Showing papers by "University of Utah published in 1999"

Intermittent Administration of Inhaled Tobramycin in Patients with Cystic Fibrosis

Abstract: Background and Methods We conducted two multicenter, double-blind, placebo-controlled trials of intermittent administration of inhaled tobramycin in patients with cystic fibrosis and Pseudomonas aeruginosa infection. A total of 520 patients (mean age, 21 years) were randomly assigned to receive either 300 mg of inhaled tobramycin or placebo twice daily for four weeks, followed by four weeks with no study drug. Patients received treatment or placebo in three on–off cycles for a total of 24 weeks. The end points included pulmonary function, the density of P. aeruginosa in sputum, and hospitalization. Results The patients treated with inhaled tobramycin had an average increase in forced expiratory volume in one second (FEV1) of 10 percent at week 20 as compared with week 0, whereas the patients receiving placebo had a 2 percent decline in FEV1 (P<0.001). In the tobramycin group, the density of P. aeruginosa decreased by an average of 0.8 log10 colony-forming units (CFU) per gram of expectorated sputum from w...

Channel Expansion Theory and the Experiential Nature of Media Richness Perceptions

Abstract: Experiences identified by channel expansion theory as contributing to media-use knowledge bases were hypothesized to be positively related to the perceived richness of a communications channel. We ...

Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse.

Abstract: Iron is essential for many cellular functions; consequently, disturbances of iron homeostasis, leading to either iron deficiency or iron overload, can have significant clinical consequences. Despite the clinical prevalence of these disorders, the mechanism by which dietary iron is absorbed into the body is poorly understood. We have identified a key component in intestinal iron transport by study of the sex-linked anaemia (sla) mouse, which has a block in intestinal iron transport. Mice carrying the sla mutation develop moderate to severe microcytic hypochromic anaemia. Although these mice take up iron from the intestinal lumen into mature epithelial cells normally, the subsequent exit of iron into the circulation is diminished. As a result, iron accumulates in enterocytes and is lost during turnover of the intestinal epithelium. Biochemical studies have failed to identify the underlying difference between sla and normal mice, therefore, we used a genetic approach to identify the gene mutant in sla mice. We describe here a novel gene, Heph, encoding a transmembrane-bound ceruloplasmin homologue that is mutant in the sla mouse and highly expressed in intestine. We suggest that the hephaestin protein is a multicopper ferroxidase necessary for iron egress from intestinal enterocytes into the circulation and that it is an important link between copper and iron metabolism in mammals.

Survey and synthesis of intra- and interspecific variation in stomatal sensitivity to vapour pressure deficit

Abstract: Responses of stomatal conductance (gs) to increasing vapour pressure deficit (D) generally follow an exponential decrease described equally well by several empirical functions. However, the magnitude of the decrease ‐ the stomatal sensitivity ‐ varies considerably both within and between species. Here we analysed data from a variety of sources employing both porometric and sap flux estimates of gs to evaluate the hypothesis that stomatal sensitivity is proportional to the magnitude of gs at low D (£ 1k Pa). To test this relationship we used the function gs = gsref ‐ m ·l nD where m is the stomatal sensitivity and gsref = gs at D = 1 kPa. Regardless of species or methodology, m was highly correlated with gsref (average r 2 = 0·75) with a slope of approximately 0·6. We demonstrate that this empirical slope is consistent with the theoretical slope derived from a simple hydraulic model that assumes stomatal regulation of leaf water potential. The theoretical slope is robust to deviations from underlying assumptions and variation in model parameters. The relationships within and among species are close to theoretical predictions, regardless of whether the analysis is based on porometric measurements of gs in relation to leaf-surface D (Ds), or on sap flux-based stomatal conductance of whole trees (GSi), or stand-level stomatal conductance (GS) in relation to D. Thus, individuals, species, and stands with high stomatal conductance at low D show a greater sensitivity to D, as required by the role of stomata in regulating leaf water potential.

