Seesaw Neutrino Mass and New U(1) Gauge Symmetry

The three electroweak doublet neutrinos $\nu_{e,\mu,\tau}$ of the Standard Model may acquire small seesaw masses, using either three Majorana fermion singlets $N$ or three Majorana fermion triplets $(\Sigma^+,\Sigma^0,\Sigma^-)$. It is well-known that the former accommodates the U(1) gauge symmetry $B-L$. It has also been shown some years ago that the latter supports a new $U(1)_X$ gauge symmetry. Here we study two variations of this $U(1)_X$, one for two $N$ and one $\Sigma$, the other for one $N$ and two $\Sigma$. Phenomenological consequences are discussed.Comment: 16 pages, 3 figures, LaTex, 2 eps files,text adde

A04 The role of splicing factor SRSF6 in incomplete splicing of the HTT transcript

Background Huntington’s disease (HD) is caused by an expanded CAG repeat in exon 1 of the HTT gene. In models of HD, an expanded CAG repeat in HTT causes premature termination of HTT RNA during transcription; this occurs by a process called incomplete splicing. Incompletely spliced HTT (HTTexon1) includes exon 1 of the coding region of HTT, as well as a 5’ region of intron 1, which is non-coding. HTTexon1 encodes a truncated exon 1 HTT protein, which is implicated in HD pathogenesis. Although the precise RNA processing mechanism of Httexon1 is unknown, splicing factor SRSF6 has been shown to co-precipitate with transcripts containing Htt intron 1 in HD mice. Aim To elucidate the role of splicing factor SRSF6 in incomplete splicing of Htt in HD mice. Methods Heterozygous Srsf6 knock-out (KO) mice (Srsf6±) were generated by CRISPR/Cas9. Characterisation of Srsf6± mice was undertaken by quantitative RT-PCR and western blotting. Viability of homozygous Srsf6 KO (Srsf6-/-) mice was examined by inbreeding of Srsf6± mice. To assess the modulation of incomplete splicing by decreasing SRSF6, Srsf6± mice were bred to HD knock in mice (zQ175) and tissues were analysed. Levels of Httexon1 were measured by Quantigene, a gene expression assay. Results Srsf6-/- homozygotes were embryonic lethal, limiting us to the use of Srsf6± mice only. In Srsf6± heterozygotes, Srsf6 mRNA was decreased by 50% in brain and peripheral regions, and SRSF6 protein was decreased by 70% in brain compared to wild type mice. However, heterozygosity for Srsf6 knock out did not modulate the level on incomplete splicing in zQ175 mice. Conclusion Ablation of a single Srsf6 allele did not reduce levels of incomplete splicing in HD mice and therefore, further Srsf6 knock down may be required. Accordingly, mouse embryonic fibroblasts (MEFs) have been generated and will be used to measure Httexon1 levels after further Srsf6 knockdown by RNA interference. This work is supported by the CHDI foundation

Scientists Want More Children

Scholars partly attribute the low number of women in academic science to the impact of the science career on family life. Yet, the picture of how men and women in science – at different points in the career trajectory – compare in their perceptions of this impact is incomplete. In particular, we know little about the perceptions and experiences of junior and senior scientists at top universities, institutions that have a disproportionate influence on science, science policy, and the next generation of scientists. Here we show that having fewer children than wished as a result of the science career affects the life satisfaction of science faculty and indirectly affects career satisfaction, and that young scientists (graduate students and postdoctoral fellows) who have had fewer children than wished are more likely to plan to exit science entirely. We also show that the impact of science on family life is not just a woman's problem; the effect on life satisfaction of having fewer children than desired is more pronounced for male than female faculty, with life satisfaction strongly related to career satisfaction. And, in contrast to other research, gender differences among graduate students and postdoctoral fellows disappear. Family factors impede talented young scientists of both sexes from persisting to research positions in academic science. In an era when the global competitiveness of US science is at risk, it is concerning that a significant proportion of men and women trained in the select few spots available at top US research universities are considering leaving science and that such desires to leave are related to the impact of the science career on family life. Results from our study may inform university family leave policies for science departments as well as mentoring programs in the sciences

Extensive Expression Analysis of Htt Transcripts in Brain Regions from the zQ175 HD Mouse Model Using a QuantiGene Multiplex Assay

Huntington’s disease (HD) is an inherited neurodegenerative disorder caused by a CAG repeat expansion within exon 1 of the huntingtin (HTT) gene. HTT mRNA contains 67 exons and does not always splice between exon 1 and exon 2 leading to the production of a small polyadenylated HTTexon1 transcript, and the full-length HTT mRNA has three 3′UTR isoforms. We have developed a QuantiGene multiplex panel for the simultaneous detection of all of these mouse Htt transcripts directly from tissue lysates and demonstrate that this can replace the more work-intensive Taqman qPCR assays. We have applied this to the analysis of brain regions from the zQ175 HD mouse model and wild type littermates at two months of age. We show that the incomplete splicing of Htt occurs throughout the brain and confirm that this originates from the mutant and not endogenous Htt allele. Given that HTTexon1 encodes the highly pathogenic exon 1 HTT protein, it is essential that the levels of all Htt transcripts can be monitored when evaluating HTT lowering approaches. Our QuantiGene panel will allow the rapid comparative assessment of all Htt transcripts in cell lysates and mouse tissues without the need to first extract RNA

The heat shock response, determined by QuantiGene multiplex, is impaired in HD mouse models and not caused by HSF1 reduction.

