Molecular dynamics simulations and docking of non-nucleoside reverse transcriptase inhibitors (NNRTIs): a possible approach to personalized HIV treatment : from 7th German Conference on Chemoinformatics: 25 CIC-Workshop Goslar, Germany, 6 - 8 November 2011

The human immunodeficiency virus (HIV) is currently ranked sixth in the worldwide causes of death [1]. One treatment approach is to inhibit reverse transcriptase (RT), an enzyme essential for reverse transcription of viral RNA into DNA before integration into the host genome [2]. By using non-nucleoside RT inhibitors (NNRTIs) [3], which target an allosteric binding site, major side effects can be evaded. Unfortunately, high genetic variability of HIV in combination with selection pressure introduced by drug treatment enables the virus to develop resistance against this drug class by developing point mutations. This situation necessitates treatment with alternative NNRTIs that target the particular RT mutants encountered in a patient. Previously, proteochemometric approaches have demonstrated some success in predicting binding of particular NNRTIs to individual mutants; however a structurebased approach may help to further improve the predictive success of such models. Hence, our aim is to rationalize the experimental activity of known NNRTIs against a variety of RT mutants by combining molecular modeling, long-timescale atomistic molecular dynamics (MD) simulation sampling and ensemble docking. Initial control experiments on known inhibitor-RT mutant complexes using this protocol were successful, and the predictivity for further complexes is currently being evaluated. In addition to predictive power, MD simulations of multiple RT mutants are providing fundamental insight into the dynamics of the allosteric NNRTI binding site which is useful for the design of future inhibitors. Overall, work of this type is hoped to contribute to the development of predictive efficacy models for individual patients, and hence towards personalized HIV treatment options

Molecular dynamics simulations and docking of non-nucleoside reverse transcriptase inhibitors (NNRTIs): a possible approach to personalized HIV treatment

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The influence of snow cover variability on the runoff in Syr Darya headwater catchments between 2000 and 2022 based on the analysis of remote sensing time series

Climate change is affecting the snow cover conditions on a global scale, leading to changes in the extent and duration of snow cover as well as variations in the start and end of snow cover seasons. These changes can have a paramount impact on runoff and water availability, especially in catchments that are characterized by nival runoff regimes, e.g., the Syr Darya in Central Asia. This time series analyses of daily MODIS snow cover products and in situ data from hydrological stations for the time series from 2000 through 2022 reveal the influences of changing snow cover on the runoff regime. All catchments showed a decrease in spring snow cover duration of -0.53 to -0.73 days per year over the 22-year period. Catchments located farther west are generally characterized by longer snow cover duration and experience a stronger decreasing trend. Runoff timing was found to be influenced by late winter and spring snow cover duration, pointing towards earlier snowmelt in most of the regions, which affects the runoff in some tributaries of the river. The results of this study indicate that the decreasing snow cover duration trends lead to an earlier runoff, which demands more coordinated water resource management in the Syr Darya catchment. Further research is recommended to understand the implications of snow cover dynamics on water resources in Central Asia, crucial for agriculture and hydropower production

A Neural Receiver for 5G NR Multi-user MIMO

We introduce a neural network (NN)-based multiuser multiple-input multiple-output (MU-MIMO) receiver with 5G New Radio (5G NR) physical uplink shared channel (PUSCH) compatibility. The NN architecture is based on convolution layers to exploit the time and frequency correlation of the channel and a graph neural network (GNN) to handle multiple users. The proposed architecture adapts to an arbitrary number of sub-carriers and supports a varying number of multiple-input multiple-output (MIMO) layers and users without the need for any retraining. The receiver operates on an entire 5G NR slot, i.e., processes the entire received orthogonal frequency division multiplexing (OFDM) time-frequency resource grid by jointly performing channel estimation, equalization, and demapping. The proposed architecture operates less than 1 dB away from a baseline using linear minimum mean square error (LMMSE) channel estimation with K-best detection but benefits from a significantly lower computational complexity. We show the importance of a carefully designed training process such that the trained receiver is universal for a wide range of different unseen channel conditions. Finally, we demonstrate the results of a hardware-in-the-loop verification based on 3GPP compliant conformance test scenarios.Comment: 6 pages, 6 figures, presented at IEEE Globecom 202

Vehicular Livestock Mobility in West Africa: Seasonal Traffic Flows of Cattle, Sheep, and Goats across Bamako

Gefördert durch den Publikationsfonds der Universität Kasse

A Precious-Metal-Free Hybrid Electrolyzer for Alcohol Oxidation Coupled to CO2 -to-Syngas Conversion.

