Inhibition of free radical generation and improved survival by protection of the hepatic microvascular endothelium by targeted erythrocytes in orthotopic rat liver transplantation

The capacity of specifically targeted erythrocytes to inhibit free radical—mediated injury to the endothelial cell after cold preservation, and improve liver function was studied in two experimental models: An isolated perfused rat liver (IPRL) system and syngeneic orthotopic rat liver transplantation. In the IPRL model, livers were preserved in University of Wisconsin solution for 24 h at 4°C. At the end of the preservation period, livers were flushed with lactated Ringer’s (control), immu- noerythrocytes (IES), or blank intact erythrocytes prior to warm reperfusion for 2 h using an assanguinous Krebs-Henseleit buffer. Production of superoxide (O2-) anion during warm reperfusion in the IES-treated liver was reduced by 65% as compared with controls (P<0.001) and by 74% (P<0.001) when compared with blank erythrocyte—treated livers. Endothelial cell preservation, as assessed by levels of purine nucleoside phos- phorylase (PNP), was much better in the IES-treated group (P<0.001) when compared with untreated livers. Hepatocellular preservation was markedly improved in the IES-treated livers. In the syngeneic liver transplantation model, livers were preserved in UW solution for 24 h at 4°C. Prior to implantation, livers were flushed with 5 ml of cold lactated Ringer’s or immunoerythrocytes. Survival after three weeks was 60% in the IES-treated group and 30% in the untreated group. Survival in the IES-treated group was not significantly different from a control (no preservation) group. IES-treated livers in both models demonstrated better endothelial cell integrity and ultimate liver function. IES treatment therefore appears to protect the hepatic microvascular endothelial cell from reperfusion injury and could prove to be an easy reproducible method of donor organ preparation after cold preservation. © 1990 by Williams & Wilkins

Effects of temperature on thick branes and the fermion (quasi-)localization

Following Campos's work [Phys. Rev. Lett. 88, 141602 (2002)], we investigate the effects of temperature on flat, de Sitter (dS), and anti-de Following Campos's work [Phys. Rev. Lett. \textbf{88}, 141602 (2002)], we investigate the effects of temperature on flat, de Sitter (dS), and anti-de Sitter (AdS) thick branes in five-dimensional (5D) warped spacetime, and on the fermion (quasi-)localization. First, in the case of flat brane, when the critical temperature reaches, the solution of the background scalar field and the warp factor is not unique. So the thickness of the flat thick brane is uncertain at the critical value of the temperature parameter, which is found to be lower than the one in flat 5D spacetime. The mass spectra of the fermion Kaluza-Klein (KK) modes are continuous, and there is a series of fermion resonances. The number and lifetime of the resonances are finite and increase with the temperature parameter, but the mass of the resonances decreases with the temperature parameter. Second, in the case of dS brane, we do not find such a critical value of the temperature parameter. The mass spectra of the fermion KK modes are also continuous, and there is a series of fermion resonances. The effects of temperature on resonance number, lifetime, and mass are the same with the case of flat brane. Last, in the case of AdS brane, {the critical value of the temperature parameter can less or greater than the one in the flat 5D spacetime.} The spectra of fermion KK modes are discrete, and the mass of fermion KK modes does not decrease monotonically with increasing temperature parameter.Comment: 24 pages, 15 figures, published versio

Crystal growth and quantum oscillations in the topological chiral semimetal CoSi

We survey the electrical transport properties of the single-crystalline, topological chiral semimetal CoSi which was grown via different methods. High-quality CoSi single crystals were found in the growth from tellurium solution. The sample's high carrier mobility enables us to observe, for the first time, quantum oscillations (QOs) in its thermoelectrical signals. Our analysis of QOs reveals two spherical Fermi surfaces around the R point in the Brillouin zone corner. The extracted Berry phases of these electron orbits are consistent with the -2 chiral charge as reported in DFT calculations. Detailed analysis on the QOs reveals that the spin-orbit coupling induced band-splitting is less than 2 meV near the Fermi level, one order of magnitude smaller than our DFT calculation result. We also report the phonon-drag induced large Nernst effect in CoSi at intermediate temperatures

A robotic system for steel bridge maintenance: Research challenges and system design

This paper presents the research on and development of a robotic system for stripping paint and rust from steel bridges, with the ultimate objective of preventing human exposure to hazardous and dangerous debris (containing rust, paint particles, lead and/or asbestos), relieving human workers from labor intensive tasks and reducing costs associated with bridge maintenance. The robot system design, the key research challenges and enabling technologies and system development are discussed in detail. Research results obtained so far and discussions on some key issues are also presented

