Formulation and Evaluation of Tramadol HCl Matrix Tablets Using Carbopol 974P and 934 as Rate-Controlling Agents

Purpose: To formulate and prepare controlled release (CR) matrix tablets of tramadol HCl using Carbopol 974P and 934 polymers as rate-controlling agents.Methods: The tablets were prepared by direct compression method using various drug to polymer (D:P) ratios. Co-excipients, including carboxymethylcellulose, starch and/or hydroxypropyl methylcellulosewere also used to modulate the formulations. Various physical tests and in vitro dissolution studies were carried out on the formulations. The dissolution data were subjected to various release modelsResults: As the concentration of the polymer (rate-controlling agent) increased, dissolution rate decreased, For the formulation containing Carbopol 974P at D:P ratio of 10:7, drug release decreased to 83 % compared with the release rate of 99 % for the formulation with D:P ratio of 10:3. Kinetic analysis indicates that drug release mechanism was anomalous non-Fickian diffusion.Conclusion: Both Carbopol 974P and 934 can be used as rate-controlling agents in the formulation of tramadol HCl CR tablets. Appropriate selection of drug/polymer ratio can be applied effectively to modulate the dissolution rate of the drug.Keywords: Tramadol, Carbopol, Carboxymethylcellulose (CMC), Hydroxypropyl methylcellulose, Controlled releas

Strain-Induced Metallization and Defect Suppression at Zipper-like Interdigitated Atomically Thin Interfaces Enabling High-Efficiency Halide Perovskite Solar Cells

Halide perovskite light absorbers have great advantages for photovoltaics such as efficient solar energy absorption, but charge accumulation and recombination at the interface with an electron transport layer (ETL) remain major challenges in realizing the absorbers’ full potential. Here we report the experimental realization of a zipper-like interdigitated interface between a Pb-based halide perovskite light absorber and an oxide ETL by the PbO capping of the ETL surface, which produces an atomically thin two-dimensional metallic layer that can significantly enhance the perovskite/ETL charge extraction process. As the atomistic origin of the emergent two-dimensional interfacial metallicity, first-principles calculations performed on the representative MAPbI₃/TiO₂ interface identify the interfacial strain induced by the simultaneous formation of stretched I-substitutional Pb bonds (and thus Pb–I–Pb bonds bridging MAPbI₃ and TiO₂) and contracted substitutional Pb–O bonds. Direct and indirect experimental evidence for the presence of interfacial metallic states are provided, and a nonconventional defect-passivating nature of the strained interdigitated perovskite/ETL interface is emphasized. It is experimentally demonstrated that the PbO capping method is generally applicable to other ETL materials, including ZnO and SrTiO₃, and that the zipper-like interdigitated metallic interface leads to about a 2-fold increase in the charge extraction rate. Finally, in terms of the photovoltaic efficiency, we observe a volcano-type behavior with the highest performance achieved at the monolayer-level PbO capping. This work establishes a general perovskite/ETL interface engineering approach to realize high-performance perovskite solar cells

Molecular Targeting of Carbonic Anhydrase IX in Mice with Hypoxic HT29 Colorectal Tumor Xenografts

Background: Carbonic anhydrase IX (CAIX) is a membrane spanning protein involved in the enzymatic regulation of tumor acid-base balance. CAIX has been shown to be elevated in a number of hypoxic tumor types. The purpose of this study was to determine the efficiency of intact and IgG fragments of cG250 to target CAIX in vivo in a hypoxic tumor model. Methodology/Principal Findings: Conventional biodistribution studies were performed with 111 In-DO3A-cG250, 111 In-DO3A-F(ab’)2-cG250 and 111 In-DO3A-Fab-cG250. Additional ex vivo analysis of the tumor was performed with markers for tumor hypoxia, blood perfusion and endogenous CAIX expression. All four data sets were digitally correlated to determine the optimal agent for determining hypoxia in a HT29 colon cancer xenograft. The HT29 human colorectal tumor xenografts show strong CAIX expression in hypoxic areas of poor blood perfusion. The intact IgG had an initial high focal uptake at the periphery of these hypoxic regions and penetration into the areas of highest CAIX expression over the 7-day study period. The lower molecular weight antibody fragments had a faster uptake into areas of high CAIX expression, but had a much lower absolute uptake at the optimal imaging times. Conclusions/Significance: For the clinical detection of hypoxia induced CAIX using cG250 antibody based agents, imagin

