bluuebunny/crossref_metadata_2025 huggingface dataset:
Alluvial fans and fluvial fans at the margins of continental sedimentary basins: geomorphic and sedimentological distinction for geo-energy exploration and development
Authors: Moscariello A.
Published: April 2017

Alluvial fans and fluvial fans are the most common depositional landforms along the margins of continental sedimentary basins. Their occurrence is determined by the area, relief and hydrology of the catchment, which ultimately control the relative ratios of sediment v. flow discharge and runoff regimes. Fundamental morphological and process distinctions exist between these two kinds of deposystem, which are seen as essentially different facies associations and internal architectures for the corresponding deposits. Alluvial fans commonly develop over short radial distances (hundreds of metres to a few kilometres) and are constructed by ephemeral, flash flow events that lead to poor organization of the sedimentary facies and overall architecture of the corresponding deposits. By contrast, fluvial (mega)fans are fed by proper river systems, which aggrade much larger volumes of clastic sediment over distances of up to a few hundred kilometres. Distinct channel belt and overbank domains are developed with a marked heterogeneity in the distribution of sedimentary facies, represented by hierarchically well-organized fluvial deposits. The general properties of alluvial and fluvial fans reflect the different potentials for the corresponding successions to host economically attractive oil and gas resources and the different approaches required in exploration and prediction.
Metabolite-Sensing G Protein–Coupled Receptors—Facilitators of Diet-Related Immune Regulation
Authors: Tan Jian K. , McKenzie Craig , Mariño Eliana , Macia Laurence , Mackay Charles R.
Published: April 2017

Nutrition and the gut microbiome regulate many systems, including the immune, metabolic, and nervous systems. We propose that the host responds to deficiency (or sufficiency) of dietary and bacterial metabolites in a dynamic way, to optimize responses and survival. A family of G protein–coupled receptors (GPCRs) termed the metabolite-sensing GPCRs bind to various metabolites and transmit signals that are important for proper immune and metabolic functions. Members of this family include GPR43, GPR41, GPR109A, GPR120, GPR40, GPR84, GPR35, and GPR91. In addition, bile acid receptors such as GPR131 (TGR5) and proton-sensing receptors such as GPR65 show similar features. A consistent feature of this family of GPCRs is that they provide anti-inflammatory signals; many also regulate metabolism and gut homeostasis. These receptors represent one of the main mechanisms whereby the gut microbiome affects vertebrate physiology, and they also provide a link between the immune and metabolic systems. Insufficient signaling through one or more of these metabolite-sensing GPCRs likely contributes to human diseases such as asthma, food allergies, type 1 and type 2 diabetes, hepatic steatosis, cardiovascular disease, and inflammatory bowel diseases.
Pregnancy and bile acid disorders
Authors: Pataia Vanessa , Dixon Peter H. , Williamson Catherine
Published: April 2017

During pregnancy, extensive adaptations in maternal metabolic and immunological physiology occur. Consequently, preexisting disease may be exacerbated or attenuated, and new disease susceptibility may be unmasked. Cholestatic diseases, characterized by a supraphysiological raise in bile acid levels, require careful monitoring during pregnancy. This review describes the latest advances in the knowledge of intrahepatic cholestasis of pregnancy (ICP), the most common bile acid disorder specific to pregnancy, with a focus on the disease etiology and potential mechanisms of ICP-associated adverse pregnancy outcomes, including fetal demise. The course of preexisting cholestatic conditions in pregnancy is considered, including primary sclerosing cholangitis, primary biliary cholangitis, biliary atresia, and Alagille syndrome. The currently accepted treatments for cholestasis in pregnancy and promising new therapeutics for the condition are described.
Autophagy upregulates (pro)renin receptor expression via reduction of P62/SQSTM1 and activation of ERK1/2 signaling pathway in podocytes
Authors: Li Caixia , Siragy Helmy M.
Published: April 2017

Autophagy plays a major role in podocytes health and disease. P62, also known as sequestosome-1 (SQSTM1), is a marker for autophagic activity and is required for the formation and degradation of ubiquitnated protein by autophagy. Knockout of p62 enhanced extracellular signal-regulated kinases (ERK1/2) activity. (pro)renin receptor (PRR) is expressed in podocytes where it contributes to the homeostasis of these cells. The influence of autophagy on PRR expression is unknown. We hypothesized that in podocytes, upregulation of autophagic activity increases PRR expression via reduction of p62 and stimulation of ERK1/2 signaling pathway. Cultured mouse podocytes were treated with the autophagy activators, rapamycin or Earle’s balanced salt solution (EBSS), for 48 h. Both rapamycin and EBSS significantly decreased p62 protein levels, increased ERK1/2 activation by phosphorylating pTpY185/187, and increased mRNA and protein expressions of PRR. Utilizing confocal microscopy demonstrated that rapamycin and EBSS significantly decreased p62/SQSTM1 and increased PRR protein expressions. Similarly, by enhancing autophagic activity by transfection with autophagy-related 5 (ATG5) cDNA or ATG7 cDNA, results similar to those observed with rapamycin and EBSS treatments were produced. Inhibition of autophagic flux with bafilomycin A1 reversed the effects of rapamycin. ERK1/2 inhibitor U0126 significantly attenuated mRNA and protein expressions of PRR in podocytes treated with rapamycin. In conclusion, upregulation of autophagy enhanced PRR expression through reduction of p62 and stimulation of ERK1/2 activity signaling pathway.
Sodium storage in human tissues is mediated by glycosaminoglycan expression
Authors: Fischereder Michael , Michalke Bernhard , Schmöckel Elisa , Habicht Antje , Kunisch Raphael , Pavelic Ivana , Szabados Bernadette , Schönermarck Ulf , Nelson Peter J. , Stangl Manfred
Published: April 2017

