bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial Modelling of Deforestation Based on Social Driving Force in South Sulawesi and West Sulawesi from 1990 to 2016
Authors: Rijal S , Nismayani  , Mahbub M A S , Pachri H , Nurmiaty  , Arif S
Published: August 2019

Deforestation is a permanent change of forest cover area to non-forest cover area. Social factors contribute more to the occurrence of deforestation, so this study was directed to examine the social factors that drive deforestation. Research location selected based on the key vulnerability of deforestation profiles. This study only used moderately vulnerability and vulnerability profile. Data analysis in this research using PCA (Principal Component Analysis) Method. The results explained that the Spatial Deforestation Model in South Sulawesi and West Sulawesi have differences based on the vulnerability profile. The dominant deforestation profiles affected were population density, productive age and employment. Population density affects deforestation because the site is always experiencing an increase in population and is not balanced with the extent of its territory, especially on vulnerable profiles. Productive age is very influential and increasing. The employment is also one of the most influencing of deforestation. The field of education itself does not give a significant effect. The spatial model of deforestation based on social factors in South Sulawesi shows that in the same profile different influences were found. In West Sulawesi, social involvement tends to be the same for each profile. The influence of population, productive age and availability of regions has a significant influence on the incidence of deforestation.
Development of National Forest/Land Fire Monitoring System Using Remote Sensing Satellite Data (Terra/Aqua Modis and SNPP) by Automation and Nearly Real-time.
Authors: Indradjad A , Sunarmodo W , Salyasari N , Pratiknyo B
Published: August 2019

Hotspot monitoring system using remote sensing satellite data such as Terra/Aqua Modis and SNPP VIIRS. In order to manage national natural disaster (such as forest/land fire disaster), accurate-real time-accessible data and information are required. In this case the use of remote sensing satellites data is use for the monitoring of natural disasters, especially forest/land fires that occur very massive need monitoring in real time and up to date. Information systems for monitoring of forest/land fires, can be built using remote sensing data of Terra/Aqua Modis and SNPP satellites that continuously monitor the condition of the land/forest by photographing the Indonesian territory respectively four times a day. The hotspot data requirement is 30 minute after the reception in ground station. The built system consists of the reception, processing, cataloguing and dissemination data, in order to fit the requirement the system need to be automation. The data receiving process is done at Parepare and Rumpin ground stations, followed by sending data to Pekayon in real time. Data processing is done in Pekayon using automated software open source module. Furthermore, data cataloguing is built using spatial and numerical based databases. The appearance system is built interactively with web-based online and mobile, user can do searching hotspot information based on location, degree of trust and time of incident. The monitoring system of forest / land fires that have been built have been published and utilized nationally, especially the BNPB in the context of the prevention and mitigation of forest / land fire disasters in Indonesia. Users can access through the website http://modis-catalog.lapan.go.id or can download android-based mobile app “Hotspot LAPAN”. It is expected that with online and mobile web based online and mobile fire monitoring system, it can be used for the prevention and mitigation of forest/land fire disaster in Indonesia.
Incremental Improvement of High resolution Satellite Imagery For Participatory Mapping in Land Registration
Authors: Andri H , Sella N , Alfita P , Putri R , Winna P P , Lasmi R , Ratri W , Rani A
Published: August 2019

Fit for purpose land administration (FFP-LA) has a purpose to inventory all of the land parcels. One of the methods in fit for purpose land administration is participatory mapping. Participatory mapping involves the people in the area mapping to create land’s parcel map. The people create a map with their knowledge about spatial objects in their area using a satellite image with high-resolution or aerial photo. The purpose of participatory mapping is to create a full land parcels map that has been validated for geometery boundaries and features by the owner or the people around it. But in some circumstance, the data in that map cannot be an inut data for land administration, cause there is some standard for satellite image with high-resolution or aerial photo that should be followed. The standard was attached in Government’s Law no. 24/1997 and The Ministry of Agrarian Affair’s Law no. 3/1997. In this research, incremental improvement for the high-resolution satellite imagery with some constraints, that is low cost, fast and good enough output and there will analyse a sample of output participatory mapping using high-resolution satellite imagery.
Determinants of Increased Central Excess Pressure in Dialysis: Role of Dialysis Modality and Arteriovenous Fistula
Authors: Paré Mathilde , Goupil Rémi , Fortier Catherine , Mac-Way Fabrice , Madore François , Marquis Karine , Hametner Bernhard , Wassertheurer Siegfried , Schultz Martin G , Sharman James E , Agharazii Mohsen
Published: August 2019

BACKGROUND

Arterial reservoir-wave analysis (RWA)—a new model of arterial hemodynamics—separates arterial wave into reservoir pressure (RP) and excess pressure (XSP). The XSP integral (XSPI) has been associated with increased risk of clinical outcomes. The objectives of the present study were to examine the determinants of XSPI in a mixed cohort of hemodialysis (HD) and peritoneal dialysis (PD) patients, to examine whether dialysis modality and the presence of an arteriovenous fistula (AVF) are associated with increased XSPI.

METHOD

In a cross-sectional study, 290 subjects (232 HD and 130 with AVF) underwent carotid artery tonometry (calibrated with brachial diastolic and mean blood pressure). The XSPI was calculated through RWA using pressure-only algorithms. Logistic regression was used for determinants of XSPI above median. Through forward conditional linear regression, we examined whether treatment by HD or the presence of AVF is associated with higher XSPI.

