Rescue with an anti-inflammatory peptide of chickens infected H5N1 avian flu

Chickens suffering from avian flu caused by H5N1 influenza virus are destined to die within 2 days due to a systemic inflammatory response. Since HVJ infection (1,2) and influenza virus infection (3,4) cause infected cells to activate homologous serum complement, the systemic inflammatory response elicited could be attributed to the unlimited generation of C5a anaphylatoxin of the complement system, which is a causative peptide of serious inflammation. In monkeys inoculated with a lethal dose of LPS (4 mg/kg body weight), inhibition of C5a by an inhibitory peptide termed AcPepA (5) rescued these animals from serious septic shock which would have resulted in death within a day (6). Therefore, we tested whether AcPepA could also have a beneficial effect on chickens with bird flu. On another front, enhanced production of endothelin-1 (ET-1) and the activation of mast cells (MCs) have been implicated in granulocyte sequestration (7). An endothelin receptor derived antisense homology box peptide (8) designated ETR-P1/fl was shown to antagonize endothelin A receptor (ET-A receptor) (9) and reduce such inflammatory responses as endotoxin-shock (10) and hemorrhagic shock (11), thereby suppressing histamine release in the circulation (12). Thus, we also administered ETR-P1/fl to bird flu chickens expecting suppression of a systemic inflammatory response

Neutralino dark matter in brane world cosmology

The thermal relic density of the neutralino dark matter in the brane world cosmology is studied. Since the expansion law at a high energy regime in the brane world cosmology is modified from the one in the standard cosmology, the resultant relic density can be altered. It has been found that, if the five dimensional Planck mass $M_5$ is lower than $10^4$ TeV, the brane world cosmological effect is significant at the decoupling time and the resultant relic density is enhanced. We calculate the neutralino relic density in the Constrained Minimal Supersymmetric Standard Model (CMSSM) and show that the allowed region is dramatically modified from the one in the standard cosmology and eventually disappears as $M_5$ is decreasing. We also find a new lower bound on $M_5 \gtrsim 600$ TeV based on the neutralino dark matter hypothesis, namely the lower bound in order for the allowed region of the neutralino dark matter to exist.Comment: 12 pages, 8 figure

Light wino dark matter in brane world cosmology

The thermal relic density of the wino-like neutralino dark matter in the brane world cosmology is studied. The expansion law at a high energy regime in the brane world cosmology is modified from the one in the standard cosmology, and the resultant relic density can be enhanced if the five dimensional Planck mass $M_5$ is low enough. We calculate the wino-like neutralino relic density in the anomaly mediated supersymmetry breaking scenario and show that the allowed region is dramatically modified from the one in the standard cosmology and the wino-like neutralino with mass of order 100 GeV can be a good candidate for the dark matter. Since the allowed region disappears eventually as $M_5$ is decreasing, we can find a lower bound on $M_5 \gtrsim 100$ TeV according to the neutralino dark matter hypothesis, namely the lower bound in order for the allowed region of the neutralino dark matter to exist.Comment: 16 pages, 9 figures, final versio

Bi-stability of mixed states in neural network storing hierarchical patterns

We discuss the properties of equilibrium states in an autoassociative memory model storing hierarchically correlated patterns (hereafter, hierarchical patterns). We will show that symmetric mixed states (hereafter, mixed states) are bi-stable on the associative memory model storing the hierarchical patterns in a region of the ferromagnetic phase. This means that the first-order transition occurs in this ferromagnetic phase. We treat these contents with a statistical mechanical method (SCSNA) and by computer simulation. Finally, we discuss a physiological implication of this model. Sugase et al. analyzed the time-course of the information carried by the firing of face-responsive neurons in the inferior temporal cortex. We also discuss the relation between the theoretical results and the physiological experiments of Sugase et al.Comment: 18 pages, 6 figure

Genetically Engineered T-Cells for Malignant Glioma: Overcoming the Barriers to Effective Immunotherapy.