An Integrated Genetic Linkage Map of the Soybean Genome

Abstract: A number of molecular genetic maps of the soybean [Glycine max (L.) Merr.] have been developed over the past 10 yr. These maps are primarily based on restriction fragment length polymorphism (RFLP) markers. Parental surveys have shown that most RFLP loci have only two known alleles. However, because the soybean is an ancient polyploid, RFLP probes typically hybridize and map to more than one position in the genome. Thus, the polymorphic potential of an RFLP probe is primarily a function of the frequency of the two alleles at each locus the probe detects. In contrast, simple sequence repeat (SSR) markers are single locus markers with multiple alleles. The polymorphic potential of an SSR marker is dependent on the number of alleles and their frequencies. Single locus markers provide an unambiguous means of defining linkage group homology across mapping populations. The objective of the work reported here was to develop and map a large set of SSR markers. A total of 606 SSR loci were mapped in one or more of three populations: the USDA/Iowa State G. max × G. soja F 2 population, the Univ. of Utah Minsoy × Noir 1 recombinant inbred population, and the Univ. of Nebraska Clark × Harosoy F 2 population. Each SSR mapped to a single locus in the genome, with a map order that was essentially identical in all three populations. Many SSR loci were segregating in two or all three populations. Thus, it was relatively simple to align the 20+ linkage groups derived from each of the three populations into a consensus set of 20 homologous linkage groups presumed to correspond to the 20 pairs of soybean chromosomes. On the basis of in situ segregation or linkage reports in the literature all but one of the classical linkage groups can now be assigned to a corresponding molecular linkage group.

Carbon isotope fractionation between diet and bioapatite in ungulate mammals and implications for ecological and paleoecological studies.

Abstract: The isotope enrichment ɛ* of 13C between tooth enamel of large ruminant mammals and their diet is 14.1 ± 0.5‰. This value was obtained by analyzing both the dental enamel of a variety of wild and captive mammals and the vegetation that comprised their foodstuffs. This isotope enrichment factor applies to a wide variety of ruminant mammals. Non-ruminant ungulates have a similar isotope enrichment, although our data cannot determine if it is significantly different. We also found a 13C isotope enrichment ɛ* of 3.1 ± 0.7‰ for horn relative to diet, and 11.1 ± 0.8‰ for enamel relative to horn for ruminant mammals. Tooth enamel is a faithful recorder of diet. Its isotopic composition can be used to track changes in the isotopic composition of the atmosphere, determine the fraction of C3 or C4 biomass in diets of modern or fossil mammals, distinguish between mammals using different subpathways of C4 photosynthesis,and identify those mammals whose diet is derived from closed-canopy habitats.

Learning dictionaries for information extraction by multi-level bootstrapping

Abstract: Information extraction systems usually require two dictionaries: a semantic lexicon and a dictionary of extraction patterns for the domain. We present a multilevel bootstrapping algorithm that generates both the semantic lexicon and extraction patterns simultaneously. As input, our technique requires only unannotated training texts and a handful of seed words for a category. We use a mutual bootstrapping technique to alternately select the best extraction pattern for the category and bootstrap its extractions into the semantic lexicon, which is the basis for selecting the next extraction pattern. To make this approach more robust, we add a second level of bootstrapping (metabootstrapping) that retains only the most reliable lexicon entries produced by mutual bootstrapping and then restarts the process. We evaluated this multilevel bootstrapping technique on a collection of corporate web pages and a corpus of terrorism news articles. The algorithm produced high-quality dictionaries for several semantic categories.

ATP Released from Astrocytes Mediates Glial Calcium Waves

Abstract: Calcium waves represent a widespread form of intercellular communication. Although they have been thought for a long time to require gap junctions, we recently demonstrated that mouse cortical astrocytes use an extracellular messenger for calcium wave propagation. The present experiments identify ATP as a major extracellular messenger in this system. Medium collected from astrocyte cultures during (but not before) calcium wave stimulation contains ATP. The excitatory effects of medium samples and of ATP are blocked by purinergic receptor antagonists and by pretreatment with apyrase; these same purinergic receptor antagonists block propagation of electrically evoked calcium waves. ATP, applied at the concentration measured in medium samples, evokes responses that are qualitatively and quantitatively similar to those evoked by those medium samples. These data implicate ATP as an important transmitter between CNS astrocytes.

The Evolution of Mating Preferences and Major Histocompatibility Complex Genes.

Abstract: House mice prefer mates genetically dissimilar at the major histocompatibility complex (MHC). The highly polymorphic MHC genes control immunological self/nonself recognition; therefore, this mating preference may function to provide “good genes” for an individual's offspring. However, the evidence for MHC‐dependent mating preferences is controversial, and its function remains unclear. Here we provide a critical review of the studies on MHC‐dependent mating preferences in mice, sheep, and humans and the possible functions of this behavior. There are three adaptive hypotheses for MHC‐dependent mating preferences. First, MHC‐disassortative mating preferences produce MHC‐heterozygous offspring that may have enhanced immunocompetence. Although this hypothesis is not supported by tests of single parasites, MHC heterozygotes may be resistant to multiple parasites. Second, we propose that MHC‐dependent mating preferences enable hosts to provide a “moving target” against rapidly evolving parasites that e...

