bluuebunny/crossref_metadata_2025 huggingface dataset:
Protein-leucine ingestion activates a regenerative inflammo-myogenic transcriptome in skeletal muscle following intense endurance exercise
Authors: Rowlands David S. , Nelson Andre R. , Raymond Frederic , Metairon Sylviane , Mansourian Robert , Clarke Jim , Stellingwerff Trent , Phillips Stuart M.
Published: October 2015

Protein-leucine supplement ingestion following strenuous endurance exercise accentuates skeletal-muscle protein synthesis and adaptive molecular responses, but the underlying transcriptome is uncharacterized. In a randomized single-blind triple-crossover design, 12 trained men completed 100 min of high-intensity cycling then ingested 70/15/180/30 g protein-leucine-carbohydrate-fat (15LEU), 23/5/180/30 g (5LEU), or 0/0/274/30 g (CON) beverages during the first 90 min of a 240 min recovery period. Vastus lateralis muscle samples (30 and 240 min postexercise) underwent transcriptome analysis by microarray followed by bioinformatic analysis. Gene expression was regulated by protein-leucine in a dose-dependent manner affecting the inflammatory response and muscle growth and development. At 30 min, 15LEU and 5LEU vs. CON activated transcriptome networks with gene-set functions involving cell-cycle arrest (Z-score 2.0–2.7, P < 0.01), leukocyte maturation (1.7, P = 0.007), cell viability (2.4, P = 0.005), promyogenic networks encompassing myocyte differentiation and myogenin (MYOD1, MYOG), and a proteinaceous extracellular matrix, adhesion, and development program correlated with plasma lysine, arginine, tyrosine, taurine, glutamic acid, and asparagine concentrations. High protein-leucine dose (15LEU-5LEU) activated an IL-1I-centered proinflammatory network and leukocyte migration, differentiation, and survival functions (2.0–2.6, <0.001). By 240 min, the protein-leucine transcriptome was anti-inflammatory and promyogenic (IL-6, NF- β, SMAD, STAT3 network inhibition), with overrepresented functions including decreased leukocyte migration and connective tissue development (−1.8–2.4, P < 0.01), increased apoptosis of myeloid and muscle cells (2.2–3.0, P < 0.002), and cell metabolism (2.0–2.4, P < 0.01). The analysis suggests protein-leucine ingestion modulates inflammatory-myogenic regenerative processes during skeletal muscle recovery from endurance exercise. Further cellular and translational research is warranted to validate amino acid-mediated myeloid and myocellular mechanisms within skeletal-muscle functional plasticity.
In VitroEvaluation of Antimicrobial Efficacy of Extracts Obtained from Raw and Fermented Wild Macrofungus,Lenzites quercina
Authors: Ogidi Olusola Clement , Oyetayo Victor Olusegun , Akinyele Bamidele Juliet
Published: October 2015

In recent time, there is a major concern about antibiotic resistance displayed by some pathogenic microorganisms and this had involved a continuous search for natural antimicrobial products. The phytochemistry as well as antimicrobial activity of extracts obtained fromLenzites quercinawas investigated. The extracts and purified fractions were, respectively, tested against indicator organisms using agar well diffusion and disc diffusion methods. The quantity of phytochemicals found in the extracts ofL. quercinaranged from 14.4 to 20.7 mg/g for alkaloids, 6.1 to 12.8 mg/g for steroids, 4.5 to 10.6 mg/g for saponins, 2.8 to 17.2 mg/g for terpenoids, and 0.41 to 17.1 mg/g for flavonoids. The gas chromatography mass spectrophotometry (GCMS) analysis of the extract reveals the presence of caprylic acid, stearic acid, tetradecanoic acid, methyl-11-octadecenoate, oleic acid, and 4-methyl-2-propyl-1-pentanol. Extracts ofL. quercinaand its purified fractions exhibited wider range of inhibition (4 mm to 26 mm) onStaphylococcus aureus(ATCC 29213),Pseudomonas aeruginosa(ATCC 27853),Escherichia coli(ATCC 35218), Methicillin ResistantStaphylococcus aureus(MRSA),Salmonella typhi, Bacillus cereus, Enterococcus faecalis, Candida albicans, andAspergillus niger. The antimicrobial effects ofL. quercinaextracts indicate that this wild macrofungus contains significant amount of pharmacological agents, which could be extracted to curb the menace of antibiotic resistances by pathogenic organisms.
Growth and Characterization of Benzimidazolium Salicylate: NLO Property from a Centrosymmetric Crystal
Authors: Amudha M. , Rajkumar R. , Thayanithi V. , Praveen Kumar P.
Published: October 2015

A new organic charge transfer molecular complex salt of benzimidazolium salicylate (BSL) single crystals was grown by the slow evaporation solution growth technique using methanol as a solvent at room temperature. The grown crystals were characterised by single crystal X-ray diffraction (XRD) which confirms that the crystal belongs to monoclinic system with the centrosymmetric space group P21/c. The crystalline perfection of the grown crystal was analyzed by high resolution X-ray diffraction (HRXRD). The presence of various functional groups was identified by FTIR spectrum. UV-Vis spectral study reveals that the BSL crystal is optically transparent in the wavelength region 342 nm–1100 nm. Dielectric measurements of the crystal at various frequencies were also determined. The mechanical properties of the grown crystal were assessed using Vickers microhardness testing. Nonlinear optical property of the crystal was confirmed using Kurtz and Perry powder technique and the SHG efficiency of the BSL crystal is 0.7 times greater than that of the standard KDP crystal.
Beneficial Effects of Qili Qiangxin Capsule on Lung Structural Remodeling in Ischemic Heart Failure via TGF-β1/Smad3 Pathway
Authors: He Yaoyao , Du Bai , Fan Huiting , Cao Jian , Liu Zi Wang , Zhao Yonglie , Zhao Mingjing , Zhao Yizhou , Zhao Xin , Cui Xiangning
Published: October 2015

