489 research outputs found

    Cyclooctatrieneium Dicarbonium Ion

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    The peculiar group of chemical molecules termed aromatic have had particular significance in all fields of chemistry because of the unusual reactions they undergo. These reactions occur because of the additional stabilization energy that these molecules possess. This stability arises from the arrangement of delocalized π - electrons in the molecules

    An Approach to Teaching Object-Oriented Analysis and Design

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    This paper presents a syllabus that attempts to address the problem of teaching systems analysis and design in the changing world of today. In the first part of the paper, major issues and constraints that affect the development of a syllabus for this discipline are identified and analyzed. The second part of the paper focuses on the key points of a methodology constructed from traditional and object-oriented techniques, designed to satisfy the academic demands of the subject and reflect current practice, while providing students with a coherent and organized approach to systems analysis and design. Analysis of the outcomes and experience of implementing the syllabus provide the basis for conclusions and identification of possible areas for future research

    Hypophosphatasia: Upcoming Treatments.

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    Evolving a DSL implementation

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    Domain Specific Languages (DSLs) are small languages designed for use in a specific domain. DSLs typically evolve quite radically throughout their lifetime, but current DSL implementation approaches are often clumsy in the face of such evolution. In this paper I present a case study of an DSL evolving in its syntax, semantics, and robustness, implemented in the Converge language. This shows how real-world DSL implementations can evolve along with changing requirements

    Increased heterozygosity in low-pass sequencing data allows identification of blood chimeras in cattle.

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    In about 90% of multiple pregnancies in cattle, shared blood circulation between fetuses leads to genetic chimerism in peripheral blood and can reduce reproductive performance in heterosexual co-twins. However, the early detection of heterosexual chimeras requires specialized tests. Here, we used low-pass sequencing data with a median coverage of 0.64× generated from blood samples of 322 F1 crosses between beef and dairy cattle and identified 20 putative blood chimeras through increased levels of genome-wide heterozygosity. In contrast, for 77 samples with routine SNP microarray data generated from hair bulbs of the same F1s, we found no evidence of chimerism, simultaneously observing high levels of genotype discordance with sequencing data. Fifteen out of 18 reported twins showed signs of blood chimerism, in line with previous reports, whereas the presence of five alleged singletons with strong signs of chimerism suggests that the in-utero death rate of co-twins is at the upper limit of former estimates. Together, our results show that low-pass sequencing data allow reliable screening for blood chimeras. They further affirm that blood is not recommended as a source of DNA for the detection of germline variants

    Four novel candidate causal variants for deficient homozygous haplotypes in Holstein cattle.

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    Mendelian variants can determine both insemination success and neonatal survival and thus influence fertility and rearing success of cattle. We present 24 deficient homozygous haplotype regions in the Holstein population of Switzerland and provide an overview of the previously identified haplotypes in the global Holstein breed. This study encompasses massive genotyping, whole-genome sequencing (WGS) and phenotype association analyses. We performed haplotype screenings on almost 53 thousand genotyped animals including 114 k SNP data with two different approaches. We revealed significant haplotype associations to several survival, birth and fertility traits. Within haplotype regions, we mined WGS data of hundreds of bovine genomes for candidate causal variants, which were subsequently evaluated by using a custom genotyping array in several thousand breeding animals. With this approach, we confirmed the known deleterious SMC2:p.Phe1135Ser missense variant associated with Holstein haplotype (HH) 3. For two previously reported deficient homozygous haplotypes that show negative associations to female fertility traits, we propose candidate causative loss-of-function variants: the HH13-related KIR2DS1:p.Gln159* nonsense variant and the HH21-related NOTCH3:p.Cys44del deletion. In addition, we propose the RIOX1:p.Ala133_Glu142del deletion as well as the PCDH15:p.Leu867Val missense variant to explain the unexpected low number of homozygous haplotype carriers for HH25 and HH35, respectively. In conclusion, we demonstrate that with mining massive SNP data in combination with WGS data, we can map several haplotype regions and unravel novel recessive protein-changing variants segregating at frequencies of 1 to 5%. Our findings both confirm previously identified loci and expand the spectrum of undesired alleles impairing reproduction success in Holstein cattle, the world's most important dairy breed

    Milk iron content in breast-feeding mothers after administration of intravenous iron sucrose complex

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    Objective: To study the transfer of parenteral iron sucrose into maternal milk in the postpartum period. Study design: Ten healthy lactating mothers with functional iron deficiency 2-3days after delivery received 100mg intravenous iron sucrose and were observed together with a control group (n=5) without iron treatment during four days. Milk samples were taken before the treatment and every day afterwards. Results: Mean milk iron levels at baseline were 0.43 and 0.46mg/kg in the treatment and control group and decreased until the end of observation in both groups by 0.11mg/kg. No significant difference between the groups was found on any study day as well as in the mean change from baseline over all four days. Conclusion: We could not show transfer of iron-sucorose into maternal milk for the given dosage. Since parenteral iron sucrose is widely used in obstetrics, the results provide information about safety of parenteral iron sucrose in the lactation period. The findings are also in agreement with other reports on active biological mammary gland regulation of milk iron concentratio

    Mining massive genomic data of two Swiss Braunvieh cattle populations reveals six novel candidate variants that impair reproductive success

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    Background: This study was carried out on the two Braunvieh populations reared in Switzerland, the dairy Brown Swiss (BS) and the dual-purpose Original Braunvieh (OB). We performed a genome-wide analysis of array data of trios (sire, dam, and offspring) from the routine genomic selection to identify candidate regions showing missing homozygosity and phenotypic associations with five fertility, ten birth, and nine growth-related traits. In addition, genome-wide single SNP regression studies based on 114,890 single nucleotide polymorphisms (SNPs) for each of the two populations were performed. Furthermore, whole-genome sequencing data of 430 cattle including 70 putative haplotype carriers were mined to identify potential candidate variants that were validated by genotyping the current population using a custom array. Results: Using a trio-based approach, we identified 38 haplotype regions for BS and five for OB that segregated at low to moderate frequencies. For the BS population, we confirmed two known haplotypes, BH1 and BH2. Twenty-four variants that potentially explained the missing homozygosity and associated traits were detected, in addition to the previously reported TUBD1:p.His210Arg variant associated with BH2. For example, for BS we identified a stop-gain variant (p.Arg57*) in the MRPL55 gene in the haplotype region on chromosome 7. This region is associated with the ‘interval between first and last insemination’ trait in our data, and the MRPL55 gene is known to be associated with early pregnancy loss in mice. In addition, we discuss candidate missense variants in the CPT1C, MARS2, and ACSL5 genes for haplotypes mapped in BS. In OB, we highlight a haplotype region on chromosome 19, which is potentially caused by a frameshift variant (p.Lys828fs) in the LIG3 gene, which is reported to be associated with early embryonic lethality in mice. Furthermore, we propose another potential causal missense variant in the TUBGCP5 gene for a haplotype mapped in OB. Conclusions: We describe, for the first time, several haplotype regions that segregate at low to moderate frequencies and provide evidence of causality by trait associations in the two populations of Swiss Braunvieh. We propose a list of six protein-changing variants as potentially causing missing homozygosity. These variants need to be functionally validated and incorporated in the breeding program
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