85 research outputs found
Therapy: Metformin takes a new route to clinical efficacy.
International audienceMetformin is currently the first-line treatment option for patients with type 2 diabetes mellitus, yet its mechanism of action remains uncertain. A new study reveals the important role for the activation of a duodenal AMPK-dependent neuronal pathway in the acute antihyperglycaemic effect of metformin and the inhibition of hepatic glucose production
Top-mass effects in differential Higgs production through gluon fusion at order \alpha_s^4
Effects from a finite top quark mass on differential distributions in the
Higgs+jet production cross section through gluon fusion are studied at
next-to-leading order in the strong coupling, i.e. . Terms
formally subleading in are calculated, and their influence on the
transverse momentum and rapidity distribution of the Higgs boson are evaluated.
We find that, for the differential K-factor, the heavy-top limit is valid at
the 2-3% level as long as the transverse momentum of the Higgs remains below
about 150 GeV.Comment: 21 pages, 12 figure
Dual Identities inside the Gluon and the Graviton Scattering Amplitudes
Recently, Bern, Carrasco and Johansson conjectured dual identities inside the
gluon tree scattering amplitudes. In this paper, we use the properties of the
heterotic string and open string tree scattering amplitudes to refine and
derive these dual identities. These identities can be carried over to loop
amplitudes using the unitarity method. Furthermore, given the -gluon (as
well as gluon-gluino) tree amplitudes, -graviton (as well as
graviton-gravitino) tree scattering amplitudes can be written down immediately,
avoiding the derivation of Feynman rules and the evaluation of Feynman diagrams
for graviton scattering amplitudes.Comment: 43 pages, 3 figures; typos corrected, a few points clarified
CHY representations for gauge theory and gravity amplitudes with up to three massive particles
We show that a wide class of tree-level scattering amplitudes involving
scalars, gauge bosons, and gravitons, up to three of which may be massive, can
be expressed in terms of a Cachazo-He-Yuan representation as a sum over
solutions of the scattering equations. These amplitudes, when expressed in
terms of the appropriate kinematic invariants, are independent of the masses
and therefore identical to the corresponding massless amplitudes.Comment: 20 pages, 1 figure; v2: minor typos corrected, published versio
The impact of heavy-quark loops on LHC dark matter searches
If only tree-level processes are included in the analysis, LHC monojet
searches give weak constraints on the dark matter-proton scattering cross
section arising from the exchange of a new heavy scalar or pseudoscalar
mediator with Yukawa-like couplings to quarks. In this letter we calculate the
constraints on these interactions from the CMS 5.0/fb and ATLAS 4.7/fb searches
for jets with missing energy including the effects of heavy-quark loops. We
find that the inclusion of such contributions leads to a dramatic increase in
the predicted cross section and therefore a significant improvement of the
bounds from LHC searches.Comment: 12 pages, 1 table, 3 figures, v2: extended discussion and improved
relic density calculation - matches published versio
Viral epidemics in a cell culture: novel high resolution data and their interpretation by a percolation theory based model
Because of its relevance to everyday life, the spreading of viral infections
has been of central interest in a variety of scientific communities involved in
fighting, preventing and theoretically interpreting epidemic processes. Recent
large scale observations have resulted in major discoveries concerning the
overall features of the spreading process in systems with highly mobile
susceptible units, but virtually no data are available about observations of
infection spreading for a very large number of immobile units. Here we present
the first detailed quantitative documentation of percolation-type viral
epidemics in a highly reproducible in vitro system consisting of tens of
thousands of virtually motionless cells. We use a confluent astroglial
monolayer in a Petri dish and induce productive infection in a limited number
of cells with a genetically modified herpesvirus strain. This approach allows
extreme high resolution tracking of the spatio-temporal development of the
epidemic. We show that a simple model is capable of reproducing the basic
features of our observations, i.e., the observed behaviour is likely to be