Qili qiangxin (QL) capsule is a traditional Chinese medicine that is widely used for the treatment of patients with chronic heart failure (CHF) of all etiologies, although the exact mechanisms of action remain unclear. CHF leads to pulmonary vascular remodelling and thickening of the alveolar-capillary barrier that may be important mechanisms in the poor clinical outcome in patients with end-stage heart failure. We examined whether QL could improve lung injury in ischemic CHF by reducing lung remodeling. Rats with myocardial infarct received QL (1.0 g/kg/day) for 4 weeks. Echocardiographic and morphometric measurements were obtained followed by echocardiography, histological staining, and immunohistochemical analysis of lung sections. CHF caused significant lung structural remodeling evidenced by collagen deposition and thickening of the alveolar septa after myocardial infarct that were greatly improved by QL. Lung weight increased after infarct with no evidence of pulmonary edema and was normalized by QL. QL also reduced lung transforming growth factor-β1 (TGF-β1), p-Smad3, tumor necrosis factor-α(TNF-α), and Toll-like receptor-4 (TLR4) expression. Thus, QL reduces lung remodeling associated with CHF, mainly by suppressing the TGF-β1/Smad3 signaling pathway. The mechanism may also involve inhibition of TLR4 intracellular signaling.
Field Results of a Navigation Architecture with Timing Constraints
Authors: Silva Jorge , Sequeira Joao , Santos Cristina
Published: October 2015

This paper presents results of field tests of a mobile robot controlled by a navigation architecture accounting for timing constraints in an indoor environment. Dependability properties characterize the effects of disturbances on the ability to successfully accomplish any assigned missions, described in terms of the stability of an equilibrium state identified with a goal location. The stability is analyzed using Contraction theory. A localization system based on artificial landmarks is used to obtain location estimates that enable the robot to autonomously cover large distances. Monte Carlo tests assess the architecture under different real environment conditions including recovering from disturbing events such as landmark detection failures, robot kidnapping, unexpected collisions, and changes in the density of obstacles in the environment. Tests include long-run missions of around 2900 m lasting for 4.5 hours.
Ray Tracing Study of Optical Characteristics of the Solar Image in the Receiver for a Thermal Solar Parabolic Dish Collector
Authors: Pavlovic Saša R. , Stefanovic Velimir P.
Published: October 2015

This study presents the geometric aspects of the focal image for a solar parabolic concentrator (SPC) using the ray tracing technique to establish parameters that allow the designation of the most suitable geometry for coupling the SPC to absorber-receiver. The efficient conversion of solar radiation into heat at these temperature levels requires a use of concentrating solar collectors. In this paper detailed optical design of the solar parabolic dish concentrator is presented. The system has diameter D=3800 mm and focal distance f=2260 mm. The parabolic dish of the solar system consists of 11 curvilinear trapezoidal reflective petals. For the construction of the solar collectors, mild steel-sheet and square pipe were used as the shell support for the reflecting surfaces. This paper presents optical simulations of the parabolic solar concentrator unit using the ray tracing software TracePro. The total flux on the receiver and the distribution of irradiance for absorbing flux on center and periphery receiver are given. The goal of this paper is to present the optical design of a low-tech solar concentrator that can be used as a potentially low cost tool for laboratory scale research on the medium-temperature thermal processes, cooling, industrial processes, polygeneration systems, and so forth.
Trust-Based Anomaly Detection in Emerging Sensor Networks
Authors: Wu Renyong , Deng Xue , Lu Rongxing , Shen Xuemin (Sherman)
Published: October 2015

Wireless sensor networks (WSNs) consist of a large number of small-size, energy-constrained nodes and generally are deployed to monitor surrounding situation or relay generated packets in other devices. However, due to the openness of wireless media and the inborn self-organization feature of WSNs, that is, frequent interoperations among neighbouring nodes, network security has been tightly related to data credibility and/or transmission reliability, thus trust evaluation of network nodes is becoming another interesting issue. Obviously, how to describe node’s behaviors and how to integrate various characteristics to make the final decision are two major research aspects of trust model. In this paper, a new trust model is proposed to detect anomaly nodes based on fuzzy theory and revised evidence theory. By monitoring the behaviors of the evaluated nodes with multidimensional characteristics and integrating these pieces of information, the malicious nodes in a network can be identified and the normal operation of the whole network can be verified. In addition, to accelerate the detection process, a weighting judgment mechanism is adopted to deal with the uncertain states of evaluated nodes. Finally extensive simulations are conducted, and the results demonstrate that the proposed trust model can achieve higher detection ratio of malicious nodes in comparison with the previously reported results.
Signal Processing for Tracking of Moving Object in Multi-Impulse Radar Network System
Authors: Kim Beom-Hun , Han Seung-Jo , Kwon Goo-Rak , Pyun Jae-Young
Published: October 2015

