bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of 4-1BB antibody for cancer immunotherapy by balancing agonistic strength with FcγR affinity
Authors: Qi Xinyue , Li Fanlin , Wu Yi , Cheng Chen , Han Ping , Wang Jieyi , Yang Xuanming
Published: May 2019

Costimulation of T cell responses with monoclonal antibody agonists (mAb-AG) targeting 4-1BB showed robust anti-tumor activity in preclinical models, but their clinical development was hampered by low efficacy (Utomilumab) or severe liver toxicity (Urelumab). Here we show that isotype and intrinsic agonistic strength co-determine the efficacy and toxicity of anti-4-1BB mAb-AG. While intrinsically strong agonistic anti-4-1BB can activate 4-1BB in the absence of FcγRs, weak agonistic antibodies rely on FcγRs to activate 4-1BB. All FcγRs can crosslink anti-41BB antibodies to strengthen co-stimulation, but activating FcγR-induced antibody-dependent cell-mediated cytotoxicity compromises anti-tumor immunity by deleting 4-1BB+cells. This suggests balancing agonistic activity with the strength of FcγR interaction as a strategy to engineer 4-1BB mAb-AG with optimal therapeutic performance. As a proof of this concept, we have developed LVGN6051, a humanized 4-1BB mAb-AG that shows high anti-tumor efficacy in the absence of liver toxicity in a mouse model of cancer immunotherapy.
Author Correction: RNA synthesis is modulated by G-quadruplex formation in Hepatitis C virus negative RNA strand
Authors: Jaubert Chloé , Bedrat Amina , Bartolucci Laura , Di Primo Carmelo , Ventura Michel , Mergny Jean-Louis , Amrane Samir , Andreola Marie-Line
Published: May 2019

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
BRAF inhibition sensitizes melanoma cells to α-amanitin via decreased RNA polymerase II assembly
Authors: Frischknecht Lukas , Britschgi Christian , Galliker Patricia , Christinat Yann , Vichalkovski Anton , Gstaiger Matthias , Kovacs Werner J. , Krek Wilhelm
Published: May 2019

Despite the great success of small molecule inhibitors in the treatment of patients with BRAFV600E mutated melanoma, the response to these drugs remains transient and patients eventually relapse within a few months, highlighting the need to develop novel combination therapies based on the understanding of the molecular changes induced by BRAFV600E inhibitors. The acute inhibition of oncogenic signaling can rewire entire cellular signaling pathways and thereby create novel cancer cell vulnerabilities. Here, we demonstrate that inhibition of BRAFV600E oncogenic signaling in melanoma cell lines leads to destabilization of the large subunit of RNA polymerase II POLR2A (polymerase RNA II DNA-directed polypeptide A), thereby preventing its binding to the unconventional prefoldin RPB5 interactor (URI1) chaperone complex and the successful assembly of RNA polymerase II holoenzymes. Furthermore, in melanoma cell lines treated with mitogen-activated protein kinase (MAPK) inhibitors, α-amanitin, a specific and irreversible inhibitor of RNA polymerase II, induced massive apoptosis. Pre-treatment of melanoma cell lines with MAPK inhibitors significantly reduced IC50 values to α-amanitin, creating a state of collateral vulnerability similar to POLR2A hemizygous deletions. Thus, the development of melanoma specific α-amanitin antibody-drug conjugates could represent an interesting therapeutic approach for combination therapies with BRAFV600E inhibitors.
Vesicular Stomatitis Virus-Based Vaccine Protects Mice against Crimean-Congo Hemorrhagic Fever
Authors: Rodriguez Sergio E. , Cross Robert W. , Fenton Karla A. , Bente Dennis A. , Mire Chad E. , Geisbert Thomas W.
Published: May 2019

Crimean-Congo hemorrhagic fever virus (CCHFV), a tick-borne bunyavirus, can cause a life-threatening hemorrhagic syndrome in humans but not in its animal host. The virus is widely distributed throughout southeastern Europe, the Middle East, Africa, and Asia. Disease management has proven difficult and there are no broadly licensed vaccines or therapeutics. Recombinant vesicular stomatitis viruses (rVSV) expressing foreign glycoproteins (GP) have shown promise as experimental vaccines for several viral hemorrhagic fevers. Here, we developed and assessed a replication competent rVSV vector expressing the CCHFV glycoprotein precursor (GPC), which encodes CCHFV structural glycoproteins. This construct drives strong expression of CCHFV-GP, in vitro. Using these vectors, we vaccinated STAT-1 knock-out mice, an animal model for CCHFV. The vector was tolerated and 100% efficacious against challenge from a clinical strain of CCHFV. Anti-CCHFV-GP IgG and neutralizing antibody titers were observed in surviving animals. This study demonstrates that a rVSV expressing only the CCHFV-GP has the potential to serve as a replication competent vaccine platform against CCHF infections.
Increased prefrontal cortex interleukin-2 protein levels and shift in the peripheral T cell population in progressive supranuclear palsy patients
Authors: Rydbirk Rasmus , Elfving Betina , Folke Jonas , Pakkenberg Bente , Winge Kristian , Brudek Tomasz , Aznar Susana
Published: May 2019

