376 research outputs found
Oblique stimulated Raman scattering of a short laser pulse in a plasma channel
The spatiotemporal evolution of parametric instabilities such as stimulated Raman scattering is studied analytically in time and two spatial dimensions. Initial and boundary conditions are chosen to represent the entrance, propagation, and exit of a laser pulse of finite extent as it progresses through a homogeneous collisional plasma channel. For most scattering angles daughter wave growth is enhanced by lateral reflections within the channel. At late times the two-dimensional interaction approaches a one-dimensional damped mode in which the dissipative loss from lateral transmission of the Stokes wave through the channel boundaries is equivalent to an overall damping of the Stokes amplitudes within the channel
Thermally Selective Formation of Subsurface Oxygen in Ag(111) and Consequent Surface Structure
A long-standing challenge in the study of heterogeneously catalyzed reactions on silver surfaces has been the determination of what oxygen species are of greatest chemical importance. This is due to the coexistence of several different surface phases on oxidized silver surfaces. A further complication is subsurface oxygen (Osub). Osub are O atoms absorbed into the near surface of a metal, and are expected to alter the surface in terms of chemistry and structure, but these effects have yet to be well characterized. We studied oxidized Ag(111) surfaces after exposure to gas-phase O atoms to determine how Osub is formed and how its presence alters the resultant surface structure. Using a combination of surface science techniques to quantify Osub formation and the resultant surface structure, we observed that once 0.1 ML of Osub has formed, the surface dramatically, and uniformly, reconstructed to a striped phase at the expense of all other surface phases. Furthermore, Osub formation was hindered at temperatures above 500 K. The thermal dependence for Osub formation suggests that at industrial catalytic conditions of 475 – 500 K for the epoxidation of ethylene-to-ethylene oxide, Osub would be present and is a factor in the subsequent reactivity of the catalysts. These findings point to the need for the incorporation of Osub into catalytic models as well as further theoretical investigation of the resultant structure observed in the presence of Osub
A dynamic link between H/ACA snoRNP components and cytoplasmic stress granules
Many cell stressors block protein translation, inducing formation of cytoplasmic aggregates. These aggregates, named stress granules (SGs), are composed by translationally stalled ribonucleoproteins and their assembly strongly contributes to cell survival. Composition and dynamics of SGs are thus important starting points for identifying critical factors of the stress response. In the present study we link components of the H/ACA snoRNP complexes, highly concentrated in the nucleoli and the Cajal bodies, to SG composition. H/ACA snoRNPs are composed by a core of four highly conserved proteins -dyskerin, Nhp2, Nop10 and Gar1- and are involved in several fundamental processes, including ribosome biogenesis, RNA pseudouridylation, stabilization of small nucleolar RNAs and telomere maintenance. By taking advantage of cells overexpressing a dyskerin splice variant undergoing a dynamic intracellular trafficking, we were able to show that H/ACA snoRNP components can participate in SG formation, this way contributing to the stress response and perhaps transducing signals from the nucleus to the cytoplasm. Collectively, our results show for the first time that H/ACA snoRNP proteins can have additional non-nuclear functions, either independently or interacting with each other, thus further strengthening the close relationship linking nucleolus to SG composition
The anti-apoptotic effect of ASC-exosomes in an in vitro ALS model and their proteomic analysis
Stem cell therapy represents a promising approach in the treatment of several neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). The beneficial effect of stem cells is exerted by paracrine mediators, as exosomes, suggesting a possible potential use of these extracellular vesicles as non-cell based therapy. We demonstrated that exosomes isolated from adipose stem cells (ASC) display a neuroprotective role in an in vitro model of ALS. Moreover, the internalization of ASC-exosomes by the cells was shown and the molecules and the mechanisms by which exosomes could exert their beneficial effect were addressed. We performed for the first time a comprehensive proteomic analysis of exosomes derived from murine ASC. We identified a total of 189 proteins and the shotgun proteomics analysis revealed that the exosomal proteins are mainly involved in cell adhesion and negative regulation of the apoptotic process. We correlated the protein content to the anti-apoptotic effect of exosomes observing a downregulation of pro-apoptotic proteins Bax and cleaved caspase-3 and upregulation of anti-apoptotic protein Bcl-2 \u3b1, in an in vitro model of ALS after cell treatment with exosomes. Overall, this study shows the neuroprotective effect of ASC-exosomes after their internalization and their global protein profile, that could be useful to understand how exosomes act, demonstrating that they can be employed as therapy in neurodegenerative diseases
Diauxie and co-utilization of carbon sources can coexist during bacterial growth in nutritionally complex environments
It is commonly thought that when multiple carbon sources are available, bacteria metabolize them either sequentially (diauxic growth) or simultaneously (co-utilization). However, this view is mainly based on analyses in relatively simple laboratory settings. Here we show that a heterotrophic marine bacterium, Pseudoalteromonas haloplanktis, can use both strategies simultaneously when multiple possible nutrients are provided in the same growth experiment. The order of nutrient uptake is partially determined by the biomass yield that can be achieved when the same compounds are provided as single carbon sources. Using transcriptomics and time-resolved intracellular 1H-13C NMR, we reveal specific pathways for utilization of various amino acids. Finally, theoretical modelling indicates that this metabolic phenotype, combining diauxie and co-utilization of substrates, is compatible with a tight regulation that allows the modulation of assimilatory pathways
