bluuebunny/crossref_metadata_2025 huggingface dataset:
JCM-16021, a Chinese Herbal Formula, Attenuated Visceral Hyperalgesia in TNBS-Induced Postinflammatory Irritable Bowel Syndrome through Reducing Colonic EC Cell Hyperplasia and Serotonin Availability in Rats
Authors: Qin Hong-Yan , Xiao Hai-Tao , Leung Fung-Ping , Yang Zhi-Jun , Wu Justin C. Y. , Sung Joseph J. Y. , Xu Hong-Xi , Tong Xu-Dong , Bian Zhao-Xiang
Published: June 2012

The present study aimed to investigate the analgesic effect of JCM-16021, a revised traditional Chinese herbal formula, on postinflammatory irritable bowel syndrome (PI-IBS) in rats. The trinitrobenzene sulfonic (TNBS) acid-induced PI-IBS model rats were orally administrated with different doses of JCM-16021 (1.2, 2.4, and 4.8 g/kg/d) for 14 consecutive days. The results showed that JCM-16021 treatment dose-dependently attenuated visceral hyperalgesia in PI-IBS rats. Further, the colonic enterochromaffin (EC) cell number, serotonin (5-HT) content, tryptophan hydroxylase expression, and mechanical-stimuli-induced 5-HT release were significantly ameliorated. Moreover, the decreased levels of mucosal cytokines in PI-IBS, especially the helper T-cell type 1- (Th1-) related cytokine TNF-α, were also elevated after JCM-16021 treatment. These data demonstrate that the analgesic effect of JCM-16021 on TNBS-induced PI-IBS rats may be medicated via reducing colonic EC cell hyperplasia and 5-HT availability.
Expression Profiling of a Heterogeneous Population of ncRNAs Employing a Mixed DNA/LNA Microarray
Authors: Skreka Konstantinia , Zywicki Marek , Karbiener Michael , Hüttenhofer Alexander , Scheideler Marcel , Rederstorff Mathieu
Published: June 2012

Mammalian transcriptomes mainly consist of non protein coding RNAs. These ncRNAs play various roles in all cells and are involved in multiple regulation pathways. More recently, ncRNAs have also been described as valuable diagnostic tools. While RNA-seq approaches progressively replace microarray-based technologies for high-throughput expression profiling, they are still not routinely used in diagnostic. Microarrays, on the other hand, are more widely used for diagnostic profiling, especially for very small ncRNA (e.g., miRNAs), employing locked nucleic acid (LNA) arrays. However, LNA microarrays are quite expensive for high-throughput studies targeting longer ncRNAs, while DNA arrays do not provide satisfying results for the analysis of small RNAs. Here, we describe a mixed DNA/LNA microarray platform, where directly labeled small and longer ncRNAs are hybridized on LNA probes or custom DNA probes, respectively, enabling sensitive and specific analysis of a complex RNA population on a unique array in one single experiment. The DNA/LNA system, requiring relatively low amounts of total RNA, which complies with diagnostic references, was successfully applied to the analysis of differential ncRNA expression in mouse embryonic stem cells and adult brain cells.
A Selection Approach for Optimized Problem‐Solving Process by Grey Relational Utility Model and Multicriteria Decision Analysis
Authors: Ke Chih-Kun , Wu Mei-Yu
Published: June 2012

In business enterprises, especially the manufacturing industry, various problem situations may occur during the production process. A situation denotes an evaluation point to determine the status of a production process. A problem may occur if there is a discrepancy between the actual situation and the desired one. Thus, a problem‐solving process is often initiated to achieve the desired situation. In the process, how to determine an action need to be taken to resolve the situation becomes an important issue. Therefore, this work uses a selection approach for optimized problem‐solving process to assist workers in taking a reasonable action. A grey relational utility model and a multicriteria decision analysis are used to determine the optimal selection order of candidate actions. The selection order is presented to the worker as an adaptive recommended solution. The worker chooses a reasonable problem‐solving action based on the selection order. This work uses a high‐tech company’s knowledge base log as the analysis data. Experimental results demonstrate that the proposed selection approach is effective.
Clinically Undiagnosed Prostate Carcinoma Metastatic to Renal Oncocytoma
Authors: Horn Adam J. , Fritz Bari E. , LaGrange Chad A. , West William W. , Lele Subodh M.
Published: June 2012

Tumors-to-tumor metastasis is an uncommon occurrence and can be a source of great diagnostic difficulty, especially when the donor tumor is undiagnosed. Here we report a case of a kidney resected for a primary neoplasm (oncocytoma) that harbored metastases from a clinically undiagnosed prostatic adenocarcinoma. The presence of the poorly differentiated metastasis within an otherwise typical oncocytoma in the absence of metastases in the surrounding nonneoplastic renal parenchyma resulted in a diagnostic dilemma. To our knowledge, this is the first report of a case in the English literature of a clinically undiagnosed prostatic adenocarcinoma metastatic to a renal oncocytoma identified on examination of the resected renal neoplasm.
Exercise Intolerance in Pulmonary Arterial Hypertension
Authors: Fowler Robin M. , Gain Kevin R. , Gabbay Eli
Published: June 2012

