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1.
PLoS One ; 18(10): e0293022, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37844120

RESUMO

The development of green finance and the promotion of green transformation and upgrading of high energy-consuming enterprises are of great significance for China to achieve the "double carbon" goal. This paper employs a dual fixed-effects model to examine the profound ramifications and intrinsic mechanisms of green finance development on the transformative innovation of high-energy-consumption enterprises, using a sample of 462 publicly traded high-energy-consuming corporations from the period spanning 2016 to 2020. The results show that the development of green finance promotes the transformation and innovation of energy-intensive enterprises and that market-incentivized environmental regulation plays a partially mediating role; the results of heterogeneity analysis show that green finance promotes the transformation and innovation of high energy-consuming enterprises with significant differences in different low-carbon pilot regions, company ownership, and enterprise size; the mechanism analysis shows that the development of green finance can increase government subsidies and alleviate financing constraints to promote the transformation and innovation of high energy-consuming enterprises; it is also found that the development of green finance can significantly improve the financial performance of enterprises. The research findings of this paper hold significant implications for promoting the sustainable development of green finance and high-energy consumption enterprises in China. They provide valuable insights and references for facilitating the green transformation and innovation of high-energy-consuming enterprises in China as well as other developing countries.


Assuntos
Carbono , Fenômenos Fisiológicos , China , Propriedade , Fenômenos Físicos
2.
Sensors (Basel) ; 23(12)2023 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-37420663

RESUMO

In order to improve the stability and economy of 4WID-4WIS (four-wheel independent drive-four-wheel independent steering) electric vehicles in trajectory tracking, this paper proposes a trajectory tracking coordinated control strategy considering energy consumption economy. First, a hierarchical chassis coordinated control architecture is designed, which includes target planning layer, and coordinated control layer. Then, the trajectory tracking control is decoupled based on the decentralized control structure. Expert PID and Model Predictive Control (MPC) are employed to realize longitudinal velocity tracking and lateral path tracking, respectively, which calculate generalized forces and moments. In addition, with the objective of optimal overall efficiency, the optimal torque distribution for each wheel is achieved using the Mutant Particle Swarm Optimization (MPSO) algorithm. Additionally, the modified Ackermann theory is used to distribute wheel angles. Finally, the control strategy is simulated and verified using Simulink. Comparing the control results of the average distribution strategy and the wheel load distribution strategy, it can be concluded that the proposed coordinated control not only provides good trajectory tracking but also greatly improves the overall efficiency of the motor operating points, which enhances the energy economy and realizes the multi-objective coordinated control of the chassis.


Assuntos
Algoritmos , Fenômenos Fisiológicos , Eletricidade , Fenômenos Físicos , Registros
3.
Food Res Int ; 170: 113027, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37316027

RESUMO

Mercury (Hg) was reported to accumulate in rice grains, and, together with the selenium (Se) was found in rice, the co-exposure of Hg-Se via rice consumption may present significant health effects to human. This research collected rice samples containing high Hg:high Se and high Se:low Hg concentrations from high Hg and high Se background areas. The physiologically based extraction test (PBET) in vitro digestion model was utilized to obtain bioaccessibility data from samples. The results showed relatively low bioaccessible for Hg (<60%) and Se (<25%) in both rice sample groups, and no statistically significant antagonism was identified. However, the correlations of Hg and Se bioaccessibility showed an inverse pattern for the two sample groups. A negative correlation was detected in the high Se background rice group and a positive correlation in the high Hg background group, suggesting various micro forms of Hg and Se in rice from different planting locations. In addition, when the benefit-risk value (BRV) was calculated, some "fake" positive results showed while Hg and Se concentrations were directly used, which indicated that bioaccessibility should not be neglected in benefit-risk assessment.