The current paradigm regarding sodium handling in animals and humans postulates that total body sodium is regulated predominately via regulation of extracellular volume. Active sodium storage independent of volume retention is thought to be negligible. However, studies in animals, hypertensive patients, and healthy humans suggest water-free storage of sodium in skin. We hypothesized that tissue sodium concentrations ([Na]T) found in humans vary and reflect regulation due to variable glycosaminoglycan content due to variable expression of XYLT-1. Twenty seven patients on dialysis and 21 living kidney transplant donors free of clinically detectable edema were studied. During surgery, abdominal skin, muscle, and arteries were biopsied. [Na]T was determined by inductively coupled plasma-optical emission spectrometry, semiquantitative glycosaminoglycan content with Alcian stain, and XYLT-1 expression by real-time PCR. [Na]T of arteries were ranging between 0.86 and 9.83 g/kg wet wt and were significantly higher in arteries (4.52 ± 1.82 g/kg) than in muscle (2.03 ± 1.41 g/kg; P < 0.001) or skin (3.24 ± 2.26 g/kg wet wt; P = 0.038). For individual patients [Na]T correlated for skin and arterial tissue ( r = 0.440, P = 0.012). [Na]T also correlated significantly with blinded semiquantitative analysis of glycosaminoglycans staining ( r = 0.588, P = 0.004). In arteries XYLT-1 expression was also correlated with [Na]T ( r = 0.392, P = 0.003). Our data confirm highly variable [Na]T in human skin and muscle and extend this observation to [Na]T in human arteries. These data support the hypothesis of water-independent sodium storage via regulated glycosaminoglycan synthesis in human tissues, including arteries.
Evidence for age-dependent air-space enlargement contributing to loss of lung tissue elastic recoil pressure and increased shear modulus in older age
Authors: Subramaniam K. , Kumar H. , Tawhai M. H.
Published: April 2017

As a normal part of mature aging, lung tissue undergoes microstructural changes such as alveolar air-space enlargement and redistribution of collagen and elastin away from the alveolar duct. The older lung also experiences an associated decrease in elastic recoil pressure and an increase in specific tissue elastic moduli, but how this relates mechanistically to microstructural remodeling is not well-understood. In this study, we use a structure-based mechanics analysis to elucidate the contributions of age-related air-space enlargement and redistribution of elastin and collagen to loss of lung elastic recoil pressure and increase in tissue elastic moduli. Our results show that age-related geometric changes can result in reduction of elastic recoil pressure and increase in shear and bulk moduli, which is consistent with published experimental data. All elastic moduli were sensitive to the distribution of stiffness (representing elastic fiber density) in the alveolar wall, with homogenous stiffness near the duct and through the septae resulting in a more compliant tissue. The preferential distribution of elastic proteins around the alveolar duct in the healthy young adult lung therefore provides for a more elastic tissue.

NEW & NOTEWORTHY We use a structure-based mechanics analysis to correlate air-space enlargement and redistribution of elastin and collagen to age-related changes in the mechanical behavior of lung parenchyma. Our study highlights that both the cause (redistribution of elastin and collagen) and the structural effect (alveolar air-space enlargement) contribute to decline in lung tissue elastic recoil with age; these results are consistent with published data and provide a new avenue for understanding the mechanics of the older lung.
A shared neural integrator for human posture control
Authors: Haggerty S. E. , Wu A. R. , Sienko K. H. , Kuo A. D.
Published: April 2017

Control of standing posture requires fusion of multiple inputs including visual, vestibular, somatosensory, and other sensors, each having distinct dynamics. We propose that postural control also entails a shared neural integrator. To test this theory, we perturbed standing subjects with classic sensory stimuli (optokinetic and galvanic vestibular stimulation) and found that our proposed shared filter reproduces the dynamics of subjects’ postural responses.
Activation mechanism of a neuromodulator-gated pacemaker ionic current
Authors: Gray Michael , Daudelin Daniel H. , Golowasch Jorge
Published: April 2017

The neuromodulator-gated current ( IMI) found in the crab stomatogastric ganglion is activated by neuromodulators that are essential to induce the rhythmic activity of the pyloric network in this system. One of these neuromodulators is also known to control the correlated expression of voltage-gated ionic currents in pyloric neurons, as well as synaptic plasticity and strength. Thus understanding the mechanism by which neuromodulator receptors activate IMIshould provide insights not only into how oscillations are initiated but also into how other processes, and currents not directly activated by them, are regulated. To determine what specific signaling molecules are implicated in this process, we used a battery of agonists and antagonists of common signal transduction pathways. We found that the G protein inhibitor GDPβS and the G protein activator GTPγS significantly affect IMIamplitude, suggesting that its activation is mediated by G proteins. Interestingly, when using the more specific G protein blocker pertussis toxin, we observed the expected inhibition of IMIamplitude but, unexpectedly, in a calcium-dependent fashion. We also found that antagonists of calcium- and calmodulin-associated signaling significantly reduce IMIamplitude. In contrast, we found little evidence for the role of cyclic nucleotide signaling, phospholipase C (PLC), or kinases and phosphatases, except two calmodulin-dependent kinases. In sum, these results suggest that proctolin-induced IMIis mediated by a G protein whose pertussis toxin sensitivity is altered by external calcium concentration and appears to depend on intracellular calcium, calmodulin, and calmodulin-activated kinases. In contrast, we found no support for IMIbeing mediated by PLC signaling or cyclic nucleotides.

