bluuebunny/crossref_metadata_2025 huggingface dataset:
22 Year Solar Magnetic Cycle and its relation to Convection Zone Dynamics
Authors: Jain Kiran , Tripathy Sushanta , Komm Rudolf , Hill Frank , Simoniello Rosaria
Published: November 2018

Using continuous observations for 22 years from ground-based network GONG and space-borne instruments MDI onboard SoHO and HMI onboard SDO, we report both global and local properties of the convection zone and their variations with time.
Properties of Coronal Holes in Solar Cycle 21-23 using McIntosh archive
Authors: Mazumder Rakesh , Bhowmik Prantika , Nandy Dibyendu
Published: November 2018

We study the properties of coronal holes during solar cycle 21-23 from the McIntosh archive. In the spatial distribution of coronal hole area we find that there is a sharp increase in coronal hole area at high latitude in agreement with expected open flux configuration there. In overall spatiotemporal distribution of coronal hole centroids, we find the dominance of high latitude coronal holes except for the maximum of the solar cycle, when coronal holes mostly appear in low latitudes. This is in agreement with the expected solar cycle evolution of surface magnetic flux.
Sunspot group tilt angles from drawings for cycles 19-24
Authors: Işık Emre , Işık Seda , Kabasakal Bahar B.
Published: November 2018

The tilt angle of a sunspot group is a critical quantity in the surface transport of magnetic flux and the solar dynamo. To contribute long-term databases of the tilt angle, we developed an IDL routine, which allows the user to interactively select and measure sunspot positions and areas on the solar disc. We measured the tilt angles of sunspot groups for solar cycles 19-24 (1954.6-2017.8), using the sunspot drawing database of Kandilli Observatory. The method is similar to that used in the discontinued Mt. Wilson and Kodaikanal databases, with the exception that sunspot groups were identified manually, which has improved the accuracy of the resulting tilt angles. We obtained cycle averages of the tilt angle and compared them with the values from other datasets, keeping the same group selection criteria. We conclude that the previously reported anti-correlation with the cycle strength needs further investigation.
A prediction of the solar cycle 25
Authors: Jiang Jie , Wang Jing-Xiu , Jiao Qi-Rong
Published: November 2018

Here we report our recent prediction of the solar cycle 25 based on a newly developed scheme, which is used to investigate the predictability of the solar cycle over one cycle. The scheme is a combination of the empirical properties of solar cycles and a surface flux transport model to get the possible axial dipole moment evolution at a few years before cycle minimum, by which to get the subsequent cycle strength based on the correlation between the axial dipole moment at cycle minimum and the subsequent cycle strength. We apply this scheme to predict the large-scale field evolution since 2018 onwards. The results show that the northern polar field will keep on increasing, while the southern polar field almost keeps flat by the end of cycle 24. This leads to the cycle 25 strength of 125 ± 32, which is about 10% stronger than cycle 24 according to the mean value.
Solar cycle variation of coronal mass ejections contribution to solar wind mass flux
Authors: Mishra Wageesh , Srivastava Nandita , Mirtoshev Zavkiddin , Wang Yuming
Published: November 2018

Coronal Mass Ejections (CMEs) contribute to the perturbation of solar wind in the heliosphere. Thus, depending on the different phases of the solar cycle and the rate of CME occurrence, contribution of CMEs to solar wind parameters near the Earth changes. In the present study, we examine the long term occurrence rate of CMEs, their speeds, angular widths and masses. We attempt to find correlation between near sun parameters of the CMEs with near the Earth measurements. Importantly, we attempt to find what fraction of the averaged solar wind mass near the Earth is provided by the CMEs during different phases of the solar cycles.
Role of the background regimes towards the Solar Mean Magnetic Field (SMMF)
Authors: Bose Souvik , Nagaraju K.
Published: November 2018

The Solar Mean Magnetic Field (SMMF) is generally defined as the disc-averaged line-of-sight (LOS) magnetic field on the sun. The role of the active regions and the large-scale magnetic field structures (also called the background) has been debated over the past few decades to understand whether the origin of the SMMF is either due to the active regions or the background. We, in this paper have investigated contribution of sunspots, plages, networks and the background towards the variability of the SMMF using the datasets from the SDO-AIA & HMI, and found that 89% of the SMMF is due to the background whereas the remaining 11% originates from the active regions and the networks.
Ca II K spectroheliograms for studies of long-term changes in solar irradiance
Authors: Chatzistergos Theodosios , Ermolli Ilaria , Krivova Natalie A. , Solanki Sami K.
Published: November 2018

We address the importance of historical full-disc Ca II K spectroheliograms for solar activity and irradiance reconstruction studies. We review our work on processing such data to enable them to be used in irradiance reconstructions. We also present our preliminary estimates of the plage areas from five of the longest available historical Ca II K archives.
Who Represents Women in Turkey? An Analysis of Gender Difference in Private Bill Sponsorship in the 2011–15 Turkish Parliament
Authors: Bektas Eda , Issever-Ekinci Esra
Published: November 2018

