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1.
J Cell Biol ; 222(12)2023 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-37787765

RESUMO

IQSEC2 (aka BRAG1) is a guanine nucleotide exchange factor (GEF) highly enriched in synapses. As a top neurodevelopmental disorder risk gene, numerous mutations are identified in Iqsec2 in patients with intellectual disabilities accompanied by other developmental, neurological, and psychiatric symptoms, though with poorly understood underlying molecular mechanisms. The atomic structures of IQSECs, together with biochemical analysis, presented in this study reveal an autoinhibition and Ca2+-dependent allosteric activation mechanism for all IQSECs and rationalize how each identified Iqsec2 mutation can alter the structure and function of the enzyme. Transgenic mice modeling two pathogenic variants of Iqsec2 (R359C and Q801P), with one activating and the other inhibiting the GEF activity of the enzyme, recapitulate distinct clinical phenotypes in patients. Our study demonstrates that different mutations on one gene such as Iqsec2 can have distinct neurological phenotypes and accordingly will require different therapeutic strategies.


Assuntos
Cálcio , Fatores de Troca do Nucleotídeo Guanina , Transtornos do Neurodesenvolvimento , Animais , Humanos , Camundongos , Fatores de Troca do Nucleotídeo Guanina/genética , Camundongos Transgênicos , Mutação , Proteínas do Tecido Nervoso , Fenótipo
2.
Chem Asian J ; 13(13): 1699-1709, 2018 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-29722159

RESUMO

The development of novel iridium(III) complexes has continued as an important area of research owing to their highly tunable photophysical properties and versatile applications. In this report, three heteroleptic dimesitylboron-containing iridium(III) complexes, [Ir(p-B-ppy)2 (N^N)]+ {p-B-ppy=2-(4-dimesitylborylphenyl)pyridine; N^N=dipyrido[3,2-a:2',3'-c]phenazine (dppz) (1), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq) (2), and 1,10-phenanthroline (phen) (3)}, were prepared and fully characterized electrochemically, photophysically, and computationally. Altering the conjugated length of the N^N ligands allowed us to tailor the photophysical properties of these complexes, especially their luminescence wavelength, which could be adjusted from λ=583 to 631 nm in CH2 Cl2 . All three complexes were evaluated as visible-light-absorbing sensitizers for the photogeneration of hydrogen from water and as photocatalysts for the photopolymerization of methyl methacrylate. The results showed that all of them were active in both photochemical reactions. High activity for the photosensitizer (over 1158 turnover numbers with 1) was observed, and the system generated hydrogen even after 20 h. Additionally, poly(methyl methacrylate) with a relatively narrow molecular-weight distribution was obtained if an initiator (i.e., ethyl α-bromophenylacetate) was used. The living character of the photoinduced polymerization was confirmed on the basis of successful chain-extension experiments.

3.
Biochemistry ; 57(14): 2132-2139, 2018 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-29589748

RESUMO

Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 1 (ARAP1), Cbl-interacting protein of 85 kDa (CIN85), and casitas B-lineage lymphoma (Cbl) play important roles in epidermal growth factor receptor (EGFR) internalization and recycling. In previous studies, ARAP1 was found to interact with CIN85, and their interaction attenuated the ubiquitination of EGFR. However, the molecular mechanism was still unclear. In this study, we first biochemically and structurally characterized the interaction between ARAP1 and CIN85, and found that the CIN85 SH3B domain bound to the ARAP1 PXPXXRX (except P) XXR/H/K motif with high affinity and specificity. Based on this binding model, we further predicted other potential CIN85 binding partners and tested their interactions biochemically. Moreover, our swapping data and structure alignment analysis suggested that the ß2-ß3 loops of the CIN85 SH3 domains and the H87ARAP1/E132CIN85 interaction were critical for ARAP1 binding specificity. Finally, our competitive analytical gel-filtration chromatography and isothermal titration calorimetry (ITC) results showed that ARAP1 could compete with Cbl for CIN85 binding, which provides a biochemical basis for the regulatory roles of ARAP1 in the CIN85-mediated EGFR internalizing process.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/química , Modelos Moleculares , Complexos Multiproteicos/química , Proteínas de Neoplasias/química , Proteínas do Tecido Nervoso/química , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Camundongos , Complexos Multiproteicos/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Ligação Proteica , Domínios Proteicos , Estrutura Quaternária de Proteína , Estrutura Secundária de Proteína , Proteínas Proto-Oncogênicas c-cbl/química , Proteínas Proto-Oncogênicas c-cbl/metabolismo , Relação Estrutura-Atividade
4.
J Hazard Mater ; 148(3): 653-9, 2007 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-17420094

