5,331 research outputs found

    Rational families of instanton bundles on P2n+1P^{2n+1}

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    This paper is devoted to the theory of symplectic instanton bundles on an odd dimensional projective space P2n+1{\mathbb P}^{2n+1} with n2n\ge 2. We study the 't Hooft instanton bundles introduced by Ottaviani and a new family of instanton bundles which generalizes one introduced on P3{\mathbb P}^3 independently by Rao and Skiti. The main result is the determination of the birational types of the moduli spaces of 't Hooft and of Rao-Skiti instanton bundles, respectively. Assuming a conjecture of Ottaviani, we show that the moduli space of all symplectic instanton bundles on P2n+1{\mathbb P}^{2n+1} with n2n\ge 2 is reducible.Comment: 37 pages. v2: minor revision. final version, to appear in Algebraic Geometry (new open access journal of the Compositio Foundation

    Experimental measurement of stress at a four-domain junction in lead zirconate titanate

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    A junction between two lamellar bands of ferroelectric domains in a lead zirconate titanate (PZT) ceramic is analysed using Kikuchi diffraction patterns in the transmission electron microscope. Indexing of the diffraction patterns allowed the determination of the 3D relative orientation of the 4 different domains at the junction and thus the characterisation of the domain boundaries. The local c/a ratio could also be determined from the misorientations at the domain boundaries. Analysis of the data showed that large stresses were concentrated at the junction, and that this is inevitable at such band junctions. Such stress concentrations could act as nuclei for cracking of the ceramic under additional loading in service, perhaps particularly as a consequence of extended electromechanical cycling. Moreover, the stresses would increase with increasing c/a making the issues all the more serious for Ti-rich compositions having larger c/a ratios

    Conclusions about Niche Expansion in Introduced Impatiens walleriana Populations Depend on Method of Analysis

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    Determining the degree to which climate niches are conserved across plant species' native and introduced ranges is valuable to developing successful strategies to limit the introduction and spread of invasive plants, and also has important ecological and evolutionary implications. Here, we test whether climate niches differ between native and introduced populations of Impatiens walleriana, globally one of the most popular horticultural species. We use approaches based on both raw climate data associated with occurrence points and ecological niche models (ENMs) developed with Maxent. We include comparisons of climate niche breadth in both geographic and environmental spaces, taking into account differences in available habitats between the distributional areas. We find significant differences in climate envelopes between native and introduced populations when comparing raw climate variables, with introduced populations appearing to expand into wetter and cooler climates. However, analyses controlling for differences in available habitat in each region do not indicate expansion of climate niches. We therefore cannot reject the hypothesis that observed differences in climate envelopes reflect only the limited environments available within the species' native range in East Africa. Our results suggest that models built from only native range occurrence data will not provide an accurate prediction of the potential for invasiveness if applied to areas containing a greater range of environmental combinations, and that tests of niche expansion may overestimate shifts in climate niches if they do not control carefully for environmental differences between distributional areas

    Hypoxia promotes breast cancer cell invasion through HIF-1a-mediated up-regulation of the invadopodial actin bundling protein CSRP2

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    Hypoxia is a common feature of solid tumours that promotes invasion and metastatic dissemination. Invadopodia are actin-rich membrane protrusions that direct extracellular matrix proteolysis and facilitate tumour cell invasion. Here, we show that CSRP2, an invadopodial actin bundling protein, is upregulated by hypoxia in various breast cancer cell lines, as well as in pre-clinical and clinical breast tumour specimens. We functionally characterized two hypoxia responsive elements within the proximal promoter of CSRP2 gene which are targeted by hypoxia-inducible factor-1 (HIF-1) and required for promoter transactivation in response to hypoxia. Remarkably, CSRP2 knockdown significantly inhibits hypoxia-stimulated invadopodium formation, ECM degradation and invasion in MDA-MB-231 cells, while CSRP2 forced expression was sufficient to enhance the invasive capacity of HIF-1a-depleted cells under hypoxia. In MCF-7 cells, CSRP2 upregulation was required for hypoxia-induced formation of invadopodium precursors that were unable to promote ECM degradation. Collectively, our data support that CSRP2 is a novel and direct cytoskeletal target of HIF-1 which facilitates hypoxia-induced breast cancer cell invasion by promoting invadopodia formation.The authors are grateful to Monika Dieterle, Arnaud Muller, Pter Nazarov and Muhammad Zaeem Noman (Oncology Department, LIH, Luxembourg) for technical assistance, support in statistical analyses and constructive discussions. The authors also warmly thank Sara A. Courtneidge for the gift of the Tks5-GFP construct (Oregon Health and Science University, Portland, USA). This work was mainly supported by a research grant from “Fondation Cancer” Luxembourg (FC/2016/02), and the National Research Fund (C16/ BM/11297905). Joshua Brown Clay is recipient of a Postdoctoral fellowship from “Fonds De La Recherche Scientifque” - FNRS “Télévie” (7.4512.16). Antoun Al Absi and Hannah Wurzer are recipients of PhD fellowships from the National Research Fund, Luxembourg (AFR7892325 and PRIDE15/10675146/CANBIO, respectively)

    Energetic metabolic profile of ewes presenting low body condition score induced to subclinical hypocalcemia in early postpartum

