Maternal obesity heritably perturbs offspring metabolism for three generations without serial programming.

Maternal obesity can program offspring metabolism across multiple generations. It is not known whether multigenerational effects reflect true inheritance of the induced phenotype, or are due to serial propagation of the phenotype through repeated exposure to a compromised gestational milieu. Here we sought to distinguish these possibilities, using the Avy mouse model of maternal obesity. In this model, F1 sons of obese dams display a predisposition to hepatic insulin resistance, which remains latent unless the offspring are challenged with a Western diet. We find that F2 grandsons and F3 great grandsons of obese dams also carry the latent predisposition to metabolic dysfunction, but remain metabolically normal on a healthy diet. Given that the breeding animals giving rise to F2 and F3 were maintained on a healthy diet, the latency of the phenotype permits exclusion of serial programming; we also confirmed that F1 females remained metabolically healthy during pregnancy. Molecular analyses of male descendants identified upregulation of hepatic Apoa4 as a consistent signature of the latent phenotype across all generations. Our results exclude serial programming as a factor in transmission of the metabolic phenotype induced by ancestral maternal obesity, and indicate inheritance through the germline, probably via some form of epigenetic inheritance.

Long duration backlighter experiments at Omega.

We have successfully demonstrated a 7.5 ns duration pinhole-apertured backlighter at the Omega laser facility. Pinhole-apertured point-projection backlighting for 8 ns will be useful for imaging evolving features in experiments at the National Ignition Facility. The backlighter consisted of a 20 microm diameter pinhole in a 75 microm thick Ta substrate separated from a Zn emitter (9 keV) by a 400 microm thick high-density carbon piece. The carbon prevented the shock from the laser-driven surface from reaching the substrate before 8 ns and helped minimize x-ray ablation of the pinhole substrate. Grid wires in x-ray framing camera images of a gold grid have a source-limited resolution significantly smaller than the pinhole diameter due to the high aspect ratio of the pinhole, but do not become much smaller at late times.

Demonstration of the density dependence of x-ray flux in a laser-driven hohlraum.

Experiments have been conducted using laser-driven cylindrical hohlraums whose walls are machined from Ta2O5 foams of 100 mg/cc and 4 g/cc densities. Measurements of the radiation temperature demonstrate that the lower density walls produce higher radiation temperatures than the high density walls. This is the first experimental demonstration of the prediction that this would occur [M. D. Rosen and J. H. Hammer, Phys. Rev. E 72, 056403 (2005)10.1103/PhysRevE.72.056403]. For high density walls, the radiation front propagates subsonically, and part of the absorbed energy is wasted by the flow kinetic energy. For the lower wall density, the front velocity is supersonic and can devote almost all of the absorbed energy to heating the wall.

The utility of flexible sigmoidoscopy after a computerized tomographic colonography revealing only rectosigmoid lesions.

BACKGROUND: Identifying polyps by computerized tomographic colonography typically prompts colonoscopy, increasing its cost, risk and inconvenience. Many polyps are confined to the rectosigmoid and theoretically amenable to resection via flexible sigmoidoscopy. AIM: To determine the prevalence of advanced proximal colonic neoplasia when computerized tomographic colonography reveals only rectosigmoid polyps, and characterize the yield of polypectomy via flexible sigmoidoscopy in such patients. METHODS: Subjects underwent computerized tomographic colonography and colonoscopy with segmental unblinding. Patients with only rectosigmoid findings by computerized tomographic colonography were identified retrospectively. Flexible sigmoidoscopy findings were estimated by including lesions distal to the descending/sigmoid colon junction during colonoscopy. Proximal lesions were also reviewed. Advanced lesions were defined as: adenocarcinoma, tubular adenoma >1 cm, > or =3 tubular adenomas, tubulovillous histology or high-grade dysplasia. RESULTS: By computerized tomographic colonography, 15% (203 of 1372) had only rectosigmoid polyps. Concomitant lesions in the proximal colon were seen in 32% (64 of 203) during colonoscopy. Advanced proximal neoplasia occurred in 2% (three of 203) with only rectosigmoid polyps on computerized tomographic colonography. CONCLUSIONS: Using flexible sigmoidoscopy to follow-up computerized tomographic colonography demonstrating only rectosigmoid polyps would eliminate 15% of subsequent colonoscopies. This strategy carries a small risk of missed proximal advanced neoplasia. This miss rate appears comparable to that of colonoscopy alone. Further study on the cost-effectiveness of this approach is warranted.

