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Antiviral capacity of the early CD8 T-cell response is predictive of natural control of SIV infection: Learning in vivo dynamics using ex vivo data
No full textWhile most individuals suffer progressive disease following HIV infection, a small fraction spontaneously controls the infection. Although CD8 T-cells have been implicated in this natural control, their mechanistic roles are yet to be established. Here, we combined mathematical modeling and analysis of previously published data from 16 SIV-infected macaques, of which 12 were natural controllers, to elucidate the role of CD8 T-cells in natural control. For each macaque, we considered, in addition to the canonical in vivo plasma viral load and SIV DNA data, longitudinal ex vivo measurements of the virus suppressive capacity of CD8 T-cells. Available mathematical models do not allow analysis of such combined in vivo-ex vivo datasets. We explicitly modeled the ex vivo assay, derived analytical approximations that link the ex vivo measurements with the in vivo effector function of CD8-T cells, and integrated them with an in vivo model of virus dynamics, thus developing a new learning framework that enabled the analysis. Our model fit the data well and estimated the recruitment rate and/or maximal killing rate of CD8 T-cells to be up to 2-fold higher in controllers than non-controllers (p = 0.013). Importantly, the cumulative suppressive capacity of CD8 T-cells over the first 4–6 weeks of infection was associated with virus control (Spearman’s ρ = -0.51; p = 0.05). Thus, our analysis identified the early cumulative suppressive capacity of CD8 T-cells as a predictor of natural control. Furthermore, simulating a large virtual population, our model quantified the minimum capacity of this early CD8 T-cell response necessary for long-term control. Our study presents new, quantitative insights into the role of CD8 T-cells in the natural control of HIV infection and has implications for remission strategies
Extensive protein pyrophosphorylation revealed in human cell lines
No full textReversible protein phosphorylation is a central signaling mechanism in eukaryotes. Although mass-spectrometry-based phosphoproteomics has become routine, identification of non-canonical phosphorylation has remained a challenge. Here we report a tailored workflow to detect and reliably assign protein pyrophosphorylation in two human cell lines, providing, to our knowledge, the first direct evidence of endogenous protein pyrophosphorylation. We manually validated 148 pyrophosphosites across 71 human proteins, the most heavily pyrophosphorylated of which were the nucleolar proteins NOLC1 and TCOF1. Detection was consistent with previous biochemical evidence relating the installation of the modification to inositol pyrophosphates (PP-InsPs). When the biosynthesis of PP-InsPs was perturbed, proteins expressed in this background exhibited no signs of pyrophosphorylation. Disruption of PP-InsP biosynthesis also significantly reduced rDNA transcription, potentially by lowering pyrophosphorylation on regulatory proteins NOLC1, TCOF1 and UBF1. Overall, protein pyrophosphorylation emerges as an archetype of non-canonical phosphorylation and should be considered in future phosphoproteomic analyses
Multicomponent steady-state modeling, performance optimization and prediction of cleaning frequency for treatment of cellulosic manmade fibre industry stream using polysodium 4- styrenesulfonate (PSS) incorporated nanofiltration membrane
No full textEffect of polysodium 4-styrenesulfonate (PSS) in the skin layer on performance of nanofiltration (NF) membrane was analyzed for treatment of saline stream from manmade fiber industry. The NF membrane with 0.05 % (w/w) PSS concentration in aqueous phase had better hydrophilicity (contact angle: 33°) and water flux of 27 L.m-2.h-1 along with significant salt rejection (Na2SO4: 90 %, CaSO4: 85 % and NaCl: 80 %) at transmembrane pressure 8.3 bar and crossflow rate 100 L.h-1. A long-term study with the wastewater showed that the intermittent cleaning of the membrane every 6 h led to 16 L.m-2.h-1 average permeate flux and sulfate rejection above 95 %.
