10,956 research outputs found

    The effect of 1 to 5 keV electrons on the reproductive integrity of microorganisms

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    Microorganisms were exposed to simulated space environment in order to assess the effect of electrons in the energy range 1 to 5 keV on their colony-forming ability. The test system consisted of an electron gun and power supply, a dosimetry subsystem, and a vacuum subsystem. The system was capable of current densities ranging from 0.1 nA/sq cm to 5 micro A/sq cm on a 25 sq on target and an ultimate vacuum of 0.0006 N/sq m (0.000004 torr). The results of the experimental program show a significant reduction in microbial reproductive integrity

    The Loudest Event Statistic: General Formulation, Properties and Applications

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    The use of the loudest observed event to generate statistical statements about rate and strength has become standard in searches for gravitational waves from compact binaries and pulsars. The Bayesian formulation of the method is generalized in this paper to allow for uncertainties both in the background estimate and in the properties of the population being constrained. The method is also extended to allow rate interval construction. Finally, it is shown how to combine the results from multiple experiments and a comparison is drawn between the upper limit obtained in a single search and the upper limit obtained by combining the results of two experiments each of half the original duration. To illustrate this, we look at an example case, motivated by the search for gravitational waves from binary inspiral.Comment: 11 pages, 8 figure

    Influence of training history and contraction velocity on hamstring muscle coactivation during maximal effort knee extension

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    When a muscle produces voluntary force, muscles on the opposite side of the joint, the antagonists, are also activated. While coactivation of the knee flexors during knee extension is presumed to increase joint stability by decreasing anterior shear force of the tibia on the femur, the coactivation of the hamstrings also produces what is called the antagonist torque. Systematic exercise in the form of resistance training can reduce antagonist muscle coactivation in healthy young adults. However, the mechanical consequence of this neurological adaptation is unclear. We thus hypothesized that previously strength-trained individuals would exhibit less antagonist coactivation, resulting in a reduced antagonist torque, and that with an increase in contraction speed there would be an increase in antagonist coactivation to slow the movement but there would be less of an increase due to speed in the trained compared with untrained individuals. Therefore, the purpose of this study was to determine the effects of training status on coactivation, i.e., antagonist torque, and on the speed-sensitivity of coactivation. Subjects for this study were fitted with surface EMG electrodes on their thigh muscles, and performed maximal effort knee extensions on a dynamometer, using shortening (concentric) and lengthening (eccentric) contractions at 30, 90, and 150°/s. As expected, trained individuals produced ~44% less coactivation at all contractions speeds. Against the hypothesis, coactivation did not increase in either group as velocity increased, as there was less than 10% difference in coactivation levels between the 3 speeds. Also against the hypothesis, as determined with an EMG-driven mathematical model, antagonist torque did not decrease with decreasing coactivation; in fact we see a trend towards the opposite for trained individuals. A borderline greater antagonist torque was noted in the trained compared to the untrained subjects even with decreased coactivation of the trained. These data suggest that antagonist muscle coactivation is less in trained healthy young adults but this reduced neural activation does not manifest itself in lower levels of antagonist torque. Therefore, leg strength training may increase muscle strength in part by reducing antagonist muscle coactivation without compromising joint stability.  M.S

    Roman Banditry: Scorning Senatorial Skullduggery in Sallust

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    A Longitudinal Study on the Drivers of Forestation

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    This paper studies the effects of population growth, income levels, and governance on forestation using longitudinal data covering 161 countries from 1996-2015. The study begins with a review of the empirical literature on deforestation and preservation of environmental quality. Then, we conduct our own empirical analysis through log differencing and analysis of annual percentage changes in forest area. We find evidence that these factors matter, but that the relationships are weak. The estimated effects do differ between our groupings of countries with regard to income levels as well as forest area sizes. Population growth generally leads to a reduction in forest area. Conversely, rising incomes slow deforestation and increase the chances of reforestation and afforestation. We witness the disappearance of a Kuznets curve relationship across all groups after individual country effects are included. A bettering of perceived rule of law, political stability, and reduction in corruption is also correlated with more positive forestation rates

    Recent changes to the Federal Reserve's survey of terms of business lending

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    The Federal Reserve's quarterly Survey of Terms of Business Lending, which has been conducted for more than twenty years, collects information on interest rates and other characteristics of commercial bank business loans. The survey has been changed from time to time to recognize innovations in bank lending practices and to improve the measurement of the desired information. The most recent changes took effect with the May 1997 survey. The major improvement was the addition of an item measuring loan risk. In addition, the reporting panel, which had been limited to domestically chartered commercial banks was expanded to include a sample of U.S. branches and agencies of foreign banks, which now account for a significant proportion of business lending to U.S. firms. This article discusses the most recent changes made to the survey and presents some information now available from the new items being reported. It also summarizes information about the use of loan risk ratings from consultations conducted with a sample of the survey respondents during the process of planning the revisions to the survey.Commercial loans

    The effects of recent mortgage refinancing

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    Rising home prices and generally falling interest rates in recent years, together with a desire to convert the accumulated equity in their homes into spendable funds, have prompted many homeowners to refinance their mortgages. In the spring of 1999, the Federal Reserve surveyed consumers to determine the extent of refinancing, the extent to which refinancing homeowners "cashed-out" some of their equity when they refinanced, how much equity they took out, and how they spent the funds. Survey results suggest that cash-out refinancings in 1998 and early 1999 likely boosted consumption spending a bit, may have had a larger effect on home improvement spending, and may have moderated the growth of consumer credit during that period.Mortgages ; Housing - Finance ; Interest rates

    The servant saint : Zita of Lucca and Sitha of England (1278-1550)