In this study, we examine substantive representation of women in the 2011–15 Turkish Parliament by focusing on sponsorship of private members’ bills by members of parliament (MPs) across eight major issue areas. The Turkish case offers new insights into women's representation, not only because this topic is unexplored in the Turkish context but also because it provides an opportunity to examine the tension between gender as a social identity and ideology as a political identity in a legislature characterized by disciplined political parties and low gender parity. Findings indicate that women MPs in Turkey substantively represent women by sponsoring more bills on women's rights and equality issues than their male colleagues, despite their low numbers in parliament and affiliation with highly disciplined parties. Party ideology also shapes women MPs’ issue priorities depending on the emphasis placed by the parties on different issue areas. Whereas left-wing women MPs sponsor more bills on women's rights and equality issues defined with a feminist accent, right-wing women MPs sponsor more bills on issues regarding children and family. Left-wing women also differ significantly from right-wing women in their sponsorship of bills on health and social affairs issues, as left-wing parties prioritize those issues more than right-wing parties.
Sexual Orientation and Gender Identity (SOGI) Human Rights Assistance in the Time of Trump
Authors: Burack Cynthia
Published: November 2018

The US government was a late adopter of support and advocacy for international sexual orientation and gender identity (SOGI) human rights. Although US support for SOGI human rights did not begin in the Obama administration, after 2011 such support was expanded, publicized, and institutionalized. Since the 2016 presidential election, many international and grassroots LGBTQI human rights activists have expressed concern about the prospects for US SOGI advocacy in the Trump administration. No definitive policy changes have been made public, but clues to the future of US advocacy for SOGI can be found in a variety of sites. These include the discourse and policy articulations of the secretary and human rights officials in the State Department as well as those of legislators who fund human rights programs and exercise oversight over it.
Fagchild Tools: Softening the Body Politic and Sexualizing Paul Ryan in a Pussy-Grabbing Era
Authors: Thomas Queer J.
Published: November 2018

This article cautions against the strong impulse in the #MeToo movement to desexualize politics. Informed by queer theory, the article argues that the public desexualization imperative, represented by indignation toward President Donald Trump's pussy-grabbing antics and the concomitant, albeit justified, movement to expose decades of his sexual harassment of women, casts a shadow across queer citizens that chills sexual expression in democratic discourse and public life. The public desexualization imperative presents a double bind that creates, on one hand, public spaces that are less threatening and discriminatory to women and, on the other, public spaces that—from a queer white cisgender man's perspective, one whose only “marking” is his sexuality—erase queers’ valued differences. The author uses personal narrative to describe and apply tools (conceptualized as fagchild tools) that help navigate tensions between women's equality movements and queer efforts to gain fuller, more open sexual citizenship. The article focuses, first, on softening the body politic (implicitly a white cisgender heterosexual male body) to provide sociopolitical space for sexual pluralism. Second, the article uses the sexualization of House Speaker Paul Ryan to argue that making space for queer sexualities may require accommodating the expression of nonqueer sexualities, including those that most of us find offensive.
Timing of Parents’ Concerns Related to Autism Spectrum Disorder and its Diagnosis: A Mediation Analysis
Authors: Garrido Dunia , Carballo Gloria , Artis Jonet , Garcia-Retamero Rocio
Published: November 2018

Parents are the first to indicate concerns about their child’s development in up to 80% of children with autism spectrum disorder (ASD). They often notice symptoms related to ASD around the first two years, but the average age of diagnosis is 3.5 years old. This study examined the relationships between parents’ early concerns and the time lag between suspicion and diagnosis. Forty-eight Spanish-speaking families were enrolled in this study. Parents were asked about early signs that made them think that their child could possibly have ASD. Mediation analyses showed that the child’s age at suspicion mediated between sibling status and the time lag between suspicion and a formal diagnosis (β = –.53,p< .01). Having another child with typical development accelerated parents’ detection of ASD signs (β = –.62,p< .001). The number of social-communication concerns that parents detected mediated this relationship (β = –.28,p< .01). Parents who reported more social-communication concerns perceived these signs earlier, but have to cope with a longer time lag until diagnosis than those who reported more concerns related to restrictive and repetitive behaviors and interests, or other developmental concerns. Moreover, this relationship between concerns of ASD and the diagnoses was explained by the child’s age. Training pediatricians on how to respond to parent questions and concerns could reduce the time lag between parents’ concerns and diagnosis of ASD.
Die Rolle des elektroanatomischen Mappings in der Rhythmologie
Authors: Kany Shinwan , Saguner Ardan M.
Published: November 2018

Zusammenfassung. Das Vorhofflimmern ist die häufigste Arrhythmie des Menschen, deren Prävalenz sich in den nächsten Jahren voraussichtlich verdreifachen wird. Die Katheterablation mittels Pulmonalvenenisolation (PVI) verspricht beim symptomatischen Patienten den grössten Therapieerfolg. Die PVI gehört in der Rhythmologie zu den komplexeren Eingriffen. Während es früher bei solchen komplexen Ablationen zu langen Prozedurdauern, Durchleuchtungszeiten und hohen Strahlendosen kam, kann dies heute mit dem dreidimensionalen (3-D) elektroanatomischen Mapping (EAM) in wesentlich kürzerer Zeit mit weniger bis teilweise ganz ohne Röntgenstrahlung erfolgen. Daher hat sich die EAM-gestützte Katheterablation als Standardverfahren bei komplexeren Ablationen etabliert. Die gängigen Systeme sind CARTO®, EnSite NavX® und Rhythmia®. Diese nutzen magnetische Felder und Impedanzverfahren, um Katheter im Herzen zu lokalisieren. Es können dabei 3-D-Landkarten der jeweiligen Herzkammer mittels lokaler Elektrogramme erzeugt werden. Diese Landkarten enthalten Informationen über die Herzanatomie, Voltage (Spannung des Myokards) und elektrische Aktivierung, was in Echtzeit dargestellt werden kann. Daten aus bildgebenden Verfahren wie CT, MRI und Echokardiografie können mit der 3-D-EAM-Karte verschmolzen werden, was die anatomische Genauigkeit des EAM verbessern kann.
High Temporal Resolution Monitoring of Small Variations in Crustal Strain by Dense Seismic Arrays
Authors: Mao Shujuan , Campillo Michel , van der Hilst Robert D. , Brenguier Florent , Stehly Laurent , Hillers Gregor
Published: November 2018

