Operator Coproduct-Realization of Quantum Group Transformations in Two Dimensional Gravity, I.

A simple connection between the universal $R$ matrix of $U_q(sl(2))$ (for spins \demi and $J$) and the required form of the co-product action of the Hilbert space generators of the quantum group symmetry is put forward. This gives an explicit operator realization of the co-product action on the covariant operators. It allows us to derive the quantum group covariance of the fusion and braiding matrices, although it is of a new type: the generators depend upon worldsheet variables, and obey a new central extension of $U_q(sl(2))$ realized by (what we call) fixed point commutation relations. This is explained by showing that the link between the algebra of field transformations and that of the co-product generators is much weaker than previously thought. The central charges of our extended $U_q(sl(2))$ algebra, which includes the Liouville zero-mode momentum in a nontrivial way are related to Virasoro-descendants of unity. We also show how our approach can be used to derive the Hopf algebra structure of the extended quantum-group symmetry U_q(sl(2))\odot U_{\qhat}(sl(2)) related to the presence of both of the screening charges of 2D gravity.Comment: 33 pages, latex, no figure

Value of Serum NEUROG1 Methylation for the Detection of Advanced Adenomas and Colorectal Cancer

Aberrant DNA methylation detected in liquid biopsies is a promising approach for colorectal cancer (CRC) detection, including premalignant advanced adenomas (AA). We evaluated the diagnostic capability of serum NEUROG1 methylation for the detection of AA and CRC. A CpG island in NEUROG1 promoter was assessed by bisulfite pyrosequencing in a case-control cohort to select optimal CpGs. Selected sites were evaluated through a nested methylation-specific qPCR custom assay in a screening cohort of 504 asymptomatic family-risk individuals. Individuals with no colorectal findings and benign pathologies showed low serum NEUROG1 methylation, similar to non-advanced adenomas. Contrarily, individuals bearing AA or CRC (advanced neoplasia-AN), exhibited increased NEUROG1 methylation. Using >1.3518% as NEUROG1 cut-off (90.60% specificity), 33.33% of AN and 32.08% of AA were identified, detecting 50% CRC cases. Nonetheless, the combination of NEUROG1 with fecal immunochemical test (FIT), together with age and gender through a multivariate logistic regression resulted in an AUC = 0.810 for AN, and 0.796 for AA, detecting all cancer cases and 35-47% AA (specificity 98-95%). The combination of NEUROG1 methylation with FIT, age and gender demonstrated a convenient performance for the detection of CRC and AA, providing a valuable tool for CRC screening programs in asymptomatic individuals

BMD loci contribute to ethnic and developmental differences in skeletal fragility across populations: Assessment of evolutionary selection pressures

Bone mineral density (BMD) is a highly heritable trait used both for the diagnosis of osteoporosis in adults and to assess bone health in children. Ethnic differences in BMD have been documented, with markedly higher levels in individuals of African descent, which partially explain disparity in osteoporosis risk across populations. To date, 63 independent genetic variants have been associated with BMD in adults of Northern-European ancestry. Here, we demonstrate that at least 61 of these variants are predictive of BMD early in life by studying their compound effect within two multiethnic pediatric cohorts. Furthermore, we show that within these cohorts and across populations worldwide the frequency of those alleles associated with increased BMD is systematically elevated in individuals of Sub-Saharan African ancestry. The amount of differentiation in the BMD genetic scores among Sub-Saharan and non-Sub-Saharan populations together with neutrality tests, suggest that these allelic differences are compatible with the hypothesis of selective pressures acting on the genetic determinants of BMD. These findings constitute an explorative contribution to the role of selection on ethnic BMD differences and likely a new example of polygenic adaptation acting on a human trait

MINERvA neutrino detector response measured with test beam data

The MINERvA collaboration operated a scaled-down replica of the solid scintillator tracking and sampling calorimeter regions of the MINERvA detector in a hadron test beam at the Fermilab Test Beam Facility. This article reports measurements with samples of protons, pions, and electrons from 0.35 to 2.0 GeV/c momentum. The calorimetric response to protons, pions, and electrons are obtained from these data. A measurement of the parameter in Birks' law and an estimate of the tracking efficiency are extracted from the proton sample. Overall the data are well described by a Geant4-based Monte Carlo simulation of the detector and particle interactions with agreements better than 4%, though some features of the data are not precisely modeled. These measurements are used to tune the MINERvA detector simulation and evaluate systematic uncertainties in support of the MINERvA neutrino cross section measurement program.Comment: as accepted by NIM

The genome sequencing of an albino Western lowland gorilla reveals inbreeding in the wild

Background The only known albino gorilla, named Snowflake, was a male wild born individual from Equatorial Guinea who lived at the Barcelona Zoo for almost 40 years. He was diagnosed with non-syndromic oculocutaneous albinism, i.e. white hair, light eyes, pink skin, photophobia and reduced visual acuity. Despite previous efforts to explain the genetic cause, this is still unknown. Here, we study the genetic cause of his albinism and making use of whole genome sequencing data we find a higher inbreeding coefficient compared to other gorillas. Results We successfully identified the causal genetic variant for Snowflake¿s albinism, a non-synonymous single nucleotide variant located in a transmembrane region of SLC45A2. This transporter is known to be involved in oculocutaneous albinism type 4 (OCA4) in humans. We provide experimental evidence that shows that this amino acid replacement alters the membrane spanning capability of this transmembrane region. Finally, we provide a comprehensive study of genome-wide patterns of autozygogosity revealing that Snowflake¿s parents were related, being this the first report of inbreeding in a wild born Western lowland gorilla. Conclusions In this study we demonstrate how the use of whole genome sequencing can be extended to link genotype and phenotype in non-model organisms and it can be a powerful tool in conservation genetics (e.g., inbreeding and genetic diversity) with the expected decrease in sequencing cost. Keywords: Gorilla; Albinism; Inbreeding; Genome; Conservatio