Assuntos
Mercúrio , Oryza , Fenômenos Fisiológicos , Selênio , Humanos , Ingestão de Alimentos
4.
PLoS One ; 18(6): e0287579, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37352276

RESUMO

Renewable energy holds a remarkable role in clean energy adaptation due to the much lower carbon footprint it releases compared to other fossil fuels. It also has a positive impact by slowing down the rate of climate change. The study has examined the links between renewable and non-renewable energy use, CO2 emissions and economic growth in developed, developing, and LDCs and Economies in Transition between 1990 and 2019 in 152 countries. Granger-causality has been used as the methodology to investigate the link between the variables. The findings of the existing studies on the relationship between the consumption of renewable and non-renewable energy sources and economic growth are inconsistent, indicating that there may or may not be a relationship between the two factors. Apart from having a few empirical studies so far have examined the link between the above-mentioned variables, analysis has yet to encompass all the regions in the four sub-groups discussed above. The results indicated that no Granger-causal relationship exists between GDP and REC outside of Economies in Transition. Additionally, the GDP and CO2 of all countries have a one-way relationship. Nevertheless, research indicates that GDP and CO2 have a bi-directional link in Economies in Transition, a uni-directional relationship in developing countries, and no meaningful association in developed and LDCs. Therefore, it is essential to emphasise actions to lower CO2 emissions and develop renewable energy while also stimulating the economy. Ultimately, more nations should choose renewable energy sources to build a more sustainable future.


Assuntos
Desenvolvimento Econômico , Fenômenos Fisiológicos , Dióxido de Carbono , Junções Comunicantes , Carbono
7.
Rev. bras. cineantropom. desempenho hum ; 20(5): 432-444, Sept.-Oct. 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-977439

RESUMO

The present study aiming to verify the interference of different conditions (treadmill vs. track) on critical velocity (CV) values, as well as on the correlation to the 3000-meter performance (v3000m), and thus infer about the specificity of each values as training parameter for this distance. Seven runners (15.3±1.4 years) were submitted to a maximal progressive test (1.0 km×h-1 increments per minute until exhaustion) to assess V̇O2max and maximal aerobic velocity (vV̇O2max). Subsequently, CV was estimated from three running performances at each test condition, with exercise intensities adjusted for different time limits (tLim) at 900, 2100 and 3300 meters in track or at 90, 95 and 115% of vV̇O2max in treadmill. From linear adjustments, using stepwise method, CV was assessed on treadmill (CVTREADMILL) and track (CVTRACK), and both compared by the Mann-Whitney test. The sample-adjusted dispersion coefficient (R2adj) analyzed the variance of v3000m with CVTRACK, CVTREADMILL and vV̇O2max. In all analyses, significance was set at P≤0.05. In progressive test, V̇O2max reached 54.2±5.2 mLO2×kg-1×min-1 and vV̇O2max reached 16.8±1.9 km×h-1. No differences were observed between CVTREADMILL and CVTRACK (14.0±1.8 vs. 12.3±3.2 km×h-1, P=0.46). Correlations were observed for v3000m with CVTREADMILL (R2adj ~0.94), CVTRACK (R2adj ~0.99) and vV̇O2max (R2adj ~0.90), all showing P=0.001. It could be concluded that no influence was observe on the ability to achieve identical CV values from different assessment conditions. The correlation to the v3000 meters suggested better specificity of CVTRACK than CVTREADMILL for training prescription and performance control.