Development of Artificial Geochemical Filter to Treat Acid Mine Drainage for Safe Disposal of Mine Water in Salt Range Portion of Indus Basin—A Lab to Pilot Scale Study

Data Availability Statement: Not applicable.Copyright © 2022 by the authors. Several passive and active treatment approaches are available for dealing with Acid Mine Drainage (AMD). Despite a range of newly emergent techniques for the treatment of AMD, pH control using low-cost neutralizing reagents has been the most common and economical technique for the treatment of AMD. Thereby, owing to their widespread availability, ease of use, and cost effectiveness, active treatment techniques utilizing calcium-based reagents (particularly limestone) are considered the prime choice for treating AMD. Limestone is a well-known option worldwide for AMD neutralization thanks to its easy availability, low cost, and excellent efficiency. Generally, acidity is reduced by the presence of CaCO3 and alkalinity (i.e., HCO−3) is increased. pH can be increased from 2.5 to 7.5 by using limestone as a treating agent, resulting in the precipitation of heavy metals, which can then be removed by precipitation and sorption. Wargal limestone, a well-known limestone from the Salt Range, Indus basin, Pakistan, has high potential for neutralization and treatment of PTEs present in mine water or AMD. After selecting a suitable neutralization material at pilot scale, two different filters were designed using selected Wargal limestone: Filter 1 A (Oxic-based, Vertical bed-type Wargal Limestone Filter) and Filter 1 B (Anoxic-based Vertical bed-type Wargal Limestone Filter with Compost). The pH of the AMD under study was elevated from 2.5 to 7.65 and 7.60, respectively, in uncoated and coated media of limestone. Although the neutralization potential decreased over time, as an overall phenomenon the Ca concentration and net alkalinity (280–360 mg/L) were increased with the removal of metals such as Fe, Cu, Pb and Mn. The respective removal efficiency of these metals was 98%, 99%, 99% and 60%, with a threshold residence time of 5 h. in all columns of the developed filters.Chinese Academy of Sciences President’s International Fellowship Initiative (Grant No. 2021VCA0010); International Science and Technology Cooperation Program of China (2018YFE0100100)

Enhanced biohydrogen production from citrus wastewater using anaerobic sludge pretreated by an electroporation technique

In the present study, the applicability of electroporation (EP) has been investigated as a pretreatment method for enriching hydrogen producers and eliminating hydrogen consumers in anaerobic sludge (AS). Citrus wastewater was used as a feed source for biohydrogen production. Different treatment intensities (TI) of EP for 0.5 min (TI = 30 kWh/m3), 1 min (TI = 60 kWh/m3), and 2 min (TI = 120 kWh/m3) were employed to observe the effects of EP on the microbial community of AS. Furthermore, sonication with a probe, sonication in a bath, and heat-shock pretreatments were also conducted to compare the hydrogen yield with EP. The cell inactivation was evaluated and visualized using colony-forming units (CFU) and field emission scanning electron microscopy (FESEM), respectively. Among the different TIs, the TI of 60 kWh/m3 achieved higher methanogen inactivation with maximum hydrogen (896 mL) production compared to other EP pretreatments after 180 h of dark fermentation. In comparison with other pretreatments, the highest hydrogen production of 896 mL was achieved with EP treatment, followed by sonication with a probe (678 mL) and sonication in a bath (563 mL). The heat-shock pretreatment exhibited the lowest ultimate hydrogen production of 545 mL among the four different methods applied in this study. The outcome of this study suggests that EP is a promising technique for pretreating mixed cultures for the enhanced production of biohydrogen

Superiority of Dynamic Weights against Fixed Weights in Merging Multi-Satellite Precipitation Datasets over Pakistan