Brief report: specific executive function profiles in three neurodevelopmental disorders

Abstract: It has been proposed that deficient executive functions, such as flexibility, set maintenance, organization, planning, and working memory, may be primary cognitive deficits of autism (Hughes, Russell, & Robbins, 1994; Ozonoff, Pennington, & Rogers, 1991). Executive deficits may also play a part in several other developmental and neurological disorders, however (Ozonoff, 1997; Pennington & Ozonoff, 1996), including attentiondeficit hyperactivity disorder (ADHD; Chelune, Ferguson, Koon, & Dickey, 1986) and Tourette syndrome (TS; Bornstein, 1990; Gladstone el al., 1993). This finding has raised the so-called "discriminant validity question" (Pennington, 1994; Pennington & Ozonoff, 1996): That is, how can disorders differing in behavioral phenotype share the same cognitive underpinnings? One answer to this question is that specific types of executive impairment may be associated with specific neurodevelopmental disorders. Since the class of executive behaviors is large and diverse, it is important to clarify precisely which functions are impaired in each disorder. We hypothesized that when the broad domain of executive function was parsed into specific components (e.g., planning, flexibility, inhibition), different disorders would demonstrate different executive profiles. Three measures, the Wisconsin Card Sorting Task (WCST), the Tower of Hanoi (TOH), and the Stroop Color-Word Test, have traditionally been used to measure executive function deficits in neurodevelopmental disorders. The WCST (Grant & Berg, 1948; Heaton, Chelune, Talley, Kay, & Curtiss, 1993) was designed primarily to test flexibility, the TOH (Borys, Spitz, &

The dynamin-related GTPase Dnm1 regulates mitochondrial fission in yeast

Abstract: The dynamin-related GTPase Dnm1 controls mitochondrial morphology in yeast. Here we show that dnm1 mutations convert the mitochondrial compartment into a planar ‘net’ of interconnected tubules. We propose that this net morphology results from a defect in mitochondrial fission. Immunogold labelling localizes Dnm1 to the cytoplasmic face of constricted mitochondrial tubules that appear to be dividing and to the ends of mitochondrial tubules that appear to have recently completed division. The activity of Dnm1 is epistatic to that of Fzo1, a GTPase in the outer mitochondrial membrane that regulates mitochondrial fusion. dnm1 mutations prevent mitochondrial fragmentation in fzo1 mutant strains.These findings indicate that Dnm1 regulates mitochondrial fission, assembling on the cytoplasmic face of mitochondrial tubules at sites at which division will occur.

Treatment of Active Rheumatoid Arthritis With Leflunomide Compared With Placebo and Methotrexate

Abstract: rheumatic drugs had failed. The ACR response and success rates for patients receiving leflunomide treatment (52% and 41%, respectively) and methotrexate treatment (46% and 35%, respectively) were significantly higher than those for patients receiving placebo (26% and 19%, respectively) (P,.001), and they were statistically equivalent, with mean time to initial response at 8.4 weeks for patients receiving leflunomide vs 9.5 weeks for patients receiving methotrexate therapy. X-ray analyses demonstrated less disease progression with leflunomide (P#.001) and methotrexate (P = .02) therapy than with placebo. Leflunomide and methotrexate treatment improved measures of physical function and health-related quality of life significantly more than placebo (P,.001 and P,.05, respectively). Common adverse events for patients receiving leflunomide treatment included gastrointestinal complaints, skin rash, and reversible alopecia. Asymptomatic transaminase elevations resulted in treatment discontinuations for 7.1% of patients receiving leflunomide therapy, 1.7% of patients receiving placebo, and 3.3% of patients receiving methotrexate therapy. Conclusions: Clinical responses following administration of leflunomide, a new therapeutic agent for the treatment of RA, were statistically superior to those with placebo and equivalent to those with methotrexate treatment. Both active treatments improved signs and symptoms of active RA, delayed disease progression as demonstrated by x-ray films, and improved function and health-related quality of life. Arch Intern Med. 1999;159:2542-2550

