Inflation with Non-minimal Gravitational Couplings and Supergravity

We explore in the supergravity context the possibility that a Higgs scalar may drive inflation via a non-minimal coupling to gravity characterised by a large dimensionless coupling constant. We find that this scenario is not compatible with the MSSM, but that adding a singlet field (NMSSM, or a variant thereof) can very naturally give rise to slow-roll inflation. The inflaton is necessarily contained in the doublet Higgs sector and occurs in the D-flat direction of the two Higgs doublets.Comment: 13 pages, 1 figur

On Inflation with Non-minimal Coupling

A simple realization of inflation consists of adding the following operators to the Einstein-Hilbert action: (partial phi)^2, lambda phi^4, and xi phi^2 R, with xi a large non-minimal coupling. Recently there has been much discussion as to whether such theories make sense quantum mechanically and if the inflaton phi can also be the Standard Model Higgs. In this note we answer these questions. Firstly, for a single scalar phi, we show that the quantum field theory is well behaved in the pure gravity and kinetic sectors, since the quantum generated corrections are small. However, the theory likely breaks down at ~ m_pl / xi due to scattering provided by the self-interacting potential lambda phi^4. Secondly, we show that the theory changes for multiple scalars phi with non-minimal coupling xi phi dot phi R, since this introduces qualitatively new interactions which manifestly generate large quantum corrections even in the gravity and kinetic sectors, spoiling the theory for energies > m_pl / xi. Since the Higgs doublet of the Standard Model includes the Higgs boson and 3 Goldstone bosons, it falls into the latter category and therefore its validity is manifestly spoiled. We show that these conclusions hold in both the Jordan and Einstein frames and describe an intuitive analogy in the form of the pion Lagrangian. We also examine the recent claim that curvature-squared inflation models fail quantum mechanically. Our work appears to go beyond the recent discussions.Comment: 14 pages, 2 figures. Version 2: Clarified findings and improved wording. Elaborated important sections and removed an unnecessary section. Added references. Version 3: Updated towards JHEP version. Version 4: Final JHEP versio

Comment on Higgs Inflation and Naturalness

We rebut the recent claim (arXiv:0912.5463) that Einstein-frame scattering in the Higgs inflation model is unitary above the cut-off energy Lambda ~ Mp/xi. We show explicitly how unitarity problems arise in both the Einstein and Jordan frames of the theory. In a covariant gauge they arise from non-minimal Higgs self-couplings, which cannot be removed by field redefinitions because the target space is not flat. In unitary gauge, where there is only a single scalar which can be redefined to achieve canonical kinetic terms, the unitarity problems arise through non-minimal Higgs-gauge couplings.Comment: 5 pages, 1 figure V3: Journal Versio

Rare coding SNP in DZIP1 gene associated with late-onset sporadic Parkinson's disease

We present the first application of the hypothesis-rich mathematical theory to genome-wide association data. The Hamza et al. late-onset sporadic Parkinson's disease genome-wide association study dataset was analyzed. We found a rare, coding, non-synonymous SNP variant in the gene DZIP1 that confers increased susceptibility to Parkinson's disease. The association of DZIP1 with Parkinson's disease is consistent with a Parkinson's disease stem-cell ageing theory.Comment: 14 page

Inflation and dark matter in two Higgs doublet models

We consider the Higgs inflation in the extension of the Standard Model with two Higgs doublets coupled to gravity non-minimally. In the presence of an approximate global U(1) symmetry in the Higgs sector, both radial and angular modes of neutral Higgs bosons drive inflation where large non-Gaussianity is possible from appropriate initial conditions on the angular mode. We also discuss the case with single-field inflation for which the U(1) symmetry is broken to a Z_2 subgroup. We show that inflationary constraints, perturbativity and stability conditions restrict the parameter space of the Higgs quartic couplings at low energy in both multi- and single-field cases. Focusing on the inert doublet models where Z_2 symmetry remains unbroken at low energy, we show that the extra neutral Higgs boson can be a dark matter candidate consistent with the inflationary constraints. The doublet dark matter is always heavy in multi-field inflation while it can be light due to the suppression of the co-annihilation in single-field inflation. The implication of the extra quartic couplings on the vacuum stability bound is also discussed in the light of the recent LHC limits on the Higgs mass.Comment: (v1) 28 pages, 8 figures; (v2) 29 pages, a new subsection 3.3 added, references added and typos corrected, to appear in Journal of High Energy Physic

