A cyclic-di-GMP receptor required for bacterial exopolysaccharide production

Bis-(3′,5′)-cyclic-dimeric-guanosine monophosphate (c-di-GMP) has been shown to be a global regulatory molecule that modulates the reciprocal responses of bacteria to activate either virulence pathways or biofilm formation. The mechanism of c-di-GMP signal transduction, including recognition of c-di-GMP and subsequent phenotypic regulation, remain largely uncharacterized. The key components of these regulatory pathways are the various adaptor proteins (c-di-GMP receptors). There is compelling evidence suggesting that, in addition to PilZ domains, there are other unidentified c-di-GMP receptors. Here we show that the PelD protein of Pseudomonas aeruginosa is a novel c-di-GMP receptor that mediates c-di-GMP regulation of PEL polysaccharide biosynthesis. Analysis of PelD orthologues identified a number of conserved residues that are required for c-di-GMP binding as well as synthesis of the PEL polysaccharide. Secondary structure similarities of PelD to the inhibitory site of diguanylate cyclase suggest that a common fold can act as a platform to bind c-di-GMP. The combination of a c-di-GMP binding site with a variety of output signalling motifs within one protein domain provides an explanation for the specificity for different cellular responses to this regulatory dinucleotide

ISO Spectroscopy of Young Stellar Objects

Observations of gas-phase and solid-state species toward young stellar objects (YSOs) with the spectrometers on board the Infrared Space Observatory are reviewed. The excitation and abundances of the atoms and molecules are sensitive to the changing physical conditions during star-formation. In the cold outer envelopes around YSOs, interstellar ices contain a significant fraction of the heavy element abundances, in particular oxygen. Different ice phases can be distinguished, and evidence is found for heating and segregation of the ices in more evolved objects. The inner warm envelopes around YSOs are probed through absorption and emission of gas-phase molecules, including CO, CO_2, CH_4 and H_2O. An overview of the wealth of observations on gas-phase H_2O in star-forming regions is presented. Gas/solid ratios are determined, which provide information on the importance of gas-grain chemistry and high temperature gas-phase reactions. The line ratios of molecules such as H_2, CO and H_2O are powerful probes to constrain the physical parameters of the gas. Together with atomic and ionic lines such as [0 I] 63 µm, [S I] 25 µm and (Si II] 35 µm, they can also be used to distinguish between photon- and shock-heated gas. Finally, spectroscopic data on circumstellar disks around young stars are mentioned. The results are discussed in the context of the physical and chemical evolution of YSOs

CP Violation in Fermion Pair Decays of Neutral Boson Particles

We study CP violation in fermion pair decays of neutral boson particles with spin 0 or 1. We study a new asymmetry to measure CP violation in $\eta, K_L \rightarrow \mu^+\mu^-$ decays and discuss the possibility of measuring it experimentally. For the spin-1 particles case, we study CP violation in the decays of $J/\psi$ to $SU(3)$ octet baryon pairs. We show that these decays can be used to put stringent constraints on the electric dipole moments of $\Lambda$, $\Sigma$ and $\Xi$.Comment: 14p, OZ-93/22, UM-93/89, OITS 51

Magnetic Barriers and their q95 dependence at DIII-D

It is well known that externally generated resonant magnetic perturbations (RMPs) can form islands in the plasma edge. In turn, large overlapping islands generate stochastic fields, which are believed to play a role in the avoidance and suppression of edge localized modes (ELMs) at DIII-D. However, large coalescing islands can also generate, in the middle of these stochastic regions, KAM surfaces effectively acting as "barriers" against field-line dispersion and, indirectly, particle diffusion. It was predicted in [H. Ali and A. Punjabi, Plasma Phys. Control. Fusion 49 (2007), 1565-1582] that such magnetic barriers can form in piecewise analytic DIII-D plasma equilibria. In the present work, the formation of magnetic barriers at DIII-D is corroborated by field-line tracing calculations using experimentally constrained EFIT [L. Lao, et al., Nucl. Fusion 25, 1611 (1985)] DIII-D equilibria perturbed to include the vacuum field from the internal coils utilized in the experiments. According to these calculations, the occurrence and location of magnetic barriers depends on the edge safety factor q95. It was thus suggested that magnetic barriers might contribute to narrowing the edge stochastic layer and play an indirect role in the RMPs failing to control ELMs for certain values of q95. The analysis of DIII-D discharges where q95 was varied, however, does not show anti-correlation between barrier formation and ELM suppression

