High spatial resolution spectroscopy of W51IRS 2E and IRS 2W: Two very massive young stars in early formation stages

We present K-band spectra of the near infrared counterparts to IRS 2E and IRS 2W which is associated with the ultracompact H II region W51d, both of them embedded sources in the Galactic compact H II region W51 IRS 2. The high spatial resolution observations were obtained with the laser guide star facility and Near-infrared Integral Field Spectrograph (NIFS) mounted at the Gemini-North observatory. The spectrum of the ionizing source of W51d shows the photospheric features N III ( 21155 angstrom) in emission and He II ( 21897 angstrom) in absorption which lead us to classify it as a young O3 type star. We detected CO overtone in emission at 23000 angstrom in the spectrum of IRS 2E, suggesting that it is a massive young object still surrounded by an accretion disk, probably transitioning from the hot core phase to an ultracompact H II region.

Ultra-high-energy cosmic rays from centaurus A: jet interaction with gaseous shells

Ultra-high-energy cosmic rays (UHECRs), with energies above similar to 6 x 10(19) eV, seem to show a weak correlation with the distribution of matter relatively near to us in the universe. It has earlier been proposed that UHECRs could be accelerated in either the nucleus or the outer lobes of the nearby radio galaxy Cen A. We show that UHECR production at a spatially intermediate location about 15 kpc northeast from the nucleus, where the jet emerging from the nucleus is observed to strike a large star-forming shell of gas, is a plausible alternative. A relativistic jet is capable of accelerating lower energy heavy seed cosmic rays (CRs) to UHECRs on timescales comparable to the time it takes the jet to pierce the large gaseous cloud. In this model, many CRs arising from a starburst, with a composition enhanced in heavy elements near the knee region around PeV, are boosted to ultra-high energies by the relativistic shock of a newly oriented jet. This model matches the overall spectrum shown by the Auger data and also makes a prediction for the chemical composition as a function of particle energy. We thus predict an observable anisotropy in the composition at high energy in the sense that lighter nuclei should preferentially be seen toward the general direction of Cen A. Taking into consideration the magnetic field models for the Galactic disk and a Galactic magnetic wind, this scenario may resolve the discrepancy between HiRes and Auger results concerning the chemical composition of UHECRs.

Control of nutrient solutions for studies at high pH

Little is known about factors effecting plant growth at high pH, with research often limited by the inability to separate nutritional deficiencies and HCO3- toxicity from the direct limitations imposed under high pH conditions. Various methods of controlling dilute nutrient solutions for studies at high pH were investigated. For short-term studies, it was found that a solution without Cu, Fe, Mn and Zn and aerated with CO2 depleted air, greatly reduced nutrient precipitation at high pH, thus eliminating nutritional differences between treatments. Manual pH adjustment and the use of ion exchange resins as pH buffers were unsuitable methods of pH control. However, pH control by automated titration had little effect on solution composition while maintaining constant pH. The system described is suitable for studies in which the pH of the bulk nutrient solution must be maintained. The system was used to examine OH- toxicity in mungbeans (Vigna radiata (L.) Wilczek cv. Emerald), with root length reduced at a bulk solution pH of 8.5 and greater.

Les mots font leurs besognes: Informe as high-low hybridity on board the Ville-de-Montereau

This article links Flaubert's L'Education sentimentale and the aesthetic project of which it is a part to Bataille's concept of 'informe', and associated notions of hybridity and materiality.

Quantification and stability of everolimus (SDZ RAD) in human blood by high-performance liquid chromatography-electrospray tandem mass spectrometry

We report here a validated method for the quantification of a new immunosuppressant drug, everolimus (SDZ RAD), using HPLC-tandem mass spectrometry. Whole blood samples (500 mul) were prepared by protein precipitation, followed by C-18 solid-phase extraction. Mass spectrometric detection was by selected reaction monitoring with an electrospray interface operating in positive ionization mode. The assay was linear from 0.5 to 100 mug/l (r(2) > 0.996, n = 9). The analytical recovery and inter-day imprecision, determined using whole blood quality control samples (n = 5) at 0.5, 1.2, 20.0, and 75.0 mug/l, was 100.3-105.4% and less than or equal to7.6%, respectively. The assay had a mean relative recovery of 94.8 +/- 3.8%. Extracted samples were stable for up to 24 h. Fortified everolimus blood samples were stable at -80 degreesC for at least 8 months and everolimus was found to be stable in blood when taken through at least three freeze-thaw cycles. The reported method provides accurate, precise and specific measurement of everolimus in blood over a wide analytical range and is currently supporting phase 11 and III clinical trials. (C) 2002 Elsevier Science B.V. All rights reserved.

