351 research outputs found
Effect of a Co-Stimulatory Endodomain on the Performance of T Cells Expressing a Chimeric Antigen Receptor Directed at CD19 in Patients With Relapsed/Refractory B-Cell Malignancies
'I'm sure we made it a better study…': Experiences of adults with intellectual disabilities and parent carers of patient and public involvement in a health research study.
Patient and public involvement is considered integral to health research in the United Kingdom; however, studies documenting the involvement of adults with intellectual disabilities and parent carers in health research studies are scarce. Through group interviews, this study explored the perspectives and experiences of a group of adults with intellectual disabilities and a group of parent carers about their collaborative/participatory involvement in a 3-year study which explored the effectiveness of annual health checks for adults with intellectual disabilities. Thematic analysis identified five key themes consistent across both groups; authenticity of participation, working together, generating new outcome measures, dissemination of findings and involvement in future research. Although reported anecdotally rather than originating from the analysis, increased self-confidence is also discussed. The groups' unique perspectives led to insights not previously considered by the research team which led to important recommendations to inform healthcare practice
Cross-Platform Comparison of Caenorhabditis elegans Tissue Extraction Strategies for Comprehensive Metabolome Coverage
Third-party umbilical cord blood-derived regulatory T cells prevent xenogenic graft-versus-host disease
Background aims: Naturally occurring regulatory T cells (Treg) are emerging as a promising approach for prevention of graft-versus-host disease (GvHD), which remains an obstacle to the successful outcome of allogeneic hematopoietic stem cell transplantation. However, Treg only constitute 1-5% of total nucleated cells in cord blood (CB) (<3× 106 cells), and therefore novel methods of Treg expansion to generate clinically relevant numbers are needed. Methods: Several methodologies are currently being used for ex vivo Treg expansion. We report a new approach to expand Treg from CB and demonstrate their efficacy in vitro by blunting allogeneic mixed lymphocyte reactions and in vivo by preventing GvHD through the use of a xenogenic GvHD mouse model. Results: With the use of magnetic cell sorting, naturally occurring Treg were isolated from CB by the positive selection of CD25+ cells. These were expanded to clinically relevant numbers by use ofCD3/28 co-expressing Dynabeads and interleukin (IL)-2. Ex vivo-expanded Treg were CD4+25+FOXP3+127lo and expressed a polyclonal T-cell receptor, Vβ repertoire. When compared with conventional T-lymphocytes (CD4+25- cells), Treg consistently showed demethylation of the FOXP3 TSDR promoter region and suppression of allogeneic proliferation responses in vitro. Conclusions: In our NOD-SCID IL-2Rγnull xenogeneic model of GvHD, prophylactic injection of third-party, CB-derived, ex vivo-expanded Treg led to the prevention of GvHD that translated into improved GvHD score, decreased circulating inflammatory cytokines and significantly superior overall survival. This model of xenogenic GvHD can be used to study the mechanism of action of CB Treg as well as other therapeutic interventions
Multidirectional Time-Dependent Effect of Sinigrin and Allyl Isothiocyanate on Metabolic Parameters in Rats
Sinigrin (SIN) and allyl isothiocyanate (AITC) are compounds found in high concentrations in Brassica family vegetables, especially in Brussels sprouts. Recently, they have been used as a nutrition supplement for their preventive and medicinal effect on some types of cancer and other diseases. In this research, nutritional significance of parent glucosinolate sinigrin 50 μmol/kg b. w./day and its degradation product allyl isothiocyanate 25 μmol/kg b. w./day and 50 μmol/kg b. w./day was studied by the evaluation of their influence on some parameters of carbohydrate and lipid metabolism in an animal rat model in vivo after their single (4 h) and 2 weeks oral administration. Additionally, the aim of this trial was to evaluate the direct action of AITC on basal and epinephrine-induced lipolysis in isolated rat adipocytes at concentration 1 μM, 10 μM and 100 μM in vitro. Sole AITC after 4 h of its ingestion caused liver triacylglycerols increment at both doses and glycaemia only at the higher dose. Multiple SIN treatment showed its putative bioconversion into AITC. It was found that SIN and AITC multiple administration in the same way strongly disturbed lipid and carbohydrate homeostasis, increasing esterified and total cholesterol, free fatty acids and lowering tracylglycerols in the blood serum. Additionally, AITC at both doses elevated insulinaemia and liver glycogen enhancement. The in vitro experiment revealed that AITC potentiated basal lipolysis process at 10 μM, and had stimulatory effect on epinephrine action at 1 μM and 10 μM. The results of this study demonstrated that the effect of SIN and AITC is multidirectional, indicating its impact on many organs like liver as well as pancreas, intestine in vivo action and rat adipocytes in vitro. Whilst consumption of cruciferous vegetables at levels currently considered “normal” seems to be beneficial to human health, this data suggest that any large increase in intake could conceivably lead to undesirable effect. This effect is potentiated with time of action of the examined compounds, whose influence is rather adverse for the majority of metabolic pathways (liver steatosis at short duration and insulinaemia, cholesterolaemia at long time treatment). Beneficial action of AITC concerned intensified hydrolysis of TG in the blood serum with a simultaneous lipolysis in adipocytes
A decade with vamdc: Results and ambitions
This paper presents an overview of the current status of the Virtual Atomic and Molecular Data Centre (VAMDC) e-infrastructure, including the current status of the VAMDC-connected (or to be connected) databases, updates on the latest technological development within the infrastructure and a presentation of some application tools that make use of the VAMDC e-infrastructure. We analyse the past 10 years of VAMDC development and operation, and assess their impact both on the field of atomic and molecular (A&M) physics itself and on heterogeneous data management in international cooperation. The highly sophisticated VAMDC infrastructure and the related databases developed over this long term make them a perfect resource of sustainable data for future applications in many fields of research. However, we also discuss the current limitations that prevent VAMDC from becoming the main publishing platform and the main source of A&M data for user communities, and present possible solutions under investigation by the consortium. Several user application examples are presented, illustrating the benefits of VAMDC in current research applications, which often need the A&M data from more than one database. Finally, we present our vision for the future of VAMDC.</jats:p
A Decade with VAMDC: Results and Ambitions
This paper presents an overview of the current status of the Virtual Atomic and Molecular Data Centre (VAMDC) e-infrastructure, including the current status of the VAMDC-connected (or to be connected) databases, updates on the latest technological development within the infrastructure and a presentation of some application tools that make use of the VAMDC e-infrastructure. We analyse the past 10 years of VAMDC development and operation, and assess their impact both on the field of atomic and molecular (A&M) physics itself and on heterogeneous data management in international cooperation. The highly sophisticated VAMDC infrastructure and the related databases developed over this long term make them a perfect resource of sustainable data for future applications in many fields of research. However, we also discuss the current limitations that prevent VAMDC from becoming the main publishing platform and the main source of A&M data for user communities, and present possible solutions under investigation by the consortium. Several user application examples are presented, illustrating the benefits of VAMDC in current research applications, which often need the A&M data from more than one database. Finally, we present our vision for the future of VAMDC
Chondrules – ubiquitous chondritic solids tracking the evolution of the solar protoplanetary disk
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