Indoor positioning systems (IPSs) have been discussed for use in entertainment, home automation, rescue, surveillance, and healthcare applications. In this paper, we present an IPS that uses an impulse radio-ultra-wideband (IR-UWB) radar network. This radar network system requires at least two radar devices to determine the current coordinates of a moving person. However, one can enlarge the monitoring area by adding more radar sensors. To track moving targets in indoor environments, for example, patients in hospitals or intruders in a home, signal processing procedures for tracking should be applied to the raw data measured using IR-UWB radars. This paper presents the signal processing method required for robust target tracking in a radar network, that is, an iterative extended Kalman filter- (IEKF-) based object tracking method, which uses two IR-UWB radars to measure the coordinates of the targets. The proposed IEKF tracking method is compared to the conventional extended Kalman filter (EKF) method. The results verify that the IEKF method improves the performance of 2D target tracking in a real-time system.
Simulation-Based Optimization for Storage Allocation Problem of Outbound Containers in Automated Container Terminals
Authors: Zhao Ning , Xia Mengjue , Mi Chao , Bian Zhicheng , Jin Jian
Published: October 2015

Storage allocation of outbound containers is a key factor of the performance of container handling system in automated container terminals. Improper storage plans of outbound containers make QC waiting inevitable; hence, the vessel handling time will be lengthened. A simulation-based optimization method is proposed in this paper for the storage allocation problem of outbound containers in automated container terminals (SAPOBA). A simulation model is built up by Timed-Colored-Petri-Net (TCPN), used to evaluate the QC waiting time of storage plans. Two optimization approaches, based on Particle Swarm Optimization (PSO) and Genetic Algorithm (GA), are proposed to form the complete simulation-based optimization method. Effectiveness of this method is verified by experiment, as the comparison of the two optimization approaches.
Impacts of Land Use Change on the Regional Climate: A Structural Equation Modeling Study in Southern China
Authors: Wang Zhanqi , Li Bingqing , Yang Jun
Published: October 2015

With the frequent human activities operating on the earth, the impacts of land use change on the regional climate are increasingly perceptible. Under the background of the rapid urbanization, understanding the impacts of land use change on the regional climate change is vital and significant. In this study, we investigated the relationships between land use change and regional climate change through a structural equation model. Southern China was selected as the study area for its rapid urbanization and different structure of land use among its counties. The results indicate that the path coefficients of “vegetation,” “Urban and surrounding area,” and “other” to “climate” are −0.42, 0.20, and 0.46, respectively. Adding vegetation area is the main method to mitigate regional climate change. Urban and surrounding area and other areas influence regional climate by increasing temperature and precipitation to a certain extent. Adding grassland and forestry, restraining sprawl of built-up area, and making the most use of unused land are efficient ways to mitigate the regional climate change in Southern China. The results can provide feasible recommendations to land use policy maker.
The Role of Focused Echocardiography in Pediatric Intensive Care: A Critical Appraisal
Authors: Gaspar Heloisa Amaral , Morhy Samira Saady
Published: October 2015

Echocardiography is a key tool for hemodynamic assessment in Intensive Care Units (ICU). Focused echocardiography performed by nonspecialist physicians has a limited scope, and the most relevant parameters assessed by focused echocardiography in Pediatric ICU are left ventricular systolic function, fluid responsiveness, cardiac tamponade and pulmonary hypertension. Proper ability building of pediatric emergency care physicians and intensivists to perform focused echocardiography is feasible and provides improved care of severely ill children and thus should be encouraged.
Formulation and Optimization of Eudragit RS PO‐Tenofovir Nanocarriers Using Box‐Behnken Experimental Design
Authors: Matlhola Kefilwe , Katata-Seru Lebogang , Tshweu Lesego , Bahadur Indra , Makgatho Gertrude , Balogun Mohammed
Published: October 2015

The objective of present study was to develop an optimized polymeric nanoparticle system for the antiretroviral drug tenofovir. A modified nanoprecipitation method was used to prepare Eudragit RS PO nanoparticles of the drug. The effect of amount of polymer, surfactant concentration, and sonication time on particle size, particle distribution, encapsulation efficiency (EE), and zeta potential were assessed and optimized utilizing a three‐factor, three‐level Box‐Behnken Design (BBD) of experiment. Fifteen formulations of nanoparticles were prepared as per BBD and evaluated for particle size, polydispersity index (PDI), EE, and zeta potential. The results showed that the measured mean particle sizes were in the range of 233 to 499 nm, PDI ranged from 0.094 to 0.153, average zeta potential ranged from −19.9 to −45.8 mV, and EE ranged between 98 and 99%. The optimized formulation was characterized for in vitro drug release and structural characterization. The mean particle size of this formulation was 233 nm with a PDI of 0.0107. It had a high EE of 98% and average zeta potential of −35 mV, an indication of particle stability. The FTIR showed some noncovalent interactions between the drug and polymer but a sustained release was observed in vitro for up to 80 hours.
The Formalization of Discrete Fourier Transform in HOL
Authors: Shi Zhiping , Zhang Yupeng , Guan Yong , Li Liming , Zhang Jie
Published: October 2015

Traditionally, Discrete Fourier Transform (DFT) is performed with numerical or symbolic computation, which cannot guarantee 100% accurate analysis which may be necessary for safety-critical applications. Machine theorem proving is one of the formal methods that perform accurate analysis with completeness to some extent. This paper proposes the formalization of DFT in a higher-order logic theorem prover named HOL. We propose the formal definition of DFT and verify the fundamental properties of DFT. Two case studies are presented to illustrate usefulness and correctness of the formalized DFT, including formal verifications of Fast Fourier Transform (FFT) and cosine frequency shift.
Constrained Power Focusing in Inhomogeneous Media as a Polarization Optimization
Authors: Iero Domenica Anna Maria
Published: October 2015

