ASCA and XMM-Newton Observations of A2029

The X-ray data of A2029 obtained with XMM-Newton show no evidence of an embedded AGN in the central region of this cluster, which was suggested from the analysis of restored ASCA image data, although some hot spots are seen within or around the central cD galaxy. The absence of AGN at the cluster center is consistentent with the result of Chandra observations. Radial profiles of the iron abundance and the 2D (surface) temperature obtained from the XMM-Newton data are in good agreement with the Chandra data as a whole.Comment: 8 pages, 13 figures, accepted for publication in Advances in Space Researc

Cannabidivarin is anticonvulsant in mouse and rat in vitro and in seizure models

Summary Background and purpose: Phytocannabinoids in Cannabis sativa have diverse pharmacological targets extending beyond cannabinoid receptors and several exert notable anticonvulsant effects. For the first time, we investigated the anticonvulsant profile of the phytocannabinoid cannabidivarin (CBDV) in vitro and in in vivo seizure models. Experimental approach: The effect of CBDV (1-100μM) on epileptiform local field potentials (LFPs) induced in rat hippocampal brain slices by 4-AP application or Mg2+-free conditions was assessed by in vitro multi-electrode array recordings. Additionally, the anticonvulsant profile of CBDV (50-200 mg kg-1) in vivo was investigated in four rodent seizure models: maximal electroshock (mES) and audiogenic seizures in mice, and pentylenetetrazole (PTZ) and pilocarpine-induced seizures in rat. CBDV effects in combination with commonly-used antiepileptic drugs were investigated in rat seizures. Finally, the motor side effect profile of CBDV was investigated using static beam and gripstrength assays. Key results: CDBV significantly attenuated status epilepticus-like epileptiform LFPs induced by 4-AP and Mg2+-free conditions. CBDV had significant anticonvulsant effects in mES (≥100 mg kg-1), audiogenic (≥50 mg kg-1) and PTZ-induced seizures (≥100 mg kg-1). CBDV alone had no effect against pilocarpine-induced seizures, but significantly attenuated these seizures when administered with valproate or phenobarbital at 200 mg kg-1 CBDV. CBDV had no effect on motor function. Conclusions and Implications: These results indicate that CBDV is an effective anticonvulsant across a broad range of seizure models, does not significantly affect normal motor function and therefore merits further investigation in chronic epilepsy models to justify human trials

Cell Migration in the Immune System: the Evolving Inter-Related Roles of Adhesion Molecules and Proteinases

Leukocyte extravasation into perivascular tissue during inflammation and lymphocyte homing to lymphoid organs involve transient adhesion to the vessel endothelium, followed by transmigration through the endothelial cell (EC) layer and establishment of residency at the tissue site for a period of time. In these processes, leukocytes undergo multiple attachments to, and detachments from, the vessel-lining endothelial cells, prior to transendothelial cell migration. Transmigrating leukocytes must traverse a subendothelial basement membrane en route to perivascular tissues and utilize enzymes known as matrix metalloproteinases to make selective clips in the extracellular matrix components of the basement membrane. This review will focus on the evidence for a link between adhesion of leukocytes to endothelial cells, the induction of matrix metalloproteinases mediated by engagement of adhesion receptors on leukocytes, and the ability to utilize these matrix metalloproteinases to facilitate leukocyte invasion of tissues. Leukocytes with invasive phenotypes express high levels of MMPs, and expression of MMPs enhances the migratory and invasive properties of these cells. Furthermore, MMPs may be used by lymphocytes to proteolytically cleave molecules such as adhesion receptors and membrane bound cytokines, increasing their efficiency in the immune response. Engagement of leukocyte adhesion receptors may modulate adhesive (modulation of integrin affinities and expression), synthetic (proteinase induction and activation), and surface organization (clustering of proteolyric complexes) behaviors of invasive leukocytes. Elucidation of these pathways will lead to better understanding of controlling mechanisms in order to develop rational therapeutic approaches in the areas of inflammation and autoimmunity