Accumulating evidence suggests neuroinflammation to be an integrated feature of neurodegeneration. Profiling inflammatory mediators across diseases may reveal common and disease-specific signatures. Here, we focused on progressive supranuclear palsy (PSP), a tauopathy presenting motor and cognitive dysfunction. We screened for 21 cytokines and growth factors in the dorsomedial prefrontal cortex of 16 PSP and 16 control brains using different quantitative techniques. We found and validated increased interleukin (IL)-2 protein levels in the PSP group expressed locally by neurons and glia cells. We further investigated central players in neuroinflammatory pathways and found increased mRNA expression of glycogen synthase kinase 3 beta (GSK3B). IL-2 and GSK3B proteins are T and natural killer (NK) cell regulators and have previously been associated with other neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and multiple system atrophy. In addition, we identified a shift in peripheral CD4+ and CD8+ T cell populations toward increased numbers of memory and reduced numbers of naive T cells. We also observed increased numbers of CD56+ NK cells, but not of CD56+CD57+ or CD57+ NK cells. Our findings suggest a role for IL-2 in PSP disease processes and point toward active and possibly dysfunctional peripheral immune responses in these patients.
Spectroscopic diagnostic for the ring-size of carbohydrates in the gas phase: furanose and pyranose forms of GalNAc
Authors: Schindler Baptiste , Legentil Laurent , Allouche Abdul-Rhaman , Ferrières Vincent , Compagnon Isabelle
Published: May 2019

Hexoses are sparingly found in nature in the furanose form (5-membered ring).
Protein deglycosylation can drastically affect the cellular uptake
Authors: Ghazaryan Artur , Landfester Katharina , Mailänder Volker
Published: May 2019

Targeted drug delivery mediated by nanocarriers is a major issue in modern-day medicine.
Novel long-wavelength emissive lysosome-targeting ratiometric fluorescent probes for imaging in live cells
Authors: Ge Jinyin , Zhang Kai , Fan Li , Wang Xiaodong , Zhang Caihong , Dong Chuan , Wong Man Shing , Shuang Shaomin
Published: May 2019

Lysosomes are acidic organelles containing many hydrolytic enzymes responsible for degrading macromolecules.
Chemiluminescent sensor for hydrogen sulfide in rat brain microdialysis based on target-induced horseradish peroxidase deactivation
Authors: Fang Zheng , Yue Guiyin , Wang Jian , Luo Fang , Guo Longhua , Qiu Bin , Lin Zhenyu
Published: May 2019

The detection of hydrogen sulfide (H2S) is important due to its role in the diagnosis of many diseases since H2S is involved in the protection of neurons from oxidative stress and neuronal transmission modulation in the brain.
Carboboration of isocyanates with tris(pentafluorophenyl)borane and evidence for dissociative FLP chemistry of an acid–base pair
Authors: Mehta Meera , Goicoechea Jose M.
Published: May 2019

We describe carboelementation reactions involving tris(pentafluorophenyl)borane [B(C6F5)3] with isocyanates, and contrast this reactivity with that of the heavier group 13 Lewis acids Al(C6F5)3 and Ga(C6F5)3.
A pentacyclic S,N-heteroacene based electron acceptor with strong near-infrared absorption for efficient organic solar cells
Authors: Chen Xiaohan , Liu Hao , Xia Lixing , Hayat Tasawar , Alsaedi Ahmed , Tan Zhan’ao
Published: May 2019

A novel non-fullerene acceptor–donor–acceptor (A–D–A) structured small molecule acceptor material with fused ring N-alkyl DTP as the central donor unit and EG-2F as the terminal acceptor unit, named DTP-C17-4F, was designed and synthesized.
Facile synthesis of porous PdCu nanoboxes for efficient chromium(vi) reduction
Authors: Qiao Bin , Zhu Jingyi , Liu Yanping , Chen Yu , Fu Gengtao , Chen Pei
Published: May 2019

Porous PdCu nanoboxes were synthesized in a facile manner through a Cu2O template-assisted strategy, exhibiting catalytic activity and reusability for hexavalent chromium (Cr(vi)) reduction.
Alkali carbonates promote CO2 capture by sodium orthosilicate
Authors: Liu Jia , Wang Zhen , Wang Zirui , Song Jinwan , Li Guangshi , Xu Qian , You Jinglin , Cheng Hongwei , Lu Xionggang
Published: May 2019

The C2O52− combined with alkali cations are the intermediates during the CO2 uptake with Na4SiO4 and alkali carbonates.
Enhancement of oil flow in shale nanopores by manipulating friction and viscosity
Authors: Ho Tuan A. , Wang Yifeng
Published: May 2019

Enhanced oil recovery in shale nanopores using supercritical carbon dioxide and water.
Role of the hydrogen bond lifetimes and rotations at the water/amorphous silica interface on proton transport
Authors: Lentz Jesse , Garofalini Stephen H.
Published: May 2019

Glass surface/water heterogeneity and proton transfer: H3O+(1) forms, transfers excess proton to other H2O; O(2) takes excess proton from a different H3O+; O(3) forms asymmetric H-bonds to (4), (5), (6) via rotations.
Dual tuning of nickel sulfide nanoflake array electrocatalyst through nitrogen doping and carbon coating for efficient and stable water splitting
Authors: Hao Qiuyan , Li Shiyun , Liu Hui , Mao Jing , Li Ying , Liu Caichi , Zhang Jun , Tang Chengchun
Published: May 2019

Simultaneous carbon coating and nitrogen incorporation of a Ni3S2 nanoflake array electrocatalyst with enhanced activity and stability for water splitting.
2-Amino-3-chloro-1,4-naphthoquinone-covalent modification of graphene nanosheets for efficient electrochemical energy storage
Authors: Hou Lijie , Hu Zhongai , Wu Hongying , Wang Xiaotong , Xie Yandong , Li Shanshan , Ma Fuquan , Zhu Cuimei
Published: May 2019

