Differential Effects of Buffer pH On Ca\u3csup\u3e2+\u3c/sup\u3e-Induced ROS Emission with Inhibited Mitochondrial Complexes I and III

Excessive mitochondrial reactive oxygen species (ROS) emission is a critical component in the etiology of ischemic injury. Complex I and complex III of the electron transport chain are considered the primary sources of ROS emission during cardiac ischemia and reperfusion (IR) injury. Several factors modulate ischemic ROS emission, such as an increase in extra-matrix Ca2+, a decrease in extra-matrix pH, and a change in substrate utilization. Here we examined the combined effects of these factors on ROS emission from respiratory complexes I and III under conditions of simulated IR injury. Guinea pig heart mitochondria were suspended in experimental buffer at a given pH and incubated with or without CaCl2. Mitochondria were then treated with either pyruvate, a complex I substrate, followed by rotenone, a complex I inhibitor, or succinate, a complex II substrate, followed by antimycin A, a complex III inhibitor. H2O2 release rate and matrix volume were compared with and without adding CaCl2 and at pH 7.15, 6.9, or 6.5 with pyruvate + rotenone or succinate + antimycin A to simulate conditions that may occur during in vivo cardiac IR injury. We found a large increase in H2O2 release with high [CaCl2] and pyruvate + rotenone at pH 6.9, but not at pHs 7.15 or 6.5. Large increases in H2O2 release rate also occurred at each pH with high [CaCl2] and succinate + antimycin A, with the highest levels observed at pH 7.15. The increases in H2O2 release were associated with significant mitochondrial swelling, and both H2O2 release and swelling were abolished by cyclosporine A, a desensitizer of the mitochondrial permeability transition pore (mPTP). These results indicate that ROS production by complex I and by complex III is differently affected by buffer pH and Ca2+ loading with mPTP opening. The study suggests that changes in the levels of cytosolic Ca2+ and pH during IR alter the relative amounts of ROS produced at mitochondrial respiratory complex I and complex III

Knowledge, attitudes and practices of obstetrical ultrasound in Conakry, Guinea

Background: The authors report an initial assessment of the practice of obstetrical ultrasound in Conakry in order to make suggestions to improve the quality of services in Guinea.Methods: It is about a cross-sectional study of three months (August 1st to October 31st, 2013) conducted in Conakry. The study population consisted of health personnel performing fetal ultrasounds in Conakry and who agreed to participate in the survey. The data collected were about the socio-professional characteristics of the service providers, their knowledge and attitudes. The data were analyzed in a simple descriptive statistical analysis way. The results were analyzed according to the norms and standards issued by the French Fetal Ultrasound College and the National Technical Committee for Prenatal Diagnosis Ultrasound.Results: Twenty one service providers over twenty-six (80.8%) were male (80.8%) aged 40-49 years old (46.2%), obstetrician-gynecologists (76.9%), working in a public hospital (46.2%) and not having an ultrasound degree (59.2%). Eight service providers over twenty-six ((30.8%) affirmed knowing the recommended period for a fetal biometry. The majority (60%) indicated measuring the nuchal translucency and 85.2% (22/26) the craniocaudal length. The anatomical landmarks were not correctly identified in 75.2% of cases for the biparietal and the head circumference and in 63.8% of cases for abdominal circumference. Nine service providers over twenty-six (34.6%) affirmed explaining the limitations of ultrasound. Eighteen devices over twenty-six (69.2%) had more than 9 years of age, 73% (19/26) of them did not have a vaginal probe and 65.3% (17/26) did not have a pulsed wave Doppler.Conclusions: Improving the quality of the practice of obstetrical ultrasound in Guinea goes through training of service providers, establishing distribution and compliance with norms and standards as well as quality control of ultrasound devices

D-Terms from Generalized NS-NS Fluxes in Type II

Orientifolds of type II string theory admit a certain set of generalized NS-NS fluxes, including not only the three-form field strength H, but also metric and non-geometric fluxes, which are related to H by T-duality. We describe in general how these fluxes appear as parameters of an effective N=1 supergravity theory in four dimensions, and in particular how certain generalized NS-NS fluxes can act as charges for R-R axions, leading to D-term contributions to the effective scalar potential. We illustrate these phenomena in type IIB with the example of a certain orientifold of T^6/Z_4.Comment: 31+1 pages, uses utarticle.cls; v2: references adde