The VCAM-1 gene that encodes the vascular cell adhesion molecule is a target of the Sry-related high mobility group box gene, Sox18

VCAM-1 (vascular cell adhesion molecule-1) and Sox18 are involved in vascular development. VCAM-1 is an important adhesion molecule that is expressed on endothelial cells and has a critical role in endothelial activation, inflammation, lymphatic pathophysiology, and atherogenesis. The Sry-related high mobility group box factor Sox18 has previously been implicated in endothelial pathologies. Mutations in human and mouse Sox18 leads to hypotrichosis and lymphedema. Furthermore, both Sox18 and VCAM-1 have very similar spatio-temporal patterns of expression, which is suggestive of crosstalk. We use biochemical techniques, cell culture systems, and the ragged opossum (RaOP) mouse model with a naturally occurring mutation in Sox18 to demonstrate that VCAM-1 is an important target of Sox18. Transfection, site-specific mutagenesis, and gel shift analyses demonstrated that Sox18 directly targeted and trans-activated VCAM-1 expression. Importantly, the naturally occurring Sox18 mutant attenuates the expression and activation of VCAM-1 in vitro. Furthermore, in vivo quantitation of VCAM-1 mRNA levels in wild type and RaOP mice demonstrates that RaOP animals show a dramatic and significant reduction in VCAM-1 mRNA expression in lung, skin, and skeletal muscle. Our observation that the VCAM-1 gene is an important target of SOX18 provides the first molecular insights into the vascular abnormalities in the mouse mutant ragged and the human hypotrichosis-lymphedematelangiectasia disorder.

High frequency of BRAF mutations in nevi

To evaluate the timing of mutations in BRAF (v-raf murine sarcoma viral oncogene homolog B1) during melanocytic neoplasia, we carried out mutation analysis on microdissected melanoma and nevi samples. We observed mutations resulting in the V599E amino-acid substitution in 41 of 60 (68%) melanoma metastases, 4 of 5 (80%) primary melanomas and, unexpectedly, in 63 of 77 (82%) nevi. These data suggest that mutational activation of the RAS/RAF/MAPK pathway in nevi is a critical step in the initiation of melanocytic neoplasia but alone is insufficient for melanoma tumorigenesis.

Elevated serum uric acid is associated with high circulating inflammatory cytokines in the population-based Colaus study.

BACKGROUND: The relation of serum uric acid (SUA) with systemic inflammation has been little explored in humans and results have been inconsistent. We analyzed the association between SUA and circulating levels of interleukin-6 (IL-6), interleukin-1beta (IL-1beta), tumor necrosis factor- alpha (TNF-alpha) and C-reactive protein (CRP). METHODS AND FINDINGS: This cross-sectional population-based study conducted in Lausanne, Switzerland, included 6085 participants aged 35 to 75 years. SUA was measured using uricase-PAP method. Plasma TNF-alpha, IL-1beta and IL-6 were measured by a multiplexed particle-based flow cytometric assay and hs-CRP by an immunometric assay. The median levels of SUA, IL-6, TNF-alpha, CRP and IL-1beta were 355 micromol/L, 1.46 pg/mL, 3.04 pg/mL, 1.2 mg/L and 0.34 pg/mL in men and 262 micromol/L, 1.21 pg/mL, 2.74 pg/mL, 1.3 mg/L and 0.45 pg/mL in women, respectively. SUA correlated positively with IL-6, TNF-alpha and CRP and negatively with IL-1beta (Spearman r: 0.04, 0.07, 0.20 and 0.05 in men, and 0.09, 0.13, 0.30 and 0.07 in women, respectively, P<0.05). In multivariable analyses, SUA was associated positively with CRP (beta coefficient +/- SE = 0.35+/-0.02, P<0.001), TNF-alpha (0.08+/-0.02, P<0.001) and IL-6 (0.10+/-0.03, P<0.001), and negatively with IL-1beta (-0.07+/-0.03, P = 0.027). Upon further adjustment for body mass index, these associations were substantially attenuated. CONCLUSIONS: SUA was associated positively with IL-6, CRP and TNF-alpha and negatively with IL-1beta, particularly in women. These results suggest that uric acid contributes to systemic inflammation in humans and are in line with experimental data showing that uric acid triggers sterile inflammation.

