305 resultados para underscore
Resumo:
The performance of prediction models is often based on ``abstract metrics'' that estimate the model's ability to limit residual errors between the observed and predicted values. However, meaningful evaluation and selection of prediction models for end-user domains requires holistic and application-sensitive performance measures. Inspired by energy consumption prediction models used in the emerging ``big data'' domain of Smart Power Grids, we propose a suite of performance measures to rationally compare models along the dimensions of scale independence, reliability, volatility and cost. We include both application independent and dependent measures, the latter parameterized to allow customization by domain experts to fit their scenario. While our measures are generalizable to other domains, we offer an empirical analysis using real energy use data for three Smart Grid applications: planning, customer education and demand response, which are relevant for energy sustainability. Our results underscore the value of the proposed measures to offer a deeper insight into models' behavior and their impact on real applications, which benefit both data mining researchers and practitioners.
Resumo:
The bglA gene of Escherichia coli encodes phospho-beta-glucosidase A capable of hydrolyzing the plant-derived aromatic beta-glucoside arbutin. We report that the sequential accumulation of mutations in bglA can confer the ability to hydrolyze the related aromatic beta-glucosides esculin and salicin in two steps. In the first step, esculin hydrolysis is achieved through the acquisition of a four-nucleotide insertion within the promoter of the bglA gene, resulting in enhanced steady-state levels of the bglA transcript. In the second step, hydrolysis of salicin is achieved through the acquisition of a point mutation within the bglA structural gene close to the active site without the loss of the original catabolic activity against arbutin. These studies underscore the ability of microorganisms to evolve additional metabolic capabilities by mutational modification of preexisting genetic systems under selection pressure, thereby expanding their repertoire of utilizable substrates.
Resumo:
The genome of Leishmania major encodes a type II fatty acid biosynthesis pathway for which no structural or biochemical information exists. Here, for the first time, we have characterized the central player of the pathway, the acyl carrier protein (LmACP), using nuclear magnetic resonance (NMR). Structurally, the LmACP molecule is similar to other type II ACPs, comprising a four-helix bundle, enclosing a hydrophobic core. Dissimilarities in sequence, however, exist in helix II (recognition helix) of the protein. The enzymatic conversion of apo-LmACP into the holo form using type I (Escherichia coli AcpS) and type II (Sfp type) phosphopantetheinyl transferases (PPTs) is relatively slow. Mutagenesis studies underscore the importance of the residues present at the protein protein interaction interface of LmACP in modulating the activity of PPTs. Interestingly, the cognate PPT for this ACP, the L. major 4'-phosphopantetheinyl transferase (LmPPT), does not show any enzymatic activity toward it, though it readily converts other type I and type II ACPs into their holo forms. NMR chemical shift perturbation studies suggest a moderately tight complex between LmACP and its cognate PPT, suggesting inhibition. We surmise that the unique surface of LmACP might have evolved to complement its cognate enzyme (LmPPT), possibly for the purpose of regulation.
Resumo:
This paper studies the macroeconomic effects of a permanent increase in foreign aid in a model that takes into account environmental quality. We develop a dynamic equilibrium model in which both public investment in infrastructure and environmental protection can be financed using domestic resources and international aid programs. The framework considers four scenarios for international aid: untied aid,aid fully tied to infrastructure, aid fully tied to abatement, and aid equally tied to both types of expenditures. We find that the effects of the transfers may depend on (i) the structural characteristics of the recipient country (the elasticity of substitution in production and its dependence on environment and natural resources) and on (ii) how recipient countries distribute their public expenditure. These results underscore the importance of these factors when deciding how and to what extent to tie aid to infrastructure and/or pollution abatement.
