Three-dimensional feedback processes in current-driven metal.

Using three-dimensional (3D) magnetohydrodynamic simulations, we study how a pit on a metal surface evolves when driven by intense electrical current density j. Redistribution of j around the pit initiates a feedback loop: j both reacts to and alters the electrical conductivity σ, through Joule heating and hydrodynamic expansion, so that j and σ are constantly in flux. Thus, the pit transforms into larger striation and filament structures predicted by the electrothermal instability theory. Both structures are important in applications of current-driven metal: The striation constitutes a density perturbation that can seed the magneto-Rayleigh-Taylor instability, while the filament provides a more rapid path to plasma formation, through 3D j redistribution. Simulations predict distinctive self-emission patterns, thus allowing for experimental observation and comparison.

Seeding the Electrothermal Instability through a Three-Dimensional, Nonlinear Perturbation.

Electrothermal instability plays an important role in applications of current-driven metal, creating striations (which seed the magneto-Rayleigh-Taylor instability) and filaments (which provide a more rapid path to plasma formation). However, the initial formation of both structures is not well understood. Simulations show for the first time how a commonly occurring isolated defect transforms into the larger striation and filament, through a feedback loop connecting current and electrical conductivity. Simulations have been experimentally validated using defect-driven self-emission patterns.

Harmonic Generation and Inverse Cascade in the z-Pinch Driven, Preseeded Multimode, Magneto-Rayleigh-Taylor Instability.

The magneto-Rayleigh-Taylor instability (MRTI) plays an essential role in astrophysical systems and in magneto-inertial fusion, where it is known to be an important degradation mechanism of confinement and target performance. In this Letter, we show for the first time experimental evidence of mode mixing and the onset of an inverse-cascade process resulting from the nonlinear coupling of two discrete preseeded axial modes (400- and 550-µm wavelengths) on an Al liner that is magnetically imploded using the 20-MA, 100-ns rise-time Z Machine at Sandia National Laboratories. Four radiographs captured the temporal evolution of the MRTI. We introduce a novel unfold technique to analyze the experimental radiographs and compare the results to simulations and to a weakly nonlinear model. We find good quantitative agreement with simulations using the radiation magnetohydrodynamics code hydra. Spectral analysis of the MRTI time evolution obtained from the simulations shows evidence of harmonic generation, mode coupling, and the onset of an inverse-cascade process. The experiments provide a benchmark for future work on the MRTI and motivate the development of new analytical theories to better understand this instability.

Strategies for the Construction of Cassava Brown Streak Disease Viral Infectious Clones.

Cassava brown streak disease (CBSD) has major impacts on yield and quality of the tuberous roots of cassava in Eastern and Central Arica. At least two Potyviridae species cause the disease: Cassava brown streak virus (CBSV) and Ugandan cassava brown streak virus (UCBSV). Cloned viral genome sequences known as infectious clones (ICs) have been important in the study of other viruses, both as a means of standardising infectious material and characterising viral gene function. IC construction is often technically challenging for Potyviridae due to sequence instability in E. coli. Here, we evaluate three methods for the construction of infectious clones for CBSD. Whilst a simple IC for in vitro transcription was made for UCBSV isolate 'Kikombe', such an approach failed to deliver full-length clones for CBSV isolates 'Nampula' or 'Tanza', necessitating more complex approaches for their construction. The ICs successfully generated symptomatic infection in the model host N. benthamiana and in the natural host cassava. This shows that whilst generating ICs for CBSV is still a technical challenge, a structured approach, evaluating both in vitro and in planta transcription systems should successfully deliver ICs, allowing further study into the symptomology and virulence factors in this important disease complex.

Experimental Demonstration of the Stabilizing Effect of Dielectric Coatings on Magnetically Accelerated Imploding Metallic Liners.

Enhanced implosion stability has been experimentally demonstrated for magnetically accelerated liners that are coated with 70 µm of dielectric. The dielectric tamps liner-mass redistribution from electrothermal instabilities and also buffers coupling of the drive magnetic field to the magneto-Rayleigh-Taylor instability. A dielectric-coated and axially premagnetized beryllium liner was radiographed at a convergence ratio [CR=Rin,0/Rin(z,t)] of 20, which is the highest CR ever directly observed for a strengthless magnetically driven liner. The inner-wall radius Rin(z,t) displayed unprecedented uniformity, varying from 95 to 130 µm over the 4.0 mm axial height captured by the radiograph.