Least-squares migration of incomplete reflection data

Abstract: A least-squares migration algorithm is presented that reduces the migration artifacts (i.e., recording footprint noise) arising from incomplete data. Instead of migrating data with the adjoint of the forward modeling operator, the normal equations are inverted by using a preconditioned linear conjugate gradient scheme that employs regularization. The modeling operator is constructed from an asymptotic acoustic integral equation, and its adjoint is the Kirchhoff migration operator. We tested the performance of the least-squares migration on synthetic and field data in the cases of limited recording aperture, coarse sampling, and acquisition gaps in the data. Numerical results show that the least-squares migrated sections are typically more focused than are the corresponding Kirchhoff migrated sections and their reflectivity frequency distributions are closer to those of the true model frequency distribution. Regularization helps attenuate migration artifacts and provides a sharper, better frequency distribution of estimated reflectivity. The least-squares migrated sections can be used to predict the missing data traces and interpolate and extrapolate them according to the governing modeling equations. Several field data examples are presented. A ground-penetrating radar data example demonstrates the suppression of the recording footprint noise due to a limited aperture, a large gap, and an undersampled receiver line. In addition, better fault resolution was achieved after applying least-squares migration to a poststack marine data set. And a reverse vertical seismic profiling example shows that the recording footprint noise due to a coarse receiver interval can be suppressed by least-squares migration.

Dietary Fiber, Weight Gain, and Cardiovascular Disease Risk Factors in Young Adults

Abstract: ContextDietary composition may affect insulin secretion, and high insulin levels, in turn, may increase the risk for cardiovascular disease (CVD).ObjectiveTo examine the role of fiber consumption and its association with insulin levels, weight gain, and other CVD risk factors compared with other major dietary components.Design and SettingThe Coronary Artery Risk Development in Young Adults (CARDIA) Study, a multicenter population-based cohort study of the change in CVD risk factors over 10 years (1985-1986 to 1995-1996) in Birmingham, Ala; Chicago, Ill; Minneapolis, Minn; and Oakland, Calif.ParticipantsA total of 2909 healthy black and white adults, 18 to 30 years of age at enrollment.Main Outcome MeasuresBody weight, insulin levels, and other CVD risk factors at year 10, adjusted for baseline values.ResultsAfter adjustment for potential confounding factors, dietary fiber showed linear associations from lowest to highest quintiles of intake with the following: body weight (whites: 174.8-166.7 lb [78.3-75.0 kg], P<.001; blacks: 185.6-177.6 lb [83.5-79.9 kg], P = .001), waist-to-hip ratio (whites: 0.813-0.801, P = .004; blacks: 0.809-0.799, P = .05), fasting insulin adjusted for body mass index (whites: 77.8-72.2 pmol/L [11.2-10.4 µU/mL], P = .007;blacks: 92.4-82.6 pmol/L [13.3-11.9 µU/mL], P = .01) and 2-hour postglucose insulin adjusted for body mass index (whites: 261.1-234.7 pmol/L [37.6-33.8 µU/mL], P = .03; blacks: 370.2-259.7 pmol/L [53.3-37.4 µU/mL], P<.001). Fiber was also associated with blood pressure and levels of triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and fibrinogen; these associations were substantially attenuated by adjustment for fasting insulin level. In comparison with fiber, intake of fat, carbohydrate, and protein had inconsistent or weak associations with all CVD risk factors.ConclusionsFiber consumption predicted insulin levels, weight gain, and other CVD risk factors more strongly than did total or saturated fat consumption. High-fiber diets may protect against obesity and CVD by lowering insulin levels.

A genomic screen of autism: evidence for a multilocus etiology.

Abstract: Summary We have conducted a genome screen of autism, by linkage analysis in an initial set of 90 multiplex sibships, with parents, containing 97 independent affected sib pairs (ASPs), with follow-up in 49 additional multiplex sibships, containing 50 ASPs. In total, 519 markers were genotyped, including 362 for the initial screen, and an additional 157 were genotyped in the follow-up. As a control, we also included in the analysis unaffected sibs, which provided 51 discordant sib pairs (DSPs) for the initial screen and 29 for the follow-up. In the initial phase of the work, we observed increased identity by descent (IBD) in the ASPs (sharing of 51.6%) compared with the DSPs (sharing of 50.8%). The excess sharing in the ASPs could not be attributed to the effect of a small number of loci but, rather, was due to the modest increase in the entire distribution of IBD. These results are most compatible with a model specifying a large number of loci (perhaps ⩾15) and are less compatible with models specifying ≤10 loci. The largest LOD score obtained in the initial scan was for a marker on chromosome 1p; this region also showed positive sharing in the replication family set, giving a maximum multipoint LOD score of 2.15 for both sets combined. Thus, there may exist a gene of moderate effect in this region. We had only modestly positive or negative linkage evidence in candidate regions identified in other studies. Our results suggest that positional cloning of susceptibility loci by linkage analysis may be a formidable task and that other approaches may be necessary.

