Heavy ion beam probe for Wendelstein 7-X measurement capabilities as projected through its design.

A heavy ion beam probe (HIBP) diagnostic is being developed for studies of plasma equilibrium and turbulence in the optimized Wendelstein 7-X (W7-X) stellarator. Operation of W7-X has experimentally demonstrated that its optimized magnetic field results in improved neoclassical particle confinement and, as a result, turbulence is the predominant cause of energy transport. The HIBP will have the unique ability to provide experimental data needed to complement models of both neoclassical and turbulent transport. It will acquire direct measurements in the W7-X plasma interior of the electric potential (needed for understanding ambipolar particle flux) and fluctuations of electron density and potential (needed for understanding turbulence). The HIBP for W7-X will inject singly charged ion beams with energies of up to 2 MeV and is designed to access the upper cross section of the W7-X plasma. We use trajectory simulations to illustrate the plasma coverage that the diagnostic can achieve in the reference magnetic configurations of W7-X. We calculate beam signal levels, discuss anticipated measurement sensitivity of broadband fluctuations of electron density and plasma potential, and show how they depend on plasma density. We also discuss the diagnostic sensitivity to equilibrium plasma potential.

Conceptual design of a heavy ion beam probe diagnostic for the Wendelstein 7-X Stellarator.

This article describes the current state of the design of the heavy ion beam probe (HIBP) for Wendelstein 7-X (W7-X). It will be the first HIBP diagnostic on an optimized stellarator and is designed to study electric fields and ion scale turbulence in all W7-X reference magnetic configurations. The use of an existing 2 MV accelerator, located outside of the torus hall, results in the need for a circuitous primary beamline. This increases the complexity of the ion optics design to deliver a focused beam to the plasma. To access most of the magnetic configuration space of W7-X, the secondary beamline and an energy analyzer are designed to pivot, thereby redirecting a wider range of secondary beam trajectories. Signal level estimates indicate that the equilibrium potential can be measured at all radii and that the radial coverage for potential and density fluctuations measurements depends on the plasma density.

Improvement in the spatial resolution of heavy ion beam probe measurements through application of ion optics.

A technique for more accurately modeling and improving the spatial resolution of heavy ion beam probe measurements is described. We use a set of particle trajectories to numerically determine the focusing properties of a complicated three-dimensional magnetic field and characterize these properties with a transfer matrix. We then modify the transfer matrix approach of traditional ion optics to include a parameter that describes the ionization location of the detected ions. The ion optics model calculated using this technique enables a more accurate description of the particle trajectories than previously feasible. The model also allows one to easily determine an initial beam focus that could be used during experimental operation to optimize the spatial resolution of measurements. The technique has been applied to the design of a heavy ion beam probe diagnostic for the Wendelstein 7-X stellarator, and improvements in the modeled spatial resolution by a factor of about 2 over previous estimates are possible. The improved spatial resolution will enable measurements of plasma fluctuations with smaller wavelengths than would otherwise be possible.

Noise mitigation methods for ion detectors operating with a direct view of high temperature plasmas.

We have developed an ion current measurement instrument with a direct view of a plasma that reduces the particle and radiation-induced noise current it detects by over three orders of magnitude, from tens of microamps to tens of nanoamps. This is accomplished using electric fields, magnetic fields, and physical shielding that limit the flux of particles and radiation into the instrument and suppress the secondary electrons produced within it by particle and radiation impact. Operation of this detector in various configurations, without an ion beam, has allowed identification of the sources of noise current. In our experimental setup, the largest noise contributors were found to be plasma ions and photoelectric emission due to UV radiation.

Disruption of Ini1 leads to peri-implantation lethality and tumorigenesis in mice.

