Limited Systemic Sclerosis Patients with Pulmonary Arterial Hypertension Show Biomarkers of Inflammation and Vascular Injury

Pulmonary arterial hypertension (PAH) is a common complication for individuals with limited systemic sclerosis (lSSc). The identification and characterization of biomarkers for lSSc-PAH should lead to less invasive screening, a better understanding of pathogenesis, and improved treatment.Forty-nine PBMC samples were obtained from 21 lSSc subjects without PAH (lSSc-noPAH), 15 lSSc subjects with PAH (lSSc-PAH), and 10 healthy controls; three subjects provided PBMCs one year later. Genome-wide gene expression was measured for each sample. The levels of 89 cytokines were measured in serum from a subset of subjects by Multi-Analyte Profiling (MAP) immunoassays. Gene expression clearly distinguished lSSc samples from healthy controls, and separated lSSc-PAH from lSSc-NoPAH patients. Real-time quantitative PCR confirmed increased expression of 9 genes (ICAM1, IFNGR1, IL1B, IL13Ra1, JAK2, AIF1, CCR1, ALAS2, TIMP2) in lSSc-PAH patients. Increased circulating cytokine levels of inflammatory mediators such as TNF-alpha, IL1-beta, ICAM-1, and IL-6, and markers of vascular injury such as VCAM-1, VEGF, and von Willebrand Factor were found in lSSc-PAH subjects.The gene expression and cytokine profiles of lSSc-PAH patients suggest the presence of activated monocytes, and show markers of vascular injury and inflammation. These genes and factors could serve as biomarkers of PAH involvement in lSSc

A note on the relationship between grid structure and metrical structure in Banawá

The stress system of Banawa ́, an endangered Arawan language spoken in the Brazilian Amazon, constitutes a puzzling case study for metrical phonology. It has been claimed that its metrical representations violate the Syllable Integrity Principle (1) (Buller, Buller, and Everett (BBE) 1993, Everett 1996, 1997), one of the core universal principles in standard metrical theory, which bans representations where a foot dis- sects a heavy syllable (e.g., *(CV.CV ́ )(V.CV ́ ), *(CV ́ .CV)(V ́ .CV), where periods indicate syllable boundaries and parentheses, foot edges)

VLT + UVES Spectroscopy of the Low-Ionization Intrinsic Absorber in SDSS J001130.56+005550.7

We analyse high-resolution VLT+UVES spectra of the low-ionization intrinsic absorber observed in the BAL QSO SDSS J001130.56+005550.7. Two narrow absorption systems at velocities -600 km/s and -22000 km/s are detected. The low-velocity system is part of the broad absorption line (BAL), while the high-velocity one is well detached. While most narrow absorption components are only detected in the high-ionization species, the lowest velocity component is detected in both high- and low-ionization species, including in the excited SiII* and CII* lines. From the analysis of doublet lines, we find that the narrow absorption lines at the low-velocity end of the BAL trough are completely saturated but do not reach zero flux, their profiles being dominated by a velocity-dependent covering factor. The covering factor is significantly smaller for MgII than for SiIV and NV, which demonstrates the intrinsic nature of absorber. From the analysis of the excited SiII* and CII* lines in the lowest velocity component, we find an electron density ~ 1000 cm^{-3}. Assuming photoionization equilibrium, we derive a distance ~ 20 kpc between the low-ionization region and the quasar core. The correspondence in velocity of the high- and low-ionization features suggests that all these species must be closely associated, hence formed at the same distance of ~ 20 kpc, much higher than the distance usually assumed for BAL absorbers.Comment: Accepted for publication in A&

Oxygen limitation modulates pH regulation of catabolism and hydrogenases, multidrug transporters, and envelope composition in Escherichia coli K-12

