The Particle Spectrum of Heterotic Compactifications

Techniques are presented for computing the cohomology of stable, holomorphic vector bundles over elliptically fibered Calabi-Yau threefolds. These cohomology groups explicitly determine the spectrum of the low energy, four-dimensional theory. Generic points in vector bundle moduli space manifest an identical spectrum. However, it is shown that on subsets of moduli space of co-dimension one or higher, the spectrum can abruptly jump to many different values. Both analytic and numerical data illustrating this phenomenon are presented. This result opens the possibility of tunneling or phase transitions between different particle spectra in the same heterotic compactification. In the course of this discussion, a classification of SU(5) GUT theories within a specific context is presented.Comment: 77 pages, 3 figure

SU(4) Instantons on Calabi-Yau Threefolds with Z_2 x Z_2 Fundamental Group

Structure group SU(4) gauge vacua of both weakly and strongly coupled heterotic superstring theory compactified on torus-fibered Calabi-Yau threefolds Z with Z_2 x Z_2 fundamental group are presented. This is accomplished by constructing invariant, stable, holomorphic rank four vector bundles on the simply connected cover of Z. Such bundles can descend either to Hermite-Yang-Mills instantons on Z or to twisted gauge fields satisfying the Hermite-Yang-Mills equation corrected by a non-trivial flat B-field. It is shown that large families of such instantons satisfy the constraints imposed by particle physics phenomenology. The discrete parameter spaces of those families are presented, as well as a lower bound on the dimension of the continuous moduli of any such vacuum. In conjunction with Z_2 x Z_2 Wilson lines, these SU(4) gauge vacua can lead to standard-like models at low energy with an additional U(1)_{B-L} symmetry. This U(1)_{B-L} symmetry is very helpful in naturally suppressing nucleon decay.Comment: 68 pages, no figure

Writing in Britain and Ireland, c. 400 to c. 800

No abstract available

Systematic Review of Medicine-Related Problems in Adult Patients with Atrial Fibrillation on Direct Oral Anticoagulants

New oral anticoagulant agents continue to emerge on the market and their safety requires assessment to provide evidence of their suitability for clinical use. There-fore, we searched standard databases to summarize the English language literature on medicine-related problems (MRPs) of direct oral anticoagulants DOACs (dabigtran, rivaroxban, apixban, and edoxban) in the treatment of adults with atri-al fibrillation. Electronic databases including Medline, Embase, International Pharmaceutical Abstract (IPA), Scopus, CINAHL, the Web of Science and Cochrane were searched from 2008 through 2016 for original articles. Studies pub-lished in English reporting MRPs of DOACs in adult patients with AF were in-cluded. Seventeen studies were identified using standardized protocols, and two reviewers serially abstracted data from each article. Most articles were inconclusive on major safety end points including major bleeding. Data on major safety end points were combined with efficacy. Most studies inconsistently reported adverse drug reactions and not adverse events or medication error, and no definitions were consistent across studies. Some harmful drug effects were not assessed in studies and may have been overlooked. Little evidence is provided on MRPs of DOACs in patients with AF and, therefore, further studies are needed to establish the safety of DOACs in real-life clinical practice

Clinical impact of genomic testing in patients with suspected monogenic kidney disease

Purpose: To determine the diagnostic yield and clinical impact of exome sequencing (ES) in patients with suspected monogenic kidney disease. Methods: We performed clinically accredited singleton ES in a prospectively ascertained cohort of 204 patients assessed in multidisciplinary renal genetics clinics at four tertiary hospitals in Melbourne, Australia. Results: ES identified a molecular diagnosis in 80 (39%) patients, encompassing 35 distinct genetic disorders. Younger age at presentation was independently associated with an ES diagnosis (p < 0.001). Of those diagnosed, 31/80 (39%) had a change in their clinical diagnosis. ES diagnosis was considered to have contributed to management in 47/80 (59%), including negating the need for diagnostic renal biopsy in 10/80 (13%), changing surveillance in 35/80 (44%), and changing the treatment plan in 16/80 (20%). In cases with no change to management in the proband, the ES result had implications for the management of family members in 26/33 (79%). Cascade testing was subsequently offered to 40/80 families (50%). Conclusion: In this pragmatic pediatric and adult cohort with suspected monogenic kidney disease, ES had high diagnostic and clinical utility. Our findings, including predictors of positive diagnosis, can be used to guide clinical practice and health service design

Policy formulation and enactment: Linked up thinking?

