Interfering directed paths and the sign phase transition

We revisit the question of the "sign phase transition" for interfering directed paths with real amplitudes in a random medium. The sign of the total amplitude of the paths to a given point may be viewed as an Ising order parameter, so we suggest that a coarse-grained theory for system is a dynamic Ising model coupled to a Kardar-Parisi-Zhang (KPZ) model. It appears that when the KPZ model is in its strong-coupling ("pinned") phase, the Ising model does not have a stable ferromagnetic phase, so there is no sign phase transition. We investigate this numerically for the case of {\ss}1+1 dimensions, demonstrating the instability of the Ising ordered phase there.Comment: 4 pages, 4 figure

Survival And Mitosis Of Myelinating Oligodendrocytes In Experimental Autoimmune Encephalomyelitis: An Immunocytochemical Study With Rip Antibody

The fate of myelin-forming oligodendrocytes in the spinal cord of Lewis rats with acute and chronic relapsing experimental autoimmune encephalomyelitis (EAE) was studied using the pre-embedding immunolabelling technique with the Rip monoclonal antibody which specifically labels the cytoplasm of the cell body and processes of the mature oligodendrocyte. Morphologically normal Rip-positive (Rip+) cells were found in close contact with demyelinated axons at the onset of demyelination and during the course of disease, indicating that oligodendrocytes survive the acute demyelinating insult. Occasional Rip+ oligodendrocytes were undergoing mitosis at the time of onset of neurological signs. These mitotic oligodendrocytes were present in both the grey and white matter. The majority of the mitotic oligodendrocytes had processes in direct contact with myelin sheaths for considerable lengths, indicating that they were myelinating cells. This study indicates that oligodendrocytes survive the acute demyelinating insult in EAE and that mature myelinating oligodendrocytes are able to undergo mitosis

Functional rescue of dystrophin deficiency in mice caused by frameshift mutations using Campylobacter jejuni Cas9

Duchenne muscular dystrophy (DMD) is a fatal, X-linked muscle wasting disease caused by mutations in the DMD gene. In 51% of DMD cases, a reading frame is disrupted because of deletion of several exons. Here, we show that CjCas9 derived from Campylobacter jejuni can be used as a gene editing tool to correct an out-of-frame Dmd exon in Dmd knockout mice. Herein, we used Cas9 derived from S. pyogenes to generate Dmd knockout (KO) mice with a frameshift mutation in Dmd gene. Then, we expressed CjCas9, its single-guide RNA, and the eGFP gene in the tibialis anterior muscle of the Dmd KO mice using an all-in-one adeno-associated virus (AAV) vector. CjCas9 cleaved the target site in the Dmd gene efficiently in vivo and induced small insertions or deletions at the target site. This treatment resulted in conversion of the disrupted Dmd reading frame from out-of-frame to in-frame, leading to the expression of dystrophin in the sarcolemma. Importantly, muscle strength was enhanced in the CjCas9-treated muscles, without off-target mutations, indicating high efficiency and specificity of CjCas9. This work suggests that in vivo DMD frame correction, mediated by CjCas9 has great potential for the treatment of DMD and other neuromuscular diseases

Photo-assisted Andreev reflection as a probe of quantum noise

Andreev reflection, which corresponds to the tunneling of two electrons from a metallic lead to a superconductor lead as a Cooper pair (or vice versa), can be exploited to measure high frequency noise. A detector is proposed, which consists of a normal lead--superconductor circuit, which is capacitively coupled to a mesoscopic circuit where noise is to be measured. We discuss two detector circuits: a single normal metal -- superconductor tunnel junction and a normal metal separated from a superconductor by a quantum dot operating in the Coulomb blockade regime. A substantial DC current flows in the detector circuit when an appropriate photon is provided or absorbed by the mesoscopic circuit, which plays the role of an environment for the junction to which it couples. Results for the current can be cast in all cases in the form of a frequency integral of the excess noise of the environment weighted by a kernel which is specific to the transport process (quasiparticle tunneling, Andreev reflection,...) which is considered. We apply these ideas to the measurement of the excess noise of a quantum point contact and we provide numerical estimates of the detector current.Comment: 19 pages, 11 figure

Macrophage apoptosis in the central nervous system in experimental autoimmune encephalomyelitis

Using light and electron microscopy, we have demonstrated that macrophage apoptosis (programmed cell death) occurs in the central nervous system (CNS) in Lewis rats with acute experimental autoimmune encephalomyelitis (EAE) and chronic relapsing EAE. Apoptotic macrophages were identified by the presence of an apoptotic nucleus in a cell with cytoplasm containing myelin debris but no intermediate filaments. They were found in the meninges, perivascular spaces and in the parenchyma of the white and grey matter of the spinal cord. In acute EAE the apoptotic macrophages were most frequently seen at the time of maximal neurological signs and during the early stages of clinical recovery. Several possible mechanisms may be responsible for the macrophage apoptosis: the release or withdrawal of cytokines; T-cell cytotoxicity; the effect of activated macrophage products, such as nitric oxide; and a direct effect of endogenous glucocorticoids. Macrophage apoptosis, together with the T-cell apoptosis we have previously described in the CNS in EAE, may contribute to the down-regulation of this autoimmune disease

Inactivation of mammalian Ero 1α is catalysed by specific protein disulfide isomerases

