On square positive extensions and cubature formulas

AbstractWe consider linear functionals Ld defined over Pd⊂P≔R[x1,…,xn] and study how to extend Ld to a square positive L:P→R, i.e. to a linear functional L with L(p2)⩾0 for all p∈P. We use the connection of square positive functionals to real ideals, to orthogonal polynomials, and to moment matrices. Finally, we report how such extension techniques are used to construct and analyse cubature formulas

Experimental noninferiority trial of synthetic small-caliber biodegradable versus stable vascular grafts

ObjectiveLong-term evolution of polycaprolactone vascular prostheses has been investigated recently. The goal of this study was to evidence a noninferiority of such grafts compared with expanded polytetrafluoroethylene (ePTFE) implants in an aortic replacement model in the rat.MethodsFourteen anesthetized Sprague-Dawley rats received an infrarenal aortic graft (biodegradable, n = 8; expanded polytetrafluoroethylene, n = 6) replacement (end to end; inner diameter, 2 mm). Biodegradable grafts (polycaprolactone) were produced by random micro-/nanofiber electrospinning. After a median survival of 16.5 months, in vivo ultrasonography and angiography as well as postexplantation microcomputed tomography, histomorphometry, immunohistochemistry, and scanning electron microscopy were performed.ResultsPatency was 100% for polycaprolactone and 67% for ePTFE. No aneurysmal dilatation or stenoses were found in either group. Compliance was significantly higher for polycaprolactone compared with ePTFE (8.2 ± 1.0%/100 mm Hg vs 5.7 ± 0.7%/100 mm Hg; P < .01), but markedly reduced compared with adjacent native aortas and the control group. Histologically, low cellular in-growth was found in ePTFE whereas polycaprolactone showed significantly greater homogenous cellularity, producing an autologous extracellular matrix (10.8% ± 4.0% vs 32.1% ± 9.2%, P < .0001). Morphometry showed 100% neo-endothelialization for both grafts with a totally confluent endothelial coverage for polycaprolactone grafts by scanning electron microscope. More intimal hyperplasia was found in ePTFE compared with polycaprolactone grafts. Calcification was higher in ePTFE than in polycaprolactone grafts (15.8% vs 7.0%, P = .04) and was absent in controls.ConclusionsOutcomes of synthetic biodegradable nanofiber polycaprolactone grafts are not inferior compared with the clinically used expanded polytetrafluoroethylene grafts after long-term implantation in the rat aorta. Moreover, these implants show better patency, compliance, endothelialization, and cell in-growth, and less intimal hyperplasia and calcification than their counterparts

Investigations of the copper peptide hepcidin-25 by LC-MS/MS and NMR+

Hepcidin-25 was identified as the main iron regulator in the human body, and it by binds to the sole iron-exporter ferroportin. Studies showed that the N-terminus of hepcidin is responsible for this interaction, the same N-terminus that encompasses a small copper(II)-binding site known as the ATCUN (amino-terminal Cu(II)- and Ni(II)-binding) motif. Interestingly, this copper-binding property is largely ignored in most papers dealing with hepcidin-25. In this context, detailed investigations of the complex formed between hepcidin-25 and copper could reveal insight into its biological role. The present work focuses on metal-bound hepcidin-25 that can be considered the biologically active form. The first part is devoted to the reversed-phase chromatographic separation of copper-bound and copper-free hepcidin-25 achieved by applying basic mobile phases containing 0.1% ammonia. Further, mass spectrometry (tandem mass spectrometry (MS/MS), high-resolution mass spectrometry (HRMS)) and nuclear magnetic resonance (NMR) spectroscopy were employed to characterize the copper-peptide. Lastly, a three-dimensional (3D) model of hepcidin-25 with bound copper(II) is presented. The identification of metal complexes and potential isoforms and isomers, from which the latter usually are left undetected by mass spectrometry, led to the conclusion that complementary analytical methods are needed to characterize a peptide calibrant or reference material comprehensively. Quantitative nuclear magnetic resonance (qNMR), inductively-coupled plasma mass spectrometry (ICP-MS), ion-mobility spectrometry (IMS) and chiral amino acid analysis (AAA) should be considered among others