Scalar geometry and masses in Calabi-Yau string models

We study the geometry of the scalar manifolds emerging in the no-scale sector of Kahler moduli and matter fields in generic Calabi-Yau string compactifications, and describe its implications on scalar masses. We consider both heterotic and orientifold models and compare their characteristics. We start from a general formula for the Kahler potential as a function of the topological compactification data and study the structure of the curvature tensor. We then determine the conditions for the space to be symmetric and show that whenever this is the case the heterotic and the orientifold models give the same scalar manifold. We finally study the structure of scalar masses in this type of geometries, assuming that a generic superpotential triggers spontaneous supersymmetry breaking. We show in particular that their behavior crucially depends on the parameters controlling the departure of the geometry from the coset situation. We first investigate the average sGoldstino mass in the hidden sector and its sign, and study the implications on vacuum metastability and the mass of the lightest scalar. We next examine the soft scalar masses in the visible sector and their flavor structure, and study the possibility of realizing a mild form of sequestering relying on a global symmetry.Comment: 36 pages, no figure

Sex and race and/or ethnicity differences in patients undergoing radiofrequency ablation for Barrett\u27s esophagus: results from the U.S. RFA Registry.

BACKGROUND: Little is known about differences in Barrett\u27s esophagus (BE) characteristics by sex and race and/or ethnicity or these differences in response to radiofrequency ablation (RFA). OBJECTIVE: We compared disease-specific characteristics, treatment efficacy, and safety outcomes by sex and race and/or ethnicity in patients treated with RFA for BE. DESIGN: The U.S. RFA patient registry is a multicenter collaboration reporting processes and outcomes of care for patients treated with RFA for BE. PATIENTS: Patients enrolled with BE. INTERVENTIONS: RFA. MAIN OUTCOME MEASUREMENTS: We assessed safety (stricture, bleeding, perforation, hospitalization), efficacy (complete eradication of intestinal metaplasia [CEIM]), complete eradication of dysplasia, and number of treatments to CEIM by sex and race and/or ethnicity. RESULTS: Among 5521 patients (4052 men; 5126 white, 137 Hispanic, 82 African American, 40 Asian, 136 heritage not identified), women were younger (60.0 vs 62.1 years) and had shorter BE segments (3.2 vs 4.4 cm) and less dysplasia (37% vs 57%) than did men. Women were almost twice as likely to stricture (odds ratio 1.7; 95% confidence interval, 1.2-2.3). Although white patients were predominantly male, about half of African Americans and Asians with BE were female. African Americans and Asians had less dysplasia than white patients. Asians and African Americans had more strictures than did white patients. There were no sex or race differences in efficacy. LIMITATIONS: Observational study with non-mandated paradigms, no central laboratory for reinterpretation of pathology. CONCLUSION: In the U.S. RFA patient registry, women had shorter BE segments and less-aggressive histology. The usual tendency toward BE in men was absent in African Americans and Asians. Posttreatment stricture was more common among women and Asians. RFA efficacy did not differ by sex or race

Towards an Explicit Model of D-brane Inflation

We present a detailed analysis of an explicit model of warped D-brane inflation, incorporating the effects of moduli stabilization. We consider the potential for D3-brane motion in a warped conifold background that includes fluxes and holomorphically-embedded D7-branes involved in moduli stabilization. Although the D7-branes significantly modify the inflaton potential, they do not correct the quadratic term in the potential, and hence do not cause a uniform change in the slow-roll parameter eta. Nevertheless, we present a simple example based on the Kuperstein embedding of D7-branes, z_1=constant, in which the potential can be fine-tuned to be sufficiently flat for inflation. To derive this result, it is essential to incorporate the fact that the compactification volume changes slightly as the D3-brane moves. We stress that the compactification geometry dictates certain relationships among the parameters in the inflaton Lagrangian, and these microscopic constraints impose severe restrictions on the space of possible models. We note that the shape of the final inflaton potential differs from projections given in earlier studies: in configurations where inflation occurs, it does so near an inflection point. Finally, we comment on the difficulty of making precise cosmological predictions in this scenario. This is the companion paper to arXiv:0705.3837.Comment: 68 pages, 6 figures; v2: fixed typos, added refs and clarifications; v3: expanded discussion of inflection point inflatio

