bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered Tnnt3 characterizes selective weakness of fast fibers in mice overexpressing FSHD region gene 1 (FRG1)
Authors: Sancisi Valentina , Germinario Elena , Esposito Alessandra , Morini Elisabetta , Peron Samantha , Moggio Maurizio , Tomelleri Giuliano , Danieli-Betto Daniela , Tupler Rossella
Published: December 2013

Facioscapulohumeral muscular dystrophy (FSHD), a common hereditary myopathy, is characterized by atrophy and weakness of selective muscle groups. FSHD is considered an autosomal dominant disease with incomplete penetrance and unpredictable variability of clinical expression within families. Mice overexpressing FRG1 (FSHD region gene 1), a candidate gene for this disease, develop a progressive myopathy with features of the human disorder. Here, we show that in FRG1-overexpressing mice, fast muscles, which are the most affected by the dystrophic process, display anomalous fast skeletal troponin T (fTnT) isoform, resulting from the aberrant splicing of the Tnnt3 mRNA that precedes the appearance of dystrophic signs. We determine that muscles of FRG1 mice develop less strength due to impaired contractile properties of fast-twitch fibers associated with an anomalous MyHC-actin ratio and a reduced sensitivity to Ca2+. We demonstrate that the decrease of Ca2+ sensitivity of fast-twitch fibers depends on the anomalous troponin complex and can be rescued by the substitution with the wild-type proteins. Finally, we find that the presence of aberrant splicing isoforms of TNNT3 characterizes dystrophic muscles in FSHD patients. Collectively, our results suggest that anomalous TNNT3 profile correlates with the muscle impairment in both humans and mice. On the basis of these results, we propose that aberrant fTnT represents a biological marker of muscle phenotype severity and disease progression.
Active Joint Mechanism Driven by Multiple Actuators Made of Flexible Bags: A Proposal of Dual Structural Actuator
Authors: Kimura Hitoshi , Matsuzaki Takuya , Kataoka Mokutaro , Inou Norio
Published: December 2013

An actuator is required to change its speed and
force depending on the situation. Using multiple actuators for
one driving axis is one of the possible solutions; however, there
is an associated problem of output power matching. This study
proposes a new active joint mechanism using multiple actuators.
Because the actuator is made of a flexible bag, it does not
interfere with other actuators when it is depressurized. The proposed
joint achieved coordinated motion of multiple actuators. This
report also discusses a new actuator which has dual cylindrical
structure. The cylinders are composed of flexible bags with
different diameters. The joint torque is estimated based on the
following factors: empirical formula for the flexible actuator
torque, geometric relationship between the joint and the actuator,
and the principle of virtual work. The prototype joint mechanism
achieves coordinated motion of multiple actuators for one axis.
With this motion, small inner actuator contributes high speed
motion, whereas large outer actuator generates high torque. The
performance of the prototype joint is examined by speed and
torque measurements. The joint showed about 30% efficiency
at 2.0 Nm load torque under 0.15 MPa air input.
Qualitative Behaviour of Elastic-Plastic Solutions for a Class of Damage Mechanics Models Near Bimaterial Interfaces: A Simple Analytical Example
Authors: Alexandrov Sergei , Mustafa Yusof
Published: December 2013

The paper presents an exact analytic solution for a class of elastic-plastic models with damage evolution. The boundary value problem consists of a planar deformation comprising the simultaneous shearing and expansion of a hollow cylindrical specimen of material and involves a bimaterial interface at which the materials stick to each other. With no loss of generality for understanding the qualitative behaviour of the solution near the bimaterial interface, an extreme case when the hard material is rigid is considered. The solution is reduced to a transcendental equation for the value of the equivalent plastic strain at the bimaterial interface. This equation predicts that the equivalent plastic strain attains a maximum under certain conditions. The existence of the solution of the boundary value problem depends on the value of the damage parameter at fracture, which is a material constant. In particular, if this value is larger than the value of the damage parameter at the bimaterial interface corresponding to the maximum possible value of the equivalent strain at this interface, then no solution exists. Experimental data available in the literature are used to assess whether Lemaitre’s model is applicable.
Efficiency Analysis and Comparison of Different Radon Progeny Measurement Methods
Authors: Kadir Abdumomin , Zhang Lei , Guo Qiuju , Liang Juncheng
Published: December 2013

Radon exposure to the public contributes more than half of all the radiation doses caused by natural radiation; accurate measurement of radon progeny is quite essential for the dose evaluation of radon exposure in environment. For the purpose of establishing a radon progeny standard and controlling measurement quality of commercial devices, it is quite important to analyze the efficiency of different measurement methods and determine which would be the most appropriate for radon progeny measurements. Through theoretical analysis and experimental measurement, some commonly used measurement methods were compared in this study and the development trends of those methods were reviewed. Results show that for radon progeny measurement, the spectroscopic analysis method is better than the gross count method, while least‐square calculation methods is better than traditional three‐count or five‐count method. Multiperiod counting of α plus β spectrum as well as using weighted least‐square calculation method might be the best choice for accurate measurement on radon progeny in standard radon chamber when calibrating commercial radon progeny monitors.
A Note on the Tail Behavior of Randomly Weighted Sums with Convolution-Equivalently Distributed Random Variables
Authors: Yang Yang , Liu Jun-feng , Zhang Yu-lin
Published: December 2013

