Distortion of Gravitational-Wave Packets Due to their Self-Gravity

When a source emits a gravity-wave (GW) pulse over a short period of time, the leading edge of the GW signal is redshifted more than the inner boundary of the pulse. The GW pulse is distorted by the gravitational effect of the self-energy residing in between these shells. We illustrate this distortion for GW pulses from the final plunge of black hole (BH) binaries, leading to the evolution of the GW profile as a function of the radial distance from the source. The distortion depends on the total GW energy released and the duration of the emission, scaled by the total binary mass, M. The effect should be relevant in finite box simulations where the waveforms are extracted within a radius of <~ 100M. For characteristic emission parameters at the final plunge between binary BHs of arbitrary spins, this effect could distort the simulated GW templates for LIGO and LISA by a fraction of 0.001. Accounting for the wave distortion would significantly decrease the waveform extraction errors in numerical simulations.Comment: accepted for publication in Physical Review

Quantum and semiclassical study of magnetic anti-dots

We study the energy level structure of two-dimensional charged particles in inhomogeneous magnetic fields. In particular, for magnetic anti-dots the magnetic field is zero inside the dot and constant outside. Such a device can be fabricated with present-day technology. We present detailed semiclassical studies of such magnetic anti-dot systems and provide a comparison with exact quantum calculations. In the semiclassical approach we apply the Berry-Tabor formula for the density of states and the Borh-Sommerfeld quantization rules. In both cases we found good agreement with the exact spectrum in the weak magnetic field limit. The energy spectrum for a given missing flux quantum is classified in six possible classes of orbits and summarized in a so-called phase diagram. We also investigate the current flow patterns of different quantum states and show the clear correspondence with classical trajectories.Comment: 14 pages, 13 figure

Finding the Electromagnetic Counterparts of Cosmological Standard Sirens

The gravitational waves (GW) emitted during the coalescence of supermassive black holes (SMBHs) in the mass range 10^4-10^7 M_sun will be detectable out to high redshifts with LISA. We calculate the size and orientation of the three-dimensional error ellipse in solid angle and redshift within which the LISA event could be localized using the GW signatures alone. We take into account uncertainties in LISA's measurements of the luminosity distance and direction to the source, in the background cosmology, in weak gravitational lensing magnification due to inhomogeneities along the line of sight, and potential source peculiar velocities. We find that weak lensing errors exceed other sources of uncertainties by nearly an order of magnitude. Under the plausible assumption that BH mergers are accompanied by gas accretion leading to Eddington-limited quasar activity, we then compute the number of quasars that would be found in a typical LISA error volume, as a function of BH mass and redshift. We find that low redshifts offer the best opportunities to identify quasar counterparts to cosmological standard sirens, and that the LISA error volume will typically contain a single near-Eddington quasar at z=1. This will allow a straightforward test of the hypothesis that BH mergers are accompanied by bright quasar activity and, if the hypothesis proves correct, will guarantee the identification of a unique quasar counterpart. This would yield unprecedented tests of the physics of SMBH accretion, and offer an alternative method to precisely constrain cosmological parameters [abridged].Comment: 11 pages, 4 figures, version accepted for publication in Ap

Cardiac miRNA Expression and their mRNA Targets in a Rat Model of Prediabetes

Little is known about the mechanism of prediabetes-induced cardiac dysfunction. Therefore, we aimed to explore key molecular changes with transcriptomic and bioinformatics approaches in a prediabetes model showing heart failure with preserved ejection fraction phenotype. To induce prediabetes, Long-Evans rats were fed a high-fat diet for 21 weeks and treated with a single low-dose streptozotocin at week 4. Small RNA-sequencing, in silico microRNA (miRNA)-mRNA target prediction, Gene Ontology analysis, and target validation with qRT-PCR were performed in left ventricle samples. From the miRBase-annotated 752 mature miRNA sequences expression of 356 miRNAs was detectable. We identified two upregulated and three downregulated miRNAs in the prediabetic group. We predicted 445 mRNA targets of the five differentially expressed miRNAs and selected 11 mRNAs targeted by three differentially expressed miRNAs, out of which five mRNAs were selected for validation. Out of these five targets, downregulation of three mRNAs i.e., Juxtaposed with another zinc finger protein 1 (Jazf1); RAP2C, member of RAS oncogene family (Rap2c); and Zinc finger with KRAB and SCAN domains 1 (Zkscan1) were validated. This is the first demonstration that prediabetes alters cardiac miRNA expression profile. Predicted targets of differentially expressed miRNAs include Jazf1, Zkscan1, and Rap2c mRNAs. These transcriptomic changes may contribute to the diastolic dysfunction and may serve as drug targets