Latin American chronic urticaria registry (CUR) contribution to the understanding and knowledge of the disease in the region

Chronic urticaria (CU) has a widespread spectrum on causal or exacerbating factors, clinical manifestations, therapeutic response and quality of life affectation. Registries are useful tools in several real-life diagnosis and management approach. We aimed to evaluate the characteristics of CU patients living in Latin America through an original cross-sectional registry with data entered by regional allergologists. Results: Three hundred patients were included, being 72% female, with median age of 36 years (1\u201385) and 20 months of CU median evolution time. The cause of CU was reported as unknown in 72% of them. Thirty-nine percent of suspected cases presented positive serology for Mycoplasma, positive autologous serum skin test (ASST) was reported in 47%, and occasional presence of thyroid or antinuclear autoantibodies and parasites. The impact of pruritus in their quality of life was moderate to severe in 60% of patients, with almost 3 out of four patients having partial or lack of urticaria control with anti-histamines. Conclusions: Our registry provides retrospective data on the real-life assistance of a large number of patients from the region. Continuous search for associated conditions and better treatment possibilities are needed, in order to control the significant impact on quality of life and the length of disease

Ultra-deep sequencing reveals the mutational landscape of classical Hodgkin lymphoma

UNLABELLED: The malignant Hodgkin and Reed Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL) are scarce in affected lymph nodes, creating a challenge to detect driver somatic mutations. As an alternative to cell purification techniques, we hypothesized that ultra-deep exome sequencing would allow genomic study of HRS cells, thereby streamlining analysis and avoiding technical pitfalls. To test this, 31 cHL tumor/normal pairs were exome sequenced to approximately 1,000× median depth of coverage. An orthogonal error-corrected sequencing approach verified \u3e95% of the discovered mutations. We identified mutations in genes novel to cHL including: CDH5 and PCDH7, novel stop gain mutations in IL4R, and a novel pattern of recurrent mutations in pathways regulating Hippo signaling. As a further application of our exome sequencing, we attempted to identify expressed somatic single-nucleotide variants (SNV) in single-nuclei RNA sequencing (snRNA-seq) data generated from a patient in our cohort. Our snRNA analysis identified a clear cluster of cells containing a somatic SNV identified in our deep exome data. This cluster has differentially expressed genes that are consistent with genes known to be dysregulated in HRS cells (e.g., PIM1 and PIM3). The cluster also contains cells with an expanded B-cell clonotype further supporting a malignant phenotype. This study provides proof-of-principle that ultra-deep exome sequencing can be utilized to identify recurrent mutations in HRS cells and demonstrates the feasibility of snRNA-seq in the context of cHL. These studies provide the foundation for the further analysis of genomic variants in large cohorts of patients with cHL. SIGNIFICANCE: Our data demonstrate the utility of ultra-deep exome sequencing in uncovering somatic variants in Hodgkin lymphoma, creating new opportunities to define the genes that are recurrently mutated in this disease. We also show for the first time the successful application of snRNA-seq in Hodgkin lymphoma and describe the expression profile of a putative cluster of HRS cells in a single patient

Limits on WWZ and WW\gamma couplings from p\bar{p}\to e\nu jj X events at \sqrt{s} = 1.8 TeV

We present limits on anomalous WWZ and WW-gamma couplings from a search for WW and WZ production in p-bar p collisions at sqrt(s)=1.8 TeV. We use p-bar p -> e-nu jjX events recorded with the D0 detector at the Fermilab Tevatron Collider during the 1992-1995 run. The data sample corresponds to an integrated luminosity of 96.0+-5.1 pb^(-1). Assuming identical WWZ and WW-gamma coupling parameters, the 95% CL limits on the CP-conserving couplings are -0.33<lambda<0.36 (Delta-kappa=0) and -0.43<Delta-kappa<0.59 (lambda=0), for a form factor scale Lambda = 2.0 TeV. Limits based on other assumptions are also presented.Comment: 11 pages, 2 figures, 2 table

Search for a Fourth Generation Charge -1/3 Quark via Flavor Changing Neutral Current Decay

We report on a search for pair production of a fourth generation charge -1/3 quark (b') in pbar p collisions at sqrt(s) = 1.8 TeV at the Fermilab Tevatron using an integrated luminosity of 93 pb^-1. Both quarks are assumed to decay via flavor changing neutral currents (FCNC). The search uses the signatures gamma + 3 jets + mu-tag and 2 gamma + 2 jets. We see no significant excess of events over the expected background. We place an upper limit on the production cross section times branching fraction that is well below theoretical expectations for a b' quark decaying exclusively via FCNC for b' quark masses up to m(Z) + m(b).Comment: Eleven pages, two postscript figures, submitted to Physical Review Letter