We investigate the tailed asymptotic behavior of the randomly weighted sums with increments with convolution-equivalent distributions. Our obtained result can be directly applied to a discrete-time insurance risk model with insurance and financial risks and derive the asymptotics for the finite-time probability of the above risk model.
Dynamic Properties of the Solow Model with Increasing or Decreasing Population and Time-to-Build Technology
Authors: Guerrini Luca , Sodini Mauro
Published: December 2013

We introduce a time-to-build technology in a Solow model with nonconstant population. Our analysis shows that the population dynamics may be a source of stability switches and Hopf bifurcations. The analytical results are obtained using the recent technique introduced by Beretta and Kuang (2002) in the studying of delayed differential equations with delay-dependent coefficients in characteristic equation. Numerical simulations are performed in order to illustrate the main dynamic features of the model.
Development of Degree-of-Priority Based Control Strategy for Emergency Vehicle Preemption Operation
Authors: Wang Jiawen , Ma Wanjing , Yang Xiaoguang
Published: December 2013

This paper proposes a degree-of-priority based control strategy for emergency vehicle preemption operation to decrease the impacts of emergency vehicles on normal traffic. The proposed model features its effectiveness to the following three aspects: (1) a multilayer fuzzy model was established to determine the degree-of-priority based on emergency vehicle preemption demand intensity and preemption influence intensity; (2) for emergency vehicles with proper classification, a travel time estimation model for emergency traffic was formulated, an optimal emergency route determines model based on the level of priority of emergency events, and the emergency vehicle travel time was developed to minimize evacuation time as well as minimize the adverse impacts of preemption on normal traffic; and (3) a conditional traffic signals priority control method at each intersection of the evacuation route was built, so that traffic queue at each intersection can be cleared before the arrival of emergency vehicles. A simulation model based on field data was developed, and the performance of the proposed strategy was compared with the conventional local detection based method under the microscopic simulation model. The results validated the efficiency of the proposed strategy in terms of minimizing the delay of emergency vehicles and reducing adverse impacts on normal traffic.
Uncertainty Analysis of Multiple Hydrologic Models Using the Bayesian Model Averaging Method
Authors: Dong Leihua , Xiong Lihua , Yu Kun-xia
Published: December 2013

Since Bayesian Model Averaging (BMA) method can combine the forecasts of different models together to generate a new one which is expected to be better than any individual model’s forecast, it has been widely used in hydrology for ensemble hydrologic prediction. Previous studies of the BMA mostly focused on the comparison of the BMA mean prediction with each individual model’s prediction. As BMA has the ability to provide a statistical distribution of the quantity to be forecasted, the research focus in this study is shifted onto the comparison of the prediction uncertainty interval generated by BMA with that of each individual model under two different BMA combination schemes. In the first BMA scheme, three models under the same Nash-Sutcliffe efficiency objective function are, respectively, calibrated, thus providing three-member predictions ensemble for the BMA combination. In the second BMA scheme, all three models are, respectively, calibrated under three different objective functions other than Nash-Sutcliffe efficiency to obtain nine-member predictions ensemble. Finally, the model efficiency and the uncertainty intervals of each individual model and two BMA combination schemes are assessed and compared.
Conformation and Catalytic Properties Studies of Candida rugosa Lip7 via Enantioselective Esterification of Ibuprofen in Organic Solvents and Ionic Liquids
Authors: Li Xiang , Huang Shuangshuang , Xu Li , Yan Yunjun
Published: December 2013

Enantioselective esterification of ibuprofen was conducted to evaluate the enzyme activity and ees of lipase from Candida rugosa (CRL7) in ten conventional organic solvents and three ionic liquids. Different alcohols were tested for selecting the most suitable acyl acceptor due to the fact that the structure of alcohols (branch and length of carbon chains; location of –OH functional group) could affect the enzyme activity and ees. The results of alcohol and solvent selection revealed that 1‐isooctanol and isooctane were the best substrate and reaction medium, respectively, because of the highest enzyme activity and ees. Compared with the control, conformational studies via FT‐IR indicate that the variations of CRL7’s secondary structure elements are probably responsible for the differences of enzyme activity and ees in the organic solvents and ionic liquids. Moreover, the effects of reaction parameters, such as molar ratio, water content, temperature, and reaction time, in the selected reaction medium, were also examined.
Strain Mapping and Nanocrystallite Size Determination by Neutron Diffraction in an Aluminum Alloy (AA5083) Severely Plastically Deformed through Equal Channel Angular Pressing
Authors: González Crespo P. A. , Luis Pérez C. , Hughes Darren J. , Turrillas X.
Published: December 2013

Six specimens of an aluminum alloy (AA‐5083) extruded by Equal Channel Angular Pressing following two different routes plus a blank sample were examined with a neutron radiation of 1.5448 Å. Macrostrain maps from the (311) reflection were obtained. A clear difference about accumulated macrostrain with the extrusion cycles between the two routes is shown. The diffraction data of annealed specimens did permit to estimate crystallite sizes that range between 89 nm and 115 nm depending on the routes.
Robustl2-l∞Filtering for Discrete-Time Delay Systems
Authors: Yang Chengming , Yu Zhandong , Wang Pinchao , Yu Zhen , Karimi Hamid Reza , Feng Zhiguang
Published: December 2013

