Autoreactive B cells in rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune disease affecting joints which is hallmarked by the presence of autoantibodies against citrrulianted protein (ACPA). This thesis describes the phenotypic and functional characteristics of ACPA-expressing autoreactive B cells which suggest potential pathologic roles of these B cells in RA pathogenesis. The thesis also describes strategies to specifically deplete ACPA-expressing B cells to improve current RA therapeutic options.The Institute for Chemical Immunology, an NWO Gravitational programLUMC / Geneeskund

Multifunctional, Multivalent PIC Polymer Scaffolds for Targeting Antigen-Specific, Autoreactive B Cells

Multivalent scaffolds that carry multiple molecules with immunophenotyping or immunomodulatory properties areinvaluable tools for studying and modulating specific functions ofhuman immune responses. So far, streptavidin-biotin-basedtetramers have been widely used for B-cell immunophenotypingpurposes. However, the utility of these tetramers is limited by theirtetravalency, the inherent immunogenicity of streptavidin (abacterial protein that can potentially be recognized by B cells),and the limited feasibility to functionalize these reagents. This has rendered tetramers suboptimal for studying rare, in particular,antigen-specific B-cell populations in the context of clinical applications. Here, we used polyisocyanopeptides (PICs), multivalentpolymeric scaffolds functionalized with around 50 peptide antigens, to detect autoreactive B cells in the peripheral blood of patientswith rheumatoid arthritis. To explore the potential immunomodulatory functionalities, we functionalized PICs with autoantigenicpeptides and a trisaccharide CD22 ligand to inhibit autoreactive B-cell activation through interference with the B-cell receptoractivation pathway, as evidenced by reduced phospho-Syk expression upon PIC binding. Given the possibilities to functionalizePICs, our data demonstrate that the modular and versatile character of PIC scaffolds makes them promising candidates for futureclinical applications in B-cell-mediated diseasesPathophysiology and treatment of rheumatic disease

Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)

The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer-reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state-of-the-art handbook for basic and clinical researchers

Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)

The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer-reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state-of-the-art handbook for basic and clinical researchers

Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)

The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer‐reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state‐of‐the‐art handbook for basic and clinical researchers.DFG, 389687267, Kompartimentalisierung, Aufrechterhaltung und Reaktivierung humaner Gedächtnis-T-Lymphozyten aus Knochenmark und peripherem BlutDFG, 80750187, SFB 841: Leberentzündungen: Infektion, Immunregulation und KonsequenzenEC/H2020/800924/EU/International Cancer Research Fellowships - 2/iCARE-2DFG, 252623821, Die Rolle von follikulären T-Helferzellen in T-Helferzell-Differenzierung, Funktion und PlastizitätDFG, 390873048, EXC 2151: ImmunoSensation2 - the immune sensory syste

Implementasi Material Handling dalam Mencari Jarak dan Ongkos Material serta Usulan Tata Letak Produksi di PT. Wijaya Karya Beton

Tata letak dalam fasilitas produksi harus direncanakan dengan baik dan jarak dibuat seefisien mungkin antara unit kerja agar tidak terjadinya peningkatan biaya. Jarak untuk aliran lintasan di PT Wijaya Karya Beton saat ini belum diketahui efisien atau tidak dengan jarak tempuh keseluruhan departemen sepanjang 300 meter, dan total biaya yaitu Rp 60.000/jam. Material Handling ialah salah satu jenis transportasi (pengangkutan) yang dilakukan dalam perusahaan industri, yang artinya memindahkan bahan baku, barang setengah jadi atau barang jadi dari tempat asal ke tempat tujuan yang telah ditetapkan. Penelitian ini ditujukan untuk mengetahui perancangan fasilitas yang cocok pada pabrik dengan dibuat layout produksi berdasarkan keterkaitan tiap-tiap departemen dengan alat material handling yaitu crane. Dalam mengetahui layout seperti apa yang baik ialah mencari ongkos material handling terlebih dahulu. Dalam hasil perhitungan diperoleh ongkos material handling yang dikeluarkan yaitu Rp. 200/m. Selanjutnya mencari jarak satu departemen ke departemen lain, ongkos tiap departemen, membuat Flow to Chart (FTC), membuat Tabel Skala Prioritas (TSP) dan yang terakhir ialah membuat Activity Relationship Diagram (ARD) dengan berdasarkan dari hasil FTC tersebut. Hasil penelitian ini menunjukan bahwa urutan aliran antar departemen pada lantai produksi yaitu A-B-C-D-E dengan layout yang dibuat berbentuk U flow. Berdasarkan hasil penelitian, layout usulan dinilai sudah efektif dan efisien karena disusun berdasarkan jarak antar departemen dan ongkos material handling pada lantai produksi