A two-component, steady-state model was used to quantify the performance of the selected membrane. Based on the fouling study, a semi-empirical theory was proposed to identify the cleaning frequency. The theory developed is useful for the operation, maintenance and recovery of the divalent salts from reject stream of such industry
Metal organic framework doped amine-functionalized polymeric beads for selective removal of Uranium (VI) from alkaline leach liquor: Batch and column study
No full textIn this work, a diethylenetriamine (DETA) functionalized metal organic framework (ZIF-67) incorporated polyacrylonitrile (PAN) bead (MFB) was developed to capture U efficiently from simulated medium and alkaline leach liquor. The synthesized beads were characterized using suitable analytical methods. Fourier transform infrared (FTIR) spectroscopy and X-ray photoelectron spectroscopy (XPS) were used to understand the U uptake mechanism. The process of adsorption was inherently heat-absorbing and spontaneous in nature. The Langmuir sorption capability (Qm) was 835 mg/g, at pH 7 and, 298 K. Surface- grafted abundant amine (–NH2) groups introduce significant coordinative interaction with the U species in aqueous medium. The adsorbent is reusable and structurally robust with >85 % U removal after five consecutive regeneration cycles. The performance of the continuous adsorption columns was simulated by a fundamental adsorption-diffusion model and the relevant transport parameters were evaluated. For real life alkaline leach liquor with U concentration 825 mg/L and 100 to 500 kg of adsorbent, the adsorption column had a breakthrough life of 46 to 108 days with constant flow rate of 500 L/day. This study showed that the synthesized MFB is an excellent adsorbent that is inexpensive, non-toxic, recyclable,environmentally compatible, and selective towards U removal from alkaline leach liquor
Arsenic removal from drinking water using treated laterite-based adsorbent
No full textAccess to safe drinking water is an essential element for sustainable life. Arsenic poisoning in groundwater has been a cause of concern since decades and is one of the most hazardous contaminants of potable groundwater. The major sources of contamination are geogenic, agricultural, and industrial as well. This chapter presents the development of a novel adsorbent using naturally occurring laterite soil that has proved to be an excellent material for the removal of arsenic from groundwater. Natural laterite has been acid-activated using acid alkali treatment process under optimized process conditions to prepare treated laterite (TL) having 40 times higher adsorption capacity compared to the untreated material. The enhanced adsorption capacity of 8 mg/g for As(III) and 24.1 mg/g for As(V) is the highest among all natural adsorbents or their derivatives reported so far and also has the advantage of a granular nature that rules out high-pressure drop during operation. The adsorbent also meets the safe disposal guidelines and can even be used for road laying purpose without any risk of leaching. The laboratory-scale column run experiments are carried out to study the effect of incoming concentration, flow rate, bed height, and the presence of co-ions. The adsorption equilibrium and kinetics using TL as an adsorbent are studied in detail, and a kinetic model has been established. The model parameters required for upscaling are determined by comparing with the experimental results. Different aspects of scale-up of the technology in the form of integrated filters designed for domestic applications (capacity 100 L/day) as well as community-scale filters (capacity 2 m3/h) are discussed in brief. A transport-based model to predict the permeate concentration and filter life is also presented in detail that can be of immense help at different stages of product life, including design, installation, and maintenance
Unveiling the mechanism of visible light-assisted peroxymonosulfate activation and carbamazepine degradation using NH<sub>2</sub>-MIL-125(Ti)@MIL-53(Fe/Co) heterojunction photocatalyst
No full textHerein, a facile hydrothermal synthesis method was used to create the visible light-responsive heterojunction composite NH2-MIL-125(Ti)@MIL-53(Fe/Co) (AMIL@MIL). This composite catalyst was investigated for the mineralization of carbamazepine (CBZ) in aqueous solution with a visible light-assisted activation of peroxymonosulfate (PMS). CBZ (initial concentration: 10 mg L-1) could be totally degraded by 0.05 g L-1of composite containing 10 wt% NH2-MIL-125(Ti) (AMIL(10)@MIL) and 0.25 g L-1 of PMS within 1 h reaction under visible light. The enhanced degradation of CBZ was attributed to the efficient activation of PMS, and subsequently the generation of SO4.-, .OH and O2.- radicals, together with the remarkable light harvesting and spatial charge separation in the direct Z-scheme heterojunction configuration. The composite catalyst could effectively treat contaminated surface and groundwater samples, overcoming the minimal to moderate inhibitory effects of coexisting ions and organics, while also exhibiting good reusability and structural integrity. The adsorbed PMS molecules are activated by several surface-confined redox cycles, including Fe2+/Fe3+, Co2+/Co3+ and Ti3++/Ti4+, aiding in the production of reactive radicals in the medium and efficient charge transfer during the reaction. A thorough study on the intermediates was carried out to determine the plausible CBZ mineralization and degradation pathway in the AMIL(10)@MIL/PMS/vis system. Overall, the suggested catalytic method is applicable and feasible for the remediation of contaminated surface and groundwater when exposed to visible light radiation