Pulmonary arterial hypertension (PAH) is associated with symptoms of dyspnea and fatigue, which contribute to exercise limitation. The origins and significance of dyspnea and fatigue in PAH are not completely understood. This has created uncertainly among healthcare professionals regarding acceptable levels of these symptoms, on exertion, for patients with PAH. Dysfunction of the right ventricle (RV) contributes to functional limitation and mortality in PAH; however, the role of the RV in eliciting dyspnea and fatigue has not been thoroughly examined. This paper explores the contribution of the RV and systemic and peripheral abnormalities to exercise limitation and symptoms in PAH. Further, it explores the relationship between exercise abnormalities and symptoms, the utility of the cardiopulmonary exercise test in identifying RV dysfunction, and offers suggestions for further research.
A Ship Collision Analysis Program Based on Upper Bound Solutions and Coupled with a Large Rotational Ship Movement Analysis Tool
Authors: Le Sourne Hervé , Besnard Nicolas , Cheylan Cedric , Buannic Natacha
Published: June 2012

This paper presents a user‐friendly rapid prediction tool of damage to struck and striking vessels in a ship collision event. To do this, the so‐called upper bound theorem is applied to calculate internal forces and energies of any substructure involved in the ships crushing process. At each increment of indentation, the total crushing force is transmitted to the external dynamics MCOL program, which calculates the global ship motion correction by solving the hydrodynamic force equilibrium equations. As a first step, the paper gives a brief description of the upper bound method originally developed for perpendicular collisions and recently enhanced for oblique ones. Then, the theory developed in MCOL program for large rotational ship movements is detailed. By comparing results obtained with and without MCOL, the importance of hydrodynamic effects is highlighted. Some simulation results are compared with results provided by classical nonlinear finite element calculations. Finally, by using the developed analytical tool, which mixes internal and external dynamics, different crushing scenarios including oblique collisions are investigated and the influence of some collision parameters like longitudinal and vertical impact location, impact angle, and struck ship velocity is studied.
Nitric Oxide Inactivation Mechanisms in the Brain: Role in Bioenergetics and Neurodegeneration
Authors: Santos Ricardo M. , Lourenço Cátia F. , Ledo Ana , Barbosa Rui M. , Laranjinha João
Published: June 2012

During the last decades nitric oxide (•NO) has emerged as a critical physiological signaling molecule in mammalian tissues, notably in the brain.•NO may modify the activity of regulatory proteins via direct reaction with the heme moiety, or indirectly, via S-nitrosylation of thiol groups or nitration of tyrosine residues. However, a conceptual understanding of how•NO bioactivity is carried out in biological systems is hampered by the lack of knowledge on its dynamicsin vivo. Key questions still lacking concrete and definitive answers include those related with quantitative issues of its concentration dynamics and diffusion, summarized in the how much, how long, and how far trilogy. For instance, a major problem is the lack of knowledge of what constitutes a physiological•NO concentration and what constitutes a pathological one and how is•NO concentration regulated. The ambient•NO concentration reflects the balance between the rate of synthesis and the rate of breakdown. Much has been learnt about the mechanism of•NO synthesis, but the inactivation pathways of•NO has been almost completely ignored. We have recently addressed these issuesin vivoon basis of microelectrode technology that allows a fine-tuned spatial and temporal measurement•NO concentration dynamics in the brain.
Re‐Encryption Method Designed by Row Complete Matrix
Authors: Chen I-Te , Tsai Jer-Min , Tzeng Jengnan
Published: June 2012

With the prevalence of Internet access, document storage has become a fundamental web service in recent years. One important topic is how to design a secure channel for efficiently sharing documents with another receiver. In this paper, we demonstrate a re‐encryption method that is designed with row complete matrices. With this new method, the document owner can share a ciphertext in the cloud with another receiver by sending a serial number to the server and giving the receiver a corresponding key at the same time. This method ensures that the server cannot obtain the information about key and plaintext and that the receiver cannot obtain the original key of the owner either. Only the owner has the knowledge of all the information. Using this re‐encryption system, the cloud server can provide a secure file‐sharing service without worrying about the shared key management problem. Moreover, the cost of re‐encryption will not increase even when the encryption is strengthened with longer encryption keys.
Strong Convergence of Viscosity Approximation Methods for Nonexpansive Mappings in CAT(0) Spaces
Authors: Shi Luo Yi , Chen Ru Dong
Published: June 2012

Viscosity approximation methods for nonexpansive mappings in CAT(0) spaces are studied. Consider a nonexpansive self‐mapping T of a closed convex subset C of a CAT(0) space X. Suppose that the set Fix(T) of fixed points of T is nonempty. For a contraction f on C and t ∈ (0,1), let xt ∈ C be the unique fixed point of the contraction x ↦ tf(x)⊕(1 − t)Tx. We will show that if X is a CAT(0) space satisfying some property, then {xt} converge strongly to a fixed point of T which solves some variational inequality. Consider also the iteration process {xn}, where x0 ∈ C is arbitrary and xn+1 = αnf(xn)⊕(1 − αn)Txn for n ≥ 1, where {αn}⊂(0,1). It is shown that under certain appropriate conditions on αn, {xn} converge strongly to a fixed point of T which solves some variational inequality.
Supply Chains Competition under Uncertainty Concerning Player’s Strategies and Customer Choice Behavior: A Generalized Nash Game Approach
Authors: Hafezalkotob A. , Makui A.
Published: June 2012

