bluuebunny/crossref_metadata_2025 huggingface dataset:
Getting Ready for TESS: an On-hand Software Tutorial
Authors: Burt J. , Barclay T.
Published: August 2019

The launch of NASA’s next exoplanet mission, the Transiting Exoplanet Survey Satellite (TESS), took place successfully on 2018 April 18, and has now commenced science operations. TESS is specifically designed to search for exoplanets transiting the closest and brightest stars using high-cadence photometric measurements. The images employed for detecting those planets can also be used for a wide variety of time-domain astronomy, especially when considering the full-frame images that TESS takes every 30 minutes. This (pre-launch) workshop familiarised participants with the details of how TESS will operate, described the expected data products and how to access them, introduced the software suite PyKE, which can be used to analyse TESS data, and highlighted ways for participants to request additional TESS targets.
25 Years of the Southern Skies Monitoring by OGLE
Authors: Wyrzykowski Ł. , Pietrukowicz P. ,   OGLE
Published: August 2019

The Optical Gravitational Lensing Experiment (OGLE) started at Las Campanas Observatory in 1992 with a pilot monitoring programme of two million stars in the Galactic Bulge. It is still operating today, collecting time-domain photometric data of a billion stars from the densest regions in the southern sky. Among its main achievements are discoveries of thousands of microlensing events, a few dozen extrasolar planets and candidates for black holes, a million variable stars, and thousands of quasars and supernovæ. It has made a major contribution to the studies of the dark-matter content of the Milky Way halo, the structure of the Galactic Bulge, the Magellanic Clouds, and new classes of variable stars. In this its 25th anniversary year, we presented a selection of the major scientific highlights of OGLE.
Accessing Data for Long-Term Variability
Authors: Griffin E. , Balona L.
Published: August 2019

Astronomy’s heritage, comprised mainly of several million photographic plates (both images and spectra), extends backwards in time for many decades. It constitutes a unique and irreplaceable resource for research into long-term variations. Unfortunately, to date rather few of the plates can be accessed in digital formats and cannot therefore be used in modern research. That lack of use encourages the attitude that ‘old’ data have no value and might as well be destroyed. This Workshop discussed ways and means to avert such threats, and prioritised a list of actions that need to be taken as soon as possible.
Testing the SALT High-Resolution Spectrograph for Pulsation Studies of roAp Stars
Authors: Holdsworth D. , Kurtz D.
Published: August 2019

We present the first time-resolved spectroscopic observations, made with the SALT HRS instrument, of a rapidly oscillating Ap star. We used the instrument in the High Stability mode, with the fastest readout settings – a setup never previously used. Over a 2.5-hr track length, we obtained 280 spectra at 8-second integration times and a cadence of 30 seconds. The target, α Circini, is the brightest of the roAp stars, and thus provides an excellent opportunity to test the instrument. Previous time-resolved spectroscopic studies of this star have been conducted by Kurtz, Elkin & Mathys† with the VLT/UVES instrument, and by Mkrtichian & Hatzes‡ with the HARPS instrument on the ESO 3.6-m telescope. Those two studies provide us with benchmarks to compare the performance of SALT/HRS for this type of project. With the upcoming TESS mission, the ability to perform high-precision, time-resolved spectroscopy of pulsating stars will be key for the scientific output of SALT.
The Beijing Twin Study (BeTwiSt): An Update
Authors: Bi Dandan , Li Xinying , Chen Jie , Jiang Nengzhi , Zhang Jianxin
Published: August 2019

The Beijing Twin Study (BeTwiSt), which was established in 2006, is an ongoing study aiming to investigate the genetic and environmental etiology of adolescent psychopathology. Resting-state brain imaging datasets have been examined for same-sex twins, and other psychological traits and emotional and behavioral variables have been examined for all twins. Based on the registry, the main findings regarding the etiological mechanism underlying adolescent development, magnetic resonance imaging results, and genetic and environmental influences on other psychological traits have been published. This article summarizes the key findings in these three areas and discusses future plans for the BeTwiSt.
Timing-Dependent Priming Effects of Anodal tDCS on Two-Hand Coordination
Authors: Azarpaikan Atefeh , Torbati Hamid Reza Taherii , Sohrabi Mehdi , Boostani Reza , Ghoshoni Majid
Published: August 2019

Abstract. The aim of study was to investigate the interaction of time of applying anodal transcranial direct current stimulation (tDCS) with motor learning using a two-hand coordination (THC) task. Sixty-four healthy participants were tested under four stimulation conditions: anodal tDCS a head of the motor task, anodal tDCS during the motor task, anodal tDCS following the motor task, and sham tDCS. Transcranial direct current stimulation (tDCS) stimulation was applied on cerebellum by using a weak direct current (15 min) of 1.5 mA generated by a battery and regulated by the drive stimulator. The results show that on-line learning increased in the anodal tDCS-during group ( p = .039). The anodal tDCS-after group relied more on off-line learning ( p = .05). The during-tDCS and after-tDCS groups achieved greater improvements in speed/accuracy than the before-tDCS and sham-tDCS groups. The cerebellar tDCS may play a significant role to speed up motor skill acquisition and improve motor skill accuracy.
Emotional Valence Modulates Low Beta Suppression and Recognition of Social Interactions
Authors: Berntsen Monica B. , Cooper Nicholas R. , Romei Vincenzo
Published: August 2019

