Crystal energy functions via the charge in types A and C

The Ram-Yip formula for Macdonald polynomials (at t=0) provides a statistic which we call charge. In types A and C it can be defined on tensor products of Kashiwara-Nakashima single column crystals. In this paper we prove that the charge is equal to the (negative of the) energy function on affine crystals. The algorithm for computing charge is much simpler and can be more efficiently computed than the recursive definition of energy in terms of the combinatorial R-matrix.Comment: 25 pages; 1 figur

Closure relations during the plateau emission of Swift GRBs and the fundamental plane

The Neil Gehrels Swift observatory observe Gamma-Ray bursts (GRBs) plateaus in X-rays. We test the reliability of the closure relations through the fireball model when dealing with the GRB plateau emission. We analyze 455 X-ray lightcurves (LCs) collected by \emph{Swift} from 2005 (January) until 2019 (August) for which the redshift is both known and unknown using the phenomenological Willingale 2007 model. Using these fits, we analyze the emission mechanisms and astrophysical environments of these GRBs through the closure relations within the time interval of the plateau emission. Finally, we test the 3D fundamental plane relation (Dainotti relation) which connects the prompt peak luminosity, the time at the end of the plateau (rest-frame), and the luminosity at that time, on the GRBs with redshift, concerning groups determined by the closure relations. This allows us to check if the intrinsic scatter \sigma_{int} of any of these groups is reduced compared to previous literature. The most fulfilled environments for the electron spectral distribution, p>2, are Wind Slow Cooling (SC) and ISM Slow Cooling for cases in which the parameter q, which indicates the flatness of the plateau emission and accounts for the energy injection, is =0 and =0.5, respectively, both in the cases with known and unknown redshifts. We also find that for the sGRBs All ISM Environments with $q=0$ have the smallest \sigma_{int}=0.04 \pm 0.15 in terms of the fundamental plane relation holding a probability of occurring by chance of p=0.005. We have shown that the majority of GRBs presenting the plateau emission fulfil the closure relations, including the energy injection, with a particular preference for the Wind SC environment. The subsample of GRBs that fulfil given relations can be used as possible standard candles and can suggest a way to reduce the intrinsic scatter of these studied relationships.Comment: 44 pages, 23 figures; Accepted to the PASJ to be published soo

Intrinsic Folding Properties of the HLA-B27 Heavy Chain Revealed by Single Chain Trimer Versions of Peptide-Loaded Class I Major Histocompatibility Complex Molecules

Peptide-loaded Major Histocompatibility Complex (pMHC) class I molecules can be expressed in a single chain trimeric (SCT) format, composed of a specific peptide fused to the light chain beta-2 microglobulin (β2m) and MHC class I heavy chain (HC) by flexible linker peptides. pMHC SCTs have been used as effective molecular tools to investigate cellular immunity and represent a promising vaccine platform technology, due to their intracellular folding and assembly which is apparently independent of host cell folding pathways and chaperones. However, certain MHC class I HC molecules, such as the Human Leukocyte Antigen B27 (HLA-B27) allele, present a challenge due to their tendency to form HC aggregates. We constructed a series of single chain trimeric molecules to determine the behaviour of the HLA-B27 HC in a scenario that usually allows for efficient MHC class I molecule folding. When stably expressed, a pMHC SCT incorporating HLA-B27 HC formed chaperone-bound homodimers within the endoplasmic reticulum (ER). A series of HLA-B27 SCT substitution mutations revealed that the F pocket and antigen binding groove regions of the HLA-B27 HC defined the folding and dimerisation of the single chain complex, independently of the peptide sequence. Furthermore, pMHC SCTs can demonstrate variability in their association with the intracellular antigen processing machinery

Asymmetric function theory

The classical theory of symmetric functions has a central position in algebraic combinatorics, bridging aspects of representation theory, combinatorics, and enumerative geometry. More recently, this theory has been fruitfully extended to the larger ring of quasisymmetric functions, with corresponding applications. Here, we survey recent work extending this theory further to general asymmetric polynomials.Comment: 36 pages, 8 figures, 1 table. Written for the proceedings of the Schubert calculus conference in Guangzhou, Nov. 201

Social Health and Change in Cognitive Capability among Older Adults: Findings from Four European Longitudinal Studies

INTRODUCTION: In this study we examine whether social health markers measured at baseline are associated with differences in cognitive capability and in the rate of cognitive decline over an 11-to-18-year period among older adults and compare results across studies. METHODS: We applied an integrated data analysis approach to 16,858 participants (mean age 65 years; 56% female) from the National Survey for Health and Development (NSHD), the English Longitudinal Study of Aging (ELSA), the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), and the Rotterdam Study. We used multilevel models to examine social health in relation to cognitive capability and the rate of cognitive decline. RESULTS: Pooled estimates show distinct relationships between markers of social health and cognitive domains e.g., a large network size (≥6 people vs none) was associated with higher executive function (0.17 SD[95%CI:0.0, 0.34], I2=27%) but not with memory (0.08 SD[95%CI: -0.02, 0.18], I2=19%). We also observed pooled associations between being married or cohabiting, having a large network size and participating in social activities with slower decline in cognitive capability, however estimates were close to zero e.g., 0.01SD/year [95%CI: 0.01 to 0.02] I2=19% for marital status and executive function. There were clear study-specific differences: results for average processing speed were the most homogenous and results for average memory were the most heterogenous. CONCLUSION: Overall, markers of good social health have a positive association with cognitive capability. However, we found differential associations between specific markers of social health and cognitive domains and differences between studies. These findings highlight the importance of examining between study differences and considering context specificity of findings in developing and deploying any interventions