SNF5/INI1 is a component of the ATP-dependent chromatin remodeling enzyme family SWI/SNF. Germ line mutations of INI1 have been identified in children with brain and renal rhabdoid tumors, indicating that INI1 is a tumor suppressor. Here we report that disruption of Ini1 expression in mice results in early embryonic lethality. Ini1-null embryos die between 3.5 and 5.5 days postcoitum, and Ini1-null blastocysts fail to hatch, form the trophectoderm, or expand the inner cell mass when cultured in vitro. Furthermore, we report that approximately 15% of Ini1-heterozygous mice present with tumors, mostly undifferentiated or poorly differentiated sarcomas. Tumor formation is associated with a loss of heterozygocity at the Ini1 locus, characterizing Ini1 as a tumor suppressor in mice. Thus, Ini1 is essential for embryo viability and for repression of oncogenesis in the adult organism.

Computer simulation of three-dimensional heavy ion beam trajectory imaging techniques used for magnetic field estimation.

A magnetic field mapping technique via heavy ion beam trajectory imaging is being developed on the Madison Symmetric Torus reversed field pinch. This paper describes the computational tools created to model camera images of the light emitted from a simulated ion beam, reconstruct a three-dimensional trajectory, and estimate the accuracy of the reconstruction. First, a computer model is used to create images of the torus interior from any candidate camera location. It is used to explore the visual field of the camera and thus to guide camera parameters and placement. Second, it is shown that a three-dimensional ion beam trajectory can be recovered from a pair of perspectively projected trajectory images. The reconstruction considers effects due to finite beam size, nonuniform beam current density, and image background noise. Third, it is demonstrated that the trajectory reconstructed from camera images can help compute magnetic field profiles, and might be used as an additional constraint to an equilibrium reconstruction code, such as MSTFit.

Effect of sodium saccharin and L-tryptophan on rat urine during bladder carcinogenesis.

We examined several parameters of urine excretion during a two-year initiation-promotion experiment in male Fischer rats using four weeks of N-[4-(5-nitro-2-furyl)-2-thiazoly]formamide at 0.2% of the diet as the initiating agent and either 5% sodium saccharin or 2% L-tryptophan in the diet as promoting agents. Rats fed sodium saccharin increased their intake of water; this was accompanied by diarrhea and an increased urinary volume. Osmolality was decreased slightly. The total amount of sodium excreted was increased, although the concentration in the urine was similar to that of the controls or slightly increased. No abnormalities were observed in urinary potassium, calcium, urea, or other parameters measured except for the pH, which was slightly increased during the first three months of the experiment. There was no increase in the size or concentration of crystals in the urine of rats fed sodium saccharin, and no calculi were observed. Hypoglycemia and hypoglycosuria were present in sodium saccharin-fed rats and to a lesser extent in L-tryptophan-fed rats. No other abnormalities were seen in the urine of rats fed L-tryptophan. These data suggest that none of the urinary factors measured in our experiment, including crystal and calculus formation, correlated with the induction of urinary bladder lesions by sodium saccharin.

Development of a beam ion velocity detector for the heavy ion beam probe.

In an axisymmetric plasma, the conservation of canonical angular momentum constrains heavy ion beam probe (HIBP) trajectories such that measurement of the toroidal velocity component of secondary ions provides a localized determination of the poloidal flux at the volume where they originated. We have developed a prototype detector which is designed to determine the beam angle in one dimension through the detection of ion current landing on two parallel planes of detecting elements. A set of apertures creates a pattern of ion current on wires in the first plane and solid metal plates behind them; the relative amounts detected by the wires and plates determine the angle which beam ions enter the detector, which is used to infer the toroidal velocity component. The design evolved from a series of simulations within which we modeled ion beam velocity changes due to equilibrium and fluctuating magnetic fields, along with the ion beam profile and velocity dispersion, and studied how these and characteristics such as the size, cross section, and spacing of the detector elements affect performance.

Control of secondary electrons from ion beam impact using a positive potential electrode.

Secondary electrons emitted when an ion beam impacts a detector can amplify the ion beam signal, but also introduce errors if electrons from one detector propagate to another. A potassium ion beam and a detector comprised of ten impact wires, four split-plates, and a pair of biased electrodes were used to demonstrate that a low-voltage, positive electrode can be used to maintain the beneficial amplification effect while greatly reducing the error introduced from the electrons traveling between detector elements.