Kaluza-Klein Cosmology With Modified Holographic Dark Energy

We investigate the compact Kaluza-Klein cosmology in which modified holographic dark energy is interacting with dark matter. Using this scenario, we evaluate equation of state parameter as well as equation of evolution of the modified holographic dark energy. Further, it is shown that the generalized second law of thermodynamics holds without any constraint.Comment: 13 pages, accepted for publication in Gen. Relativ. Gravi

Cervical Artery Dissection in Young Adults in the Stroke in Young Fabry Patients (sifap1) Study

Background: Patients with carotid artery dissection (CAD) have been reported to have different vascular risk factor profiles and clinical outcomes to those with vertebral artery dissection (VAD). However, there are limited data from recent, large international studies comparing risk factors and clinical features in patients with cervical artery dissection (CeAD) with other TIA or ischemic stroke (IS) patients of similar age and sex. Methods: We analysed demographic, clinical and risk factor profiles in TIA and IS patients ≤55 years of age with and without CeAD in the large European, multi-centre, Stroke In young FAbry Patients 1 (sifap1) study. Patients were further categorised according to age (younger: 18-44 years; middle-aged: 45-55 years), sex, and site of dissection. Results: Data on the presence of dissection were available in 4,208 TIA and IS patients of whom 439 (10.4%) had CeAD: 196 (50.1%) had CAD, 195 (49.9%) had VAD, and 48 had multiple artery dissections or no information regarding the dissected artery. The prevalence of CAD was higher in women than in men (5.9 vs. 3.8%, p < 0.01), whereas the prevalence of VAD was similar in women and men (4.6 vs. 4.7%, n.s.). Patients with VAD were younger than patients with CAD (median = 41 years (IQR = 35-47 years) versus median = 45 years (IQR = 39-49 years); p < 0.01). At stroke onset, about twice as many patients with either CAD (54.0 vs. 23.1%, p < 0.001) or VAD (63.4 vs. 36.6%, p < 0.001) had headache than patients without CeAD and stroke in the anterior or posterior circulation, respectively. Compared to patients without CeAD, hypertension, concomitant cardiovascular diseases and a patent foramen ovale were significantly less prevalent in both CAD and VAD patients, whereas tobacco smoking, physical inactivity, obesity and a family history of cerebrovascular diseases were found less frequently in CAD patients, but not in VAD patients. A history of migraine was observed at a similar frequency in patients with CAD (31%), VAD (27.8%) and in those without CeAD (25.8%). Conclusions: We identified clinical features and risk factor profiles that are specific to young patients with CeAD, and to subgroups with either CAD or VAD compared to patients without CeAD. Therefore, our data support the concept that certain vascular risk factors differentially affect the risk of CAD and VAD

Measurements of Direct CP Violation, CPT Symmetry, and Other Parameters in the Neutral Kaon System

We present a series of measurements based on K -> pi+pi- and K -> pi0pi0 decays collected in 1996-1997 by the KTeV experiment (E832) at Fermilab. We compare these four K -> pipi decay rates to measure the direct CP violation parameter Re(e'/e) = (20.7 +- 2.8) x 10^-4. We also test CPT symmetry by measuring the relative phase between the CP violating and CP conserving decay amplitudes for K->pi+pi- (phi+-) and for K -> pi0pi0 (phi00). We find the difference between the relative phases to be Delta-phi = phi00 - phi+- = (+0.39 +- 0.50) degrees and the deviation of phi+- from the superweak phase to be phi+- - phi_SW =(+0.61 +- 1.19) degrees; both results are consistent with CPT symmetry. In addition, we present new measurements of the KL-KS mass difference and KS lifetime: Delta-m = (5261 +- 15) x 10^6 hbar/s and tauS = (89.65 +- 0.07) x 10^-12 s.Comment: Submitted to Phys. Rev. D, August 6, 2002; 37 pages, 32 figure

Innovative solutions to novel drug development in mental health

There are many new advances in neuroscience and mental health which should lead to a greater understanding of the neurobiological dysfunction in neuropsychiatric disorders and new developments for early, effective treatments. To do this, a biomarker approach combining genetic, neuroimaging, cognitive and other biological measures is needed. The aim of this article is to highlight novel approaches for pharmacological and non-pharmacological treatment development. This article suggests approaches that can be taken in the future including novel mechanisms with preliminary clinical validation to provide a toolbox for mechanistic studies and also examples of translation and back-translation. The review also emphasizes the need for clinician-scientists to be trained in a novel way in order to equip them with the conceptual and experimental techniques required, and emphasizes the need for private-public partnership and pre-competitive knowledge exchange. This should lead the way for important new holistic treatment developments to improve cognition, functional outcome and well-being of people with neuropsychiatric disorders