Abstract. Emotional valence may have evolutionary adaptive purposes as negative stimuli can be related to survival against threat and positive stimuli to facilitating relationships. This can be seen in the different impact positive and negative stimuli have on human health and well-being, and in the valence-specific cortical activity and neurophysiological patterns reported; for example, negative stimuli are processed more rapidly than positive. Valence-specific patterns are affected by individual differences and personality traits such as empathy, where levels of empathy relate to different reactivity patterns to valence. Here we investigated the effect of valence on neurophysiological responses and interpretation of social interactions depicted by point-light biological motion (PLBM) displays. The meaning of each PLBM display is revealed as the sequence unfolds and is therefore not readily available for snap assessments such as fight or flight responses. We compared electroencephalogram (EEG) reactivity during observation of the displays between individuals with low, moderate, or high levels of empathy. Results indicated that positive displays induced significantly larger suppression in lower beta (13–20 Hz) compared to control displays, while negative displays revealed no difference in suppression compared to scrambled versions. However, no difference between positive and negative displays was observed, suggesting that the rapid processing of negative displays may have been minimized by revealing meaning more slowly. Positive displays were interpreted more accurately, while levels of empathy did not modulate either neurophysiological responses or interpretation, suggesting that empathy under these conditions did not influence the way in which valence was processed or interpreted.
Effectiveness of Programs for the Prevention of Child Sexual	Abuse
Authors: Del Campo Amaia , Fávero Marisalva
Published: August 2019

Abstract. During the last decades, several studies have been conducted on the effectiveness of sexual abuse prevention programs implemented in different countries. In this article, we present a review of 70 studies (1981–2017) evaluating prevention programs, conducted mostly in the United States and Canada, although with a considerable presence also in other countries, such as New Zealand and the United Kingdom. The results of these studies, in general, are very promising and encourage us to continue this type of intervention, almost unanimously confirming its effectiveness. Prevention programs encourage children and adolescents to report the abuse experienced and they may help to reduce the trauma of sexual abuse if there are victims among the participants. We also found that some evaluations have not considered the possible negative effects of this type of programs in the event that they are applied inappropriately. Finally, we present some methodological considerations as critical analysis to this type of evaluations.
Clinically Meaningful Change
Authors: Ferrer Rodrigo , Pardo Antonio
Published: August 2019

Abstract. In a recent paper, Ferrer and Pardo (2014) tested several distribution-based methods designed to assess when test scores obtained before and after an intervention reflect a statistically reliable change. However, we still do not know how these methods perform from the point of view of false negatives. For this purpose, we have simulated change scenarios (different effect sizes in a pre-post-test design) with distributions of different shapes and with different sample sizes. For each simulated scenario, we generated 1,000 samples. In each sample, we recorded the false-negative rate of the five distribution-based methods with the best performance from the point of view of the false positives. Our results have revealed unacceptable rates of false negatives even with effects of very large size, starting from 31.8% in an optimistic scenario (effect size of 2.0 and a normal distribution) to 99.9% in the worst scenario (effect size of 0.2 and a highly skewed distribution). Therefore, our results suggest that the widely used distribution-based methods must be applied with caution in a clinical context, because they need huge effect sizes to detect a true change. However, we made some considerations regarding the effect size and the cut-off points commonly used which allow us to be more precise in our estimates.
Assessing the Quality and Effectiveness of the Factor Score Estimates	in Psychometric Factor-Analytic Applications
Authors: Ferrando Pere J. , Navarro-González David , Lorenzo-Seva Urbano
Published: August 2019

Abstract. This article proposes an approach, intended for factor-analytic (FA) psychometric applications, which aims to assess the extent to which the FA-derived individual score estimates are accurate and allow the respondents to be consistently ordered and effectively differentiated over the range of trait values that is appropriate given the purposes of the test. Three groups of properties are assessed: (a) fineness, (b) probability, and (c) range, and, within each group, different indices are proposed. Overall, the proposal is comprehensive in that it can be used with (a) different factor score estimates derived from both the linear model and the categorical variable methodology model, and (b) any type of unrestricted or restricted FA solution. All the indices proposed have been implemented in a non-commercial and widely known program for exploratory factor analysis. The usefulness of the proposal is illustrated with a real-data example in the personality domain.
Long‐Term Wetting and Drying Trends in Land Water Storage Derived From GRACE and CMIP5 Models
Authors: Jensen L. , Eicker A. , Dobslaw H. , Stacke T. , Humphrey V.
Published: August 2019