Novel Schizophrenia Risk Gene TCF4 Influences Verbal Learning and Memory Functioning in Schizophrenia Patients

Background: Recently, a role of the transcription factor 4 (TCF4) gene in schizophrenia has been reported in a large genome-wide association study. It has been hypothesized that TCF4 affects normal brain development and TCF4 has been related to different forms of neurodevelopmental disorders. Schizophrenia patients exhibit strong impairments of verbal declarative memory (VDM) functions. Thus, we hypothesized that the disease-associated C allele of the rs9960767 polymorphism of the TCF4 gene led to impaired VDM functioning in schizophrenia patients. Method: The TCF4 variant was genotyped in 401 schizophrenia patients. VDM functioning was measured using the Rey Auditory Verbal Learning Test (RAVLT). Results: Carriers of the C allele were less impaired in recognition compared to those carrying the AA genotype (13.76 vs. 13.06; p = 0.049). Moreover, a trend toward higher scores in patients with the risk allele was found for delayed recall (10.24 vs. 9.41; p = 0.088). The TCF4 genotype did not influence intelligence or RAVLT immediate recall or total verbal learning. Conclusion: VDM function is influenced by the TCF4 gene in schizophrenia patients. However, the elevated risk for schizophrenia is not conferred by TCF4-mediated VDM impairment. Copyright (C) 2011 S. Karger AG, Base

Mirroring everyday clinical practice in clinical trial design: a new concept to improve the external validity of randomized double-blind placebo-controlled trials in the pharmacological treatment of major depression

Background: Randomized, double-blind, placebo-controlled trials constitute the gold standard in clinical research when testing the efficacy of new psychopharmacological interventions in the treatment of major depression. However, the blinded use of placebo has been found to influence clinical trial outcomes and may bias patient selection. Discussion: To improve clinical trial design in major depression so as to reflect clinical practice more closely we propose to present patients with a balanced view of the benefits of study participation irrespective of their assignment to placebo or active treatment. In addition every participant should be given the option to finally receive the active medication. A research agenda is outlined to evaluate the impact of the proposed changes on the efficacy of the drug to be evaluated and on the demographic and clinical characteristics of the enrollment fraction with regard to its representativeness of the eligible population. Summary: We propose a list of measures to be taken to improve the external validity of double-blind, placebocontrolled trials in major depression. The recommended changes to clinical trial design may also be relevant for other psychiatric as well as medical disorders in which expectations regarding treatment outcome may affect the outcome itself

Miocene initiation and acceleration of extension in the South Lunggar rift, western Tibet: Evolution of an active detachment system from structural mapping and (U-Th)/He thermochronology

This is the publisher's version, also available electronically from http://onlinelibrary.wiley.com/doi/10.1002/tect.20053/abstractOngoing extension in Tibet may have begun in the middle to late Miocene, but there are few robust estimates of the rates, timing, or magnitude of Neogene deformation within the Tibetan plateau. We present a comprehensive study of the seismically active South Lunggar rift in southwestern Tibet incorporating mapping, U-Pb geochronology and zircon (U-Th)/He thermochronology. The South Lunggar rift is the southern continuation of the North Lunggar rift and comprises a ~50 km N-S central horst bound by two major normal faults, the west-dipping South Lunggar detachment and the east-dipping Palung Co fault. The SLD dips at the rangefront ~20°W and exhumes a well-developed mylonite zone in its footwall displaying fabrics indicative of normal-sense shear. The range is composed of felsic orthogneiss, mafic amphibolite, and leucogranite intrusions dated at ~16 and 63 Ma. Zircon (U-Th)/He cooling ages are Oligocene through late Pliocene, with the youngest ages observed in the footwall of the SLD. We tested ~25,000 unique thermokinematic forward models in Pecube against the structural and (U-Th)/He data to fully bracket the allowable ranges in fault initiations, accelerations, and slip rates. We find that normal faulting in the SLR began in the middle Miocene with horizontal extension rates of ~1 mm a−1, and in the north accelerated at 8 Ma to 2.5–3.0 mm a−1 as faulting commenced on the SLD. Cumulative horizontal extension across the SLR ranges from <10 km in the south to 19–21 km in the north