Multi-electron transitions induced by neutron impact on helium

We explore excitation and ionization by neutron impact as a novel tool for the investigation of electron-electron correlations in helium. We present single and double ionization spectra calculated in accurate numerical ab-initio simulations for incoming neutrons with kinetic energies of up to 150 keV. The resulting electron spectra are found to be fundamentally different from photoioniza- tion or charged particle impact due to the intrinsic many-body character of the interaction. In particular, doubly excited resonances that are strongly suppressed in electron or photon impact become prominent. The ratio of double to single ionization is found to differ significantly from those of photon and charged particle impact.Comment: 5 pages, 5 figure

Towards a novel biologically-inspired cloud elasticity framework

With the widespread use of the Internet, the popularity of web applications has significantly increased. Such applications are subject to unpredictable workload conditions that vary from time to time. For example, an e-commerce website may face higher workloads than normal during festivals or promotional schemes. Such applications are critical and performance related issues, or service disruption can result in financial losses. Cloud computing with its attractive feature of dynamic resource provisioning (elasticity) is a perfect match to host such applications. The rapid growth in the usage of cloud computing model, as well as the rise in complexity of the web applications poses new challenges regarding the effective monitoring and management of the underlying cloud computational resources. This thesis investigates the state-of-the-art elastic methods including the models and techniques for the dynamic management and provisioning of cloud resources from a service provider perspective. An elastic controller is responsible to determine the optimal number of cloud resources, required at a particular time to achieve the desired performance demands. Researchers and practitioners have proposed many elastic controllers using versatile techniques ranging from simple if-then-else based rules to sophisticated optimisation, control theory and machine learning based methods. However, despite an extensive range of existing elasticity research, the aim of implementing an efficient scaling technique that satisfies the actual demands is still a challenge to achieve. There exist many issues that have not received much attention from a holistic point of view. Some of these issues include: 1) the lack of adaptability and static scaling behaviour whilst considering completely fixed approaches; 2) the burden of additional computational overhead, the inability to cope with the sudden changes in the workload behaviour and the preference of adaptability over reliability at runtime whilst considering the fully dynamic approaches; and 3) the lack of considering uncertainty aspects while designing auto-scaling solutions. This thesis seeks solutions to address these issues altogether using an integrated approach. Moreover, this thesis aims at the provision of qualitative elasticity rules. This thesis proposes a novel biologically-inspired switched feedback control methodology to address the horizontal elasticity problem. The switched methodology utilises multiple controllers simultaneously, whereas the selection of a suitable controller is realised using an intelligent switching mechanism. Each controller itself depicts a different elasticity policy that can be designed using the principles of fixed gain feedback controller approach. The switching mechanism is implemented using a fuzzy system that determines a suitable controller/- policy at runtime based on the current behaviour of the system. Furthermore, to improve the possibility of bumpless transitions and to avoid the oscillatory behaviour, which is a problem commonly associated with switching based control methodologies, this thesis proposes an alternative soft switching approach. This soft switching approach incorporates a biologically-inspired Basal Ganglia based computational model of action selection. In addition, this thesis formulates the problem of designing the membership functions of the switching mechanism as a multi-objective optimisation problem. The key purpose behind this formulation is to obtain the near optimal (or to fine tune) parameter settings for the membership functions of the fuzzy control system in the absence of domain experts’ knowledge. This problem is addressed by using two different techniques including the commonly used Genetic Algorithm and an alternative less known economic approach called the Taguchi method. Lastly, we identify seven different kinds of real workload patterns, each of which reflects a different set of applications. Six real and one synthetic HTTP traces, one for each pattern, are further identified and utilised to evaluate the performance of the proposed methods against the state-of-the-art approaches

Prenatal Cocaine Exposure Increases Synaptic Localization of a Neuronal RasGEF, GRASP-1 via Hyperphosphorylation of AMPAR Anchoring Protein, GRIP

Prenatal cocaine exposure causes sustained phosphorylation of the synaptic anchoring protein, glutamate receptor interacting protein (GRIP1/2), preventing synaptic targeting of the GluR2/3-containing alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors (AMPARs; J. Neurosci. 29: 6308–6319, 2009). Because overexpression of GRIP-associated neuronal rasGEF protein (GRASP-1) specifically reduces the synaptic targeting of AMPARs, we hypothesized that prenatal cocaine exposure enhances GRASP-1 synaptic membrane localization leading to hyper-activation of ras family proteins and heightened actin polymerization. Our results show a markedly increased GRIP1-associated GRASP-1 content with approximately 40% reduction in its rasGEF activity in frontal cortices (FCX) of 21-day-old (P21) prenatal cocaine-exposed rats. This cocaine effect is the result of a persistent protein kinase C (PKC)- and downstream Src tyrosine kinase-mediated GRIP phosphorylation. The hyperactivated PKC also increased membrane-associated GRASP-1 and activated small G-proteins RhoA, cdc42/Rac1 and Rap1 as well as filamentous actin (F-actin) levels without an effect on the phosphorylation state of actin. Since increased F-actin facilitates protein transport, our results suggest that increased GRASP-1 synaptic localization in prenatal cocaine-exposed brains is an adaptive response to restoring the synaptic expression of AMPA-GluR2/3. Our earlier data demonstrated that persistent PKC-mediated GRIP phosphorylation reduces GluR2/3 synaptic targeting in prenatal cocaine-exposed brains, we now show that the increased GRIP-associated GRASP-1 may contribute to the reduction in GluR2/3 synaptic expression and AMPAR signaling defects