Huntington's disease (HD) is a devastating neurodegenerative disorder, caused by a CAG/polyglutamine repeat expansion, that results in the aggregation of the huntingtin protein, culminating in the deposition of inclusion bodies in HD patient brains. We have previously shown that the heat shock response becomes impaired with disease progression in mouse models of HD. The disruption of this inducible arm of the proteostasis network is likely to exacerbate the pathogenesis of this protein-folding disease. To allow a rapid and more comprehensive analysis of the heat shock response, we have developed, and validated, a 16-plex QuantiGene assay that allows the expression of Hsf1 and nine heat shock genes, to be measured directly, and simultaneously, from mouse tissue. We used this QuantiGene assay to show that, following pharmacological activation in vivo, the heat shock response impairment in tibialis anterior, brain hemispheres and striatum was comparable between zQ175 and R6/2 mice. In contrast, although a heat shock impairment could be detected in R6/2 cortex, this was not apparent in the cortex from zQ175 mice. Whilst the mechanism underlying this impairment remains unknown, our data indicated that it is not caused by a reduction in HSF1 levels, as had been reported

A multi-scale model for stresses, strains and swelling of reactor components under irradiation

Predicting strains, stresses and swelling in nuclear power plant components exposed to irradiation directly from the observed or computed defect and dislocation microstructure is a fundamental problem of fusion power plant design that has so far eluded a practical solution. We develop a model, free from parameters not accessible to direct evaluation or observation, that is able to provide estimates for irradiation-induced stresses and strains on a macroscopic scale, using information about the distribution of radiation defects produced by high-energy neutrons in the microstructure of materials. The model exploits the fact that elasticity equations involve no characteristic spatial scale, and hence admit a mathematical treatment that is an extension to that developed for the evaluation of elastic fields of defects on the nanoscale. In the analysis given below we use, as input, the radiation defect structure data derived from ab initio density functional calculations and large-scale molecular dynamics simulations of high-energy collision cascades. We show that strains, stresses and swelling can be evaluated using either integral equations, where the source function is given by the density of relaxation volumes of defects, or they can be computed from heterogeneous partial differential equations for the components of the stress tensor, where the density of body forces is proportional to the gradient of the density of relaxation volumes of defects. We perform a case study where strains and stresses are evaluated analytically and exactly, and develop a general finite element method implementation of the method, applicable to a broad range of predictive simulations of strains and stresses induced by irradiation in materials and components of any geometry in fission or fusion nuclear power plants.Peer reviewe

Prediction of Patients with Acute Cholecystitis Requiring Emergent Cholecystectomy: A Simple Score

The objective was to develop a score, to stratify patients with acute cholecystitis into high, intermediate, or low probability of gangrenous cholecystitis. The probability of gangrenous cholecystitis (score) was derived from a logistic regression of a clinical and pathological review of 245 patients undergoing urgent cholecystectomy. Sixty-eight patients had gangrenous inflammation, 132 acute, and 45 no inflammation. The score comprised of: age > 45 years (1 point), heart rate > 90 beats/min (1 point), male (2 points), Leucocytosis > 13,000/mm3 (1.5 points), and ultrasound gallbladder wall thickness > 4.5 mm (1 point). The prevalence of gangrenous cholecystitis was 13% in the low-probability (0–2 points), 33% in the intermediate-probability (2–4.5 points), and 87% in the high probability category (>4.5 points). A cutoff score of 2 identified 31 (69%) patients with no acute inflammation (PPV 90%). This scoring system can prioritize patients for emergent cholecystectomy based on their expected pathology

Gas phase potassium release from a single particle of biomass during high temperature combustion

A notable characteristic of solid biomass fuels as compared to coal is their significantly higher potassium content. Potassium influences ash deposition and corrosion mechanisms in furnaces and boilers, the effects of which may differ depending on phase transformations of potassium species in the gas phase and condensed phase. An understanding of how potassium is released from biomass fuels during the combustion process is therefore useful for plant designers and operators assessing means of avoiding or mitigating these potential problems. An experimental method is used to measure release patterns from single particles of biomass fuels using flame emission spectroscopy and a single-particle combustion rig. The experimental arrangement also allowed simultaneous thermal imaging of the combusting particle in order to determine the surface temperature. A model of the single particle combustion is presented. Using experimental data on devolatilisation and burnout times for different sized particles and the measured surface temperature profiles, the thermal and kinetic sub-models are verified. A model for potassium release is described and this is integrated to the single particle combustion model to allow prediction of the temporal patterns of release of gas-phase potassium. The modelled release patterns were compared with those observed. Good agreement between modelled and measured potassium release patterns was attained confirming that the proposed mechanisms affecting potassium release are valid