Succinimide-N-sulfonic acid as an efficient recyclable catalyst for the synthesis of some fused indolo pyrano pyrimidinone derivatives

A new, simple, thermally efficient and solvent-free condensation of 2-amino-4,5-dihydro-4-phenylpyrano[3,2-b]indole-3-carbonitrile derivatives with coumarin-3-carboxylic acid employing succinimide-N-sulfonic acid (SuSA) as catalyst for the synthesis of a series of 5,6-dihydro-2-(2-oxo-2H-chromen-3-yl)-5-phenyl-indolo[2',3':5,6]pyrano[2,3-d]pyrimidin-4(3H)-one derivatives is described. This method has the advantages of high yield, simple methodology, and short reaction time, as well as being green in terms of avoiding the use of toxic catalysts and solvents. Furthermore, the catalyst could be recycled and reused four times without significant loss of activity. Thiourea dioxide (TUD) catalyzed efficient three-component coupling reactions of aromatic aldehydes, 3-hydroxyindole and malononitrile in water at 70 ºC was described as the preparation of 2-amino-4,5-dihydro-4-phenylpyrano[3,2-b]indole-3-carbonitrile derivatives. KEY WORDS: Succinimide-N-sulfonic acid, Thiourea dioxide, Coumarin-3-carboxylic acid, Indolo pyrano  pyrimidineone derivatives Bull. Chem. Soc. Ethiop. 2015, 29(3), 457-471.DOI: http://dx.doi.org/10.4314/bcse.v29i3.1

Using a fuzzy inference system to control a pumped storage hydro plant

The paper discusses the development of a fuzzy inference system (FIS) based governor control for a pumped storage hydroelectric plant. The First Hydro Company's plant at Dinorwig in North Wales is the largest of its kind in Europe and is mainly used for frequency control of the UK electrical grid. In previous investigations, a detailed model of the plant was developed using MATLAB(R)/SIMULINK(R) and this is now being used to compare FIS governor operation with the proportional-integral-derivative (PID) controller currently used. The paper describes the development of an FIS governor, and shows that its response to a step increase in load is superior to the PID under certain conditions of load. The paper proceeds to discuss the implications of these results in view of the possible practical application of an FIS governor at the Dinorwig plant

Adverse Events among HIV/MDR-TB Co-Infected Patients Receiving Antiretroviral and Second Line Anti-TB Treatment in Mumbai, India.

Significant adverse events (AE) have been reported in patients receiving medications for multidrug- and extensively-drug-resistant tuberculosis (MDR-TB & XDR-TB). However, there is little prospective data on AE in MDR- or XDR-TB/HIV co-infected patients on antituberculosis and antiretroviral therapy (ART) in programmatic settings

Comparing the immune response to a novel intranasal nanoparticle PLGA vaccine and a commercial BPI3V vaccine in dairy calves

peer-reviewedBackground There is a need to improve vaccination against respiratory pathogens in calves by stimulation of local immunity at the site of pathogen entry at an early stage in life. Ideally such a vaccine preparation would not be inhibited by the maternally derived antibodies. Additionally, localized immune response at the site of infection is also crucial to control infection at the site of entry of virus. The present study investigated the response to an intranasal bovine parainfluenza 3 virus (BPI3V) antigen preparation encapsulated in PLGA (poly dl-lactic-co-glycolide) nanoparticles in the presence of pre-existing anti-BPI3V antibodies in young calves and comparing it to a commercially available BPI3V respiratory vaccine. Results There was a significant (P < 0.05) increase in BPI3V-specific IgA in the nasal mucus of the BPI3V nanoparticle vaccine group alone. Following administration of the nanoparticle vaccine an early immune response was induced that continued to grow until the end of study and was not observed in the other treatment groups. Virus specific serum IgG response to both the nanoparticle vaccine and commercial live attenuated vaccine showed a significant (P < 0.05) rise over the period of study. However, the cell mediated immune response observed didn’t show any significant rise in any of the treatment groups. Conclusion Calves administered the intranasal nanoparticle vaccine induced significantly greater mucosal IgA responses, compared to the other treatment groups. This suggests an enhanced, sustained mucosal-based immunological response to the BPI3V nanoparticle vaccine in the face of pre-existing antibodies to BPI3V, which are encouraging and potentially useful characteristics of a candidate vaccine. However, ability of nanoparticle vaccine in eliciting cell mediated immune response needs further investigation. More sustained local mucosal immunity induced by nanoparticle vaccine has obvious potential if it translates into enhanced protective immunity in the face of virus outbreak

