Supermassive Black-hole Demographics & Environments With Pulsar Timing Arrays

Precision timing of large arrays (>50) of millisecond pulsars will detect the nanohertz gravitational-wave emission from supermassive binary black holes within the next ~3-7 years. We review the scientific opportunities of these detections, the requirements for success, and the synergies with electromagnetic instruments operating in the 2020s.Comment: Submitted to the Astro2020 Decadal Survey. One of 5 core white-papers authored by members of the NANOGrav Collaboration. 9 pages, 2 figure

Multivariate classification with random forests for gravitational wave searches of black hole binary coalescence

Searches for gravitational waves produced by coalescing black hole binaries with total masses ≳25  M_⊙ use matched filtering with templates of short duration. Non-Gaussian noise bursts in gravitational wave detector data can mimic short signals and limit the sensitivity of these searches. Previous searches have relied on empirically designed statistics incorporating signal-to-noise ratio and signal-based vetoes to separate gravitational wave candidates from noise candidates. We report on sensitivity improvements achieved using a multivariate candidate ranking statistic derived from a supervised machine learning algorithm. We apply the random forest of bagged decision trees technique to two separate searches in the high mass (≳25  M_⊙) parameter space. For a search which is sensitive to gravitational waves from the inspiral, merger, and ringdown of binary black holes with total mass between 25  M_⊙ and 100  M_⊙, we find sensitive volume improvements as high as 70_(±13)%–109_(±11)% when compared to the previously used ranking statistic. For a ringdown-only search which is sensitive to gravitational waves from the resultant perturbed intermediate mass black hole with mass roughly between 10  M_⊙ and 600  M_⊙, we find sensitive volume improvements as high as 61_(±4)%–241_(±12)% when compared to the previously used ranking statistic. We also report how sensitivity improvements can differ depending on mass regime, mass ratio, and available data quality information. Finally, we describe the techniques used to tune and train the random forest classifier that can be generalized to its use in other searches for gravitational waves

Implementation of an efficient Bayesian search for gravitational wave bursts with memory in pulsar timing array data

The standard Bayesian technique for searching pulsar timing data for gravitational wave (GW) bursts with memory (BWMs) using Markov Chain Monte Carlo (MCMC) sampling is very computationally expensive to perform. In this paper, we explain the implementation of an efficient Bayesian technique for searching for BWMs. This technique makes use of the fact that the signal model for Earth-term BWMs (BWMs passing over the Earth) is fully factorizable. We estimate that this implementation reduces the computational complexity by a factor of 100. We also demonstrate that this technique gives upper limits consistent with published results using the standard Bayesian technique, and may be used to perform all of the same analyses that standard MCMC techniques can perform.Comment: 19 pages, 3 figures, 1 table. Submitted to Astrophysical Journa

Nanomaterial cytotoxicity is composition, size, and cell type dependent

<p>Abstract</p> <p>Background</p> <p>Despite intensive research efforts, reports of cellular responses to nanomaterials are often inconsistent and even contradictory. Additionally, relationships between the responding cell type and nanomaterial properties are not well understood. Using three model cell lines representing different physiological compartments and nanomaterials of different compositions and sizes, we have systematically investigated the influence of nanomaterial properties on the degrees and pathways of cytotoxicity. In this study, we selected nanomaterials of different compositions (TiO₂and SiO₂nanoparticles, and multi-wall carbon nanotubes [MWCNTs]) with differing size (MWCNTs of different diameters < 8 nm, 20-30 nm, > 50 nm; but same length 0.5-2 μm) to analyze the effects of composition and size on toxicity to 3T3 fibroblasts, RAW 264.7 macrophages, and telomerase-immortalized (hT) bronchiolar epithelial cells.</p> <p>Results</p> <p>Following characterization of nanomaterial properties in PBS and serum containing solutions, cells were exposed to nanomaterials of differing compositions and sizes, with cytotoxicity monitored through reduction in mitochondrial activity. In addition to cytotoxicity, the cellular response to nanomaterials was characterized by quantifying generation of reactive oxygen species, lysosomal membrane destabilization and mitochondrial permeability. The effect of these responses on cellular fate - apoptosis or necrosis - was then analyzed. Nanomaterial toxicity was variable based on exposed cell type and dependent on nanomaterial composition and size. In addition, nanomaterial exposure led to cell type dependent intracellular responses resulting in unique breakdown of cellular functions for each nanomaterial: cell combination.</p> <p>Conclusions</p> <p>Nanomaterials induce cell specific responses resulting in variable toxicity and subsequent cell fate based on the type of exposed cell. Our results indicate that the composition and size of nanomaterials as well as the target cell type are critical determinants of intracellular responses, degree of cytotoxicity and potential mechanisms of toxicity.</p

