bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality and Risk of Bias inPanax ginsengRandomized Controlled Trials: A Review
Authors: Shergis Johannah L. , Zhang Anthony L. , Zhou Wenyu , Xue Charlie C.
Published: April 2013

Panax ginseng is one of the most frequently used herbs in the world. Numerous trials have evaluated its clinical benefits. However, the quality of these studies has not been comprehensively and systematically assessed. We reviewed randomized controlled trials (RCTs) of Panax ginseng to evaluate their quality and risk of bias. We searched four English databases, without publication date restriction. Two reviewers extracted details about the studies' methodological quality, guided by the Consolidated Standards of Reporting Trials (CONSORT) checklist and its extension for herbal interventions. Risk of bias was determined using the Cochrane Risk of Bias tool. Of 475 potentially relevant studies, 58 met our inclusion criteria. In these 58 studies, 48.3% of the suggested CONSORT checklist items and 35.9% of the extended herbal items were reported. The quality of RCTs published after the CONSORT checklist improved. Until 1995 (before CONSORT) (n = 4), 32.8% of the items were reported in studies. From 1996–2006 (CONSORT published and revised) (n = 30), 46.1% were reported, and from 2007 (n = 24), 53.5% were reported (p = 0.005). After the CONSORT extension for herbal interventions was published in 2006, RCT quality also improved, although not significantly. Until 2005 (n = 34), 35.2% of the extended herbal items were reported in studies; and from 2006 onwards (n = 24), 37.3% were reported (p = 0.64). Most studies classified risk of bias as "unclear". Overall, the quality of Panax ginseng RCT methodology has improved since the CONSORT checklist was introduced. However, more can be done to improve the methodological quality of, and reporting in, RCTs.
The Prevalence and Determinants of Chinese Medicine Use by Australian Women: Analysis of a Cohort of 10,287 Women Aged 56–61 Years
Authors: Sibbritt David , Adams Jon , Murthy Vijayendra
Published: April 2013

This study aimed to examine the factors associated with Chinese medicine use amongst a sample of 10,287 Australian women aged 56–61 years. Data was obtained from a cross-sectional postal questionnaire conducted in 2007, this being the fifth survey of the Australian Longitudinal Study on Women's Health. This representative sample of 10,287 women was randomly selected from the Health Insurance Commission (Medicare) database. The outcome measure was the use of Chinese medicine in the previous 12 months. The predictive factors included demographics, health status measures and health service utilization measures. Statistical analyses included univariate chi-square and ANOVA tests and backward stepwise multiple logistic regression modelling. The use of Chinese medicine amongst women aged 56–61 years appears to be strongly influenced by their country of birth, consultation with a range of CAM practitioners, and the use of some self-prescribed CAM. Interestingly, severe tiredness was the only symptom or diagnosis that predicted Chinese medicine use. Given the substantial prevalence of Chinese medicine use and the finding that the use of Chinese medicine is heavily integrated alongside the use of many other CAM and conventional treatments, it is imperative for the safety of patients that health professionals (across complementary and conventional healthcare) fully recognise the possible Chinese medicine use amongst their practice populations. In order to help inform relevant practice and policy development it is also important that future research further examining women's decision-making, motivations and evaluations regarding Chinese medicine use considers such issues within the context of broader CAM and conventional health care utilization.
Polysaccharide from Fuzi Likely Protects Against Starvation-Induced Cytotoxicity in H9c2 Cells by Increasing Autophagy Through Activation of the AMPK/mTOR Pathway
Authors: Liao Li-Zhen , Chen Yan-Ling , Lu Li-He , Zhao Yong-Hua , Guo Hua-Lei , Wu Wei-Kang
Published: April 2013

There is increasing evidence that starvation induces autophagy, which may be protective during starvation, in an AMPK-dependent manner. Polysaccharides from Fuzi (FPS) reportedly have protective effects on nutrition-limited livers. The present study was designed to determine whether FPS protected H9c2 cells against starvation-induced cytotoxicity using an AMPK/mTOR-dependent mechanism. H9c2 cells were incubated in serum and glucose starvation media for 12 hours to establish a cell injury model. 3-Methyladenine (3MA, an autophagy inhibitor) was used to identify the exact role of autophagy in starvation. Cells were incubated with different FPS concentrations, and the cell injury levels, autophagy activity and AMPK/mTOR phosphorylation were measured. Adenine 9-β-D-arabinofuranoside (Ara-A, an AMPK inhibitor) and 5-amino-4-imidazole-carboxamide riboside (AICAR, an AMPK activator) were used to identify whether the AMPK/mTOR pathway was involved in FPS-mediated cardioprotection. We demonstrated that starvation decreased cell viability in a time-dependent manner, and 3MA-induced autophagy inhibition aggravated the reduced cell viability. FPS treatment attenuated the cell viability decrement and the starvation-induced decline in the mitochondrial membrane potential (MMP), and autophagy; also, the AMPK/mTOR pathways were activated during treatment. Ara-A treatment abolished the protective effect of FPS, while AICAR treatment had a similar effect to FPS. We conclude that autophagy attenuates starvation-induced cardiomyocyte death, and FPS increases autophagy activity to protect against starvation-induced cytotoxicity in H9c2 cells, likely through AMPK/mTOR pathway activation.
Inhibition of Monocarboxylate Transporter-Mediated Absorption of Valproic Acid by Gegen-Qinlian-Tang
Authors: Liu Hsueh-Jung , Yu Chung-Ping , Hsieh Yow-Wen , Tsai Shang-Yuan , Hou Yu-Chi
Published: April 2013