Coupled climate models participating in the CMIP5 (Coupled Model Intercomparison Project Phase 5) exhibit a large intermodel spread in the representation of long‐term trends in soil moisture and snow in response to anthropogenic climate change. We evaluate long‐term (January 1861 to December 2099) water storage trends from 21 CMIP5 models against observed trends in terrestrial water storage (TWS) obtained from 14 years (April 2002 to August 2016) of the GRACE (Gravity Recovery And Climate Experiment) satellite mission. This is complicated due to the incomplete representation of TWS in CMIP5 models and interannual climate variability masking long‐term trends in observations. We thus evaluate first the spread in projected trends among CMIP5 models and identify regions of broad model consensus. Second, we assess the extent to which these projected trends are already present during the historical period (January 1861 to August 2016) and thus potentially detectable in observational records available today. Third, we quantify the degree to which 14‐year tendencies can be expected to represent long‐term trends, finding that regional long‐term trends start to emerge from interannual variations after just 14 years while stable global trend patterns are detectable after 30 years. We classify regions of strong model consensus into areas where (1) climate‐related TWS changes are supported by the direction of GRACE trends, (2) mismatch of trends hints at possible model deficits, (3) the short observation time span and/or anthropogenic influences prevent reliable conclusions about long‐term wetting or drying. We thereby demonstrate the value of satellite observations of water storage to further constrain the response of the terrestrial water cycle to climate change.
Potential Influence of Climate Change on Grain Self‐Sufficiency at the Country Level Considering Adaptation Measures
Authors: Wei Taoyuan , Zhang Tianyi , Cui Xuefeng , Glomsrød Solveig , Liu Yu
Published: August 2019

In recent decades, grain self‐sufficiency has been a key security issue for certain countries, such as Russia, China, India, and France. Climate change may affect agricultural production and possibly influence the grain self‐sufficiency of some countries, threatening their food security. This article provides an updated integrated assessment of the impact of climate change on grain self‐sufficiency at the country level. The study links climatic variables projected by global climate models to economic variables simulated by a global multiregion multisector economic model. Although climate change may considerably reduce land productivity, our simulation results show that climate change in the long term modestly impacts regional grain self‐sufficiency, as the direct effects on yield are largely canceled out by changes in grain production via adaptation measures taken by producers in response to market signals. Behavioral changes of consumers also contribute modestly to cancel out the adverse impact on land productivity. In the RCP8.5 climate change scenario, the adverse impact of climate change on land productivity in 2100 may reach to 25% of the current level, but declines to 5% when changes in production and consumption are considered, thus indicating the role of long‐term adaptation by economic agents.
Scientists Share Results of Dust Belt Research
Authors: Althausen Dietrich , Abdullaev Sabur , Hofer Julian
Published: August 2019

Central Asian Dust Conference; Dushanbe, Tajikistan, 8–12 April 2019
The Effects of Crustal Magnetic Fields and Solar EUV Flux on Ionopause Formation at Mars
Authors: Chu F. , Girazian Z. , Gurnett D. A. , Morgan D. D. , Halekas J. , Kopf A. J. , Thiemann E. M. B. , Duru F.
Published: August 2019

We study the ionopause of Mars using a database of 6,893 ionopause detections obtained over 11 years by the MARSIS (Mars Advanced Radar for Subsurface and Ionosphere Sounding) experiment. The ionopause, in this work, is defined as a steep density gradient that appears in MARSIS remote sounding ionograms as a horizontal line at frequencies below 0.4 MHz. We find that the ionopause is located on average at an altitude of 363±65 km. We also find that the ionopause altitude has a weak dependence on solar zenith angle and varies with the solar extreme ultraviolet (EUV) flux on annual and solar cycle time scales. Furthermore, our results show that very few ionopauses are observed when the crustal field strength at 400 km is greater than 40 nT. The strong crustal fields act as minimagnetospheres that alter the solar wind interaction and prevent the ionopause from forming.
Nighttime Magnetic Perturbation Events Observed in Arctic Canada: 2. Multiple‐Instrument Observations
Authors: Engebretson M. J. , Steinmetz E. S. , Posch J. L. , Pilipenko V. A. , Moldwin M. B. , Connors M. G. , Boteler D. H. , Mann I. R. , Hartinger M. D. , Weygand J. M. , Lyons L. R. , Nishimura Y. , Singer H. J. , Ohtani S. , Russell C. T. , Fazakerley A. , Kistler L. M.
Published: August 2019

The rapid changes of magnetic fields associated with nighttime magnetic perturbations with amplitudes |ΔB| of hundreds of nanoteslas and 5‐ to 10‐min periods can induce bursts of geomagnetically induced currents that can harm technological systems. This paper presents three cases of intervals of intense and complex nighttime magnetic perturbations in eastern Arctic Canada in 2015, augmented by observations from auroral imagers and high‐altitude spacecraft in the nightside magnetosphere. Each case occurred within 1 hr after substorm onsets. None occurred during the main phase of a geomagnetic storm, and only the first during the early recovery phase (of a moderate storm). The cases were similar in that two or three intervals occurred in this region over a span of ~1 hr; these showed a spatial progression, in that successive intervals occurred later at more western and northern stations. During several intervals, individual peak Bx impulses occurred nearly simultaneously (within 1–2 min) at several stations, while during others the impulses occurred later at more western and northern stations, and during one interval they occurred later at southern stations. During both of the cases for which auroral images were available, a westward traveling surge and a poleward auroral expansion and/or poleward boundary intensification occurred, and during two events auroral streamers coincided in time and location with magnetic perturbations. These observations appear to be consistent with several earlier studies connecting nighttime magnetic perturbation events to localized auroral structures and to dipolarizing flux bundles and bursty bulk flows in the magnetotail.
Isopycnal Mixing in the North Atlantic Oxygen Minimum Zone Revealed by RAFOS Floats
Authors: Rudnickas Donald , Palter Jaime , Hebert David , Rossby H. Thomas
Published: August 2019