NEW & NOTEWORTHY Neuronal rhythmic activity is generated by either network-based or cell-autonomous mechanisms. In the pyloric network of decapod crustaceans, the activation of a neuromodulator-gated pacemaker current is crucial for the generation of rhythmic activity. This current is activated by several neuromodulators, including peptides and acetylcholine, presumably via metabotropic receptors. We have previously demonstrated a novel extracellular calcium-sensitive voltage-dependence mechanism of this current. We presently report that the activation mechanism depends on intracellular and extracellular calcium-sensitive components.
Review: DNA Barcoding and Chromatography Fingerprints for the Authentication of Botanicals in Herbal Medicinal Products
Authors: Mohammed Abubakar Bashir , Mohd Salleh Faezah , Shamsir Omar Mohd Shahir , Wagiran Alina
Published: April 2017

In the last two decades, there has been a tremendous increase in the global use of herbal medicinal products (HMPs) due to their claimed health benefits. This has led to increase in their demand and consequently, also, resulted in massive adulteration. This is due to the fact that most of the traditional methods cannot identify closely related species in a process product form. Therefore the urgent need for simple and rapid identification methods resulted in the discovery of a novel technique. DNA barcoding is a process that uses short DNA sequence from the standard genome for species identification. This technique is reliable and is not affected by external factors such as climates, age, or plant part. The difficulties in isolation of DNA of high quality in addition to other factors are among the challenges encountered using the DNA barcoding in the authentication of HMP. These limitations indicated that using DNA barcoding alone may ineffectively authenticate the HMP. Therefore, the combination of DNA barcoding with chromatographic fingerprint, a popular and generally accepted technique for the assessment and quality control of HMP, will offer an efficient solution to effectively evaluate the authenticity and quality consistency of HMP. Detailed and quality information about the main composition of the HMPs will help to ascertain their efficacy and safety as these are very important for quality control.
Validation of Nomograms for Survival and Metastases after Hysterectomy and Adjuvant Therapy in Uterine Cervical Cancer with Risk Factors
Authors: Yoon Won Sup , Yang Dae Sik , Lee Jung Ae , Lee Nam Kwon , Park Young Je , Kim Chul Yong , Lee Nak Woo , Hong Jin Hwa , Lee Jae Kwan , Song Jae Yun
Published: April 2017

Background. Three nomogram models for early stage uterine cervical cancer have been developed (KROG 13-03 for overall survival [OS], SNUH/AMC for disease-free survival [DFS], and KROG 12-08 for distant metastases-free survival [DMFS]) after radical hysterectomy (RH) and pelvic lymph node dissection (PLND). This study aimed to validate these models using our cohort with adjuvant radiotherapy. Methods. According to the eligibility criteria of nomogram studies, patients were enrolled in Group A (N=109) for the two KROG models (RH with PLND and whole pelvic irradiation) and Group B (N=101) for the SNUH/AMC model (RH with PLND and squamous histology). Using Cox-regression hazard models, the prognostic factors of our cohorts were evaluated. The risk probabilities induced from published nomogram scores were calculated and the concordance indices were evaluated. Results. Group A had 88.1% 5-year OS and 86.0% 5-year DMFS. Group B had 83.0% 5-year DFS. In multivariate analyses, large tumor size for OS (HR 8.62, P<0.001) and DMFS (HR 5.13, P=0.003), young age (≤40 versus 41–64 years) for OS (HR 4.63, P=0.097) and DFS (HR 3.44, P=0.051), and multiple lymph node metastases (0 versus ≥3) for DMFS (HR 4.03, P=0.031) and DFS (HR 3.90, P=0.038) were significantly correlated. The concordance indices for OS, DMFS, and DFS were 0.612 (P=0.002), 0.597 (P=0.014), and 0.587 (P=0.020), respectively. Conclusion. The developed nomogram models after RH and PLND are clinically useful in predicting various types of survival with significance.
Cardiac Protection of Valsartan on Juvenile Rats with Heart Failure by Inhibiting Activity of CaMKII via Attenuating Phosphorylation
Authors: Wu Yao , Si Feifei , Ji Xiaojuan , Jiang Kunfeng , Song Sijie , Yi Qijian
Published: April 2017

Background. This study was undertaken to determine relative contributions of phosphorylation and oxidation to the increased activity of calcium/calmodulin-stimulated protein kinase II (CaMKII) in juveniles with cardiac myocyte dysfunction due to increased pressure overload.Methods. Juvenile rats underwent abdominal aortic constriction to induce heart failure. Four weeks after surgery, rats were then randomly divided into two groups: one group given valsartan (HF + Val) and the other group given placebo (HF + PBO). Simultaneously, the sham-operated rats were randomly given valsartan (Sham + Val) or placebo (Sham + PBO). After 4 weeks of treatment, Western blot analysis was employed to quantify CaMKII and relative calcium handling proteins (RyR2 and PLN) in all groups.Results. The deteriorated cardiac function was reversed by valsartan treatment. In ventricular muscle cells of group HF + PBO, Thr287 phosphorylation of CaMKII and S2808 phosphorylation of RyR2 and PLN were increased and S16 phosphorylation of PLN was decreased compared to the other groups, while Met281 oxidation was not significantly elevated. In addition, these changes in the expression of calcium handling proteins were ameliorated by valsartan administration.Conclusions. The phosphorylation of Thr286 is associated with the early activation of CaMKII rather than the oxidation of Met281.
An Efficient Context-Aware Privacy Preserving Approach for Smartphones
Authors: Zhang Lichen , Li Yingshu , Wang Liang , Lu Junling , Li Peng , Wang Xiaoming
Published: April 2017

