Prenatal Insecticide Exposures and Birth Weight and Length among an Urban Minority Cohort

We reported previously that insecticide exposures were widespread among minority women in New York City during pregnancy and that levels of the organophosphate chlorpyrifos in umbilical cord plasma were inversely associated with birth weight and length. Here we expand analyses to include additional insecticides (the organophosphate diazinon and the carbamate propoxur), a larger sample size (n = 314 mother–newborn pairs), and insecticide measurements in maternal personal air during pregnancy as well as in umbilical cord plasma at delivery. Controlling for potential confounders, we found no association between maternal personal air insecticide levels and birth weight, length, or head circumference. For each log unit increase in cord plasma chlorpyrifos levels, birth weight decreased by 42.6 g [95% confidence interval (CI), −81.8 to −3.8, p = 0.03] and birth length decreased by 0.24 cm (95% CI, −0.47 to −0.01, p = 0.04). Combined measures of (ln)cord plasma chlorpyrifos and diazinon (adjusted for relative potency) were also inversely associated with birth weight and length (p < 0.05). Birth weight averaged 186.3 g less (95% CI, −375.2 to −45.5) among newborns with the highest compared with lowest 26% of exposure levels (p = 0.01). Further, the associations between birth weight and length and cord plasma chlorpyrifos and diazinon were highly significant (p ≤ 0.007) among newborns born before the 2000–2001 U.S. Environmental Protection Agency’s regulatory actions to phase out residential use of these insecticides. Among newborns born after January 2001, exposure levels were substantially lower, and no association with fetal growth was apparent (p > 0.8). The propoxur metabolite 2-isopropoxyphenol in cord plasma was inversely associated with birth length, a finding of borderline significance (p = 0.05) after controlling for chlorpyrifos and diazinon. Results indicate that prenatal chlorpyrifos exposures have impaired fetal growth among this minority cohort and that diazinon exposures may have contributed to the effects. Findings support recent regulatory action to phase out residential uses of the insecticides

Optimization of the powering tests of the LHC superconducting circuits

The Large Hadron Collider has (LHC) 1572 superconducting circuits which are distributed along the eight 3.5 km LHC sectors [1]. Time and resources during the commissioning of the LHC technical systems were mostly consumed by the powering tests of each circuit. The tests consisted in carrying out several powering cycles at different current levels for each superconducting circuit. The Hardware Commissioning Coordination was in charge of planning, following up and piloting the execution of the test program. The first powering test campaign was carried out in summer 2007 for sector 7-8 with an expected duration of 12 weeks. The experience gained during these tests was used by the commissioning team for minimising the duration of the following powering campaigns to comply with the stringent LHC project deadlines. Improvements concerned several areas: strategy, procedures, control tools, automatization, and resource allocation led to an average daily test rate increase from 25 to 200 tests per day. This paper describes these improvements and details their impact on the operation during the last months of LHC Hardware Commissioning

Information Management within the LHC Hardware Commissioning Project

The core task of the commissioning of the LHC technical systems was the individual test of the 1572 superconducting circuits of the collider, the powering tests. The two objectives of these tests were the validation of the different sub-systems making each superconducting circuit as well as the validation of the superconducting elements of the circuits in their final configuration in the tunnel. A wide set of software applications were developed by the team in charge of coordinating the powering activities (Hardware Commissioning Coordination) in order to manage the amount of information required for the preparation, execution and traceability of the tests. In all the cases special care was taken in order to keep the tools consistent with the LHC quality assurance policy, avoid redundancies between applications, ensure integrity and coherence of the test results and optimise their usability within an accelerator operation environment. This paper describes the main characteristics of these tools; it details their positive impact on the completion on time of the LHC Hardware Commissioning Project and presents usage being envisaged during the coming years of operation of the LHC

Methods to detect faulty splices in the superconducting magnet system of the LHC

The incident of 19 September 2008 at the LHC was caused by a faulty inter-magnet splice of about 200 nΩ resistance. Cryogenic and electrical techniques have been developed to detect other abnormal splices, either between or inside the magnets. The existing quench protection system can be used to detect internal splices with R&gt;20 nΩ. Since this system does not cover the bus between magnets, the cryogenic system is used to measure the rate of temperature rise due to ohmic heating. Accuracy of a few mK/h, corresponding to a few Watts, has been achieved, allowing detection of excess resistance, if it is more than 40 nΩ in a cryogenic subsector (two optical cells). Follow-up electrical measurements are made in regions identified by the cryogenic system. These techniques have detected two abnormal internal magnet splices of 100 nΩ and 50 nΩ respectively. In 2009, this ad hoc system will be replaced with a permanent one to monitor all splices at the nΩ level

Benzothiazinones Are Suicide Inhibitors of Mycobacterial Decaprenylphosphoryl-β-

Benzothiazinones (BTZs) are antituberculosis drug candidates with nanomolar bactericidal activity against tubercle bacilli. Here we demonstrate that BTZs are suicide substrates of the FAD-dependent decaprenylphosphoryl-beta-D-ribofuranose 2'-oxidase DprE1, an enzyme involved in cell-wall biogenesis. BTZs are reduced by DprE1 to an electrophile, which then reacts in a near-quantitative manner with an active-site cysteine of DprE1, thus providing a rationale for the extraordinary potency of BTZs. Mutant DprE1 enzymes from BTZ-resistant strains reduce BTZs to inert metabolites while avoiding covalent inactivation. Our results explain the basis for drug sensitivity and resistance to an exceptionally potent class of antituberculosis agents

