Duality covariant non-BPS first order systems

We study extremal black hole solutions to four dimensional N=2 supergravity based on a cubic symmetric scalar manifold. Using the coset construction available for these models, we define the first order flow equations implied by the corresponding nilpotency conditions on the three-dimensional scalar momenta for the composite non-BPS class of multi-centre black holes. As an application, we directly solve these equations for the single-centre subclass, and write the general solution in a manifestly duality covariant form. This includes all single-centre under-rotating non-BPS solutions, as well as their non-interacting multi-centre generalisations.Comment: 31 pages, v2: Discussion of the quadratic constraint clarified, references added, typos corrected, published versio

First-order flows and stabilisation equations for non-BPS extremal black holes

We derive a generalised form of flow equations for extremal static and rotating non-BPS black holes in four-dimensional ungauged N = 2 supergravity coupled to vector multiplets. For particular charge vectors, we give stabilisation equations for the scalars, analogous to the BPS case, describing full known solutions. Based on this, we propose a generic ansatz for the stabilisation equations, which surprisingly includes ratios of harmonic functions.Comment: 27 pages; v2: presentation improved and references added as in the published versio

Major Role for Amphotericin B–Flucytosine Combination in Severe Cryptococcosis

BACKGROUND: The Infectious Diseases Society of America published in 2000 practical guidelines for the management of cryptococcosis. However, treatment strategies have not been fully validated in the various clinical settings due to exclusion criteria during therapeutic trials. We assessed here the optimal therapeutic strategies for severe cryptococcosis using the observational prospective CryptoA/D study after analyzing routine clinical care of cryptococcosis in university or tertiary care hospitals. METHODOLOGY/PRINCIPAL FINDINGS: Patients were enrolled if at least one culture grew positive with Cryptococcus neoformans. Control of sterilization was warranted 2 weeks (Wk2) and 3 months (Mo3) after antifungal therapy onset. 208 HIV-positive or -negative adult patients were analyzed. Treatment failure (death or mycological failure) at Wk2 and Mo3 was the main outcome measured. Combination of amphotericin B+flucytosine (AMB+5FC) was the best regimen for induction therapy in patients with meningoencephalitis and in all patients with high fungal burden and abnormal neurology. In those patients, treatment failure at Wk2 was 26% in the AMB+5FC group vs. 56% with any other treatments (p<0.001). In patients treated with AMB+5FC, factors independently associated with Wk2 mycological failure were high serum antigen titer (OR [95%CI] = 4.43[1.21-16.23], p = 0.025) and abnormal brain imaging (OR = 3.89[1.23-12.31], p = 0.021) at baseline. Haematological malignancy (OR = 4.02[1.32-12.25], p = 0.015), abnormal neurology at baseline (OR = 2.71[1.10-6.69], p = 0.030) and prescription of 5FC for less than 14 days (OR = 3.30[1.12-9.70], p = 0.030) were independently associated with treatment failure at Mo3. CONCLUSION/SIGNIFICANCE: Our results support the conclusion that induction therapy with AMB+5FC for at least 14 days should be prescribed rather than any other induction treatments in all patients with high fungal burden at baseline regardless of their HIV serostatus and of the presence of proven meningoencephalitis

Calcium Homeostasis in Myogenic Differentiation Factor 1 (MyoD)-Transformed, Virally-Transduced, Skin-Derived Equine Myotubes

