bluuebunny/crossref_metadata_2025_split huggingface dataset:
Properties of reionization-era galaxies from JWST luminosity functions and 21-cm interferometry
Authors: Park Jaehong , Gillet Nicolas , Mesinger Andrei , Greig Bradley 
Published: November 2019

ABSTRACT
Upcoming observations will probe the first billion years of our Universe in unprecedented detail. Foremost among these are 21-cm interferometry with the Hydrogen Epoch of Reionization Arrays (HERA) and the Square Kilometre Array (SKA), and high-z galaxy observations with the James Webb Space Telescope (JWST). Here, we quantify how observations from these instruments can be used to constrain the astrophysics of high-z galaxies. We generate several mock JWST luminosity functions (LFs) and SKA1 21-cm power spectra, which are consistent with current observations, but assume different properties for the unseen, ultrafaint galaxies driving the epoch of reionization (EoR). Using only JWST data, we predict up to a factor of 2–3 improvement (compared with Hubble Space Telescope, HST) in the fractional uncertainty of the star formation rate to halo mass relation and the turnover magnitude. Most parameters regulating the ultraviolet (UV) galaxy properties can be constrained at the level of ∼10 per cent or better, if either (i) we are able to better characterize systematic lensing uncertainties than currently possible; or (ii) the intrinsic LFs peak at magnitudes brighter than MUV ≲ −13. Otherwise, improvement over HST-based inference is modest. When combining with upcoming 21-cm observations, we are able to significantly mitigate degeneracies, and constrain all of our astrophysical parameters, even for our most pessimistic assumptions about upcoming JWST LFs. The 21-cm observations also result in an order of magnitude improvement in constraints on the EoR history.
Both starvation and outflows drive galaxy quenching
Authors: Trussler James , Maiolino Roberto , Maraston Claudia , Peng Yingjie , Thomas Daniel , Goddard Daniel , Lian Jianhui 
Published: November 2019

ABSTRACT
Star-forming galaxies can in principle be transformed into passive systems by a multitude of processes that quench star formation, such as the halting of gas accretion (starvation) or the rapid removal of gas in AGN-driven outflows. However, it remains unclear which processes are the most significant, primary drivers of the SF-passive bimodality. We address this key issue in galaxy evolution by studying the chemical properties of 80 000 local galaxies in Sloan Digital Sky Survey Data Release 7. In order to distinguish between different quenching mechanisms, we analyse the stellar metallicities of star-forming, green valley, and passive galaxies. We find that the significant difference in stellar metallicity between passive galaxies and their star-forming progenitors implies that for galaxies at all masses, quenching must have involved an extended phase of starvation. However, some form of gas ejection also has to be introduced into our models to best match the observed properties of local passive galaxies, indicating that, while starvation is likely to be the prerequisite for quenching, it is the combination of starvation and outflows that is responsible for quenching the majority of galaxies. Closed-box models indicate that the duration of the quenching phase is 2–3 Gyr, with an e-folding time of 2–4 Gyr, after which further star formation is prevented by an ejective/heating mode. Alternatively, leaky-box models find a longer duration for the quenching phase of 5–7 Gyr and an e-folding time of ∼1 Gyr, with outflows becoming increasingly important with decreasing stellar mass. Finally, our analysis of local green valley galaxies indicates that quenching is slower in the local Universe than at high redshift.
LTBK-08. TOCA 511 & TOCA FC VERSUS STANDARD OF CARE IN PATIENTS WITH RECURRENT HIGH GRADE GLIOMA
Authors: Cloughesy Timothy , Petrecca Kevin , Walbert Tobias , Butowski Nicholas , Salacz Michael , Perry James , Damek Denise , Bota Daniela , Bettegowda Chetan , Zhu Jay-Jiguang , Iwamoto Fabio , Placantonakis Dimitris , Martinez Nina , Elder J Bradley , Kaptain George , Cachia David , Moshel Yaron , Brem Steven , Picconi David , Tran Nam , Nam Do-Hyun , Park Chul-Kee , Landolfi Joseph , Tran David , Ramakrishna Rohan , Fink Karen , Heros Deborah , Zadeh Gelareh , Nicholas Garth , Mehta Vivek , Ian Robins H , Chen Clark , Pitz Marshall , Heth Jason , Nagpal Seema , Pearlman Michael , Ahluwalia Manmeet , Mohile Nimish , Merrell Ryan , Schiff David , Thompson Reid , Davis Raphael , Macdonald David , Kheoh Thian , Kabbinavar Fairooz , Lossos Alexander , Vogelbaum Michael 
Published: November 2019

Abstract

BACKGROUND
Toca 511 (vocimagene amiretrorepvec) is a cancer-selective, retroviral replicating vector encoding a codon optimized, heat stabilized cytosine deaminase that converts Toca FC (extended-release 5-fluorocytosine, 5-FC) into the anticancer agent 5-fluorouracil. Three Ph1 studies in patients with recurrent high grade glioma have demonstrated a tolerable safety profile and encouraging efficacy.

