Genistein induces a protective immunomodulatory effect in a mouse model of cervical cancer

Background: Genistein (GEN), a naturally occurring flavonoid present in soy bean, has attracted scientific interest for its possible benefits in cancer. Objective: The potential immunomodulatory effects of genistein on the immune system and against TC-1 tumor cell line were evaluated in adult female C57BL/6 mice. Methods: Mice were treated with GEN 10 days before to 10 days after the tumor induction. Thirty days after the last GEN treatment, lymphocyte proliferation, Lactase Dehydrogenase (LDH) cytolytic activity and cytokine secretion were analyzed in GEN and control groups. Results: The results showed that ingestion of genistein significantly increased lymphocyte proliferation and LDH release. Furthermore, the treatment with genistein also caused a significant increment in interferon gamma (IFN-γ). In addition, the treatment achieved significant therapeutic effect in tumor models compared to the control group. These results indicated that the effect of GEN on tumor growth may be attributed to its effect on lymphocyte proliferation, cytolytic activity and IFN-γ production. Conclusion: These results demonstrate that GEN exerts an immunomodulatory effect in a mouse model of Human Papillomavirus (HPV) associated-cervical cancer

Immunomodulatory Effect of Toll-Like Receptor-3 Ligand Poly I:C on Cortical Spreading Depression

The release of inflammatory mediators following cortical spreading depression (CSD) is suggested to play a role in pathophysiology of CSD-related neurological disorders. Toll-like receptors (TLR) are master regulators of innate immune function and involved in the activation of inflammatory responses in the brain. TLR3 agonist poly I:C exerts anti-inflammatory effect and prevents cell injury in the brain. The aim of the present study was to examine the effect of systemic administration of poly I:C on the release of cytokines (TNF-α, IFN-γ, IL-4, TGF-β1, and GM-CSF) in the brain and spleen, splenic lymphocyte proliferation, expression of GAD65, GABAAα, GABAAβ as well as Hsp70, and production of dark neurons after induction of repetitive CSD in juvenile rats. Poly I:C significantly attenuated CSD-induced production of TNF-α and IFN-γ in the brain as well as TNF-α and IL-4 in the spleen. Poly I:C did not affect enhancement of splenic lymphocyte proliferation after CSD. Administration of poly I:C increased expression of GABAAα, GABAAβ as well as Hsp70 and decreased expression of GAD65 in the entorhinal cortex compared to CSD-treated tissues. In addition, poly I:C significantly prevented production of CSD-induced dark neurons. The data indicate neuroprotective and anti-inflammatory effects of TLR3 activation on CSD-induced neuroinflammation. Targeting TLR3 may provide a novel strategy for developing new treatments for CSD-related neurological disorders. © 2014, Springer Science+Business Media New York

Immunomodulatory Effect of Toll-Like Receptor-3 Ligand Poly I:C on Cortical Spreading Depression

The release of inflammatory mediators following cortical spreading depression (CSD) is suggested to play a role in pathophysiology of CSD-related neurological disorders. Toll-like receptors (TLR) are master regulators of innate immune function and involved in the activation of inflammatory responses in the brain. TLR3 agonist poly I:C exerts anti-inflammatory effect and prevents cell injury in the brain. The aim of the present study was to examine the effect of systemic administration of poly I:C on the release of cytokines (TNF-α, IFN-γ, IL-4, TGF-β1, and GM-CSF) in the brain and spleen, splenic lymphocyte proliferation, expression of GAD65, GABAAα, GABAAβ as well as Hsp70, and production of dark neurons after induction of repetitive CSD in juvenile rats. Poly I:C significantly attenuated CSD-induced production of TNF-α and IFN-γ in the brain as well as TNF-α and IL-4 in the spleen. Poly I:C did not affect enhancement of splenic lymphocyte proliferation after CSD. Administration of poly I:C increased expression of GABAAα, GABAAβ as well as Hsp70 and decreased expression of GAD65 in the entorhinal cortex compared to CSD-treated tissues. In addition, poly I:C significantly prevented production of CSD-induced dark neurons. The data indicate neuroprotective and anti-inflammatory effects of TLR3 activation on CSD-induced neuroinflammation. Targeting TLR3 may provide a novel strategy for developing new treatments for CSD-related neurological disorders. © 2014, Springer Science+Business Media New York

