Long-range repression by multiple polycomb group (PcG) proteins targeted by fusion to a defined DNA-binding domain in Drosophila.

A tethering assay was developed to study the effects of Polycomb group (PcG) proteins on gene expression in vivo. This system employed the Su(Hw) DNA-binding domain (ZnF) to direct PcG proteins to transposons that carried the white and yellow reporter genes. These reporters constituted naive sensors of PcG effects, as bona fide PcG response elements (PREs) were absent from the constructs. To assess the effects of different genomic environments, reporter transposons integrated at nearly 40 chromosomal sites were analyzed. Three PcG fusion proteins, ZnF-PC, ZnF-SCM, and ZnF-ESC, were studied, since biochemical analyses place these PcG proteins in distinct complexes. Tethered ZnF-PcG proteins repressed white and yellow expression at the majority of sites tested, with each fusion protein displaying a characteristic degree of silencing. Repression by ZnF-PC was stronger than ZnF-SCM, which was stronger than ZnF-ESC, as judged by the percentage of insertion lines affected and the magnitude of the conferred repression. ZnF-PcG repression was more effective at centric and telomeric reporter insertion sites, as compared to euchromatic sites. ZnF-PcG proteins tethered as far as 3.0 kb away from the target promoter produced silencing, indicating that these effects were long range. Repression by ZnF-SCM required a protein interaction domain, the SPM domain, which suggests that this domain is not primarily used to direct SCM to chromosomal loci. This targeting system is useful for studying protein domains and mechanisms involved in PcG repression in vivo.

Differences in insulator properties revealed by enhancer blocking assays on episomes.

Insulators are genomic elements that define domains of transcriptional autonomy. Although a large number of insulators have been isolated, it is unclear whether these elements function by shared molecular mechanisms. Novel applications of FLP recombinase technology were used to dissect and compare the function of the Drosophila: gypsy and scs insulators. Inter actions between FLP monomers bound to chromosomally integrated FRT sites were unimpeded by either insulator, demonstrating that these insulators do not establish a chromosomal environment capable of disrupting all types of protein-protein interactions. The gypsy insulator blocked enhancer-activated transcription on FLP-generated extra-chromosomal episomes, whereas the scs insulator displayed silencing effects. These data indicate that these insulators differ in the mechanisms used to prevent enhancer function. That the gypsy insulator blocked enhancer-promoter communication within small episomes suggests that these effects may be accomplished without a global reorganization of chromatin structure. Instead, the gypsy insulator may disrupt enhancer-activated transcription by direct interference with transmission of the enhancer signal to the promoter.

Photonuclear fission from high energy electrons from ultraintense laser-solid interactions

A new regime of laser-matter interactions in which the quiver motion of plasma electrons is fully relativistic, with energies extending well above the threshold for nuclear processes, is studied using a petawatt laser system. In solid target experiments with focused intensities exceeding 10(20) W/cm(2), high energy electron generation, hard bremsstrahlung, and nuclear phenomena have been observed. We report here a quantitative comparison of the high energy electrons and the bremsstrahlung spectrum, as measured by photonuclear reaction yields, including the photoinduced fission of 238U.

Association of MSX1 and TGFB3 with nonsyndromic clefting in humans.

Nonsyndromic cleft lip with or without cleft palate (CL/P) and nonsyndromic cleft palate only (CPO) are common congenital anomalies with significant medical, psychological, social, and economic ramifications. Both CL/P and CPO are examples of complex genetic traits. There exists sufficient evidence to hypothesize that disease loci for CL/P and CPO can be identified by a candidate-gene linkage-disequilibrium (LD) strategy. Candidate genes for clefting, including TGFA, BCL3, DLX2, MSX1, and TGFB3, were screened for LD with either CL/P or CPO in a predominantly Caucasian population, with both case-control- and nuclear-family-based approaches. Previously reported LD for TGFA with both CL/P and CPO could not be confirmed, except in CL/P patients with a positive family history. Also, in contrast to previous studies, no LD was found between BCL3 and either CL/P or CPO. Significant LD was found between CL/P and both MSX1 and TGFB3 and between CPO and MSX1, suggesting that these genes are involved in the pathogenesis of clefting. In addition, a mutation search in the genes DLX2, MSX1, and TGFB3 was performed in 69 CPO patients and in a subset of the CL/P patients. No common mutations were found in the coding regions of these genes; however, several rare variants of MSX1 and TGFB3 were found that may alter the latters' normal function. These results form the basis for future research, including (a) mutation searches in the MSX1 and TGFB3 genes in Caucasian CL/P patients and (b) extension of the search for MSX1 mutations in CPO patients to the noncoding regions.