The Eastern Tropical North Atlantic Oxygen Minimum Zone (OMZ) is a biogeochemically important area. The low oxygen in this region is thought to be maintained by a balance between the slow mixing supply of O2 and its removal by respiration. We use data from 90 isopycnal RAFOS floats to characterize the mixing coefficients responsible for the supply of oxygen to the region. One group was ballasted to drift on the isopycnal where oxygen is at its minimum and the other about 300 m deeper. Using the record of the float positions at each 6‐hr interval, we calculate the relative dispersion of pairs of floats. The time derivative of this dispersion provides a diffusivity coefficient that captures the net effect of eddy‐driven mixing along each isopycnal. Float pairs deployed at shared locations but across the two target densities reveal that the influence of vertically sheared currents is to accelerate the dispersion by 10–15% relative to true isopycnal dispersion. Relative dispersion of the floats in the OMZ area obeyed the canonical four‐thirds power scaling, representative of two‐dimensional turbulence. At the length scale of the maximum energy‐containing eddy (approximately 100 km), the effective diffusivity is 1,400±500 m2/s in the zonal direction and 800±300 m2/s in the meridional. Within the uncertainty, the diffusivities on the two isopycnals are indistinguishable from one another. An idealized model suggests that meridional mixing across the large‐scale O2 gradient is the leading supply term of oxygen to the OMZ.
Temporal Modeling of Anomalous Coastal Sea Level Values Using Synoptic Climatological Patterns
Authors: Sheridan Scott C. , Lee Cameron C. , Adams Ryan E. , Smith Erik T. , Pirhalla Douglas E. , Ransibrahmanakul Varis
Published: August 2019

Short‐term changes in sea level can have substantial impacts on coastlines, and increases in coastal flooding have been observed as the mean sea level continues to climb. While extreme events such as hurricanes have been well studied in terms of their impacts on anomalous sea level values, anomalous sea levels due to less extreme atmospheric events have been less well studied, despite the increases in nuisance flood events that have occurred. In this study, we assess the relationship between short‐term atmospheric circulation patterns and anomalous coastal sea level values for all oceanic tidal gauges in the conterminous United States for the period 1979–2016. Atmospheric patterns are depicted using self‐organizing maps for four variables: sea level pressure, 10‐m wind, 850‐mb temperature, and 700‐mb geopotential height. We then reconstruct the time series of anomalous sea level through nonlinear autoregressive models with exogenous input (NARX models), an artificial neural network‐based time series model. Results show that these four atmospheric variables can successfully model sea level, with a correlation between model and observation using a closed‐loop (open‐loop) architecture of 0.83 (0.64), with a median absolute error of 3.34 (4.90) cm. The model generally performs better in winter than summer, and along the Pacific Coast than the Atlantic and Gulf Coasts. By using the NARX methodology, we intend to next assess its utility as a forecasting tool.
Temporal and Spatial Evolutions of a Large Sunspot Group and Great Auroral Storms Around the Carrington Event in 1859
Authors: Hayakawa Hisashi , Ebihara Yusuke , Willis David M. , Toriumi Shin , Iju Tomoya , Hattori Kentaro , Wild Matthew N. , Oliveira Denny M. , Ermolli Ilaria , Ribeiro José R. , Correia Ana P. , Ribeiro Ana I. , Knipp Delores J.
Published: August 2019

The Carrington event is considered to be one of the most extreme space weather events in observational history within a series of magnetic storms caused by extreme interplanetary coronal mass ejections from a large and complex active region that emerged on the solar disk. In this article, we study the temporal and spatial evolutions of the source sunspot active region and visual aurorae and compare this storm with other extreme space weather events on the basis of their auroral spatial evolution. Sunspot drawings by Schwabe, Secchi, and Carrington describe the position and morphology of the source active region at that time. Visual auroral reports from the Russian Empire, Iberia, Ireland, Oceania, and Japan fill the spatial gap of auroral visibility and revise the time series of auroral visibility in middle to low magnetic latitudes. The reconstructed time series is compared with magnetic measurements and shows the correspondence between low‐latitude to mid‐latitude aurorae and the phase of magnetic storms. The spatial evolution of the auroral oval is compared with those of other extreme space weather events in 1872, 1909, 1921, and 1989 as well as their storm intensity and contextualizes the Carrington event, as one of the most extreme space weather events, but likely not unique.
Soft-packaged sensory glove system for human-like natural interaction and control of prosthetic hands
Authors: Kim Min Ku , Parasuraman Ramviyas Nattanmai , Wang Liu , Park Yeonsoo , Kim Bongjoong , Lee Seung Jun , Lu Nanshu , Min Byung-Cheol , Lee Chi Hwan
Published: August 2019

People with hand amputations experience strenuous daily life challenges, often leading to lifelong use of a prosthetic hand(s) and services. Modern advanced prosthetic hands must be able to provide human hand-like sensory perceptions to receive external stimuli during daily activities while simultaneously replicating a realistic appearance and physical properties to naturally integrate in social contexts; however, the practical realization of these issues are impeded by a lack of effective methodologies. Herein, we present an optimal set of materials, design layouts, and fabrication schemes to construct an easy-to-wear seamless electronic glove (e-glove) suitable for arbitrary hand shapes that provides all of the desired human hand-like features. The system configuration involves a connection to a control wristwatch unit for real-time display of sensory data measured and remote transmission to the user. The experimental and computational studies provide details regarding the underlying principles of the materials selection, mechanics design, and operational management of the entire system. The demonstration of the e-glove system in interactions with human subjects illustrates the utility, comfort, and convenience of this device.
An inoculum-dependent culturing strategy (IDC) for the cultivation of environmental microbiomes and the isolation of novel endophytic Actinobacteria
Authors: Sarhan Mohamed S. , Mourad Elhussein F. , Nemr Rahma A. , Abdelfadeel Mohamed R. , Daanaa Hassan-Sibroe A. , Youssef Hanan H. , Goda Hanan A. , Hamza Mervat A. , Fayez Mohamed , Eichler-Löbermann Bettina , Ruppel Silke , Hegazi Nabil A.
Published: August 2019