applicable to many different kinds of systems. Statistical physics inspired
approaches to our data, such as fractal dimension of the infected clusters as
well as their size distribution, seem to fit into a percolation theory based
interpretation. We suggest that our observations may be used to model epidemics
in more complex systems, which are difficult to study in isolation.Comment: To appear in PLoS ONE. Supporting material can be downloaded from
http://amur.elte.hu/BDGVirus
Metformin and the gastrointestinal tract
Metformin is an effective agent with a good safety profile that is widely used as a first-line treatment for type 2 diabetes, yet its mechanisms of action and variability in terms of efficacy and side effects remain poorly understood. Although the liver is recognised as a major site of metformin pharmacodynamics, recent evidence also implicates the gut as an important site of action. Metformin has a number of actions within the gut. It increases intestinal glucose uptake and lactate production, increases GLP-1 concentrations and the bile acid pool within the intestine, and alters the microbiome. A novel delayed-release preparation of metformin has recently been shown to improve glycaemic control to a similar extent to immediate-release metformin, but with less systemic exposure. We believe that metformin response and tolerance is intrinsically linked with the gut. This review examines the passage of metformin through the gut, and how this can affect the efficacy of metformin treatment in the individual, and contribute to the side effects associated with metformin intolerance
Endothelin-1 Inhibits Prolyl Hydroxylase Domain 2 to Activate Hypoxia-Inducible Factor-1α in Melanoma Cells
The endothelin B receptor (ET(B)R) promotes tumorigenesis and melanoma progression through activation by endothelin (ET)-1, thus representing a promising therapeutic target. The stability of hypoxia-inducible factor (HIF)-1alpha is essential for melanomagenesis and progression, and is controlled by site-specific hydroxylation carried out by HIF-prolyl hydroxylase domain (PHD) and subsequent proteosomal degradation.Here we found that in melanoma cells ET-1, ET-2, and ET-3 through ET(B)R, enhance the expression and activity of HIF-1alpha and HIF-2alpha that in turn regulate the expression of vascular endothelial growth factor (VEGF) in response to ETs or hypoxia. Under normoxic conditions, ET-1 controls HIF-alpha stability by inhibiting its degradation, as determined by impaired degradation of a reporter gene containing the HIF-1alpha oxygen-dependent degradation domain encompassing the PHD-targeted prolines. In particular, ETs through ET(B)R markedly decrease PHD2 mRNA and protein levels and promoter activity. In addition, activation of phosphatidylinositol 3-kinase (PI3K)-dependent integrin linked kinase (ILK)-AKT-mammalian target of rapamycin (mTOR) pathway is required for ET(B)R-mediated PHD2 inhibition, HIF-1alpha, HIF-2alpha, and VEGF expression. At functional level, PHD2 knockdown does not further increase ETs-induced in vitro tube formation of endothelial cells and melanoma cell invasiveness, demonstrating that these processes are regulated in a PHD2-dependent manner. In human primary and metastatic melanoma tissues as well as in cell lines, that express high levels of HIF-1alpha, ET(B)R expression is associated with low PHD2 levels. In melanoma xenografts, ET(B)R blockade by ET(B)R antagonist results in a concomitant reduction of tumor growth, angiogenesis, HIF-1alpha, and HIF-2alpha expression, and an increase in PHD2 levels.In this study we identified the underlying mechanism by which ET-1, through the regulation of PHD2, controls HIF-1alpha stability and thereby regulates angiogenesis and melanoma cell invasion. These results further indicate that targeting ET(B)R may represent a potential therapeutic treatment of melanoma by impairing HIF-1alpha stability
Higgs production via gluon fusion in the POWHEG approach in the SM and in the MSSM
We consider the gluon fusion production cross section of a scalar Higgs boson
at NLO QCD in the SM and in the MSSM. We implement the calculation in the
POWHEG approach, and match the NLO-QCD results with the PYTHIA and HERWIG QCD
parton showers. We discuss a few representative scenarios in the SM and MSSM
parameter spaces, with emphasis on the fermion and squark mass effects on the
Higgs boson distributions.Comment: 27 pages, 36 eps figures; v2: 2 eps figures added, section 3.2
expanded, version published in JHE
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