bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of new EphA4 inhibitors by virtual screening of FDA-approved drugs
Authors: Gu Shuo , Fu Wing-Yu , Fu Amy K. Y. , Tong Estella Pui Sze , Ip Fanny C. F. , Huang Xuhui , Ip Nancy Y.
Published: May 2018

The receptor tyrosine kinase, erythropoietin-producing hepatocellular A4 (EphA4), was recently identified as a molecular target for Alzheimer’s disease (AD). We found that blockade of the interaction of the receptor and its ligands, ephrins, alleviates the disease phenotype in an AD transgenic mouse model, suggesting that targeting EphA4 is a potential approach for developing AD interventions. In this study, we identified five FDA-approved drugs—ergoloid, cyproheptadine, nilotinib, abiraterone, and retapamulin—as potential inhibitors of EphA4 by using an integrated approach combining virtual screening with biochemical and cellular assays. We initially screened a database of FDA-approved drugs using molecular docking against the ligand-binding domain of EphA4. Then, we selected 22 candidate drugs and examined their inhibitory activity towards EphA4. Among them, five drugs inhibited EphA4 clustering induced by ephrin-A in cultured primary neurons. Specifically, nilotinib, a kinase inhibitor, inhibited the binding of EphA4 and ephrin-A at micromolar scale in a dosage-dependent manner. Furthermore, nilotinib inhibited the activation of EphA4 and EphA4-dependent growth cone collapse in cultured hippocampal neurons, demonstrating that the drug exhibits EphA4 inhibitory activity in cellular context. As demonstrated in our combined computational and experimental approaches, repurposing of FDA-approved drugs to inhibit EphA4 may provide an alternative fast-track approach for identifying and developing new treatments for AD.
Electrochemistry and capillary condensation theory reveal the mechanism of corrosion in dense porous media
Authors: Stefanoni Matteo , Angst Ueli M. , Elsener Bernhard
Published: May 2018

Corrosion in carbonated concrete is an example of corrosion in dense porous media of tremendous socio-economic and scientific relevance. The widespread research endeavors to develop novel, environmentally friendly cements raise questions regarding their ability to protect the embedded steel from corrosion. Here, we propose a fundamentally new approach to explain the scientific mechanism of corrosion kinetics in dense porous media. The main strength of our model lies in its simplicity and in combining the capillary condensation theory with electrochemistry. This reveals that capillary condensation in the pore structure defines the electrochemically active steel surface, whose variability upon changes in exposure relative humidity is accountable for the wide variability in measured corrosion rates. We performed experiments that quantify this effect and find good agreement with the theory. Our findings are essential to devise predictive models for the corrosion performance, needed to guarantee the safety and sustainability of traditional and future cements.
Rivaroxaban does not influence hemorrhagic transformation in a diabetes ischemic stroke and endovascular thrombectomy model
Authors: Liu Feng-Di , Zhao Rong , Feng Xiao-Yan , Shi Yan-Hui , Wu Yi-Lan , Shen Xiao-Lei , Li Ge-Fei , Liu Yi-Sheng , Zhao Ying , He Xin-Wei , Yin Jia-Wen , Zhuang Mei-Ting , Zhao Bing-Qiao , Liu Jian-Ren
Published: May 2018

Managing endovascular thrombectomy (ET) in diabetic ischemic stroke (IS) with novel anticoagulants is challenging due to putative risk of intracerebral hemorrhage. The study evaluates increased hemorrhagic transformation (HT) risk in Rivaroxaban-treated diabetic rats post ET. Diabetes was induced in male Sprague-Dawley rats by intraperitoneal injection of 60 mg/kg streptozotocin. After 4-weeks, rats were pretreated orally with 30 mg/kg Rivaroxaban/saline; prothrombin time was monitored. IS and ET was induced after 1 h, by thread-induced transient middle cerebral artery occlusion (tMCAO) that mimicked mechanical ET for proximal MCA occlusion at 60 min. After 24 h reperfusion, infarct volumes, HT, blood-brain barrier (BBB) permeability, tight junction at peri-ischemic lesion and matrix metalloproteinase-9 (MMP-9) activity was measured. Diabetic rats seemed to exhibit increased infarct volume and HT at 24 h after ET than normal rats. Infarct volumes and functional outcomes did not differ between Rivaroxaban and diabetic control groups. A significant increase in HT volumes and BBB permeability under Rivaroxaban treatment was not detected. Compared to diabetic control group, neither the occludin expression was remarkably lower in the Rivaroxaban group nor the MMP-9 activity was higher. Together, Rivaroxaban does not increase HT after ET in diabetic rats with proximal MCA occlusion, since Rivaroxaban has fewer effects on post-ischemic BBB permeability.
Preoperative screening for illicit drug use in patients undergoing emergency surgery: A prospective observational study
Authors: Li Jingyi , Ma He , Liao Ren , Huang Yanjuan , Chen Guiyong
Published: May 2018

Knowledge of illicit drug users (IDUs) is important because of the comorbidity related to drug use. In this prospective, observational study, we screened 1007 patients undergoing emergency surgery and found that 75 of them (7.5%) were IDUs The results of preoperative screening showed that the rates of HIV and syphilis infection were significantly higher in IDUs (HIV (+) 2.6%, syphilis (+) 10.7%) than in non-IDUs (HIV (+) 0, syphilis (+) 0.5%). Intraoperative consumption of remifentanil (IDUs: 1.85 ± 1.30 vs. non-IDUs: 1.31 ± 0.86, p = 0.009), midazolam (IDUs: 4.82 ± 1.52 vs. non-IDUs: 4.15 ± 1.81, p = 0.002), and atracurium (IDUs: 31.5 ± 15.1 vs. non-IDUs: 25.5 ± 11.9, p = 0.006) and the proportion of patients requiring postoperative fentanyl (IDUs: 15 (20.0%) vs. non-IDUs: 95 (1.2%), p = 0.031) were significantly increased in IDUs compared to non-IDUs. Postoperative complications were observed in 22.7% (17/75) of patients who were IDUs, which was significantly increased when compared with non-IDUs (6.0%, 56/932, p < 0.001). The mortality rate within 30 days after surgery was similar between the two groups. These findings suggested that the IDUs were associated with increased rates of HIV and syphilis infection; greater consumption of intraoperative opioids, sedatives, and muscle relaxants; increased postoperative complications and a similar mortality rate within 30 days after surgery when compared with non-IDUs.
Structural, optoelectronic and charge transport properties of the complexes of indigo encapsulated in carbon nanotubes
Authors: Joshi Ankita , Ramachandran C. N.
Published: May 2018

