Disruption of the Non-Canonical WNT Pathway in Lung Squamous Cell Carcinoma

Disruptions of beta-catenin and the canonical Wnt pathway are well documented in cancer. However, little is known of the non-canonical branch of the Wnt pathway. In this study, we investigate the transcript level patterns of genes in the Wnt pathway in squamous cell lung cancer using reverse-transcriptase (RT)-PCR. It was found that over half of the samples examined exhibited dysregulated gene expression of multiple components of the non-canonical branch of the WNT pathway. In the cases where beta catenin (CTNNB1) was not over-expressed, we identified strong relationships of expression between wingless-type MMTV integration site family member 5A (WNT5A)/frizzled homolog 2 (FZD2), frizzled homolog 3 (FZD3)/dishevelled 2 (DVL2), and low density lipoprotein receptor-related protein 5 (LRP5)/secreted frizzled-related protein 4 (SFRP4). This is one of the first studies to demonstrate expression of genes in the non-canonical pathway in normal lung tissue and its disruption in lung squamous cell carcinoma. These findings suggest that the non-canonical pathway may have a more prominent role in lung cancer than previously reported

String Indexing for Patterns with Wildcards

We consider the problem of indexing a string $t$ of length $n$ to report the occurrences of a query pattern $p$ containing $m$ characters and $j$ wildcards. Let $occ$ be the number of occurrences of $p$ in $t$, and $\sigma$ the size of the alphabet. We obtain the following results. - A linear space index with query time $O(m+\sigma^j \log \log n + occ)$. This significantly improves the previously best known linear space index by Lam et al. [ISAAC 2007], which requires query time $\Theta(jn)$ in the worst case. - An index with query time $O(m+j+occ)$ using space $O(\sigma^{k^2} n \log^k \log n)$, where $k$ is the maximum number of wildcards allowed in the pattern. This is the first non-trivial bound with this query time. - A time-space trade-off, generalizing the index by Cole et al. [STOC 2004]. We also show that these indexes can be generalized to allow variable length gaps in the pattern. Our results are obtained using a novel combination of well-known and new techniques, which could be of independent interest

Wigner Crystalization in the Lowest Landau Level for ν≥1/5\nu \ge 1/5

By means of exact diagonalization we study the low-energy states of seven electrons in the lowest Landau level which are confined by a cylindric external potential modelling the rest of a macroscopic system and thus controlling the filling factor $\nu$. Wigner crystal is found to be the ground state for filling factors between $\nu = 1/3$ and $\nu = 1/5$ provided electrons interact via the bare Coulomb potential. Even at $\nu =1/5$ the solid state has lower energy than the Laughlin's one, although the two energies are rather close. We also discuss the role of pseudopotential parameters in the lowest Landau level and demonstrate that the earlier reported gapless state, appearing when the short-range part of the interaction is suppressed, has nothing in common with the Wigner crystalization in pure Coulomb case.Comment: 9 pages, LaTex, 8 figure

Virtual photon fragmentation functions

We introduce operator definitions for virtual photon fragmentation functions, which are needed for reliable calculations of Drell-Yan transverse momentum ($Q_T$) distributions when $Q_T$ is much larger than the invariant mass $Q$. We derive the evolution equations for these fragmentation functions. We calculate the leading order evolution kernels for partons to fragment into a unpolarized as well as a polarized virtual photon. We find that fragmentation functions to a longitudinally polarized virtual photon are most important at small $z$, and the fragmentation functions to a transversely polarized virtual photon dominate the large $z$ region. We discuss the implications of this finding to the J/$\psi$ mesons' polarization at large transverse momentum.Comment: Latex, 19 pages including 6 figures. An error in the first version has been corrected, and references update

Sustainable bio-economy that delivers the environment-food-energy-water nexus objectives::the current status in Malaysia

Biomass is a promising resource in Malaysia for energy, fuels, and high value-added products. However, regards to biomass value chains, the numerous restrictions and challenges related to the economic and environmental features must be considered. The major concerns regarding the enlargement of biomass plantation is that it requires large amounts of land and environmental resources such as water and soil that arises the danger of creating severe damages to the ecosystem (e.g. deforestation, water pollution, soil depletion etc.). Regarded concerns can be diminished when all aspects associated with palm biomass conversion and utilization linked with environment, food, energy and water (EFEW) nexus to meet the standard requirement and to consider the potential impact on the nexus as a whole. Therefore, it is crucial to understand the detail interactions between all the components in the nexus once intended to look for the best solution to exploit the great potential of biomass. This paper offers an overview regarding the present potential biomass availability for energy production, technology readiness, feasibility study on the techno-economic analyses of the biomass utilization and the impact of this nexus on value chains. The agro-biomass resources potential and land suitability for different crops has been overviewed using satellite imageries and the outcomes of the nexus interactions should be incorporated in developmental policies on biomass. The paper finally discussed an insight of digitization of the agriculture industry as future strategy to modernize agriculture in Malaysia. Hence, this paper provides holistic overview of biomass competitiveness for sustainable bio-economy in Malaysia