The problem of robustl2-l∞filtering for discrete-time system with interval time-varying delay and uncertainty is investigated, where the time delay and uncertainty considered are varying in a given interval and norm-bounded, respectively. The filtering problem based on thel2-l∞performance is to design a filter such that the filtering error system is asymptotically stable with minimizing the peak value of the estimation error for all possible bounded energy disturbances. Firstly, sufficientl2-l∞performance analysis condition is established in terms of linear matrix inequalities (LMIs) for discrete-time delay systems by utilizing reciprocally convex approach. Then a less conservative result is obtained by introducing some variables to decouple the Lyapunov matrices and the filtering error system matrices. Moreover, the robustl2-l∞filter is designed for systems with time-varying delay and uncertainty. Finally, a numerical example is given to demonstrate the effectiveness of the filter design method.
High Intestinal and Systemic Levels of Interleukin-23/T-Helper 17 Pathway in Chinese Patients with Inflammatory Bowel Disease
Authors: Song Lu , Zhou Rui , Huang Sha , Zhou Feng , Xu Shufang , Wang Wei , Yi Fengming , Wang Xiaobing , Xia Bing
Published: December 2013

Interleukin-23/T-helper 17 (IL-23/Th17) pathway plays a key role in the pathogenesis of inflammatory bowel disease (IBD), but little is known about its expression in Chinese population. In this study, we investigated the mRNA and protein levels of IL-12p40, tumor necrosis factor-like cytokine 1A (TL1A), Janus kinase 2 (JAK2), and IL-23R both locally and systemically in Chinese IBD patients. Our results indicated that the mRNA levels of IL-12p40 and TL1A were increased in ulcerative colitis (UC) patients. Furthermore, serum IL-12p40 and TL1A levels were higher in active UC patients, especially in patients with disease course less than 1.25 years or initial onset. No correlation was found between the genotype and serum levels of IL-12p40 or TL1A in UC patients. Additionally, the mRNA and protein expression of JAK2 and IL-23R were increased in UC and Crohn’s disease (CD) patients. Taken together, our results provided evidence that IL-23/Th17 pathway genes may represent important biomarkers of active stage of IBD and serve as novel therapeutic targets for IBD in Chinese population.
Multiple Beam Selection for Combing M2M Communication Networks and Cellular Networks with Limited Feedback
Authors: Zhang Xiaoning , Bai Lin , Guan Wenyang
Published: December 2013

We study the scenario in which a large number of machine-type communication devices (MTCDs) communicate with each other by utilizing the help of the base station (BS) through some MTCD gateways. We consider an overlay mode of an orthogonal frequency division multiple access (OFDMA) based cellular system using orthogonal beamforming to provide broadband wireless access for the MTCD gateways. In order to avoid the interference with mobile users, the beamforming vectors to the MTCD gateways have to be orthogonal to the channel vectors of mobile users, which become a beamforming constraint for the MTCD gateways. However, with limited feedback of channel state information (CSI) at a BS, the orthogonal beamforming constraints may not be achieved. In such a practical case, conventional feedback schemes are feasible but not efficient due to the orthogonality constraints. In this paper, we propose a novel multiple beam selection (MBS) approach with limited feedback for MTCD gateways by taking into account the previous orthogonality constraints. Simulation results show that the performance improvement of the proposed approach over the conventional ones is generally about 10% when a BS is equipped with an array of 6 elements.
A Sarsa(λ) Algorithm Based on Double-Layer Fuzzy Reasoning
Authors: Liu Quan , Mu Xiang , Huang Wei , Fu Qiming , Zhang Yonggang
Published: December 2013

Solving reinforcement learning problems in continuous space with function approximation is currently a research hotspot of machine learning. When dealing with the continuous space problems, the classicQ-iteration algorithms based on lookup table or function approximation converge slowly and are difficult to derive a continuous policy. To overcome the above weaknesses, we propose an algorithm named DFR-Sarsa(λ) based on double-layer fuzzy reasoning and prove its convergence. In this algorithm, the first reasoning layer uses fuzzy sets of state to compute continuous actions; the second reasoning layer uses fuzzy sets of action to compute the components ofQ-value. Then, these two fuzzy layers are combined to compute theQ-value function of continuous action space. Besides, this algorithm utilizes the membership degrees of activation rules in the two fuzzy reasoning layers to update the eligibility traces. Applying DFR-Sarsa(λ) to the Mountain Car and Cart-pole Balancing problems, experimental results show that the algorithm not only can be used to get a continuous action policy, but also has a better convergence performance.
Scenario Analyses of Land Use Conversion in the North China Plain: An Econometric Approach
Authors: Zhan Jinyan , Wu Feng , Shi Chenchen , Zhang Fan , Li Zhihui
Published: December 2013

Scenario analysis and dynamic prediction of land use structure which involve many driving factors are helpful to investigate the mechanism of land use changes and even to optimize land use allocation for sustainable development. In this study, land use structure changes during 1988–2010 in North China Plain were discerned and the effects of various natural and socioeconomic driving factors on land use structure changes were quantitatively analyzed based on an econometric model. The key drivers of land use structure changes in the model are county-level net returns of land resource. In this research, we modified the net returns of each land use type for three scenarios, including business as usual (BAU) scenario, rapid economic growth (REG) scenario, and coordinated environmental sustainability (CES) scenario. The simulation results showed that, under different scenarios, future land use structures were different due to the competition among various land use types. The land use structure changes in North China Plain in the 40-year future will experience a transfer from cultivated land to built-up area, an increase of forestry, and decrease of grassland. The research will provide some significant references for land use management and planning in the study area.
The Elicitation Effect of Pathogenic Fungi on Trichodermin Production by Trichoderma brevicompactum
Authors: Shentu Xu-Ping , Liu Wei-Ping , Zhan Xiao-Huan , Yu Xiao-Ping , Zhang Chuan-Xi
Published: December 2013