The complexes of indigo encapsulated in carbon nanotubes of different diameters are investigated using the dispersion corrected density functional method and their optoelectronic and charge transport properties are discussed.
Mixed-scale poly(methyl methacrylate) channel network-based single-particle manipulation via diffusiophoresis
Authors: Hong Jisoo , Kim Beomsang , Shin Heungjoo
Published: May 2018

Simple and controllable single-particle manipulation via diffusiophoresis was demonstrated using a mixed-scale PMMA channel network including 3D microfunnels working as chambers.
Quercetin-coated Fe3O4 nanoparticle sensors based on low-field NMR for determination and removal of Pb2+ and Cu2+ in biological samples
Authors: Jiang Weina , Yang Shilong , Sun Xu , Lu Wen , Jiang Dong , Xu Li , Xu Haijun , Gao Buhong , Ma Mengtao , Cao Fuliang
Published: May 2018

In this paper, we develop quercetin-coated Fe3O4 nanoparticles (QMNPS) as a sensor for the detection and removal of Pb2+ and Cu2+ based on low-field NMR.
“Low-coordinate” 1,2-oxaphosphetanes – a new opportunity in coordination and main group chemistry
Authors: Kyri A. W. , Gleim F. , García Alcaraz A. , Schnakenburg G. , Espinosa Ferao A. , Streubel R.
Published: May 2018

While 1,2σ5λ5-oxaphosphetanes are well known intermediates from the Wittig-reaction, no 1,2σ3λ3-oxaphosphetanes have been described, so far. First investigations towards metal coordination and P-oxidation, as well as DFT calculations on retro-[2+2] cycloaddition reactions of the 1,2-oxaphosphetane ring are presented.
Synthetic studies on daphniglaucins
Authors: Qiu Yuanyou , Zhong Jiaxin , Du Shan , Gao Shuanhu
Published: May 2018

The synthetic approach to the core framework of daphniglaucin-type Daphniphyllum alkaloids is described herein.
F-Doping effects on carbon-coated Li3V2(PO4)3 as a cathode for high performance lithium rechargeable batteries: combined experimental and DFT studies
Authors: Wu Jinggao , Xu Maowen , Tang Chun , Li Guannan , He Hong , Li Chang Ming
Published: May 2018

F-Doping effects on a Li3V2(PO4)3−xFx@C cathode for high performance Li rechargeable batteries are systematically investigated with a combined experimental and DFT theoretical calculation approach.
Probing the tricationic ionic liquid/vacuum interface: insights from molecular dynamics simulations
Authors: Sedghamiz Elaheh , Moosavi Majid
Published: May 2018

The surface properties of three symmetric linear tricationic ionic liquids (LTILs) with the common anion, bis(trifluoromethylsulfonyl)imide ([NTf2]−), were studied using atomistic molecular dynamics simulation and identification of the truly interfacial molecules (ITIM) analysis.
Upgrading the value of anaerobic digestion via chemical production from grid injected biomethane
Authors: Verbeeck Kristof , Buelens Lukas C. , Galvita Vladimir V. , Marin Guy B. , Van Geem Kevin M. , Rabaey Korneel
Published: May 2018

Coupling decentralized biomethane generation to centralized CO production via gas grid redistribution can be an economically viable CO2 utilization strategy.
Co-catalysis over a bi-functional ligand-based Pd-catalyst for tandem bis-alkoxycarbonylation of terminal alkynes
Authors: Yang Da , Liu Huan , Wang Dong-Liang , Luo Zhoujie , Lu Yong , Xia Fei , Liu Ye
Published: May 2018

The one-pot tandem bis-alkoxycarbonylation of alkynes was accomplished over a bi-functional ligand-based Pd-catalyst with co-catalysis function.
Correction: Reactions of metallodrugs with proteins: selective binding of phosphane-based platinum(ii) dichlorides to horse heart cytochrome c probed by ESI MS coupled to enzymatic cleavage
Authors: Mügge Carolin , Michelucci Elena , Boscaro Francesca , Gabbiani Chiara , Messori Luigi , Weigand Wolfgang
Published: May 2018

Correction for ‘Reactions of metallodrugs with proteins: selective binding of phosphane-based platinum(ii) dichlorides to horse heart cytochrome c probed by ESI MS coupled to enzymatic cleavage’ by Carolin Mügge et al., Metallomics, 2011, 3, 987–990.
Regulation of antibiotic production in Actinobacteria: new perspectives from the post-genomic era
Authors: van der Heul Helga U. , Bilyk Bohdan L. , McDowall Kenneth J. , Seipke Ryan F. , van Wezel Gilles P.
Published: May 2018

The antimicrobial activity of many of their natural products has brought prominence to theStreptomycetaceae, a family of Gram-positive bacteria that inhabit both soil and aquatic sediments.
Stabilization of planar tetra-coordinate silicon in a 2D-layered extended system and design of a high-capacity anode material for Li-ion batteries
Authors: Sun Ming-Jun , Cao Xinrui , Cao Zexing
Published: May 2018