RESULTS

Patients with XSPI above median were older, had a higher prevalence of diabetes and cardiovascular disease, had a higher body mass index, and were more likely to be on HD. After adjustment for confounders, HD was associated with a higher risk of higher XSPI (odds ratio = 2.39, 95% confidence interval: 1.16–4.98). In a forward conditional linear regression analysis, HD was associated with higher XSPI (standardized coefficient: 0.126, P = 0.012), but on incorporation of AVF into the model, AVF was associated with higher XSPI (standardized coefficient: 0.130, P = 0.008) and HD was excluded as a predictor.

CONCLUSION

This study suggests that higher XSPI in HD patients is related to the presence of AVF.
Stomatal anatomy coordinates leaf size with Rubisco kinetics in the Balearic Limonium
Authors: Conesa Miquel À , Muir Christopher D , Molins Arantzazu , Galmés Jeroni
Published: August 2019

Trait integration arises through both selection on functional coordination and shared developmental pathways. Different anatomical components must both work well and develop together to generate individuals with the appropriate physiology to survive and reproduce in their environment. In this study, we used a common garden experiment and Bayesian multilevel models to test whether stomatal anatomy coordinates leaf gas exchange, Rubisco kinetics, and leaf size across 10 closely related species of Limonium from the Balearic Islands. The results indicate that the anatomical determinants of maximum stomatal conductance, stomatal density and size, were functionally coordinated with Rubisco kinetics – species whose stomatal anatomy was correlated with low stomatal conductance have evolved Rubisco enzymes better adapted to low operational chloroplastic CO2 concentrations. Lower stomatal density was associated with greater leaf size, which can be explained by a greater proportion of pavement cells in large-leaved species. These results suggest that both selection for functional coordination (stomata and Rubisco kinetics) and shared development pathways (stomatal density and leaf area) likely shape patterns of trait integration between species.
Fractionation of Adipose Tissue Procedure With a Disposable One-Hole Fractionator
Authors: Van Dongen Joris A , Gostelie Olivier F E , Vonk Lucienne A , De Bruijn Julia J , Van Der Lei Berend , Harmsen Martin C , Stevens Hieronymus P
Published: August 2019

Background

Adipose tissue has been widely used in regenerative surgery for its therapeutic potential. This potential is often ascribed to the stromal vascular fraction (SVF), which can be mechanically isolated. Mechanical isolation results in an SVF that retains intact cell-cell communication including extracellular matrix and is therefore named tissue-SVF (tSVF).

Objectives

The aim of this study was to evaluate a new disposable 1-hole fractionator for fractionation of adipose tissue (FAT), and compare this new device with the existing reusable 3-hole fractionator.

Methods

The composition of tSVF obtained via the 1-hole fractionator was histologically and histochemically compared to unprocessed adipose tissue. The number of viable nuclear cells in tSVF obtained by the 1-hole and 3-hole fractionators as well as unprocessed adipose tissue were compared after enzymatic isolation and tested for colony-forming capacity. Flow cytometry was used to compare different cell compositions based on surface marker expression between tSVF isolated by the two types of fractionators.

Results

Fractionation of adipose tissue with the 1-hole fractionator condenses vasculature and extracellular matrix by disrupting adipocytes. The number of viable nuclear cells in tSVF obtained with the two fractionators was comparable and significantly higher than unprocessed lipoaspirate. Furthermore, tSVF isolated by both fractionators showed similar cell compositions and comparable colony-forming capacities.

Conclusions

FAT with a disposable 1-hole fractionator effectively isolates tSVF with a cell count and cell composition comparable to the fraction obtained with the 3-hole reusable fractionator. The disposable 1-hole fractionator, however, is safer and more user friendly.
Androgens are essential for epithelial cell recovery after efferent duct ligation in the initial segment of the mouse epididymis†
Authors: Kim Bongki , Breton Sylvie
Published: August 2019

Efferent duct ligation (EDL) induces epithelial cell degeneration followed by regeneration in the epididymal initial segment. We tested here the role of androgens in the recovery phase. EDL was performed at post-natal weeks (PNW) 3, 4, 5, 6, and 7, and apoptotic and proliferating epithelial cells were quantified 24 h, and at days 2 and 2.5 post-EDL, respectively. A progressive increase in the number of apoptotic basal cells (BCs) and principal cells (PCs) was detected from PNW3 to 6, 24 h after EDL. Two days after EDL, no increase in proliferating BCs and PCs was observed at PNW3 and 4, despite the induction of apoptosis by EDL. A progressive increase in the number of proliferating BCs was then observed from PNW5 to 6, while the number of proliferating PCs remained low. 2.5 days after EDL, the number of proliferating BCs and PCs remained low at PNW3, 4, and 5, but a marked increase in the number of proliferating PCs was observed at PNW6. Flutamide pretreatment for 3 weeks followed by EDL at PNW7 dramatically decreased the number of proliferating BCs on EDL day 2, and the number of proliferating PCs on EDL day 2.5, compared to controls. We conclude that (1) BCs are the first to show recovery after EDL, followed by PCs; (2) androgens are essential for BC and PC repair after injury in the postpubertal epididymis; and (3) the prepubertal epididymis lacks repair ability following injury.
Expression and functional analyses of ephrin type-A receptor 2 in mouse spermatogonial stem cells†
Authors: Morimoto Hiroko , Kanatsu-Shinohara Mito , Orwig Kyle E , Shinohara Takashi
Published: August 2019

