Forecasting of stage-discharge in a non-perennial river using machine learning with gamma test.

Knowledge of the stage-discharge rating curve is useful in designing and planning flood warnings; thus, developing a reliable stage-discharge rating curve is a fundamental and crucial component of water resource system engineering. Since the continuous measurement is often impossible, the stage-discharge relationship is generally used in natural streams to estimate discharge. This paper aims to optimize the rating curve using a generalized reduced gradient (GRG) solver and the test the accuracy and applicability of the hybridized linear regression (LR) with other machine learning techniques, namely, linear regression-random subspace (LR-RSS), linear regression-reduced error pruning tree (LR-REPTree), linear regression-support vector machine (LR-SVM) and linear regression-M5 pruned (LR-M5P) models. An application of these hybrid models was performed and test to modeling the Gaula Barrage stage-discharge problem. For this, 12-year historical stage-discharge data were collected and analyzed. The 12-year historical daily flow data (m3/s) and stage (m) from during the monsoon season, i.e., June to October only from 03/06/2007 to 31/10/2018, were used for discharge simulation. The best suitable combination of input variables for LR, LR-RSS, LR-REPTree, LR-SVM, and LR-M5P models was identified and decided using the gamma test. GRG-based rating curve equations were found to be as effective and more accurate as conventional rating curve equations. The outcomes from GRG, LR, LR-RSS, LR-REPTree, LR-SVM, and LR-M5P models were compared to observed values of daily discharge based on Nash Sutcliffe model efficiency coefficient (NSE), Willmott Index of Agreement (d), Kling-Gupta efficiency (KGE), mean absolute error (MAE), mean bias error (MBE), relative bias in percent (RE), root mean square error (RMSE) Pearson correlation coefficient (PCC) and coefficient of determination (R2). The LR-REPTree model (combination 1: NSE = 0.993, d = 0.998, KGE = 0.987, PCC(r) = 0.997, and R2 = 0.994 and minimum value of RMSE = 0.109, MAE = 0.041, MBE = -0.010 and RE = -0.1%; combination 2; NSE = 0.941, d = 0.984, KGE = 0. 923, PCC(r) = 0. 973, and R2 = 0. 947 and minimum value of RMSE = 0. 331, MAE = 0.143, MBE = -0.089 and RE = -0.9%) performed superior to the GRG, LR, LR-RSS, LR-SVM, and LR-M5P models in all input combinations during the testing period. It was also noticed that the performance of the alone LR and its hybrid models (i.e., LR-RSS, LR-REPTree, LR-SVM, and LR-M5P) was better than the conventional stage-discharge rating curve, including the GRG method.

Cost-effective management measures for coastal aquifers affected by saltwater intrusion and climate change.

Sustainable management of natural water resources and food security in the face of changing climate conditions is critical to the livelihood of coastal communities. Increasing inundation and saltwater intrusion (SWI) will likely adversely affect agricultural production and the associated beach access for tourism. This study uses an integrated surface-ground water model to introduce a new approach for retardation of SWI that consists of placing aquifer fill materials along the existing shoreline using Coastal Land Reclamation (CLR). The modeling results suggest that the artificial aquifer materials could be designed to decrease SWI by increasing the infiltration area of coastal precipitation, collecting runoffs from the catchment area, and applying treated wastewater or desalinated brackish water-using coastal wave energy to reduce water treatment costs. The SEAWAT model was applied to verify that it correctly addressed Henry's problem and then applied to the Biscayne aquifer, Florida, USA. In this study, to better inform Coastal Aquifer Management (CAM), we developed four modeling scenarios, namely, Physical Surface Barriers (PSB), including the artificial aquifer widths, permeability, and side slopes and recharge. In the base case scenario without artificial aquifer placement, results show that seawater levels would increase aquifer salinity and displace large amounts of presently available fresh groundwater. More specifically, for the Biscayne aquifer, approximately 0.50% of available fresh groundwater will be lost (that is, 41,192 m3) per km of the width of the aquifer considering the increasing seawater level. Furthermore, the results suggest that placing the PSB aquifer with a smaller permeability of <100 m per day at a width of approximately 615 m increases the available fresh groundwater by approximately 45.20 and 43.90% per km of shoreline, respectively. Similarly, decreasing the slope on the aquifer-ocean side and increasing the aquifer recharge will increase freshwater availability by about 43.90 and 44.50% per km of the aquifer. Finally, placing an aquifer fill along the shallow shoreline increases net revenues to the coastal community through increased agricultural production and possibly tourism that offset fill placement and water treatment costs. This study is useful for integrated management of coastal zones by delaying aquifer salinity, protecting fresh groundwater bodies, increasing agricultural lands, supporting surface water supplies by harvesting rainfall and flash flooding, and desalinating saline water using wave energy. Also, the feasibility of freshwater storage and costs for CAM is achieved in this study.

