Orbital evolution of a particle around a black hole: II. Comparison of contributions of spin-orbit coupling and the self force

We consider the evolution of the orbit of a spinning compact object in a quasi-circular, planar orbit around a Schwarzschild black hole in the extreme mass ratio limit. We compare the contributions to the orbital evolution of both spin-orbit coupling and the local self force. Making assumptions on the behavior of the forces, we suggest that the decay of the orbit is dominated by radiation reaction, and that the conservative effect is typically dominated by the spin force. We propose that a reasonable approximation for the gravitational waveform can be obtained by ignoring the local self force, for adjusted values of the parameters of the system. We argue that this approximation will only introduce small errors in the astronomical determination of these parameters.Comment: 11 pages, 7 figure

Gravitational waves from eccentric compact binaries: Reduction in signal-to-noise ratio due to nonoptimal signal processing

Inspiraling compact binaries have been identified as one of the most promising sources of gravitational waves for interferometric detectors. Most of these binaries are expected to have circularized by the time their gravitational waves enter the instrument's frequency band. However, the possibility that some of the binaries might still possess a significant eccentricity is not excluded. We imagine a situation in which eccentric signals are received by the detector but not explicitly searched for in the data analysis, which uses exclusively circular waveforms as matched filters. We ascertain the likelihood that these filters, though not optimal, will nevertheless be successful at capturing the eccentric signals. We do this by computing the loss in signal-to-noise ratio incurred when searching for eccentric signals with those nonoptimal filters. We show that for a binary system of a given total mass, this loss increases with increasing eccentricity. We show also that for a given eccentricity, the loss decreases as the total mass is increased.Comment: 14 pages, 4 figures, ReVTeX; minor changes made after referee's comment

High-pressure CO2/CH4 separation of Zr-MOFs based mixed matrix membranes

The gas separation properties of 6FDA-DAM mixed matrix membranes (MMMs) with three types of zirconium-based metal organic framework nanoparticles (MOF NPs, ca. 40 nm) have been investigated up to 20 bar. Both NPs preparation and MMMs development were presented in an earlier publication that reported outstanding CO2/CH4 separation performances (50:50 vol% CO2/CH4 feed at 2 bar pressure difference, 35 °C) and this subsequent study is to demonstrate its usefulness to the natural gas separation application. In the current work, CO2/CH4 separation has been investigated at high pressure (2–20 bar feed pressure) with different CO2 content in the feed (10–50 vol%) in the temperature range 35–55 °C. Moreover, the plasticization, competitive sorption effects, and separation of the acid gas hydrogen sulfide (H2S) have been investigated in a ternary feed mixture of CO2:H2S:CH4 (vol% ratio of 30:5:65) at 20 bar and 35 °C. The incorporation of the Zr-MOFs in 6FDA-DAM enhances both CO2 permeability and CO2/CH4 selectivity of this polymer. These MMMs exhibit high stability under separation conditions relevant to an actual natural gas sweetening process. The presence of H2S does not induce plasticization but increases the total acid gas permeability, acid gas/CH4 selectivity and only causes reversible competitive sorption. The overall study suggests a large potential for 6FDA-DAM Zr-MOF MMMs to be applied in natural gas sweetening, with good performance and stability under the relevant process conditions

Gravitational radiation reaction in compact binary systems: Contribution of the magnetic dipole-magnetic dipole interaction

We study the gravitational radiation reaction in compact binary systems composed of neutron stars with spin and huge magnetic dipole moments (magnetars). The magnetic dipole moments undergo a precessional motion about the respective spins. At sufficiently high values of the magnetic dipole moments, their interaction generates second post-Newtonian order contributions both to the equations of motion and to the gravitational radiation escaping the system. We parametrize the radial motion and average over a radial period in order to find the secular contributions to the energy and magnitude of the orbital angular momentum losses, in the generic case of \textit{eccentric} orbits. Similarly as for the spin-orbit, spin-spin, quadrupole-monopole interactions, here too we deduce the secular evolution of the relative orientations of the orbital angular momentum and spins. These equations, supplemented by the evolution equations for the angles characterizing the orientation of the dipole moments form a first order differential system, which is closed. The circular orbit limit of the energy loss agrees with Ioka and Taniguchi's earlier result

Development of tumor mutation burden as an immunotherapy biomarker: utility for the oncology clinic.

Treatment with immune checkpoint blockade (ICB) with agents such as anti-programmed cell death protein 1 (PD-1), anti-programmed death-ligand 1 (PD-L1), and/or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) can result in impressive response rates and durable disease remission but only in a subset of patients with cancer. Expression of PD-L1 has demonstrated utility in selecting patients for response to ICB and has proven to be an important biomarker for patient selection. Tumor mutation burden (TMB) is emerging as a potential biomarker. However, refinement of interpretation and contextualization is required. In this review, we outline the evolution of TMB as a biomarker in oncology, delineate how TMB can be applied in the clinic, discuss current limitations as a diagnostic test, and highlight mechanistic insights unveiled by the study of TMB. We review available data to date studying TMB as a biomarker for response to ICB by tumor type, focusing on studies proposing a threshold for TMB as a predictive biomarker for ICB activity. High TMB consistently selects for benefit with ICB therapy. In lung, bladder and head and neck cancers, the current predictive TMB thresholds proposed approximate 200 non-synonymous somatic mutations by whole exome sequencing (WES). PD-L1 expression influences response to ICB in high TMB tumors with single agent PD-(L)1 antibodies; however, response may not be dependent on PD-L1 expression in the setting of anti-CTLA4 or anti-PD-1/CTLA-4 combination therapy. Disease-specific TMB thresholds for effective prediction of response in various other malignancies are not well established. TMB, in concert with PD-L1 expression, has been demonstrated to be a useful biomarker for ICB selection across some cancer types; however, further prospective validation studies are required. TMB determination by selected targeted panels has been correlated with WES. Calibration and harmonization will be required for optimal utility and alignment across all platforms currently used internationally. Key challenges will need to be addressed before broader use in different tumor types

Parallel microarray profiling identifies ErbB4 as a determinant of cyst growth in ADPKD and a prognostic biomarker for disease progression.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the fourth most common cause of end-stage renal disease. The disease course can be highly variable and treatment options are limited. To identify new therapeutic targets and prognostic biomarkers of disease, we conducted parallel discovery microarray profiling in normal and diseased human PKD1 cystic kidney cells. A total of 1515 genes and 5 miRNA were differentially expressed by more than two-fold in PKD1 cells. Functional enrichment analysis identified 30 dysregulated signalling pathways including the epidermal growth factor (EGF) receptor pathway. In this paper, we report that the EGF family receptor, ErbB4, is a major factor driving cyst growth in ADPKD. Expression of ErbB4 in vivo was increased in human ADPKD and Pkd1 cystic kidneys, both transcriptionally and post-transcriptionally by mir-193b-3p. Ligand-induced activation of ErbB4 drives cystic proliferation and expansion suggesting a pathogenic role in cystogenesis. Our results implicate ErbB4 activation as functionally relevant in ADPKD, both as a marker of disease activity and as a new therapeutic target in this major kidney disease