METHODS
Toca 5 is a multi-national, randomized, open-label Ph3 trial (NCT02414165) of Toca 511 & Toca FC versus standard of care (SOC) options that comprises Investigator’s choice of single agent chemotherapy (lomustine, temozolomide) or bevacizumab in patients who have undergone resection for first or second recurrence of glioblastoma or anaplastic astrocytoma. 403 patients were randomized 1:1 to the Toca arm or the SOC arm and stratified by IDH1 status, KPS, and geographic region. Primary endpoint was overall survival (OS), and secondary endpoints were durable response rate, durable clinical benefit rate, duration of durable response, and 12-month survival rate. The study used group sequential design including 2 interim analyses and 1 final analysis, and the stratified log-rank test are used for the analysis.

RESULTS
271 events were observed for this analysis. Median follow-up was 22.8 months, and the Toca arm missed the primary endpoint (OS) compared to the SOC arm (11.1 months median compared to 12.2 months, HR=1.06, p=0.6154). All secondary endpoints showed no meaningful difference between the arms of the trial. The safety, tolerability and adverse event profile of Toca 511 and Toca FC was as expected for this patient population, with low incidences of Grade 3–4 adverse events. Pre-planned subgroup analyses showed compelling OS improvement in patients with secondary recurrence, and favorable trends in IDH1 mutant and AA population. Detailed data will be presented at the time of the conference.
LTBK-12. EORTC 26951, RANDOMIZED STUDY OF ADJUVANT PCV AFTER 59.4 GY RADIOTHERAPY: VERY LONG TERM FOLLOW-UP
Authors: van den Bent Martin , Hoang-Xuan Khe , Brandes Alba , Kros Johan , Kouwenhoven M C M , Taphoorn Martin , Delattre Jean-Yves , Bernsen Hans , Frenay Marc , Synhaeve Nathalie , Weller Michael , Enting Roelien , French Pim , Dinjens Winand , Golfinopoulos Vassilis , Gorlia Thierry 
Published: November 2019

Abstract

BACKGROUND
Between 1995 and 2002 the EORTC Brain Tumor Group conducted a prospective phase III study on adjuvant procarbazine, CCNU and vincristine (PCV) chemotherapy in anaplastic oligodendroglioma (AOD). A mature follow-up presented in 2012 showed survival benefit of the addition of PCV, in particular in 1p/19q co-deleted tumors and tumors with MGMT promoter methylation. We now present very long term follow-up.

MATERIALS AND METHODS
Patients were eligible if locally diagnosed with a newly diagnosed AOD. They were randomized between radiotherapy (RT, 33 x 1.8 Gy) and the same RT followed by 6 cycles PCV (RT/PCV). Primary endpoints were overall survival (OS) and progression free survival (PFS). 1p/19q status (FISH) was determined in 300 patient. Kaplan- Meier technique and Cox modeling were used for long term survival analysis. Primary analyses were adjusted for known prognostic factors. For other analyses no adjustment was performed.

RESULTS
With 368 patients included, a median follow-up of 18.4 years and 307 (83%) survival events, median and 20-year survival after RT/PCV versus RT alone were 42.3 mo and 16.8% vs 30.6 months and 10.1% (HR 0.78; 95% CI (0.63, 0.98), adjusted p=0.06). Eighty patients were 1p/19q codel of which 26 (33%) were still alive, in this subgroup median and 20-year survival after RT/PCV versus RT alone were 14 years and 37.1% versus 9.3 years and 13.6% (HR 0.60, 95% CI (0.35, 1.03), unadjusted p=0.06). Twenty year PFS in 1p/19q codel was 31.3% in RT/PCV treated patients and 10.8% in RT only treated patients (HR 0.49, 95% CI (0.29, 0.83), unadjusted p=0.007). In the 1p/19q codel subgroup age, WHO PS and necrosis at pathology were identified to be of independent prognostic value for OS.

