Bystander suppression of collagen-induced arthritis in mice fed ovalbumin

We wanted to assess whether B-cell and/or T-cell responses to collagen and thereby the course of collagen-induced arthritis could be suppressed by regulatory mechanisms associated with oral tolerance to an unrelated protein. DBA/1 mice were fed ovalbumin (OVA)-containing pellets ad libitum for 1 week and subsequently coimmunized twice, with a mixture of bovine collagen type II (BCII) and OVA in Freund's complete adjuvant. Mice fed OVA before coimmunization with BCII and OVA had significantly lower arthritic scores than mice immunized with BCII only. Their body weight increased during the study period and their anti-BCII antibody activity was significantly IgG(2a )lower. The frequency of spleen cells producing IgG anti-BCII antibody was also reduced. Coimmunization per se slightly ameliorated the development of arthritis, resulting in an early, transient reduction. It resulted in significantly higher IgG(1 )anti-BCII antibody activity and increased splenocyte secretion of IFN-γ and IL-10 in response to BCII. Our findings demonstrate that OVA-specific regulatory events induced by feeding OVA, i.e. bystander suppression, reduced the severity of arthritis in animals immunized with BCII and OVA. Anti-BCII specific antibody responses and cytokine secretion by types 1 and 2 T helper cells were also decreased

On Reconfigurable On-Chip Data Caches

Abstract Cache memory has shown to be the most important technique to bridge the gap between the processor speed and the memory access time. The advent of high-speed RISC and superscalar processors, however, calls for small on-chip data caches. Due to physical limitations, these should be simply designed and yet yield good performance. In this paper, we present new cache architectures that address the problems of conflict misses and non-optimal line sizes in the context of direct-mapped caches. Our cache architectures can be reconfigured by software in a way that matches the reference pattern for array data structures. We show that the implementation cost of the reconfiguration capability is neglectable. We also show simulation results !M demons tratc sign i fican t performance improvements for both methods

Study protocol for locoregional precision treatment of hepatocellular carcinoma with transarterial chemoembolisation (TACTida), a clinical study:idarubicin dose selection, tissue response and survival

INTRODUCTION: Hepatocellular carcinoma (HCC) is a common cause of cancer-related death, often detected in the intermediate stage. The standard of care for intermediate-stage HCC is transarterial chemoembolisation (TACE), where idarubicin (IDA) is a promising drug. Despite the fact that TACE has been used for several decades, treatment success is unpredictable. This clinical trial has been designed believing that further improvement might be achieved by increasing the understanding of interactions between local pharmacology, tumour targeting, HCC pathophysiology, metabolomics and molecular mechanisms of drug resistance. METHODS AND ANALYSIS: The study population of this single-centre clinical trial consists of adults with intermediate-stage HCC. Each tumour site will receive TACE with two different IDA doses, 10 and 15 mg, on separate occasions. Before and after each patient's first TACE blood samples, tissue and liquid biopsies, and positron emission tomography (PET)/MRI will be performed. Blood samples will be used for pharmacokinetics (PK) and liver function evaluation. Tissue biopsies will be used for histopathology analyses, and culturing of primary organoids of tumour and non-tumour tissue to measure cell viability, drug response, multiomics and gene expression. Multiomics analyses will also be performed on liquid biopsies. PET/MRI will be used to evaluate tumour viability and liver metabolism. The two doses of IDA will be compared regarding PK, antitumour effects and safety. Imaging, molecular biology and multiomics data will be used to identify HCC phenotypes and their relation to drug uptake and metabolism, treatment response and survival. ETHICS AND DISSEMINATION: Participants give informed consent. Personal data are deidentified. A patient will be withdrawn from the study if considered medically necessary, or if it is the wish of the patient. The study has been approved by the Swedish Ethical Review Authority (Dnr. 2021-01928) and by the Medical Product Agency, Uppsala, Sweden. TRIAL REGISTRATION NUMBER: EudraCT number: 2021-001257-31

Developmental trajectory of the healthy human gut microbiota during the first 5 years of life

The gut is inhabited by a densely populated ecosystem, the gut microbiota, that is established at birth. However, the succession by which different bacteria are incorporated into the gut microbiota is still relatively unknown. Here, we analyze the microbiota from 471 Swedish children followed from birth to 5 years of age, collecting samples after 4 and 12 months and at 3 and 5 years of age as well as from their mothers at birth using 16S rRNA gene profiling. We also compare their microbiota to an adult Swedish population. Genera follow 4 different colonization patterns during establishment where Methanobrevibacter and Christensenellaceae colonize late and do not reached adult levels at 5 years. These late colonizers correlate with increased alpha diversity in both children and adults. By following the children through age-specific community types, we observe that children have individual dynamics in the gut microbiota development trajectory

EFFECTIVE STRUCTURE THEOREMS FOR SPACES OF COMPACTLY SUPPORTED DISTRIBUTIONS

supported distribution

Effective Distribution Theory

In this thesis we introduce and study a notion of effectivity (or computability) for test functions and for distributions. This is done using the theory of effective (Scott-Ershov) domains and effective domain representations. To be able to construct effective domain representations of the spaces of test functions considered in distribution theory we need to develop the theory of admissible domain representations over countable pseudobases. This is done in the first paper of the thesis. To construct an effective domain representation of the space of distributions, we introduce and develop a notion of partial continuous function on domains. This is done in the second paper of the thesis. In the third paper we apply the results from the first two papers to develop an effective theory of distributions using effective domains. We prove that the vector space operations on each space, as well as the standard embeddings into the space of distributions effectivise. We also prove that the Fourier transform (as well as its inverse) on the space of tempered distributions is effective. Finally, we show how to use convolution to compute primitives on the space of distributions. In the last paper we investigate the effective properties of a structure theorem for the space of distributions with compact support. We show that each of the four characterisations of the class of compactly supported distributions in the structure theorem gives rise to an effective domain representation of the space. We then use effective reductions (and Turing-reductions) to study the reducibility properties of these four representations. We prove that three of the four representations are effectively equivalent, and furthermore, that all four representations are Turing-equivalent. Finally, we consider a similar structure theorem for the space of distributions supported at 0