Duplex DNA from Sites of Helicase-Polymerase Uncoupling Links Non-B DNA Structure Formation to Replicative Stress

BACKGROUND: Replication impediments can produce helicase-polymerase uncoupling allowing lagging strand synthesis to continue for as much as 6 kb from the site of the impediment. MATERIALS AND METHODS: We developed a cloning procedure designed to recover fragments from lagging strand near the helicase halt site. RESULTS: A total of 62% of clones from a p53-deficient tumor cell line (PC3) and 33% of the clones from a primary cell line (HPS-19I) were within 5 kb of a G-quadruplex forming sequence. Analyses of a RACK7 gene sequence, that was cloned multiple times from the PC3 line, revealed multiple deletions in region about 1 kb from the cloned region that was present in a non-B conformation. Sequences from the region formed G-quadruplex and i-motif structures under physiological conditions. CONCLUSION: Defects in components of non-B structure suppression systems (e.g. p53 helicase targeting) promote replication-linked damage selectively targeted to sequences prone to G-quadruplex and i-motif formation

Serum dioxin concentrations and endometriosis: a cohort study in Seveso, Italy.

Dioxin, a ubiquitous contaminant of industrial combustion processes including medical waste incineration, has been implicated in the etiology of endometriosis in animals. We sought to determine whether dioxin exposure is associated with endometriosis in humans. We conducted a population-based historical cohort study 20 years after the 1976 factory explosion in Seveso, Italy, which resulted in the highest known population exposure to 2,3,7,8-tetrachlorodibenzo-(italic)p(/italic)-dioxin (TCDD). Participants were 601 female residents of the Seveso area who were (3/4) 30 years old in 1976 and had adequate stored sera. Endometriosis disease status was defined by pelvic surgery, current transvaginal ultrasound, pelvic examination, and interview (for history of infertility and pelvic pain). "Cases" were women who had surgically confirmed disease or an ultrasound consistent with endometriosis. "Nondiseased" women had surgery with no evidence of endometriosis or no signs or symptoms. Other women had uncertain status. To assess TCDD exposure, individual levels of TCDD were measured in stored sera collected soon after the accident. We identified 19 women with endometriosis and 277 nondiseased women. The relative risk ratios (RRRs) for women with serum TCDD levels of 20.1-100 ppt and >100 ppt were 1.2 [90% confidence interval (CI) = 0.3-4.5] and 2.1 (90% CI = 0.5-8.0), respectively, relative to women with TCDD levels (3/4) 20 ppt. Tests for trend using the above exposure categories and continuous log TCDD were nonsignificant. In conclusion, we report a doubled, nonsignificant risk for endometriosis among women with serum TCDD levels of 100 ppt or higher, but no clear dose response. Unavoidable disease misclassification in a population-based study may have led to an underestimate of the true risk of endometriosis

Serum Dioxin Concentrations and Age at Menopause

2,3,7,8-Tetrachlorobenzo-p-dioxin (TCDD), a halogenated compound that binds the aryl hydrocarbon receptor, is a by-product of numerous industrial processes including waste incineration. Studies in rats and monkeys suggest that TCDD may affect ovarian function. We examined the relationship of TCDD and age at menopause in a population of women residing near Seveso, Italy, in 1976, at the time of a chemical plant explosion. We included 616 of the women who participated 20 years later in the Seveso Women’s Health Study. All women were premenopausal at the time of the explosion, had TCDD levels measured in serum collected soon after the explosion, and were ≥ 35 years of age at interview. Using proportional hazards modeling, we found a 6% nonsignificant increase in risk of early menopause with a 10-fold increase in serum TCDD. When TCDD levels were categorized, compared with women in the lowest quintile (< 20.4 ppt), women in quintile 2 (20.4–34.2 ppt) had a hazard ratio (HR) of 1.1 (p = 0.77), quintile 3 (34.3–54.1 ppt) had an HR of 1.4 (p = 0.14), quintile 4 (54.2–118 ppt) had an HR of 1.6 (p = 0.10), and quintile 5 (> 118 ppt) had an HR of 1.1 (p = 0.82) for risk of earlier menopause. The trend toward earlier menopause across the first four quintiles is statistically significant (p = 0.04). These results suggest a nonmonotonic dose-related association with increasing risk of earlier menopause up to about 100 ppt TCDD, but not above

Quantifying Low Energy Proton Damage in Multijunction Solar Cells

An analysis of the effects of low energy proton irradiation on the electrical performance of triple junction (3J) InGaP2/GaAs/Ge solar cells is presented. The Monte Carlo ion transport code (SRIM) is used to simulate the damage profile induced in a 3J solar cell under the conditions of typical ground testing and that of the space environment. The results are used to present a quantitative analysis of the defect, and hence damage, distribution induced in the cell active region by the different radiation conditions. The modelling results show that, in the space environment, the solar cell will experience a uniform damage distribution through the active region of the cell. Through an application of the displacement damage dose analysis methodology, the implications of this result on mission performance predictions are investigated