Inherited thrombophilia in unprovoked venous thromboembolism: Is non 'O' blood group an additional culprit in Indian patients?

BACKGROUND: Venous thromboembolism (VTE) is a known situation of considerable mortality and morbidity and occurs due to the convergence of multiple acquired and genetic risk factors. METHODS: In this study, we have comprehensively analyzed the effect of ABO blood groups and inherited thrombophilia factors [Protein C (PC), Protein S (PS), Antithrombin III (AT III), Activated Protein C Resistance (APCR) and Homocysteine (Hcy)] on 150 unprovoked VTE patients, comparing with normal healthy controls. ABO phenotyping was done using gel cards and thrombophilia workup done using standard kits on coagulation autoanalyzer. RESULTS: Non O blood group was significantly more frequent among cases than controls (77.3% vs. 62.7%) and had higher odds of VTE (OR = 2.03, 95%CI: 1.22-3.37).Positivity for at least one marker of thrombophilia was more in cases (40%) than controls (16%), and led to significantly higher odds (OR = 3.5, 95%CI: 2.03-6.04) of VTE. Deficiency of PS was the commonest thrombophilia abnormality.Combination of non O group with positivity for thrombophilia markers was also more among cases (OR = 5.67, 95%CI: 2.76-11.65). Highest odds of VTE in cases were associated with non O group in combination with increased Homocystein (OR = 10.8, 95%CI: 2.27-51.5). CONCLUSION: The study results show non O blood group and positivity for factors of inherited thrombophilia in cases impart higher odds of VTE individually. Also combination of both non O blood group and positivity for factors of inherited thrombophilia in cases further increases the odds of VTE. This awareness could assist physicians in identifying those at higher risk of VTE and tailor-made the thromboprophylaxis accordingly.

Accidental acetamiprid poisoning in a buffalo.

Acetamiprid is a first generation systemic neonicotinoid insecticide, routinely used for crop protection against sucking type insects. It is likely to be of low toxicity in mammals but severe poisoning may occur if ingested in large amount. A case of buffalo with accidental ingestion of acetamiprid was presented with severe gastrointestinal symptoms and respiratory distress. The patient was managed successfully with symptomatic and supportive treatment. As far as the present report is concerned, it is the first report of acute acetamiprid poisoning in buffalo from India. From this report it is concluded that awareness programs about safe use of pesticides should be implemented.

Drug susceptibility pattern of Mycobacterium tuberculosis isolates from patients of category-II failure of pulmonary tuberculosis under directly observed treatment short-course from north India.

