STUDIES ON ANTIBODY AFFINITY AT THE CELLULAR LEVEL : CORRELATION BETWEEN BINDING PROPERTIES OF SECRETED ANTIBODY AND CELLULAR RECEPTOR FOR ANTIGEN ON IMMUNOLOGICAL MEMORY CELLS

Heterogeneity with regard to affinity of anti-hapten antibody was demonstrated at the cellular level in mice. The heterogeneity was shown at the level of single antibody-forming cells using hapten inhibition of hemolytic antibody plaque formation as a measure of affinity. The affinity increased with time after immunization. A high antigen dose initially resulted in relatively low affinity antibody production as compared to the affinity of the antibody production in animals immunized with a low dose. Affinity specialization of immunological memory cells was demonstrated, since it was possible to specifically fractionate such cells with regard to affinity on hapten-protein-coated plastic bead columns. High affinity memory cells showed a higher tendency to become retained in the columns than did low affinity memory cells. The data in a direct way demonstrate that memory cells carrying membrane-associated receptors of a certain affinity for the antigen are determined to release antibody of a similar affinity after stimulation with antigen

STUDIES ON THE REGULATION OF AVIDITY AT THE LEVEL OF THE SINGLE ANTIBODY-FORMING CELL : THE EFFECT OF ANTIGEN DOSE AND TIME AFTER IMMUNIZATION

The hemolytic plaque formation of cells producing antibody against heterologous albumins was tested for sensitivity to specific inhibition by free antigen. The inhibition characteristics of plaques in this system were found to be a measure for the avidity of the antibody produced by the plaque-forming cells (PFC:s). High avidity-producing PFC:s were more sensitive to inhibition than low avidity PFC:s. Immunization with a high dose of antigen induced PFC:s that produced antibody with a lower avidity as compared to PFC:s from animals immunized with a low dose. The avidity was increased with time. Determinations of avidity at the serum level were also made, and the results were in agreement with the findings at the cellular level. The present method made it possible to demonstrate differences in avidity of antibody at the level of the single antibody-forming cell. It may also constitute a useful tool for the analysis of the cellular events leading to the production of antibodies with varying affinities during the immune response

CELL SEPARATION ON ANTIGEN-COATED COLUMNS : ELIMINATION OF HIGH RATE ANTIBODY-FORMING CELLS AND IMMUNOLOGICAL MEMORY CELLS

Glass and plastic bead columns coated with antigenic protein molecules were used as an immunological filter for cell populations containing immune cells of relevant specificity. A selective elimination of these immune cells from the passing cell suspension was regularly noted and it approached, in some experiments, complete abolition of the specific immune reactivity of the filtered cell population. This specific retention of immune cells by antigenic columns could be selectively blocked by the presence of free antigen molecules in the medium during filtration. The results obtained support the concept of a cell-associated antigen-specific receptor being present on the outer surface of immune cells, displaying the same antigen-binding specificity as the potential product of the cell, the humoral antibody. Using the present bead column system, results were obtained indicating that this receptor was an active product of the immune cells and not any passively adsorbed, cytophilic antibody. Antigenic bead columns may very well constitute a tool for the production in vitro of cell populations being specifically deprived of immune reactivity and allow detailed analysis of the characteristics of the cell-associated antibody of immune cells

Building and Exploiting a Business Process Model for Lobbying: Experience Report

The paper describes a project in the domain of business process modeling that concerns loosely-structured business processes, i.e. processes for which it is difficult to establish an order of activities. The process in focus is the lobbying process, i.e. a process aimed at influencing decisions of others, e.g. politicians. The project was carried out at a non-profit interest organization, and the paper describes the project’s motivation, structure, methodology, results, and how the results were exploited, including a short description of an IT system built to support the lobbying process. As the commonly spread workflow technique is not particularly suitable for loosely-structured business processes, the project exploited an original state-flow technique for developing a model of the lobbying process. The state-flow technique is based on the state-oriented view on business processes that has been used as a foundation for building the support system. The paper reports a number of problems encountered during the introduction of the system into operational practice. These problems led to the needs of reducing the level of details initially introduced into the system; they will be reintroduced at the later stage when the users become more accustomed to work in the process-oriented manner. In the conclusion, the paper discusses success factors important for modeling projects, and pros and cons of the modeling method used, as well as a broader research context of which the work presented in the paper is a part