The recent introduction of plant-only-based culture media enabled cultivation of not-yet-cultured bacteria that exceed 90% of the plant microbiota communities. Here, we further prove the competence and challenge of such culture media, and further introduce “the inoculum-dependent culturing strategy, IDC”. The strategy depends on direct inoculating plant serial dilutions onto plain water agar plates, allowing bacteria to grow only on the expense of natural nutrients contained in the administered inoculum. Developed colonies are successively transferred/subcultured onto plant-only-based culture media, which contains natural nutrients very much alike to those found in the prepared plant inocula. Because of its simplicity, the method is recommended as a powerful tool in screening programs that require microbial isolation from a large number of diverse plants. Here, the method comfortably and successfully recovered several isolates of endophytic Actinobacteria represented by the six genera of Curtobacterium spp., Plantibacter spp., Agreia spp., Herbiconiux spp., Rhodococcus spp., and Nocardioides spp. Furthermore, two of the isolates are most likely novel species belonging to Agreia spp. and Herbiconiux spp.
A null model of the mouse whole-neocortex micro-connectome
Authors: Reimann Michael W. , Gevaert Michael , Shi Ying , Lu Huanxiang , Markram Henry , Muller Eilif
Published: August 2019

In connectomics, the study of the network structure of connected neurons, great advances are being made on two different scales: that of macro- and meso-scale connectomics, studying the connectivity between populations of neurons, and that of micro-scale connectomics, studying connectivity between individual neurons. We combine these two complementary views of connectomics to build a first draft statistical model of the micro-connectome of a whole mouse neocortex based on available data on region-to-region connectivity and individual whole-brain axon reconstructions. This process reveals a targeting principle that allows us to predict the innervation logic of individual axons from meso-scale data. The resulting connectome recreates biological trends of targeting on all scales and predicts that an established principle of scale invariant topological organization of connectivity can be extended down to the level of individual neurons. It can serve as a powerful null model and as a substrate for whole-brain simulations.
Atomic and electronic modulation of self-supported nickel-vanadium layered double hydroxide to accelerate water splitting kinetics
Authors: Wang Dewen , Li Qun , Han Ce , Lu Qingqing , Xing Zhicai , Yang Xiurong
Published: August 2019

Herein, ruthenium (Ru) and iridium (Ir) are introduced to tailor the atomic and electronic structure of self-supported nickel-vanadium (NiV) layered double hydroxide to accelerate water splitting kinetics, and the origin of high hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) activities are analyzed at atomic level. X-ray photoelectron spectroscopy and X-ray absorption near-edge structure spectroscopy studies reveal synergistic electronic interactions among Ni, V, and Ru (Ir) cations. Raman spectra and Fourier and wavelet transform analyses of the extended X-ray absorption fine structure indicate modulated local coordination environments around the Ni and V cations, and the existence of V vacancies. The Debye–Waller factor suggests a severely distorted octahedral V environment caused by the incorporation of Ru and Ir. Theoretical calculations further confirm that Ru or Ir doping could optimize the adsorption energy of intermediates in the Volmer and Heyrovsky steps for HER and accelerate the whole kinetic process for OER.
CSL controls telomere maintenance and genome stability in human dermal fibroblasts
Authors: Bottoni Giulia , Katarkar Atul , Tassone Beatrice , Ghosh Soumitra , Clocchiatti Andrea , Goruppi Sandro , Bordignon Pino , Jafari Paris , Tordini Fabio , Lunardi Thomas , Hoetzenecker Wolfram , Neel Victor , Lingner Joachim , Paolo Dotto G.
Published: August 2019

Genomic instability is a hallmark of cancer. Whether it also occurs in Cancer Associated Fibroblasts (CAFs) remains to be carefully investigated. Loss of CSL/RBP-Jκ, the effector of canonical NOTCH signaling with intrinsic transcription repressive function, causes conversion of dermal fibroblasts into CAFs. Here, we find that CSL down-modulation triggers DNA damage, telomere loss and chromosome end fusions that also occur in skin Squamous Cell Carcinoma (SCC)-associated CAFs, in which CSL is decreased. Separately from its role in transcription, we show that CSL is part of a multiprotein telomere protective complex, binding directly and with high affinity to telomeric DNA as well as to UPF1 and Ku70/Ku80 proteins and being required for their telomere association. Taken together, the findings point to a central role of CSL in telomere homeostasis with important implications for genomic instability of cancer stromal cells and beyond.
Impaired mitochondrial calcium efflux contributes to disease progression in models of Alzheimer’s disease
Authors: Jadiya Pooja , Kolmetzky Devin W. , Tomar Dhanendra , Di Meco Antonio , Lombardi Alyssa A. , Lambert Jonathan P. , Luongo Timothy S. , Ludtmann Marthe H. , Praticò Domenico , Elrod John W.
Published: August 2019