Collaboration of high activity soil and geological structure factors in Pagelaran soil creep occurrence, Indonesia

Soil creep is a landslide that moves slowly but it does not mean harmless. Soil creep that succeeded in forcing the citizens to migrate occurred in Pagelaran by wiping out 13 houses. This paper aims to know the contribution of geological structures and physical properties of soil toward the creeping occurrence. The methods used in this research consist of geological structure mapping; soil sampling; laboratory works; and analysis of geological structures and soil activity. Geological structures analysis indicates that the main force worked predominantly in NE-SW direction, parallel with creeping. It expresses that the creep was influenced by the orientation of them. Additionally, their distribution can be used as access for rainwater to infiltrate and add to the burden of the slopes. While laboratory results show that, the soil is classified into MH and CH. Calculation of activity numbers of soil indicates that it has a high – very high activity with value between 0.705 – 1.4931 (Skempton, 1953). It means that the soil will swell easily if contaminated by water

Rap1 Can Bypass the FAK-Src-Paxillin Cascade to Induce Cell Spreading and Focal Adhesion Formation

We developed new image analysis tools to analyse quantitatively the extracellular-matrix-dependent cell spreading process imaged by live-cell epifluorescence microscopy. Using these tools, we investigated cell spreading induced by activation of the small GTPase, Rap1. After replating and initial adhesion, unstimulated cells exhibited extensive protrusion and retraction as their spread area increased, and displayed an angular shape that was remodelled over time. In contrast, activation of endogenous Rap1, via 007-mediated stimulation of Epac1, induced protrusion along the entire cell periphery, resulting in a rounder spread surface, an accelerated spreading rate and an increased spread area compared to control cells. Whereas basal, anisotropic, spreading was completely dependent on Src activity, Rap1-induced spreading was refractory to Src inhibition. Under Src inhibited conditions, the characteristic Src-induced tyrosine phosphorylations of FAK and paxillin did not occur, but Rap1 could induce the formation of actomyosin-connected adhesions, which contained vinculin at levels comparable to that found in unperturbed focal adhesions. From these results, we conclude that Rap1 can induce cell adhesion and stimulate an accelerated rate of cell spreading through mechanisms that bypass the canonical FAK-Src-Paxillin signalling cascade

Collaboration of high activity soil and geological structure factors in Pagelaran soil creep occurrence, Indonesia

Soil creep is a landslide that moves slowly but it does not mean harmless. Soil creep that succeeded in forcing the citizens to migrate occurred in Pagelaran by wiping out 13 houses. This paper aims to know the contribution of geological structures and physical properties of soil toward the creeping occurrence. The methods used in this research consist of geological structure mapping; soil sampling; laboratory works; and analysis of geological structures and soil activity. Geological structures analysis indicates that the main force worked predominantly in NE-SW direction, parallel with creeping. It expresses that the creep was influenced by the orientation of them. Additionally, their distribution can be used as access for rainwater to infiltrate and add to the burden of the slopes. While laboratory results show that, the soil is classified into MH and CH. Calculation of activity numbers of soil indicates that it has a high – very high activity with value between 0.705 – 1.4931 (Skempton, 1953). It means that the soil will swell easily if contaminated by water