Development of a high throughput PCR to detect Coxiella burnetii and its application in a diagnostic laboratory over a 7-year period.

Q fever is a worldwide zoonotic infectious disease due to Coxiella burnetii. The clinical presentation may be acute (pneumonia and/or hepatitis) or chronic (most commonly endocarditis). Diagnosis mainly relies on serology and PCR. We therefore developed a quantitative real-time PCR. We first tested blindly its performance on various clinical samples and then, when thoroughly validated, we applied it during a 7-year period for the diagnosis of both acute and persistent C. burnetii infection. Analytical sensitivity (< 10 copies/PCR) was excellent. When tested blindly on 183 samples, the specificity of the PCR was 100% (142/142) and the sensitivity was 71% (29/41). The sensitivity was 88% (7/8) on valvular samples, 69% (20/29) on blood samples and 50% (2/4) on urine samples. This new quantitative PCR was then successfully applied for the diagnosis of acute Q fever and endovascular infection due to C. burnetii, allowing the diagnosis of Q fever in six patients over a 7-year period. During a local small cluster of cases, the PCR was also applied to blood from 1355 blood donors; all were negative confirming the high specificity of this test. In conclusion, we developed a highly specific method with excellent sensitivity, which may be used on sera for the diagnosis of acute Q fever and on various samples such as sera, valvular samples, aortic specimens, bone and liver, for the diagnosis of persistent C. burnetii infection.

Alcohol drinking, the metabolic syndrome and diabetes in a population with high mean alcohol consumption.

AIMS: To investigate the relationship of alcohol consumption with the metabolic syndrome and diabetes in a population-based study with high mean alcohol consumption. Few data exist on these conditions in high-risk drinkers. METHODS: In 6172 adults aged 35-75 years, alcohol consumption was categorized as 0, 1-6, 7-13, 14-20, 21-27, 28-34 and ≥ 35 drinks/week or as non-drinkers (0), low-risk (1-13), medium-to-high-risk (14-34) and very-high-risk (≥ 35) drinkers. Alcohol consumption was objectively confirmed by biochemical tests. In multivariate analysis, we assessed the relationship of alcohol consumption with adjusted prevalence of the metabolic syndrome, diabetes and insulin resistance, determined with the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Seventy-three per cent of participants consumed alcohol, 16% were medium-to-high-risk drinkers and 2% very-high-risk drinkers. In multivariate analysis, the prevalence of the metabolic syndrome, diabetes and mean HOMA-IR decreased with low-risk drinking and increased with high-risk drinking. Adjusted prevalence of the metabolic syndrome was 24% in non-drinkers, 19% in low-risk (P<0.001 vs. non-drinkers), 20% in medium-to-high-risk and 29% in very-high-risk drinkers (P=0.005 vs. low-risk). Adjusted prevalence of diabetes was 6.0% in non-drinkers, 3.6% in low-risk (P<0.001 vs. non-drinkers), 3.8% in medium-to-high-risk and 6.7% in very-high-risk drinkers (P=0.046 vs. low-risk). Adjusted HOMA-IR was 2.47 in non-drinkers, 2.14 in low-risk (P<0.001 vs. non-drinkers), 2.27 in medium-to-high-risk and 2.53 in very-high-risk drinkers (P=0.04 vs. low-risk). These relationships did not differ according to beverage types. CONCLUSIONS: Alcohol has a U-shaped relationship with the metabolic syndrome, diabetes and HOMA-IR, without differences between beverage types.