bluuebunny/crossref_metadata_2025_split huggingface dataset:
Local Hole revisited: evidence for bulk motions and self-consistent outflow
Authors: Shanks T , Hogarth L M , Metcalfe N , Whitbourn J 
Published: October 2019

ABSTRACT
We revisit our mapping of the ‘Local Hole’, a large underdensity in the local galaxy redshift distribution that extends out to redshift z ≈ 0.05 and a potential source of outflows that may perturb the global expansion rate and thus help mitigate the present ‘H0 tension’. First, we compare local peculiar velocities measured via the galaxy average redshift–magnitude Hubble diagram, $\overline{z}(m)$, with a simple dynamical outflow model based on the average underdensity in the Local Hole. We find that this outflow model is in good agreement with our peculiar velocity measurements from $\overline{z}(m)$ and not significantly inconsistent with Type Ia supernova peculiar velocity measurements from at least the largest previous survey. This outflow could cause an ≈2–3 per cent increase in the local value of Hubble’s constant. Second, considering anisotropic motions, we find that the addition of the outflow model may improve the $\overline{z}(m)$ fit of a bulk flow where galaxies are otherwise at rest in the Local Group frame. We conclude that the Local Hole plus neighbouring overdensities such as the Shapley Supercluster may cause outflow and bulk motions out to ≈150 h−1 Mpc that are cosmologically significant and that need to be taken into account in estimating Hubble’s constant.
Periodic orbits of the retrograde coorbital problem
Authors: Morais M H M , Namouni F 
Published: October 2019

ABSTRACT
Asteroid (514107) Ka‘epaoka‘awela is the first example of an object in the 1/1 mean motion resonance with Jupiter with retrograde motion around the Sun. Its orbit was shown to be stable over the age of the Solar system, which implies that it must have been captured from another star when the Sun was still in its birth cluster. Ka‘epaoka‘awela orbit is also located at the peak of the capture probability in the coorbital resonance. Identifying the periodic orbits that Ka‘epaoka‘awela and similar asteroids followed during their evolution is an important step towards precisely understanding their capture mechanism. Here, we find the families of periodic orbits in the two-dimensional retrograde coorbital problem and analyse their stability and bifurcations into three-dimensional periodic orbits. Our results explain the radical differences observed in 2D and 3D coorbital capture simulations. In particular, we find that analytical and numerical results obtained for planar motion are not always valid at infinitesimal deviations from the plane.
Architectures of exoplanetary systems – I. A clustered forward model for exoplanetary systems around Kepler’s FGK stars
Authors: He Matthias Y , Ford Eric B , Ragozzine Darin 
Published: October 2019

ABSTRACTObservations of exoplanetary systems provide clues about the intrinsic distribution of planetary systems, their architectures, and how they formed. We develop a forward modelling framework for generating populations of planetary systems and ‘observed’ catalogues by simulating the Kepler detection pipeline (SysSim). We compare our simulated catalogues to the Kepler DR25 catalogue of planet candidates, updated to include revised stellar radii from Gaia DR2. We constrain our models based on the observed 1D marginal distributions of orbital periods, period ratios, transit depths, transit depth ratios, transit durations, transit duration ratios, and transit multiplicities. Models assuming planets with independent periods and sizes do not adequately account for the properties of the multiplanet systems. Instead, a clustered point process model for exoplanet periods and sizes provides a significantly better description of the Kepler population, particularly the observed multiplicity and period ratio distributions. We find that $0.56^{+0.18}_{-0.15}$ of FGK stars have at least one planet larger than 0.5R⊕ between 3 and 300 d. Most of these planetary systems ($\sim 98{{\ \rm per\ cent}}$) consist of one or two clusters with a median of three planets per cluster. We find that the Kepler dichotomy is evidence for a population of highly inclined planetary systems and is unlikely to be solely due to a population of intrinsically single planet systems. We provide a large ensemble of simulated physical and observed catalogues of planetary systems from our models, as well as publicly available code for generating similar catalogues given user-defined parameters.
Secondary CMB temperature anisotropies from magnetic reheating
Authors: Saga Shohei , Ota Atsuhisa , Tashiro Hiroyuki , Yokoyama Shuichiro 
Published: October 2019

