Microarray analyses demonstrate the involvement of type i interferons in psoriasiform pathology development in D6-deficient mice

The inflammatory response is normally limited by mechanisms regulating its resolution. In the absence of resolution, inflammatory pathologies can emerge, resulting in substantial morbidity and mortality. We have been studying the D6 chemokine scavenging receptor, which played an indispensable role in the resolution phase of inflammatory responses and does so by facilitating removal of inflammatory CC chemokines. In D6-deficient mice, otherwise innocuous cutaneous inflammatory stimuli induce a grossly exaggerated inflammatory response that bears many similarities to human psoriasis. In the present study, we have used transcriptomic approaches to define the molecular make up of this response. The data presented highlight potential roles for a number of cytokines in initiating and maintaining the psoriasis-like pathology. Most compellingly, we provide data indicating a key role for the type I interferon pathway in the emergence of this pathology. Neutralizing antibodies to type I interferons are able to ameliorate the psoriasis-like pathology, confirming a role in its development. Comparison of transcriptional data generated from this mouse model with equivalent data obtained from human psoriasis further demonstrates the strong similarities between the experimental and clinical systems. As such, the transcriptional data obtained in this preclinical model provide insights into the cytokine network active in exaggerated inflammatory responses and offer an excellent tool to evaluate the efficacy of compounds designed to therapeutically interfere with inflammatory processes

Prenatal development is linked to bronchial reactivity: epidemiological and animal model evidence

Chronic cardiorespiratory disease is associated with low birthweight suggesting the importance of the developmental environment. Prenatal factors affecting fetal growth are believed important, but the underlying mechanisms are unknown. The influence of developmental programming on bronchial hyperreactivity is investigated in an animal model and evidence for comparable associations is sought in humans. Pregnant Wistar rats were fed either control or protein-restricted diets throughout pregnancy. Bronchoconstrictor responses were recorded from offspring bronchial segments. Morphometric analysis of paraffin-embedded lung sections was conducted. In a human mother-child cohort ultrasound measurements of fetal growth were related to bronchial hyperreactivity, measured at age six years using methacholine. Protein-restricted rats' offspring demonstrated greater bronchoconstriction than controls. Airway structure was not altered. Children with lesser abdominal circumference growth during 11-19 weeks' gestation had greater bronchial hyperreactivity than those with more rapid abdominal growth. Imbalanced maternal nutrition during pregnancy results in offspring bronchial hyperreactivity. Prenatal environmental influences might play a comparable role in humans

The steady state quantum statistics of a non-Markovian atom laser

We present a fully quantum mechanical treatment of a single-mode atomic cavity with a pumping mechanism and an output coupling to a continuum of external modes. This system is a schematic description of an atom laser. In the dilute limit where atom-atom interactions are negligible, we have been able to solve this model without making the Born and Markov approximations. When coupling into free space, it is shown that for reasonable parameters there is a bound state which does not disperse, which means that there is no steady state. This bound state does not exist when gravity is included, and in that case the system reaches a steady state. We develop equations of motion for the two-time correlation in the presence of pumping and gravity in the output modes. We then calculate the steady-state output energy flux from the laser.Comment: 14 pages (twocloumn), 6 figure

Mode Selectivity and Stability of Continuously Pumped Atom Lasers

A semiclassical, multimode model of a continuously pumped atom laser is presented. For a spatially independent coupling process it is found that the system is unstable below a critical scattering length. As large atomic interactions will increase the phase diffusion of the lasing mode, it is desirable to obtain a stable atom laser with low nonlinearity. It is shown that spatially dependent pumping stabilizes the atom laser to a finite number of modes, and can induce single-mode operation

Granular Solid Hydrodynamics

Granular elasticity, an elasticity theory useful for calculating static stress distribution in granular media, is generalized to the dynamic case by including the plastic contribution of the strain. A complete hydrodynamic theory is derived based on the hypothesis that granular medium turns transiently elastic when deformed. This theory includes both the true and the granular temperatures, and employs a free energy expression that encapsulates a full jamming phase diagram, in the space spanned by pressure, shear stress, density and granular temperature. For the special case of stationary granular temperatures, the derived hydrodynamic theory reduces to {\em hypoplasticity}, a state-of-the-art engineering model.Comment: 42 pages 3 fi

Spinor condensates and light scattering from Bose-Einstein condensates

These notes discuss two aspects of the physics of atomic Bose-Einstein condensates: optical properties and spinor condensates. The first topic includes light scattering experiments which probe the excitations of a condensate in both the free-particle and phonon regime. At higher light intensity, a new form of superradiance and phase-coherent matter wave amplification were observed. We also discuss properties of spinor condensates and describe studies of ground--state spin domain structures and dynamical studies which revealed metastable excited states and quantum tunneling.Comment: 58 pages, 33 figures, to appear in Proceedings of Les Houches 1999 Summer School, Session LXXI

Order and Chaos in some Trigonometric Series: Curious Adventures of a Statistical Mechanic