The 2-amino-3-chloro-1,4-naphthoquinone molecules are covalently grafted onto graphene nanosheets by diazotization for efficient electrochemical energy storage.
Insights into the mechanisms of Ag-catalyzed synthesis of CF3-substituted heterocycles via [3+2]-cycloaddition from α-trifluoromethylated methyl isocyanides: effects of DBU and exploration of diastereoselectivity
Authors: Yuan Binfang , Chen Jinyang , Xie Xiaohua , He Shuhua , Luo Yafei , Guo Xiaogang , Huang Huisheng , He Rongxing
Published: May 2019

The diastereoselectivity of [3+2]-cycloaddition can be reasonably explained by the analysis of steric hindrance using DFT calculations.
Production of propylene glycol (1,2-propanediol) by the hydrogenolysis of glycerol in a fixed-bed downflow tubular reactor over a highly effective Cu–Zn bifunctional catalyst: effect of an acidic/basic support
Authors: Pandey Dinesh Kumar , Biswas Prakash
Published: May 2019

Very high glycerol conversion of 98.5% with ∼89% selectivity to propylene glycol was achieved at a very low pressure (0.72 MPa) over Cu–Zn/MgO catalyst for vapor phase hydrogenolysis of glycerol. Uniformly distributed partially reduced copper species (Cu2O, CuO, and Cu0) and higher basicity of the catalyst were the governing factors for higher selectivity to propylene glycol.
Facile synthesis of Cu2MoS4 nanosheet/multi-walled carbon nanotube composites as a high-efficiency electrocatalyst for hydrogen evolution
Authors: Zhou Jiamin , Xu Gang , Zhang Zewu , Wang Hongyong
Published: May 2019

A Cu2MoS4/MWCNT electrocatalyst with enhanced HER performance was synthesized for the first time, in which Cu2MoS4 nanosheets are intimately interlinked by MWCNTs.
Thiographene synthesized from fluorographene via xanthogenate with immobilized enzymes for environmental remediation
Authors: Sturala Jiri , Hermanová Soňa , Artigues Lucie , Sofer Zdeněk , Pumera Martin
Published: May 2019

Thiographene with a high content of thiol groups and it was used as a platform for anchoring both hydrolytic and oxidoreductase-based enzymes to produce efficient biocatalytic systems with no leaking of immobilized enzymatic molecules during storage.
The structure-based traceless specific fluorescence labeling of the smoothened receptor
Authors: Xue Dongxiang , Ye Lintao , Zheng Jun , Wu Yiran , Zhang Xianjun , Xu Yueming , Li Tao , Stevens Raymond C. , Xu Fei , Zhuang Min , Zhao Suwen , Zhao Fei , Tao Houchao
Published: May 2019

Inspired by recent progress in structural studies of the smoothened receptor (SMO), a group of affinity probes were developed to specifically light up SMO by grafting a small fluorescent group at the specific residue K395.
Preparation and in vitro release kinetics of nitrendipine-loaded PLLA–PEG–PLLA microparticles by supercritical solution impregnation process
Authors: Zhan Shiping , Wang Jingchang , Wang Weijing , Cui Liyun , Zhao Qicheng
Published: May 2019

In this work, drug-loaded polymer microparticles were prepared by a supercritical solution impregnation (SSI) process with nitrendipine as the model drug and PLLA–PEG–PLLA as the drug carrier.
Down-regulation of lncRNA GAS5 attenuates neuronal cell injury through regulating miR-9/FOXO3 axis in cerebral ischemic stroke
Authors: Wang Lijun , Niu Yanliang , He Gangrui , Wang Jianping
Published: May 2019

Cerebral ischemic stroke is a leading cause of neurological disability worldwide.
An explanative basis for the differential performance of students with low math aptitude in general chemistry
Authors: Rosa Vanessa , Lewis Scott E.
Published: May 2019

Students who score within the bottom quartile on cognitive measures of math aptitude have been identified as at-risk for low performance in chemistry courses, with less attention as to why such differential performance persists. At-risk students struggle most differentially on assessment items related to the mole concept and stoichiometry. An exploration as to the nature of the differential performance observed became of great interest as the assessment of these topics rarely progresses beyond multiplication or division, and at-risk students who achieved proficiency with the mole concept and stoichiometry had no noticeable gaps in academic chemistry performance when compared to students scoring in the top three quartiles of math aptitude. Thus, students in first-semester general chemistry were surveyed to describe their solution processes toward assessment items involving the mole concept and stoichiometry. Three hundred and forty-eight students responded to all survey prompts with 101 identified as at-risk. Findings suggest that while all students were observed to struggle in the conceptualization of the algorithms by which they execute solution processes, not-at-risk chemistry students were more likely to achieve correct answers via chemically implausible solution pathways. Rather than suggest the removal of assessment practices involving algorithmic, multiple-choice assessment on these topics, the implications include practical suggestions and opportunities for further research toward improving the equitability of measures used to assess proficiency with stoichiometry.
Investigating the effect of teacher mediation on student expressed reasoning
Authors: Moreira Patricia , Marzabal Ainoa , Talanquer Vicente
Published: May 2019