Decision makers in a supply chain confront two main sources of uncertainty in market environment including uncertainty about customers purchasing behaviors and rival chains strategies. Focusing on competition between two supply chains, it is considered that each customer as an independent player selects products of these chains based on random utility model. Similar to quantal response equilibrium approach, we take account of customer rationality as an exogenous parameter. Moreover, it is assumed that decision makers in a supply chain can perceive an estimation of rival strategies about price and service level formulated in the model by fuzzy strategies. In the competition model, chain’s decision makers consider a subjective probability for wining each customer which is formulated by coupled constraints. These constraints connect chains strategies regarding to each customer and yield a generalized Nash equilibrium problem. Since price cutting and increasing service level are main responses to rival supply chain, after calculating optimal strategies, we show that more efficient responses depend on customer preferences.
A New Four‐Scroll Chaotic Attractor Consisted of Two‐Scroll Transient Chaotic and Two‐Scroll Ultimate Chaotic
Authors: Xu Yuhua , Li Bing , Wang Yuling , Zhou Wuneng , Fang Jian-an
Published: June 2012

A new four‐scroll chaotic attractor is found by feedback controlling method in this paper. The novel chaotic system can generate four scrolls two of which are transient chaotic and the other two of which are ultimate chaotic. Of particular interest is that this novel chaotic system can generate one‐scroll, two 2‐scroll and four‐scroll chaotic attractor with variation of a single parameter. We analyze the new system by means of phase portraits, Lyapunov exponents, fractional dimension, bifurcation diagram, and Poincaré map, respectively. The analysis results show clearly that this is a new chaotic system which deserves further detailed investigation.
Nonself‐Adjoint Second‐Order Difference Operators in Limit‐Circle Cases
Authors: Allahverdiev Bilender P.
Published: June 2012

We consider the maximal dissipative second‐order difference (or discrete Sturm‐Liouville) operators acting in the Hilbert space (ℤ: = {0, ±1, ±2, …}), that is, the extensions of a minimal symmetric operator with defect index (2,2) (in the Weyl‐Hamburger limit‐circle cases at ±∞). We investigate two classes of maximal dissipative operators with separated boundary conditions, called “dissipative at −∞” and “dissipative at ∞.” In each case, we construct a self‐adjoint dilation of the maximal dissipative operator and its incoming and outgoing spectral representations, which make it possible to determine the scattering matrix of the dilation. We also establish a functional model of the maximal dissipative operator and determine its characteristic function through the Titchmarsh‐Weyl function of the self‐adjoint operator. We prove the completeness of the system of eigenvectors and associated vectors of the maximal dissipative operators.
Widespread Structural and Functional Connectivity Changes in Amyotrophic Lateral Sclerosis: Insights from Advanced Neuroimaging Research
Authors: Trojsi Francesca , Monsurrò Maria Rosaria , Esposito Fabrizio , Tedeschi Gioacchino
Published: June 2012

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease principally affecting motor neurons. Besides motor symptoms, a subset of patients develop cognitive disturbances or even frontotemporal dementia (FTD), indicating that ALS may also involve extramotor brain regions. Both neuropathological and neuroimaging findings have provided further insight on the widespread effect of the neurodegeneration on brain connectivity and the underlying neurobiology of motor neurons degeneration. However, associated effects on motor and extramotor brain networks are largely unknown. Particularly, neuropathological findings suggest that ALS not only affects the frontotemporal network but rather is part of a wide clinicopathological spectrum of brain disorders known as TAR-DNA binding protein 43 (TDP-43) proteinopathies. This paper reviews the current state of knowledge concerning the neuropsychological and neuropathological sequelae of TDP-43 proteinopathies, with special focus on the neuroimaging findings associated with cognitive change in ALS.
Myositic Type of Idiopathic Orbital Pseudotumor in a 4-Year-Old Child: A Case Report
Authors: Bakan Selim , Bakan Ayse Ahsen , Cingu Abdullah Kursat , Beker Acay Mehtap , Gocmez Ahmet , Elbeyli Ahmet , Sencer Serra
Published: June 2012

Idiopathic orbital pseudotumor is a benign, noninfectious, and nonneoplastic disease with unknown cause. It is the third most common orbital disease after thyroid orbitopathy and lymphoproliferative disorder. Idiopathic orbital pseudotumor is extremely rare in pediatric age group and may cause real diagnostic problems. This paper describes a 4-year-old girl who presented with sudden ptosis in the right eye and swollen eyelid. She recovered completely with high-dose steroid therapy. We report clinical and magnetic resonance imaging findings of orbital myositis, which is a rare subtype of idiopathic orbital pseudotumor in children and needs to be differentiated from other orbital disease especially malignancy.
Failure Assessment Methodologies for Pressure-Retaining Components under Severe Accident Loading
Authors: Arndt J. , Grebner H. , Sievers J.
Published: June 2012

During postulated high-pressure core melt accident scenarios, temperature values of more than 800°C can be reached in the reactor coolant line and the surge line of a pressurised water reactor (PWR), before the bottom of the reactor pressure vessel experiences a significant temperature increase due to core melting. For the assessment of components of the primary cooling circuit, two methods are used by GRS. One is the simplified method ASTOR (approximated structural time of rupture). This method employs the hypothesis of linear damage accumulation for modeling damage progression. A failure time surface which is generated by structural finite element (FE) analysis of varying pressure and temperature loads serves as a basis for estimations of failure times. The second method is to perform thermohydraulic and structure mechanic calculations for the accident scenario under consideration using complex calculation models. The paper shortly describes both assessment procedures. Validation of the ASTOR method concerning a large-scale test on a pipe section with geometric properties similar to a reactor coolant line is presented as well as severe accident scenarios investigated with both methods.
Electrospinning Preparation and Photocatalytic Activity of Porous TiO2 Nanofibers
Authors: Liu Shanhu , Liu Baoshun , Nakata Kazuya , Ochiai Tsuyoshi , Murakami Taketoshi , Fujishima Akira
Published: June 2012

