the average values within, at least, four weeks. Absence of reliable correlation (R = -0.09) of ¹³⁷Cs volume activity in the air near to the machine hall and near to the aerosol sampler 1,4 km remote from it testifies the localization of pollution within the industrial site.Досліджено мінливість об'ємної активності ¹³⁷Cs у приземному шарі атмосфери ближньої зони об'єкта «Укриття» під час проведення робіт зі спорудження нового безпечного конфайнмента у 2016 р. Продемонстровано вплив виду та місця проведення робіт, метеорологічних умов, а також місця відбору проб. За час спостережень не зафіксовано перевищення середніх допустимих концентрацій ¹³⁷Cs в повітрі. Однак унаслідок усереднення виміряних значень об'ємної активності за часом експозиції фільтра та використання стаціонарних пробовідбірників даний факт не може гарантувати відсутність перевищень у місцях проведення робіт і по шляху поширення факелів локальних викидів. У 2016 р., як і в 2013 - 2015 рр., високі рівні об'ємної активності ¹³⁷Cs в повітрі були переважно локалізовані поблизу машинного залу 4-го блока та біля місць проведення земляних робіт на промисловому майданчику [1]. При цьому самі рівні об'ємної активності істотно зросли (практично на порядок) у зв'язку з інтенсивними роботами по трансформації машинного залу. Консервативна оцінка об'ємної активності ізотопів плутонію, виконана у припущенні паливного складу гарячих частинок, показала наявність істотних перевищень допустимих рівнів навіть для усереднених величин, у крайньому випадку, протягом чотирьох тижнів. Відсутність достовірної кореляції об'ємної активності ¹³⁷Cs в повітрі поблизу машинного залу та біля віддаленого від нього на 1,4 км пробовідбірника (R = -0,09) свідчить про локалізацію забруднень у межах промислового майданчика.Исследована изменчивость объемной активности ¹³⁷Cs в приземном слое атмосферы ближней зоны объекта «Укрытие» во время проведения работ по сооружению нового безопасного конфайнмента в 2016 г. Продемонстрировано влияние вида и места проведения работ, метеорологических условий, а также места отбора проб. За время наблюдений не зафиксированы превышения средних допустимых концентраций ¹³⁷Cs в воздухе. Однако вследствие усреднения измеренных значений объемной активности по времени экспозиции фильтра и использования стационарных пробоотборников данный факт не может гарантировать отсутствие превышений в местах проведения работ и по пути распространения факелов локальных выбросов. В 2016 г., как и в 2013 – 2015 гг., высокие уровни объемной активности ¹³⁷Cs в воздухе были преимущественно локализованы вблизи машинного зала 4-го блока и около мест проведения земляных работ на промышленной площадке [1]. При этом сами уровни объемной активности существенно выросли (практически на порядок) в связи с интенсивными работами по преобразованию машинного зала. Консервативная оценка объемной активности изотопов плутония, выполненная в предположении топливного состава горячих частиц, показала наличие существенных превышений допустимых уровней даже для усредненных величин, по крайней мере, в течение четырех недель. Отсутствие достоверной корреляции объемной активности ¹³⁷Cs в воздухе возле машинного зала и возле удаленного от него на 1,4 км пробоотборника (R = -0,09) свидетельствует о локализации загрязнений в пределах промышленной площадки

    Threats of common method variance in student assessment of instruction instruments

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    Purpose – The purpose of this paper is to demonstrate that common method variance, specifically single-source bias, threatens the validity of a university-created student assessment of instructor instrument, suggesting that decisions made from these assessments are inherently flawed or skewed. Single-source bias leads to generalizations about assessments that might influence the ability of raters to separate multiple behaviors of an instructor. Design/methodology/approach – Exploratory factor analysis, nested confirmatory factor analysis and within-and-between analysis are used to assess a university-developed, proprietary student assessment of instructor instrument to determine whether a hypothesized factor structure is identifiable. The instrument was developed over a three-year period by a university-mandated committee. Findings – Findings suggest that common method variance, specifically single-source bias, resulted in the inability to identify hypothesized constructs statistically. Additional information is needed to identify valid instruments and an effective collection method for assessment. Practical implications – Institutions are not guaranteed valid or useful instruments even if they invest significant time and resources to produce one. Without accurate instrumentation, there is insufficient information to assess constructs for teaching excellence. More valid measurement criteria can result from using multiple methods, altering collection times and educating students to distinguish multiple traits and behaviors of individual instructors more accurately. Originality/value – This paper documents the three-year development of a university-wide student assessment of instructor instrument and carries development through to examining the psychometric properties and appropriateness of using this instrument to evaluate instructors

    Transcriptome Analysis of the Planarian Eye Identifies ovo as a Specific Regulator of Eye Regeneration

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    Among the millions of invertebrate species with visual systems, the genetic basis of eye development and function is well understood only in Drosophila melanogaster. We describe an eye transcriptome for the planarian Schmidtea mediterranea. Planarian photoreceptors expressed orthologs of genes required for phototransduction and microvillus structure in Drosophila and vertebrates, and optic pigment cells expressed solute transporters and melanin synthesis enzymes similar to those active in the vertebrate retinal pigment epithelium. Orthologs of several planarian eye genes, such as bestrophin-1 and Usher syndrome genes, cause eye defects in mammals when perturbed and were not previously described to have roles in invertebrate eyes. Five previously undescribed planarian eye transcription factors were required for normal eye formation during head regeneration. In particular, a conserved, transcription-factor-encoding ovo gene was expressed from the earliest stages of eye regeneration and was required for regeneration of all cell types of the eye.National Institutes of Health (U.S.) (NIH (R01GM08063)W. M. Keck Foundatio
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