An improved technique for isolated perfusion of rat livers and an evaluation of perfusates

We have modified the apparatus for isolated rat liver perfusion (IPRL) in order to be able to perform two perfusions simultaneously. In addition, we studied the quality and stability of livers by comparison of five different perfusates: Blood (Group A), Original Krebs Henseleit buffer (Group B), Krebs buffer with glucose (Group C) or bovine serum albumin (BSA) added, (Group D). In a last group (E) albumin, glucose, and taurocholic acid were added to Krebs. After 180 min of perfusion, livers perfused with solutions including 2% albumin (Group D, E) had a significantly higher release of hepatocellular and endothelial cell (purine nucleoside phosphorylase) enzymes and lower bile production as compared to Groups A, B, and C (P < 0.0001). Increasing levels of purine nucleoside phosphorylase (PNP), a reflection of damage to the microvascular endothelium preceded the increases in hepatocellular enzymes. Histologically, damages of sinusoidal endothelial cells and hepatocytes are appreciated moderate to severe in Groups D and E, slight to mild in Groups A and B, and not significant in Group C. These results suggest that BSA may have toxic effects to the perfused rat liver. These data also confirm that the IPRL modified for simultaneous perfusion of two livers is efficient, and that with this technique the rat liver can be optimally perfused for up to 3 hr with oxygenated Krebs Henseleit buffer without additives (Group B) and without blood. These two improvements should allow those performing studies with perfused rat livers to obtain data in a more efficient, accurate, and inexpensive fashion. © 1992

Electronic transport in polycrystalline graphene

Most materials in available macroscopic quantities are polycrystalline. Graphene, a recently discovered two-dimensional form of carbon with strong potential for replacing silicon in future electronics, is no exception. There is growing evidence of the polycrystalline nature of graphene samples obtained using various techniques. Grain boundaries, intrinsic topological defects of polycrystalline materials, are expected to dramatically alter the electronic transport in graphene. Here, we develop a theory of charge carrier transmission through grain boundaries composed of a periodic array of dislocations in graphene based on the momentum conservation principle. Depending on the grain boundary structure we find two distinct transport behaviours - either high transparency, or perfect reflection of charge carriers over remarkably large energy ranges. First-principles quantum transport calculations are used to verify and further investigate this striking behaviour. Our study sheds light on the transport properties of large-area graphene samples. Furthermore, purposeful engineering of periodic grain boundaries with tunable transport gaps would allow for controlling charge currents without the need of introducing bulk band gaps in otherwise semimetallic graphene. The proposed approach can be regarded as a means towards building practical graphene electronics.Comment: accepted in Nature Material

Desynchronizing effect of high-frequency stimulation in a generic cortical network model

Transcranial Electrical Stimulation (TCES) and Deep Brain Stimulation (DBS) are two different applications of electrical current to the brain used in different areas of medicine. Both have a similar frequency dependence of their efficiency, with the most pronounced effects around 100Hz. We apply superthreshold electrical stimulation, specifically depolarizing DC current, interrupted at different frequencies, to a simple model of a population of cortical neurons which uses phenomenological descriptions of neurons by Izhikevich and synaptic connections on a similar level of sophistication. With this model, we are able to reproduce the optimal desynchronization around 100Hz, as well as to predict the full frequency dependence of the efficiency of desynchronization, and thereby to give a possible explanation for the action mechanism of TCES.Comment: 9 pages, figs included. Accepted for publication in Cognitive Neurodynamic

Downregulation of Mcl-1 has anti-inflammatory pro-resolution effects and enhances bacterial clearance from the lung

