Evolutionary genomics of Chlamydomonas

The unicellular green alga Chlamydomonas reinhardtii is one of the primary model organisms in plant and algal biology. Although the species is fundamental to several research areas, including the study of photosynthesis, cilia and the cell cycle, very little is known about its evolutionary biology. Furthermore, C. reinhardtii research is generally limited to a single line of laboratory strains and no genomic resources exist for any closely related species. Consequently, the species has predominantly been studied in isolation, from both a population and phylogenetic perspective. In this thesis, I explore several aspects of the evolutionary genomics of C. reinhardtii and its closest relatives in the genus Chlamydomonas. I use population genomics approaches to characterise population structure across all known C. reinhardtii field isolates, presenting some of the first insights into the evolutionary ecology of the species. I use long read sequencing technology to produce highly contiguous genome assemblies for the three closest relatives of C. reinhardtii. Using these comparative resources, I describe several novel features of Chlamydomonas genomics, including the putative centromeric repeat. I present near complete reference assemblies for two laboratory strains of C. reinhardtii, characterising structural mutations that have occurred in the laboratory and revealing numerous misassemblies in previous versions. Finally, I present an exhaustively curated library of C. reinhardtii transposable elements and I describe a major new clade of retrotransposons present across the green lineage and animals. This collective work greatly expands our understanding of Chlamydomonas evolutionary genomics and is expected to be integral to the continued development of C. reinhardtii as a model for evolutionary biology research

Systematic calibration error requirements for gravitational-wave detectors via the Cramér-Rao bound

Gravitational-wave (GW) laser interferometers such as Advanced LIGO (The LIGO Scientific Collaboration 2015 Class. Quantum Grav. 32 074001) transduce spacetime strain into optical power fluctuation. Converting this optical power fluctuation back into an estimated spacetime strain requires a calibration process that accounts for both the interferometer's optomechanical response and the feedback control loop used to control the interferometer test masses. Systematic errors in the calibration parameters lead to systematic errors in the GW strain estimate, and hence to systematic errors in the astrophysical parameter estimates in a particular GW signal. In this work we examine this effect for a GW signal similar to GW150914, both for a low-power detector operation similar to the first and second Advanced LIGO observing runs and for a higher-power operation with detuned signal extraction. We set requirements on the accuracy of the calibration such that the astrophysical parameter estimation is limited by errors introduced by random detector noise, rather than calibration systematics. We also examine the impact of systematic calibration errors on the possible detection of a massive graviton

Architecture and evolution of subtelomeres in the unicellular green alga Chlamydomonas reinhardtii

International audienceIn most eukaryotes, subtelomeres are dynamic genomic regions populated by multi-copy sequences of different origins, which can promote segmental duplications and chromosomal rearrangements. However, their repetitive nature has complicated the efforts to sequence them, analyse their structure and infer how they evolved. Here, we use recent genome assemblies of Chlamydomonas reinhardtii based on long-read sequencing to comprehensively describe the subtelomere architecture of the 17 chromosomes of this model unicellular green alga. We identify three main repeated elements present at subtelomeres, which we call Sultan, Subtile and Suber, alongside three chromosome extremities with ribosomal DNA as the only identified component of their subtelomeres. The most common architecture, present in 27 out of 34 subtelomeres, is a heterochromatic array of Sultan elements adjacent to the telomere, followed by a transcribed Spacer sequence, a G-rich microsatellite and transposable elements. Sequence similarity analyses suggest that Sultan elements underwent segmental duplications within each subtelomere and rearranged between subtelomeres at a much lower frequency. Analysis of other green algae reveals species-specific repeated elements that are shared across subtelomeres, with an overall organization similar to C. reinhardtii. This work uncovers the complexity and evolution of subtelomere architecture in green algae

