Accurate Machine Learning for Predicting the Viscosities of Deep Eutectic Solvents.

Deep eutectic solvents (DESs) are emerging as environmentally friendly designer solvents for mass transport and heat transfer processes in industrial applications; however, the lack of accurate tools to predict and thus control their viscosities under both a range of environmental factors and formulations hinders their general application. While DESs may serve as designer solvents, with nearly unlimited combinations, this unfortunately makes it experimentally infeasible to comprehensively measure the viscosities of all DESs of potential industrial interest. To assist in the design of DESs, we have developed several new machine learning (ML) models that accurately and rapidly predict the viscosities of a diverse group of DESs at different temperatures and molar ratios using, to date, one of the most comprehensive data sets containing the properties of over 670 DESs over a wide range of temperatures (278.15-385.25 K). Three ML models, including support vector regression (SVR), feed forward neural networks (FFNNs), and categorical boosting (CatBoost), were developed to predict DES viscosity as a function of temperature and molar ratio and contrasted with multilinear and two-factor polynomial regression baselines. Quantum chemistry-based, COSMO-RS-derived sigma profile (σ-profile) features were used as inputs for the ML models. The CatBoost model is excellent at externally predicting DES viscosity, as indicated by high R2 (0.99) and low root-mean-square-error (RMSE) and average absolute relative deviations (AARD) (5.22%) values for the testing data sets, and 98% of the data points lie within the 15% of AARD deviations. Furthermore, SHapley additive explanation (SHAP) analysis was employed to interpret the ML results and rationalize the viscosity predictions. The result is an ML approach that accurately predicts viscosity and will aid in accelerating the design of appropriate DESs for industrial applications.

Strategies to detect and manage latent tuberculosis infection among household contacts of pulmonary TB patients in high TB burden countries - a systematic review and meta-analysis.

OBJECTIVE: To summarise latent tuberculosis infection (LTBI) management strategies among household contacts of bacteriologically confirmed pulmonary tuberculosis (TB) patients in high-TB burden countries. METHODS: PubMed/MEDLINE (NCBI) and Scopus were searched (January 2006 to December 2021) for studies reporting primary data on LTBI management. Study selection, data management and data synthesis were protocol-driven (PROSPERO-CRD42021208715). Primary outcomes were the proportions of LTBI, initiating and completing tuberculosis preventive treatment (TPT). Reported factors influencing the LTBI care cascade were qualitatively synthesised. RESULTS: From 3694 unique records retrieved, 58 studies from 23 countries were included. Most identified contacts were screened (median 99%, interquartile range [IQR] 82%-100%; 46 studies). Random-effects meta-analysis yielded pooled proportions for: LTBI 41% (95% confidence interval [CI] 33%-49%; 21,566 tested contacts); TPT initiation 91% (95% CI 79%-97%; 129,573 eligible contacts, 34 studies); TPT completion 65% (95% CI 54%-74%; 108,679 TPT-initiated contacts, 28 studies). Heterogeneity was significant (I2 ≥ 95%-100%) and could not be explained in subgroup analyses. Median proportions (IQR) were: LTBI 44% (28%-59%); TPT initiation 86% (60%-100%); TPT completion 68% (44%-82%). Nine broad themes related to diagnostic testing, health system structure and functions, risk perception, documentation and adherence were considered likely to influence the LTBI care cascade. CONCLUSION: The proportions of household contacts screened, detected with LTBI and initiated on TPT, though variable was high, but the proportions completing TPT were lower indicating current strategies used for LTBI management in high TB burden countries are not sufficient.