Understanding how chemistry teachers' interventions shape the reasoning that students express after a lesson is critical to support prospective and in-service teachers as they work with students' ideas in the classroom. In this qualitative research study, we analysed changes in the reasoning expressed by 10th grade students in a Chilean school in their written explanations about freezing point depression before and after a lesson on the topic. We also investigated how the teacher's interventions shaped the type of reasoning expressed by participating students. Our findings revealed significant shifts in the types of explanations generated after the lesson. A significant number of students transitioned from relational to simple causal reasoning in their pre- and post-lesson explanations. After the lesson most of the explanations were based on the activities of one or more of the system's entities. Analysis of teacher–student interactions during the observed lesson suggests that the teacher's mediation played a central role in the shift towards simple causal reasoning with centralized causality that was observed. The teacher in our study was more skilled at eliciting students' ideas than at helping students develop them with proper scaffolding. Thus, the observed classroom talk could not be considered as accountable talk, as most of the key ideas were introduced, selected, or reshaped by the teacher.
A novel mass spectrometry-cleavable, phosphate-based enrichable and multi-targeting protein cross-linker
Authors: Huang Rong , Zhu Wei , Wu Yue , Chen Jiakang , Yu Jianghui , Jiang Biao , Chen Hongli , Chen Wenzhang
Published: May 2019

A novel water soluble, phosphate-based enrichable, retro-Michael addition-driven MS-cleavable and multi-targeting cross-linker was developed.
1D/2D nitrogen-doped carbon nanorod arrays/ultrathin carbon nanosheets: outstanding catalysts for the highly efficient electroreduction of CO2 to CO
Authors: Zhu Ying , Lv Kuilin , Wang Xingpu , Yang Hequn , Xiao Guozheng , Zhu Ying
Published: May 2019

1D/2D NR/CS-X displayed an excellent electroreduction CO2 performance with low onset overpotential and high Faraday efficiency, impressive stability and fast kinetics.
Directional oxygen activation by oxygen-vacancy-rich WO2 nanorods for superb hydrogen evolution via formaldehyde reforming
Authors: Qian Kaicheng , Du Leilei , Zhu Xiaohui , Liang Shipan , Chen Shuang , Kobayashi Hisayoshi , Yan Xiaoqing , Xu Min , Dai Yihu , Li Renhong
Published: May 2019

Molecular oxygen activation (MOA) into reactive oxygen species (ROS) is extremely crucial in numerous catalytic processes, while precise control of ROS products remains difficult.
Shape-tailorable high-energy asymmetric micro-supercapacitors based on plasma reduced and nitrogen-doped graphene oxide and MoO2 nanoparticles
Authors: Zhang Liangzhu , Chen Zhiqiang , Zheng Shuanghao , Qin Si , Wang Jiemin , Chen Cheng , Liu Dan , Wang Lifeng , Yang Guoliang , Su Yuyu , Wu Zhong-Shuai , Bao Xinhe , Razal Joselito , Lei Weiwei
Published: May 2019

High-energy asymmetric micro-supercapacitors have been fabricated with diversified planar geometries.
Palladium structure engineering induced by electrochemical H intercalation boosts hydrogen evolution catalysis
Authors: Wang Guangxia , Liu Jinyang , Sui Yongming , Wang Ming , Qiao Liang , Du Fei , Zou Bo
Published: May 2019

Structure engineering by electrochemical H intercalation boosts the performance of Pd due to weakened Pd–H bonding.
Rod-shaped 1D polymer-assisted anisotropic self-assembly of 0D nanoparticles by a solution-drying method
Authors: Hayashi Hiroki , Kikuchi Ryosuke , Kumai Reiji , Takeguchi Masaki , Goto Hiromasa
Published: May 2019

Geometrically anisotropic 1D rod-shaped polymers facilitate the unidirectional assembly of clusters of 0D nanoparticles.
Stimuli responsive and reversible crystalline–amorphous transformation in a molecular solid: fluorescence switching and enhanced phosphorescence in the amorphous state
Authors: Sudhakar Pagidi , Radhakrishnan T. P.
Published: May 2019

A diaminodicyanoquinodimethane molecule based material undergoes reversible crystalline–amorphous transformation upon external stimuli. Significantly, delayed fluorescence and phosphorescence are observed in the material, with an unusual enhancement of the latter in the amorphous state, in sharp contrast to the decrease in fluorescence.
Anion-exchange synthesis of thermoelectric layered SnS0.1Se0.9−xTex nano/microstructures in aqueous solution: complexity and carrier concentration
Authors: Huang Lisi , Han Guang , Zhang Bin , Gregory Duncan H.
Published: May 2019

Nanostructured SnS0.1Se0.9−xTex quaternary chalcogenides have been synthesized via anion exchange; sintered SnS0.1Se0.88Te0.02 achieves enhanced electrical properties in the low-temperature range.
Knocking down of LINC01220 inhibits proliferation and induces apoptosis of endometrial carcinoma through silencing MAPK11
Authors: Li Yong , Kong Chengcai , Wu Chaoying , Wang Yingqiao , Xu Boqun , Liang Shenglian , Ying Xiaoyan
Published: May 2019

Background: Endometrial carcinoma (EC) still threatens the health of women. Thus, to explore how long intergenic non-protein coding RNA 01220 regulates the development of EC.

Methods: Whole genome expression profile data of EC and paracancerous tissues in TCGA database were downloaded. LINC01220 expression in EC and paracancerous tissues of patients in our hospital were detected by qRT-PCR. Furthermore, the relationship between LINC01220 expression and clinicopathological features of EC patients was analyzed. After transfection with sh-LINC01220 and pcDNA-MAPK11 (mitogen-activated protein kinase) in EC cells, proliferative, colony formation abilities and apoptosis were determined by cell counting kit-8 (CCK-8), colony formation assay and flow cytometry, respectively. Western blot was conducted to determine the regulatory role of LINC01220 on MAPK11.