Dysfunctional skeletal muscle calcium homeostasis plays a central role in the pathophysiology of several human and animal skeletal muscle disorders, in particular, genetic disorders associated with ryanodine receptor 1 (RYR1) mutations, such as malignant hyperthermia, central core disease, multiminicore disease and certain centronuclear myopathies. In addition, aberrant skeletal muscle calcium handling is believed to play a pivotal role in the highly prevalent disorder of Thoroughbred racehorses, known as Recurrent Exertional Rhabdomyolysis. Traditionally, such defects were studied in human and equine subjects by examining the contractile responses of biopsied muscle strips exposed to caffeine, a potent RYR1 agonist. However, this test is not widely available and, due to its invasive nature, is potentially less suitable for valuable animals in training or in the human paediatric setting. Furthermore, increasingly, RYR1 gene polymorphisms (of unknown pathogenicity and significance) are being identified through next generation sequencing projects. Consequently, we have investigated a less invasive test that can be used to study calcium homeostasis in cultured, skin-derived fibroblasts that are converted to the muscle lineage by viral transduction with a MyoD (myogenic differentiation 1) transgene. Similar models have been utilised to examine calcium homeostasis in human patient cells, however, to date, there has been no detailed assessment of the cells’ calcium homeostasis, and in particular, the responses to agonists and antagonists of RYR1. Here we describe experiments conducted to assess calcium handling of the cells and examine responses to treatment with dantrolene, a drug commonly used for prophylaxis of recurrent exertional rhabdomyolysis in horses and malignant hyperthermia in humans

A special road to AdS vacua

We apply the techniques of special Kaehler geometry to investigate AdS_4 vacua of general N=2 gauged supergravities underlying flux compactifications of type II theories. We formulate the scalar potential and its extremization conditions in terms of a triplet of prepotentials P_x and their special Kaehler covariant derivatives only, in a form that recalls the potential and the attractor equations of N=2 black holes. We propose a system of first order equations for the P_x which generalize the supersymmetry conditions and yield non-supersymmetric vacua. Special geometry allows us to recast these equations in algebraic form, and we find an infinite class of new N=0 and N=1 AdS_4 solutions, displaying a rich pattern of non-trivial charges associated with NSNS and RR fluxes. Finally, by explicit evaluation of the entropy function on the solutions, we derive a U-duality invariant expression for the cosmological constant and the central charges of the dual CFT's.Comment: 41 pages; v2, v3: minor improvements, references added, published versio

Extremal Multicenter Black Holes: Nilpotent Orbits and Tits Satake Universality Classes

Four dimensional supergravity theories whose scalar manifold is a symmetric coset manifold U[D=4]/Hc are arranged into a finite list of Tits Satake universality classes. Stationary solutions of these theories, spherically symmetric or not, are identified with those of an euclidian three-dimensional sigma-model, whose target manifold is a Lorentzian coset U[D=3]/H* and the extremal ones are associated with H* nilpotent orbits in the K* representation emerging from the orthogonal decomposition of the algebra U[D=3] with respect to H*. It is shown that the classification of such orbits can always be reduced to the Tits-Satake projection and it is a class property of the Tits Satake universality classes. The construction procedure of Bossard et al of extremal multicenter solutions by means of a triangular hierarchy of integrable equations is completed and converted into a closed algorithm by means of a general formula that provides the transition from the symmetric to the solvable gauge. The question of the relation between H* orbits and charge orbits W of the corresponding black holes is addressed and also reduced to the corresponding question within the Tits Satake projection. It is conjectured that on the vanishing locus of the Taub-NUT current the relation between H*-orbit and W-orbit is rigid and one-to-one. All black holes emerging from multicenter solutions associated with a given H* orbit have the same W-type. For the S^3 model we provide a complete survey of its multicenter solutions associated with all of the previously classified nilpotent orbits of sl(2) x sl(2) within g[2,2]. We find a new intrinsic classification of the W-orbits of this model that might provide a paradigm for the analogous classification in all the other Tits Satake universality classes.Comment: 83 pages, LaTeX; v2: few misprints corrected and references adde

HLA Class I Binding 9mer Peptides from Influenza A Virus Induce CD4+ T Cell Responses