O presente estudo averiguou se as diferenças nas circunstâncias (esteira vs. pista) de avaliação da velocidade crítica (VC) interferem no valor e na relação com a desempenho em 3000 metros (v3000m) e, assim, indicar a especificidade de cada valor como parâmetro de treinamento para esta distância. Sete corredores (15,3±1,4 anos) submeteram-se a um teste progressivo máximo (incrementos de 1,0 km×h-1×min-1, até a exaustão) para avaliação do V̇O2max e velocidade aeróbia máxima (vV̇O2max). A seguir, a VC foi estimada a partir do desempenho de corrida em três diferentes intensidades do exercício, em cada ambiente de avaliação, registrando-se o tempo-limite (tLim) nas distâncias de 900, 2100 e 3300 metros na pista, e à 90, 95 e 115% vV̇O2max em esteira. Ajustes lineares, pelo método "stepwise", forneceram os parâmetros VC em esteira (VCESTEIRA) e pista (VCPISTA), que foram comparados pelo teste de Mann-Whitney. O coeficiente de dispersão ajustado à amostra (R2aj) averiguou a variância de v3000m com VCPISTA, VCESTEIRA e vV̇O2max. Em todas as análises adotou-se .≤0,05. No teste progressivo, o V̇O2max atingiu 54,2±5,2 mLO2∙kg-1∙min-1 e a vV̇O2max foi 16,8±1,9 km×h-1. Não se observaram diferenças entre VCESTEIRA e VCPISTA (14,0±1,8 vs. 12,3±3,2 km∙h-1, P=0,46). Houveram correlações entre v3000m com VCESTEIRA (R2aj ~0,94), VCPISTA (R2aj~0,99) e vV̇O2max (R2aj ~0,90), todas com P=0,001. Conclui-se que o contexto de avaliação não interfere na consistência do valor de VC. Porém, quanto à relação com v3000 metros, a VCPISTA apresenta melhor especificidade, tornando-a mais autêntica que VCESTEIRA para a prescrição do treino e monitoramento do desempenho.


Assuntos
Humanos , Adolescente , Atletismo , Desempenho Atlético , Fenômenos Fisiológicos , Tolerância ao Exercício , Teste de Esforço
8.
PLoS One ; 13(7): e0199752, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29975779

RESUMO

Physiological processes and gross energy budget of the longline-cultured Pacific oyster Crassostrea gigas were investigated in Geoje-Hansan Bay, Korea during two entire culturing periods. Based on physiological measurements of food consumption, feces production, ammonium excretion, and respiration from July 2008 to February 2009 and from July 2013 to February 2014, scope for growth appeared to be positive during most of the culturing period, except for one period with extremely high temperatures (up to 25°C). Estimates of physiological energy production matched well with tissue energy increment measured by gross biochemical composition during the culturing period, suggesting that the oysters might adjust their physiological performance to relatively low concentrations of suspended particulate matter in the bay to optimize energy acquisition. Such an adaptive adjustment includes an increased absorption of energy and a reduced loss of metabolic and excretory energy, resulting in positive production under high culturing density. Using physiological measurements, we further assessed the feedback effects of the longline aquaculture of oysters on the bay system. Ecological efficiency, estimated by a series of energetic efficiencies at the whole bay level, was low compared with Lindeman's law of trophic efficiency. Biodeposition and ammonia excretion rates in this study were relatively low compared with other intertidal plastic bag cultures. These results indicate that the cultured oysters might have only minor effects on benthic and pelagic environments of the bay. Overall, our results suggest that the adaptive physiological performance of oysters and consequently weak feedback effects on ambient habitats should facilitate sustainable longline aquaculture in the bay for a prolonged period without severe habitat deterioration.


Assuntos
Adaptação Fisiológica/fisiologia , Crassostrea/fisiologia , Ecossistema , Fenômenos Fisiológicos , Amônia/análise , Animais , Metabolismo Energético , Fezes/química , Respiração
9.
Drug Metab Pharmacokinet ; 33(1): 40-42, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29217459

RESUMO

Microphysiological systems (MPS) are currently attracting a lot of interest from pharmaceutical companies worldwide. In the United States and European Union, several large government projects related to MPS have been initiated, and, in Japan, pharmaceutical companies interested in MPS are watching the recent trends and developments in the field. In July 2017, the Japan Agency for Medical Research and Development initiated a research program to develop chip-based MPS. In this review, we examine the technical aspects of commercializing chip-based MPS.


