Multivariate statistics and entropy theory for irrigation water quality and entropy-weighted index development in a subtropical urban river, Bangladesh.

Currently, a well-developed combination of irrigation water quality index (IWQIs) and entropy water quality index (EWQIs) for surface water appraisal in a polluted subtropical urban river is very scarce in the literature. To close this gap, we developed IWQIs by establishing statistics-based weights of variables recommended by FAO 29 standard value using the National Sanitation Foundation Water Quality Index (NSFWQI) compared with the proposed EWQIs based on information entropy in the Dhaleshwari River, Bangladesh. Fifty surface water samples were collected from five sampling locations during the dry and wet seasons and analyzed for sixteen variables. Principal component analysis (PCA), factor analysis (FA), Moran's spatial autocorrelation, and random forest (RF) model were employed in the datasets. Weights were allocated for primary variables to compute IWQI-1, 2 and EWQI-1, 2, respectively. The resultant IWQIs showed a similar trend with EWQIs and revealed poor to good quality water, with IWQI-1 for the dry season and IWQI-2 for the wet season is further suggested. The entropy theory recognized that Mg2+, Cr, TDS, and Cl- for the dry season and Cd, Cr, Cl-, and SO42- for the wet season are the major contaminants that affect irrigation water quality. The primary input variables were lessened to ultimately shortlisted ten variables, which revealed good performance in demonstrating water quality status since weights have come effectively from PCA than FA. The results of the RF model depict NO3-, Mg2+, and Cr as the most predominant variables influencing surface water quality. A significant dispersed pattern was detected for IWQImin-3 in the wet season (Moran's I>0). Overall, both IWQIs and EWQIs will generate water quality control cost-effective, completely objective to establish a scientific basis of sustainable water management in the study basin.

Lead validation and SAR development via chemical similarity searching; application to compounds targeting the pY+3 site of the SH2 domain of p56lck.

Compound selection based on chemical similarity has been used to validate active "parent" compounds identified via database searching as viable lead compounds and to obtain initial structure-activity relationships for those leads. Twelve parent compounds that have inhibitory activity against the SH2 domain of the p56 T-cell tyrosine kinase (Lck) are the focus of this study. Lck is involved in the T-cell mediated immune response, and inhibitors of Lck protein-protein interactions could potentially be used to develop novel immunosuppressants. Similarity searches for each parent compound were performed using 2D structural fingerprints on a database containing 1,300,000 commercially available compounds. The inhibitory activity of the selected compounds was assessed using enzyme immunoassay (EIA). In general, the most active parent compounds yield the most high activity similar compounds; however, in two cases low activity parent compounds (i.e. inhibitory activity < 25% at 100 microM) yielded multiple similar compounds with activities > 60%. Such compounds may, therefore, be considered as viable lead compounds for optimization. Structure-activity relationships were explored by examining both ligand structures and their computed bound conformations to the protein. Functional groups common to the active compounds as well as key amino acid residues that form hydrogen bonds with the active compounds were identified. This information will act as the basis for the rational optimization of the lead compounds.

Heat shock protein 65-reactive T cells are involved in the pathogenesis of non-antigenic dimethyl dioctadecyl ammonium bromide-induced arthritis.

Dimethyl dioctadecyl ammonium bromide (DDA) (C(38)H(80)NBr) is a nonantigenic lipoid material. DDA-induced arthritis (DIA) in the Lewis (LEW) (RT.1(l)) rat is a new experimental model for human rheumatoid arthritis (RA). DIA is a T cell-mediated autoimmune disease. However, the precise self/foreign Ags associated with the disease process in DIA are not yet known. We observed that LEW rats with DIA spontaneously raised a vigorous T cell response both to 65-kDa self (rat) heat shock protein (Rhsp65) and mycobacterial hsp65 (Bhsp65), but not to another arthritis-related Ag, bovine collagen type II. The T cell response to Rhsp65 was focused predominantly on determinant regions 120-134 and 213-227 of the self protein. Interestingly, pretreatment of adult LEW rats using either a mixture of peptides 120-134 and 213-227 of Rhsp65 or a low nonarthritogenic dose of DDA induced protection against subsequent DIA. Intriguingly, the protection induced by the latter was associated with spontaneous priming of T cells specific for peptide 213-227 of Rhsp65. Similarly, LEW rats neonatally tolerized against either Rhsp65 or Bhsp65 were significantly protected from subsequently induced DIA at adult stage, showing the disease-modulating attribute of the hsp65-specific T cells. Taken together, the above findings demonstrate that the hsp65-directed T cell repertoire is of significance in the pathogenesis of autoimmune arthritis induced by nonantigenic DDA. Like other animal models of RA involving hsp65, these first insights into the disease-associated Ags in the DIA model would pave the way for further understanding of the immunological aspects of induction and regulation of RA.