55 research outputs found
Thermodynamic formalism for contracting Lorenz flows
We study the expansion properties of the contracting Lorenz flow introduced
by Rovella via thermodynamic formalism. Specifically, we prove the existence of
an equilibrium state for the natural potential for the contracting Lorenz flow and for in an interval
containing . We also analyse the Lyapunov spectrum of the flow in terms
of the pressure
Murine mesothelin: characterization, expression, and inhibition of tumor growth in a murine model of pancreatic cancer
Background
Mesothelin has attracted much interest as a tumor specific antigen; it has been reported to promote tumor development and to be a good target for cancer treatment. Most studies to date have used human mesothelin in immunocompromised mice. Since these models do not allow for study of the natural immune response to mesothelin expressing tumors, we have undertaken the characterization of mouse mesothelin so the effects of this protein can be assessed in immunocompetent mouse strains.
Methods
We analyzed mouse mesothelin expression, tissue distribution, shedding and biochemistry. In addition we constructed stable mesothelin overexpressing lines of the pancreatic cancer line Panc02 by two methods and tested them for growth and tumorigencity in vitro and in vivo.
Results
We show here that mouse mesothelin is similar to human mesothelin in biochemical characteristics, tumor expression and tissue distribution, suggesting the mouse may be a suitable model for study of mesothelin. Stable overexpression of mesothelin in a pancreatic cancer cell line did not increase cell proliferation or anchorage-independent growth in vitro, suggesting that mesothelin is not necessarily a tumor progression factor. Surprisingly overexpression of mesothelin inhibited tumor formation in vivo in immunocompetent mice.
Conclusion
The mouse may be a good model for studying mesothelin in the context of an intact immune response. Mesothelin is not necessarily a tumor progression factor, and indeed mesothelin overexpression inhibited tumor growth in immunocompetent mice
Design, analysis, and presentation of crossover trials
OBJECTIVE: Although crossover trials enjoy wide use, standards for analysis and reporting have not been established. We reviewed methodological aspects and quality of reporting in a representative sample of published crossover trials. METHODS: We searched MEDLINE for December 2000 and identified all randomized crossover trials. We abstracted data independently, in duplicate, on 14 design criteria, 13 analysis criteria, and 14 criteria assessing the data presentation. RESULTS: We identified 526 randomized controlled trials, of which 116 were crossover trials. Trials were drug efficacy (48%), pharmacokinetic (28%), and nonpharmacologic (30%). The median sample size was 15 (interquartile range 8-38). Most (72%) trials used 2 treatments and had 2 periods (64%). Few trials reported allocation concealment (17%) or sequence generation (7%). Only 20% of trials reported a sample size calculation and only 31% of these considered pairing of data in the calculation. Carry-over issues were addressed in 29% of trial's methods. Most trials reported and defended a washout period (70%). Almost all trials (93%) tested for treatment effects using paired data and also presented details on by-group results (95%). Only 29% presented CIs or SE so that data could be entered into a meta-analysis. CONCLUSION: Reports of crossover trials frequently omit important methodological issues in design, analysis, and presentation. Guidelines for the conduct and reporting of crossover trials might improve the conduct and reporting of studies using this important trial design
A half-site multimeric enzyme achieves its cooperativity without conformational changes
Cooperativity is a feature many multimeric proteins use to control activity. Here we show that the bacterial heptose isomerase GmhA displays homotropic positive and negative cooperativity among its four protomers. Most similar proteins achieve this through conformational changes: GmhA instead employs a delicate network of hydrogen bonds, and couples pairs of active sites controlled by a unique water channel. This network apparently raises the Lewis acidity of the catalytic zinc, thus increasing the activity at one active site at the cost of preventing substrate from adopting a reactive conformation at the paired negatively cooperative site – a “half-site” behavior. Our study establishes the principle that multimeric enzymes can exploit this cooperativity without conformational changes to maximize their catalytic power and control. More broadly, this subtlety by which enzymes regulate functions could be used to explore new inhibitor design strategies
Pionic decay of a possible d' dibaryon and the short-range NN interaction
