Phase-Resolved Rydberg Atom Field Sensing using Quantum Interferometry

Although Rydberg atom-based electric field sensing provides key advantages over traditional antenna-based detection, it remains limited by the need for a local oscillator (LO) for low-field and phase resolved detection. In this work, we demonstrate that closed-loop quantum interferometric schemes can be used to generate a system-internal reference that can directly replace an external LO for Rydberg field sensing. We reveal that this quantum-interferometrically defined internal reference phase and frequency can be used analogously to a traditional LO for atom-based down-mixing to an intermediate frequency for lock-in phase detection. We demonstrate that this LO-equivalent functionality provides analogous benefits to an LO, including full 360$^\circ$ phase resolution as well as improved sensitivity. The general applicability of this approach is confirmed by demodulating a four phase-state signal broadcast on the atoms. Our approach opens up new sensing schemes and provides a clear path towards all-optical Rydberg atom sensing implementations

Evaluation of individual and ensemble probabilistic forecasts of COVID-19 mortality in the United States

Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. Starting in April 2020, the US COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized tens of millions of specific predictions from more than 90 different academic, industry, and independent research groups. A multimodel ensemble forecast that combined predictions from dozens of groups every week provided the most consistently accurate probabilistic forecasts of incident deaths due to COVID-19 at the state and national level from April 2020 through October 2021. The performance of 27 individual models that submitted complete forecasts of COVID-19 deaths consistently throughout this year showed high variability in forecast skill across time, geospatial units, and forecast horizons. Two-thirds of the models evaluated showed better accuracy than a naïve baseline model. Forecast accuracy degraded as models made predictions further into the future, with probabilistic error at a 20-wk horizon three to five times larger than when predicting at a 1-wk horizon. This project underscores the role that collaboration and active coordination between governmental public-health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks

The United States COVID-19 Forecast Hub dataset

Academic researchers, government agencies, industry groups, and individuals have produced forecasts at an unprecedented scale during the COVID-19 pandemic. To leverage these forecasts, the United States Centers for Disease Control and Prevention (CDC) partnered with an academic research lab at the University of Massachusetts Amherst to create the US COVID-19 Forecast Hub. Launched in April 2020, the Forecast Hub is a dataset with point and probabilistic forecasts of incident cases, incident hospitalizations, incident deaths, and cumulative deaths due to COVID-19 at county, state, and national, levels in the United States. Included forecasts represent a variety of modeling approaches, data sources, and assumptions regarding the spread of COVID-19. The goal of this dataset is to establish a standardized and comparable set of short-term forecasts from modeling teams. These data can be used to develop ensemble models, communicate forecasts to the public, create visualizations, compare models, and inform policies regarding COVID-19 mitigation. These open-source data are available via download from GitHub, through an online API, and through R packages

Global urban environmental change drives adaptation in white clover

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale

The contribution of X-linked coding variation to severe developmental disorders

Abstract: Over 130 X-linked genes have been robustly associated with developmental disorders, and X-linked causes have been hypothesised to underlie the higher developmental disorder rates in males. Here, we evaluate the burden of X-linked coding variation in 11,044 developmental disorder patients, and find a similar rate of X-linked causes in males and females (6.0% and 6.9%, respectively), indicating that such variants do not account for the 1.4-fold male bias. We develop an improved strategy to detect X-linked developmental disorders and identify 23 significant genes, all of which were previously known, consistent with our inference that the vast majority of the X-linked burden is in known developmental disorder-associated genes. Importantly, we estimate that, in male probands, only 13% of inherited rare missense variants in known developmental disorder-associated genes are likely to be pathogenic. Our results demonstrate that statistical analysis of large datasets can refine our understanding of modes of inheritance for individual X-linked disorders

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Phylogenetic analysis of the salinipostin γ-butyrolactone gene cluster uncovers new potential for bacterial signalling-molecule diversity