Assuntos
Avaliação Pré-Clínica de Medicamentos/métodos , Indústria Farmacêutica/tendências , Preparações Farmacêuticas/metabolismo , Fenômenos Fisiológicos/fisiologia , Análise Serial de Proteínas/tendências , Indústria Farmacêutica/métodos , Humanos , Preparações Farmacêuticas/administração & dosagem , Fenômenos Fisiológicos/efeitos dos fármacos , Análise Serial de Proteínas/métodos
10.
Clin Pharmacol Ther ; 102(1): 98-105, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-27770430

RESUMO

Physiologically based pharmacokinetic (PBPK) modeling is a valuable tool in drug development and regulatory assessment, as it offers the opportunity to simulate the pharmacokinetics of a compound, with a mechanistic understanding, in a variety of populations and situations. This work reviews the use and impact of such modeling in selected regulatory procedures submitted to the European Medicines Agency (EMA) before the end of 2015, together with its subsequent reflection in public documents relating to the assessment of these procedures. It is apparent that the reference to PBPK modeling in regulatory public documents underrepresents its use. A positive trend over time of the number of PBPK models submitted is shown, and in a number of cases the results of these may impact the decision-making process or lead to recommendations in the product labeling. These results confirm the need for regulatory guidance in this field, which is currently under development by the EMA.


Assuntos
Desenvolvimento de Medicamentos , Controle de Medicamentos e Entorpecentes , Modelos Biológicos , Farmacocinética , Desenvolvimento de Medicamentos/métodos , Desenvolvimento de Medicamentos/normas , Controle de Medicamentos e Entorpecentes/métodos , Controle de Medicamentos e Entorpecentes/organização & administração , Europa (Continente) , Órgãos Governamentais , Humanos , Avaliação das Necessidades , Fenômenos Fisiológicos/efeitos dos fármacos , Formulação de Políticas
11.
PLoS One ; 11(12): e0168753, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28005994

RESUMO

Do scaling relations always provide the means to anticipate the relationships between the size of cities, costs of maintenance, and the socio-economic benefits resulting from their growth? Scaling laws are considered a universal principle that describes the development of complex systems such as cities. It seems that regardless of their location or history, the growth of cities is associated with the super-linear or sublinear scaling of features such as the amount of space required, infrastructure, or human activities. However, the results of our research, based on grouping by Self-Organizing Maps, reveal some limitations in the application of scaling laws: the trends of urban growth behave in a different manner when we consider both a large and diverse collection of cities and a subset of cities alike. This finding complements the existing body of knowledge on the growth of cities and allows for a more accurate prediction of their future.


Assuntos
Cidades/legislação & jurisprudência , Geografia/legislação & jurisprudência , Redes Neurais de Computação , Densidade Demográfica , População Urbana/estatística & dados numéricos , Algoritmos , Fenômenos Biológicos , Atividades Humanas , Humanos , Fenômenos Fisiológicos , Fatores Socioeconômicos
12.
J Pharmacokinet Pharmacodyn ; 43(4): 427-46, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27377311

RESUMO

Accurate prediction of the clinical pharmacokinetics of new therapeutic entities facilitates decision making during drug discovery, and increases the probability of success for early clinical trials. Standard strategies employed for predicting the pharmacokinetics of small-molecule drugs (e.g., allometric scaling) are often not useful for predicting the disposition monoclonal antibodies (mAbs), as mAbs frequently demonstrate species-specific non-linear pharmacokinetics that is related to mAb-target binding (i.e., target-mediated drug disposition, TMDD). The saturable kinetics of TMDD are known to be influenced by a variety of factors, including the sites of target expression (which determines the accessibility of target to mAb), the extent of target expression, the rate of target turnover, and the fate of mAb-target complexes. In most cases, quantitative information on the determinants of TMDD is not available during early phases of drug discovery, and this has complicated attempts to employ mechanistic mathematical models to predict the clinical pharmacokinetics of mAbs. In this report, we introduce a simple strategy, employing physiologically-based modeling, to predict mAb disposition in humans. The approach employs estimates of inter-antibody variability in rate processes of extravasation in tissues and fluid-phase endocytosis, estimates for target concentrations in tissues derived through use of categorical immunohistochemical scores, and in vitro measures of the turnover of target and target-mAb complexes. Monte Carlo simulations were performed for four mAbs (cetuximab, figitumumab, dalotuzumab, trastuzumab) directed against three targets (epidermal growth factor receptor, insulin-like growth factor receptor 1, human epidermal growth factor receptor 2). The proposed modeling strategy was able to predict well the pharmacokinetics of cetuximab, dalotuzumab, and trastuzumab at a range of doses, but trended towards underprediction of figitumumab concentrations, particularly at high doses. The general agreement between model predictions and experimental observations suggests that PBPK modeling may be useful for the a priori prediction of the clinical pharmacokinetics of mAb therapeutics.