Malignant gliomas carry a dismal prognosis. Conventional treatment using chemo- and radiotherapy has limited efficacy with adverse events. Therapy with genetically engineered T-cells, such as chimeric antigen receptor (CAR) T-cells, may represent a promising approach to improve patient outcomes owing to their potential ability to attack highly infiltrative tumors in a tumor-specific manner and possible persistence of the adaptive immune response. However, the unique anatomical features of the brain and susceptibility of this organ to irreversible tissue damage have made immunotherapy especially challenging in the setting of glioma. With safety concerns in mind, multiple teams have initiated clinical trials using CAR T-cells in glioma patients. The valuable lessons learnt from those trials highlight critical areas for further improvement: tackling the issues of the antigen presentation and T-cell homing in the brain, immunosuppression in the glioma microenvironment, antigen heterogeneity and off-tumor toxicity, and the adaptation of existing clinical therapies to reflect the intricacies of immune response in the brain. This review summarizes the up-to-date clinical outcomes of CAR T-cell clinical trials in glioma patients and examines the most pressing hurdles limiting the efficacy of these therapies. Furthermore, this review uses these hurdles as a framework upon which to evaluate cutting-edge pre-clinical strategies aiming to overcome those barriers

Myocardial clearance of technetium-99m-teboroxime in reperfused injured canine myocardium

Background: Recent technical developments using solid-state technology have enabled rapid image acquisition with single photon emission computed tomography (SPECT) and have led to a renewed interest in technetium-99m-teboroxime (Tc-99m-teboroxime) as a myocardial imaging agent. Tc-99m-teboroxime has demonstrated high myocardial extraction, linear myocardial uptake relative to flow even at high flow rates, rapid uptake and clearance kinetics, and differential clearance in the setting of ischemia. However, the myocardial clearance kinetics of Tc-99m-teboroxime in a model of myocardial injury has not been previously reported. Thus, the purposes of this study were to use a canine model of ischemia-reperfusion to (1) compare Tc-99m-teboroxime clearance kinetics in normal and ischemic-reperfused myocardium and (2) assess the utility of Tc-99m-teboroxime clearance kinetics in determining the severity of injury following ischemia-reperfusion. Methods: Thirteen dogs underwent left circumflex coronary artery (LCx) occlusion for either 30 min (IR30, n = 6) or 120 min (IR120, n = 7), followed by reperfusion, and finally Tc-99m-teboroxime administration 120 min after reperfusion. Microsphere blood flows were determined at baseline, during occlusion, after reperfusion, and before euthanasia. Post-mortem, area at risk was determined using Evans blue dye, and viability was determined using triphenytetrazolium chloride (TTC) staining. The hearts were then subdivided into 24 pieces and Tc-99m activity was measured in a well counter. Results: TTC-determined infarct area as a percentage of total left ventricular myocardium was 1.1% ± 0.3% for the IR30 group and 7.5% ± 2.9% for the IR120 group (p < 0.05). During coronary occlusion, both the IR30 and IR120 groups demonstrated decreases in percent wall thickening in the ischemia-reperfusion zone (IRZ) as compared with the normal zone (NZ). In the IR30 group, percent wall thickening in the IRZ recovered during the reperfusion phase as compared with the NZ. In the IR120 group, percent wall thickening in the IRZ remained depressed during the reperfusion phase and through the end of the experiment as compared with the NZ. Final Tc-99m-teboroxime myocardial IRZ/NZ activity ratio was 0.94 ± 0.01 for the IR30 group, compared to 0.80 ± 0.01 for the IR120 group (p < 0.05). Conclusions: Tc-99m-teboroxime demonstrates moderate differential clearance in a model of severe injury with 120 min of ischemia-reperfusion, but only minimal differential clearance in a model of mild injury with 30 min of ischemia-reperfusion. Thus, Tc-99m-teboroxime clearance kinetics may be helpful in differentiating normal and minimally injured from severely injured myocardium

Thermal leptogenesis in brane world cosmology

The thermal leptogenesis in brane world cosmology is studied. In brane world cosmology, the expansion law is modified from the four-dimensional standard cosmological one at high temperature regime in the early universe. As a result, the well-known upper bound on the lightest light neutrino mass induced by the condition for the out-of-equilibrium decay of the lightest heavy neutrino, $\tilde{m}_1 \lesssim 10^{-3}$ eV, can be moderated to be $\tilde{m}_1 \lesssim 10^{-3} {eV} \times (M_1/T_t)^2$ in the case of $T_t \leq M_1$ with the lightest heavy neutrino mass ($M_1$) and the ``transition temperature'' ($T_t$), at which the modified expansion law in brane world cosmology is smoothly connecting with the standard one. This implies that the degenerate mass spectrum of the light neutrinos can be consistent with the thermal leptogenesis scenario. Furthermore, as recently pointed out, the gravitino problem in supersymmetric case can be solved if the transition temperature is low enough $T_t \lesssim 10^{6-7}$ GeV. Therefore, even in the supersymmetric case, thermal leptogenesis scenario can be successfully realized in brane world cosmology.Comment: 9 pages, final versio

