New Sum Rules from Low Energy Compton Scattering on Arbitrary Spin Target

We derive two sum rules by studying the low energy Compton scattering on a target of arbitrary (nonzero) spin j. In the first sum rule, we consider the possibility that the intermediate state in the scattering can have spin |j \pm 1| and the same mass as the target. The second sum rule applies if the theory at hand possesses intermediate narrow resonances with masses different from the mass of the scatterer. These sum rules are generalizations of the Gerasimov-Drell-Hearn-Weinberg sum rule. Along with the requirement of tree level unitarity, they relate different low energy couplings in the theory. Using these sum rules, we show that in certain cases the gyromagnetic ratio can differ from the "natural" value g=2, even at tree level, without spoiling perturbative unitarity. These sum rules can be used as constraints applicable to all supergravity and higher-spin theories that contain particles charged under some U(1) gauge field. In particular, applied to four dimensional N=8 supergravity in a spontaneously broken phase, these sum rules suggest that for the theory to have a good ultraviolet behavior, additional massive states need to be present, such as those coming from the embedding of the N=8 supergravity in type II superstring theory. We also discuss the possible implications of the sum rules for QCD in the large-N_c limit.Comment: 18 pages, v2: discussion on black hole contribution is included, references added; v3: extended discussion in introduction, version to appear in JHE

A natural little hierarchy for RS from accidental SUSY

We use supersymmetry to address the little hierarchy problem in Randall-Sundrum models by naturally generating a hierarchy between the IR scale and the electroweak scale. Supersymmetry is broken on the UV brane which triggers the stabilization of the warped extra dimension at an IR scale of order 10 TeV. The Higgs and top quark live near the IR brane whereas light fermion generations are localized towards the UV brane. Supersymmetry breaking causes the first two sparticle generations to decouple, thereby avoiding the supersymmetric flavour and CP problems, while an accidental R-symmetry protects the gaugino mass. The resulting low-energy sparticle spectrum consists of stops, gauginos and Higgsinos which are sufficient to stabilize the little hierarchy between the IR scale and the electroweak scale. Finally, the supersymmetric little hierarchy problem is ameliorated by introducing a singlet Higgs field on the IR brane.Comment: 37 pages, 3 figures; v2: minor corrections, version published in JHE

Deep Inelastic Scattering in Conformal QCD

We consider the Regge limit of a CFT correlation function of two vector and two scalar operators, as appropriate to study small-x deep inelastic scattering in N=4 SYM or in QCD assuming approximate conformal symmetry. After clarifying the nature of the Regge limit for a CFT correlator, we use its conformal partial wave expansion to obtain an impact parameter representation encoding the exchange of a spin j Reggeon for any value of the coupling constant. The CFT impact parameter space is the three-dimensional hyperbolic space H3, which is the impact parameter space for high energy scattering in the dual AdS space. We determine the small-x structure functions associated to the exchange of a Reggeon. We discuss unitarization from the point of view of scattering in AdS and comment on the validity of the eikonal approximation. We then focus on the weak coupling limit of the theory where the amplitude is dominated by the exchange of the BFKL pomeron. Conformal invariance fixes the form of the vector impact factor and its decomposition in transverse spin 0 and spin 2 components. Our formalism reproduces exactly the general results predict by the Regge theory, both for a scalar target and for gamma*-gamma* scattering. We compute current impact factors for the specific examples of N=4 SYM and QCD, obtaining very simple results. In the case of the R-current of N=4 SYM, we show that the transverse spin 2 component vanishes. We conjecture that the impact factors of all chiral primary operators of N=4 SYM only have components with 0 transverse spin.Comment: 44+16 pages, 7 figures. Some correction

Inhibiting mevalonate pathway enzymes increases stromal cell resilience to a cholesterol-dependent cytolysin

Animal health depends on the ability of immune cells to kill invading pathogens, and on the resilience of tissues to tolerate the presence of pathogens. Trueperella pyogenes causes tissue pathology in many mammals by secreting a cholesterol-dependent cytolysin, pyolysin (PLO), which targets stromal cells. Cellular cholesterol is derived from squalene, which is synthesized via the mevalonate pathway enzymes, including HMGCR, FDPS and FDFT1. The present study tested the hypothesis that inhibiting enzymes in the mevalonate pathway to reduce cellular cholesterol increases the resilience of stromal cells to PLO. We first verified that depleting cellular cholesterol with methyl-β-cyclodextrin increased the resilience of stromal cells to PLO. We then used siRNA to deplete mevalonate pathway enzyme gene expression, and used pharmaceutical inhibitors, atorvastatin, alendronate or zaragozic acid to inhibit the activity of HMGCR, FDPS and FDFT1, respectively. These approaches successfully reduced cellular cholesterol abundance, but mevalonate pathway enzymes did not affect cellular resilience equally. Inhibiting FDFT1 was most effective, with zaragozic acid reducing the impact of PLO on cell viability. The present study provides evidence that inhibiting FDFT1 increases stromal cell resilience to a cholesterol-dependent cytolysin

The role of qualitative research in adding value to a randomised controlled trial: lessons from a pilot study of a guided e-learning intervention for managers to improve employee wellbeing and reduce sickness absence

The GEM study was funded by the National Institute for Health Research Public Health Research Programme (project number 10/3007/06)

Tennis Service Stroke Benefits Humerus Bone: Is Torsion the Cause?