Results: TCGA data showed that LINC01220 expression is markedly higher in EC tissues than that of paracancerous tissues, which was consistent without detection in EC patients of our hospital. LINC01220 expression was positively correlated to pathological grade and International Federation of Gynecology and Obstetrics (FIGO) stage of EC patients. After knockdown of LINC01220 in EC cells, proliferative and colony formation abilities decreased, whereas apoptotic rate increased. Cor function analysis revealed the positive correlation between LINC01220 and MAPK11 in EC. MAPK11 expression was regulated by LINC01220 in EC cells. Overexpression of MAPK11 can reverse the tumor suppressing effect of LINC01220 on EC.

Conclusions: LINC01220 promotes EC development by stimulating proliferation and inhibiting apoptosis of EC cells through up-regulating MAPK11.
Knockdown of hsa_circ_0023028 inhibits cell proliferation, migration, and invasion in laryngeal cancer by sponging miR-194-5p
Authors: Chen Xiaofeng , Su Xiaoqing , Zhu Chuansai , Zhou Jing
Published: May 2019

Emerging evidences have proposed that circular RNAs (circRNAs) play a major role in carcinogenesis. Hsa_circ_0023028 has been reported to be aberrantly expressed in laryngeal cancer (LCa). However, the role and the mechanism of hsa_circ_0023028 in LCa have not been adequately studied. In the present study, we demonstrated that hsa_circ_0023028 expression was up-regulated in LCa tissues and cell lines. miR-194-5p was down-regulated in LCa cells. Functionally, knockdown of hsa_circ_0023028 inhibited the proliferation, migration, and invasion of LCa cells, as evidenced by the reduced number of 5-Ethynyl-2′-deoxyuridine (EdU)-positive cells and decreased number of migrated and invaded cells. Additionally, hsa_circ_0023028 was identified as an miR-194-5p sink. A negative correlation between miR-194-5p and hsa_circ_0023028 expression was observed in LCa tissues. Besides, down-regulation of miR-194-5p attenuated the inhibitory effects of hsa_circ_0023028 silencing on LCa cell proliferation, migration, and invasion. In summary, hsa_circ_0023028 functions as an miR-194-5p sponge to promote the proliferation, migration, and invasion of LCa cells.
The treatment role of Cyperus rotundus L. to triple-negative breast cancer cells
Authors: Wang Fukai , Song Xiang , Ma Shuangshuang , Liu Chenyu , SUN Xiaohui , Wang Xinzhao , Liu Zhaoyun , Liang Dong , Yu Zhiyong
Published: May 2019

Cyperus rotundus L. is widely used in Traditional Chinese Medicine and studies have reported its anticancer effect, but its chemical composition and therapy mechanism remains unknown. This research aims to analyze the chemical components of the ethanol extract of Cyperus rotundus L. (EECR), detect its treatment effects on human Triple-negative breast cancer (TNBC) cells, and elucidate possible therapy mechanisms. The chemical components of EECR were detected by the Waters UPLC combined with Bruker Q-TOF mass spectrometer (UPLC-Q-TOF-MS). The phytochemical compounds were identified by comparing the mass fragmentations of each metabolite with databases such as METLIN, HMDB, and NCBI. A total of 21 compounds were identified in EECR. MDA-MB-231 and MDA-MB-468 cells were treated with various concentrations of EECR. Cell proliferation was examined using Cell Counting Kit-8 (CCK-8) and colony formation assays. Cell apoptosis and cell cycle were detected by flow cytometry. Apoptosis- and autophagy-related protein expression was detected by Western blot. EECR inhibits the proliferation of TNBC cells (MDA-MB-231 and MDA-MB-468) in a dose-dependent manner, which may be related to the arrest of cell cycle in G0/G1 phase. It induces apoptosis by promoting the expression of BAX and inhibiting the expression of BCL-2. In addition, autophagy inhibitor 3-Methyladenine (3-MA) inhibited TNBC cells pro-survival autophagy and increased the sensitivity of EECR. The present results demonstrated that EECR has potential effects on inhibits the proliferation and induction apoptosis in TNBC.
Deep‐learning‐based power distribution network switch action identification leveraging dynamic features of distributed energy resources
Authors: Duan Nan , Stewart Emma M.
Published: May 2019

This study proposes a data‐driven approach for identifying switch actions in power distribution networks. Simulated micro‐phasor measurement unit data is utilised to train a convolutional neural network (CNN) model. The trained CNN model can identify multi‐phase multi‐switch actions. Instead of working as a blackbox, the proposed approach extracts the features from the hidden layers of the trained CNN for engineering interpretation and error check. In addition, a random‐forest‐based feature ranking algorithm is proposed to identify the most important features. The proposed approach is validated on the IEEE 123‐node feeder modelled in GridLAB‐D. The CNN model is built and trained using TensorFlow. The proposed approach achieves 96.57% identification accuracy.
Adaptive cruise control radar‐based positioning in GNSS challenging environment
Authors: Abosekeen Ashraf , Karamat Tashfeen B. , Noureldin Aboelmagd , Korenberg Michael J.
Published: May 2019

Autonomous and land vehicles’ navigation in urban canyons requires aiding from other systems to the Global Navigation Satellite System (GNSS). This kind of environment is characterised by containing high rise buildings and long tunnels which interfere with the GPS satellite's signals causing its partial or total blockage. Therefore, the utilisation of another positioning source with high fidelity solution is essential during long outage periods. The Adaptive Cruise Control (ACC) system is a critical unit in the Advanced Drive Assistant System. The ACC measures the relative speed and distance between the on‐board vehicle and the vehicle in front. In this study, the ACC radar and an azimuth gyroscope are utilised to produce a self‐contained positioning system. The position solution of this system is utilised to update the Inertial Navigation System during the GNSS outage periods. The proposed system was tested over real road trajectories which were conducted in an urban canyon to validate the efficiency of the system.
Analysis of partial discharge sources in stator insulation system using variable excitation frequency
Authors: Nair Ramesh P. , Vishwanath Sumangala B.
Published: May 2019

