Computational Study of Plasmon Interaction in Organic Media: a Comparison Between Analytical and Numerical Model for Dimer

Plasmonics - In the present work, an investigation of wavelength-dependent absorption spectrum of spherical nanoparticles with different arrangements in organic medium using discrete dipole...     

Next-Generation Sequencing (NGS) in COVID-19: A Tool for SARS-CoV-2 Diagnosis,Monitoring New Strains and Phylodynamic Modeling in Molecular Epidemiology

This review discusses the current testing methodologies for COVID-19 diagnosis and explores next-generation sequencing (NGS) technology for the detection of SARS-CoV-2 and monitoring phylogenetic evolution in the current COVID-19 pandemic. The review addresses the development, fundamentals, assay quality control and bioinformatics processing of the NGS data. This article provides a comprehensive review of the obstacles and opportunities facing the application of NGS technologies for the diagnosis, surveillance, and study of SARS-CoV-2 and other infectious diseases. Further, we have contemplated the opportunities and challenges inherent in the adoption of NGS technology as a diagnostic test with real-world examples of its utility in the fight against COVID-19.     

Evaluation of oxygen mass transfer in Aspergillus niger fermentation using data reconciliation

Fermentation experiments using Aspergillus niger result in a very viscous broth due to the growth of filamentous microorganism. For viscous fermentation processes, it is difficult to estimate with confidence the volumetric oxygen mass transfer coefficient (K(L)a), which can be used for scale-up or design of bioreactors. In the present study, four methods based on dynamic and stationary approaches were used to measure K(L)a throughout the fermentation. Data reconciliation was used to obtain a more reliable and consistent K(L)a. The K(L)a value obtained by a data reconciliation technique was found to be more reliable since it takes into consideration both the reliability of all measured variables and the accuracy of all mass balance equations.     

Incidence of HIV and the Prevalence of HIV,Hepatitis B and Syphilis among Youths in Maputo,Mozambique: A Cohort Study

Background

Prevalence of HIV in Mozambique among individuals aged 15–49 years is 11.5%. The HIV prevalence is higher in women than in men across the country, peaking at ages 25–29 years and 35–39 years, respectively. In this study, we aimed at determining the prevalence and incidence of HIV, prevalence of Hepatitis B (HBV), and prevalence of syphilis in youths. We also characterized a cohort of youths for future participation in phase I/II HIV vaccine trials.

Methods

The study was conducted at a youth clinic in Maputo Central Hospital from August 2009 to October 2011. Youths of both genders aged 18–24 years (n = 1380) were screened for HIV using a sequential algorithm of two immunochromatographic assays, HBV using an enzyme linked immunosorbant test, and syphilis using a treponemal immunochromatographic strip test. The HIV seronegative participants (n = 1309) were followed-up for 12 months with quarterly study visits. The clinical and behavioral data were collected using structured questionnaires. The HIV seroconversions were confirmed by a molecular assay.

Results

The study population was female dominant (76.8%). All participants had a formal education, with 44.6% studying for technical or higher education degrees. The mean age at sexual debut was 16.6 years (SD: ±1.74), with 85.6% reporting more than one sexual partner in life. The screening showed the prevalence of HIV, HBV, and syphilis at 5.1% (95% CI: 3.97–6.31), 12.2% (95% CI 10.5%–14.0%), and 0.36% (95% CI 0.15%–0.84%), respectively. The HIV incidence rate was found to be 1.14/100 person years (95% CI: 0.67–1.92). Retention rates were stable throughout the study being 85.1% at the last visit.

Conclusion

Incidence of HIV in this cohort of youths in Maputo was relatively low. Also, the prevalence of HIV and syphilis was lower than the national values in this age group. However, the HBV prevalence was higher than in previous reports in the country.     

Development of Biotechnology Products in Pre-filled Syringes: Technical Considerations and Approaches

A monoclonal antibody (mAb) product development case study is presented to address some of the issues faced during developing a pre-filled syringe (PFS) product for a biotherapeutic. In particular, issues involving incompatibility with silicone oil and a stability-based approach for selection of PFS barrel and tip cap components have been discussed. Silicone spiking studies followed by exposure to agitation stress or accelerated temperature conditions were used to check for incompatibilities of the mAb with silicone oil, a necessary product contact material in PFS. In addition, screening studies to compare various closure materials as well as syringe barrel processing methods were used to select the optimum closure materials as well as the correct syringe processing method. Results indicate that the model mAb formulation used was sensitive to high levels of silicone oil especially under accelerated temperature conditions resulting in formation of protein–silicone particles in the solution for samples that were spiked with the silicone oil. Agitation stress did not have any significant impact on the quality attributes tested. Samples stored in syringe barrels that were processed with sprayed-on silicone had higher levels of subvisible particles as compared to those that were processed with the baked-on process. The tip cap comparability study resulted in one tip cap material having superior compatibility among the three that were tested. The quality attribute that was most impacted by the tip cap materials was mAb oxidation. An approach for evaluation of primary packaging components during the development of pre-filled syringe presentations for biotechnology-based compounds has been highlighted.     