Stabilization of planar tetracoordinate silicon (ptSi) was achieved in a 2D-layered extended system, and the newly designed ptSi SiC8 siligraphene shows novel structural and electron-storage features.
Hyperbranched poly(ether amine) nanomicelles as nanoreactors for the unexpected ultrafast photolysis of fluorescein dyes
Authors: Tao Tao , Wang Ruiqing , Xu Hongjie , Yin Jie , Jiang Xuesong
Published: May 2018

hPEA nanomicelles can encapsulate fluorescein dyes as a nanoreactor, leading to the fast photobleaching of dyes.
Ultraviolet light-, temperature- and pH-responsive fluorescent sensors based on cellulose nanocrystals
Authors: Yuan Weizhong , Wang Chunyao , Lei Shize , Chen Jiangdi , Lei Shaorong , Li Zhihong
Published: May 2018

Intelligent CNC-g-P(AzoC6MA-co-DMAEMA) fluorescent nanosensors present ultraviolet light-, temperature- and pH-responsive properties.
Pressure-induced electrical transport properties, texture, and microstructure of the (Bi,Sb)2Te3 alloys
Authors: Guo Xin , Qin Jieming , Jia Xiaopeng , Jiang Dayong
Published: May 2018

High pressure can effectively modulate intrinsic point defects to induce a donor-like effect and then optimize the carrier concentration.
Valeriana wallichii root extract as a green & sustainable corrosion inhibitor for mild steel in acidic environments: experimental and theoretical study
Authors: Haldhar Rajesh , Prasad Dwarika , Saxena Akhil , Singh Priyanka
Published: May 2018

Corrosion inhibition analysis and the adsorption behaviour of Valeriana wallichii root extract for mild steel in 0.5 M H2SO4 solution has been investigated utilizing weight loss, electrochemical, FT-IR, UV along with SEM and AFM.
Dibenzopyridoimidazocinnolinium cations: a new family of light-up fluorescent DNA probes
Authors: Bosch Pedro , Sucunza David , Mendicuti Francisco , Domingo Alberto , Vaquero Juan J.
Published: May 2018

A new family of weakly fluorescent azonia cations with DNA-binding ability by intercalation whose fluorescence intensity increases significantly upon DNA addition is reported. A live-cell staining cells analysis showed the capacity of these new compounds for active uptake and accumulation by living cells.
Diastereoselective synthesis ofcis-1,3-disubstituted isoindolinesviaa highly site-selective tandem cyclization reaction
Authors: Xing Siyang , Cui Hong , Qin Jiajing , Gu Nan , Zhang Bowei , Wang Kui , Wang Ying , Xia Li , Wang Yumeng
Published: May 2018

A highly site-selective tandem reaction involving regioselective ring opening of aziridines and Michael addition of electron-deficient alkenes has been described.
Nanofibrous artificial skin substitute composed of mPEG–PCL grafted gelatin/hyaluronan/chondroitin sulfate/sericin for 2nddegree burn care:in vitroandin vivostudy
Authors: Bhowmick Sirsendu , Thanusha A. V. , Kumar Arun , Scharnweber Dieter , Rother Sandra , Koul Veena
Published: May 2018

The paper demonstrates the fabrication of sericin loaded hybrid polymeric composite nanofibrous scaffold and evaluation of its cytocompatibilty in three human monocultures and biocompatibility in second degree burn wound model in Wistar rats.
An eco-compatible pathway to the synthesis of mono and bis-multisubstituted imidazoles over novel reusable ionic liquids: an efficient and green sonochemical process
Authors: Ahmed Arafa Wael Abdelgayed
Published: May 2018

Novel and environmentally benign ionic liquids are synthesized and used as robust catalysts for a sonochemical one pot multi-component synthetic route to functionalized annulated imidazoles in water with excellent yields.
Effect of fluorination of naphthalene diimide–benzothiadiazole copolymers on ambipolar behavior in field-effect transistors
Authors: An Cunbin , Makowska Hanna , Hu Benlin , Duan Ruomeng , Pisula Wojciech , Marszalek Tomasz , Baumgarten Martin
Published: May 2018

Two naphthalene diimide (NDI)–benzothiadiazole (BT) based conjugated polymers with high molecular weight,P1andP2, were synthesized and compared for their electron-donating ability by varying F-atoms at the BT moiety.
The chemical identity, state and structure of catalytically active centers during the electrochemical CO2 reduction on porous Fe–nitrogen–carbon (Fe–N–C) materials
Authors: Leonard Nathaniel , Ju Wen , Sinev Ilya , Steinberg Julian , Luo Fang , Varela Ana Sofia , Roldan Cuenya Beatriz , Strasser Peter
Published: May 2018

We report novel structure–activity relationships and explore the chemical state and structure of catalytically active sites under operando conditions during the electrochemical CO2 reduction reaction (CO2RR) catalyzed by a series of porous iron–nitrogen–carbon (FeNC) catalysts.
Nanoparticle-supported polymer brushes for temperature-regulated glycoprotein separation: investigation of structure–function relationship
Authors: Ma Huiting , Jiang Lingdong , Hajizadeh Solmaz , Gong Haiyue , Lu Bin , Ye Lei
Published: May 2018

Nanoparticle-supported polymer brushes enable temperature-regulated protein binding and release.
The developmental toxicity, bioaccumulation and distribution of oxidized single walled carbon nanotubes in Artemia salina
Authors: Zhu Bin , Zhu Song , Li Jian , Hui Xin , Wang Gao-Xue
Published: May 2018

The developmental toxicity, bioaccumulation and distribution of SWCNTs in Artemia salina.
Four novel mutations in the ALPL gene in Chinese patients with odonto, childhood, and adult hypophosphatasia
Authors: Xu Lijun , Pang Qianqian , Jiang Yan , Wang Ou , Li Mei , Xing Xiaoping , Xia Weibo
Published: May 2018

