Rare mutations and potentially damaging missense variants in genes encoding fibrillar collagens and proteins involved in their production are candidates for risk for preterm premature rupture of membranes

Preterm premature rupture of membranes (PPROM) is the leading identifiable cause of preterm birth with ~ 40% of preterm births being associated with PPROM and occurs in 1% - 2% of all pregnancies. We hypothesized that multiple rare variants in fetal genes involved in extracellular matrix synthesis would associate with PPROM, based on the assumption that impaired elaboration of matrix proteins would reduce fetal membrane tensile strength, predisposing to unscheduled rupture. We performed whole exome sequencing (WES) on neonatal DNA derived from pregnancies complicated by PPROM (49 cases) and healthy term deliveries (20 controls) to identify candidate mutations/variants. Genotyping for selected variants from the WES study was carried out on an additional 188 PPROM cases and 175 controls. All mothers were self-reported African Americans, and a panel of ancestry informative markers was used to control for genetic ancestry in all genetic association tests. In support of the primary hypothesis, a statistically significant genetic burden (all samples combined, SKAT-O p-value = 0.0225) of damaging/potentially damaging rare variants was identified in the genes of interest—fibrillar collagen genes, which contribute to fetal membrane strength and integrity. These findings suggest that the fetal contribution to PPROM is polygenic, and driven by an increased burden of rare variants that may also contribute to the disparities in rates of preterm birth among African Americans

Text-to-4D dynamic scene generation

We present MAV3D (Make-A-Video3D), a method for generating three-dimensional dynamic scenes from text descriptions. Our approach uses a 4D dynamic Neural Radiance Field (NeRF), which is optimized for scene appearance, density, and motion consistency by querying a Text-to-Video (T2V) diffusion-based model. The dynamic video output generated from the provided text can be viewed from any camera location and angle, and can be composited into any 3D environment. MAV3D does not require any 3D or 4D data and the T2V model is trained only on Text-Image pairs and unlabeled videos. We demonstrate the effectiveness of our approach using comprehensive quantitative and qualitative experiments and show an improvement over previously established internal baselines. To the best of our knowledge, our method is the first to generate 3D dynamic scenes given a text description. Generated samples can be viewed at make-a-video3d.github.i

Production of 26Al in stellar hydrogen-burning environments: spectroscopic properties of states in 27Si

Model predictions of the amount of the radioisotope 26Al produced in hydrogen-burning environments require reliable estimates of the thermonuclear rates for the 26gAl(p,{\gamma})27Si and 26mAl(p,{\gamma})27Si reactions. These rates depend upon the spectroscopic properties of states in 27Si within about 1 MeV of the 26gAl+p threshold (Sp = 7463 keV). We have studied the 28Si(3He,{\alpha})27Si reaction at 25 MeV using a high-resolution quadrupole-dipole-dipole-dipole magnetic spectrograph. For the first time with a transfer reaction, we have constrained J{\pi} values for states in 27Si over Ex = 7.0 - 8.1 MeV through angular distribution measurements. Aside from a few important cases, we generally confirm the energies and spin-parity assignments reported in a recent {\gamma}-ray spectroscopy study. The magnitudes of neutron spectroscopic factors determined from shell-model calculations are in reasonable agreement with our experimental values extracted using this reaction.Comment: accepted for publication in Phys. Rev.

Classical and semi-classical energy conditions

The standard energy conditions of classical general relativity are (mostly) linear in the stress-energy tensor, and have clear physical interpretations in terms of geodesic focussing, but suffer the significant drawback that they are often violated by semi-classical quantum effects. In contrast, it is possible to develop non-standard energy conditions that are intrinsically non-linear in the stress-energy tensor, and which exhibit much better well-controlled behaviour when semi-classical quantum effects are introduced, at the cost of a less direct applicability to geodesic focussing. In this article we will first review the standard energy conditions and their various limitations. (Including the connection to the Hawking--Ellis type I, II, III, and IV classification of stress-energy tensors). We shall then turn to the averaged, nonlinear, and semi-classical energy conditions, and see how much can be done once semi-classical quantum effects are included.Comment: V1: 25 pages. Draft chapter, on which the related chapter of the book "Wormholes, Warp Drives and Energy Conditions" (to be published by Springer), will be based. V2: typos fixed. V3: small typo fixe

The information paradox and the locality bound

Hawking's argument for information loss in black hole evaporation rests on the assumption of independent Hilbert spaces for the interior and exterior of a black hole. We argue that such independence cannot be established without incorporating strong gravitational effects that undermine locality and invalidate the use of quantum field theory in a semiclassical background geometry. These considerations should also play a role in a deeper understanding of horizon complementarity.Comment: 21 pages, harvmac; v2-3. minor corrections, references adde

Aspects of Quantum Gravity in de Sitter Spaces

In these lectures we give a review of recent attempts to understand quantum gravity on de Sitter spaces. In particular, we discuss the holographic correspondence between de Sitter gravity and conformal field theories proposed by Hull and by Strominger, and how this may be reconciled with the finite-dimensional Hilbert space proposal by Banks and Fischler. Furthermore we review the no-go theorems that forbid an embedding of de Sitter spaces in string theory, and discuss how they can be circumvented. Finally, some curious issues concerning the thermal nature of de Sitter space are elucidated.Comment: 36+1 pages, 5 Postscript figures, introduction and section 6 extended, further references, final version to appear in JCA

Decrease of pro-angiogenic monocytes predicts clinical response to anti-angiogenic treatment in patients with metastatic renal cell carcinoma

The modulation of subpopulations of pro-angiogenic monocytes (VEGFR-1+ CD14 and Tie2+ CD14) was analyzed in an ancillary study from the prospective PazopanIb versus Sunitinib patient preferenCE Study (PISCES) (NCT01064310), where metastatic renal cell carcinoma (mRCC) patients were treated with two anti-angiogenic drugs, either sunitinib or pazopanib. Blood samples from 86 patients were collected prospectively at baseline (T1), and at 10 weeks (T2) and 20 weeks (T3) after starting anti-angiogenic therapy. Various subpopulations of myeloid cells (monocytes, VEGFR-1+ CD14 and Tie2+ CD14 cells) decreased during treatment. When patients were divided into two subgroups with a decrease (defined as a >20% reduction from baseline value) (group 1) or not (group 2) at T3 for VEGFR-1+ CD14 cells, group 1 patients presented a median PFS and OS of 24 months and 37 months, respectively, compared with a median PFS of 9 months (p = 0.032) and a median OS of 16 months (p = 0.033) in group 2 patients. The reduction in Tie2+ CD14 at T3 predicted a benefit in OS at 18 months after therapy (p = 0.04). In conclusion, in this prospective clinical trial, a significant decrease in subpopulations of pro-angiogenic monocytes was associated with clinical response to anti-angiogenic drugs in patients with mRCC

On higher derivative gravity, c-theorems and cosmology

We consider higher derivative gravity lagrangians in 3 and 4 dimensions, which admit simple c-theorems, including upto six derivative curvature invariants. Following a suggestion by Myers, these lagrangians are restricted such that the fluctuations around (anti) de Sitter spaces have second order linearized equations of motion. We study c-theorems both in the context of AdS/CFT and cosmology. In the context of cosmology, the monotonic function is the entropy defined on the apparent horizon through Wald's formula. Exact black hole solutions which are asymptotically (anti) de Sitter are presented. An interesting lower bound for entropy is found in de Sitter space. Some aspects of cosmology in both D=3 and D=4 are discussed.Comment: 23 pages, v3: clarifications added, references adde