Disulfide formation within the endoplasmic reticulum is a complex process requiring a disulfide exchange protein such as protein disulfide isomerase and a mechanism to form disulfides de novo. In mammalian cells, the major pathway for de novo disulfide formation involves the enzyme Ero1α which couples oxidation of thiols to the reduction of molecular oxygen to form hydrogen peroxide. Ero1α activity is tightly regulated by a mechanism that requires the formation of regulatory disulfides. These regulatory disulfides are reduced to activate and reform to inactive the enzyme. To investigate the mechanism of inactivation we analysed regulatory disulfide formation in the presence of various oxidants under controlled oxygen concentration. Neither molecular oxygen, nor hydrogen peroxide was able to oxidise Ero1α efficiently to form the correct regulatory disulfides. However, specific members of the PDI family such as PDI or ERp46 were able to catalyse this process. Further studies showed that both active sites of PDI contribute to the formation of regulatory disulfides in Ero1α and that the PDI substrate binding domain is crucial to allow electron transfer between the two enzymes. These results demonstrate a simple feedback mechanism of regulation of mammalian Ero1α involving its primary substrate

Smoke-free environment policy in Vietnam : what did people see and how did they react when they visited various public places?

Introduction. Since Vietnam has signed WHO framework on tobacco control (FCTC) in 2003 and has issued tobacco control law in 2013, there has been little research concerning about what impacts smoke-free regulations have had on public compliance. The objective of this study was to assess public exposure to secondhand smoke and reaction toward smoke-free policy regulations in Vietnam and the associated factor. Methods. Using the design of GATS (Global Adult Tobacco Survey), a nationally representative sample of 8,996 adults were approached for data collection. Logistic regression was used to examine the associated factor. Results. The study revealed that the prevalence of respondents exposed to secondhand smoke was much higher in bars/café/tea shops (90.07%) and restaurants (81.81%) than in any other public places, universities (36.70%), government buildings (31.12%), public transport (20.04%), healthcare facilities (17.85%) and schools (15.84%). 13.23% of respondents saw smokers violate smoke-free regulations. Among those who saw them violate smoke-free regulations, just onethird cautioned them to stop smoking. Strikingly, a higher rate of cautioning smokers to stop smoking was observed among the older, married, and better educated respondents. Respondents who were married, better educated and in lower economic status were more likely to remind smokers to stop smoking. Conclusions. The study has called for strengthening two of the six MPOWER (Monitor, Protect, Offer, Warn, Enforce and Raise) components of the tobacco free initiative introduced by WHO, Monitoring tobacco use and prevention policies and Protecting people from tobacco smoke. © 2019 Pacini Editore SPA. All rights reserved. **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Huy Nguyen” is provided in this record*

Apoptosis of αβ T lymphocytes in the nervous system in experimental autoimmune encephalomyelitis: Its possible implications for recovery and acquired tolerance

We have recently shown that apoptosis, an active process of cellular self-destruction, occurs in the central nervous system in Lewis rats with acute experimental autoimmune encephalomyelitis (EAE) induced by inoculation with myelin basic protein (MBP) and adjuvants. Conventional light and electron microscopic studies suggested that some of the apoptotic cells were oligodendrocytes and that others were hematogenous mononuclear cells. To determine whether any of the apoptotic cells were T lymphocytes, we used the technique of pre-embedding immunolabelling which allows sufficient preservation of the ultrastructure to permit recognition of apoptotic changes while at the same time preserving surface antigens so that the identity of the apoptotic cells can be determined by immunocytochemistry. Light microscopic immunocytochemistry using the mono-clonal antibodies OX-34 (CD2) and R73 (alpha beta T-cell receptor) revealed that 10% of the CD2+ cells and 5% of the alpha beta T lymphocytes in the parenchyma of the spinal cord were dying by apoptosis. The presence of apoptotic alpha beta T cells was confirmed by electron microscopy. About half of all the apoptotic cells within the spinal cord were labelled by these antibodies. It is possible that some of the unlabelled apoptotic cells were also T lymphocytes but that others were glial cells such as oligodendrocytes. One possible interpretation of this T-cell apoptosis is that it represents activation-induced cell death, which has recently been shown to provide a mechanism of clonal elimination of mature as well as immature autoreactive T cells. Another possible interpretation is that it is a result of corticosterone released during the course of EAE. The apoptotic elimination of target-antigen-specific lymphocytes within the target organ in this autoimmune disease may contribute to the subsidence of inflammation and, if ongoing, to the development of tolerance

Ultraviolet irradiation accelerates apoptosis in human polymorphonuclear leukocytes: protection by LPS and GM‐CSF

Polymorphonuclear leukocytes (PMN) play a central role in host response to injury and infection. Understanding factors that regulate PMN survival may therefore have a major influence on the development of novel treatment strategies for controlling life‐threatening infections, as well as local and systemic inflammatory responses. Unfortunately, the presently utilized in vitro culture model of PMN apoptosis makes the examination of early biochemical events surrounding PMN apoptosis very difficult. This study demonstrates that a short course of UV irradiation (15 min) can be used to induce rapid progression of PMN through the apoptotic process with 70–90% of PMN displaying features of apoptosis by 4 h after UV exposure. Bacterial lipopolysaccharide and granulocyte‐macrophage colony‐stimulating factor, which are known to prolong PMN survival during in vitro culture, also protected PMN from UV‐accelerated apoptosis. The UV‐accelerated model of PMN apoptosis provides another valuable tool for the investigation of early signaling pathways associated with inducing or delaying PMN apoptosis. J. Leukoc. Biol. 62: 517–523; 1997.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142305/1/jlb0517.pd