An assessment of the resolution limitation due to radiation-damage in x-ray diffraction microscopy

X-ray diffraction microscopy (XDM) is a new form of x-ray imaging that is being practiced at several third-generation synchrotron-radiation x-ray facilities. Although only five years have elapsed since the technique was first introduced, it has made rapid progress in demonstrating high-resolution threedimensional imaging and promises few-nm resolution with much larger samples than can be imaged in the transmission electron microscope. Both life- and materials-science applications of XDM are intended, and it is expected that the principal limitation to resolution will be radiation damage for life science and the coherent power of available x-ray sources for material science. In this paper we address the question of the role of radiation damage. We use a statistical analysis based on the so-called "dose fractionation theorem" of Hegerl and Hoppe to calculate the dose needed to make an image of a lifescience sample by XDM with a given resolution. We conclude that the needed dose scales with the inverse fourth power of the resolution and present experimental evidence to support this finding. To determine the maximum tolerable dose we have assembled a number of data taken from the literature plus some measurements of our own which cover ranges of resolution that are not well covered by reports in the literature. The tentative conclusion of this study is that XDM should be able to image frozen-hydrated protein samples at a resolution of about 10 nm with "Rose-criterion" image quality.Comment: 9 pages, 4 figure

Zeros of analytic functions, with or without multiplicities

The classical Mason-Stothers theorem deals with nontrivial polynomial solutions to the equation $a+b=c$. It provides a lower bound on the number of distinct zeros of the polynomial $abc$ in terms of the degrees of $a$, $b$ and $c$. We extend this to general analytic functions living on a reasonable bounded domain $\Omega\subset\mathbb C$, rather than on the whole of $\mathbb C$. The estimates obtained are sharp, for any $\Omega$, and a generalization of the original result on polynomials can be recovered from them by a limiting argument.Comment: This is a retitled and slightly revised version of my paper arXiv:1004.359

Search for CP Violation in D^0--> K_S^0 pi^+pi^-

We report on a search for CP violation in the decay of D0 and D0B to Kshort pi+pi-. The data come from an integrated luminosity of 9.0 1/fb of e+e- collisions at sqrt(s) ~ 10 GeV recorded with the CLEO II.V detector. The resonance substructure of this decay is well described by ten quasi-two-body decay channels (K*-pi+, K*0(1430)-pi+, K*2(1430)-pi+, K*(1680)-pi+, Kshort rho, Kshort omega, Kshort f0(980), Kshort f2(1270), Kshort f0(1370), and the ``wrong sign'' K*+ pi-) plus a small non-resonant component. We observe no evidence for CP violation in the amplitudes and phases that describe the decay D0 to K_S^0 pi+pi-.Comment: 10 pages, 3 figures, also available at http://w4.lns.cornell.edu/public/CLNS/, submitted to PR

Factors Associated with Severity of COVID-19 Disease in a Multicenter Cohort of People with HIV in the United States, March-December 2020

Background: Understanding the spectrum of COVID-19 in people with HIV (PWH) is critical to provide clinical guidance and risk reduction strategies.Setting:Centers for AIDS Research Network of Integrated Clinic System, a US multisite clinical cohort of PWH in care.Methods:We identified COVID-19 cases and severity (hospitalization, intensive care, and death) in a large, diverse HIV cohort during March 1, 2020-December 31, 2020. We determined predictors and relative risks of hospitalization among PWH with COVID-19, adjusted for disease risk scores. Results: Of 16,056 PWH in care, 649 were diagnosed with COVID-19 between March and December 2020. Case fatality was 2%; 106 (16.3%) were hospitalized, and 12 died. PWH with current CD4 count <350 cells/mm3[aRR 2.68; 95% confidence interval (CI): 1.93 to 3.71; P < 0.001] or lowest recorded CD4 count <200 cells/mm3(aRR 1.67; 95% CI: 1.18 to 2.36; P < 0.005) had greater risks of hospitalization. HIV viral load and antiretroviral therapy status were not associated with hospitalization, although most of the PWH were suppressed (86%). Black PWH were 51% more likely to be hospitalized with COVID-19 compared with other racial/ethnic groups (aRR 1.51; 95% CI: 1.04 to 2.19; P = 0.03). Chronic kidney disease, chronic obstructive pulmonary disease, diabetes, hypertension, obesity, and increased cardiovascular and hepatic fibrosis risk scores were associated with higher hospitalization risk. PWH who were older, not on antiretroviral therapy, and with current CD4 count <350 cells/mm3, diabetes, and chronic kidney disease were overrepresented among PWH who required intubation or died. Conclusions: PWH with CD4 count <350 cells/mm3, and a history of CD4 count <200 cells/mm3, have a clear excess risk of severe COVID-19, accounting for comorbidities associated with severe outcomes. PWH with these risk factors should be prioritized for COVID-19 vaccination and early treatment and monitored closely for worsening illness

Racial and ethnic disparities in coronavirus disease 2019 disease incidence independent of comorbidities, among people with HIV in the United States