ABSTRACT
Spatially fluctuating primordial magnetic fields (PMFs) inhomogeneously reheat the Universe when they dissipate deep inside the horizon before recombination. Such an energy injection turns into an additional photon temperature perturbation. We investigate secondary cosmic microwave background (CMB) temperature anisotropies originated from this mechanism, which we call inhomogeneous magnetic reheating. We find that it can bring us information about non-linear coupling between PMFs and primordial curvature perturbations parametrized by bNL, which should be important for probing the generation mechanism of PMFs. In fact, by using current CMB observations, we obtain an upper bound on the non-linear parameter as log (bNL(Bλ/nG)2) ≲ − 36.5nB − 94.0 with Bλ and nB being a magnetic field amplitude smoothed over λ = 1 Mpc scale and a spectral index of the PMF power spectrum, respectively. Our constraints are far stronger than a previous forecast based on the future CMB spectral distortion anisotropy measurements because inhomogeneous magnetic reheating covers a much wider range of scales, i.e. 1 Mpc−1 ≲ k ≲ 1015 Mpc−1.
Constraining ν-process production of fluorine through cosmic ray nucleosynthesis
Authors: Olive Keith A , Vangioni Elisabeth 
Published: October 2019

ABSTRACT
Fluorine is massive enough that it is not considered to be a light (Z ≤ 5) element, yet compared to its near neighbours, C, N, O, and Ne, it is far underproduced in the course of stellar evolution, making its origin more complex. In fact, the abundance of fluorine is the lowest among all elements between Z = 5 and 21 and is roughly 3–4 orders of magnitude below that of C, N, O, and Ne. There are several plausible sources for F beyond standard stellar evolution. These include the production in the asymptotic giant branch phase (AGB) in intermediate-mass stars, production in Wolf–Rayet stars, and the production through neutrino spallation in supernovae. The latter, known as the ν-process, is an important source for 11B, and may contribute to the abundance of 7Li as well. We combine a simple model of Galactic chemical evolution with a standard Galactic cosmic ray nucleosynthesis model to treat self-consistently the evolution of the Li, Be, and B isotopes. We include massive star production of F, as well as contributions from AGB stars, and the ν-process. Given the uncertainties in neutrino energies in supernovae, we normalize the ν-process using the observed 11B/10B ratio as a constraint. As a consequence, we are able to determine the relative importance of each contribution to the F abundance. We find that although the ν-process dominates at early times (low metallicity), the present-day F abundance is found to originate primarily from AGB stars.
LnCeVar: a comprehensive database of genomic variations that disturb ceRNA network regulation
Authors: Wang Peng , Li Xin , Gao Yue , Guo Qiuyan , Ning Shangwei , Zhang Yunpeng , Shang Shipeng , Wang Junwei , Wang Yanxia , Zhi Hui , Fang Ying , Shen Weitao , Zhang Guangmei , Chen Steven Xi , Li Xia 
Published: October 2019

Abstract
LnCeVar (http://www.bio-bigdata.net/LnCeVar/) is a comprehensive database that aims to provide genomic variations that disturb lncRNA-associated competing endogenous RNA (ceRNA) network regulation curated from the published literature and high-throughput data sets. LnCeVar curated 119 501 variation–ceRNA events from thousands of samples and cell lines, including: (i) more than 2000 experimentally supported circulating, drug-resistant and prognosis-related lncRNA biomarkers; (ii) 11 418 somatic mutation–ceRNA events from TCGA and COSMIC; (iii) 112 674 CNV–ceRNA events from TCGA; (iv) 67 066 SNP–ceRNA events from the 1000 Genomes Project. LnCeVar provides a user-friendly searching and browsing interface. In addition, as an important supplement of the database, several flexible tools have been developed to aid retrieval and analysis of the data. The LnCeVar–BLAST interface is a convenient way for users to search ceRNAs by interesting sequences. LnCeVar–Function is a tool for performing functional enrichment analysis. LnCeVar–Hallmark identifies dysregulated cancer hallmarks of variation–ceRNA events. LnCeVar–Survival performs COX regression analyses and produces survival curves for variation–ceRNA events. LnCeVar–Network identifies and creates a visualization of dysregulated variation–ceRNA networks. Collectively, LnCeVar will serve as an important resource for investigating the functions and mechanisms of personalized genomic variations that disturb ceRNA network regulation in human diseases.
The PATRIC Bioinformatics Resource Center: expanding data and analysis capabilities
Authors: Davis James J , Wattam Alice R , Aziz Ramy K , Brettin Thomas , Butler Ralph , Butler Rory M , Chlenski Philippe , Conrad Neal , Dickerman Allan , Dietrich Emily M , Gabbard Joseph L , Gerdes Svetlana , Guard Andrew , Kenyon Ronald W , Machi Dustin , Mao Chunhong , Murphy-Olson Dan , Nguyen Marcus , Nordberg Eric K , Olsen Gary J , Olson Robert D , Overbeek Jamie C , Overbeek Ross , Parrello Bruce , Pusch Gordon D , Shukla Maulik , Thomas Chris , VanOeffelen Margo , Vonstein Veronika , Warren Andrew S , Xia Fangfang , Xie Dawen , Yoo Hyunseung , Stevens Rick 
Published: October 2019