High-speed horizontal-path atmospheric turbulence correction with a large-actuator-number microelectromechanical system spatial light modulator in an interferometric phase-conjugation engine.

Results of atmospheric propagation for a high-speed, large-actuator-number adaptive optics system are presented. The system uses a microelectromechanical system- (MEMS-) based spatial light modulator correction device with 1024 actuators. Tests over a 1.35-km path achieved correction speeds in excess of 800 Hz and Strehl ratios close to 0.5. The wave-front sensor was based on a quadrature interferometer that directly measures phase. This technique does not require global wave-front reconstruction, making it relatively insensitive to scintillation and phase residues. The results demonstrate the potential of large-actuator-number MEMS-based spatial light modulators to replace conventional deformable mirrors.

Performance of a phase-conjugate engine implementing a finite-bit phase correction.

The achievable Strehl ratio when a finite-bit correction to an aberrated wave front is implemented is examined. The phase-conjugate engine used to measure the aberrated wave front consists of a quadrature interferometric wave-front sensor, a liquid-crystal spatial light modulator, and computer hardware-software to calculate and apply the correction. A finite-bit approximation to the conjugate phase is calculated and applied to the spatial light modulator to remove the aberrations from the optical beam. The experimentally determined Strehl ratio of the corrected beam is compared with analytical expressions for the expected Strehl ratio and shown to be in good agreement with those predictions.

Investigation of the onset and development of forward scattering in an underdense plasma.

We investigate the distortion of a spatial intensity modulation imposed on a 527 nm f/10 probe beam as it transmits through an underdense plasma characterized with Thomson scattering. Combining the measurements with full wave simulations of beam propagation through the entire plasma show that the key features of the data can be reproduced using the Kaiser thermal transport model.

Observation of saturation of energy transfer between copropagating beams in a flowing plasma.

Experiments demonstrate energy and power transfer between copropagating, same frequency, beams crossing at a small angle in a plasma with a Mach 1 flow. The process is interpreted as amplification of the low intensity probe beam by the stimulated scatter of the high intensity pump beam. The observed probe amplification increases slowly with pump intensity and decreases with probe intensity, indicative of saturation limiting the energy and power transfer due to ion-wave nonlinearities and localized pump depletion. The results are consistent with numerical modeling including ion-wave nonlinearities.

K-shell spectroscopy of an independently diagnosed uniaxially expanding laser-produced aluminum plasma.

We present detailed spectroscopic analysis of the primary K-shell emission lines from a uniaxially expanding laser-produced hydrogenic and heliumlike aluminum plasma. The spectroscopic measurements are found to be consistent with time-dependent hydrodynamic properties of the plasma, measured using Thomson scattering and shadowgraphy. The K-shell population kinetics code FLY with the measured hydrodynamic parameters is used to generate spectra that are compared to the experimental spectra. Excellent agreement is found between the measured and calculated spectra for a variety of experimental target widths employed to produce plasmas with different optical depths. The peak emission from the hydrogenic Lyman series is determined to be from a temporal and spatial region where the hydrodynamic parameters are essentially constant. This allows a single steady-state solution of FLY to be used to deduce the electron temperature and density, from the measured line ratios and linewidths, for comparison with the Thomson and shadowgraphy data. These measurements are found to agree well with time-dependent calculations, and provide further validation for the FLY calculations of the ionization and excitation balance for a K-shell aluminum plasma. We also discuss the possible application of this data as a benchmark for hydrodynamic simulations and ionization/excitation balance calculations.

Human APC2 localization and allelic imbalance.

