4,602 research outputs found

    Absorption on horizon-wrapped branes

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    We compute the absorption cross section of space-time scalars on a static D2 rane, in global coordinates, wrapped on the S^2 of an AdS_2 X S^2 X CY_3 geometry. We discuss its relevance for the construction of the dual quantum mechanics of Calabi-Yau black holes.Comment: 18 pages, 2 figure

    Dhvar5 antimicrobial peptide (AMP) chemoselective covalent immobilization results on higher antiadherence effect than simple physical adsorption

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    Bacterial colonization and subsequent biofilm formation is still one of the major problems associated with medical devices. Antimicrobial peptides (AMP) immobilization onto biomaterials surface is a promising strategy to avoid bacterial colonization. However, a correct peptide orientation and exposure from the surface is essential to maintain AMP antimicrobial activity. This work aims to evaluate the effect of the immobilization on antibacterial activity of Dhvar5 (LLLFLLKKRKKRKY), an AMP with a head-to-tail amphipathicity. Dhvar5 was linked to thin chitosan coatings in i) a controlled orientation and exposure, testing covalent immobilization of its N- or C-terminus and using spacers with different lengths and flexibilities or in ii) a random orientation by physical adsorption. Chitosan coating was chosen due to its antimicrobial properties and readiness to be functionalized. Surface characterization demonstrated the chemoselective immobilization of the peptide with different spacers in a similar concentration (∌2 ng/cm2). Efficacy assays demonstrated that covalent immobilization of Dhvar5 exposing its cationic end, improves the chitosan coating antimicrobial effect by decreasing Methicillin-resistant Staphylococcus aureus (MRSA) colonization. This effect was enhanced when longer spacers were used independently of their flexibility. In opposite, immobilized Dhvar5 exposing its hydrophobic end has no effect on bacterial adhesion to chitosan, and when adsorbed in a random orientation even induces bacterial adhesion to chitosan coating.This work was financed by FEDER funds through the Programa Operacional Factores de Competitividade (COMPETE) and by Portuguese funds through FCT (Fundacao para a Ciencia e a Tecnologia) in the framework of the projects: PTDC/CTM/101484/2008; PEst-C/SAU/LA0002/2013; Pest-C/QUI/UI0081/2013. Fabiola Costa acknowledges FCT for the PhD grant SFRH/BD/72471/2010

    First report of Meloidogyne naasi parasitizing turfgrass in Portugal

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    In an exploratory sampling of a football field in Porto, Portugal, the root-knot nematode, Meloidogyne naasi, previously unreported from the Iberian Peninsula, was detected. Diagnosis was based on the analysis of perineal patterns and esterase phenotypes of females excised from grass roots, morphometrics and molecular analysis (PCR with specific primers and analysis of partial 28S sequences obtained by amplification using the primers D2A/D3B) of second- stage juveniles (J2) extracted from soil. When collected in water, J2 aggregated into a worm-star. Endospores of Pasteuria penetrans were frequently found attached to the J2. To our knowledge, this is the first report of M. naasi in Portugal and in the Iberian Peninsula, and the first report of worm-star formation in Meloidogyne.The authors would like to thank Dr. M. LuĂ­sa Moura and JosĂ© F. Azevedo for collaboration in sampling and sample processing. This work was supported by the strategic program UID/BIA/04050/2019 (POCI01-0145-FEDER-007569), funded by national funds through the Portuguese Foundation For Science and Technology (FCT) I.P. and by the ERDF through the COMPETE2020 – Programa Operacional Competitividade e Internacionalização (POCI)

    What do Îł\gamma-ray bursts look like?

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    There have been great and rapid progresses in the field of Îł\gamma-ray bursts (denoted as GRBs) since BeppoSAX and other telescopes discovered their afterglows in 1997. Here, we will first give a brief review on the observational facts of GRBs and direct understanding from these facts, which lead to the standard fireball model. The dynamical evolution of the fireball is discussed, especially a generic model is proposed to describe the whole dynamical evolution of GRB remnant from highly radiative to adiabatic, and from ultra-relativistic to non-relativistic phase. Then, Various deviations from the standard model are discussed to give new information about GRBs and their environment. In order to relax the energy crisis, the beaming effects and their possible observational evidences are also discussed in GRB's radiations.Comment: 10 pages, Latex. Invited talk at the Pacific Rim Conference on Stellar Astrophysics, Hong Kong, China, Aug. 199

    Characterisation of the fumarate hydratase repertoire in Trypanosoma cruzi.