With the proliferation of smartphones and the usage of the smartphone apps, privacy preservation has become an important issue. The existing privacy preservation approaches for smartphones usually have less efficiency due to the absent consideration of the active defense policies and temporal correlations between contexts related to users. In this paper, through modeling the temporal correlations among contexts, we formalize the privacy preservation problem to an optimization problem and prove its correctness and the optimality through theoretical analysis. To further speed up the running time, we transform the original optimization problem to an approximate optimal problem, a linear programming problem. By resolving the linear programming problem, an efficient context-aware privacy preserving algorithm (CAPP) is designed, which adopts active defense policy and decides how to release the current context of a user to maximize the level of quality of service (QoS) of context-aware apps with privacy preservation. The conducted extensive simulations on real dataset demonstrate the improved performance of CAPP over other traditional approaches.
The Critical Role of Long Noncoding RNA in Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells
Authors: Qiu Xiaoling , Jia Bo , Sun Xiang , Hu Weitao , Chu Hongxing , Xu Shuaimei , Zhao JianJiang
Published: April 2017

Objective. Long noncoding RNAs (lncRNAs) have been demonstrated to regulate many biological processes including differentiation. However, their role in osteogenic differentiation was poorly known. Materials and Methods. In this study, we first globally profiled the differentially expressed lncRNAs and mRNAs during osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMMSCs). Bioinformatics analysis was performed to further analyze these significantly changed molecules. Then the role of lncRNA ENST00000502125.2 in the osteogenic differentiation was determined. Results. A number of lncRNAs and mRNAs were significantly differentially expressed during hBMMSC osteogenic differentiation. Among them, 433 lncRNAs and 956 mRNAs were continuously upregulated, while 232 lncRNAs and 229 mRNAs were continuously downregulated. Gene Ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis showed that carbohydrate derivative binding and complement and coagulation cascades were most correlated molecular function and pathway, respectively. Downregulation of lncRNA ENST00000502125.2 promoted the osteogenic differentiation of hBMMSCs, and opposite results were found when lncRNA ENST00000502125.2 was upregulated. Conclusions. lncRNAs play a critical role in the osteogenic differentiation of hBMMSCs and targeting lncRNA ENST00000502125.2 might be a promising strategy to promote osteogenic differentiation.
A Miniaturized 4 : 1 Unequal Wilkinson Power Divider Using Artificial Transmission Lines and Double-Sided Parallel-Strip Lines
Authors: Huang Wen , Ruan Wei , Tan Fei
Published: April 2017

A 4 : 1 unequal Wilkinson power divider using microstrip artificial transmission lines (ATLs) is proposed. For the ATL, a series of meandered-line inductors, parallel-plate capacitors, and interdigital capacitors are employed. The designed power divider is composed of three ATLs, and a method has been proposed using technology of ATLs and double-sided parallel-strip lines (DSPSLs) to design line of high characteristic impedance. Microstrip line with very high characteristic impedance of over 150 Ω has been achieved by this method, which cannot be easily achieved by conventional transmission lines because of comparably thin conductor width. The fabricated 4 : 1 unequal power divider has good operational performance and occupies55.3 mm×37.8 mm, which is only about 40% of area compared to a conventional one at 0.9 GHz.
Fabrication and Evaluation of Electrospun, 3D-Bioplotted, and Combination of Electrospun/3D-Bioplotted Scaffolds for Tissue Engineering Applications
Authors: Mellor Liliana F. , Huebner Pedro , Cai Shaobo , Mohiti-Asli Mahsa , Taylor Michael A. , Spang Jeffrey , Shirwaiker Rohan A. , Loboa Elizabeth G.
Published: April 2017

Electrospun scaffolds provide a dense framework of nanofibers with pore sizes and fiber diameters that closely resemble the architecture of native extracellular matrix. However, it generates limited three-dimensional structures of relevant physiological thicknesses. 3D printing allows digitally controlled fabrication of three-dimensional single/multimaterial constructs with precisely ordered fiber and pore architecture in a single build. However, this approach generally lacks the ability to achieve submicron resolution features to mimic native tissue. The goal of this study was to fabricate and evaluate 3D printed, electrospun, and combination of 3D printed/electrospun scaffolds to mimic the native architecture of heterogeneous tissue. We assessed their ability to support viability and proliferation of human adipose derived stem cells (hASC). Cells had increased proliferation and high viability over 21 days on all scaffolds. We further tested implantation of stacked-electrospun scaffold versus combined electrospun/3D scaffold on a cadaveric pig knee model and found that stacked-electrospun scaffold easily delaminated during implantation while the combined scaffold was easier to implant. Our approach combining these two commonly used scaffold fabrication technologies allows for the creation of a scaffold with more close resemblance to heterogeneous tissue architecture, holding great potential for tissue engineering and regenerative medicine applications of osteochondral tissue and other heterogeneous tissues.
Assessment of Helicopter Pilot-in-the-Loop Models
Authors: Gennaretti Massimo , Porcacchia Federico , Migliore Simone , Serafini Jacopo
Published: April 2017

The aim of this paper is the evaluation of several pilot models found in the literature, suited for helicopter pilot-assisted and pilot-induced oscillations analyses. Three main topics are discussed: (i) sensitivity of rotorcraft-pilot couplings simulations on the application of the different pilot models available in the literature; (ii) effect of vehicle modeling on active pilot modeling; (iii) effects of interactions between active and passive pilot models. The focus is on hovering flight, where a specific adverse rotorcraft-pilot coupling phenomenon, the vertical bounce, may occur. Pilot models are coupled with a comprehensive aeroservoelastic model of a mid-weight helicopter. The numerical investigations are performed in frequency domain, in terms of eigenanalysis and frequency response analysis.
Successful Use of Extracorporeal Membrane Oxygenation for the Treatment of Cardiogenic Shock due to Scorpion Envenomation
Authors: Tarmiz Amine , Mgarrech Imene , Kortas Chokri , Jerbi Sofiane
Published: April 2017

