Photoassociation spectroscopy of cold calcium atoms

Photoassociation spectroscopy experiments on 40Ca atoms close to the dissociation limit 4s4s 1S0 - 4s4p 1P1 are presented. The vibronic spectrum was measured for detunings of the photoassociation laser ranging from 0.6 GHz to 68 GHz with respect to the atomic resonance. In contrast to previous measurements the rotational splitting of the vibrational lines was fully resolved. Full quantum mechanical numerical simulations of the photoassociation spectrum were performed which allowed us to put constraints on the possible range of the calcium scattering length to between 50 a_0 and 300 a_0

Plasma Metabolomics Implicate Modified Transfer RNAs and Altered Bioenergetics in the Outcome of Pulmonary Arterial Hypertension.

BACKGROUND: -Pulmonary arterial hypertension (PAH) is a heterogeneous disorder with high mortality. METHODS: -We conducted a comprehensive study of plasma metabolites using ultra-performance liquid chromatography mass-spectrometry to (1) identify patients at high risk of early death, (2) identify patients who respond well to treatment and (3) provide novel molecular insights into disease pathogenesis. RESULTS: -53 circulating metabolites distinguished well-phenotyped patients with idiopathic or heritable PAH (n=365) from healthy controls (n=121) following correction for multiple testing (p<7.3e-5) and confounding factors, including drug therapy, renal and hepatic impairment. A subset of 20/53 metabolites also discriminated PAH patients from disease controls (symptomatic patients without pulmonary hypertension, n=139). 62 metabolites were prognostic in PAH, with 36/62 independent of established prognostic markers. Increased levels of tRNA-specific modified nucleosides (N2,N2-dimethylguanosine, N1-methylinosine), TCA cycle intermediates (malate, fumarate), glutamate, fatty acid acylcarnitines, tryptophan and polyamine metabolites and decreased levels of steroids, sphingomyelins and phosphatidylcholines distinguished patients from controls. The largest differences correlated with increased risk of death and correction of several metabolites over time was associated with a better outcome. Patients who responded to calcium channel blocker therapy had metabolic profiles similar to healthy controls. CONCLUSIONS: -Metabolic profiles in PAH are strongly related to survival and should be considered part of the deep phenotypic characterisation of this disease. Our results support the investigation of targeted therapeutic strategies that seek to address the alterations in translational regulation and energy metabolism that characterize these patients

Temporal fluctuations of waves in weakly nonlinear disordered media

We consider the multiple scattering of a scalar wave in a disordered medium with a weak nonlinearity of Kerr type. The perturbation theory, developed to calculate the temporal autocorrelation function of scattered wave, fails at short correlation times. A self-consistent calculation shows that for nonlinearities exceeding a certain threshold value, the multiple-scattering speckle pattern becomes unstable and exhibits spontaneous fluctuations even in the absence of scatterer motion. The instability is due to a distributed feedback in the system "coherent wave + nonlinear disordered medium". The feedback is provided by the multiple scattering. The development of instability is independent of the sign of nonlinearity.Comment: RevTeX, 15 pages (including 5 figures), accepted for publication in Phys. Rev.

Active Brownian Particles. From Individual to Collective Stochastic Dynamics

We review theoretical models of individual motility as well as collective dynamics and pattern formation of active particles. We focus on simple models of active dynamics with a particular emphasis on nonlinear and stochastic dynamics of such self-propelled entities in the framework of statistical mechanics. Examples of such active units in complex physico-chemical and biological systems are chemically powered nano-rods, localized patterns in reaction-diffusion system, motile cells or macroscopic animals. Based on the description of individual motion of point-like active particles by stochastic differential equations, we discuss different velocity-dependent friction functions, the impact of various types of fluctuations and calculate characteristic observables such as stationary velocity distributions or diffusion coefficients. Finally, we consider not only the free and confined individual active dynamics but also different types of interaction between active particles. The resulting collective dynamical behavior of large assemblies and aggregates of active units is discussed and an overview over some recent results on spatiotemporal pattern formation in such systems is given.Comment: 161 pages, Review, Eur Phys J Special-Topics, accepte

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

Growth and mortality of coccolithophores during spring in a temperate Shelf Sea (Celtic Sea, April 2015)