The effects of six species of phytopathogenic fungi mycelia as elicitors on trichodermin yield by Trichoderma brevicompactum were investigated. Neither nonviable nor viable mycelia of Botrytis cinerea, Alternaria solani, Colletotrichum lindemuthianum, and Thanatephorus cucumeris demonstrated any elicitation on the accumulation of trichodermin. However, the production of trichodermin was increased by the presence of viable/nonviable Rhizoctonia solani and Fusarium oxysporum mycelia. The strongest elicitation effect was found at the presence of nonviable R. solani. At the presence of nonviable R. solani, the maximum yield of trichodermin (144.55 mg/L) was significantly higher than the Control (67.8 mg/L), and the cultivation time to obtain the maximum yield of trichodermin decreased from 72 h to 60 h. No difference of trichodermin accumulation was observed by changing the concentration of nonviable R. solani from 0.1 to 1.6 g/L. It was observed that the optimum time for adding nonviable R. solani is immediately after inoculation. The diameter of T. brevicompactum mycelial globule after 72 h cultivation with nonviable R. solani elicitor was smaller than that of the Control.
The Game Analysis of Manufacturers’ Political Connections on Product Safety in Supply Chain: Evidence from China
Authors: Na Zhao , Fusheng Wang
Published: December 2013

This paper studied the political connections on product safety in supply chain. In market economy, information asymmetry exists throughout the entirety of supply chains that ought to ensure product safety. Due to the existence of game relations between the government and manufacturers in the aspects of product safety and regulation, the formation of market equilibrium depends on political connections between the government and manufacturers. Based on study and analyses of a static game model and a dynamic game model, this paper reveals that governments and manufacturers must use positive political connections to achieve product protection and supervision of safety throughout the supply chain. On the other hand, negative political connections lead to losses of both governmental credibility and social profits. This study indicates that inherent mechanism of political connections exists in the supply chain; it will help to enrich the theory of supply chain.
Utility of Two PANSS 5-Factor Models for Assessing Psychosocial Outcomes in Clinical Programs for Persons with Schizophrenia
Authors: Jerrell Jeanette M. , Hrisko Stephanie
Published: December 2013

Using symptom factors derived from two models of the Positive and Negative Syndrome Scale (PANSS) as covariates, change over time in consumer psychosocial functioning, medication adherence/compliance, and treatment satisfaction outcomes are compared based on a randomized, controlled trial assessing the effectiveness of antipsychotic medications for 108 individuals diagnosed with schizophrenia. Random effects regression analysis was used to determine the relative performance of these two 5-factor models as covariates in estimating change over time and the goodness of fit of the regression equations for each outcome. Self-reported psychosocial functioning was significantly associated with the relief of positive and negative syndromes, whereas patient satisfaction was more closely and significantly associated with control of excited/activation symptoms. Interviewer-rated psychosocial functioning was significantly associated with relief of positive and negative symptoms, as well as excited/activation and disoriented/autistic preoccupation symptoms. The VDG 5-factor model of the PANSS represents the best “goodness of fit” model for assessing symptom-related change associated with improved psychosocial outcomes and functional recovery. Five-factor models of the syndromes of schizophrenia, as assessed using the PANSS, are differentially valuable in determining the predictors of psychosocial and satisfaction changes over time, but not of improved medication adherence/compliance.
Photonic Processing for Wideband Cancellation and Spectral Discrimination of RF Signals
Authors: Benton David M.
Published: December 2013

Photonic signal processing is used to implement common mode signal cancellation across a very wide bandwidth utilising phase modulation of radio frequency (RF) signals onto a narrow linewidth laser carrier. RF spectra were observed using narrow-band, tunable optical filtering using a scanning Fabry Perot etalon. Thus functions conventionally performed using digital signal processing techniques in the electronic domain have been replaced by analog techniques in the photonic domain. This technique was able to observe simultaneous cancellation of signals across a bandwidth of 1400 MHz, limited only by the free spectral range of the etalon.
Corrosion Response of Ti6Al4V and Ti15Mo Dental Implant Alloys in the Presence of Listerine Oral Rinse
Authors: Bhola Rahul , Chandra Charu , Alabbas Faisal M. , Kundu Sukumar , Mishra Brajendra , Olson David L.
Published: December 2013

The influence of a commonly used antibacterial mouth rinse, Listerine, on the corrosion behavior of one of the commonly used titanium alloys Ti6Al4V (two-phase structure, i.e.,αandβ) and a newer Ti15Mo (singleβphase) in normal saline solution has been investigated using electrochemical techniques. Interfacial electrochemical changes occurring at the oxide-solution interface have been analysed using EIS circuit modeling. Listerine acts as a corrosion inhibitor for Ti15Mo alloy and a corrosion promoter for Ti6Al4V alloy.
Model Organisms and Traditional Chinese Medicine Syndrome Models
Authors: Ling Shuang , Xu Jin-Wen
Published: December 2013

Traditional Chinese medicine (TCM) is an ancient medical system with a unique cultural background. Nowadays, more and more Western countries due to its therapeutic efficacy are accepting it. However, safety and clear pharmacological action mechanisms of TCM are still uncertain. Due to the potential application of TCM in healthcare, it is necessary to construct a scientific evaluation system with TCM characteristics and benchmark the difference from the standard of Western medicine. Model organisms have played an important role in the understanding of basic biological processes. It is easier to be studied in certain research aspects and to obtain the information of other species. Despite the controversy over suitable syndrome animal model under TCM theoretical guide, it is unquestionable that many model organisms should be used in the studies of TCM modernization, which will bring modern scientific standards into mysterious ancient Chinese medicine. In this review, we aim to summarize the utilization of model organisms in the construction of TCM syndrome model and highlight the relevance of modern medicine with TCM syndrome animal model. It will serve as the foundation for further research of model organisms and for its application in TCM syndrome model.
A Two-Sided Market Model of Optimal Price Structure for Instant Messenger
Authors: Xu Jun
Published: December 2013