Abstract
The PathoSystems Resource Integration Center (PATRIC) is the bacterial Bioinformatics Resource Center funded by the National Institute of Allergy and Infectious Diseases (https://www.patricbrc.org). PATRIC supports bioinformatic analyses of all bacteria with a special emphasis on pathogens, offering a rich comparative analysis environment that provides users with access to over 250 000 uniformly annotated and publicly available genomes with curated metadata. PATRIC offers web-based visualization and comparative analysis tools, a private workspace in which users can analyze their own data in the context of the public collections, services that streamline complex bioinformatic workflows and command-line tools for bulk data analysis. Over the past several years, as genomic and other omics-related experiments have become more cost-effective and widespread, we have observed considerable growth in the usage of and demand for easy-to-use, publicly available bioinformatic tools and services. Here we report the recent updates to the PATRIC resource, including new web-based comparative analysis tools, eight new services and the release of a command-line interface to access, query and analyze data.
ClinVar: improvements to accessing data
Authors: Landrum Melissa J , Chitipiralla Shanmuga , Brown Garth R , Chen Chao , Gu Baoshan , Hart Jennifer , Hoffman Douglas , Jang Wonhee , Kaur Kuljeet , Liu Chunlei , Lyoshin Vitaly , Maddipatla Zenith , Maiti Rama , Mitchell Joseph , O’Leary Nuala , Riley George R , Shi Wenyao , Zhou George , Schneider Valerie , Maglott Donna , Holmes J Bradley , Kattman Brandi L 
Published: October 2019

AbstractClinVar is a freely available, public archive of human genetic variants and interpretations of their relationships to diseases and other conditions, maintained at the National Institutes of Health (NIH). Submitted interpretations of variants are aggregated and made available on the ClinVar website (https://www.ncbi.nlm.nih.gov/clinvar/), and as downloadable files via FTP and through programmatic tools such as NCBI’s E-utilities. The default view on the ClinVar website, the Variation page, was recently redesigned. The new layout includes several new sections that make it easier to find submitted data as well as summary data such as all diseases and citations reported for the variant. The new design also better represents more complex data such as haplotypes and genotypes, as well as variants that are in ClinVar as part of a haplotype or genotype but have no interpretation for the single variant. ClinVar's variant-centric XML had its production release in April 2019. The ClinVar website and E-utilities both have been updated to support the VCV (variation in ClinVar) accession numbers found in the variant-centric XML file. ClinVar's search engine has been fine-tuned for improved retrieval of search results.
Targeting brain tumours: apoferritin nanocage for delivery of novel analogues of temozolomide
Authors: Bouzinab Kaouthar , Thomas Neil R , Turyanska Lyudmila , Gershkovich Pavel , Weston Nicola , Ashford Marianne B , Bradshaw Tracey D 
Published: October 2019

Abstract
Treatment for glioblastoma multiforme (GBM) consists of surgery, radiotherapy and temozolomide (TMZ) chemotherapy. Nevertheless, patient prognosis remains poor; in England 5-year survival is < 10%. Resistance to TMZ is a major obstacle thwarting successful treatment, due to overexpression of the O6-methylguanine DNA-methyltransferase (MGMT) and deficiency in mismatch repair (MMR). To overcome resistance, novel N3-substituted analogues of TMZ have been developed. An N3-propargyl analogue, T3, has promising activity irrespective of MGMT or MMR status. However, poor brain drug bioavailability and systemic toxicity remain to be resolved. We use apoferritin (AFt) as a biocompatible nano-delivery system for encapsulation of therapeutic agents via molecular diffusion, through channels in the AFt cage. Around 520 molecules of TMZ and T3 per AFt cage were encapsulated. AFt`s small size (diameter: 12 nm) and numerous transferrin receptor recognition sites on its surface; alongside enhanced expression of transferrin receptors (TfR1; which sequester AFt) on the membranes of cancer cells, offer a dual targeting approach towards greater cancer-selectivity. The encapsulated agents have demonstrated significantly increased anti-tumour activity in brain cancer GBM cell lines, U373V (vector control) and U373M (MGMT over-expressing), with growth inhibition GI50 values < 1 μM, compared to > 30 μM for naked drugs. Clonogenic and cell cycle analyses further corroborate these findings. Hence, the AFt nano-delivery system offers a promising route for enhanced specificity, selectivity and potency of TMZ analogues.
Advanced molecular characterization using Digital Spatial Profiling Technology on immuno-oncology targets in methylated compared with unmethylated IDH-wildtype glioblastoma
Authors: Barber Hannah , Lander Beatrice , Daniels Aled , Tofias Antonis , Jing Gong Jing , Ren Yuqi , Ren Xing , Liang Yan , White Paul , Kurian Kathreena M 
Published: October 2019