Resumo:
Recently, the size dependence of mechanical behaviors, particularly the yield strength and plastic deformation mode, of bulk metallic glasses (BMG) has created a great deal of interest. Contradicting conclusions have been drawn by different research groups, based on various experiments on different BMG systems. Based on in situ compression transmission electron microscopy (TEM) experiments on Zr41Ti14Cu12.5Ni10Be22.5 (Vit 1) nanopillars, this paper provides strong evidence that shear banding still prevails at specimen length scales as small as 150 nm in diameter. This is supported by in situ and ex situ images of shear bands, and by the carefully recorded displacement bursts under load control its well as load drops under displacement control. Finite element modeling of the stress state within the pillar shows that the unavoidable geometry constraints accompanying such experiments impart a strong effect on the experimental results, including non-uniform stress distributions and high level hydrostatic pressures. The seemingly improved compressive ductility is believed to be due to such geometry constraints. Observations underscore the notion that the mechanical behavior of metallic glasses, including strength and plastic deformation mode, is size independent at least in Vit 1. (C) 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Resumo:
The epidemic of HIV/AIDS in the United States is constantly changing and evolving, starting from patient zero to now an estimated 650,000 to 900,000 Americans infected. The nature and course of HIV changed dramatically with the introduction of antiretrovirals. This discourse examines many different facets of HIV from the beginning where there wasn't any treatment for HIV until the present era of highly active antiretroviral therapy (HAART). By utilizing statistical analysis of clinical data, this paper examines where we were, where we are and projections as to where treatment of HIV/AIDS is headed.
Chapter Two describes the datasets that were used for the analyses. The primary database utilized was collected by myself from an outpatient HIV clinic. The data included dates from 1984 until the present. The second database was from the Multicenter AIDS Cohort Study (MACS) public dataset. The data from the MACS cover the time between 1984 and October 1992. Comparisons are made between both datasets.
Chapter Three discusses where we were. Before the first anti-HIV drugs (called antiretrovirals) were approved, there was no treatment to slow the progression of HIV. The first generation of antiretrovirals, reverse transcriptase inhibitors such as AZT (zidovudine), DDI (didanosine), DDC (zalcitabine), and D4T (stavudine) provided the first treatment for HIV. The first clinical trials showed that these antiretrovirals had a significant impact on increasing patient survival. The trials also showed that patients on these drugs had increased CD4+ T cell counts. Chapter Three examines the distributions of CD4 T cell counts. The results show that the estimated distributions of CD4 T cell counts are distinctly non-Gaussian. Thus distributional assumptions regarding CD4 T cell counts must be taken, into account when performing analyses with this marker. The results also show the estimated CD4 T cell distributions for each disease stage: asymptomatic, symptomatic and AIDS are non-Gaussian. Interestingly, the distribution of CD4 T cell counts for the asymptomatic period is significantly below that of the CD4 T cell distribution for the uninfected population suggesting that even in patients with no outward symptoms of HIV infection, there exists high levels of immunosuppression.
Chapter Four discusses where we are at present. HIV quickly grew resistant to reverse transcriptase inhibitors which were given sequentially as mono or dual therapy. As resistance grew, the positive effects of the reverse transcriptase inhibitors on CD4 T cell counts and survival dissipated. As the old era faded a new era characterized by a new class of drugs and new technology changed the way that we treat HIV-infected patients. Viral load assays were able to quantify the levels of HIV RNA in the blood. By quantifying the viral load, one now had a faster, more direct way to test antiretroviral regimen efficacy. Protease inhibitors, which attacked a different region of HIV than reverse transcriptase inhibitors, when used in combination with other antiretroviral agents were found to dramatically and significantly reduce the HIV RNA levels in the blood. Patients also experienced significant increases in CD4 T cell counts. For the first time in the epidemic, there was hope. It was hypothesized that with HAART, viral levels could be kept so low that the immune system as measured by CD4 T cell counts would be able to recover. If these viral levels could be kept low enough, it would be possible for the immune system to eradicate the virus. The hypothesis of immune reconstitution, that is bringing CD4 T cell counts up to levels seen in uninfected patients, is tested in Chapter Four. It was found that for these patients, there was not enough of a CD4 T cell increase to be consistent with the hypothesis of immune reconstitution.
In Chapter Five, the effectiveness of long-term HAART is analyzed. Survival analysis was conducted on 213 patients on long-term HAART. The primary endpoint was presence of an AIDS defining illness. A high level of clinical failure, or progression to an endpoint, was found.
