2D QSAR and similarity studies on cruzain inhibitors aimed at improving selectivity over cathepsin L

Hologram quantitative structure-activity relationships (HQSAR) were applied to a data set of 41 cruzain inhibitors. The best HQSAR model (Q(2) = 0.77; R-2 = 0.90) employing Surflex-Sim, as training and test sets generator, was obtained using atoms, bonds, and connections as fragment distinctions and 4-7 as fragment size. This model was then used to predict the potencies of 12 test set compounds, giving satisfactory predictive R-2 value of 0,88. The contribution maps obtained from the best HQSAR model are in agreement with the biological activities of the study compounds. The Trypanosoma cruzi cruzain shares high similarity with the mammalian homolog cathepsin L. The selectivity toward cruzam was checked by a database of 123 compounds, which corresponds to the 41 cruzain inhibitors used in the HQSAR model development plus 82 cathepsin L inhibitors. We screened these compounds by ROCS (Rapid Overlay of Chemical Structures), a Gaussian-shape volume overlap filter that can rapidly identify shapes that match the query molecule. Remarkably, ROCS was able to rank the first 37 hits as being only cruzain inhibitors. In addition, the area under the curve (AUC) obtained with ROCS was 0.96, indicating that the method was very efficient to distinguishing between cruzain and cathepsin L inhibitors. (c) 2007 Elsevier Ltd. All rights reserved.

Electricity Supply Solutions for an Educational Center in Tanzania

The aim of this study was to investigate electricity supply solutions for an educationalcenter that is being built in Chonyonyo Tanzania. Off-grid power generation solutions andfurther optimization possibilities were studied for the case.The study was done for Engineers Without Borders in Sweden. Who are working withMavuno Project on the educational center. The school is set to start operating in year 2015with 40 girl students in the beginning. The educational center will help to improve genderequality by offering high quality education in a safe environment for girls in rural area.It is important for the system to be economically and environmentally sustainable. Thearea has great potential for photovoltaic power generation. Thus PV was considered as theprimary power generation and a diesel generator as a reliable backup. The system sizeoptimization was done with HOMER. For the simulations HOMER required componentdata, weather data and load data. Common components were chose with standardproperties, the loads were based on load estimations from year 2011 and the weather datawas acquired from NASA database. The system size optimization result for this base casewas a system with 26 kW PW; 5.5 kW diesel generator, 15 kW converter and 112 T-105batteries. The initial cost of the system was 55 875 €, the total net present cost 92 121 €and the levelized cost of electricity 0.264 €/kWh.In addition three optimization possibilities were studied. First it was studied how thesystem should be designed and how it would affect the system size to have night loads(security lights) use DC and could the system then be extended in blocks. As a result it wasfound out that the system size could be decreased as the inverter losses would be avoided.Also the system extension in blocks was found to be possible. The second study was aboutinverter stacking where multiple inverters can work as one unit. This type of connectionallows only the required number of inverters to run while shutting down the excess ones.This would allow the converter-unit to run with higher efficiency and lower powerconsumption could be achieved. In future with higher loads the system could be easilyextendable by connecting more inverters either in parallel or series depending on what isneeded. Multiple inverters would also offer higher reliability than using one centralizedinverter. The third study examined how the choice of location for a centralized powergeneration affects the cable sizing for the system. As a result it was found that centralizedpower generation should be located close to high loads in order to avoid long runs of thickcables. Future loads should also be considered when choosing the location. For theeducational center the potential locations for centralized power generation were found outto be close to the school buildings and close to the dormitories.

Acceptability of home-assessment post medical abortion and medical abortion in a low-resource setting in Rajasthan, India : Secondary outcome analysis of a non-inferiority randomized controlled trial

Background: Studies evaluating acceptability of simplified follow-up after medical abortion have focused on high-resource or urban settings where telephones, road connections, and modes of transport are available and where women have formal education. Objective: To investigate women's acceptability of home-assessment of abortion and whether acceptability of medical abortion differs by in-clinic or home-assessment of abortion outcome in a low-resource setting in India. Design: Secondary outcome of a randomised, controlled, non-inferiority trial. Setting Outpatient primary health care clinics in rural and urban Rajasthan, India. Population: Women were eligible if they sought abortion with a gestation up to 9 weeks, lived within defined study area and agreed to follow-up. Women were ineligible if they had known contraindications to medical abortion, haemoglobin < 85mg/l and were below 18 years. Methods: Abortion outcome assessment through routine clinic follow-up by a doctor was compared with home-assessment using a low-sensitivity pregnancy test and a pictorial instruction sheet. A computerized random number generator generated the randomisation sequence (1: 1) in blocks of six. Research assistants randomly allocated eligible women who opted for medical abortion (mifepristone and misoprostol), using opaque sealed envelopes. Blinding during outcome assessment was not possible. Main outcome measures: Women's acceptability of home-assessment was measured as future preference of follow-up. Overall satisfaction, expectations, and comparison with previous abortion experiences were compared between study groups. Results: 731 women were randomized to the clinic follow-up group (n = 353) or home-assessment group (n = 378). 623 (85%) women were successfully followed up, of those 597 (96%) were satisfied and 592 (95%) found the abortion better or as expected, with no difference between study groups. The majority, 355 (57%) women, preferred home-assessment in the event of a future abortion. Significantly more women, 284 (82%), in the home-assessment group preferred home-assessment in the future, as compared with 188 (70%) of women in the clinic follow-up group, who preferred clinic follow-up in the future (p < 0.001). Conclusion: Home-assessment is highly acceptable among women in low-resource, and rural, settings. The choice to follow-up an early medical abortion according to women's preference should be offered to foster women's reproductive autonomy.