Instant messenger (IM) is one of the most popular Internet applications all over the world. This paper examines the pricing problem of IM based on two-sided market model. IM serves as a two-sided platform, which gets both Internet users and advertisers on board. This paper concludes that IM operator adopts a heavily skewed price structure that favors IM users both under monopolistic case and under horizontal differentiated duopolistic case. When advertising revenue is large enough relatively to marginal cost for serving IM users, IM users can enjoy free service provided by IM operators. The competitive equilibrium of duopolistic case is not necessarily symmetric when advertisers choose singlehoming. Even in the symmetric equilibrium platform would rather deter all advertisers.
Preparation and Biological Properties of Platinum(II) Complex‐Loaded Copolymer PLA‐TPGS
Authors: Phuong Thu Ha , Thi Hong Tuyet Phan , Thi Thu Trang Mai , Hoai Nam Nguyen , Thi Nhu Hieu Truong , Quang Duong Le , Thi Nhu Hang Tran , Ha Tran Thi Hong , Nghi Do Huu , Huu Cuong Le , Huong Le Mai
Published: December 2013

A new nanodrug system containing bis(menthone thiosemicarbazonato) Platinum(II) complex (Pt‐thiomen) encapsulated with the block copolymers polylactide‐d‐α‐tocopheryl polyethylene glycol 1000 succinate (PLA‐TPGS) was prepared by a modified solvent extraction/evaporation technique. The characteristics of the nanoparticles including surface morphology, size distribution, structure, and biological activities such as antimicrobial and cytotoxic activities were in vitro investigated. The spherical nanoparticles were around 50 nm in size with core‐shell structure and narrow‐size distribution. The encapsulated Pt‐thiomen can avoid interaction with proteins in the blood plasma. The inhibitory activity of Pt‐thiomen‐loaded PLA‐TPGS nanoparticles on the growth of some bacteria, fungi, and Hep‐G2 cells suggests a possibility of developing PLA‐TPGS‐Pt‐thiomen nanoparticles as one of the potential chemotherapeutic agents.
Performance of Dual-Axis Solar Tracker versus Static Solar System by Segmented Clearness Index in Malaysia
Authors: Lee Jhee Fhong , Rahim Nasrudin Abd. , Al-Turki Yusuf A.
Published: December 2013

The performance of Dual-Axis Solar Tracker (DAST) and Static Solar System (SSS) with respect to clearness index in Malaysia is presented. An attempt to investigate the correlation between clearness index with energy gain and efficiency of DAST over SSS is being done experimentally. A good correlation could not be found out from the daily clearness index. It is due to the more profound advantage of DAST in the morning and evening compared to midday as it is able to follow the sun’s position. Hence, the daily clearness index is divided into three segments which are morning, midday, and evening to interpret the energy gain and efficiency better. A clearer correlation with low standard deviation can be observed on the segmented clearness index analysis. The energy gain and efficiency of seven cities in Malaysia is being estimated with the segmented clearness index and compared to the result generated from anisotropic radiation model. A similar trend is obtained and it has shown that the segmented clearness index could be utilized as a graphical method for estimation of energy gain and efficiency of DAST over SSS.
Effect of Korean Herbal Medicine Combined with a Probiotic Mixture on Diarrhea-Dominant Irritable Bowel Syndrome: A Double-Blind, Randomized, Placebo-Controlled Trial
Authors: Ko Seok-Jae , Han Gajin , Kim Seul-Ki , Seo Jae-Gu , Chung Won-Seok , Ryu Bongha , Kim Jinsung , Yeo Inkwon , Lee Beom-Joon , Lee Jin-Moo , Park Jae-Woo
Published: December 2013

Introduction. Although combination therapy with herbal medicine and probiotics is gaining popularity for controlling diarrhea-dominant irritable bowel syndrome (D-IBS) symptoms, few studies have investigated its clinical effects.Materials and Methods. Fifty-three patients with D-IBS were randomly allocated into 1 of the following 4 groups: herbal medicine (Gwakhyangjeonggisan; GJS) plus probiotics (Duolac7S; DUO), GJS plus placebo DUO, placebo GJS plus DUO, and placebo GJS plus placebo DUO. The study period consisted of a 2-week run-in, 8 weeks of administration, and 2 weeks of follow-up. The primary outcomes were weekly adequate relief (AR) of overall IBS symptoms and the proportion of responders (PR) during the administration period. The secondary outcomes included individual IBS symptoms, stool assessment, and quality of life. Changes of intestinal microbiota and intestinal permeability were also analyzed.Results and Discussion. Weekly AR was not different among the 4 groups throughout the treatment period. However, the 3 treatment groups exhibited significant improvements in PR compared to the findings in the placebo group. In the intestinal microbiota assessment, herbal medicine and probiotics synergistically increased beneficial bacteria counts.Conclusion. Combination therapy with herbal medicine and probiotics appears to relieve overall IBS symptoms by synergistically increasing beneficial intestinal microbe counts.
Design and Implementation of an Application for Deploying Vehicular Networks with Smartphones
Authors: Caballero-Gil P. , Caballero-Gil C. , Molina-Gil J.
Published: December 2013