We demonstrate the feasibility of detecting very weak deformation in the shallow crust with high temporal resolution by monitoring the relative changes in seismic wave velocity (dv/v) using dense arrays of seismometers. We show that the dv/v variations are consistent between independent measurements from two seismic arrays. Dominant peaks in the observed dv/v spectrum suggest that tides and temperature changes are the major causes of daily and subdaily velocity changes, in accordance with theoretical strain modeling. Our analysis illustrates that dv/v perturbations of the order of 10−4, corresponding to crustal strain changes of the order of 10−8, can be measured from ambient seismic noise with a temporal resolution of 1 hr. This represents a low‐cost technique for high precision and high time‐resolution monitoring of crustal deformation that is complementary to existing geodetic measurements and is instrumental in both the detection and understanding of low‐amplitude precursory processes of natural catastrophic events.
Magnetotelluric Image of Transcrustal Magmatic System Beneath the Tulu Moye Geothermal Prospect in the Ethiopian Rift
Authors: Samrock Friedemann , Grayver Alexander V. , Eysteinsson Hjalmar , Saar Martin O.
Published: November 2018

Continental rifting is initiated by a dynamic interplay between tectonic stretching and mantle upwelling. Decompression melting assists continental breakup through lithospheric weakening and enforces upflow of melt to the Earth's surface. However, the details about melt transport through the brittle crust and storage under narrow rift‐aligned magmatic segments remain largely unclear. Here we present a crustal‐scale electrical conductivity model for a magmatic segment in the Ethiopian Rift, derived from 3‐D phase tensor inversion of magnetotelluric data. Our subsurface model shows that melt migrates along preexisting weak structures and is stored in different concentrations on two major interconnected levels, facilitating the formation of a convective hydrothermal system. The obtained model of a transcrustal magmatic system offers new insights into rifting mechanisms, evolution of magma ascent, and prospective geothermal reservoirs.
Rupture Termination in Laboratory‐Generated Earthquakes
Authors: Ke Chun‐Yu , McLaskey Gregory C. , Kammer David S.
Published: November 2018

Earthquakes are dynamic rupture events that initiate, propagate, and terminate on faults within the Earth's crust. Understanding rupture termination is essential for accurately estimating the maximum magnitude earthquake a region might experience. We study termination on sequences of M − 2.5 earthquakes that rupture a 3‐m granite laboratory sample. At this large scale, nucleation, propagation, and termination are either completely or partially confined within the sample–unique observations for experiments on rock. We compare measured termination locations to estimates from a fracture mechanics‐based model to quantify the fracture energy of the laboratory earthquakes, which compare well with estimates from small natural quakes. Our results provide a mathematical framework that links micrometer‐scale friction parameters to meter‐scale earthquake mechanics, shows that a 3‐m slab of granite can behave similar to a 200‐mm sheet of glassy polymer, and demonstrates how small events can prime a fault for larger, damaging ones.
Tsunami versus Infragravity Surge: Comparison of the Physical Character of Extreme Runup
Authors: Montoya Luis , Lynett Patrick
Published: November 2018

Recent observations of energetic infragravity (IG) flooding events, such as those in the Philippines during Typhoon Haiyan, suggest that IG surges may approach the coast as breaking bores with periods of minutes: a very tsunami‐like characteristic. Energetic IG waves have been observed in various locations around the world and have led to loss of lives and damages to property. In this study, a comparison of overland flow characteristics between tsunamis and energetic IG wave events is presented. In general, whenever the tsunamis and energetic IG waves have similar runup, tsunamis tend to generate greater flow depths and longer flood durations than IG. However, flow velocities and Froude number are larger for IG primarily due to bore‐bore capture. This study provides a statistical and physical discriminant between tsunami and IG, such that in areas exposed to both, a proper interpretation of overland transport, deposition, and damage is possible.
Predictability of Multiyear Trends of the Pacific Decadal Oscillation in an MPI‐ESM Hindcast Ensemble
Authors: Wiegand K. N. , Brune S. , Baehr J.
Published: November 2018

While hindcast skill for the Pacific Decadal Oscillation (PDO) has so far been limited to a few years, we present hindcast skill for PDO trends up to 10 years ahead. Our analysis is based on an initialized hindcast ensemble with the global Max Planck Institute Earth System Model (MPI‐ESM). As in previous studies, we find hindcast skill limited to a few years, when we first construct a lead‐year time series, from which we second calculate the PDO. We find similar hindcast skill when we first calculate the PDO for each start year and second construct a lead‐year time series. However, we find hindcast skill considerably increased, when we first calculate the PDO for each start year, second estimate multiyear trends, and third construct a lead‐year time series. Our results suggest hindcast skill for the low‐frequency variability of the PDO, which holds important implications for predictability analyses of other modes of long‐term climate variability.
Examining the Impact of Tropical Cyclones on Air‐Sea CO2 Exchanges in the Bay of Bengal Based on Satellite Data and In Situ Observations
Authors: Ye Haijun , Sheng Jinyu , Tang Danling , Morozov Evgeny , Kalhoro Muhsan Ali , Wang Sufen , Xu Huabing
Published: November 2018