Observations of modified three-dimensional instability structure for imploding z-pinch liners that are premagnetized with an axial field.

Novel experimental data are reported that reveal helical instability formation on imploding z-pinch liners that are premagnetized with an axial field. Such instabilities differ dramatically from the mostly azimuthally symmetric instabilities that form on unmagnetized liners. The helical structure persists at nearly constant pitch as the liner implodes. This is surprising since, at the liner surface, the azimuthal drive field presumably dwarfs the axial field for all but the earliest stages of the experiment. These fundamentally 3D results provide a unique and challenging test for 3D-magnetohydrodynamics simulations.

Acute anti-emetic withdrawal associated with a hemorrhagic cerebellar arteriovenous malformation.

We present a 67-year-old right-handed male with a brachium pontis arteriovenous malformation on continuous anti-emetic therapy who demonstrated acute withdrawal symptoms after the abrupt discontinuation of ondansetron, a 5-HT(3) receptor antagonist. Removal of anti-emetic therapy led to the development of extreme flushing and tremor, but subsequent return of ondansetron resulted in the resolution of these symptoms. This is the first clinical report demonstrating acute withdrawal from an anti-emetic agent and we further highlight the need for future studies evaluating not only arterial supply with pressure gradients and anatomical location, but also the association with periventricular venous drainage, venous drainage stenosis, and mass effect from venous stasis as this may contribute partly to the sensitivity of the serotonergic receptors seen here.

Measurements of magneto-Rayleigh-Taylor instability growth during the implosion of initially solid Al tubes driven by the 20-MA, 100-ns Z facility.

The first controlled experiments measuring the growth of the magneto-Rayleigh-Taylor instability in fast (∼100 ns) Z-pinch plasmas are reported. Sinusoidal perturbations on the surface of an initially solid Al tube (liner) with wavelengths of 25-400 µm were used to seed the instability. Radiographs with 15 µm resolution captured the evolution of the outer liner surface. Comparisons with numerical radiation magnetohydrodynamic simulations show remarkably good agreement down to 50 µm wavelengths.

In vitro and in vivo characterisation of anti-murine IL-13 antibodies recognising distinct functional epitopes.

Interleukin-13 (IL-13) sequentially binds to IL-13Ralpha1 and IL-4Ralpha forming a high affinity signalling complex. This receptor complex is expressed on multiple cell types in the airway and signals through signal transducer and activator of transcription factor-6 (STAT-6) to stimulate the production of chemokines, cytokines and mucus. Antibodies have been generated, using the UCB Selected Lymphocyte Antibody Method (UCB SLAM), that block either binding of murine IL-13 (mIL-13) to mIL-13Ralpha1 and mIL-13Ralpha2, or block recruitment of mIL-4Ralpha to the mIL-13/mIL-13Ralpha1 complex. Monoclonal antibody (mAb) A was shown to bind to mIL-13 with high affinity (K(D) 11 pM) and prevent binding of mIL-13 to mIL-13Ralpha1. MAb B, that also bound mIL-13 with high affinity (K(D) 8 pM), was shown to prevent recruitment of mIL-4Ralpha to the mIL-13/mIL-13Ralpha1 complex. In vitro, mAbs A and B similarly neutralised mIL-13-stimulated STAT-6 activation and TF-1 cell proliferation. In vivo, mAbs A and B demonstrated equipotent, dose-dependent inhibition of eotaxin generation in mice stimulated by intraperitoneal administration of recombinant mIL-13. In an allergic lung inflammation model in mice, mAbs A and B equipotently inhibited muc5ac mucin mRNA upregulation in lung tissue measured two days after intranasal allergen challenge. These data support the design of therapeutics for the treatment of allergic airway disease that inhibits assembly of the high affinity IL-13 receptor signalling complex, by blocking the binding of IL-13 to IL-13Ralpha1 and IL-13Ralpha2, or the subsequent recruitment of IL-4Ralpha.

NAD malic enzyme and the control of carbohydrate metabolism in potato tubers.

