Coupling a single atomic quantum bit to a high finesse optical cavity

The quadrupole S$_{1/2}$ -- D$_{5/2}$ optical transition of a single trapped Ca$^+$ ion, well suited for encoding a quantum bit of information, is coherently coupled to the standing wave field of a high finesse cavity. The coupling is verified by observing the ion's response to both spatial and temporal variations of the intracavity field. We also achieve deterministic coupling of the cavity mode to the ion's vibrational state by selectively exciting vibrational state-changing transitions and by controlling the position of the ion in the standing wave field with nanometer-precision

Old vaccines for new infections: Exploiting innate immunity to control COVID-19 and prevent future pandemics

The COVID-19 pandemic triggered an unparalleled pursuit of vaccines to induce specific adaptive immunity, based on virus-neutralizing antibodies and T cell responses. Although several vaccines have been developed just a year after SARS-CoV-2 emerged in late 2019, global deployment will take months or even years. Meanwhile, the virus continues to take a severe toll on human life and exact substantial economic costs. Innate immunity is fundamental to mammalian host defense capacity to combat infections. Innate immune responses, triggered by a family of pattern recognition receptors, induce interferons and other cytokines and activate both myeloid and lymphoid immune cells to provide protection against a wide range of pathogens. Epidemiological and biological evidence suggests that the live-attenuated vaccines (LAV) targeting tuberculosis, measles, and polio induce protective innate immunity by a newly described form of immunological memory termed “trained immunity.” An LAV designed to induce adaptive immunity targeting a particular pathogen may also induce innate immunity that mitigates other infectious diseases, including COVID-19, as well as future pandemic threats. Deployment of existing LAVs early in pandemics could complement the development of specific vaccines, bridging the protection gap until specific vaccines arrive. The broad protection induced by LAVs would not be compromised by potential antigenic drift (immune escape) that can render viruses resistant to specific vaccines. LAVs might offer an essential tool to “bend the pandemic curve,” averting the exhaustion of public health resources and preventing needless deaths and may also have therapeutic benefits if used for postexposure prophylaxis of disease

One vaccine to counter many diseases? Modeling the economics of oral polio vaccine against child mortality and COVID-19

INTRODUCTION: Recent reviews summarize evidence that some vaccines have heterologous or non-specific effects (NSE), potentially offering protection against multiple pathogens. Numerous economic evaluations examine vaccines\u27 pathogen-specific effects, but less than a handful focus on NSE. This paper addresses that gap by reporting economic evaluations of the NSE of oral polio vaccine (OPV) against under-five mortality and COVID-19. MATERIALS AND METHODS: We studied two settings: (1) reducing child mortality in a high-mortality setting (Guinea-Bissau) and (2) preventing COVID-19 in India. In the former, the intervention involves three annual campaigns in which children receive OPV incremental to routine immunization. In the latter, a susceptible-exposed-infectious-recovered model was developed to estimate the population benefits of two scenarios, in which OPV would be co-administered alongside COVID-19 vaccines. Incremental cost-effectiveness and benefit-cost ratios were modeled for ranges of intervention effectiveness estimates to supplement the headline numbers and account for heterogeneity and uncertainty. RESULTS: For child mortality, headline cost-effectiveness was $650 per child death averted. For COVID-19, assuming OPV had 20$23,000-65,000 if it were administered simultaneously with a COVID-19 vaccine \u3c200 days into a wave of the epidemic. If the COVID-19 vaccine availability were delayed, the cost per averted death would decrease to $2600-6100. Estimated benefit-to-cost ratios vary but are consistently high. DISCUSSION: Economic evaluation suggests the potential of OPV to efficiently reduce child mortality in high mortality environments. Likewise, within a broad range of assumed effect sizes, OPV (or another vaccine with NSE) could play an economically attractive role against COVID-19 in countries facing COVID-19 vaccine delays. FUNDING: The contribution by DTJ was supported through grants from Trond Mohn Foundation (BFS2019MT02) and Norad (RAF-18/0009) through the Bergen Center for Ethics and Priority Setting

From Majorana theory of atomic autoionization to Feshbach resonances in high temperature superconductors

The Ettore Majorana paper - Theory of incomplete P triplets- published in 1931, focuses on the role of selection rules for the non-radiative decay of two electron excitations in atomic spectra, involving the configuration interaction between discrete and continuum channels. This work is a key step for understanding the 1935 work of Ugo Fano on the asymmetric lineshape of two electron excitations and the 1958 Herman Feshbach paper on the shape resonances in nuclear scattering arising from configuration interaction between many different scattering channels. The Feshbach resonances are today of high scientific interest in many different fields and in particular for ultracold gases and high Tc superconductivity.Comment: 13 pages, 7 figures. Journal of Superconductivity and Novel Magnetism to be publishe

Defective Hepatic Response to Interferon and Activation of Suppressor of Cytokine Signaling 3 in Chronic Hepatitis C

Approximately half of hepatitis C virus (HCV)-infected patients do not respond to current interferon (IFN)-α combination therapy. To understand IFN-α resistance in vivo, we examined the dynamic responses to both type I and type II IFNs, human IFN (hIFN)- α, -γ, and consensus IFN, in the chimpanzee model

The Substitutions L50F, E166A, and L167F in SARS-CoV-2 3CLpro Are Selected by a Protease Inhibitor In Vitro and Confer Resistance To Nirmatrelvir.