The impact of tropical cyclones (TCs) on the CO2 partial pressure at the sea surface (pCO2sea) and air‐sea CO2 flux (FCO2) in the Bay of Bengal (BoB) was quantified based on satellite data and in situ observations between November 2013 and January 2017. The in situ observations were made at the BoB Ocean Acidification mooring buoy. A weak time‐mean net source of 55.78 ± 11.16 mmol CO2 m−2 year−1 at the BoB Ocean Acidification site was estimated during this period. A wide range in increases of pCO2sea (1.0–14.8 μatm) induced by TCs occurred in postmonsoon (October–December), and large decreases of pCO2sea (−14.0 μatm) occurred in premonsoon (March–May). Large vertical differences in the ratio of dissolved inorganic carbon (DIC) to total alkalinity (TA) in the upper layer (ΔDIC/TA) were responsible for increasing pCO2sea in postmonsoon. Relatively small values of ΔDIC/TA were responsible for decreasing pCO2sea in premonsoon. Five TCs (Hudhud, Five, Kyant, Vardah, and Roanu) were considered. Hudhud significantly enhanced CO2 efflux (18.49 ± 3.70 mmol CO2/m2) in oversaturated areas due to the wind effect during the storm and wind‐pump effects after the storm. Vardah insignificantly changed FCO2 (1.22 ± 0.24 mmol CO2/m2) in undersaturated areas because of the counteraction of these two effects. Roanu significantly enhanced CO2 efflux (19.08 ± 3.82 mmol CO2/m2) in highly oversaturated conditions (ΔpCO2 > 20 μatm) since the wind effect greatly exceeded the wind‐pump effects. These five TCs were estimated to account for 55 ± 23% of the annual‐mean CO2 annual efflux, suggesting that TCs have significant impacts on the carbon cycle in the BoB.
Quantifying the Economic Value of Space Weather Forecasting for Power Grids: An Exploratory Study
Authors: Eastwood J. P. , Hapgood M. A. , Biffis E. , Benedetti D. , Bisi M. M. , Green L. , Bentley R. D. , Burnett C.
Published: November 2018

An accurate understanding of space weather socioeconomic impact is fundamental to the development of appropriate operational services, forecasting capabilities, and mitigation strategies. One way to approach this problem is by developing physics‐based models and frameworks that can lead to a bottom‐up estimate of risk and likely impact. Here we describe the development of a new framework to assess the economic impact of space weather on power distribution networks and the supply of electricity. In particular, we focus on the phenomenon of the geomagnetic substorm, which is relatively localized in time and space, and occurs multiple times with varying severity during a geomagnetic storm. The framework uses the AE index to characterize substorm severity, and the impact of the substorm is modulated by the resilience of the power grid and the nature of available forecast. Possible scenarios for substorm sequences during a 1‐in‐10‐, a 1‐in‐30‐, and a 1‐in‐100‐year geomagnetic storm events are generated based on the 2003, 1989, and 1859 geomagnetic storms. Economic impact, including international spill over, can then be calculated using standard techniques, based on the duration and the geographical footprint of the power outage. Illustrative calculations are made for the European sector, for a variety of forecast and resilience scenarios. However, currently available data are highly regionally inhomogeneous, frustrating attempts to define an overall global economic impact at the present time.
Effect of dried fruit on postprandial glycemia: a randomized acute-feeding trial
Authors: Viguiliouk Effie , Jenkins Alexandra L , Blanco Mejia Sonia , Sievenpiper John L , Kendall Cyril W C
Published: November 2018

Background/Objectives

To investigate the effect of dried fruit in modifying postprandial glycemia, we assessed the ability of 4 dried fruits (dates, apricots, raisins, sultanas) to decrease postprandial glycemia through three mechanisms: a glycemic index (GI) effect, displacement effect, or ‘catalytic’ fructose effect.

Subjects/Methods

We conducted an acute randomized, multiple-crossover trial in an outpatient setting in 10 healthy adults. Participants received 3 white bread control meals and 12 dried fruit test meals in random order. The test meals included each of 4 dried fruits (dates, apricots, raisins, sultanas) alone (GI effect), 4 of the dried fruits displacing half the available carbohydrate in white bread (displacement effect), or 4 of the dried fruits providing a small ‘catalytic’ dose (7.5 g) of fructose added to white bread (‘catalytic’ fructose effect). The protocol followed the ISO method for the determination of GI (ISO 26642:2010). The primary outcome was mean ± SEM GI (glucose scale) for ease of comparison across the three mechanisms.

Results

Ten healthy participants (7 men, 3 women; mean ± SD age and BMI: 39 ± 12 years and 25 ± 2 kg/m2) were recruited and completed the trial. All dried fruit had a GI below that of white bread (GI = 71); however, only dried apricots (GI = 42 ± 5), raisins (GI = 55 ± 5), and sultanas (51 ± 4) showed a significant GI effect (P < 0.05). When displacing half the available carbohydrate in white bread, all dried fruit lowered the GI; however, only dried apricots (GI = 57 ± 5) showed a significant displacement effect (P = 0.025). None of the dried fruits showed a beneficial ‘catalytic’ fructose effect.

Conclusions

In conclusion, dried fruits have a lower GI and reduce the glycemic response of white bread through displacement of half of the available carbohydrate. Longer-term randomized trials are needed to confirm whether dried fruit can contribute to sustainable improvements in glycemic control.