Potato (Solanum tuberosum) plants were transformed with a cDNA encoding the 59-kD subunit of the potato tuber NAD-dependent malic enzyme (NADME) in the antisense orientation. Measurements of the maximum catalytic activity of NADME in tubers revealed a range of reductions in the activity of this enzyme down to 40% of wild-type activity. There were no detrimental effects on plant growth or tuber yield. Biochemical analyses of developing tubers indicated that a reduction in NADME activity had no detectable effects on flux through the tricarboxylic acid cycle. However, there was an effect on glycolytic metabolism with significant increases in the concentration of 3-phosphoglycerate and phosphoenolpyruvate. These results suggest that alterations in the levels of intermediates toward the end of the glycolytic pathway may allow respiratory flux to continue at wild-type rates despite the reduction in NADME. There was also a statistically significant negative correlation between NADME activity and tuber starch content, with tubers containing reduced NADME having an increased starch content. The effect on plastid metabolism may result from the observed glycolytic perturbations.

The gender specificity of emotional, situational, and behavioral indicators of binge eating in a diet-seeking obese population.

OBJECTIVE: This study investigated the unique gender correlates of binge eating severity in a diet-seeking population. METHOD: This sample consisted of 288 self-admitted patients enrolled in a residential weight loss program between 1996 and 1997. Subjects were administered several questionnaires including (a) the Binge Eating Scale, (b) the Beck Depression Inventory, (c) the Rosenberg Self-Esteem Scale, (d) 5-point scales of eating related foci, and (e) 7-point scales of subject confidence in controlling their eating under various circumstances. Data were analyzed in terms of stepwise regression analyses. RESULTS: Regression results revealed that while men and women share some common predictors of binge eating severity, there are also some gender-specific correlates. Men in our sample were prone to binge eat because of negative emotions (i.e., depression and anger), while binge eating severity for women in our sample was most strongly related to diet failure and tests of moderate eating. DISCUSSION: The strength of the distinctive gender-specific regressions for binge eating severity suggests that the problems of binging in obese males and females are derivatives of differential sex role expectations. This interpretation and clinical implications are the focus of the discussion.

Mutations in the gene encoding starch synthase II profoundly alter amylopectin structure in pea embryos.

Mutations at the rug5 (rugosus5) locus have been used to elucidate the role of the major soluble isoform of starch synthase II (SSII) in amylopectin synthesis in the developing pea embryo. The SSII gene maps to the rug5 locus, and the gene in one of three rug5 mutant lines has been shown to carry a base pair substitution that introduces a stop codon into the open reading frame. All three mutant alleles cause a dramatic reduction or loss of the SSII protein. The mutations have pleiotropic effects on the activities of other isoforms of starch synthase but apparently not on those of other enzymes of starch synthesis. These mutations result in abnormal starch granule morphology and amylopectin structure. Amylopectin contains fewer chains of intermediate length (B2 and B3 chains) and more very short and very long chains than does amylopectin from wild-type embryos. The results suggest that SSII may play a specific role in the synthesis of B2 and B3 chains of amylopectin. The extent to which these findings can be extrapolated to other species is discussed.

Central effects of substance P and somatostatin in conscious, streptozotocin-treated rats.

Cardiovascular responses to intracerebroventricular (icv) injections of substance P and somatostatin were measured in Long-Evans and Brattleboro rats treated with streptozotocin (STZ) or saline. Substance P icv evoked similar pressor responses and tachycardia in STZ-treated and saline-treated Long-Evans rats, together with signs of behavioral activation (i.e., arousal). As a group, Brattleboro rats did not respond significantly to icv substance P, although some individual rats showed clear cardiovascular and behavioral responses. These findings may indicate a reduced sensitivity to icv substance P in Brattleboro rats but show no differences attributable to STZ treatment. Hence, diminished pressor responses to icv angiotensin II (observed previously) may be specific to sympathoadrenal activation associated with drinking. Somatostatin caused a pressor effect in saline-treated, but not in STZ-treated, Long-Evans rats, which was probably due to arginine vasopressin (AVP)-mediated mechanisms because it was not present in either saline-treated or STZ-treated Brattleboro rats. Both control and STZ-treated Long-Evans rats showed a bradycardic response to somatostatin that was not seen in Brattleboro rats. These results indicate that different AVP-mediated mechanisms might be responsible for the pressor and bradycardic effects of icv somatostatin. It is possible that impairment of central somatostatin-mediated AVP release contributes to the diminished role of AVP in blood pressure recovery following ganglion blockade in STZ-treated rats described previously.