BACKGROUND: Identification of human leukocyte antigen class I (HLA-I) restricted cytotoxic T cell (CTL) epitopes from influenza virus is of importance for the development of new effective peptide-based vaccines. METHODOLOGY/PRINCIPAL FINDINGS: In the present work, bioinformatics was used to predict 9mer peptides derived from available influenza A viral proteins with binding affinity for at least one of the 12 HLA-I supertypes. The predicted peptides were then selected in a way that ensured maximal coverage of the available influenza A strains. One hundred and thirty one peptides were synthesized and their binding affinities for the HLA-I supertypes were measured in a biochemical assay. Influenza-specific T cell responses towards the peptides were quantified using IFNgamma ELISPOT assays with peripheral blood mononuclear cells (PBMC) from adult healthy HLA-I typed donors as responder cells. Of the 131 peptides, 21 were found to induce T cell responses in 19 donors. In the ELISPOT assay, five peptides induced responses that could be totally blocked by the pan-specific anti-HLA-I antibody W6/32, whereas 15 peptides induced responses that could be completely blocked in the presence of the pan-specific anti-HLA class II (HLA-II) antibody IVA12. Blocking of HLA-II subtype reactivity revealed that 8 and 6 peptide responses were blocked by anti-HLA-DR and -DP antibodies, respectively. Peptide reactivity of PBMC depleted of CD4(+) or CD8(+) T cells prior to the ELISPOT culture revealed that effectors are either CD4(+) (the majority of reactivities) or CD8(+) T cells, never a mixture of these subsets. Three of the peptides, recognized by CD4(+) T cells showed binding to recombinant DRA1*0101/DRB1*0401 or DRA1*0101/DRB5*0101 molecules in a recently developed biochemical assay. CONCLUSIONS/SIGNIFICANCE: HLA-I binding 9mer influenza virus-derived peptides induce in many cases CD4(+) T cell responses restricted by HLA-II molecules

Defining the Boundaries of Development wih Plasticity

International audienceThe concept of plasticity has always been present in the history of developmental biology, both within the theory of epigenesis and within morphogenesis studies. However this tradition relies also upon a genetic conception of plasticity. Founded upon the concepts of "phenotypic plasticity" and "reaction norm," this genetic conception focuses on the array of possible phenotypic change in relation to diversified environments. Another concept of plasticity can be found in recent publications by some developmental biologists (Gilbert, West-Eberhard). I argue that these authors adopt a "broad conception of plasticity" that is closely related to a notion of development as something that is ongoing throughout an organism's lifecycle, and has no clear-cut boundaries. However, I suggest that given a narrow conception of plasticity, one can define temporal boundaries for development that are linked to specific features of the morphological process, which are different from behavioral and physiological processes

Cardiac damage after treatment of childhood cancer: A long-term follow-up

<p>Abstract</p> <p>Background</p> <p>With improved childhood cancer cure rate, long term sequelae are becoming an important factor of quality of life. Signs of cardiovascular disease are frequently found in long term survivors of cancer. Cardiac damage may be related to irradiation and chemotherapy.</p> <p>We have evaluated simultaneous influence of a series of independent variables on the late cardiac damage in childhood cancer survivors in Slovenia and identified groups at the highest risk.</p> <p>Methods</p> <p>211 long-term survivors of different childhood cancers, at least five years after treatment were included in the study. The evaluation included history, physical examination, electrocardiograpy, exercise testing and echocardiograpy. For analysis of risk factors, beside univariate analysis, multivariate classification tree analysis statistical method was used.</p> <p>Results and Conclusion</p> <p>Patients treated latest, from 1989–98 are at highest risk for any injury to the heart (73%). Among those treated earlier are at the highest risk those with Hodgkin's disease treated with irradiation above 30 Gy and those treated for sarcoma. Among specific forms of injury, patients treated with radiation to the heart area are at highest risk of injury to the valves. Patients treated with large doses of anthracyclines or concomitantly with anthracyclines and alkylating agents are at highest risk of systolic function defect and enlarged heart chambers. Those treated with anthracyclines are at highest risk of diastolic function defect. The time period of the patient's treatment is emerged as an important risk factor for injury of the heart.</p