Strategies for enhancing quantum entanglement by local photon subtraction

Subtracting photons from a two-mode squeezed state is a well-known method to increase entanglement. We analyse different strategies of local photon subtraction from a two-mode squeezed state in terms of entanglement gain and success probability. We develop a general framework that incorporates imperfections and losses in all stages of the process: before, during, and after subtraction. By combining all three effects into a single efficiency parameter, we provide analytical and numerical results for subtraction strategies using photon-number-resolving and threshold detectors. We compare the entanglement gain afforded by symmetric and asymmetric subtraction scenarios across the two modes. For a given amount of loss, we identify an optimised set of parameters, such as initial squeezing and subtraction beam splitter transmissivity, that maximise the entanglement gain rate. We identify regimes for which asymmetric subtraction of different Fock states on the two modes outperforms symmetric strategies. In the lossless limit, subtracting a single photon from one mode always produces the highest entanglement gain rate. In the lossy case, the optimal strategy depends strongly on the losses on each mode individually, such that there is no general optimal strategy. Rather, taking losses on each mode as the only input parameters, we can identify the optimal subtraction strategy and required beam splitter transmissivities and initial squeezing parameter. Finally, we discuss the implications of our results for the distillation of continuous-variable quantum entanglement.Comment: 13 pages, 11 figures. Updated version for publicatio

Diatom Proteomics Reveals Unique Acclimation Strategies to Mitigate Fe Limitation

Phytoplankton growth rates are limited by the supply of iron (Fe) in approximately one third of the open ocean, with major implications for carbon dioxide sequestration and carbon (C) biogeochemistry. To date, understanding how alteration of Fe supply changes phytoplankton physiology has focused on traditional metrics such as growth rate, elemental composition, and biophysical measurements such as photosynthetic competence (Fv/Fm). Researchers have subsequently employed transcriptomics to probe relationships between changes in Fe supply and phytoplankton physiology. Recently, studies have investigated longer-term (i.e. following acclimation) responses of phytoplankton to various Fe conditions. In the present study, the coastal diatom, Thalassiosira pseudonana, was acclimated (10 generations) to either low or high Fe conditions, i.e. Fe-limiting and Fe-replete. Quantitative proteomics and a newly developed proteomic profiling technique that identifies low abundance proteins were employed to examine the full complement of expressed proteins and consequently the metabolic pathways utilized by the diatom under the two Fe conditions. A total of 1850 proteins were confidently identified, nearly tripling previous identifications made from differential expression in diatoms. Given sufficient time to acclimate to Fe limitation, T. pseudonana up-regulates proteins involved in pathways associated with intracellular protein recycling, thereby decreasing dependence on extracellular nitrogen (N), C and Fe. The relative increase in the abundance of photorespiration and pentose phosphate pathway proteins reveal novel metabolic shifts, which create substrates that could support other well-established physiological responses, such as heavily silicified frustules observed for Fe-limited diatoms. Here, we discovered that proteins and hence pathways observed to be down-regulated in short-term Fe starvation studies are constitutively expressed when T. pseudonana is acclimated (i.e., nitrate and nitrite transporters, Photosystem II and Photosystem I complexes). Acclimation of the diatom to the desired Fe conditions and the comprehensive proteomic approach provides a more robust interpretation of this dynamic proteome than previous studies.This work was supported by National Science Foundation grants OCE1233014 (BLN) and the Office of Polar Programs Postdoctoral Fellowship grant 0444148 (BLN). DRG was supported by National Institutes of Health 5P30ES007033-10. AH and MTM were supported by Natural Sciences and Engineering Research Council of Canada. RFS and PWB were supported by the New Zealand Royal Society Marsden Fund and the Ministry of Science. This work is supported in part by the University of Washington's Proteomics Computer Resource Centre (UWPR95794). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

HIV Clustering in Mississippi: Spatial Epidemiological Study to Inform Implementation Science in the Deep South