Association of opioid prescribing practices with chronic pain and benzodiazepine co-prescription:a primary care data linkage study

Background: Opioid prescribing is increasing worldwide with associated increases in misuse and other harms. We studied variations in national opioid prescription rates, indicators of prescribing quality, co-prescribing of benzodiazepines and relationship with pain severity in Scotland. Methods: Electronic linkages of opioid prescribing in Scotland were determined from: (i) national data from Information Services Division, NHS Scotland (2003–2012); and (ii) individual data from Generation Scotland: Scottish Family Health Study. Descriptive analyses were conducted on national data, multilevel modelling to examine factors associated with variations in prescribing rates. χ2 tests examined associations between individual pain severity and opioid prescriptions. Results: The number of strong opioid prescriptions more than doubled from 474 385 in 2003 to 1 036 446 in 2012, and weak opioid prescribing increased from 3 261 547 to 4 852 583. In Scotland, 938 674 individuals were prescribed an opioid in 2012 (18% of the population). Patients in the most deprived areas were 3.5 times more likely to receive a strong opioid than patients in the least deprived. There was significant variation in prescribing rates between geographical areas, with much of this explained by deprivation. Of women aged 25–40 yr prescribed a strong opioid, 40% were also prescribed a benzodiazepine. There was significant association between pain severity and receipt of opioid prescription. Over 50% of people reporting severe pain were not prescribed an opioid analgesic. Conclusions: We found opioid prescribing in primary care to be common and increasing in Scotland, particularly for severe pain. Co-prescribing of opioids and benzodiazepines was common

Discovering study-specific gene regulatory networks

This article has been made available through the Brunel Open Access Publishing Fund.Microarrays are commonly used in biology because of their ability to simultaneously measure thousands of genes under different conditions. Due to their structure, typically containing a high amount of variables but far fewer samples, scalable network analysis techniques are often employed. In particular, consensus approaches have been recently used that combine multiple microarray studies in order to find networks that are more robust. The purpose of this paper, however, is to combine multiple microarray studies to automatically identify subnetworks that are distinctive to specific experimental conditions rather than common to them all. To better understand key regulatory mechanisms and how they change under different conditions, we derive unique networks from multiple independent networks built using glasso which goes beyond standard correlations. This involves calculating cluster prediction accuracies to detect the most predictive genes for a specific set of conditions. We differentiate between accuracies calculated using cross-validation within a selected cluster of studies (the intra prediction accuracy) and those calculated on a set of independent studies belonging to different study clusters (inter prediction accuracy). Finally, we compare our method's results to related state-of-the art techniques. We explore how the proposed pipeline performs on both synthetic data and real data (wheat and Fusarium). Our results show that subnetworks can be identified reliably that are specific to subsets of studies and that these networks reflect key mechanisms that are fundamental to the experimental conditions in each of those subsets

Identification of disease-causing genes using microarray data mining and gene ontology

Background: One of the best and most accurate methods for identifying disease-causing genes is monitoring gene expression values in different samples using microarray technology. One of the shortcomings of microarray data is that they provide a small quantity of samples with respect to the number of genes. This problem reduces the classification accuracy of the methods, so gene selection is essential to improve the predictive accuracy and to identify potential marker genes for a disease. Among numerous existing methods for gene selection, support vector machine-based recursive feature elimination (SVMRFE) has become one of the leading methods, but its performance can be reduced because of the small sample size, noisy data and the fact that the method does not remove redundant genes. Methods: We propose a novel framework for gene selection which uses the advantageous features of conventional methods and addresses their weaknesses. In fact, we have combined the Fisher method and SVMRFE to utilize the advantages of a filtering method as well as an embedded method. Furthermore, we have added a redundancy reduction stage to address the weakness of the Fisher method and SVMRFE. In addition to gene expression values, the proposed method uses Gene Ontology which is a reliable source of information on genes. The use of Gene Ontology can compensate, in part, for the limitations of microarrays, such as having a small number of samples and erroneous measurement results. Results: The proposed method has been applied to colon, Diffuse Large B-Cell Lymphoma (DLBCL) and prostate cancer datasets. The empirical results show that our method has improved classification performance in terms of accuracy, sensitivity and specificity. In addition, the study of the molecular function of selected genes strengthened the hypothesis that these genes are involved in the process of cancer growth. Conclusions: The proposed method addresses the weakness of conventional methods by adding a redundancy reduction stage and utilizing Gene Ontology information. It predicts marker genes for colon, DLBCL and prostate cancer with a high accuracy. The predictions made in this study can serve as a list of candidates for subsequent wet-lab verification and might help in the search for a cure for cancers