Assuntos
Anticorpos Monoclonais/farmacocinética , Modelos Biológicos , Fenômenos Fisiológicos , Anticorpos Monoclonais/administração & dosagem , Simulação por Computador , Endocitose/fisiologia , Humanos , Método de Monte Carlo , Especificidade de Órgãos/fisiologia , Farmacologia Clínica , Pinocitose/fisiologia , Distribuição Tecidual/fisiologia
13.
Soc Sci Med ; 150: 221-30, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26773705

RESUMO

Given documented links between individual socioeconomic status (SES) and health, it is likely that-in addition to its impacts on individuals' wallets and bank accounts-the Great Recession also took a toll on individuals' disease and mortality risk. Exploiting a quasi-natural experiment design, this study utilizes nationally representative, longitudinal data from the National Social Life, Health, and Aging Project (NSHAP) (2005-2011) (N = 930) and individual fixed effects models to examine how household-level wealth shocks experienced during the Great Recession relate to changes in biophysiological functioning in older adults. Results indicate that wealth shocks significantly predicted changes in physiological functioning, such that losses in net worth from the pre-to the post-Recession period were associated with increases in systolic blood pressure and C-reactive protein over the six year period. Further, while the association between wealth shocks and changes in blood pressure was unattenuated with the inclusion of other indicators of SES, psychosocial well-being, and health behaviors in analytic models, we document some evidence of mediation in the association between changes in wealth and changes in C-reactive protein, which suggests specificity in the social and biophysiological mechanisms relating wealth shocks and health at older ages. Linking macro-level conditions, meso-level household environments, and micro-level biological processes, this study provides new insights into the mechanisms through which economic inequality contributes to disease and mortality risk in late life.


Assuntos
Recessão Econômica/estatística & dados numéricos , Comportamentos Relacionados com a Saúde , Nível de Saúde , Fenômenos Fisiológicos , Pobreza/economia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Proteína C-Reativa/análise , Proteína C-Reativa/fisiologia , Feminino , Humanos , Masculino
14.
PLoS One ; 9(6): e98529, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24896085

RESUMO

Size-dependent mortality influences the recolonization success of juvenile corals transplanted for reef restoration and assisting juvenile corals attain a refuge size would thus improve post-transplantation survivorship. To explore colony size augmentation strategies, recruits of the scleractinian coral Pocillopora damicornis were fed with live Artemia salina nauplii twice a week for 24 weeks in an ex situ coral nursery. Fed recruits grew significantly faster than unfed ones, with corals in the 3600, 1800, 600 and 0 (control) nauplii/L groups exhibiting volumetric growth rates of 10.65 ± 1.46, 4.69 ± 0.9, 3.64 ± 0.55 and 1.18 ± 0.37 mm3/week, respectively. Corals supplied with the highest density of nauplii increased their ecological volume by more than 74 times their initial size, achieving a mean final volume of 248.38 ± 33.44 mm3. The benefits of feeding were apparent even after transplantation to the reef. The corals in the 3600, 1800, 600 and 0 nauplii/L groups grew to final sizes of 4875 ± 260 mm3, 2036 ± 627 mm3, 1066 ± 70 mm3 and 512 ± 116 mm3, respectively. The fed corals had significantly higher survival rates than the unfed ones after transplantation (63%, 59%, 56% and 38% for the 3600, 1800, 600 and 0 nauplii/L treatments respectively). Additionally, cost-effectiveness analysis revealed that the costs per unit volumetric growth were drastically reduced with increasing feed densities. Corals fed with the highest density of nauplii were the most cost-effective (US$0.02/mm3), and were more than 12 times cheaper than the controls. This study demonstrated that nutrition enhancement can augment coral growth and post-transplantation survival, and is a biologically and economically viable option that can be used to supplement existing coral mariculture procedures and enhance reef restoration outcomes.