Background: In recent years, more than half of new HIV infections in the United States occur among African Americans in the Southeastern United States. Spatial epidemiological analyses can inform public health responses in the Deep South by identifying HIV hotspots and community-level factors associated with clustering. Objective: The goal of this study was to identify and characterize HIV clusters in Mississippi through analysis of state-level HIV surveillance data. Methods: We used a combination of spatial epidemiology and statistical modeling to identify and characterize HIV hotspots in Mississippi census tracts (n=658) from 2008 to 2014. We conducted spatial analyses of all HIV infections, infections among men who have sex with men (MSM), and infections among African Americans. Multivariable logistic regression analyses identified community-level sociodemographic factors associated with HIV hotspots considering all cases. Results: There were HIV hotspots for the entire population, MSM, and African American MSM identified in the Mississippi Delta region, Southern Mississippi, and in greater Jackson, including surrounding rural counties (P \u3c .05). In multivariable models for all HIV cases, HIV hotspots were significantly more likely to include urban census tracts (adjusted odds ratio [AOR] 2.01, 95% CI 1.20-3.37) and census tracts that had a higher proportion of African Americans (AOR 3.85, 95% CI 2.23-6.65). The HIV hotspots were less likely to include census tracts with residents who had less than a high school education (AOR 0.95, 95% CI 0.92-0.98), census tracts with residents belonging to two or more racial/ethnic groups (AOR 0.46, 95% CI 0.30-0.70), and census tracts that had a higher percentage of the population living below the poverty level (AOR 0.51, 95% CI 0.28-0.92). Conclusions: We used spatial epidemiology and statistical modeling to identify and characterize HIV hotspots for the general population, MSM, and African Americans. HIV clusters concentrated in Jackson and the Mississippi Delta. African American race and urban location were positively associated with clusters, whereas having less than a high school education and having a higher percentage of the population living below the poverty level were negatively associated with clusters. Spatial epidemiological analyses can inform implementation science and public health response strategies, including improved HIV testing, targeted prevention and risk reduction education, and tailored preexposure prophylaxis to address HIV disparities in the South

Social, structural, behavioral and clinical factors influencing retention in Pre-Exposure Prophylaxis (PrEP) care in Mississippi

Pre-exposure prophylaxis (PrEP) is a biomedical intervention that can reduce rates of HIV transmission when taken once daily by HIV-negative individuals. Little is understood about PrEP uptake and retention in care among the populations most heavily impacted by the HIV epidemic, particularly among young men who have sex with men (YMSM) in the Deep South. Therefore, this study explored the structural, social, behavioral, and clinical factors that affect PrEP use and retention in care among YMSM in Jackson, Mississippi. Thirty MSM who were prescribed PrEP at an outpatient primary care clinic were interviewed and included 23 men who had been retained in PrEP care and seven who had not been retained. The mean age of participants was 26.6 years. Most (23) participants were African American. Major factors affecting PrEP use and retention in PrEP care included 1) structural factors such as cost and access to financial assistance for medications and clinical services; 2) social factors such as stigma and relationship status; 3) behavioral factors including sexual risk behaviors; and 4) clinical factors such as perceived and actual side effects. Many participants also discussed the positive spillover effects of PrEP use and reported that PrEP had a positive impact on their health. Four of the seven individuals who had not been retained re-enrolled in PrEP care after completing their interviews, suggesting that case management and ongoing outreach can enhance retention in PrEP care. Interventions to enhance retention in PrEP care among MSM in the Deep South will be most effective if they address the complex structural, social, clinical, and behavioral factors that influence PrEP uptake and retention in PrEP care

Projected effects of disruptions to human immunodeficiency virus (HIV) prevention services during the coronavirus disease 2019 pandemic among Black/African American men who have sex with men in an Ending the HIV Epidemic priority jurisdiction

