The Gordon-Haus effect for modified NLS solitons

Random jitter in the soliton arrival time (the Gordon-Haus effect) is analyzed for solitons being solutions of the integrable modified nonlinear Schroedinger equation. It is shown that the mean square fluctuation of the soliton position depends on the soliton parameters which can be properly adjusted to suppress the Gordon-Haus jitter.Comment: LaTeX, 7 pages, 3 figures, to be published in Europhys. Let

Varieties of sawtooth behavior in TFTR plasmas

The side-viewing soft-x-ray camera on the Tokamak Fusion Test Reactor (TFTR) has made possible the observation of several different forms of sawtooth oscillation, which can be categorized according to their position in the plasma, sequence of occurrence, and patterns of associated MHD oscillation. Some insight into the plasma conditions involved can be gained by examining the waveforms in detail, along with electron temperature profiles from electron cyclotron emission measurements

Tokamak x ray diagnostic instrumentation

Three classes of x-ray diagnostic instruments enable measurement of a variety of tokamak physics parameters from different features of the x-ray emission spectrum. (1) The soft x-ray (1 to 50 keV) pulse-height-analysis (PHA) diagnostic measures impurity concentrations from characteristic line intensities and the continuum enhancement, and measures the electron temperature from the continuum slope. (2) The Bragg x-ray crystal spectrometer (XCS) measures the ion temperature and neutral-beam-induced toroidal rotation velocity from the Doppler broadening and wavelength shift, respectively, of spectral lines of medium-Z impurity ions. Impurity charge state distributions, precise wavelengths, and inner-shell excitation and recombination rates can also be studied. X rays are diffracted and focused by a bent crystal onto a position-sensitive detector. The spectral resolving power E/..delta..E is greater than 10/sup 4/ and time resolution is 10 ms. (3) The x-ray imaging system (XIS) measures the spatial structure of rapid fluctuations (0.1 to 100 kHZ) providing information on MHD phenomena, impurity transport rates, toroidal rotation velocity, plasma position, and the electron temperature profile. It uses an array of silicon surface-barrier diodes which view different chords of the plasma through a common slot aperture and operate in current (as opposed to counting) mode. The effectiveness of shields to protect detectors from fusion-neutron radiation effects has been studied both theoretically and experimentally

Biological, clinical and population relevance of 95 loci for blood lipids.

Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD

Lung eQTLs to Help Reveal the Molecular Underpinnings of Asthma

Genome-wide association studies (GWAS) have identified loci reproducibly associated with pulmonary diseases; however, the molecular mechanism underlying these associations are largely unknown. The objectives of this study were to discover genetic variants affecting gene expression in human lung tissue, to refine susceptibility loci for asthma identified in GWAS studies, and to use the genetics of gene expression and network analyses to find key molecular drivers of asthma. We performed a genome-wide search for expression quantitative trait loci (eQTL) in 1,111 human lung samples. The lung eQTL dataset was then used to inform asthma genetic studies reported in the literature. The top ranked lung eQTLs were integrated with the GWAS on asthma reported by the GABRIEL consortium to generate a Bayesian gene expression network for discovery of novel molecular pathways underpinning asthma. We detected 17,178 cis- and 593 trans- lung eQTLs, which can be used to explore the functional consequences of loci associated with lung diseases and traits. Some strong eQTLs are also asthma susceptibility loci. For example, rs3859192 on chr17q21 is robustly associated with the mRNA levels of GSDMA (P = 3.55 × 10(-151)). The genetic-gene expression network identified the SOCS3 pathway as one of the key drivers of asthma. The eQTLs and gene networks identified in this study are powerful tools for elucidating the causal mechanisms underlying pulmonary disease. This data resource offers much-needed support to pinpoint the causal genes and characterize the molecular function of gene variants associated with lung diseases

Speech Cues Contribute to Audiovisual Spatial Integration

Speech is the most important form of human communication but ambient sounds and competing talkers often degrade its acoustics. Fortunately the brain can use visual information, especially its highly precise spatial information, to improve speech comprehension in noisy environments. Previous studies have demonstrated that audiovisual integration depends strongly on spatiotemporal factors. However, some integrative phenomena such as McGurk interference persist even with gross spatial disparities, suggesting that spatial alignment is not necessary for robust integration of audiovisual place-of-articulation cues. It is therefore unclear how speech-cues interact with audiovisual spatial integration mechanisms. Here, we combine two well established psychophysical phenomena, the McGurk effect and the ventriloquist's illusion, to explore this dependency. Our results demonstrate that conflicting spatial cues may not interfere with audiovisual integration of speech, but conflicting speech-cues can impede integration in space. This suggests a direct but asymmetrical influence between ventral ‘what’ and dorsal ‘where’ pathways

Using Combined Morphological, Allometric and Molecular Approaches to Identify Species of the Genus Raillietiella (Pentastomida)