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    The aim of the present study is to assess plasma concentrations of metabolites related to energy balance in ewes showing low body condition score (BCS) induced to subclinical hypocalcemia in early postpartum. Sixteen crossbred ewes (Ideal x Corriedale) presenting BCS <3 were divided in two groups: 1) control group (n = 9), which received no treatment, and 2) hypocalcemia group (n = 7), which was subjected to twelve hours of induced subclinical hypocalcemia through intravenous Na2EDTA infusion six hours postpartum. Ionized calcium levels were monitored and kept between 0.62 and 0.87 mmol/L. All ewes were subjected to daily blood sampling for five days in order to set the postpartum metabolic profile. There was no interaction between day and treatment in total and ionized calcium concentrations (P>0.05), whereas the mean concentrations of these marks after five days were lower in the hypocalcemia group (P<0.05). However, neither the mean group were different at glucose, non-esterified fatty acids, beta-hydroxybutyrate and insulin (P>0.05) level. These results evidence that, despite the subclinical hypocalcemia induction at early postpartum, ewes presenting low body condition do not change the concentrations of energy balance-related metabolites in the following five days

    Pharmacokinetics and Target Attainment of Ceftobiprole in Asian and Non-Asian Subjects

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    Ceftobiprole is a broad-spectrum cephalosporin. The objective of this study was to test the hypothesis that the pharmacokinetics (PK) and exposure of ceftobiprole in Asian subjects are similar to those in non-Asian subjects. Three approaches were followed. The first compared the individual PK estimates between the 2 subgroups derived from a population PK model previously built. Next, it was determined whether “Asian subject” was a significant covariate. Finally, a pharmacodynamic analysis was performed by comparing measures of exposure and target attainment. No significant differences were found between PK parameter estimates for Asian and non-Asian subjects, with median values (range) for clearance of 4.82 L/h (2.12–10.47) and 4.97 L/h (0.493–20.6), respectively (P =.736). “Asian subject” was not a significant covariate in the population PK model. There were no significant differences between the measures of exposure. The geometric mean ratio for the fAUC was 1.022 (90%CI, 0.91–1.15), indicating bioequivalence. Taking a target of 60% coverage of the dose interval, more than 90% of the population in both subgroups was adequately exposed. This analysis demonstrated that there are no PK or pharmacodynamic differences between Asian and non-Asian subjects for a ceftobiprole dose of 500 mg every 8 hours as a 2-hour infusion

    Genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy (ALDH7A1 deficiency)

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    Pyridoxine-dependent epilepsy was recently shown to be due to mutations in the ALDH7A1 gene, which encodes antiquitin, an enzyme that catalyses the nicotinamide adenine dinucleotide-dependent dehydrogenation of L-{alpha}-aminoadipic semialdehyde/L-{Delta}1-piperideine 6-carboxylate. However, whilst this is a highly treatable disorder, there is general uncertainty about when to consider this diagnosis and how to test for it. This study aimed to evaluate the use of measurement of urine L-{alpha}-aminoadipic semialdehyde/creatinine ratio and mutation analysis of ALDH7A1 (antiquitin) in investigation of patients with suspected or clinically proven pyridoxine-dependent epilepsy and to characterize further the phenotypic spectrum of antiquitin deficiency. Urinary L-{alpha}-aminoadipic semialdehyde concentration was determined by liquid chromatography tandem mass spectrometry. When this was above the normal range, DNA sequencing of the ALDH7A1 gene was performed. Clinicians were asked to complete questionnaires on clinical, biochemical, magnetic resonance imaging and electroencephalography features of patients. The clinical spectrum of antiquitin deficiency extended from ventriculomegaly detected on foetal ultrasound, through abnormal foetal movements and a multisystem neonatal disorder, to the onset of seizures and autistic features after the first year of life. Our relatively large series suggested that clinical diagnosis of pyridoxine dependent epilepsy can be challenging because: (i) there may be some response to antiepileptic drugs; (ii) in infants with multisystem pathology, the response to pyridoxine may not be instant and obvious; and (iii) structural brain abnormalities may co-exist and be considered sufficient cause of epilepsy, whereas the fits may be a consequence of antiquitin deficiency and are then responsive to pyridoxine. These findings support the use of biochemical and DNA tests for antiquitin deficiency and a clinical trial of pyridoxine in infants and children with epilepsy across a broad range of clinical scenarios

    Assessing the complex sponge microbiota: core, variable and species-specific bacterial communities in marine sponges

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    Marine sponges are well known for their associations with highly diverse, yet very specific and often highly similar microbiota. The aim of this study was to identify potential bacterial sub-populations in relation to sponge phylogeny and sampling sites and to define the core bacterial community. 16S ribosomal RNA gene amplicon pyrosequencing was applied to 32 sponge species from eight locations around the world's oceans, thereby generating 2567 operational taxonomic units (OTUs at the 97% sequence similarity level) in total and up to 364 different OTUs per sponge species. The taxonomic richness detected in this study comprised 25 bacterial phyla with Proteobacteria, Chloroflexi and Poribacteria being most diverse in sponges. Among these phyla were nine candidate phyla, six of them found for the first time in sponges. Similarity comparison of bacterial communities revealed no correlation with host phylogeny but a tropical sub-population in that tropical sponges have more similar bacterial communities to each other than to subtropical sponges. A minimal core bacterial community consisting of very few OTUs (97%, 95% and 90%) was found. These microbes have a global distribution and are probably acquired via environmental transmission. In contrast, a large species-specific bacterial community was detected, which is represented by OTUs present in only a single sponge species. The species-specific bacterial community is probably mainly vertically transmitted. It is proposed that different sponges contain different bacterial species, however, these bacteria are still closely related to each other explaining the observed similarity of bacterial communities in sponges in this and previous studies. This global analysis represents the most comprehensive study of bacterial symbionts in sponges to date and provides novel insights into the complex structure of these unique associations
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