Improved ethanol productivity and ethanol tolerance through genome shuffling of Saccharomyces cerevisiae and Pichia stipitis

Genome shuffling by recursive protoplast fusion between Saccharomyces cerevisiae and Pichia stipitis also known as Scheffersomyces stipitis resulted in a promising yeast hybrid strain with superior qualities than those of the parental strains in enhancing biofuel production. Our study focused on the substrate utilization, ethanol fermentation, and ethanol tolerance of the hybrids and the parental strains. The parental strain S. cerevisiae is limited to utilize only hexose sugars, and this leads to decrease in the ethanol yield when they are subjected to ethanol production from lignocellulosic biomass which is rich in pentose sugars. To overcome this limitation, we constructed a hybrid yeast strain through genome shuffling which can assimilate all the sugars present in the fermentation medium. After two rounds of recursive protoplast fusion, there was a higher increase in substrate utilization by hybrid SP2-18 compared to parental strain S. cerevisiae. SP2-18 was able to consume 34% of xylose sugar present in the fermentation medium, whereas S. cerevisiae was not able to utilize xylose. Further, the hybrid strain SP2-18 was able to reach an ethanol productivity of 1.03 g L−1 h−1, ethanol yield 0.447 g/g, and ethanol concentration 74.65 g L−1 which was relatively higher than that of the parental strain S. cerevisiae. Furthermore, the hybrid SP2-18 was found to be stable in the production of ethanol. The random amplified polymorphic DNA profile of the yeast hybrid SP2-18 shows the polymorphism between the parental strains indicating the migration of specific sugar metabolizing genes from P. stipitis, while the maximum similarity was with the parent S. cerevisiae

No disponible

Improved ethanol productivity and ethanol tolerance through genome shuffling of Saccharomyces cerevisiae and Pichia stipitis.

Genome shuffling by recursive protoplast fusion between Saccharomyces cerevisiae and Pichia stipitis also known as Scheffersomyces stipitis resulted in a promising yeast hybrid strain with superior qualities than those of the parental strains in enhancing biofuel production. Our study focused on the substrate utilization, ethanol fermentation, and ethanol tolerance of the hybrids and the parental strains. The parental strain S. cerevisiae is limited to utilize only hexose sugars, and this leads to decrease in the ethanol yield when they are subjected to ethanol production from lignocellulosic biomass which is rich in pentose sugars. To overcome this limitation, we constructed a hybrid yeast strain through genome shuffling which can assimilate all the sugars present in the fermentation medium. After two rounds of recursive protoplast fusion, there was a higher increase in substrate utilization by hybrid SP2-18 compared to parental strain S. cerevisiae. SP2-18 was able to consume 34% of xylose sugar present in the fermentation medium, whereas S. cerevisiae was not able to utilize xylose. Further, the hybrid strain SP2-18 was able to reach an ethanol productivity of 1.03 g L-1 h-1, ethanol yield 0.447 g/g, and ethanol concentration 74.65 g L-1 which was relatively higher than that of the parental strain S. cerevisiae. Furthermore, the hybrid SP2-18 was found to be stable in the production of ethanol. The random amplified polymorphic DNA profile of the yeast hybrid SP2-18 shows the polymorphism between the parental strains indicating the migration of specific sugar metabolizing genes from P. stipitis, while the maximum similarity was with the parent S. cerevisiae.

Identification of second arginine-glycine-aspartic acid motif of ovine vitronectin as the complement C9 binding site and its implication in bacterial infection.

Vitronectin (Vn), a multifunctional protein of blood and extracellular matrix, interacts with complement C9. This interaction may modulate innate immunity. Details of Vn-C9 interactions are limited. Vn-C9 interactions were assessed by employing a goat homologous system and observing Vn binding to C9 in three different assays. Using recombinant fragments, C9 binding was mapped to the N-terminus of Vn. Site directed mutagenesis was performed to alter the second arginine glycine aspartic acid (RGD) sequence (RGD-2) of Vn. Changing R to G or D to A in RGD-2 caused significant decrease in Vn binding to C9 whereas changing of R to G in the first RGD motif (RGD-1) had no effect on Vn binding to C9. These results imply that the RGD-2 of goat Vn is involved in C9 binding. In a competitive binding assay, the presence of soluble RGD peptide inhibited Vn binding to C9 whereas heparin had no effect. Vn binding to C9 was also evaluated in terms of bacterial pathogenesis. Serum dependent inhibition of Escherichia coli growth was significantly reverted when Vn or its N-fragment were included in the assay. The C-fragment, which did not support C9 binding, also partly nullified serum-dependent inhibition of bacterial growth, probably through other serum component(s).