A vehicular ad hoc network (VANET) is a wireless network that provides communications between nearby vehicles. Among the different types of information that can be made available to vehicles through VANETs, road traffic information is the most important one. This work is part of an experimental development of a wireless communication platform oriented to applications that allow improving road efficiency and safety, managing and monitoring road traffic, encouraging cooperative driving, and offering pedestrian services and other added-value uses. The proposed system consists of smartphones, sensors, and Wi-Fi hotspots 2.0, as well as complementary functionalities including access to network infrastructure via 3G, GPRS, and 4G. The developed wireless network prototype allows taking advantage of the potential benefits of VANETs. At the same time, the use of smartphones does not require large money investments either in public or restricted areas. The first implementations with smartphones have been useful to test the behaviour of the proposal in a real environment. We have also implemented a large-scale simulation by using NS-2 simulator. From the obtained data, we have estimated the minimum requirements necessary for the correct working of a VANET and the problems that can happen in case of possible attacks or communication overhead.
Amelioration of Prallethrin-Induced Oxidative Stress and Hepatotoxicity in Rat by the Administration ofOriganum majoranaEssential Oil
Authors: Mossa Abdel-Tawab H. , Refaie Amel A. , Ramadan Amal , Bouajila Jalloul
Published: December 2013

This study was carried out to evaluate the adverse effects of exposure to prallethrin on oxidant/antioxidant status and liver dysfunction biomarkers and the protective role ofOriganum majoranaessential oil (EO) in rat. Male rats were divided into 4 groups: (i) received only olive oil (ii) treated with 64.0 mg/kg body weight prallethrin (1/10 LD50) in olive oil via oral route daily for 28 days, (iii) treated with 64.0 mg/kg body weight prallethrin (1/10 LD50) and EO (160 μL/kg b.wt.) in olive oil and (iv) received EO (160 μL/kg b.wt.) in olive oil via oral route twice daily for 28 days. Prallethrin treatment caused decrease in body weight gain and increase in relative liver weight. There was a significant increase in the activity of serum marker enzymes, aspartate transaminase, alanine transaminase, and alkaline phosphatase. It caused increase in thiobarbituric acid reactive substances and reduction in the activities of superoxide dismutase, catalase, and glutathione-S-transferase in liver. Consistent histological changes were found in the liver of prallethrin treatment. EO showed significant protection with the depletion of serum marker enzymes and replenishment of antioxidant status and brought all the values to near normal, indicating the protective effect of EO. We can conclude that prallethrin caused oxidative damage and liver injury in male rat and co-administration of EO attenuated the toxic effect of prallethrin. These results demonstrate that administration of EO may be useful, easy, and economical to protect human against pyrethroids toxic effects.
Molybdate Reduction to Molybdenum Blue by an Antarctic Bacterium
Authors: Ahmad S. A. , Shukor M. Y. , Shamaan N. A. , Mac Cormack W. P. , Syed M. A.
Published: December 2013

A molybdenum-reducing bacterium from Antarctica has been isolated. The bacterium converts sodium molybdate or Mo6+to molybdenum blue (Mo-blue). Electron donors such as glucose, sucrose, fructose, and lactose supported molybdate reduction. Ammonium sulphate was the best nitrogen source for molybdate reduction. Optimal conditions for molybdate reduction were between 30 and 50 mM molybdate, between 15 and 20°C, and initial pH between 6.5 and 7.5. The Mo-blue produced had a unique absorption spectrum with a peak maximum at 865 nm and a shoulder at 710 nm. Respiratory inhibitors such as antimycin A, sodium azide, potassium cyanide, and rotenone failed to inhibit the reducing activity. The Mo-reducing enzyme was partially purified using ion exchange and gel filtration chromatography. The partially purified enzyme showed optimal pH and temperature for activity at 6.0 and 20°C, respectively. Metal ions such as cadmium, chromium, copper, silver, lead, and mercury caused more than 95% inhibition of the molybdenum-reducing activity at 0.1 mM. The isolate was tentatively identified asPseudomonassp. strain DRY1 based on partial 16s rDNA molecular phylogenetic assessment and the Biolog microbial identification system. The characteristics of this strain would make it very useful in bioremediation works in the polar and temperate countries.
Factor of Safety Reduction Factors for Accounting for Progressive Failure for Earthen Levees with Underlying Thin Layers of Sensitive Soils
Authors: Lobbestael Adam J. , Athanasopoulos-Zekkos Adda , Colley Josh
Published: December 2013

The effects of progressive failure on flood embankments with underlying thin layers of soft, sensitive soils are investigated. Finite element analysis allows for investigation of strain-softening effects and progressive failure in soft and sensitive soils. However, limit equilibrium methods for slope stability analysis, widely used in industry, cannot capture these effects and may result in unconservative factors of safety. A parametric analysis was conducted to investigate the effect of thin layers of soft sensitive soils on the stability of flood embankments. A flood embankment was modeled using both the limit equilibrium method and the finite element method. The foundation profile was altered to determine the extent to which varying soft and sensitive soils affected the stability of the embankment, with respect to progressive failure. The results from the two methods were compared to determine reduction factors that can be applied towards factors of safety computed using limit equilibrium methods, in order to capture progressive failure.
Simultaneous Determination of Reserpine, Rescinnamine, and Yohimbine in Human Plasma by Ultraperformance Liquid Chromatography Tandem Mass Spectrometry
Authors: Iqbal Muzaffar , Alam Aftab , Wani Tanveer A. , Khalil Nasr Y.
Published: December 2013