High Spectral and Spatial Resolution Observations of the PDR Emission in the NGC2023 Reflection Nebula with SOFIA and APEX

We have mapped the NGC 2023 reflection nebula in [CII] and CO(11--10) with the heterodyne receiver GREAT on SOFIA and obtained slightly smaller maps in 13CO(3--2), CO(3--2), CO(4--3), CO(6--5), and CO(7--6) with APEX in Chile. We use these data to probe the morphology, kinematics, and physical conditions of the C II region, which is ionized by FUV radiation from the B2 star HD37903. The [CII] emission traces an ellipsoidal shell-like region at a position angle of ~ -50 deg, and is surrounded by a hot molecular shell. In the southeast, where the C II region expands into a dense, clumpy molecular cloud ridge, we see narrow and strong line emission from high-J CO lines, which comes from a thin, hot molecular shell surrounding the [CII] emission. The [CII] lines are broader and show photo evaporating gas flowing into the C II region. Based on the strength of the [13CII] F=2--1 line, the [CII] line appears to be somewhat optically thick over most of the nebula with an optical depth of a few. We model the physical conditions of the surrounding molecular cloud and the PDR emission using both RADEX and simple PDR models. The temperature of the CO emitting PDR shell is ~ 90 -- 120 K, with densities of 10^5 -- 10^6 cm^-3, as deduced from RADEX modeling. Our PDR modeling indicates that the PDR layer where [CII] emission dominates has somewhat lower densities, 10^4 to a few times 10^5 cm^-3Comment: Accepted by A&

The X-ray binary population in M33: II. X-ray spectra and variability

In this paper we investigate the X-ray spectra and X-ray spectral variability of compact X-ray sources for 3 Chandra observations of the Local Group galaxy M33. The observations are centered on the nucleus and the star forming region NGC 604. In the observations 261 sources have been detected. For a total of 43 sources the number of net counts is above 100, sufficient for a more detailed spectral fitting. Of these sources, 25 have been observed in more than one observation, allowing the study of spectral variability on ~months timescales. A quarter of the sources are found to be variable between observations. However, except for two foreground sources, no source is variable within any observation above the 99% confidence level. Only six sources show significant spectral variability between observations. A comparison of N_H values with HI observations shows that X-ray absorption values are consistent with Galactic X-ray binaries and most sources in M33 are intrinsically absorbed. The pattern of variability and the spectral parameters of these sources are consistent with the M33 X-ray source population being dominated by X-ray binaries: Two thirds of the 43 bright sources have spectral and timing properties consistent with X-ray binaries; we also find two candidates for super-soft sources and two candidates for quasi-soft sources.Comment: 25 pages, ApJ accepte

Evidence-Based Dialogue Maps as a research tool to evaluate the quality of school pupils’ scientific argumentation

This pilot study focuses on the potential of Evidence-based Dialogue Mapping as a participatory action research tool to investigate young teenagers’ scientific argumentation. Evidence-based Dialogue Mapping is a technique for representing graphically an argumentative dialogue through Questions, Ideas, Pros, Cons and Data. Our research objective is to better understand the usage of Compendium, a Dialogue Mapping software tool, as both (1) a learning strategy to scaffold school pupils’ argumentation and (2) as a method to investigate the quality of their argumentative essays. The participants were a science teacher-researcher, a knowledge mapping researcher and 20 pupils, 12-13 years old, in a summer science course for “gifted and talented” children in the UK. This study draws on multiple data sources: discussion forum, science teacher-researcher’s and pupils’ Dialogue Maps, pupil essays, and reflective comments about the uses of mapping for writing. Through qualitative analysis of two case studies, we examine the role of Evidence-based Dialogue Maps as a mediating tool in scientific reasoning: as conceptual bridges for linking and making knowledge intelligible; as support for the linearisation task of generating a coherent document outline; as a reflective aid to rethinking reasoning in response to teacher feedback; and as a visual language for making arguments tangible via cartographic conventions