Calcium/calmodulin-dependent kinase II and long-term potentiation enhance synaptic transmission by the same mechanism.

Ca(2+)-sensitive kinases are thought to play a role in long-term potentiation (LTP). To test the involvement of Ca2+/calmodulin-dependent kinase II (CaM-K II), truncated, constitutively active form of this kinase was directly injected into CA1 hippocampal pyramidal cells. Inclusion of CaM-K II in the recording pipette resulted in a gradual increase in the size of excitatory postsynaptic currents (EPSCs). No change in evoked responses occurred when the pipette contained heat-inactivated kinase. The effects of CaM-K II mimicked several features of LTP in that it caused a decreased incidence of synaptic failures, an increase in the size of spontaneous EPSCs, and an increase in the amplitude of responses to iontophoretically applied alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate. To determine whether the CaM-K II-induced enhancement and LTP share a common mechanism, occlusion experiments were carried out. The enhancing action of CaM-K II was greatly diminished by prior induction of LTP. In addition, following the increase in synaptic strength by CaM-K II, tetanic stimulation failed to evoke LTP. These findings indicate that CaM-K II alone is sufficient to augment synaptic strength and that this enhancement shares the same underlying mechanism as the enhancement observed with LTP.

Systemic gene therapy: biodistribution and long-term expression of a transgene in mice.

We have investigated the in vivo efficacy of a systemic gene transfer method, which combines a liposomal delivery system (DLS liposomes) with episomally replicative DNA plasmids to effect long-term expression of a transgene in cells. A single i.v. injection of a plasmid DNA vector containing the luciferase gene as a marker was administered with the DLS liposomes in BALB/c mice. The luciferase gene and its product were found in all mouse tissues tested as determined by PCR analysis and immunohistochemistry. Luciferase activity was also detected in all tissues tested and was present in lung, liver, spleen, and heart up to 3 months postinjection. In contrast to the nonepisomal vectors tested (pRSV-luc and pCMVintlux), human papovavirus (BKV)-derived episomal vectors showed long-term transgene expression. We found that these episomal vectors replicated extrachromosomally in lung 2 weeks postinjection. Results indicated that transgene expression in specific tissues depended on the promoter element used, DNA/liposome formulation, dose of DNA per injection, and route of administration.

Contribuições ao processo de inserção das PMES no mercado de capitais brasileiro

O crescimento de uma empresa pode ser apoiado com recursos de terceiros provenientes do mercado de crédito ou do mercado de capitais. Credores ou potenciais investidores disponibilizam recursos a partir de um processo de avaliação de indicadores de performance. Para as PMEs que consideram o crescimento, conhecer como os indicadores relevantes se comportam ao longo de um ciclo de crescimento é uma questão estratégica. Fatores como tamanho, lucratividade, oportunidades de crescimento, composição de ativos das empresas, risco inerente aos resultados, têm sido vinculados a determinantes de uma estrutura de capital. Assim sendo, este trabalho busca verificar quais indicadores podem nortear o desempenho empresarial de PMEs ao longo de um ciclo de crescimento. Como contribuição original, este trabalho apresenta um painel com indicadores em diferentes estágios de crescimento que resultam na geração de valor para os proprietários e potenciais investidores do mercado de capitais. A amostra inicial é composta por 1.610 empresas para o período de 2010 a 2014. Entretanto, considerando a disponibilidade de informações, a amostra final é composta por 28 empresas de porte médio/grande, 387 empresas grandes e 138 empresas listadas na BM&FBOVESPA, totalizando 553 empresas. A metodologia adotada envolve a classificação de porte de empresa do BNDES como critério para definir ciclo de crescimento, e testes de estatística descritiva, análise fatorial, análise de correlação, regressão múltipla linear e montagem de painel. Como resultado, verificou-se que as variáveis tamanho, composição de ativos e lucratividade são fatores que explicam o endividamento de curto prazo para o estágio médias/grandes empresas. Ainda, que esses fatores explicam o endividamento de longo prazo para os estágios grandes e empresas listadas na BM&FBOVESPA. Tais resultados estão de acordo com estudos prévios, mas as variáveis relacionadas a volatilidade e crescimento não foram significantes nos modelos para os estágios de empresas. O painel montado a partir das variáveis de composição de ativos e lucratividade indicou que endividamento de curto prazo, endividamento de longo prazo, receita líquida, retorno sobre o patrimônio líquido e lucros antes de juros, impostos, depreciação e amortização (EBITDA) sinalizam empresas, em cada estágio de ciclo de crescimento do estudo, que buscam o crescimento com rentabilidade acima da média e atendem a critérios valorizados pelo investidor do mercado de capitais. Estes indicadores podem sinalizar o desempenho empresarial de PMEs ao longo de um ciclo de crescimento

The Role of Hope in Rehabilitation and Long-term Outcomes among patients with Comorbid Spinal Cord and Traumatic Brain Injuries.

