Pharmacophore-based 3D QSAR studies on a series of high affinity 5-HT(1A) receptor ligands

5-HT(1A) receptor antagonists have been employed to treat depression, but the lack of structural information on this receptor hampers the design of specific and selective ligands. In this study, we have performed CoMFA studies on a training set of arylpiperazines (high affinity 5-HT(1A) receptor ligands) and to produce an effective alignment of the data set, a pharmacophore model was produced using Galahad. A statistically significant model was obtained, indicating a good internal consistency and predictive ability for untested compounds. The information gathered from our receptor-independent pharmacophore hypothesis is in good agreement with results from independent studies using different approaches. Therefore, this work provides important insights on the chemical and structural basis involved in the molecular recognition of these compounds. (C) 2010 Elsevier Masson SAS. All rights reserved.

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.

Small-Scale Farmers Land Use and Socioeconomic Situation in the Mount Elgon District in Northwestern Kenya : A Minor Field Study - Combined Field Mapping and Interview

This Minor Field Study was carried out during November and December in 2011 in the Mount Elgon District in Western Kenya. The objective was to examine nine small-scale farming household´s land use and socioeconomic situation when they have joined a non-governmental organization (NGO) project, which specifically targets small-scale farming households to improve land use system and socioeconomic situation by the extension of soil and water conservation measures. The survey has worked along three integral examinations methods which are mapping and processing data using GIS, semi structured interviews and literature studies.   This study has adopted a theoretical approach referred to as political ecology, in which landesque capital is a central concept. The result shows that all farmers, except one, have issues with land degradation. However, the extent of the problem and also implemented sustainable soil and water conservation measures were diverse among the farmers. The main causes of this can both be linked to how the farmers themselves utilized their farmland and how impacts from the climate change have modified the terms of the farmers working conditions. These factors have consequently resulted in impacts on the informants’ socioeconomic conditions. Furthermore it was also registered that social and economic elements, in some cases, were the causes of how the farmers manage their farmland. The farmer who had no significant problem with soil erosion had invested in trees and opportunities to irrigate the farmland. In addition, it was also recorded that certain farmers had invested in particular soil and water conservation measures without any significant result. This was probably due to the time span these land measures cover before they start to generate revenue.  The outcome of this study has traced how global, national and local elements exist in a context when it comes to the conditions of the farmers´ land use and their socioeconomic situation. The farmers atMt.Elgon are thereby a component of a wider context when they are both contributory to their socioeconomic situation, mainly due to their land management, and also exposed to core-periphery relationships on which the farmers themselves have no influence.

The priority of temporal aspects in L2-Swedish prosody : Studies in perception and production

Foreign accent can be everything from hardly detectable to rendering the second language speech unintelligible. It is assumed that certain aspects of a specific target language contribute more to making the foreign accented speech intelligible and listener friendly, than others. The present thesis examines a teaching strategy for Swedish pronunciation in second language education. The teaching strategy “Basic prosody” or BP, gives priority to temporal aspects of Swedish prosody, which means the temporal phonological contrasts word stress and quantity, as well as the durational realizations of these contrasts. BP does not prescribe any specific tonal realizations. This standpoint is based on the great regional variety in realization and distribution of Swedish word accents. The teaching strategy consists virtually of three directives: · Stress the proper word in the sentence. · Stress proper syllables in stressed words and make them longer. · Lengthen the proper segment – vowel or subsequent consonant – in the stressed syllable. These directives reflect the view that all phonological length is stress-induced, and that vowel length and consonant length are equally important as learning goals. BP is examined in the light of existing findings in the field of second language pronunciation and with respect to the phonetic correlates of Swedish stress and quantity. Five studies examine the relation between segment durations and the categorization made by native Swedish listeners. The results indicate that the postvocalic consonant duration contributes to quantity categorization as well as giving the proper duration to stressed syllables. Furthermore, native Swedish speakers are shown to apply the complementary /V: C/ - /VC:/ pattern also when speaking English and German, by lengthening postvocalic consonants. The correctness of the priority is not directly addressed but important aspects of BP are supported by earlier findings as well as the results from the present studies.