Spermatogonial stem cells (SSCs) undergo continuous self-renewal division in response to self-renewal factors. The present study identified ephrin type-A receptor 2 (EPHA2) on mouse SSCs and showed that supplementation of glial cell-derived neurotrophic factor (GDNF) and fibroblast growth factor 2 (FGF2), which are both SSC self-renewal factors, induced EPHA2 expression in cultured SSCs. Spermatogonial transplantation combined with magnetic-activated cell sorting or fluorescence-activated cell sorting also revealed that EPHA2 was expressed in SSCs. Additionally, ret proto-oncogene (RET) phosphorylation levels decreased following the knockdown (KD) of Epha2 expression via short hairpin ribonucleic acid (RNA). Although the present immunoprecipitation experiments did not reveal an association between RET with EPHA2, RET interacted with FGFR2. The Epha2 KD decreased the proliferation of cultured SSCs and inhibited the binding of cultured SSCs to laminin-coated plates. The Epha2 KD also significantly reduced the colonization of testis cells by spermatogonial transplantation. EPHA2 was also expressed in human GDNF family receptor alpha 1-positive spermatogonia. The present results indicate that SSCs express EPHA2 and suggest that it is a critical modifier of self-renewal signals in SSCs.
The testis-specific serine proteases PRSS44, PRSS46, and PRSS54 are dispensable for male mouse fertility†
Authors: Holcomb Richard J , Oura Seiya , Nozawa Kaori , Kent Katarzyna , Yu Zhifeng , Robertson Matthew J , Coarfa Cristian , Matzuk Martin M , Ikawa Masahito , Garcia Thomas X
Published: August 2019

High-throughput transcriptomics and proteomics approaches have recently identified a large number of germ cell–specific genes with many that remain to be studied through functional genetics approaches. Serine proteases (PRSS) constitute nearly one-third of all proteases, and, in our bioinformatics screens, we identified many that are testis specific. In this study, we chose to focus on Prss44, Prss46, and Prss54, which we confirmed as testis specific in mouse and human. Based on the analysis of developmental expression in the mouse, expression of all four genes is restricted to the late stage of spermatogenesis concomitant with a potential functional role in spermiogenesis, spermiation, or sperm function. To best understand the male reproductive requirement and functional roles of these serine proteases, each gene was individually ablated by CRISPR/Cas9-mediated ES cell or zygote approach. Homozygous deletion mutants for each gene were obtained and analyzed for phenotypic changes. Analyses of testis weights, testis and epididymis histology, sperm morphology, and fertility revealed no significant differences in Prss44, Prss46, and Prss54 knockout mice in comparison to controls. Our results thereby demonstrate that these genes are not required for normal fertility in mice, although do not preclude the possibility that these genes may function in a redundant manner. Elucidating the individual functional requirement or lack thereof of these novel genes is necessary to build a better understanding of the factors underlying spermatogenesis and sperm maturation, which has implications in understanding the etiology of male infertility and the development of male contraceptives.
Reversal of Age-Related Changes in Cortical Sound-Azimuth Selectivity with Training
Authors: Cheng Yuan , Zhang Yifan , Wang Fang , Jia Guoqiang , Zhou Jie , Shan Ye , Sun Xinde , Yu Liping , Merzenich Michael M , Recanzone Gregg
H , Yang Lianfang , Zhou Xiaoming
Published: August 2019

The compromised abilities to understand speech and localize sounds are two hallmark deficits in aged individuals. Earlier studies have shown that age-related deficits in cortical neural timing, which is clearly associated with speech perception, can be partially reversed with auditory training. However, whether training can reverse aged-related cortical changes in the domain of spatial processing has never been studied. In this study, we examined cortical spatial processing in ~21-month-old rats that were trained on a sound-azimuth discrimination task. We found that animals that experienced 1 month of training displayed sharper cortical sound-azimuth tuning when compared to the age-matched untrained controls. This training-induced remodeling in spatial tuning was paralleled by increases of cortical parvalbumin-labeled inhibitory interneurons. However, no measurable changes in cortical spatial processing were recorded in age-matched animals that were passively exposed to training sounds with no task demands. These results that demonstrate the effects of training on cortical spatial domain processing in the rodent model further support the notion that age-related changes in central neural process are, due to their plastic nature, reversible. Moreover, the results offer the encouraging possibility that behavioral training might be used to attenuate declines in auditory perception, which are commonly observed in older individuals.
Externalization Errors of Olfactory Source Monitoring in Healthy Controls—An fMRI Study
Authors: Leclerc Marcel P , Kellermann Thilo , Freiherr Jessica , Clemens Benjamin , Habel Ute , Regenbogen Christina
Published: August 2019

Using a combined approach of functional magnetic resonance imaging (fMRI) and noninvasive brain stimulation (transcranial direct current stimulation [tDCS]), the present study investigated source memory and its link to mental imagery in the olfactory domain, as well as in the auditory domain. Source memory refers to the knowledge of the origin of mental experiences, differentiating events that have occurred and memories of imagined events. Because of a confusion between internally generated and externally perceived information, patients that are prone to hallucinations show decreased source memory accuracy; also, vivid mental imagery can lead to similar results in healthy controls. We tested source memory following cathodal tDCS stimulation using a mental imagery task, which required participants to perceive or imagine a set of the same olfactory and auditory stimuli during fMRI. The supplementary motor area (SMA) is involved in mental imagery across different modalities and potentially linked to source memory. Therefore, we attempted to modulate participants’ SMA activation before entering the scanner using tDCS to influence source memory accuracy in healthy participants. Our results showed the same source memory accuracy between the olfactory and auditory modalities with no effects of stimulation. Finally, we found SMA’s subregions differentially involved in olfactory and auditory imagery, with activation of dorsal SMA correlated with auditory source memory.
Use of Intrauterine Devices and Risk of Human Immunodeficiency Virus Acquisition Among Insured Women in the United States
Authors: Marcus Julia L , Snowden Jonathan M , Murray Horwitz Mara E , Toh Sengwee , Horgan Casie , Tilney Rong Chen , Rajbhandari Rajani , Back Soowoo , Westreich Daniel J
Published: August 2019

