Neutrino induced transitions between the ground states of the A=12 triad

Neutrino induced reactions on $^{12}$C, an ingredient of liquid scintillators, have been studied in several experiments. We show that for currently available neutrino energies, $E_{\nu} \le$ 300 MeV, calculated exclusive cross sections $^{12}$C$_{gs}(\nu,l)$$^{12}$N$_{gs}$ for both muon and electron neutrinos are essentially model independent, provided the calculations simultaneously describe the rates of several other reactions involving the same states or their isobar analogs. The calculations agree well with the measured cross sections, which can be therefore used to check the normalization of the incident neutrino spectrum and the efficiency of the detector.Comment: 9 pages REVTEX, 2 postscript figures, text and figures available at http://www.krl.caltech.edu/preprints/MAP.htm

Experimental study of the e+e- -> pi0 gamma process in the energy region sqrt(s)=0.60-0.97 GeV

Results of the study of the e+e-->pi0 gamma process with SND detector at VEPP-2M collider in the c.m.s. energy range sqrt(s)=0.60-0.97 GeV are presented. Using 36513 selected events corresponding to a total integrated luminosity of 3.4 pb^-1 the e+e-->pi0 gamma cross section was measured. The energy dependence of the cross section was analyzed in the framework of the vector meson dominance model. The data are well described by a sum of phi,omega,rho0->pi0 gamma decay contributions with measured decay probabilities: Br(omega->pi0 gamma)=(9.34+-0.15+-0.31)% and Br(rho0->pi0 gamma)=(5.15+-1.16+-0.73)*10^-4 . The rho-omega relative interference phase is phi(rho,omega}=(-10.2+-6.5+-2.5) degree

Identification of potential non-invasive biomarkers in diastrophic dysplasia.

Diastrophic dysplasia (DTD) is a recessive chondrodysplasia caused by pathogenic variants in the SLC26A2 gene encoding for a cell membrane sulfate/chloride antiporter crucial for sulfate uptake and glycosaminoglycan (GAG) sulfation. Research on a DTD animal model has suggested possible pharmacological treatment approaches. In view of future clinical trials, the identification of non-invasive biomarkers is crucial to assess the efficacy of treatments. Urinary GAG composition has been analyzed in several metabolic disorders including mucopolysaccharidoses. Moreover, the N-terminal fragment of collagen X, known as collagen X marker (CXM), is considered a real-time marker of endochondral ossification and growth velocity and was studied in individuals with achondroplasia and osteogenesis imperfecta. In this work, urinary GAG sulfation and blood CXM levels were investigated as potential biomarkers for individuals affected by DTD. Chondroitin sulfate disaccharide analysis was performed on GAGs isolated from urine by HPLC after GAG digestion with chondroitinase ABC and ACII, while CXM was assessed in dried blood spots. Results from DTD patients were compared with an age-matched control population. Undersulfation of urinary GAGs was observed in DTD patients with some relationship to the clinical severity and underlying SLC26A2 variants. Lower than normal CXM levels were observed in most patients, even if the marker did not show a clear pattern in our small patient cohort because CXM values are highly dependent on age, gender and growth velocity. In summary, both non-invasive biomarkers are promising assays targeting various aspects of the disorder including overall metabolism of sulfated GAGs and endochondral ossification

Tomato: a crop species amenable to improvement by cellular and molecular methods

Tomato is a crop plant with a relatively small DNA content per haploid genome and a well developed genetics. Plant regeneration from explants and protoplasts is feasable which led to the development of efficient transformation procedures. In view of the current data, the isolation of useful mutants at the cellular level probably will be of limited value in the genetic improvement of tomato. Protoplast fusion may lead to novel combinations of organelle and nuclear DNA (cybrids), whereas this technique also provides a means of introducing genetic information from alien species into tomato. Important developments have come from molecular approaches. Following the construction of an RFLP map, these RFLP markers can be used in tomato to tag quantitative traits bred in from related species. Both RFLP's and transposons are in the process of being used to clone desired genes for which no gene products are known. Cloned genes can be introduced and potentially improve specific properties of tomato especially those controlled by single genes. Recent results suggest that, in principle, phenotypic mutants can be created for cloned and characterized genes and will prove their value in further improving the cultivated tomato.

