Negative Electron-electron Drag Between Narrow Quantum Hall Channels

Momentum transfer due to Coulomb interaction between two parallel, two-dimensional, narrow, and spatially separated layers, when a current I_{drive} is driven through one layer, is studied in the presence of a perpendicular magnetic field B. The current induced in the drag layer, I_{drag}, is evaluated self-consistently with I_{drive} as a parameter. I_{drag} can be positive or negative depending on the value of the filling factor \nu of the highest occupied bulk Landau level (LL). For a fully occupied LL, I_{drag} is negative, i.e., it flows opposite to I_{drive}, whereas it is positive for a half-filled LL. When the circuit is opened in the drag layer, a voltage \Delta V_{drag} develops in it; it is negative for a half-filled LL and positive for a fully occupied LL. This positive \Delta V_{drag}, expressing a negative Coulomb drag, results from energetically favored near-edge inter-LL transitions that occur when the highest occupied bulk LL and the LL just above it become degenerate.Comment: Text file in Latex/Revtex/preprint format, 7 separate PS figures, Physical Review B, in pres

Remote surface inspection system

This paper reports on an on-going research and development effort in remote surface inspection of space platforms such as the Space Station Freedom (SSF). It describes the space environment and identifies the types of damage for which to search. This paper provides an overview of the Remote Surface Inspection System that was developed to conduct proof-of-concept demonstrations and to perform experiments in a laboratory environment. Specifically, the paper describes three technology areas: (1) manipulator control for sensor placement; (2) automated non-contact inspection to detect and classify flaws; and (3) an operator interface to command the system interactively and receive raw or processed sensor data. Initial findings for the automated and human visual inspection tests are reported

An update on the lithogenic mechanisms of cholecystokinin a receptor (Cckar), an important gallstone gene for lith13

The cholecystokinin A receptor (CCKAR) is expressed predominantly in the gallbladder and small intestine in the digestive system, where it is responsible for CCK’s regulation of gallbladder and small intestinal motility. The effect of CCKAR on small intestinal transit is a physiological response for regulating intestinal cholesterol absorption. The Cckar gene has been identified to be an important gallstone gene, Lith13, in inbred mice by a powerful quantitative trait locus analysis. Knockout of the Cckar gene in mice enhances cholesterol cholelithogenesis by impairing gallbladder contraction and emptying, promoting cholesterol crystallization and crystal growth, and increasing intestinal cholesterol absorption. Clinical and epidemiological studies have demonstrated that several variants in the CCKAR gene are associated with increased prevalence of cholesterol cholelithiasis in humans. Dysfunctional gallbladder emptying in response to exogenously administered CCK-8 is often found in patients with cholesterol gallstones, and patients with pigment gallstones display an intermediate degree of gallbladder motility defect. Gallbladder hypomotility is also revealed in some subjects without gallstones under several conditions: pregnancy, total parenteral nutrition, celiac disease, oral contraceptives and conjugated estrogens, obesity, diabetes, the metabolic syndrome, and administration of CCKAR antagonists. The physical–chemical, genetic, and molecular studies of Lith13 show that dysfunctional CCKAR enhances susceptibility to cholesterol gallstones through two primary mechanisms: impaired gallbladder emptying is a key risk factor for the development of gallbladder hypomotility, biliary sludge (the precursor of gallstones), and microlithiasis, as well as delayed small intestinal transit augments cholesterol absorption as a major source for the hepatic hypersecretion of biliary cholesterol and for the accumulation of excess cholesterol in the gallbladder wall that further worsens impaired gallbladder motor function. If these two defects in the gallbladder and small intestine could be prevented by the potent CCKAR agonists, the risk of developing cholesterol gallstones could be dramatically reduced

Bone morphogenetic protein 7 sensitizes O6-methylguanine methyltransferase expressing-glioblastoma stem cells to clinically relevant dose of temozolomide.