Porous TiO2 nanofibers were prepared via a facile electrospinning method. The carbon nanospheres were mixed with the ethanol solution containing both poly(vinylpyrrolidone) and titanium tetraisopropoxide for electrospinning; and subsequent calcination of as‐spun nanofibers led to thermal decomposition of carbon nanospheres, leaving behind pores in the TiO2 nanofibers. The morphology and phase structure of the products were investigated with scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X‐ray diffraction (XRD). Furthermore, the photocatalytic activity of porous TiO2 nanofibers was evaluated by photodecomposition of methylene blue under UV light. Results showed that the porous TiO2 nanofibers have higher surface area and enhanced photocatalysis activity, compared to nonporous TiO2 nanofibers.
IgG4-Related Lymphadenopathy
Authors: Sato Yasuharu , Yoshino Tadashi
Published: June 2012

Lymphadenopathy is frequently observed in patients with immunoglobulin G4-related disease (IgG4-RD) and sometimes appears as the first manifestation of the disease. The diagnosis of IgG4-related lymphadenopathy is complicated owing to a great histological diversity, with at least 5 histological subtypes. Indeed, lymph node biopsy may be performed under the suspicion that the lymphadenopathy is a malignant lymphoma or other lymphoproliferative disorder. The diagnosis of IgG4-RD is characterized by both elevated serum IgG4 (>135?mg/dL) and histopathological features, including a dense lymphoplasmacytic infiltrate rich in IgG4+plasma cells (IgG4+/IgG+plasma cell ratio >40%). However, patients with hyper-interleukin (IL-) 6 syndromes such as multicentric Castleman’s disease, rheumatoid arthritis, and other immune-mediated conditions frequently show lymph node involvement and often fulfill the diagnostic criteria for IgG4-RD. Owing to these factors, IgG4-RD cannot be differentiated from hyper-IL-6 syndromes on the basis of histological findings alone. Laboratory analyses are crucial to differentiate between the 2 diseases. Hyper-IL-6 syndromes are characterized by elevated serum levels of IgG, IgA, IgM, and C-reactive protein (CRP); thrombocytosis; anemia; hypoalbuminemia; hypocholesterolemia. In contrast, IgG4-RD does not share any of these characteristics. Therefore, the diagnosis of IgG4-RD requires not only pathological findings but also clinical and laboratory analyses.
Triggering Apoptotic Death of Human Malignant Melanoma A375.S2 Cells by Bufalin: Involvement of Caspase Cascade-Dependent and Independent Mitochondrial Signaling Pathways
Authors: Hsiao Yu-Ping , Yu Chun-Shu , Yu Chien-Chih , Yang Jai-Sing , Chiang Jo-Hua , Lu Chi-Cheng , Huang Hui-Ying , Tang Nou-Ying , Yang Jen-Hung , Huang An-Cheng , Chung Jing-Gung
Published: June 2012

Bufalin was obtained from the skin and parotid venom glands of toad and has been shown to induce cytotoxic effects in various types of cancer cell lines, but there is no report to show that whether bufalin affects human skin cancer cells. The aim of this investigation was to study the effects of bufalin on human malignant melanoma A375.S2 cells and to elucidate possible mechanisms involved in induction of apoptosis. A375.S2 cells were treated with different concentrations of bufalin for a specific time period and investigated for effects on apoptotic analyses. Our results indicated that cells after exposure to bufalin significantly decreased cell viability, and induced cell morphological changes and chromatin condensation in a concentration-dependent manner. Flow cytometric assays indicated that bufalin promoted ROS productions, loss of mitochondrial membrane potential (ΔΨm), intracellular Ca2+release, and nitric oxide (NO) formations in A375.S2 cells. Additionally, the apoptotic induction of bufalin on A375.S2 cells resulted from mitochondrial dysfunction-related responses (disruption of theΔΨmand releases of cytochromec, AIF, and Endo G), and activations of caspase-3, caspase-8 and caspase-9 expressions. Based on those observations, we suggest that bufalin-triggered apoptosis in A375.S2 cells is correlated with extrinsic- and mitochondria-mediated multiple signal pathways.
A New Proof to the Necessity of a Second Moment Stability Condition of Discrete‐Time Markov Jump Linear Systems with Real States
Authors: Ling Qiang , Deng Haojiang
Published: June 2012

This paper studies the second moment stability of a discrete‐time jump linear system with real states and the system matrix switching in a Markovian fashion. A sufficient stability condition was proposed by Fang and Loparo (2002), which only needs to check the eigenvalues of a deterministic matrix and is much more computationally efficient than other equivalent conditions. The proof to the necessity of that condition, however, is a challenging problem. In the paper by Costa and Fragoso (2004), a proof was given by extending the state domain to the complex space. This paper proposes an alternative necessity proof, which does not need to extend the state domain. The proof in this paper demonstrates well the essential properties of the Markov jump systems and achieves the desired result in the real state space.
Notch Signaling during Oogenesis inDrosophila melanogaster
Authors: Xu Jingxia , Gridley Thomas
Published: June 2012

The Notch signaling pathway is an evolutionarily conserved intercellular signaling mechanism that is required for embryonic development, cell fate specification, and stem cell maintenance. Discovered and studied initially inDrosophila melanogaster, the Notch pathway is conserved and functionally active throughout the animal kingdom. In this paper, we summarize the biochemical mechanisms of Notch signaling and describe its role in regulating one particular developmental pathway, oogenesis inDrosophila.
A Regularity Criterion for the Navier‐Stokes Equations in the Multiplier Spaces
Authors: Zhu Xiang′ou
Published: June 2012

