Genome sequence of the Lebeckia ambigua-nodulating 'Burkholderia sprentiae' strain WSM5005T

"Burkholderia sprentiae" strain WSM5005(T) is an aerobic, motile, Gram-negative, non-sporeforming rod that was isolated in Australia from an effective N-2-fixing root nodule of Lebeckia ambigua collected in Klawer, Western Cape of South Africa, in October 2007. Here we describe the features of "Burkholderia sprentiae" strain WSM5005T, together with the genome sequence and its annotation. The 7,761,063 bp high-quality-draft genome is arranged in 8 scaffolds of 236 contigs, contains 7,147 protein-coding genes and 76 RNA-only encoding genes, and is one of 20 rhizobial genomes sequenced as part of the DOE Joint Genome Institute 2010 Community Sequencing Program

Placenta-specific methylation of the vitamin D 24-hydroxylase gene: implications for feedback autoregulation of active vitamin D levels at the fetomaternal interface

Plasma concentrations of biologically active vitamin D (1,25- (OH)2D) are tightly controlled via feedback regulation of renal 1-hydroxylase (CYP27B1; positive) and 24-hydroxylase (CYP24A1; catabolic) enzymes. In pregnancy, this regulation is uncoupled, and 1,25-(OH)2D levels are significantly elevated, suggesting a role in pregnancy progression. Epigenetic regulation of CYP27B1 and CYP24A1 has previously been described in cell and animal models, and despite emerging evidence for a critical role of epigenetics in placentation generally, little is known about the regulation of enzymes modulating vitamin D homeostasis at the fetomaternal interface. In this study, we investigated the methylation status of genes regulating vitamin D bioavailability and activity in the placenta. No methylation of the VDR (vitamin D receptor) and CYP27B1 genes was found in any placental tissues. In contrast, the CYP24A1 gene is methylated in human placenta, purified cytotrophoblasts, and primary and cultured chorionic villus sampling tissue. No methylation was detected in any somatic human tissue tested. Methylation was also evident in marmoset and mouse placental tissue. All three genes were hypermethylated in choriocarcinoma cell lines, highlighting the role of vitaminDderegulation in this cancer. Gene expression analysis confirmed a reduced capacity for CYP24A1 induction with promoter methylation in primary cells and in vitro reporter analysis demonstrated that promoter methylation directly down-regulates basal promoter activity and abolishes vitamin D-mediated feedback activation. This study strongly suggests that epigenetic decoupling of vitamin D feedback catabolism plays an important role in maximizing active vitamin D bioavailability at the fetomaternal interface

A binary tree approach to template placement for searches for gravitational waves from compact binary mergers

We demonstrate a new geometric method for fast template placement for searches for gravitational waves from the inspiral, merger and ringdown of compact binaries. The method is based on a binary tree decomposition of the template bank parameter space into non-overlapping hypercubes. We use a numerical approximation of the signal overlap metric at the center of each hypercube to estimate the number of templates required to cover the hypercube and determine whether to further split the hypercube. As long as the expected number of templates in a given cube is greater than a given threshold, we split the cube along its longest edge according to the metric. When the expected number of templates in a given hypercube drops below this threshold, the splitting stops and a template is placed at the center of the hypercube. Using this method, we generate aligned-spin template banks covering the mass range suitable for a search of Advanced LIGO data. The aligned-spin bank required ~24 CPU-hours and produced 2 million templates. In general, we find that other methods, namely stochastic placement, produces a more strictly bounded loss in match between waveforms, with the same minimal match between waveforms requiring about twice as many templates with our proposed algorithm. Though we note that the average match is higher, which would lead to a higher detection efficiency. Our primary motivation is not to strictly minimize the number of templates with this algorithm, but rather to produce a bank with useful geometric properties in the physical parameter space coordinates. Such properties are useful for population modeling and parameter estimation

Template bank for compact binary mergers in the fourth observing run of Advanced LIGO, Advanced Virgo, and KAGRA

Template banks containing gravitational wave (GW) waveforms are essential for matched-filtering GW search pipelines. We describe the generation method, the design, and validation of the template bank used by the GstLAL-based inspiral pipeline to analyze data from the fourth observing run of LIGO scientific, Virgo, and KAGRA collaboration. This paper presents a template bank containing $1.8 \times 10^6$ templates that include merging neutron star - neutron star, neutron star - black hole, and black hole - black hole systems up to a total mass of $400$ $M_\odot$. Motivated by observations, component masses below $3$ $M_\odot$ have dimensionless spins ranging between $\pm 0.05$, while component masses between $3$ to $200$ $M_\odot$ have dimensionless spins ranging between $\pm 0.99$, where we assume spin-aligned systems. The low-frequency cutoff is $15$ Hz. The templates are placed in the parameter space according to the metric via a binary tree approach which took $\mathcal{O}\left(10\right)$ minutes when jobs were parallelized. The template bank generated with this method has a $98\%$ match or higher for $90\%$ of the injections, thus being as effective as the template placement method used for the previous observation runs. The volumes of the templates are computed prior to template placement and the nearby templates have similar volumes in the coordinate space, henceforth, enabling a more efficient and less biased implementation of population models. SVD sorting of the O4 template bank has been renewed to use post-Newtonian phase terms, which improved the computational efficiency of SVD by nearly $4 \sim 5$ times as compared to conventional SVD sorting schemes. Template banks and searches focusing on the sub-solar mass parameter space and intermediate-mass black hole parameter space are conducted separately