Chapter Six yields insights into where we are going. New technology such as viral genotypic testing, that looks at the genetic structure of HIV and determines where mutations have occurred, has shown that HIV is capable of producing resistance mutations that confer multiple drug resistance. This section looks at resistance issues and speculates, ceterus parabis, where the state of HIV is going. This section first addresses viral genotype and the correlates of viral load and disease progression. A second analysis looks at patients who have failed their primary attempts at HAART and subsequent salvage therapy. It was found that salvage regimens, efforts to control viral replication through the administration of different combinations of antiretrovirals, were not effective in 90 percent of the population in controlling viral replication. Thus, primary attempts at therapy offer the best change of viral suppression and delay of disease progression. Documentation of transmission of drug-resistant virus suggests that the public health crisis of HIV is far from over. Drug resistant HIV can sustain the epidemic and hamper our efforts to treat HIV infection. The data presented suggest that the decrease in the morbidity and mortality due to HIV/AIDS is transient. Deaths due to HIV will increase and public health officials must prepare for this eventuality unless new treatments become available. These results also underscore the importance of the vaccine effort.
The final chapter looks at the economic issues related to HIV. The direct and indirect costs of treating HIV/AIDS are very high. For the first time in the epidemic, there exists treatment that can actually slow disease progression. The direct costs for HAART are estimated. It is estimated that the direct lifetime costs for treating each HIV infected patient with HAART is between $353,000 to $598,000 depending on how long HAART prolongs life. If one looks at the incremental cost per year of life saved it is only $101,000. This is comparable with the incremental costs per year of life saved from coronary artery bypass surgery.
Policy makers need to be aware that although HAART can delay disease progression, it is not a cure and HIV is not over. The results presented here suggest that the decreases in the morbidity and mortality due to HIV are transient. Policymakers need to be prepared for the eventual increase in AIDS incidence and mortality. Costs associated with HIV/AIDS are also projected to increase. The cost savings seen recently have been from the dramatic decreases in the incidence of AIDS defining opportunistic infections. As patients who have been on HAART the longest start to progress to AIDS, policymakers and insurance companies will find that the cost of treating HIV/AIDS will increase.
Resumo:
Metal complexes that utilize the 9,10-phenanthrene quinone diimine (phi) moiety bind to DNA through the major groove. These metallointercalators can recognize DNA sites and perform reactions on DNA as a substrate. The site-specific metallointercalator Λ-1-Rh(MGP)_2phi^(5+) competitively disrupts the major groove binding of a transcription factor, yAP-1, from an oligonucleotide that contains a common binding site. The demonstration that metal complexes can prevent transcription factor binding to DNA site-specifically is an important step in using metallointercalators as therapeutics.
The distinctive photochemistry of metallointercalators can also be applied to promote long range charge transport in DNA. Experiments using duplexes with regions 4 to 10 nucleotides long containing strictly adenine and thymine sequences of varying order showed that radical migration is more dependent on the sequence of bases, and less dependent on the distance between the guanine doublets. This result suggests that mechanistic proposals of long range charge transport must involve all the bases.
RNA/DNA hybrids show charge migration to guanines from a remote site, thus demonstrating that nucleic acid stacking other than B-form can serve as a radical bridge. Double crossover DNA assemblies also provide a medium for charge transport at distances up to 100 Å from the site of radical introduction by a tethered metal complex. This radical migration was found to be robust to mismatches, and limited to individual, electronically distinct base stacks. In single DNA crossover assemblies, which have considerably greater flexibility, charge migration proceeds to both base stacks due to conformational isomers not present in the rigid and tightly annealed double crossovers.
Finally, a rapid, efficient, gel-based technique was developed to investigate thymine dimer repair. Two oligonucleotides, one radioactively labeled, are photoligated via the bases of a thymine-thymine interface; reversal of this ligation is easily visualized by gel electrophoresis. This assay was used to show that the repair of thymine dimers from a distance through DNA charge transport can be accomplished with different photooxidants.
Thus, nucleic acids that support long range charge transport have been shown to include A-track DNA, RNA/DNA hybrids, and single and double crossovers, and a method for thymine dimer repair detection using charge transport was developed. These observations underscore and extend the remarkable finding that DNA can serve a medium for charge transport via the heteroaromatic base stack.