A second adenomatous polyposis coli (APC)-like gene, APC2/APCL, was recently described and localized to chromosome 19. We have fine mapped APC2 to a small region of chromosome 19p13.3 containing markers D19S883 and WI-19632, a region commonly lost in a variety of cancers, particularly ovarian cancer. Interphase fluorescence in situ hybridization analysis revealed an APC2 allelic imbalance in 19 of 20 ovarian cancers screened and indicates that APC2 could be a potential tumor suppressor gene in ovarian cancer. When overexpressed in SKOV3 ovarian cancer cells, which express low levels of APC2, exogenous APC2 localized to the Golgi apparatus, actin-containing structures, and occasionally to microtubules. Antibodies against the NH2 terminus of human APC2 show that endogenous APC2 is diffusely distributed in the cytoplasm and colocalizes with both the Golgi apparatus and actin filaments. APC2 remained associated with actin filaments after treatment with the actin-disrupting agent, cytochalasin D. These results suggest that APC2 is involved in actin-associated events and could influence cell motility or adhesion through interaction with actin filaments, as well as functioning independently or in cooperation with APC to down-regulate beta-catenin signaling.

Thomson scattering measurements of saturated ion waves in laser fusion plasmas.

We have measured the characteristics of saturated ion-acoustic waves in inertial confinement fusion plasmas. A 263-nm probe laser has been applied to simultaneous Thomson scatter on both ion-acoustic waves excited by thermal electrostatic fluctuations and by stimulated Brillouin scattering of a kilojoule laser beam of varying intensity. The Thomson scattering spectra show saturated ion-wave amplitudes for intensities above 5x10(14) W cm(-2) consistent with three dimensional nonlinear wave modeling.

Backscatter reduction using combined spatial, temporal, and polarization beam smoothing in a long-scale-length laser plasma.

Spatial, temporal, and polarization smoothing schemes are combined for the first time to reduce to a few percent the total stimulated backscatter of a NIF-like probe laser beam (2x10(15) W/cm (2), 351 nm, f/8) in a long-scale-length laser plasma. Combining temporal and polarization smoothing reduces simulated Brillouin scattering and simulated Raman scattering (SRS) up to an order of magnitude although neither smoothing scheme by itself is uniformly effective. The results agree with trends observed in simulations performed with the laser-plasma interaction code F3D simulations [R. L. Berger et al., Phys. Plasma 6, 1043 (1999)].

NRG-3 in human breast cancers: activation of multiple erbB family proteins.

Ligands of the EGF/Heregulin family control the growth of epithelial cells by binding to receptors of the erbB family. By searching a large database of cDNA sequences at Human Genome Sciences Inc. we have identified a new encoded protein sequence containing all the conserved elements of the EGF/Heregulin family. The same sequence has recently been independently identified as NRG-3. The EGF-like domain of NRG-3 was generated as a recombinant protein in E. coli and used to test the specificity of receptor binding. In human breast cancer cells and in 32D cells transfected by erbB family members, NRG-3 activated multiple erbB family members. These include EGF receptor (erbB1) and erbB4 when expressed individually and erbB2 and erbB3 when expressed together. Recombinant NRG-3 altered the growth of human breast cancer cells growing in vitro. NRG-3 was expressed in cell lines derived from breast cancer. These results indicate that NRG-3 is a potential regulator of normal and malignant breast epithelial cells in vivo.

A new short practical quality of life questionnaire for use in head and neck oncology outpatient clinics.

A new short questionnaire to assess the quality of life of head and neck patients has been designed at the University of Liverpool Head and Neck Oncology Department. The questionnaire is short, simple and can be easily completed by a patient whilst in the waiting room before consultation. It is filled in 6 months after completion of treatment and shows very good correlation with the standard long exhaustive questionnaires that are difficult to complete on every patient in a busy National Health Service clinic. The University of Liverpool questionnaire provides a simple score from 0%-100% which should prove valuable in the assessment of quality of care and help with decisions regarding treatment options in head and neck cancer patients.

Occult abdominal injuries to airbag-protected crash victims: a challenge to trauma systems.

A multidisciplinary, automobile crash investigation team at the University of Miami School of Medicine, William Lehman Injury Research Center of Jackson Memorial Hospital/Ryder Trauma Center in Miami, Florida, is conducting a detailed medical and engineering study. The focus is restrained (seatbelts, airbag, or both) occupants involved in frontal crashes who have been severely injured. More than 60 crashes have been included in the study to date. Analysis of the initial data supports the general conclusion that restraint systems are working to reduce many of the head and chest injuries suffered by unrestrained occupants. However, abdominal injuries among airbag-protected occupants still occur. Some are found among occupants who appeared uninjured at the scene. Case examples are provided to illustrate abdominal injuries associated with airbag-protected crashes. The challenges of recognizing injuries to airbag-protected occupants are discussed. To assist in recognizing the extent of injuries to occupants protected by airbags, it is suggested that evidence from the crash scene be used in the triage decision. For the abdominal injury cases observed in this study, deformation of the steering system was the vehicle characteristic most frequently observed. The presence of steering wheel deformation is an indicator of increased likelihood of internal injury. This may justify transporting the victim to a trauma center for a closer examination for abdominal injuries.