Tolerance induction by costimulator blockade in 100 cGy treated hosts with varying degrees of genetic disparity.

Long-term multilineage allochimerism can be obtained in H2-mismatched B6.SJL to BALB/c transplants with host irradiation of 100 cGy, donor spleen cell pre-exposure and costimulator blockade with anti-CD40 ligand (CD40L) antibody. We evaluated this allochimerism approach in murine marrow transplants with different degrees of major histocompatibility complexe (MHC) mismatching; these include: (1) H2-mismatched transplant H2Kk to H2Kb, (2) full haplo-identical transplant H2Kbd to H2Kbk, (3) a partial haplo-identical transplant H2Kd to H2Kbd and (4) an MHC class II mismatch. Levels of chimerism increased up to 12 weeks and then stayed relatively stable up to 1 year after transplant. At 18 weeks post-transplant, the H2-mismatched, haplo-identical, partial haplo-identical and class II-mismatch transplants evidenced 17.9+/-4.4, 40.7+/-0.9, 25.1+/-4.19 and 33.7+/-3.5% donor chimerism, respectively. Dropping the anti-CD40 antibody treatment and spleen cells or changing the schedule of antibody to one injection, in haplo-identical or full-mismatched transplants resulted in no donor-derived chimerism. On the other hand, these still resulted in minor chimerism in class II-mismatched transplants. Lineage analysis of peripheral blood at 6 and 12 months post-transplant demonstrated a significant shift toward increased chimeric lymphocytes and decreased chimeric granulocytes in the full H2 as compared with haplo-identical or class II transplants. Transplantation with anti-CD40L antibody eliminated both graft-versus-leukemia and graft-versus-host disease (GVHD) and delayed lymphocyte infusion did not rescue animals from fatal leukemia. In conclusion, under the conditions of our tolerization regimen, a haplo transplant gives higher engraftment levels than a full H2 mismatch, and despite lower engraftment levels, a class II-mismatched transplant can be successfully accomplished with only 100 cGy and no CD40L blockade.

The marrow cell continuum: stochastic determinism.

Traditional models of hematopoiesis have been hierarchical in nature. Over the past 10 years, we have developed data indicating that hematopoiesis is regulated in a continuum with deterministic and stochastic components. We have shown that the most primitive stem cells, as represented by lineage negative rhodamine(low) Hoechst(low) murine marrow cells are continuously or intermittently cycling as determined by in vivo BrdU labeling. When marrow stem cells are induced to transit cell cycle by in vitro exposure to cytokines, either IL-3, IL-6, IL-11, and steel factor or thrombopoietin, FLT3 ligand, and steel factor, they progress through cycle in a highly synchronized fashion. We have determined that when the stem cells progress through a cytokine stimulated cell cycle the homing, engraftment, adhesion protein, global gene expression, and hematopoietic differentiation phenotypes all change in a reversible fashion. This has led to the continuum model, in which, with cycle transit, chromatin is continually changing altering open transcription areas and providing a continually changing landscape of transcriptional opportunity. More recently, we have extended the changing differentiation profiles to differentiation into lung cells and found that non-hematopoietic differentiation also shows cycle related reversibly modulation. These observations all together support a continuum model of stem cell regulation in which the phenotype of the marrow stem cells is continually and reversibly changing over time.

Multiple lobster tubulin isoforms are encoded by a simple gene family.

Microtubule proteins isolated from pleopod tegumental gland (PTG) tissue of the American lobster, Homarus americanus, reveal a complex tubulin (Tub) profile. To determine whether Tub heterogeneity in PTG is due to expression of a large tub gene family or the result of post-translational modification, a PTG cDNA library was constructed. Clones coding for both alpha- and beta-Tub were isolated, sequenced and found to contain open reading frames (ORFs) of 451 amino acids (aa). Alignments reveal phylogenetic clustering with other arthropods and identify unique changes in primary structure which may have functional significance. These clones, when used to probe restriction enzyme-digested lobster genomic DNA in transfer-hybridization experiments, revealed a simple banding pattern indicating a lobster tub gene family of limited complexity. Lobsters appear to make use of a small tub gene family and fulfill the varied functional requirements imposed upon cellular microtubules through post-translational modifications of relatively few gene products.