We exhibit a regularity condition concerning the pressure gradient for the Navier‐Stokes equations in a special class. It is shown that if the pressure gradient belongs to , where is the multipliers between Sobolev spaces whose definition is given later for 0 < r < 1, then the Leray‐Hopf weak solution to the Navier‐Stokes equations is actually regular.
Total Pelvic Exenteration for Gynecologic Malignancies
Authors: Diver Elisabeth J. , Rauh-Hain J. Alejandro , del Carmen Marcela G.
Published: June 2012

Total pelvic exenteration (PE) is a radical operation, involving en bloc resection of pelvic organs, including reproductive structures, bladder, and rectosigmoid. In gynecologic oncology, it is most commonly indicated for the treatment of advanced primary or locally recurrent cancer. Careful patient selection and counseling are of paramount importance when considering someone for PE. Part of the evaluation process includes comprehensive assessment to exclude unresectable or metastatic disease. PE can be curative for carefully selected patients with gynecologic cancers. Major complications can be seen in as many as 50% of patients undergoing PE, underscoring the need to carefully discuss risks and benefits of this procedure with patients considering exenterative surgery.
Estimation for Non-Gaussian Locally Stationary Processes with Empirical Likelihood Method
Authors: Ogata Hiroaki
Published: June 2012

An application of the empirical likelihood method to non-Gaussian locally stationary processes is presented. Based on the central limit theorem for locally stationary processes, we give the asymptotic distributions of the maximum empirical likelihood estimator and the empirical likelihood ratio statistics, respectively. It is shown that the empirical likelihood method enables us to make inferences on various important indices in a time series analysis. Furthermore, we give a numerical study and investigate a finite sample property.
Sickling Cells, Cyclic Nucleotides, and Protein Kinases: The Pathophysiology of Urogenital Disorders in Sickle Cell Anemia
Authors: Claudino Mário Angelo , Fertrin Kleber Yotsumoto
Published: June 2012

Sickle cell anemia is one of the best studied inherited diseases, and despite being caused by a single point mutation in theHBBgene, multiple pleiotropic effects of the abnormal hemoglobin S production range from vaso-occlusive crisis, stroke, and pulmonary hypertension to osteonecrosis and leg ulcers. Urogenital function is not spared, and although priapism is most frequently remembered, other related clinical manifestations have been described, such as nocturia, enuresis, increased frequence of lower urinary tract infections, urinary incontinence, hypogonadism, and testicular infarction. Studies on sickle cell vaso-occlusion and priapism using bothin vitroandin vivomodels have shed light on the pathogenesis of some of these events. The authors review what is known about the deleterious effects of sickling on the genitourinary tract and how the role of cyclic nucleotides signaling and protein kinases may help understand the pathophysiology underlying these manifestations and develop novel therapies in the setting of urogenital disorders in sickle cell disease.
Bounding the Practical Error of Path Loss Models
Authors: Phillips Caleb , Sicker Douglas , Grunwald Dirk
Published: June 2012

We seek to provide practical lower bounds on the prediction accuracy of path loss models. We describe and implement 30 propagation models of varying popularity that have been proposed over the last 70 years. Our analysis is performed using a large corpus of measurements collected on production networks operating in the 2.4 GHz ISM, 5.8 GHz UNII, and 900 MHz ISM bands in a diverse set of rural and urban environments. We find that the landscape of path loss models is precarious: typical best-case performance accuracy of these models is on the order of 12–15 dB root mean square error (RMSE) and in practice it can be much worse. Models that can be tuned with measurements and explicit data fitting approaches enable a reduction in RMSE to 8-9 dB. These bounds on modeling error appear to be relatively constant, even in differing environments and at differing frequencies. Based on our findings, we recommend the use of a few well-accepted and well-performing standard models in scenarios wherea prioripredictions are needed and argue for the use of well-validated, measurement-driven methods whenever possible.
Kinetic Modeling of the Mitochondrial Energy Metabolism of Neuronal Cells: The Impact of Reducedα-Ketoglutarate Dehydrogenase Activities on ATP Production and Generation of Reactive Oxygen Species
Authors: Berndt Nikolaus , Bulik Sascha , Holzhütter Hermann-Georg
Published: June 2012

Reduced activity of brain α-ketoglutarate dehydrogenase complex (KGDHC) occurs in a number of neurodegenerative diseases like Parkinson's disease and Alzheimer's disease. In order to quantify the relation between diminished KGDHC activity and the mitochondrial ATP generation, redox state, transmembrane potential, and generation of reactive oxygen species (ROS) by the respiratory chain (RC), we developed a detailed kinetic model. Model simulations revealed a threshold-like decline of the ATP production rate at about 60% inhibition of KGDHC accompanied by a significant increase of the mitochondrial membrane potential. By contrast, progressive inhibition of the enzyme aconitase had only little impact on these mitochondrial parameters. As KGDHC is susceptible to ROS-dependent inactivation, we also investigated the reduction state of those sites of the RC proposed to be involved in ROS production. The reduction state of all sites except one decreased with increasing degree of KGDHC inhibition suggesting an ROS-reducing effect of KGDHC inhibition. Our model underpins the important role of reduced KGDHC activity in the energetic breakdown of neuronal cells during development of neurodegenerative diseases.
Generation of Biotechnology-DerivedFlavobacterium columnareGhosts by PhiX174 GeneE-Mediated Inactivation and the Potential as Vaccine Candidates against Infection in Grass Carp
Authors: Zhu Wenxing , Yang Guiwen , Zhang Yuyu , Yuan Jinduo , An Liguo
Published: June 2012

