The Gerasimov-Drell-Hearn Sum Rule and the Spin Structure of the Nucleon

The Gerasimov-Drell-Hearn sum rule is one of several dispersive sum rules that connect the Compton scattering amplitudes to the inclusive photoproduction cross sections of the target under investigation. Being based on such universal principles as causality, unitarity, and gauge invariance, these sum rules provide a unique testing ground to study the internal degrees of freedom that hold the system together. The present article reviews these sum rules for the spin-dependent cross sections of the nucleon by presenting an overview of recent experiments and theoretical approaches. The generalization from real to virtual photons provides a microscope of variable resolution: At small virtuality of the photon, the data sample information about the long range phenomena, which are described by effective degrees of freedom (Goldstone bosons and collective resonances), whereas the primary degrees of freedom (quarks and gluons) become visible at the larger virtualities. Through a rich body of new data and several theoretical developments, a unified picture of virtual Compton scattering emerges, which ranges from coherent to incoherent processes, and from the generalized spin polarizabilities on the low-energy side to higher twist effects in deep inelastic lepton scattering.Comment: 32 pages, 19 figures, review articl

Patients' experiences of transitioning between different renal replacement therapy modalities : a qualitative study

BACKGROUND: Different kidney replacement therapy modalities are available to manage end-stage kidney disease, such as home-based dialysis, in-center hemodialysis, and kidney transplantation. Although transitioning between modalities is common, data on how patients experience these transitions are scarce. This study explores patients' perspectives of transitioning from a home-based to an in-center modality. METHODS: Patients transitioning from peritoneal dialysis to in-center hemodialysis were purposively selected. Semi-structured interviews were performed, digitally recorded, and transcribed verbatim. Data analysis, consistent with Charmaz' constructivist approach of grounded theory was performed. RESULTS: Fifteen patients (10 males; mean age 62 years) participated. The conditions of the transitioning process impacted the participants' experiences, resulting in divergent experiences and associated emotions. Some participants experienced a loss of control due to the therapy-related changes. Some felt tied down and having lost independence, whereas others stated they regained control as they felt relieved from responsibility. This paradox of control was related to the patient having or not having (1) experienced a fit of hemodialysis with their personal lifestyle, (2) a frame of reference, (3) higher care requirements, (4) insight into the underlying reasons for transitioning, and (5) trust in the healthcare providers. CONCLUSIONS: Care teams need to offer opportunities to elicit patients' knowledge and fears, dispel myths, forge connections with other patients, and visit the dialysis unit before transition to alleviate anxiety. Interventions that facilitate a sense of control should be grounded in the meaning that the disorder has for the person and how it impacts their sense of self

Optimizing agents with genetic programming : an evaluation of hyper-heuristics in dynamic real-time logistics

Dynamic pickup and delivery problems (PDPs) require online algorithms for managing a fleet of vehicles. Generally, vehicles can be managed either centrally or decentrally. A common way to coordinate agents decentrally is to use the contract-net protocol (CNET) that uses auctions to allocate tasks among agents. To participate in an auction, agents require a method that estimates the value of a task. Typically this method is an optimization algorithm. Recently, hyper-heuristics has been proposed for automated design of heuristics. Two properties of automatically designed heuristics are particularly promising: 1) a generated heuristic computes quickly, it is expected therefore that hyper-heuristics heuristics perform especially well for urgent problems, and 2) by using simulationbased evaluation, hyper-heuristics can learn from the past and can therefore create a ‘rule of thumb’ that anticipates situations in the future. In the present paper we empirically evaluate whether hyper-heuristics, more specifically genetic programming (GP), can be used to improve agents decentrally coordinated via CNET. We compare several GP settings and compare the resulting heuristic with existing centralized and decentralized algorithms on a dynamic PDP dataset with varying levels of dynamism, urgency, and scale. The results indicate that the evolved heuristic always outperforms the optimization algorithm in the decentralized MAS and often outperforms the centralized optimization algorithm. Our paper shows that designing MASs using genetic programming is an effective way to obtain competitive performance compared to traditional operational research approaches. These results strengthen the relevance of decentralized agent based approaches in dynamic logistics

Interleukin-1 Receptor-Associated Kinase-3 Is a Key Inhibitor of Inflammation in Obesity and Metabolic Syndrome