Cutting Edge: Inflammatory Signaling by Borrelia burgdorferi Lipoproteins Is Mediated by Toll-Like Receptor 2

Abstract: The agent of Lyme disease, Borrelia burgdorferi, produces membrane lipoproteins possessing potent inflammatory properties linked to disease pathology. The recent association of toll-like receptors (TLR) 2 and 4 with LPS responses prompted the examination of TLR involvement in lipoprotein signaling. The ability of human cell lines to respond to lipoproteins was correlated with the expression of TLR2. Transfection of TLR2 into cell lines conferred responsiveness to lipoproteins, lipopeptides, and sonicated B. burgdorferi, as measured by nuclear translocation of NF-kappaB and cytokine production. The physiological importance of this interaction was demonstrated by the 10-fold greater sensitivity of TLR2-transfected cells to lipoproteins than LPS. Futhermore, TLR2-dependent signaling by lipoproteins was facilitated by CD14. These data indicate that TLR2 facilitates the inflammatory events associated with Lyme arthritis. In addition, the widespread expression of lipoproteins by other bacterial species suggests that this interaction may have broad implications in microbial inflammation and pathogenesis.

Members of the YABBY gene family specify abaxial cell fate in Arabidopsis.

Abstract: Lateral organs produced by shoot apical and flower meristems exhibit a fundamental abaxial-adaxial asymmetry. We describe three members of the YABBY gene family, FILAMENTOUS FLOWER, YABBY2 and YABBY3, isolated on the basis of homology to CRABS CLAW. Each of these genes is expressed in a polar manner in all lateral organ primordia produced from the apical and flower meristems. The expression of these genes is precisely correlated with abaxial cell fate in mutants in which abaxial cell fates are found ectopically, reduced or eliminated. Ectopic expression of either FILAMENTOUS FLOWER or YABBY3 is sufficient to specify the development of ectopic abaxial tissues in lateral organs. Conversely, loss of polar expression of these two genes results in a loss of polar differentiation of tissues in lateral organs. Taken together, these observations indicate that members of this gene family are responsible for the specification of abaxial cell fate in lateral organs of Arabidopsis. Furthermore, ectopic expression studies suggest that ubiquitous abaxial cell fate and maintenance of a functional apical meristem are incompatible.

Breast Cancer Risk After Bilateral Prophylactic Oophorectomy in BRCA1 Mutation Carriers

Abstract: Background The availability of genetic testing for inherited mutations in the BRCA1 gene provides potentially valuable information to women at high risk of breast or ovarian cancer; however, carriers of BRCA1 mutations have few clinical management options to reduce their cancer risk. Decreases in ovarian hormone exposure following bilateral prophylactic oophorectomy (i.e., surgical removal of the ovaries) may alter cancer risk in BRCA1 mutation carriers. This study was undertaken to evaluate whether bilateral prophylactic oophorectomy is associated with a reduction in breast cancer risk in BRCA1 mutation carriers. Methods We studied a cohort of women with disease-associated germline BRCA1 mutations who were assembled from five North American centers. Surgery subjects (n = 43) included women with BRCA1 mutations who underwent bilateral prophylactic oophorectomy but had no history of breast or ovarian cancer and had not had a prophylactic mastectomy. Control subjects included women with BRCA1 mutations who had no history of oophorectomy and no history of breast or ovarian cancer (n = 79). Control subjects were matched to the surgery subjects according to center and year of birth. Results We found a statistically significant reduction in breast cancer risk after bilateral prophylactic oophorectomy, with an adjusted hazard ratio (HR) of 0.53 (95% confidence interval [CI] = 0.33-0.84). This risk reduction was even greater in women who were followed 5-10 (HR = 0. 28; 95% CI = 0.08-0.94) or at least 10 (HR = 0.33; 95% CI = 0.12-0.91) years after surgery. Use of hormone replacement therapy did not negate the reduction in breast cancer risk after surgery. Conclusions Bilateral prophylactic oophorectomy is associated with a reduced breast cancer risk in women who carry a BRCA1 mutation. The likely mechanism is reduction of ovarian hormone exposure. These findings have implications for the management of breast cancer risk in women who carry BRCA1 mutations.