Resumo:
James Joyce’s Ulysses celebrates all facets of daily life in its refusal to censor raw human emotions and emissions. He adopts a critically medical perspective to portray this honest, unfiltered narrative. In doing so, he reveals the ineffectiveness of the physician-patient relationship due to doctors’ paternalistic attitudes that hinder nonjudgmental, open listening of this unfiltered narrative. His exploration of the doctor’s moral scrutiny, cultural prejudices, and authoritative estrangement from the patient underscore the importance in remembering that physicians and patients alike are ultimately just fellow human beings. Wryly, he drives this point to literal nausea, as his narrative proudly asserts the revulsive details of public health, digestion, and death. In his gritty ruminations on the human body’s material reality, Joyce mocks the physician’s highbrow paternalism by forcing him to identify with the farting, vomiting, decaying bodies around him. In celebrating the uncensored human narrative, Joyce challenges physician and patient alike to openly listen to the stories of others.
Resumo:
Este trabalho pretende problematizar as concepções de coletivo que se apresentam nos discursos da psicologia brasileira contemporânea. Tomamos como campo os artigos da revista Psicologia e Sociedade e construímos duas imagens: a imagem do coletivo representação é acompanhada por concepções naturalizantes das categorias com as quais trabalha. Nesta imagem de coletivo a separação entre indivíduo e sociedade é bem marcada e acaba produzindo construções abstratas dos seus fenômenos. Ao percorrer uma breve história da psicologia vemos esta surgir como uma tecnologia voltada para a ?gestão? dos coletivos, construindo e reproduzindo conhecimentos acerca dos indivíduos e do social. A imagem dos coletivos clandestinos é pautada em referências que desestabilizam as fronteiras impostas das ciências modernas e concebem tanto o indivíduo quanto o social efeito de uma produção simultânea, problematizando as fprmas de cpnhecimento das ciências tradicionais. A metodologia conta com a perspectiva histórica de Michel Foucault que afirma a primazia das relações de poder, e com as contribuições de Bruno Latour e suas conexões criando hibridismos. A proposta metodológica foi um importante instrumento ara romper com as barreiras separatistas, acentuando a presença do pesquisadpr como participante igual aos outros elementos do campo de pesquisa, enfatizando que o modo de pesquisar é com o outro e não sobre o outro. Desta forma As histórias de coletivos para uma psicologia brasileira pretende desnaturalizar modos de produzir conhecimento e categorias de coletivos herméticas. Para finalizar entre formas de fazer e perceber o coletivo temos o trabalho de campo atravessado pordois sociólogos, Emile Durkheim e Gabriel Tarde, contribuindo com as problematizações dos coletivos representação e clandestinos. Gabriel Tarde contribui produzindo uma concepção de coletivo processual, onde a imitação e a invenção ressaltam o caráter relacional do indivíduo e do social e os coloca numa produção de dupla emergência.
Resumo:
O presente estudo abordou a possibilidade de materialização do atual Projeto Ético-Político do Serviço Social brasileiro na direção social impressa no trabalho dos assistentes sociais que atuam na Secretaria de Administração Penitenciária do Rio de Janeiro (SEAP), com vínculos trabalhistas precários. Selecionamos os profissionais com contratos temporários, ou seja, precários, por entendermos que a fragilidade do vínculo trabalhista pode ser um importante fator de acirramento e de agudização da tensão inerente ao trabalho profissional do assistente social nesse campo sócio-ocupacional, impactando prejudicialmente não só nas condições de trabalho dos profissionais, mas, de modo importante, na qualidade dos serviços prestados aos usuários e, por conseguinte, nas possibilidades e limites de materialização do atual Projeto Profissional crítico. Daí por que considerarmos necessários estudos que se voltem aos profissionais com vínculos trabalhistas precários, especialmente profissionais que atuam em locais complexos como a Secretaria de Administração Penitenciária. Destacamos a relevância de investigações que se atenham ao trabalho profissional, na medida em que se constitui locus privilegiado de contato entre o assistente social e aqueles que atende, tendo em vista o caráter interventivo da profissão. A pesquisa empírica foi realizada por meio de entrevistas com assistentes sociais que trabalham na SEAP, com o perfil selecionado, ou seja, vínculo trabalhista precário. Utilizamos, ainda, nossa experiência como assistente social, as observações no campo e as conversas informais com os entrevistados. Esta investigação foi orientada pela teoria social crítica, ou seja, o materialismo histórico e dialético.