Spinal cord injury (SCI) and traumatic brain injury (TBI) are two potentially devastating conditions alone; when they co-occur in an individual they can be doubly so. The role of hope in rehabilitating oneself and recovering emotionally is examined in this paper. More specifically, Snyder's Model of Hope (1991) is examined as a tool that can aid in the rehabilitative process and help treatment providers, their patients, and the families of patients keep hope alive during a time of physical and emotional upheaval. This paper further examines the roles of hope in a rehabilitation program at Craig Hospital, a private, non-profit hospital dedicated exclusively to the rehabilitation of SCIs and TBIs and designated as a TBI and SCI Model Systems Center.

Dynamic bonding of metallic nanocontacts: Insights from experiments and atomistic simulations

The conductance across an atomically narrow metallic contact can be measured by using scanning tunneling microscopy. In certain situations, a jump in the conductance is observed right at the point of contact between the tip and the surface, which is known as “jump to contact” (JC). Such behavior provides a way to explore, at a fundamental level, how bonding between metallic atoms occurs dynamically. This phenomenon depends not only on the type of metal but also on the geometry of the two electrodes. For example, while some authors always find JC when approaching two atomically sharp tips of Cu, others find that a smooth transition occurs when approaching a Cu tip to an adatom on a flat surface of Cu. In an attempt to show that all these results are consistent, we make use of atomistic simulations; in particular, classical molecular dynamics together with density functional theory transport calculations to explore a number of possible scenarios. Simulations are performed for two different materials: Cu and Au in a [100] crystal orientation and at a temperature of 4.2 K. These simulations allow us to study the contribution of short- and long-range interactions to the process of bonding between metallic atoms, as well as to compare directly with experimental measurements of conductance, giving a plausible explanation for the different experimental observations. Moreover, we show a correlation between the cohesive energy of the metal, its Young's modulus, and the frequency of occurrence of a jump to contact.

Coast of Rhode Island, Connecticut and Long Island, New York, Nautical Chart, 1779 (Image 1 of 2) (Raster Image)

This layer is a georeferenced raster image of the untitled, historic nautical chart: [Coast of New England from Point Judith, Rhode Island, to Great Bay, Long Island] (sheet originally published in 1779). The map is [sheet 3] from the Atlantic Neptune atlas Vol. 3 : Charts of the coast and harbors of New England, from surveys taken by Samuel Holland and published by J.F.W. Des Barres, 1781. Scale [ca. 1:128,000]. This layer is image 1 of 2 total images of the two sheet source map, representing the western portion of the map. Covers portions of Long Island Sound and the coasts of Long Island, New York (including Gardiners Island and Plum Island) and Connecticut near New London. The image is georeferenced to the surface of the earth and fit to the 'World Mercator' (WGS 84) projected coordinate system. All map collar information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, or other information associated with the principal map. This map shows coastal features such as harbors, inlets, rocks, channels, points, coves, shoals, islands, and more. Includes also selected land features such as cities and towns. Relief is shown by hachures; depths by soundings and shading. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection. The entire Atlantic Neptune atlas Vol. 3 : Charts of the coast and harbors of New England has been scanned and georeferenced as part of this selection.

Coast of Rhode Island, Connecticut and Long Island, New York, Nautical Chart, 1779 (Image 2 of 2) (Raster Image)

This layer is a georeferenced raster image of the untitled, historic nautical chart: [Coast of New England from Point Judith, Rhode Island, to Great Bay, Long Island] (sheet originally published in 1779). The map is [sheet 4] from the Atlantic Neptune atlas Vol. 3 : Charts of the coast and harbors of New England, from surveys taken by Samuel Holland and published by J.F.W. Des Barres, 1781. Scale [ca. 1:128,000]. This layer is image 2 of 2 total images of the two sheet source map, representing the eastern portion of the map. Covers portions of Long Island Sound and the coasts of Long Island (Montauk Point), New York, Connecticut, and Rhode Island (including Block Island and Narragansett Bay). The image is georeferenced to the surface of the earth and fit to the 'World Mercator' (WGS 84) projected coordinate system. All map collar information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, or other information associated with the principal map. This map shows coastal features such as harbors, inlets, rocks, channels, points, coves, shoals, islands, and more. Includes also selected land features such as cities and towns. Relief is shown by hachures; depths by soundings and shading. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection. The entire Atlantic Neptune atlas Vol. 3 : Charts of the coast and harbors of New England has been scanned and georeferenced as part of this selection.