The Merging of Two Dynasties—Identification of an African Cotton Leaf Curl Disease-Associated Begomovirus with Cotton in Pakistan

Cotton leaf curl disease (CLCuD) is a severe disease of cotton that occurs in Africa and Pakistan/northwestern India. The disease is caused by begomoviruses in association with specific betasatellites that differ between Africa and Asia. During survey of symptomatic cotton in Sindh (southern Pakistan) Cotton leaf curl Gezira virus (CLCuGV), the begomovirus associated with CLCuD in Africa, was identified. However, the cognate African betasatellite (Cotton leaf curl Gezira betasatellite) was not found. Instead, two Asian betasatellites, the CLCuD-associated Cotton leaf curl Multan betasatellite (CLCuMB) and Chilli leaf curl betasatellite (ChLCB) were identified. Inoculation of the experimental plant species Nicotiana benthamiana showed that CLCuGV was competent to maintain both CLCuMB and ChLCB. Interestingly, the enations typical of CLCuD were only induced by CLCuGV in the presence of CLCuMB. Also in infections involving both CLCuMB and ChLCB the enations typical of CLCuMB were less evident. This is the first time an African begomovirus has been identified on the Indian sub-continent, highlight the growing threat of begomoviruses and particularly the threat of CLCuD causing viruses to cotton cultivation in the rest of the world

The Effect of Chloroquine, Hydroxychloroquine and Azithromycin on the Corrected QT Interval in Patients with SARS-CoV-2 Infection

Background - The novel SARs-CoV-2 coronavirus is responsible for the global COVID-19 pandemic. Small studies have shown a potential benefit of chloroquine/hydroxychloroquine ± azithromycin for the treatment of COVID-19. Use of these medications alone, or in combination, can lead to a prolongation of the QT interval, possibly increasing the risk of Torsade de pointes (TdP) and sudden cardiac death. Methods - Hospitalized patients treated with chloroquine/hydroxychloroquine ± azithromycin from March 1st through the 23rd at three hospitals within the Northwell Health system were included in this prospective, observational study. Serial assessments of the QT interval were performed. The primary outcome was QT prolongation resulting in TdP. Secondary outcomes included QT prolongation, the need to prematurely discontinue any of the medications due to QT prolongation and arrhythmogenic death. Results - Two hundred one patients were treated for COVID-19 with chloroquine/hydroxychloroquine. Ten patients (5.0%) received chloroquine, 191 (95.0%) received hydroxychloroquine and 119 (59.2%) also received azithromycin. The primary outcome of TdP was not observed in the entire population. Baseline QTc intervals did not differ between patients treated with chloroquine/hydroxychloroquine (monotherapy group) vs. those treated with combination group (chloroquine/hydroxychloroquine and azithromycin) (440.6 ± 24.9 ms vs. 439.9 ± 24.7 ms, p =0.834). The maximum QTc during treatment was significantly longer in the combination group vs the monotherapy group (470.4 ± 45.0 ms vs. 453.3 ± 37.0 ms, p = 0.004). Seven patients (3.5%) required discontinuation of these medications due to QTc prolongation. No arrhythmogenic deaths were reported. Conclusions - In the largest reported cohort of COVID-19 patients to date treated with chloroquine/hydroxychloroquine {plus minus} azithromycin, no instances of TdP or arrhythmogenic death were reported. Although use of these medications resulted in QT prolongation, clinicians seldomly needed to discontinue therapy. Further study of the need for QT interval monitoring is needed before final recommendations can be made