Assuntos
Antozoários/crescimento & desenvolvimento , Recifes de Corais , Fenômenos Fisiológicos/fisiologia , Animais , Análise Custo-Benefício
15.
Zhongguo Yi Liao Qi Xie Za Zhi ; 38(2): 84-7, 2014 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-24941767

RESUMO

In order to meet the requirements of the multi-physiological signal measurement of the 3D-TV health assessment, try to find the suitable biological acquisition chips and design the hardware system which can detect different physiological signals in real time. The systems mainly uses ARM11/S3C6410 microcontroller to control the EEG/EOG acquisition chip RHA2116 and the ECG acquisition chip ADS1298, and then the microcontroller transfer the data collected by the chips to the PC software by the USB port which can display and save the experimental data in real time, then use the Matlab software for further processing of the data, finally make a final health assessment. In the meantime, for the different varieties in the different brain regions of watching 3D-TV, developed the special brain electrode placement and the experimental data processing methods, then effectively disposed the multi-signal data in the multilevel.


Assuntos
Simulação por Computador , Fenômenos Fisiológicos , Processamento de Sinais Assistido por Computador/instrumentação , Desenho de Equipamento , Microcomputadores , Software
16.
Biotechnol Prog ; 30(3): 689-99, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24616429

RESUMO

Optimization of productivity and economics of industrial bioprocesses requires characterization of interdependencies between process parameters and process performance. In the case of penicillin production, as in other processes, process performance is often closely interlinked with the physiology and morphology of the organism used for production. This study presents a systematic approach to efficiently characterize the physiological effects of multivariate interdependencies between bioprocess design parameters (spore inoculum concentration, pO2 control level and substrate feed rate), morphology, and physiology. Method development and application was performed using the industrial model process of penicillin production. Applying traditional, statistical bioprocess analysis, multivariate correlations of raw bioprocess design parameters (high spore inoculum concentration, low pO2 control as well as reduced glucose feeding) and pellet morphology were identified. A major drawback of raw design parameter correlation models; however, is the lack of transferability across different process scales and regimes. In this context, morphological and physiological bioprocess modeling based on scalable physiological parameters is introduced. In this study, raw parameter effects on pellet morphology were efficiently summarized by the physiological parameter of the biomass yield per substrate. Finally, for the first time to our knowledge, the specific growth rate per spore was described as time-independent determinant for switching from pellet to disperse growth during penicillin production and thus introduced as a novel, scalable key process parameter for pellet morphology and process performance.


Assuntos
Reatores Biológicos , Penicilinas/biossíntese , Fenômenos Fisiológicos , Técnicas de Cultura Celular por Lotes , Biomassa , Microbiologia Industrial/economia , Microbiologia Industrial/métodos , Modelos Teóricos , Penicilinas/química
17.
Br J Math Stat Psychol ; 67(1): 94-116, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23432382

RESUMO

Multi-group latent growth modelling in the structural equation modelling framework has been widely utilized for examining differences in growth trajectories across multiple manifest groups. Despite its usefulness, the traditional maximum likelihood estimation for multi-group latent growth modelling is not feasible when one of the groups has no response at any given data collection point, or when all participants within a group have the same response at one of the time points. In other words, multi-group latent growth modelling requires a complete covariance structure for each observed group. The primary purpose of the present study is to show how to circumvent these data problems by developing a simple but creative approach using an existing estimation procedure for growth mixture modelling. A Monte Carlo simulation study was carried out to see whether the modified estimation approach provided tangible results and to see how these results were comparable to the standard multi-group results. The proposed approach produced results that were valid and reliable under the mentioned problematic data conditions. We also present a real data example and demonstrate that the proposed estimation approach can be used for the chi-square difference test to check various types of measurement invariance as conducted in a standard multi-group analysis.