The SARS-CoV-2 main protease (3CLpro) has an indispensable role in the viral life cycle and is a therapeutic target for the treatment of COVID-19. The potential of 3CLpro-inhibitors to select for drug-resistant variants needs to be established. Therefore, SARS-CoV-2 was passaged in vitro in the presence of increasing concentrations of ALG-097161, a probe compound designed in the context of a 3CLpro drug discovery program. We identified a combination of amino acid substitutions in 3CLpro (L50F E166A L167F) that is associated with a >20× increase in 50% effective concentration (EC50) values for ALG-097161, nirmatrelvir (PF-07321332), PF-00835231, and ensitrelvir. While two of the single substitutions (E166A and L167F) provide low-level resistance to the inhibitors in a biochemical assay, the triple mutant results in the highest levels of resistance (6× to 72×). All substitutions are associated with a significant loss of enzymatic 3CLpro activity, suggesting a reduction in viral fitness. Structural biology analysis indicates that the different substitutions reduce the number of inhibitor/enzyme interactions while the binding of the substrate is maintained. These observations will be important for the interpretation of resistance development to 3CLpro inhibitors in the clinical setting. IMPORTANCE Paxlovid is the first oral antiviral approved for treatment of SARS-CoV-2 infection. Antiviral treatments are often associated with the development of drug-resistant viruses. In order to guide the use of novel antivirals, it is essential to understand the risk of resistance development and to characterize the associated changes in the viral genes and proteins. In this work, we describe for the first time a pathway that allows SARS-CoV-2 to develop resistance against Paxlovid in vitro. The characteristics of in vitro antiviral resistance development may be predictive for the clinical situation. Therefore, our work will be important for the management of COVID-19 with Paxlovid and next-generation SARS-CoV-2 3CLpro inhibitors

Q^2 Dependence of the S_{11}(1535) Photocoupling and Evidence for a P-wave resonance in eta electroproduction

New cross sections for the reaction $ep \to e'\eta p$ are reported for total center of mass energy $W$=1.5--2.3 GeV and invariant squared momentum transfer $Q^2$=0.13--3.3 GeV$^2$. This large kinematic range allows extraction of new information about response functions, photocouplings, and $\eta N$ coupling strengths of baryon resonances. A sharp structure is seen at $W\sim$ 1.7 GeV. The shape of the differential cross section is indicative of the presence of a $P$-wave resonance that persists to high $Q^2$. Improved values are derived for the photon coupling amplitude for the $S_{11}$(1535) resonance. The new data greatly expands the $Q^2$ range covered and an interpretation of all data with a consistent parameterization is provided.Comment: 31 pages, 9 figure

A comparison of hepatitis B viral markers of patients in different clinical stages of chronic infection

Hepatitis B viral markers may be useful for predicting outcomes such as liver-related deaths or development of hepatocellular carcinoma. We determined the frequency of these markers in different clinical stages of chronic hepatitis B infection. We compared baseline hepatitis B viral markers in 317 patients who were enrolled in a prospective study and identified the frequency of these tests in immune-tolerant (IT) patients, in inactive carriers , and in patients with either hepatitis B e antigen ( HBeAg)- positive or HBeAg-negative chronic hepatitis or cirrhosis. IT patients were youngest (median age 27 years) and HBeAg- negative patients with cirrhosis were oldest (median age 58 years) (p = 0.03 to < 0.0001). The male to female ratio was similar both in IT patients and in inactive carriers, but there was a male preponderance both in patients with chronic hepatitis and in patients with cirrhosis (p < 0.0001). The A1896 precore mutants were most prevalent in inactive carriers (36.4%) and HBeAg- negative patients with chronic hepatitis (38.8%; p < 0.0001), and the T 1762/A1764 basal core promoter mutants were most often detected in HBeAg- negative patients with cirrhosis (65.1%; p = 0.02). Genotype A was detected only in 5.3% of IT patients, and genotype B was least often detected in both HBeAg-Positive patients with chronic hepatitis and cirrhosis (p = 0.03). The hepatitis B viral DNA levels were lowest in inactive carriers (2.69 log(10) IU/mL) and highest in IT patients (6. 80 log(10) IU/mL; p = 0.02 to < 0.0001). At follow-up, HBeAg-positive and HBeAg-negative patients with cirrhosis accounted for 57 of 64 (89.1%) liver-related deaths (p < 0. 0001). Differences in baseline hepatitis B viral markers were detected in patients in various clinical stages of hepatitis B virus infection. HBeAg-positive and HBeAg- negative patients with cirrhosis accounted for the majority of the liver-related fatalities

GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment