Análise conformacional e determinação de descritores quânticos de adutos de Baylis-Hillman com propriedades antineoplásicas por métodos AM1 e HF/6-31G

Adutos de Baylis-Hillman derivados do 2-[fenil(hidroxi)metil]acrilato de metila (1) são compostoscom conhecida atividade antineoplásica. Neste trabalho, são apresentados os resultados de análiseconformacional e cálculo dos descritores quânticos do 1 e dez derivados aril-substituídos, obtidos pelosmétodos de orbital molecular semi-empírico AM1 e ab initio HF/6-31G*, para posterior estudo deQSAR. Foram calculados o calor de formação, a energia total, as energias dos OMF, o momento dedipolo e as cargas parciais sobre os átomos do sistema carbonilado a,b-insaturado. A partir das energiasde HOMO e LUMO, foram estimados o potencial químico, a dureza e a eletrofilicidade. Os resultadosmostram que os aductos estudados apresentam baixa dureza, baixo potencial químico e alta eletrofilicidade.Palavras-chave: modelagem molecular, HF/6-31G*, AM1, Baylis-Hillman, QSAR

Synthesis of polyimides from α,αʹ-bis(3-aminophenoxy)-p-xylene: Spectroscopic, single crystal XRD and thermal studies

The final publication is available at Elsevier via http://dx.doi.org/10.1016/j.molstruc.2018.01.098 © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/The meta-catenated ether-based diamine monomer α,αʹ-bis(3-aminophenoxy)-p-xylene (3APX) was synthesized from dinitro precursor α,αʹ-bis(3-nitrophenoxy)-p-xylene (3NPX). FTIR, 1H and 13C NMR spectroscopic studies accompanied by elemental analysis were performed for structural elucidations of 3NPX and 3APX. The spatial orientations of 3APX were explored by single crystal X-ray diffraction analysis. Its crystal system was found to be monoclinic, adopting the space group P21/c. The synthesized diamine monomer (3APX) was used for preparation of new series of polyimides by reacting with three different dianhydrides (BTDA, ODPA, 6FDA). The relevant copolyimides were developed via incorporation of 4,4ʹ-methylenedianiline (MDA) in the backbone of afore-synthesized polyimides. The structures of polyimides and copolyimides were verified by FTIR and 1H NMR spectroscopic techniques. Their properties were evaluated by dynamic and isothermal TGA (nitrogen and air atmospheres) and WAXRD studies. Polyimides displayed significantly high thermal stability as their degradation started around 400 °C and it was improved further by execution of copolymerization strategy with MDA. The 5% weight loss temperature (T5) of polyimides under nitrogen atmosphere was in the range of 425–460 °C while for copolyimides it increased to 454–498 °C. Thermal decomposition in air was slower than nitrogen between 400 and 550 °C however it was accelerated above 550 °C. Isothermal TGA disclosed that copolyimides have the ability to endure elevated temperatures for extended period. WAXRD analysis showed the amorphous nature of polyimides and copolyimides.Indigenous 5000 Ph.D. Fellowship Program (Phase II)International Research Support Initiative Program (IRSIP)Quaid-i-Azam University, Pakistan under University Research Fund (URF)University of Waterloo, Canada under Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Gran

Test 1157: John Deere 2630 and 2640 Diesel

EXPLANATION OF TEST REPORT GENERAL CONDITIONS East tractor is a production model equipped for common usage. Power consuming accessories can be disconnected only when it is convenient for the operator to do so in practice. Additional weight can be added as ballast if the manufacturer regularly supplies it for sale. The static tire loads and the inflation pressures muse conform to recommendations in the Tire Standards published by the Society of Automotive Engineers. PREPARATION FOR PERFORMANCE RUNS The engine crank case is drained and refilled with a measured amount of new oil conforming to specifications in the operator’s manual. The fuel used and the maintenance operations must also conform to the published information delivered with the tractor. The tractor is then limbered-up for 1 hour on drawbar work in accordance with the manufacturers published recommendations. The manufacturer’s representative is present to make appropriate decisions regarding mechanical adjustments. The tractor is equipped with approximately the amount of added ballast that is used during maximum drawbar tests. The tire tread-bar height must be at least 65% of new tread height prior to the maximum power run. BELT OR POWER TAKE-OFF PERFORMANCE Maximum Power and Fuel Consumption. The manufacturer’s representative makes carburetor, fuel pump, ignition and governor control settings which remain unchanged throughout tall subsequent runs. The governor and the manually operated governor control lever is set to provide the high-idle speed specified by the manufacturer for maximum power. Maximum power is measured by connecting the belt pulley or the power take-off to a dynamometer. The dynamometer load is then gradually increased until the engine is operating at the rated speed specified by the manufacturer for maximum power. The corresponding fuel consumption is measured. Varying Power and Fuel Consumption. Six different horsepower levels are used to show corresponding fuel consumption rates and how the governor causes the engine to react to the following changes in dynamometer load: 85% of the dynamometer torque at maximum power; minimum dynamometer torque, ½ the 85% torque; maximum power; ¼ and ¾ of the 85% torque. Since at tractor is generally subjected to varying loads the average of the results in this test serve well for predicting the fuel consumption of a tractor in general usage. DRAWBAR PERFORMANCE All engine adjustments are the same as those used in the belt or power take-off tests. If the manufacturer specifies a different rated crankshaft speed for drawbar operations, then the position of the manually operated governor control is changed to provide the high-idle speed specified by the manufacturer in the operating instructions. Varying Power and Fuel Consumption With Ballast. The varying power runs are made to show the effect of speed-control devices (engine governor, automatic transmissions, etc.) on horsepower, speed and fuel consumption. These runs are made around the entire test course with has two 180 degree turns with a minimum radius of 50 feet. The drawbar pull is set at 3 different levels as follows: (1) as near to the pull a maximum power as possible and still have the tractor maintain the travel speed at maximum horsepower on the straight sections of the test course; (2) 75% of the pull at maximum power; and (3) 50% of the pull at maximum power. Prior to 1958, fuel consumption data (10 hour test) were shown only for the pull obtained at maximum power for tractors having torque converters and at 75% of the pull obtained at maximum power for gear-type tractors. Maximum Power With Ballast. Maximum power is measured on straight level sections of the test course. Data are shown for not more that 12 different gears or travel speeds. Some gears or travel speeds may be omitted because of high slippage of the traction members or because the travel speed may exceed the safe-limit for the test course. The maximum safe speed for the Nebraska Test course has been set at 15 miles per hour. The slippage limits have been set at 15% and 7% for pneumatic tires and steel tracks or lugs, respectively. Higher slippage gives widely varying results. Maximum Power Without Ballast. All added ballast is removed from the tractor. The maximum drawbar power of the tractor is determined by the same procedure used for getting maximum power with ballast. The gear (or travel speed) is the same as that used in the 10-hours test. Varying Power and Travel Speed With Ballast. Travel speeds corresponding to drawbar pulls beyond the maximum power range are obtained to show the “lugging ability” of the tractor. The run starts with the pull at maximum power; then additional drawbar pull is applied to cause decreasing speeds. The run is ended by one of three conditions; (1) maximum pull is obtained, (2) the maximum slippage limit is reached, or (3) some other operating limit is reached

Genetic control of mRNA splicing as a potential mechanism for incomplete penetrance of rare coding variants

Exonic variants present some of the strongest links between genotype and phenotype. However, these variants can have significant inter-individual pathogenicity differences, known as variable penetrance. In this study, we propose a model where genetically controlled mRNA splicing modulates the pathogenicity of exonic variants. By first cataloging exonic inclusion from RNA-sequencing data in GTEx V8, we find that pathogenic alleles are depleted on highly included exons. Using a large-scale phased whole genome sequencing data from the TOPMed consortium, we observe that this effect may be driven by common splice-regulatory genetic variants, and that natural selection acts on haplotype configurations that reduce the transcript inclusion of putatively pathogenic variants, especially when limiting to haploinsufficient genes. Finally, we test if this effect may be relevant for autism risk using families from the Simons Simplex Collection, but find that splicing of pathogenic alleles has a penetrance reducing effect here as well. Overall, our results indicate that common splice-regulatory variants may play a role in reducing the damaging effects of rare exonic variants.</p

Genetic control of mRNA splicing as a potential mechanism for incomplete penetrance of rare coding variants

Exonic variants present some of the strongest links between genotype and phenotype. However, these variants can have significant inter-individual pathogenicity differences, known as variable penetrance. In this study, we propose a model where genetically controlled mRNA splicing modulates the pathogenicity of exonic variants. By first cataloging exonic inclusion from RNA-sequencing data in GTEx V8, we find that pathogenic alleles are depleted on highly included exons. Using a large-scale phased whole genome sequencing data from the TOPMed consortium, we observe that this effect may be driven by common splice-regulatory genetic variants, and that natural selection acts on haplotype configurations that reduce the transcript inclusion of putatively pathogenic variants, especially when limiting to haploinsufficient genes. Finally, we test if this effect may be relevant for autism risk using families from the Simons Simplex Collection, but find that splicing of pathogenic alleles has a penetrance reducing effect here as well. Overall, our results indicate that common splice-regulatory variants may play a role in reducing the damaging effects of rare exonic variants.</p