Introduction. The occurrence of a cardiogenic shock is a rare presentation after scorpion envenomation. The treatment includes classically the use of inotropes and specific vasodilators. Case Presentation. We report a case of an 11-year-old boy presenting with cardiogenic shock and pulmonary edema after a scorpion sting. Despite adequate management at the emergency department and intensive care unit, the patient’s hemodynamic status worsened rapidly, justifying his transfer to our department for ventricular mechanical assistance by venoarterial extracorporeal membrane oxygenation. The following outcomes were favorable and the boy was discharged home on day 29 without aftereffects. Conclusion. This is the first report of successful use of extracorporeal membrane oxygenation for the treatment of cardiogenic shock after scorpion envenomation.
Identification of Abnormal Biliary Anatomy Utilizing Real-Time Near-Infrared Cholangiography: A Report of Two Cases
Authors: Bozzay Joseph , Vicente Diego , Jessie Elliot M. , Rodriguez Carlos J.
Published: April 2017

Biliary duct anomalies are commonly encountered during laparoscopic cholecystectomy. Advancements in the field of surgery allow for enhanced intraoperative detection of these abnormalities. Fluorophore injection and near-infrared (NIR) imaging can provide real-time intraoperative anatomic feedback without intraoperative delays and ionizing radiation. This report details two cases where the PINPOINT Endoscopic Fluorescence Imaging System (NOVADAQ, Ontario, Canada) was used to identify anomalies of the biliary tree and guide operative decision-making.
Using Simplified Models to Assist Fault Detection and Diagnosis in Large Hydrogenerators
Authors: Brito Junior Geraldo Carvalho , Machado Roberto Dalledone , Chaves Neto Anselmo
Published: April 2017

Based on experimental evidence collected in a set of twenty 700 MW hydrogenerators, this article shows that the operating conditions of large hydrogenerators journal bearings may have unpredictable and significant changes, without apparent reasons. These changes prevent the accurate determination of bearing dynamic coefficients and make the prediction of these machines dynamic behavior unfeasible, even using refined models. This makes it difficult to differentiate the normal changes in hydrogenerators dynamics from the changes created by a fault event. To overcome such difficulty, this article proposes a back-to-basics step, the using of simplified mathematical models to assist hydrogenerators vibration monitoring and exemplifies this proposal by modeling a 700 MW hydrogenerator. A first model estimates the influence of changes in bearing operating conditions in the bearing stiffnesses, considering only the hydrodynamic effects of an isoviscous oil film with linear thickness distribution. A second model simulates hydrogenerators dynamics using only 10 degrees of freedom, giving the monitored vibrations as outputs, under normal operating conditions or in the presence of a fault. This article shows that simplified models may give satisfactory results when bearing operating conditions are properly determined, results comparable to those obtained by more refined models or by measurements in the modeled hydrogenerator.
Robust Relay in Narrow-Band Communications for Ubiquitous IoT Access
Authors: Du Qinghe , Lu Nan , Sun Li , Zhang Xuelin , Sun Bo
Published: April 2017

We propose a robust wireless relay scheme in narrow-band communications for IoT access, which matches the typical features of IoT often carrying relatively low data rate with limited bandwidth. This framework is towards offering robustness in QoS guarantees with emphases on security and/or reliability, and we use the security-assured network as the typical scenario. In particular, we consider a dual-hop relay network including a transmitter, a receiver, an amplify-and-forward (AF) untrusted relay, and a jamming node. The jamming node is treated as a helper. Specifically, the jammer broadcasts artificial noise (AN), which in fact pollutes both the untrusted relay and the destination node’s signals. However, we show that such AN can be effectively mitigated after the destination node obtains the forwarded signal from the relay, while the untrusted relay node cannot do so. The core idea for robustness assurance is to exploit higher signal dimensions at the receiver over the untrusted relay node. Simulations and analyses are also conducted to demonstrate that our proposed scheme can make the performance at the untrusted relay an interference-limited manner while completely removing the interferences at the receiver, therefore corroborating our claim in robustness in terms of security and reliability.
Calpain-1 Expression in Triple-Negative Breast Cancer: A Potential Prognostic Factor Independent of the Proliferative/Apoptotic Index
Authors: Al-Bahlani Shadia M. , Al-Rashdi Ruqaya M. , Kumar Shiyam , Al-Sinawi Shadia S. , Al-Bahri Maiya A. , Shalaby Asem A.
Published: April 2017

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer in which calpain system plays an important role in its cellular processes including apoptosis and proliferation. Although such roles have been assessed in tumor pathogenesis, the correlation of its expression to the proliferating/apoptotic index has not been studied yet. Immunohistochemical staining of calpain-1 was performed on paraffin-embedded tissues to correlate its expression with clinicopathological variables and outcome. The proliferation activity was determined by calculating the percentage of cells expressing the Ki-67 antigen. The apoptotic index was assessed morphologically and biochemically using Haematoxylin & Eosin method and Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, respectively. Calpain-1 was significantly expressed in TNBC tissues varying from low to high with a significant correlation to lymph node status but not with the other clinicopathological variables, suggesting its role as a prognostic factor. In addition, a positive correlation was found between both apoptotic counts assays (P<0.001, r=0.547) as well as with proliferation (P=0.045). Calpain-1 expression had no significant correlation with either proliferation (P=0.29) or apoptotic indices (P=0.071 and P=0.100). Determining calpain-1 expression may provide relevant prognostic value for TNBC cancer patients.
Acute Torsion of Appendicular Mucocele
Authors: Ejtehadi Farshid , Brooks James , Ali Hebah Hassan , Vijay Vardhini
Published: April 2017