Hypophosphatasia (HPP) is a rare inherited disorder characterized by defective bone and/or dental mineralization, and decreased serum alkaline phosphatase (ALP) activity. ALPL, the only gene related with HPP, encodes tissue non-specific ALP (TNSALP). Few studies were carried out in ALPL gene mutations in the Chinese population with HPP. The purpose of the present study is to elucidate the clinical and genetic characteristics of HPP in five unrelated Chinese families and two sporadic patients. Ten clinically diagnosed HPP patients from five unrelated Chinese families and two sporadic patients and fifty healthy controls were genetically investigated. All 12 exons and exon–intron boundaries of the ALPL gene were amplified by PCR and directly sequenced. The laboratory and radiological investigations were conducted simultaneously in these HPP ten patients. A 3D model of the TNSALP was used to predict the dominant negative effect of identified missense mutations. Three odonto, three childhood, and four adult types of HPP were clinically diagnosed. Ten mutations were identified in five unrelated Chinese families and two sporadic patients, including eight missense mutations and two frameshift mutations. Of which, four were novel: one frameshift mutation (p.R138Pfsx45); three missense mutations (p.C201R, p.V459A, p.C497S). No identical mutations and any other new ALPL mutations were found in unrelated 50 healthy controls. Our study demonstrated that the ALPL gene mutations are responsible for HPP in these Chinese families. These findings will be useful for clinicians to improve understanding of this heritable bone disorder.
Synthesising KV‐DRRs from MV‐DRs with fractal hourglass convolutional network
Authors: Liu Cong , Huang Miao , Ma Longhua , Lu Zheming
Published: May 2018

During a radiation treatment, the images of kilovoltage digital reconstructed radiograph (KV‐DRR) and megavoltage digital radiograph (MV‐DR) are registered to guide the therapy. Such registration is difficult since the images belong to different modalities. To reduce the difficulty, a fractal convolutional network is developed to map MV‐DR images into the modality of KV‐DRRs. The key idea is to split a hourglass‐shape network into multiple similar networks at reduced scale, yielding a fractal topology that is self‐similar at multiple scales. This division allows to predict images of unprecedented high resolution at low graphics processing unit memory usage. Experiments demonstrate that perceptual plausible and numerical accurate results are achieved out‐competing recent alternative architectures.
Ultra‐compact pulse compressor for generating ultrawideband short pulses
Authors: Hong S.K. , Park H.S.
Published: May 2018

An ultra‐compact pulse compressor for generating ultrawideband short pulses is proposed and tested. The proposed pulse compressor consists of a thin copper‐coated dielectric laminate to form an ‘ultra‐compact’ reverberant cavity, where a time‐reversal‐based input pulse is compressed into an ultrawideband short pulse. The proposed pulse compressor is validated via numerical simulation and measurement, and results show that a short pulse is generated with a peak gain of >10 dB.
Busy tone based coexistence algorithm for WRAN and WLAN systems in TV white space
Authors: Karatalay Onur , Erküçük Serhat , Baykaş Tunçer
Published: May 2018

TV White Space (TVWS) refers to frequency band reserved only for licensed terrestrial TV broadcasting and is opened to unlicensed use under regulatory conditions. While regulations protect licensed systems from interference, interference among unlicensed systems is left mainly to manufacturers. Consequently, there is a need to develop new coexistence approaches between TVWS networks. Busy tone broadcasting is a coexistence method, which can be used by TVWS networks to announce the selected frequency band is occupied. In this paper, a busy tone based coexistence algorithm is proposed for IEEE 802.11af and IEEE 802.22 networks and analyzed by considering different client distributions experiencing log‐normal shadowing, where the exact interfering packet rate and successful packet transmission rate expressions are obtained and validated by simulations for different scenarios. The results show that with the proposed coexistence approach, a WLAN can reliably detect the busy tone signal to change its frequency band and can reduce interference to WRAN. Even if there is no available frequency band for the WLAN, the WRAN still maintains its enhanced successful packet transmission performance. The deployment of the proposed algorithm is important for successful coexistence between cognitive wireless networks, where interference is not regulated, such as in TVWS bands.
Mobile physical layer spoofing detection based on sparse representation
Authors: Li Weiwei , Huang Jingjing
Published: May 2018

Recently, physical layer authentication techniques are emerging to detect spoofing attacks in wireless networks based on high consistency between two legitimate successive channel information. However, this high consistency is not always available, especially in dynamic networks, such as mobile scenarios. In this study, the authors propose a physical layer spoofing detection scheme based on sparse signal processing that exploit sparse representation and Savitzky–Golay filter, and use machine learning strategy to improve the spoofing detection accuracy under the case of low channel consistency. Simulation results show that the proposed technique can significantly improve the detection accuracy under the condition of low channel consistency.
Channel estimation using a reduced rate of pilot subcarriers for OFDM systems over doubly‐selective channels
Authors: Baouni Abdekhalek , Farrouki Atef
Published: May 2018

This study presents an improved channel estimation method for orthogonal frequency division multiplexing (OFDM) over doubly‐selective channels. Channel variation has been approximated by the basis expansion model using a specific comb‐type pilot approach. Since the data are transmitted as successive symbols in OFDM systems, the authors derive a channel estimation technique exploiting the additional information provided by adjacent symbols pilots. The main idea of the proposed method is to reduce the pilots to useful data ratio in order to improve the effective throughput and to increase the model accuracy in high mobility situations. The proposed algorithm has been investigated by considering both the conventional linear minimum mean square error and the least squares estimator. Various simulations have been conducted by considering different pilot rates with high Doppler effects and additive white Gaussian noise. The obtained results, in terms of the mean square error and binary error rate, show that the proposed algorithm outperforms the conventional techniques which are based on comb pilot‐assisted estimation.
Impact of measurement error on performance of pilot‐based power allocation in mobile femtocells
Authors: Alizadeh Sajjad , Saadat Reza
Published: May 2018