Localized well-differentiated thyroid carcinoma: survival analysis of prognostic factors and (131)I therapy.

BACKGROUND: Recommendations regarding therapeutic use of (131)I for patients with well-differentiated thyroid cancer remain controversial. Between 1969 and 1993, 1171 patients with papillary (including mixed) or follicular thyroid cancer were reported to the New Mexico Tumor Registry. Of these, 1075 cases (77.6% female, median age 41 years) were available for analysis of survival plots and previously recognized risk factors. Extent of operation was documented for 344 patients. METHODS: One hundred twenty-seven (37%) patients underwent postoperative (131)I ablation. Median follow-up was 99 months. A proportional hazards model was constructed using age, gender, stage, histology, and use of radioiodine. The same variables plus extent of operation were examined in the smaller group. RESULTS: Kaplan-Meier survival estimates at 12 years were 96.2% for patients younger than 45 years and 68.6% for those older than 45 years. Age, gender, and histology, but not stage, were important survival variables (P <.05). Adjusting for other risk factors, there was no apparent survival benefit associated with radioiodine following clinically appropriate thyroidectomy. Findings from the small group mirrored those of the large group. CONCLUSIONS: (131)I may not be as efficacious as previously believed for patients with well-differentiated thyroid cancer confined to the neck.

Induced radioactivity of LDEF materials and structural components.

We present an overview of the Long Duration Exposure Facility (LDEF) induced activation measurements. The LDEF, which was gravity-gradient stabilized, was exposed to the low Earth orbit (LEO) radiation environment over a 5.8 year period. Retrieved activation samples and structural components from the spacecraft were analyzed with low and ultra-low background HPGe gamma spectrometry at several national facilities. This allowed a very sensitive measurement of long-lived radionuclides produced by proton- and neutron-induced reactions in the time-dependent, non-isotropic LEO environment. A summary of major findings from this study is given that consists of directionally dependent activation, depth profiles, thermal neutron activation, and surface beryllium-7 deposition from the upper atmosphere. We also describe a database of these measurements that has been prepared for use in testing radiation environmental models and spacecraft design.

Coexistent thyroid cancer and pregnancy.

OBJECTIVE: A study was performed to determine the appropriate time for the initiation of therapy for thyroid carcinoma first diagnosed during pregnancy. DATA SOURCES: Material on thyroid cancer cases was obtained from the New Mexico Tumor Registry, Albuquerque, a computerized population-based registry for the state of New Mexico, and the Indian reservation facilities in New Mexico and Arizona (a Surveillance, Epidemiology, and End Results Registry funded by the National Cancer Institute, Bethesda, Md) for the period 1970 to 1991. STUDY SELECTION: All cases of thyroid cancer, except medullary and anaplastic, in patients aged 18 to 46 years were evaluated. Subgroups were established for (1) all women who were noted to be pregnant at the time of their initial diagnosis and (2) all women with thyroid cancer in the 18- to 46-year-old age group. DATA EXTRACTION: The information was extracted by a certified tumor registrar for age, sex, thyroid cancer, specific type of thyroid cancer, period, race, year of diagnosis, accession date, last date seen, tumor status, treatment, and patient status. DATA SYNTHESIS: There have been no deaths in the pregnant group with a follow-up ranging from 0.5 to 20 years. There was no statistically significant difference in observed survival rates between the pregnant group and 465 women, aged 18 to 46 years, with comparable thyroid cancers or in the death rates of women aged 18 to 67 years in the general population. CONCLUSIONS: Surgical treatment for patients with well-differentiated thyroid cancer diagnosed during pregnancy can be delayed until after parturition.