CONCLUSION
This long term analysis confirms the earlier conclusions and provides data on long term survival in this patient group. In 1p/19q codel patients treated with RT/PCV, the 20-year PFS and OS rates are 31% and 37% respectively.
European institutional integration, trade unions and income inequality
Authors: Tober Tobias 
Published: November 2019

Abstract
What are the distributional implications of European institutional integration? This article argues that European institutional integration exerts a moderating effect on the relationship between trade union strength and income inequality—particularly inequality at the top—within countries of the European Union (EU). I contend that European institutional integration reduces the bargaining power of trade unions due to rising market competition and decreasing union control over the supply of labor. Thus, the effectiveness of trade unions in reducing inequality should decline with progressing European institutional integration. On the basis of a long-term within-country analysis of the EU15, I will show that the effect of trade unions on inequality varies strongly with European institutional integration. Consistent with the theoretical argument, the inequality-reducing effect of trade unions becomes substantially lower the more a country integrates in the EU.
Detection of Drug-Induced Torsades de Pointes Arrhythmia Mechanisms Using hiPSC-CM Syncytial Monolayers in a High-Throughput Screening Voltage Sensitive Dye Assay
Authors: da Rocha Andre Monteiro , Creech Jeffery , Thonn Ethan , Mironov Sergey , Herron Todd J 
Published: November 2019

Abstract
We validated 3 distinct hiPSC-CM cell lines—each of different purity and a voltage sensitive dye (VSD)-based high-throughput proarrhythmia screening assay as a noncore site in the recently completed CiPA Myocyte Phase II Validation Study. Blinded validation was performed using 12 drugs linked to low, intermediate, or high risk for causing Torsades de Pointes (TdP). Commercially sourced hiPSC-CMs were obtained either from Cellular Dynamics International (CDI, Madison, Wisconsin, iCell Cardiomyoyctes2) or Takara Bio (CLS, Cellartis Cardiomyocytes). A third hiPSC-CM cell line (MCH, Michigan) was generated in house. Each cell type had distinct baseline electrophysiological function (spontaneous beat rate, action potential duration, and conduction velocity) and drug responsiveness. Use of VSD and optical mapping enabled the detection of conduction slowing of sodium channel blockers (quinidine, disopyramide, and mexiletine) and drug-induced TdP-like activation patterns (rotors) for some high- and intermediate-risk compounds. Low-risk compounds did not induce rotors in any cell type tested. These results further validate the utility of hiPSC-CMs for predictive proarrhythmia screening and the utility of VSD technology to detect drug-induced APD prolongation, arrhythmias (rotors), and conduction slowing. Importantly, results indicate that different ratios of cardiomyocytes and noncardiomyocytes have important impact on drug response that may be considered during risk assessment of new drugs. Finally, we present the first blinded CiPA hiPSC-CM validation results to simultaneously detect drug-induced conduction slowing, action potential duration prolongation, action potential triangulation, and drug-induced rotors in a proarrhythmia assay.
Approaches to the law applicable to proprietary effects of transactions in securities taken in uniform law: a lesson for the EU
Authors: Müller Michael F 
Published: November 2019

Abstract
The modern practice of securities trading has led to almost insurmountable tensions with classical conflict-of-laws doctrine. The Hague Securities Convention set out to provide for a new and uniform solution. In a recent communication from the Commission, the topic has resurfaced on the European agenda. Against this background, this article poses the question of whether the discussion around the Convention can serve as a lesson for the European Union (EU). It is submitted that neither the status quo of EU law is satisfactory nor does the adoption of the Convention offer a fully convincing solution but that the problem should be targeted at its root: the outdated concept of some national substantive laws in intermediated securities.
Journals in Aging, Geriatrics, and Gerontology: A Survey
Authors: Wolff Robert J. , Bowser Hannah L. 
Published: November 2019

AbstractAging, geriatrics, gerontology, and related areas are important areas of research as the population of older people increases in relationship to the total population. Researchers in these fields would benefit from guidance regarding sources for publishing and finding relevant scholarly journals and articles. Multiple database sites of journals were searched to provide a list of relevant publications. This list was expanded via perusal of published citation lists and searches in general search engines. A total of 243 journals were identified and examined. Of those journals, 198 journals are currently publishing and 45 journals have ceased publication. In terms of publication medium, 39% of the currently publishing journals are online-only, 4% are print-only and 59% of the journals publish both online and in print. Journals with aging in the title represent 36%, geriatrics 30% and gerontology 23%. Less than 10% have been identified as predatory journals. An expected increase in journals in the broad field of aging is indicated by the 49% of listed titles beginning in 2000 or later. This recent increase in available journals provides a need for the information listed in this paper.
Drivers of Frailty from Adulthood into Old Age: Results from a 27-year Longitudinal Population-Based Study in Sweden
Authors: Raymond Emma , Reynolds Chandra A. , Dahl Aslan Anna K. , Finkel Deborah , Ericsson Malin , Hägg Sara , Pedersen Nancy L. , Jylhävä Juulia 
Published: November 2019

