92 research outputs found

    Purification of diesel fractions from silicon compounds with NiMo/Al2O3 catalysts

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    The influence of chemical composition and textural properties of NiMo/Al2O3 on the removal of silicon compounds from diesel fractions was studied. It was found that the increase of the average pore diameter from 80 to 130-185 A provides the increase in Si capacity from 1,4 to 2,7 wt. %. Maximal Si capacity for studied NiMo/Al2O3 samples was 3 wt. %. The composition of NiMo/Al2O3 guard bed catalyst with optimal textural characteristics for silicon removal from diesel fractions was proposed

    Mode choice and ride-pooling simulation: A comparison of mobiTopp, Fleetpy, and MATSim

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    On-demand ride-pooling systems have gained a lot of attraction in the past years as they promise to reduce traffic and vehicle fleets compared to private vehicles. Transport simulations show that automation of vehicles and resulting fare reductions enable large-scale ride-pooling systems to have a high potential to drastically change urban transportation. For a realistic simulation of the new transport mode it is essential to model the interplay of ride-pooling demand and supply. Hence, these simulations should incorporate (1) a mode choice model to measure demand levels and (2) a dynamic model of the on-demand ride-pooling system to measure the service level and fleet performance. We compare two different simulation frameworks that both incorporate both aspects and compare their results with an identical input. It is shown that both systems are capable of generating realistic results and assessing mode choice and ride-pooling schemes. Commonalities and differences are identified and discussed

    Рынок страховых услуг и его роль в стабилизации российской экономики

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    Цель работы - определить основные проблемы и направления, а также перспективы развития рынка страховых услуг, на примере филиала ООО «Росгосстрах». В процессе исследования проводились: аналитическая работа по выявлению тенденции развития рынка страховых услуг России, рассмотрение деятельности ООО «Росгосстрах». В результате исследования были выявлены основные факторы влияния на развитие рынка. В работе представлены результаты аналитического анализа рынка страховых услуг на примере ООО "Росгосстрах".The paper presents the results of the analytical analysis of the insurance services market by the example of Rosgosstrakh LLC. As a result of the study, the main factors influencing the development of the insurance market were identified

    Вероятностный анализ перетоков по межсистемным связям

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    В результате проведенного анализа определен характер связей, а также характеристики, определяющие нагрузку ЛЭП, и их динамика. Исследована связь величин активных и реактивных мощностей при согласованных и встречных перетоках. Установлены достаточные статистические выборки, с приемлемой точностью описывающие процесс в целом

    Исследование процесса непрерывного сублимационного разделения фтораммонийных комплексов титана, железа, кремния, алюминия и других металлов, производительностью 10000 т/год по исходному концентрату

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    Дипломная работа посвящена исследованиям процесса непрерывной сублимационной очистки фтораммонийных комплексов титана от примесей, таких как железо, кремний алюминий и других металлов.Diploma work is devoted to investigation of process of on-stream freeze-drying treatment process of clearing of the fluorinated product of containing fluorammonium titanium complex salts of titan, iron, silicon, aluminium and other metal

    Ridepooling in der Modellierung des Gesamtverkehrs - Methodenbericht zur MOIA Begleitforschung

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    In der MOIA Begleitforschung wurden über zwei Jahre Effekte von Ridepooling auf das Hamburger Verkehrssystem untersucht. Die Studie liefert auf Basis umfassender empirischer Daten und einer Modellierung in hohem Detailgrad Erkenntnisse zu der noch neuen Verkehrsform und trägt dazu bei, die Potenziale von Ridepooling künftig noch zielgerichteter zu erschließen. Das im Rahmen der Begleitforschung entwickelte Verkehrsmodell besteht aus dem agentenbasierten Verkehrsnachfragemodell mobiTopp sowie dem Flottensimulationsmodell FleetPy und berücksichtigt die Angebots- und Nachfrageseite. mobiTopp bildet die Mobilität der gesamten Bevölkerung von Hamburg und Umland sowie der Privat- und Geschäftsreisenden im Wochenverlauf ab. Die Implementierung aktueller empirischer Erkenntnisse zur Nutzung neuer Mobilitätsangebote wie Ridepooling aber auch Car- , Bike- oder E-Scootersharing resultiert in besonders belastbaren Ergebnissen. Die Kopplung mit dem Flottenmodell sorgt für eine realitätsnahe Abbildung des Ridepooling-Dienstes, der Angebotsqualität und der verkehrlichen Wirkungen. Im Rahmen der Simulationsstudie wurden vier Szenarien entwickelt, die zeigen, wie sich die Mobilität in der Hansestadt zukünftig entwickeln kann

    The prominent role of the S100A8/S100A9-CD147 axis in the progression of penile cancer