Predictors of mortality and disability in stroke-associated pneumonia

Whilst stroke-associated pneumonia (SAP) is common and associated with poor outcomes, less is known about the determinants of these adverse clinical outcomes in SAP. To identify the factors that influence mortality and morbidity in SAP. Data for patients with SAP (n = 854) were extracted from a regional Hospital Stroke Register in Norfolk, UK (2003-2015). SAP was defined as pneumonia occurring within 7 days of admission by the treating clinicians. Mutlivariable regression models were constructed to assess factors influencing survival and the level of disability at discharge using modified Rankin Scale [mRS]. Mean (SD) age was 83.0 (8.7) years and ischaemic stroke occurred in 727 (85.0%). Mortality was 19.0% at 30 days and 44.0% at 6 months. Stroke severity assessment using National Institutes of Health Stroke Scale was not recorded in the data set although Oxfordshire Community Stroke Project was Classification. In the multivariable analyses, 30-day mortality was independently associated with age (OR 1.04, 95% CI 1.01-1.07, p = 0.01), haemorrhagic stroke (2.27, 1.07-4.78, p = 0.03) and pre-stroke disability (mRS 4-5 v 0-1: 6.45, 3.12-13.35, p < 0.001). 6-month mortality was independently associated with age (< 0.001), pre-stroke disability (p < 0.001) and certain comorbidities, including the following: dementia (6.53, 4.73-9.03, p < 0.001), lung cancer (2.07, 1.14-3.77, p = 0.017) and previous transient ischemic attack (1.94, 1.12-3.36, p = 0.019). Disability defined by mRS at discharge was independently associated with age (1.10, 1.05-1.16, p < 0.001) and plasma C-reactive protein (1.02, 1.01-1.03, p = 0.012). We have identified non-modifiable determinants of poor prognosis in patients with SAP. Further studies are required to identify modifiable factors which may guide areas for intervention to improve the prognosis in SAP in these patients

Triamidoamine-supported zirconium: Hydrogen activation, Lewis acidity, and: Rac -lactide polymerization

Investigation of a triamidoamine-supported zirconium hydride intermediate, important to a range of catalytic reactions, revealed the potential Lewis acidity of [κ5-N,N,N,N,C-(Me3SiNCH2CH2)2NCH2CH2NSiMe2CH2]Zr (1). A preliminary study of 1 as a precursor for the polymerization of rac-lactide showed modest activity but indicated that five-coordinate zirconium complexes with tetra-N donor ligands may be an avenue for further development in group 4 metal lactide polymerization catalysis

Ground-based estimates of outer radiation belt energetic electron precipitation fluxes into the atmosphere

AARDDVARK data from a radio wave receiver in Sodankyla, Finland have been used to monitor transmissions across the auroral oval and just into the polar cap from the very low frequency communications transmitter, call sign NAA (24.0 kHz, 44 degrees N, 67 degrees W, L = 2.9), in Maine, USA, since 2004. The transmissions are influenced by outer radiation belt (L = 3-7) energetic electron precipitation. In this study, we have been able to show that the observed transmission amplitude variations can be used to determine routinely the flux of energetic electrons entering the upper atmosphere along the total path and between 30 and 90 km. Our analysis of the NAA observations shows that electron precipitation fluxes can vary by 3 orders of magnitude during geomagnetic storms. Typically when averaging over L = 3-7 we find that the >100 keV POES "trapped" fluxes peak at about 10(6) el. cm(-2) s(-1) sr(-1) during geomagnetic storms, with the DEMETER >100 keV drift loss cone showing peak fluxes of 105 el. cm(-2) s(-1) sr(-1), and both the POES >100 keV "loss" fluxes and the NAA ground-based >100 keV precipitation fluxes showing peaks of similar to 10(4) el. cm(-2) s(-1) sr(-1). During a geomagnetic storm in July 2005, there were systematic MLT variations in the fluxes observed: electron precipitation flux in the midnight sector (22-06 MLT) exceeded the fluxes from the morning side (0330-1130 MLT) and also from the afternoon sector (1130-1930 MLT). The analysis of NAA amplitude variability has the potential of providing a detailed, near real-time, picture of energetic electron precipitation fluxes from the outer radiation belts

Systematic calibration error requirements for gravitational-wave detectors via the Cramér-Rao bound

Gravitational-wave (GW) laser interferometers such as Advanced LIGO (The LIGO Scientific Collaboration 2015 Class. Quantum Grav. 32 074001) transduce spacetime strain into optical power fluctuation. Converting this optical power fluctuation back into an estimated spacetime strain requires a calibration process that accounts for both the interferometer's optomechanical response and the feedback control loop used to control the interferometer test masses. Systematic errors in the calibration parameters lead to systematic errors in the GW strain estimate, and hence to systematic errors in the astrophysical parameter estimates in a particular GW signal. In this work we examine this effect for a GW signal similar to GW150914, both for a low-power detector operation similar to the first and second Advanced LIGO observing runs and for a higher-power operation with detuned signal extraction. We set requirements on the accuracy of the calibration such that the astrophysical parameter estimation is limited by errors introduced by random detector noise, rather than calibration systematics. We also examine the impact of systematic calibration errors on the possible detection of a massive graviton