The major contributing factors for the causation of treatment failure in cases of pulmonary tuberculosis under Category-II directly observed treatment short-course treatment (DOTS) are treatment after default, poor treatment compliance, and development of multi-drug resistant (MDR) tuberculosis. The objective of the present study is to find out the demographic profile and drug susceptibility pattern in Category-II failure patients of pulmonary tuberculosis under Revised National Tuberculosis Control Programme (RNTCP) of India. Two hundred and twenty four patients with Category-II treatment failure of pulmonary tuberculosis were enrolled from Department of Pulmonary Medicine, at Chatrapati Sahuji Maharaj Medical University, UP, Lucknow, India, from August 2003 to July 2008. Their complete bacteriological assessment in terms of sputum smear for acid-fast bacilli, culture for Mycobacterium tuberculosis and drug sensitivity pattern were done in the Department of Microbiology. Among 224 patients, 16 (7.1%) patients were lost to follow-up and the final analysis was done among 208 (92.8%) cases. The reasons for inclusion of these 224 cases in the Category II regimen were treatment failure in the previous regimen (n = 75, 33%), default in 57% (n = 129 cases), and relapse in 8.9% (n = 20 cases). Among 208 patients, culture was positive in 170 (81.7%) cases, negative in 17 (8.1%) cases and contaminated in 21 (10%) cases. The drug sensitivity pattern of culture positive cases of Category-II failure patients revealed that, 58.2% (n = 99) had MDR tuberculosis and 40.5% (n = 69) were resistant but were non-MDR tuberculosis and 1.1 % (n = 2) cases were sensitive to all first line antituberculosis drugs.

Recent trends on the future of graduate education in the pharmaceutical sciences and research.

Harmonization of pharmacy education has to be made a global agenda that will encompass the developments that have taken place in basic, medical, pharmaceutical sciences in serving the needs and expectations of the society. The professional pharmacy curriculum is designed to produce pharmacists who have the abilities and skills to provide drug information, education, and pharmaceutical care to patients; manage the pharmacy and its medication distribution and control systems; and promote public health. Required coursework for all pharmacy students includes pharmaceutical chemistry; pharmaceutics (drug dosage forms, delivery, and disposition in the human body) pharmacology; therapeutics (the clinical use of drugs and dietary supplements in patients); drug information and analysis; pharmacy administration (including pharmacy law, bioethics, health systems, pharmacoeconomics, medical informatics); clinical skills (physical assessment, patient counseling, drug therapy monitoring for appropriate selection, dose, effect, interactions, use); and clinical pharmacy practice in pharmacies, industry, health maintenance organizations, hospital wards, and ambulatory care clinics.

A critical protein kinase C phosphorylation site on the 5-HT(1A) receptor controlling coupling to N-type calcium channels.

The importance of specific protein kinase C (PKC) sites for modulation of the inhibitory coupling of 5-HT(1A) receptors to N-type Ca(2+) channels was examined using patch-clamp techniques in F11 rat dorsal root ganglion x mouse neuroblastoma hybrid cells. The PKC activator phorbol 12-myristate 13-acetate (PMA, 10 nM) reduced by 28.6 +/- 6.8 % 5-HT-mediated, but not GTP-gamma-S-induced, inhibition of Ca(2+) current, whereas a higher concentration of PMA (500 nM) inhibited both the actions of 5-HT and GTP-gamma-S. 5-HT(1A) receptor expression plasmids with or without mutation of a single PKC site in the second intracellular loop (i2, T149A) or of three PKC sites located in the third intracellular loop (i3, T229A-S253G-T343A) were stably transfected into F11 cells. The T149A 5 HT(1A) receptor inhibited forskolin-stimulated cyclic AMP levels but was largely uncoupled from Ca(2+) channel modulation. In one (i2) clone a response rate to 5-HT of 31.6 % was obtained. The T149A mutant displayed markedly reduced sensitivity to PMA (10 nM) compared to wild-type 5-HT(1A) receptors, with only a 13.4 +/- 3 % reduction in 5-HT-induced channel inhibition; when exposed to 500 nM PMA, reductions in the action of 5-HT were comparable to those of the wild-type receptor. By contrast, the i3 mutant displayed comparable sensitivity to the wild-type 5-HT(1A) receptor to either concentration of PMA. PMA at 10 nM exhibited a similar uncoupling effect on the response of the endogenous opiate receptor to the agonist D-alanine-5-leucine-enkephalin (DADLE) in wild-type and T149A mutant-expressing clones. The T149 site of the 5-HT(1A) receptor is crucial for receptor uncoupling by sub-maximal PKC activation while at maximal PKC activation, downstream sites uncouple G proteins from the N-type Ca(2+) channel.