Reducing environmental risk associated with laboratory decommissioning and property transfer.

The need for more or less space is a common laboratory problem. Solutions may include renovating existing space, leaving or demolishing old space, or acquiring new space or property for building. All of these options carry potential environmental risk. Such risk can be the result of activities related to the laboratory facility or property (e.g., asbestos, underground storage tanks, lead paint), or the research associated with it (e.g., radioactive, microbiological, and chemical contamination). Regardless of the option chosen to solve the space problem, the potential environmental risk must be mitigated and the laboratory space and/or property must be decommissioned or rendered safe prior to any renovation, demolition, or property transfer activities. Not mitigating the environmental risk through a decommissioning process can incur significant financial liability for any costs associated with future decommissioning cleanup activities. Out of necessity, a functioning system, environmental due diligence auditing, has evolved over time to assess environmental risk and reduce associated financial liability. This system involves a 4-phase approach to identify, document, manage, and clean up areas of environmental concern or liability, including contamination. Environmental due diligence auditing includes a) historical site assessment, b) characterization assessment, c) remedial effort and d) final status survey. General practice standards from the American Society for Testing and Materials are available for conducting the first two phases. However, standards have not yet been developed for conducting the third and final phases of the environmental due diligence auditing process. Individuals involved in laboratory decommissioning work in the biomedical research industry consider this a key weakness.

Antimicrobial drug suspensions: a blinded comparison of taste of twelve common pediatric drugs including cefixime, cefpodoxime, cefprozil and loracarbef.

We conducted a blinded taste test evaluating 12 antimicrobial suspensions by smell, texture, taste, aftertaste and overall acceptance. Drugs received cumulative scores in each category as well as a total score ranking. Overall Lorabid scored highest but not significantly higher than Keflex, Suprax and Ceclor, all of which score higher than the other test drugs. Cefzil and Augmentin scored just below this group of drugs and higher than all other test drugs. Vantin was inferior to these drugs primarily because of its low score in aftertaste. It was ranked along with V-Cillin-K, Veetids, Sulfatrim and Pediazole, the lowest scoring group of drugs other than Dynapen which scored lower than all other test drugs. No difference overall was detected between the two penicillin VK suspensions evaluated, V-Cillin-K and Veetids.

The marrow stem cell: the continuum.

The marrow hematopoietic stem cell is currently being redefined as to all aspects of its phenotype and its total differentiation capacity. This redefinition now includes its plasticity as to production of nonhematopoietic and hematopoietic cell types, the determinants of its in vivo engraftment potential and its expression of stem cell functional characteristics.

Marrow stem cell potential within a continuum.

On the basis of our studies of the fluctuation of the hematopoietic stem cell phenotype with cell cycle trnsit, we hypothesize that the ability of marrow stem cells to convert to nonhematopoietic cells will also vary at different points in the cell cycle. The new biology of stem cells has an impact on many fields including developmental biology and stem cell biology and the clinical potential is enormous.

Molecular analysis of the RhD genotype in fetuses at risk for RhD hemolytic disease.

The objective of this study was to evaluate the accuracy of a DNA-based testing methodology in determining the RhD genotypes of fetuses at risk for RhD hemolytic disease. We designed a multiplex polymerase chain reaction-based test based on recent RhD and RhCE sequence information. To improve the accuracy of the results, two different portions of the RhD gene were examined. Deoxyribonucleic acid was extracted from fetal specimens, portions of the RhD gene were amplified by the polymerase chain reaction, and the amplified product was run on a polyacrylamide gel to look for the presence or absence of the RhD gene. We tested 67 amniotic fluid and two chorionic villus specimens to determine the fetal RhD genotype in pregnancies at risk for RhD hemolytic disease. Forty-seven of the 69 specimens were determined to be Rh-positive, and 22 were Rh-negative. Fifty of the 69 fetal specimens--31 Rh-positive and 19 Rh-negative--were serotyped at birth. In all 50, there was complete correlation between the DNA analysis and the serotyping results. RhD gene analysis is a rapid and reliable method that provides an accurate fetal genotype to aid in the prenatal care of RhD-alloimmunized women.