Flavobacterium columnareis a bacterial pathogen causing high mortality rates for many freshwater fish species. Fish vaccination with a safe and effective vaccine is a potential approach for prevention and control of fish disease. Here, in order to produce bacterial ghost vaccine, a specificFlavobacteriumlysis plasmid pBV-E-cat was constructed by cloning PhiX174 lysis geneEand thecatgene with the promoter ofF. columnareinto the prokaryotic expression vector pBV220. The plasmid was successfully electroporated into the strainF. columnareG4cpN22 after curing of its endogenous plasmid.F. columnareG4cpN22 ghosts (FCGs) were generated for the first time by geneE-mediated lysis, and the vaccine potential of FCG was investigated in grass carp (Ctenopharyngodon idellus) by intraperitoneal route. Fish immunized with FCG showed significantly higher serum agglutination titers and bactericidal activity than fish immunized with FKC or PBS. Most importantly, after challenge with the parent strain G4, the relative percent survival (RPS) of fish in FCG group (70.9%) was significantly higher than FKC group (41.9%). These results showed that FCG could confer immune protection againstF. columnareinfection. As a nonliving whole cell envelope preparation, FCG may provide an ideal alternative to pathogen-based vaccines against columnaris in aquaculture.
Development and Validation of Stability-Indicating GC-FID Method for the Quantitation of Memantine Hydrochloride and Its Nonchromophoric Impurities in Bulk and Pharmaceutical Dosages
Authors: Jadhav Sanjay A. , Landge Shashikant B. , Niphade Navanath C. , Bembalkar Saroj R. , Mathad Vijayavitthal T.
Published: June 2012

A stability-indicating method has been developed and validated for the quantitative determination of memantine hydrochloride and its nonchromophoric impurities in drug substance and drug product using gas chromatography coupled with flame ionization detector (GC-FID). The stability-indicating nature of the method has been proved by establishing peak purity and confirming the mass balance of all samples by subjecting them to stress conditions like hydrolysis, oxidation, photolysis, and thermal degradation studies. The chromatographic separation was performed on a fused silica capillary (HP-5, 30 meter, 0.32 mm and 0.25 μm film thickness) column. The method validation results indicate that the method has acceptable specificity, accuracy, linearity, precision, robustness, and high sensitivity with detection limits and quantitation limits ranging from 0.001% to 0.01% and 0.004% to 0.03%, respectively. The effectiveness of the technique was demonstrated by analysis of different bulk sample of Memantine hydrochloride. The proposed GC-FID method was also found to be specific and selective for the analysis of commercial formulation samples.
The Effects of New Alibernet Red Wine Extract on Nitric Oxide and Reactive Oxygen Species Production in Spontaneously Hypertensive Rats
Authors: Kondrashov Alexey , Vranková Stanislava , Dovinová Ima , Ševčík Rudolf , Parohová Jana , Barta Andrej , Pecháňová Olga , Kovacsová Maria
Published: June 2012

We aimed to perform a chemical analysis of both Alibernet red wine and an alcohol-free Alibernet red wine extract (AWE) and to investigate the effects of AWE on nitric oxide and reactive oxygen species production as well as blood pressure development in normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHRs). Total antioxidant capacity together with total phenolic and selected mineral content was measured in wine and AWE. Young 6-week-old male WKY and SHR were treated with AWE (24,2 mg/kg/day) for 3 weeks. Total NOS and SOD activities, eNOS and SOD1 protein expressions, and superoxide production were determined in the tissues. Both antioxidant capacity and phenolic content were significantly higher in AWE compared to wine. The AWE increased NOS activity in the left ventricle, aorta, and kidney of SHR, while it did not change NOS activity in WKY rats. Similarly, increased SOD activity in the plasma and left ventricle was observed in SHR only. There were no changes in eNOS and SOD1 expressions. In conclusion, phenolics and minerals included in AWE may contribute directly to increased NOS and SOD activities of SHR. Nevertheless, 3 weeks of AWE treatment failed to affect blood pressure of SHR.
Characterization of the Equilibrium Strategy of Fuzzy Bimatrix Games Based on L‐R Fuzzy Variables
Authors: Li Cun-lin
Published: June 2012

This paper deals with bimatrix games in uncertainty environment based on several types of ordering, which Maeda proposed. But Maeda’s models was just made based on symmetrical triangle fuzzy
variable. In this paper, we generalized Maeda’s model to the non‐symmetrical environment. In other words, we investigated the fuzzy bimatrix games based on nonsymmetrical L‐R fuzzy variables. Then the pseudoinverse of a nonconstant monotone function was given and the concept of crisp parametric bimatrix games was introduced. At last, the existence condition of Nash equilibrium strategies of the fuzzy bimatrix games is proposed and (weak) Pareto equilibrium of the fuzzy bimatrix games was obtained through the Nash equilibrium of the crisp parametric bimatrix.
Development of -N4-NIM for Molecular Imaging of Tumor Hypoxia
Authors: Ali Mohammad S. , Kong Fan-Lin , Rollo Alex , Mendez Richard , Kohanim Saady , Smith Daniel Lee , Yang David J.
Published: June 2012