BackgroundTemozolomide (TMZ) is an oral DNA-alkylating agent used for treating patients with glioblastoma. However, therapeutic benefits of TMZ can be compromised by the expression of O6-methylguanine methyltransferase (MGMT) in tumor tissue. Here we used MGMT-expressing glioblastoma stem cells (GSC) lines as a model for investigating the molecular mechanism underlying TMZ resistance, while aiming to explore a new treatment strategy designed to possibly overcome resistance to the clinically relevant dose of TMZ (35 μM).MethodsMGMT-expressing GSC cultures are resistant to TMZ, and IC50 (half maximal inhibitory concentration) is estimated at around 500 μM. Clonogenic GSC surviving 500 μM TMZ (GSC-500 μM TMZ), were isolated. Molecular signatures were identified via comparative analysis of expression microarray against parental GSC (GSC-parental). The recombinant protein of top downregulated signature was used as a single agent or in combination with TMZ, for evaluating therapeutic effects of treatment of GSC.ResultsThe molecular signatures characterized an activation of protective stress responses in GSC-500 μM TMZ, mainly including biotransformation/detoxification of xenobiotics, blocked endoplasmic reticulum stress-mediated apoptosis, epithelial-to-mesenchymal transition (EMT), and inhibited growth/differentiation. Bone morphogenetic protein 7 (BMP7) was identified as the top down-regulated gene in GSC-500 μM TMZ. Although augmenting BMP7 signaling in GSC by exogenous BMP7 treatment did not effectively stop GSC growth, it markedly sensitized both GSC-500 μM TMZ and GSC-parental to 35 μM TMZ treatment, leading to loss of self-renewal and migration capacity. BMP7 treatment induced senescence of GSC cultures and suppressed mRNA expression of CD133, MGMT, and ATP-binding cassette drug efflux transporters (ABCB1, ABCG2), as well as reconfigured transcriptional profiles in GSC by downregulating genes associated with EMT/migration/invasion, stemness, inflammation/immune response, and cell proliferation/tumorigenesis. BMP7 treatment significantly prolonged survival time of animals intracranially inoculated with GSC when compared to those untreated or treated with TMZ alone (p = 0.0017), whereas combination of two agents further extended animal survival compared to BMP7 alone (p = 0.0489).ConclusionsThese data support the view that reduced endogenous BMP7 expression/signaling in GSC may contribute to maintained stemness, EMT, and chemoresistant phenotype, suggesting that BMP7 treatment may provide a novel strategy in combination with TMZ for an effective treatment of glioblastoma exhibiting unmethylated MGMT

Similarities and differences between biliary sludge and microlithiasis: Their clinical and pathophysiological significances

The terms biliary sludge and cholesterol microlithiasis (hereafter referred to as microlithiasis) were originated from different diagnostic techniques and may represent different stages of cholesterol gallstone disease. Although the pathogenesis of biliary sludge and microlithiasis may be similar, microlithiasis could be preceded by biliary sludge, followed by persistent precipitation and aggregation of solid cholesterol crystals, and eventually, gallstone formation. Many clinical conditions are clearly associated with the formation of biliary sludge and microlithiasis, including total parenteral nutrition, rapid weight loss, pregnancy, organ transplantation, administration of certain medications, and a variety of acute and chronic illnesses. Numerous studies have demonstrated complete resolution of biliary sludge in approximately 40% of patients, a cyclic pattern of disappearing and reappearing in about 40%, and progression to gallstones in nearly 20%. Although only a minority of patients with ultrasonographic demonstration of biliary sludge develop gallstones, it is still a matter of controversy whether microlithiasis could eventually evolve to cholesterol gallstones. Biliary sludge and microlithiasis are asymptomatic in the vast majority of patients; however, they can cause biliary colic, acute cholecystitis, and acute pancreatitis. Biliary sludge and microlithiasis are most often diagnosed ultrasonographically and bile microscopy is considered the gold standard for their diagnosis. Specific measures to prevent the development of biliary sludge are not practical or cost-effective in the general population. Laparoscopic cholecystectomy offers the most definitive therapy on biliary sludge. Endoscopic sphincterotomy or surgical intervention is effective for microlithiasis-induced pancreatitis. Ursodeoxycholic acid can effectively prevent the recurrence of solid cholesterol crystals and significantly reduce the risk of recurrent pancreatitis. Keywords: Biliary sludge, Cholesterol microlithiasis, Acute cholecystitis, Acute pancreatitis, Biliary colic, Cholesterol monohydrate crystals, Lithogenic bil