BACKGROUND: In Escherichia coli, pH regulates genes for amino-acid and sugar catabolism, electron transport, oxidative stress, periplasmic and envelope proteins. Many pH-dependent genes are co-regulated by anaerobiosis, but the overall intersection of pH stress and oxygen limitation has not been investigated. RESULTS: The pH dependence of gene expression was analyzed in oxygen-limited cultures of E. coli K-12 strain W3110. E. coli K-12 strain W3110 was cultured in closed tubes containing LBK broth buffered at pH 5.7, pH 7.0, and pH 8.5. Affymetrix array hybridization revealed pH-dependent expression of 1,384 genes and 610 intergenic regions. A core group of 251 genes showed pH responses similar to those in a previous study of cultures grown with aeration. The highly acid-induced gene yagU was shown to be required for extreme-acid resistance (survival at pH 2). Acid also up-regulated fimbriae (fimAC), periplasmic chaperones (hdeAB), cyclopropane fatty acid synthase (cfa), and the "constitutive" Na+/H+ antiporter (nhaB). Base up-regulated core genes for maltodextrin transport (lamB, mal), ATP synthase (atp), and DNA repair (recA, mutL). Other genes showed opposite pH responses with or without aeration, for example ETS components (cyo,nuo, sdh) and hydrogenases (hya, hyb, hyc, hyf, hyp). A hypF strain lacking all hydrogenase activity showed loss of extreme-acid resistance. Under oxygen limitation only, acid down-regulated ribosome synthesis (rpl,rpm, rps). Acid up-regulated the catabolism of sugar derivatives whose fermentation minimized acid production (gnd, gnt, srl), and also a cluster of 13 genes in the gadA region. Acid up-regulated drug transporters (mdtEF, mdtL), but down-regulated penicillin-binding proteins (dacACD, mreBC). Intergenic regions containing regulatory sRNAs were up-regulated by acid (ryeA, csrB, gadY, rybC). CONCLUSION: pH regulates a core set of genes independently of oxygen, including yagU, fimbriae, periplasmic chaperones, and nhaB. Under oxygen limitation, however, pH regulation is reversed for genes encoding electron transport components and hydrogenases. Extreme-acid resistance requires yagU and hydrogenase production. Ribosome synthesis is down-regulated at low pH under oxygen limitation, possibly due to the restricted energy yield of catabolism. Under oxygen limitation, pH regulates metabolism and transport so as to maximize alternative catabolic options while minimizing acidification or alkalinization of the cytoplasm

Bacterial vaginosis in female facility workers in north-western Tanzania: prevalence and risk factors

OBJECTIVES: To determine prevalence of, and risk factors for, bacterial vaginosis (BV) among herpes simplex virus (HSV) 2 seropositive Tanzanian women at enrollment into a randomised, placebo-controlled trial of HSV suppressive treatment. METHODS: 1305 HSV-2 seropositive women aged 16-35 years working in bars, guesthouses and similar facilities were interviewed, examined and tested for HIV, syphilis, Neisseria gonorrhoeae, Chlamydia trachomatis, BV, candidiasis and trichomoniasis. Factors associated with BV were analysed using logistic regression to estimate odds ratios and 95% confidence intervals. RESULTS: BV prevalence was 62.9%; prevalence of Nugent score 9-10 was 16.1%. Independent risk factors for BV were work facility type, fewer dependents, increasing alcohol consumption, sex in the last week (adjusted OR 2.03; 95% CI 1.57 to 2.62), using cloths or cotton wool for menstrual hygiene, HIV (adjusted OR 1.41; 95% CI 1.09 to 1.83) and Trichomonas vaginalis infection. There was no association between BV and the frequency or method of vaginal cleansing. However, BV was less prevalent among women who reported inserting substances to dry the vagina for sex (adjusted OR 0.44; 95% CI 0.25 to 0.75). CONCLUSION: BV was extremely prevalent among our study population of HSV-2 positive female facility workers in North-western Tanzania. Although recent sex was associated with increased BV prevalence, vaginal drying was associated with lower BV prevalence. Further studies of the effects of specific practices on vaginal flora are warranted

Three-Dimensional Simulations of Dynamics of Accretion Flows Irradiated by a Quasar

We study the axisymmetric and non-axisymmetric, time-dependent hydrodynamics of gas that is under the influence of the gravity of a super massive black hole (SMBH) and the radiation force produced by a radiatively efficient flow accreting onto the SMBH. We have considered two cases: (1) the formation of an outflow from the accretion of the ambient gas without rotation and (2) that with weak rotation. The main goals of this study are: (1) to examine if there is a significant difference between the models with identical initial and boundary conditions but in different dimensionality (2-D and 3-D), and (2) to understand the gas dynamics in AGN. Our 3-D simulations of a non-rotating gas show small yet noticeable non-axisymmetric small-scale features inside the outflow. The outflow as a whole and the inflow do not seem to suffer from any large-scale instability. In the rotating case, the non-axisymmetric features are very prominent, especially in the outflow which consists of many cold dense clouds entrained in a smoother hot flow. The 3-D outflow is non-axisymmetric due to the shear and thermal instabilities. In both 2-D and 3-D simulations, gas rotation increases the outflow thermal energy flux, but reduces the outflow mass and kinetic energy fluxes. Rotation also leads to time variability and fragmentation of the outflow in the radial and latitudinal directions. The collimation of the outflow is reduced in the models with gas rotation. The time variability in the mass and energy fluxes is reduced in the 3-D case because of the outflow fragmentation in the azimuthal direction. The virial mass estimated from the kinematics of the dense cold clouds found in our 3-D simulations of rotating gas underestimates the actual mass used in the simulations by about 40 %. (Abbreviated)Comment: 19 pages, 14 figures. Accepted by ApJ. Movies and a full resolution version of the preprint can be downloaded at "http://www.physics.unlv.edu/~rk/research/agn_3d_rot.html