AbstractBackgroundFrailty is a strong predictor of adverse aging outcomes. However, the longitudinal drivers of frailty are not well understood. This study aimed at investigating the longitudinal trajectories of a frailty index (FI) from adulthood to late life and identifying the predictors of the level and rate of change in FI.MethodsAn age-based latent growth curve analysis was performed in the Swedish Adoption/Twin Study of Aging (N=1,842; aged 29-102 years) using data from up to 15 measurement waves across 27 years. A 42-item FI was used to measure frailty at each wave.ResultsA bilinear, two-slope model with a turning point at age 65 best described the age-related change in FI, showing that the rate of increase in frailty was more than twice as fast after age 65. Underweight, obesity, female sex, overweight, being separated from one’s co-twin during childhood, smoking, poor social support and low physical activity were associated with a higher level of FI at age 65, with underweight having the largest effect size. When tested as time-varying predictors, underweight and higher social support were associated with a steeper increase in FI before age 65, whereas overweight and obesity were associated with less steep increase in FI after age 65.ConclusionsPredictors for the level and rate of change in frailty are largely actionable and could provide targets for intervention. Underweight increased the risk of higher FI trajectory until age 65, whereas being overweight or obese were associated with slower progression of frailty towards the oldest ages.
Type II Alexander disease caused by splicing errors and aberrant overexpression of an uncharacterized GFAP isoform
Authors: Helman Guy , Takanohashi Asako , Hagemann Tracy L. , Perng Ming D. , Walkiewicz Marzena , Woidill Sarah , Sase Sunetra , Cross Zachary , Du Yangzhu , Zhao Ling , Waldman Amy , Haake Bret C. , Fatemi Ali , Brenner Michael , Sherbini Omar , Messing Albee , Vanderver Adeline , Simons Cas 
Published: November 2019

AbstractAlexander disease results from gain of function mutations in the gene encoding glial fibrillary acidic protein (GFAP), an intermediate filament protein expressed in astrocytes. At least eight GFAP isoforms have been described, however, the predominant alpha isoform accounts for approximately 90% of GFAP protein in the central nervous system. Here we describe exonic variants identified in three unrelated families with Type II Alexander disease that alter the splicing of GFAP pre-mRNA and result in upregulation of a previously uncharacterized GFAP lambda isoform (NM 001363846.1). Affected members of Family 1 and Family 2 shared the same missense variant, NM 001363846.1:c.1289G>A;p.(Arg430His) while in Family 3 we identified a synonymous variant in the adjacent nucleotide, NM 001363846.1:c.1290C>A;p.(Arg430Arg). Using RNA and protein analysis of brain autopsy samples, and a mini-gene splicing reporter assay, we demonstrate both variants result in upregulation of the lambda isoform. We assessed other GFAP variants in the ClinVar database for predicted aberrant splicing and using the same assay demonstrated significant changes to splicing for two selected variants. Our approach demonstrates the importance of characterizing the effect of GFAP variants on mRNA splicing in order to inform future pathophysiologic and therapeutic study for Alexander disease.
Dynamic evolution of euchromatic satellites on the X chromosome inDrosophila melanogasterand thesimulansclade
Authors: Sproul J.S. , Khost D.E. , Eickbush D.G. , Negm S. , Wei X. , Wong I. , Larracuente A.M. 
Published: November 2019