G z Can Mediate the Acute Actions of -and -Opioids but Is Not Involved in Opioid-Induced Adenylyl Cyclase Supersensitization 1

ABSTRACT The three subtypes of opioid receptors (␦, , and ) are known to regulate multiple effectors through either pertussis toxinsensitive or -insensitive G proteins. In opioid-induced inhibition of adenylyl cyclase, both G i and G z proteins can serve as the signal transducer. Our previous study showed that opioid-induced adenylyl cyclase supersensitization in human embryonic kidney (HEK) 293 cells expressing the ␦-opioid receptor requires G i but not G z proteins. Herein, we studied the ability ofand -opioid receptors to regulate the activities of adenylyl cyclase through G z . In HEK 293 cells coexpressing G z with the -or -opioid receptors, opioid agonists induced inhibition of adenylyl cyclase in a pertussis toxin-insensitive manner. However, adenylyl cyclase supersensitization induced by chronic opioid treatments remained sensitive to pertussis toxin. We also showed that the responsiveness of cAMP-dependent response element-binding proteins to forskolin was not altered after prolonged opioid treatment but was higher in cells coexpressing G z . Although the -and -opioid receptors mediated acute activation of extracellular signal-regulated protein kinase 1/2 via both G i and G z , these responses were abolished by chronic opioid treatment. These studies showed that G z could mediate acute actions of -and -opioids but G z alone was insufficient to mediate adenylyl cyclase supersensitization induced by the chronic activation of opioid receptors. Opioids induce their biological effects by binding to three subtypes of opioid receptors (␦, , and ). The opioid receptors are distributed throughout the central and peripheral nervous systems Adenylyl cyclase (AC) is the typical effector of opioid receptors. Acute stimulation of opioid receptors leads to inhibition of AC activity. A compensatory increase in AC activity is often induced after chronic opioid treatment. This phenomenon is observed in a variety of cell types, including the simian kidney fibroblast COS-7, Chinese hamster ovary, and neuroblastoma ϫ glioma hybrid NG 108-15 cell

Analysis of pultrusion processing for long fiber reinforced thermoplastic composite system

Pultrusion is one of the composite processing technology, commonly recognized as a simple and cost-effective means for the manufacturing of fiber-reinforced, resin matrix composite parts with different regular geometries. Previously, because the majority of the pultruded composite parts were made of thermosetting resin matrix, emphasis of the analysis on the process has been on the conservation of energy from various sources, such as heat conduction and the curing kinetics of the resin system. Analysis on the flow aspect of the process was almost absent in the literature for thermosetting process. With the increasing uses of thermoplastic materials, it is desirable to obtain the detailed velocity and pressure profiles inside the pultrusion die. Using a modified Darcy's law for flow through porous media, closed form analytical solutions for the velocity and pressure distributions inside the pultrusion die are obtained for the first time. This enables us to estimate the magnitude of viscous dissipation and it's effects on the pultruded parts. Pulling forces refined in the pultrusion processing are also analyzed. The analytical model derived in this study can be used to advance our knowledge and control of the pultrusion process for fiber reinforced thermoplastic composite parts

