The Landscape of Long Non-Coding RNA Dysregulation and Clinical Relevance in Muscle Invasive Bladder Urothelial Carcinoma.

Bladder cancer is one of the most common cancers in the United States, but few advancements in treatment options have occurred in the past few decades. This study aims to identify the most clinically relevant long non-coding RNAs (lncRNAs) to serve as potential biomarkers and treatment targets for muscle invasive bladder cancer (MIBC). Using RNA-sequencing data from 406 patients in The Cancer Genome Atlas (TCGA) database, we identified differentially expressed lncRNAs in MIBC vs. normal tissues. We then associated lncRNA expression with patient survival, clinical variables, oncogenic signatures, cancer- and immune-associated pathways, and genomic alterations. We identified a panel of 20 key lncRNAs that were most implicated in MIBC prognosis after differential expression analysis and prognostic correlations. Almost all lncRNAs we identified are correlated significantly with oncogenic processes. In conclusion, we discovered previously undescribed lncRNAs strongly implicated in the MIBC disease course that may be leveraged for diagnostic and treatment purposes in the future. Functional analysis of these lncRNAs may also reveal distinct mechanisms of bladder cancer carcinogenesis

E5 protein of human papillomavirus 16 downregulates HLA class I and interacts with the heavy chain via its first hydrophobic domai

Human papillomavirus type 16 E5 protein (HPV-16 E5) is expressed early in papillomavirus infection and is localised primarily in the cell Golgi apparatus (GA) and endoplasmic reticulum. E5 prevents transport of the major histocompatibility class I (MHC I; HLA class I in humans) to the cell surface and retains the complex in the GA. We report that these effects are due, at least in part, to the interaction between E5 and HLA I heavy chain (HC). We also demonstrate that the down-regulation of surface HLA I and interaction with HC are mediated by the first hydrophobic domain of E5. Although E5 downregulates classical HLA selectively as it does not downregulate non-classical HLA, the interaction with the HC of classical HLA I is not specific for a particular haplotype of HLA I. This suggests that E5 can interfere with antigen presentation by most, if not all, classical HLA I haplotypes, with potentially serious consequences as the ability of infected cells to present antigenic peptides to effector T cells would be compromised

A two-base encoded DNA sequence alignment problem in computational biology

The recent introduction of instruments capable of producing millions of DNA sequence reads in a single run is rapidly changing the landscape of genetics. The primary objective of the "sequence alignment" problem is to search for a new algorithm that facilitates the use of two-base encoded data for large-scale re-sequencing projects. This algorithm should be able to perform local sequence alignment as well as error detection and correction in a reliable and systematic manner, enabling the direct comparison of encoded DNA sequence reads to a candidate reference DNA sequence. We will first briefly review two well-known sequence alignment approaches and provide a rudimentary improvement for implementation on parallel systems. Then, we carefully examin a unique sequencing technique known as the SOLiDTM System that can be implemented, and follow by the results from the global and local sequence alignment. In this report, the team presents an explanation of the algorithms for color space sequence data from the high-throughput re-sequencing technology and a theoretical parallel approach to the dynamic programming method for global and local alignment. The combination of the di-base approach and dynamic programming provides a possible viewpoint for large-scale re-sequencing projects. We anticipate the use of distributed computing to be the next-generation engine for large-scale problems like such

Studies of chain substitution caused sub-fibril level differences in stiffness and ultrastructure of wildtype and oim/oim collagen fibers using multifrequency-AFM and molecular modeling.

Molecular alteration in type I collagen, i.e., substituting the α2 chain with α1 chain in tropocollagen molecule, can cause osteogenesis imperfecta (OI), a brittle bone disease, which can be represented by a mouse model (oim/oim). In this work, we use dual-frequency Atomic Force Microscopy (AFM) and incorporated with molecular modeling to quantify the ultrastructure and stiffness of the individual native collagen fibers from wildtype (+/+) and oim/oim diseased mice humeri. Our work presents direct experimental evidences that the +/+ fibers have highly organized and compact ultrastructure and corresponding ordered stiffness distribution. In contrast, oim/oim fibers have ordered but loosely packed ultrastructure with uncorrelated stiffness distribution, as well as local defects. The molecular model also demonstrates the structural and molecular packing differences between +/+ and oim/oim collagens. The molecular mutation significantly altered sub-fibril structure and mechanical property of collagen fibers. This study can give the new insight for the mechanisms and treatment of the brittle bone disease