Impairments in neuronal intracellular calcium (iCa2+) handling may contribute to Alzheimer’s disease (AD) development. Metabolic dysfunction and progressive neuronal loss are associated with AD progression, and mitochondrial calcium (mCa2+) signaling is a key regulator of both of these processes. Here, we report remodeling of the mCa2+ exchange machinery in the prefrontal cortex of individuals with AD. In the 3xTg-AD mouse model impaired mCa2+ efflux capacity precedes neuropathology. Neuronal deletion of the mitochondrial Na+/Ca2+ exchanger (NCLX, Slc8b1 gene) accelerated memory decline and increased amyloidosis and tau pathology. Further, genetic rescue of neuronal NCLX in 3xTg-AD mice is sufficient to impede AD-associated pathology and memory loss. We show that mCa2+ overload contributes to AD progression by promoting superoxide generation, metabolic dysfunction and neuronal cell death. These results provide a link between the calcium dysregulation and metabolic dysfunction hypotheses of AD and suggest mCa2+ exchange as potential therapeutic target in AD.
Distinct methylation levels of mature microRNAs in gastrointestinal cancers
Authors: Konno Masamitsu , Koseki Jun , Asai Ayumu , Yamagata Akira , Shimamura Teppei , Motooka Daisuke , Okuzaki Daisuke , Kawamoto Koichi , Mizushima Tsunekazu , Eguchi Hidetoshi , Takiguchi Shuji , Satoh Taroh , Mimori Koshi , Ochiya Takahiro , Doki Yuichiro , Ofusa Ken , Mori Masaki , Ishii Hideshi
Published: August 2019

The biological significance of micro (mi)RNAs has traditionally been evaluated according to their RNA expression levels based on the assumption that miRNAs recognize and regulate their targets in an unvarying fashion. Here we show that a fraction of mature miRNAs including miR-17-5p, -21-5p, and -200c-3p and let-7a-5p harbor methyl marks that potentially alter their stability and target recognition. Importantly, methylation of these miRNAs was significantly increased in cancer tissues as compared to paired normal tissues. Furthermore, miR-17-5p methylation level in serum samples distinguished early pancreatic cancer patients from healthy controls with extremely high sensitivity and specificity. These findings provide a basis for diagnostic strategies for early-stage cancer and add a dimension to our understanding of miRNA biology.
Ultrabright gap-enhanced Raman tags for high-speed bioimaging
Authors: Zhang Yuqing , Gu Yuqing , He Jing , Thackray Benjamin D. , Ye Jian
Published: August 2019

Surface-enhanced Raman spectroscopy (SERS) is advantageous over fluorescence for bioimaging due to ultra-narrow linewidth of the fingerprint spectrum and weak photo-bleaching effect. However, the existing SERS imaging speed lags far behind practical needs, mainly limited by Raman signals of SERS nanoprobes. In this work, we report ultrabright gap-enhanced Raman tags (GERTs) with strong electromagnetic hot spots from interior sub-nanometer gaps and external petal-like shell structures, larger immobilization surface area, and Raman cross section of reporter molecules. These GERTs reach a Raman enhancement factor beyond 5 × 109and a detection sensitivity down to a single-nanoparticle level. We use a 370 μW laser to realize high-resolution cell imaging within 6 s and high-contrast (a signal-to-background ratio of 80) wide-area (3.2 × 2.8 cm2) sentinel lymph node imaging within 52 s. These nanoprobes offer a potential solution to overcome the current bottleneck in the field of SERS-based bioimaging.
A phenotypic and genomics approach in a multi-ethnic cohort to subtype systemic lupus erythematosus
Authors: Lanata Cristina M. , Paranjpe Ishan , Nititham Joanne , Taylor Kimberly E. , Gianfrancesco Milena , Paranjpe Manish , Andrews Shan , Chung Sharon A. , Rhead Brooke , Barcellos Lisa F. , Trupin Laura , Katz Patricia , Dall’Era Maria , Yazdany Jinoos , Sirota Marina , Criswell Lindsey A.
Published: August 2019

Systemic lupus erythematous (SLE) is a heterogeneous autoimmune disease in which outcomes vary among different racial groups. Here, we aim to identify SLE subgroups within a multiethnic cohort using an unsupervised clustering approach based on the American College of Rheumatology (ACR) classification criteria. We identify three patient clusters that vary according to disease severity. Methylation association analysis identifies a set of 256 differentially methylated CpGs across clusters, including 101 CpGs in genes in the Type I Interferon pathway, and we validate these associations in an external cohort. A cis-methylation quantitative trait loci analysis identifies 744 significant CpG-SNP pairs. The methylation signature is enriched for ethnic-associated CpGs suggesting that genetic and non-genetic factors may drive outcomes and ethnic-associated methylation differences. Our computational approach highlights molecular differences associated with clusters rather than single outcome measures. This work demonstrates the utility of applying integrative methods to address clinical heterogeneity in multifactorial multi-ethnic disease settings.
Facilitating nitrogen accessibility to boron-rich covalent organic frameworks via electrochemical excitation for efficient nitrogen fixation
Authors: Liu Sisi , Wang Mengfan , Qian Tao , Ji Haoqing , Liu Jie , Yan Chenglin
Published: August 2019

