bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antidiabetic and cardiovascular beneficial effects of a liver-localized mitochondrial uncoupler
Authors: Kanemoto Naohide , Okamoto Takashi , Tanabe Koji , Shimada Takahiro , Minoshima Hitomi , Hidoh Yuya , Aoyama Masashi , Ban Takashi , Kobayashi Yusuke , Ando Hikaru , Inoue Yuki , Itotani Motohiro , Sato Seiji 
Published: May 2019

AbstractInducing mitochondrial uncoupling (mUncoupling) is an attractive therapeutic strategy for treating metabolic diseases because it leads to calorie-wasting by reducing the efficiency of oxidative phosphorylation (OXPHOS) in mitochondria. Here we report a safe mUncoupler, OPC-163493, which has unique pharmacokinetic characteristics. OPC-163493 shows a good bioavailability upon oral administration and primarily distributed to specific organs: the liver and kidneys, avoiding systemic toxicities. It exhibits insulin-independent antidiabetic effects in multiple animal models of type I and type II diabetes and antisteatotic effects in fatty liver models. These beneficial effects can be explained by the improvement of glucose metabolism and enhancement of energy expenditure by OPC-163493 in the liver. Moreover, OPC-163493 treatment lowered blood pressure, extended survival, and improved renal function in the rat model of stroke/hypertension, possibly by enhancing NO bioavailability in blood vessels and reducing mitochondrial ROS production. OPC-163493 is a liver-localized/targeted mUncoupler that ameliorates various complications of diabetes.
Local floods induce large-scale abrupt failures of road networks
Authors: Wang Weiping , Yang Saini , Stanley H. Eugene , Gao Jianxi 
Published: May 2019

AbstractThe adverse effect of climate change continues to expand, and the risks of flooding are increasing. Despite advances in network science and risk analysis, we lack a systematic mathematical framework for road network percolation under the disturbance of flooding. The difficulty is rooted in the unique three-dimensional nature of a flood, where altitude plays a critical role as the third dimension, and the current network-based framework is unsuitable for it. Here we develop a failure model to study the effect of floods on road networks; the result covers 90.6% of road closures and 94.1% of flooded streets resulting from Hurricane Harvey. We study the effects of floods on road networks in China and the United States, showing a discontinuous phase transition, indicating that a small local disturbance may lead to a large-scale systematic malfunction of the entire road network at a critical point. Our integrated approach opens avenues for understanding the resilience of critical infrastructure networks against floods.
Interferon inducible X-linked gene CXorf21 may contribute to sexual dimorphism in Systemic Lupus Erythematosus
Authors: Odhams Christopher A. , Roberts Amy L. , Vester Susan K. , Duarte Carolina S. T. , Beales Charlie T. , Clarke Alexander J. , Lindinger Sonja , Daffern Samuel J. , Zito Antonino , Chen Lingyan , Jones Leonardo L. , Boteva Lora , Morris David L. , Small Kerrin S. , Fernando Michelle M. A. , Cunninghame Graham Deborah S. , Vyse Timothy J. 
Published: May 2019

AbstractSystemic lupus erythematosus (SLE) is an autoimmune disease, characterised by increased expression of type I interferon (IFN)-regulated genes and a striking sex imbalance towards females. Through combined genetic, in silico, in vitro, and ex vivo approaches, we defineCXorf21, a gene of hitherto unknown function, which escapes X-chromosome inactivation, as a candidate underlying the Xp21.2 SLE association. We demonstrate thatCXorf21is an IFN-response gene and that the sexual dimorphism in expression is magnified by immunological challenge. Fine-mapping reveals a single haplotype as a potential causal cis-eQTL forCXorf21. We propose that expression is amplified through modification of promoter and 3′-UTR chromatin interactions. Finally, we show that the CXORF21 protein colocalises with TLR7, a pathway implicated in SLE pathogenesis. Our study reveals modulation in gene expression affected by the combination of two hallmarks of SLE:CXorf21expression increases in a both an IFN-inducible and sex-specific manner.
Hydro-Seq enables contamination-free high-throughput single-cell RNA-sequencing for circulating tumor cells
Authors: Cheng Yu-Heng , Chen Yu-Chih , Lin Eric , Brien Riley , Jung Seungwon , Chen Yu-Ting , Lee Woncheol , Hao Zhijian , Sahoo Saswat , Min Kang Hyun , Cong Jason , Burness Monika , Nagrath Sunitha , S. Wicha Max , Yoon Euisik 
Published: May 2019

