Is the vagus nerve our neural connectome?

What are the implications of the vagus nerve being able to mediate the time-dependent plasticity of an array of sensorimotor networks

Plasma actuator: influence of dielectric surface temperature

Plasma actuators have become the topic of interest of many researchers for the purpose of flow control. They have the advantage of manipulating the flow without the need for any moving parts, a small surface profile which does not disturb the free stream flow, and the ability to switch them on or off depending on the particular situation (active flow control). Due to these characteristics they are becoming very popular for flow control over aircraft wings. The objective of the current study is to examine the effect of the actuator surface temperature on its performance. This is an important topic to understand when dealing with real life aircraft equipped with plasma actuators. The temperature variations encountered during a flight envelope may have adverse effects in actuator performance. A peltier heater along with dry ice are used to alter the actuator temperature, while particle image velocimetry (PIV) is utilised to analyse the flow field. The results show a significant change in the induced flow field by the actuator as the surface temperature is varied. It is found that for a constant peak-to-peak voltage the maximum velocity produced by the actuator depends directly on the dielectric surface temperature. The findings suggest that by changing the actuator temperature the performance can be maintained or even altered at different environmental conditions

Non-steady state operation of polymer/TiO2 photovoltaic devices

We present data on the initial period of operation of Gilch-route NMH-PPV/TiO2 composite solar cells (CSCs) which show that during this period the CSCs operate in a non-steady state regime. The behavior is complex and may include a gradual rise of the open circuit voltage (V-oc) and of the short-circuit current density (J(sc)) with time, a passage through a maximum of either or both parameters, and even a sign reversal. The mechanisms most probably contributing to the transient processes are: i) diffusion driven redistribution of charges resulting in the build up of a quasi steady state charge density profile across the device; ii) photo-doping resulting in a relatively slow increase of the average charge carrier concentration and consequently of the conductivity of the device. The latter is responsible for a strong decrease in V-oc, and is evidenced by the significant increase in dark current after device illumination

Nanocomposite titanium dioxide/polymer photovoltaic cells: effects of TiO2 microstructure, time and illumination power.

Nanocomposite titanium dioxide/polymer photovoltaic cells have been fabricated using poly[2-(2-ethylhexyloxy)-5-methoxy-1,4-phenylenevinylene] (MEHPPV). Two different types of titanium dioxide were used, one synthesized using a sol-gel method, the other was a commercial paste. The crystal structure, porosity and absorption spectra of the titanium dioxide layers were measured, and the titanium dioxide synthesized using the sol-gel method had a much lower level of anatase. The photovoltaic properties of the ITO/TiO2/MEHPPV/Au cells, which were similar for both types of TiO2, were measured as a function of illumination power and compared with equivalent circuit models. A simple equivalent circuit model incorporating a diode, two resistances and a light induced current was inconsistent with the illumination - dependent data and was improved by adding an illumination dependent shunt resistance. A very long lived, photo-induced increase in dark current was observed, which could not be explained by a polymer degradation mechanism or an increase in temperature under illumination, but was more likely to be due to trapped charge

Karonudib is a promising anticancer therapy in hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) is the most common form of liver cancer and is generally caused by viral infections or consumption of mutagens, such as alcohol. While liver transplantation and hepatectomy is curative for some patients, many relapse into disease with few treatment options such as tyrosine kinase inhibitors, for example, sorafenib or lenvatinib. The need for novel systemic treatment approaches is urgent. Methods: MTH1 expression profile was first analyzed in a HCC database and MTH1 mRNA/protein level was determined in resected HCC and paired paracancerous tissues with polymerase chain reaction (PCR) and immunohistochemistry. HCC cancer cell lines were exposed in vitro to MTH1 inhibitors or depleted of MTH1 by siRNA. 8-oxoG was measured by the modified comet assay. The effect of MTH1 inhibition on tumor growth was explored in HCC xenograft in vivo models. Results: MTH1 protein level is elevated in HCC tissue compared with paracancerous liver tissue and indicates poor prognosis. The MTH1 inhibitor Karonudib (TH1579) and siRNA effectively introduce toxic oxidized nucleotides into DNA, 8-oxoG, and kill HCC cell lines in vitro. Furthermore, we demonstrate that HCC growth in a xenograft mouse model in vivo is efficiently suppressed by Karonudib. Conclusion: Altogether, these data suggest HCC relies on MTH1 for survival, which can be targeted and may open up a novel treatment option for HCC in the future