DNA-based prenatal determination of the RhEe genotype.

BACKGROUND: Maternal antibodies to RhE may cause severe hemolytic disease. Based on recent RhD and RhCE sequence information, we have developed a DNA-based testing methodology to determine the RhEe genotype of fetuses at risk for RhE hemolytic disease from amniotic fluid (AF) or chorionic villus samples. CASE: RhEe testing was undertaken in a fetus at risk for RhE hemolytic disease. Maternal serum anti-E titers had risen between 12-15 weeks' gestation. Optical density (OD450) AF readings also rose slightly between 22-24 weeks' gestation. Both maternal serum titers and AF bilirubin measurements provided early indications that the fetus might have the RhE antigen. Using amniotic cells obtained at the first amniocentesis, DNA was extracted and analyzed for the RhE gene sequence. The use of two primer pairs from distinct sites in the RhCE gene, plus analysis of parental DNA, greatly minimized the possibility of false results. The fetus was determined to be Rhe/Rhe by molecular analysis. The DNA result was confirmed by serologic typing at birth. CONCLUSION: DNA-based RhEe genotyping of at-risk fetuses provides accurate and timely information that is useful in the management of RhE-sensitized pregnancies.

Cigarette smoke inhalation affects the reproductive system of female hamsters.

The purpose of this study was to determine if inhalation of mainstream (MS) or sidestream (SS) smoke affects the reproductive organs of female hamsters. Females inhaled smoke from one or two cigarettes twice per day for 30 d prior to mating using a smoking machine equipped for nose breathing. Serum cotinine levels were within the ranges found in active and passive humans smokers. On day 7 of pregnancy, the reproductive organs of controls and smokers were evaluated for the total number of corpora lutea (CL), the percentage of normal, pink, and small CL, the vascular area in the CL, the ultrastructure of the oviductal epithelium, the ratio of ciliated to secretory cells in the ampulla of the oviduct, the stretchability of the uterine horns, the percentage of implantation sites, and the percentage of touching implantation sites. All parameters, except the percentages of implantation sites and of small CL, were affected by exposure to smoke. To determine if the effects of smoking on the ovary and uterus could be reversed, females smoked for 30 d, remained in their cages without smoking for 30 d, and then were mated and evaluated on day 7 of pregnancy. In this reversal experiment, all ovarian and uterine parameters (except total CL) previously affected by smoking were normal in MS and SS females. These experimental observations show that components in both MS and SS smoke, when delivered at levels comparable to those human smokers receive, can affect the ovary, oviduct, and uterus.

A prediction equation for estimating body fat percentage using readily accessible measures: a multivariate study of 200 adult women.

PURPOSE: This study was conducted to develop a regression equation that accurately estimates body fat percentage using relatively easy and inexpensive methods that do not require women to remove clothing. DESIGN: A cross-sectional design was employed. SETTING: All data were collected at the University. SUBJECTS: Subjects were 200 white women ages 20 to 65 years. The sample was equally distributed across four age groups, 20-29, 30-39, 40-49, and 50-65, and within each age group, one-third of the women were lean, one-third were of average weight, and one-third were obese. MEASURES: Subjects were hydrostatically weighed and participated in a variety of anthropometric and lifestyle assessments, including skinfolds, circumferences, and questionnaire responses. RESULTS: The full regression model included six measures: hip circumference, triceps skinfold (observed and quadratic), age (quadratic), self-reported physical activity, and calf skinfold (quadratic). This equation accounted for 81% of the variance in body weight measured by hydrostatic weighing (SEE = 3.5%). A simpler, five-variable equation was also formed that did not include the calf skinfold assessment (R2 = .800, SEE = 3.6%). CONCLUSIONS: The prediction equations in this study afford accurate and relatively easy and inexpensive means of estimating body fat percentage in a wide range of white women without having them remove their clothing.