188 research outputs found

    Validation of immunomonitoring methods for application in clinical studies: the HLA-peptide multimer staining assay

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    Background: Validated assays are essential to generate data with defined specificity, consistency, and reliability. Although the process of validation is required for applying immunoassays in the context of clinical studies, reports on systematic validation of in vitro T cell assays are scarce so far. We recently validated our HLA-peptide multimer staining assay in a systematic manner so as to qualify the method for monitoring antigen-specific T cell responses after immunotherapy. Methods: Parameters of the assay, specificity, precision, linearity, sensitivity, and robustness were assessed systematically. Experiments were designed to address specifically each parameter and are detailed. Results: Nonspecific multimer staining was below the acceptance limit of 0.02% multimer(+) CD8(+) cells. The assay showed acceptable precision in all dimensions it was repeated (CV &lt; 10%) and also demonstrated a linear detection (R2 &gt; 0.99) of antigen specific cells. Conclusions: We succeeded in validating the HLA-multimer staining assay in a systematic manner. Additionally, we propose a technical framework and recommendations that can be applied for validating other T cell assessment methods.</p

    Vertigo Clinic Patients: A 2-Year Clinical Audit

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    IMPACT OF CORRUPTION ON FOREIGN DIRECT INVESTMENTS (FDI) IN MALAYSIA

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    Abstract: his paper discusses the impact of corruption on foreign direct investment (FDI) in Malaysia. Corruption is an abuse of power to obtain personal benefits while foreign direct investment (FDI) refers to a growing investment relationship between nation, people and economic activities. In this regard, this study examines the relationship between corruption and FDI in Malaysia. Since this study need the latest information, this study uses quantitative secondary data. The data were obtained from 1995 to 2016. This study covers time series data, then the statistical test such as Unit Root Test, Vector Autoregression Estimates (VAR) Test, ARDL Method Test, Breusch-Godfrey Test, White Test Heteroskedasticity and the Ramsey Reset Test are used. The results of the study shows that when foreign direct investment in a country increases, the level of corruption in the country will increases as well. The corruption can be reduced by certain actions and strict laws. Keywords: Corruption, Foreign Direct Investment, Malaysia. Title: IMPACT OF CORRUPTION ON FOREIGN DIRECT INVESTMENTS (FDI) IN MALAYSIA Author: KAVITHA CHANDRAN International Journal of Recent Research in Commerce Economics and Management (IJRRCEM) ISSN 2349-7807 Vol. 10, Issue 1, January 2023 - March 2023 Page No: 89-97 Paper Publications Website: www.paperpublications.org Published Date: 14-March-2023 DOI: https://doi.org/10.5281/zenodo.7732593 Paper Download Link (Source) https://www.paperpublications.org/upload/book/IMPACT%20OF%20CORRUPTION-14032023-5.pdfInternational Journal of Recent Research in Commerce Economics and Management (IJRRCEM), ISSN 2349-7807, Paper Publications, Website: www.paperpublications.or

    Racial disparities in nutritional factors and breast cancer risk

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    The current evidence on nutritional factors and breast cancer risk is largely based on studies in white women while research in women of African ancestry (AA) is severely limited. We examined racial differences in the relationship between consuming foods of animal origin (never investigated) and alcohol (limited evidence) and breast cancer risk. We also assessed racial disparities in behaviors consistent with evidence-based cancer prevention recommendations and association with breast cancer risk. Investigations were conducted in AA and white women participating in the Women’s Circle of Health Study, a case-control study based in NY and NJ. A total of 1692 AA and 1455 white women completed a questionnaire on important risk factors and a Food Frequency Questionnaire. Risk estimates and 95% confidence intervals were calculated using logistic regression adjusting for potential covariates. Racial differences in consumption levels of red meat, poultry, dairy, and alcohol as well as adherence to guidelines on body fatness and physical activity were observed in our study. We found increased risks for greater consumption of red meat and poultry and reduced risks for dairy foods in white but not in AA women. Further differences emerged in subgroup analyses. Lifetime alcohol consumption was inversely related to decreased breast cancer risk in AA women but no association between recent or lifetime drinking was observed in white women. While assessing racial differences in behaviors that are consistent with cancer prevention recommendations and breast cancer risk, we observed that recommendations pertaining to foods and drinks that promote weight gain, sodium, alcohol, and red meat intakes were suggestive of reduced breast cancer risk among subgroups of AA women. Restricting red meat intake and caloric dense foods appeared to be beneficial in sub groups of white women. A positive relationship between physical activity and disease risk was observed in AA women. Overall, this study observed racial disparities in nutritional factors and highlighted relationships warranting replication, particularly in AA women given the dearth of research in this group. Put together, the findings contribute towards filling the large gap in understanding disease-environment associations that could be modified by race to facilitate effective prevention strategies.Ph. D.Includes bibliographical referencesby Urmila Chandra

