bluuebunny/crossref_metadata_2025_split huggingface dataset:
DSA-10: a prototype array for localizing fast radio bursts
Authors: Kocz J , Ravi V , Catha M , D’Addario L , Hallinan G , Hobbs R , Kulkarni S , Shi J , Vedantham H , Weinreb S , Woody D 
Published: August 2019

ABSTRACT
The Deep Synoptic Array 10-dish prototype (DSA-10) is an instrument designed to detect and localize fast radio bursts with arcsecond accuracy in real time. Deployed at Owens Valley Radio Observatory, it consists of ten 4.5-m diameter dishes, equipped with a 250-MHz bandwidth dual polarization receiver, centred at 1.4 GHz. The 20 input signals are digitized and field programmable gate arrays are used to transform the data to the frequency domain and transmit it over ethernet. A series of computer servers buffer both raw data samples and perform a real time search for fast radio bursts on the incoherent sum of all inputs. If a pulse is detected, the raw data surrounding the pulse are written to disc for coherent processing and imaging. The prototype system was operational from 2017 June to 2018 February conducting a drift scan search. Giant pulses from the Crab Pulsar were used to test the detection and imaging pipelines. The 10-dish prototype system was brought online again in 2019 March, and will gradually be replaced with the new DSA-110, a 110-dish system, over the next 2 yr to improve sensitivity and localization accuracy.
Dark-ages reionization and galaxy formation simulation – XVI. The thermal memory of reionization
Authors: Davies James E , Mutch Simon J , Qin Yuxiang , Mesinger Andrei , Poole Gregory B , Wyithe J Stuart B 
Published: August 2019

Abstract
Intergalactic medium temperature is a powerful probe of the epoch of reionization, as information is retained long after reionization itself. However, mean temperatures are highly degenerate with the timing of reionization, with the amount heat injected during the epoch, and with the subsequent cooling rates. We post-process a suite of semi-analytic galaxy formation models to characterize how different thermal statistics of the intergalactic medium can be used to constrain reionization. Temperature is highly correlated with redshift of reionization for a period of time after the gas is heated. However as the gas cools, thermal memory of reionization is lost, and a power-law temperature–density relation is formed, T = T0(1 + δ)1 − γ with γ ≈ 1.5. Constraining our model against observations of electron optical depth and temperature at mean density, we find that reionization likely finished at $z_{\rm {reion}} = 6.8 ^{+ 0.5} _{-0.8}$ with a soft spectral slope of $\alpha = 2.8 ^{+ 1.2} _{-1.0}$. By restricting spectral slope to the range [0.5, 2.5] motivated by population II synthesis models, reionization timing is further constrained to $z_{\rm {reion}} = 6.9 ^{+ 0.4} _{-0.5}$. We find that, in the future, the degeneracies between reionization timing and background spectrum can be broken using the scatter in temperatures and integrated thermal history.
Modelling the AGN broad line region using single-epoch spectra – I. The test case of Arp 151
Authors: Raimundo S I , Pancoast A , Vestergaard M , Goad M R , Barth A J 
Published: August 2019

ABSTRACT
We show that individual (single-epoch) spectra of active galactic nuclei (AGNs) can constrain some of the geometry and dynamics of the AGN broad line region. Studies of the cosmic influence of supermassive black holes are limited by the current large uncertainties in the determination of black hole masses. One dominant limitation is the unknown geometry, dynamics, and line-of-sight inclination of the broad line region, used to probe the central black hole mass. Recent progress has been made to constrain the spatial and kinematic structure of the broad line region using dynamical modelling of AGN monitoring data and an underlying physical model for the broad line region. In this work we test the ability of a modified version of this dynamical modelling code to constrain the broad line region structure using single-epoch spectra. We test our modelling code on single-epoch spectra of nearby Arp 151 by comparing our results with those obtained with monitoring data of this same object. We find that a significant fraction of the broad line region parameters can indeed be adequately constrained, with uncertainties that are comparable to, or at most a factor of approximately a few higher than those obtained from modelling of monitoring data. Considering the wealth of available single-epoch spectroscopic observations, this method is promising for establishing the overall AGN population trends in the geometry and dynamics of the broad line region. This method can be applied to spectra of AGNs at low and high redshift making it valuable for studies of cosmological black hole and AGN evolution.
A year in the life of GW170817: the rise and fall of a structured jet from a binary neutron star merger
Authors: Troja E , van Eerten H , Ryan G , Ricci R , Burgess J M , Wieringa M H , Piro L , Cenko S B , Sakamoto T 
Published: August 2019

