A Fast Frequency-Domain Algorithm for Gravitational Self-Force: I, Circular Orbits in Schwarzschild Spacetime

Fast, reliable orbital evolutions of compact objects around massive black holes will be needed as input for gravitational wave search algorithms in the data stream generated by the planned Laser Interferometer Space Antenna (LISA). Currently, the state of the art is a time-domain code by [Phys. Rev. D{\bf 81}, 084021, (2010)] that computes the gravitational self-force on a point-particle in an eccentric orbit around a Schwarzschild black hole. Currently, time-domain codes take up to a few days to compute just one point in parameter space. In a series of articles, we advocate the use of a frequency-domain approach to the problem of gravitational self-force (GSF) with the ultimate goal of orbital evolution in mind. Here, we compute the GSF for a particle in a circular orbit in Schwarzschild spacetime. We solve the linearized Einstein equations for the metric perturbation in Lorenz gauge. Our frequency-domain code reproduces the time-domain results for the GSF up to $\sim 1000$ times faster for small orbital radii. In forthcoming companion papers, we will generalize our frequency-domain methods to include bound (eccentric) orbits in Schwarzschild and (eventually) Kerr spacetimes for computing the GSF, where we will employ the method of extended homogeneous solutions [Phys. Rev. D {\bf 78}, 084021 (2008)].Comment: 26 pages, 4 figures, with minor typos now fixe

Gravitational self-force and the effective-one-body formalism between the innermost stable circular orbit and the light ring

We compute the conservative piece of the gravitational self-force (GSF) acting on a particle of mass m_1 as it moves along an (unstable) circular geodesic orbit between the innermost stable circular orbit (ISCO) and the light ring of a Schwarzschild black hole of mass m_2>> m_1. More precisely, we construct the function h_{uu}(x) = h_{\mu\nu} u^{\mu} u^{\nu} (related to Detweiler's gauge-invariant "redshift" variable), where h_{\mu\nu} is the regularized metric perturbation in the Lorenz gauge, u^{\mu} is the four-velocity of m_1, and x= [Gc^{-3}(m_1+m_2)\Omega]^{2/3} is an invariant coordinate constructed from the orbital frequency \Omega. In particular, we explore the behavior of h_{uu} just outside the "light ring" at x=1/3, where the circular orbit becomes null. Using the recently discovered link between h_{uu} and the piece a(u), linear in the symmetric mass ratio \nu, of the main radial potential A(u,\nu) of the Effective One Body (EOB) formalism, we compute a(u) over the entire domain 0<u<1/3. We find that a(u) diverges at the light-ring as ~0.25 (1-3u)^{-1/2}, explain the physical origin of this divergence, and discuss its consequences for the EOB formalism. We construct accurate global analytic fits for a(u), valid on the entire domain 0<u<1/3 (and possibly beyond), and give accurate numerical estimates of the values of a(u) and its first 3 derivatives at the ISCO, as well as the O(\nu) shift in the ISCO frequency. In previous work we used GSF data on slightly eccentric orbits to compute a certain linear combination of a(u) and its first two derivatives, involving also the O(\nu) piece \bar d(u) of a second EOB radial potential {\bar D}(u,\nu). Combining these results with our present global analytic representation of a(u), we numerically compute {\bar d}(u)$ on the interval 0<u\leq 1/6.Comment: 44 pages, 8 figures. Extended discussion in Section V and minor typographical corrections throughout. Version to be published in PR

Translocation of Non-Canonical Polypeptides into Cells Using Protective Antigen

A variety of pathogenic bacteria infect host eukaryotic cells using protein toxins, which enter the cytosol and exert their cytotoxic effects. Anthrax lethal toxin, for example, utilizes the membrane-spanning translocase, protective antigen (PA) pore, to deliver the protein toxin lethal factor (LF) from the endosome into the cytosol of cells. Previous work has investigated the delivery of natural peptides and enzymatic domains appended to the C-terminus of the PA-binding domain of lethal factor (LF[subscript N]) into the cytosol via PA pore. Here, we move beyond natural amino acids and systematically investigate the translocation of polypeptide cargo containing non-canonical amino acids and functionalities through PA pore. Our results indicate translocation is not perturbed with alterations to the peptide backbone or side-chain. Moreover, despite their structural complexity, we found that the small molecule drugs, doxorubicin and monomethyl auristatin F (MMAF) translocated efficiently through PA pore. However, we found cyclic peptides and the small molecule drug docetaxel abrogated translocation due to their large size and structural rigidity. For cargos that reached the cytosol, we demonstrated that each remained intact after translocation. These studies show PA is capable of translocating non-canonical cargo provided it is in a conformational state conducive for passage through the narrow pore.MIT Start-up FundsMassachusetts Institute of Technology. Charles E. Reed Faculty Initiative FundDamon Runyon Cancer Research Foundation (Innovation Award)National Science Foundation (U.S.) (CAREER Award CHE-1351807)National Science Foundation (U.S.). Graduate Research Fellowshi