Corticosterone Regulates Both Naturally Occurring and Cocaine‐Induced Dopamine Signaling by Selectively Decreasing Dopamine Uptake

Stressful and aversive events promote maladaptive reward‐seeking behaviors such as drug addiction by acting, in part, on the mesolimbic dopamine system. Using animal models, data from our laboratory and others show that stress and cocaine can interact to produce a synergistic effect on reward circuitry. This effect is also observed when the stress hormone corticosterone is administered directly into the nucleus accumbens (NAc), indicating that glucocorticoids act locally in dopamine terminal regions to enhance cocaine\u27s effects on dopamine signaling. However, prior studies in behaving animals have not provided mechanistic insight. Using fast‐scan cyclic voltammetry, we examined the effect of systemic corticosterone on spontaneous dopamine release events (transients) in the NAc core and shell in behaving rats. A physiologically relevant systemic injection of corticosterone (2 mg/kg i.p.) induced an increase in dopamine transient amplitude and duration (both voltammetric measures sensitive to decreases in dopamine clearance), but had no effect on the frequency of transient release events. This effect was compounded by cocaine (2.5 mg/kg i.p.). However, a second experiment indicated that the same injection of corticosterone had no detectable effect on the dopaminergic encoding of a palatable natural reward (saccharin). Taken together, these results suggest that corticosterone interferes with naturally occurring dopamine uptake locally, and this effect is a critical determinant of dopamine concentration specifically in situations in which the dopamine transporter is pharmacologically blocked by cocaine

Status of vaccine research and development of vaccines for GBS

Streptococcus agalactiae (group B streptococcus (GBS)) is the leading cause of neonatal sepsis and meningitis in many countries. Intrapartum antibiotic strategies have reduced the incidence of early-onset neonatal GBS in a number of countries but have had no impact on late onset GBS infection (LOD). In low/middle income settings, the disease burden remains uncertain although in several countries of Southern Africa appears comparable to or higher than that of high-income countries. As disease may be rapidly fulminating cases can be missed before appropriate samples are obtained and this may lead to underestimation of the true burden. Given the rapid onset and progression within hours of birth as well as the deficiencies in IAP strategies and absence of a solution for preventing LOD, it is clear that administration of a suitable vaccine in pregnancy could provide a better solution in all settings; it should also be cost effective. The current leading vaccine candidates are CPS-protein conjugate vaccines but protein-based vaccines are also in development and one has recently commenced clinical trials

Local and systemic in vivo responses to osseointegrative titanium nanotube surfaces

Orthopedic implants requiring osseointegration are often surface modified; however, implants may shed these coatings and generate wear debris leading to complications. Titanium nanotubes (TiNT), a new surface treatment, may promote osseointegration. In this study, in vitro (rat marrow-derived bone marrow cell attachment and morphology) and in vivo (rat model of intramedullary fixation) experiments characterized local and systemic responses of two TiNT surface morphologies, aligned and trabecular, via animal and remote organ weight, metal ion, hematologic, and nondecalcified histologic analyses. In vitro experiments showed total adherent cells on trabecular and aligned TiNT surfaces were greater than control at 30 min and 4 h, and cells were smaller in diameter and more eccentric. Control animals gained more weight, on average; however, no animals met the institutional trigger for weight loss. No hematologic parameters (complete blood count with differential) were significantly different for TiNT groups vs. control. Inductively coupled plasma mass spectrometry (ICP-MS) showed greater aluminum levels in the lungs of the trabecular TiNT group than in those of the controls. Histologic analysis demonstrated no inflammatory infiltrate, cytotoxic, or necrotic conditions in proximity of K-wires. There were significantly fewer eosinophils/basophils and neutrophils in the distal region of trabecular TiNT-implanted femora; and, in the midshaft of aligned TiNT-implanted femora, there were significantly fewer foreign body giant/multinucleated cells and neutrophils, indicating a decreased immune response in aligned TiNT-implanted femora compared to controls