Phagocytes not only coordinate acute inflammation and host defense at mucosal sites, but also contribute to tissue damage. Respiratory infection causes a globally significant disease burden and frequently progresses to acute respiratory distress syndrome, a devastating inflammatory condition characterized by neutrophil recruitment and accumulation of protein-rich edema fluid causing impaired lung function. We hypothesized that targeting the intracellular protein myeloid cell leukemia 1 (Mcl-1) by a cyclin-dependent kinase inhibitor (AT7519) or a flavone (wogonin) would accelerate neutrophil apoptosis and resolution of established inflammation, but without detriment to bacterial clearance. Mcl-1 loss induced human neutrophil apoptosis, but did not induce macrophage apoptosis nor impair phagocytosis of apoptotic neutrophils. Neutrophil-dominant inflammation was modelled in mice by either endotoxin or bacteria (Escherichia coli). Downregulating inflammatory cell Mcl-1 had anti-inflammatory, pro-resolution effects, shortening the resolution interval (R(i)) from 19 to 7 h and improved organ dysfunction with enhanced alveolar–capillary barrier integrity. Conversely, attenuating drug-induced Mcl-1 downregulation inhibited neutrophil apoptosis and delayed resolution of endotoxin-mediated lung inflammation. Importantly, manipulating lung inflammatory cell Mcl-1 also accelerated resolution of bacterial infection (R(i); 50 to 16 h) concurrent with enhanced bacterial clearance. Therefore, manipulating inflammatory cell Mcl-1 accelerates inflammation resolution without detriment to host defense against bacteria, and represents a target for treating infection-associated inflammation

A mediation approach to understanding socio-economic inequalities in maternal health-seeking behaviours in Egypt.

BACKGROUND: The levels and origins of socio-economic inequalities in health-seeking behaviours in Egypt are poorly understood. This paper assesses the levels of health-seeking behaviours related to maternal care (antenatal care [ANC] and facility delivery) and their accumulation during pregnancy and childbirth. Secondly, it explores the mechanisms underlying the association between socio-economic position (SEP) and maternal health-seeking behaviours. Thirdly, it examines the effectiveness of targeting of free public ANC and delivery care. METHODS: Data from the 2008 Demographic and Health Survey were used to capture two latent constructs of SEP: individual socio-cultural capital and household-level economic capital. These variables were entered into an adjusted mediation model, predicting twelve dimensions of maternal health-seeking; including any ANC, private ANC, first ANC visit in first trimester, regular ANC (four or more visits during pregnancy), facility delivery, and private delivery. ANC and delivery care costs were examined separately by provider type (public or private). RESULTS: While 74.2% of women with a birth in the 5-year recall period obtained any ANC and 72.4% delivered in a facility, only 48.8% obtained the complete maternal care package (timely and regular facility-based ANC as well as facility delivery) for their most recent live birth. Both socio-cultural capital and economic capital were independently positively associated with receiving any ANC and delivering in a facility. The strongest direct effect of socio-cultural capital was seen in models predicting private provider use of both ANC and delivery. Despite substantial proportions of women using public providers reporting receipt of free care (ANC: 38%, delivery: 24%), this free-of-charge public care was not effectively targeted to women with lowest economic resources. CONCLUSIONS: Socio-cultural capital is the primary mechanism leading to inequalities in maternal health-seeking in Egypt. Future studies should therefore examine the objective and perceived quality of care from different types of providers. Improvements in the targeting of free public care could help reduce the existing SEP-based inequalities in maternal care coverage in the short term

Evidence for Two Modes of Synergistic Induction of Apoptosis by Mapatumumab and Oxaliplatin in Combination with Hyperthermia in Human Colon Cancer Cells

Colorectal cancer is the third leading cause of cancer-related mortality in the world-- the main cause of death from colorectal cancer is hepatic metastases, which can be treated with isolated hepatic perfusion (IHP). Searching for the most clinically relevant approaches for treating colorectal metastatic disease by isolated hepatic perfusion (IHP), we developed the application of oxaliplatin concomitantly with hyperthermia and humanized death receptor 4 (DR4) antibody mapatumumab (Mapa), and investigated the molecular mechanisms of this multimodality treatment in human colon cancer cell lines CX-1 and HCT116 as well as human colon cancer stem cells Tu-12, Tu-21 and Tu-22. We showed here, in this study, that the synergistic effect of the multimodality treatment-induced apoptosis was caspase dependent and activated death signaling via both the extrinsic apoptotic pathway and the intrinsic pathway. Death signaling was activated by c-Jun N-terminal kinase (JNK) signaling which led to Bcl-xL phosphorylation at serine 62, decreasing the anti-apoptotic activity of Bcl-xL, which contributed to the intrinsic pathway. The downregulation of cellular FLICE inhibitory protein long isoform (c-FLIPL) in the extrinsic pathway was accomplished through ubiquitination at lysine residue (K) 195 and protein synthesis inhibition. Overexpression of c-FLIPL mutant (K195R) and Bcl-xL mutant (S62A) completely abrogated the synergistic effect. The successful outcome of this study supports the application of multimodality strategy to patients with colorectal hepatic metastases who fail to respond to standard chemoradiotherapy that predominantly targets the mitochondrial apoptotic pathway. © 2013 Song et al