In this study, the authors investigate the effect of the measurement error on the performance of the pilot‐based power allocation of the wireless backhaul for the heterogeneous mobile femtocell networks. To implement the pilot‐assisted power allocation, it is essential to measure the received power on the backhaul. However, due to the dynamic feature of the wireless backhaul, the perfect measurement is approximately impossible in practice. Moreover, in spite of the signal to interference plus noise ratio (SINR) balancing, the pilot‐assisted power allocation is significantly sensitive to the measurement error. Accordingly, we specifically evaluate the effect of the measurement error of the uplink received power in the macro base stations on the performance of the pilot‐assisted power allocation in terms of the SINR balancing and the outage probability of the mobile femto base stations at the convergence point. Then, a minimum mean‐squared error (MMSE)‐based approach is proposed to mitigate the effects of the measurement error. Analytical and simulation results demonstrate that the SINR balancing is degraded when the measurement error on the backhaul link is increased. Also, the effectiveness of the MMSE‐based approach under the imperfect measurement condition is denoted in terms of the SINR balancing especially in high measurement error.
Occlusion detection via correlation filters for robust object tracking
Authors: Zhang Wei , Kang Baosheng
Published: May 2018

This study presents a robust object tracking method based on occlusion detection via correlation filters. In the proposed method, multi‐feature kernelised correlation filter is employed to estimate the preliminary location of the tracked target. To predict target occlusion state, the intrinsic relationship between the most reliable tracked target and its context information is exploited via correlation filters, together with a response stability constraint to make the detection more reliable. A long‐term filter is activated to recover the target if the occlusion occurs. Furthermore, the model is updated adaptively based on the changes of occlusion state and target appearance to make the tracking process robust. Extensive experimental results demonstrate that the proposed tracking method with occlusion detection performs favourably against 15 state‐of‐the‐art trackers over 100 challenge sequences on the object tracking benchmark OTB‐2015.
Mineralocorticoid Receptor Blockers and Aldosterone to Renin Ratio: A Randomized Controlled Trial and Observational Data
Authors: Pilz Stefan , Trummer Christian , Verheyen Nicolas , Schwetz Verena , Pandis Marlene , Aberer Felix , Grübler Martin , Meinitzer Andreas , Bachmann Antonia , Voelkl Jakob , Alesutan Ioana , Catena Cristiana , Sechi Leonardo , März Winfried , Obermayer-Pietsch Barbara , Tomaschitz Andreas
Published: May 2018

Current guidelines recommend to withdraw mineralocorticoid receptor (MR) blocker treatment for at least 4 weeks when measuring the aldosterone to renin ratio (ARR) as a screening test for primary aldosteronism (PA). We aimed to evaluate the effect of MR blocker treatment on ARR and its components, plasma aldosterone concentration (PAC), and direct renin concentration (DRC). First, we performed a post-hoc analysis of the effect of eplerenone on parathyroid hormone levels in primary hyperparathyroidism (EPATH) study, a randomized controlled trial (RCT) in 110 patients with primary hyperparathyroidism (pHPT). Patients were 1:1 randomly assigned to receive either 25 mg eplerenone once daily (up-titration after 4 weeks to 50 mg/day) or placebo for 8 weeks. Second, we measured the ARR in 4 PA patients from the Graz Endocrine Causes of Hypertension Study (GECOH) before and after MR blocker treatment. Ninety-seven participants completed the EPATH trial, and the mean treatment effect (95% confidence interval) for log(e)ARR was 0.08 (–0.32 to 0.48) ng/dl/μU/ml (p=0.694). The treatment effect was 0.71 (0.47 to 0.96; p<0.001) ng/dl for log(e)PAC and 0.64 (0.19 to 1.10; p=0.006) μU/ml for log(e)DRC, respectively. In the 4 PA patients, the ARR decreased from 11.24±3.58 at baseline to 2.70±1.03 (p=0.013) ng/dl/μU/ml after MR blocker treatment. In this study with limited sample size, MR blocker treatment did not significantly alter the ARR in pHPT patients but significantly reduced the ARR in PA patients. Diagnostic utility of ARR and its components for PA diagnostics under MR blocker treatment warrants further study.
An Easy Access to Sulfur Derivatives of 6,8-Dioxabicyclo[3.2.1]octanes, Naturally Abundant Scaffolds
Authors: Schmidt Elena , Bidusenko Ivan , Ushakov Igor , Protsuk Nadezhda , Trofimov Boris
Published: May 2018

Sulfur derivatives of 6,8-dioxabicyclo[3.2.1]octanes related to a number of natural products have been synthesized by the click hydrothiolation (AIBN or UV irradiation) of 7-methylene-6,8-dioxabicy­clo[3.2.1]octanes, assembled from acetylene and ketones in a one-pot transition-metal-free synthetic operation. An unusual feature of this free-radical reaction is that it is accelerated in the presence of bases due to involvement of the latter in a competition between the thiol addition and proton-catalyzed isomerization of the starting bicyclooctanes.
Peri-operative Adverse Outcomes in Patients with Atrial Fibrillation Taking Warfarin or Edoxaban: Analysis of the ENGAGE AF-TIMI 48 Trial
Authors: Douketis James , Murphy Sabina , Antman Elliott , Grip Laura , Mercuri Michele , Ruff Christian , Weitz Jeffrey , Braunwald Eugene , Giugliano Robert
Published: May 2018

Background Peri-operative management of anticoagulated patients with atrial fibrillation (AF) is challenging. To gain information on the peri-operative management of edoxaban, we compared outcomes in patients on warfarin or edoxaban enrolled in ENGAGE AF-TIMI 48 who underwent a surgery or invasive procedure.

Methods Data from patients undergoing their first surgery/procedure were analysed and results compared by anticoagulant (warfarin vs. higher- or lower-dose edoxaban regimen [HDER and LDER, respectively]). Patients were classified by procedural management: anticoagulant interrupted (last dose 4–10 days pre-procedure) or anticoagulant continued (last dose ≤ 3 days pre-procedure). Stroke/systemic embolism (SSE), major bleeding (MB), MB or clinically relevant non-MB (CRNMB) and death were assessed from 7 days pre- until 30 days post-procedure. The chi-square test was used to compare outcomes across treatment groups.