Central effects of angiotensins I and II in conscious streptozotocin-treated rats.

Responses to intracerebroventricular (icv) angiotensin II (ANG II) were measured in Long-Evans rats treated with the diabetogenic agent, streptozotocin (STZ), or saline 28 days earlier. STZ-treated Long-Evans rats showed normal pressor responses to ANG II in the absence of drinking water, but bradycardic responses were impaired although there was no reduction in baroreflex sensitivity. When allowed to drink, saline-treated, but not STZ-treated, rats showed an enhanced pressor response to icv ANG II and a tachycardia. Peripheral V1-receptor antagonism attenuated the pressor response to icv ANG II, leaving a residual response that was greater in saline-treated than in STZ-treated rats. STZ-treated rats had attenuated pressor and heart rate responses to icv angiotensin I (ANG I). Although some cardiovascular responses to icv ANG I and ANG II were reduced in STZ-treated rats, these animals showed enhanced sensitivity to the dipsogenic effects of the peptides. Vasopressin-deficient Brattleboro rats showed little pressor response to icv ANG II unless drinking was allowed, in which case the pressor response was less in STZ-treated than in saline-treated Brattleboro rats, although there was no difference in drinking response.

Hypotensive effects of angiotensin II analogues and angiotensin converting enzyme inhibitors in water-deprived Brattleboro rats.

The hypotensive effects of three different angiotensin converting enzyme (ACE) inhibitors (captopril, enalapril, and lisinopril) and two angiotensin II (AII) analogues ([Sar1Ile5Ala8]AII and [Sar1Ile5Thr8]AII) were compared in conscious, freely-moving Brattleboro rats after 14 h of water deprivation. There was no difference between the hypotensive effects of the three ACE inhibitors. Neither was there any difference between the hypotensive effects of the two AII antagonists, although when administered following ACE inhibition, [Sar1Ile5Thr8]AII caused a transient pressor effect that was significantly less than that caused by [Sar1Ile5Ala8]AII. ACE inhibition caused a greater fall in blood pressure (BP) than AII antagonism and caused an additional fall in BP during AII antagonism. These results indicate an additional hypotensive effect of ACE inhibitors, over that of AII antagonists, that is not readily accounted for in terms of nonspecific effects of the former or agonistic properties of the latter.

Blood pressure in streptozotocin-treated Brattleboro and Long-Evans rats.

The diabetogenic agent streptozotocin (STZ) was injected intraperitoneally in Long-Evans and arginine vasopressin (AVP)-deficient Brattleboro rats. Twenty-eight days later both strains had a bradycardia and systolic hypotension; STZ-treated Brattleboro rats also had diastolic hypotension. The vasopressin (V1-receptor) antagonist, d(CH2)5[Tyr(Et)]DAVP, had no effect on resting blood pressure (BP) or heart rate (HR) in either strain of rat, indicating the relative maintenance of diastolic BP in STZ-treated Long-Evans rats was not dependent on acute vascular actions of AVP. Captopril caused a modest hypotension in all groups of rats, indicating that BP was not differentially dependent on the renin-angiotensin system in the different groups. In the presence of captopril and the ganglion blocker, pentolinium tartrate, the AVP-mediated recovery in BP was impaired in STZ-treated Long-Evans rats. During administration of d(CH2)5[Tyr(Et)]DAVP and pentolinium, the angiotensin II (ANG II)-mediated BP recovery was smaller in both groups of STZ-treated rats, indicating that this abnormality was not likely to be caused by inhibition of renin release by AVP. The abnormalities in ANG II- and AVP-mediated recovery were prevented by insulin treatment.

Indicators of effective cytological sampling of the uterine cervix.

A case-control comparison of adequate and inadequate cervical smears (adequacy being defined as the successful detection of cervical intraepithelial neoplasia and inadequacy as the failure to do so when disease was almost certainly present) was undertaken to determine whether indicators of effective cytological sampling could be identified. The association between inadequate smears and the absence of two types of normal epithelial cells (columnar cells of endocervical origin and immature metaplastic cells) was measured. A significant and substantial association was found between inadequate cervical smears and immature metaplastic cells and between inadequate smears and both types of cell. Endocervical cells alone were less likely to be found in inadequate than in adequate smears, but this association was not statistically significant.