Regular tennis play is associated with impressive asymmetries in bone strength in favor of the racquet arm, particularly in the humerus. However, the relative effects of service and ground strokes are not known. Serendipitously, we encountered a 46-year-old regular tennis player who has played service and ground strokes with different arms for over 30 years, and thus allowed differentiation of stroke effects. Grip strength and peripheral quantitative computed tomography scans of both arms of radius at 4 % distal–proximal ulna length, radius and ulna at 60 % distal–proximal ulna length, and at distal (35 % length) humerus were analyzed in this player, and 12 male veteran players of similar age, height, and mass who played a conventional single-sided style. Confidence intervals (95 %) were calculated for asymmetries and bone, muscle and force parameters in the control players—values in the case study player were compared to these intervals. Sizeable differences in bone strength in favor of the serving arm humerus were observed in this player—comparable to those found in the control players. While asymmetries in favor of the ground stroke arm ulna were also evident, no sizeable asymmetry was found in proximal or distal radius, forearm or upper arm muscle size or hand grip force. These results suggest that the service stroke is responsible for the humeral hypertrophy observed in tennis players, and that ulna adaptation may be attributable to the ground strokes. The osteogenic potential of the service stroke may be related to the large torsional stresses it produces

Th17 cells are more protective than Th1 cells against the intracellular parasite Trypanosoma cruzi

Th17 cells are a subset of CD4+ T cells known to play a central role in the pathogenesis of many autoimmune diseases, as well as in the defense against some extracellular bacteria and fungi. However, Th17 cells are not believed to have a significant function against intracellular infections. In contrast to this paradigm, we have discovered that Th17 cells provide robust protection against Trypanosoma cruzi, the intracellular protozoan parasite that causes Chagas disease. Th17 cells confer significantly stronger protection against T. cruzi-related mortality than even Th1 cells, traditionally thought to be the CD4+ T cell subset most important for immunity to T. cruzi and other intracellular microorganisms. Mechanistically, Th17 cells can directly protect infected cells through the IL-17A-dependent induction of NADPH oxidase, involved in the phagocyte respiratory burst response, and provide indirect help through IL-21-dependent activation of CD8+ T cells. The discovery of these novel Th17 cell-mediated direct protective and indirect helper effects important for intracellular immunity highlights the diversity of Th17 cell roles, and increases understanding of protective T. cruzi immunity, aiding the development of therapeutics and vaccines for Chagas disease

Loss of Sugar Detection by GLUT2 Affects Glucose Homeostasis in Mice

International audienceBACKGROUND: Mammals must sense the amount of sugar available to them and respond appropriately. For many years attention has focused on intracellular glucose sensing derived from glucose metabolism. Here, we studied the detection of extracellular glucose concentrations in vivo by invalidating the transduction pathway downstream from the transporter-detector GLUT2 and measured the physiological impact of this pathway. METHODOLOGY/PRINCIPAL FINDINGS: We produced mice that ubiquitously express the largest cytoplasmic loop of GLUT2, blocking glucose-mediated gene expression in vitro without affecting glucose metabolism. Impairment of GLUT2-mediated sugar detection transiently protected transgenic mice against starvation and streptozotocin-induced diabetes, suggesting that both low- and high-glucose concentrations were not detected. Transgenic mice favored lipid oxidation, and oral glucose was slowly cleared from blood due to low insulin production, despite massive urinary glucose excretion. Kidney adaptation was characterized by a lower rate of glucose reabsorption, whereas pancreatic adaptation was associated with a larger number of small islets. CONCLUSIONS/SIGNIFICANCE: Molecular invalidation of sugar sensing in GLUT2-loop transgenic mice changed multiple aspects of glucose homeostasis, highlighting by a top-down approach, the role of membrane glucose receptors as potential therapeutic targets

Endothelial Cells in Co-culture Enhance Embryonic Stem Cell Differentiation to Pancreatic Progenitors and Insulin-Producing Cells through BMP Signaling

Endothelial cells (ECs) represent the major component of the embryonic pancreatic niche and play a key role in the differentiation of insulin-producing β cells in vivo. However, it is unknown if ECs promote such differentiation in vitro. We investigated whether interaction of ECs with mouse embryoid bodies (EBs) in culture promotes differentiation of pancreatic progenitors and insulin-producing cells and the mechanisms involved. We developed a co-culture system of mouse EBs and human microvascular ECs (HMECs). An increase in the expression of the pancreatic markers PDX-1, Ngn3, Nkx6.1, proinsulin, GLUT-2, and Ptf1a was observed at the interface between EBs and ECs (EB-EC). No expression of these markers was found at the periphery of EBs cultured without ECs or those co-cultured with mouse embryonic fibroblasts (MEFs). At EB-EC interface, proinsulin and Nkx6.1 positive cells co-expressed phospho-Smad1/5/8 (pSmad1/5/8). Therefore, EBs were treated with HMEC conditioned media (HMEC-CM) suspecting soluble factors involved in bone morphogenetic protein (BMP) pathway activation. Upregulation of PDX-1, Ngn3, Nkx6.1, insulin-1, insulin-2, amylin, SUR1, GKS, and amylase as well as down-regulation of SST were detected in treated EBs. In addition, higher expression of BMP-2/-4 and their receptor (BMPR1A) were also found in these EBs. Recombinant human BMP-2 (rhBMP-2) mimicked the effects of the HMEC-CM on EBs. Noggin (NOG), a BMP antagonist, partially inhibited these effects. These results indicate that the differentiation of EBs to pancreatic progenitors and insulin-producing cells can be enhanced by ECs in vitro and that BMP pathway activation is central to this process