Abstract
We present the results of our year-long afterglow monitoring of GW170817, the first binary neutron star (NS) merger detected by advanced LIGO and advanced Virgo. New observations with the Australian Telescope Compact Array (ATCA) and the Chandra X-ray Telescope were used to constrain its late-time behavior. The broadband emission, from radio to X-rays, is well-described by a simple power-law spectrum with index β ∼0.585 at all epochs. After an initial shallow rise ∝ t0.9, the afterglow displayed a smooth turn-over, reaching a peak X-ray luminosity of LX≈5 ×1039 erg s−1 at 160 d, and has now entered a phase of rapid decline, approximately ∝ t−2. The latest temporal trend challenges most models of choked jet/cocoon systems, and is instead consistent with the emergence of a relativistic structured jet seen at an angle of ≈22○ from its axis. Within such model, the properties of the explosion (such as its blastwave energy EK ≈ 2 × 1050 erg, jet width θc ≈4○, and ambient density n ≈3 × 10−3 cm−3) fit well within the range of properties of cosmological short GRBs.
Machine learning and Kolmogorov analysis to reveal gravitational lenses
Authors: Mirzoyan S S , Khachatryan H , Yegorian G , Gurzadyan V G 
Published: August 2019

ABSTRACT
We present an automated approach to detect and extract information from the astronomical data sets on the shapes of such objects as galaxies, star clusters and, especially, elongated ones such as the gravitational lenses. First, the Kolmogorov stochasticity parameter is used to retrieve the sub-regions that are worth further attention. Then we turn to image processing and machine learning Principal Component Analysis algorithm to retrieve the sought objects and reveal the information on their morphologies. We show the capability of our automated method to identify distinct objects and to classify them based on the input parameters. A catalogue of possible lensing objects is retrieved as an output of the software, then their inspection is performed for the candidates that survive the filters applied.
Evidence for C ii diffuse line emission at redshift z ∼ 2.6
Authors: Yang Shengqi , Pullen Anthony R , Switzer Eric R 
Published: August 2019

ABSTRACT
C ii is one of the brightest emission lines from star-forming galaxies and is an excellent tracer for star formation. Recent work measured the C ii emission line amplitude for redshifts 2 &lt; z &lt; 3.2 by cross-correlating Planck High Frequency Instrument emission maps with tracers of overdensity from the Baryon Oscillation Spectroscopic Sky Survey, finding ${I}_{{\text C}\,\rm {\small II}}=6.6^{+5.0}_{-4.8}\times {10}^{4}$ Jy sr−1 at $95\,{\text{per cent}}$ confidence level. In this paper, we present a refinement of this earlier work by improving the mask weighting in each of the Planck bands and the precision in the covariance matrix. We report a detection of excess emission in the 545 GHz Planck band separate from the cosmic infrared background (CIB) present in the 353–857 GHz Planck bands. This excess is consistent with redshifted C ii emission, in which case we report $b_{{\text C} \,\rm {\small II}}I_{{\text C} \,\rm {\small II}} =2.0^{+1.2}_{-1.1}\times 10^5$ Jy sr−1 at $95\ {\text {per cent}}$ confidence level, which strongly favours many collisional excitation models of C ii emission. Our detection shows strong evidence for a model with a non-zero C ii parameter, though line intensity mapping observations at high spectral resolution will be needed to confirm this result.
The Evolution of Reverse Gyrase Suggests a Nonhyperthermophilic Last Universal Common Ancestor
Authors: Catchpole Ryan J , Forterre Patrick 
Published: August 2019

AbstractReverse gyrase (RG) is the only protein found ubiquitously in hyperthermophilic organisms, but absent from mesophiles. As such, its simple presence or absence allows us to deduce information about the optimal growth temperature of long-extinct organisms, even as far as the last universal common ancestor of extant life (LUCA). The growth environment and gene content of the LUCA has long been a source of debate in which RG often features. In an attempt to settle this debate, we carried out an exhaustive search for RG proteins, generating the largest RG data set to date. Comprising 376 sequences, our data set allows for phylogenetic reconstructions of RG with unprecedented size and detail. These RG phylogenies are strikingly different from those of universal proteins inferred to be present in the LUCA, even when using the same set of species. Unlike such proteins, RG does not form monophyletic archaeal and bacterial clades, suggesting RG emergence after the formation of these domains, and/or significant horizontal gene transfer. Additionally, the branch lengths separating archaeal and bacterial groups are very short, inconsistent with the tempo of evolution from the time of the LUCA. Despite this, phylogenies limited to archaeal RG resolve most archaeal phyla, suggesting predominantly vertical evolution since the time of the last archaeal ancestor. In contrast, bacterial RG indicates emergence after the last bacterial ancestor followed by significant horizontal transfer. Taken together, these results suggest a nonhyperthermophilic LUCA and bacterial ancestor, with hyperthermophily emerging early in the evolution of the archaeal and bacterial domains.
A deep learning genome-mining strategy for biosynthetic gene cluster prediction
Authors: Hannigan Geoffrey D , Prihoda David , Palicka Andrej , Soukup Jindrich , Klempir Ondrej , Rampula Lena , Durcak Jindrich , Wurst Michael , Kotowski Jakub , Chang Dan , Wang Rurun , Piizzi Grazia , Temesi Gergely , Hazuda Daria J , Woelk Christopher H , Bitton Danny A 
Published: August 2019