Concerns have been raised about progestin-containing contraceptives and the risk of human immunodeficiency virus (HIV) acquisition. Based on health insurance data from women in the United States with intrauterine device (IUD) insertions during 2011–2018, there was no increased risk of incident HIV diagnosis for levonorgestrel-releasing IUDs versus copper IUDs.
Impact of manganese on biofilm formation and cell morphology of Candida parapsilosis clinical isolates with different biofilm forming abilities
Authors: Shafeeq Sulman , Pannanusorn Srisuda , Elsharabasy Youssef , Ramírez-Zavala Bernardo , Morschhäuser Joachim , Römling Ute
Published: August 2019

The commensal species Candida parapsilosis is an emerging human pathogen that has the ability to form biofilms. In this study, we explored the impact of the divalent cations cobalt (Co2+), copper (Cu2+), iron (Fe3+), manganese (Mn2+), nickel (Ni2+) and zinc (Zn2+) on biofilm formation of clinical isolates of C. parapsilosis with no, low and high biofilm forming abilities at 30 and 37°C. All strains besides one isolate showed a concentration-dependent enhancement of biofilm formation at 30°C in the presence of Mn2+ with a maximum at 2 mM. The biofilm forming ability of no and low biofilm forming isolates was >2-fold enhanced in the presence of 2 mM Mn2+, while the effect in high biofilm forming isolate was significantly less pronounced. Of note, cells in the biofilms of no and low biofilm forming strains differentiated into yeast and pseudohyphal cells similar in morphology to high biofilm formers. The biofilm transcriptional activator BCR1 has a dual developmental role in the absence and presence of 2 mM Mn2+ as it promoted biofilm formation of no biofilm forming strains, and, surprisingly, suppressed cells of no biofilm forming strains to develop into pseudohyphae and/or hyphae. Thus, environmental conditions can significantly affect the amount of biofilm formation and cell morphology of C. parapsilosis with Mn2+ to overcome developmental blocks to trigger biofilm formation and to partially relieve BCR1 suppressed cell differentiation.
From enhanceropathies to the epigenetic manifold underlying human cognition
Authors: Vitriolo Alessandro , Gabriele Michele , Testa Giuseppe
Published: August 2019

A vast portion of intellectual disability and autism spectrum disorders is genetically caused by mutations in chromatin modulators. These proteins play key roles in development and are also highly expressed in the adult brain. Specifically, the pivotal role of chromatin regulation in transcription has placed enhancers at the core of neurodevelopmental disorders (NDDs) studies, ushering in the coining of the term enhanceropathies. The convergence of these disorders is multilayered, spanning from molecular causes to pathophysiological traits, including extensive overlaps between enhanceropathies and neurocristopathies. The reconstruction of epigenetic circuitries wiring development and underlying cognitive functions has gone hand in hand with the development of tools that increase the sensitivity of identifying regulatory regions and linking enhancers to their target genes. The available models, including loop extrusion and phase separation, have been bringing into relief complementary aspects to interpret gene regulation datasets, reinforcing the idea that enhancers are not all the same and that regulatory regions possess shades of enhancer-ness and promoter-ness. The current limits in enhancer definition, within the emerging broader understanding of chromatin dynamics in time and space, are now on the verge of being transformed by the possibility to interrogate developmentally relevant three-dimensional cellular models at single-cell resolution. Here we discuss the contours of how these technological advances, as well as the epistemic limitations they are set to overcome, may well usher in a change of paradigm for NDDs, moving the quest for convergence from enhancers to the four-dimensional (4D) genome.
Venous pectoralis minor syndrome: a rare subdivision of the thoracic outlet syndrome
Authors: Elsayed Hany Hasan , Soliman Saleh , Hamed Ahmed Magdy , El-Saqqa Asser , Hussein Ahmed Tarek , BinMelhi Edhah , Nassar Wael A M
Published: August 2019

We analysed data of all patients who had received surgery for rare, isolated venous pectoralis minor syndrome at our tertiary institution from January 2015 to December 2018. Venous duplex scan was the preferred mode of diagnosis in all our patients. We operated on patients via a 5–6 cm deltopectoral groove incision. Ten procedures were performed on 6 patients, of whom 5 were female. The median age was 23 years (range 17–33 years). Three patients (2 female, 1 male) with bilateral pectoralis minor syndrome had separate procedures performed over a course of a few weeks. The median operating time was 22 min (range 15–95 min). Median blood loss was 20 ml (range 5–410 ml). The median hospital stay was 2 days (range 1–5 days). There was one complication in the form of a recurrence on the right side in a patient who had bilateral pectoralis minor syndrome. No other morbidities were recorded. Nine of 10 procedures (90%) were classified by patients as being satisfactory, where symptoms had partially or completely resolved. Our experience emphasizes the need for a systematic search and to maintain a high index of suspicion for venous pectoralis minor syndrome in all patients complaining of painful symptoms related to thoracic outlet syndrome. The deltopectoral groove approach is a simple and straightforward incision with a gentle learning curve.
Genetic Mapping with Background Control for Quantitative Trait Locus (QTL) in 8-Parental Pure-Line Populations
Authors: Shi Jinhui , Wang Jiankang , Zhang Luyan
Published: August 2019