Mutations in the gene encoding B1 subunit of H+-ATPase cause renal tubular acidosis with sensorineural deafness

Abstract: H+-ATPases are ubiquitous in nature; V-ATPases pump protons against an electrochemical gradient, whereas F-ATPases reverse the process, synthesizing ATP. We demonstrate here that mutations in ATP6B1, encoding the B-subunit of the apical proton pump mediating distal nephron acid secretion, cause distal renal tubular acidosis, a condition characterized by impaired renal acid secretion resulting in metabolic acidosis. Patients with ATP6B1 mutations also have sensorineural hearing loss; consistent with this finding, we demonstrate expression of ATP6B1 in cochlea and endolymphatic sac. Our data, together with the known requirement for active proton secretion to maintain proper endolymph pH, implicate ATP6B1 in endolymph pH homeostasis and in normal auditory function. ATP6B1 is the first member of the H+-ATPase gene family in which mutations are shown to cause human disease.

One GABA and two acetylcholine receptors function at the C. elegans neuromuscular junction.

Abstract: We describe an electrophysiological preparation of the neuromuscular junction of the nematode C. elegans, which adds to its considerable genetic and genomic resources. Mutant analysis, pharmacology and patch-clamp recording showed that the body wall muscles of wild-type animals expressed a GABA receptor and two acetylcholine receptors. The muscle GABA response was abolished in animals lacking the GABA receptor gene unc-49. One acetylcholine receptor was activated by the nematocide levamisole. This response was eliminated in mutants lacking either the unc-38 or unc-29 genes, which encode alpha and non-alpha acetylcholine receptor subunits, respectively. The second, previously undescribed, acetylcholine receptor was activated by nicotine, desensitized rapidly and was selectively blocked by dihydro-β-erythroidine, thus explaining the residual motility of unc-38 and unc-29 mutants. By recording spontaneous endogenous currents and selectively eliminating each of these receptors, we demonstrated that all three receptor types function at neuromuscular synapses.

Polarization Effects in Intermediate Temperature, Anode‐Supported Solid Oxide Fuel Cells

Abstract: Anode-supported sold oxide fuel cells with yttria-stabilized zirconia (YSZ) electrolyte, Sr-doped LaMnO{sub 3} (LSM) + YSZ cathode, and Ni + YSZ anode were fabricated and their performance was evaluated between 650 and 800 C with humidified hydrogen as the fuel and air as the oxidant. Maximum power densities measured were {approximately} 1.8 W/cm{sup 2} at 800 C and {approximately} 0.82 W/cm{sup 2} at 650 C. Voltage (V) vs. current density (i) traces were nonlinear; V vs. i exhibited a concave-up curvature [d{sup 2}V/di{sup 2} {ge} 0] at low values of i and a convex-up curvature [d{sup 2}V/di{sup 2} {le} 0] at higher values of i, typical of many low temperature fuel cells. Analysis of concentration polarization based on transport of gaseous species through porous electrodes, in part, is used to explain nonlinear V vs. i traces. The effects of activation polarization in the Tafel limit are also included. It is shown that in anode-supported cells, the initial concave-up curvature can be due either to activation or concentration polarization, or both. By contrast, in cathode-supported cells, the initial concave-up curvature is entirely due to activation polarization. From the experimentally observed V vs. i traces for anode-supported cells, effective binary diffusivity of more » gaseous species on the anodic side was estimated to be between {approximately} 0.1 cm{sup 2}/s at 650 C and {approximately} 0.2 cm{sup 2}/s at 800 C. The area specific resistance of the cell (ohmic part), varied between {approximately} 0.18 {Omega} cm{sup 2} at 650 C and {approximately} 0.07 {Omega} cm{sup 2} at 800 C with an activation energy of {approximately} 65 kJ/mol. « less

CTLA4Ig-mediated blockade of T cell costimulation in patients with psoriasis vulgaris