Hierarchical Black Hole Mergers in Active Galactic Nuclei

The origins of the stellar-mass black hole mergers discovered by LIGO/Virgo are still unknown. Here we show that, if migration traps develop in the \add{accretion} disks of Active Galactic Nuclei (AGNs) and promote the mergers of their captive black holes, the majority of black holes within disks will undergo hierarchical mergers---with one of the black holes being the remnant of a previous merger. 40% of AGN-assisted mergers detected by LIGO/Virgo will include a black hole with mass $\gtrsim 50$ M$_\odot$, the mass limit from stellar core collapse. Hierarchical mergers at traps in AGNs will exhibit black hole spins (anti-)aligned with the binary's orbital axis, a distinct property from other hierarchical channels. Our results are suggestive, although not definitive (with Odds ratio of $\sim 1$), that LIGO's heaviest merger so far, GW170729, could have originated from this channel.Comment: 6 pages, 3 figures; accepted in PR

Association of combined PD- L1 expression and tumour- infiltrating lymphocyte features with survival and treatment outcomes in patients with metastatic melanoma

BackgroundRecent advances obtained with immune checkpoint inhibitors (ICIs) targeting the programmed cell death- 1 (PD- 1) protein have significantly improved the outcome of patients with metastatic melanoma. The PD- L1 expression in tumour cells as detected by immunohistochemistry is a predictive biomarker in some solid tumours, but appears insufficient as prognostic or predictive factor of response to ICIs in metastatic melanomas.ObjectivesWe investigated whether the presence and the features of pretreatment CD8+tumour- infiltrating T lymphocytes (TILs) could be a complementary prognostic or predictive biomarker in patients with metastatic melanoma.MethodsIn this retrospective study, we evaluated the association of PD- L1 expression - ¥5% of tumour cells combined with TIL features (CD8, CD28, Ki67) with the overall survival (OS) among 51 patients treated with ICIs and 54 patients treated with other treatment options (non- ICIs).ResultsPD- L1 positivity was observed in 33% and 39% of primary melanomas and matched metastases, respectively, with, however, poor concordance between the primary and the matched metastatic site (κ = 0.283). No significant association was noted between PD- L1 expression and CD8+TIL profile analysed as single markers and OS or response to immunotherapy. Instead, their combined analysis in primary melanoma samples showed that the PD- L1- /CD8+status was significantly associated with prolonged OS in the whole population (P = 0.04) and in the subgroup treated with non- ICIs (P = 0.009). Conversely, the PD- L1+/CD8+ status was a good prognostic factor in patients treated with ICIs (P = 0.022), whereas was significantly associated with poor prognosis in patients treated with non- ICIs (P = 0.014). While the expression of CD28 was not related to outcome, the Ki67 expression was significantly associated with poor OS in the subgroup CD8+TIL+/PD- L1- (P = 0.02).ConclusionsThe pretreatment combination of PD- L1 expression with the level of CD8+TILs could better assess OS and predict therapeutic response of patients with metastatic melanoma treated by either immunotherapy or other treatment regimens.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155478/1/jdv16016_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155478/2/jdv16016.pd

Cardioceptive accuracy is associated with arousal but not with valence and perceived exertion under physical load

Under resting conditions, cardioceptive accuracy-the acuity of the perception of heartbeats-is associated with the self-reported intensity of affective states but not with reported valence. Physical exertion elicits positive affect below the anaerobic threshold and negative affect above the threshold while arousal gradually increases. The current research aimed to study the associations between cardioceptive accuracy and characteristics of the affective response (arousal and valence) during physical activity. About 67 undergraduate students completed the Schandry task and rated their perceived exertion (Borg-scale) and affective experience (arousal and valence) under three physical loads (running on a treadmill below, around, and above the anaerobic threshold). Cardioceptive accuracy was associated with the arousal component of the affective states during physical activity but not with valence and perceived exertion