Monte Carlo Approaches to Parameterized Poker Squares

The paper summarized a variety of Monte Carlo approaches employed in the top three performing entries to the Parameterized Poker Squares NSG Challenge competition. In all cases AI players benefited from real-time machine learning and various Monte Carlo game-tree search techniques

Effects of canine-assisted intervention on the mental health of higher education students: a systematic review

The aim of this systematic review was to evaluate existing literature exploring the effects of canine assisted intervention (CAI) on the mental health of Higher Education (HE) students. A literature search was performed on 14th January 2021 for studies that investigated the effects of CAI on HE students. Thirty three papers (6093 participants) encompassing 37 studies were included in this review. Study design varied in research objective, intervention type, timing, procedure, and measures. The Effective Public Health Practice Project Quality Assessment Tool found studies ranged in quality from moderate (n=7) to weak (n=30). The review identified CAI has a positive effect on levels of anxiety and stress in HE students. Key limitations of the studies include confounding influences during the intervention as well as a lack of control groups and standardized measures. Furthermore, intervention and procedures ranged substantially in design and application making direct comparisons difficult. The authors conclude two main outcomes from the review. Firstly, CAI improves mental health in HE students, in particular anxiety and stress. Secondly, CAI has a social benefit, encouraging communication and a shared experience. However, a number of methodological limitations of the studies are identified and reviewed. To conclude, this systematic review reveals strong support for the use of CAI in HE students as a form of therapy

T cell epitope clustering in the highly immunogenic BZLF1 antigen of Epstein-Barr virus

Polymorphism in the human leukocyte antigen (HLA) loci ensures that the CD8 T cell response to viruses is directed against a diverse range of antigenic epitopes, thereby minimizing the impact of virus escape mutation across the population. The BZLF1 antigen of Epstein-Barr virus is an immunodominant target for CD8 T cells, but the response has been characterized only in the context of a limited number of HLA molecules due to incomplete epitope mapping. We have now greatly expanded the number of defined CD8 T cell epitopes from BZLF1, allowing the response to be evaluated in a much larger proportion of the population. Some regions of the antigen fail to be recognized by CD8 T cells, while others include clusters of overlapping epitopes presented by different HLA molecules. These highly immunogenic regions of BZLF1 include polymorphic sequences, such that up to four overlapping epitopes are impacted by a single amino acid variation common in different regions of the world. This focusing of the immune response to limited regions of the viral protein could be due to sequence similarity to human proteins creating "immune blind spots" through self-tolerance. This study significantly enhances the understanding of the immune response to BZLF1, and the precisely mapped T cell epitopes may be directly exploited in vaccine development and adoptive immunotherapy

Multivariate analysis using high definition flow cytometry reveals distinct T cell repertoires between the fetal–maternal interface and the peripheral blood

The human T cell compartment is a complex system and while some information is known on repertoire composition and dynamics in the peripheral blood, little is known about repertoire composition at different anatomical sites. Here, we determine the T cell receptor beta variable (TRBV) repertoire at the decidua and compare it with the peripheral blood during normal pregnancy and pre-eclampsia. We found total T cell subset disparity of up to 58% between sites, including large signature TRBV expansions unique to the fetal–maternal interface. Defining the functional nature and specificity of compartment-specific T cells will be necessary if we are to understand localized immunity, tolerance, and pathogenesis

Dynamic processes happening during the evaporation of films of fusible materials

Optical waveguides on glass substrates are a promising area in their application in simple and cheap optoelectronic devices. As shown in [1], the highest refractive index is achieved during the formation of waveguides by oxidized film diffusion. However, realization of a number of electro-optical effects is restrained by probabilistic repeatability of wave guiding layers which holds down the development of optoelectronics [1-3]. This happens due to the fact that film formation in gas exchange mode isn't explored enough. One of the reasons of probabilistic repeatability of local thickness and film composition is dynamic processes which happen during the material evaporation. The regularities of evaporation, which were earlier found by Knudsen, Langmuir and other scientists for point sources, fail when it comes to the line where one material escape into another state. Most materials, which have three states - solid, liquid, gaseous - at ambient pressure heating, in vacuum, lose their liquid state partly or completely. Moreover, the film distribution over the substrate is quite unclear because of the poor study of molecular vapor flow and substrate interaction