Valproic acid (VPA), an anti-epileptic drug with a narrow therapeutic index, is a substrate of the monocarboxylate transporter (MCT). In this study, we investigated the effect of Gegen-Qinlian-Tang (GQT), a Chinese Medicine prescription containing Puerariae Radix (PR), Scutellariae Radix (SR), Coptidis Rhizoma (CR) and Glycyrrhizae Radix (GR), on the pharmacokinetics of VPA, as a probe drug of MCT, in rats and the underlying mechanism. Sprague–Dawley rats were orally administered VPA with and without GQT in crossover design. The serum concentrations of VPA were determined by a fluorescence polarization immunoassay. The results showed that coadministration with 2.0 and 4.0 g/kg of GQT remarkably decreased the Cmax of VPA by 72% and 74% and reduced the AUC 0-t by 63% and 53%, respectively. The mechanism study using Caco-2 cells revealed that the uptake function of MCT was inhibited by GQT and each component herb. In conclusion, the MCT-mediated absorption of VPA was significantly decreased by GQT and its component herbs.
CONSTRAINTS ON TeV SCALE MAJORANA NEUTRINO PHENOMENOLOGY FROM THE VACUUM STABILITY OF THE HIGGS
Authors: CHAKRABORTTY JOYDEEP , DAS MOUMITA , MOHANTY SUBHENDRA
Published: April 2013

The vacuum stability condition of the Standard Model (SM) Higgs potential with mass in the range of 124–127 GeV puts an upper bound on the Dirac mass of the neutrinos. We study this constraint with the right-handed neutrino masses up to TeV scale. The heavy neutrinos contribute to ΔL = 2 processes like neutrinoless double beta decay and same-sign-dilepton (SSD) production in the colliders. The vacuum stability criterion also restricts the light-heavy neutrino mixing and constrains the branching ratio (BR) of lepton flavor-violating process, like μ→eγ mediated by the heavy neutrinos. We show that neutrinoless double beta decay with a lifetime ~1025 years can be observed if the lightest heavy neutrino mass is <4.5 TeV. We show that the vacuum stability condition and the experimental bound on μ→e γ together put a constrain on heavy neutrino mass MR>3.3 TeV. Finally we show that the observation of SSDs associated with jets at the LHC needs much larger luminosity than available at present. We have estimated the possible maximum cross-section for this process at the LHC and show that with an integrated luminosity 100 fb-1 it may be possible to observe the SSD signals as long as MR < 400 GeV.
MICROSCOPIC BLACK HOLE AND UNCERTAINTY PRINCIPLE WITH MINIMAL LENGTH AND MOMENTUM
Authors: STETSKO M. M.
Published: April 2013

We investigate a microscopic black hole in the case of modified generalized uncertainty principle with a minimal uncertainty in position as well as in momentum. We calculate thermodynamical functions of a Schwarzschild black hole such as temperature, entropy and heat capacity. It is shown that the incorporation of minimal uncertainty in momentum leads to minimal temperature of a black hole. Minimal temperature gives rise to appearance of a phase transition. Emission rate equation and black hole's evaporation time are also obtained.
DEAD CONE DUE TO PARTON VIRTUALITY
Authors: BHATTACHARYYA TRAMBAK , ALAM JAN-E
Published: April 2013

A general expression for the dead cone of gluons radiated by virtual partons has been derived. The conventional dead cone for massive on-shell quarks and the dead cone for the virtual partons have been obtained by using different limits of the general expression. Radiative suppression due to the virtuality of initial parton jets in heavy-ion collisions has been discussed. It is observed that the suppression caused by the high virtuality is overwhelmingly large as compared to that on account of conventional dead cone of heavy quarks.
EVERY OUTER-1-PLANE GRAPH HAS A RIGHT ANGLE CROSSING DRAWING
Authors: DEHKORDI HOOMAN REISI , EADES PETER
Published: April 2013

There is strong empirical evidence that human perception of a graph drawing is negatively correlated with the number of edge crossings. However, recent experiments show that one can reduce the negative effect by ensuring that the edges that cross do so at large angles. These experiments have motivated a number of mathematical and algorithmic studies of “right angle crossing (RAC)” drawings of graphs, where the edges cross each other perpendicularly.

In this paper we give an algorithm for constructing RAC drawings of “outer-1-plane” graphs, that is, topological graphs in which each vertex appears on the outer face, and each edge crosses at most one other edge. The drawing algorithm preserves the embedding of the input graph. This is one of the few algorithms available to construct RAC drawings.
1-EXTENSIONS AND GLOBAL RIGIDITY OF GENERIC DIRECTION-LENGTH FRAMEWORKS
Authors: NGUYEN VIET-HANG
Published: April 2013

The problem of deciding the unique realizability of a graph in a Euclidean space with distance and/or direction constraints on the edges of the graph has applications in CAD (Computer-Aided Design) and localization in sensor networks. One approach, which has been proved to be efficient in the similar problem for graphs with distance constraints, is to study operations to construct a uniquely realizable graph from a smaller one. In this paper, we extend a result of Jackson and Jordán on the unique realizability preservingness of the so-called “1-extension” in dimension 2 to all dimensions.
CONSTRUCTION OF SPHERICAL PATTERNS FROM PLANAR DYNAMIC SYSTEMS
Authors: CHEN NING , LUO NANNAN
Published: April 2013