Multiparental advanced generation intercross (MAGIC) populations provide abundant genetic variation for use in plant genetics and breeding. In this study, we developed a method for quantitative trait locus (QTL) detection in pure-line populations derived from 8-way crosses, based on the principles of inclusive composite interval mapping (ICIM). We considered 8 parents carrying different alleles with different effects. To estimate the 8 genotypic effects, 1-locus genetic model was first built. Then, an orthogonal linear model of phenotypes against marker variables was established to explain genetic effects of the locus. The linear model was estimated by stepwise regression and finally used for phenotype adjustment and background genetic variation control in QTL mapping. Simulation studies using 3 genetic models demonstrated that the proposed method had higher detection power, lower false discovery rate (FDR), and unbiased estimation of QTL locations compared with other methods. Marginal bias was observed in the estimation of QTL effects. An 8-parental recombinant inbred line (RIL) population previously reported in cowpea and analyzed by interval mapping (IM) was reanalyzed by ICIM and genome-wide association mapping implemented in software FarmCPU. The results indicated that ICIM identified more QTLs explaining more phenotypic variation than did IM; ICIM provided more information on the detected QTL than did FarmCPU; and most QTLs identified by IM and FarmCPU were also detected by ICIM.
The dust in M31
Authors: Whitworth A P , Marsh K A , Cigan P J , Dalcanton J J , Smith M W L , Gomez H L , Lomax O , Griffin M J , Eales S A
Published: August 2019

We have analysed Herschel observations of M31, using the ppmap procedure. The resolution of ppmap images is sufficient ($\sim 31\, {\rm pc}$ on M31) that we can analyse far-IR dust emission on the scale of giant molecular clouds. By comparing ppmap estimates of the far-IR emission optical depth at $300\, \mu {\rm m}\, (\tau _{{300}})$, and the near-IR extinction optical depth at $1.1\, \mu {\rm m}\, (\tau _{{1.1}})$ obtained from the reddening of Red Giant Branch (RGB) stars, we show that the ratio ${\cal R}^{\mathrm{ obs.}}_\tau \equiv \tau _{{1.1}}/\tau _{{300}}$ falls in the range $500\lesssim {\cal R}^{\mathrm{ obs.}}_\tau \lesssim 1500$. Such low values are incompatible with many commonly used theoretical dust models, which predict values of ${\cal R}^{\mathrm{ model}}_\kappa \equiv \kappa _{{1.1}}/\kappa _{{300}}$ (where κ is the dust opacity coefficient) in the range $2500\lesssim {\cal R}^{\mathrm{ model}}_\kappa \lesssim 4000$. That is, unless a large fraction, $\gtrsim 60{{\ \rm per\ cent}}$, of the dust emitting at $300\, \mu {\rm m}$ is in such compact sources that they are unlikely to intercept the lines of sight to a distributed population like RGB stars. This is not a new result: variants obtained using different observations and/or different wavelengths have already been reported by other studies. We present two analytic arguments for why it is unlikely that $\gtrsim 60{{\ \rm per\ cent}}$ of the emitting dust is in sufficiently compact sources. Therefore it may be necessary to explore the possibility that the discrepancy between observed values of ${\cal R}^{\mathrm{ obs.}}_\tau$ and theoretical values of ${\cal R}^{\mathrm{ model}}_\kappa$ is due to limitations in existing dust models. ppmap also allows us to derive optical-depth weighted mean values for the emissivity index, β ≡ −dln (κλ)/dln (λ), and the dust temperature, T, denoted ${\bar{\beta }}$ and ${\bar{T}}$. We show that, in M31, ${\cal R}^{\mathrm{ obs.}}_\tau$ is anticorrelated with ${\bar{\beta }}$ according to ${\cal R}^{\mathrm{ obs.}}_\tau \simeq 2042(\pm 24)-557(\pm 10){\bar{\beta }}$. If confirmed, this provides a challenging constraint on the nature of interstellar dust in M31.
Simultaneous calibration of spectro-photometric distances and the Gaia DR2 parallax zero-point offset with deep learning
Authors: Leung Henry W , Bovy Jo
Published: August 2019

Gaia measures the five astrometric parameters for stars in the Milky Way, but only four of them (positions and proper motion, but not distance) are well measured beyond a few kpc from the Sun. Modern spectroscopic surveys such as APOGEE cover a large area of the Milky Way disc and we can use the relation between spectra and luminosity to determine distances to stars beyond Gaia’s parallax reach. Here, we design a deep neural network trained on stars in common between Gaia and APOGEE that determines spectro-photometric distances to APOGEE stars, while including a flexible model to calibrate parallax zero-point biases in Gaia DR2. We determine the zero-point offset to be $-52.3 \pm 2.0\, \mu \mathrm{as}$ when modelling it as a global constant, but also train a multivariate zero-point offset model that depends on G, GBP − GRP colour, and Teff and that can be applied to all ≈58 million stars in Gaia DR2 within APOGEE’s colour–magnitude range and within APOGEE’s sky footprint. Our spectro-photometric distances are more precise than Gaia at distances ${\gtrsim} 2\, \mathrm{kpc}$ from the Sun. We release a catalogue of spectro-photometric distances for the entire APOGEE DR14 data set which covers Galactocentric radii $2\, \mathrm{kpc} \lesssim R \lesssim 19\, \mathrm{kpc}$; ${\approx} 150\, 000$ stars have ${\lt} 10{{\ \rm per\ cent}}$ uncertainty, making this a powerful sample to study the chemo-dynamical structure of the disc. We use this sample to map the mean [Fe/H] and 15 abundance ratios [X/Fe] from the Galactic Centre to the edge of the disc. Among many interesting trends, we find that the bulge and bar region at $R \lesssim 5\, \mathrm{kpc}$ clearly stands out in [Fe/H] and most abundance ratios.
Testing the blast-wave AGN feedback scenario in MCG-03-58-007
Authors: Sirressi M , Cicone C , Severgnini P , Braito V , Dotti M , Della Ceca R , Reeves J N , Matzeu G A , Vignali C , Ballo L
Published: August 2019