Induced pseudoscalar coupling of the proton weak interaction

The induced pseudoscalar coupling $g_p$ is the least well known of the weak coupling constants of the proton's charged--current interaction. Its size is dictated by chiral symmetry arguments, and its measurement represents an important test of quantum chromodynamics at low energies. During the past decade a large body of new data relevant to the coupling $g_p$ has been accumulated. This data includes measurements of radiative and non radiative muon capture on targets ranging from hydrogen and few--nucleon systems to complex nuclei. Herein the authors review the theoretical underpinnings of $g_p$, the experimental studies of $g_p$, and the procedures and uncertainties in extracting the coupling from data. Current puzzles are highlighted and future opportunities are discussed.Comment: 58 pages, Latex, Revtex4, prepared for Reviews of Modern Physic

Plasma triglyceride concentrations are rapidly reduced following individual bouts of endurance exercise in women

It is known that chronic endurance training leads to improvements in the lipoprotein profile, but less is known about changes that occur during postexercise recovery acutely. We analyzed triglyceride (TG), cholesterol classes and apolipoproteins in samples collected before, during and after individual moderate- and hard-intensity exercise sessions in men and women that were isoenergetic between intensities. Young healthy men (n = 9) and young healthy women (n = 9) were studied under three different conditions with diet unchanged between trials: (1) before, during and 3 h after 90 min of exercise at 45% VO2peak (E45); (2) before, during and 3 h after 60 min of exercise at 65% VO2peak (E65), and (3) in a time-matched sedentary control trial (C). At baseline, high-density lipoprotein cholesterol (HDL-C) was higher in women than men (P < 0.05). In men and in women, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), HDL-C, apolipoprotein A-I (apoA-I), apolipoprotein B (apoB), and LDL peak particle size were unaltered by exercise either during exertion or after 3 h of recovery. In women, but not in men, average plasma TG was significantly reduced below C at 3 h postexercise by approximately 15% in E45 and 25% in E65 (P < 0.05) with no significant difference between exercise intensities. In summary, plasma TG concentration rapidly declines following exercise in women, but not in men. These results demonstrate an important mechanism by which each individual exercise session may incrementally reduce the risk for cardiovascular disease (CVD) in women

Topiramate-Induced Modulation of Hepatic Molecular Mechanisms: An Aspect for Its Anti-Insulin Resistant Effect

Topiramate is an antiepileptic drug known to ameliorate insulin resistance besides reducing body weight. Albeit liver plays a fundamental role in regulation of overall insulin resistance, yet the effect of topiramate on this organ is controversial and is not fully investigated. The current work aimed to study the potential hepatic molecular mechanistic cassette of the anti-insulin resistance effect of topiramate. To this end, male Wistar rats were fed high fat/high fructose diet (HFFD) for 10 weeks to induce obese, insulin resistant, hyperglycemic animals, but with no overt diabetes. Two HFFD-groups received oral topiramate, 40 or 100 mg/kg, for two weeks. Topiramate, on the hepatic molecular level, has opposed the high fat/high fructose diet effect, where it significantly increased adiponectin receptors, GLUT2, and tyrosine kinase activity, while decreased insulin receptor isoforms. Besides, it improved the altered glucose homeostasis and lipid profile, lowered the ALT level, caused subtle, yet significant decrease in TNF-α, and boosted adiponectin in a dose dependent manner. Moreover, topiramate decreased liver weight/, visceral fat weight/, and epididymal fat weight/body weight ratios. The study proved that insulin-resistance has an effect on hepatic molecular level and that the topiramate-mediated insulin sensitivity is ensued partly by modulation of hepatic insulin receptor isoforms, activation of tyrosine kinase, induction of GLUT2 and elevation of adiponectin receptors, as well as their ligand, adiponectin, besides its known improving effect on glucose tolerance and lipid homeostasis

Astrocytes: biology and pathology

Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential complex functions in the healthy CNS. Astrocytes respond to all forms of CNS insults through a process referred to as reactive astrogliosis, which has become a pathological hallmark of CNS structural lesions. Substantial progress has been made recently in determining functions and mechanisms of reactive astrogliosis and in identifying roles of astrocytes in CNS disorders and pathologies. A vast molecular arsenal at the disposal of reactive astrocytes is being defined. Transgenic mouse models are dissecting specific aspects of reactive astrocytosis and glial scar formation in vivo. Astrocyte involvement in specific clinicopathological entities is being defined. It is now clear that reactive astrogliosis is not a simple all-or-none phenomenon but is a finely gradated continuum of changes that occur in context-dependent manners regulated by specific signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy with preservation of cellular domains and tissue structure, to long-lasting scar formation with rearrangement of tissue structure. Increasing evidence points towards the potential of reactive astrogliosis to play either primary or contributing roles in CNS disorders via loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.