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    Nifurtimox and benznidazole represent the only treatments options available targeting Chagas disease, the most important parasitic infection in the Americas. However, use of these is problematic as they are toxic and ineffective against the more severe stages of the disease. In this work, we used a multidisciplinary approach to characterise the fumarases from Trypanosoma cruzi, the causative agent of Chagas Disease. We showed this trypanosome expresses cytosolic and mitochondrial fumarases that via an iron-sulfur cluster mediate the reversible conversion of fumarate to S-malate. Based on sequence, biochemical properties and co-factor binding, both T. cruzi proteins share characteristics with class I fumarases, enzymes found in bacteria and some other protozoa but absent from humans, that possess class II isoforms instead. Gene disruption suggested that although the cytosolic or mitochondrial fumarase activities are individually dispensable their combined activity is essential for parasite viability. Finally, based on the mechanistic differences with the human (host) fumarase, we designed and validated a selective inhibitor targeting the parasite enzyme. This study showed that T. cruzi fumarases should be exploited as targets for the development of new chemotherapeutic interventions against Chagas disease

    The a-theorem and conformal symmetry breaking in holographic RG flows

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    We study holographic models describing an RG flow between two fixed points driven by a relevant scalar operator. We show how to introduce a spurion field to restore Weyl invariance and compute the anomalous contribution to the generating functional in even dimensional theories. We find that the coefficient of the anomalous term is proportional to the difference of the conformal anomalies of the UV and IR fixed points, as expected from anomaly matching arguments in field theory. For any even dimensions the coefficient is positive as implied by the holographic a-theorem. For flows corresponding to spontaneous breaking of conformal invariance, we also compute the two-point functions of the energy-momentum tensor and the scalar operator and identify the dilaton mode. Surprisingly we find that in the simplest models with just one scalar field there is no dilaton pole in the two-point function of the scalar operator but a stronger singularity. We discuss the possible implications.Comment: 50 pages. v2: minor changes, added references, extended discussion. v3: we have clarified some of the calculations and assumptions, results unchanged. v4: published version in JHE

    Centre selection for clinical trials and the generalisability of results: a mixed methods study.

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    BACKGROUND: The rationale for centre selection in randomised controlled trials (RCTs) is often unclear but may have important implications for the generalisability of trial results. The aims of this study were to evaluate the factors which currently influence centre selection in RCTs and consider how generalisability considerations inform current and optimal practice. METHODS AND FINDINGS: Mixed methods approach consisting of a systematic review and meta-summary of centre selection criteria reported in RCT protocols funded by the UK National Institute of Health Research (NIHR) initiated between January 2005-January 2012; and an online survey on the topic of current and optimal centre selection, distributed to professionals in the 48 UK Clinical Trials Units and 10 NIHR Research Design Services. The survey design was informed by the systematic review and by two focus groups conducted with trialists at the Birmingham Centre for Clinical Trials. 129 trial protocols were included in the systematic review, with a total target sample size in excess of 317,000 participants. The meta-summary identified 53 unique centre selection criteria. 78 protocols (60%) provided at least one criterion for centre selection, but only 31 (24%) protocols explicitly acknowledged generalisability. This is consistent with the survey findings (n = 70), where less than a third of participants reported generalisability as a key driver of centre selection in current practice. This contrasts with trialists' views on optimal practice, where generalisability in terms of clinical practice, population characteristics and economic results were prime considerations for 60% (n = 42), 57% (n = 40) and 46% (n = 32) of respondents, respectively. CONCLUSIONS: Centres are rarely enrolled in RCTs with an explicit view to external validity, although trialists acknowledge that incorporating generalisability in centre selection should ideally be more prominent. There is a need to operationalize 'generalisability' and incorporate it at the design stage of RCTs so that results are readily transferable to 'real world' practice