Coccolithophores are key components of phytoplankton communities, exerting a critical impact on the global carbon cycle and the Earth’s climate through the production of coccoliths made of calcium carbonate (calcite) and bioactive gases. Microzooplankton grazing is an important mortality factor in coccolithophore blooms, however little is currently known regarding the mortality (or growth) rates within non-bloom populations. Measurements of coccolithophore calcite production (CP) and dilution experiments to determine microzooplankton (≤63 µm) grazing rates were made during a spring cruise (April 2015) at the Central Celtic Sea (CCS), shelf edge (CS2), and within an adjacent April bloom of the coccolithophore Emiliania huxleyi at station J2. CP at CCS ranged from 10.4 to 40.4 µmol C m−3 d−1 and peaked at the height of the spring phytoplankton bloom (peak chlorophyll-a concentrations ∼6 mg m−3). Cell normalised calcification rates declined from ∼1.7 to ∼0.2 pmol C cell−1 d−1, accompanied by a shift from a mixed coccolithophore species community to one dominated by the more lightly calcified species E. huxleyi and Calciopappus caudatus. At the CCS, coccolithophore abundance increased from 6 to 94 cells mL−1, with net growth rates ranging from 0.06 to 0.21 d−1 from the 4th to the 28th April. Estimates of intrinsic growth and grazing rates from dilution experiments, at the CCS ranged from 0.01 to 0.86 d−1 and from 0.01 to 1.32 d−1, respectively, which resulted in variable net growth rates during April. Microzooplankton grazers consumed 59 to >100% of daily calcite production at the CCS. Within the E. huxleyi bloom a maximum density of 1986 cells mL−1 was recorded, along with CP rates of 6000 µmol C m−3 d−1 and an intrinsic growth rate of 0.29 d−1, with ∼80% of daily calcite production being consumed. Our results show that microzooplankton can exert strong top-down control on both bloom and non-bloom coccolithophore populations, grazing over 60% of daily growth (and calcite production). The fate of consumed calcite is unclear, but may be lost either through dissolution in acidic food vacuoles, and subsequent release as CO2, or export to the seabed after incorporation into small faecal pellets. With such high microzooplankton-mediated mortality losses, the fate of grazed calcite is clearly a high priority research direction

Parkinson's disease age at onset genome-wide association study : Defining heritability, genetic loci, and α-synuclein mechanisms

Background Increasing evidence supports an extensive and complex genetic contribution to PD. Previous genome-wide association studies (GWAS) have shed light on the genetic basis of risk for this disease. However, the genetic determinants of PD age at onset are largely unknown. Objectives To identify the genetic determinants of PD age at onset. Methods Using genetic data of 28,568 PD cases, we performed a genome-wide association study based on PD age at onset. Results We estimated that the heritability of PD age at onset attributed to common genetic variation was similar to 0.11, lower than the overall heritability of risk for PD (similar to 0.27), likely, in part, because of the subjective nature of this measure. We found two genome-wide significant association signals, one at SNCA and the other a protein-coding variant in TMEM175, both of which are known PD risk loci and a Bonferroni-corrected significant effect at other known PD risk loci, GBA, INPP5F/BAG3, FAM47E/SCARB2, and MCCC1. Notably, SNCA, TMEM175, SCARB2, BAG3, and GBA have all been shown to be implicated in alpha-synuclein aggregation pathways. Remarkably, other well-established PD risk loci, such as GCH1 and MAPT, did not show a significant effect on age at onset of PD. Conclusions Overall, we have performed the largest age at onset of PD genome-wide association studies to date, and our results show that not all PD risk loci influence age at onset with significant differences between risk alleles for age at onset. This provides a compelling picture, both within the context of functional characterization of disease-linked genetic variability and in defining differences between risk alleles for age at onset, or frank risk for disease. (c) 2019 International Parkinson and Movement Disorder SocietyPeer reviewe

The Drosophila melanogaster Genetic Reference Panel

A major challenge of biology is understanding the relationship between molecular genetic variation and variation in quantitative traits, including fitness. This relationship determines our ability to predict phenotypes from genotypes and to understand how evolutionary forces shape variation within and between species. Previous efforts to dissect the genotype-phenotype map were based on incomplete genotypic information. Here, we describe the Drosophila melanogaster Genetic Reference Panel (DGRP), a community resource for analysis of population genomics and quantitative traits. The DGRP consists of fully sequenced inbred lines derived from a natural population. Population genomic analyses reveal reduced polymorphism in centromeric autosomal regions and the X chromosome, evidence for positive and negative selection, and rapid evolution of the X chromosome. Many variants in novel genes, most at low frequency, are associated with quantitative traits and explain a large fraction of the phenotypic variance. The DGRP facilitates genotype-phenotype mapping using the power of Drosophila genetics

Localization of the murine cholecystokinin A and B receptor genes

We have determined the chromosomal locations of the two cholecystokinin (CCK) receptor genes in the mouse. Genetic localization utilized an interspecific backcross panel formed from the cross (C57BL/6J x Mus spretus ) F 1 x Mus spretus . Genomic DNAs from 94 individuals in the backcross were analyzed by Southern hybridization with rat CCK A and CCK B receptor cDNA probes. Unique map positions were determined by haplotype analysis with 650 previously mapped loci in the mouse backcross. The CCK A receptor gene ( Cckar ) mapped to mouse Chromosome (Chr) 5, in tight linkage with the DNA marker D5Bir8 . The CCK B receptor gene ( Cckbr ) mapped to mouse Chr 7, tightly linked to the β-hemoglobin locus ( Hbb ). This localization places Cckbr in the same region as the mouse obesity mutation tubby ( tub ), which also maps near Hbb (2.4±1.4 cM). Since CCK can function as a satiety factor when administered to rodents, localization of Cckbr near the tub mutation identifies this receptor as a possible candidate gene for this obesity mutation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47021/1/335_2004_Article_BF00352408.pd