Toroidal Orientifolds in IIA with General NS-NS Fluxes

Type IIA toroidal orientifolds offer a promising toolkit for model builders, especially when one includes not only the usual fluxes from NS-NS and R-R field strengths, but also fluxes that are T-dual to the NS-NS three-form flux. These new ingredients are known as metric fluxes and non-geometric fluxes, and can help stabilize moduli or can lead to other new features. In this paper we study two approaches to these constructions, by effective field theory or by toroidal fibers twisted over a toroidal base. Each approach leads us to important observations, in particular the presence of D-terms in the four-dimensional effective potential in some cases, and a more subtle treatment of the quantization of the general NS-NS fluxes. Though our methods are general, we illustrate each approach on the example of an orientifold of T^6/Z_4.Comment: 59 pages, references adde

D3-brane Potentials from Fluxes in AdS/CFT

We give a comprehensive treatment of the scalar potential for a D3-brane in a warped conifold region of a compactification with stabilized moduli. By studying general ultraviolet perturbations in supergravity, we systematically incorporate `compactification effects' sourced by supersymmetry breaking in the compact space. Significant contributions to the D3-brane potential, including the leading term in the infrared, arise from imaginary anti-self-dual (IASD) fluxes. For an arbitrary Calabi-Yau cone, we determine the most general IASD fluxes in terms of scalar harmonics, then compute the resulting D3-brane potential. Specializing to the conifold, we identify the operator dual to each mode of flux, and for chiral operators we confirm that the potential computed in the gauge theory matches the gravity result. The effects of four-dimensional curvature, including the leading D3-brane mass term, arise directly from the ten-dimensional equations of motion. Furthermore, we show that gaugino condensation on D7-branes provides a local source for IASD flux. This flux precisely encodes the nonperturbative contributions to the D3-brane potential, yielding a promising ten-dimensional representation of four-dimensional nonperturbative effects. Our result encompasses all significant contributions to the D3-brane potential discussed in the literature, and does so in the single coherent framework of ten-dimensional supergravity. Moreover, we identify new terms with irrational scaling dimensions that were inaccessible in prior works. By decoupling gravity in a noncompact configuration, then systematically reincorporating compactification effects as ultraviolet perturbations, we have provided an approach in which Planck-suppressed contributions to the D3-brane effective action can be computed.Comment: 70 page

New Examples of Flux Vacua

Type IIB toroidal orientifolds are among the earliest examples of flux vacua. By applying T-duality, we construct the first examples of massive IIA flux vacua with Minkowski space-times, along with new examples of type IIA flux vacua. The backgrounds are surprisingly simple with no four-form flux at all. They serve as illustrations of the ingredients needed to build type IIA and massive IIA solutions with scale separation. To check that these backgrounds are actually solutions, we formulate the complete set of type II supergravity equations of motion in a very useful form that treats the R-R fields democratically.Comment: 38 pages, LaTeX; references updated; additional minor comments added; published versio

Revisiting the Immune Trypanolysis Test to Optimise Epidemiological Surveillance and Control of Sleeping Sickness in West Africa

Human African trypanosomiasis (HAT) due to Trypanosoma brucei (T.b.) gambiense is usually diagnosed using two sequential steps: first the card agglutination test for trypanosomiasis (CATT) used for serological screening, followed by parasitological methods to confirm the disease. Currently, CATT will continue to be used as a test for mass screening because of its simplicity and high sensitivity; however, its performance as a tool of surveillance in areas where prevalence is low is poor because of its limited specificity. Hence in the context of HAT elimination, there is a crucial need for a better marker of contact with T.b. gambiense in humans. We evaluated here an existing highly specific serological tool, the trypanolysis test (TL). We evaluated TL in active, latent and historical HAT foci in Guinea, Côte d'Ivoire and Burkina Faso. We found that TL was a marker for exposure to T.b. gambiense. We propose that TL should be used as a surveillance tool to monitor HAT elimination