Data Availability Statement: The data utilized in this study were acquired through purchase from the Pakistan Meteorology Department (PMD) and the Water and Power Development Authority. Information about the data is available at https://www.pmd.gov.pk/en/ (accessed on 1 January 2023) and http://www.wapda.gov.pk/ (accessed on 1 January 2023), respectively.Satellite precipitation products (SPPs) are undeniably subject to uncertainty due to retrieval algorithms and sampling issues. Many research efforts have concentrated on merging SPPs to create high-quality merged precipitation datasets (MPDs) in order to reduce these uncertainties. This study investigates the efficacy of dynamically weighted MPDs in contrast to those using static weights. The analysis focuses on comparing MPDs generated using the “dynamic clustered Bayesian averaging (DCBA)” approach with those utilizing the “regional principal component analysis (RPCA)” under fixed-weight conditions. These MPDs were merged from SPPs and reanalysis precipitation data, including TRMM (Tropical Rainfall Measurement Mission) Multi-satellite Precipitation Analysis (TMPA) 3B42V7, PERSIANN-CDR, CMORPH, and the ERA-Interim reanalysis precipitation data. The performance of these datasets was evaluated in Pakistan’s diverse climatic zones—glacial, humid, arid, and hyper-arid—employing data from 102 rain gauge stations. The effectiveness of the DCBA model was quantified using Theil’s U statistic, demonstrating its superiority over the RPCA model and other individual merging methods in the study area The comparative performances of DCBA and RPCA in these regions, as measured by Theil’s U, are 0.49 to 0.53, 0.38 to 0.45, 0.37 to 0.42, and 0.36 to 0.43 in glacial, humid, arid, and hyper-arid zones, respectively. The evaluation of DCBA and RPCA compared with SPPs at different elevations showed poorer performance at high altitudes (>4000 m). The comparison of MPDs with the best performance of SPP (i.e., TMPA) showed significant improvement of DCBA even at altitudes above 4000 m. The improvements are reported as 49.83% for mean absolute error (MAE), 42.31% for root-mean-square error (RMSE), 27.94% for correlation coefficient (CC), 40.15% for standard deviation (SD), and 13.21% for Theil’s U. Relatively smaller improvements are observed for RPCA at 13.04%, 1.56%, 10.91%, 1.67%, and 5.66% in the above indices, respectively. Overall, this study demonstrated the superiority of DCBA over RPCA with static weight. Therefore, it is strongly recommended to use dynamic variation of weights in the development of MPDs.National Natural Science Foundation of China (grant numbers 51839006 and 52250410336)

Toward a first-principles integrated simulation of tokamak edge plasmas

Performance of the ITER is anticipated to be highly sensitive to the edge plasma condition. The edge pedestal in ITER needs to be predicted from an integrated simulation of the necessary first-principles, multi-scale physics codes. The mission of the SciDAC Fusion Simulation Project (FSP) Prototype Center for Plasma Edge Simulation (CPES) is to deliver such a code integration framework by (1) building new kinetic codes XGC0 and XGC1, which can simulate the edge pedestal buildup; (2) using and improving the existing MHD codes ELITE, M3D-OMP, M3D-MPP and NIMROD, for study of large-scale edge instabilities called Edge Localized Modes (ELMs); and (3) integrating the codes into a framework using cutting-edge computer science technology. Collaborative effort among physics, computer science, and applied mathematics within CPES has created the first working version of the End-to-end Framework for Fusion Integrated Simulation (EFFIS), which can be used to study the pedestal-ELM cycles

Absence of Both IL-7 and IL-15 Severely Impairs the Development of CD8+ T Cell Response against Toxoplasma gondii