AbstractMolecular analysis of circulating tumor cells (CTCs) at single-cell resolution offers great promise for cancer diagnostics and therapeutics from simple liquid biopsy. Recent development of massively parallel single-cell RNA-sequencing (scRNA-seq) provides a powerful method to resolve the cellular heterogeneity from gene expression and pathway regulation analysis. However, the scarcity of CTCs and the massive contamination of blood cells limit the utility of currently available technologies. Here, we present Hydro-Seq, a scalable hydrodynamic scRNA-seq barcoding technique, for high-throughput CTC analysis. High cell-capture efficiency and contamination removal capability of Hydro-Seq enables successful scRNA-seq of 666 CTCs from 21 breast cancer patient samples at high throughput. We identify breast cancer drug targets for hormone and targeted therapies and tracked individual cells that express markers of cancer stem cells (CSCs) as well as of epithelial/mesenchymal cell state transitions. Transcriptome analysis of these cells provides insights into monitoring target therapeutics and processes underlying tumor metastasis.
Reconstructed Skin Models Revealed Unexpected Differences in Epidermal African and Caucasian Skin
Authors: Girardeau-Hubert Sarah , Deneuville Céline , Pageon Hervé , Abed Kahina , Tacheau Charlotte , Cavusoglu Nükhet , Donovan Mark , Bernard Dominique , Asselineau Daniel 
Published: May 2019

AbstractClinical observations of both normal and pathological skin have shown that there is a heterogeneity based on the skin origin type. Beside external factors, intrinsic differences in skin cells could be a central element to determine skin types. This study aimed to understand the in vitro behaviour of epidermal cells of African and Caucasian skin types in the context of 3D reconstructed skin. Full-thickness skin models were constructed with site matched human keratinocytes and papillary fibroblasts to investigate potential skin type related differences. We report that reconstructed skin epidermis exhibited remarkable differences regarding stratification and differentiation according to skin types, as demonstrated by histological appearance, gene expression analysed by DNA microarray and quantitative proteomic analysis. Signalling pathways and processes related to terminal differentiation and lipid/ceramide metabolism were up-regulated in epidermis constructed with keratinocytes from Caucasian skin type when compared to that of keratinocytes from African skin type. Specifically, the expression of proteins involved in the processing of filaggrins was found different between skin models. Overall, we show unexpected differences in epidermal morphogenesis and differentiation between keratinocytes of Caucasian and African skin types in in vitro reconstructed skin containing papillary fibroblasts that could explain the differences in ethnic related skin behaviour.
Unusual terahertz waveforms from a resonant medium controlled by diffractive optical elements
Authors: Pakhomov A. V. , Arkhipov R. M. , Arkhipov M. V. , Demircan A. , Morgner U. , Rosanov N. N. , Babushkin I. 
Published: May 2019

AbstractUp to now, full tunability of waveforms was possible only in electronics, up to radio-frequencies. Here we propose a new concept of producing few-cycle terahertz (THz) pulses with widely tunable waveforms. It is based on control of the phase delay between different parts of the THz wavefront using linear diffractive optical elements. Suitable subcycle THz wavefronts can be generated via coherent excitation of nonlinear low-frequency oscillators by few-cycle optical pulses. Using this approach it is possible to shape the electric field rather than the slow pulse envelope, obtaining, for instance, rectangular or triangular waveforms in the THz range. The method is upscalable to the optical range if the attosecond pump pulses are used.
Ancient DNA from mastics solidifies connection between material culture and genetics of mesolithic hunter–gatherers in Scandinavia
Authors: Kashuba Natalija , Kırdök Emrah , Damlien Hege , Manninen Mikael A. , Nordqvist Bengt , Persson Per , Götherström Anders 
Published: May 2019

AbstractHuman demography research in grounded on the information derived from ancient DNA and archaeology. For example, the study on the early postglacial dual-route colonisation of the Scandinavian Peninsula is largely based on associating genomic data with the early dispersal of lithic technology from the East European Plain. However, a clear connection between material culture and genetics has been lacking. Here, we demonstrate that direct connection by analysing human DNA from chewed birch bark pitch mastics. These samples were discovered at Huseby Klev in western Sweden, a Mesolithic site with eastern lithic technology. We generated genome-wide data for three individuals, and show their affinity to the Scandinavian hunter–gatherers. Our samples date to 9880-9540 calBP, expanding the temporal range and distribution of the early Scandinavian genetic group. We propose that DNA from ancient mastics can be used to study environment and ecology of prehistoric populations.
Zinc induces iron uptake and DMT1 expression in Caco-2 cells via a PI3K/IRP2 dependent mechanism
Authors: Kondaiah Palsa , Aslam Mohamad F. , Mashurabad Purna Chandra , Sharp Paul A. , Pullakhandam Raghu 
Published: May 2019