The problem of focusing a field into inhomogeneous media is a canonic open problem relevant in many engineering areas. Several approaches have been developed, for example, Time Reversal, Inverse Filter, and Eigenvalues approach, but they suffer from several drawbacks which are counteracted by Optimal Constrained Power Focusing (OCPF) technique. OCPF was first introduced to deal with scalar fields and, recently, it has been extended to tackle the problem of focusing vector fields. In particular, the proposed approach allows reducing the focusing problem, which is NP-hard in case of vector fields, to a series of convex programming (CP) ones. In this paper, an alternative OCPF formulation is presented, which consists in the research of the most suitable polarization of the field into the target point and relies on the convexity of the problem when fixing this polarization. Such a result allows the development of two different solution procedures: an enumerative one that can take advantage of parallel programming in order to explore all possible polarizations and hybrid one which relies on the exploitation of global search algorithm just to solve the nonconvex part of the problem at hand.
An Experimental Study on Concrete Flat Slabs Prestressed with Carbon Fibre Reinforced Polymer Sheets
Authors: Shen Yin , Lu Shaohui , Li Fangyuan
Published: October 2015

Carbon fibre reinforced polymer (CFRP) is currently used to reinforce buildings in civil engineering in the common forms of sheets, while the utilization efficiency of a CFRP materials greatly decreased when the CFRP material is directly bonded to the structure because of the lack of the effect of the exertion of a prestress. A paper spool-inspired anchoring method is proposed to overcome the shearing problem in the anchoring system through the friction between layers. Anchoring and jack-up tensioning devices for CFRP sheets are also designed and produced. A prestress is successfully applied to single and multiple CFRP sheets (80% tensioning strength is achieved), thus verifying the tensioning effect of the prestress. Based on these results, prestressed concrete flat slabs were designed with pretensioned CFRP sheets. The corresponding mechanical properties of the concrete flat slabs are tested to verify the feasibility of using CFRP sheets to apply a prestress. The results show that the uniformity of the fibre stress during the tensioning of the CFRP sheet is the key to the success of the application of the prestress.
Biodegradation of PAHs byBurkholderiasp. VITRSB1 Isolated from Marine Sediments
Authors: Revathy T. , Jayasri M. A. , Suthindhiran K.
Published: October 2015

The polycyclic aromatic hydrocarbons (PAHs) pollution to the environment is a major threat to the living organisms, and hence the degradation of these PAHs is necessary. Studies on PAHs degrading bacteria have focussed on terrestrial microbes and the potential of marine derived microbes is undermined. Herein we report the isolation and characterization of PAHs degradingBurkholderiasp. from lagoon sediments collected at the Southern coast of India. The strain was Gram negative, rod-shaped, motile, and ∼2–5 μm in length. Based on the phylogenetic data the strain was identified asBurkholderiaand designated as VITRSB1. Initial PAHs degradation ability of the strain was assessed using basal salt medium supplemented with diesel, kerosene, toluene, aniline, naphthalene, and phenol. The strain was found to be effectively degrading kerosene, diesel, toluene, and aniline even at higher concentration (1%). However, naphthalene and aniline were degraded only at lower concentration (0.1%) and phenol, camphor, and DAP inhibited the growth of the strain. Furthermore, the degraded end products of the PAHs were determined using FTIR. Notably, none of the end products were found to be toxic to the biosphere. Our results indicate that the isolatedBurkholderiasp. could be a prospective candidate for the effective degradation of selective PAHs.
Nonconsumptive Effects of Predation and Impaired Chemosensory Risk Assessment on an Aquatic Prey Species
Authors: Elvidge Chris K. , Brown Grant E.
Published: October 2015

Weak levels of acidity impair chemosensory risk assessment by aquatic species which may result in increased predator mortalities in the absence of compensatory avoidance mechanisms. Using replicate populations of wild juvenile Atlantic salmon (Salmo salar) in neutral and acidic streams, we conducted a series of observational studies and experiments to identify differences in behaviours that may compensate for the loss of chemosensory information on predation risk. Comparing the behavioural strategies of fish between neutral and acidic streams may elucidate the influence of environmental degradation on nonconsumptive effects (NCEs) of predation. Salmon in acidic streams are more active during the day than their counterparts in neutral streams, and are more likely to avoid occupying territories offering fewer physical refugia from predators. Captive cross-population transplant experiments indicate that at equal densities, salmon in acidic streams do not demonstrate relative decreases in growth rate as a result of their different behavioural strategies. Instead, altering diel activity patterns to maximize visual information use and occupying relatively safer territories appear sufficient to offset increased predation risk in acidic streams. Additional strategies such as elevated foraging rates during active periods or adopting riskier foraging tactics are necessary to account for the observed similarities in growth rates.
Global Stabilization of Nonlinear Networked Control System with System Delays and Packet Dropouts via Dynamic Output Feedback Controller
Authors: Bouazza Kheir Eddine
Published: October 2015

The stabilization problem is investigated for a class of nonlinear discrete-time networked control systems (NCSs). Nonideal network Quality of Services (QoS) are considered, more specifically data packet dropouts and network-induced delays. A state feedback controller for a class of NCSs is proposed. Subsequently, an observer is designed to estimate the state space. Based on the Lyapunov-Krasovskii functional, sufficient conditions (expressed in terms of LMIs) for the existence of a dynamic output feedback controller are derived. The stabilization is achieved without mathematical transformations or fuzzy logic approximations and without state space augmentation. Finally, illustrative examples are provided to show the effectiveness of the proposed method.
Visual Analysis of Multimodal Movie Network Data Based on the Double-Layered View
Authors: Tang Ying , Yu Jia , Li Chen , Fan Jing
Published: October 2015