Trial registration

ClinicalTrials.gov identifier, NCT02960373
A psychometric investigation of the Chinese version of the Internal, Personal and Situational Attributions Questionnaire (C-IPSAQ)
Authors: Gao Bin , Wang Yiquan , Zhu Yihong , Tian Qi , Chen Zhiyu , Cohen Zachary , Landa Yulia , Mueser Kim T.
Published: November 2018

The IPSAQ is a self-administered instrument designed to evaluate individuals’ attributional style (AS). The purpose of this study is to examine the psychometric properties of the Chinese version of the Internal, Personal and Situational Attributions Questionnaire (C-IPSAQ). We also investigate if patients with depression and patients with delusions exhibit attributional biases. The English version of IPSAQ was translated into Chinese and back-translated into English for use in this study. 200 normal control individuals, 47 depressed patients, and 41 delusional patients diagnosed with schizophrenia were recruited for this study. Psychometric properties of this questionnaire were evaluated. The IPSAQ was found to have good internal consistency as a scale. The mean Cronbach’s alpha of the six subscales was 0.697. The inter-rater reliability was also acceptable. The concurrent validity analysis revealed that the C-IPSAQ was significantly correlated with ASQ. The group-comparison analyses showed differences in attributional style between patients with depression and patients with delusions compared to normal controls. We confirmed the reliability and validity of the C-IPSAQ, and that the instrument can discriminate specific attributional biases between different patient populations. The C-IPSAQ is a valid instrument to assess attributional style in delusional and depressed patients.
DNA interference and beyond: structure and functions of prokaryotic Argonaute proteins
Authors: Lisitskaya Lidiya , Aravin Alexei A. , Kulbachinskiy Andrey
Published: November 2018

Recognition and repression of RNA targets by Argonaute proteins guided by small RNAs is the essence of RNA interference in eukaryotes. Argonaute proteins with diverse structures are also found in many bacterial and archaeal genomes. Recent studies revealed that, similarly to their eukaryotic counterparts, prokaryotic Argonautes (pAgos) may function in cell defense against foreign genetic elements but, in contrast, preferably act on DNA targets. Many crucial details of the pAgo action, and the roles of a plethora of pAgos with non-conventional architecture remain unknown. Here, we review available structural and biochemical data on pAgos and discuss their possible functions in host defense and other genetic processes in prokaryotic cells.
Cooperative adsorption of carbon disulfide in diamine-appended metal–organic frameworks
Authors: McGuirk C. Michael , Siegelman Rebecca L. , Drisdell Walter S. , Runčevski Tomče , Milner Phillip J. , Oktawiec Julia , Wan Liwen F. , Su Gregory M. , Jiang Henry Z. H. , Reed Douglas A. , Gonzalez Miguel I. , Prendergast David , Long Jeffrey R.
Published: November 2018

Over one million tons of CS2 are produced annually, and emissions of this volatile and toxic liquid, known to generate acid rain, remain poorly controlled. As such, materials capable of reversibly capturing this commodity chemical in an energy-efficient manner are of interest. Recently, we detailed diamine-appended metal–organic frameworks capable of selectively capturing CO2 through a cooperative insertion mechanism that promotes efficient adsorption–desorption cycling. We therefore sought to explore the ability of these materials to capture CS2 through a similar mechanism. Employing crystallography, spectroscopy, and gas adsorption analysis, we demonstrate that CS2 is indeed cooperatively adsorbed in N,N-dimethylethylenediamine-appended M2(dobpdc) (M = Mg, Mn, Zn; dobpdc4- = 4,4′-dioxidobiphenyl-3,3′-dicarboxylate), via the formation of electrostatically paired ammonium dithiocarbamate chains. In the weakly thiophilic Mg congener, chemisorption is cleanly reversible with mild thermal input. This work demonstrates that the cooperative insertion mechanism can be generalized to other high-impact target molecules.
A non-canonical BRD9-containing BAF chromatin remodeling complex regulates naive pluripotency in mouse embryonic stem cells
Authors: Gatchalian Jovylyn , Malik Shivani , Ho Josephine , Lee Dong-Sung , Kelso Timothy W. R. , Shokhirev Maxim N. , Dixon Jesse R. , Hargreaves Diana C.
Published: November 2018

The role of individual subunits in the targeting and function of the mammalian BRG1-associated factors (BAF) complex in embryonic stem cell (ESC) pluripotency maintenance has not yet been elucidated. Here we find that the Bromodomain containing protein 9 (BRD9) and Glioma tumor suppressor candidate region gene 1 (GLTSCR1) or its paralog GLTSCR1-like (GLTSCR1L) define a smaller, non-canonical BAF complex (GBAF complex) in mouse ESCs that is distinct from the canonical ESC BAF complex (esBAF). GBAF and esBAF complexes are targeted to different genomic features, with GBAF co-localizing with key regulators of naive pluripotency, which is consistent with its specific function in maintaining naive pluripotency gene expression. BRD9 interacts with BRD4 in a bromodomain-dependent fashion, which leads to the recruitment of GBAF complexes to chromatin, explaining the functional similarity between these epigenetic regulators. Together, our results highlight the biological importance of BAF complex heterogeneity in maintaining the transcriptional network of pluripotency.
Discovery of a potent HMG-CoA reductase degrader that eliminates statin-induced reductase accumulation and lowers cholesterol
Authors: Jiang Shi-You , Li Hui , Tang Jing-Jie , Wang Jie , Luo Jie , Liu Bing , Wang Jin-Kai , Shi Xiong-Jie , Cui Hai-Wei , Tang Jie , Yang Fan , Qi Wei , Qiu Wen-Wei , Song Bao-Liang
Published: November 2018