We present the case of an 81-year-old man with a known appendicular mucocele who presented to the emergency department with acute abdominal pain. A CT scan showed a change in orientation of the previously seen ovoid mass with surrounding fat stranding suggesting torsion. An emergency laparotomy with appendicectomy and resection of the caecal pole was performed. We discuss the findings and histopathology.
Role of GntR Family Regulatory GeneSCO1678in Gluconate Metabolism inStreptomyces coelicolorM145
Authors: Tsypik Olga , Makitrynskyy Roman , Bera Agnieszka , Song Lijiang , Wohlleben Wolfgang , Fedorenko Victor , Ostash Bohdan
Published: April 2017

Here we report functional characterization of theStreptomyces coelicolorM145 geneSCO1678,which encodes a GntR-like regulator of the FadR subfamily. Bioinformatic analysis suggested thatSCO1678is part of putative operon(gnt)involved in gluconate metabolism. Combining the results ofSCO1678knockout, transcriptional analysis ofgntoperon, and Sco1678 protein-DNA electromobility shift assays, we established that Sco1678 protein controls the gluconate operon. It does so via repression of its transcription from a single promoter located between genesSCO1678andSCO1679. The knockout also influenced, in a medium-dependent manner, the production of secondary metabolites byS. coelicolor. In comparison to the wild type, on gluconate-containing minimal medium, theSCO1678mutant produced much less actinorhodin and accumulated a yellow-colored pigment, likely to be the cryptic polyketide coelimycin. Possible links between gluconate metabolism and antibiotic production are discussed.
Clinical Features and Outcomes of Patients with Colorectal Cancers Harboring NRAS Mutations
Authors: Cercek Andrea , Braghiroli Maria Ignez , Chou Joanne F. , Hechtman Jaclyn F. , Kemeny Nancy , Saltz Leonard , Capanu Marinela , Yaeger Rona
Published: April 2017

Purpose: NRAS mutations are now routinely included in RAS testing prior to EGFR inhibitor therapy for metastatic colorectal cancer (mCRC). The clinical implications of NRAS mutation beyond lack of response to anti-EGFR therapy, however, are not known. We undertook this study to determine the clinical features and treatment outcomes of patients with NRAS-mutant mCRC.

Experimental Design: We reviewed clinical characteristics, concurrent mutations, and outcomes for all mCRC cases with NRAS mutations undergoing standard genotyping at our institution from 2008 to 2015. Comparison groups consisted of RAS wild-type and KRAS-mutant mCRC consecutive cases genotyped from 2008 to 2012.

Results: Three percent (87/2764) of mCRC patients had NRAS-mutant tumors (45% exon 2 and 55% exon 3), including three cases with concurrent NRAS and KRAS mutations. Left-sided primary site and African American self-reported race were associated with NRAS mutation (P < 0.01). Resection rate at 12 months was lower for NRAS-mutant mCRC than for RAS wild-type or KRAS-mutant mCRC. Median survival from time of first known metastasis was 33 months for NRAS-mutant, 47 months for KRAS-mutant, and 78 months for RAS wild-type cases (P < 0.001). Multivariate analysis assigned an HR for overall survival of 2.0 for NRAS mutation and 1.5 for KRAS mutation (P < 0.01).

Conclusions: NRAS defines a molecular subset with distinct clinical characteristics from KRAS-mutant and wild-type mCRC. NRAS mutations are enriched in left-sided primary tumors and among African Americans. Mutations in NRAS are associated with poor survival and worse outcomes than either KRAS-mutant or wild-type mCRC. Clin Cancer Res; 23(16); 4753–60. ©2017 AACR.
Risk of Pneumonitis Associated with Programmed Cell Death 1 Inhibitors in Cancer Patients: A Meta-analysis
Authors: Zhang Sheng , Liang Fei , Zhu Ji , Chen Qiang
Published: April 2017

Pneumonitis, a rare but potentially life-threatening adverse event in cancer patients receiving programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors, has been reported in case reports, clinical trials, and retrospective studies. We performed a systematic review and meta-analysis to calculate the RR of pneumonitis associated with the use of PD-1/L1 inhibitors in randomized clinical trials (RCT). We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, trial registers, conference proceedings, review articles, and reference lists of trial publications for all relevant RCTs comparing PD-1/L1 inhibitors to control with available data on pneumonitis. The pooled incidence, RR, and 95% confidence intervals (CI) were calculated using fixed effects or random effects model according to the heterogeneity of included trials. Twelve RCTs were eligible for the meta-analysis, yielding a total of 5,775 patients included in trials evaluating a PD-1 inhibitor; no eligible trials evaluated a PD-L1 inhibitor. The pooled incidence of all-grade pneumonitis for patients treated with PD-1 inhibitors was 3.2% (95% CI, 2.3–4.5), and that of high-grade pneumonitis was 1.1% (95% CI, 0.7–1.7). The RR of all-grade and high-grade pneumonitis was 4.36 (95% CI, 2.58–7.38) and 2.86 (95% CI, 1.30–6.31), respectively. In a sensitivity analysis, PD-1 inhibitors were also associated with significantly increased risk of pneumonitis per person-month (for all grade, RR = 3.37; 95% CI, 1.97–5.76; for high grade, RR = 2.25; 95% CI, 1.03–4.94). PD-1 inhibitors were associated with a significant increase of all-grade and high-grade pneumonitis both per treatment episode and per person-month. Mol Cancer Ther; 16(8); 1588–95. ©2017 AACR.
PAX3–FOXO1 Establishes Myogenic Super Enhancers and Confers BET Bromodomain Vulnerability
Authors: Gryder Berkley E. , Yohe Marielle E. , Chou Hsien-Chao , Zhang Xiaohu , Marques Joana , Wachtel Marco , Schaefer Beat , Sen Nirmalya , Song Young , Gualtieri Alberto , Pomella Silvia , Rota Rossella , Cleveland Abigail , Wen Xinyu , Sindiri Sivasish , Wei Jun S. , Barr Frederic G. , Das Sudipto , Andresson Thorkell , Guha Rajarshi , Lal-Nag Madhu , Ferrer Marc , Shern Jack F. , Zhao Keji , Thomas Craig J. , Khan Javed
Published: April 2017