Data rescue of national and international meteorological observations at Deutscher Wetterdienst

KlimawandelHistorischen Klimadaten wird in der Diskussion um den Klimawandel eine immer größere Bedeutung zugemessen. Die weltweit in vielen Archiven auf Papier vorliegenden Daten sind in dieser Form für wissenschaftliche Auswertungen nicht nutzbar. Deshalb laufen verschiedene nationale und internationale Datenrettungsaktivitäten. Beim Deutschen Wetterdienst werden aktuell 4 Datenarchive digitalisiert. Dabei handelt es sich um 1) die nationalen Klimadaten, 2) weltweite Beobachtungen von Handelsschiffen, 3) Landstationen in vielen Teilen der Welt sowie 4) Signalstationen an den deutschen Küsten von Nord- und Ostsee. Während die nationalen Klimadaten im Zentralarchiv des DWD in Offenbach liegen sind die anderen drei Archive Erbe der Deutschen Seewarte Hamburg. In allen vier Archiven werden die Unterlagen gescannt und die Werte per Hand digitalisiert. Nach einer Qualitätskontrolle gehen die Daten in die Datenbanken des DWD ein und werden über das Climate Data Centre des DWD kostenlos zur Verfügung gestellt. Die Daten sind eine wichtige Grundlage für die Beurteilung des regionalen Klimawandels sowie Grundlage für die Erstellung regionaler und globaler Reanalysen der Atmosphäre. Im Beitrag wird der aktuelle Stand der Digitalisierung erläutert sowie die nationalen und internationalen Kooperationen des DWD auf dem Gebiet der Datenrettung vorgestellt

A Search for Instantons at HERA

A search for QCD instanton (I) induced events in deep-inelastic scattering (DIS) at HERA is presented in the kinematic range of low x and low Q^2. After cutting into three characteristic variables for I-induced events yielding a maximum suppression of standard DIS background to the 0.1% level while still preserving 10% of the I-induced events, 549 data events are found while 363^{+22}_{-26} (CDM) and 435^{+36}_{-22} (MEPS) standard DIS events are expected. More events than expected by the standard DIS Monte Carlo models are found in the data. However, the systematic uncertainty between the two different models is of the order of the expected signal, so that a discovery of instantons can not be claimed. An outlook is given on the prospect to search for QCD instanton events using a discriminant based on range searching in the kinematical region Q^2\gtrsim100\GeV^2 where the I-theory makes safer predictions and the QCD Monte Carlos are expected to better describe the inclusive data.Comment: Invited talk given at the Ringberg Workshop on HERA Physics on June 19th, 2001 on behalf of the H1 collaboratio

Patterns-based Evaluation of Open Source BPM Systems: The Cases of jBPM, OpenWFE, and Enhydra Shark

In keeping with the proliferation of free software development initiatives and the increased interest in the business process management domain, many open source workflow and business process management systems have appeared during the last few years and are now under active development. This upsurge gives rise to two important questions: what are the capabilities of these systems? and how do they compare to each other and to their closed source counterparts? i.e. in other words what is the state-of-the-art in the area?. To gain an insight into the area, we have conducted an in-depth analysis of three of the major open source workflow management systems - jBPM, OpenWFE and Enhydra Shark, the results of which are reported here. This analysis is based on the workflow patterns framework and provides a continuation of the series of evaluations performed using the same framework on closed source systems, business process modeling languages and web-service composition standards. The results from evaluations of the three open source systems are compared with each other and also with the results from evaluations of three representative closed source systems - Staffware, WebSphere MQ and Oracle BPEL PM, documented in earlier works. The overall conclusion is that open source systems are targeted more toward developers rather than business analysts. They generally provide less support for the patterns than closed source systems, particularly with respect to the resource perspective which describes the various ways in which work is distributed amongst business users and managed through to completion