Identification of partial discharge (PD) sources in stator insulation is an important and challenging task. Distinct phase‐resolved PD (PRPD) pattern of different PD sources are well established at power frequency (50/60 Hz) and can help to identify each source. In this study, different sources of PD commonly found in stator insulation were created on a 6.6 kV epoxy‐mica stator coil. Each PD source was experimentally investigated at a variable excitation frequency in the range of 50–0.1 Hz. PRPD pattern and PD parameters such as integrated charge per cycle and number of discharge pulses per cycle of each discharge source were compared at different frequencies. The comparison suggests that the parameter of each PD source was dependent on excitation frequency. Some discharge sources have shown a distinct variation in their characteristics with excitation frequency. These distinct characteristics are additional information to the existing ones, which will help to correlate PD characteristics with the source of PD in stator insulation.
Dust of comet 67P/Churyumov-Gerasimenko collected by Rosetta/MIDAS: classification and extension to the nanometer scale
Authors: Mannel T. , Bentley M. S. , Boakes P. D. , Jeszenszky H. , Ehrenfreund P. , Engrand C. , Koeberl C. , Levasseur-Regourd A. C. , Romstedt J. , Schmied R. , Torkar K. , Weber I.
Published: May 2019

Context. The properties of the smallest subunits of cometary dust contain information on their origin and clues to the formation of planetesimals and planets. Compared to interplanetary dust particles or particles collected during the Stardust mission, dust collected in the coma of comet 67P/Churyumov-Gerasimenko (67P) during the Rosetta mission provides a resource of minimally altered material with known origin whose structural properties can be used to further the investigation of the early solar system.

Aims. The cometary dust particle morphologies found at comet 67P on the micrometer scale are classified, and their structural analysis is extended to the nanometer scale.

Methods. We present a novel method for achieving the highest spatial resolution of imaging obtained with the MIDAS Atomic Force Microscope on board Rosetta. 3D topographic images with resolutions down to 8 nm were analyzed to determine the subunit sizes of particles on the nanometer scale.

Results. Three morphological classes can be determined: (i) fragile agglomerate particles of sizes larger than about 10 μm comprised of micrometer-sized subunits that may themselves be aggregates and show a moderate packing density on the surface of the particles. (ii) A fragile agglomerate with a size of about a few tens of micrometers comprised of micrometer-sized subunits that are suggested to be aggregates themselves and are arranged in a structure with a fractal dimension lower than two. (iii) Small micrometer-sized particles comprised of subunits in the size range of hundreds of nanometers that show surface features that are again suggested to represent subunits. Their differential size distributions follow a log-normal distribution with means of about 100 nm and standard deviations between 20 and 35 nm.

Conclusions. The properties of the dust particles found by MIDAS represent an extension of the dust results of Rosetta to the micro- and nanometer scale. All micrometer-sized particles are hierarchical dust agglomerates of smaller subunits. The arrangement, appearance, and size distribution of the smallest determined surface features are reminiscent of those found in chondritic porous interplanetary dust particles. They represent the smallest directly detected subunits of comet 67P.
SHALOS: StatisticalHerschel-ATLAS lensed objects selection
Authors: González-Nuevo J. , Suárez Gómez S. L. , Bonavera L. , Sánchez-Lasheras F. , Argüeso F. , Toffolatti L. , Herranz D. , González-Gutiérrez C. , García Riesgo F. , de Cos Juez F. J.
Published: May 2019

Context. The statistical analysis of large sample of strong lensing events can be a powerful tool to extract astrophysical or cosmological valuable information. Their selection using submillimetre galaxies has been demonstrated to be very effective with more than ∼200 proposed candidates in the case ofHerschel-ATLAS data and several tens in the case of the South Pole Telescope. However, the number of confirmed events is still relatively low, i.e. a few tens, mostly because of the lengthy observational validation process on individual events.

Aims. In this work we propose a new methodology with a statistical selection approach to increase by a factor of ∼5 the number of such events within theHerschel-ATLAS data set. Although the methodology can be applied to address several selection problems, it has particular benefits in the case of the identification of strongly lensed galaxies: objectivity, minimal initial constrains in the main parameter space, and preservation of statistical properties.

Methods. The proposed methodology is based on the Bhattacharyya distance as a measure of the similarity between probability distributions of properties of two different cross-matched galaxies. The particular implementation for the aim of this work is called SHALOS and it combines the information of four different properties of the pair of galaxies: angular separation, luminosity percentile, redshift, and the ratio of the optical to the submillimetre flux densities.