Statins are inhibitors of HMG-CoA reductase, the rate-limiting enzyme of cholesterol biosynthesis, and have been clinically used to treat cardiovascular disease. However, a paradoxical increase of reductase protein following statin treatment may attenuate the effect and increase the side effects. Here we present a previously unexplored strategy to alleviate statin-induced reductase accumulation by inducing its degradation. Inspired by the observations that cholesterol intermediates trigger reductase degradation, we identify a potent degrader, namely Cmpd 81, through structure–activity relationship analysis of sterol analogs. Cmpd 81 stimulates ubiquitination and degradation of reductase in an Insig-dependent manner, thus dramatically reducing protein accumulation induced by various statins. Cmpd 81 can act alone or synergistically with statin to lower cholesterol and reduce atherosclerotic plaques in mice. Collectively, our work suggests that inducing reductase degradation by Cmpd 81 or similar chemicals alone or in combination with statin therapy can be a promising strategy for treating cardiovascular disease.
Caveolin-1 mediates cellular distribution of HER2 and affects trastuzumab binding and therapeutic efficacy
Authors: Pereira Patrícia M. R. , Sharma Sai Kiran , Carter Lukas M. , Edwards Kimberly J. , Pourat Jacob , Ragupathi Ashwin , Janjigian Yelena Y. , Durack Jeremy C. , Lewis Jason S.
Published: November 2018

Human epidermal growth factor receptor 2 (HER2) gene amplification and/or protein overexpression in tumors is a prerequisite for initiation of trastuzumab therapy. Although HER2 is a cell membrane receptor, differential rates of endocytosis and recycling engender a dynamic surface pool of HER2. Since trastuzumab must bind to the extracellular domain of HER2, a depressed HER2 surface pool hinders binding. Using in vivo biological models and cultures of fresh human tumors, we find that the caveolin-1 (CAV1) protein is involved in HER2 cell membrane dynamics within the context of receptor endocytosis. The translational significance of this finding is highlighted by our observation that temporal CAV1 depletion with lovastatin increases HER2 half-life and availability at the cell membrane resulting in improved trastuzumab binding and therapy against HER2-positive tumors. These data show the important role that CAV1 plays in the effectiveness of trastuzumab to target HER2-positive tumors.
B cells inhibit bone formation in rheumatoid arthritis by suppressing osteoblast differentiation
Authors: Sun Wen , Meednu Nida , Rosenberg Alexander , Rangel-Moreno Javier , Wang Victor , Glanzman Jason , Owen Teresa , Zhou Xichao , Zhang Hengwei , Boyce Brendan F. , Anolik Jennifer H. , Xing Lianping
Published: November 2018

The function of B cells in osteoblast (OB) dysfunction in rheumatoid arthritis (RA) has not been well-studied. Here we show that B cells are enriched in the subchondral and endosteal bone marrow (BM) areas adjacent to osteocalcin+OBs in two murine RA models: collagen-induced arthritis and the TNF-transgenic mice. Subchondral BM B cells in RA mice express high levels of OB inhibitors, CCL3 and TNF, and inhibit OB differentiation by activating ERK and NF-κB signaling pathways. The inhibitory effect of RA B cells on OB differentiation is blocked by CCL3 and TNF neutralization, and deletion of CCL3 and TNF in RA B cells completely rescues OB function in vivo, while B cell depletion attenuates bone erosion and OB inhibition in RA mice. Lastly, B cells from RA patients express CCL3 and TNF and inhibit OB differentiation, with these effects ameliorated by CCL3 and TNF neutralization. Thus, B cells inhibit bone formation in RA by producing multiple OB inhibitors.
Prospective observational study validating the German version of the Control of Allergic Rhinitis and Asthma Test (CARAT10)
Authors: Werner Christoph Ulrich , Koch Luisa , Linde Klaus , Kriston Levente , Schultz Konrad , Atmann Oxana , Schneider Antonius
Published: November 2018

The Control of Allergic Rhinitis and Asthma Test (CARAT10), developed by Portuguese experts, is the only questionnaire assessing asthma control under additional consideration of a frequently concurrent allergic rhinitis (AR), providing sub-scores for both diseases. Aims of this study were the translation and validation of its German version. Asthma patients both with and without AR were included at three primary care pulmologists´ practices in Southern Germany. After translation process, patients completed the CARAT10, the Asthma Control Questionnaire (ACQ), the Asthma Control Test (ACT), and the Standardised Asthma Quality of Life Questionnaire (AQLQ(S)). Item and scale characteristics as well as measures of reliability and validity of the CARAT10 were determined. A confirmatory factor analysis was conducted to test factorial validity. Data of 213 patients were analysed, 101 (47%) of them with concurrent AR. Missing responses were minimal and unsystematic. Cronbach´s α was 0.87 for the CARAT10 total score (TS) and 0.84 for each sub-score. Spearman´s correlation coefficients for the association of the CARAT10 TS with ACQ, ACT and AQLQ(S) were moderate to high and slightly higher in patients with AR. Higher correlations were found for its lower airway sub-score than the upper airway sub-score (all around 0.8 to all around 0.3). Confirmatory factor analysis confirmed the two-factorial scale structure of the CARAT10, with a two-factor model showing a better fit to the data than a one-factor model. The German version of the CARAT10 is an acceptable, reliable and valid tool. Our results suggest a recommended use in asthma patients with AR.
Towards manufacturing high uniformity polysilicon circuits through TFT contact barrier engineering
Authors: Sporea Radu A. , Wheeler Luke J. , Stolojan Vlad , Silva S. Ravi P.
Published: November 2018