BACKGROUND: Visceral obesity is associated with the rising incidence of type 2 diabetes and metabolic syndrome. Low-grade chronic inflammation and oxidative stress synergize in obesity and obesity-induced disorders. OBJECTIVE: We searched a cluster of molecules that support interactions between these stress conditions in monocytes. METHODS: RNA expressions in blood monocytes of two independent cohorts comprising 21 and 102 obese persons and 46 age-matched controls were determined by microarray and independently validated by quantitative RT-PCR analysis. The effect of three-month weight loss after bariatric surgery was determined. The effect of RNA silencing on inflammation and oxidative stress was studied in human monocytic THP-1 cells. RESULTS: Interleukin-1 receptor-associated kinase-3 (IRAK3), key inhibitor of IRAK/NFκB-mediated chronic inflammation, is downregulated in monocytes of obese persons. Low IRAK3 was associated with high superoxide dismutase-2 (SOD2), a marker of mitochondrial oxidative stress. A comparable expression profile was also detected in visceral adipose tissue of the same obese subjects. Low IRAK3 and high SOD2 was associated with a high prevalence of metabolic syndrome (odds ratio: 9.3; sensitivity: 91%; specificity: 77%). By comparison, the odds ratio of high-sensitivity C-reactive protein, a widely used marker of systemic inflammation, was 4.3 (sensitivity: 69%; specificity: 66%). Weight loss was associated with an increase in IRAK3 and a decrease in SOD2, in association with a lowering of systemic inflammation and a decreasing number of metabolic syndrome components. We identified the increase in reactive oxygen species in combination with obesity-associated low adiponectin and high glucose and interleukin-6 as cause of the decrease in IRAK3 in THP-1 cells in vitro. CONCLUSION: IRAK3 is a key inhibitor of inflammation in association with obesity and metabolic syndrome. Our data warrant further evaluation of IRAK3 as a diagnostic and prognostic marker, and as a target for intervention

Structural identification of oxidized acyl-phosphatidylcholines that induce platelet activation

Oxidation of low-density lipoprotein (LDL) generates proinflammatory and prothrombotic mediators that may play a crucial role in cardiovascular and inflammatory diseases. In order to study platelet-activating components of oxidized LDL 1-stearoyl-2-arachidonoyl-sn-glycero-3- phosphocholine, a representative of the major phospholipid species in LDL, the 1-acyl-phosphatidylcholines (PC), was oxidized by CuCl2 and H2O2. After separation by high-performance liquid chromatography, three compounds were detected which induced platelet shape change at low micromolar concentrations. Platelet activation by these compounds was distinct from the pathways stimulated by platelet-activating factor, lysophosphatidic acid, lyso-PC and thromboxane A(2), as evidenced by the use of specific receptor antagonists. Further analyses of the oxidized phospholipids by electrospray ionization mass spectrometry structurally identified them as 1-stearoyl-2-azelaoyl-sn-glycero-3-phosphocholine (m/z 694; SAzPC), 1-stearoyl-2-glutaroyl-snglycero-3- phosphocholine (m/z 638; SGPC), and 1-stearoyl-2-( 5-oxovaleroyl)-sn-glycero-3-phosphocholine (m/z 622; SOVPC). These observations demonstrate that novel 1-acyl-PC which had previously been found to stimulate interaction of monocytes with endothelial cells also induce platelet activation, a central step in acute thrombogenic and atherogenic processes. Copyright (C) 2005 S. Karger AG, Basel

Decrease of miR-146b-5p in Monocytes during Obesity Is Associated with Loss of the Anti-Inflammatory but Not Insulin Signaling Action of Adiponectin

