D7-Brane Chaotic Inflation

We analyze string-theoretic large-field inflation in the regime of spontaneously-broken supergravity with conventional moduli stabilization by fluxes and non-perturbative effects. The main ingredient is a shift-symmetric Kahler potential, supplemented by flux-induced shift symmetry breaking in the superpotential. The central technical observation is that all these features are present for D7-brane position moduli in Type IIB orientifolds, allowing for a realization of the axion monodromy proposal in a controlled string theory compactification. On the one hand, in the large complex structure regime the D7-brane position moduli inherit a shift symmetry from their mirror-dual Type IIA Wilson lines. On the other hand, the Type IIB flux superpotential generically breaks this shift symmetry and allows, by appealing to the large flux discretuum, to tune the relevant coefficients to be small. The shift-symmetric direction in D7-brane moduli space can then play the role of the inflaton: While the D7-brane circles a certain trajectory on the Calabi-Yau many times, the corresponding F-term energy density grows only very slowly, thanks to the above-mentioned tuning of the flux. Thus, the large-field inflationary trajectory can be realized in a regime where Kahler, complex structure and other brane moduli are stabilized in a conventional manner, as we demonstrate using the example of the Large Volume Scenario.Comment: 8 pages, 2 figures; v2: references adde

Recovery of scandium from acidic waste solutions by means of polymer inclusion membranes

Scandium is a raw material with properties that promise considerable potential for application in alloys to enable aviation fuel savings and as dopants for use in sustainable energy production using solid oxide fuel cells. Despite these attractive properties, scandium is rarely used due to its scarcity and unreliable supply. Therefore, new strategies for scandium recovery are of economic priority. In this study, polymer inclusion membranes (PIMs) consisting of PVDF-HFP, 2-NPOE and DEHPA, were optimised for selective scandium separation from real TiO2 production waste. With the optimised system, >60% of the scandium was recovered with high selectivity, resulting in scandium mole fraction at more than two orders of magnitude higher in the receiving phase than in the original waste. This suggests PIMs may be an effective way to recover scandium from bulk waste, thus easing the scarcity and insecurity that currently limit its bulk application

Viscous Brane Cosmology with a Brane-Bulk Energy Interchange Term

We assume a flat brane located at y=0, surrounded by an AdS space, and consider the 5D Einstein equations when the energy flux component of the energy-momentum tensor is related to the Hubble parameter through a constant Q. We calculate the metric tensor, as well as the Hubble parameter on the brane, when Q is small. As a special case, if the brane is tensionless, the influence from Q on the Hubble parameter is absent. We also consider the emission of gravitons from the brane, by means of the Boltzmann equation. Comparing the energy conservation equation derived herefrom with the energy conservation equation for a viscous fluid on the brane, we find that the entropy change for the fluid in the emission process has to be negative. This peculiar effect is related to the fluid on the brane being a non-closed thermodynamic system. The negative entropy property for non-closed systems is encountered in other areas in physics also, in particular, in connection with the Casimir effect at finite temperature.Comment: 12 pages, latex, no figure

Extreme Asymmetry in the Disk of V1247 Ori

We present the first near-infrared scattered-light detection of the transitional disk around V1247 Ori, which was obtained using high-resolution polarimetric differential imaging observations with Subaru/HiCIAO. Our imaging in the H band reveals the disk morphology at separations of ~0.14"-0.86" (54-330 au) from the central star. The polarized intensity (PI) image shows a remarkable arc-like structure toward the southeast of the star, whereas the fainter northwest region does not exhibit any notable features. The shape of the arm is consistent with an arc of 0.28" $\pm$ 0.09" in radius (108 au from the star), although the possibility of a spiral arm with a small pitch angle cannot be excluded. V1247 Ori features an exceptionally large azimuthal contrast in scattered, polarized light; the radial peak of the southeastern arc is about three times brighter than the northwestern disk measured at the same distance from the star. Combined with the previous indication of an inhomogeneous density distribution in the gap at $\lesssim$46 au, the notable asymmetry in the outer disk suggests the presence of unseen companions and/or planet-forming processes ongoing in the arc.Comment: 21 pages, 5 figures, accepted for publication in PAS