Resumo:
A proposta deste trabalho é investigar a ficcionalização do discurso do eu na construção do passado, em Graciliano Ramos, que, utilizando a observação, a experiência, a sensibilidade e imaginação, reflete a respeito da interação entre homem e sociedade, negando o aspecto narcísico associado ao gênero autobiográfico e atingindo o universal pelo particular. Para este objetivo, sublinhamos a relação entre autobiografia e individualidade e buscamos destacar aquilo que nos permite realizar uma leitura de viés autobiográfico em Infância, não esquecendo que se trata também de uma composição literária, cujos recursos e técnicas o autor manejava com capricho. Prosseguimos traçando um breve panorama da década de 30 e sucintos comentários sobre o conjunto da obra do romancista alagoano. Alcançamos, então, o capítulo principal, no qual baseamos a nossa proposta na obra que é o foco desta pesquisa, elaborada por um escritor já maduro e seguro de sua concepção de literatura; nele se busca demonstrar a relevância da memória na construção da história social, ressaltando a condição fragmentária própria da constituição do sujeito e destacando a função da escrita como instrumento de organização e construção, para si e para outros, de uma ideia de identidade. Na conclusão, retomamos alguns pontos elencados ao longo deste trabalho, procurando comprovar a articulação entre eles, pertinente a nossa proposta
Resumo:
The lacunae in fishing-community engagement in the management and governance of marine and coastal protected areas (MCPAs) were discussed in the 2009 Chennai Workshop organized by the International Collective in Support of Fishworkers (ICSF). To continue the discussion, a second, two-day workshop to review existing legal and institutional mechanisms for implemention and monitoring of MCPAs, titled ‘Fishery-dependent Livelihoods, Conservation and Sustainable Use of Biodiversity: The Case of Marine and Coastal Protected Areas in India’, was held in New Delhi during 1-2 March 2012. The objective was to understand the impact of MCPAs on fishing communities, from an environmental-justice and human-rights perspective, and make specific proposals for better conservation while securing the livelihoods of small-scale fishers. The workshop also served to underscore these issues in light of the upcoming Conference of the Parties (COP) to the Convention on Biological Diversity (CBD), to be held at Hyderabad in October 2012. This publication contains the prospectus of the workshop and a report of the proceedings. It will be useful for fishworkers, non-governmental organizations, policymakers, trade unions, researchers and others interested in natural resource management and coastal and fishing communities.
Resumo:
A study was conducted in June 2009 to assess the current status of ecological condition and potential human-health risks throughout subtidal estuarine waters of the Sapelo Island National Estuarine Research Reserve (SINERR) along the coast of Georgia. Samples were collected for multiple indicators of ecosystem condition, including water quality (dissolved oxygen, salinity, temperature, pH, nutrients and chlorophyll, suspended solids, fecal coliform bacteria and coliphages), sediment quality (granulometry, organic matter content, chemical contaminant concentrations), biological condition (diversity and abundance of benthic fauna, fish tissue contaminant levels and pathologies), and human dimensions (fish-tissue contaminant levels relative to human-health consumption limits, various aesthetic properties). Use of a probabilistic sampling design facilitated the calculation of statistics to estimate the spatial extent of the Reserve classified according to various categories (i.e., Good, Fair, Poor) of ecological condition relative to established thresholds of these indicators, where available. Overall, the majority of subtidal habitat in the SINERR appeared to be healthy, with over half (56.7 %) of the Reserve area having water quality, sediment quality, and benthic biological condition indicators rated in the healthy to intermediate range of corresponding guideline thresholds. None of the stations sampled had one or more indicators in all three categories rated as poor/degraded. While these results are encouraging, it should be noted that one or more indicators were rated as poor/degraded in at least one of the three categories over 40% of the Reserve study area, represented by 12 of the 30 stations sampled. Although measures of fish tissue chemical contamination were not included in any of the above estimates, a number of trace