Results. The SHALOS method provides a ranked list of strongly lensed galaxies. The number of candidates within ∼340 deg2of theHerschel-ATLAS surveyed area for the final associated probability,Ptot >  0.7, is 447 and they have an estimated mean amplification factor of 3.12 for a halo with a typical cluster mass. Additional statistical properties of the SHALOS candidates, as the correlation function or the source number counts, are in agreement with previous results indicating the statistical lensing nature of the selected sample.
Energy-corrected FEM and explicit time-stepping for parabolic problems
Authors: Swierczynski Piotr , Wohlmuth Barbara
Published: May 2019

The presence of corners in the computational domain, in general, reduces the regularity of solutions of parabolic problems and diminishes the convergence properties of the finite element approximation introducing a so-called “pollution effect”. Standard remedies based on mesh refinement around the singular corner result in very restrictive stability requirements on the time-step size when explicit time integration is applied. In this article, we introduce and analyse the energy-corrected finite element method for parabolic problems, which works on quasi-uniform meshes, and, based on it, create fast explicit time discretisation. We illustrate these results with extensive numerical investigations not only confirming the theoretical results but also showing the flexibility of the method, which can be applied in the presence of multiple singular corners and a three-dimensional setting. We also propose a fast explicit time-stepping scheme based on a piecewise cubic energy-corrected discretisation in space completed with mass-lumping techniques and numerically verify its efficiency.
Predictors of a Successful Bipolar Radiofrequency Endometrial Ablation
Authors: Eisele Lilly , Köchli Lea , Städele Patricia , Welter JoEllen , Fehr-Kuhn Maja , Fehr Mathias
Published: May 2019

Introduction The studyʼs objectives were to determine the success rate following radiofrequency endometrial ablation to treat abnormal menstrual bleeding and to assess risk factors for failure of the method.

Materials and Methods 195 women who were treated with bipolar radiofrequency endometrial ablation between 01/2009 and 06/2016 were included in this prospective cohort study. Postoperative data from 187 women were collected at a median of 17.5 months (IQR 4.5–34.9; 1–82). Multivariate analyses of risk factors were performed. Success was defined as amenorrhoea or spotting.

Results Patient characteristics were as follows: mean age 44 years (SD ± 5), median parity 2 (IQR 2–3), median hysterometer 8.7 cm (SD ± 1.1), and median BMI 23.5 kg/m2 (IQR 21–27). 30 patients (19.5%) had intramural masses that could be measured with ultrasound. Postoperative success rate was 86.1%. 10 patients (5%) had a hysterectomy postoperatively – 6 for heavy bleeding, 3 due to prolapse, and 1 due to dysmenorrhoea. Multivariate analyses showed the presence of intramural masses in women < 45 years was a significant risk factor for therapeutic failure (p = 0.033; 95% CI 1.08–12.57), with an increased risk of hysterectomy (OR 7.9, 95% CI 1.2–52.7, p = 0.033).

Conclusion Bipolar radio frequency endometrial ablation was highly successful in the absence of an intramural mass (88%). Even smaller intramural fibroids (DD: adenomyomas of a median of 15 mm) reduce the success rate (76%), which is why preoperative ultrasound is recommended. In the presence of intramural masses, the risk of a hysterectomy for women < 45 years increases eightfold.
Female Adnexal Tumour of Probable Wolffian Origin (FATWO): Review of the Literature
Authors: Hübner Theresa , Schwab Michael , Hartmann Elena , Mayr Doris , Thurner Annette , Bley Thorsten , Wöckel Achim , Herr Daniel
Published: May 2019

FATWO (female adnexal tumour of probable Wolffian origin) denotes a rare tumour of the female adnexa which has been described in nearly 80 cases worldwide and which presumably originates in the remains of the Wolffian ducts. In 10 to 20 percent of patients, a metastasis or recurrence was seen subsequently and for this reason, a malignant potential is attributed to the FATWO. Because of the small number of cases, there is no clear therapeutic recommendation. The method of choice currently is surgical treatment with hysterectomy and adnexectomy. The benefit of radio- and chemotherapies is not clear and a small number of treatment attempts with imatinib have been made in cases of CD117 positivity or treatment attempts on an endocrine basis. This work provides an overview of the literature on epidemiology, imaging and histopathological diagnostic features as well as therapeutic options of this same tumour form.
Postpartum Depressive Disorder – Psychosomatic Aspects
Authors: Schipper-Kochems Stephanie , Fehm Tanja , Bizjak Gabriele , Fleitmann Ann , Balan Percy , Hagenbeck Carsten , Schäfer Ralf , Franz Matthias
Published: May 2019

Postpartum depression (PPD) is the most common mental illness in mothers following the birth of a child. Since the symptoms of PPD are similar to the normal stress of healthy women following childbirth, it is often difficult for the attending gynaecologist or midwife to diagnose this illness in a timely manner and thus initiate adequate treatment and comprehensive support for the patient. Even if there are options for a screening using evaluated questionnaires and subsequent psychotherapy and/or drug therapy in the treatment of PPD which has proven effective, it is seen that, in most treatment approaches, little consideration is given to the affect-controlled interaction and the bonding behaviour between mother and child. This article presents diagnostic measures and current therapeutic approaches as well as their integration in practice in order to achieve awareness of this topic in everyday clinical practice and show the pathways of appropriate treatment. Specific multiprofessional treatment approaches which centre on the mother-child relationship demonstrate successes with regard to depression in the mothers and also on the development of a secure mother-child bond and are thus a protective factor in the development of the affected children. The now well-known effects of PPD on the fathers as well as the negative impacts of paternal depression on child development make it clear that the treatment should not focus solely on maternal depression, but also always on the family bond between the mother, child and father in the treatment.
Unterschiedliche Häufigkeiten pneumologischer Krankheitsbilder in der ambulanten und stationären Medizin
Authors: Herkenrath S. , Mülleneisen N. , Treml M. , Kietzmann I. , Hagmeyer L. , Randerath W.
Published: May 2019

Hintergrund Die Evaluation von Behandlungsschwerpunkten in der stationären und ambulanten pneumologischen Patientenversorgung ist von besonderem gesundheitspolitischem Interesse, da sie Auswirkungen auf Arzt, Patient und die Forschung hat. Diese Arbeit beschreibt Unterschiede und Gemeinsamkeiten der Behandlungsschwerpunkte heutiger ambulanter und stationärer pneumologischer Patientenversorgung und diskutiert deren Auswirkungen auf Patient, Arzt und Forschung.