AbstractNatural products represent a rich reservoir of small molecule drug candidates utilized as antimicrobial drugs, anticancer therapies, and immunomodulatory agents. These molecules are microbial secondary metabolites synthesized by co-localized genes termed Biosynthetic Gene Clusters (BGCs). The increase in full microbial genomes and similar resources has led to development of BGC prediction algorithms, although their precision and ability to identify novel BGC classes could be improved. Here we present a deep learning strategy (DeepBGC) that offers reduced false positive rates in BGC identification and an improved ability to extrapolate and identify novel BGC classes compared to existing machine-learning tools. We supplemented this with random forest classifiers that accurately predicted BGC product classes and potential chemical activity. Application of DeepBGC to bacterial genomes uncovered previously undetectable putative BGCs that may code for natural products with novel biologic activities. The improved accuracy and classification ability of DeepBGC represents a major addition to in-silico BGC identification.
Global prediction of chromatin accessibility using small-cell-number and single-cell RNA-seq
Authors: Zhou Weiqiang , Ji Zhicheng , Fang Weixiang , Ji Hongkai 
Published: August 2019

Abstract
Conventional high-throughput genomic technologies for mapping regulatory element activities in bulk samples such as ChIP-seq, DNase-seq and FAIRE-seq cannot analyze samples with small numbers of cells. The recently developed low-input and single-cell regulome mapping technologies such as ATAC-seq and single-cell ATAC-seq (scATAC-seq) allow analyses of small-cell-number and single-cell samples, but their signals remain highly discrete or noisy. Compared to these regulome mapping technologies, transcriptome profiling by RNA-seq is more widely used. Transcriptome data in single-cell and small-cell-number samples are more continuous and often less noisy. Here, we show that one can globally predict chromatin accessibility and infer regulatory element activities using RNA-seq. Genome-wide chromatin accessibility predicted by RNA-seq from 30 cells can offer better accuracy than ATAC-seq from 500 cells. Predictions based on single-cell RNA-seq (scRNA-seq) can more accurately reconstruct bulk chromatin accessibility than using scATAC-seq. Integrating ATAC-seq with predictions from RNA-seq increases the power and value of both methods. Thus, transcriptome-based prediction provides a new tool for decoding gene regulatory circuitry in samples with limited cell numbers.
TRLS-06. PHASE 1 EXPANSION STUDY OF IRINOTECAN LIPOSOME INJECTION (nal-IRI) IN PATIENTS WITH METASTATIC BREAST CANCER (mBC): FINDINGS FROM THE COHORT WITH ACTIVE BRAIN METASTASIS (BM)
Authors: Anders Carey , Munster Pamela , Northfelt Donald , Han Hyo Sook , Ma Cynthia , Maxwell Fiona , Wang Tiffany , Belanger Bruce , Zhang Bin , Moore Yan , Sachdev Jasgit C 
Published: August 2019