A sensitive and selective UPLC-MS/MS method was developed and validated for the determination of three indolic alkaloids (reserpine, rescinnamine, and yohimbine) in human plasma using papaverine as internal standard (IS). After a one step protein precipitation with acetonitrile, separation was carried out using C18 column (50 × 2.1 mm, i.d. 1.7 μm) and mobile phase consisting of acetonitrile : water : formic acid (60 : 40 : 0.1%, v/v/v) pumped at a flow rate of 0.2 mL/min. The mass spectrometric determination was carried out using an electrospray interface operated in the positive mode with multiple reaction monitoring (MRM) mode. The precursor to product ion transitions ofm/z609.32 > 195.01,m/z635.34 > 221.03,m/z355.19 > 144, andm/z340.15 > 202.02 were selected for the quantification of reserpine, rescinnamine, yohimbine, and IS, respectively. The analytical response was found to be linear in the range of 0.36–400, 0.27–300, and 0.23–250 ng/mL with lower limit of quantification of 0.36, 0.27, and 0.23 ng/mL for reserpine, rescinnamine, and yohimbine, respectively. Validation was made following official guidelines. The proposed method enabled reproducible results and hence could be reliable for pharmacokinetic and toxicological analysis.
Metabolic Effects of Mulberry Leaves: Exploring Potential Benefits in Type 2 Diabetes and Hyperuricemia
Authors: Hunyadi A. , Liktor-Busa E. , Márki Á. , Martins A. , Jedlinszki N. , Hsieh T. J. , Báthori M. , Hohmann J. , Zupkó I.
Published: December 2013

The leaves ofMorus albaL. have a long history in Traditional Chinese Medicine and also became valued by the ethnopharmacology of many other cultures. The worldwide known antidiabetic use of the drug has been suggested to arise from a complex combination effect of various constituents. Moreover, the drug is also a potential antihyperuricemic agent. Considering that type 2 diabetes and hyperuricemia are vice-versa in each other’s important risk factors, the use of mulberry originated phytotherapeutics might provide an excellent option for the prevention and/or treatment of both conditions. Here we report a series of relevantin vitroandin vivostudies on the bioactivity of an extract of mulberry leaves and its fractions obtained by a stepwise gradient on silica gel.In vivoantihyperglycemic and antihyperuricemic activity, plasma antioxidant status, as well asin vitroglucose consumption by adipocytes in the presence or absence of insulin, xanthine oxidase inhibition, free radical scavenging activity, and inhibition of lipid peroxidation were tested. Known bioactive constituents ofM. alba(chlorogenic acid, rutin, isoquercitrin, and loliolide) were identified and quantified from the HPLC-DAD fingerprint chromatograms. Iminosugar contents were investigated by MS/MS, 1-deoxynojirimycin was quantified, and amounts of 2-O-alpha-D-galactopyranosyl-1-deoxynojirimicin and fagomine were additionally estimated.
Dramatic Antitumor Effects of the Dual MET/RON Small-Molecule Inhibitor LY2801653 in Non–Small Cell Lung Cancer
Authors: Kawada Ichiro , Hasina Rifat , Arif Qudsia , Mueller Jeffrey , Smithberger Erin , Husain Aliya N. , Vokes Everett E. , Salgia Ravi
Published: December 2013

Lung cancer is a heterogeneous disease encompassing a wide array of genetic abnormalities. The MET receptor tyrosine kinase is altered in many lung cancers, especially non–small cell lung cancer (NSCLC), and clinical trials of MET inhibitors that are under way are documenting cases of acquired resistance. On the basis of the evidence that the RON tyrosine kinase receptor can also be overexpressed in NSCLC, we evaluated the potent MET/RON dual kinase inhibitor LY2801653 in this setting. LY2801653 was more efficacious than the MET/ALK/RON/ROS inhibitor crizotinib with a distinct pattern of downstream signaling effects. Using the PamGene platform, we found that inhibition of MET and RON was associated with decreased phosphorylation of CBL, PI3K, and STAT3. In classic and orthotopic mouse xenograft models of lung cancer, LY2801653 decreased tumor growth, dramatically inhibiting mitotic events and angiogenesis. Taken together, our results argued that specific targeting of the MET/RON kinases could provide robust inhibition of cell proliferation and tumor outgrowth in multiple in vitro and in vivo models of NSCLC. These findings offer a robust preclinical proof of concept for MET/RON targeting by LY2801653 as a promising small-molecule modality to treat NSCLC. Cancer Res; 74(3); 884–95. ©2013 AACR.
MDR1 Synonymous Polymorphisms Alter Transporter Specificity and Protein Stability in a Stable Epithelial Monolayer
Authors: Fung King Leung , Pan James , Ohnuma Shinobu , Lund Paul E. , Pixley Jessica N. , Kimchi-Sarfaty Chava , Ambudkar Suresh V. , Gottesman Michael M.
Published: December 2013