Methodik Der Vergleich zwischen ambulantem und stationärem Sektor erfolgt in der hier vorliegenden Studie auf Basis der Häufigkeiten verschlüsselter ICD-Codes einer pneumologischen Fachklinik (5211 Fälle des Jahres 2016) sowie der seitens der kassenärztliche Vereinigung Nordrhein veröffentlichten häufigsten ICD-10-Codes pneumologischer Arztpraxen im dritten Quartal 2016 (142431 Fälle).

Ergebnisse Viele pneumologische Krankheitsbilder werden in relativ ähnlichen Anteilen sowohl in der Praxis als auch im Krankenhaus behandelt. Bei anderen Krankheitsbildern zeigen sich erhebliche Unterschiede in der relativen Häufigkeit in Praxis und Klinik. So werden allergische Erkrankungen wie die allergische Rhinopathie und das Asthma bronchiale v. a. ambulant behandelt, während die respiratorische Insuffizienz und das Lungenkarzinom vorwiegend eine Domäne der stationären pneumologischen Medizin sind.

Schlussfolgerung Die Behandlungsschwerpunkte in der ambulanten und stationären pneumologischen Versorgung unterscheiden sich ungeachtet vieler Gemeinsamkeiten dennoch zum Teil erheblich. Dies hat Auswirkungen auf die ärztliche Weiterbildung, die Durchführung klinischer Studien, aber auch und v. a. auf die Patientenversorgung. Zur Erhaltung eines hohen medizinischen Versorgungsniveaus in allen Bereichen der Pneumologie scheint daher ein enger inhaltlicher Austausch zwischen ambulantem und stationärem Sektor unverzichtbar. Von einer sektorenübergreifenden Verfügbarkeit medizinischer Expertise profitieren am Ende alle: Ärzte, Patienten und Wissenschaft.
Surgical and Non-surgical Treatment of Vertebral Fractures in Elderly
Authors: Chmielnicki Marc , Prokop Axel , Kandziora Frank , Pingel Andreas
Published: May 2019

Demographic development in Germany has led to an aging of the population. Particularly for these patients, osteoporosis-induced vertebral fractures represent a significant decrease in quality of life and level of activity. According to current guidelines, the initial treatment of stable osteoporotic vertebral fractures is conservative management with analgesic, anti-osteoporotic, physical therapy, and orthotic measures as first line options. Personal experience, however, suggests that patients benefit from timely surgical treatment through rapid improvement of pain symptoms and thus, more rapid mobilization. The poor bone quality of elderly patients presents the treating spine surgeon a challenge in achieving stable spinal fusion with or without support, for example, through augmentation. Minimally invasive procedures have increasingly established themselves for such purposes in recent years. With over 1000 fracture treatments in the last 3.5 years, we have developed a differentiated treatment concept depending on patient age and fracture morphology, which we would like to introduce. Unstable fractures with posterior edge involvement are stabilized from posterior with a percutaneous fixator. Patients over 60 years were treated percutaneously with a polyaxial screw system. Increased stability was achieved by PMMA cement augmentation of the fenestrated screws. In elderly patients with Magerl A3 fractures without neurologic deficit, the index vertebra is supplementally treated with kyphoplasty (hybrid treatment). In acute, stable osteoporotic vertebral fractures with severe pain despite analgesics, we perform kyphoplasty, which is possible even in high thoracic fractures to T3 with smaller balloons and thinner trocars. Vertebroplasty is another option in the lumbar and lower thoracic spine. Because of invasiveness, extended posterior–anterior correction procedures are generally avoided in this population, which has frequent multiple comorbidities.
Serum Vitamin D Levels in Fertile and Infertile Women with Polycystic Ovary Syndrome
Authors: Kokanalı Demet , Karaca Mujdegul , Ozakşit Gulnur , Elmas Burak , Engin Üstün Yaprak
Published: May 2019

Introduction In polycystic ovary syndrome, serum vitamin D levels are known to correlate with metabolic conditions such as diabetes mellitus, metabolic syndrome and cardiovascular disease. However, there are not enough studies showing such a relationship with female fertility. We aimed to compare serum vitamin D levels in fertile and infertile women with polycystic ovary syndrome to evaluate whether vitamin D may play a role in the pathogenesis of fertility problems in women with polycystic ovary syndrome.

Materials and Methods 274 infertile and 111 fertile women with polycystic ovary syndrome were included in this retrospective study. Infertile and fertile groups were matched by age, body mass index and homeostasis model assessment of insulin resistance. Anthropometric, clinical and laboratory characteristics of the women were recorded. Serum 25(OH)D3 levels were used to assess serum vitamin D levels.

Results No significant differences were detected between groups in terms of anthropometric, clinical and laboratory features except for serum 25(OH)D3 levels and the incidence of vitamin D deficiency. Vitamin D levels were significantly lower and vitamin D deficiency was more common in the infertile group compared to the fertile group. When the groups were stratified into obese/non-obese or insulin resistance positive/negative, infertile obese and infertile insulin resistance-positive women had the lowest serum 25(OH)D3 levels.

Conclusion Serum vitamin D levels are lower in infertile women with polycystic ovary syndrome compared to fertile women. When insulin resistance or obesity was present, vitamin D levels were reduced further. Thus, in polycystic ovary syndrome, lower vitamin D levels may play a role in the pathogenesis of fertility problems.