Abstract

Introduction
Glioblastoma (GBM) is the most common primary adult brain tumour with 12–15 months median overall survival. Molecular characterization of multiple immuno-onology targets in GBM is required to optimise immunotherapeutic strategies. Advanced molecular characterisation using Digital Spatial Profiling Technology allows assessment of multiple immuno-oncology protein targets in methylated compared with unmethylated Glioblastoma IDH-wildtype.

Methods
Nanostring DSP uses multiple primary antibodies conjugated to indexing DNA oligos with a UV photocleavable linker. Tissue Regions of interest (ROI) are selected with bound fluorescent antibodies, oligos are released via a UV-mediated linker and quantitated. We used DSP multiplex analysis of 31 immuno-oncology proteins and controls (PD-1, PD-L1, B7-H3, VISTA, CD45, CD45RO, CD3, MS4A1 (CD20), CD4, CD8A, CD68, STAT3, STAT3 (Phopshory705), GZMB, Beta-2-microglobulin, CD56, Beta-catenin, FOXP3, CD14, CD19, AKT, P-AKT, PTEN, Bcl-2, CD44, Histone H3, S6, IgG Rabbit Control, Mouse IgG Control, Pan-Cytokeratin, Ki67) from ROIs in a cohort of 10 Glioblastomas IDH-wildtype (5 methylated, 5 unmethylated). An nCounter platform allowed quantitative comparisons of antibodies between ROIs in MGMT methylated and unmethylated tumours. Mean protein expression counts between methylated and unmethylated GBM were compared using a linear mixed effect model for technical and biological replicates.

Results
GeoMx DSP showed 10/27 immuno-oncology target proteins were significantly increased in methylated versus unmethylated Glioblastoma IDH-wildtype (false discovery rate FDR <0.1 by Benjamini-Hocheberg Procedure).

Conclusions
Increased immuno-oncology protein target expression in methylated versus unmethylated glioblastoma IDH-wildtype using DSP platform has been identified. Advanced multiplex immuno-oncological biomarker analysis is required to identify predictive biomarkers for novel immunotherapeutic agents in GBMs.
Ketogenic diet and metabolic regulation of brain microglia
Authors: Benito Adrian , Hajji Nabil , O’Neill Kevin , Keun Hector C , Syed Nelofer 
Published: October 2019

Abstract
Ketogenic diet (KD) has been proposed as a coadjuvant therapy in the treatment of brain tumours. Reduction of blood glucose and increase in ketone bodies concentration are amongst the most important changes induced by KD in patients. Preliminary data collected in our lab indicates that KD induces substantial changes in the immune system in mice bearing brain tumours. Microglia are brain-resident immune cells that account for around 30% of the tumour mass and play a major role in controlling tumour progression by adopting a protumour (M2 polarisation) or antitumour (M1 polarisation) phenotype. We are interested in understating the molecular and metabolic determinants of microglia polarisation and how these can be modulated by the metabolic microenvironment and KD. We report some initial findings that indicate microglia adapt to changes in the metabolic microenvironment and that nutrient availability can modulate microglia activation and polarisation. We believe that the study of microglia metabolism and nutritional interventions like KD can provide new knowledge about the regulation of the brain immune system and unveil novel routes for brain cancer treatment.
Choroid plexus papillomas are induced by c-Myc overexpression in the choroid plexus via a T-cell inflammatory mechanism
Authors: Merve Ashirwad , Zhang Xinyu , Pomella Nicola , Acquati Serena , Hoeck Joerg , Dumas Anaelle , Rosser Gabriel , Li Yichen , Jeyapalan Jennie , Vicenzi Silvia , Sabò Arianna , Sheer Denise , Behrens Axel , Marino Silvia 
Published: October 2019

