Studies of rotationally inelastic collisions in argon + hydrogen fluoride

In this dissertation we examine rotationally inelastic collisions involving an atom plus a diatom. We concentrate specifically on the Ar + HF system. In these investigations we employ a number of theoretical methods, including classical trajectories, quantum close-coupled calculations and semiclassical methods, to examine the differential cross sections in Ar + HF. We also investigate the effects of various sudden approximations on the scattering dynamics and the limitations of these approximations. Through this work we were able to identify a new quantum feature in rotationally inelastic scattering. By studying the time evolution of transition amplitudes (rather than probabilities) we are able to ascribe this feature to a balance between the attractive and repulsive parts of the potential energy surface governing the collision system. We propose that this feature will be a general scattering feature in systems with a potential that has substantial repulsive anisotropy and a significant attractive well. We present a classical trajectory method for direct simulation of a scattering experiment. We use this method to calculate laboratory frame differential cross sections for rotationally inelastic scattering in the Ar + HF system. We find that the results of this method are in excellent agreement with more standard approaches for the comparison of theoretical to experimental results

From non-Hermitian effective operators to large-scale no-core shell model calculations for light nuclei

No-core shell model (NCSM) calculations using ab initio effective interactions are very successful in reproducing experimental nuclear spectra. The main theoretical approach is the use of effective operators, which include correlations left out by the truncation of the model space to a numerically tractable size. We review recent applications of the effective operator approach, within a NCSM framework, to the renormalization of the nucleon-nucleon interaction, as well as scalar and tensor operators.Comment: To be submited to J. Phys. A, special issue on "The Physics of Non-Hermitian Operators

Smoothed Particle Hydrodynamics Simulations of Apsidal and Nodal Superhumps

In recent years a handful of systems have been observed to show "negative" (nodal) superhumps, with periods slightly shorter than the orbital period. It has been suggested that these modes are a consequence of the slow retrograde precession of the line of nodes in a disk tilted with respect to the orbital plane. Our simulations confirm and refine this model: they suggest a roughly axisymmetric, retrogradely-precessing, tilted disk that is driven at a period slightly less than half the orbital period as the tidal field of the orbiting secondary encounters in turn the two halves of the disk above and below the midplane. Each of these passings leads to viscous dissipation on one face of an optically-thick disk -- observers on opposite sides of the disk would each observe one brightening per orbit, but 180 degrees out of phase with each other.Comment: 11 pages. Accepted for publication in The ApJ Letter

Key ethical issues discussed at CDC-sponsored international, regional meetings to explore cultural perspectives and contexts on pandemic influenza preparedness and response

Background: Recognizing the importance of having a broad exploration of how cultural perspectives may shape thinking about ethical considerations, the Centers for Disease Control and Prevention (CDC) funded four regional meetings in Africa, Asia, Latin America, and the Eastern Mediterranean to explore these perspectives relevant to pandemic influenza preparedness and response. The meetings were attended by 168 health professionals, scientists, academics, ethicists, religious leaders, and other community members representing 40 countries in these regions. Methods: We reviewed the meeting reports, notes and stories and mapped outcomes to the key ethical challenges for pandemic influenza response described in the World Health Organization’s (WHO’s) guidance, Ethical Considerations in Developing a Public Health Response to Pandemic Influenza: transparency and public engagement, allocation of resources, social distancing, obligations to and of healthcare workers, and international collaboration. Results: The important role of transparency and public engagement were widely accepted among participants. However, there was general agreement that no “one size fits all” approach to allocating resources can address the variety of economic, cultural and other contextual factors that must be taken into account. The importance of social distancing as a tool to limit disease transmission was also recognized, but the difficulties associated with this measure were acknowledged. There was agreement that healthcare workers often have competing obligations and that government has a responsibility to assist healthcare workers in doing their job by providing appropriate training and equipment. Finally, there was agreement about the importance of international collaboration for combating global health threats. Conclusion: Although some cultural differences in the values that frame pandemic preparedness and response efforts were observed, participants generally agreed on the key ethical principles discussed in the WHO’s guidance. Most significantly the input gathered from these regional meetings pointed to the important role that procedural ethics can play in bringing people and countries together to respond to the shared health threat posed by a pandemic influenza despite the existence of cultural differences

Impact of reduction of susceptibility to SARS-CoV-2 on epidemic dynamics in four early-seeded metropolitan regions