BACKGROUND: Disruptions in access to in-person human immunodeficiency virus (HIV) preventive care during the coronavirus disease 2019 (COVID-19) pandemic may have a negative impact on our progress towards the Ending the HIV Epidemic goals in the United States. METHODS: We used an agent-based model to simulate HIV transmission among Black/African American men who have sex with men in Mississippi over 5 years to estimate how different reductions in access affected the number of undiagnosed HIV cases, new pre-exposure prophylaxis (PrEP) starts, and HIV incidence. RESULTS: We found that each additional 25% decrease in HIV testing and PrEP initiation was associated with decrease of 20% in the number of cases diagnosed and 23% in the number of new PrEP starts, leading to a 15% increase in HIV incidence from 2020 to 2022. CONCLUSIONS: Unmet need for HIV testing and PrEP prescriptions during the COVID-19 pandemic may temporarily increase HIV incidence in the years immediately after the disruption period

Diatom Proteomics Reveals Unique Acclimation Strategies to Mitigate Fe Limitation

Phytoplankton growth rates are limited by the supply of iron (Fe) in approximately one third of the open ocean, with major implications for carbon dioxide sequestration and carbon (C) biogeochemistry. To date, understanding how alteration of Fe supply changes phytoplankton physiology has focused on traditional metrics such as growth rate, elemental composition, and biophysical measurements such as photosynthetic competence (Fv/Fm). Researchers have subsequently employed transcriptomics to probe relationships between changes in Fe supply and phytoplankton physiology. Recently, studies have investigated longer-term (i.e. following acclimation) responses of phytoplankton to various Fe conditions. In the present study, the coastal diatom, Thalassiosira pseudonana, was acclimated (10 generations) to either low or high Fe conditions, i.e. Fe-limiting and Fe-replete. Quantitative proteomics and a newly developed proteomic profiling technique that identifies low abundance proteins were employed to examine the full complement of expressed proteins and consequently the metabolic pathways utilized by the diatom under the two Fe conditions. A total of 1850 proteins were confidently identified, nearly tripling previous identifications made from differential expression in diatoms. Given sufficient time to acclimate to Fe limitation, T. pseudonana up-regulates proteins involved in pathways associated with intracellular protein recycling, thereby decreasing dependence on extracellular nitrogen (N), C and Fe. The relative increase in the abundance of photorespiration and pentose phosphate pathway proteins reveal novel metabolic shifts, which create substrates that could support other well-established physiological responses, such as heavily silicified frustules observed for Fe-limited diatoms. Here, we discovered that proteins and hence pathways observed to be down-regulated in short-term Fe starvation studies are constitutively expressed when T. pseudonana is acclimated (i.e., nitrate and nitrite transporters, Photosystem II and Photosystem I complexes). Acclimation of the diatom to the desired Fe conditions and the comprehensive proteomic approach provides a more robust interpretation of this dynamic proteome than previous studies

Prolonged and tunable residence time using reversible covalent kinase inhibitors.

Drugs with prolonged on-target residence times often show superior efficacy, yet general strategies for optimizing drug-target residence time are lacking. Here we made progress toward this elusive goal by targeting a noncatalytic cysteine in Bruton's tyrosine kinase (BTK) with reversible covalent inhibitors. Using an inverted orientation of the cysteine-reactive cyanoacrylamide electrophile, we identified potent and selective BTK inhibitors that demonstrated biochemical residence times spanning from minutes to 7 d. An inverted cyanoacrylamide with prolonged residence time in vivo remained bound to BTK for more than 18 h after clearance from the circulation. The inverted cyanoacrylamide strategy was further used to discover fibroblast growth factor receptor (FGFR) kinase inhibitors with residence times of several days, demonstrating the generalizability of the approach. Targeting of noncatalytic cysteines with inverted cyanoacrylamides may serve as a broadly applicable platform that facilitates 'residence time by design', the ability to modulate and improve the duration of target engagement in vivo