Abstract
The absorption of iron is influenced by numerous dietary and physiological factors. We have previously demonstrated that zinc treatment of intestinal cells increases iron absorption via induction of the apical membrane iron transporter divalent metal ion transporter-1 (DMT1). To better understand the mechanisms of zinc-induced iron absorption, we have studied the effect of zinc on iron uptake, iron transporter and iron regulatory protein (IRP 1 and 2) expression and the impact of the PI3K pathway in differentiated Caco-2 cells, an intestinal cell culture model. We found that zinc induces DMT1 protein and mRNA expression. Zinc-induced DMT1 expression and iron absorption were inhibited by siRNA silencing of DMT1. Furthermore, zinc treatment led to increased abundance of IRP2 protein in cell lysates and in polysomal fractions, implying its binding to target mRNAs. Zinc treatment induced Akt phosphorylation, indicating the activation of the PI3K pathway. LY294002, a specific inhibitor of PI3K inhibited zinc-induced Akt phosphorylation, iron uptake, DMT1 and IRP2 expression. Furthermore, LY294002 also decreased the basal level of DMT1 mRNA but not protein expression. siRNA silencing of IRP2 led to down-regulation of both basal and zinc-induced DMT1 protein expression, implying possible involvement of post-transcriptional regulatory mechanisms. In agreement with these findings, zinc treatment stabilized DMT1 mRNA levels in actinomycin D-treated cells. Based on these findings, we conclude that zinc-induced iron absorption involves elevation of DMT1 expression by stabilization of its mRNA, by a PI3K/IRP2-dependent mechanism.
Perceived Gaps in Genetics Training Among Audiologists and Speech-Language Pathologists: Lessons From a National Survey
Authors: Peter Beate , Dougherty Michael J. , Reed E. Kate , Edelman Emily , Hanson Karen 
Published: May 2019

Purpose
The aim of this study was to assess knowledge, self-rated confidence, and perceived relevance of genetics in the clinical practice of audiologists and speech-language pathologists (SLPs) toward a better understanding of the need for genetics education, given that genetics plays a growing role in the diagnosis of hearing impairment and communication disorders.

Method
A survey consisting of 8 demographic items and 16 content questions was returned by 233 audiologists and 283 SLPs. Knowledge of applied genetics was queried with clinical scenarios in a multiple-choice format. Self-assessment of clinical confidence and perceived relevance of genetics in one's field was queried with questions and statements rated on 5-point Likert scales. The benefit of additional training in genetics was rated with a yes/no question, and if answered with yes, suggested topics were entered.

Results
A large significant gap between confidence in one's own genetics skills and the perceived relevance of genetics was evident, regardless of professional group. Over one third of the audiologists and over two thirds of the SLPs indicated low or somewhat low confidence in their own ability to implement principles of genetics, whereas over two thirds of both groups agreed that genetics is relevant for their field. Regardless of group, confidence scores were significantly and positively associated with relevance scores. Over 80% of respondents in both groups indicated that they would benefit from additional training in genetics. Most commonly suggested topics included genetic causes, general information about genetics, and making referrals.

Conclusion
Both audiologists and SLPs felt that genetics is relevant for their fields and that additional training in genetics would be beneficial. Future studies should evaluate the effect of genetics training on patient outcomes and the need for incorporating genetics more extensively into audiology and speech-language pathology training programs.
60 GHz compact broadband antenna arrays with wide‐angle beam steering
Authors: Aziz Imran , Dahlbäck Robin , Öjefors Erik , Sjögren Kristoffer , Rydberg Anders , Dancila Dragos 
Published: May 2019