Cytokine and protein markers of leprosy reactions in skin and nerves: baseline results for the North Indian INFIR cohort.

BACKGROUND: Previous studies investigating the role of cytokines in the pathogenesis of leprosy have either been on only small numbers of patients or have not combined clinical and histological data. The INFIR Cohort study is a prospective study of 303 new multibacillary leprosy patients to identify risk factors for reaction and nerve damage. This study characterised the cellular infiltrate in skin and nerve biopsies using light microscopic and immunohistochemical techniques to identify any association of cytokine markers, nerve and cell markers with leprosy reactions. METHODOLOGY/PRINCIPAL FINDINGS: TNF-α, TGF-ß and iNOS protein in skin and nerve biopsies were detected using monoclonal antibody detection immunohistochemistry techniques in 299 skin biopsies and 68 nerve biopsies taken from patients at recruitment. The tissues were stained with hematoxylin and eosin, modified Fite Faraco, CD68 macrophage cell marker and S100. CONCLUSIONS/SIGNIFICANCE: Histological analysis of the biopsies showed that 43% had borderline tuberculoid (BT) leprosy, 27% borderline lepromatous leprosy, 9% lepromatous leprosy, 13% indeterminate leprosy types and 7% had no inflammation. Forty-six percent had histological evidence of a Type 1 Reaction (T1R) and 10% of Erythema Nodosum Leprosum. TNF-α was detected in 78% of skin biopsies (181/232), iNOS in 78% and TGF-ß in 94%. All three molecules were detected at higher levels in patients with BT leprosy. TNF-α was localised within macrophages and epithelioid cells in the granuloma, in the epidermis and in dermal nerves in a few cases. TNF-α, iNOS and TGF-ß were all significantly associated with T1R (p<0.001). Sixty-eight nerve biopsies were analysed. CD68, TNF-α and iNOS staining were detectable in 88%, 38% and 28% of the biopsies respectively. The three cytokines TNF-α, iNOS and TGF-ß detected by immunohistochemistry showed a significant association with the presence of skin reaction. This study is the first to demonstrate an association of iNOS and TGF-ß with T1R.

Protein phosphorylation pattern in the immune cells of leprosy affected individuals.

BACKGROUND: Leprosy is an infectious disease in which the susceptibility to the pathogen Mycobacterium leprae and the clinical manifestations are attributed to host immune cell response. Receptor mediated events and signalling in the immune cells are mediated by protein phosphorylation. The main signalling pathways and protein kinases known to be involved in the regulation of immune cells are cAMP dependent kinases, calcium/calmodulin dependent kinases, protein kinase C and mitogen activated protein kinases. The cumulative consequence of alterations in signalling pathways can be evaluated by intrinsic cellular protein phosphorylation by gamma-P32 ATP. The present study was designed to assess the protein phosphorylation in the immune cells of leprosy patients as compared with normal individuals. METHODOLOGY: Lymphocyte protein phosphorylation was conducted in 15 leprosy patients and 9 normal individuals. Protein phosphorylation of lymphocytes was carried out in the presence/absence of protein kinase modulators. The phosphorylation patterns were documented and analysed consequent to SDS-PAGE, staining, destaining, drying and autoradiography. RESULTS: The major phosphorylated proteins in lymphocytes were of molecular weights 20-22, 24-29, 30-35, 43, 46-50 and 66-68 kDa. In general, the major phosphorylated proteins were similar in the controls and in the patients. The phosphorylatability of these proteins varied with different modulators. Variations in the phosphorylation pattern were observed in 25% of the leprosy patients where there was a decrease of the 66 kDa protein and a decrease of 20-22 kDa protein phosphorylation. CONCLUSION: The observed alterations in the protein phosphorylation pattern could be due to alteration in kinases and/or their substrates or due to the effect of M. leprae on immune cells.