The nitro group of 2-nitroimidazole (NIM) enters the tumor cells and is bioreductively activated and fixed in the hypoxia cells. 1,4,8,11-tetraazacyclotetradecane (N4) has shown to be a stable chelator for . The present study was aimed to develop -cyclam-2-nitroimidazole (-N4-NIM) for tumor hypoxia imaging. N4-NIM precursor was synthesized by reacting N4-oxalate and 1,3-dibromopropane-NIM, yielded 14% (total synthesis). Cell uptake of -N4-NIM and -N4 was obtained in 13762 rat mammary tumor cells and mesothelioma cells in 6-well plates. Tissue distribution of -N4-NIM was evaluated in breast-tumor-bearing rats at 0.5–4 hrs. Tumor oxygen tension was measured using an oxygen probe. Planar imaging was performed in the tumor-bearing rat and rabbit models. Radiochemical purity of -N4-NIM was >96% by HPLC. Cell uptake of -N4-NIM was higher than -N4 in both cell lines. Biodistribution of -N4-NIM showed increased tumor-to-blood and tumor-to-muscle count density ratios as a function of time. Oxygen tension in tumor tissue was 6–10 mmHg compared to 40–50 mmHg in normal muscle tissue. Planar imaging studies confirmed that the tumors could be visualized clearly with -N4-NIM in animal models. Efficient synthesis of N4-NIM was achieved. -N4-NIM is a novel hypoxic probe and may be useful in evaluating cancer therapy.
Low-Level Laser Therapy and Calcitonin in Bone Repair: Densitometric Analysis
Authors: Ribeiro Tatiana Pinto , Nascimento Simone Bustamante , Cardoso Claúdia Alessandra , Hage Raduan , Almeida Janete Dias , Arisawa Emilia Angela Loschiavo
Published: June 2012

The aim of this work was to evaluate the association of low-level laser therapy (LLLT, 830 nm) and calcitonin in bone repair considering that bone healing remains a challenge to health professionals. Calcitonin has antiosteoclastic action and LLLT is a treatment that uses low-level lasers or light-emitting diodes to alter cellular function. Both are used to improve bone healing. Densitometry is a clinical noninvasive valuable tool used to evaluate bone mineral density (BMD). Sixty male rats were submitted to bone defect with a trephine bur, randomly divided into four groups of 15 animals each: control (C); synthetic salmon calcitonin (Ca); LLLT (La); LLLT combined with calcitonin (LaCa). Animals from Ca and LaCa received 2 UI/Kg synthetic salmon calcitonin intramuscularly on alternate days after surgery. Animals from groups La and LaCa were treated with infrared LLLT (830 nm, 10 mW, 20 J/cm2, 6 s, contact mode). Five animals from each group were euthanized 7, 14, and 21 days after surgery and bone defects were analyzed by densitometry. Statistical analysis showed a significant difference in BMD values in LaCa group at 7 and 21 days (). The results of the densitometric study showed that LLLT (830 nm) combined with calcitonin improved bone repair.
Mixed Initial-Boundary Value Problem for Telegraph Equation in Domain with Variable Borders
Authors: Ostapenko V. A.
Published: June 2012

Mixed initial-boundary value problem for telegraph equation in domain with variable borders is considered. On one part of domain’s border are the boundary conditions of the first type, on other part of the boundary are set boundary conditions of the second type. Besides, the sizes of area are variable. The solution of such problem demands development of special methods. With the help of consecutive application of procedure of construction waves reflected from borders of domain, it is possible to obtain the solution of this problem in quadratures. In addition, for construction of the waves reflected from mobile border, it is necessary to apply the procedure specially developed for these purposes.
Epigenetic Changes in Response to Tai Chi Practice: A Pilot Investigation of DNA Methylation Marks
Authors: Ren Hua , Collins Veronica , Clarke Sandy J. , Han Jin-Song , Lam Paul , Clay Fiona , Williamson Lara M. , Andy Choo K. H.
Published: June 2012

Tai chi exercise has been shown to improve physiological and psychosocial functions, well-being, quality of life, and disease conditions. The biological mechanisms by which tai chi exerts its holistic effects remain unknown. We investigated whether tai chi practice results in positive epigenetic changes at the molecular level.Design. The DNA methylation profiles of sixty CpG-dinucleotide marks in female tai chi practitioners (N=237; 45–88 years old) who have been practising tai chi for three or more years were compared with those of age-matched control females (N=263) who have never practised tai chi.Results. Six CpG marks originating from three different chromosomes reveal a significant difference (P<0.05) between the two cohorts. Four marks show losses while two marks show gains in DNA methylation with age in the controls. In the tai chi cohort all six marks demonstrate significant slowing (by 5–70%) of the age-related methylation losses or gains observed in the controls, suggesting that tai chi practice may be associated with measurable beneficial epigenetic changes.Conclusions. The results implicate the potential use of DNA methylation as an epigenetic biomarker to better understand the biological mechanisms and the health and therapeutic efficacies of tai chi.
Self-Tuning Vibration Control of a Rotational Flexible Timoshenko Arm Using Neural Networks
Authors: Sasaki Minoru , Shimizu Toshimi , Inoue Yoshihiro , Book Wayne J.
Published: June 2012

A self-tuning vibration control of a rotational flexible arm using neural networks is presented. To the self-tuning control system, the control scheme consists of gain tuning neural networks and a variable-gain feedback controller. The neural networks are trained so as to make the root moment zero. In the process, the neural networks learn the optimal gain of the feedback controller. The feedback controller is designed based on Lyapunov's direct method. The feedback control of the vibration of the flexible system is derived by considering the time rate of change of the total energy of the system. This approach has the advantage over the conventional methods in the respect that it allows one to deal directly with the system's partial differential equations without resorting to approximations. Numerical and experimental results for the vibration control of a rotational flexible arm are discussed. It verifies that the proposed control system is effective at controlling flexible dynamical systems.
Förster Resonance Energy Transfer between Core/Shell Quantum Dots and Bacteriorhodopsin
Authors: Griep Mark H. , Winder Eric M. , Lueking Donald R. , Garrett Gregory A. , Karna Shashi P. , Friedrich Craig R.
Published: June 2012