Highly integrated multilayered printed circuit board‐based patch antenna arrays are proposed in this study for 60 GHz wireless communications. Electromagnetic coupling between two stacked patches is used to achieve the broadband performance. Different structures of single element antennas, two‐element antenna arrays and four‐element antenna arrays are presented. The two compact four‐element antenna arrays show < −10 dB impedance bandwidth of 13 and 14.6% with 12 dBi peak gain. The arrays have the 3 dB gain bandwidth of 9 and 13%. A single column, four‐element sub‐array is used to design 4 × 16 antenna array. This array delivers 20.8 dBi peak gain with 13% impedance and gain bandwidth. Furthermore, a two‐element series fed array is used to realise a 2 × 16 phased antenna array. This array is fed through a 16 × channel radio frequency IC to achieve the beam steering in range.
Effects of proton irradiation on 60 GHz CMOS transceiver chip for multi‐Gbps communication in high‐energy physics experiments
Authors: Aziz Imran , Dancila Dragos , Dittmeier Sebastian , Siligaris Alexandre , Dehos Cedric , De Lurgio Patrik Martin , Djurcic Zelimir , Drake Gary , Gonzalez Jimenez Jose Luis , Gustaffson Leif , Kim Don‐Won , Locci Elizabeth , Pfeiffer Ulrich , Rodriquez Vazquez Pedro , Röhrich Dieter , Schöning Andre , Soltveit Hans Kristian , Ullaland Kjetil , Vincent Pierre , Yang Shiming , Brenner Richard 
Published: May 2019

This article presents the experimental results of 17 MeV proton irradiation on a 60 GHz low power, half‐duplex transceiver (TRX) chip implemented in 65 nm CMOS technology. It supports short range point‐to‐point data rate up to 6 Gbps by employing on‐off keying (OOK). To investigate the irradiation hardness for high‐energy physics (HEP) applications, two TRX chips were irradiated with total ionising doses (TID) of 74 and 42 kGy and fluence of and for RX and TX modes, respectively. The chips were characterised by pre‐ and post‐irradiation analogue voltage measurements on different circuit blocks as well as through the analysis of wireless transmission parameters like bit error rate (BER), eye diagram, jitter etc. Post‐irradiation measurements have shown certain reduction in performance but both TRX chips have been found operational through over the air measurements at 5 Gbps. Moreover, very small shift in the carrier frequency was observed after the irradiation.
FEM approach for diagnosis of induction machines' non‐adjacent broken rotor bars by short‐time Fourier transform spectrogram
Authors: Panagiotou Panagiotis A. , Arvanitakis Ioannis , Lophitis Neophytos , Antonino‐Daviu Jose A. , Gyftakis Konstantinos N. 
Published: May 2019

Rotor electrical faults are an issue frequently encountered when applying condition monitoring and fault diagnosis on induction machines. The detection via the analysis of the stator current becomes challenging when the rotor cage suffers from multiple breakages at non‐adjacent positions. In that case, electromagnetic asymmetries induced by the broken bars can be masked in such a way, that the diagnostic ability is highly likely to be obscured, thus leading to misinterpretation of the monitored signals' signatures. A new approach is proposed in this work to overcome this problem while the motor is at steady state. In this study, an industrial 6.6 kV, 1.1 MW induction motor is simulated with finite element analysis (FEM) and its electromagnetic variables are analysed and studied under healthy state and several faulty conditions. The analysis of the stator current and stray flux waveforms is executed in both the transient and the steady state and aims to diagnose the challenging cases where the rotor breakages are non‐consecutive with regard to their spatial location. The results show the potential of flux analysis to fault severity regardless of the spatial position of the broken bars.
rPICARD: A CASA-based calibration pipeline for VLBI data
Authors: Janssen M. , Goddi C. , van Bemmel I. M. , Kettenis M. , Small D. , Liuzzo E. , Rygl K. , Martí-Vidal I. , Blackburn L. , Wielgus M. , Falcke H. 
Published: May 2019

Context. The Common Astronomy Software Application (CASA) software suite, which is a state-of-the-art package for radio astronomy, can now reduce very long baseline interferometry (VLBI) data with the recent addition of a fringe fitter.
Aims. Here, we present the Radboud PIpeline for the Calibration of high Angular Resolution Data (rPICARD), which is an open-source VLBI calibration and imaging pipeline built on top of the CASA framework. The pipeline is capable of reducing data from different VLBI arrays. It can be run non-interactively after only a few non-default input parameters are set and delivers high-quality calibrated data. CPU scalability based on a message-passing interface (MPI) implementation ensures that large bandwidth data from future arrays can be processed within reasonable computing times.
Methods. Phase calibration is done with a Schwab–Cotton fringe fit algorithm. For the calibration of residual atmospheric effects, optimal solution intervals are determined based on the signal-to-noise ratio (S/N) of the data for each scan. Different solution intervals can be set for different antennas in the same scan to increase the number of detections in the low S/N regime. These novel techniques allow rPICARD to calibrate data from different arrays, including high-frequency and low-sensitivity arrays. The amplitude calibration is based on standard telescope metadata, and a robust algorithm can solve for atmospheric opacity attenuation in the high-frequency regime. Standard CASA tasks are used for CLEAN imaging and self-calibration.
Results. In this work we demonstrate the capabilities of rPICARD by calibrating and imaging 7 mm Very Long Baseline Array (VLBA) data of the central radio source in the M 87 galaxy. The reconstructed jet image reveals a complex collimation profile and edge-brightened structure, in accordance with previous results. A potential counter-jet is detected that has 10% of the brightness of the approaching jet. This constrains jet speeds close to the radio core to about half the speed of light for small inclination angles.
Nicht nur ein Verdauungsförderer – der Gelbe Enzian (Gentiana lutea L.)
Authors: Brendieck-Worm Cäcilia 
Published: May 2019

