39 research outputs found

    Simulations of the TJNAF FEL with tapered and inversely tapered undulators

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    Experiments using the TJNAF FEL have explored the operation with both tapered and inversely tapered undulators. We present here numerical simulations using the TJNAF experimental parameters, including the effects of taper. Singlemode simulations show the effect of taper on gain. Multimode simulations describe the evolution of short optical pulses in the far infrared, and show how taper affects single-pass gain and steady-state power as a function of desynchronism. A short optical pulse presents an ever-changing field strength to each section of the electron pulse so that idealized operation is not possible. Yet, advantages for the recirculation of the electron beam can be explored.The authors are grateful for support by the Naval Postgraduate School

    Differences in HIV Burden and Immune Activation within the Gut of HIV-Positive Patients Receiving Suppressive Antiretroviral Therapy

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    Background. The gut is a major reservoir for human immunodeficiency virus (HIV) in patients receiving antiretroviral therapy (ART). We hypothesized that distinct immune environments within the gut may support varying levels of HIV. Methods. In 8 HIV-1-positive adults who were receiving ART and had CD4+ T cell counts of >200 cells/µL and plasma viral loads of <40 copies/mL, levels of HIV and T cell activation were measured in blood samples and endoscopic biopsy specimens from the duodenum, ileum, ascending colon, and rectum. Results. HIV DNA and RNA levels per CD4+ T cell were higher in all 4 gut sites compared with those in the blood. HIV DNA levels increased from the duodenum to the rectum, whereas the median HIV RNA level peaked in the ileum. HIV DNA levels correlated positively with T cell activation markers in peripheral blood mononuclear cells (PBMCs) but negatively with T cell activation markers in the gut. Multiply spliced RNA was infrequently detected in gut, and ratios of unspliced RNA to DNA were lower in the colon and rectum than in PBMCs, which reflects paradoxically low HIV transcription, given the higher level of T cell activation in the gut. Conclusions. HIV DNA and RNA are both concentrated in the gut, but the inverse relationship between HIV DNA levels and T cell activation in the gut and the paradoxically low levels of HIV expression in the large bowel suggest that different processes drive HIV persistence in the blood and gut. Trial registration. ClinicalTrials.gov identifier: NCT00884793 (PLUS1

    Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

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    Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

    Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

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    Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

    Free-electron-laser oscillator with a linear taper

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    The article of record as published may be found at http://dx.doi.org/10.1103/PhysRevE.66.056502We present experiments and simulations showing the behavior of a free-electron laser !FEL" with both positive and negative linear tapers along the wiggler. We show the power desynchronism curve widths, efficiency, exhaust electron energy spread, and wavelength dependence as a function of taper for 3- and 6-#m optical wavelengths and for resonators with 10% and 2% loss/pass. Simulations of the experiments, using a multimode analysis, are seen to be in general agreement with the experimental results, carried out at the IR Demo FEL at Thomas Jefferson National Accelerator Facility. We find that short-pulse effects are more effective than tapers in producing high efficiency with low exhaust energy spread, and the expected performance enhancement of FEL tapering is not achieved.This work was supported by the Naval Postgraduate School, the Office of Naval Research, the Commonwealth of Virginia, the Laser Processing Consortium, and the U.S. Department of Energy under Contract No. AC05-84-ER40150

    Observational and Numerical Study of a Tornado Outbreak in Attica and Euboea

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    On October 22, 2015, a rare tornado outbreak occurred in Attica and southern parts of Euboea island, in central Greece. Seven tornado events were recorded by several storm-cells, accompanied with 3.5 cm hail and large amounts of precipitation up to 180 mm, resulting in flash flood causing severe structural damage and 3 human casualties. In this study we investigate the synoptic and mesoscale weather conditions triggering and sustaining ingredients for deep convection and physical mechanisms leading to this extreme tornadogenesis by using upper-air measurements, satellite and Doppler radar data. Furthermore, an interesting interaction between gravity waves and tornadogenesis is also studied through numerical simulations of the Weather Research Forecast model (WRF) in fine resolution. The model was able to fairly reproduce the mesoscale environment associated with the formation of these supercells, showing the presence of 1500 J/kg MLCAPE which overlapped with 20 m/s of 0-6 km Bulk Shear. Furthermore a southwesterly low level flow forced unstable air masses from Saronicos gulf

    Simulations of the TJNAF 10 kW free electron laser

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    The TJNAF Free Electron Laser (FEL) will be upgraded to operate at 10kW average power in the near future. Multimode simulations are used to analyze the operation describing the evolution of short optical pulses in the far infrared wavelength regime. In an FEL that recirculates the electron beam, performance can depend on the electron beam distribution exiting the undulator. The effects of varying the undulator field strength and Rayleigh length of the resonator are explored, as well as the possibility of using an optical klystron. The simulations indicate that the FEL output power can reach the design goal of 10 kW.The authors are grateful for the support by the Naval Postgraduate School, and S. Benson for many useful discussions

    Attitudes and perceptions of Greek drivers towards Autonomous and Connected Vehicles

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    The rapid evolution of digital technology, which is referred to as the "Fourth Industrial Revolution", has radically changed daily routine of people and generally the way in which society works. The gradual penetration of autonomous vehicles into traffic and into lives of people, marks the beginning of a new era, which has caused ambiguous reactions among Greek drivers. Hence, the present study aims to carry out a preliminary analysis of the acceptance of Autonomous and Interconnected Vehicles by Greek drivers. For this purpose, a dedicated questionnaire was formulated and distributed to 91 participants from the city of Volos, Greece between May 2020 and June 2020. By using chi-square tests, the preliminary analysis showed that the acceptance of this new technology mainly depends on the age as well as the road experience of the respondents. Lastly, semi-autonomous vehicles seem to be generally more accepted than autonomous vehicles. © 2022 ACM

    Network support mechanisms for scalable media streaming

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