TH1579, MTH1 inhibitor, delays tumour growth and inhibits metastases development in osteosarcoma model

Background Osteosarcoma (OS) is the most common primary malignant bone tumour. Unfortunately, no new treatments are approved and over the last 30 years the survival rate remains only 30% at 5 years for poor responders justifying an urgent need of new therapies. The Mutt homolog 1 (MTH1) enzyme prevents incorporation of oxidized nucleotides into DNA and recently developed MTH1 inhibitors may offer therapeutic potential as MTH1 is overexpressed in various cancers. Methods The aim of this study was to evaluate the therapeutic benefits of targeting MTH1 with two chemical inhibitors, TH588 and TH1579 on human osteosarcoma cells. Preclinical efficacy of TH1579 was assessed in human osteosarcoma xenograft model on tumour growth and development of pulmonary metastases. Findings MTH1 is overexpressed in OS patients and tumour cell lines, compared to mesenchymal stem cells. In vitro, chemical inhibition of MTH1 by TH588 and TH1579 decreases OS cells viability, impairs their cell cycle and increases apoptosis in OS cells. TH1579 was confirmed to bind MTH1 by CETSA in OS model. Moreover, 90 mg/kg of TH1579 reduces in vivo tumour growth by 80.5% compared to non-treated group at day 48. This result was associated with the increase in 8-oxo-dG integration into tumour cells DNA and the increase of apoptosis. Additionally, TH1579 also reduces the number of pulmonary metastases. Interpretation All these results strongly provide a pre-clinical proof-of-principle that TH1579 could be a therapeutic option for patients with osteosarcoma

Toxicology in the Fast Lane: Application of High-Throughput Bioassays to Detect Modulation of Key Enzymes and Receptors

BackgroundLegislation at state, federal, and international levels is requiring rapid evaluation of the toxicity of numerous chemicals. Whole-animal toxicologic studies cannot yield the necessary throughput in a cost-effective fashion, leading to a critical need for a faster and more cost-effective toxicologic evaluation of xenobiotics.ObjectivesWe tested whether mechanistically based screening assays can rapidly provide information on the potential for compounds to affect key enzymes and receptor targets, thus identifying those compounds requiring further in-depth analysis.MethodsA library of 176 synthetic chemicals was prepared and examined in a high-throughput screening (HTS) manner using nine enzyme-based and five receptor-based bioassays.ResultsAll the assays have high Z' values, indicating good discrimination among compounds in a reliable fashion, and thus are suitable for HTS assays. On average, three positive hits were obtained per assay. Although we identified compounds that were previously shown to inhibit a particular enzyme class or receptor, we surprisingly discovered that triclosan, a microbiocide present in personal care products, inhibits carboxylesterases and that dichlone, a fungicide, strongly inhibits the ryanodine receptors.ConclusionsConsidering the need to rapidly screen tens of thousands of anthropogenic compounds, our study shows the feasibility of using combined HTS assays as a novel approach toward obtaining toxicologic data on numerous biological end points. The HTS assay approach is very useful to quickly identify potentially hazardous compounds and to prioritize them for further in-depth studies