Fluxbrane Inflation

As a first step towards inflation in genuinely F-theoretic setups, we propose a scenario where the inflaton is the relative position of two 7-branes on holomorphic 4-cycles. Non-supersymmetric gauge flux induces an attractive inter-brane potential. The latter is sufficiently flat in the supergravity regime of large volume moduli. Thus, in contrast to brane-antibrane inflation, fluxbrane inflation does not require warping. We calculate the inflaton potential both in the supergravity approximation and via an open-string one-loop computation on toroidal backgrounds. This leads us to propose a generalisation to genuine Calabi-Yau manifolds. We also comment on competing F-term effects. The end of inflation is marked by the condensation of tachyonic recombination fields between the 7-branes, triggering the formation of a bound state described as a stable extension along the 7-brane divisor. Hence our model fits in the framework of hybrid D-term inflation. We work out the main phenomenological properties of our D-term inflaton potential. In particular, our scenario of D7/D7 inflation avoids the familiar observational constraints associated with cosmic strings.Comment: 49 pages, 3 figures; v3: refs adde

Quantifying Absolute Neutralization Titers against SARS-CoV-2 by a Standardized Virus Neutralization Assay Allows for CrossCohort Comparisons of COVID-19 Sera

The global coronavirus disease 2019 (COVID-19) pandemic has mobilized efforts to develop vaccines and antibody-based therapeutics, including convalescent-phase plasma therapy, that inhibit viral entry by inducing or transferring neutralizing antibodies (nAbs) against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (CoV2-S). However, rigorous efficacy testing requires extensive screening with live virus under onerous biosafety level 3 (BSL3) conditions, which limits high-throughput screening of patient and vaccine sera. Myriad BSL2-compatible surrogate virus neutralization assays (VNAs) have been developed to overcome this barrier. Yet, there is marked variability between VNAs and how their results are presented, making intergroup comparisons difficult. To address these limitations, we developed a standardized VNA using CoV2-S pseudotyped particles (CoV2pp) based on vesicular stomatitis virus bearing the Renilla luciferase gene in place of its G glyco-protein (VSVDG); this assay can be robustly produced at scale and generate accurate neutralizing titers within 18 h postinfection. Our standardized CoV2pp VNA showed a strong positive correlation with CoV2-S enzyme-linked immunosorbent assay (ELISA) results and live-virus neutralizations in confirmed convalescent-patient sera. Three independent groups subsequently validated our standardized CoV2pp VNA (n . 120). Our data (i) show that absolute 50% inhibitory concentration (absIC50), absIC80, and absIC90 values can be legitimately compared across diverse cohorts, (ii) highlight the substantial but consistent variability in neutralization potency across these cohorts, and (iii) support the use of the absIC80 as a more meaningful metric for assessing the neutralization potency of a vaccine or convalescent-phase sera. Lastly, we used our CoV2pp in a screen to identify ultrapermissive 293T clones that stably express ACE2 or ACE2 plus TMPRSS2. When these are used in combination with our CoV2pp, we can produce CoV2pp sufficient for 150,000 standardized VNAs/week. IMPORTANCE Vaccines and antibody-based therapeutics like convalescent-phase plasma therapy are premised upon inducing or transferring neutralizing antibodies that inhibit SARS-CoV-2 entry into cells. Virus neutralization assays (VNAs) for measuring neutralizing antibody titers (NATs) are an essential part of determining vaccine or therapeutic efficacy. However, such efficacy testing is limited by the inherent dangers of working with the live virus, which requires specialized high-level biocontainment facilities. We there-fore developed a standardized replication-defective pseudotyped particle system that mimics the entry of live SARS-CoV-2. This tool allows for the safe and efficient measurement of NATs, determination of other forms of entry inhibition, and thorough investigation of virus entry mechanisms. Four independent labs across the globe validated our standardized VNA using diverse cohorts. We argue that a standardized and scalable assay is necessary for meaningful comparisons of the myriad of vaccines and antibody-based therapeutics becoming available. Our data provide generalizable metrics for assessing their efficacy.Fil: Oguntuyo, Kasopefoluwa. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Stevens, Christian S.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Hung, Chuan Tien. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Ikegame, Satoshi. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Acklin, Joshua A.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Kowdle, Shreyas S.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Carmichael, Jillian C.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Chiu, Hsin Ping. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Azarm, Kristopher D.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Haas, Griffin D.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Amanat, Fatima. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Klingler, Jéromine. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Baine, Ian. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Arinsburg, Suzanne. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Bandres, Juan C.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Siddiquey, Mohammed N. A.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Schilke, Robert M.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Woolard, Matthew D.. State University of Louisiana; Estados UnidosFil: Zhang, Hongbo. State University of Louisiana; Estados UnidosFil: Duty, Andrew J.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Kraus, Thomas A.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Moran, Thomas M.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Tortorella, Domenico. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Lim, Jean K.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Gamarnik, Andrea Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Hioe, Catarina E.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Zolla Pazner, Susan. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Ivanov, Stanimir S.. State University of Louisiana; Estados UnidosFil: Kamil, Jeremy. State University of Louisiana; Estados UnidosFil: Krammer, Florian. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Lee, Benhur. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Ojeda, Diego Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: González López Ledesma, María Mora. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Costa Navarro, Guadalupe Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Pallarés, H. M.. No especifíca;Fil: Sanchez, Lautaro Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Perez, P.. No especifíca;Fil: Ostrowsk, M.. No especifíca;Fil: Villordo, S. M.. No especifíca;Fil: Alvarez, D. E.. No especifíca;Fil: Caramelo, J. J.. No especifíca;Fil: Carradori, J.. No especifíca;Fil: Yanovsky, M. J.. No especifíca