Bacteria communicate by small-molecule chemicals that facilitate intra- and inter-species interactions. These extracellular signalling molecules mediate diverse processes including virulence, bioluminescence, biofilm formation, motility and specialized metabolism. The signalling molecules produced by members of the phylum Actinobacteria generally comprise γ-butyrolactones, γ-butenolides and furans. The best-known actinomycete γ-butyrolactone is A-factor, which triggers specialized metabolism and morphological differentiation in the genus Streptomyces . Salinipostins A–K are unique γ-butyrolactone molecules with rare phosphotriester moieties that were recently characterized from the marine actinomycete genus Salinispora . The production of these compounds has been linked to the nine-gene biosynthetic gene cluster (BGC) spt. Critical to salinipostin assembly is the γ-butyrolactone synthase encoded by spt9. Here, we report the surprising distribution of spt9 homologues across 12 bacterial phyla, the majority of which are not known to produce γ-butyrolactones. Further analyses uncovered a large group of spt-like gene clusters outside of the genus Salinispora , suggesting the production of new salinipostin-like diversity. These gene clusters show evidence of horizontal transfer and location-specific recombination among Salinispora strains. The results suggest that γ-butyrolactone production may be more widespread than previously recognized. The identification of new γ-butyrolactone BGCs is the first step towards understanding the regulatory roles of the encoded small molecules in Actinobacteria

The Wide Range Achievement Test-4 Reading subtest "holds" in HIV-infected individuals.

BackgroundIn order to detect HIV-associated neurocognitive decline, it is important to accurately estimate individuals' premorbid levels of cognitive functioning. Although previous studies have operated under the assumption that word reading tests are valid and stable indicators of premorbid abilities in HIV infection, studies of other populations have found that this is not always the case. Therefore, it is important to empirically examine the validity of word reading tests as estimates of premorbid functioning specifically within the HIV population.MethodThe Wide Range Achievement Test-4 Reading subtest (WRAT-4 Reading) was administered along with comprehensive neurocognitive assessments to 150 HIV seropositive (HIV+) and 76 HIV seronegative (HIV-) age-, education-, and sex-matched participants; a subset of 48 HIV+ individuals completed a second study visit (M = 14.4 months), in which the alternate version of the WRAT-4 was administered.ResultsAlthough HIV+ individuals evidenced worse current neurocognitive functioning than HIV- participants, WRAT-4 Reading performance was comparable between groups. Longitudinally, HIV+ participants evidenced improved disease and neuropsychological functioning, yet WRAT-4 Reading demonstrated strong test-retest reliability and no practice effect, and did not differ between the initial and follow-up assessments. Test-retest differences in reading performance were minor and were not associated with changes in neurocognitive performance or changes in HIV disease.ConclusionsWe found no evidence of WRAT-4 Reading performance decline in HIV infection, despite HIV+/HIV- group differences in neurocognitive functioning. Additionally, reading performances among HIV+ individuals demonstrated consistency across study visits. These results begin to support the validity of the WRAT-4 Reading subtest as an indicator of premorbid cognitive functioning in HIV+ individuals

The Wide Range Achievement Test-4 Reading subtest "holds" in HIV-infected individuals.

BackgroundIn order to detect HIV-associated neurocognitive decline, it is important to accurately estimate individuals' premorbid levels of cognitive functioning. Although previous studies have operated under the assumption that word reading tests are valid and stable indicators of premorbid abilities in HIV infection, studies of other populations have found that this is not always the case. Therefore, it is important to empirically examine the validity of word reading tests as estimates of premorbid functioning specifically within the HIV population.MethodThe Wide Range Achievement Test-4 Reading subtest (WRAT-4 Reading) was administered along with comprehensive neurocognitive assessments to 150 HIV seropositive (HIV+) and 76 HIV seronegative (HIV-) age-, education-, and sex-matched participants; a subset of 48 HIV+ individuals completed a second study visit (M = 14.4 months), in which the alternate version of the WRAT-4 was administered.ResultsAlthough HIV+ individuals evidenced worse current neurocognitive functioning than HIV- participants, WRAT-4 Reading performance was comparable between groups. Longitudinally, HIV+ participants evidenced improved disease and neuropsychological functioning, yet WRAT-4 Reading demonstrated strong test-retest reliability and no practice effect, and did not differ between the initial and follow-up assessments. Test-retest differences in reading performance were minor and were not associated with changes in neurocognitive performance or changes in HIV disease.ConclusionsWe found no evidence of WRAT-4 Reading performance decline in HIV infection, despite HIV+/HIV- group differences in neurocognitive functioning. Additionally, reading performances among HIV+ individuals demonstrated consistency across study visits. These results begin to support the validity of the WRAT-4 Reading subtest as an indicator of premorbid cognitive functioning in HIV+ individuals