Pre-emptive and therapeutic adoptive immunotherapy for nasopharyngeal carcinoma: Phenotype and effector function of T cells impact on clinical response

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Day-4 Myeloid Dendritic Cells Pulsed with Whole Tumor Lysate Are Highly Immunogenic and Elicit Potent Anti-Tumor Responses

“Day-7” myeloid DCs are commonly used in the clinic. However, there is a strong need to develop DCs faster that have the same potent immunostimulatory capacity as “Day-7” myeloid DCs and at the same time minimizing time, labor and cost of DC preparations. Although “2 days” DCs can elicit peptide-specific responses, they have not been demonstrated to engulf, process and present complex whole tumor lysates, which could be more convenient and personalized source of tumor antigens than defined peptides. In this preclinical study, we evaluated the T-cell stimulatory capacity of Day-2, Day-4, and Day-7 cultured monocyte-derived DCs loaded with SKOV3 cell whole lysate prepared by freeze-thaw or by UVB-irradiation followed by freeze-thaw, and matured with lipopolysaccharide (LPS) and interferon (IFN)-gamma. DCs were evaluated for antigen uptake, and following maturation with LPS and IFN-gamma, DCs were assessed for expression of CD80, CD40, CD86, ICAM-1 and CCR7, production of IL-12p70 and IP-10, and induction of tumor-specific T-cell responses. Day-4 and Day-7 DCs exhibited similar phagocytic abilities, which were superior to Day-2 DCs. Mature Day-7 DCs expressed the highest CD40 and ICAM-1, but mature Day-4 DCs produced the most IL-12p70 and IP-10. Importantly, Day-4 and Day-7 DCs derived from ovarian cancer patients stimulated equally strongly tumor-specific T-cell responses. This is the first study demonstrating the highly immunogenic and strong T-cell stimulatory properties of Day-4 myeloid DCs, and provided important preclinical data for rapid development of potent whole tumor lysate-loaded DC vaccines that are applicable to many tumor types

Allelic polymorphism in the T cell receptor and its impact on immune responses

In comparison to human leukocyte antigen (HLA) polymorphism, the impact of allelic sequence variation within T cell receptor (TCR) loci is much less understood. Particular TCR loci have been associated with autoimmunity, but the molecular basis for this phenomenon is undefined. We examined the T cell response to an HLA-B*3501-restricted epitope (HPVGEADYFEY) from Epstein-Barr virus (EBV), which is frequently dominated by a TRBV9*01 public TCR (TK3). However, the common allelic variant TRBV9*02, which differs by a single amino acid near the CDR2β loop (Gln55→His55), was never used in this response. The structure of the TK3 TCR, its allelic variant, and a nonnaturally occurring mutant (Gln55→Ala55) in complex with HLA-B*3501 revealed that the Gln55→His55 polymorphism affected the charge complementarity at the TCR-peptide-MHC interface, resulting in reduced functional recognition of the cognate and naturally occurring variants of this EBV peptide. Thus, polymorphism in the TCR loci may contribute toward variability in immune responses and the outcome of infection

CD8+ T cells from a novel T cell receptor transgenic mouse induce liver-stage immunity that can be boosted by blood-stage infection in rodent malaria

To follow the fate of CD8+ T cells responsive to Plasmodium berghei ANKA (PbA) infection, we generated an MHC I-restricted TCR transgenic mouse line against this pathogen. T cells from this line, termed PbT-I T cells, were able to respond to blood-stage infection by PbA and two other rodent malaria species, P. yoelii XNL and P. chabaudi AS. These PbT-I T cells were also able to respond to sporozoites and to protect mice from liver-stage infection. Examination of the requirements for priming after intravenous administration of irradiated sporozoites, an effective vaccination approach, showed that the spleen rather than the liver was the main site of priming and that responses depended on CD8α+ dendritic cells. Importantly, sequential exposure to irradiated sporozoites followed two days later by blood-stage infection led to augmented PbT-I T cell expansion. These findings indicate that PbT-I T cells are a highly versatile tool for studying multiple stages and species of rodent malaria and suggest that cross-stage reactive CD8+ T cells may be utilized in liver-stage vaccine design to enable boosting by blood-stage infections