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    Dissertação de mestrado em Biotecnologia Farmacêutica, apresentada à Faculdade de Farmácia da Universidade de CoimbraO glioblastoma é o tipo de tumor cerebral mais comum e agressivo, caraterizando-se por alta capacidade proliferativa, elevados níveis de angiogénese e grande resistência à quimioterapia. O tratamento médico habitual envolve a remoção do tecido tumoral através de cirurgia, seguida de radioterapia com concomitante ou subsequente administração do agente alquilante temozolomida (TMZ). No entanto, a evolução clínica está longe de ser satisfatória, sendo a taxa de sobrevivência média dos doentes de apenas 15 meses após o diagnóstico. Tendo em consideração que a maior causa de insucesso do tratamento desta patologia reside na resistência intrínseca e adquirida aos fármacos, este trabalho teve por principal objectivo o desenvolvimento de estratégias terapêuticas capazes de sensibilizar as células de GBM a agentes quimioterapêuticos. Com este propósito, foram implementadas duas estratégias de terapia génica não-viral, envolvendo o uso de tensioativos gemini catiónicos (CGS) e explorando o seu potencial para a vectorização de ácidos nucleicos e fármacos. Numa das estratégias foram utilizados CGS como vectores de siRNAs em células humanas de glioblastoma (U87), a fim de diminuir a expressão da proteína anti-apoptótica survivina, sobre-expressa em tecidos tumorais, e aumentar, consequentemente, a susceptibilidade das células a agentes quimioterapêuticos. A segunda estratégia usufruiu da vantagem dos GSC promoverem a transferência de pDNA tanto para o núcleo como para as mitocôndrias de células de uma linha de glioblastoma estabelecida a partir de um tumor recorrente (DBTRG-05MG), e explorou a capacidade desses mesmos sistemas de entrega induzirem a libertação, em ambos os organelos, do fármaco anticancerígeno cisplatina (CDDP), cuja ação farmacológica envolve a formação de aductos com moléculas de DNA. Neste trabalho ficou patente que a redução da expressão de survivina potencia sinergisticamente a acção tóxica dos compostos TMZ e etopósido nas células U87. Por outro lado, a exposição de células DBTRG-05MG a CDDP incorporada em complexos de pDNA e tensioativos gemini derivados de serina conduziu a uma diminuição drástica da viabilidade e da proliferação das células, bem como à paragem do ciclo celular na fase S, efeitos que mostraram ser mais severos do que os induzidos por CDDP na forma livre, na mesma concentração. Adicionalmente, o pDNA usado como veículo de CDDP, complexado com tensioativos gemini, demonstrou não ter perdido a capacidade de promover expressão génica, quando transferido para o núcleo ou para a mitocôndria. Desta forma, as estratégias implementadas neste estudo revelaram a possibilidade de reduzir as doses terapêuticas de fármacos anticancerígenos, contribuindo para prevenir o desenvolvimento de quimiorresistência e obviar efeitos colaterais dos fármacos. Além disso, demonstrando a versatilidade e o elevado potencial das formulações contendo tensioativos gemini para a 5 vectorização de ácidos nucleicos e fármacos em células de GBM, este estudo abre caminho a abordagens terapêuticas multi-modais que, aliando a quimioterapia à terapia génica, permitem vencer com elevada eficiência a quimiorresistência de GBMGlioblastoma (GBM) is the most common and aggressive primary brain tumor, being characterized by its propensity for proliferation, strong angiogenesis and resistance to chemotherapy. The standard treatment involves maximal surgical resection, radiotherapy and adjuvant or concomitant administration of the alkylating drug temozolomide (TMZ). However, the clinical outcome has proven to be far from being satisfactory, patients having a median survival of only 15 months after diagnosis. Taking into account that the major cause of treatment failure in GBM patients is the intrinsic and acquired drug resistance, the objective of the present work was centered in the development of therapeutic strategies aiming at sensitizing GBM cells to chemotherapeutics. To accomplish this objective, two gene therapy-based approaches were developed, involving the use of cationic gemini surfactants (CGS) and exploiting their potential for drug delivery. The first strategy took advantage of the ability of CGS to deliver siRNA, in order to promote downregulation of the anti-apoptotic protein survivin, aberrantly expressed in tumor tissues, so that GBM cells (U87) become more susceptible to chemotherapeutics. The second strategy benefited from the potential of GCS to deliver pDNA into nucleus and mitochondria in human recurrent glioblastoma cells (DBTRG-05MG), exploring their capacity to promote in both organelles a co-delivery of the anti-cancer drug cisplatin (CDDP), whose pharmacological activity is based on the formation of adducts with DNA molecules. Significant results were obtained showing that survivin knockdown combined with temozolomide or etoposide administration resulted in a synergistic toxic effect on U87 cells. Additionally, the delivery of CDDP formulated in serine-derived gemini surfactant-based complexes led to a drastic decrease of viability of DBTRG-05MG cells, an efficient inhibition of cell growth and a significant arrest of the cell cycle in the S phase, effects that showed to be much more severe than those induced by free CDDP, at the same concentrations. Moreover, it was observed that the pDNA, used as a vehicle of CDDP formulated in gemini surfactant-based complexes, did not lose its capacity to promote gene expression, when delivered both in the nucleus and in mitochondria. Therefore, both strategies implemented in this study revealed the possibility of reducing the doses of anti-cancer drugs to prevent the emergence of chemoresistance and drug side-effects. Additionally, benefiting from the versatility and potential of gemini surfactant-based formulations for drug delivery in GBM cells, this study opens windows towards the establishment of multimodal therapeutic approaches, allying chemotherapeutics to gene therapy, aiming at surpassing the chemoresistance of GBM

    Punishment for Negligence: A Reply to Professor Hall

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