The Need for New Search Strategies for Fourth Generation Quarks at the LHC

Most limits on the fourth generation heavy top quark (the t') are based on the assumed dominance of t' -> Wb, which is expected to be case in the minimal fourth generation framework with a single Higgs (the so called SM4). Here we show, within a variant of a Two Higgs Doublet Model with four generations of fermions, that, in general, a different t' detection strategy is required if the physics that underlies the new heavy fermionic degrees of freedom goes beyond the "naive" SM4. We find that the recent CMS lower bounds: m_{t'}< 450 GeV in the semi-leptonic channel pp -> t't' -> l\nu qqbb and m_{t'}< 557 GeV in the dilepton channel pp -> t't' ->ll\nu \nu bb, that were obtained using the customary (SM4-driven) detection strategies, do not apply. In particular, we demonstrate that if the decay t' -> ht dominates, then applying the "standard" CMS search tools leads to a considerably relaxed lower bound: m_{t'} >~350 GeV. We, therefore, suggest an alternative search strategy that is more sensitive to beyond SM4 dynamics of the fourth generation fermions.Comment: 12 pages, 8 figure

CP Violation in Top Physics

CP violation in top physics is reviewed. The Standard Model has negligible effects, consequently CP violation searches involving the top quark may constitute the best way to look for physics beyond the Standard Model. Non-standard sources of CP violation due to an extended Higgs sector with and without natural flavor conservation and supersymmetric theories are discussed. Experimental feasibility of detecting CP violation effects in top quark production and decays in high energy e+ e-, gamma-gamma, mu+ mu-, pp and p-bar p colliders are surveyed. Searches for the electric, electro-weak and the chromo-electric dipole moments of the top quark in e+ e- -> t-bar t and in p p -> t-bar t X are descibed. In addition, other mechanisms that appear promising for experiments, e.g., tree-level CP violation in e+ e- -> t-bar t h, t-bar t Z, t-bar t nu_e-bar nu_e and in the top decay t -> b tau nu_tau and CP violation driven by s-channel Higgs exchanges in p p, gamma gamma, mu+ mu- -> t-bar t etc., are also discussed.Comment: 253 pages, 70 figures, A 2-up version of this postscript file may be obtained at http://thy.phy.bnl.gov/~soni/topreview.htm

Effects of coagulation on the two-phase peristaltic pumping of magnetized Prandtl biofluid through an endoscopic annular geometry containing a porous medium

In this article, motivated by more accurate simulation of electromagnetic blood flow in annular vessel geometries in intravascular thrombosis, a mathematical model is developed for elucidating the effects of coagulation (i.e. a blood clot) on peristaltically induced motion of an electrically-conducting (magnetized) Prandtl fluid physiological suspension through a non-uniform annulus containing a homogenous porous medium. Magnetohydrodynamics is included owing to the presence of iron in the hemoglobin molecule and also the presence of ions in real blood. Hall current which generates a secondary (cross) flow at stronger magnetic field is also considered in the present study. A small annular tube (endoscopic) with sinusoidal peristaltic waves traveling along the inner and outer walls at constant velocity with a clot present is analyzed. The governing conservation equations which comprise the continuity and momentum equations for the fluid phase and particle phase are simplified under lubrication approximations (long wavelength and creeping flow conditions). The moving boundary value problem is normalized and solved analytically (with appropriate wall conditions) for the fluid phase and particle phase using the homotopy perturbation method (HPM) with MATHEMATICA software. Validation is conducted with MAPLE numerical quadrature. A parametric study of the influence of clot height (δ), particle volume fraction (C), Prandtl fluid material parameters (α, β), Hartmann number (M), Hall parameter (m), permeability parameter (k), peristaltic wave amplitude (φ) and wave number (δ̅ ) on pressure difference and wall shear (friction forces) is included. Pressure rise is elevated with clot height, medium permeability and Prandtl rheological material parameters whereas it is reduced with increasing particle volume fraction and magnetic Hartmann number. Friction forces on the outer and inner tubes of the endoscope annulus are enhanced with clot height and particle volume fraction whereas they are decreased with Prandtl rheological material parameters, Hall parameter and permeability parameter. The simulations provide a good benchmark for more general computational fluid dynamics studies of magnetic endoscopic multi-phase peristaltic pumping