426 research outputs found

    A Gaussian distribution for refined DT invariants and 3D partitions

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    We show that the refined Donaldson-Thomas invariants of C3, suitably normalized, have a Gaussian distribution as limit law. Combinatorially these numbers are given by weighted counts of 3D partitions. Our technique is to use the Hardy-Littlewood circle method to analyze the bivariate asymptotics of a q-deformation of MacMahon's function. The proof is based on that of E.M. Wright who explored the single variable case.Comment: 11 pages and 3 figure

    Differential Regulation of Tyrosinase Activity in Skin of White and Black Individuals In Vivo by Topical Retinoic Acid

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    Tyrosinase activity is a key determinant of melanin production in skin. Because retinoic acid regulates tyrosinase activity in melanoma cells, we analyzed modulation of pigmentation in vivo by retinoic acid. Black and white subjects were either not treated, or treated topically for 4 d under occlusion with vehicle, retinoic acid (0.1%), or the irritant sodium lauryl sulfate (2%). In untreated skin, tyrosinase activity and melanin content were significantly greater (2.3 times, and 3.2 times, respectively) in blacks versus whites. Four days of treatment with topical retinoic acid did not alter tyrosinase activity or melanin content in black skin. In contrast, retinoic acid treatment significantly induced (2.7 times, n = 8) tyrosinase activity, compared to vehicle treatment, in white skin. Melanin content, however, remained unchanged at 4 d. In separate experiments, tyrosinase activity in white subjects (n = 25) was increased 16% (p = 0.01) in sodium lauryl sulfate – treated skin, and 77% (p = 0.0005) in retinoic acid – treated skin, compared to vehicle-treated skin. The effect of retinoic acid on tyrosinase activity could be differentiated from non-specific irritation, because tyrosinase activity in retinoic acid – treated skin was significantly greater (52%, p = 0.004) than sodium lauryl sulfate-treated skin. Similar results were obtained with the dihydroxyphenylalanine reaction done on vehicle, sodium lauryl sulfate-, and retinoic acid – treated white skin. Northern analysis (n = 6) and semi-quantitative polymerase chain reaction (n = 6) demonstrated that retinoic acid treatment did not alter tyrosinase mRNA levels in white skin. Western analysis revealed that induction of tyrosinase activity by retinoic acid also was not associated with increased tyrosinase protein content (n = 9), indicating that regulation of tyrosinase activity by retinoic acid occurs through a post-translational mechanism. These data demonstrate that low tyrosinase activity in white skin in vivio is retinoic acid inducible and high tyrosinase activity in black skin in vivo is neither further induced nor reduced by retinoic aci

    [La microstructure 3D des matériaux polycristallins vue sous la lumière synchrotron]

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    International audienceSynchrotron radiation X-ray imaging and diffraction techniques offer new possibilities for non-destructive bulk characterization of polycrystalline materials. Minute changes in electron density (different crystallographic phases, cracks, porosities) can be detected using 3D imaging modes exploiting Fresnel diffraction and the coherence properties of third generation synchrotron beams. X-ray diffraction contrast tomography, a technique based on Bragg diffraction imaging, provides access to the 3D shape, orientation and elastic strain state of the individual grains from polycrystalline sample volumes containing several hundred up to a few thousand grains. Combining both imaging modalities allows a comprehensive description of the microstructure of the material at the micrometer length scale. Repeated observations during (interrupted) mechanical tests provide unprecedented insight into crystallographic and grain microstructure related aspects of polycrystal deformation and degradation mechanisms in materials, fulfilling some conditions on grain size and deformation state.Les techniques d'imagerie et de diffraction au rayonnement synchrotron offrent de nouvelles possibilités pour la caractérisation tridimensionnelle et non destructive des matériaux polycristallins. De faibles variations de densité électronique (phases secondaires, fissures, porosités) peuvent êtres détectées grâce à des modes d'imagerie qui exploitent la diffraction de Fresnel ainsi que la cohérence des faisceaux issus des sources synchrotron de troisième génération. La tomographie par contraste de diffraction, autre technique d'imagerie 3D basée sur la diffraction de Bragg, donne accès à la forme, l'orientation et l'état de déformation élastique des grains dans des volumes polycristallins contenant jusqu'à mille grains. La combinaison de ces deux modes d'imagerie permet de caractériser des matériaux polycristallins à l'échelle du micron. Des observations répétées lors d'essais mécaniques (interrompus) permettent d'analyser le rôle de la cristallographie locale sur les mécanismes de déformation et de dégradation dans des matériaux polycristallins, respectant certaines conditions sur la taille de grains, et/ou leur état de déformation

    Prescribing non-opioid drugs in end-stage kidney disease

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    Palliative care services are increasingly involved in the care of patients with chronic kidney disease, either alone or as a comorbid condition. Because renal impairment often changes the pharmacokinetic and/or pharmacodynamic effects of a drug, this presents a challenge for prescribers. This article provides guidance for prescribing non-opioid drugs commonly used for palliative care symptom relief in patients with end-stage kidney disease (ESKD; i.e. Chronic Kidney Disease Stage 5, eGFR <15mL/min/1.73m²) whether or not they are receiving dialysis. Opioids are not included, nor symptom relief in the last hours–days of life, because specific guidance is available elsewhere. Tables have been produced to highlight, when possible, the most, intermediate and least ‘renally safe’ drugs for chronic use. However, sometimes the cautious use of a familiar drug may be preferable to an unfamiliar (albeit ‘renally safer’) one. Similarly, we do not advocate the automatic switching of patients to a ‘renally safer’ drug when an alternative is proving satisfactory. Finally, this article aims to complement and not replace specialist renal unit guidance