Background: Low adiponectin, a well-recognized antidiabetic adipokine, has been associated with obesity-related inflammation, oxidative stress and insulin resistance. Globular adiponectin is an important regulator of the interleukin-1 receptor-associated kinase (IRAK)/NFkB pathway in monocytes of obese subjects. It protects against inflammation and oxidative stress by inducing IRAK3. microRNA (miR)-146b-5p inhibits NFkB-mediated inflammation by targeted repression of IRAK1 and TNF receptor-associated factor-6 (TRAF6). Therefore, we measured the expression of miR-146b-5p in monocytes of obese subjects. Because it was low we determined the involvement of this miR in the anti-inflammatory, antioxidative and insulin signaling action of globular adiponectin. Methods: miR-146b-5p expression in monocytes of obese subjects was determined by qRT-PCR. The effect of miR-146b-5p silencing on molecular markers of inflammation, oxidative stress and insulin signaling and the association with globular adiponectin was assessed in human THP-1 monocytes. Results: miR-146b-5p was downregulated in monocytes of obese persons. Low globular adiponectin decreased miR-146b-5p and IRAK3 in THP-1 monocytes, associated with increased mitochondrial reactive oxygen species (ROS). Intracellular ROS and insulin receptor substrate-1 (IRS1) protein were unchanged. Silencing of miR-146b-5p with an antisense inhibitor resulted in increased expression of IRAK1 and TRAF6 leading to more NFkB p65 DNA binding activity and TNFa. As

Partially Hydrolysed Whey-Based Infant Formula Improves Skin Barrier Function

Specific partially hydrolysed whey-based infant formulas (pHF-W) have been shown to decrease the risk of atopic dermatitis (AD) in infants. Historically, AD has been associated primarily with milk allergy; however, defective skin barrier function can be a primary cause of AD. We aimed to ascertain whether oral supplementation with pHF-W can improve skin barrier function. The effect of pHF-W was assessed on transepidermal water loss (TEWL) and antibody productions in mice epicutaneously exposed to Aspergillus fumigatus. Human primary keratinocytes were stimulated in vitro, and the expression of genes related to skin barrier function was measured. Supplementation with pHF-W in neonatal mice led to a significant decrease in TEWL and total IgE, but not in allergen-specific antibody levels. The whey hydrolysate was sufficient to decrease both TEWL and total IgE. Aquaporin-3 gene expression, linked with skin hydration, was modulated in the skin of mice and human primary keratinocytes following protein hydrolysate exposure. Skin barrier improvement may be an additional mechanism by which pHF-W may potentially reduce the risk of AD development in infants. Further human studies are warranted to confirm the clinical efficacy of these observations

Clinical relevance of biomarkers of oxidative stress

SIGNIFICANCE Oxidative stress is considered to be an important component of various diseases. A vast number of methods have been developed and used in virtually all diseases to measure the extent and nature of oxidative stress, ranging from oxidation of DNA to proteins, lipids, and free amino acids. Recent Advances: An increased understanding of the biology behind diseases and redox biology has led to more specific and sensitive tools to measure oxidative stress markers, which are very diverse and sometimes very low in abundance. CRITICAL ISSUES The literature is very heterogeneous. It is often difficult to draw general conclusions on the significance of oxidative stress biomarkers, as only in a limited proportion of diseases have a range of different biomarkers been used, and different biomarkers have been used to study different diseases. In addition, biomarkers are often measured using nonspecific methods, while specific methodologies are often too sophisticated or laborious for routine clinical use. FUTURE DIRECTIONS Several markers of oxidative stress still represent a viable biomarker opportunity for clinical use. However, positive findings with currently used biomarkers still need to be validated in larger sample sizes and compared with current clinical standards to establish them as clinical diagnostics. It is important to realize that oxidative stress is a nuanced phenomenon that is difficult to characterize, and one biomarker is not necessarily better than others. The vast diversity in oxidative stress between diseases and conditions has to be taken into account when selecting the most appropriate biomarker. Antioxid. Redox Signal. 00, 000-000

First measurement of the Gerasimov-Drell-Hearn integral for Hydrogen from 200 to 800 MeV

A direct measurement of the helicity dependence of the total photoabsorption cross section on the proton was carried out at MAMI (Mainz) in the energy range 200 < E_gamma < 800 MeV. The experiment used a 4$\pi$ detection system, a circularly polarized tagged photon beam and a frozen spin target. The contributions to the Gerasimov-Drell-Hearn sum rule and to the forward spin polarizability $\gamma_0$ determined from the data are 226 \pm 5 (stat)\pm 12(sys) \mu b and -187 \pm 8 (stat)\pm 10(sys)10^{-6} fm^4, respectively, for 200 < E_\gamma < 800 MeV.Comment: 6 pages, 3 figures, 3 table