Influence of Short-Term Glucocorticoid Therapy on Regulatory T Cells In Vivo

Background: Pre- and early clinical studies on patients with autoimmune diseases suggested that induction of regulatory T(Treg) cells may contribute to the immunosuppressive effects of glucocorticoids(GCs). Objective: We readdressed the influence of GC therapy on Treg cells in immunocompetent human subjects and naı¨ve mice. Methods: Mice were treated with increasing doses of intravenous dexamethasone followed by oral taper, and Treg cells in spleen and blood were analyzed by FACS. Sixteen patients with sudden hearing loss but without an inflammatory disease received high-dose intravenous prednisolone followed by stepwise dose reduction to low oral prednisolone. Peripheral blood Treg cells were analyzed prior and after a 14 day GC therapy based on different markers. Results: Repeated GC administration to mice for three days dose-dependently decreased the absolute numbers of Treg cells in blood (100 mg dexamethasone/kg body weight: 2.861.86104 cells/ml vs. 336116104 in control mice) and spleen (dexamethasone: 2.861.96105/spleen vs. 956226105/spleen in control mice), which slowly recovered after 14 days taper in spleen but not in blood. The relative frequency of FOXP3+ Treg cells amongst the CD4+ T cells also decreased in a dose dependent manner with the effect being more pronounced in blood than in spleen. The suppressive capacity of Treg cells was unaltered by GC treatment in vitro. In immunocompetent humans, GCs induced mild T cell lymphocytosis. However, it did not change the relative frequency of circulating Treg cells in a relevant manner, although there was some variation depending on the definition of the Treg cells (FOXP3+: 4.061.5% vs 3.461.5%*; AITR+: 0.660.4 vs 0.560.3%, CD127low: 4.061.3 vs 5.063.0%* and CTLA4+: 13.8611.5 vs 15.6612.5%; * p,0.05). Conclusion: Short-term GC therapy does not induce the hitherto supposed increase in circulating Treg cell frequency, neither in immunocompetent humans nor in mice. Thus, it is questionable that the clinical efficacy of GCs is achieved by modulating Treg cell numbers

In vivo measures of cartilage deformation: patterns in healthy and osteoarthritic female knees using 3T MR imaging

ObjectiveTo explore and to compare the magnitude and spatial pattern of in vivo femorotibial cartilage deformation in healthy and in osteoarthritic (OA) knees.MethodsOne knee each in 30 women (age: 55 ± 6 years; BMI: 28 ± 2.4 kg/m(2); 11 healthy and 19 with radiographic femorotibial OA) was examined at 3Tesla using a coronal fat-suppressed gradient echo SPGR sequence. Regional and subregional femorotibial cartilage thickness was determined under unloaded and loaded conditions, with 50% body weight being applied to the knee in 20° knee flexion during imaging.ResultsCartilage became significantly (p < 0.05) thinner during loading in the medial tibia (-2.7%), the weight-bearing medial femur (-4.1%) and in the lateral tibia (-1.8%), but not in the lateral femur (+0.1%). The magnitude of deformation in the medial tibia and femur tended to be greater in osteoarthritic knees than in healthy knees. The subregional pattern of cartilage deformation was similar for the different stages of radiographic OA.ConclusionOsteoarthritic cartilage tended to display greater deformation upon loading than healthy cartilage, suggesting that knee OA affects the mechanical properties of cartilage. The pattern of in vivo deformation indicated that cartilage loss in OA progression is mechanically driven