Electrolyzers combining CO2 reduction (CO2 R) with organic substrate oxidation can produce fuel and chemical feedstocks with a relatively low energy requirement when compared to systems that source electrons from water oxidation. Here, we report an anodic hybrid assembly based on a (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) electrocatalyst modified with a silatrane-anchor (STEMPO), which is covalently immobilized on a mesoporous indium tin oxide (mesoITO) scaffold for efficient alcohol oxidation (AlcOx). This molecular anode was subsequently combined with a cathode consisting of a polymeric cobalt phthalocyanine on carbon nanotubes to construct a hybrid, precious-metal-free coupled AlcOx-CO2 R electrolyzer. After three-hour electrolysis, glycerol is selectively oxidized to glyceraldehyde with a turnover number (TON) of ≈1000 and Faradaic efficiency (FE) of 83 %. The cathode generated a stoichiometric amount of syngas with a CO:H2 ratio of 1.25±0.25 and an overall cobalt-based TON of 894 with a FE of 82 %. This prototype device inspires the design and implementation of nonconventional strategies for coupling CO2 R to less energy demanding, and value-added, oxidative chemistry

Проектирование системы электроснабжения перевалопогрузочного комплекса морского порта

Объектом исследования является электрическая часть перевалопогрузочного комплекса ОАО «Восточный порт». Цель работы – проектирование системы электроснабжения перевалопогрузочного комплекса морского порта. В процессе исследования проводился сбор исходных данных в ходе производственной практики на объекте исследования. В результате была спроектирована схема электроснабжения от подстанции энергосистемы, до конечного электроприемника. Были выбраны кабели и провода, коммутационное оборудование. Также был произведен экономический расчет капитальных затрат на сооружение данной схемы, определены условия безопасности и гигиены труда рабочих предприятия.The object of the research is part of an electric perevalopogruzochnogo complex JSC "Vostochny Port". The purpose of the work - design of power supply system perevalopogruzochnogo seaport complex. The study was conducted to collect baseline data in the course of practical training on the subject of the study. As a result, power supply circuit has been designed from the substation grid, appliance, to the end. Cables and wires, switching equipment were chosen. There was also made economic calculation of capital costs for the construction of the scheme, identified the security conditions and hygiene of workers of the enterprise

Physiologic MR imaging of the tumor microenvironment revealed switching of metabolic phenotype upon recurrence of glioblastoma in humans

Treating recurrent glioblastoma (GB) is one of the challenges in modern neurooncology. Hypoxia, neovascularization, and energy metabolism are of crucial importance for therapy failure and recurrence. Twenty-one patients with initially untreated GB who developed recurrence were examined with a novel MRI approach for noninvasive visualization of the tumor microenvironment (TME). Imaging biomarker information about oxygen metabolism (mitochondrial oxygen tension) and neovascularization (microvascular density and type) were fused for classification of five different TME compartments: necrosis, hypoxia with/without neovascularization, oxidative phosphorylation, and glycolysis. Volume percentages of these TME compartments were compared between untreated and recurrent GB. At initial diagnosis, all 21 GB showed either the features of a glycolytic dominant phenotype with a high percentage of functional neovasculature (N = 12) or those of a necrotic/hypoxic dominant phenotype with a high percentage of defective tumor neovasculature (N = 9). At recurrence, all 21 GB revealed switching of the initial metabolic phenotype: either from the glycolytic to the necrotic/hypoxic dominant phenotype or vice-versa. A necrotic/hypoxic phenotype at recurrence was associated with a higher rate of multifocality of the recurrent lesions. Our MRI approach may be helpful for a better understanding of treatment-induced metabolic phenotype switching and for future studies developing targeted therapeutic strategies for recurrent GB

Concomitant Irradiation to Checkpoint Inhibitor Therapy of Hepatocellular Carcinoma Patients: A Systematic Retrospective, Single-Center Analysis

Introduction: Immunotherapy has been established as the standard treatment option for patients with advanced hepatocellular carcinoma (aHCC). Despite the increased efficacy, disease progression occurs in a relevant proportion of patients even after an objective response. Combination concepts with locoregional therapy are currently under investigation for hepatic disease but are also in discussion for the control of distant metastasis. Radiotherapy is a highly effective treatment modality for local tumor control. It is also thought to increase the efficacy of checkpoint inhibition and sensitize distant lesions to the effects of immunotherapy, but may potentially increase adverse effects. In our center, few patients with aHCC treated with immune checkpoint inhibitors (ICIs) received concomitant radiotherapy for symptom or disease control. The aim of this study was to retrospectively analyze adverse effects and efficacy of concomitant radiotherapy in patients with aHCC treated with checkpoint inhibition. Methods: To this aim, patients who received a combination of ICI and radiotherapy in our institution were retrospectively considered for analysis. The predefined inclusion criterion was radiotherapy after initiated checkpoint inhibition and continuation of ICI therapy for at least 8 weeks. Adverse effects and efficacy measurements were performed according to local standards. Results: The database search of 2016–2021 revealed six consecutive patients fulfilling the predefined criteria for concomitant ICI and radiotherapy. Three patients received high-dose-rate brachytherapy (15 Gy) to treat progredient hepatic lesions. Two patients received stereotactic body radiotherapy (SBRT) (25–30 Gy) for symptom control, and 1 patient received brachytherapy and SBRT to treat metastases. No severe adverse events were reported in the period (<6 months) after concomitant radiotherapy. In 5 out of 6 cases, long-term tumor control could be achieved by this therapeutic combination. Conclusion: A good efficacy of concomitant radiotherapy and checkpoint inhibition has been achieved with no safety concerns. Further investigations should evaluate the safety, appropriate clinical context, and efficacy of this promising approach