Modelling hCDKL5 heterologous expression in bacteria
hCDKL5 refers to the human cyclin-dependent kinase like 5 that is primarily expressed in the brain. Mutations in its coding sequence are often causative of hCDKL5 deficiency disorder, a devastating neurodevelopmental disorder currently lacking a cure. The large-scale recombinant production of hCDKL5 is desirable to boost the translation of preclinical therapeutic approaches into the clinic. However, this is hampered by the intrinsically disordered nature of almost two-thirds of the hCDKL5 sequence, making this region more susceptible to proteolytic attack, and the observed toxicity when the enzyme is accumulated in the cytoplasm of eukaryotic host cells. The bacterium Pseudoalteromonas haloplanktis TAC125 (PhTAC125) is the only prokaryotic host in which the full-length production of hCDKL5 has been demonstrated. To date, a system-level understanding of the metabolic burden imposed by hCDKL5 production is missing, although it would be crucial for upscaling of the production process. Here, we combined experimental data on protein production and nutrients assimilation with metabolic modelling to infer the global consequences of hCDKL5 production in PhTAC125 and to identify potential overproduction targets. Our analyses showed a remarkable accuracy of the model in simulating the recombinant strain phenotype and also identified priority targets for optimised protein production
Importância clínica dos custos diretos hospitalares em pacientes com hipertensão arterial em tratamento num hospital universitário, Rio de Janeiro, Brasil
The authors analysed retrospectively 503 adult patients (; 140/90 mmHg). The 96 cases initially analysed were studied for the determination of the direct hospital costs involved in the evaluation, follow-up and treatment of such cases. The initial diastolic BP was distributed as follows: 90 to 104 mmHg-67 cases (69.8%); 105 to 114 mmHg-17 cases (17.7%); >; 115 mmHg - 12 cases (12.5%). The mean follow-up period of this population was 653 days and at the last hospital visit only 1/3 had their BP under control ( ;20 anos foram separados aleatoriamente e 483 destes possuiam registro de pressão arterial (PA) com 138 casos (28,6%) apresentando hipertensão arterial (HA) (PA >;140/90 mmHg). Nos 96 hipertensos inicialmente analisados procedeu-se estudos dos custos diretos hospitalares com a avaliação, acompanhamento e tratamento desta população. A PA diastólica inicial destes casos estava assim distribuída: entre 90 e 104 mmHg - 67 casos (69,8%); entre 105 e 114 mmHg - 17 casos (17,7%); maior ou igual a 115 mmHg - 12 casos (12,5%). O período médio de acompanhamento destes grupos foi de 653 dias e somente 1/3 estava com PA controlada ( < 140/90 mmHg) na última consulta. Em 1982, 68,7% já haviam abandonado tratamento no HU-UFRJ. O custo direto total anual por paciente hipertenso em dólares foi de 33.44; atendimentos de emergência 29.92; exames complementares 26.34. As consultas e internações representam 64% dos custos e foram em grande parte determinadas pelas complicações da doença. Estas também ocasionam elevados índices de incapacidade temporária e permanente da população de hipertensos com graves repercussões e custos sociais. A análise dos fatores que contribuem para estes custos indicam a adoção das seguintes medidas para minimizá-los: a) Desenvolvimento de programas que visem melhor controle de HA e menor abandono de tratamento da população já detectada nas próprias unidades do Sistema de Saúde com conseqüente redução da morbidade da doença; b) Padronização da avaliação laboratorial e do tratamento com base em estudos de custo-eficácia; c) Hierarquização do sistema de saúde - o hipertenso deve ser tratado em unidades de saúde onde os custos indiretos hospitalares pouco influenciem os custos das consultas e das internações
Tyr25, Tyr58 and Trp133 of Escherichia coli bacterioferritin transfer electrons between iron in the central cavity and the ferroxidase centre
Ferritins are 24meric proteins that overcome problems of toxicity, insolubility and poor bioavailability of iron in all types of cells by storing it in the form of a ferric mineral within their central cavities. In the bacterioferritin (BFR) from Escherichia coli iron mineralization kinetics have been shown to be dependent on an intra-subunit catalytic diiron cofactor site (the ferroxidase centre), three closely located aromatic residues and an inner surface iron site. One of the aromatic residues, Tyr25, is the site of formation of a transient radical, but the roles of the other two residues, Tyr58 and Trp133, are unknown. Here we show that these residues are important for the rates of formation and decay of the Tyr25 radical and decay of a secondary radical observed during Tyr25 radical decay. The data support a mechanism in which these aromatic residues function in electron transfer from the inner surface site to the ferroxidase centre
What do cyclists need to see to avoid single-bicycle crashes?
The number of single-bicycle crash victims is substantial in countries with high levels of cycling. To study the role of visual characteristics of the infrastructure, such as pavement markings, in single-bicycle crashes, a study in two steps was conducted. In Study 1, a questionnaire study was conducted among bicycle crash victims (n = 734). Logistic regression was used to study the relationship between the crashes and age, light condition, alcohol use, gaze direction and familiarity with the crash scene. In Study 2, the image degrading and edge detection method (IDED-method) was used to investigate the visual characteristics of 21 of the crash scenes. The results of the studies indicate that crashes, in which the cyclist collided with a bollard or road narrowing or rode off the road, were related to the visual characteristics of bicycle facilities. Edge markings, especially in curves of bicycle tracks, and improved conspicuity of bollards are recommended. Statement of Relevance: Elevated single-bicycle crash numbers are common in countries with high levels of cycling. No research has been conducted on what cyclists need to see to avoid this type of crash. The IDED-method to investigate crash scenes is new and proves to be a powerful tool to quantify 'visual accessibility'. © 2011 Taylor & Francis
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