    Structural and thermoelectric properties of Zintl-phase CaLiPn (Pn: As, Sb, Bi)

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    First-principles calculations were carried out to study the structural, mechanical, dynamical and\ud transport properties of zintl phase materials CaLiPn (Pn = As, Sb and Bi). We have used two\ud distinct density functional approaches to investigate these properties. The plane wave pseudopotential\ud approach was used to study the structural and dynamical properties. The full potential linear\ud augment plane wave method has been used to study the electronic structure, mechanical and thermoelectric\ud properties. The calculated ground-state properties agree quite well with experimental\ud values. The calculated electronic structure shows the investigated compounds to be direct band gap\ud semiconductors. Further we have calculated the thermoelectric properties of all the investigated\ud compounds as a function of both carriers at various temperatures. We found a high thermopower\ud for both the concentrations, especially with n-type doping to be more favourable, which enabled us\ud to predict that CaLiPn might have promising applications as a good thermoelectric material. Further\ud the phonon dispersion curves of the investigated compounds showed \ud at nature of the phonon\ud bands and we also �nd low lying optical and acoustic modes are cutting each other at the lower\ud frequency range, which indicate that the investigated compounds might have an reasonable low\ud thermal conductivity

    Identifizierung und funktionelle Charakterisierung von TGF-β induzierbaren, immunsuppressiven miRNAs in humanen CD8+ T Zellen

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    While TGF-β is able to regulate miRNA expression in numerous cell types, TGF-β-dependent changes in the miRNA profile of CD8+ T cells had not been studied before. Considering that TGF-β suppresses CD8+ T cell effector functions in numerous ways, we wondered whether induction of immune-regulatory miRNAs could add to the known transcriptional effects of TGF-β on immune effector molecules. In this study, we used miRNA arrays, deep sequencing and qRT-PCR to identify miRNAs that are modulated by TGF-β in human CD8+ T cells. Having found that the TGF-β-dependent downregulation of NKG2D surface expression in NK cells and CD8+ T cells does not go along with a corresponding reduction in mRNA levels, this pathway appeared to be a possible target of TGF-β-inducible miRNAs. However, this hypothesis could not be confirmed by miRNA reporter assays. Instead, we observed that DAP10 transcription is suppressed by TGF-β which in turn negatively affects NKG2D surface expression. In spite of promising preliminary experiments, technical difficulties associated with the transfection of primary NK cells and NK cell lines unfortunately precluded the final proof of this hypothesis. Instead, we focused on the TGF-β-induced changes in the miRNome of CD8+ T cells and confirmed the induction of the miR-23a cluster members, namely miR-23a, miR-27a and miR-24 by three different techniques. Searching for potential targets of these miRNAs which could contribute to the immunosuppressive action of TGF-β in T cells, we identified and confirmed a previously unknown regulation of IFN-γ mRNA by miR-27a and miR-24. Newly generated miRNA reporter constructs further revealed that LAMP1 mRNA is a target of miR-23a. Upon modulation of the miR-23a cluster in CD8+ T cells by the respective miRNA antagomirs and mimics, significant changes in IFN-γ expression confirmed the functional relevance of our findings. Effects on CD107a/LAMP1 expression were, in contrast, rather minimal. Still, overexpression of the miR-23a cluster attenuated the cytotoxic activity of antigen-specific CD8+ T cells. Taken together, these functional data reveal that the miR-23a cluster not only is induced by TGF-β, but also exerts a suppressive effect on CD8+ T-cell effector functions, even in the absence of TGF-β signaling.Obwohl bekannt war, dass TGF- die miRNA Expression in zahlreichen Zelltypen moduliert, waren TGF- abhängige Veränderung des miRNA Profils in CD8+ T Zellen noch nicht untersucht worden. Da TGF-β die Effektorfunktionen von CD8+ T Zellen aber in vielfältiger Weise inhibiert, fragten wir uns, ob die transkriptionellen Effekte, die TGF-β bekanntermaßen auf Immuneffektormoleküle ausübt, noch durch die Induktion immunregulatorischer miRNAs ergänzt werden. Daher nutzten wir miRNA Arrays, Genomsequenzierungstechniken und Echtzeit-PCR um miRNAs zu identifizieren, welche in humane CD8+ T Zellen von TGF- moduliert werden. Die Beobachtung, dass die TGF--abhängige Herunterregulation der NKG2D Oberflächenexpression in Natürlichen Killerzellen und CD8+ T Zellen nicht mit einer entsprechenden Verringerung der mRNA Menge einhergeht, ließ zudem vermuten, dass dieser Signalweg über miRNAs reguliert werden könnte. Nach verschiedenen miRNA Reporterassays musste diese Hpothese jedoch verworfen werden. Stattdessen zeigte sich, dass TGF- die Transkription von DAP10 inhibiert was wiederum die Oberflächenexpression von NKG2D limitieren sollte. Trotz viel versprechender initialer Experimente scheiterte der letzgültige Beweis dieser Hypothese aber an der ungenügenden Transfizierbarkeit von primären NK Zellen sowie von NK Zelllinien. Daher konzentrierten wir uns im Weiteren auf die durch TGF- induzierten Veränderungen im miRNom von CD8+ T Zellen und konnten mit drei verschiedenen Techniken die Induktion des miR-23a Clusters (mit den einzelnen miRNAs miR-23a, miR-27a und miR-24) bestätigen. Auf der Suche nach potentiellen immunregulatorisch relevanten Zielgenen dieser miRNAs konnten wir erstmals eine Regulation von IFN- durch miR-27a und miR-24 nachweisen. Zu diesem Zweck generierte miRNA Reporterkonstrukte zeigten zudem, dass LAMP1 durch miR-23a reguliert wird. Nach Modulation des miR-23a Clusters durch die entsprechenden miRNA Antagomir und Surrogat-Konstrukte konnten wir auch in CD8+ T Zellen signifikante Veränderungen der IFN-γ Expression nachweisen und somit die funktionelle Relevanz unserer Befunde bestätigen. Die Effekte auf die Expression von CD107a/LAMP1 waren hingegen nur minimal. Trotzdem führte die Überexpression des miR-23a Clusters zu einer Verringerung der zytotoxischen Aktivität von antigenspezifischen CD8+ T Zellen. Zusammen genommen belegen diese funktionellen Untersuchungen, dass das miRNA-23a Cluster, welches durch TGF-β induziert wird, zur Hemung der Effektorfunktionen in CD8+ T Zellen beiträgt, und zwar sowohl in Gegenwart als auch in Abwesenheit von TGF-β