When do fractured media become seismically anisotropic? Some implications on quantifying fracture properties

Fractures are pervasive features within the Earth's crust and they have a significant influence on the multi-physical response of the subsurface. The presence of coherent fracture sets often leads to observable seismic anisotropy enabling seismic techniques to remotely locate and characterise fracture systems. In this study, we confirm the general scale-dependence of seismic anisotropy and provide new results specific to shear-wave splitting (SWS). We find that SWS develops under conditions when the ratio of wavelength to fracture size (λS/d) is greater than 3, where Rayleigh scattering from coherent fractures leads to an effective anisotropy such that effective medium model (EMM) theory is qualitatively valid. When 1<λS/d<3 there is a transition from Rayleigh to Mie scattering, where no effective anisotropy develops and hence the SWS measurements are unstable. When λS/d<1 we observe geometric scattering and begin to see behaviour similar to transverse isotropy. We find that seismic anisotropy is more sensitive to fracture density than fracture compliance ratio. More importantly, we observe that the transition from scattering to an effective anisotropic regime occurs over a propagation distance between 1 and 2 wavelengths depending on the fracture density and compliance ratio. The existence of a transition zone means that inversion of seismic anisotropy parameters based on EMM will be fundamentally biased. More importantly, we observe that linear slip EMM commonly used in inverting fracture properties is inconsistent with our results and leads to errors of approximately 400% in fracture spacing (equivalent to fracture density) and 60% in fracture compliance. Although EMM representations can yield reliable estimates of fracture orientation and spatial location, our results show that EMM representations will systematically fail in providing quantitatively accurate estimates of other physical fracture properties, such as fracture density and compliance. Thus more robust and accurate quantitative estimates of in situ fracture properties will require improvements to effective medium models as well as the incorporation of full-waveform inversion techniques

SPECTRA OF YOUNG GALAXIES

Invited review, Ringberg conference on "Galaxies in the Young Universe" (Sept94)Comment: 12 pages, uuencoded compressed Postscript fil

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Whole-genome sequencing in diverse subjects identifies genetic correlates of leukocyte traits: The NHLBI TOPMed program

Many common and rare variants associated with hematologic traits have been discovered through imputation on large-scale reference panels. However, the majority of genome-wide association studies (GWASs) have been conducted in Europeans, and determining causal variants has proved challenging. We performed a GWAS of total leukocyte, neutrophil, lymphocyte, monocyte, eosinophil, and basophil counts generated from 109,563,748 variants in the autosomes and the X chromosome in the Trans-Omics for Precision Medicine (TOPMed) program, which included data from 61,802 individuals of diverse ancestry. We discovered and replicated 7 leukocyte trait associations, including (1) the association between a chromosome X, pseudo-autosomal region (PAR), noncoding variant located between cytokine receptor genes (CSF2RA and CLRF2) and lower eosinophil count; and (2) associations between single variants found predominantly among African Americans at the S1PR3 (9q22.1) and HBB (11p15.4) loci and monocyte and lymphocyte counts, respectively. We further provide evidence indicating that the newly discovered eosinophil-lowering chromosome X PAR variant might be associated with reduced susceptibility to common allergic diseases such as atopic dermatitis and asthma. Additionally, we found a burden of very rare FLT3 (13q12.2) variants associated with monocyte counts. Together, these results emphasize the utility of whole-genome sequencing in diverse samples in identifying associations missed by European-ancestry-driven GWASs

Whole genome sequence analysis of platelet traits in the NHLBI Trans-Omics for Precision Medicine (TOPMed) initiative

Platelets play a key role in thrombosis and hemostasis. Platelet count (PLT) and mean platelet volume (MPV) are highly heritable quantitative traits, with hundreds of genetic signals previously identified, mostly in European ancestry populations. We here utilize whole genome sequencing (WGS) from NHLBI's Trans-Omics for Precision Medicine initiative (TOPMed) in a large multi-ethnic sample to further explore common and rare variation contributing to PLT (n = 61 200) and MPV (n = 23 485). We identified and replicated secondary signals at MPL (rs532784633) and PECAM1 (rs73345162), both more common in African ancestry populations. We also observed rare variation in Mendelian platelet-related disorder genes influencing variation in platelet traits in TOPMed cohorts (not enriched for blood disorders). For example, association of GP9 with lower PLT and higher MPV was partly driven by a pathogenic Bernard-Soulier syndrome variant (rs5030764, p.Asn61Ser), and the signals at TUBB1 and CD36 were partly driven by loss of function variants not annotated as pathogenic in ClinVar (rs199948010 and rs571975065). However, residual signal remained for these gene-based signals after adjusting for lead variants, suggesting that additional variants in Mendelian genes with impacts in general population cohorts remain to be identified. Gene-based signals were also identified at several genome-wide association study identified loci for genes not annotated for Mendelian platelet disorders (PTPRH, TET2, CHEK2), with somatic variation driving the result at TET2. These results highlight the value of WGS in populations of diverse genetic ancestry to identify novel regulatory and coding signals, even for well-studied traits like platelet traits