We investigated the generation of spherical continuous-tilings of the chaotic attractors or the filled-in Julia sets from the plane mappings. We build three plane mappings, which can be used to construct the continuous patterns on the surfaces of the hexahedron and the unit sphere. We discuss the coordinate transformation for a spatial point between the different coordinate systems and further discuss how to project a spherical point onto a surface of the inscribed hexahedron. We present a method of constructing a spherical pattern with the pattern of a square on the inscribed hexahedron from an arbitrary projective angle, and generate spherical patterns from the three plane mappings. The results show that we can construct a great number of spherical patterns of the chaotic attractors and the filled-in Julia sets from the plane mappings, which are based on the square lattice and meet the requirements of the continuity and the four rotation symmetries on the lattice's boundaries.
DEFORMATION OF GRAPHENE INDUCED BY ADSORPTION OF PEPTIDES: A MOLECULAR DYNAMICS STUDY
Authors: CHENG YUAN , ZHANG ZUOQI , TEO ZHISHIUN
Published: April 2013

Graphene has potential applications in a variety of fields including electronics, photonics and chemical-biosensing. In this study, we perform molecular dynamics (MD) simulations to study the interactions between graphene sheets and biomolecules. The bending behavior of graphene induced by adsorption of peptides is investigated. The influence of peptide size, number, and alignment on the deflection of graphene sheets is studied in detail. The van der Waals (VDW) interaction plays a dominant role in the interaction between peptides and graphene. Our study provides valuable information for the experimental design of nanodevices incorporating graphene with biomolecules.
From flesh to fossils – Nicolaus Steno’s anatomy of the Earth
Authors: Bek-Thomsen Jakob
Published: April 2013

This paper concerns the Danish anatomist Nicolaus Steno’s years in the service of the Medici Court and argues that his studies of the Earth in
Canis cacharia dissectum caput
from 1667 and
De Solido intra solidum contento dissertationis prodromus
from 1669 must be interpreted within this context and in relation to the epistemological approach of the
historia
-genre present in many early modern medical textbooks. The use of
historia
enabled Steno to produce knowledge that was both useful as a Medicean instrument of power and allowed him to produce a truthful geological thesis without referral to Aristotelian causes. Traditionally, Steno’s geological work has been interpreted teleologically, as a break from contemporary natural philosophy and as an example of a foresight which would not be appreciated properly until several hundred years after his death. Challenging the untenable presentist interpretation, this paper argues that Steno’s work on the transformation of the Earth must be understood as inherently connected to the Medici court and their experimental academy – the Accademia del Cimento.
Britain’s spa heritage: a hydrogeological appraisal
Authors: Mather John D.
Published: April 2013

The managed exploitation of thermal and mineral waters began at British spas in the middle of the 16th century when the first scientific treatises were written. The peak in popularity was reached in the 18th century, after which usage declined. Britain’s spa heritage is well preserved at some sites and 14 of these are selected for detailed discussion. These heritage spas are divided into three groups on the basis of their hydrogeology. In the first group, spa locations are both controlled and constrained by the hydrogeological conditions. Flows are reliable and the waters are generally highly mineralized as a result of long groundwater flow paths and residence times. In the second group, hydrogeology is of secondary importance and locations owe more to chance and the endeavours of local entrepreneurs. The waters are vulnerable to contamination and flows are often unreliable. The third group exists only because of human disturbance to natural groundwater flow paths. Of the hundreds of mineral springs in Britain, many of which were promoted as spas, most fell into the second group and have disappeared; these are remembered only by a street sign or a trickle of water.
Groundwater – Medicine by the Glassful?
Authors: Robins N. S. , Smedley P. L.
Published: April 2013

Knowledge of the healing properties of some groundwater sources has been passed down through the generations. A complex array of hydrogeological environments yields a rich and diverse range of chemical compositions, and cures for a variety of ailments were available from some spring waters. Many were sourced with associated religious overtones. It is likely that exposure to clean cold water alleviates the symptoms of leprosy and probable also that it relieves rheumatic pain. However, the only demonstrable medicinal properties of groundwater are its purging effects wherever MgSO
4
or Epsom salts prevailed. Clean and potable groundwater is certainly a key to human health and some of the minerals dissolved within it are essential to the human body, although many of these minerals become toxic if present in excess. The modern fashion for bottled groundwater, often perceived to be associated with health-giving and medicinal properties, for the most part, merely offer a safe form of drinking water.
Sex steroid hormones regulate constitutive expression ofCyp2e1in female mouse liver
Authors: Konstandi Maria , Cheng Jie , Gonzalez Frank J.
Published: April 2013

CYP2E1 is of paramount toxicological significance because it metabolically activates a large number of low-molecular-weight toxicants and carcinogens. In this context, factors that interfere with Cyp2e1 regulation may critically affect xenobiotic toxicity and carcinogenicity. The aim of this study was to investigate the role of female steroid hormones in the regulation of CYP2E1, as estrogens and progesterone are the bases of contraceptives and hormonal replacement therapy in menopausal women. Interestingly, a fluctuation in the hepatic expression pattern of Cyp2e1 was revealed in the different phases of the estrous cycle of female mice, with higher Cyp2e1 expression at estrus (E) and lower at methestrus (ME), highly correlated with that in plasma gonadal hormone levels. Depletion of sex steroids by ovariectomy repressed Cyp2e1 expression to levels similar to those detected in males and cyclic females at ME. Hormonal supplementation brought Cyp2e1 expression back to levels detected at E. The role of progesterone appeared to be more prominent than that of 17β-estradiol. Progesterone-induced Cyp2e1 upregulation could be attributed to inactivation of the insulin/PI3K/Akt/FOXO1 signaling pathway. Tamoxifen, an anti-estrogen, repressed Cyp2e1 expression potentially via activation of the PI3K/Akt/FOXO1 and GH/STAT5b-linked pathways. The sex steroid hormone-related changes in hepatic Cyp2e1 expression were highly correlated with those observed in Hnf-1α, β-catenin, and Srebp-1c. In conclusion, female steroid hormones are clearly involved in the regulation of CYP2E1, thus affecting the metabolism of a plethora of toxicants and carcinogenic agents, conditions that may trigger several pathologies or exacerbate the outcomes of various pathophysiological states.
Development and Validation of Acupuncture Fear Scale
Authors: Kim Ho-Sun , Kim Yun-Ji , Lee Hwa-Jin , Kim Song-Yi , Lee Hyangsook , Chang Dong-Seon , Lee Hyejung , Park Hi-Joon , Chae Younbyoung
Published: April 2013