Mars Earth Return Vehicle (MERV) Propulsion Options

The COMPASS Team was tasked with the design of a Mars Sample Return Vehicle. The current Mars sample return mission is a joint National Aeronautics and Space Administration (NASA) and European Space Agency (ESA) mission, with ESA contributing the launch vehicle for the Mars Sample Return Vehicle. The COMPASS Team ran a series of design trades for this Mars sample return vehicle. Four design options were investigated: Chemical Return /solar electric propulsion (SEP) stage outbound, all-SEP, all chemical and chemical with aerobraking. The all-SEP and Chemical with aerobraking were deemed the best choices for comparison. SEP can eliminate both the Earth flyby and the aerobraking maneuver (both considered high risk by the Mars Sample Return Project) required by the chemical propulsion option but also require long low thrust spiral times. However this is offset somewhat by the chemical/aerobrake missions use of an Earth flyby and aerobraking which also take many months. Cost and risk analyses are used to further differentiate the all-SEP and Chemical/Aerobrake options

Non-conformal examples of AdS/CFT

Asymptotically anti-de Sitter spacetimes with Poincare invariance along the boundary can describe, via the AdS/CFT correspondence, either relevant deformations of a conformal field theory or non-conformal vacuum states. I consider examples of both types constructed in the framework of five-dimensional gauged supergravity. I explain the proof and motivation of a gravitational ``c-theorem'' which is independent of dimension. I show how one class of examples can be elevated to ten-dimensional geometries involving distributions of parallel D3-branes. For these cases some peculiar properties of two-point functions emerge, and I close with speculations on their physical origin.Comment: 16 pages, two figures, latex. Strings '99 tal

Human Exploration Using Real-Time Robotic Operations (HERRO)- Crew Telerobotic Control Vehicle (CTCV) Design

The HERRO concept allows real time investigation of planets and small bodies by sending astronauts to orbit these targets and telerobotically explore them using robotic systems. Several targets have been put forward by past studies including Mars, Venus, and near Earth asteroids. A conceptual design study was funded by the NASA Innovation Fund to explore what the HERRO concept and it's vehicles would look like and what technological challenges need to be met. This design study chose Mars as the target destination. In this way the HERRO studies can define the endpoint design concepts for an all-up telerobotic exploration of the number one target of interest Mars. This endpoint design will serve to help planners define combined precursor telerobotics science missions and technology development flights. A suggested set of these technologies and demonstrator missions is shown in Appendix B. The HERRO concept includes a crewed telerobotics orbit vehicle as well three Truck rovers, each supporting two teleoperated geologist robots Rockhounds (each truck/Rockhounds set is landed using a commercially launched aeroshell landing system.) Options include a sample ascent system teamed with an orbital telerobotic sample rendezvous and return spacecraft (S/C) (yet to be designed). Each truck rover would be landed in a science location with the ability to traverse a 100 km diameter area, carrying the Rockhounds to 100 m diameter science areas for several week science activities. The truck is not only responsible for transporting the Rockhounds to science areas, but also for relaying telecontrol and high-res communications to/from the Rockhound and powering/heating the Rockhound during the non-science times (including night-time). The Rockhounds take the place of human geologists by providing an agile robotic platform with real-time telerobotics control to the Rockhound from the crew telerobotics orbiter. The designs of the Truck rovers and Rockhounds will be described in other publications. This document focuses on the CTCV design

Serum Dioxin Concentrations and Quality of Ovarian Function in Women of Seveso

BACKGROUND: Although 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been associated with alterations in ovarian function and hormones in animals, it has not been studied in humans. On 10 July 1976, an explosion exposed residents of Seveso, Italy, to the highest levels of TCDD in a population. Twenty years later, we initiated the Seveso Women’s Health Study to study reproductive health. OBJECTIVE: We related TCDD levels measured in sera collected near the time of explosion and ovarian function (ovarian cysts, ovarian follicles, ovulation rate, serum hormones) at follow-up. METHODS: We included 363 women who were 20–40 years of age and nonusers of oral contraceptives. We examined the relationship of 1976 serum TCDD levels with ultrasound-detected ovarian follicles among 96 women in the menstrual follicular phase and serum hormone levels (estradiol, progesterone) among 129 women in the menstrual luteal phase at follow-up. Ovulation was defined by serum progesterone levels > 3 ng/mL. RESULTS: The median serum TCDD level was 77.3 ppt, lipid-adjusted. Serum TCDD was not associated with number or size of ovarian follicles. Of women in the luteal phase, 87 (67%) ovulated. Serum log(10)TCDD was not associated with odds of ovulation [adjusted odds ratio = 0.99; 95% confidence interval (CI), 0.5 to 1.9]. Among those who had ovulated, serum log(10)TCDD was not associated with serum progesterone [adjusted beta (adj-β ) = −0.70; 95% CI, −2.4 to 1.0] or estradiol (adj-β = −1.81; 95% CI, −10.4 to 6.8). CONCLUSIONS: We found no clear evidence that 1976 TCDD exposure was associated with ovarian function 20 years later in women exposed to relatively high levels in Seveso, Italy