Comparison of model predictions with LDEF satellite radiation measurements.

Some early results are summarized from a program under way to utilize LDEF satellite data for evaluating and improving current models of the space radiation environment in low Earth orbit. Reported here are predictions and comparisons with some of the LDEF dose and induced radioactivity data, which are used to check the accuracy of current models describing the magnitude and directionality of the trapped proton environment. Preliminary findings are that the environment models underestimate both dose and activation from trapped protons by a factor of about two, and the observed anisotropy is higher than predicted.

LDEF radiation measurements: preliminary results.

The Long Duration Exposure Facility (LDEF), retrieved by the Space Shuttle mission STS-32 after nearly 6 yr in orbit, is the focus of a broad-based study of the radiation environment in low Earth orbit (LEO) and its effects on materials. A combination of passive techniques has been used to study this environment via detectors which were contained in experiments aboard the LDEF spacecraft and through analysis of induced radioactivities. Preliminary results for absorbed dose measurements and for induced activities in various materials are presented. A number of effects have been observed which reflect the anisotropy of the charged particle flux in low Earth orbit. Quantitative results from these measurements should provide an accurate means of confirming environmental flux models and techniques for predicting radiation encountered in future LEO missions, particularly those of extended duration.

Cosmic ray LET spectra and doses on board Cosmos-2044 biosatellite.

Results of the experiments on board Cosmos-2044 (Biosatellite 9) are presented. Various nuclear track detectors (NTD) (dielectric, AgCl-based, nuclear emulsions) were used to obtain the LET spectra inside and outside the satellite. The spectra from the different NTDs have proved to be in general agreement. The results of LET spectra calculations using two different models are also presented. The resultant LET distributions are used to calculate the absorbed and equivalent doses and the orbit-averaged quality factors (QF) of the cosmic rays (CR). Absorbed dose rates inside (approximately 20 g cm-2 shielding) and outside (1 g cm-2) the spacecraft, omitting electrons, were found to be 4.8 and 8.6 mrad d-1, respectively, while the corresponding equivalent doses were 8.8 and 19.7 mrem d-1. The effects of the flight parameters on the total fluence of, and on the dose from, the CR particles are analyzed. Integral dose distributions of the detected particles are also determined. The LET values which separate absorbed and equivalent doses into 50% intervals are estimated. The CR-39 dielectric NTD is shown to detect 20-30% of the absorbed dose and 60-70% of the equivalent dose in the Cosmos-2044 orbit. The influence of solar activity phase on the magnitude of CR flux is discussed.

Ionizing radiation exposure of LDEF (pre-recovery estimates).

The long duration exposure facility (LDEF), launched into a 258 nautical mile orbit with an inclination of 28.5 degrees, remained in space for nearly 6 yr. The 21,500 lb NASA satellite was one of the largest payloads ever deployed by the Space Shuttle. LDEF completed 32,422 orbits and carried 57 major experiments representing more than 200 investigators from 33 private companies, 21 universities and nine countries. The experiments covered a wide range of disciplines including basic science, electronics, optics, materials, structures and power and propulsion. A number of the experiments were specifically designed to measure the radiation environment. These experiments are of specific interest, since the LDEF orbit is essentially the same as that of the Space Station Freedom. Consequently, the radiation measurements on LDEF will play a significant role in the design of radiation shielding of the space station. The contributions of the various authors presented here attempt to predict the major aspects of the radiation exposure received by the various LDEF experiments and therefore should be helpful to investigators who are in the process of analyzing experiments which may have been affected by exposure to ionizing radiation. The paper discusses the various types and sources of ionizing radiation including cosmic rays, trapped particles (both protons and electrons) and secondary particles (including neutrons, spallation products and high-LET recoils), as well as doses and LET spectra as a function of shielding. Projections of the induced radioactivity of LDEF are also discussed.