Taxonomic studies of parasites can be severely compromised if the host species affects parasite morphology; an uncritical analysis might recognize multiple taxa simply because of phenotypically plastic responses of parasite morphology to host physiology. Pentastomids of the genus Raillietiella are endoparasitic crustaceans primarily infecting the respiratory system of carnivorous reptiles, but also recorded from bufonid anurans. The delineation of pentastomids at the generic level is clear, but the taxonomic status of many species is not. We collected raillietiellids from lungs of the invasive cane toad (Rhinella marina), the invasive Asian house gecko (Hemidactylus frenatus), and a native tree frog (Litoria caerulea) in tropical Australia, and employed a combination of genetic analyses, and traditional and novel morphological methods to clarify their identity. Conventional analyses of parasite morphology (which focus on raw values of morphological traits) revealed two discrete clusters in terms of pentastome hook size, implying two different species of pentastomes: one from toads and a tree frog (Raillietiella indica) and another from lizards (Raillietiella frenatus). However, these clusters disappeared in allometric analyses that took pentastome body size into account, suggesting that only a single pentastome taxon may be involved. Our molecular data revealed no genetic differences between parasites in toads versus lizards, confirming that there was only one species: R. frenatus. This pentastome (previously known only from lizards) clearly is also capable of maturing in anurans. Our analyses show that the morphological features used in pentastomid taxonomy change as the parasite transitions through developmental stages in the definitive host. To facilitate valid descriptions of new species of pentastomes, future taxonomic work should include both morphological measurements (incorporating quantitative measures of body size and hook bluntness) and molecular data

Molecular markers of response and toxicity to FOLFOX chemotherapy in metastatic colorectal cancer

BACKGROUND: To investigate three genetic alterations (TP53 mutation, Kras mutation and microsatellite instability (MSI)) and three polymorphisms (methylene tetrahydrofolate reductase (MTHFR) C677T, excision repair cross complementing group 1 (ERCC1)-118 and X-ray repair cross complementing group 1 (XRCC1)-399) for their ability to predict response, survival and toxicity to FOLFOX first line chemotherapy in the treatment of metastatic colorectal cancer (mCRC). METHODS: Tumour tissues from 118 mCRC patients who underwent FOLFOX treatment from three successive phase II trials were evaluated for mutations in TP53 (exons 5–8) and Kras (codons 12 and 13) and for MSI using PCR-based analysis. Genotyping for common single nucleotide polymorphisms in the MTHFR (codon 677), ERCC1 (codon 118) and XRCC1 (codon 399) genes was also carried out using PCR techniques. These genetic markers were correlated with clinical response, survival and toxicity to treatment. RESULTS: Patients with the T allele of ERCC1-118 showed significantly worse progression-free survival in univariate analysis (HR 2.62; 95 % CI 1.14–6.02; P 0.02). None of the genetic alterations or polymorphisms showed significant association with clinical response to FOLFOX. The MTHFR, ERCC1 and XRCC1 polymorphisms showed no associations with overall haematological, gastrointestinal or neurological toxicity to FOLFOX, although MTHFR 677 TT genotype patients showed a significantly higher incidence of grade 3 or 4 diarrhoea (26%) compared with CC or CT genotype patients (6%, P 0.02). CONCLUSIONS: The ERCC1-118 and MTHFR C677T polymorphisms were associated with progression and severe diarrhoea

Interpreting Metabolomic Profiles using Unbiased Pathway Models

Human disease is heterogeneous, with similar disease phenotypes resulting from distinct combinations of genetic and environmental factors. Small-molecule profiling can address disease heterogeneity by evaluating the underlying biologic state of individuals through non-invasive interrogation of plasma metabolite levels. We analyzed metabolite profiles from an oral glucose tolerance test (OGTT) in 50 individuals, 25 with normal (NGT) and 25 with impaired glucose tolerance (IGT). Our focus was to elucidate underlying biologic processes. Although we initially found little overlap between changed metabolites and preconceived definitions of metabolic pathways, the use of unbiased network approaches identified significant concerted changes. Specifically, we derived a metabolic network with edges drawn between reactant and product nodes in individual reactions and between all substrates of individual enzymes and transporters. We searched for “active modules”—regions of the metabolic network enriched for changes in metabolite levels. Active modules identified relationships among changed metabolites and highlighted the importance of specific solute carriers in metabolite profiles. Furthermore, hierarchical clustering and principal component analysis demonstrated that changed metabolites in OGTT naturally grouped according to the activities of the System A and L amino acid transporters, the osmolyte carrier SLC6A12, and the mitochondrial aspartate-glutamate transporter SLC25A13. Comparison between NGT and IGT groups supported blunted glucose- and/or insulin-stimulated activities in the IGT group. Using unbiased pathway models, we offer evidence supporting the important role of solute carriers in the physiologic response to glucose challenge and conclude that carrier activities are reflected in individual metabolite profiles of perturbation experiments. Given the involvement of transporters in human disease, metabolite profiling may contribute to improved disease classification via the interrogation of specific transporter activities

Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals

Correction: Volume53, Issue5 Page 762-762 DOI: 10.1038/s41588-021-00832-z Published MAY 2021Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequencyPeer reviewe