Objectives: To define the incidence of clinically detected coronavirus disease 2019 (COVID-19) in people with HIV (PWH) in the United States and evaluate how racial and ethnic disparities, comorbidities, and HIV-related factors contribute to risk of COVID-19. Design: Observational study within the CFAR Network of Integrated Clinical Systems cohort in seven cities during 2020. Methods: We calculated cumulative incidence rates of COVID-19 diagnosis among PWH in routine care by key characteristics including race/ethnicity, current and lowest CD4þ cell count, and geographic area. We evaluated risk factors for COVID-19 among PWH using relative risk regression models adjusted with disease risk scores. Results: Among 16 056 PWH in care, of whom 44.5% were black, 12.5% were Hispanic, with a median age of 52 years (IQR 40 - 59), 18% had a current CD4þ cell count less than 350 cells/ml, including 7% less than 200; 95.5% were on antiretroviral therapy (ART), and 85.6% were virologically suppressed. Overall in 2020, 649 PWH were diagnosed with COVID-19 for a rate of 4.94 cases per 100 person-years. The cumulative incidence of COVID-19 was 2.4-fold and 1.7-fold higher in Hispanic and black PWH respectively, than non-Hispanic white PWH. In adjusted analyses, factors associated with COVID-19 included female sex, Hispanic or black identity, lowest historical CD4þ cell count less than 350 cells/ml (proxy for CD4þ nadir), current low CD4þ : CD8þ ratio, diabetes, and obesity. Conclusion: Our results suggest that the presence of structural racial inequities above and beyond medical comorbidities increased the risk of COVID-19 among PWH. PWH with immune exhaustion as evidenced by lowest historical CD4þ cell count or current low CD4þ : CD8þ ratio had greater risk of COVID-19

Size Doesn't Matter: Towards a More Inclusive Philosophy of Biology

notes: As the primary author, O’Malley drafted the paper, and gathered and analysed data (scientific papers and talks). Conceptual analysis was conducted by both authors.publication-status: Publishedtypes: ArticlePhilosophers of biology, along with everyone else, generally perceive life to fall into two broad categories, the microbes and macrobes, and then pay most of their attention to the latter. ‘Macrobe’ is the word we propose for larger life forms, and we use it as part of an argument for microbial equality. We suggest that taking more notice of microbes – the dominant life form on the planet, both now and throughout evolutionary history – will transform some of the philosophy of biology’s standard ideas on ontology, evolution, taxonomy and biodiversity. We set out a number of recent developments in microbiology – including biofilm formation, chemotaxis, quorum sensing and gene transfer – that highlight microbial capacities for cooperation and communication and break down conventional thinking that microbes are solely or primarily single-celled organisms. These insights also bring new perspectives to the levels of selection debate, as well as to discussions of the evolution and nature of multicellularity, and to neo-Darwinian understandings of evolutionary mechanisms. We show how these revisions lead to further complications for microbial classification and the philosophies of systematics and biodiversity. Incorporating microbial insights into the philosophy of biology will challenge many of its assumptions, but also give greater scope and depth to its investigations

All-sky search for long-duration gravitational wave transients with initial LIGO

We present the results of a search for long-duration gravitational wave transients in two sets of data collected by the LIGO Hanford and LIGO Livingston detectors between November 5, 2005 and September 30, 2007, and July 7, 2009 and October 20, 2010, with a total observational time of 283.0 days and 132.9 days, respectively. The search targets gravitational wave transients of duration 10-500 s in a frequency band of 40-1000 Hz, with minimal assumptions about the signal waveform, polarization, source direction, or time of occurrence. All candidate triggers were consistent with the expected background; as a result we set 90% confidence upper limits on the rate of long-duration gravitational wave transients for different types of gravitational wave signals. For signals from black hole accretion disk instabilities, we set upper limits on the source rate density between 3.4×10-5 and 9.4×10-4 Mpc-3 yr-1 at 90% confidence. These are the first results from an all-sky search for unmodeled long-duration transient gravitational waves. © 2016 American Physical Society

All-sky search for long-duration gravitational wave transients with initial LIGO

We present the results of a search for long-duration gravitational wave transients in two sets of data collected by the LIGO Hanford and LIGO Livingston detectors between November 5, 2005 and September 30, 2007, and July 7, 2009 and October 20, 2010, with a total observational time of 283.0 days and 132.9 days, respectively. The search targets gravitational wave transients of duration 10-500 s in a frequency band of 40-1000 Hz, with minimal assumptions about the signal waveform, polarization, source direction, or time of occurrence. All candidate triggers were consistent with the expected background; as a result we set 90% confidence upper limits on the rate of long-duration gravitational wave transients for different types of gravitational wave signals. For signals from black hole accretion disk instabilities, we set upper limits on the source rate density between 3.4×10-5 and 9.4×10-4 Mpc-3 yr-1 at 90% confidence. These are the first results from an all-sky search for unmodeled long-duration transient gravitational waves. © 2016 American Physical Society