Abstract
BACKGROUND: nal-IRI is a liposomal formulation of irinotecan (topoisomerase-1 inhibitor). Preclinical data show that nal-IRI accumulates in BMs and prolongs survival in animal models of BM. Findings from a phase 1 expansion study (NCT01770353), evaluating patients with mBC and active BM, are reported. METHODS: This phase 1 expansion study enrolled patients with mBC who received multiple prior lines of cytotoxic therapy in the metastatic setting, including one cohort with mBC and active BM, defined as radiographic evidence of new or progressive central nervous system (CNS) metastases after radiation therapy with ≥1 lesion of ≥1 cm in the longest dimension on gadolinium-enhanced magnetic resonance imaging. Patients received nal-IRI 50 mg/m2 (free-base equivalent; FBE) every two weeks (q2w) as an intravenous infusion over 90 minutes, escalating to 70 mg/m2 FBE q2w, if tolerated. RECIST v1.1 and modified RECIST criteria were used to assses non-CNS and CNS disease, respectively. RESULTS: In total, 30 patients were enrolled (10 with active BM). Median age was 53 years (range 29–70 years) and median number of prior cytotoxic anti-cancer regimens was 3 (range 0–6); 29 patients received ≥1 dose of nal-IRI 50 mg/m2 FBE. Overall, nal-IRI monotherapy appeared to be well tolerated, and achieved ≥30% objective response rates for both CNS and non-CNS disease. Among the 10 patients with active BM, 6 achieved CNS disease control (3 partial responses [PRs] and 3 stable disease [SD]), including one patient with durable CNS SD and non-CNS PR for 2 years. Among 7 patients with serial evaluation of CNS metastases posttreatment, 6 patients achieved a reduction in target CNS lesions compared with baseline. CONCLUSION: Treatment with nal-IRI resulted in CNS disease control among 6 of 10 heavily pretreated patients with mBC and active BM. Further exploration of nal-IRI in patients with mBC and active BM is warranted.
THER-15. DEVELOPING TUMOR-HOMING CYTOTOXIC HUMAN INDUCED NEURAL STEM CELL THERAPY FOR BRAIN METASTASES
Authors: Mercer-Smith Alison , Jiang Wulin , Bago Juli , Khagi Simon , Anders Carey , Hingtgen Shawn 
Published: August 2019

Abstract
INTRODUCTION: Non-small cell lung cancer (NSCLC) and breast cancer are the most common cancers that metastasize to the brain. New therapies are needed to seek out and eradicate metastases. Genetically engineered neural stem cells (NSCs) have shown unique tumor-homing capacity, allowing them to deliver cytotoxic proteins directly to tumors. An ideal NSC drug carrier would be readily available and autologous. We have transdifferentiated human fibroblasts into induced NSCs (hiNSCs) that home to tumors and engineered the hiNSCs to release the cytotoxic protein TRAIL. Here we used intracerebroventricular (ICV) injections to deliver hiNSCs to metastatic foci. METHODS: We performed an in vitro efficacy co-culture assay, used in vivo studies to determine the migration, persistence, and efficacy of therapeutic hiNSCs against H460 NSCLC and triple-negative breast cancer MB231-Br tumors in the brain. Following the establishment of tumors in the brains of nude mice, hiNSCs were injected directly into the tumor or the ventricle contralateral to the site of tumor. The migration and persistence of hiNSCs was investigated by following the bioluminescence of the hiNSCs. The therapeutic efficacy of the hiNSCs was determined by following the bioluminescece of the tumor. RESULTS/CONCLUSION: Co-culture results demonstrated that hiNSC therapy reduced the viability of H460 and MB231-Br up to 75% and 99.8% respectively compared to non-treated controls. ICV-administered hiNSC serial imaging show that cells persisted for more than one week. Fluorescent analysis of tissue sections showed that hiNSCs co-localized with lateral and a contralateral tumors within 7 days. Using H460 and MB231-Br models, kinetic tracking of intracranial tumor volumes showed intratumoral or ICV-injected therapeutic hiNSCs reduced the growth rate of brain tumors by 31-fold and 3-fold, respectively. This work demonstrates for the first time that we can effectively deliver personalized cytotoxic tumor-homing cells through the ventricles to target brain metastases.
MLTI-16. SYSTEMIC THERAPY FOLLOWING CRANIOTOMY IN PATIENTS WITH A SOLITARY BREAST CANCER BRAIN METASTASIS
Authors: Hulsbergen Alexander , Cho Logan , Mammi Marco , Lamba Nayan , Smith Timothy , Broekman Marike , Lin Nancy 
Published: August 2019