Results A total of 7,193 patients (34%) underwent surgery/procedure: 3,116 had anticoagulant interrupted, 4,077 had anticoagulant continued. Among patients on warfarin, HDER and LDER who had anticoagulant interrupted, rates of SSE were 0.6, 0.5 and 0.9% (p = 0.53), rates of MB were 1.0, 1.2 and 1.1% (p = 0.94) and rates of MB or CRNMB were 3.9, 4.2 and 3.6% (p = 0.78); among patients on warfarin, HDER and LDER who had anticoagulant continued, rates of SSE were 1.1, 0.7 and 0.9% (p = 0.51), rates of MB were 3.6, 2.6 and 2.4% (p = 0.13) and rates of MB or CRNMB were 8.5, 7.9 and 6.6% (p = 0.17).

Conclusion In patients requiring surgery/procedure in ENGAGE AF-TIMI 48, peri-operative rates of SSE, MB and death were not significantly different in patients who received edoxaban or warfarin.
Dynamic Changes of CHA2DS2-VASc Score and the Risk of Ischaemic Stroke in Asian Patients with Atrial Fibrillation: A Nationwide Cohort Study
Authors: Yoon Minjae , Yang Pil-Sung , Jang Eunsun , Yu Hee , Kim Tae-Hoon , Uhm Jae-Sun , Kim Jong-Youn , Pak Hui-Nam , Lee Moon-Hyoung , Lip Gregory , Joung Boyoung
Published: May 2018

Background Stroke risk in atrial fibrillation (AF) is often assessed at initial presentation, and risk stratification performed as a ‘one off’. In validation studies of risk prediction, baseline values are often used to ‘predict’ events that occur many years later. Many clinical variables have ‘dynamic’ changes over time, as the patient is followed up. These dynamic changes in risk factors may increase the CHA2DS2-VASc score, stroke risk category and absolute ischaemic stroke rate.

Objective This article evaluates the ‘dynamic’ changes of CHA2DS2-VASc variables and its effect on prediction of stroke risk.

Patients and Methods From the Korea National Health Insurance Service database, a total of 167,262 oral anticoagulant-naive non-valvular AF patients aged ≥ 18 years old were enrolled between January 1, 2002, and December 31, 2005. These patients were followed up until December 31, 2015.

Results At baseline, the proportions of subjects categorized as ‘low’, ‘intermediate’ or ‘high risk’ by CHA2DS2-VASc score were 15.4, 10.6 and 74.0%, respectively. Mean CHA2DS2-VASc score increased annually by 0.14, particularly due to age and hypertension. During follow-up of 10 years, 46.6% of ‘low-risk’ patients and 72.0% of ‘intermediate risk’ patients were re-classified to higher stroke risk categories. Among the original ‘low-risk’ patients, annual ischaemic stroke rates were significantly higher in the re-classified ‘intermediate’ (1.17 per 100 person-years, p < 0.001) or re-classified ‘high-risk’ groups (1.44 per 100 person-years, p = 0.048) than consistently ‘low-risk’ group (0.29 per 100 person-years). The most recent CHA2DS2-VASc score and the score change with the longest follow-up had the best prediction for ischaemic stroke.

Conclusion In AF patients, stroke risk as assessed by the CHA2DS2-VASc score is dynamic and changes over time. Rates of ischaemic stroke increased when patients accumulated risk factors, and were re-classified into higher CHA2DS2-VASc score categories. Stroke risk assessment is needed at every patient contact, as accumulation of risk factors with increasing CHA2DS2-VASc score translates to greater stroke risks over time.
Das Lambert-Eaton-Myasthenie-Syndrom: ein Überblick
Authors: Kohler Siegfried , Meisel Andreas
Published: May 2018

Das Lambert-Eaton-Myasthenie-Syndrom (LEMS) hat eine Prävalenz von etwa 5/1 000 000 und ist damit im Vergleich zur Myasthenia gravis (MG) ca. 10 – 20-mal seltener. Obwohl LEMS viele Ähnlichkeiten zur Myasthenia gravis aufweist, gibt es wichtige Unterschiede. Klinisch besteht eine vorwiegend proximal betonte belastungsabhängige Muskelschwäche, die bis hin zu einer respiratorischen Insuffizienz führen kann und häufig mit autonomen Störungen assoziiert ist. Ursächlich dafür sind Auto-Antikörper, welche gegen spannungsabhängige Kalziumkanäle (VGCC) vom P/Q-Typ an der Präsynapse gerichtet sind. Die Diagnosesicherung beruht vor allem auf der Detektion des pathologischen anti-VGCC Antikörpers sowie dem spezifischen Nachweis eines Inkrements von mindestens 60 % in der elektrophysiologischen Untersuchung eines betroffenen Muskels. Ein Inkrement ist dabei durch eine Steigerung des in Ruhe reduzierten Muskelsummenaktionspotenzials entweder nach maximaler Willkürinnervation oder hochfrequenter (≥ 20 Hz) Stimulation definiert. In einem Drittel der Patienten ist das LEMS paraneoplastischer Ätiologie, eine umfassende Tumorsuche nach Diagnosestellung ist daher notwendig. Klinisch gibt es einige Unterschiede zwischen dem paraneoplastischen (pLEMS) und dem rein autoimmunen (aiLEMS) Lambert-Eaton-Syndrom, die Hinweise geben können für die Ätiologie. Einen Anhalt dafür liefert der DELTA-P-Score und der SOX1-Antikörperstatus. Die häufigste zugrunde liegende Tumorerkrankung ist das kleinzellige Lungenkarzinom. Die Therapie basiert zunächst auf der Unterscheidung zwischen paraneoplastischer und autoimmuner Genese. pLEMS erfordert die Therapie der Tumorerkrankung. In der Regel profitieren aiLEMS- wie pLEMS-Patienten von einer symptomatischen Therapie mittels 3,4-Diaminopyridin (3,4-DAP), ggf. ergänzend Pyridostigmin sowie einer immunsuppressiven Langzeit-Therapie. Krisenhafte Verschlechterungen werden analog zur Myasthenia gravis mit Immunglobulinen, Plasmapherese oder Immunadsorption behandelt. Basierend auf positiven Erfahrungsberichten können auch moderne immunmodulatorische Ansätze, z. B. mit therapeutischen Antikörpern wie dem anti-CD20-Antikörper Rituximab, bei therapierefraktären Verläufen sinnvoll sein. Die Langzeitprognose des autoimmunen LEMS für eine klinische Stabilisierung mit weitgehender (pharmakologischer) Remission ist unserer Erfahrung nach gut, allerdings bestehen bei etwa 75 % deutliche Einschränkungen der Lebensqualität. Die Prognose der tumorassoziierten Form wird zu einem großen Teil von der Tumorerkrankung selbst und deren Therapie bestimmt. Kurative Verläufe der Tumorerkrankung und weitgehende Remission des pLEMS sind nicht selten.
Wie bewerten Nierenlebendspender die Spende und deren Folgen? Eine Befragung von 144 Betroffenen
Authors: Schieber Katharina , Gaag Sonja , Heller Katharina , Erim Yesim
Published: May 2018