Objectives. Strong aversions to acupuncture have been an obstacle to understanding its intrinsic action of acupuncture. Thus, it is necessary to evaluate the nature and extent of fear of acupuncture treatment. Our study aims to develop and validate an instrument that evaluates a patient’s fear of acupuncture treatment.Methods. We have developed an acupuncture fear scale, a 16-item instrument which assesses the acupuncture fear score and uses it to survey 275 participants in South Korea, thus testing the reliability and validity of the instrument.Results. Internal consistency was high (Cronbach’s alpha = 0.935). Test-retest reliability (Spearman’s rank correlation coefficient) among 33 participants out of 275 ranged from 0.565 to 0.797 (P<0.001). Principal component analysis revealed two factors accounting for 68% of the variance, which are painful sensation and possible adverse events, respectively. The acupuncture fear scale was positively correlated with the total of fear of pain questionnaire-III (r=0.423,P<0.001).Conclusions. The acupuncture fear scale can be a valid and reliable instrument that can measure fear of acupuncture treatment. These results strongly suggest that it would be a clinically useful tool to assess fear of acupuncture in the acupuncture clinic setting and an important instrument to understand the complex social-behavioral component of acupuncture modality.
A Pilot Study of Increasing Nonpurposeful Movement Breaks at Work as a Means of Reducing Prolonged Sitting
Authors: Cooley Dean , Pedersen Scott
Published: April 2013

There is a plethora of workplace physical activity interventions designed to increase purposeful movement, yet few are designed to alleviate prolonged occupational sitting time. A pilot study was conducted to test the feasibility of a workplace e-health intervention based on a passive approach to increase nonpurposeful movement as a means of reducing sitting time. The study was trialled in a professional workplace with forty-six participants (33 females and 13 males) for a period of twenty-six weeks. Participants in the first thirteen weeks received a passive prompt every 45 minutes on their computer screen reminding them to stand and engage in nonpurposeful activity throughout their workday. After thirteen weeks, the prompt was disabled, and participants were then free to voluntary engage the software. Results demonstrated that when employees were exposed to a passive prompt, as opposed to an active prompt, they were five times more likely to fully adhere to completing a movement break every hour of the workday. Based on this pilot study, we suggest that the notion that people are willing to participate in a coercive workplace e-health intervention is promising, and there is a need for further investigation.
Vulnerability Analysis of Power Grids Using Modified Centrality Measures
Authors: Gutierrez Francisco , Barocio E. , Uribe F. , Zuniga P.
Published: April 2013

The aim of this paper is to propose modified centrality measures as a tool to identify critical nodes before a vulnerability analysis is performed in an electrical power grid. Pair dependency centrality is weighted using the grid active power flow, and this becomes the basis to define closeness and betweenness of its nodes, and hence to identify the most critical ones. To support the idea of using modified centralities, four power grids are tested to be either exponential or scale-free. To evaluate the proposal, information obtained via modified centrality measures is used to calculate global efficiency of the power grids.
From Acupuncture to Interaction betweenδ-Opioid Receptors and Na+Channels: A Potential Pathway to Inhibit Epileptic Hyperexcitability
Authors: Chao Dongman , Shen Xueyong , Xia Ying
Published: April 2013

Epilepsy is one of the most common neurological disorders affecting about 1% of population. Although the precise mechanism of its pathophysiological changes in the brain is unknown, epilepsy has been recognized as a disorder of brain excitability characterized by recurrent unprovoked seizures that result from the abnormal, excessive, and synchronous activity of clusters of nerve cells in the brain. Currently available therapies, including medical, surgical, and other strategies, such as ketogenic diet and vagus nerve stimulation, are symptomatic with their own limitations and complications. Seeking new strategies to cure this serious disorder still poses a big challenge to the field of medicine. Our recent studies suggest that acupuncture may exert its antiepileptic effects by normalizing the disrupted neuronal and network excitability through several mechanisms, including lowering the overexcited neuronal activity, enhancing the inhibitory system, and attenuating the excitatory system in the brain via regulation of the interaction betweenδ-opioid receptors (DOR) and Na+channels. This paper reviews the progress in this field and summarizes new knowledge based on our work and those of others.
A Note on Fractional Order Derivatives and Table of Fractional Derivatives of Some Special Functions
Authors: Atangana Abdon , Secer Aydin
Published: April 2013

The purpose of this note is to present the different fractional order derivatives definition that are commonly used in the literature on one hand and to present a table of fractional order derivatives of some functions in Riemann-Liouville sense On other the hand. We present some advantages and disadvantages of these fractional derivatives. And finally we propose alternative fractional derivative definition.
Feature Extraction from 3D Point Cloud Data Based on Discrete Curves
Authors: An Yi , Li Zhuohan , Shao Cheng
Published: April 2013

Reliable feature extraction from 3D point cloud data is an important problem in many application domains, such as reverse engineering, object recognition, industrial inspection, and autonomous navigation. In this paper, a novel method is proposed for extracting the geometric features from 3D point cloud data based on discrete curves. We extract the discrete curves from 3D point cloud data and research the behaviors of chord lengths, angle variations, and principal curvatures at the geometric features in the discrete curves. Then, the corresponding similarity indicators are defined. Based on the similarity indicators, the geometric features can be extracted from the discrete curves, which are also the geometric features of 3D point cloud data. The threshold values of the similarity indicators are taken from[0,1], which characterize the relative relationship and make the threshold setting easier and more reasonable. The experimental results demonstrate that the proposed method is efficient and reliable.
Adaptive High Order Sliding Mode Controller Design for Hypersonic Vehicle with Flexible Body Dynamics
Authors: Tian Bailing , Fan Wenru , Zong Qun , Wang Jie , Wang Fang
Published: April 2013