No effect of remdesivir or betamethasone on upper respiratory tract SARS-CoV-2 RNA kinetics in hospitalised COVID-19 patients: a retrospective observational study

Background The viral kinetics of SARS-CoV-2 has been considered clinically important. While remdesivir and corticosteroids are recommended for COVID-19 patients requiring oxygen support, there is a limited number of published reports on viral kinetics in hospitalised patients with COVID-19 treated with remdesivir or corticosteroids. Methods We conducted a retrospective study by collecting longitudinal samples from the nasopharynx/throat of 123 hospitalised patients (median age 55 years, 74% male) with COVID-19, to evaluate the effects of remdesivir and corticosteroid treatment on viral RNA levels. The subjects were divided into four groups: those receiving remdesivir (n = 25), betamethasone (n = 41), both (n = 15), or neither (n = 42). Time to viral RNA clearance was analysed using Kaplan-Meier plots, categorical data were analysed using Fisher\u27s exact test, and Kruskal-Wallis for continuous data. Viral RNA decline rate was analysed using a mixed effect model. Results We found no significant difference in SARS-CoV-2 RNA decline rate or time to SARS-CoV-2 RNA clearance between the groups. Moreover, clinical status at baseline was not correlated with time to viral clearance. Conclusions Since SARS-CoV-2 RNA kinetics was not affected by treatment, repeated sampling from the upper respiratory tract cannot be used to evaluate treatment response

Gene Expression Profiling and Chromatin Immunoprecipitation Identify DBN1, SETMAR and HIG2 as Direct Targets of SOX11 in Mantle Cell Lymphoma

The SRY (sex determining region Y)-box 11 (SOX11) gene, located on chromosome 2p25, encodes for a transcription factor that is involved in tissue remodeling during embryogenesis and is crucial for neurogenesis. The role for SOX11 in hematopoiesis has not yet been defined. Two genes under direct control of SOX11 are the class- III β-tubulin gene (TUBB3) in neural cells and the transcription factor TEA domain family member 2 (TEAD2) in neural and mesenchymal progenitor cells. Normal, mature lymphocytes lack SOX11 but express SOX4, another member of the same group of SOX transcription factors. We and others recently identified SOX11 as aberrantly expressed in mantle cell lymphoma (MCL). Since SOX11 is variably expressed in MCL it may not be essential for tumorigenesis, but may carry prognostic information. Currently, no specific functional effects have been linked to SOX11 expression in MCL and it is not known which genes are under influence of SOX11 in lymphoma. In this study we found variable expression of SOX11, SOX4 and SOX12 mRNA in mantle cell lymphoma cell lines. Downregulation of SOX11 expression by siRNA verified that SOX11 controlled the expression of the gene TUBB3 in the MCL cell line Granta 519. Furthermore we identified, by global gene expression analysis, 26 new target genes influenced by siRNA SOX11 downmodulation. Among these genes, DBN1, SETMAR and HIG2 were found to be significantly correlated to SOX11 expression in two cohorts of primary mantle cell lymphomas. Chromatin immunoprecipitation (ChIP) analysis showed that these genes are direct targets of the SOX11 protein. In spite of almost complete downregulation of the SOX11 protein no significant effects on Granta 519 cell proliferation or survival in short term in vitro experiments was found. In summary we have identified a number of genes influenced by SOX11 expression in MCL cell lines and primary MCL. Among these genes, DBN1, SETMAR and HIG2 are direct transcriptional targets of the SOX11 protein