As we enter a chronic phase of the SARS-CoV-2 pandemic, with uncontrolled infection rates in many places, relative regional susceptibilities are a critical unknown for policy planning. Tests for SARS-CoV-2 infection or antibodies are indicative but unreliable measures of exposure. Here instead, for four highly-affected countries, we determine population susceptibilities by directly comparing country-wide observed epidemic dynamics data with that of their main metropolitan regions. We find significant susceptibility reductions in the metropolitan regions as a result of earlier seeding, with a relatively longer phase of exponential growth before the introduction of public health interventions. During the post-growth phase, the lower susceptibility of these regions contributed to the decline in cases, independent of intervention effects. Forward projections indicate that non-metropolitan regions will be more affected during recurrent epidemic waves compared with the initially heavier-hit metropolitan regions. Our findings have consequences for disease forecasts and resource utilisation

MARCH6 and TRC8 facilitate the quality control of cytosolic and tail-anchored proteins.

Misfolded or damaged proteins are typically targeted for destruction by proteasome-mediated degradation, but the mammalian ubiquitin machinery involved is incompletely understood. Here, using forward genetic screens in human cells, we find that the proteasome-mediated degradation of the soluble misfolded reporter, mCherry-CL1, involves two ER-resident E3 ligases, MARCH6 and TRC8. mCherry-CL1 degradation is routed via the ER membrane and dependent on the hydrophobicity of the substrate, with complete stabilisation only observed in double knockout MARCH6/TRC8 cells. To identify a more physiological correlate, we used quantitative mass spectrometry and found that TRC8 and MARCH6 depletion altered the turnover of the tail-anchored protein heme oxygenase-1 (HO-1). These E3 ligases associate with the intramembrane cleaving signal peptide peptidase (SPP) and facilitate the degradation of HO-1 following intramembrane proteolysis. Our results highlight how ER-resident ligases may target the same substrates, but work independently of each other, to optimise the protein quality control of selected soluble and tail-anchored proteins

Proteomic analysis of embryonic Fasciola hepatica: Characterization and antigenic potential of a developmentally regulated heat shock protein

Fasciola hepatica is responsible for human disease and economic livestock loss on a global scale. We report the first post-genomic investigation of cellular proteins expressed by embryonic F. hepatica via two-dimensional electrophoresis, image analysis and tandem mass spectrometry. Antioxidant proteins and protein chaperones are prominently expressed by embryonic F. hepatica. Molecular differences between the egg and other characterized F. hepatica lifecycle stages were noted. Furthermore, proteins expressed within liver fluke eggs differ to those isolated from the well-characterized eggs of the human blood flatworm Schistosoma mansoni were revealed. Plasticity in expression of major proteins, particularly a prominently expressed 65 kDa protein cluster was seen between natural populations of embryonating F. hepatica eggs suggesting that liver fluke embryogenisis is a plastic process. Immunoblotting revealed that the abundant 65 kDa protein cluster is recognised by infection sera from three F. hepatica challenged host species. Mass spectrometry and BLAST analyses demonstrated that the 65 kDa antigen shows homology to egg antigens of other flatworm parasites, and is represented in a F. hepatica EST database constructed from adult fluke transcripts. EST clones encoding the egg antigen were re-sequenced, predicting two forms of the protein. Four clones predict a 312 aa polypeptide, three clones encode a putative 110 amino acid extension at the N-terminus which may be involved in protein secretion, although this extension was not expressed by natively extracted proteins. Consistent expression of alpha crystallin domains confirmed the protein to be a member of the alpha crystallin containing small heat shock protein (AC/sHSP) superfamily. AC/sHSPs are ubiquitous in nature, however, this is the first time a member of this protein superfamily has been described from F. hepatica. The antigenic AC/sHSP was named Fh-HSP35α based on predictions of molecular weight. Production of recombinant Fh-HSP35α reveals considerable mass discrepancy between native and recombinant proteins, although descriptions of other characterized flatworm AC/sHSPs, suggest that the native form is a dimer. Immunoblot analyses confirm that the recombinant protein is recognised by F. hepatica challenged hosts, but does not react with sera from non-infected animals. We discuss the potential of recombinant Fh-HSP35α as an egg-based diagnostic marker for liver fluke infection

A case report and genetic characterization of a massive acinic cell carcinoma of the parotid with delayed distant metastases.

We describe the presentation, management, and clinical outcome of a massive acinic cell carcinoma of the parotid gland. The primary tumor and blood underwent exome sequencing which revealed deletions in CDKN2A as well as PPP1R13B, which induces p53. A damaging nonsynonymous mutation was noted in EP300, a histone acetylase which plays a role in cellular proliferation. This study provides the first insights into the genetic underpinnings of this cancer. Future large-scale efforts will be necessary to define the mutational landscape of salivary gland malignancies to identify therapeutic targets and biomarkers of treatment failure