The dynamic characteristics of the mouse horizontal vestibulo-ocular and optokinetic response

In the present study the optokinetic reflex, vestibulo-ocular reflex and their interaction were investigated in the mouse, using a modified subconjunctival search coil technique. Gain of the ocular response to sinusoidal optokinetic stimulation was relatively constant for peak velocities lower than 8°/s, ranging from 0.7 to 0.8. Gain decreased proportionally to velocity for faster stimuli. The vestibulo-ocular reflex acted to produce a sinusoidal compensatory eye movement in response to sinusoidal stimuli. The phase of the eye movement with respect to head movement advanced as stimulus frequency decreased, the familiar signature of the torsion pendulum behavior of the semicircular canals. The first-order time constant of the vestibulo-ocular reflex, as measured from the eye velocity decay after a vestibular velocity step, was 660 ms. The response of the vestibulo-ocular reflex changed with stimulus amplitude, having a higher gain and smaller phase lead when stimulus amplitude was increased. As a result of this nonlinear behavior, reflex gain correlated strongly with stimulus acceleration over the 0.1-1.6 Hz frequency range. When whole body rotation was performed in the light the optokinetic and vestibular system combined to generate nearly constant response gain (approximately 0.8) and phase (approximately 0°) over the tested frequency range of 0.1-1.6 Hz. We conclude that the compensatory eye movements of the mouse are similar to those found in other afoveate mammals, but there are also significant differences, namely shorter apparent time constants of the angular VOR and stronger nonlinearities

Disk winds of B[e] supergiants

The class of B[e] supergiants is characterized by a two-component stellar wind consisting of a normal hot star wind in the polar zone and a slow and dense disk-like wind in the equatorial region. The properties of the disk wind are discussed using satellite UV spectra of stars seen edge-on, i.e. through the equatorial disk. These observations show that the disk winds are extremely slow, 50-90 km/s, i.e. a factor of about 10 slower than expected from the spectral types. Optical emission lines provide a further means to study the disk wind. This is discussed for line profiles of forbidden lines formed in the disk.Comment: 7 pages, LaTeX, 3 ps figures, uses lamuphys.sty from Springer-Verlag, to be published in the proceedings of IAU Coll. 169 "Variable and Non-spherical Stellar Winds in Luminous Hot Stars" held in Heidelberg 199

Moderation of Arabidopsis Root Stemness by CLAVATA1 and ARABIDOPSIS CRINKLY4 Receptor Kinase Complexes

SummaryBackgroundThe root system of higher plants originates from the activity of a root meristem, which comprises a group of highly specialized and long-lasting stem cells. Their maintenance and number is controlled by the quiescent center (QC) cells and by feedback signaling from differentiated cells. Root meristems may have evolved from structurally distinct shoot meristems; however, no common player acting in stemness control has been found so far.ResultsWe show that CLAVATA1 (CLV1), a key receptor kinase in shoot stemness maintenance, performs a similar but distinct role in root meristems. We report that CLV1 is signaling, activated by the peptide ligand CLAVATA3/EMBRYO SURROUNDING REGION40 (CLE40), together with the receptor kinase ARABIDOPSIS CRINKLY4 (ACR4) to restrict root stemness. Both CLV1 and ACR4 overlap in their expression domains in the distal root meristem and localize to the plasma membrane (PM) and plasmodesmata (PDs), where ACR4 preferentially accumulates. Using multiparameter fluorescence image spectroscopy (MFIS), we show that CLV1 and ACR4 can form homo- and heteromeric complexes that differ in their composition depending on their subcellular localization.ConclusionsWe hypothesize that these homo- and heteromeric complexes may differentially regulate distal root meristem maintenance. We conclude that essential components of the ancestral shoot stemness regulatory system also act in the root and that the specific interaction of CLV1 with ACR4 serves to moderate and control stemness homeostasis in the root meristem. The structural differences between these two meristem types may have necessitated this recruitment of ACR4 for signaling by CLV1