Aufgrund des weltweiten Organmangels und der steigenden Anzahl an Patienten, die ein Organ benötigen, rückt die Lebendorganspende immer mehr in den Vordergrund. Um den Prozess der Lebendorganspende zu verbessern, wurde am Universitätsklinikum Erlangen eine Befragung zur Evaluation der Nierenlebendspende initiiert. Dabei sollten Erfahrungen und berichtete Folgen von Seiten der Lebendspender erfasst werden. Zwischen 2003–2014 wurden N=199 Lebendnierenspenden am Universitätsklinikum Erlangen durchgeführt. Von diesen willigten n=144 Lebendnierenspender (65,3% weiblich, Altersdurchschnitt 58,7 Jahre) ein, an der Studie teilzunehmen. Im Allgemeinen zeigte sich die große Mehrheit der Befragten mit der Lebendspende zufrieden. Nahezu alle Lebendnierenspender (98%) würden die Spende erneut durchführen, wenn sie könnten. Eine Belastung des körperlichen oder psychischen Befindens durch die Lebendspende wurde vom Großteil der Lebendspender verneint. Dennoch berichtete etwa ein Viertel der Befragten körperliche Einschränkungen, die nicht nur kurzfristige Operationsfolgen, wie Wundheilung oder Schmerzen beinhalten, sondern auch langfristige Beschwerden wie Bluthochdruck. Zudem wurden einzelne Problembereiche deutlich, wie z. B. mangelnde psychologische Versorgung oder ärztliche Nachsorge, die auf eine nötige Weiterentwicklung der Versorgungsstruktur hinweisen.
Intense, directed neutron beams from a laser-driven neutron source at PHELIX
Authors: Kleinschmidt A. , Bagnoud V. , Deppert O. , Favalli A. , Frydrych S. , Hornung J. , Jahn D. , Schaumann G. , Tebartz A. , Wagner F. , Wurden G. , Zielbauer B. , Roth M.
Published: May 2018

Laser-driven neutrons are generated by the conversion of laser-accelerated ions via nuclear reactions inside a converter material. We present results from an experimental campaign at the PHELIX laser at GSI in Darmstadt where protons and deuterons were accelerated from thin deuterated plastic foils with thicknesses in the μm and sub-μm range. The neutrons were generated inside a sandwich-type beryllium converter, leading to reproducible neutron numbers around 1011 neutrons per shot. The angular distribution was measured with a high level of detail using up to 30 bubble detectors simultaneously. It shows a laser forward directed component of up to 1.42 × 1010 neutrons per steradian, corresponding to a dose of 43 mrem scaled to a distance of 1 m from the converter.
Prospect for a 60 GHz multicharged ECR ion source
Authors: Thuillier T. , Bondoux D. , Angot J. , Baylac M. , Froidefond E. , Jacob J. , Lamy T. , Leduc A. , Sole P. , Debray F. , Trophime C. , Skalyga V. , Izotov I.
Published: May 2018

The conceptual design of a fourth generation hybrid electron cyclotron resonance (ECR) ion source operated at 60 GHz is proposed. The axial magnetic mirror is generated with a set of three Nb3Sn coils, while the hexapole is made with room temperature (RT) copper coils. The motivations for such a hybrid development are to study further the ECR plasma physics and the intense multicharged ion beams’ production and transport at a time when a superconducting (SC) hexapole appears unrealistic at 60 GHz. The RT hexapole coil designed is an evolution of the polyhelix technology developed at the French High Magnetic Field Facility. The axial magnetic field is generated by means of 3 Nb3Sn SC coils operated with a maximum current density of 350 A/mm2 and a maximum coil load line factor of 81%. The ECR plasma chamber resulting from the design features an inner radius of 94 mm and a length of 500 mm. The radial magnetic intensity is 4.1 T at the wall. Characteristic axial mirror peaks are 8 and 4.5 T, with 1.45 T minimum in between.
Calibration of a rotating accelerometer gravity gradiometer using centrifugal gradients
Authors: Yu Mingbiao , Cai Tijing
Published: May 2018