The effects of trauma on intimate relationships: A qualitative study with clinical couples

Research has traditionally focused on the development of symptoms in those who experienced trauma directly but has overlooked the impact of trauma on victims' families. In recent years, researchers and clinicians have begun to examine how individual exposure to traumatic events affects the spouses or partners, children, and professional helpers of trauma survivors. The current study examines qualitative interview data from 17 individuals, analyzed using a retroductive methodology to identify how intimate relationships are affected when there is a history of trauma exposure. The following primary themes were identified: increased communication, decreased communication, increased cohesion/connection, decreased cohesion/connection, increased understanding, decreased understanding, sexual intimacy problems, symptoms of relationship distress, support from partner, and relationship resources. Areas for future research and clinical implications are identified

Correlates of HIV-1 Genital Shedding in Tanzanian Women

Background: Understanding the correlates of HIV shedding is important to inform strategies to reduce HIV infectiousness. We examined correlates of genital HIV-1 RNA in women who were seropositive for both herpes simplex virus (HSV)-2 and HIV-1 and who were enrolled in a randomised controlled trial of HSV suppressive therapy (aciclovir 400 mg b.i.d vs. placebo) in Tanzania.Methodology: Samples, including a cervico-vaginal lavage, were collected and tested for genital HIV-1 and HSV and reproductive tract infections (RTIs) at randomisation and 6, 12 and 24 months follow-up. Data from all women at randomisation and women in the placebo arm during follow-up were analysed using generalised estimating equations to determine the correlates of cervico-vaginal HIV-1 RNA detection and load.Principal Findings: Cervico-vaginal HIV-1 RNA was detected at 52.0% of 971 visits among 482 women, and was independently associated with plasma viral load, presence of genital ulcers, pregnancy, bloody cervical or vaginal discharge, abnormal vaginal discharge, cervical ectopy, Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, an intermediate bacterial vaginosis score and HSV DNA detection. Similar factors were associated with genital HIV-1 RNA load.Conclusions: RTIs were associated with increased presence and quantity of genital HIV-1 RNA in this population. These results highlight the importance of integrating effective RTI treatment into HIV care services

Prompt, early, and afterglow optical observations of five gamma-ray bursts (GRBs 100901A, 100902A, 100905A, 100906A, and 101020A)

We present results of the prompt, early, and afterglow optical observations of five gamma-ray bursts, GRBs 100901A, 100902A, 100905A, 100906A, and 101020A, made with the Mobile Astronomical System of TElescope-Robots in Russia (MASTER-II net), the 1.5-m telescope of Sierra-Nevada Observatory, and the 2.56-m Nordic Optical Telescope. For two sources, GRB 100901A and GRB 100906A, we detected optical counterparts and obtained light curves starting before cessation of gamma-ray emission, at 113 s and 48 s after the trigger, respectively. Observations of GRB 100906A were conducted with two polarizing filters. Observations of the other three bursts gave the upper limits on the optical flux; their properties are briefly discussed. More detailed analysis of GRB 100901A and GRB 100906A supplemented by Swift data provides the following results and indicates different origins of the prompt optical radiation in the two bursts. The light curves patterns and spectral distributions suggest a common production site of the prompt optical and high-energy emission in GRB 100901A. Results of spectral fits for GRB 100901A in the range from the optical to X-rays favor power-law energy distributions with similar values of the optical extinction in the host galaxy. GRB 100906A produced a smoothly peaking optical light curve suggesting that the prompt optical radiation in this GRB originated in a front shock. This is supported by a spectral analysis. We have found that the Amati and Ghirlanda relations are satisfied for GRB 100906A. An upper limit on the value of the optical extinction on the host of GRB 100906A is obtained.Comment: 18 pages, 14 figures, 14 tables, 5 machine readable tables; accepted for publication in MNRA