Consensus kNN QSAR: a versatile method for predicting the estrogenic activity of organic compounds in silico. A comparative study with five estrogen receptors and a large, diverse set of ligands

Quantitative structure-activity relationships (QSARs) have proved increasingly useful for predicting the biological activities of molecules (e.g., their binding affinities to different receptors) and can be used in environmental chemistry as a preliminary tool for screening the activities of untested molecules, producing valuable information on which compounds should be tested more thoroughly with experimental affinity assays or in animals. The predictive ability of the consensus kNN QSAR method is corroborated here using a diverse set of 245 compounds, which have been assayed for their relative binding affinities to the estrogen receptor of four species: human (ER alpha and ER beta), calf, mouse, and rat. Leave-one-out cross-validation (LOO-CV) and gamma-randomization tests were applied to the QSAR models for internal validation, and separate training and test sets were used for external validation. The internal predictive abilities of the consensus models for all five data sets were convincing, with cross-validated correlation coefficients (LOO-CV q2 values) varying from 0.69 (human ER beta data) to 0.79 (human ER alpha data). The external predictive abilities were also encouraging, as the predictive r2 scores (pr-r2 values) varied from 0.62 (human ER beta data) to 0.77 (calf and mouse data). The results indicate that consensus kNN QSAR is a feasible method for rapid screening of the estrogenic activity of organic compounds.     

Effect of hot drawing on properties of wet‐spun poly(L,D‐lactide) copolymer multifilament fibers

Polylactide stereocopolymer multifilament fibers were prepared by wet spinning and subsequent hot drawing. The stereocopolymers were poly‐(L,D ‐lactide) [P(L,D )LA], L/D ratio 96/4, and poly‐(L,DL ‐lactide) [P(L,DL )LA], L/DL ratio 70/30. They were dissolved in dichloromethane and coagulated in a spin bath containing ethanol. The hot‐drawing temperature was 65°C. The draw ratios (DR) were upto 4.5 to the P(L,D )LA 96/4 filaments and upto 3 to the P(L,DL )LA 70/30 filaments. Wet spinning decreased crystallinities of both copolymers. Hot drawing increased the crystallinity of the P(L,D )LA 96/4 filament but not to the level of the original copolymer, whereas the as‐spun and the hot‐drawn P(L,DL )LA 70/30 filaments were amorphous. The filament diameter, tenacity, Young's modulus, and elongation at break were dependent on the DR. The maximum tenacity (285 MPa) and Young's modulus (2.0 GPa) were achieved with the P(L,D )LA 96/4 filament at the DR of 4.5. Respectively, the maximum tenacity of the hot‐drawn P(L,DL )LA 70/30 filament was 175 MPa and Young's modulus 1.3 GPa at the DR of 3. Hot drawing slowed down in vitro degradation rate of both stereocopolymer filaments. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Effect of purified Trichoderma reesei cellulases on formation of cotton powder from cotton fabric

The mode of action of monocomponent purified Trichoderma reesei cellobiohydrolases (CBHI and CBHII) and endoglucanases (EGI and EGII) on cotton fabrics was studied by analyzing the weight loss of the fabric, the reducing sugars, the soluble oligosaccharides and the molecular weight of the cotton powder formed. The impact of mechanical action on these factors was also evaluated. EGI and EGII released the highest amounts of reducing sugars and soluble oligosaccharides in both treatments with or without additional mechanical action. After cellulase treatment without additional mechanical action, all of the cellulases were found to have reduced the molecular weight of cotton poplin powder. When mechanical action was combined with enzyme treatments, only EGII reduced the molecular weight. The weight loss of EG‐treated fabrics was clearly higher than the weight loss of CBH‐treated fabrics with both low and high mechanical action levels. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 1917–1922, 2003     

The effect of fluvoxamine on the pharmacokinetics and pharmacodynamics of buspirone

OBJECTIVE: The effects of fluvoxamine, a selective serotonin (5-HT) reuptake inhibitor antidepressant, on the pharmacokinetics and pharmacodynamics of buspirone, a non-benzodiazepine anxiolytic agent, were investigated. METHODS: In a randomized, placebo-controlled, two-phase cross-over study, ten healthy volunteers took either 100 mg fluvoxamine or matched placebo orally once daily for 5 days. On day 6, 10 mg buspirone was taken orally. Plasma concentrations of buspirone and its active metabolite, 1-(2-pyrimidinyl)-piperazine (1-PP), were measured up to 18 h and the pharmacodynamic effects of buspirone up to 8 h. RESULTS: The total area under the plasma buspirone concentration-time curve was increased 2.4-fold (P < 0.05) and the peak plasma buspirone concentration 2.0-fold (P < 0.05) by fluvoxamine, compared with placebo. The half-life of buspirone was not affected. The ratio of the total area under the plasma concentration-time curve of 1-PP to that of buspirone was decreased from 7.4 [6.3 (SD)] to 4.4 (3.6) by fluvoxamine (P < 0.05). The results of the six pharmacodynamic tests remained unchanged. CONCLUSION: Fluvoxamine moderately increased plasma buspirone concentrations and decreased the production of the active 1-PP metabolite of buspirone. The mechanism of this interaction is probably inhibition of the CYP3A4-mediated first-pass metabolism of buspirone by fluvoxamine. However, this pharmacokinetic interaction was not associated with impairment of psychomotor performance and it is probably of limited clinical significance.     

