Activation Energy of Metastable Amorphous Ge2Sb2Te5 from Room Temperature to Melt

Resistivity of metastable amorphous Ge2Sb2Te5 (GST) measured at device level show an exponential decline with temperature matching with the steady-state thin-film resistivity measured at 858 K (melting temperature). This suggests that the free carrier activation mechanisms form a continuum in a large temperature scale (300 K - 858 K) and the metastable amorphous phase can be treated as a super-cooled liquid. The effective activation energy calculated using the resistivity versus temperature data follow a parabolic behavior, with a room temperature value of 333 meV, peaking to ~377 meV at ~465 K and reaching zero at ~930 K, using a reference activation energy of 111 meV (3kBT/2) at melt. Amorphous GST is expected to behave as a p-type semiconductor at Tmelt ~ 858 K and transitions from the semiconducting-liquid phase to the metallic-liquid phase at ~ 930 K at equilibrium. The simultaneous Seebeck (S) and resistivity versus temperature measurements of amorphous-fcc mixed-phase GST thin-films show linear S-T trends that meet S = 0 at 0 K, consistent with degenerate semiconductors, and the dS/dT and room temperature activation energy show a linear correlation. The single-crystal fcc is calculated to have dS/dT = 0.153 {\mu}V/K for an activation energy of zero and a Fermi level 0.16 eV below the valance band edge.Comment: 5 pages, 5 figure

HTLV-1 Tax Mediated Downregulation of miRNAs Associated with Chromatin Remodeling Factors in T Cells with Stably Integrated Viral Promoter

RNA interference (RNAi) is a natural cellular mechanism to silence gene expression and is predominantly mediated by microRNAs (miRNAs) that target messenger RNA. Viruses can manipulate the cellular processes necessary for their replication by targeting the host RNAi machinery. This study explores the effect of human T-cell leukemia virus type 1 (HTLV-1) transactivating protein Tax on the RNAi pathway in the context of a chromosomally integrated viral long terminal repeat (LTR) using a CD4+ T-cell line, Jurkat. Transcription factor profiling of the HTLV-1 LTR stably integrated T-cell clone transfected with Tax demonstrates increased activation of substrates and factors associated with chromatin remodeling complexes. Using a miRNA microarray and bioinformatics experimental approach, Tax was also shown to downregulate the expression of miRNAs associated with the translational regulation of factors required for chromatin remodeling. These observations were validated with selected miRNAs and an HTLV-1 infected T cells line, MT-2. miR-149 and miR-873 were found to be capable of directly targeting p300 and p/CAF, chromatin remodeling factors known to play critical role in HTLV-1 pathogenesis. Overall, these results are first in line establishing HTLV-1/Tax-miRNA-chromatin concept and open new avenues toward understanding retroviral latency and/or replication in a given cell type

Identification of the Allosteric Regulatory Site of Insulysin

Background: Insulin degrading enzyme (IDE) is responsible for the metabolism of insulin and plays a role in clearance of the Ab peptide associated with Alzheimer's disease. Unlike most proteolytic enzymes, IDE, which consists of four structurally related domains and exists primarily as a dimer, exhibits allosteric kinetics, being activated by both small substrate peptides and polyphosphates such as ATP.Principal Findings: the crystal structure of a catalytically compromised mutant of IDE has electron density for peptide ligands bound at the active site in domain 1 and a distal site in domain 2. Mutating residues in the distal site eliminates allosteric kinetics and activation by a small peptide, as well as greatly reducing activation by ATP, demonstrating that this site plays a key role in allostery. Comparison of the peptide bound IDE structure (using a low activity E111F IDE mutant) with unliganded wild type IDE shows a change in the interface between two halves of the clamshell-like molecule, which may enhance enzyme activity by altering the equilibrium between closed and open conformations. in addition, changes in the dimer interface suggest a basis for communication between subunits.Conclusions/Significance: Our findings indicate that a region remote from the active site mediates allosteric activation of insulysin by peptides. Activation may involve a small conformational change that weakens the interface between two halves of the enzyme.United States Public Health ServicesUniv Kentucky, Dept Mol & Cellular Biochem, Lexington, KY 40536 USAUniv Kentucky, Struct Biol Ctr, Lexington, KY USAUniversidade Federal de São Paulo, Dept Biophys, Escola Paulista Med, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biophys, Escola Paulista Med, São Paulo, BrazilUnited States Public Health Services: NS38041United States Public Health Services: DA02243United States Public Health Services: DA016176United States Public Health Services: P20 RR20171United States Public Health Services: T32 DA016176Web of Scienc

Strongyloses ratti and S. stercoralis: effects of cambendazole, thiabendazole and mebendazole in vitro

The effects of in vitro incubation of three henzimidazole anthelmintics, thiabendazole, mebendazole and cambendazole on Strongyloides were compared. No drug affected hatching of S. ratti eggs or the viability of infective larvae or parasitic adult worms, but all three inhibited moulting of S. ratti larvae. In addition, cambendazole, but not thiabendazole or mebendazole, impaired the viability of S. ratti first- and second-stage larvae. The three drugs had no effect on isolated S. stercorais free-living adult worms, but they all prevented development of S. stercoralis rhabditiform larvae. Thiabendazole and mebendazole had no effect on the infectivity of either S. ratti or S. stercoralis infective larvae, but infection with these worms was abrogated by prior incubation with cambendazole. These results indicate that cambendazole acts in a different manner to the other two drugs. Since it is active against larvae migrating through the tissues, it is potentially of much greater value than thiabendazole or mebendazole in the therapy of strongyloidiasis

Common sports injuries seen by the primary care physician. Part II: Lower extremity.

Sports medicine is the science of caring for the medical and surgical needs of athletes and their injuries. Injuries of the upper extremity were dealt with in Part I in a previous article. Part II deals with injuries of the lower extremity. Trochanteric bursitis and hamstring strains are treated with rest, rehabilitation, and correction of training errors. Patellofemoral pain syndromes require accurate diagnosis and usually a rehabilitative program. Injuries to the medial collateral ligament are very common, but can be associated with tears of the meniscus and cruciate ligaments. The latter two often require surgical intervention. Ankle sprains are graded by severity. The most severe can result in chronic pain or instability, but most respond well to functional bracing and progressive return to activity