Multimodal visualization of network data is a method considering various types of nodes and visualizing them based on their types, or modes. Compared to traditional network visualization of nodes of the same mode, the new method treats different modes of entities in corresponding ways and presents the relations between them more clearly. In this paper, we apply the new method to visualize movie network data, a typical multimodal graph data that contains nodes of different types and connections between them. We use an improved force-directed layout algorithm to present the movie persons as the foreground and a density map to present films as the background. By combining the foreground and background, the movie network data are presented in one picture properly. User interactions are provided including detailed pie charts visible/invisible, zooming, and panning. We apply our visualization method to the Chinese movie data from Douban website. In order to testify the effectiveness of our method, we design and perform the user study of which the statistics are analyzed.
Anticancer and Cancer Prevention Effects of Piperine-Free Piper nigrum Extract on N-nitrosomethylurea-Induced Mammary Tumorigenesis in Rats
Authors: Sriwiriyajan Somchai , Tedasen Aman , Lailerd Narissara , Boonyaphiphat Pleumjit , Nitiruangjarat Anupong , Deng Yan , Graidist Potchanapond
Published: October 2015

Piper nigrum (P. nigrum) is commonly used in traditional medicine. This current study aimed to investigate the anticancer and cancer preventive activity of a piperine-free P. nigrum extract (PFPE) against breast cancer cells and N-nitrosomethylurea (NMU)–induced mammary tumorigenesis in rats. The cytotoxic effects and the mechanism of action were investigated in breast cancer cells using the MTT assay and Western blot analysis, respectively. An acute toxicity study was conducted according to the Organization for Economic Co-operation and Development guideline. Female Sprague-Dawley rats with NMU-induced mammary tumors were used in preventive and anticancer studies. The results showed that PFPE inhibited the growth of luminal-like breast cancer cells more so than the basal-like ones by induction of apoptosis. In addition, PFPE exhibited greater selectivity against breast cancer cells than colorectal cancer, lung cancer, and neuroblastoma cells. In an acute toxicity study, a single oral administration of PFPE at a dose of 5,000 mg/kg body weight resulted in no mortality and morbidity during a 14-day observation period. For the cancer preventive study, the incidence of tumor-bearing rats was 10% to 20% in rats treated with PFPE. For the anticancer activity study, the growth rate of tumors in the presence of PFPE-treated groups was much slower when compared with the control and vehicle groups. The extract itself caused no changes to the biochemical and hematologic parameters when compared with the control and vehicle groups. In conclusion, PFPE had a low toxicity and a potent antitumor effect on mammary tumorigenesis in rats. Cancer Prev Res; 9(1); 74–82. ©2015 AACR.
Preclinical In Vitro, In Vivo, and Pharmacokinetic Evaluations of FLLL12 for the Prevention and Treatment of Head and Neck Cancers
Authors: Anisuzzaman Abu Syed Md , Haque Abedul , Rahman Mohammad Aminur , Wang Dongsheng , Fuchs James R. , Hurwitz Selwyn , Liu Yuan , Sica Gabriel , Khuri Fadlo R. , Chen Zhuo (Georgia) , Shin Dong M. , Amin A.R.M. Ruhul
Published: October 2015

Despite its high promise for cancer prevention and therapy, the potential utility of curcumin in cancer is compromised by its low bioavailability and weak potency. The purpose of the current study was to assess the in vitro and in vivo efficacy and pharmacokinetic parameters of the potent curcumin analogue FLLL12 in SCCHN and identify the mechanisms of its antitumor effect. IC50 values against a panel of one premalignant and eight malignant head and neck cancer cell lines as well as apoptosis assay results suggested that FLLL12 is 10- to 24-fold more potent than natural curcumin depending on the cell line and induces mitochondria-mediated apoptosis. In vivo efficacy (xenograft) and pharmacokinetic studies also suggested that FLLL12 is significantly more potent and has more favorable pharmacokinetic properties than curcumin. FLLL12 strongly inhibited the expression of p-EGFR, EGFR, p-AKT, AKT, Bcl-2, and Bid and increased the expression of Bim. Overexpression of constitutively active AKT or Bcl-2 or ablation of Bim or Bid significantly inhibited FLLL12-induced apoptosis. Further mechanistic studies revealed that FLLL12 regulated EGFR and AKT at transcriptional levels, whereas Bcl-2 was regulated at the translational level. Finally, FLLL12 strongly inhibited the AKT downstream targets mTOR and FOXO1a and 3a. Taken together, our results strongly suggest that FLLL12 is a potent curcumin analogue with more favorable pharmacokinetic properties that induces apoptosis of head and neck cancer cell lines by inhibition of survival proteins including EGFR, AKT, and Bcl-2 and increasing of the proapoptotic protein Bim. Cancer Prev Res; 9(1); 63–73. ©2015 AACR.
Hsa-miR-21 and Hsa-miR-29 in Tissue as Potential Diagnostic and Prognostic Biomarkers for Gastric Cancer
Authors: Wang Dahu , Fan Zhisong , Liu Fengling , Zuo Jing
Published: October 2015