Efficacy of Dupilumab in a Phase 2 Randomized Trial of Adults With Active Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is an allergen-mediated inflammatory disease with no approved treatment in the United States. Dupilumab, a VelocImmune-derived human monoclonal antibody against the interleukin (IL) 4 receptor, inhibits IL4 and IL13 signaling. Dupilumab is effective in the treatment of allergic, atopic, and type 2 diseases, so we assessed its efficacy and safety in patients with EoE. We performed a phase 2 study of adults with active EoE (2 episodes of dysphagia/week with peak esophageal eosinophil density of 15 or more eosinophils per high-power field), from May 12, 2015, through November 9, 2016, at 14 sites. Participants were randomly assigned to groups that received weekly subcutaneous injections of dupilumab (300 mg, n = 23) or placebo (n = 24) for 12 weeks. The primary endpoint was change from baseline to week 10 in Straumann Dysphagia Instrument (SDI) patient-reported outcome (PRO) score. We also assessed histologic features of EoE (peak esophageal intraepithelial eosinophil count and EoE histologic scores), endoscopically visualized features (endoscopic reference score), esophageal distensibility, and safety. The mean SDI PRO score was 6.4 when the study began. In the dupilumab group, SDI PRO scores were reduced by a mean value of 3.0 at week 10 compared with a mean reduction of 1.3 in the placebo group (P = .0304). At week 12, dupilumab reduced the peak esophageal intraepithelial eosinophil count by a mean 86.8 eosinophils per high-power field (reduction of 107.1%; P < .0001 vs placebo), the EoE-histologic scoring system (HSS) severity score by 68.3% (P < .0001 vs placebo), and the endoscopic reference score by 1.6 (P = .0006 vs placebo). Dupilumab increased esophageal distensibility by 18% vs placebo (P < .0001). Higher proportions of patients in the dupilumab group developed injection-site erythema (35% vs 8% in the placebo group) and nasopharyngitis (17% vs 4% in the placebo group). In a phase 2 trial of patients with active EoE, dupilumab reduced dysphagia, histologic features of disease (including eosinophilic infiltration and a marker of type 2 inflammation), and abnormal endoscopic features compared with placebo. Dupilumab increased esophageal distensibility and was generally well tolerated. ClinicalTrials.gov, Number: NCT02379052

Measurement of event shape distributions and moments in e+e- -> hadrons at 91-209 GeV and a determination of alpha_s

We have studied hadronic events from e+e- annihilation data at centre-of-mass energies from 91 to 209 GeV. We present distributions of event shape observables and their moments at each energy and compare with QCD Monte Carlo models. From the event shape distributions we extract the strong coupling alpha_s and test its evolution with energy scale. The results are consistent with the running of alpha_s expected from QCD. Combining all data, the value of alpha_s(M_Z) is determined to be alpha_s(M_Z) = 0.1191 +- 0.0005 (stat.) +- 0.0010 (expt.) +- 0.0011 (hadr.) +- 0.0044 (theo.). The energy evolution of the moments is also used to determine a value of alpha_s with slightly larger errors: alpha_s(M_Z) = 0.1223 +- 0.0005 (stat.) +- 0.0014 (expt.) +- 0.0016 (hadr.) +0.0054 -0.0036 (theo.).Comment: 63 pages 26 fi

Genetic mapping of semi-polar metabolites in pepper fruits (Capsicum sp.): towards unravelling the molecular regulation of flavonoid quantitative trait loci

Untargeted LCMS profiling of semi-polar metabolites followed by metabolite quantitative trait locus (mQTL) analysis was performed in ripe pepper fruits of 113 F2 plants derived from a cross between Capsicum annuum AC1979 (no. 19) and Capsicum chinense No. 4661 Selection (no. 18). The parental accessions were selected based on their variation in fruit morphological characteristics and fruit content of some target phytonutrients. Clear segregation of fruit colour and fruit metabolite profiles was observed in the F2 population. The F2 plants formed three clusters based on their metabolite profiles. Of the total of 542 metabolites, 52 could be annotated, including a range of flavonoids, such as flavone C-glycosides, flavonol O-glycosides and naringenin chalcone, as well as several phenylpropanoids, a capsaicin analogue, fatty acid derivatives and amino acid derivatives. Interval mapping revealed 279 mQTLs in total. Two mQTL hotspots were found on chromosome 9. These two chromosomal regions regulated the relative levels of 35 and 103 metabolites, respectively. Analysis also revealed an mQTL for a capsaicin analogue, located on chromosome 7. Confirmation of flavonoid mQTLs using a set of six flavonoid candidate gene markers and their corresponding expression data (expression QTLs) indicated the Ca-MYB12 transcription factor gene on chromosome 1 and the gene encoding flavone synthase (FS-2) on chromosome 6 as likely causative genes determining the variation in naringenin chalcone and flavone C-glycosides, respectively, in this population. The combination of large-scale metabolite profiling and QTL analysis provided valuable insight into the genomic regions and genes important for the production of (secondary) metabolites in pepper fruit. This will impact breeding strategies aimed at optimising the content of specific metabolites in pepper frui

Searches for Gauge-Mediated Supersymmetry Breaking Topologies in e+e- collisions at LEP2