metals, pesticides, polybrominated diphenyl ethers (PBDEs), and polychlorinated biphenyls (PCBs) were found at low yet detectable levels in some fish at stations where fish were caught. Levels of mercury and total PCBs in some fish specimens fell within EPA guideline values considered safe, given a consumption rate of no more than four fish meals per month. Moreover, PCB congener profiles in sediments and fish in the SINERR exhibit a relative abundance of higher-chlorinated homologs which are uniquely characteristic of Aroclor 1268. It has been well-documented that sediments and fish in the creeks and marshes near the LCP Chemicals Superfund site, near Brunswick, Georgia, also display this congener pattern associated with Aroclor 1268, a highly chlorinated mixture of PCBs used extensively at a chlor-alkali plant that was in operation at the LCP site from 1955-1994. This report provides results suggesting that the protected habitats lying within the boundaries of the SINERR may be experiencing the effects of a legacy of chemical contamination at a site over 40km away. These effects, as well as other potential stressors associated with increased development of nearby coastal areas, underscore the importance of establishing baseline ecological conditions that can be used to track potential changes in the future and to guide management and stewardship of the otherwise relatively unspoiled ecosystems of the SINERR.
Resumo:
Dopamine (DA) D-1 receptor compounds were examined in monkeys for effects on the working memory functions of the prefrontal cortex and on the fine motor abilities of the primary motor cortex. The D-1 antagonist, SCH23390, the partial D-1 agonist, SKF38393, and the full D-1 agonist, dihydrexidine, were characterized in young control monkeys, and in aged monkeys with naturally occurring catecholamine depletion. In addition, SKF38393 was tested in young monkeys experimentally depleted of catecholamines with chronic reserpine treatment. Injections of SCH23390 significantly impaired the memory performance of young control monkeys, but did not impair aged monkeys with presumed catecholamine depletion. Conversely, the partial agonist, SKF38393, improved the depleted monkeys (aged or reserpine-treated) but did not improve young control animals. The full agonist, dihydrexidine, did improve memory performance in young control monkeys, as well as in a subset of aged monkeys. Consistent with D, receptor mechanisms, agonist-induced improvements were blocked by SCH23390. Drug effects on memory performance occurred independently of effects on fine motor performance. These results underscore the importance of DA D-1 mechanisms in cognitive function, and provide functional evidence of DA system degeneration in aged monkeys. Finally, high doses of D-1 agonists impaired memory performance in aged monkeys, suggesting that excessive D-1 stimulation may be deleterious to cognitive function.
Resumo:
Ecological responses to dam construction are poorly understood, especially for downstream benthic algal communities. We examined the responses of benthic algal communities in downstream reaches of a tributary of the Xiangxi River, China, to the construction of a small run-of-river dam. From February 2003 to August 2006, benthic algae, chemical factors, and habitat characteristics were monitored upstream and downstream of the dam site. This period spanned 6 mo before dam construction and 37 mo after dam construction. Benthic algal sampling yielded 199 taxa in 59 genera that belonged to Bacillariophyta, Chlorophyta, and Cyanophyta. Some physical factors (flow velocity, water depth, and channel width) and 3 algal metrics (diatom species richness, Margalef diversity, and % erect individuals) were significantly affected by the dam construction, whereas chemical factors (e.g., NH4-N, total N, SiO2) were not. Nonmetric multidimensional scaling (NMS) ordinations showed that overall algal assemblage structure downstream of the dam sites was similar to that of upstream control sites before dam construction and for 1 year after dam construction (p > 0.05). However, sites belonging to upstream and downstream reaches were well separated on NMS axis 1 during the 2(nd) and 3(rd) years after dam construction. Our results suggest that impacts of dam construction on benthic algal communities took 2 to 3 y to emerge. Further development of a complete set of indicators is needed to address the impact of small-dam construction. Our observations underscore the need for additional studies that quantify ecological responses to dam construction over longer time spans.