This paper describes the design of a nonlinear robust adaptive controller for a flexible hypersonic vehicle model which is nonlinear, multivariable, and unstable, and includes uncertain parameters. Firstly, a control-oriented model is derived for controller design. Then, the model analysis is conducted for this model via input-output (I/O) linearized technique. Secondly, the sliding mode manifold is designed based on the homogeneity theory. Then, the adaptive high order sliding mode controller is designed to achieve the tracking for hypersonic vehicle where the upper bounds of the uncertainties are not known in advance. Furthermore, the stability of the system is proved via the Lyapunov theory. Finally, the Monte-Carlo simulation results on the full-order nonlinear model with aerodynamic uncertainties are provided to demonstrate the effectiveness of the proposed control strategy.
Compounds from the Fruits of the Popular European Medicinal PlantVitex agnus-castusin Chemoprevention via NADP(H):Quinone Oxidoreductase Type 1 Induction
Authors: Li Shenghong , Qiu Shengxiang , Yao Ping , Sun Handong , Fong Harry H. S. , Zhang Hongjie
Published: April 2013

As part of our continuing efforts in the search for potential biologically active compounds from medicinal plants, we have isolated 18 compounds including two novel nitrogen containing diterpenes from extracts of the fruits ofVitex agnus-castus. These isolates, along with our previously obtained novel compound vitexlactam A (1), were evaluated for potential biological effects, including cancer chemoprevention. Chemically, the nitrogenous isolates were found to be two labdane diterpene alkaloids, each containing anα,β-unsaturatedγ-lactam moiety. Structurally, they were elucidated to be 9α-hydroxy-13(14)-labden-16,15-amide (2) and 6β-acetoxy-9α-hydroxy-13(14)-labden-15,16-amide (3), which were named vitexlactams B and C, respectively. The 15 known isolates were identified as vitexilactone (4), rotundifuran (5), 8-epi-manoyl oxide (6), vitetrifolin D (7), spathulenol (8),cis-dihydro-dehydro-diconiferylalcohol-9-O-β-D-glucoside (9), luteolin-7-O-glucoside (10), 5-hydroxy-3,6,7,4′-tetramethoxyflavone (11), casticin (12), artemetin (13), aucubin (14), agnuside (15),β-sitosterol (16),p-hydroxybenzoic acid (17), andp-hydroxybenzoic acid glucose ester (18). All compound structures were determined/identified on the basis of 1D and/or 2D NMR and mass spectrometry techniques. Compounds6,8,9, and18were reported from aVitexspieces for the first time. The cancer chemopreventive potentials of these isolates were evaluated for NADP(H):quinone oxidoreductase type 1 (QR1) induction activity. Compound7demonstrated promising QR1 induction effect, while the new compound vitexlactam (3) was only slightly active.
Approximation for the Hierarchical Constrained Variational Inequalities over the Fixed Points of Nonexpansive Semigroups
Authors: Zhu Li-Jun
Published: April 2013

The purpose of the present paper is to study the hierarchical constrained variational inequalities of finding a pointx*such thatx*∈Ω,〈(A-γf)x*-(I-B)Sx*,x-x*〉≥0,  ∀x∈Ω, whereΩis the set of the solutions of the following variational inequality:x*∈Ϝ,〈(A-S)x*,x-x*〉≥0,  ∀x∈Ϝ, whereA,Bare two strongly positive bounded linear operators,fis aρ-contraction,Sis a nonexpansive mapping, andϜis the fixed points set of a nonexpansive semigroup{T(s)}s≥0. We present a double-net convergence hierarchical to some elements inϜwhich solves the above hierarchical constrained variational inequalities.
The Effects of Trace Elements on the Lipid Productivity and Fatty Acid Composition ofNannochloropis oculata
Authors: Dou Xiao , Lu Xiang-Hong , Lu Mei-Zhen , Yu Li-Sheng , Xue Rong , Ji Jian-Bing
Published: April 2013

The effects of trace elements on the lipid productivity and fatty acid composition ofNannochloropis oculata (N. oculata)were studied. The results showed that trace elements had a strong influence on not only the lipid productivity but also the fatty acid composition. The addition of Fe3+, Zn2+, Mn2+, Mo6+, and EDTA and the deletion of Cu2+and Co2+can increase the lipid productivity. The optimum concentrations of the trace elements in the culture medium are 6 times of Fe3+and EDTA, the same concentration of Zn2+, Mn2+, and Mo6+as the control group, but the optimum medium has no Cu2+or Co2+. Fe3+, Zn2+, Mn2+, Mo6+, and EDTA are indispensable during the EPA formation ofN. oculata. The addition of Fe3+, Zn2+, Mn2+, Mo6+, and EDTA can strongly increase the content of EPA in the lipid ofN. oculata, but the concentration of the trace elements had little influence on the level of EPA.
Successful Treatment with Bosentan of Lower Extremity Ulcers in a Scleroderma Patient
Authors: Naert Alix , De Haes Petra
Published: April 2013