We report the first Atacama large millimeter/submillimeter array observations of MCG-03-58-007, a local (z = 0.03236 ± 0.00002, this work) AGN ($L_{\mathrm{ AGN}\mathrm{ }}\sim 10^{45}~\rm erg~s^{-1}$), hosting a powerful X-ray ultrafast (v = 0.1c) outflow (UFO). The CO(1-0) line emission is observed across ∼18 kpc scales with a resolution of $\sim 1\, \rm kpc$. About 78 per cent of the CO(1-0) luminosity traces a galaxy-size rotating disc. However, after subtracting the emission due to such rotating disc, we detect with a S/N = 20 a residual emission in the central ∼4 kpc. Such residuals may trace a low velocity (vLOS = 170 km s−1) outflow. We compare the momentum rate ($\dot{P}$) and kinetic power ($\dot{E}$) of such putative molecular outflow with that of the X-ray UFO and find $\dot{P}_{\mathrm{ mol}}/\dot{P}_{\mathrm{ UFO}}\sim 0.4$ and $\dot{E}_{\mathrm{ mol}}/\dot{E}_{\mathrm{ UFO}}\sim 4\times 10^{-3}$. This result is at odds with the energy-conserving scenario suggested by the large momentum boosts measured in some other molecular outflows. An alternative interpretation of the residual CO emission would be a compact rotating structure, distinct from the main disc, which would be a factor of ∼10–100 more extended and massive than typical circumnuclear discs revealed in Seyferts. In conclusion, in both scenarios, our results rule out the hypothesis of a momentum-boosted molecular outflow in this AGN, despite the presence of a powerful X-ray UFO.
The frequency of Kozai–Lidov disc oscillation driven giant outbursts in Be/X-ray binaries
Authors: Martin Rebecca G , Franchini Alessia
Published: August 2019

Giant outbursts of Be/X-ray binaries may occur when a Be-star disc undergoes strong eccentricity growth due to the Kozai–Lidov (KL) mechanism. The KL effect acts on a disc that is highly inclined to the binary orbital plane provided that the disc aspect ratio is sufficiently small. The eccentric disc overflows its Roche lobe and material flows from the Be star disc over to the companion neutron star causing X-ray activity. With N-body simulations and steady state decretion disc models we explore system parameters for which a disc in the Be/X-ray binary 4U 0115+634 is KL unstable and the resulting time-scale for the oscillations. We find good agreement between predictions of the model and the observed giant outburst time-scale provided that the disc is not completely destroyed by the outburst. This allows the outer disc to be replenished between outbursts and a sufficiently short KL oscillation time-scale. An initially eccentric disc has a shorter KL oscillation time-scale compared to an initially circular orbit disc. We suggest that the chaotic nature of the outbursts is caused by the sensitivity of the mechanism to the distribution of material within the disc. The outbursts continue provided that the Be star supplies material that is sufficiently misaligned to the binary orbital plane. We generalize our results to Be/X-ray binaries with varying orbital period and find that if the Be star disc is flared, it is more likely to be unstable to KL oscillations in a smaller orbital period binary, in agreement with observations.
Choice of endpoint in kidney outcome trials: considerations from the EMPA-REG OUTCOME® trial
Authors: Perkovic Vlado , Koitka-Weber Audrey , Cooper Mark E , Schernthaner Guntram , Pfarr Egon , Woerle Hans J , von Eynatten Maximilian , Wanner Christoph
Published: August 2019

Background

Doubling of serum creatinine [equivalent to 57% reduction in estimated glomerular filtration rate (eGFR)] is an established surrogate for end-stage kidney disease (ESKD); however, this endpoint necessitates lengthy follow-up and large sample sizes in clinical trials. We explored whether alternative eGFR decline thresholds provide more feasible surrogate kidney endpoints.

Methods

The study involved post hoc analysis of the EMPA-REG OUTCOME® trial. Adults with type 2 diabetes, high cardiovascular risk and eGFR ≥30 mL/min/1.73 m2 were assigned empagliflozin 10 mg or 25 mg (n = 4687) or placebo (n = 2333), on top of standard of care. We assessed composite endpoints incorporating different eGFR decline thresholds (≥30, ≥40, ≥50 or ≥57%) combined with initiation of renal replacement therapy (RRT) or renal death. This trial is registered with ClinicalTrials.gov (NCT01131676).

Results

Empagliflozin versus placebo significantly lowered the risk of decline in eGFR for each threshold listed above, combined with initiation of RRT or renal death, ranging from a hazard ratio (HR) of 0.81 [95% confidence interval (CI) 0.72–0.91] for endpoints based on 30% eGFR decline to an HR of 0.37 (0.23–0.61) for endpoints based on 57% eGFR decline. Lower thresholds (e.g. 30%) were associated with higher event rates but weaker treatment effects. The time to the 95% CI of the HR falling to <1.0 decreased with increasing eGFR threshold.