Spanning tree generating functions and Mahler measures

We define the notion of a spanning tree generating function (STGF) $\sum a_n z^n$, which gives the spanning tree constant when evaluated at $z=1,$ and gives the lattice Green function (LGF) when differentiated. By making use of known results for logarithmic Mahler measures of certain Laurent polynomials, and proving new results, we express the STGFs as hypergeometric functions for all regular two and three dimensional lattices (and one higher-dimensional lattice). This gives closed form expressions for the spanning tree constants for all such lattices, which were previously largely unknown in all but one three-dimensional case. We show for all lattices that these can also be represented as Dirichlet $L$-series. Making the connection between spanning tree generating functions and lattice Green functions produces integral identities and hypergeometric connections, some of which appear to be new.Comment: 26 pages. Dedicated to F Y Wu on the occasion of his 80th birthday. This version has additional references, additional calculations, and minor correction

Phase Separation of Edge States in the Integer Quantum Hall Regime

Coulomb effects on the edge states of a two dimensional electron gas in the presence of a high magnetic field are studied for different widths of the boundaries. Schr\"odinger and Poisson equations are selfconsistently solved in the integer Quantum Hall regime. Regions of flat bands at the Fermi level appear for smooth interfaces in order to minimize the electrostatic energy related to the existence of dipoles induced by the magnetic field. These plateaus determine the phase separation in stripes of compressible and incompressible electron liquids.Comment: 8 pages, Revtex 3.0, 3 postscript figure

Potential of Equatorial Atlantic Variability to Enhance El Nino Prediction

Extraordinarily strong El Niño events, such as those of 1982/83 and 1997/98, have been poorly predicted by operational seasonal forecasts made before boreal spring, despite significant advances in understanding, improved models, and enhanced observational networks. The Equatorial Atlantic Zonal Mode – a phenomenon similar to El Niño but much weaker and peaking in boreal summer – impacts winds over the Pacific, and hence affects El Niño, and also potentially its predictability. Here we use a climate model to perform a suite of seasonal predictions with and without SST in the Atlantic restored to observations. We show for the first time that knowledge of Equatorial Atlantic sea surface temperature (SST) significantly improves the prediction across boreal spring of major El Niño events and also weaker variability. This is because Atlantic SST acts to modulate El Niño variability, rather than triggering events. Our results suggest that better prediction of major El Niño events might be achieved through model improvement in the Equatorial Atlantic

Studies of chain substitution caused sub-fibril level differences in stiffness and ultrastructure of wildtype and oim/oim collagen fibers using multifrequency-AFM and molecular modeling

Molecular alteration in type I collagen, i.e., substituting the α2 chain with α1 chain in tropocollagen molecule, can cause osteogenesis imperfecta (OI), a brittle bone disease, which can be represented by a mouse model (oim/oim). In this work, we use dual-frequency Atomic Force Microscopy (AFM) and incorporated with molecular modeling to quantify the ultrastructure and stiffness of the individual native collagen fibers from wildtype (+/+) and oim/oim diseased mice humeri. Our work presents direct experimental evidences that the +/+ fibers have highly organized and compact ultrastructure and corresponding ordered stiffness distribution. In contrast, oim/oim fibers have ordered but loosely packed ultrastructure with uncorrelated stiffness distribution, as well as local defects. The molecular model also demonstrates the structural and molecular packing differences between +/+ and oim/oim collagens. The molecular mutation significantly altered sub-fibril structure and mechanical property of collagen fibers. This study can give the new insight for the mechanisms and treatment of the brittle bone disease

Quantum critical behavior in the heavy Fermion single crystal Ce(Ni0.935_{0.935}Pd0.065_{0.065})2_2Ge2_2

We have performed magnetic susceptibility, specific heat, resistivity, and inelastic neutron scattering measurements on a single crystal of the heavy Fermion compound Ce(Ni$_{0.935}$Pd$_{0.065}$)$_2$Ge$_2$, which is believed to be close to a quantum critical point (QCP) at T = 0. At lowest temperature(1.8-3.5 K), the magnetic susceptibility behaves as $\chi(T)-\chi (0)$ $\propto$ $T^{-1/6}$ with $\chi (0) = 0.032 \times 10^{-6}$ m$^3$/mole (0.0025 emu/mole). For $T<$ 1 K, the specific heat can be fit to the formula $\Delta C/T = \gamma_0 - T^{1/2}$ with $\gamma_0$ of order 700 mJ/mole-K$^2$. The resistivity behaves as $\rho = \rho_0 + AT^{3/2}$ for temperatures below 2 K. This low temperature behavior for $\gamma (T)$ and $\rho (T)$ is in accord with the SCR theory of Moriya and Takimoto\cite{Moriya}. The inelastic neutron scattering spectra show a broad peak near 1.5 meV that appears to be independent of $Q$; we interpret this as Kondo scattering with $T_K =$ 17 K. In addition, the scattering is enhanced near $Q$=(1/2, 1/2, 0) with maximum scattering at $\Delta E$ = 0.45 meV; we interpret this as scattering from antiferromagnetic fluctuations near the antiferromagnetic QCP.Comment: to be published in J. Phys: Conference Serie