Background/Aims: Gastric cancer (GC) is the fourth most common cancer and the second most common cause of cancer deaths worldwide. Endoscopic examination is the most used method to detect the GC nowadays, whereas this method is expensive and invasive. MicroRNAs (miRNAs) are a group of recently discovered small non-protein-coding RNAs. They regulate the expression of hundreds of target genes; thereby control a wide range of tumorigenic processes. In this study, we selected two miRNAs, hsa-miR-21 and hsa-miR-29, as the targets to assess their diagnostic and prognostic value for GC. Methods: A total of 50 GC patients including 24 females and 26 males were recruited. Tumor and adjacent non-tumor tissue samples were collected from all these participants during the endoscopic examination. RNAs were extracted from these samples, then quantified via qRT-PCR and normalized with RNU43 as the internal control. Statistical analyses were conducted using the GraphPad Prism 5.0. Results: We discovered a higher expression of hsa-miR-21 and a relatively lower expression of hsa-miR-29hsa-miR-29 in the tumor tissue than in the adjacent non-tumor tissue. Moreover, both the two miRNAs showed moderate diagnostic performance (hsa-miR-21: AUC = 0.75, sensitivity = 0.70, specificity = 0.78; hsa-miR-29hsa-miR-29: AUC = 0.73, sensitivity = 0.70, specificity = 0.68). In the follow-up research, we found that higher tissue hsa-miR-21 level was related to a lower overall survival rate, whereas higher tissue hsa-miR-29hsa-miR-29 level was associated with the higher overall survival rate. These results indicated that both hsa-miR-21 and hsa-miR-29 had the potential to be the biomarkers for GC prognosis. Conclusion: In summary, we verified the diagnostic and prognostic value of tissue hsa-miR-21hsa-miR-21 and hsa-miR-29 in GC. Both of them can be potentially applied as novel and non-invasive biomarkers for GC.
Downregulation of MicroRNA-145 Caused by Hepatitis B Virus X Protein Promotes Expression of CUL5 and Contributes to Pathogenesis of Hepatitis B Virus-Associated Hepatocellular Carcinoma
Authors: Gao Feng , Sun Xiaoyu , Wang Likun , Tang Shunxiong , Yan Changqing
Published: October 2015

Background: Hepatitis B viral infection-induced hepatocellular carcinoma (HCC) is a major threat to human health in China. Hepatitis B virus X protein (HBX), an HBV protein, has been reported to be involved in regulating the cellular activities of the host cells and is responsible for HCC oncogenesis. Methods and Results: In this study, we performed real-time PCR in tumor tissue samples collected from 53 HCC patients (25 HBV-positive cases and 28 HBV-negative cases) to screen the candidate miRNAs that have previously been reported to be aberrantly expressed in HBV-associated HCC and found that miR-145 was significantly downregulated. The following computational analysis identified CUL5 and RAB5C as virtual targets of miR-145, whereas only CUL5 was verified as a validated target gene of miR-145 in liver cells via luciferase reporter assay. In line with this result, we found that both the mRNA and protein expression levels of CUL5 were significantly higher in HBV-positive than in HBV-negative HCC. An in vitro experiment demonstrated a significant decrease in the expression of miRNA-145, a substantial increase in the mRNA and protein expression of CUL5, and an enhanced proliferation of HBX over-expressing HepG2 cells compared with the control. In HepG2.2.15, we found significant decreases in both the expression of CUL5 and the cell growth rate of H cells transfected with 60 nM miR-145 mimics compared with the scramble controls. Conclusion: HBV infection promotes cell growth, at least partially, through the HBX-induced downregulation of miRNA-145 expression, which is responsible for the oncogenesis of HBV-associated HCC.
Clarithromycin Synergistically Enhances Thalidomide Cytotoxicity in Myeloma Cells
Authors: Qiu Xu-Hua , Shao Jing-Jing , Mei Jian-Gang , Li Han-Qing , Cao Hong-Qin
Published: October 2015

Clarithromycin (CAM) is a macrolide antibiotic that is widely used in the treatment of respiratory tract infections, sexually transmitted diseases and infections caused by the Helicobacter pylori and Mycobacterium avium complex. Recent studies showed that CAM was highly effective against multiple myeloma (MM) when used in combination with immunomodulatory drugs and dexamethasone. However, the related mechanism is still unknown. As 3 immunomodulatory agents are all effective in the respective regimen, we postulated that CAM might enhance the effect of immunomodulatory drugs. We evaluated the interaction effects of CAM and thalidomide on myeloma cells. Taking into consideration that thalidomide did not affect the proliferation of myeloma cells in vitro, we cocultured myeloma cells with peripheral blood monocytes and evaluated the effects of CAM and thalidomide on the cocultured cell model. Data showed that thalidomide and CAM synergistically inhibited the proliferation of the cells. On this same model, we also found that thalidomide and CAM synergistically decreased the secretion of tumor necrosis factor-α and interleukin-6. This might be caused by the effect of the 2 drugs on inhibiting the activation of ERK1/2 and AKT. These data suggest that the efficacy of CAM against MM was partly due to its synergistic action with the immunomodulatory agents.
Primary Plasma Cell Leukemia in the Era of Novel Agents: A Multicenter Study of the Japanese Society of Myeloma
Authors: Iriuchishima Hirono , Ozaki Shuji , Konishi Jun , Matsumoto Morio , Murayama Kayoko , Nakamura Fumihiko , Yamamoto Go , Handa Hiroshi , Saitoh Takayuki , Nagura Eiichi , Shimizu Kazuyuki , Nojima Yoshihisa , Murakami Hirokazu
Published: October 2015

We investigated the treatment and outcome of Japanese patients with primary plasma cell leukemia (pPCL) in the era of novel agents and analyzed the risk factors affecting survival. Among 3,318 patients with symptomatic multiple myeloma (MM), 38 patients were diagnosed with pPCL. The median overall survival (OS) of the pPCL patients was 2.85 years, which was significantly extended compared with that in previous reports. The proportion of patients treated with novel agents was 61%. The OS of the patients treated with novel agents was significantly extended compared with that of patients treated without novel agents according to the generalized Wilcoxon test (2.85 vs. 1.16 years, p = 0.049). This statistical finding suggests that treatment with novel agents could have prevented early death in the patients with pPCL. Age was the only statistically significant prognostic factor associated with an inferior OS (hazard ratio 4.57). Five patients received maintenance therapy with novel agents, and their OS tended to be longer than that of the other patients without maintenance (4.45 vs. 2.85 years). Unlike MM, OS for pPCL has not been improved significantly over the last decade, especially in elderly patients. Therefore, it is important to establish the treatment strategy, particularly after induction treatment.
Peculiarities and Patterns of Cervical Spine Injuries in Children and Adolescents: A Retrospective Series of 84 Patients from a Single Institute
Authors: Babu R. Arun , Arivazhagan Arimappamagan , Devi B. Indira , Bhat Dhananjaya I. , Sampath Somanna , Chandramouli B.A.
Published: October 2015