Abstract: Engagement of the B7 family of molecules on antigen-presenting cells with their T cell-associated ligands, CD28 and CD152 (cytotoxic T lymphocyte-associated antigen-4 [CTLA-4]), provides a pivotal costimulatory signal in T-cell activation. We investigated the role of the CD28/CD152 pathway in psoriasis in a 26-week, phase I, open-label dose-escalation study. The importance of this pathway in the generation of humoral immune responses to T cell-dependent neoantigens, bacteriophage phiX174 and keyhole limpet hemocyanin, was also evaluated. Forty-three patients with stable psoriasis vulgaris received 4 infusions of the soluble chimeric protein CTLA4Ig (BMS-188667). Forty-six percent of all study patients achieved a 50% or greater sustained improvement in clinical disease activity, with progressively greater effects observed in the highest-dosing cohorts. Improvement in these patients was associated with quantitative reduction in epidermal hyperplasia, which correlated with quantitative reduction in skin-infiltrating T cells. No markedly increased rate of intralesional T-cell apoptosis was identified, suggesting that the decreased number of lesional T cells was probably likely attributable to an inhibition of T-cell proliferation, T-cell recruitment, and/or apoptosis of antigen-specific T cells at extralesional sites. Altered antibody responses to T cell-dependent neoantigens were observed, but immunologic tolerance to these antigens was not demonstrated. This study illustrates the importance of the CD28/CD152 pathway in the pathogenesis of psoriasis and suggests a potential therapeutic use for this novel immunomodulatory approach in an array of T cell-mediated diseases.

Thermoreversible Gelation of PEG−PLGA−PEG Triblock Copolymer Aqueous Solutions

Abstract: Aqueous solutions of new biodegradable triblock copolymers, poly(ethylene glycol-b-(dl-lactic acid-co-glycolic acid)-b-ethylene glycol) (PEG−PLGA−PEG), have shown to have sol-to-gel (lower transiti...

Focusing geophysical inversion images

Abstract: A critical problem in inversion of geophysical data is developing a stable inverse problem solution that can simultaneously resolve complicated geological structures. The traditional way to obtain a stable solution is based on maximum smoothness criteria. This approach, however, provides smoothed unfocused images of real geoelectrical structures. Recently, a new approach to reconstruction of images has been developed based on a total variational stabilizing functional. However, in geophysical applications it still produces distorted images. In this paper we develop a new technique to solve this problem which we call focusing inversion images. It is based on specially selected stabilizing functionals, called minimum gradient support (MGS) functionals, which minimize the area where strong model parameter variations and discontinuity occur. We demonstrate that the MGS functional, in combination with the penalization function, helps to generate clearer and more focused images for geological structures than conventional maximum smoothness or total variation functionals. The method has been successfully tested on synthetic models and applied to real gravity data.

UNC-13 is required for synaptic vesicle fusion in C. elegans

Abstract: We analyzed the synaptic physiology of unc-13 mutants in the nematode C. elegans. Mutants of unc-13 had normal nervous system architecture, and the densities of synapses and postsynaptic receptors were normal at the neuromuscular junction. However, the number of synaptic vesicles at neuromuscular junctions was two- to threefold greater in unc-13 mutants than in wild-type animals. Most importantly, evoked release at both GABAergic and cholinergic synapses was almost absent in unc-13 null alleles, as determined by whole-cell, voltage-clamp techniques. Although mutant synapses had morphologically docked vesicles, these vesicles were not competent for release as assayed by spontaneous release in calcium-free solution or by the application of hyperosmotic saline. These experiments support models in which UNC-13 mediates either fusion of vesicles during exocytosis or priming of vesicles for fusion.

Self-assembly of nanoscale cuboctahedra by coordination chemistry

Abstract: Self-assembled polyhedral structures are common in biology. The coats of many viruses, for example, have a structure based on icosahedral symmetry. The preparation of synthetic polyhedral molecular assemblies represents a challenging problem, but supramolecular chemistry has now advanced to the point where the task may be addressed. Macromolecular and supramolecular entities of predefined geometric shape and with well-defined internal environments are potentially important for inclusion phenomena, molecular recognition and catalysis. Here we report the use of self-assembly of molecular units driven by coordination to transition-metal ions to prepare a cuboctahedron from 20 tridentate and bidentate subunits in a single step. The cuboctahedron is an archimedean semiregular polyhedron that combines square and triangular faces. Our self-assembled polyhedral capsules, characterized by NMR and electrospray mass spectrometry, are around 5 nanometres in diameter.