    Greenhouse gas emissions from membrane bioreactors: Analysis of a two-year survey on different MBR configurations

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    This study aimed at evaluating the nitrous oxide (N2O) emissions from membrane bioreactors (MBRs) for wastewater treatment. The study investigated the N2O emissions considering multiple influential factors over a two-year period: (i) different MBR based process configurations; (ii) wastewater composition (municipal or industrial); (iii) operational conditions (i.e. sludge retention time, carbon-to-nitrogen ratio, C/N, hydraulic retention time); (iv) membrane modules. Among the overall analysed configurations, the highest N2O emission occurred from the aerated reactors. The treatment of industrial wastewater, contaminated with salt and hydrocarbons, provided the highest N2O emission factor (EF): 16% of the influent nitrogen for the denitrification/nitrification-MBR plant. The lowest N2O emission (EF 1⁄4 0.5% of the influent nitrogen) was obtained in the biological phosphorus removal-moving bed-MBR plant likely due to an improvement in biological performances exerted by the co-presence of both suspended and attached biomass. The influent C/N ratio has been identified as a key factor affecting the N2O production. Indeed, a decrease of the C/N ratio (from 10 to 2) promoted the increase of N2O emissions in both gaseous and dissolved phases, mainly related to a decreased efficiency of the denitrification processes

    Structural and thermoelectric properties of Zintl-phase CaLiPn (Pn: As, Sb, Bi)

    No full text
    First-principles calculations were carried out to study the structural, mechanical, dynamical and transport properties of zintl phase materials CaLiPn (Pn = As, Sb and Bi). We have used two distinct density functional approaches to investigate these properties. The plane wave pseudopotential approach was used to study the structural and dynamical properties. The full potential linear augment plane wave method has been used to study the electronic structure, mechanical and thermoelectric properties. The calculated ground-state properties agree quite well with experimental values. The calculated electronic structure shows the investigated compounds to be direct band gap semiconductors. Further we have calculated the thermoelectric properties of all the investigated compounds as a function of both carriers at various temperatures. We found a high thermopower for both the concentrations, especially with n-type doping to be more favourable, which enabled us to predict that CaLiPn might have promising applications as a good thermoelectric material. Further the phonon dispersion curves of the investigated compounds showed at nature of the phonon bands and we also �nd low lying optical and acoustic modes are cutting each other at the lower frequency range, which indicate that the investigated compounds might have an reasonable low thermal conductivity
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