Cervical spine injuries occur infrequently in children but are associated with significant disability and mortality. A retrospective analysis was performed of 84 consecutive pediatric spine injuries treated at our institute from January 2002 to December 2011. The mean age was 14.7 years. There were 18 patients (21%) in group A (0-12 years) and 66 patients (79%) in group B (13-18 years). Overall, injury was more common in boys (ratio of 6:1). Trivial fall was the predominant cause in group A and fall from height in group B. There were 30 children (36%) with injuries of the upper cervical spine, 53 (63%) with injuries of the lower cervical spine and 1 patient (1%) with a combined injury of upper cervical spine and thoracic spine. Overall, 22% of the group A children and 67% of the group B patients had more severe injuries (Frankel grades A, B and C); 21% (18/84) were treated by surgical fusion. Where follow-up was available, 17 out of 22 children (77%) had good outcome (Frankel grade >C). In conclusion, mechanisms and patterns of injury in children are age related and the majority of the children had good outcome.
Differential Effects of Axin2 Deficiency on the Fibrogenic and Regenerative Response in Livers of Bile Duct-Ligated Mice
Authors: Abshagen Kerstin , Senne Moritz , Genz Berit , Thomas Maria , Vollmar Brigitte
Published: October 2015

Background: Wnt signaling is involved in the pathogenesis of liver fibrosis. Axin2 is a negative regulator of the canonical Wnt pathway by promoting β-catenin degradation. β-Catenin-activating and loss-of-function mutations of Axin2 are thought to be functionally relevant for liver diseases and cancer. Thus, we hypothesized that Axin2 deficiency promotes fibrogenesis. Methods: As the functions and mechanisms of how Axin2/β-catenin signaling participates in the progression of liver fibrosis are unclear, we investigated the progression of liver fibrosis in Axin2-deficient mice using Axin2-LacZ reporter mice (Axin2+/-, Axin2-/-, and Axin2+/+) which underwent bile duct ligation (BDL). Results: Here, we show that the expression of Axin2 is downregulated during fibrogenesis in wild-type mice, which is consistent with a decreased expression of the reporter gene LacZ in Axin2+/- and Axin2-/- mice. Surprisingly, no alteration in active β-catenin/Wnt signaling occurs in Axin2-deficient mice upon BDL. Despite a less pronounced liver injury, Axin2 deficiency had only minor and no significant effects on the fibrogenic response upon BDL, i.e. slightly reduced hepatic stellate cell activity and collagen mRNA expression. However, livers of Axin2-/- mice shared a stronger cell proliferation both already at baseline as well as immediately after BDL. Conclusion: Our results strongly suggest, contrary to expectation, that a deficiency in Axin2 is not equivalent to an increase in active β-catenin and target genes, indicating no functional relevance of Axin2-dependent regulation of the canonical Wnt/β-catenin pathway in the progression of cholestatic liver injury. This also suggests that the negligible effects of Axin2 deficiency during fibrogenesis may be related to an alternative pathway.
Blood Bag Plasticizers Influence Red Blood Cell Vesiculation Rate without Altering the Lipid Composition of the Vesicles
Authors: Bicalho Beatriz , Serrano Katherine , dos Santos Pereira Alberto , Devine Dana V. , Acker Jason P.
Published: October 2015

Background: Polyvinyl chloride (PVC) plasticized with di(2-ethylhexyl) phthalate (DEHP) is commonly used for blood collection and storage. DEHP has protective effects on RBC membranes, but is also a toxin. Methods: A paired study was conducted to investigate the influence of DEHP and two alternative plasticizers, 1,2-cyclohexane-dicarboxylic acid diisononyl ester (DINCH) and n-butyryl-tri-n-hexyl citrate (BTHC), on the preservation of RBCs stored for 42 days in PVC pediatric bags. The RBC membrane was evaluated for supernatant hemoglobin (Hb), release of extracellular microvesicles (EVs), osmotic fragility, deformability, and lipid composition. Results: In BTHC-plasticized bags, the supernatant Hb increase during storage was 2 times greater than in DINCH- and DEHP-plasticized bags. By day 21, EV concentrations had doubled from day-5 levels in DINCH- and DEHP-, and trebled in BTHC-plasticized bags. RBC mean cell volumes were greater in BTHC- than in DINCH- or DEHP-plasticized bags (p < 0.001). Osmotic fragility differed significantly among plasticizers (p < 0.01). After day 21, RBC deformability decreased in all, but to a greater extent in the bags with BTHC. Phospholipid composition of RBCs and EVs was not different among plasticizers. Conclusion: Membrane stabilization capacity differed among the plasticizers. RBC in BTHC bags stored more poorly, while DEHP and DINCH bags offered better protection against vesiculation, osmotic stress, and Hb loss.
Relationship Between Physician and Hospital Procedure Volume and Mortality After Carotid Artery Stenting Among Medicare Beneficiaries
Authors: Jalbert Jessica J. , Gerhard-Herman Marie D. , Nguyen Louis L. , Jaff Michael R. , Kumamaru Hiraku , Williams Lauren A. , Chen Chih-Ying , Liu Jun , Seeger John D. , Rothman Andrew T. , Schneider Peter , Brott Thomas G. , Tsai Thomas T. , Aronow Herbert D. , Johnston Joseph A. , Setoguchi Soko
Published: October 2015

Background—

Clinical trials demonstrated the efficacy of carotid artery stenting (CAS) relative to carotid endarterectomy when performed by physicians with demonstrated proficiency. It is unclear how CAS performance may be influenced by the diversity in CAS and non-CAS provider volumes in routine clinical practice.