In gauge-mediated supersymmetry (SUSY) breaking (GMSB) models the lightest supersymmetric particle (LSP) is the gravitino and the phenomenology is driven by the nature of the next-to-lightest SUSY particle (NLSP) which is either the lightest neutralino, the stau or mass degenerate sleptons. Since the NLSP decay length is effectively unconstrained, searches for all possible lifetime and NLSP topologies predicted by GMSB models in e+e- collisions are performed on the data sample collected by OPAL at centre-of-mass energies up to 209 GeV at LEP. Results independent of the NLSP lifetime are presented for all relevant final states including direct NLSP pair-production and, for the first time, also NLSP production via cascade decays of heavier SUSY particles. None of the searches shows evidence for SUSY particle production. Cross-section limits are presented at the 95% confidence level both for direct NLSP production and for cascade decays, providing the most general, almost model independent results. These results are then interpreted in the framework of the minimal GMSB (mGMSB) model, where large areas of the accessible parameter space are excluded. In the mGMSB model, the NLSP masses are constrained to be larger than 53.5 GeV/c^2, 87.4 GeV/c^2 and 91.9 GeV/c^2 in the neutralino, stau and slepton co-NLSP scenarios, respectively. A complete scan on the parameters of the mGMSB model is performed, constraining the universal SUSY mass scale Lambda from the direct SUSY particle searches: Lambda > 40, 27, 21, 17, 15 TeV/c^2 for messenger indices N=1, 2, 3, 4, 5 respectively, for all NLSP lifetimes.Comment: 4 pages, 2 figures. To appear in Proceedings of SUSY06, the 14th International Conference on Supersymmetry and the Unification of Fundamental Interactions, UC Irvine, California, 12-17 June 200

Flavour Independent hA Search and Two Higgs Doublet Model Interpretation of Neutral Higgs Boson Searches at LEP

Upper limits on the cross-section of the pair-production process e+e- -> h0A0 assuming 100% decays into hadrons, are derived from a new search for the h0A0 -> hadrons topology, independent of the hadronic flavour of the decay products. Searches for the neutral Higgs bosons h0 and A0, are used to obtain constraints on the Type II Two Higgs Doublet Model (2HDM(11)) with no CP violation in the Higgs sector and no additional non Standard Model particles besides the five Higgs bosons. The analysis combines LEP1 and LEP2 data collected with the OPAL detctor up to the highest available centre-of-mass energies. The searches are sensitive to the h0, A0 -> qq, gg,tau+tau- and h0 -> A0A0 decay modes of the Higgs bosons. The 2HDM(II) parameter space is explored in a detailed scan. Large regions of the 2HDM(II) parameter space are excluded at the 95% CL in the (mh, mA), (mh, tanb) and (mA, tanb) planes, using both direct neutral Higgs boson searches and indirect limits derived from Standard Model high precision measurements. The region 1 lesssim mh lesssim 55 GeV and 3 lesssim mA lesssim 63 GeV is excluded at 95% CL independently of the choice of the 2HDM(II) parameters.Comment: 37 pages, 11 figures, Submitted to Eur. Phys. J.

First Measurement of Z/gamma* Production in Compton Scattering of Quasi-real Photons

We report the first observation of Z/gamma* production in Compton scattering of quasi-real photons. This is a subprocess of the reaction e+e- to e+e-Z/gamma*, where one of the final state electrons is undetected. Approximately 55 pb-1 of data collected in the year 1997 at an e+e- centre-of-mass energy of 183 GeV with the OPAL detector at LEP have been analysed. The Z/gamma* from Compton scattering has been detected in the hadronic decay channel. Within well defined kinematic bounds, we measure the product of cross-section and Z/gamma* branching ratio to hadrons to be (0.9+-0.3+-0.1) pb for events with a hadronic mass larger than 60 GeV, dominated by (e)eZ production. In the hadronic mass region between 5 GeV and 60 GeV, dominated by (e)egamma* production, this product is found to be (4.1+-1.6+-0.6) pb. Our results agree with the predictions of two Monte Carlo event generators, grc4f and PYTHIA.Comment: 18 pages, LaTeX, 5 eps figures included, submitted to Physics Letters

Development of functionally selective, small molecule agonists at kappa opioid receptors

The kappa opioid receptor (KOR) is widely expressed in the CNS and can serve as a means to modulate pain perception, stress responses, and affective reward states. Therefore, the KOR has become a prominent drug discovery target toward treating pain, depression, and drug addiction. Agonists at KOR can promote G protein coupling and βarrestin2 recruitment as well as multiple downstream signaling pathways, including ERK1/2 MAPK activation. It has been suggested that the physiological effects ofKORactivation result from different signaling cascades, with analgesia being G protein-mediated and dysphoria being mediated through βarrestin2 recruitment. Dysphoria associated with KOR activation limits the therapeutic potential in the use of KOR agonists as analgesics; therefore, it may be beneficial to develop KOR agonists that are biased toward G protein coupling and away from βarrestin2 recruitment. Here, we describe two classes of biased KOR agonists that potently activateGprotein coupling but weakly recruitβarrestin2. These potent and functionally selective small molecule compounds may prove to be useful tools for refining the therapeutic potential of KOR-directed signaling in vivo