bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of Pulmonary Gas Transport in Rabbits Using Hyperpolarized Xenon-129 Magnetic Resonance Imaging
Authors: Ruppert Kai , Hamedani Hooman , Amzajerdian Faraz , Xin Yi , Duncan Ian F. , Profka Harrilla , Siddiqui Sarmad , Pourfathi Mehrdad , Kadlecek Stephen , Rizi Rahim R. 
Published: May 2018

AbstractMany forms of lung disease manifest themselves as pathological changes in the transport of gas to the circulatory system, yet the difficulty of imaging this process remains a central obstacle to the comprehensive diagnosis of lung disorders. Using hyperpolarized xenon-129 as a surrogate marker for oxygen, we derived the temporal dynamics of gas transport from the ratio of two lung images obtained with different timing parameters. Additionally, by monitoring changes in the total hyperpolarized xenon signal intensity in the left side of the heart induced by depletion of xenon signal in the alveolar airspaces of interest, we quantified the contributions of selected lung volumes to the total pulmonary gas transport. In a rabbit model, we found that it takes at least 200 ms for xenon gas to enter the lung tissue and travel the distance from the airspaces to the heart. Additionally, our method shows that both lungs contribute fairly equally to the gas transport in healthy rabbits, but that this ratio changes in a rabbit model of acid aspiration. These results suggest that hyperpolarized xenon-129 MRI may improve our ability to measure pulmonary gas transport and detect associated pathological changes.
Molecular mechanism of ER stress-induced pre-emptive quality control involving association of the translocon, Derlin-1, and HRD1
Authors: Kadowaki Hisae , Satrimafitrah Pasjan , Takami Yasunari , Nishitoh Hideki 
Published: May 2018

AbstractThe maintenance of endoplasmic reticulum (ER) homeostasis is essential for cell function. ER stress-induced pre-emptive quality control (ERpQC) helps alleviate the burden to a stressed ER by limiting further protein loading. We have previously reported the mechanisms of ERpQC, which includes a rerouting step and a degradation step. Under ER stress conditions, Derlin family proteins (Derlins), which are components of ER-associated degradation, reroute specific ER-targeting proteins to the cytosol. Newly synthesized rerouted polypeptides are degraded via the cytosolic chaperone Bag6 and the AAA-ATPase p97 in the ubiquitin-proteasome system. However, the mechanisms by which ER-targeting proteins are rerouted from the ER translocation pathway to the cytosolic degradation pathway and how the E3 ligase ubiquitinates ERpQC substrates remain unclear. Here, we show that ERpQC substrates are captured by the carboxyl-terminus region of Derlin-1 and ubiquitinated by the HRD1 E3 ubiquitin ligase prior to degradation. Moreover, HRD1 forms a large ERpQC-related complex composed of Sec61α and Derlin-1 during ER stress. These findings indicate that the association of the degradation factor HRD1 with the translocon and the rerouting factor Derlin-1 may be necessary for the smooth and effective clearance of ERpQC substrates.
Cloning and characterization of a pyrethroid pesticide decomposing esterase gene, Est3385, from Rhodopseudomonas palustris PSB-S
Authors: Luo Xiangwen , Zhang Deyong , Zhou Xuguo , Du Jiao , Zhang Songbai , Liu Yong 
Published: May 2018

AbstractFull length open reading frame of pyrethroid detoxification gene, Est3385, contains 963 nucleotides. This gene was identified and cloned based on the genome sequence of Rhodopseudomonas palustris PSB-S available at the GneBank. The predicted amino acid sequence of Est3385 shared moderate identities (30–46%) with the known homologous esterases. Phylogenetic analysis revealed that Est3385 was a member in the esterase family I. Recombinant Est3385 was heterologous expressed in E. coli, purified and characterized for its substrate specificity, kinetics and stability under various conditions. The optimal temperature and pH for Est3385 were 35 °C and 6.0, respectively. This enzyme could detoxify various pyrethroid pesticides and degrade the optimal substrate fenpropathrin with a Km and Vmax value of 0.734 ± 0.013 mmol·l−1 and 0.918 ± 0.025 U·µg−1, respectively. No cofactor was found to affect Est3385 activity but substantial reduction of enzymatic activity was observed when metal ions were applied. Taken together, a new pyrethroid degradation esterase was identified and characterized. Modification of Est3385 with protein engineering toolsets should enhance its potential for field application to reduce the pesticide residue from agroecosystems.
Development of a lab-on-a-chip method for rapid assay of Xylella fastidiosa subsp. pauca strain CoDiRO
Authors: Chiriacò Maria Serena , Luvisi Andrea , Primiceri Elisabetta , Sabella Erika , De Bellis Luigi , Maruccio Giuseppe 
Published: May 2018

