Schottky barrier formation at amorphous-crystalline interfaces of GeSb phase change materials

The electrical properties of amorphous-crystalline interfaces in phase change materials, which are important for rewritable optical data storage and for random access memory devices, have been investigated by surface scanning potential microscopy. Analysis of GeSb systems indicates that the surface potential of the crystalline phase is similar to 30-60 mV higher than that of the amorphous phase. This potential asymmetry is explained qualitatively by the presence of a Schottky barrier at the amorphous-crystalline interface and supported also by quantitative Schottky model calculations. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.3691179

Anomalous Proximity Effect in Underdoped YBaCuO Josephson Junctions

Josephson junctions were photogenerated in underdoped thin films of the YBa$_2$Cu$_3$O$_{6+x}$ family using a near-field scanning optical microscope. The observation of the Josephson effect for separations as large as 100 nm between two wires indicates the existence of an anomalously large proximity effect and show that the underdoped insulating material in the gap of the junction is readily perturbed into the superconducting state. The critical current of the junctions was found to be consistent with the conventional Josephson relationship. This result constrains the applicability of SO(5) theory to explain the phase diagram of high critical temperature superconductors.Comment: 11 pages, 4 figure

Mechanisms of viral entry: sneaking in the front door

Recent developments in methods to study virus internalisation are providing clearer insights into mechanisms used by viruses to enter host cells. The use of dominant negative constructs, specific inhibitory drugs and RNAi to selectively prevent entry through particular pathways has provided evidence for the clathrin-mediated entry of hepatitis C virus (HCV) as well as the caveolar entry of Simian Virus 40. Moreover, the ability to image and track fluorescent-labelled virus particles in real-time has begun to challenge the classical plasma membrane entry mechanisms described for poliovirus and human immunodeficiency virus. This review will cover both well-documented entry mechanisms as well as more recent discoveries in the entry pathways of enveloped and non-enveloped viruses. This will include viruses which enter the cytosol directly at the plasma membrane and those which enter via endocytosis and traversal of internal membrane barrier(s). Recent developments in imaging and inhibition of entry pathways have provided insights into the ill-defined entry mechanism of HCV, bringing it to the forefront of viral entry research. Finally, as high-affinity receptors often define viral internalisation pathways, and tropism in vivo, host membrane proteins to which viral particles specifically bind will be discussed throughout

What does the structure-function relationship of the HIV-1 Tat protein teach us about developing an AIDS vaccine?

The human immunodeficiency virus type 1 (HIV-1) trans-activator of transcription protein Tat is an important factor in viral pathogenesis. In addition to its function as the key trans-activator of viral transcription, Tat is also secreted by the infected cell and taken up by neighboring cells where it has an effect both on infected and uninfected cells. In this review we will focus on the relationship between the structure of the Tat protein and its function as a secreted factor. To this end we will summarize some of the exogenous functions of Tat that have been implicated in HIV-1 pathogenesis and the impact of structural variations and viral subtype variants of Tat on those functions. Finally, since in some patients the presence of Tat-specific antibodies or CTL frequencies are associated with slow or non-progression to AIDS, we will also discuss the role of Tat as a potential vaccine candidate, the advances made in this field, and the importance of using a Tat protein capable of eliciting a protective or therapeutic immune response to viral challenge

The role of unintegrated DNA in HIV infection

Integration of the reverse transcribed viral genome into host chromatin is the hallmark of retroviral replication. Yet, during natural HIV infection, various unintegrated viral DNA forms exist in abundance. Though linear viral cDNA is the precursor to an integrated provirus, increasing evidence suggests that transcription and translation of unintegrated DNAs prior to integration may aid productive infection through the expression of early viral genes. Additionally, unintegrated DNA has the capacity to result in preintegration latency, or to be rescued and yield productive infection and so unintegrated DNA, in some circumstances, may be considered to be a viral reservoir. Recently, there has been interest in further defining the role and function of unintegrated viral DNAs, in part because the use of anti-HIV integrase inhibitors leads to an abundance of unintegrated DNA, but also because of the potential use of non-integrating lentiviral vectors in gene therapy and vaccines. There is now increased understanding that unintegrated viral DNA can either arise from, or be degraded through, interactions with host DNA repair enzymes that may represent a form of host antiviral defence. This review focuses on the role of unintegrated DNA in HIV infection and additionally considers the potential implications for antiviral therapy

Effects of 15-Deoxy-Δ12,14-Prostaglandin J2 (15d-PGJ2) and Rosiglitazone on Human Vδ2+ T Cells

BACKGROUND:Thiazolidinediones (TZD) class of drugs, and 15-deoxy-D12,14-prostaglandin J2 (15d-PGJ2) are immune regulators predicted to modulate human autoimmune disease. Their effects on gammadelta T cells, which are involved in animal model and human and animal autoimmune diseases, are unknown. METHODOLOGY/PRINCIPAL FINDINGS:We characterized the activity of rosiglitazone (from the TZD class of drugs) and 15d-PGJ2 in human Vdelta2 T cells. We found that 15d-PGJ2 and rosiglitazone had different effects on Vdelta2 T cell functions. Both 15d-PGJ2 and rosiglitazone suppressed Vdelta2 T cell proliferation in response to IPP and IL2. However, only 15d-PGJ2 suppressed functional responses including cytokine production, degranulation and cytotoxicity against tumor cells. The mechanism for 15d-PGJ2 effects on Vdelta2 T cells acts through inhibiting Erk activation. In contrast, rosiglitazone did not affect Erk activation but the IL2 signaling pathway, which accounts for rosiglitazone suppression of IL2-dependent, Vdelta2 T cell proliferation without affecting TCR-dependent functions. Rosiglitazone and 15d-PGJ2 are designed to be peroxisome proliferator-activated receptor gamma (PPARgamma) ligands and PPARgamma was expressed in Vdelta2 T cell. Surprisingly, when PPARgamma levels were lowered by specific siRNA, 15d-PGJ2 and rosiglitazone were still active, suggesting their target of action induces cellular proteins other than PPARgamma. CONCLUSIONS/SIGNIFICANCE:The current findings expand our understanding of how the immune system is regulated by rosiglitazone and 15d-PGJ2 and will be important to evaluate these compounds as therapeutic agents in human autoimmune disease