The purpose of this study is to calibrate scale factors and equivalent zero biases of a rotating accelerometer gravity gradiometer (RAGG). We calibrate scale factors by determining the relationship between the centrifugal gradient excitation and RAGG response. Compared with calibration by changing the gravitational gradient excitation, this method does not need test masses and is easier to implement. The equivalent zero biases are superpositions of self-gradients and the intrinsic zero biases of the RAGG. A self-gradient is the gravitational gradient produced by surrounding masses, and it correlates well with the RAGG attitude angle. We propose a self-gradient model that includes self-gradients and the intrinsic zero biases of the RAGG. The self-gradient model is a function of the RAGG attitude, and it includes parameters related to surrounding masses. The calibration of equivalent zero biases determines the parameters of the self-gradient model. We provide detailed procedures and mathematical formulations for calibrating scale factors and parameters in the self-gradient model. A RAGG physical simulation system substitutes for the actual RAGG in the calibration and validation experiments. Four point masses simulate four types of surrounding masses producing self-gradients. Validation experiments show that the self-gradients predicted by the self-gradient model are consistent with those from the outputs of the RAGG physical simulation system, suggesting that the presented calibration method is valid.
An electron beam ion trap and source for re-acceleration of rare-isotope ion beams at TRIUMF
Authors: Blessenohl M. A. , Dobrodey S. , Warnecke C. , Rosner M. K. , Graham L. , Paul S. , Baumann T. M. , Hockenbery Z. , Hubele R. , Pfeifer T. , Ames F. , Dilling J. , Crespo López-Urrutia J. R.
Published: May 2018

Electron beam driven ionization can produce highly charged ions (HCIs) in a few well-defined charge states. Ideal conditions for this are maximally focused electron beams and an extremely clean vacuum environment. A cryogenic electron beam ion trap fulfills these prerequisites and delivers very pure HCI beams. The Canadian rare isotope facility with electron beam ion source-electron beam ion sources developed at the Max-Planck-Institut für Kernphysik (MPIK) reaches already for a 5 keV electron beam and a current of 1 A with a density in excess of 5000 A/cm2 by means of a 6 T axial magnetic field. Within the trap, the beam quickly generates a dense HCI population, tightly confined by a space-charge potential of the order of 1 keV times the ionic charge state. Emitting HCI bunches of ≈107 ions at up to 100 Hz repetition rate, the device will charge-breed rare-isotope beams with the mass-over-charge ratio required for re-acceleration at the Advanced Rare IsotopE Laboratory (ARIEL) facility at TRIUMF. We present here its design and results from commissioning runs at MPIK, including X-ray diagnostics of the electron beam and charge-breeding process, as well as ion injection and HCI-extraction measurements.
Bulk viscosity of molecular fluids
Authors: Jaeger Frederike , Matar Omar K. , Müller Erich A.
Published: May 2018

The bulk viscosity of molecular models of gases and liquids is determined by molecular simulations as a combination of a dilute gas contribution, arising due to the relaxation of internal degrees of freedom, and a configurational contribution, due to the presence of intermolecular interactions. The dilute gas contribution is evaluated using experimental data for the relaxation times of vibrational and rotational degrees of freedom. The configurational part is calculated using Green-Kubo relations for the fluctuations of the pressure tensor obtained from equilibrium microcanonical molecular dynamics simulations. As a benchmark, the Lennard-Jones fluid is studied. Both atomistic and coarse-grained force fields for water, CO2, and n-decane are considered and tested for their accuracy, and where possible, compared to experimental data. The dilute gas contribution to the bulk viscosity is seen to be significant only in the cases when intramolecular relaxation times are in the μs range, and for low vibrational wave numbers (<1000 cm−1); This explains the abnormally high values of bulk viscosity reported for CO2. In all other cases studied, the dilute gas contribution is negligible and the configurational contribution dominates the overall behavior. In particular, the configurational term is responsible for the enhancement of the bulk viscosity near the critical point.
Polarization-induced hole doping in N-polar III-nitride LED grown by metalorganic chemical vapor deposition
Authors: Yan Long , Zhang Yuantao , Han Xu , Deng Gaoqiang , Li Pengchong , Yu Ye , Chen Liang , Li Xiaohang , Song Junfeng
Published: May 2018

Polarization-induced doping has been shown to be effective for wide-bandgap III-nitrides. In this work, we demonstrated a significantly enhanced hole concentration via linearly grading an N-polar AlxGa1-xN (x = 0–0.3) layer grown by metal-organic chemical vapor deposition. The hole concentration increased by ∼17 times compared to that of N-polar p-GaN at 300 K. The fitting results of temperature-dependent hole concentration indicated that the holes in the graded p-AlGaN layer comprised both polarization-induced and thermally activated ones. By optimizing the growth conditions, the hole concentration was further increased to 9.0 × 1017 cm−3 in the graded AlGaN layer. The N-polar blue-violet light-emitting device with the graded p-AlGaN shows stronger electroluminescence than the one with the conventional p-GaN. The study indicates the potential of the polarization doping technique in high-performance N-polar light-emitting devices.
Hollow microgels squeezed in overcrowded environments
Authors: Scotti A. , Brugnoni M. , Rudov A. A. , Houston J. E. , Potemkin I. I. , Richtering W.
Published: May 2018

We study how a cavity changes the response of hollow microgels with respect to regular ones in overcrowded environments. The structural changes of hollow poly(N-isopropylacrylamide) microgels embedded within a matrix of regular ones are probed by small-angle neutron scattering with contrast variation. The form factors of the microgels at increasing compressions are directly measured. The decrease of the cavity size with increasing concentration shows that the hollow microgels have an alternative way with respect to regular cross-linked ones to respond to the squeezing due to their neighbors. The structural changes under compression are supported by the radial density profiles obtained with computer simulations. The presence of the cavity offers to the polymer network the possibility to expand toward the center of the microgels in response to the overcrowded environment. Furthermore, upon increasing compression, a two step transition occurs: First the microgels are compressed but the internal structure is unchanged; then, further compression causes the fuzzy shell to collapse completely and reduce the size of the cavity. Computer simulations also allow studying higher compression degrees than in the experiments leading to the microgel’s faceting.