Digital ulcers are a well-known problem in patients with systemic sclerosis. Lower extremity ulcers are less prevalent but are also a challenging and underestimated complication of the disease causing important pain and morbidity. Bosentan, an oral dual endothelin receptor antagonist, has been shown to be effective in preventing digital ulcers in patients with systemic sclerosis. A few recent observations showed the efficacy of bosentan for accelerating the healing of nondigital ulcers in scleroderma patients. This report deals with a 48-year-old patient with systemic sclerosis who developed painful ulcers on the left ankle and hallux. The ulcers were refractory to a combination of vasodilator therapy with a calcium antagonist and several courses of intravenous prostanoids, low molecular weight heparin, aspirin, simvastatin, and intensive local treatment. Bosentan treatment showed spectacular healing of the ulcers already after 4 months of therapy. This case supports the previous few observations of accelerating wound healing of lower extremity ulcers in systemic sclerosis patients with bosentan treatment.
Content-Based Image Retrieval Based on Electromagnetism-Like Mechanism
Authors: Jalab Hamid A. , Abdullah Nor Aniza
Published: April 2013

Recently, many researchers in the field of automatic content-based image retrieval have devoted a remarkable amount of research looking for methods to retrieve the best relevant images to the query image. This paper presents a novel algorithm for increasing the precision in content-based image retrieval based on electromagnetism optimization technique. The electromagnetism optimization is a nature-inspired technique that follows the collective attraction-repulsion mechanism by considering each image as an electrical charge. The algorithm is composed of two phases: fitness function measurement and electromagnetism optimization technique. It is implemented on a database with 8,000 images spread across 80 classes with 100 images in each class. Eight thousand queries are fired on the database, and the overall average precision is computed. Experimental results of the proposed approach have shown significant improvement in the retrieval performance in regard to precision.
Asynchronous Realization of Algebraic Integer-Based 2D DCT Using Achronix Speedster SPD60 FPGA
Authors: Rajapaksha Nilanka , Edirisuriya Amila , Madanayake Arjuna , Cintra Renato J. , Onen Dennis , Amer Ihab , Dimitrov Vassil S.
Published: April 2013

Transformation and quantization play a critical role in video codecs. Recently proposed algebraic-integer-(AI-) based discrete cosine transform (DCT) algorithms are analyzed in the presence of quantization, using the High Efficiency Video Coding (HEVC) standard. AI DCT is implemented and tested on asynchronous quasi delay-insensitive logic, using Achronix SPD60 field programmable gate array (FPGA), which leads to lower complexity, higher speed of operation, and insensitivity to process-voltage-temperature variations. Performance of AI DCT with HEVC is measured in terms of the accuracy of the transform coefficients and the overall rate-distortion (R-D) characteristics, using HM 7.1 reference software. Results indicate a 31% improvement over the integer DCT in the number of transform coefficients having error within 1%. The performance of the 65 nm asynchronous hardware in terms of speed of operation is investigated and compared with the 65 nm synchronous Xilinx FPGA. Considering word lengths of 5 and 6 bits, a speed increase of 230% and 199% is observed, respectively. These results indicate that AI DCT can be potentially utilized in HEVC for applications demanding high accuracy as well as high throughput. However, novel quantization schemes are required to allow the accuracy improvements obtained.
Accurate Solutions of Conservative Nonlinear Oscillators by the Enhanced Cubication Method
Authors: Elías-Zúñiga Alex , Martínez-Romero Oscar
Published: April 2013

The enhanced cubication method is applied to develop approximate solutions for the most common nonlinear oscillators found in the literature. It is shown that this procedure leads to amplitude-time response curves and angular frequency values with maximum relative errors lower than those found by previously developed approximate solutions.
New Algorithm of Two-Point Block Method for Solving Boundary Value Problem with Dirichlet and Neumann Boundary Conditions
Authors: Phang Pei See , Abdul Majid Zanariah , Ismail Fudziah , Othman Khairil Iskandar , Suleiman Mohamed
Published: April 2013

Two-point block method with variable step-size strategy is presented to obtain the solutions for boundary value problems directly. Dirichlet type and Neumann type of boundary conditions are studied in this paper. Multiple shooting techniques adapted with the three-step iterative method are employed for generating the guessing value. Six boundary value problems are solved using the proposed method, and the numerical results are compared to the existing methods. The results suggest a significant improvement in the efficiency of the proposed methods in terms of the number of steps, execution time, and accuracy.
A Discrete Dynamical Model of Signed Partitions
Authors: Chiaselotti G. , Marino G. , Oliverio P. A. , Petrassi D.
Published: April 2013

We use a discrete dynamical model with three evolution rules in order to analyze the structure of a partially ordered set of signed integer partitions whose main properties are actually not known. This model is related to the study of some extremal combinatorial sum problems.
Cisplatin Resistance Associated with PARP Hyperactivation
Authors: Michels Judith , Vitale Ilio , Galluzzi Lorenzo , Adam Julien , Olaussen Ken André , Kepp Oliver , Senovilla Laura , Talhaoui Ibtissam , Guegan Justine , Enot David Pierre , Talbot Monique , Robin Angélique , Girard Philippe , Oréar Cédric , Lissa Delphine , Sukkurwala Abdul Qader , Garcia Pauline , Behnam-Motlagh Parviz , Kohno Kimitoshi , Wu Gen Sheng , Brenner Catherine , Dessen Philippe , Saparbaev Murat , Soria Jean-Charles , Castedo Maria , Kroemer Guido
Published: April 2013