Cost-effectiveness of Simvastatin plus Ezetimibe for Cardiovascular Prevention in CKD:Results of the Study of Heart and Renal Protection (SHARP)

Background Simvastatin, 20 mg, plus ezetimibe, 10 mg, daily (simvastatin plus ezetimibe) reduced major atherosclerotic events in patients with moderate to severe chronic kidney disease (CKD) in the Study of Heart and Renal Protection (SHARP), but its cost-effectiveness is unknown. Study Design Cost-effectiveness of simvastatin plus ezetimibe in SHARP, a randomized controlled trial. Setting & Population 9,270 patients with CKD randomly assigned to simvastatin plus ezetimibe versus placebo; participants in categories by 5-year cardiovascular risk (low, = 20%) and CKD stage (3, 4, 5 not on dialysis, or on dialysis therapy). Model, Perspective, & Timeline Assessment during SHARP follow-up from the UK perspective; long-term projections. Intervention Simvastatin plus ezetimibe (2015 UK 1.19 pound per day) during 4.9 years median follow-up in SHARP; scenario analyses with high-intensity statin regimens (2015 UK 0.05- pound 1.06 pound per day). Outcomes Additional health care costs per major atherosclerotic event avoided and per quality-adjusted life-year (QALY) gained. Results In SHARP, the proportional reductions per 1 mmol/L of low-density lipoprotein (LDL) cholesterol reduction with simvastatin plus ezetimibe in all major atherosclerotic events of 20% (95% CI, 6%-32%) and in the costs of vascular hospital episodes of 17% (95% CI, 4%-28%) were similar across participant categories by cardiovascular risk and CKD stage. The 5-year reduction in major atherosclerotic events per 1,000 participants ranged from 10 in low-risk to 58 in high-risk patients and from 28 in CKD stage 3 to 36 in patients on dialysis therapy. The net cost per major atherosclerotic event avoided with simvastatin plus ezetimibe compared to no LDL-lowering regimen ranged from 157,060 pound in patients at low risk to 15,230 pound in those at high risk (30,500- pound 39,600 pound per QALY); and from 47,280 pound in CKD stage 3 to 28,180 pound in patients on dialysis therapy (13,000- pound 43,300 pound per QALY). In scenario analyses, generic high-intensity statin regimens were estimated to yield similar benefits at substantially lower cost. Limitations High-intensity statin-alone regimens were not studied in SHARP. Conclusions Simvastatin plus ezetimibe prevented atherosclerotic events in SHARP, but other less costly statin regimens are likely to be more cost-effective for reducing cardiovascular risk in CKD. (C) 2016 The Authors. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc

Exile Vol. XXXV No. 2

Peter Goes Groovy, by Carolyn Bern (cover) I Hate Poetry by Craig Bagno 1 Truancy by Richard Latimer 2 I ate a Star Last Night by Rory Herbster 3 Delivery by Amy Judge 4 Untitled by Sue McLain 5 Road Signs by Richard Latimer 7-8 Haiku for Me to Possess by Shannon J. Salser 9 Patches by Michael Payne 10 Untitled by Laura Johnson 11 He by Kent Lambert 13 At the Corner Grill by Lynn Pendleton 14-15 Black Licorice by Richard Latimer 16-17 Blue Shirt by Michael Payne 18 ...Loves a Clown by Margaret Dawson 21-24 The Surreal Sonnet by Shannon J. Salser 26 Untitled by Mat Benson 27 Swimming Lessons by Richard Latimer 29 Communion by Amy Judge 30 Beth\u27s Last Funny Joke by Ted Gould 31-35 Hope for a Peaceful Coming Around by Shannon J. Salser 36 Untitled by Laura Johnson 37 A Child\u27s Moment by Peter Witonsky 39 Observation by Rosemary Walsh 40 Untitled by Carolyn Burns 41 To My Sister by Amy B. Judge 43 Ideas In Bloom by Randy Casden 44 Untitled by Deb Tily 45 A Child of Mind by Charles Riedinger 47 Ars Poetica by Rory Herbster 48 Untitled by Mat Benson 49 REPRINTS Dancer by Bradford Cover 52 Skin Deep by Eric Whitney 53-55 Sunset by Chris Rynd 56 Editorial decision is shared equally among the Editorial Board Members -cover page The editors of Exile would like to formally apologize to those contributors whose works were misprinted in the Fall issue. We have reprinted a few of the pieces that contained the most errors. -51 NOTE: An uncredited and untitled piece of artwork appears on page 19. NOTE: Carolyn Bern (cover) Burns (41) and Berns (contributor notes) all appear to refer to the same artist