ZusammenfassungDer therapeutische Einsatz des Gelben Enzians wurde schon vor ca. 2000 Jahren dokumentiert. Im Mittelalter galt Gelber Enzian nahezu als Universalheilmittel. In der Tierheilkunde spielte er eine herausragende Rolle und fand insbesondere bei Verdauungsstörungen breite Anwendung. Im 20. Jh. verlor er in der Tiermedizin massiv an Bedeutung, nicht jedoch in der Volksheilkunde. Seit der Entdeckung der ersten Bitterstoffrezeptoren im Jahr 2000 gewinnen Bitterstoffdrogen wie der Gelbe Enzian wieder an Bedeutung.
Early Basal Cortisol Level as a Predictor of Hypothalamic-Pituitary-Adrenal (HPA) Axis Function After Pituitary Tumor Surgery
Authors: Polovina Tanja Skoric , Kraljevic Ivana , Solak Mirsala , Balasko Annemarie , Haxhiu Arta , Haxhiu Arita , Dusek Tina , Poljicanin Tamara , Kastelan Darko 
Published: May 2019

Abstract
Purpose The purpose of this study was to evaluate the clinical relevance of the early postoperative basal cortisol level in assessing the postoperative hypothalamic-pituitary-adrenal (HPA) axis function after pituitary tumor surgery.
Methods We performed a prospective observational study that enrolled 83 patients operated for pituitary adenoma or other sellar lesions at the University Hospital Center Zagreb between December 2013 and April 2017 (44 nonfunctioning pituitary adenomas, 28 somatotropinomas, 5 craniopharyngiomas, 2 prolactinomas resistant to medical therapy and 4 other lesions - Rathke's cleft cyst, arachnoid cyst, chondroma and gangliocytoma). Exclusion criteria were Cushing's disease, chronic therapy with glucocorticoids prior to surgery and preoperative adrenal insufficiency. Early postoperative basal cortisol levels (measured on the second postoperative day) and the Synacthen stimulation test (performed 3 months after the surgery with the peak cortisol level of>500 nmol/L considered as a normal response) were analyzed to assess HPA axis function during follow-up.
Results ROC analysis showed a cut-off of the basal cortisol level of ≥300 nmol/L measured on the second postoperative day to predict normal postoperative HPA axis function with the sensitivity of 92.31%, specificity of 87.14% and positive predictive value of 57.14%.
Conclusion The basal cortisol level on the second postoperative day is a valuable tool to predict integrity of the HPA axis after pituitary tumor surgery. Our data suggest that the cortisol level of ≥300 nmol/L accurately predicts adrenal sufficiency and that in these patients glucocorticoid therapy can be withdrawn.
Thermal Ablations for Colorectal Liver Metastases
Authors: Gennaro Nicolò , Mauri Giovanni , Varano Gianluca Maria , Monfardini Lorenzo , Pedicini Vittorio , Poretti Dario , Solbiati Luigi Alessandro 
Published: May 2019

AbstractApproximately 25% of colorectal cancers patients will develop hepatic metastases in the course of their disease. Surgical resection of hepatic metastases remains the first treatment choice for these patients, when feasible. However, only approximately 30% of metastatic lesions are resectable at the time of diagnosis. Thermal ablations have played an increasing role over the last few decades in the palliative and curative setting of colorectal liver metastases (CRLMs) in nonsurgical candidates with a liver-predominant disease. Several different techniques have been used to perform image-guided thermal ablations in the liver, including radiofrequency ablation, microwave ablation, cryoablation, and laser thermal ablation. We review the current ablation techniques, image-guidance modalities, indications, and debated topics of image-guided thermal ablation in CRLMs. Moreover, recent results from clinical trials are discussed along with future trends in liver thermal ablations.