Coulomb Drag Between Parallel Ballistic Quantum Wires

The Coulomb drag between parallel, {\it ballistic} quantum wires is studied theoretically in the presence of a perpendicular magnetic field B. The transresistance R_D shows peaks as a function of the Fermi level and splitting energy between the 1D subbands of the wires. The sharpest peaks appear when the Fermi level crosses the subband extrema so that the Fermi momenta are small. Two other kinds of peaks appear when either {\it intra}- or {\it inter}-subband transitions of electrons have maximum probability; the {\it intra}-subband transitions correspond to a small splitting energy. R_D depends on the field B in a nonmonotonic fashion: it decreases with B, as a result of the suppression of backscattering, and increases sharply when the Fermi level approaches the subband bottoms and the suppression is outbalanced by the increase of the Coulomb matrix elements and of the density of states.Comment: Text 14 pages in Latex/Revtex format, 4 Postscript figures. Phys. Rev. B,in pres

Frictional drag between non-equilibrium charged gases

The frictional drag force between separated but coupled two-dimensional electron gases of different temperatures is studied using the non-equilibrium Green function method based on the separation of center-of-mass and relative dynamics of electrons. As the mechanisms of producing the frictional force we include the direct Coulomb interaction, the interaction mediated via virtual and real TA and LA phonons, optic phonons, plasmons, and TA and LA phonon-electron collective modes. We found that, when the distance between the two electron gases is large, and at intermediate temperature where plasmons and collective modes play the most important role in the frictional drag, the possibility of having a temperature difference between two subsystems modifies greatly the transresistivity.Comment: 8figure

Ribosomal Proteins RPS11 and RPS20, Two Stress-Response Markers of Glioblastoma Stem Cells, Are Novel Predictors of Poor Prognosis in Glioblastoma Patients.

Glioblastoma stem cells (GSC) co-exhibiting a tumor-initiating capacity and a radio-chemoresistant phenotype, are a compelling cell model for explaining tumor recurrence. We have previously characterized patient-derived, treatment-resistant GSC clones (TRGC) that survived radiochemotherapy. Compared to glucose-dependent, treatment-sensitive GSC clones (TSGC), TRGC exhibited reduced glucose dependence that favor the fatty acid oxidation pathway as their energy source. Using comparative genome-wide transcriptome analysis, a series of defense signatures associated with TRGC survival were identified and verified by siRNA-based gene knockdown experiments that led to loss of cell integrity. In this study, we investigate the prognostic value of defense signatures in glioblastoma (GBM) patients using gene expression analysis with Probeset Analyzer (131 GBM) and The Cancer Genome Atlas (TCGA) data, and protein expression with a tissue microarray (50 GBM), yielding the first TRGC-derived prognostic biomarkers for GBM patients. Ribosomal protein S11 (RPS11), RPS20, individually and together, consistently predicted poor survival of newly diagnosed primary GBM tumors when overexpressed at the RNA or protein level [RPS11: Hazard Ratio (HR) = 11.5, p<0.001; RPS20: HR = 4.5, p = 0.03; RPS11+RPS20: HR = 17.99, p = 0.001]. The prognostic significance of RPS11 and RPS20 was further supported by whole tissue section RPS11 immunostaining (27 GBM; HR = 4.05, p = 0.01) and TCGA gene expression data (578 primary GBM; RPS11: HR = 1.19, p = 0.06; RPS20: HR = 1.25, p = 0.02; RPS11+RPS20: HR = 1.43, p = 0.01). Moreover, tumors that exhibited unmethylated O-6-methylguanine-DNA methyltransferase (MGMT) or wild-type isocitrate dehydrogenase 1 (IDH1) were associated with higher RPS11 expression levels [corr (IDH1, RPS11) = 0.64, p = 0.03); [corr (MGMT, RPS11) = 0.52, p = 0.04]. These data indicate that increased expression of RPS11 and RPS20 predicts shorter patient survival. The study also suggests that TRGC are clinically relevant cells that represent resistant tumorigenic clones from patient tumors and that their properties, at least in part, are reflected in poor-prognosis GBM. The screening of TRGC signatures may represent a novel alternative strategy for identifying new prognostic biomarkers