RESUMO

A bench-scale biofilter was used to demonstrate the treatability of off-gas containing nitric oxide (NO) by examining selected operational parameters. After 6 days of operation, the biofilter reached to a steady state and NO reduction was significant, reducing from 200 ppm to 95 and 40 ppm after 6 and 40 days of continuous operation. The oxygen concentrations in the inlet would affect NO removal performance significantly; as oxygen content decreasing from 6% to 0%, the NO removal efficiency increased from 55% to 99%, indicating that oxygen inhibited the progress of denitrification. NO removal was inversely proportional to inlet NO concentration, removal efficiency decreased from 88% to 40 % as NO concentration increasing from 60 to 500 ppm. Column height would significant effect on the NO removal efficiency, under column height=6.5m and O(2)=6% conditions, 90% of removal efficiency was achievable. The effect of glucose added into biofilter would significantly enhance the NO removal efficiencies for both anaerobic and aerobic conditions of which 99% and 55%, respectively.


Assuntos
Poluentes Atmosféricos/metabolismo , Bactérias/metabolismo , Filtração/instrumentação , Óxido Nítrico/metabolismo , Biodegradação Ambiental , Reatores Biológicos , Desenho de Equipamento , Oxigênio/metabolismo
5.
J Environ Manage ; 85(4): 908-17, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17222500

RESUMO

The purpose of this study is to develop a model for optimal nonpoint source pollution control for the Fei-Tsui Reservoir watershed in Northern Taiwan. Several structural best management practices (BMPs) are selected to treat stormwater runoff. The complete model consists of two interacting components: an optimization model based on discrete differential dynamic programming (DDDP) and a zero-dimensional reservoir water quality model. A predefined procedure is used to locate suitable sites for construction of various selected BMPs in the watershed. In the optimization model, the objective function is to find the best combination of BMP type and placement, which minimizes the total construction and operation, maintenance, and repair (OMR) costs of the BMPs. The constraints are the water quality standards for total phosphorus (TP) and total suspended solids (TSS) concentrations in the reservoir. A zero-dimensional reservoir water quality model of the Vollenweider type is embedded in the optimization framework to simulate pollutant concentrations in Fei-Tsui Reservoir. The resulting optimal cost and benefit of water quality improvement are depicted by the model-derived trade-off curves. The modeling framework developed in the present study could be used as an efficient tool for planning a watershed-wide implementation of BMPs for mitigating stormwater pollution impact on the receiving water bodies.


Assuntos
Poluição da Água/prevenção & controle , Abastecimento de Água/análise , Análise Custo-Benefício , Geografia , Taiwan , Poluição da Água/análise , Poluição da Água/economia
6.
Waste Manag ; 27(2): 209-19, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-16529920

RESUMO

This paper reviews several models developed to support decision making in municipal solid waste management (MSWM). The concepts underlying sustainable MSWM models can be divided into two categories: one incorporates social factors into decision making methods, and the other includes public participation in the decision-making process. The public is only apprised or takes part in discussion, and has little effect on decision making in most research efforts. Few studies have considered public participation in the decision-making process, and the methods have sought to strike a compromise between concerned criteria, not between stakeholders. However, the source of the conflict arises from the stakeholders' complex web of value. Such conflict affects the feasibility of implementing any decision. The purpose of this study is to develop a sustainable decision making model for MSWM to overcome these shortcomings. The proposed model combines multicriteria decision making (MCDM) and a consensus analysis model (CAM). The CAM is built up to aid in decision-making when MCDM methods are utilized and, subsequently, a novel sustainable decision making model for MSWM is developed. The main feature of CAM is the assessment of the degree of consensus between stakeholders for particular alternatives. A case study for food waste management in Taiwan is presented to demonstrate the practicality of this model.