The drug efflux function of P-glycoprotein (P-gp) encoded by MDR1 can be influenced by genetic polymorphisms, including two synonymous changes in the coding region of MDR1. Here we report that the conformation of P-gp and its drug efflux activity can be altered by synonymous polymorphisms in stable epithelial monolayers expressing P-gp. Several cell lines with similar MDR1 DNA copy number were developed and termed LLC-MDR1-WT (expresses wild-type P-gp), LLC-MDR1-3H (expresses common haplotype P-gp), and LLC-MDR1-3HA (a mutant that carries a different valine codon in position 3435). These cell lines express similar levels of recombinant mRNA and protein. P-gp in each case is localized on the apical surface of polarized cells. However, the haplotype and its mutant P-gps fold differently from the wild-type, as determined by UIC2 antibody shift assays and limited proteolysis assays. Surface biotinylation experiments suggest that the non-wild-type P-gps have longer recycling times. Drug transport assays show that wild-type and haplotype P-gp respond differently to P-gp inhibitors that block efflux of rhodamine 123 or mitoxantrone. In addition, cytotoxicity assays show that the LLC-MDR1-3H cells are more resistant to mitoxantrone than the LLC-MDR1-WT cells after being treated with a P-gp inhibitor. Expression of polymorphic P-gp, however, does not affect the host cell's morphology, growth rate, or monolayer formation. Also, ATPase activity assays indicate that neither basal nor drug-stimulated ATPase activities are affected in the variant P-gps. Taken together, our findings indicate that “silent” polymorphisms significantly change P-gp function, which would be expected to affect interindividual drug disposition and response. Cancer Res; 74(2); 598–608. ©2013 AACR.
Protective mechanisms of adenosine 5′-monophosphate in platelet activation and thrombus formation
Authors: Fuentes Eduardo , Badimon Lina , Caballero Julio , Padró Teresa , Vilahur Gemma , Alarcón Marcelo , Pérez Pablo , Palomo Iván
Published: December 2013

Platelet activation is relevant to a variety of acute thrombotic events. We sought to examine adenosine 5′-monophosphate (AMP) mechanisms of action in preventing platelet activation, thrombus formation and platelet-related inflammatory response. We assessed the effect of AMP on 1) P-selectin expression and GPIIb/IIIa activation by flow cytometry; 2) Platelet aggregation and ATP secretion induced by ADP, collagen, TRAP-6, convulxin and thrombin; 3) Platelet rolling and firm adhesion, and platelet-leukocyte interactions under flow-controlled conditions; and, 4) Platelet cAMP levels, sP-selectin, sCD40L, IL-1β, TGF-β1 and CCL5 release, PDE3A activity and PKA phosphorylation. The effect of AMP on in vivo thrombus formation was also evaluated in a murine model. The AMP docking with respect to A2 adenosine receptor was determined by homology. AMP concentration-dependently (0.1 to 3 mmol/l) inhibited P-selectin expression and GPIIb/IIIa activation, platelet secretion and aggregation induced by ADP, collagen, TRAP-6 and convulxin, and diminished platelet rolling and firm adhesion. Furthermore, AMP induced a marked increase in the rolling speed of leukocytes retained on the platelet surface. At these concentrations AMP significantly decreased inflammatory mediator from platelet, increased intraplatelet cAMP levels and inhibited PDE3A activity. Interestingly, SQ22536, ZM241385 and SCH58261 attenuated the antiplatelet effect of AMP. Docking experiments revealed that AMP had the same orientation that adenosine inside the A2 adenosine receptor binding pocket. These in vitro antithrombotic properties were further supported in an in vivo model of thrombosis. Considering the successful use of combined antiplatelet therapy, AMP may be further developed as a novel antiplatelet agent.
Lack of Phospholipase A
2
Receptor Increases Susceptibility to Cardiac Rupture After Myocardial Infarction
Authors: Mishina Hideto , Watanabe Kazuhiro , Tamaru Shun , Watanabe Yosuke , Fujioka Daisuke , Takahashi Soichiro , Suzuki Koji , Nakamura Takamitsu , Obata Jun-ei , Kawabata Kenichi , Yokota Yasunori , Inoue Osamu , Murakami Makoto , Hanasaki Kohji , Kugiyama Kiyotaka
Published: December 2013

Rationale:

Recent evidence indicates that the biological effects of secretory phospholipase A
2
(sPLA
2
) cannot be fully explained by its catalytic activity. A cell surface receptor for sPLA
2
(PLA
2
receptor 1 [PLA
2
R]) and its high-affinity ligands (including sPLA
2
-IB, sPLA
2
-IIE, and sPLA
2
-X) are expressed in the infarcted myocardium.

Objective:

This study asked whether PLA
2
R might play a pathogenic role in myocardial infarction (MI) using mice lacking PLA
2
R (PLA
2
R
–/–
).

Methods and Results:

MI was induced by permanent ligation of the left coronary artery. PLA
2
R
–/–
mice exhibited higher rates of cardiac rupture after MI compared with PLA
2
R wild-type (PLA
2
R
+/+
) mice (46% versus 21%, respectively;
P
=0.015). PLA
2
R
–/–
mice had a 31% decrease in collagen content and a 45% decrease in the number of α-smooth muscle actin–positive fibroblasts in the infarcted region compared with PLA
2
R
+/+
mice. PLA
2
R was primarily found in myofibroblasts in the infarcted region. PLA
2
R
–/–
myofibroblasts were impaired in collagen-dependent migration, proliferation, and activation of focal adhesion kinase in response to sPLA
2
-IB. Binding of sPLA
2
-IB to PLA
2
R promoted migration and proliferation of myofibroblasts through functional interaction with integrin β1, independent of the catalytic activity of sPLA
2
-IB. In rescue experiments, the injection of PLA
2
R
+/+
myofibroblasts into the infarcted myocardium prevented post-MI cardiac rupture and reversed the decrease in collagen content in the infarcted region in PLA
2
R
–/–
mice.

Conclusions:

PLA
2
R deficiency increased the susceptibility to post-MI cardiac rupture through impaired healing of the infarcted region. This might be partly explained by a reduction in integrin β1–mediated migratory and proliferative responses of PLA
2
R
–/–
myofibroblasts.