Depth distribution of absorbed dose on the external surface of Cosmos 1887 biosatellite.

Significant absorbed dose levels exceeding 1.0 Gy day-1 have been measured on the external surface of the Cosmos 1887 biosatellite as functions of depth in stacks of thin thermoluminescent detectors (TLDs) of U.S.S.R. and U.S.A. manufacture. The dose was found to decrease rapidly with increasing absorber thickness, thereby indicating the presence of intensive fluxes of low-energy particles. Comparison between the U.S.S.R. and U.S.A. results and calculations based on the Vette Model environment are in satisfactory agreement. The major contribution to the dose under thin shielding thickness is shown to be from electrons. The fraction of the dose due to protons and heavier charged particles increases with shielding thickness.

Linear energy transfer (LET) spectra of cosmic radiation in low Earth orbit.

Integral linear energy transfer (LET) spectra of cosmic radiation (CR) particles were measured on five Cosmos series spacecraft in low Earth orbit (LEO). Particular emphasis is placed on results of the Cosmos 1887 biosatellite which carried a set of joint U.S.S.R.-U.S.A. radiation experiments involving passive detectors that included thermoluminescent detectors (TLDs), plastic nuclear track detectors (PNTDs), fission foils, nuclear photo-emulsions, etc. which were located both inside and outside the spacecraft. Measured LET spectra are compared with those theoretically calculated. Results show that there is some dependence of LET spectra on orbital parameters. The results are used to estimate the CR quality factor (QF) for the Cosmos 1887 mission.

The measured radiation environment within Spacelabs 1 and 2 and comparison with predictions.

To measure the radiation environment in the Spacelab (SL) module and on the pallet, a set of passive and active radiation detectors was flown as part of the Verification Flight Instrumentation (VFI). SL 1 carried 4 passive and 2 active detector packages which, with the data from the 26 passive detectors of Experiment INS006, provided a comprehensive survey of the radiation environment within the spacecraft. SL 2 carried 2 passive VFI units on the pallet. Thermoluminescent dosimeters (TLDs) measured the low linear energy transfer (LET) dose component; the HZE fluence and LET spectra were mapped with CR-39 track detectors; thermal and epithermal neutrons were measured with the use of fission foils; metal samples analyzed by gamma ray spectroscopy measured low levels of several activation lines. The TLDs registered from 97 to 143 mrad in the SL 1 module. Dose equivalents of 330 +/- 70 mrem in the SL 1 module and 537 +/- 37 mrem on the SL 2 pallet were measured. The active units in the SL 1 module each contained an integrating tissue-equivalent ion chamber and two differently-shielded xenon-filled proportional counters. The ion chambers accumulated 125 and 128 mrads for the mission with 17 and 12 mrads accumulated during passages through the South Atlantic Anomaly (SAA). The proportional counter rates (approximately 1 cps at sea level) were approximately 100 cps in the middle of the SAA (mostly protons), approximately 35 cps at large geomagnetic latitudes (cosmic rays) and approximately 100 cps in the South Horn of the electron belts (mostly bremsstrahlung). Detailed results of the measurements and comparison with calculated values are described.

Radiation measurements aboard Spacelab 1.

The radiation environment inside Spacelab 1 was measured by a set of passive radiation detectors distributed throughout the volume inside the module, in the access tunnel, and outside on the pallet. Measurements of the low-LET (linear energy transfer) component obtained from the thermoluminescence detectors ranged from 102 to 190 millirads, yielding an average low-LET dose rate of 11.2 millirads per day inside the module, about twice the low-LET dose rate measured on previous flights of the space shuttle. Because of the higher inclination of the orbit (57 degrees versus 28.5 degrees for previous shuttle flights), substantial fluxes of highly ionizing HZE particles (high charge and energy galactic cosmic rays were observed, yielding an overall average mission dose-equivalent of about 150 millirems, more than three times higher than measured on previous shuttle missions.