Synthesis, X-ray structure determination and germination studies on some smoke-derived karrikins

AbstractThe discovery of the karrikin class of plant growth regulators (PGRs) is a milestone accomplishment in plant biochemistry and physiology, with significant potential in agriculture and horticulture. These compounds have in common a fused furano-pyran ring system featuring various permutations of methyl substitution. Chief amongst these compounds is karrikinolide (KAR1), identified as the key germination stimulant present in plant-derived smoke, which together with five other closely-related structures (KAR2–KAR6) make up the karrikin class of PGRs. By contrast, the germination inhibitor 3,4,5-trimethyl-2(5H)-furanone has also been identified in plant-derived smoke. Various synthetic endeavours have been undertaken for structure–activity relationship study purposes as well as to probe the molecular mechanics of these compounds. In this study, syntheses of KAR1, KAR3 and S-KAR1 were carried out and their structures verified by X-ray crystallography. Effects on germination were measured against the inhibitor 3,4,5-trimethyl-2(5H)-furanone in Grand Rapids lettuce seeds. X-ray crystallographic data and germination promotory activity for S-KAR1 are described for the first time

Thermal history of the string universe

Thermal history of the string universe based on the Brandenberger and Vafa's scenario is examined. The analysis thereby provides a theoretical foundation of the string universe scenario. Especially the picture of the initial oscillating phase is shown to be natural from the thermodynamical point of view. A new tool is employed to evaluate the multi state density of the string gas. This analysis points out that the well-known functional form of the multi state density is not applicable for the important region $T \leq T_H$, and derives a correct form of it.Comment: 39 pages, no figures, use revtex.sty, aps.sty, aps10.sty & preprint.st

Time-Space Noncommutativity in Gravitational Quantum Well scenario

A novel approach to the analysis of the gravitational well problem from a second quantised description has been discussed. The second quantised formalism enables us to study the effect of time space noncommutativity in the gravitational well scenario which is hitherto unavailable in the literature. The corresponding first quantized theory reveals a leading order perturbation term of noncommutative origin. Latest experimental findings are used to estimate an upper bound on the time--space noncommutative parameter. Our results are found to be consistent with the order of magnitude estimations of other NC parameters reported earlier.Comment: 7 pages, revTe

Genetic associations of psoriasis in a Pakistani population

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99639/1/bjd12313.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99639/2/bjd12313-sup-0001-TableS1-S2.pd

Determine Optimal Stimulus Amplitude for Using Vestibular Stochastic Stimulation to Improve Balance Function

Sensorimotor changes such as postural and gait instabilities can affect the functional performance of astronauts when they transition across different gravity environments. We are developing a method, based on stochastic resonance (SR), to enhance information transfer by applying non-zero levels of external noise on the vestibular system (vestibular stochastic resonance, VSR). Our previous work has shown the advantageous effects of VSR in a balance task of standing on an unstable surface [1]. This technique to improve detection of vestibular signals uses a stimulus delivery system that provides imperceptibly low levels of white noise-based binaural bipolar electrical stimulation of the vestibular system. The goal of this project is to determine optimal levels of stimulation for SR applications by using a defined vestibular threshold of motion detection. A series of experiments were carried out to determine a robust paradigm to identify a vestibular threshold that can then be used to recommend optimal stimulation levels for sensorimotor adaptability (SA) training applications customized to each crewmember. The amplitude of stimulation to be used in the VSR application has varied across studies in the literature such as 60% of nociceptive stimulus thresholds [2]. We compared subjects' perceptual threshold with that obtained from two measures of body sway. Each test session was 463s long and consisted of several 15s long sinusoidal stimuli, at different current amplitudes (0-2 mA), interspersed with 20-20.5s periods of no stimulation. Subjects sat on a chair with their eyes closed and had to report their perception of motion through a joystick. A force plate underneath the chair recorded medio-lateral shear forces and roll moments. Comparison of threshold of motion detection obtained from joystick data versus body sway suggests that perceptual thresholds were significantly lower. In the balance task, subjects stood on an unstable surface and had to maintain balance, and the stimulation was administered from 20-400% of subjects' vestibular threshold. Optimal stimulation amplitude was determined at which the balance performance was best compared to control (no stimulation). Preliminary results show that, in general, using stimulation amplitudes at 40-60% of perceptual motion threshold significantly improved the balance performance. We hypothesize that VSR stimulation will act synergistically with SA training to improve adaptability by increasing utilization of vestibular information and therefore will help us to optimize and personalize a SA countermeasure prescription. This combination may help to significantly reduce the number of days required to recover functional performance to preflight levels after long-duration spaceflight