An energy transfer relationship between core-shell CdSe/ZnS quantum dots (QDs) and the optical protein bacteriorhodopsin (bR) is shown, demonstrating a distance-dependent energy transfer with 88.2% and 51.1% of the QD energy being transferred to the bR monomer at separation distances of 3.5 nm and 8.5 nm, respectively. Fluorescence lifetime measurements isolate nonradiative energy transfer, other than optical absorptive mechanisms, with the effective QD excited state lifetime reducing from 18.0 ns to 13.3 ns with bR integration, demonstrating the Förster resonance energy transfer contributes to 26.1% of the transferred QD energy at the 3.5 nm separation distance. The established direct energy transfer mechanism holds the potential to enhance the bR spectral range and sensitivity of energies that the protein can utilize, increasing its subsequent photocurrent generation, a significant potential expansion of the applicability of bR in solar cell, biosensing, biocomputing, optoelectronic, and imaging technologies.
Cancer Network Disruption by a Single Molecule Inhibitor Targeting Both Histone Deacetylase Activity and Phosphatidylinositol 3-Kinase Signaling
Authors: Qian Changgeng , Lai Cheng-Jung , Bao Rudi , Wang Da-Gong , Wang Jing , Xu Guang-Xin , Atoyan Ruzanna , Qu Hui , Yin Ling , Samson Maria , Zifcak Brian , Ma Anna Wai See , DellaRocca Steven , Borek Mylissa , Zhai Hai-Xiao , Cai Xiong , Voi Maurizio
Published: June 2012

Purpose: Given that histone deacetylase (HDAC) inhibitors are known to induce multiple epigenetic modifications affecting signaling networks and act synergistically with phosphatidylinositol 3-kinase (PI3K) inhibitors, we developed a strategy to simultaneously inhibit HDACs and PI3K in cancer cells.

Experimental Design: We constructed dual-acting inhibitors by incorporating HDAC inhibitory functionality into a PI3K inhibitor pharmacophore. CUDC-907, a development candidate selected from these dual inhibitors, was evaluated in vitro and in vivo to determine its pharmacologic properties, anticancer activity, and mechanism of action.

Results: CUDC-907 potently inhibits class I PI3Ks as well as classes I and II HDAC enzymes. Through its integrated HDAC inhibitory activity, CUDC-907 durably inhibits the PI3K-AKT-mTOR pathway and compensatory signaling molecules such as RAF, MEK, MAPK, and STAT-3, as well as upstream receptor tyrosine kinases. CUDC-907 shows greater growth inhibition and proapoptotic activity than single-target PI3K or HDAC inhibitors in both cultured and implanted cancer cells.

Conclusions: CUDC-907 may offer improved therapeutic benefits through simultaneous, sustained disruption of multiple oncogenic signaling networks. Clin Cancer Res; 18(15); 4104–13. ©2012 AACR.
A Multicenter Phase I Trial of PX-866, an Oral Irreversible Phosphatidylinositol 3-Kinase Inhibitor, in Patients with Advanced Solid Tumors
Authors: Hong David S. , Bowles Daniel W. , Falchook Gerald S. , Messersmith Wells A. , George Goldy C. , O'Bryant Cindy L. , Vo Alex C. H. , Klucher Kevin , Herbst Roy S. , Eckhardt S. Gail , Peterson Scott , Hausman Diana F. , Kurzrock Razelle , Jimeno Antonio
Published: June 2012

Purpose: The objectives of the study were to evaluate the maximum tolerated dose (MTD), safety, pharmacodynamics, pharmacokinetics, and antitumor activity of PX-866 in patients with incurable cancers.

Experimental Design: This was a phase I, open-label, dose-escalation study. Drug was administered orally once per day either on an intermittent (arm 1; days 1–5 and 8–12 of a 28-day cycle) or continuous (arm 2; days 1–28 of a 28-day cycle) schedule. Additional patients were treated at the arm 2 MTD in a food effects substudy.

Results: Eighty-four patients were treated in the arm 1 (n = 51), arm 2 (n = 20), and food effects (n = 13) cohorts. The most frequent study drug–related adverse events were gastrointestinal disorders (69.0%), with diarrhea being the most common (48.8%). The MTD was 12 and 8 mg for arm 1 and 2, respectively. The dose-limiting toxicities (DLT) consisted of grade III diarrhea (n = 3) and grade III elevated aspartate aminotransferase (AST; n = 1). The pharmacokinetics profile was dose proportional, with no evidence of drug accumulation. PX-866–associated inhibition of platelet pAKTSER473 was observed at the arm 2 MTD. The best response per Response Evaluation Criteria in Solid Tumors (RECIST) was stable disease in 22% of evaluable patients in arm 1, 53% in arm 2, and 11% in the food effects cohort. Eight patients were on study for 4 or more months.

Conclusions: This first-in-human study shows that PX-866, an irreversible small-molecule inhibitor of phosphatidylinositol 3-kinase (PI3K), was well tolerated and was associated with prolonged stable disease, particularly when using a continuous dosing schedule. Clin Cancer Res; 18(15); 4173–82. ©2012 AACR.