Nuclear effects in the Drell-Yan process at very high energies

We study Drell-Yan (DY) dilepton production in proton(deuterium)-nucleus and in nucleus-nucleus collisions within the light-cone color dipole formalism. This approach is especially suitable for predicting nuclear effects in the DY cross section for heavy ion collisions, as it provides the impact parameter dependence of nuclear shadowing and transverse momentum broadening, quantities that are not available from the standard parton model. For p(D)+A collisions we calculate nuclear shadowing and investigate nuclear modification of the DY transverse momentum distribution at RHIC and LHC for kinematics corresponding to coherence length much longer than the nuclear size. Calculations are performed separately for transversely and longitudinally polarized DY photons, and predictions are presented for the dilepton angular distribution. Furthermore, we calculate nuclear broadening of the mean transverse momentum squared of DY dileptons as function of the nuclear mass number and energy. We also predict nuclear effects for the cross section of the DY process in heavy ion collisions. We found a substantial nuclear shadowing for valence quarks, stronger than for the sea.Comment: 46 pages, 18 figures, title changed and some discussion added, accepted for publication in PR

Re-examining the widespread policy of stopping sodium-glucose cotransporter-2 inhibitors during acute illness: A perspective based on the updated evidence

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are now seen as an integral part of therapy in type 2 diabetes to control not only blood glucose but to improve cardiovascular and kidney outcomes. Diabetic ketoacidosis (DKA) is an uncommon but serious complication of type 2 diabetes, which has a high case fatality rate. The absolute risk of DKA in large, prospective randomized clinical trials in people with type 2 diabetes using SGLT2 inhibitors has been low, although the relative risk is higher in those assigned to SGLT2 inhibitors compared with placebo. In those without diabetes but prescribed SGLT2 inhibitors for heart failure or chronic kidney disease, the risk of DKA is similar to placebo. Over the course of the COVID-19 pandemic, cases of DKA have also been reported in cases of COVID-19 hospitalizations. Consensus guidelines have recommended that SGLT2 inhibitors should be avoided in cases of serious illness and suggest they are not recommended for routine in-hospital use. However, recent data suggest potential beneficial effects of SGLT2 inhibitors in the setting of acute illness with COVID-19 with no increase in adverse events and low rates of DKA, which were non-severe. Given the low rates of DKA in cardiovascular outcome trials and in hospitalized patients with type 2 diabetes, the potential for SGLT2 inhibitors not being re-initiated following discharge and their cardiovascular and kidney benefits, we believe the practice of routine ‘sick day’ guidance should be re-examined based on current evidence with a call for further research in this area. Furthermore, high-quality trials of initiation of SGLT2 inhibitors in people admitted to hospital with cardiovascular disease or kidney disease, and trials of continuation of SGLT2 inhibitors in people, with careful monitoring of DKA should be conducted. These should be further supplemented with large observational studies

Hamiltonian Description of Composite Fermions: Magnetoexciton Dispersions

A microscopic Hamiltonian theory of the FQHE, developed by Shankar and myself based on the fermionic Chern-Simons approach, has recently been quite successful in calculating gaps in Fractional Quantum Hall states, and in predicting approximate scaling relations between the gaps of different fractions. I now apply this formalism towards computing magnetoexciton dispersions (including spin-flip dispersions) in the $\nu=1/3$, 2/5, and 3/7 gapped fractions, and find approximate agreement with numerical results. I also analyse the evolution of these dispersions with increasing sample thickness, modelled by a potential soft at high momenta. New results are obtained for instabilities as a function of thickness for 2/5 and 3/7, and it is shown that the spin-polarized 2/5 state, in contrast to the spin-polarized 1/3 state, cannot be described as a simple quantum ferromagnet.Comment: 18 pages, 18 encapsulated ps figure

HDAC6 modulates myofibril stiffness and diastolic function of the heart

Passive stiffness of the heart is determined largely by extracellular matrix and titin, which functions as a molecular spring within sarcomeres. Titin stiffening is associated with the development of diastolic dysfunction (DD), while augmented titin compliance appears to impair systolic performance in dilated cardiomyopathy. We found that myofibril stiffness was elevated in mice lacking histone deacetylase 6 (HDAC6). Cultured adult murine ventricular myocytes treated with a selective HDAC6 inhibitor also exhibited increased myofibril stiffness. Conversely, HDAC6 overexpression in cardiomyocytes led to decreased myofibril stiffness, as did ex vivo treatment of mouse, rat, and human myofibrils with recombinant HDAC6. Modulation of myofibril stiffness by HDAC6 was dependent on 282 amino acids encompassing a portion of the PEVK element of titin. HDAC6 colocalized with Z-disks, and proteomics analysis suggested that HDAC6 functions as a sarcomeric protein deacetylase. Finally, increased myofibril stiffness in HDAC6-deficient mice was associated with exacerbated DD in response to hypertension or aging. These findings define a role for a deacetylase in the control of myofibril function and myocardial passive stiffness, suggest that reversible acetylation alters titin compliance, and reveal the potential of targeting HDAC6 to manipulate the elastic properties of the heart to treat cardiac diseases