Not by transmission alone: the role of invention in cultural evolution

Innovation—the combination of invention and social learning—can empower species to invade new niches via cultural adaptation. Social learning has typically been regarded as the fundamental driver for the emergence of traditions and thus culture. Consequently, invention has been relatively understudied outside the human lineage—despite being the source of new traditions. This neglect leaves basic questions unanswered: what factors promote the creation of new ideas and practices? What affects their spread or loss? We critically review the existing literature, focusing on four levels of investigation: traits (what sorts of behaviours are easiest to invent?), individuals (what factors make some individuals more likely to be inventors?), ecological contexts (what aspects of the environment make invention or transmission more likely?), and populations (what features of relationships and societies promote the rise and spread of new inventions?). We aim to inspire new research by highlighting theoretical and empirical gaps in the study of innovation, focusing primarily on inventions in non-humans. Understanding the role of invention and innovation in the history of life requires a well-developed theoretical framework (which embraces cognitive processes) and a taxonomically broad, cross-species dataset that explicitly investigates inventions and their transmission. We outline such an agenda here. This article is part of the theme issue ‘Foundations of cultural evolution’

Diazoxide-responsive hyperinsulinemic hypoglycemia caused by HNF4A gene mutations

Objective: The phenotype associated with heterozygous HNF4A gene mutations has recently been extended to include diazoxide responsive neonatal hypoglycemia in addition to maturity-onset diabetes of the young (MODY). To date, mutation screening has been limited to patients with a family history consistent with MODY. In this study, we investigated the prevalence of HNF4A mutations in a large cohort of patients with diazoxide responsive hyperinsulinemic hypoglycemia (HH). Subjects and methods: We sequenced the ABCC8, KCNJ11, GCK, GLUD1, and/or HNF4A genes in 220 patients with HH responsive to diazoxide. The order of genetic testing was dependent upon the clinical phenotype. Results: A genetic diagnosis was possible for 59/220 (27%) patients. KATP channel mutations were most common (15%) followed by GLUD1 mutations causing hyperinsulinism with hyperammonemia (5.9%), and HNF4A mutations (5%). Seven of the 11 probands with a heterozygous HNF4A mutation did not have a parent affected with diabetes, and four de novo mutations were confirmed. These patients were diagnosed with HI within the first week of life (median age 1 day), and they had increased birth weight (median +2.4 SDS). The duration of diazoxide treatment ranged from 3 months to ongoing at 8 years. Conclusions: In this large series, HNF4A mutations are the third most common cause of diazoxide responsive HH. We recommend that HNF4A sequencing is considered in all patients with diazoxide responsive HH diagnosed in the first week of life irrespective of a family history of diabetes, once KATP channel mutations have been excluded

Area Invariance of Apparent Horizons under Arbitrary Boosts

It is a well known analytic result in general relativity that the 2-dimensional area of the apparent horizon of a black hole remains invariant regardless of the motion of the observer, and in fact is independent of the $t=constant$ slice, which can be quite arbitrary in general relativity. Nonetheless the explicit computation of horizon area is often substantially more difficult in some frames (complicated by the coordinate form of the metric), than in other frames. Here we give an explicit demonstration for very restricted metric forms of (Schwarzschild and Kerr) vacuum black holes. In the Kerr-Schild coordinate expression for these spacetimes they have an explicit Lorentz-invariant form. We consider {\it boosted} versions with the black hole moving through the coordinate system. Since these are stationary black hole spacetimes, the apparent horizons are two dimensional cross sections of their event horizons, so we compute the areas of apparent horizons in the boosted space with (boosted) $t = constant$, and obtain the same result as in the unboosted case. Note that while the invariance of area is generic, we deal only with black holes in the Kerr-Schild form, and consider only one particularly simple change of slicing which amounts to a boost. Even with these restrictions we find that the results illuminate the physics of the horizon as a null surface and provide a useful pedagogical tool. As far as we can determine, this is the first explicit calculation of this type demonstrating the area invariance of horizons. Further, these calculations are directly relevant to transformations that arise in computational representation of moving black holes. We present an application of this result to initial data for boosted black holes.Comment: 19 pages, 3 figures. Added a new section and 2 plots along with a coautho