Alveolar rhabdomyosarcoma is a life-threatening myogenic cancer of children and adolescent young adults, driven primarily by the chimeric transcription factor PAX3–FOXO1. The mechanisms by which PAX3–FOXO1 dysregulates chromatin are unknown. We find PAX3–FOXO1 reprograms the cis-regulatory landscape by inducing de novo super enhancers. PAX3–FOXO1 uses super enhancers to set up autoregulatory loops in collaboration with the master transcription factors MYOG, MYOD, and MYCN. This myogenic super enhancer circuitry is consistent across cell lines and primary tumors. Cells harboring the fusion gene are selectively sensitive to small-molecule inhibition of protein targets induced by, or bound to, PAX3–FOXO1-occupied super enhancers. Furthermore, PAX3–FOXO1 recruits and requires the BET bromodomain protein BRD4 to function at super enhancers, resulting in a complete dependence on BRD4 and a significant susceptibility to BRD inhibition. These results yield insights into the epigenetic functions of PAX3–FOXO1 and reveal a specific vulnerability that can be exploited for precision therapy.

Significance: PAX3–FOXO1 drives pediatric fusion-positive rhabdomyosarcoma, and its chromatin-level functions are critical to understanding its oncogenic activity. We find that PAX3–FOXO1 establishes a myoblastic super enhancer landscape and creates a profound subtype-unique dependence on BET bromodomains, the inhibition of which ablates PAX3–FOXO1 function, providing a mechanistic rationale for exploring BET inhibitors for patients bearing PAX-fusion rhabdomyosarcoma. Cancer Discov; 7(8); 884–99. ©2017 AACR.

This article is highlighted in the In This Issue feature, p. 783
Anaemia following Artemisinin-Based Combination Treatments of Uncomplicated Plasmodium falciparum Malaria in Children: Temporal Patterns of Haematocrit and the Use of Uncomplicated Hyperparasitaemia as a Model for Evaluating Late-Appearing Anaemia
Authors: Sowunmi Akin , Akano Kazeem , Ntadom Godwin , Ayede Adejumoke , Oguche Stephen , Agomo Chimere , Okafor Henrietta , Watila Ismaila , Meremikwu Martin , Ogala William , Agomo Philip , Adowoye Elsie , Fatunmbi Bayo , Aderoyeje Temitope , Happi Christian , Gbotosho Grace , Folarin Onikepe
Published: April 2017

Background: In severe malaria, intravenous artesunate may cause delayed haemolytic anaemia but there has been little evaluation of the propensity of oral artemisinin-based combination treatments (ACTs) to cause late-appearing anaemia. Methods: The frequency of anaemia (haematocrit <30%), and temporal changes in haematocrit were evaluated in 1,191 malarious children following ACTs. “Haematocrit conservation” was evaluated by using the fall in haematocrit/1,000 asexual parasites cleared from the peripheral blood (FIH/1,000 asexual parasites cpb), and the ratio of the average haematocrit (on the first 3 days of starting treatment):total parasitaemia cleared. Results: The frequency of anaemia decreased significantly following treatment. FIH/1,000 asexual parasites cpb, average haematocrit:total parasitaemia cleared, and mean haematocrit 5 weeks after treatment began were significantly lower in hyperparasitaemic children than in children without hyperparasitaemia, suggesting haematocrit conservation during treatment followed later by a loss of haematocrit. Asymptomatic late-appearing anaemia occurred in 6% of the children. Conclusion: Artesunate-amodiaquine and artemether-lumefantrine contribute to haematocrit conservation at high parasitaemias but may cause late-appearing anaemia.
A Role for Oxytocin-Like Receptor in Social Habituation in a Teleost
Authors: Weitekamp Chelsea A. , Solomon-Lane Tessa K. , Del Valle Pamela , Triki Zegni , Nugent Bridget M. , Hofmann Hans A.
Published: April 2017

Oxytocin (OT) mediates social habituation in rodent model systems, but its role in mediating this effect in other vertebrates is unknown. We used males of the African cichlid fish, Astatotilapia burtoni, to investigate two aspects of isotocin (IT; an OT homolog) signaling in social habituation. First, we examined the expression of IT receptor 2 (ITR2) as well as two immediate early genes in brain regions implicated in social recognition. Next, we examined IT neuron activity using immunohistochemistry. Patterns of gene expression in homologs of the amygdala and hippocampus implicate IT signaling in these regions in social habituation to a territorial neighbor. In the preoptic area, the expression of the ITR2 subtype and IT neuron activity respond to the presence of a male, independent of familiarity. Our results implicate IT in mediating social habituation in a teleost.
Downregulations of CD36 and Calpain-1, Inflammation, and Atherosclerosis by Simvastatin in Apolipoprotein E Knockout Mice
Authors: Yin Meihui , Liu Qianqian , Yu Lan , Yang Yueyan , Lu Meili , Wang Hongxin , Luo Duosheng , Rong Xianglu , Tang Futian , Guo Jiao
Published: April 2017