Covalent organic frameworks with abundant active sites are potential metal-free catalysts for the nitrogen reduction reaction. However, the utilization ratio of active sites is restricted in an actual reaction process due to the limited nitrogen transport. Here, we demonstrate that facilitating the N2 accessibility to boron-rich covalent organic frameworks through electrochemical excitation can achieve highly efficient nitrogen reduction activity. Simulations show that the boron sites are bonded with nitrogenous species under electrochemical condition and the resultant amorphous phase of covalent organic frameworks has much stronger affinity toward N2 to enhance the molecule collision. Combined with experimental results, the excitation process is confirmed to be a virtuous cycle of more excited sites and stronger N2 affinity, which continuously proceed until the whole system reaches the optimum reaction status. As expected, the electrochemically excited catalyst delivers significantly enhanced reaction activity, with a high Faradaic efficiency of 45.43%.
Mycobacterial dynamin-like protein IniA mediates membrane fission
Authors: Wang Manfu , Guo Xiangyang , Yang Xiuna , Zhang Bing , Ren Jie , Liu Aijun , Ran Yajun , Yan Bing , Chen Fang , Guddat Luke W. , Hu Junjie , Li Jun , Rao Zihe
Published: August 2019

Mycobacterium tuberculosis infection remains a major threat to human health worldwide. Drug treatments against tuberculosis (TB) induce expression of several mycobacterial proteins, including IniA, but its structure and function remain poorly understood. Here, we report the structures of Mycobacterium smegmatis IniA in both the nucleotide-free and GTP-bound states. The structures reveal that IniA folds as a bacterial dynamin-like protein (BDLP) with a canonical GTPase domain followed by two helix-bundles (HBs), named Neck and Trunk. The distal end of its Trunk domain exists as a lipid-interacting (LI) loop, which binds to negatively charged lipids for membrane attachment. IniA does not form detectable nucleotide-dependent dimers in solution. However, lipid tethering indicates nucleotide-independent association of IniA on the membrane. IniA also deforms membranes and exhibits GTP-hydrolyzing dependent membrane fission. These results confirm the membrane remodeling activity of BDLP and suggest that IniA mediates TB drug-resistance through fission activity to maintain plasma membrane integrity.
In vitro fusion of single synaptic and dense core vesicles reproduces key physiological properties
Authors: Kreutzberger Alex J. B. , Kiessling Volker , Stroupe Christopher , Liang Binyong , Preobraschenski Julia , Ganzella Marcelo , Kreutzberger Mark A. B. , Nakamoto Robert , Jahn Reinhard , Castle J. David , Tamm Lukas K.
Published: August 2019

Regulated exocytosis of synaptic vesicles is substantially faster than of endocrine dense core vesicles despite similar molecular machineries. The reasons for this difference are unknown and could be due to different regulatory proteins, different spatial arrangements, different vesicle sizes, or other factors. To address these questions, we take a reconstitution approach and compare regulated SNARE-mediated fusion of purified synaptic and dense core chromaffin and insulin vesicles using a single vesicle-supported membrane fusion assay. In all cases, Munc18 and complexin are required to restrict fusion in the absence of calcium. Calcium triggers fusion of all docked vesicles. Munc13 (C1C2MUN domain) is required for synaptic and enhanced insulin vesicle fusion, but not for chromaffin vesicles, correlating inversely with the presence of CAPS protein on purified vesicles. Striking disparities in calcium-triggered fusion rates are observed, increasing with curvature with time constants 0.23 s (synaptic vesicles), 3.3 s (chromaffin vesicles), and 9.1 s (insulin vesicles) and correlating with rate differences in cells.
Molecular ground-state dissociation in the condensed phase employing plasmonic field enhancement of chirped mid-infrared pulses
Authors: Morichika Ikki , Murata Kei , Sakurai Atsunori , Ishii Kazuyuki , Ashihara Satoshi
Published: August 2019

Selective bond cleavage via vibrational excitation is the key to active control over molecular reactions. Despite its great potential, the practical implementation in condensed phases have been hampered to date by poor excitation efficiency due to fast vibrational relaxation. Here we demonstrate vibrationally mediated, condensed-phase molecular dissociation by employing intense plasmonic near-fields of temporally-shaped mid-infrared (mid-IR) pulses. Both down-chirping and substantial field enhancement contribute to efficient ladder climbing of the carbonyl stretch vibration of W(CO)6 in n-hexane solution and to the resulting CO dissociation. We observe an absorption band emerging with laser irradiation at the excitation beam area, which indicates that the dissociation is followed by adsorption onto metal surfaces. This successful demonstration proves that the combination of ultrafast optics and nano-plasmonics in the mid-IR range is useful for mode-selective vibrational ladder climbing, paving the way toward controlled ground-state chemistry.
EGR1 recruits TET1 to shape the brain methylome during development and upon neuronal activity
Authors: Sun Zhixiong , Xu Xiguang , He Jianlin , Murray Alexander , Sun Ming-an , Wei Xiaoran , Wang Xia , McCoig Emmarose , Xie Evan , Jiang Xi , Li Liwu , Zhu Jinsong , Chen Jianjun , Morozov Alexei , Pickrell Alicia M. , Theus Michelle H. , Xie Hehuang
Published: August 2019