AbstractXylella fastidiosa subsp. pauca strain CoDiRO, a pathogen responsible for Olive Quick Decline Syndrome (OQDS), is strongly threatening the agricultural-based economy of South Italy and making its typical landscape collapse. The bacteria can also infect more than other twenty woody or shrub species and quarantine programs are carried out in Italy. Since symptoms of OQDS like leaf scorching and wilting of canopy may appear several months after infection and some hosts are asymptomatic, a tool for the rapid and early screening of plants is desirable, in order to plan a sudden control strategy and apply programs for pest management. X. fastidiosa detection is usually performed by ELISA and PCR methods. In this work, the two standard methods are compared with an innovative on-chip detection strategy for X. fastidiosa assay from leaves samples, based on an electrochemical transduction method. The realized lab-on-chip includes also a microfluidic module and its performances are competitive with conventional diagnostic methods in terms of reliability, but with further advantages of portability, low-costs and ease of use. Thus, the proposed technology has the potential to provide a useful assay method for large-scale monitoring programs.
MHD convective heat transfer in a discretely heated square cavity with conductive inner block using two-phase nanofluid model
Authors: Alsabery A. I. , Sheremet M. A. , Chamkha A. J. , Hashim I. 
Published: May 2018

AbstractThe problem of steady, laminar natural convection in a discretely heated and cooled square cavity filled by an alumina/water nanofluid with a centered heat-conducting solid block under the effects of inclined uniform magnetic field, Brownian diffusion and thermophoresis is studied numerically by using the finite difference method. Isothermal heaters and coolers are placed along the vertical walls and the bottom horizontal wall, while the upper horizontal wall is kept adiabatic. Water-based nanofluids with alumina nanoparticles are chosen for investigation. The governing parameters of this study are the Rayleigh number (103 ≤ Ra ≤ 106), the Hartmann number (0 ≤ Ha ≤ 50), thermal conductivity ratio (0.28 ≤ k
w
≤ 16), centered solid block size (0.1 ≤ D ≤ 0.7) and the nanoparticles volume fraction (0 ≤ ϕ ≤ 0.04). The developed computational code is validated comprehensively using the grid independency test and numerical and experimental data of other authors. The obtained results reveal that the effects of the thermal conductivity ratio, centered solid block size and the nanoparticles volume fraction are non-linear for the heat transfer rate. Therefore, it is possible to find optimal parameters for the heat transfer enhancement in dependence on the considered system. Moreover, high values of the Rayleigh number and nanoparticles volume fraction characterize homogeneous distributions of nanoparticles inside the cavity. High concentration of nanoparticles can be found near the centered solid block where thermal plumes from the local heaters interact.
Substrate specificity of human MCPIP1 endoribonuclease
Authors: Wilamowski Mateusz , Gorecki Andrzej , Dziedzicka-Wasylewska Marta , Jura Jolanta 
Published: May 2018

AbstractMCPIP1, also known as Regnase-1, is a ribonuclease crucial for regulation of stability of transcripts related to inflammatory processes. Here, we report that MCPIP1 acts as an endonuclease by degrading several stem-loop RNA structures and single-stranded RNAs. Our studies revealed cleavage sites present in the stem-loops derived from the 3′ untranslated region of the interleukin-6 transcript. Furthermore, MCPIP1 induced endonuclease cleavage at the loop motif of stem-loop structures. Additionally, we observed that MCPIP1 could cleave single-stranded RNA fragments. However, RNA substrates shorter than 6 nucleotides were not further affected by MCPIP1 nucleolytic activity. In this study, we also determined the dissociation constants of full-length MCPIP1D141N and its ribonuclease domain PIN D141N with twelve oligonucleotides substrates. The equilibrium binding constants (Kd) for MCPIP1D141N and the RNA targets were approximately 10 nM. Interestingly, we observed that the presence of a zinc finger in the PIN domain increases the affinity of this protein fragment to 25-nucleotide-long stem-loop RNA but not to shorter ones. Furthermore, size exclusion chromatography of the MCPIP1 and PIN proteins suggested that MCPIP1 undergoes homooligomerization during interaction with RNA substrates. Our results provide insight into the mechanism of MCPIP1 substrate recognition and its affinity towards various oligonucleotides.
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

AbstractThe 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

AbstractCorrosion 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

AbstractManaging 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

AbstractKnowledge 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.
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.
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.
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

AbstractCurrent 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.
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.