We study the pionic decay of a possible dibaryon d′→N+N+π in the microscopic quark shell model. The initial d′ dibaryon wave function (JP=0-, T=0) consists of one 1ħω six-quark shell-model s5p[51]X configuration. The most important final six-quark configurations s6[6]X, s4p2[42]X, and (s4p2-s52s)[6]X are properly projected onto the NN channel. The final state NN interaction is investigated by means of two phase-equivalent—but off-shell different—potential models. We demonstrate that the decay width Γd′ depends strongly on the short-range behavior of the NN wave function. In addition, the width Γd′ is very sensitive to the mass and size of the d′ dibaryon. For dibaryon masses slightly above the experimentally suggested value Md′=2.065GeV, we obtain a pionic decay width of Γd′≈0.18–0.32MeV close to the experimental value Γd′≈0.5MeV.Obukhovsky, I. Itonaga, K. ; Wagner, Georg ; Buchmann, A. ; Faessler, Aman
Suicide assessment and treatment in pediatric primary care settings
TopicThis article will briefly review screening for depression and suicidal ideation in primary care and school-based clinics, with a focus on in-depth screening for imminent suicide risk, developing a safety plan, and incorporating handoffs to urgent and emergency mental health care personnel. The article will cover current definitions of levels of suicidal risk and clinic-based protocols for a team approach to adolescents in crisis.PurposeTo provide primary care and behavioral health nurses with evidence-based suicide risk screening and assessment tools and best practices for using them in patient-centered encounters with adolescents with suicidal thinking or behavior.Sources usedJournal articles, books, and reports.ConclusionPast studies have shown that many individuals who died by suicide had seen a primary care provider in 30 days before their deaths. Nurses in primary care settings should develop clinic-based protocols for screening all adolescents for suicide risk, developing safety plans, and providing suicidal youth and families with monitoring, appropriate referrals, follow-up, and support
High-density compression experiments at ILE, Osaka
Direct-drive implosion experiments on the GEKKO XII laser (9 kJ, 0.5 μm, 2 ns) with deuterium and tritium (DT) exchanged plastic hollow shell targets demonstrated fuel areal densities (ρR) of approximately 0.1 g/cm2 and fuel densities of approximately 600 times liquid density at fuel temperatures of approximately 0.3 keV. (The density and ρR values refer only to DT and do not include carbons in the plastic targets.) These values are to be compared with thermonuclear ignition conditions, i.e., fuel densities of 500-1000 times liquid density, fuel areal densities greater than 0.3 g/cm2, and fuel temperatures greater than 5 keV. The irradiation nonuniformity in these experiments was significantly reduced to a level of <5% in root mean square by introducing random-phase plates. The target irregularity was controlled to a 1% level. The fuel ρR was directly measured with the neutron activation of Si, which was originally compounded in the plastic targets. The fuel densities were estimated from the ρR values using the mass conservation relation, where the ablated mass was separately measured using the time-dependent X-ray emission from multilayer targets. Although the observed densities were in agreement with one-dimensional calculation results with convergence ratios of 25-30, the observed neutron yields were significantly lower than those of the calculations. This suggests the implosion uniformity is not sufficient to create a hot spark in which most neutrons should be generated
X-ray and particle diagnostics of a high-density plasma by laser implosion (invited)
A series of laser fusion implosion experiments of plastic hollow shell targets was performed by using the Gekko XII glass laser in order to achieve the required fuel areal density for ignition. Introducing random phase plates to improve illumination uniformity, high-density compression of more than 600 times deuterium liquid density has been achieved. The implosion dynamics and symmetry were observed with a spatially resolved x-ray streak camera and an x-ray multiframing camera. The three-dimensional emission profile of the laser-heated plasma was reconstructed from the x-ray images by use of computed tomography and was compared with the laser illumination profiles. The areal density of the imploded core was measured by the neutron activation of a silicon tracer, the secondary reaction method, and the knock-on proton method. Although the measured density and areal density were consistent with those from 1-D hydrodynamic simulation, experimental neutron yields were significantly lower than those predicted by the simulation for convergence ratios larger than 20. This suggests that better implosion uniformity is required to create a hot spark
- …