Synthesis and biological activity of 5-chloro-N4-substituted phenyl-9H-pyrimido[4,5-b]indole-2,4-diamines as vascular endothelial growth factor receptor-2 inhibitors and antiangiogenic agents

Inhibition of receptor tyrosine kinase (RTK) signaling pathways is an important area for the development of novel anticancer agents. Numerous multikinase inhibitors (MKIs) have been recently approved for the treatment of cancer. Vascular endothelial growth factor receptor-2 (VEGFR-2) is the principal mediator of tumor angiogenesis. In an effort to develop ATP-competitive VEGFR-2 selective inhibitors the 5-chloro-N⁴-substituted phenyl-9H-pyrimido[4,5-b]indole-2,4-diamine scaffold was designed. The synthesis of the target compounds involved N-(4,5-dichloro-9H-pyrimido[4,5-b]indol-2-yl)-2,2-dimethylpropanamide) as a common intermediate. A nucleophilic displacement of the 4-chloro group of the common intermediate by appropriately substituted anilines afforded the target compounds. Biological evaluation indicated that compound 5 is a potent and selective VEGFR-2 inhibitor comparable to sunitinib and semaxinib.     

Pinda shrirangii,a new elegant species of Apiaceae from the northern Western Ghats,India

A new species, Pinda shrirangii Gosavi & Chandore, is described and illustrated from a high-elevation region of northern Western Ghats, India. The new species is closely allied to the only other species in the genus, Pinda concanensis (Dalzell) P.K.Mukh. & Constance which was also described from the northern Western Ghats of Maharashtra state of India. Coloured photographs and illustrations are provided to facilitate the identification.     

Splenectomy exacerbates lung injury after ischemic acute kidney injury in mice

Patients with acute kidney injury (AKI) have increased serum proinflammatory cytokines and an increased occurrence of respiratory complications. The aim of the present study was to examine the effect of renal and extrarenal cytokine production on AKI-mediated lung injury in mice. C57Bl/6 mice underwent sham surgery, splenectomy, ischemic AKI, or ischemic AKI with splenectomy and kidney, spleen, and liver cytokine mRNA, serum cytokines, and lung injury were examined. The proinflammatory cytokines IL-6, CXCL1, IL-1β, and TNF-α were increased in the kidney, spleen, and liver within 6 h of ischemic AKI. Since splenic proinflammatory cytokines were increased, we hypothesized that splenectomy would protect against AKI-mediated lung injury. On the contrary, splenectomy with AKI resulted in increased serum IL-6 and worse lung injury as judged by increased lung capillary leak, higher lung myeloperoxidase activity, and higher lung CXCL1 vs. AKI alone. Splenectomy itself was not associated with increased serum IL-6 or lung injury vs. sham. To investigate the mechanism of the increased proinflammatory response, splenic production of the anti-inflammatory cytokine IL-10 was determined and was markedly upregulated. To confirm that splenic IL-10 downregulates the proinflammatory response of AKI, IL-10 was administered to splenectomized mice with AKI, which reduced serum IL-6 and improved lung injury. Our data demonstrate that AKI in the absence of a counter anti-inflammatory response by splenic IL-10 production results in an exuberant proinflammatory response and lung injury.     

Post-translational protein modification by carotenoid cleavage products

Carotenoids are known to generate various aldehydes, known as carotenoid-derived aldehydes (CDAs), which could efficiently react with protein or DNA. In this in vitro model study, interaction between CDA and protein has been studied. Various proteins were incubated with CDA, and protein modification and adduct formation were confirmed by using matrix-assisted laser desorption and ionization time-of-flight, amino acid analysis, and measuring enzyme activity on modification with CDA. Using radiolabeled NaB((3) H)H(4) and Raney nickel as well as sulfhydryl assay (Ellman's reagent), we confirmed that CDA could conjugate with cysteine through a thioether linkage. The carbonyl assay using 2,4-dinitrophenylhydrazine revealed the possible involvement of Schiff's base reaction between CDA and lysine. The adducts formed between β-apo-8-carotenal (BA8C) and N-acetylcysteine and BA8C and N-acetyllysine were confirmed by HPLC and ESI-MS. Our results suggest that CDA could alter protein function by post-translational interaction with cysteine and lysine by thioether linkage and by schiff's based bonds, respectively. Thus, the formation of CDA adducts with proteins could alter functional properties of proteins responsible for maintaining cell homeostasis and thereby cause cellular toxicity. In view of these observations, further studies are required to understand the delicate balance between beneficial and/or harmful effects of carotenoids as a dietary supplement to slow age-related macular degeneration progression.