ABSTRACTSatellite DNAs (satDNAs) are among the most dynamically evolving components of eukaryotic genomes and play important roles in genome regulation, genome evolution, and speciation. Despite their abundance and functional impact, we know little about the evolutionary dynamics and molecular mechanisms that shape satDNA distributions in genomes. Here we use high-quality genome assemblies to study evolutionary dynamics of two complex satDNAs,Rsp-likeand1.688gm/cm3, inDrosophila melanogasterand its three nearest relatives in thesimulansclade. We show that large blocks of these repeats are highly dynamic in the heterochromatin, where their genomic location varies across species. We discovered that small blocks of satDNA that are abundant in X chromosome euchromatin are similarly dynamic, with repeats changing in abundance, location, and composition among species. We detail the proliferation of a rare satellite (Rsp-like) across the X chromosome inD. simulansandD. mauritiana. Rsp-likespreads by inserting into existing clusters of the older, more abundant1.688satellite, in events that were likely facilitated by microhomology-mediated repair pathways. We show thatRsp-likeis abundant on extrachromosomal circular DNA inD. simulans, which may have contributed to its dynamic evolution. Intralocus satDNA expansions via unequal exchange and the movement of higher-order repeats also contribute to the fluidity of the repeat landscape. We find evidence that euchromatic satDNA repeats experience cycles of proliferation and diversification somewhat analogous to bursts of transposable element proliferation. Our study lays a foundation for mechanistic studies of satDNA proliferation and the functional and evolutionary consequences of satDNA movement.
A highly sensitive and specific SYBR Green quantitative polymerase chain reaction (qPCR) method for rapid detection of scale drop disease virus in Asian sea bass, Lates calcarifer
Authors: Sriisan Sukhontip , Boonchird Chuenchit , Thitamadee Siripong , Sonthi Molruedee , Dong Ha Thanh , Senapin Saengchan 
Published: November 2019

AbstractScale drop disease virus (SDDV) is a novel Megalocytivirus causing scale drop disease (SDD) in Asian sea bass in Southeast Asia. In order to support disease diagnosis and surveillance, the present study developed a highly sensitive and specific SYBR Green qPCR assay for rapid detection of SDDV. Specific primers targeting a 135-bp fragment of ATPase coding gene of the SDDV genome were newly designed and subsequent gradient PCR assays were conducted to investigate their optimal annealing temperature. The optimized qPCR assay could detect as low as 2 viral copies per reaction and showed no cross amplification with DNA extracted from 12 viruses and bacteria commonly found in aquatic animals. The SDDV ATPase qPCR method was subsequently validated with field samples (n= 86). The results revealed that all clinically sick fish (n=34) from 5 affected farms gave positive results. Interestingly, 30/52 samples of apparently healthy fish from 8 unaffected farms which previously tested negative for SDDV by semi-nested PCR assay were positive by the newly developed qPCR method. This suggested that qPCR method is highly sensitive and suitable for early screening of SDDV from clinically healthy fish and for disease confirmation of sick fish. Investigation of tissue tropism and viral load of SDDV revealed systemic viral infection with relatively high viral load (8 × 102 to 6.8 × 104 copies per 200 ng of DNA template) in all 9 tested organs including eyes, brain, fin, gills, kidney, liver, kidney, spleen, and muscle. The newly developed qPCR method in this study delivered an accurate and reliable method for rapid detection of SDDV that may facilitate active surveillance and prevent widespread of the virus.HighlightsThis study developed a SYBR Green qPCR assay for rapid detection of SDDVThe developed qPCR assay is specific for SDDV with limit of detection of 2 viral copies per reactionThe assay could detect the virus from subclinically infected fish with low viral loadWe recommend this qPCR assay for active surveillance and early screening of SDDV
Differential transcription of expanded gene families in central carbon metabolism of Streptomyces coelicolor A3(2)
Authors: Schniete Jana K , Reumerman Richard , Kerr Leena , Tucker Nicholas P , Hunter Iain S , Herron Paul R , Hoskisson Paul A 
Published: November 2019

AbstractBackgroundStreptomycete bacteria are prolific producers of specialised metabolites, many of which have clinically relevant bioactivity. A striking feature of their genomes is the expansion of gene families that encode the same enzymatic function. Genes that undergo expansion events, either by horizontal gene transfer or duplication, can have a range of fates: genes can be lost, or they can undergo neo-functionalisation or sub-functionalisation. To test whether expanded gene families in Streptomyces exhibit differential expression, an RNA-Seq approach was used to examine cultures of wild-type Streptomyces coelicolor grown with either glucose or tween as the sole carbon source.ResultsRNA-Seq analysis showed that two-thirds of genes within expanded gene families show transcriptional differences when strains were grown on tween compared to glucose. In addition, expression of specialised metabolite gene clusters (actinorhodin, isorenieratane, coelichelin and a cryptic NRPS) was also influenced by carbon source.ConclusionsExpression of genes encoding the same enzymatic function had transcriptional differences when grown on different carbon sources. This transcriptional divergence enables partitioning to function under different physiological conditions. These approaches can inform metabolic engineering of industrial Streptomyces strains and may help develop cultivation conditions to activate the so-called silent biosynthetic gene clusters.