Non–small cell lung carcinoma patients are frequently treated with cisplatin (CDDP), most often yielding temporary clinical responses. Here, we show that PARP1 is highly expressed and constitutively hyperactivated in a majority of human CDDP-resistant cancer cells of distinct histologic origin. Cells manifesting elevated intracellular levels of poly(ADP-ribosyl)ated proteins (PARhigh) responded to pharmacologic PARP inhibitors as well as to PARP1-targeting siRNAs by initiating a DNA damage response that translated into cell death following the activation of the intrinsic pathway of apoptosis. Moreover, PARP1-overexpressing tumor cells and xenografts displayed elevated levels of PAR, which predicted the response to PARP inhibitors in vitro and in vivo more accurately than PARP1 expression itself. Thus, a majority of CDDP-resistant cancer cells appear to develop a dependency to PARP1, becoming susceptible to PARP inhibitor–induced apoptosis. Cancer Res; 73(7); 2271–80. ©2013 AACR.
The Endogenous Tryptophan Metabolite and NAD+ Precursor Quinolinic Acid Confers Resistance of Gliomas to Oxidative Stress
Authors: Sahm Felix , Oezen Iris , Opitz Christiane A. , Radlwimmer Bernhard , von Deimling Andreas , Ahrendt Tilman , Adams Seray , Bode Helge B. , Guillemin Gilles J. , Wick Wolfgang , Platten Michael
Published: April 2013

Quinolinic acid is a product of tryptophan degradation and may serve as a precursor for NAD+, an important enzymatic cofactor for enzymes such as the DNA repair protein PARP. Pathologic accumulation of quinolinic acid has been found in neurodegenerative disorders including Alzheimer and Huntington disease, where it is thought to be toxic for neurons by activating the N-methyl-D-aspartate (NMDA) receptor and inducing excitotoxicity. Although many tumors including gliomas constitutively catabolize tryptophan, it is unclear whether quinolinic acid is produced in gliomas and whether it is involved in tumor progression. Here, we show that quinolinic acid accumulated in human gliomas and was associated with a malignant phenotype. Quinolinic acid was produced by microglial cells, as expression of the quinolinic acid-producing enzyme 3-hydroxyanthranilate oxygenase (3-HAO) was confined to microglia in glioma tissue. Human malignant glioma cells, but not nonneoplastic astrocytes, expressed quinolinic acid phosphoribosyltransferase (QPRT) to use quinolinic acid for NAD+ synthesis and prevent apoptosis when de novo NAD+ synthesis was blocked. Oxidative stress, temozolomide, and irradiation induced QPRT in glioma cells. QPRT expression increased with malignancy. In recurrent glioblastomas after radiochemotherapy, QPRT expression was associated with a poor prognosis in two independent datasets. Our data indicate that neoplastic transformation in astrocytes is associated with a QPRT-mediated switch in NAD+ metabolism by exploiting microglia-derived quinolinic acid as an alternative source of replenishing intracellular NAD+ pools. The elevated levels of QPRT expression increase resistance to oxidative stress induced by radiochemotherapy, conferring a poorer prognosis. These findings have implications for therapeutic approaches inducing intracellular NAD+ depletion, such as alkylating agents or direct NAD+ synthesis inhibitors, and identify QPRT as a potential therapeutic target in malignant gliomas. Cancer Res; 73(11); 3225–34. ©2013 AACR.
ATR Inhibition Broadly Sensitizes Ovarian Cancer Cells to Chemotherapy Independent of BRCA Status
Authors: Huntoon Catherine J. , Flatten Karen S. , Wahner Hendrickson Andrea E. , Huehls Amelia M. , Sutor Shari L. , Kaufmann Scott H. , Karnitz Larry M.
Published: April 2013

Replication stress and DNA damage activate the ATR-Chk1 checkpoint signaling pathway that licenses repair and cell survival processes. In this study, we examined the respective roles of the ATR and Chk1 kinases in ovarian cancer cells using genetic and pharmacologic inhibitors in combination with cisplatin, topotecan, gemcitabine, and the PARP inhibitor veliparib (ABT-888), four agents with clinical activity in ovarian cancer. RNA interference (RNAi)–mediated depletion or inhibition of ATR sensitized ovarian cancer cells to all four agents. In contrast, while cisplatin, topotecan, and gemcitabine each activated Chk1, RNAi-mediated depletion or inhibition of this kinase in cells sensitized them only to gemcitabine. Unexpectedly, we found that neither the ATR kinase inhibitor VE-821 nor the Chk1 inhibitor MK-8776 blocked ATR-mediated Chk1 phosphorylation or autophosphorylation, two commonly used readouts for inhibition of the ATR-Chk1 pathway. Instead, their ability to sensitize cells correlated with enhanced CDC25A levels. In addition, we also found that VE-821 could further sensitize BRCA1-depleted cells to cisplatin, topotecan, and veliparib beyond the potent sensitization already caused by their deficiency in homologous recombination. Taken together, our results established that ATR and Chk1 inhibitors differentially sensitize ovarian cancer cells to commonly used chemotherapy agents and that Chk1 phosphorylation status may not offer a reliable marker for inhibition of the ATR-Chk1 pathway. A key implication of our work is the clinical rationale it provides to evaluate ATR inhibitors in combination with PARP inhibitors in BRCA1/2-deficient cells. Cancer Res; 73(12); 3683–91. ©2013 AACR.
Dual Targeting of the Type 1 Insulin-like Growth Factor Receptor and Its Ligands as an Effective Antiangiogenic Strategy
Authors: Bid Hemant K. , London Cheryl A. , Gao Jin , Zhong Haihong , Hollingsworth Robert E. , Fernandez Soledad , Mo Xiaokui , Houghton Peter J.
Published: April 2013

Background: In pediatric tumor xenograft models, tumor-derived insulin growth factor (IGF-2) results in intrinsic resistance to IGF-IR–targeted antibodies, maintaining continued tumor angiogenesis. We evaluated the antiangiogenic activity of a ligand-binding antibody (MEDI-573) alone or in combination with IGF-I receptor binding antibodies (MAB391, CP01-B02).