Assuntos
Cidades/legislação & jurisprudência , Tomada de Decisões , Modelos Teóricos , Eliminação de Resíduos/legislação & jurisprudência
7.
J Hazard Mater ; 137(3): 1742-9, 2006 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-16787702

RESUMO

This paper presents parts of the results from a research project sponsored by Taiwan Environmental Protection Administration (TEPA), investigating both the physical and environmental properties of asphalt mixtures using different amount of incinerator bottom ash (IBA) as fine aggregate substitution. The Marshall mix design method was used to determine the design asphalt content and evaluate the potential performance of these IBA-asphalt mixtures. Water sensitivity and wheel track rutting were also performed on these mixtures. Leachates, from both laboratory and outdoor leaching tests, were performed to measure the concentration of selected heavy metals and the level of daphnia toxicity. While with adequate Marshall stability, the IBA-asphalt mixtures were shown to have excessively high Marshall flow and excessively low VMA (voids in the mineral aggregate). The results of the wheel tracking tests also indicated that the IBA-asphalt mixtures had low rutting resistance. The results of the water sensitivity test according to procedure of AASHTO T283 method showed that the IBA-asphalt mixtures had a higher tensile strength ratio (TSR) as compared with the conventional asphalt mixtures. Considering the environmental aspects, outdoor leaching tests showed that IBA had a high level of daphnia toxicity. From an ecological perspective, IBA could be identified as hazardous waste in Taiwan. However, after being mixed with asphalt binder, the concentration of heavy metals and the levels of daphnia toxicity were significantly reduced. The leachates of 10-day flat plate leaching tests on Marshall specimens containing IBA indicated that the heavy metal were undetectable and the daphnia toxicity was ineffective.


Assuntos
Meio Ambiente , Hidrocarbonetos , Incineração/métodos , Animais , Daphnia , Metais Pesados/química
8.
J Hazard Mater ; 129(1-3): 58-63, 2006 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-16309828

RESUMO

A method was used to investigate the potential for using water clarifier sludge to remove copper in a fluidized-bed reactor (FBR). This study was conducted to evaluate the removal of copper in an aquatic system without prior treatment. Chemical analyses of water clarifier sludge through inductively coupled plasma-atomic emission spectrophotometry indicated that silicon, aluminum and iron oxides made up more than 84% of this average composition, similar to the composition of clay. The experimental results indicated that the copper removal efficiency was highly dependent on the pH. pH values also influence the character of the water clarifier sludge. After the copper was adsorbed by the water clarifier sludge, the pH of the solution was slightly increased. In the FBR, the copper removal efficiency reached 90% when the initial copper concentration was 20 mg/L, the pH was 4 and the operating time was 60 min. In addition, copper precipitation occured on the surface of clarifier sludge when the initial copper concentration was 20 mg/L and the pH was 7.0. The kinetics of copper ion adsorption at pH 5 showed that 94% copper ion was removed in 60 min and the adsorption equilibrium was attained in 5 h. The mechanisms of adsorption of copper ions on water clarifier sludge including the formation of surface complexation and surface precipitate.


Assuntos
Cobre , Resíduos Industriais , Gerenciamento de Resíduos/métodos , Poluentes Químicos da Água/isolamento & purificação , Purificação da Água/métodos , Água/química , Adsorção , Cobre/isolamento & purificação , Filtração
9.
Waste Manag ; 26(9): 979-87, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16297611

RESUMO

By 2004, there were 19 municipal solid waste incinerators (MSWI) with a total yearly treatment capacity of 7.72 million tons in service in Taiwan. All 19 incinerators operated daily to generate about 1.05 million tons of incinerator ash, including bottom ash and stabilized fly ash in 2003, and the average ash yield is 18.67%. The total number of incinerators is expected to increase to 27, serving almost all cities in Taiwan by 2007. The authors have suggested a set of criteria based on the yield of incinerator ash (Phi) to study the ash recycle and reuse potential. The Taiwan Environmental Protection Administration has studied the treatment and reuse of MSWI ashes for many years and collected references on international experience accumulated by developed nations for establishing policies on treatment and reuse of MSWI ashes. These citations were analyzed as the basis for current governmental decision making on policies and factors to be considered for establishing policies on recycle and reuse of MSWI ashes. Feasible applications include utilization of ashes, which after sieving and separation of metal particles, produce granular materials. When granular materials comply with TCLP limitations, they can be utilized as cement additives or road base. The procedures of evaluation have been proposed in the performance criteria to be included in the proposed decision-making process of ash utilization.