Main Determinants of Supplementary Health Insurance Demand: (Case of Iran)

INTRODUCTION: In the majority of developing countries, the volume of medical insurance services, provided by social insurance organizations is inadequate. Thus, supplementary medical insurance is proposed as a means to address inadequacy of medical insurance. Accordingly, in this article, we attempted to provide the context for expansion of this important branch of insurance through identification of essential factors affecting demand for supplementary medical insurance. METHOD: In this study, two methods were used to identify essential factors affecting choice of supplementary medical insurance including Classification and Regression Trees (CART) and Bayesian logit. To this end, Excel® software was used to refine data and R® software for estimation. The present study was conducted during 2012, covering all provinces in Iran. Sample size included 18,541 urban households, selected by Statistical Center of Iran using 3-stage cluster sampling approach. In this study, all data required were collected from the Statistical Center of Iran. RESULTS: In 2012, an overall 8.04 of the Iranian population benefited from supplementary medical insurance. Demand for supplementary insurance is a concave function of age of the household head, and peaks in middle-age when savings and income are highest. The present study results showed greater likelihood of demand for supplementary medical insurance in households with better economic status, higher educated heads, female heads, and smaller households with greater expected medical expenses, and household income is the most important factor affecting demand for supplementary medical insurance. CONCLUSION: Since demand for supplementary medical insurance is hugely influenced by households' economic status, policy-makers in the health sector should devise measures to improve households' economic or financial access to supplementary insurance services, by identifying households in the lower economic deciles, and increasing their financial ability to pay. Moreover, insurance companies should adjust their insurance policy according to clients' needs, household characteristics, and their incomes

Trend analysis using non-stationary time series clustering based on the finite element method

In order to analyze low-frequency variability of climate, it is useful to model the climatic time series with multiple linear trends and locate the times of significant changes. In this paper, we have used non-stationary time series clustering to find change points in the trends. Clustering in a multi-dimensional non-stationary time series is challenging, since the problem is mathematically ill-posed. Clustering based on the finite element method (FEM) is one of the methods that can analyze multidimensional time series. One important attribute of this method is that it is not dependent on any statistical assumption and does not need local stationarity in the time series. In this paper, it is shown how the FEM-clustering method can be used to locate change points in the trend of temperature time series from in situ observations. This method is applied to the temperature time series of North Carolina (NC) and the results represent region-specific climate variability despite higher frequency harmonics in climatic time series. Next, we investigated the relationship between the climatic indices with the clusters/trends detected based on this clustering method. It appears that the natural variability of climate change in NC during 1950–2009 can be explained mostly by AMO and solar activity

Fractional electro-magneto transport of blood modeled with magnetic particles in cylindrical tube without singular kernel

The electro-kinetic transport of blood flow mixed with magnetic particles in the circular channel was investigated. The flow was subjected to an external electric and uniform magnetic field. The fluid was driven by pressure gradient and perpendicular magnetic field to the flow direction. Due to the usefulness and suitability of Caputo–Fabrizio fractional order derivative without singular kernel in fluid flow modeling and mass transfer phenomena, the governing equations were modeled as Caputo–Fabrizio time fractional partial differential equations and solved for a 2 ð0; 1�. The analytical solutions for the velocities of blood flow and magnetic particles were obtained by using Laplace, finite Hankel transforms and Robotnov and Hartley’s functions, respectively. Mathematica software was used to simulate the influences of fractional parameter a, Hartmann number and Reynolds number on the velocities of blood and magnetic particles. The findings are important for controlling bio-liquids in the devices used for analysis and diagnosis in biological and medical applications

