Solar g-mode oscillations: Comparison of SMM-ACRIM and ground-based observations

Progress was made in access to data and in developing programs for its analysis. The difficulties in completing the work in the planned time can be traced to several factors. The correction of the Stanford oscillation using gridded intensity data was not successful. It was concluded that due to poor continuity of the 1985 and 1986 data due to clouds, that a joint analysis with the ACRIM data (best solar oscillation data to date) on the summer 1987 observations should be performed. The 1988 Stanford oscillation data are being examined and the cross comparison of the ACRIM spectrum with the Standford spectrum for 1987 in the g-mode regime will shortly begin

On-Orbit Performance of the Helioseismic and Magnetic Imager Instrument onboard the Solar Dynamics Observatory

The Helioseismic and Magnetic Imager (HMI) instrument is a major component of NASA's Solar Dynamics Observatory (SDO) spacecraft. Since beginning normal science operations on 1 May 2010, HMI has operated with remarkable continuity, e.g. during the more than five years of the SDO prime mission that ended 30 September 2015, HMI collected 98.4% of all possible 45-second velocity maps; minimizing gaps in these full-disk Dopplergrams is crucial for helioseismology. HMI velocity, intensity, and magnetic-field measurements are used in numerous investigations, so understanding the quality of the data is important. We describe the calibration measurements used to track HMI performance and detail trends in important instrument parameters during the mission. Regular calibration sequences provide information used to improve and update the HMI data calibration. The set-point temperature of the instrument front window and optical bench is adjusted regularly to maintain instrument focus, and changes in the temperature-control scheme have been made to improve stability in the observable quantities. The exposure time has been changed to compensate for a 15% decrease in instrument throughput. Measurements of the performance of the shutter and tuning mechanisms show that they are aging as expected and continue to perform according to specification. Parameters of the tunable-optical-filter elements are regularly adjusted to account for drifts in the central wavelength. Frequent measurements of changing CCD-camera characteristics, such as gain and flat field, are used to calibrate the observations. Infrequent expected events, such as eclipses, transits, and spacecraft off-points, interrupt regular instrument operations and provide the opportunity to perform additional calibration. Onboard instrument anomalies are rare and seem to occur quite uniformly in time. The instrument continues to perform very well.Comment: 50 pages, 18 figures, 20 table

Phosphomimetic Modulation of eNOS Improves Myocardial Reperfusion and Mimics Cardiac Postconditioning in Mice

Objective: Myocardial infarction resulting from ischemia-reperfusion injury can be reduced by cardiac postconditioning, in which blood flow is restored intermittently prior to full reperfusion. Although key molecular mechanisms and prosurvival pathways involved in postconditioning have been identified, a direct role for eNOS-derived NO in improving regional myocardial perfusion has not been shown. The objective of this study is to measure, with high temporal and spatial resolution, regional myocardial perfusion during ischemia-reperfusion and postconditioning, in order to determine the contribution of regional blood flow effects of NO to infarct size and protection. Methods and Results: We used myocardial contrast echocardiography to measure regional myocardial blood flow in mice over time. Reperfusion after myocardial ischemia-reperfusion injury is improved by postconditioning, as well as by phosphomimetic eNOS modulation. Knock-in mice expressing a phosphomimetic S1176D form of eNOS showed improved myocardial reperfusion and significantly reduced infarct size. eNOS knock-out mice failed to show cardioprotection from postconditioning. The size of the no-reflow zone following ischemia-reperfusion is substantially reduced by postconditioning and by the phosphomimetic eNOS mutation. Conclusions and Significance: Using myocardial contrast echocardiography, we show that temporal dynamics of regional myocardial perfusion restoration contribute to reduced infarct size after postconditioning. eNOS has direct effects on myocardial blood flow following ischemia-reperfusion, with reduction in the size of the no-reflow zone. These results have important implications for ongoing clinical trials on cardioprotection, because the degree of protective benefit may be significantly influenced by the regional hemodynamic effects of eNOS-derived NO.American Heart Association (Predoctoral Fellowship)National Institutes of Health (U.S.) (R01 NS33335)National Institutes of Health (U.S.) (R01 HL57818

Origin of Minority Drug-Resistant HIV-1 Variants in Primary HIV-1 Infection

Background. Drug-resistant human immunodeficiency virus type 1 (HIV-1) minority variants (MVs) are present in some antiretroviral therapy (ART)-naive patients. They may result from de novo mutagenesis or transmission. To date, the latter has not been proven. Methods. MVs were quantified by allele-specific polymerase chain reaction in 204 acute or recent seroconverters from the Zurich Primary HIV Infection study and 382 ART-naive, chronically infected patients. Phylogenetic analyses identified transmission clusters. Results. Three lines of evidence were observed in support of transmission of MVs. First, potential transmitters were identified for 12 of 16 acute or recent seroconverters harboring M184V MVs. These variants were also detected in plasma and/or peripheral blood mononuclear cells at the estimated time of transmission in 3 of 4 potential transmitters who experienced virological failure accompanied by the selection of the M184V mutation before transmission. Second, prevalence between MVs harboring the frequent mutation M184V and the particularly uncommon integrase mutation N155H differed highly significantly in acute or recent seroconverters (8.2% vs 0.5%; P < .001). Third, the prevalence of less-fit M184V MVs is significantly higher in acutely or recently than in chronically HIV-1-infected patients (8.2% vs 2.5%; P = .004). Conclusions. Drug-resistant HIV-1 MVs can be transmitted. To what extent the origin—transmission vs sporadic appearance—of these variants determines their impact on ART needs to be further explore

A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A

Human genetic variation contributes to differences in susceptibility to HIV-1 infection. To search for novel host resistance factors, we performed a genome-wide association study (GWAS) in hemophilia patients highly exposed to potentially contaminated factor VIII infusions. Individuals with hemophilia A and a documented history of factor VIII infusions before the introduction of viral inactivation procedures (1979-1984) were recruited from 36 hemophilia treatment centers (HTCs), and their genome-wide genetic variants were compared with those from matched HIV-infected individuals. Homozygous carriers of known CCR5 resistance mutations were excluded. Single nucleotide polymorphisms (SNPs) and inferred copy number variants (CNVs) were tested using logistic regression. In addition, we performed a pathway enrichment analysis, a heritability analysis, and a search for epistatic interactions with CCR5 Δ32 heterozygosity. A total of 560 HIV-uninfected cases were recruited: 36 (6.4%) were homozygous for CCR5 Δ32 or m303. After quality control and SNP imputation, we tested 1 081 435 SNPs and 3686 CNVs for association with HIV-1 serostatus in 431 cases and 765 HIV-infected controls. No SNP or CNV reached genome-wide significance. The additional analyses did not reveal any strong genetic effect. Highly exposed, yet uninfected hemophiliacs form an ideal study group to investigate host resistance factors. Using a genome-wide approach, we did not detect any significant associations between SNPs and HIV-1 susceptibility, indicating that common genetic variants of major effect are unlikely to explain the observed resistance phenotype in this populatio

Profound Depletion of HIV-1 Transcription in Patients Initiating Antiretroviral Therapy during Acute Infection

Early intervention resulted in profound depletion of PBMC expressing HIV-1 RNA. This is contrary to chronically infected patients who predominantly showed continuous UsRNA expression on cART. Thus, antiretroviral treatment initiated during the acute phase of infection prevented establishment or expansion of long-lived transcriptionally active viral cellular reservoirs in peripheral blood