Gravitational Lensing at Millimeter Wavelengths

With today's millimeter and submillimeter instruments observers use gravitational lensing mostly as a tool to boost the sensitivity when observing distant objects. This is evident through the dominance of gravitationally lensed objects among those detected in CO rotational lines at z>1. It is also evident in the use of lensing magnification by galaxy clusters in order to reach faint submm/mm continuum sources. There are, however, a few cases where millimeter lines have been directly involved in understanding lensing configurations. Future mm/submm instruments, such as the ALMA interferometer, will have both the sensitivity and the angular resolution to allow detailed observations of gravitational lenses. The almost constant sensitivity to dust emission over the redshift range z=1-10 means that the likelihood for strong lensing of dust continuum sources is much higher than for optically selected sources. A large number of new strong lenses are therefore likely to be discovered with ALMA, allowing a direct assessment of cosmological parameters through lens statistics. Combined with an angular resolution <0.1", ALMA will also be efficient for probing the gravitational potential of galaxy clusters, where we will be able to study both the sources and the lenses themselves, free of obscuration and extinction corrections, derive rotation curves for the lenses, their orientation and, thus, greatly constrain lens models.Comment: 69 pages, Review on quasar lensing. Part of a LNP Topical Volume on "Dark matter and gravitational lensing", eds. F. Courbin, D. Minniti. To be published by Springer-Verlag 2002. Paper with full resolution figures can be found at ftp://oden.oso.chalmers.se/pub/tommy/mmviews.ps.g

A deep cut ellipsoid algorithm for convex programming

This paper proposes a deep cut version of the ellipsoid algorithm for solving a general class of continuous convex programming problems. In each step the algorithm does not require more computational effort to construct these deep cuts than its corresponding central cut version. Rules that prevent some of the numerical instabilities and theoretical drawbacks usually associated with the algorithm are also provided. Moreover, for a large class of convex programs a simple proof of its rate of convergence is given and the relation with previously known results is discussed. Finally some computational results of the deep and central cut version of the algorithm applied to a min—max stochastic queue location problem are reported

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Widespread aberrant alternative splicing despite molecular remission in chronic myeloid leukaemia patients

Vast transcriptomics and epigenomics changes are characteristic of human cancers, including leukaemia. At remission, we assume that these changes normalise so that omics-profiles resemble those of healthy individuals. However, an in-depth transcriptomic and epigenomic analysis of cancer remission has not been undertaken. A striking exemplar of targeted remission induction occurs in chronic myeloid leukaemia (CML) following tyrosine kinase inhibitor (TKI) therapy. Using RNA sequencing and whole-genome bisulfite sequencing, we profiled samples from chronic-phase CML patients at diagnosis and remission and compared these to healthy donors. Remarkably, our analyses revealed that abnormal splicing distinguishes remission samples from normal controls. This phenomenon is independent of the TKI drug used and in striking contrast to the normalisation of gene expression and DNA methylation patterns. Most remarkable are the high intron retention (IR) levels that even exceed those observed in the diagnosis samples. Increased IR affects cell cycle regulators at diagnosis and splicing regulators at remission. We show that aberrant splicing in CML is associated with reduced expression of specific splicing factors, histone modifications and reduced DNA methylation. Our results provide novel insights into the changing transcriptomic and epigenomic landscapes of CML patients during remission. The conceptually unanticipated observation of widespread aberrant alternative splicing after remission induction warrants further exploration. These results have broad implications for studying CML relapse and treating minimal residual disease.Ulf Schmitz, Jaynish S. Shah, Bijay P. Dhungel, Geoffray Monteuuis, Phuc-Loi Luu, Veronika Petrova, Cynthia Metierre, Shalima S. Nair, Charles G. Bailey, Verity A. Saunders, Ali G. Turhan, Deborah L. White, Susan Branford, Susan J. Clark, Timothy P. Hughes, Justin J.-L. Wong, and John E.J. Rask

Genome-wide asociation analysis identifies three psoriasis susceptibility loci

We carried out a meta-analysis of two recent psoriasis genome-wide asociation studies with a combined discovery sample of 1,831 affected individuals (cases) and 2,546 controls. One hundred and two loci selected based on P value rankings were foLowed up in a thrE-stage replication study including 4,064 cases and 4,685 controls from Michigan, Toronto, Newfoundland and Germany. In the combined meta-analysis, we identified thrE new susceptibility loci, including one at NOS2 (rs4795067, combined P = 4-10-11), one at FBXL19 (rs10782001, combined P = 9-10-10) and one near PSMA6-NFKBIA (rs12586317, combined P = 2-10-8). AL thrE loci were also aSociated with psoriatic arthritis (rs4795067, combined P = 1-10-5; rs10782001, combined P = 4-10-8; and rs12586317, combined P = 6-10-5) and purely cutaneous psoriasis (rs4795067, combined P = 1-10-8; rs10782001, combined P = 2-10-6; and rs12586317, combined P = 1-10-6). We also replicated a recently identified asociation signal near RNF114 (rs495337, combined P = 2-10-7)