Abstract
Choroid plexus tumours (CPT) account for up to 20% of brain tumours in children under 2 years of age. Histologically CPTs are classified into three categories - Choroid Plexus Papilloma (CPP), Atypical Choroid Plexus Papilloma (ACPP) and Choroid Plexus Carcinoma (CPC). Recent literature demonstrates that CPP and ACPP are molecularly distinct from CPC. Initial management for CPT include surgery followed by adjuvant therapy in selected patients. Currently there are no disease-specific chemotherapeutic agents available, possibly because of their rarity and paucity of faithful pre-clinical experimental models.
In this study we show that c-Myc overexpression in the choroid plexus epithelium induces T-cell inflammation-dependent choroid plexus papillomas in a mouse model. We demonstrate that c-MYC is expressed in a substantial proportion of human choroid plexus tumours and that this subgroup of tumours is characterised by an inflammatory transcriptome and significant inflammatory infiltrates. We observed that triple transgenic compound mutant mouse model with c-Myc overexpression in an immune-suppressed background led to a decreased incidence of CPP and reduced tumour bulk. A reduced tumour size was also observed when c-Myc overexpressing mice were treated with anti-CD3 antibodies.
Our data raise the possibility that benign choroid plexus tumours expressing c-MYC could be amenable to medical therapy with anti-inflammatory drugs.
Reliability of DCE MRI data in primary brain tumours: a comparison of Tofts and Shutter Speed Models
Authors: Inglese Marianna , Honeyfield Lesley , Aboagye Eric , Waldman Adam , Grech-Sollars Matthew 
Published: October 2019

Abstract
The accuracy of quantitative measurements of perfusion parameters by DCE-MRI is crucial as it can significantly impact the clinical care of cancer patients. In this study, we provide a method to identify reliable DCE-MRI brain data for perfusion quantification with different pharmacokinetic models.
We analysed DCE-MRI data of 14 patients with primary brain tumours using the Tofts model (TM), the extended-Tofts model (ETM), the shutter speed model (SSM) and the extended shutter speed model (ESSM). Due to the presence of the blood brain barrier, which can block the leakage of the CA into the interstitium, we also implemented the no-exchange model (NEM). For each lesion, we produced a 3D model selection map with the evaluation of the Akaike Information Criteria. The variability of each pharmacokinetic parameter extracted from the fitting of the model of choice was assessed with a noise propagation procedure, resulting in distributions of the coefficient of variation (CV).
Results showed the NEM to be the most frequent model of choice (35.5%), followed by the ETM (32%), the TM (28.2%), the SSM (4.3%) and the ESSM (<0.1%). In analysing the reliability of Ktrans, when considering regions with a CV<20%, ≈25% of voxels were found to be stable. The remaining 75% of voxels were considered to be unreliable.
In conclusion, an appropriate model selection, considering tissue biology and its effects on BBB permeability and exchange conditions, together with an analysis on the reliability and stability of the calculated parameters, is critical in the identification of reliable brain DCE-MRI data.
Inhibitors of poly(ADP-ribose) glycohydrolase (PARG) exhibit single agent therapeutic activity and sensitize glioblastoma cells to ionizing radiation
Authors: Jackson Mark , Gomez-Roman Natividad , Chalmers Anthony 
Published: October 2019

Abstract

Objective
The lack of an effective therapy for glioblastoma (GBM) largely results from the intrinsic resistance of GBM cells. The radiosensitizing activity of inhibitors of poly(ADP-ribose) polymerases (PARPs) highlights the important role of poly(ADP-ribose) (PAR) in the DNA damage response. In contrast to PARPs, inhibition of poly(ADP-ribose) glycohydrolase (PARG), the enzyme responsible for degrading PAR chains, has shown single agent therapeutic activity in non-glioma cancer cells. This work aims to validate the therapeutic potential of PARG inhibitors (PARGi) in GBM.

Results
Baseline PAR levels were found to vary between different primary and commercial GBM cells, with PARylation increasing upon exposure of cells to ionizing radiation (IR), as expected. Target engagement of a novel PARGi, PDD00017273, was confirmed by the accumulation of nuclear PAR in treated cells. Inhibitor specificity was demonstrated using an inactive control compound and by combining PARGi with the PARP inhibitor olaparib, which blocked the effect. Single agent treatment with PARGi reduced the clonogenic survival of GBM cells in a concentration-dependent manner. Importantly, PARGi also sensitized GBM cells to IR (sensitizer enhancement ratios, SER, ≥ 1.40)

Conclusion
In contrast to PARP inhibitors, novel PARGi exhibit single agent activity against a panel of GBM cell lines, and also show robust radiosensitizing activity. PARGi therefore have therapeutic potential in this cancer of unmet need.