Spectral metric spaces for Gibbs measures

We construct spectral metric spaces for Gibbs measures on a one-sided topologically exact subshift of finite type. That is, for a given Gibbs measure we construct a spectral triple and show that Connes' corresponding pseudo-metric is a metric and that its metric topology agrees with the weak-*-topology on the state space over the set of continuous functions defined on the subshift. Moreover, we show that each Gibbs measure can be fully recovered from the noncommutative integration theory and that the noncommutative volume constant of the associated spectral triple is equal to the reciprocal of the measure theoretical entropy of the shift invariant Gibbs measure.Comment: 25 page

Epigenetic Features of Human Mesenchymal Stem Cells Determine Their Permissiveness for Induction of Relevant Transcriptional Changes by SYT-SSX1

BACKGROUND: A characteristic SYT-SSX fusion gene resulting from the chromosomal translocation t(X;18)(p11;q11) is detectable in almost all synovial sarcomas, a malignant soft tissue tumor widely believed to originate from as yet unidentified pluripotent stem cells. The resulting fusion protein has no DNA binding motifs but possesses protein-protein interaction domains that are believed to mediate association with chromatin remodeling complexes. Despite recent advances in the identification of molecules that interact with SYT-SSX and with the corresponding wild type SYT and SSX proteins, the mechanisms whereby the SYT-SSX might contribute to neoplastic transformation remain unclear. Epigenetic deregulation has been suggested to be one possible mechanism. METHODOLOGY/PRINCIPAL FINDINGS: We addressed the effect of SYT/SSX expression on the transcriptome of four independent isolates of primary human bone marrow mesenchymal stem cells (hMSC). We observed transcriptional changes similar to the gene expression signature of synovial sarcoma, principally involving genes whose regulation is linked to epigenetic factors, including imprinted genes, genes with transcription start sites within a CpG island and chromatin related genes. Single population analysis revealed hMSC isolate-specific transcriptional changes involving genes that are important for biological functions of stem cells as well as genes that are considered to be molecular markers of synovial sarcoma including IGF2, EPHRINS, and BCL2. Methylation status analysis of sequences at the H19/IGF2 imprinted locus indicated that distinct epigenetic features characterize hMSC populations and condition the transcriptional effects of SYT-SSX expression. CONCLUSIONS/SIGNIFICANCE: Our observations suggest that epigenetic features may define the cellular microenvironment in which SYT-SSX displays its functional effects

CIC-DUX4 chromatin profiling reveals new epigenetic dependencies and actionable therapeutic targets in CIC-rearranged sarcomas

CIC-DUX4-rearranged sarcoma (CDS) is a rare and aggressive soft tissue tumor that occurs most frequently in young adults. The key oncogenic driver of this disease is the expression of the CIC-DUX4 fusion protein as a result of chromosomal rearrangements. CIC-DUX4 displays chromatin binding properties, and is therefore believed to function as an aberrant transcription factor. However, the chromatin remodeling events induced by CIC-DUX4 are not well understood, limiting our ability to identify new mechanism-based therapeutic strategies for these patients. Here, we generated a genome-wide profile of CIC-DUX4 DNA occupancy and associated chromatin states in human CDS cell models and primary tumors. Combining chromatin profiling, proximity ligation assays, as well as genetic and pharmacological perturbations, we show that CIC-DUX4 operates as a potent transcriptional activator at its binding sites. This property is in contrast with the repressive function of the wild-type CIC protein, and is mainly mediated through the direct interaction of CIC-DUX4 with the acetyltransferase p300. In keeping with this, we show p300 to be essential for CDS tumor cell proliferation; additionally, we find its pharmacological inhibition to significantly impact tumor growth in vitro and in vivo. Taken together, our study elucidates the mechanisms underpinning CIC-DUX4-mediated transcriptional regulation

Biomass Burning Measurements in Earlinet

The biomass burning events are analyzed using the EARLINET-ACTRIS atmospheric profiling of aerosols using lidars. The period of 2008-2017 was chosen to analyze all the events assigned in the EARLINET database under Forest Fire category. A number of fourteen stations were considered. The data provided, ranged from complete data sets (backscatter, extinction and particle linear depolarization ratio) to single profiles (backscatter coefficient). A thorough quality control was performed. Smoke layers geometry was evaluated and the mean properties within each layer were computed. The Hysplit backward-trajectory technique and the FIRMS fire database were used to double check the source of each layer. Discussions were made under the following scenarios: fire events seen by two stations, long range transport from North America, and geographical clusters

Biomass Burning Measurements in Earlinet

The biomass burning events are analyzed using the EARLINET-ACTRIS atmospheric profiling of aerosols using lidars. The period of 2008-2017 was chosen to analyze all the events assigned in the EARLINET database under Forest Fire category. A number of fourteen stations were considered. The data provided, ranged from complete data sets (backscatter, extinction and particle linear depolarization ratio) to single profiles (backscatter coefficient). A thorough quality control was performed. Smoke layers geometry was evaluated and the mean properties within each layer were computed. The Hysplit backward-trajectory technique and the FIRMS fire database were used to double check the source of each layer. Discussions were made under the following scenarios: fire events seen by two stations, long range transport from North America, and geographical clusters

Tissue Biomarkers for Prognosis in Cutaneous Melanoma: A Systematic Review and Meta-analysis

In the clinical management of early-stage cutaneous melanoma, it is critical to determine which patients are cured by surgery alone and which should be treated with adjuvant therapy. To assist in this decision, many groups have made an effort to use molecular information. However, although there are hundreds of studies that have sought to assess the potential prognostic value of molecular markers in predicting the course of cutaneous melanoma, at this time, no molecular method to improve risk stratification is part of recommended clinical practice. To help understand this disconnect, we conducted a systematic review and meta-analysis of the published literature that reported immunohistochemistry-based protein biomarkers of melanoma outcome. Three parallel search strategies were applied to the PubMed database through January 15, 2008, to identify cohort studies that reported associations between immunohistochemical expression and survival outcomes in melanoma that conformed to the REMARK criteria. Of the 102 cohort studies, we identified only 37 manuscripts, collectively describing 87 assays on 62 distinct proteins, which met all inclusion criteria. Promising markers that emerged included melanoma cell adhesion molecule (MCAM)/MUC18 (all-cause mortality [ACM] hazard ratio [HR] = 16.34; 95% confidence interval [CI] = 3.80 to 70.28), matrix metalloproteinase-2 (melanoma-specific mortality [MSM] HR = 2.6; 95% CI = 1.32 to 5.07), Ki-67 (combined ACM HR = 2.66; 95% CI = 1.41 to 5.01), proliferating cell nuclear antigen (ACM HR = 2.27; 95% CI = 1.56 to 3.31), and p16/INK4A (ACM HR = 0.29; 95% CI = 0.10 to 0.83, MSM HR = 0.4; 95% CI = 0.24 to 0.67). We further noted incomplete adherence to the REMARK guidelines: 14 of 27 cohort studies that failed to adequately report their methods and nine studies that failed to either perform multivariable analyses or report their risk estimates were published since 2005