Life experience can leave lasting marks, such as epigenetic changes, in the brain. How life experience is translated into storable epigenetic information remains largely unknown. With unbiased data-driven approaches, we predicted that Egr1, a transcription factor important for memory formation, plays an essential role in brain epigenetic programming. We performed EGR1 ChIP-seq and validated thousands of EGR1 binding sites with methylation patterns established during postnatal brain development. More specifically, these EGR1 binding sites become hypomethylated in mature neurons but remain heavily methylated in glia. We further demonstrated that EGR1 recruits a DNA demethylase TET1 to remove the methylation marks and activate downstream genes. The frontal cortices from the knockout mice lacking Egr1 or Tet1 share strikingly similar profiles in both gene expression and DNA methylation. In summary, our study reveals EGR1 programs the brain methylome together with TET1 providing new insight into how life experience may shape the brain methylome.
Metabolomic analysis of serum may refine 21-gene expression assay risk recurrence stratification
Authors: McCartney Amelia , Vignoli Alessia , Tenori Leonardo , Fornier Monica , Rossi Lorenzo , Risi Emanuela , Luchinat Claudio , Biganzoli Laura , Di Leo Angelo
Published: August 2019

Despite recent refinements to the 21-gene g score, allowing a better identification of patients who may derive no benefit from the addition of adjuvant chemotherapy to that of endocrine therapy, patients with early breast cancer still stand to be over-treated in the setting of clinical and/or genomic uncertainty or discordance. Here we describe and demonstrate a potential approach of further refining the OncotypeDX risk score by metabolomic analysis of serum. In a clinical dataset (N = 87), the risk of recurrence was further sub-stratified by metabolomic signature, with an effective splitting of each Oncotype risk classification. A total of seven recurrences were recorded, with metabolomic analysis accurately predicting six of these. Contrastingly, the genomic risk score of the seven recurrences ranged across all three Oncotype classifications (one recurrence occurred in the “low”-risk group, three in the “intermediate” group and three in the “high”-risk group).
A dataset describing a suite of novel antibody reagents for the RAS signaling network
Authors: Schoenherr Regine M. , Huang Dongqing , Voytovich Uliana J. , Ivey Richard G. , Kennedy Jacob J. , Saul Richard G. , Colantonio Simona , Roberts Rhonda R. , Knotts Joseph G. , Kaczmarczyk Jan A. , Perry Candice , Hewitt Stephen M. , Bocik William , Whiteley Gordon R. , Hiltke Tara , Boja Emily S. , Rodriguez Henry , Whiteaker Jeffrey R. , Paulovich Amanda G.
Published: August 2019

RAS genes are frequently mutated in cancer and have for decades eluded effective therapeutic attack. The National Cancer Institute’s RAS Initiative has a focus on understanding pathways and discovering therapies for RAS-driven cancers. Part of these efforts is the generation of novel reagents to enable the quantification of RAS network proteins. Here we present a dataset describing the development, validation (following consensus principles developed by the broader research community), and distribution of 104 monoclonal antibodies (mAbs) enabling detection of 27 phosphopeptides and 69 unmodified peptides from 20 proteins in the RAS network. The dataset characterizes the utility of the antibodies in a variety of applications, including Western blotting, immunoprecipitation, protein array, immunohistochemistry, and targeted mass spectrometry. All antibodies and characterization data are publicly available through the CPTAC Antibody Portal, Panorama Public Repository, and/or PRIDE databases. These reagents will aid researchers in discerning pathways and measuring expression changes in the RAS signaling network.
The prognostic significance of MRI-detected extramural venous invasion, mesorectal extension, and lymph node status in clinical T3 mid-low rectal cancer
Authors: Gu Chaoyang , Yang Xuyang , Zhang Xubing , Zheng Erliang , Deng Xiangbing , Hu Tao , Wu Qingbin , Bi Liang , Wu Bing , Su Minggang , Wang Ziqiang
Published: August 2019

The purpose of this study was to evaluate the prognostic significance of the magnetic resonance imaging-detected extramural venous invasion (MR-EMVI), the depth of mesorectal extension (MR-DME), and lymph node status (MR-LN) in clinical T3 mid-low rectal cancer. One hundred and forty-six patients with clinical T3 mid-low rectal cancer underwent curative surgery were identified. Pretreatment high-resolution MRI was independently reviewed by two experienced radiologists to evaluate MR-EMVI score (0–4), MR-DME (≤4 mm or >4 mm), and MR-LN (positive or negative). The Cox-multivariate regression analysis revealed that the MR-EMVI was the only independent prognostic factor that correlated with overall 3-year disease-free survival (DFS) (p = 0.01). The survival analysis showed that patients with positive MR-EMVI, MR-DME > 4 mm, and positive MR-LN had a poorer prognosis in the overall 3-year DFS (HR 3.557, 95% CI 2.028 to 13.32, p < 0.01; HR 3.744, 95% CI:1.165 to 5.992, p = 0.002; HR 2.946, 95% CI: 1.386 to 6.699, p < 0.01). By combining MR-EMVI with MR-DME or MR-LN, the prognostic significance was more remarkable. Our study suggested that the MR-EMVI, MR-DME, and MR-LN were the important prognostic factors for patients with clinical T3 mid-low rectal cancer and the MR-EMVI was an independent prognostic factor.