First aid in acute stroke: Introducing a concept of first action to laypersons

OBJECTIVE: First aid training is well established to teach the public how to recognize a medical emergency and take appropriate action. Though it is now handled as a high priority emergency stroke is not among the main topics of first aid. We investigated if first aid training may be useful for enhancing stroke awareness. METHODS: We developed a 15–20 minute teaching session about stroke as an emergency including signs and symptoms and first hands-on measures. The session was integrated in standard first aid training of the St John Ambulance of Germany and participants were asked to fill out a questionnaire regarding their knowledge about stroke. Subjects were questioned before the stroke lesson and again at the end of the training. RESULTS: 532 participants of the training responded to the questionnaire (mean age 28.6 years, 53.6% male). There was a significant increase in proportion of subjects correctly defining what stroke is (28.4% vs. 69.9%, p < 0,001) and in the mean number of stroke symptoms listed (1.52 vs. 3.35, p < 0,001) by the participants. The number of participants unable to list at least 1 symptom decreased significantly (12.8 vs. 3.6%, p<0.001). CONCLUSIONS: In our study a teaching lesson integrated in first aid training was effective in improving stroke knowledge of participants. First aid training should be used for stroke information complementary to other activities like mass media campaigns as it is effective, could reach younger people that are not primarily interested in stroke and provides connections to other health topics

Metabolic investigation of host/pathogen interaction using MS2-infected Escherichia coli

<p>Abstract</p> <p>Background</p> <p>RNA viruses are responsible for a variety of illnesses among people, including but not limited to the common cold, the flu, HIV, and ebola. Developing new drugs and new strategies for treating diseases caused by these viruses can be an expensive and time-consuming process. Mathematical modeling may be used to elucidate host-pathogen interactions and highlight potential targets for drug development, as well providing the basis for optimizing patient treatment strategies. The purpose of this work was to determine whether a genome-scale modeling approach could be used to understand how metabolism is impacted by the host-pathogen interaction during a viral infection. <it>Escherichia coli</it>/MS2 was used as the host-pathogen model system as MS2 is easy to work with, harmless to humans, but shares many features with eukaryotic viruses. In addition, the genome-scale metabolic model of <it>E. coli </it>is the most comprehensive model at this time.</p> <p>Results</p> <p>Employing a metabolic modeling strategy known as "flux balance analysis" coupled with experimental studies, we were able to predict how viral infection would alter bacterial metabolism. Based on our simulations, we predicted that cell growth and biosynthesis of the cell wall would be halted. Furthermore, we predicted a substantial increase in metabolic activity of the pentose phosphate pathway as a means to enhance viral biosynthesis, while a break down in the citric acid cycle was predicted. Also, no changes were predicted in the glycolytic pathway.</p> <p>Conclusions</p> <p>Through our approach, we have developed a technique of modeling virus-infected host metabolism and have investigated the metabolic effects of viral infection. These studies may provide insight into how to design better drugs. They also illustrate the potential of extending such metabolic analysis to higher order organisms, including humans.</p

The pathogenic mechanism of the Mycobacterium ulcerans virulence factor, mycolactone, depends on blockade of protein translocation into the ER.

Infection with Mycobacterium ulcerans is characterised by tissue necrosis and immunosuppression due to mycolactone, the necessary and sufficient virulence factor for Buruli ulcer disease pathology. Many of its effects are known to involve down-regulation of specific proteins implicated in important cellular processes, such as immune responses and cell adhesion. We have previously shown mycolactone completely blocks the production of LPS-dependent proinflammatory mediators post-transcriptionally. Using polysome profiling we now demonstrate conclusively that mycolactone does not prevent translation of TNF, IL-6 and Cox-2 mRNAs in macrophages. Instead, it inhibits the production of these, along with nearly all other (induced and constitutive) proteins that transit through the ER. This is due to a blockade of protein translocation and subsequent degradation of aberrantly located protein. Several lines of evidence support this transformative explanation of mycolactone function. First, cellular TNF and Cox-2 can be once more detected if the action of the 26S proteasome is inhibited concurrently. Second, restored protein is found in the cytosol, indicating an inability to translocate. Third, in vitro translation assays show mycolactone prevents the translocation of TNF and other proteins into the ER. This is specific as the insertion of tail-anchored proteins into the ER is unaffected showing that the ER remains structurally intact. Fourth, metabolic labelling reveals a near-complete loss of glycosylated and secreted proteins from treated cells, whereas cytosolic proteins are unaffected. Notably, the profound lack of glycosylated and secreted protein production is apparent in a range of different disease-relevant cell types. These studies provide a new mechanism underlying mycolactone's observed pathological activities both in vitro and in vivo. Mycolactone-dependent inhibition of protein translocation into the ER not only explains the deficit of innate cytokines, but also the loss of membrane receptors, adhesion molecules and T-cell cytokines that drive the aetiology of Buruli ulcer