Assuntos
Simulação por Computador , Modelos Estatísticos , Método de Monte Carlo , Humanos , Funções Verossimilhança , Fenômenos Fisiológicos
18.
Microbiologyopen ; 2(3): 402-14, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23520129

RESUMO

Despite the recent and significant increase in the study of aquatic microbial communities, little is known about the microbial diversity of complex ecosystems such as running waters. This study investigated the biodiversity of biofilm communities formed in a river with 454 Sequencing™. This river has the particularity of integrating both organic and microbiological pollution, as receiver of agricultural pollution in its upstream catchment area and urban pollution through discharges of the wastewater treatment plant of the town of Billom. Different regions of the small subunit (SSU) ribosomal RNA gene were targeted using nine pairs of primers, either universal or specific for bacteria, eukarya, or archaea. Our aim was to characterize the widest range of rDNA sequences using different sets of polymerase chain reaction (PCR) primers. A first look at reads abundance revealed that a large majority (47-48%) were rare sequences (<5 copies). Prokaryotic phyla represented the species richness, and eukaryotic phyla accounted for a small part. Among the prokaryotic phyla, Proteobacteria (beta and alpha) predominated, followed by Bacteroidetes together with a large number of nonaffiliated bacterial sequences. Bacillariophyta plastids were abundant. The remaining bacterial phyla, Verrucomicrobia and Cyanobacteria, made up the rest of the bulk biodiversity. The most abundant eukaryotic phyla were annelid worms, followed by Diatoms, and Chlorophytes. These latter phyla attest to the abundance of plastids and the importance of photosynthetic activity for the biofilm. These findings highlight the existence and plasticity of multiple trophic levels within these complex biological systems.


Assuntos
Archaea/classificação , Bactérias/classificação , Biofilmes/crescimento & desenvolvimento , Biota , Eucariotos/classificação , Rios/microbiologia , Rios/parasitologia , Archaea/genética , Bactérias/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Eucariotos/genética , França , Genes de RNAr , Fenômenos Fisiológicos , Análise de Sequência de DNA
20.
Biopharm Drug Dispos ; 33(2): 111-21, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22383166

RESUMO

PURPOSE: A case example is presented in which the physiologically based modeling approach has been used to model the absorption of a lipophilic BCS Class II compound predominantly metabolized by CYP3A4, and to assess the interplay of absorption related parameters with the drug-drug interaction (DDI) potential. METHODS: The PBPK model was built in the rat using Gastroplus® to study the absorption characteristics of the compound. Subsequently relevant model parameters were used to predict the non-linear human PK observed during first-in-human study after optimizing the absorption model for colonic absorption, bile micelle solubilization and unbound fraction in gut enterocytes (fu(gut)) using SIMCYP® simulator. The model fitted absorption parameters were then used to assess the drug-drug interaction (DDI) potential of the test compound when administered along with multiple doses of a potent CYP 3A4 inhibitor, ketoconazole. The impact of fu(gut) in the extent of DDI was assessed using parameter sensitivity analysis. RESULTS AND CONCLUSIONS: After optimizing the preclinical model and taking into consideration bile micelle solubilization and colonic absorption, the non-linear pharmacokinetics of the test compound was satisfactorily predicted in man. Sensitivity analysis performed with the absorption parameter fu(gut) indicated that it could be an important parameter in predicting oral absorption. In addition, DDI simulations using SIMCYP® suggest that C(max) and AUC ratios may also be sensitive to the fu(gut) input in the model. Since fu(gut) cannot be measured experimentally, sensitivity analysis may help in assessing the importance of fu(gut) in human PK and DDI prediction using SIMCYP®.


Assuntos
Indústria Farmacêutica/tendências , Interações Medicamentosas/fisiologia , Modelos Biológicos , Preparações Farmacêuticas/metabolismo , Software/tendências , Fluxo de Trabalho , Absorção/efeitos dos fármacos , Absorção/fisiologia , Administração Oral , Animais , Indústria Farmacêutica/métodos , Previsões , Humanos , Preparações Farmacêuticas/administração & dosagem , Fenômenos Fisiológicos/efeitos dos fármacos , Fenômenos Fisiológicos/fisiologia , Ratos
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