Methods and Results—

We linked Medicare claims to the Centers for Medicare and Medicaid Services’ CAS Database (2005–2009). We assessed the association between 30-day mortality and past-year physician (0, 1–4, 5–9, 10–19, ≥20) and hospital (<10, 10–19, 20–39, ≥40) CAS volumes and past-year hospital coronary and peripheral stenting volumes (<200, 200–399, 400–849, ≥850) among beneficiaries at least 66 years of age. Unadjusted 30-day mortality risk was 1.8% (95% confidence interval [CI], 1.6–2.0) for 19 724 patients undergoing CAS by 2045 physicians in 729 hospitals. Median past-year CAS volume was 9 (interquartile range, 4–19) for physicians and 23 (interquartile range, 12–41) for hospitals. Compared to physicians performing ≥20 CAS in the past year, lower CAS volumes were associated with higher adjusted risks of 30-day morality (P value for trend < 0.05): 1.4 (95% CI, 0.9–2.3) for 0 past-year CAS, 1.3 (95% CI, 0.9–1.8) for 1 to 4, 1.1 (95% CI, 0.8–1.6) for 5 to 9, and 0.9 (95% CI, 0.7–1.4) for 10 to 19. An inverse relationship between 30-day mortality and past-year CAS hospital volume as well as past-year hospital non-CAS volume, past-year hospital non-CAS volume, and 30-day mortality was also noted.

Conclusions—

Among Medicare patients, an inverse relationship exists between physician and hospital CAS volumes and hospital non-CAS stenting volume and 30-day mortality, even after adjusting for all pertinent patient- and hospital-level factors.
Effects of Vegetarian Diets on Blood Lipids: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials
Authors: Wang Fenglei , Zheng Jusheng , Yang Bo , Jiang Jiajing , Fu Yuanqing , Li Duo
Published: October 2015

Background

Vegetarian diets exclude all animal flesh and are being widely adopted by an increasing number of people; however, effects on blood lipid concentrations remain unclear. This meta‐analysis aimed to quantitatively assess the overall effects of vegetarian diets on blood lipids.

Methods and Results

We searched PubMed, Scopus, Embase,
ISI
Web of Knowledge, and the Cochrane Library through March 2015. Studies were included if they described the effectiveness of vegetarian diets on blood lipids (total cholesterol, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, and triglyceride). Weighted mean effect sizes were calculated for net changes by using a random‐effects model. We performed subgroup and univariate meta‐regression analyses to explore sources of heterogeneity. Eleven trials were included in the meta‐analysis. Vegetarian diets significantly lowered blood concentrations of total cholesterol, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, and non–high‐density lipoprotein cholesterol, and the pooled estimated changes were −0.36 mmol/L (95%
CI
−0.55 to −0.17;
P
<0.001), −0.34 mmol/L (95%
CI
−0.57 to −0.11;
P
<0.001), −0.10 mmol/L (95%
CI
−0.14 to −0.06;
P
<0.001), and −0.30 mmol/L (95%
CI
−0.50 to −0.10;
P
=0.04), respectively. Vegetarian diets did not significantly affect blood triglyceride concentrations, with a pooled estimated mean difference of 0.04 mmol/L (95%
CI
−0.05 to 0.13;
P
=0.40).

Conclusions

This systematic review and meta‐analysis provides evidence that vegetarian diets effectively lower blood concentrations of total cholesterol, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, and non–high‐density lipoprotein cholesterol. Such diets could be a useful nonpharmaceutical means of managing dyslipidemia, especially hypercholesterolemia.
WRF-Solar: Description and Clear-Sky Assessment of an Augmented NWP Model for Solar Power Prediction
Authors: Jimenez Pedro A. , Hacker Joshua P. , Dudhia Jimy , Haupt Sue Ellen , Ruiz-Arias Jose A. , Gueymard Chris A. , Thompson Gregory , Eidhammer Trude , Deng Aijun
Published: October 2015

WRF-Solar is a specific configuration and augmentation of the Weather Research and Forecasting (WRF) Model designed for solar energy applications. Recent upgrades to the WRF Model contribute to making the model appropriate for solar power forecasting and comprise 1) developments to diagnose internally relevant atmospheric parameters required by the solar industry, 2) improved representation of aerosol–radiation feedback, 3) incorporation of cloud–aerosol interactions, and 4) improved cloud–radiation feedback. The WRF-Solar developments are presented together with a comprehensive characterization of the model performance for forecasting during clear skies. Performance is evaluated with numerical experiments using a range of different external and internal treatment of the atmospheric aerosols, including both a model-derived climatology of aerosol optical depth and temporally evolving aerosol optical properties from reanalysis products. The necessity of incorporating the influence of atmospheric aerosols to obtain accurate estimations of the surface shortwave irradiance components in clear-sky conditions is evident. Improvements of up to 58%, 76%, and 83% are found in global horizontal irradiance, direct normal irradiance, and diffuse irradiance, respectively, compared to a standard version of the WRF Model. Results demonstrate that the WRF-Solar model is an improved numerical tool for research and applications in support of solar energy.