Homology modeling and metabolism prediction of human carboxylesterase-2 using docking analyses by GriDock: a parallelized tool based on AutoDock 4.0.

Metabolic problems lead to numerous failures during clinical trials, and much effort is now devoted to developing in silico models predicting metabolic stability and metabolites. Such models are well known for cytochromes P450 and some transferases, whereas less has been done to predict the activity of human hydrolases. The present study was undertaken to develop a computational approach able to predict the hydrolysis of novel esters by human carboxylesterase hCES2. The study involved first a homology modeling of the hCES2 protein based on the model of hCES1 since the two proteins share a high degree of homology (congruent with 73%). A set of 40 known substrates of hCES2 was taken from the literature; the ligands were docked in both their neutral and ionized forms using GriDock, a parallel tool based on the AutoDock4.0 engine which can perform efficient and easy virtual screening analyses of large molecular databases exploiting multi-core architectures. Useful statistical models (e.g., r (2) = 0.91 for substrates in their unprotonated state) were calculated by correlating experimental pK(m) values with distance between the carbon atom of the substrate's ester group and the hydroxy function of Ser228. Additional parameters in the equations accounted for hydrophobic and electrostatic interactions between substrates and contributing residues. The negatively charged residues in the hCES2 cavity explained the preference of the enzyme for neutral substrates and, more generally, suggested that ligands which interact too strongly by ionic bonds (e.g., ACE inhibitors) cannot be good CES2 substrates because they are trapped in the cavity in unproductive modes and behave as inhibitors. The effects of protonation on substrate recognition and the contrasting behavior of substrates and products were finally investigated by MD simulations of some CES2 complexes.

MoniTo 4.0, una herramienta de monitorización de clusters

La herramienta de monitorización de clusters MoniTo debe estar preparada ante los constantes cambios en el kernel de Linux que la pudieran dejar inutilizable. Para evitarlo se ha modificado su implementación utilizando librerías Libgtop. También se ha modificado su interfaz web para adaptarla a los nuevos tiempos, optimizar su funcionamiento y dotarla de nuevas posibilidades.

The Brief Psychiatric Rating Scale (version 4.0) factorial structure and its sensitivity in the treatment of outpatients with unipolar depression.

The 24-item Brief Psychiatric Rating Scale (BPRS, version 4.0) enables the rater to measure psychopathology severity. Still, little is known about the BPRS's reliability and validity outside of the psychosis spectrum. The aim of this study was to examine the factorial structure and sensitivity to change of the BPRS in patients with unipolar depression. Two hundred and forty outpatients with unipolar depression were administered the 24-item BPRS. Assessments were conducted at intake and at post-treatment in a Crisis Intervention Centre. An exploratory factor analysis of the 24-item BPRS produced a six-factor solution labelled "Mood disturbance", "Reality distortion", "Activation", "Apathy", "Disorganization", and "Somatization". The reduction of the total BPRS score and dimensional scores, except for "Activation", indicates that the 24-item BPRS is sensitive to change as shown in patients that appeared to have benefited from crisis treatment. The findings suggest that the 24-item BPRS could be a useful instrument to measure symptom severity and change in symptom status in outpatients presenting with unipolar depression.

Simulação das perdas de água por evaporação e arraste, no aspersor NY-7 (4,6 mm x 4,0 mm), em sistemas de aspersão convencional

As perdas de água por evaporação e arraste em sistemas de irrigação por aspersão podem assumir valores consideráveis, reduzindo a eficiência do sistema. Os objetivos do presente trabalho foram avaliar a capacidade preditiva de cinco modelos empíricos para estimar perdas de água por evaporação e arraste em aspersores modelo NY-7 (bocais de 4,6 mm x 4,0 mm), trabalhando sob diferentes condições operacionais e ambientais, e ajustar modelos específicos para o aspersor NY-7. Comparando os resultados medidos em ensaios de campo, com os resultados simulados, foi possível concluir que os cinco modelos empíricos considerados apresentaram pouca ou nenhuma adequação, tanto para os ensaios com um único aspersor (quadrado do erro-médio de 5,27; 20,70; 5,07; 6,95 e 7,06% para os modelos empíricos 1; 2; 3; 4 e 5, respectivamente) quanto para os ensaios com linhas laterais contendo aspersores (quadrado do erro-médio de 7,41; 24,43; 6,72; 3,16 e 2,9% para os modelos empíricos 1; 2; 3; 4 e 5, respectivamente). Comparados aos cinco modelos empíricos considerados, os novos modelos ajustados apresentaram menores erros, indicando que a aplicação de modelos empíricos deve ser limitada às condições de operação (diâmetro de bocal, pressão de operação, etc.) similares àquelas em que os modelos foram desenvolvidos.