Specializing Interpreters using Offline Partial Deduction

We present the latest version of the Logen partial evaluation system for logic programs. In particular we present new binding-types, and show how they can be used to effectively specialise a wide variety of interpreters.We show how to achieve Jones-optimality in a systematic way for several interpreters. Finally, we present and specialise a non-trivial interpreter for a small functional programming language. Experimental results are also presented, highlighting that the Logen system can be a good basis for generating compilers for high-level languages

Just-In-Time GPU Compilation for Interpreted Languages with Partial Evaluation

Computer systems are increasingly featuring powerful parallel devices with the advent of many-core CPUs and GPUs. This offers the opportunity to solve computationally-intensive problems at a fraction of the time traditional CPUs need. However, exploiting heterogeneous hardware requires the use of low-level programming language approaches such as OpenCL, which is incredibly challenging, even for advanced programmers. On the application side, interpreted dynamic languages are increasingly becoming popular in many domains due to their simplicity, expressiveness and flexibility. However, this creates a wide gap between the high-level abstractions offered to programmers and the low-level hardware-specific interface. Currently, programmers must rely on high performance libraries or they are forced to write parts of their application in a low-level language like OpenCL. Ideally, non-expert programmers should be able to exploit heterogeneous hardware directly from their interpreted dynamic languages. In this paper, we present a technique to transparently and automatically offload computations from interpreted dynamic languages to heterogeneous devices. Using just-in-time compilation, we automatically generate OpenCL code at runtime which is specialized to the actual observed data types using profiling information. We demonstrate our technique using R, which is a popular interpreted dynamic language predominately used in big data analytic. Our experimental results show the execution on a GPU yields speedups of over 150x compared to the sequential FastR implementation and the obtained performance is competitive with manually written GPU code. We also show that when taking into account start-up time, large speedups are achievable, even when the applications run for as little as a few seconds

Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report.

We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease

A Symmetric Approach to Compilation and Decompilation

Just as specializing a source interpreter can achieve compilation from a source language to a target language, we observe that specializing a target interpreter can achieve compilation from the target language to the source language. In both cases, the key issue is the choice of whether to perform an evaluation or to emit code that represents this evaluation. We substantiate this observation by specializing two source interpreters and two target interpreters. We first consider a source language of arithmetic expressions and a target language for a stack machine, and then the lambda-calculus and the SECD-machine language. In each case, we prove that the target-to-source compiler is a left inverse of the source-to-target compiler, i.e., it is a decompiler. In the context of partial evaluation, compilation by source-interpreter specialization is classically referred to as a Futamura projection. By symmetry, it seems logical to refer to decompilation by target-interpreter specialization as a Futamura embedding

Maximal operator in variable exponent generalized morrey spaces on quasi-metric measure space

We consider generalized Morrey spaces on quasi-metric measure spaces , in general unbounded, with variable exponent p(x) and a general function defining the Morrey-type norm. No linear structure of the underlying space X is assumed. The admission of unbounded X generates problems known in variable exponent analysis. We prove the boundedness results for maximal operator known earlier only for the case of bounded sets X. The conditions for the boundedness are given in terms of the so called supremal inequalities imposed on the function , which are weaker than Zygmund-type integral inequalities often used for characterization of admissible functions . Our conditions do not suppose any assumption on monotonicity of in r

Generation and Characterization of Conditional Heparin-Binding EGF-Like Growth Factor Knockout Mice

Recently, neurotrophic factors and cytokines have been shown to be associated in psychiatric disorders, such as schizophrenia, bipolar disorder, and depression. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the EGF family, serves as a neurotrophic molecular and plays a significant role in the brain. We generated mice in which HB-EGF activity is disrupted specifically in the ventral forebrain. These knockout mice showed (a) behavioral abnormalities similar to those described in psychiatric disorders, which were ameliorated by typical or atypical antipsychotics, (b) altered dopamine and serotonin levels in the brain, (c) decreases in spine density in neurons of the prefrontal cortex, (d) reductions in the protein levels of the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor and post-synaptic protein-95 (PSD-95), (e) decreases in the EGF receptor, and in the calcium/calmodulin-dependent protein kinase II (CaMK II) signal cascade. These results suggest the alterations affecting HB-EGF signaling could comprise a contributing factor in psychiatric disorder