This paper tells the story how a MAPLE-assisted quest for an interesting undergraduate problem in trigonometric series led some "amateurs" to the discovery that the one-parameter family of deterministic trigonometric series \pzcS_p: t\mapsto \sum_{n\in\Nset}\sin(n^{-{p}}t), $p>1$, exhibits both order and apparent chaos, and how this has prompted some professionals to offer their expert insights. It is proved that \pzcS_p(t) = \alpha_p\rm{sign}(t)|t|^{1/{p}}+O(|t|^{1/{(p+1)}})\;\forall\;t\in\Rset, with explicitly computed constant $\alpha_p$. Experts' commentaries are reproduced stating the fluctuations of \pzcS_p(t) - \alpha_p{\rm{sign}}(t)|t|^{1/{p}} are presumably not Gaussian. Inspired by a central limit type theorem of Marc Kac, a well-motivated conjecture is formulated to the effect that the fluctuations of the $\lceil t^{1/(p+1)}\rceil$-th partial sum of \pzcS_p(t), when properly scaled, do converge in distribution to a standard Gaussian when $t\to\infty$, though --- provided that $p$ is chosen so that the frequencies \{n^{-p}\}_{n\in\Nset} are rationally linear independent; no conjecture has been forthcoming for rationally dependent \{n^{-p}\}_{n\in\Nset}. Moreover, following other experts' tip-offs, the interesting relationship of the asymptotics of \pzcS_p(t) to properties of the Riemann $\zeta$ function is exhibited using the Mellin transform.Comment: Based on the invited lecture with the same title delivered by the author on Dec.19, 2011 at the 106th Statistical Mechanics Meeting at Rutgers University in honor of Michael Fisher, Jerry Percus, and Ben Widom. (19 figures, colors online). Comments of three referees included. Conjecture 1 revised. Accepted for publication in J. Stat. Phy

A gene variant near ATM is significantly associated with metformin treatment response In type 2 diabetes: A replication and meta-analysis of five cohorts

_Aims/hypothesis:_ In this study we aimed to replicate the previously reported association between the glycaemic response to metformin and the SNP rs11212617 at a locus that includes the ataxia telangiectasia mutated (ATM) gene in multiple additional populations. _Methods:_ Incident users of metformin selected from the Diabetes Care System West-Friesland (DCS, n=929) and the Rotterdam Study (n=182) from the Netherlands, and the CARDS Trial (n=254) from the UK were genotyped for rs11212617 and tested for an association with both HbA1c reduction and treatment success, defined as the ability to reach the treatment target of an HbA1c ≤7 % (53 mmol/mol). Finally, a meta-analysis including data from literature was performed. _Results:_ In the DCS cohort, we observed an association between rs11212617 genotype and treatment success on metformin (OR 1.27, 95% CI 1.03, 1.58, p=0.028); in the smaller Rotterdam Study cohort, a numerically similar but non-significant trend was observed (OR 1.45, 95% CI 0.87, 2.39, p=0.15); while in the CARDS cohort there was no significant association. In meta-analyses of these three cohorts separately or combined with the previously published cohorts, rs11212617 genotype is associated with metformin treatment success (OR 1.24, 95% CI 1.04, 1.49, p=0.016 and OR 1.25, 95% CI 1.33, 1.38, p=7.8×10-6, respectively). _ Conclusions/inte

Time-integrated luminosity recorded by the BABAR detector at the PEP-II e+e- collider

This article is the Preprint version of the final published artcile which can be accessed at the link below.We describe a measurement of the time-integrated luminosity of the data collected by the BABAR experiment at the PEP-II asymmetric-energy e+e- collider at the ϒ(4S), ϒ(3S), and ϒ(2S) resonances and in a continuum region below each resonance. We measure the time-integrated luminosity by counting e+e-→e+e- and (for the ϒ(4S) only) e+e-→μ+μ- candidate events, allowing additional photons in the final state. We use data-corrected simulation to determine the cross-sections and reconstruction efficiencies for these processes, as well as the major backgrounds. Due to the large cross-sections of e+e-→e+e- and e+e-→μ+μ-, the statistical uncertainties of the measurement are substantially smaller than the systematic uncertainties. The dominant systematic uncertainties are due to observed differences between data and simulation, as well as uncertainties on the cross-sections. For data collected on the ϒ(3S) and ϒ(2S) resonances, an additional uncertainty arises due to ϒ→e+e-X background. For data collected off the ϒ resonances, we estimate an additional uncertainty due to time dependent efficiency variations, which can affect the short off-resonance runs. The relative uncertainties on the luminosities of the on-resonance (off-resonance) samples are 0.43% (0.43%) for the ϒ(4S), 0.58% (0.72%) for the ϒ(3S), and 0.68% (0.88%) for the ϒ(2S).This work is supported by the US Department of Energy and National Science Foundation, the Natural Sciences and Engineering Research Council (Canada), the Commissariat à l’Energie Atomique and Institut National de Physique Nucléaire et de Physiquedes Particules (France), the Bundesministerium für Bildung und Forschung and Deutsche Forschungsgemeinschaft (Germany), the Istituto Nazionale di Fisica Nucleare (Italy), the Foundation for Fundamental Research on Matter (The Netherlands), the Research Council of Norway, the Ministry of Education and Science of the Russian Federation, Ministerio de Ciencia e Innovación (Spain), and the Science and Technology Facilities Council (United Kingdom). Individuals have received support from the Marie-Curie IEF program (European Union) and the A.P. Sloan Foundation (USA)