The predicted 50 billion devices connected to the Internet of Things by 2020 has renewed interest in polysilicon technology for high performance new sensing and control circuits, in addition to traditional display usage. Yet, the polycrystalline nature of the material presents significant challenges when used in transistors with strongly scaled channel lengths due to non-uniformity in device performance. For these new applications to materialize as viable products, uniform electrical characteristics on large areas will be essential. Here, we report on the effect of deliberately engineered potential barrier at the source of polysilicon thin-film transistors, yielding highly-uniform on-current (<8% device-to-device, accounting for material, as well as substantial geometrical, variations). The contact-controlled architecture of these transistors significantly reduces kink effect and produces high intrinsic gain over a wide range of drain voltage (2–20 V). TCAD simulations associate critical grain boundary position and the two current injection mechanisms in this type of device, showing that, for the geometry considered, the most unfavorable location is ~150 nm inside the source area. At this point, grain boundary contributes to increasing the resistance of the source pinch-off region, reducing the current injection from the bulk of the source area. Nevertheless, the effect is marginal, and the probability of a grain boundary existing at this position is low. This new understanding is instrumental in the design of new signal conversion and gain circuits for flexible and low-power sensors, without the need for complex compensation methods.
Crosstalk between SOX2 and cytokine signaling in endometrial carcinoma
Authors: Lee Chang-Jung , Sung Pi-Lin , Kuo Ming-Han , Tsai Min-Hwa , Wang Cheng-Kuang , Pan Shien-Tung , Chen Yi-Jen , Wang Peng-Hui , Wen Kuo-Chang , Chou Yu-Ting
Published: November 2018

Endometrial carcinoma is a cancer derived from oncogenesis of the regenerating uterine cavity, in which cytokine stimulation shapes cell differentiation and tissue remodeling. Expression of the stem cell factors SOX2, OCT4, NANOG, and MYC has been linked to tumor malignancy in several cancers. However, how these stem cell factors crosstalk with cytokine signaling to promote malignancy in endometrial carcinoma is still elusive. Here we report that the expression of SOX2 and MYC, but not that of OCT4 and NANOG, correlate with poor histological differentiation and prognosis, while SOX2 expression is negatively associated with MYC level. We found that SOX2-high endometrial carcinoma cells possessed a higher colony-forming ability than their SOX2-low counterparts, and knockdown of SOX2 attenuated the colony-forming ability. We observed that SOX2 regulated EGFR expression in a SOX2–EGFR positive feedback loop. EGF stimulation induced SOX2 expression and promoted migration of endometrial carcinoma cells, whereas TGF-β stimulation inhibited SOX2 expression and attenuated the colony-forming ability. Immunohistochemistry analysis revealed that SOX2 expression correlated with lymph node infiltration of endometrial carcinoma. Our findings support that cytokine-induced stem cell factor SOX2 possesses oncogenic properties, with the potential to serve as a prognostic biomarker in endometrial carcinoma.
Olfactory cleft proteome does not reflect olfactory performance in patients with idiopathic and postinfectious olfactory disorder: A pilot study
Authors: Wolf Axel , Liesinger Laura , Spoerk Stefan , Schittmayer Matthias , Lang-Loidolt Doris , Birner-Gruenberger Ruth , Tomazic Peter V.
Published: November 2018

Technical advances including liquid chromatography–tandem mass spectrometry and its data analysis enable detailed proteomic analysis of the nasal mucus. Alterations of the nasal mucus proteome may provoke substantial changes of the nasal physiology and have already been associated with rhinologic diseases such as allergic rhinitis. This study was conducted as a pilot study to map the olfactory cleft proteome using current techniques for proteomic analysis. Furthermore, we aimed to investigate proteomic changes as potential biomarkers in patients suffering from idiopathic and postinfectious olfactory disorders compared to healthy controls. Seven patients with idiopathic hyposmia and anosmia, seven patients with postinfectious hyposmia and anosmia and seven healthy controls were included in this study. In total, 1117 different proteins were detected in at least five patients in at least one group. Results of this study did not reveal significant differences regarding the proteomic composition of the olfactory cleft mucus between patients versus healthy controls. Among proteins involved in olfactory perception the G protein family was detected but also found unchanged between groups. Investigation of protein composition by liquid chromatography–tandem mass spectrometry enabled us to perform an in–depth analysis of the olfactory cleft mucus proteome regarding the diversity of different proteins in individual patients. However untargeted proteomics of the olfactory cleft mucus may not be an applicable approach to develop biomarkers for olfactory disorders. Targeted analyses of distinct proteins known to be involved in olfactory perception but not detected by our approach, e.g. odorant binding proteins, may provide more information regarding pathophysiology of olfactory diseases.
Prevalence of Sarcocystis calchasi in free-ranging host species: Accipiter hawks and Common Woodpigeon in Germany
Authors: Parmentier Sylvia L. , Maier-Sam Kristina , Failing Klaus , Enderlein Dirk , Gruber Achim D. , Lierz Michael
Published: November 2018