Estudo experimental comparando o uso do 2-octil cianoAcrilato ao nylon 4-0 na sutura da pele

OBJETIVO: Comparar o 2-octil cianoacrilato com o fio de "nylon" no fechamento da pele em ratos. MÉTODOS: Vinte e cinco ratos da linhagem Wistar, foram submetidos à incisão de 3 cm de cada lado do abdome. A síntese foi feita utilizando em um dos lados o "nylon" 4.0, pontos intradérmicos, e do outro o 2-octil cianoacrilato. Após sete dias, o fio foi removido e as incisões, analisadas quanto às complicações. Após 40 dias, o resultado da cicatriz foi avaliado. Os ratos foram sacrificados, as cicatrizes foram ressecadas, fixadas e enviadas ao patologista, sem informação sobre qual o método utilizado. RESULTADOS: Houve dois óbitos durante a anestesia e um tardio. O tempo de operação foi de 136 segundos com a cola e 176 segundos, com o "nylon" (P=0,003). Dentre as 50 operações realizadas, as complicações foram: um hematoma com cada método (P=0,80), quinze deiscências da cola contra 11 do "nylon" (P=0,20), sete cicatrizes de aspecto ruim ou razoável da cola contra quatro do "nylon" (P=0,30), três infecções na cola contra duas (P=0,40). Ao exame patológico, a mediana da largura da cicatriz foi de 1.119 micra com a cola e 1.800 com o "nylon" (P=0,40). A espessura foi de 1.795 contra 1.705 micra (P=0,40). CONCLUSÃO: O 2-octil cianoacrilato apresentou o mesmo aspecto cicatricial, a mesma resistência e as mesmas complicações que a sutura com o "nylon" 4.0, porém permitindo redução no tempo cirúrgico.

Fedora 4.0 Deep Dive

Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

AOD 2.0: A category based submission add-on for DSpace 4.0

Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

The Met Office unified model global atmosphere 4.0 and JULES global land 4.0 configurations

We describe Global Atmosphere 4.0 (GA4.0) and Global Land 4.0 (GL4.0): configurations of the Met Office Unified Model and JULES (Joint UK Land Environment Simulator) community land surface model developed for use in global and regional climate research and weather prediction activities. GA4.0 and GL4.0 are based on the previous GA3.0 and GL3.0 configurations, with the inclusion of developments made by the Met Office and its collaborators during its annual development cycle. This paper provides a comprehensive technical and scientific description of GA4.0 and GL4.0 as well as details of how these differ from their predecessors. We also present the results of some initial evaluations of their performance. Overall, performance is comparable with that of GA3.0/GL3.0; the updated configurations include improvements to the science of several parametrisation schemes, however, and will form a baseline for further ongoing development.

Entity Framework 4.0, enutvärdering av ett ORMramverk

När man kombinerar ett objektorienterat programmeringsspråk och en relationsdatabas uppstår en del problem för utvecklare eftersom objektorienterade programmeringsspråk och relationsdatabaser har olika fokus, objektorienterade programmeringsspråk fokuserar på att avbilda verkliga objekt och relationsdatabaser fokuserar på data. De problem som uppstår kallas med ett samlingsnamn för object-relational mismatch. Det finns flertalet ramverk för att hantera dessa problem. Ett av dem är Entity Framework.Syftet med detta projekt var att utvärdera hur utvecklare tycker att Entity Framework fungerar för att lösa problematiken runt object-relational mismatch, hur det är för utvecklare att lära sig använda Entity Framework samt hur tillgången på inlärningsmaterial är.Under vår studie har vi lärt oss använda Entity Framework samtidigt som vi gjort en studie av tillgången på inlärningsmaterial. Vi har också byggt om en applikation så att den använder Entity Framework. Vi har jämfört den ombyggda applikationen med den gamla applikationen för att kunna se vilken skillnad som Entity Framework bidrog till.Vi kom fram till att Entity Framework hanterar object-relational mismatch på ett bra sätt som bland annat gör att utvecklingsprocessen kortas ner då inte lika mycket kod behöver skrivas. Utvecklare med tidigare kunskaper i .NET-programmering upplever att det är lätt att lära sig Entity Framework. Att det upplevs lätt att lära sig Entity Framework hänger förmodligen ihop med att tillgången på inlärningsmaterial är god.

GDP 4.0 transfer to SGP 3.0 for SCIAMACHY no2 column processing: Verification with SDOAS / GDOAS prototype algorithms and delta-validation with NDACC / UV-visible network data

Until mid 2006, SCIAMACHY data processors for the operational retrieval of nitrogen dioxide (NO2) column data were based on the historical version 2 of the GOME Data Processor (GDP). On top of known problems inherent to GDP 2, ground-based validations of SCIAMACHY NO2 data revealed issues specific to SCIAMACHY, like a large cloud-dependent offset occurring at Northern latitudes. In 2006, the GDOAS prototype algorithm of the improved GDP version 4 was transferred to the off-line SCIAMACHY Ground Processor (SGP) version 3.0. In parallel, the calibration of SCIAMACHY radiometric data was upgraded. Before operational switch-on of SGP 3.0 and public release of upgraded SCIAMACHY NO2 data, we have investigated the accuracy of the algorithm transfer: (a) by checking the consistency of SGP 3.0 with prototype algorithms; and (b) by comparing SGP 3.0 NO2 data with ground-based observations reported by the WMO/GAW NDACC network of UV-visible DOAS/SAOZ spectrometers. This delta-validation study concludes that SGP 3.0 is a significant improvement with respect to the previous processor IPF 5.04. For three particular SCIAMACHY states, the study reveals unexplained features in the slant columns and air mass factors, although the quantitative impact on SGP 3.0 vertical columns is not significant.

Características principais de pacientes com PSA menor ou igual a 4,0 ng/ml, submetidos à biópsia de próstata guiada pelo ultrassom transretal

Pós-graduação em Bases Gerais da Cirurgia - FMB

Análise da resposta dielétrica e varistora de compostos cerâmicos multifásicos à base de Ca2CU2Ti4-xSnxO12 (0,0 < x< 4,0)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)