APAF1 is a key transcriptional target for p53 in the regulation of neuronal cell death.

p53 is a transcriptional activator which has been implicated as a key regulator of neuronal cell death after acute injury. We have shown previously that p53-mediated neuronal cell death involves a Bax-dependent activation of caspase 3; however, the transcriptional targets involved in the regulation of this process have not been identified. In the present study, we demonstrate that p53 directly upregulates Apaf1 transcription as a critical step in the induction of neuronal cell death. Using DNA microarray analysis of total RNA isolated from neurons undergoing p53-induced apoptosis a 5-6-fold upregulation of Apaf1 mRNA was detected. Induction of neuronal cell death by camptothecin, a DNA-damaging agent that functions through a p53-dependent mechanism, resulted in increased Apaf1 mRNA in p53-positive, but not p53-deficient neurons. In both in vitro and in vivo neuronal cell death processes of p53-induced cell death, Apaf1 protein levels were increased. We addressed whether p53 directly regulates Apaf1 transcription via the two p53 consensus binding sites in the Apaf1 promoter. Electrophoretic mobility shift assays demonstrated p53-DNA binding activity at both p53 consensus binding sequences in extracts obtained from neurons undergoing p53-induced cell death, but not in healthy control cultures or when p53 or the p53 binding sites were inactivated by mutation. In transient transfections in a neuronal cell line with p53 and Apaf1 promoter-luciferase constructs, p53 directly activated the Apaf1 promoter via both p53 sites. The importance of Apaf1 as a p53 target gene in neuronal cell death was evaluated by examining p53-induced apoptotic pathways in primary cultures of Apaf1-deficient neurons. Neurons treated with camptothecin were significantly protected in the absence of Apaf1 relative to those derived from wild-type littermates. Together, these results demonstrate that Apaf1 is a key transcriptional target for p53 that plays a pivotal role in the regulation of apoptosis after neuronal injury.

Heterodimerization of mineralocorticoid and glucocorticoid receptors at a novel negative response element of the 5-HT1A receptor gene.

Negative regulation of neuronal serotonin (5-HT1A) receptor levels by glucocorticoids in vivo may contribute to depression. Both types I (mineralocorticoid) and II (glucocorticoid) receptors (MR and GR, respectively) participate in corticosteroid-induced transcriptional repression of the 5-HT1A gene; however, the precise mechanism is unclear. A direct repeat 6-base pair glucocorticoid response element (GRE) half-site 5'-TGTCCT separated by 6 nucleotides was conserved in human, mouse, and rat 5-HT1A receptor promoters. In SN-48 neuronal cells that express MR, GR, and 5-HT1A receptors, deletion or inactivation of the nGRE (negative GRE) eliminated negative regulation of the rat 5-HT1A or heterologous promoters by corticosteroids, whereas its inclusion conferred corticosteroid-induced inhibition to a heterologous promoter. Bacterially expressed recombinant MR and GR preferentially bound to the nGRE as a heterodimer, as identified in nuclear extracts of MR/GR-transfected COS-7 cells, and with higher affinity than MR or GR homodimers. In SN48 and COS-7 cells, concentration-dependent coactivation of MR and GR was required for maximal inhibitory action by corticosteroids and was abrogated in the L501P-GR mutant lacking DNA binding activity. Corticosteroid-mediated transcriptional inhibition was greater for MR/GR in combination than for MR or GR alone. These data represent the first identification of an nMRE/GRE and indicate that heterodimerization of MR and GR mediates direct corticosteroid-induced transrepression of the 5-HT1A receptor promoter.

Gene content and organization of a 281-kbp contig from the genome of the extremely thermophilic archaeon, Sulfolobus solfataricus P2.

The sequence of a 281-kbp contig from the crenarchaeote Sulfolobus solfataricus P2 was determined and analysed. Notable features in this region include 29 ribosomal protein genes, 12 tRNA genes (four of which contain archaeal-type introns), operons encoding enzymes of histidine biosynthesis, pyrimidine biosynthesis, and arginine biosynthesis, an ATPase operon, numerous genes for enzymes of lipopolysaccharide biosynthesis, and six insertion sequences. The content and organization of this contig are compared with sequences from crenarchaeotes, euryarchaeotes, bacteria, and eukaryotes.