When to Point Your Telescopes: Gravitational Wave Trigger Classification for Real-Time Multi-Messenger Followup Observations

We develop a robust and self-consistent framework to extract and classify gravitational wave candidates from noisy data, for the purpose of assisting in real-time multi-messenger follow-ups during LIGO-Virgo-KAGRA's fourth observing run~(O4). Our formalism implements several improvements to the low latency calculation of the probability of astrophysical origin~(\PASTRO{}), so as to correctly account for various factors such as the sensitivity change between observing runs, and the deviation of the recovered template waveform from the true gravitational wave signal that can strongly bias said calculation. We demonstrate the high accuracy with which our new formalism recovers and classifies gravitational wave triggers, by analyzing replay data from previous observing runs injected with simulated sources of different categories. We show that these improvements enable the correct identification of the majority of simulated sources, many of which would have otherwise been misclassified. We carry out the aforementioned analysis by implementing our formalism through the \GSTLAL{} search pipeline even though it can be used in conjunction with potentially any matched filtering pipeline. Armed with robust and self-consistent \PASTRO{} values, the \GSTLAL{} pipeline can be expected to provide accurate source classification information for assisting in multi-messenger follow-up observations to gravitational wave alerts sent out during O4.Comment: v2 upload was accidental. revert back to v

Performance of the low-latency GstLAL inspiral search towards LIGO, Virgo, and KAGRA's fourth observing run

GstLAL is a stream-based matched-filtering search pipeline aiming at the prompt discovery of gravitational waves from compact binary coalescences such as the mergers of black holes and neutron stars. Over the past three observation runs by the LIGO, Virgo, and KAGRA (LVK) collaboration, the GstLAL search pipeline has participated in several tens of gravitational wave discoveries. The fourth observing run (O4) is set to begin in May 2023 and is expected to see the discovery of many new and interesting gravitational wave signals which will inform our understanding of astrophysics and cosmology. We describe the current configuration of the GstLAL low-latency search and show its readiness for the upcoming observation run by presenting its performance on a mock data challenge. The mock data challenge includes 40 days of LIGO Hanford, LIGO Livingston, and Virgo strain data along with an injection campaign in order to fully characterize the performance of the search. We find an improved performance in terms of detection rate and significance estimation as compared to that observed in the O3 online analysis. The improvements are attributed to several incremental advances in the likelihood ratio ranking statistic computation and the method of background estimation.Comment: 19 pages, 21 figure

Fundamental Symmetries, Neutrons, and Neutrinos (FSNN): Whitepaper for the 2023 NSAC Long Range Plan

This whitepaper presents the research priorities decided on by attendees of the 2022 Town Meeting for Fundamental Symmetries, Neutrons and Neutrinos, which took place December 13-15, 2022 in Chapel Hill, NC, as part of the Nuclear Science Advisory Committee (NSAC) 2023 Long Range Planning process. A total of 275 scientists registered for the meeting. The whitepaper makes a number of explicit recommendations and justifies them in detail

Targeting Huntington’s disease through histone deacetylases

Huntington’s disease (HD) is a debilitating neurodegenerative condition with significant burdens on both patient and healthcare costs. Despite extensive research, treatment options for patients with this condition remain limited. Aberrant post-translational modification (PTM) of proteins is emerging as an important element in the pathogenesis of HD. These PTMs include acetylation, phosphorylation, methylation, sumoylation and ubiquitination. Several families of proteins are involved with the regulation of these PTMs. In this review, I discuss the current evidence linking aberrant PTMs and/or aberrant regulation of the cellular machinery regulating these PTMs to HD pathogenesis. Finally, I discuss the evidence suggesting that pharmacologically targeting one of these protein families the histone deacetylases may be of potential therapeutic benefit in the treatment of HD

Design and Simulated Performance of Calorimetry Systems for the ECCE Detector at the Electron Ion Collider

We describe the design and performance the calorimeter systems used in the ECCE detector design to achieve the overall performance specifications cost-effectively with careful consideration of appropriate technical and schedule risks. The calorimeter systems consist of three electromagnetic calorimeters, covering the combined pseudorapdity range from -3.7 to 3.8 and two hadronic calorimeters. Key calorimeter performances which include energy and position resolutions, reconstruction efficiency, and particle identification will be presented.Comment: 19 pages, 22 figures, 5 table