Methods: IGF-stimulated signaling was monitored by increased Akt phosphorylation in sarcoma and human umbilical cord vascular endothelial cells (HUVEC). Angiogenesis was determined in vitro using capillary tube formation in HUVECs and in vivo using a VEGF-stimulated Matrigel assay. Tumor growth delay was examined in 4 sarcoma xenograft models.

Results: The IGF ligand-binding antibody MEDI-573 suppressed Akt phosphorylation induced by exogenous IGF-I and IGF-2 in sarcoma cells. Receptor-binding antibodies suppressed IGF-I stimulation of Akt phosphorylation, but IGF-2 circumvented this effect and maintained HUVEC tube formation. MEDI-573 inhibited HUVEC proliferation and tube formation in vitro, but did not inhibit angiogenesis in vivo, probably because MEDI-573 binds murine IGF-I with low affinity. However, in vitro antiangiogenic activity of MEDI-573 was also circumvented by human recombinant IGF-I. The combination of receptor- and ligand-binding antibodies completely suppressed VEGF-stimulated proliferation of HUVECs in the presence of IGF-I and IGF-2, prevented ligand-induced phosphorylation of IGF-IR/IR receptors, and suppressed VEGF/IGF-2–driven angiogenesis in vivo. The combination of CP1-BO2 plus MEDI-573 was significantly superior to therapy with either antibody alone against IGF-I and IGF-2 secreting pediatric sarcoma xenograft models.

Conclusions: These results suggest that combination of antibodies targeting IGF receptor and ligands may be an effective therapeutic strategy to block angiogenesis for IGF-driven tumors. Clin Cancer Res; 19(11); 2984–94. ©2013 AACR.
Concomitant BRAF and PI3K/mTOR Blockade Is Required for Effective Treatment of BRAFV600E Colorectal Cancer
Authors: Coffee Erin M. , Faber Anthony C. , Roper Jatin , Sinnamon Mark J. , Goel Gautam , Keung Lily , Wang Wei Vivian , Vecchione Loredana , de Vriendt Veerle , Weinstein Barbara J. , Bronson Roderick T. , Tejpar Sabine , Xavier Ramnik J. , Engelman Jeffrey A. , Martin Eric S. , Hung Kenneth E.
Published: April 2013

Purpose: BRAFV600E mutations are associated with poor clinical prognosis in colorectal cancer (CRC). Although selective BRAF inhibitors are effective for treatment of melanoma, comparable efforts in CRC have been disappointing. Here, we investigated potential mechanisms underlying this resistance to BRAF inhibitors in BRAFV600E CRC.

Experimental Design: We examined phosphoinositide 3-kinase (PI3K)/mTOR signaling in BRAFV600E CRC cell lines after BRAF inhibition and cell viability and apoptosis after combined BRAF and PI3K/mTOR inhibition. We assessed the efficacy of in vivo combination treatment using a novel genetically engineered mouse model (GEMM) for BRAFV600E CRC.

Results: Western blot analysis revealed sustained PI3K/mTOR signaling upon BRAF inhibition. Our BRAFV600E GEMM presented with sessile serrated adenomas/polyps, as seen in humans. Combination treatment in vivo resulted in induction of apoptosis and tumor regression.

Conclusions: We have established a novel GEMM to interrogate BRAFV600E CRC biology and identify more efficacious treatment strategies. Combination BRAF and PI3K/mTOR inhibitor treatment should be explored in clinical trials. Clin Cancer Res; 19(10); 2688–98. ©2013 AACR.
Identification of Prognosis-Relevant Subgroups in Patients with Chemoresistant Triple-Negative Breast Cancer
Authors: Yu Ke-Da , Zhu Rui , Zhan Ming , Rodriguez Angel A. , Yang Wei , Wong Stephen , Makris Andreas , Lehmann Brian D. , Chen Xi , Mayer Ingrid , Pietenpol Jennifer A. , Shao Zhi-Ming , Symmans W. Fraser , Chang Jenny C.
Published: April 2013

Purpose: Patients with triple-negative breast cancer (TNBC) and residual disease after neoadjuvant chemotherapy generally have worse outcome; however, some patients with residual tumor after neoadjuvant chemotherapy do not relapse. We hypothesize that there are subgroups of patients with chemoresistant TNBC with different prognosis.

Experimental Design: Forty-nine chemoresistant cases from 111 patients with TNBC treated with neoadjuvant chemotherapy (M.D. Anderson Cancer Center, Houston, TX) constituted the discovery cohort, and 25 chemoresistant samples from 47 neoadjuvant chemotherapy-treated TNBC (The Methodist Hospital, Houston, TX) were chosen for validation. Extended validation was carried out in 269 operable TNBC predicted to be chemoresistant by expression pattern from published datasets.

Results: We established a seven-gene prognostic signature using dChip and gene set enrichment analyses. In the independent validation cohort, the classifier predicted correctly with positive predictive value of 75.0% and negative predictive value (i.e., relapse-free survival; RFS) of 76.9% at 3 years. Those predicted to relapse had a HR of 4.67 [95% confidence interval (CI): 1.27–17.15] for relapse in 3 years. In extended validation, patients predicted not to relapse exhibited 3-year RFS of 78.9%, whereas the 3-year RFS was 48.5% for patients predicted to relapse, with HR of 2.61 (95% CI: 1.52–4.49). The TNBC subgroup that predicted to have relatively favorable prognosis was characterized by high expression of “luminal-like” genes [androgen-receptor (AR) and GATA3], whereas the subgroup with worse prognosis was characterized by expression of cancer stem-cell markers.

Conclusion: We developed a clinically relevant signature for patients with chemoresistant TNBC. For these women, new therapeutic strategies like targeting AR activation or cancer stem cells may need to be developed. Clin Cancer Res; 19(10); 2723–33. ©2013 AACR.