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    Currently, no established biomarkers are recommended for the routine diagnosis of penile carcinoma (PeCa). The rising incidence of this human papillomavirus (HPV)–related cancer entity highlights the need for promising candidates. The Calprotectin subunits S100A8 and S100A9 mark myeloid-derived suppressor cells in other HPV-related entities while their receptor CD147 was discussed to identify patients with PeCa at a higher risk for poor prognoses and treatment failure. We thus examined their expression using immunohistochemistry staining of PeCa specimens from 74 patients on tissue microarrays of the tumor center, the invasion front, and lymph node metastases. Notably, whereas the tumor center was significantly more intensively stained than the invasion front, lymph node metastases were thoroughly positive for both S100 subunits. An HPV-positive status combined with an S100A8+S100A9+ profile was related with an elevated risk for metastases. We observed several PeCa specimens with S100A8+S100A9+-infiltrating immune cells overlapping with CD15 marking neutrophils. The S100A8+S100A9+CD15+ profile was associated with dedifferentiated and metastasizing PeCa, predominantly of HPV-associated subtype. These data suggest a contribution of neutrophil-derived suppressor cells to the progression of HPV-driven penile carcinogenesis. CD147 was elevated, expressed in PeCa specimens, prominently at the tumor center and in HPV-positive PeCa cell lines. CD147+HPV+ PeCa specimens were with the higher-frequency metastasizing cancers. Moreover, an elevated expression of CD147 of HPV-positive PeCa cell lines correlated negatively with the susceptibility to IgA-based neutrophil-mediated tumor cell killing. Finally, stratifying patients regarding their HPV/S100A8/S100A9/CD15/CD147 profile may help identify patients with progressing cancer and tailor immunotherapeutic treatment strategies

    Focal accumulation of aromaticity at the CDRH3 loop mitigates 4E10 polyreactivity without altering its HIV neutralization profile

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    Broadly neutralizing antibodies (bnAbs) against HIV-1 are frequently associated with the presence of autoreactivity/polyreactivity, a property that can limit their use as therapeutic agents. The bnAb 4E10, targeting the conserved Membrane proximal external region (MPER) of HIV-1, displays almost pan-neutralizing activity across globally circulating HIV-1 strains but exhibits nonspecific off-target interactions with lipid membranes. The hydrophobic apex of the third complementarity-determining region of the heavy chain (CDRH3) loop, which is essential for viral neutralization, critically contributes to this detrimental effect. Here, we have replaced the aromatic/hydrophobic residues from the apex of the CDRH3 of 4E10 with a single aromatic molecule through chemical modification to generate a variant that preserves the neutralization potency and breadth of 4E10 but with reduced autoreactivity. Collectively, our study suggests that the localized accumulation of aromaticity by chemical modification provides a pathway to ameliorate the adverse effects triggered by the CDRH3 of anti-HIV-1 MPER bnAbs.This study was supported by the following Grants: European Commission (790012 SI H2020-MSCA-IF-2017) (E.R.); US NIAID, NIH grant R01 AI143563 (M.B. Z.); James B. Pendleton Charitable Trust (M.B.Z.); JSPS grant 20H03228 (J. M.M.C.); Spanish MCIU (RTI2018-095624-B-C21; MCIU/AEI/FEDER, UE) (J.L.N.), Basque Government (IT1196-19) (J.L.N.). C.E. acknowledges funding from Medical Research Council (grant number MC_UU_12010/unit programs G0902418 and MC_UU_12025), Wolfson Foundation, Deutsche Forschungsgemeinschaft (Excellence Cluster Balance of the Microverse, Collaborative Research Center 1278 Polytarget), Leibniz Association (Leibniz Campus Infectooptics), Wellcome Institutional Strategic Support Fund, Oxford internal funds (EPA Cephalosporin Fund and John Fell Fund), and support from the Micron Oxford Advanced Bioimaging Unit (Wellcome Trust funding 107457/Z/15/Z). This work was also supported by the Platform Project for Supporting Drug Discovery and Life Science Research [Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)] from AMED (JP21am0101091). S.I. received a predoctoral fellowship from the BasqueGovernment. P.C. would like to acknowledge the University of the Basque Country (DOCREC18/01), the Basque Government (POS_2018_1_0066) and the European Commission (H2020-MSCA-IF-2019-ST project 892232 FILM-HIV) for funding his position. This research was also supported by the CIFAR Azrieli Global Scholar program (J-P.J.), the Ontario Early Researcher Awards program (J-P.J.), and the Canada Research Chairs program (J-P.J.). Part of the biophysical data presented in this manuscript were collected at the Hospital for Sick Children Structural & Biophysical Core facility supported by the Canada Foundation for Innovation and Ontario Research Fund

    Affinity for the Interface Underpins Potency of Antibodies Operating In Membrane Environments