    A Diagnostic Algorithm for Posterior Fossa Tumors in Children: A Validation Study

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    BACKGROUND AND PURPOSE: Primary posterior fossa tumors comprise a large group of neoplasias with variable aggressiveness and short and long-term outcomes. This study aimed to validate the clinical usefulness of a radiologic decision flow chart based on previously published neuroradiologic knowledge for the diagnosis of posterior fossa tumors in children. MATERIALS AND METHODS: A retrospective study was conducted (from January 2013 to October 2019) at 2 pediatric referral centers, Children's Hospital of Philadelphia, United States, and Great Ormond Street Hospital, United Kingdom. Inclusion criteria were younger than 18 years of age and histologically and molecularly confirmed posterior fossa tumors. Subjects with no available preoperative MR imaging and tumors located primarily in the brain stem were excluded. Imaging characteristics of the tumors were evaluated following a predesigned, step-by-step flow chart. Agreement between readers was tested with the Cohen Îș, and each diagnosis was analyzed for accuracy. RESULTS: A total of 148 cases were included, with a median age of 3.4 years (interquartile range, 2.1-6.1 years), and a male/female ratio of 1.24. The predesigned flow chart facilitated identification of pilocytic astrocytoma, ependymoma, and medulloblastoma sonic hedgehog tumors with high sensitivity and specificity. On the basis of the results, the flow chart was adjusted so that it would also be able to better discriminate atypical teratoid/rhabdoid tumors and medulloblastoma groups 3 or 4 (sensitivity = 75%-79%; specificity = 92%-99%). Moreover, our adjusted flow chart was useful in ruling out ependymoma, pilocytic astrocytomas, and medulloblastoma sonic hedgehog tumors. CONCLUSIONS: The modified flow chart offers a structured tool to aid in the adjunct diagnosis of pediatric posterior fossa tumors. Our results also establish a useful starting point for prospective clinical studies and for the development of automated algorithms, which may provide precise and adequate diagnostic tools for these tumors in clinical practice

    Suppression of ovarian hormones in adolescent rats has no effect on anxiety-like behaviour or c-fos activation in the amygdala

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    Support was provided the British Society for Neuroendocrinology, Carnegie Trust for the Universities of Scotland and School of Psychology & Neuroscience, University of St Andrews.In humans, sex differences in mood disorders emerge during adolescence, with prevalence rates being consistently higher in females than males. It has been hypothesised that exposure to endogenous ovarian hormones during adolescence enhances the susceptibility of females to mood disorders from this stage of life onwards. However, experimental evidence in favour of this hypothesis is lacking. In the present study, we examined the long‐term effects of suppressing adolescent gonadal hormone levels in a group of female Lister‐hooded rats via administration of a gonadotrophin‐releasing hormone antagonist (Antide; administered on postnatal day [PND] 28 and 42) compared to control females and males (n = 14 per group). We predicted that, in adulthood, Antide‐treated female rats would exhibit more male‐like behaviour than control females in novel environments (elevated‐plus maze, open field and light‐dark box), in response to novel objects and novel social partners, and in an acoustic startle task. Progesterone and luteinising hormone assays (which were conducted on blood samples collected on PND 55/56 and 69/70) confirmed that the hypothalamic‐pituitary‐gonadal axis was temporarily suppressed by Antide treatment. In addition, Antide‐treated females were found to exhibit a modest pubertal delay, as measured by vaginal opening, which was comparable in length to the pubertal delay that has been induced by adolescent exposure to alcohol or stress in previous studies of female rats. However, Antide‐treated females did not substantially differ from control females on any of the behavioural tests, despite the evidence for predicted sex differences in some measures. Following the acoustic startle response task, all subjects were culled and perfused, and c‐Fos staining was conducted in the medial and basolateral amygdala, with the results showing no significant differences in cell counts between the groups. These findings suggest that ovarian hormone exposure during adolescence does not have long‐term effects on anxiety‐related responses in female rats.Publisher PDFPeer reviewe
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