Properties of monocytes generated from haematopoietic CD34+ stem cells from bone marrow of colon cancer patients

Monocytes exhibit direct and indirect antitumour activities and may be potentially useful for various forms of adoptive cellular immunotherapy of cancer. However, blood is a limited source of them. This study explored whether monocytes can be obtained from bone marrow haematopoietic CD34(+) stem cells of colon cancer patients, using previously described protocol of expansion and differentiation to monocytes of cord blood-derived CD34(+) haematopoietic progenitors. Data show that in two-step cultures, the yield of cells was increased approximately 200-fold, and among these cells, up to 60 % of CD14(+) monocytes were found. They consisted of two subpopulations: CD14(++)CD16(+) and CD14(+)CD16(−), at approximately 1:1 ratio, that differed in HLA-DR expression, being higher on the former. No differences in expression of costimulatory molecules were observed, as CD80 was not detected, while CD86 expression was comparable. These CD14(+) monocytes showed the ability to present recall antigens (PPD, Candida albicans) and neoantigens expressed on tumour cells and tumour-derived microvesicles (TMV) to autologous CD3(+) T cells isolated from the peripheral blood. Monocytes also efficiently presented the immunodominant HER-2/neu(369–377) peptide (KIFGSLAFL), resulting in the generation of specific cytotoxic CD8(+) T lymphocytes (CTL). The CD14(++)CD16(+) subset exhibited enhanced cytotoxicity, though nonsignificant, towards tumour cells in vitro. These observations indicate that generation of monocytes from CD34(+) stem cells of cancer patients is feasible. To our knowledge, it is the first demonstration of such approach that may open a way to obtain autologous monocytes for alternative forms of adaptive and adoptive cellular immunotherapy of cancer

APPL Proteins FRET at the BAR: Direct Observation of APPL1 and APPL2 BAR Domain-Mediated Interactions on Cell Membranes Using FRET Microscopy

Human APPL1 and APPL2 are homologous RAB5 effectors whose binding partners include a diverse set of transmembrane receptors, signaling proteins, and phosphoinositides. APPL proteins associate dynamically with endosomal membranes and are proposed to function in endosome-mediated signaling pathways linking the cell surface to the cell nucleus. APPL proteins contain an N-terminal Bin/Amphiphysin/Rvs (BAR) domain, a central pleckstrin homology (PH) domain, and a C-terminal phosphotyrosine binding (PTB) domain. Previous structural and biochemical studies have shown that the APPL BAR domains mediate homotypic and heterotypic APPL-APPL interactions and that the APPL1 BAR domain forms crescent-shaped dimers. Although previous studies have shown that APPL minimal BAR domains associate with curved cell membranes, direct interaction between APPL BAR domains on cell membranes in vivo has not been reported.Herein, we used a laser-scanning confocal microscope equipped with a spectral detector to carry out fluorescence resonance energy transfer (FRET) experiments with cyan fluorescent protein/yellow fluorescent protein (CFP/YFP) FRET donor/acceptor pairs to examine interactions between APPL minimal BAR domains at the subcellular level. This comprehensive approach enabled us to evaluate FRET levels in a single cell using three methods: sensitized emission, standard acceptor photobleaching, and sequential acceptor photobleaching. We also analyzed emission spectra to address an outstanding controversy regarding the use of CFP donor/YFP acceptor pairs in FRET acceptor photobleaching experiments, based on reports that photobleaching of YFP converts it into a CFP-like species.All three methods consistently showed significant FRET between APPL minimal BAR domain FRET pairs, indicating that they interact directly in a homotypic (i.e., APPL1-APPL1 and APPL2-APPL2) and heterotypic (i.e., APPL1-APPL2) manner on curved cell membranes. Furthermore, the results of our experiments did not show photoconversion of YFP into a CFP-like species following photobleaching, supporting the use of CFP donor/YFP acceptor FRET pairs in acceptor photobleaching studies

A Multicassette Gateway Vector Set for High Throughput and Comparative Analyses in Ciona and Vertebrate Embryos

BACKGROUND: The past few years have seen a vast increase in the amount of genomic data available for a growing number of taxa, including sets of full length cDNA clones and cis-regulatory sequences. Large scale cross-species comparisons of protein function and cis-regulatory sequences may help to understand the emergence of specific traits during evolution. PRINCIPAL FINDINGS: To facilitate such comparisons, we developed a Gateway compatible vector set, which can be used to systematically dissect cis-regulatory sequences, and overexpress wild type or tagged proteins in a variety of chordate systems. It was developed and first characterised in the embryos of the ascidian Ciona intestinalis, in which large scale analyses are easier to perform than in vertebrates, owing to the very efficient embryo electroporation protocol available in this organism. Its use was then extended to fish embryos and cultured mammalian cells. CONCLUSION: This versatile vector set opens the way to the mid- to large-scale comparative analyses of protein function and cis-regulatory sequences across chordate evolution. A complete user manual is provided as supplemental material