Emissions of DEHP‐free PVC flooring

Degrading 2‐ethylhexyl‐containing PVC floorings (eg DEHP‐PVC floorings) and adhesives emit 2‐ethylhexanol (2‐EH) in the indoor air. The danger of flooring degradation comes from exposing occupants to harmful phthalates plasticisers (eg DEHP), but not from 2‐EH as such. Since the EU banned the use of phthalates in sensitive applications, the market is shifting to use DEHP‐free and alternative types of plasticisers in PVC products. However, data on emissions from DEHP‐free PVC floorings are scarce. This study aimed at assessing the surface and bulk emissions of two DEHP‐free PVC floorings over three years. The floorings were glued on the screed layer of concrete casts at 75%, 85%, and 95% RH. The volatile organic compounds (VOCs) were actively sampled using FLEC (surface emissions) and micro‐chamber/thermal extractor (µ‐CTE, bulk emissions) onto Tenax TA adsorbents and analyzed with TD‐GC‐MS. 2‐EH, C9‐alcohols, and total volatile organic compound (TVOC) emissions are reported. Emissions at 75% and 85% RH were similar. As expected, the highest emissions occurred at 95% RH. 2‐EH emissions originated from the adhesive. Because the two DEHP‐free floorings tested emitted C9‐alcohols at all tested RH, it makes the detection of flooring degradation harder, particularly if the adhesive used does not emit 2‐EH.     

The effect of water‐soluble polymers on rheology of microfibrillar cellulose suspension and dynamic mechanical properties of paper sheet

Rheological properties of fiber/polymer suspensions and dynamic mechanical analysis (DMA) of paper sheets containing the same polymers were measured. Correlations between viscoelastic properties of suspensions and strength of paper sheet are presented. Rheological properties of suspensions of microfibrillar cellulose (MFC) and a set of water soluble polymers were measured. Rheological properties of these complex fluids vary considerably depending on the added polymer. A suspension of fiber and carboxymethyl cellulose (CMC) exhibits a viscosity higher than the sum of the viscosity of the individual components in the suspension. In contrast, when cationic starch (CS) is used together with the fiber, the yielding behavior rather than the viscosity is characteristic of the suspension. Dynamic mechanical properties of paper sheets containing CMC or CS as additives were studied at different humidity levels. Different yielding behavior observed in oscillatory rheology can be correlated with straining behavior in dynamic mechanical properties. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Farmers’ attitudes about growing energy crops: A choice experiment approach

The present study adapts the choice experiment (CE) method for an analysis of how Swedish farmers assess the relative value of the characteristics associated with growing energy crops. An additional goal was to find out the willingness of farmers to grow energy crops relative to different levels of income and subsidies based on predictions of acreage of energy crop cultivation. In the first CE, farmers were presented with two energy crops and six of their characteristics and asked to choose the alternative he or she preferred most. In the second CE the respondent was asked how many hectares for each crop he/she would be willing to grow on arable land with an energy crop subsidy and how many hectares he/she would be willing to grow on set-aside land without an energy crop subsidy. The results suggest that among the included characteristics in the first experiment, the visual impact on the landscape and the rotation period of the energy crop appear to have a significant impact on the utility derived from growing an energy crop. An increased utility of a crop increases the arable land used for that crop and the income associated with it. Farm characteristics such as leased land, rented land, share of set-aside land, and type of farming had an insignificant effect on the willingness to grow energy crops. Significant characteristics were age of the farmer, size of the farm, and the geographical area.     

Do ergonomically designed school workstations decrease musculoskeletal symptoms in children? A 26-month prospective follow-up study

Workstations at school are among several factors that contribute to musculoskeletal symptoms among school-aged children. The aim of this study was to investigate the effects of ergonomically designed workstations on schoolchildren's musculoskeletal symptoms as compared to conventional workstations. In the first 14-month phase of the study (2002-2003, two schools), 42 from the intervention and 46 from the control school participated. In the total follow-up of 26 months (2002-2004), 23 in the intervention group and 20 in the control group participated. Anthropometrics and musculoskeletal symptoms were measured. In general, the ergonomically designed school workstations did not decrease present neck-shoulder, upper back, low back and lower limbs strain and pain, compared to conventional ones during follow-ups.     

Comparing the effects of two school workstations on spine positions and mobility, and opinions on the workstations – A 2-year controlled intervention

A wide variety of conventional design workstations are used in schools and workstations have often been described as inappropriate for children's body dimensions. The present study aimed to investigate the effects of saddle chairs and desks with comfort curve for the body on schoolchildren's spine positions and mobility and opinions of workstations compared to conventional workstations. During the first 12-month study period, the number of participants was 98, 48 in the intervention and 50 in the control group. Since the older control group (9th graders, n = 29) decided against participation after the first 12 months, the number of participants in the entire follow-up of 24 months, was 47 (27 intervention and 20 control participants). During the follow-up, the intervention group used new chairs and desks while the controls used conventional workstations. Spine positions and mobility were measured and both groups completed a questionnaire, concerning opinions of workstations. The results indicated that no difference between groups was found when comparing workstation effects on spine positions and mobility during the whole follow-up. Schoolchildren preferred the ergonomic workstations to the conventional workstations during the first year (p < 0.001), but no difference was seen during the second year.

Relevance to industry

: The present results indicated that new design workstations had no effects on spine positions compared to conventional workstations. However, some intra-group positive effects were observed among intervention group. Therefore, the authors believe further development of both school workstations and school environment should be encouraged to ensure better long-term back health in children.