Abstract
INTRODUCTION: Between 15–50% of patients with metastatic breast cancer will develop brain metastases, with the frequency more common in patients with HER2-positive or triple-negative subtypes. Surgical resection is often indicated for diagnostic and/or therapeutic intent for patients presenting with a solitary lesion and/or symptomatic lesion(s) with mass effect. Practice patterns and patient outcomes with respect to the use of postoperative systemic therapy (ST) after resection of a solitary breast cancer brain metastasis (BCBM) have not been previously well-described, particularly in the modern era. METHODS: A multi-institutional retrospective review of 44 patients was performed to assess the impact of types of ST on site of recurrence, progression-free survival (PFS) and overall survival (OS) after resection of solitary BCBM. RESULTS: Stratified estimated survival was 15, 24 and 23 months for patients with triple negative, estrogen receptor positive (ER+), and human epidermal growth factor receptor 2 positive (HER2+) BCBMs. Patients receiving postoperative ST had a longer median PFS (8 versus 4 months) and OS (32 versus 15 months). Nine patients (20%) had extracranial progression, 23 (52%) had intracranial progression, three (8%) had both, and nine (20%) did not experience progression at last follow-up. Multivariate analysis showed that postoperative hormonal therapy was associated with longer OS in estrogen receptor (ER) positive patients (HR = 0.26; CI = 0.08 – 0.89; p = 0.03), but not with longer PFS. Postoperative human epidermal growth factor receptor 2 (HER2)-targeted therapy was not associated with longer PFS or OS in HER2+ patients. CONCLUSIONS: Disease progression occurred intracranially more often than extracranially following resection of a solitary BCBM. In ER+ patients, postoperative hormonal therapy was associated with longer OS. Postoperative HER2-targeted therapy did not show survival benefits in HER2+ patients. These results should be validated in larger cohorts.
OTHR-11. TUMOR RELATED IMPAIRMENTS OF NEUROCOGNITIVE FUNCTIONS IN PATIENTS WITH BRAIN METASTASES
Authors: Zhen Junjie , Li Shaoqun , Wen Lei , Peng Zhangrui , Lai Mingyao , Zhou Cheng , Cai Linbo 
Published: August 2019

Abstract
OBJECTIVE: To study whether the neurocognitive functions were affected by brain metastases in patients, and what are the potential risk factors. METHODS: A total of 172 patients with brain metastases were retrospectively analyzed. Prior to radiotherapy of brain metastases, the neurocognitive function was evaluated by a wide range of tests including MOCA, VFT, HVLT-R, TMT-A, TMT-B and TOL. Kappa test was used to analyze the consistency of physical examination and neurocognitive assessment results. The related factors were analyzed with univariate and multivariate analysis. RESULTS: 53 out of 172 patients (30.8%) were identified with cognitive impairments by physical examination. The assessment with neurocognitive scales revealed that there were 148 cases of cognitive impairment (86.0%) and 24 cases of normal cognition (14.0%). Kappa=0.025, indicating that the difference between neurocognitive assessment results and physical examination was significant. The univariate analysis on the factors related to neurocognitive impairment revealed that the risk factors that may affect the neurocognitive functions included age, KPS, m-GPA score, RPA classification, whether the original tumor was under control, with or without brain metastases. After adjusting for education, the multivariate analysis showed that age≥45 years old, KPS≤70, RPA classification &gt;2 and m-GPA score&lt; 3 were independent risk factors for neurocognitive impairment. CONCLUSION: Patients with brain metastases were found to have various degrees of neurocognitive impairment prior to radiotherapy. The neurocognitive functions of patients can be more precisely evaluated by a comprehensive scale assessment. Age, KPS, RPA classification and m-GPA score are the main factors associated with neurocognitive impairment.
OTHR-16. MOLECULAR PROFILING USING THE 92-GENE ASSAY FOR TUMOR CLASSIFICATION OF BRAIN METASTASES
Authors: Brenner Andrew , Collazo Raul , Schnabel Catherine , Greco Anthony 
Published: August 2019

Abstract
BACKGROUND: Nearly 200,000 patients are diagnosed with brain metastases in the US annually. Advances in targeted therapies make definitive diagnosis of the primary tumor type important but can be challenging in many patients. The 92-gene assay is a validated gene expression classifier of 50 tumor types for patients with uncertain tissue of origin diagnoses. Results from a clinical series of brain biopsies and potential impact on treatment were evaluated. METHODS: An IRB approved, de-identified database of clinical and molecular information from biopsies (N = 24,486) submitted for testing with the 92-gene assay (CancerTYPE ID, Biotheranostics, Inc.) as part of routine care were reviewed. Descriptive analysis included patient demographics and molecular diagnoses. RESULTS: Analysis included 464 brain biopsies. A molecular diagnosis was provided in 433 (93.3%) tested (&lt; 5% assay failure rate) with 24 different tumor types. Six primary tumor types made up the majority (67.4%) with almost one-third of the molecular predictions being Lung (31.2%), followed by Neuroendocrine (NET) (9.9%), Sarcoma (7.9%), Skin (6.4%), Gastroesophageal (6.2%), and Urinary bladder (5.8%). All of these 6 tumor types, for which activity in the CNS has been documented, have immune checkpoint inhibitors or other targeted therapies approved in selected cases by the US Federal Drug Administration (FDA). CONCLUSIONS: Molecular classification of brain metastases can identify distinct tumor types for which there are FDA approved targeted medications. Improving diagnostic precision with the 92-gene assay helps identify a subset of therapy-responsive metastatic brain tumors, thus improving therapy and possibly providing better outcomes and survival.