Conclusions

The composite of 40% decline in eGFR, ESKD or renal death appears to provide reliable results similar to the traditional 57% decline in eGFR.
BSCI-18. ABLATION OF Csf2 MITIGATES RADIATION-INDUCED NEUROCOGNITIVE DECLINE INDEPENDENT OF HIPPOCAMPAL NEUROGENESIS
Authors: Gokhan Sölen , Aronson Kyle , Altun Yagiz , Chitu Violeta , Brodin N Patrik , Stanley E Richard , Mehler Mark , Tomé Wolfgang
Published: August 2019

PURPOSE: The results of the RTOG 0933 and NRG CC001 clinical trials have shown that physical sparing of the hippocampus during cranial irradiation (CI) is associated with preservation of memory functions at 4- and 6-months following therapy. Whereas the putative roles of protection of neural stem cells (NSCs) residing within the subgranular zone (SGZ) of the dentate gyrus are presently poorly defined, suppression of inflammation may be involved because ablation of microglia (MG) through blockade of the CSF-1R or selective targeting of CCR2+ macrophages using an appropriate CCR2 inhibitor leads to the retention of hippocampal-dependent cognitive abilities following CI. Inhibition of Colony stimulating factor 2 (CSF-2), a proinflammatory cytokine causing the proliferation and activation of microglia, may be a suitable alternative strategy to alleviate inflammation. METHODS: Our studies have evaluated the effects of ablation of Csf2 and also the inducible ablation of MG on the properties of neuroinflammation, neurogenesis and CI-associated cognitive impairments employing the requisite mouse models. RESULTS: We demonstrate that preservation of cognitive functions following CI does not require ablation of MG. In addition, the reduction in neuroinflammation following Csf2ablation was sufficient to prevent CI-induced cognitive decline. Moreover, Csf2 ablation did not prevent the deficit in neurogenesis, thereby suggesting that NSC-mediated SGZ neurogenesis is not required for the prevention of radiation-induced cognitive dysfunction. CONCLUSION: We have previously shown that MG play seminal roles in neural development and adult homeostasis and plasticity. Our present study demonstrates that selective modulation of MG-associated neuroinflammatory signaling without MG ablation is a novel therapeutic strategy to preserve cognitive functions following CI. These experimental observations have seminal implications for patients undergoing radiation therapy for tumors of the brain or head and neck in which the hippocampus inevitably exposed to a high dose of radiation leading to potentially debilitating and possibly avoidable cognitive deficits.
BSCI-20. THERAPEUTIC TARGETING OF HLA-G IN BRAIN METASTASES
Authors: Singh Sheila , Bassey-Archibong Blessing , Aghaei Nikoo , Kieliszek Agata , Venugopal Chitra , Chokshi Chirayu , Savage Neil
Published: August 2019

Brain metastases (BM) are the most common brain tumor in adults, with an incidence ten times greater than that of primary brain tumors. The most common sources of BM in adult cancer patients include cancers of the lung, breast and melanoma, which together account for almost 80% of all BM. Current clinical modalities for BM include surgery, whole brain radiation therapy and stereotactic radiosurgery but these therapies still offer limited efficacy and reduced survival of only months in treated patients, emphasizing the need for novel BM research approaches and better therapeutic strategies. Our laboratory recently discovered that stem-like cells exist in patient-derived BM from lung, breast and melanoma cancers, which we termed “brain metastasis-initiating cells” or BMICs. Through clinically relevant human-mouse xenograft models established with these patient-derived BMICs, we captured lung, breast and melanoma BMICs at pre-metastasis – a key stage where circulating metastatic cells extravasate and initially seed the brain, prior to organization into micro-metastatic foci. Transcriptome analysis of pre-metastatic BMICs revealed a unique genetic profile and several genes commonly up-regulated among lung, breast and melanoma BM, including the non-classical human leukocyte class I antigen-G (HLA-G). Loss of HLA-G in lung, breast and melanoma BMICs using two HLA-G specific shRNAs attenuated sphere formation, migratory and tumor initiating abilities of lung, breast and melanoma BMICs compared to control BMICs. HLA-G knockdown also resulted in reduced phospho(p)-STAT3 expression in patient-derived BMICs suggesting a potential cooperative role between HLA-G and pSTAT3 in BM. Since HLA-G is highly expressed at the cell surface in control tumors, ongoing experiments are focused on developing HLA-G specific chimeric antigen receptor -T cells (CAR-Ts) and determining their efficacy in targeting lung-, breast- and melanoma-BM as blocking the brain metastatic process will markedly extend patient survival and ultimately transform a fatal systemic disease into a more treatable one.
BSCI-27. MELATONIN REDUCES MALIGNANCY OF BREAST CANCER BRAIN METASTATIC CELLS
Authors: Gil Beatriz Fernandez , Rodriguez Katherine , Schiapparelli Paula , Ramos Carla Vazquez , Escames Germaine , Quinones-Hinojosa Alfredo , Sarabia-Estrada Rachel
Published: August 2019