Assuntos
Conservação dos Recursos Naturais , Eliminação de Resíduos , Gerenciamento de Resíduos , Materiais de Construção , Poluentes Ambientais , Incineração , Resíduos Industriais , Indústrias , Material Particulado , Saúde Pública , Política Pública , Taiwan
10.
J Hazard Mater ; 114(1-3): 45-51, 2004 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-15511573

RESUMO

This study was performed in a fluidized-bed reactor (FBR) filled with manganese-coated sand (MCS) to treat copper-contaminated wastewater. The adsorption characteristics of MCS, the adsorption equilibrium of MCS, and the copper removal capacity by MCS in FBR were investigated. In terms of the adsorption characteristics of MCS, the surface of MCS was evaluated using a scanning electron microscope (SEM). Energy dispersive analysis (EDS) of X-rays indicated the composition of MCS, and the quantity of manganese on MCS was determined by means of acid digestion analysis. The experimental results indicated that copper was removed by both sorption (ion exchange and adsorption) and coprecipitation on the surface of MCS in FBR. Copper removal efficiency was highly dependent on the pH and increased with increasing pH from pH 2 to 8. After the copper adsorption by MCS, the pH in solution was decreased. When the MCS concentration was greater than 10 g/l, the copper adsorptivities obtained by FBR were almost the same as that from the shaker and when the MCS concentration reached 40 g/l, the copper adsorptivity in FBR was greater than that from the shaker. The adsorption sites of MCS could be used efficiently by the FBR. A Langmuir adsorption isotherm equation fit the measured adsorption data from the batch equilibrium adsorption test better than the Freundlich adsorption isotherm equation did. In addition, the adsorption rate increased when the influent wastewater was aerated.


Assuntos
Cobre/isolamento & purificação , Manganês/química , Eliminação de Resíduos Líquidos , Poluentes Químicos da Água/análise , Adsorção , Cor , Filtração , Concentração de Íons de Hidrogênio , Dióxido de Silício , Propriedades de Superfície , Termodinâmica
11.
Chemosphere ; 57(9): 1173-80, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15504477

RESUMO

In this study, a fluidized-bed reactor (FBR) was employed to treat copper-containing wastewater by mean of copper precipitation on the surface of sand grains. The conditions for optimum copper removal efficiency were also investigated. This technology was controlled so as to keep supersaturation low to induce the nucleated precipitation of copper coating on the sand surface in an FBR. The effects of relevant parameters, such as the pH value, the molar ratio of [C(T)] to [Cu(2+)], hydraulic loading and the types of chemical reagents used, were examined. The experimental results indicated that 96% copper removal efficiency could be achieved when the influent copper concentration was 10mg l(-1). The optimum chemical reagent was Na(2)CO(3); the molar ratio of [C(T)]/[Cu(2+)] was 2, and the optimal hydraulic loading was not be more than 25m h(-1). In addition, preventing homogeneous nucleation in the FBR was an important operation parameter. Homogeneous nucleation and molecular growth would lead to undesirable microparticle formation in the effluent. A good mixture of carbonate and copper in the presence of sand grains could reduce the level of homogeneous nucleation in the bottom of the reactor. Energy dispersive analysis (EDS) of X-rays provided insight into the copper coating on the sand surface, and element analysis indicated the weight percentages of CuCO(3) and Cu(OH)(2) in precipitate.


Assuntos
Cobre/química , Dióxido de Silício/química , Purificação da Água/métodos , Água/química , Carbonatos , Precipitação Química , Concentração de Íons de Hidrogênio , Microscopia Eletrônica de Varredura , Análise Espectral , Purificação da Água/instrumentação
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