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    The contribution of membrane interfacial interactions to recognition of membrane-embedded antigens by antibodies is currently unclear. This report demonstrates the optimization of this type of antibodies via chemical modification of regions near the membrane but not directly involved in the recognition of the epitope. Using the HIV-1 antibody 10E8 as a model, linear and polycyclic synthetic aromatic compounds are introduced at selected sites. Molecular dynamics simulations predict the favorable interactions of these synthetic compounds with the viral lipid membrane, where the epitope of the HIV-1 glycoprotein Env is located. Chemical modification of 10E8 with aromatic acetamides facilitates the productive and specific recognition of the native antigen, partially buried in the crowded environment of the viral membrane, resulting in a dramatic increase of its capacity to block viral infection. These observations support the harnessing of interfacial affinity through site-selective chemical modification to optimize the function of antibodies that target membrane-proximal epitopes.We are grateful to Professor Ueda (Kyushu University) for valuable advice. C.D. acknowledges RES (Red Espanola de Supercomputacio ' n) for providing computational resources. S.I. received a pre-doctoral fellowship from the Basque Government. P.C. acknowledges a research associate contract from the University of the Basque Country (DOCREC18/01) and a postdoctoral fellowship from the Basque Government (POS_2018_1_0066).This study was supported by the following grants: European Commission (790012 SI H2020MSCA-IF-2017 to E.R., J.-P.J., and J.L.N.); US NIAID (NIH) (R01 AI143563 to M.B.Z.); James B. Pendleton Charitable Trust (to M.B.Z.); Grant-in-Aid for Scientific Research on Innovative Areas "Chemistry for Multimolecular Crowding Biosystems, JSPS KAKENHI (JP17H06349 to A.O.); JSPS KAKENHI (15K06962 and 20H03228 to J.M.M.C.); Spanish MINECO (BIO2015-64421R and MINECO/AEI/FEDER, UE to J.L.N.); Spanish MCIU (RTI2018-095624B-C21 and MCIU/AEI/FEDER, UE to J.L.N.); and the Basque Government (IT1196-19) (to J.L.N.). C.E. acknowledges funding from Medical Research Council (MC_UU_12010/unit programs G0902418 and MC_UU_12025), Wolfson Foundation, Deutsche Forschungsgemeinschaft (Research unit 1905, Excellence Cluster Balance of the Microverse, Collaborative Research Centre 1278 Polytarget), Wellcome Institutional Strategic Support Fund, Oxford internal funds (EPA Cephalosporin Fund and John Fell Fund), and support from the Micron Oxford Advanced Bioimaging Unit (Wellcome Trust funding 107457/Z/15/Z). This research was undertaken, in part, thanks to funding from the CIFAR Azrieli Global Scholar program (to J.-P.J.) and the Canada Research Chairs program (950-231604 to J.-P.J.). This work was also supported by the Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research [BINDS] from AMED JP19am0101091)

    Comparison of Antibody Repertoires Produced by HIV-1 Infection, Other Chronic and Acute Infections, and Systemic Autoimmune Disease

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    Background Antibodies (Abs) produced during HIV-1 infection rarely neutralize a broad range of viral isolates; only eight broadly-neutralizing (bNt) monoclonal (M)Abs have been isolated. Yet, to be effective, an HIV-1 vaccine may have to elicit the essential features of these MAbs. The V genes of all of these bNt MAbs are highly somatically mutated, and the VH genes of five of them encode a long (≥20 aa) third complementarity-determining region (CDR-H3). This led us to question whether long CDR-H3s and high levels of somatic mutation (SM) are a preferred feature of anti-HIV bNt MAbs, or if other adaptive immune responses elicit them in general. Methodology and Principal Findings We assembled a VH-gene sequence database from over 700 human MAbs of known antigen specificity isolated from chronic (viral) infections (ChI), acute (bacterial and viral) infections (AcI), and systemic autoimmune diseases (SAD), and compared their CDR-H3 length, number of SMs and germline VH-gene usage. We found that anti-HIV Abs, regardless of their neutralization breadth, tended to have long CDR-H3s and high numbers of SMs. However, these features were also common among Abs associated with other chronic viral infections. In contrast, Abs from acute viral infections (but not bacterial infections) tended to have relatively short CDR-H3s and a low number of SMs, whereas SAD Abs were generally intermediate in CDR-H3 length and number of SMs. Analysis of VH gene usage showed that ChI Abs also tended to favor distal germline VH-genes (particularly VH1-69), especially in Abs bearing long CDR-H3s. Conclusions and Significance The striking difference between the Abs produced during chronic vs. acute viral infection suggests that Abs bearing long CDR-H3s, high levels of SM and VH1-69 gene usage may be preferentially selected during persistent infection
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