This chapter explores the role and responsibility of teaching values through Design and Technology. It considers the values encountered through the authentic contexts and topical controversies in which Design and Technology learning tend to be located. Design and Technology education contributes to the development of young people's sensitivity to human and environmental concerns, both locally and globally. It can do much to encourage moral thinking and social responsibility in people, whether they are working as specialist technologists or thinking and acting as consumers, users or citizens. This chapter explores the influence designing and making, to meet needs, wants and desires, have on our environment, society, systems and ethics. It considers the way in which design activity not only reflects the values and beliefs of the community in which it is located, but shapes the values of the wider cultural context in which it is undertaken. The approaches to teaching and learning illustrated encourage pupils to recognise the interconnections of conflicting demands, constraints economic, aesthetic, political, environmental, ethical and moral, as well as ergonomic, technical and scientific values of designing and the consequences of the outcomes. The key intention is support teachers in embedding values based approaches into their own teaching and planning for Design and Technology learning. <br/

Vaccine Efficacy in Senescent Mice Challenged with Recombinant SARS-CoV Bearing Epidemic and Zoonotic Spike Variants

BACKGROUND: In 2003, severe acute respiratory syndrome coronavirus (SARS-CoV) was identified as the etiological agent of severe acute respiratory syndrome, a disease characterized by severe pneumonia that sometimes results in death. SARS-CoV is a zoonotic virus that crossed the species barrier, most likely originating from bats or from other species including civets, raccoon dogs, domestic cats, swine, and rodents. A SARS-CoV vaccine should confer long-term protection, especially in vulnerable senescent populations, against both the 2003 epidemic strains and zoonotic strains that may yet emerge from animal reservoirs. We report the comprehensive investigation of SARS vaccine efficacy in young and senescent mice following homologous and heterologous challenge. METHODS AND FINDINGS: Using Venezuelan equine encephalitis virus replicon particles (VRP) expressing the 2003 epidemic Urbani SARS-CoV strain spike (S) glycoprotein (VRP-S) or the nucleocapsid (N) protein from the same strain (VRP-N), we demonstrate that VRP-S, but not VRP-N vaccines provide complete short- and long-term protection against homologous strain challenge in young and senescent mice. To test VRP vaccine efficacy against a heterologous SARS-CoV, we used phylogenetic analyses, synthetic biology, and reverse genetics to construct a chimeric virus (icGDO3-S) encoding a synthetic S glycoprotein gene of the most genetically divergent human strain, GDO3, which clusters among the zoonotic SARS-CoV. icGD03-S replicated efficiently in human airway epithelial cells and in the lungs of young and senescent mice, and was highly resistant to neutralization with antisera directed against the Urbani strain. Although VRP-S vaccines provided complete short-term protection against heterologous icGD03-S challenge in young mice, only limited protection was seen in vaccinated senescent animals. VRP-N vaccines not only failed to protect from homologous or heterologous challenge, but resulted in enhanced immunopathology with eosinophilic infiltrates within the lungs of SARS-CoV–challenged mice. VRP-N–induced pathology presented at day 4, peaked around day 7, and persisted through day 14, and was likely mediated by cellular immune responses. CONCLUSIONS: This study identifies gaps and challenges in vaccine design for controlling future SARS-CoV zoonosis, especially in vulnerable elderly populations. The availability of a SARS-CoV virus bearing heterologous S glycoproteins provides a robust challenge inoculum for evaluating vaccine efficacy against zoonotic strains, the most likely source of future outbreaks