The apicomplexan parasite Sarcocystis calchasi (S. calchasi) triggers pigeon protozoal encephalitis, a neurologic disease in columbids. Accipiter hawks have been identified as the final host, and Columbidae and Psittaciformes as intermediate hosts. In this study, 368 free-ranging Accipiter hawks and 647 free-ranging common woodpigeons were sampled in a country-wide study in order to identify the prevalence of S. calchasi in these populations. A semi-nested PCR specific for S. calchasi tested positive in 7.3% (4.9–10.5) of submitted samples from Accipiter hawks. Juvenile Accipiter hawks (13.7%; 7.7–22.0) had a significantly higher infection rate with S. calchasi than adult Accipiter hawks (5.8%; 2.7–9.3). The prevalence of S. calchasi in common woodpigeons was 3.3% (5.4–9.7). Positive pigeons were identified in 14/16 federal states, and a region-dependency was detected, with higher rates of infection in the eastern parts of Germany. The results of this study suggest that the common woodpigeon is a natural reservoir for S. calchasi. In a study of one region for four consecutive years, an increase in prevalence was not detected. Findings indicate that the parasite is not newly introduced to Germany, but rather long established. The prevalence suggests that there is a substantial risk of S. calchasi infections in other free-ranging as well as captive host species.
Phototransduction and circadian entrainment are the key pathways in the signaling mechanism for the baculovirus induced tree-top disease in the lepidopteran larvae
Authors: Bhattarai Upendra Raj , Li Fengjiao , Katuwal Bhattarai Mandira , Masoudi Abolfazl , Wang Dun
Published: November 2018

The tree-top disease is an altered behavioral state, displayed by baculovirus-infected lepidopteran larvae, and characterized by climbing to an elevated position before death. The detailed molecular mechanism underlying this phenomenal behavior change has not been reported yet. Our study focused on the transcriptomic changes in the host larvae due to baculovirus infection from pre-symptomatic to tree-top disease stage. Enrichment map visualization of the gene sets grouped based on the functional annotation similarity revealed 34 enriched pathways in signaling mechanism cluster during LdMNPV induced tree-top disease in third instarLymantria dispar asiaticalarvae. Directed light bioassay demonstrated the positively phototactic larvae during tree-top disease and the gene expression analysis showed altered rhythmicity of the host’s core circadian genes (perandtim) during the course of infection emphasizing the role of Circadian entrainment and Phototransduction pathways in the process, which also showed maximum interactions (>50% shared genes with 24 and 23 pathways respectively) among other signaling pathways in the enrichment map. Our study provided valuable insights into different pathways and genes, their coordinated response and molecular regulation during baculovirus infection and also improved our understanding regarding signaling mechanisms in LdMNPV induced tree-top disease.
Author Correction: Neighbor-Neighbor Correlations Explain Measurement Bias in Networks
Authors: Wu Xin-Zeng , Percus Allon G. , Lerman Kristina
Published: November 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Recordings in an integrating central neuron provide a quick way for identifying appropriate anaesthetic use in fish
Authors: Machnik Peter , Schirmer Elisabeth , Glück Laura , Schuster Stefan
Published: November 2018

In animal husbandry, livestock industry and research facilities, anaesthetic agents are frequently used to moderate stressful intervention. For mammals and birds, procedures have been established to fine-tune anaesthesia according to the intervention. In ectothermic vertebrates, however, and despite changes in legislation and growing evidence on their cognitive abilities, the presently available information is insufficient to make similarly informed decisions. Here we suggest a straightforward way for rapidly filling this gap. By recording from a command neuron in the brain of fish whose crucial role requires it to integrate and process information from all sensory systems and to relay it to motor output pathways, the specific effects of candidate anaesthesia on central processing of sensory information can directly and efficiently be probed. Our approach allows a rapid and reliable way of deciding if and at which concentration a given anaesthetic affects the central nervous system and sensory processing. We employ our method to four anaesthetics commonly used in fish and demonstrate that our method quickly and with small numbers of animals provides the critical data for informed decisions on anaesthetic use.
Immunogenetics of glioblastoma: the future of personalized patient management
Authors: Abedalthagafi Malak , Barakeh Duna , Foshay Kara M.
Published: November 2018

The prognosis of glioblastoma has changed little over the past two decades, with only minor improvements in length of overall survival through the addition of temozolomide (temodal) to standard of care and the recommended use of alternating electric field therapy (optune) to newly diagnosed patients. In an effort to define novel therapeutic targets across molecularly heterogeneous disease subgroups, researchers have begun to uncover the complex interplay between epigenetics, cell signaling, metabolism, and the immunosuppressive tumor microenvironment. Indeed, IDH mutations are now recognized as a defining differential factor not only influencing global hypermethylation and patient prognosis but also degree of immune infiltration within individual tumors. Likewise, next-generation sequencing has defined subgroup-specific transcriptional profiles that correlate with different mechanisms of immune evasion, including increased PD-L1 and CTLA-4 among mesenchymal tumors. Interestingly, sequencing of the T cell repertoire from numerous patient samples suggests that the correlation between mutational burden and enrichment of tumor-specific peptides may be less convincing than originally suspected. While this raises questions over the efficacy of dendritic cell or tumor-lysate vaccines and CAR-T therapies, these avenues continue to be explored. In addition to these active immunotherapies, inhibitors of molecular hubs with wide reaching effects, including STAT3, IDO, and TGF-β, are now in early-phase clinical trials. With the potential to block intrinsic biological properties of tumor growth and invasion while bolstering the immunogenic profile of the tumor microenvironment, these new targets represent a new direction for GBM therapies. In this review, we show the advances in molecular profiling and immunophenotyping of GBM, which may lead to the development of new personalized therapeutic strategies.