Review on wastewater treatment for man-made cellulosic fibre industries: recent advancement and future prospects
No full textMan-made cellulosic fibres (MMCF) are gaining attention due to their sustainability compared to other fibres. The demand for MMCF has increased due to improved standard of living leading to their accelerated production. Substantial amount of water and chemicals are required for the production of MMCF generating a significant volume of wastewater. This review highlights the type of effluents generated in MMCF industries, their characterization, along with global discharge standards. Chemical oxygen demand, dissolved salts, and heavy metals are found as the major source of impurities. Current effluent treatment methods are critically reviewed to identify the challenges and scope for technological advancement focusing on impurities reduction, value recovery, and water recycling to meet the stringent disposal norms. Additionally, the criteria for the selection of a techno-economically feasible treatment solution are also discussed. Further, the areas for improvement in conventional zero liquid discharge system for MMCF industries have been highlighted. Graphical abstrac
Anti-Emetics in Children Receiving Chemotherapy for Solid Tumors and Leukemia: Pharmacology and Optimization of Therapy for Nausea and Vomiting
No full textThe management of chemotherapy-induced nausea and vomiting (CINV) in children remains challenging due to differences in the chemotherapy regimens, their relative emetogenicity compared to that in adults and differences in drug metabolism and the available formulations. The common four classes of anti-emetics used for the treatment and prophylaxis of CINV in children include dexamethasone, neurokinin-1 receptor antagonists, 5-hydroxytryptamine-3 receptor antagonists (5HT3RAs), and olanzapine. The appropriate dose of dexamethasone for CINV prophylaxis in children is unknown, with a significant variability in dosage ranging between 6 and 32 mg/m2/day. The dose of dexamethasone is decreased by 30% when this drug is combined with (fos)aprepitant in children, in contrast to a decrease of 50% required in adults. The use of aprepitant in younger children (<12 years) is often hampered by the non-availability of oral suspension formulations in many countries; alternatively, 80 mg capsules are administered for 1–3 days in certain institutes to children weighing between 15 and 40 kg. Among the different 5HT3RAs, palonosetron is comparatively metabolized faster in children than in adults, requiring a higher dosage for similar efficacy to that achieved in adults. Olanzapine is a newer agent, used in doses between 0.1 and 0.14 mg/kg/day in children, with good anti-emetic efficacy, but has sedation and hyperglycemia as concerning adverse effects. Drug interactions between anti-emetics and between anti-emetics and chemotherapy/supportive agents (azole antifungals, cyclosporine, arsenic trioxide), especially QTc prolongation, should be considered during prescription
Recent progress on polymeric probes for formaldehyde sensing: a comprehensive review.
No full textFormaldehyde (FA) is a reactive toxic volatile organic compound (VOC), produced both exogenously from the environment and endogenously within most organisms, and poses significant health risks to humans at elevated concentrations. Consequently, the development of reliable and sensitive FA sensing technologies is crucial for environmental monitoring, industrial safety, and public health protection. This review will provide a concise overview of FA sensing methodologies, highlighting key principles, sensing mechanisms, and recent advancements. The main aim of this review article is to comprehensively discuss recent advancements in FA sensors utilizing small molecules, nanoparticles, organic materials, and polymers, along with their successful applications across various fields, with particular emphasis on in situ FA sensing using polymeric probes due to their advantages over small molecular probes. Additionally, it will discuss prospects for future design and research in this area. We anticipate that this article will aid in the development of next-generation polymeric FA sensing probed with improved physicochemical properties
Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo
No full textDespite the growing number of binary black hole coalescences confidently observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include the effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that have already been identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total source-frame mass M > 70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz emitted gravitational-wave frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place a conservative upper limit for the merger rate density of high-mass binaries with eccentricities 0 < e ≤ 0.3 at 16.9 Gpc−3 yr−1 at the 90% confidence level