    Effective ecosystem monitoring requires a multi-scaled approach

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    Ecosystem monitoring is fundamental to our understanding of how ecosystem change is impacting our natural resources and is vital for developing evidence-based policy and management. However, the different types of ecosystem monitoring, along with their recommended applications, are often poorly understood and contentious. Varying definitions and strict adherence to a specific monitoring type can inhibit effective ecosystem monitoring, leading to poor program development, implementation and outcomes. In an effort to develop a more consistent and clear understanding of ecosystem monitoring programs, we here review the main types of monitoring and recommend the widespread adoption of three classifications of monitoring, namely, targeted, surveillance and landscape monitoring. Landscape monitoring is conducted over large areas, provides spatial data, and enables questions relating to where and when ecosystem change is occurring to be addressed. Surveillance monitoring uses standardised field methods to inform on what is changing in our environments and the direction and magnitude of that change, whilst targeted monitoring is designed around testable hypotheses over defined areas and is the best approach for determining the causes of ecosystem change. The classification system is flexible and can incorporate different interests, objectives, targets and characteristics as well as different spatial scales and temporal frequencies, while also providing valuable structure and consistency across distinct ecosystem monitoring programs. To support our argument, we examine the ability of each monitoring type to inform on six key types of questions that are routinely posed for ecosystem monitoring programs, such as where and when change is occurring, what is the magnitude of change, and how can the change be managed? As we demonstrate, each type of ecosystem monitoring has its own strengths and weaknesses, which should be carefully considered relative to the desired results. Using this scheme, scientists and land managers can design programs best suited to their needs. Finally, we assert that for our most serious environmental challenges, it is essential that we include information from each of these monitoring scales to inform on all facets of ecosystem change, and this is best achieved through close collaboration between the scales. With a renewed understanding of the importance of each monitoring type, along with greater commitment to monitor cooperatively, we will be well placed to address some of our greatest environmental challenges

    Multipole interaction between atoms and their photonic environment

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    Macroscopic field quantization is presented for a nondispersive photonic dielectric environment, both in the absence and presence of guest atoms. Starting with a minimal-coupling Lagrangian, a careful look at functional derivatives shows how to obtain Maxwell's equations before and after choosing a suitable gauge. A Hamiltonian is derived with a multipolar interaction between the guest atoms and the electromagnetic field. Canonical variables and fields are determined and in particular the field canonically conjugate to the vector potential is identified by functional differentiation as minus the full displacement field. An important result is that inside the dielectric a dipole couples to a field that is neither the (transverse) electric nor the macroscopic displacement field. The dielectric function is different from the bulk dielectric function at the position of the dipole, so that local-field effects must be taken into account.Comment: 17 pages, to be published in Physical Review

    Diminished Neural and Cognitive Responses to Facial Expressions of Disgust in Patients with Psoriasis: A Functional Magnetic Resonance Imaging Study

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    Psoriasis produces significant psychosocial disability; however, little is understood about the neurocognitive mechanisms that mediate the adverse consequences of the social stigma associated with visible skin lesions, such as disgusted facial expressions of others. Both the feeling of disgust and the observation of disgust in others are known to activate the insula cortex. We investigated whether the social impact of psoriasis is associated with altered cognitive processing of disgust using (i) a covert recognition of faces task conducted using functional magnetic resonance imaging (fMRI) and (ii) the facial expression recognition task (FERT), a decision-making task, conducted outside the scanner to assess the ability to recognize overtly different intensities of disgust. Thirteen right-handed male patients with psoriasis and 13 age-matched male controls were included. In the fMRI study, psoriasis patients had significantly (P<0.005) smaller signal responses to disgusted faces in the bilateral insular cortex compared with healthy controls. These data were corroborated by FERT, in that patients were less able than controls to identify all intensities of disgust tested. We hypothesize that patients with psoriasis, in this case male patients, develop a coping mechanism to protect them from stressful emotional responses by blocking the processing of disgusted facial expressions

    Using Real-World Data to Guide Ustekinumab Dosing Strategies for Psoriasis: A Prospective Pharmacokinetic-Pharmacodynamic Study.

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    Variation in response to biologic therapy for inflammatory diseases, such as psoriasis, is partly driven by variation in drug exposure. Real-world psoriasis data were used to develop a pharmacokinetic/pharmacodynamic (PK/PD) model for the first-line therapeutic antibody ustekinumab. The impact of differing dosing strategies on response was explored. Data were collected from a UK prospective multicenter observational cohort (491 patients on ustekinumab monotherapy, drug levels, and anti-drug antibody measurements on 797 serum samples, 1,590 measurements of Psoriasis Area Severity Index (PASI)). Ustekinumab PKs were described with a linear one-compartment model. A maximum effect (Emax ) model inhibited progression of psoriatic skin lesions in the turnover PD mechanism describing PASI evolution while on treatment. A mixture model on half-maximal effective concentration identified a potential nonresponder group, with simulations suggesting that, in future, the model could be incorporated into a Bayesian therapeutic drug monitoring "dashboard" to individualize dosing and improve treatment outcomes
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