The sialomucin CD34 is expressed on hematopoietic cells and blood vessels during murine development.

The processes of angiogenesis and hematopoiesis require a high degree of coordination during embryogenesis. Whereas much is understood about the development of the vascular system in avian embryos, little information has been attained in mammals, predominantly because there are no specific markers for either blood vessels or hematopoietic cells in any developing mammalian system. We have recently shown that murine CD34 (mCD34) is expressed on the vascular endothelium in all organs and tissues of the adult mouse as well as on a small percentage of presumably hematopoietic stem cells in the bone marrow and fetal liver. Here we show that mCD34 is also expressed on the endothelium of blood vessels and on a subset of hematopoietic-like cells throughout murine development. mCD34 is first observed on the yolk sac endothelium of day 7.5 embryos and on a subset of hematopoietic cells within these yolk sacs. mCD34 expression is maintained on vessels and hematopoietic cells in all organs and tissues throughout embryogenesis. In addition, mCD34 is localized on growth conelike filopodial processes that appear at the budding edge of newly sprouted capillaries. Double staining of capillaries for mCD34 and laminin shows that these growth conelike processes seem to be free of laminin, whereas the formed capillaries seem to be coated with this extracellular matrix protein. Analysis of vessels in developing brain shows that these filopodial processes seem to be directed toward the ventricular epithelium, a previously described site of vascular endothelial growth factor synthesis. Finally, we show that the vascular structures of developing murine embryoid bodies also express mCD34. These data suggest that mCD34 is a useful marker for the analysis of the development of the blood vascular system in murine embryos.

Development of Leishmania chagasi (Kinetoplastida: Trypanosomatidae) in the second blood-meal of its vector Lutzomyia longipalpis (Diptera: Psychodidae).

Light and electron microscopy investigations were carried out to compare the development of Leishmania chagasi in Lutzomyia longipalpis females that took a second blood-meal and others that took a single blood-meal. The establishment of the parasite in the foregut and the thoracic midgut of the vector was not severely affected by the intake of the second blood-meal. At 3 days after the intake of the second blood-meal, a rapid increase in the proportion of metacyclic promastigotes detected in the midgut and proboscis of the vector was noticed. No similar increase in the proportion of metacyclic promastigotes observed in the females that took a single blood-meal was noticeable. The results indicate a higher probability of transmission of the parasite to the vertebrate host at the third bite of the vector than at the second bite.

Structure and chromosomal localization of the murine gene encoding GLYCAM 1. A mucin-like endothelial ligand for L selectin.

We recently described the molecular cloning of a murine cDNA encoding an endothelial cell surface ligand for the leukocyte adhesion molecule, L Selectin (Lasky, L. A., Singer, M., Dowbenko, D., Ima, Y., Henzel, W., Grimley, C., Gennie, C., Gillett, N., Watson, S., and Rosen, S. D (1992) Cell 69, 927-938). This glycoprotein ligand was found to resemble mucins in that it contained a large percentage of serine and threonine residues that were apparently O-glycosylated. At least one of the O-linked carbohydrates found on this endothelial ligand interacts with the lectin domain of L Selectin. These data suggest that this endothelial ligand is an adhesion molecule that accomplishes cell binding by presenting carbohydrate(s) to the lectin domain of L Selectin, and the name GLYCAM 1 (GLY-cosylation-dependent Cell Adhesion Molecule 1) has been proposed. In this paper we describe the genomic structure and chromosomal localization of this unique Selectin ligand. The gene has been found to be encoded on four separate exons, and it thus differs from the cell surface mucin leukosialin, whose coding region is contained on one exon, but is similar to glycophorin and CD34, other cell surface mucins whose genes are divided into multiple coding exons. While there is some correlation between exon division and protein domain structure, these relationships are not as clear as they are in other genes. The gene encoding GLYCAM 1 was found to map to murine chromosome 15.