The photochemistry of N-p-toluenesulfonyl peptides: the peptide bond as an electron donor

The scope of photobiological processes that involve absorbers within a protein matrix may be limited by the vulnerability of the peptide group to attack by highly reactive redox centers consequent upon electronic excitation. We have explored the nature of this vulnerability by undertaking comprehensive product analyses of aqueous photolysates of 12 N-p-toluene-sulfonyl peptides with systematically selected structures. The results indicate that degradation includes a major pathway that is initiated by intramolecular electron transfer in which the peptide bond serves as electron donor, and the data support the likelihood of a relay process in dipeptide derivatives

Performance of the Main Dipole Magnet Circuits of the LHC during Commissioning

During hardware commissioning of the Large Hadron Collider (LHC), 8 main dipole circuits are tested at 1.9 K and up to their nominal current. Each dipole circuit contains 154 magnets of 15 m length, and has a total stored energy of up to 1.3 GJ. All magnets are wound from Nb-Ti superconducting Rutherford cables, and contain heaters to quickly force the transition to the normal conducting state in case of a quench, and hence reduce the hot spot temperature. In this paper the performance of the first three of these circuits is presented, focussing on quench detection, heater performance, operation of the cold bypass diodes, and magnet-to-magnet quench propagation. The results as measured on the entire circuits will be compared to the test results obtained during the reception tests of the individual magnets

Performance of the Superconducting Corrector Magnet Circuits during the Commissioning of the LHC

The LHC is a complex machine requiring more than 7400 superconducting corrector magnets distributed along a circumference of 26.7 km. These magnets are powered in 1446 different electrical circuits at currents ranging from 60 A up to 600 A. Among the corrector circuits the 600 A corrector magnets form the most diverse and differentiated group. All together, about 60000 high current connections had to be made. A fault in a circuit or one of the superconducting connections would have severe consequences for the accelerator operation. All magnets are wound from various types of Nb-Ti superconducting strands, and many contain parallel protection resistors to by-pass the current still flowing in the other magnets of the same circuit when they quench. In this paper the performance of these magnet circuits is presented, focussing on the quench behaviour of the magnets. Quench detection and the performance of the electrical interconnects will be dealt with. The results as measured on the entire circuits are compared to the test results obtained at the reception of the individual magnets

New Zealand blackcurrant extract enhances fat oxidation during prolonged cycling in endurance-trained females.

PURPOSE: New Zealand blackcurrant (NZBC) extract has previously been shown to increase fat oxidation during prolonged exercise, but this observation is limited to males. We examined whether NZBC intake also increases fat oxidation during prolonged exercise in females, and whether this was related to greater concentrations of circulating fatty acids. METHODS: In a randomised, crossover, double-blind design, 16 endurance-trained females (age: 28 ± 8 years, BMI: 21.3 ± 2.1 kg·m-2, VO2max: 43.7 ± 1.1 ml·kg-1·min-1) ingested 600 mg·day-1NZBC extract (CurraNZ™) or placebo (600 mg·day-1microcrystalline cellulose) for 7 days. On day 7, participants performed 120 min cycling at 65% VO2max, using online expired air sampling with blood samples collected at baseline and at 15 min intervals throughout exercise for analysis of glucose, NEFA and glycerol. RESULTS: NZBC extract increased mean fat oxidation by 27% during 120 min moderate-intensity cycling compared to placebo (P = 0.042), and mean carbohydrate oxidation tended to be lower (P = 0.063). Pre-exercise, plasma NEFA (P = 0.034) and glycerol (P = 0.051) concentrations were greater following NZBC intake, although there was no difference between conditions in the exercise-induced increase in plasma NEFA and glycerol concentrations (P > 0.05). Mean fat oxidation during exercise was moderately associated with pre-exercise plasma NEFA concentrations (r = 0.45, P = 0.016). CONCLUSIONS: Intake of NZBC extract for 7 days elevated resting concentrations of plasma NEFA and glycerol, indicative of higher lipolytic rates, and this may underpin the observed increase in fat oxidation during prolonged cycling in endurance-trained females

Virulence Regulator EspR of Mycobacterium tuberculosis Is a Nucleoid-Associated Protein

The principal virulence determinant of Mycobacterium tuberculosis (Mtb), the ESX-1 protein secretion system, is positively controlled at the transcriptional level by EspR. Depletion of EspR reportedly affects a small number of genes, both positively or negatively, including a key ESX-1 component, the espACD operon. EspR is also thought to be an ESX-1 substrate. Using EspR-specific antibodies in ChIP-Seq experiments (chromatin immunoprecipitation followed by ultra-high throughput DNA sequencing) we show that EspR binds to at least 165 loci on the Mtb genome. Included in the EspR regulon are genes encoding not only EspA, but also EspR itself, the ESX-2 and ESX-5 systems, a host of diverse cell wall functions, such as production of the complex lipid PDIM (phenolthiocerol dimycocerosate) and the PE/PPE cell-surface proteins. EspR binding sites are not restricted to promoter regions and can be clustered. This suggests that rather than functioning as a classical regulatory protein EspR acts globally as a nucleoid-associated protein capable of long-range interactions consistent with a recently established structural model. EspR expression was shown to be growth phase-dependent, peaking in the stationary phase. Overexpression in Mtb strain H37Rv revealed that EspR influences target gene expression both positively or negatively leading to growth arrest. At no stage was EspR secreted into the culture filtrate. Thus, rather than serving as a specific activator of a virulence locus, EspR is a novel nucleoid-associated protein, with both architectural and regulatory roles, that impacts cell wall functions and pathogenesis through multiple genes