Use of biochemical and protein profiles of seminal plasma to prediction of semen quality and fertility in stallions

The identification of various substances in seminal plasma has opened the way to study their functionality. It was aimed to identify the electrophoretic protein profile (EPP) and biochemical parameters (BP) of seminal plasma (SP) as predictors of semen quality and fertility in stallion. Forty-six ejaculates from 7 fertile stallions, aged between 6-26 years, were collected from May to July and 117 mares were used to obtain fertility data. For each ejaculate, volume, sperm motility, concentration were determined and seminal plasma samples were collected to perform one-dimensional electrophoresis and biochemical profiling. Following the estrus detection, mares were inseminated with fresh sperm. Pregnancy rates and foal rates were recorded. The concentration of 15-18 kDa molecular weight (MW) proteins has shown a positive correlation with sperm concentration and foal rate. Besides, a strong positive correlation was found between sperm concentration and 23-28 kDa MW proteins (r=0.77). The volume of 19-22 kDa MW proteins was negatively correlated with pregnancy and foal rate. Similarly, the volume of high MW proteins (173-385 kDa) correlated negatively with sperm motility and foal rate. Apart from the protein profile, while Magnesium and Glucose levels were negatively correlated with sperm quality and foal rate, Cholesterol level was a positive indicator of the quality of semen as well as the foaling rate. Moreover, the total protein level was correlated negatively with the sperm concentration whereas triglyceride was correlated positively. In conclusion, EPP and BP of seminal plasma are valuable clinical tools as predictors of fertility and semen quality in the stallion.Fil: Stelletta, C.. Università di Padova; ItaliaFil: Alberti, S.. Università di Padova; ItaliaFil: Cil, B.. Ankara University; TurquíaFil: Tekin, K.. Ankara University; TurquíaFil: Tirpan, M. B.. Ankara University; TurquíaFil: Argañaraz, Martin Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Akcay, E.. Ankara University; TurquíaFil: Daskin, A.. Ankara University; Turquí

Characteristics of patients operated for primary hyperparathyroidism at university hospitals in Türkiye: Differences among Türkiye's geographical regions

Purpose: The aim of this study was to define the clinical and laboratory characteristics of patients operated on for primary hyperpatathyroidism (PHPT) at university hospitals in Türkiye, and to investigate the differences in the clinical presentations of the disease between different geographical regions. Methods: Patients operated on for PHPT in the university hospitals of Türkiye were included in the study. The demographic, clinical, and laboratory findings and the operational data of the patients were investigated according to the whole country and to different geographical regions. Comparisons were performed according to whole country and regions. Results: A total of 1,162 cases were included in the study from different regions and 20 university hospitals. The mean age of patients was 52.4 ± 0.38 (mean ± standard error) in the general population of Türkiye. The rates of hypertension, urolithiasis, bone disease and 25-hydroxyvitamin D insufficiency were 35%, 18.6%, 67.6%, and 63%, respectively. The median parathormone (PTH), serum total calcium (Ca+2) and phosphorus value were 220 pg/mL (range, 70-2,500 pg/mL), 11.2 mg/dL (range, 9.5-11.2 mg/dL), and 2.4 mg/dL (range, 1-4.7 mg/dL), respectively. The median size of the adenomas resected was 16 mm (range, 4-70 mm). Significant differences were observed in the clinical and laboratory findings of the patients operated on due to PHPT between different geographical regions of Türkiye (P &lt; 0.05). Conclusion: The clinical and laboratory characteristics of the patients with PHPT in different geographical regions of Türkiye differ. Furthermore, the general findings of the cases in Türkiye give us a hint that the severity of the disease here is somewhere between Eastern and Western countries. Copyright © 2016, the Korean Surgical Society

Spin–orbit precession for eccentric black hole binaries at first order in the mass ratio

We consider spin–orbit ('geodetic') precession for a compact binary in strong-field gravity. Specifically, we compute ψ, the ratio of the accumulated spin-precession and orbital angles over one radial period, for a spinning compact body of mass m 1 and spin s 1, with ${{s}_{1}}\ll Gm_{1}^{2}/c$ , orbiting a non-rotating black hole. We show that ψ can be computed for eccentric orbits in both the gravitational self-force and post-Newtonian frameworks, and that the results appear to be consistent. We present a post-Newtonian expansion for ψ at next-to-next-to-leading order, and a Lorenz-gauge gravitational self-force calculation for ψ at first order in the mass ratio. The latter provides new numerical data in the strong-field regime to inform the effective one-body model of the gravitational two-body problem. We conclude that ψ complements the Detweiler redshift z as a key invariant quantity characterizing eccentric orbits in the gravitational two-body problem