Around fifteen to thirty percent of stage IV breast cancer metastasizes to the brain, severely decreasing the quality of life of these patients by causing neurological decline and eventually death. In metastatic cancers there is a small subset of cells in the primary tumor bulk called Metastatic Tumor Initiating Cells (MTICs) which are able to escape and produce a niche establishment at distal sites where they can quickly become resistant to surgery and radiation. Melatonin has shown an inhibitory role in the viability and invasiveness of breast cancer and in modulating the expression of proteins related to Breast Cancer Stem Cells (BCSCs). These findings suggest its potential anti-metastatic role in different breast cancer cell lines. In this study we aimed to evaluate the effects of melatonin treatment in vitro for breast cancer brain metastasis. The cell line MDA-BT was originally obtained from MDA-MB-231, passed through the rat’s heart and then isolated once engrafted as a tumor in the brain. After a dose response assay, cells were treated with melatonin at doses of 1500 and 3000 µM for 48hrs. Clonogenic assay, MTT, as well as a stem cell signature through RT-qPCR, including CD44, CD24 and ALDH1 markers, were performed to evaluate the malignancy of the MTICs. The results showed that melatonin at high doses impacts morphology, declines viability, reduces colony formation ability, and decreases stemness in MDA-BT cells. Therefore, our findings highlight melatonin as a relevant therapeutic candidate to target breast cancer brain metastases.
LPTO-01. LEPTOMENINGEAL METASTASIS FROM OVARIAN CARCINOMA TREATED WITH SYSTEMIC HIGH-DOSE METHOTREXATE
Authors: Coffee Elizabeth , Lobbous Mina , Nabors L Burt
Published: August 2019

BACKGROUND: Central nervous system metastasis in ovarian cancer is reported in approximately 1% of cases and typically localizes to the parenchyma. Leptomeningeal disease (LMD) is exceedingly rare. Prognosis is extremely poor with median survival of 60 days. Given the rarity of LMD in ovarian cancers, there is no consensus on the optimal treatment approach. High-dose systemic methotrexate (HD-MTX) has been studied in LMD. CASE REPORT: A 41-year-old Caucasian woman with a history of BRCA-positive stage IIIC ovarian carcinoma who was treated with cytoreduction and multiple rounds of intravenous and intraperitoneal chemotherapy presented to the emergency room with progressive headaches, vomiting and neck pain. Contrasted MRI of the brain showed nodular enhancement along the cerebellar folia, concerning for leptomeningeal disease. Cerebrospinal fluid cytology analysis was positive for malignancy and she was diagnosed with leptomeningeal metastasis 2.5 years after her diagnosis with ovarian carcinoma. Induction therapy with systemic HD-MTX was given every other week and complete response was achieved after two induction cycles. Serum CA-125 level decreased from 565.7 U/mL (prior to treatment) to 50.4 U/ML after the sixth induction cycle and she was transitioned to maintenance HD-MTX. Approximately 6 months after initiation of HD-MTX, contrasted MRI demonstrated LMD recurrence with corresponding rise in CA-125 to 395 U/mL. Whole body CT imaging did not show local disease recurrence. Temozolomide was added to the HD-MTX regimen and craniospinal radiation therapy was planned but her neurologic condition continued to decline. She died 8 months after her diagnosis of LMD. CONCLUSION: LMD has a dismal prognosis. HD-MTX may prolong the overall survival in patients with LMD secondary to ovarian carcinoma. In these patients, serum CA-125 level may serve as a biomarker for monitoring CNS disease burden. Due to the rarity of LMD, multi-institutional prospective studies are needed to explore novel therapeutics in LMD.
LPTO-06. A NOVEL BRAIN-PERMEANT CHEMOTHERAPEUTIC AGENT FOR THE TREATMENT OF BREAST CANCER LEPTOMENINGEAL METASTASIS
Authors: Deng Jiaojiao , Chernikova Sophia , Fischer Wolf-Nicolas , Koller Kerry , Jandeleit Bernd , Ringold Gordon , Gephart Melanie
Published: August 2019

Leptomeningeal metastasis (LM), a spread of cancer to the cerebrospinal fluid and meninges, is universally and rapidly fatal due to poor detection and no effective treatment. Breast cancers account for a majority of LMs from solid tumors, with triple-negative breast cancers (TNBCs) having the highest propensity to metastasize to LM. The treatment of LM is challenged by poor drug penetration into CNS and high neurotoxicity. Therefore, there is an urgent need for new modalities and targeted therapies able to overcome the limitations of current treatment options. Quadriga has discovered a novel, brain-permeant chemotherapeutic agent that is currently in development as a potential treatment for glioblastoma (GBM). The compound is active in suppressing the growth of GBM tumor cell lines implanted into the brain. Radiolabel distribution studies have shown significant tumor accumulation in intracranial brain tumors while sparing the adjacent normal brain tissue. Recently, we have demonstrated dose-dependent in vitro and in vivo anti-tumor activity with various breast cancer cell lines including the human TNBC cell line MDA-MB-231. To evaluate the in vivo antitumor activity of the compound on LM, we used the mouse model of LM based on the internal carotid injection of luciferase-expressing MDA-MB-231-BR3 cells. Once the bioluminescence signal intensity from the metastatic spread reached (0.2 - 0.5) x 106 photons/sec, mice were dosed i.p. twice a week with either 4 or 8 mg/kg for nine weeks. Tumor growth was monitored by bioluminescence. The compound was well tolerated and caused a significant delay in metastatic growth resulting in significant extension of survival. Tumors regressed completely in ~ 28 % of treated animals. Given that current treatments for LM are palliative with only few studies reporting a survival benefit, Quadriga’s new agent could be effective as a therapeutic for both primary and metastatic brain tumors such as LM. REF: https://onlinelibrary.wiley.com/doi/full/10.1002/pro6.43