A multi-step finite-state automaton for arbitrarily deterministic Tsetlin Machine learning

submittedVersio

Temporal acceleration of a turbulent channel flow

We report new laboratory experiments of a flow accelerating from an initially turbulent state following the opening of a valve, together with large eddy simulations of the experiments and extended Stokes first problem solutions for the early stages of the flow. The results show that the transient flow closely resembles an accelerating laminar flow superimposed on the original steady turbulent flow. The primary consequence of the acceleration is the temporal growth of a boundary layer from the wall, gradually leading to a strong instability causing transition. This extends the findings of previous direct numerical simulations of transient flow following a near-step increase in flow rate. In this interpretation, the initial turbulence is not the primary characteristic of the resulting transient flow, but can be regarded as noise, the evolution of which is strongly influenced by the development of the boundary layer. We observe the spontaneous appearance of turbulent spots and discontinuities in the velocity signals in time and space, revealing rich detail of the transition process, including a striking contrast between streamwise and wall-normal fluctuating velocities

Applicability of frozen-viscosity models of unsteady wall shear stress

The validity of assumed frozen-viscosity conditions underpinning an important class of theoretical models of unsteady wall shear stress in transient flows in pipes and channels is assessed using detailed computational fluid dynamics (CFD) simulations. The need for approximate one-dimensional ð1DÞfx; tg models of the wall stress is unavoidable in analyses of transient flows in extensive pipe networks because it would be economically impracticable to use higher order methods of analysis. However, the bases of the various models have never been established rigorously. It is shown herein that a commonly used approach developed by the first authors is flawed in the case of smoothwall flows although it is more plausible for rough-wall flows. The assessment process is undertaken for a particular, but important, unsteady flow case, namely, a uniform acceleration from an initially steady turbulent flow. First, detailed predictions from a validated CFD method are used to derive baseline solutions with which predictions based on approximate models can be compared. Then, alternative solutions are obtained using various prescribed frozen-viscosity distributions. Differences between these solutions and the baseline solutions are used to determine which frozen-viscosity distributions are the most promising starting points for developing 1Dfx; tg models of unsteady components of wall shear stress. It is shown that no frozen-viscosity distribution performs well for large times after the commencement of an acceleration. However, even the simplest approximation (laminar) performs well for short durations—which is when the greatest amplitudes of the unsteady components occu

Grain boundary oxide layers in NdFeB-based permanent magnets

The microstructure of grain boundaries (GBs) in the commercial NdFeB-based alloy for permanent magnets has been studied. It is generally accepted that the unique hard magnetic properties of such alloys are controlled by the thin layers of a Nd-rich phase in Nd$_{2}$Fe$_{14}$B/Nd$_{2}$Fe$_{14}$B GBs. These GB layers ensure the magnetic isolation of Nd$_{2}$Fe$_{14}$B grains from each other. It is usually supposed that such GB layers contain metallic Nd or Nd-rich intermetallic compounds. However, the commercial NdFeB-based permanent magnets frequently contain a tangible amount of neodymium oxide Nd$_{2}$O$_{3}$ at the triple junctions between Nd$_{2}$Fe$_{14}$B grains. The goal of this work was to check whether the Nd$_{2}$Fe$_{14}$B/Nd$_{2}$Fe$_{14}$B GBs could also contain the thin layers of Nd$_{2}$O$_{3}$ oxide phase. Indeed, the screening with EELS-based elemental analysis permitted to observe that some of these Nd-rich layers in Nd$_{2}$Fe$_{14}$B/Nd$_{2}$Fe$_{14}$B GBs contain not only neodymium, but also oxygen. More detailed analysis of such GBs with high-resolution transmission electron microscopy (HR TEM) showed these GB layers are crystalline and have the lattice of neodymium oxide Nd$_{2}$O$_{3}$. In turn, the Lorentz micro-magnetic contrast in TEM permitted to observe that the Nd-oxide GB layers prevent the migration of domain walls from one Nd$_{2}$Fe$_{14}$B grain to another during remagnetization. This finding proves that the GB oxide layers, similar to those of metallic Nd or Nd-rich intermetallic compounds, can ensure the magnetic isolation between Nd$_{2}$Fe$_{14}$B grains needed for high coercivity. Therefore, the GB oxide layers can be used for further development of NdFeB-based permanent magnets