Background: In the previous in vitro study, we found that simvastatin decreased the protein expression of CD36, the scavenger receptor, and calpain-1, the Ca2+-sensitive cysteine protease, in oxidized low-density lipoprotein (oxLDL)-treated macrophages. In this in vivo study, we investigated whether simvastatin downregulates the expression of CD36 and calpain-1 and inhibits the inflammation and atherosclerosis in apolipoprotein E knockout (ApoE KO) mice. Methods: Twenty male 6-week-old ApoE KO mice were divided into 2 groups: the ApoE KO group and the ApoE KO + simvastatin (ApoE KO + Sim) group. Atherosclerotic lesions were evaluated and the expressions of CD68, CD36, and calpain-1 in aorta were examined. Results: Simvastatin inhibited the atherosclerotic lesion in ApoE KO mice. In addition, simvastatin reduced the contents of oxLDL, thiobarbituric acid reactive substances, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in serum, decreased the mRNA and protein expressions of CD36 and reduced the mRNA expression of TNF-α and IL-6 in the aortas. Furthermore, simvastatin reduced the calpain activity and the protein expression of calpain-1 in the aorta. Conclusion: The results suggested that the attenuation of atherosclerotic lesions in ApoE KO mice by simvastatin might be associated with the downregulations of CD36 and calpain-1 and with inflammation.
The Feasibility and Safety of Interventional Occlusion Treatment of Intracristal Ventricular Septal Defects: Clinical Report of 56 Cases
Authors: Cui Ting , Sun Wanfeng , He Yanhong , Zhang Guopei , Wang Dajie , Xia Yudong , Wang Feng , Zhu Mingxing
Published: April 2017

Background: To investigate the feasibility and safety of the O eccentric shape occluder in the interventional occlusion treatment of intracristal ventricular septal defect (IVSD). Methods: A retrospective analysis of the clinical data of 56 IVSD patients treated by interventional occlusion at our center, as well as recording of their intraoperative and postoperative status, was performed. Results: Of the 56 patients, a total of 48 patients underwent successful occlusion during the first surgical attempt. Four patients were transferred to the Surgery Department after occlusion when the largest occluder failed because of large defects. Two patients exhibited aortic valve regurgitation; 1 patient had mild regurgitation, which was not worsened after 6 months of follow-up. One patient had severe aortic regurgitation, and 2 days after the operation, the patient underwent a second operation. One patient exhibited a residual shunt, which was above the occluder; after 1 year of follow-up, re-occlusion was successful and eliminated the shunt. One patient developed complete right bundle branch block. Conclusion: Most IVSD interventional occlusion treatments are feasible and safe.
Is Human Oxoguanine Glycosylase 1 Genetic Variant Successful Even on Oral Squamous Cell Carcinoma?
Authors: Aydemir Levent , Bireller Elif Sinem , Avci Hakan , Boy Metin Zeynep , Deger Kemal , Unur Meral , Cakmakoglu Bedia
Published: April 2017

Background: Oral squamous cell carcinoma (OSCC) is one of the most widespread cancer types that arise from different sites of oral cavity and has a 5-year survival rate. This study is aimed at investigating the human oxoguanine glycosylase 1 (hOGG1)-Ser326Cys and APE-Asp148Glu polymorphisms of DNA repair genes in OSCC. Materials and Methods: We investigated the hOGG1-Ser326Cys and APE-Asp148Glu polymorphisms of DNA repair genes in the oral cavity. Genotyping was conducted using polymerase chain reaction-restriction fragment length polymorphism analysis based on 132 patients who were diagnosed as having OSCC and 160 healthy subjects. Results: Individuals with the genotype hOGG1-Ser326Cys, Cys allele carriers, were found significantly more frequently in the patient group compared to the control group as increase in risk (p < 0.001). Furthermore, it was observed that there were significantly more individuals with the Ser allele in the control group (p < 0.001). Individuals with genotype APE-Asp148Glu were not statistically significant; however, they were still more in the control group and provided protection against the disease. Conclusion: Our findings showed that hOGG1-Ser326Cys Cys allele is statistically important and relevant with respect to the development of oral squamous cancer. In view of our results, further studies including expression levels are required in which hOGG1-Ser326Cys should be investigated as molecular biomarkers for the early prediction of squamous cell carcinoma.
Validation of a Case-Finding Algorithm for Hidradenitis Suppurativa Using Administrative Coding from a Clinical Database
Authors: Strunk Andrew , Midura Margaretta , Papagermanos Vassiliki , Alloo Allireza , Garg Amit
Published: April 2017

Background: Requisite to the application of clinical databases for observational research in hidradenitis suppurativa (HS) is the identification of an accurate case cohort. Objective: To assess the validity of utilizing administrative codes to establish the HS cohort from a large clinical database. Methods: In this retrospective study using chart review as the reference standard, we calculated several estimates of the diagnostic accuracy of at least 1 ICD-9 code for HS. Results: Estimates of the diagnostic accuracy of at least 1 ICD-9 code for HS include sensitivity 100% (95% CI 98-100), specificity 83% (95% CI 77-88), positive predictive value 79% (95% CI 72-85), negative predictive value 100% (95% CI 98-100), accuracy 90% (95% CI 86-93), and kappa statistic 79% (95% CI 73-86). Conclusion: The case-finding algorithm employing at least 1 ICD-9 code for HS provides balance in achieving accuracy and adequate power, both necessary in the evaluation of a less common disease and its potential association with uncommon or even rare events.