CD8+ T cells play an essential role in the protection against both acute as well as chronic Toxoplasma gondii infection. Although the role of IL-15 has been reported to be important for the development of long-term CD8+ T cell immunity against the pathogen, the simultaneous roles played by both IL-15 and related γ-chain family cytokine IL-7 in the generation of this response during acute phase of infection has not been described. We demonstrate that while lack of IL-7 or IL-15 alone has minimal impact on splenic CD8+ T cell maturation or effector function development during acute Toxoplasmosis, absence of both IL-7 and IL-15 only in the context of infection severely down-regulates the development of a potent CD8+ T cell response. This impairment is characterized by reduction in CD44 expression, IFN-γ production, proliferation and cytotoxicity. However, attenuated maturation and decreased effector functions in these mice are essentially downstream consequences of reduced number of antigen-specific CD8+ T cells. Interestingly, the absence of both cytokines did not impair initial CD8+ T cell generation but affected their survival and differentiation into memory phenotype IL-7Rαhi cells. Significantly lack of both cytokines severely affected expression of Bcl-2, an anti-apoptotic protein, but minimally affected proliferation. The overarching role played by these cytokines in eliciting a potent CD8+ T cell immunity against T. gondii infection is further evidenced by poor survival and high parasite burden in anti IL-7 treated IL-15−/− mice. These studies demonstrate that the two cytokines, IL-7 and IL-15, are exclusively important for the development of protective CD8+ T cell immune response against T. gondii. To the best of our knowledge this synergism between IL-7 and IL-15 in generating an optimal CD8+ T cell immunity against intracellular parasite or any other infectious disease model has not been previously reported

Specific Alleles of CLN7/MFSD8, a Protein That Localizes to Photoreceptor Synaptic Terminals, Cause a Spectrum of Nonsyndromic Retinal Dystrophy

Purpose: Recessive mutations in CLN7/MFSD8 usually cause variant late-infantile onset neuronal ceroid lipofuscinosis (vLINCL), a poorly understood neurodegenerative condition, though mutations may also cause nonsyndromic maculopathy. A series of 12 patients with nonsyndromic retinopathy due to novel CLN7/MFSD8 mutation combinations were investigated in this study. Methods: Affected patients and their family members were recruited in ophthalmic clinics at each center where they were examined by retinal imaging and detailed electrophysiology. Whole exome or genome next generation sequencing was performed on genomic DNA from at least one affected family member. Immunofluorescence confocal microscopy of murine retina cross-sections were used to localize the protein. Results: Compound heterozygous alleles were identified in six cases, one of which was always p.Glu336Gln. Such combinations resulted in isolated macular disease. Six further cases were homozygous for the variant p.Met454Thr, identified as a founder mutation of South Asian origin. Those patients had widespread generalized retinal disease, characterized by electroretinography as a rod-cone dystrophy with severe macular involvement. In addition, the photopic single flash electroretinograms demonstrated a reduced b- to a-wave amplitude ratio, suggesting dysfunction occurring after phototransduction. Immunohistology identified MFSD8 in the outer plexiform layer of the retina, a site rich in photoreceptor synapses. Conclusions: This study highlights a hierarchy of MFSD8 variant severity, predicting three consequences of mutation: (1) nonsyndromic localized maculopathy, (2) nonsyndromic widespread retinopathy, or (3) syndromic neurological disease. The data also shed light on the underlying pathogenesis by implicating the photoreceptor synaptic terminals as the major site of retinal disease

A Non-Death Role of the Yeast Metacaspase: Yca1p Alters Cell Cycle Dynamics

Caspase proteases are a conserved protein family predominantly known for engaging and executing apoptotic cell death. Nevertheless, in higher eukaryotes, caspases also influence a variety of cell behaviors including differentiation, proliferation and growth control. S. cerevisiae expresses a primordial caspase, yca1, and exhibits apoptosis-like death under certain stresses; however, the benefit of a dedicated death program to single cell organisms is controversial. In the absence of a clear rationale to justify the evolutionary retention of a death only pathway, we hypothesize that yca1 also influences non-apoptotic events. We report that genetic ablation and/or catalytic inactivation of Yca1p leads to a longer G1/S transition accompanied by slower growth in fermentation conditions. Downregulation of Yca1p proteolytic activity also results in failure to arrest during nocodazole treatment, indicating that Yca1p participates in the G2/M mitotic checkpoint. 20s proteasome activity and ROS staining of the Δyca1 strain is indistinguishable from its isogenic control suggesting that putative regulation of the oxidative stress response by Yca1p does not instigate the cell cycle phenotype. Our results demonstrate multiple non-death roles for yca1 in the cell cycle