bluuebunny/crossref_metadata_2025 huggingface dataset:
EFFECT OF A LOCALLY REPULSIVE INTERACTION ON s-WAVE SUPERCONDUCTORS
Authors: BRU J.-B , DE SIQUEIRA PEDRA W.
Published: April 2010

The thermodynamic impact of the Coulomb repulsion on s-wave superconductors is analyzed via a rigorous study of equilibrium and ground states of the strong coupling BCS-Hubbard Hamiltonian. We show that the one-site electron repulsion can favor superconductivity at fixed chemical potential by increasing the critical temperature and/or the Cooper pair condensate density. If the one-site repulsion is not too large, a first or a second order superconducting phase transition can appear at low temperatures. The Meißner effect is shown to be rather generic but coexistence of superconducting and ferromagnetic phases is also shown to be feasible, for instance, near half-filling and at strong repulsion. Our proof of a superconductor-Mott insulator phase transition implies a rigorous explanation of the necessity of doping insulators to create superconductors. These mathematical results are consequences of "quantum large deviation" arguments combined with an adaptation of the proof of Størmer's theorem [1] to even states on the CAR algebra.
ON SEMICLASSICAL AND UNIVERSAL INEQUALITIES FOR EIGENVALUES OF QUANTUM GRAPHS
Authors: DEMIREL SEMRA , HARRELL EVANS M.
Published: April 2010

We study the spectra of quantum graphs with the method of trace identities (sum rules), which are used to derive inequalities of Lieb–Thirring, Payne–Pólya–Weinberger, and Yang types, among others. We show that the sharp constants of these inequalities and even their forms depend on the topology of the graph. Conditions are identified under which the sharp constants are the same as for the classical inequalities. In particular, this is true in the case of trees. We also provide some counterexamples where the classical form of the inequalities is false.
PREDICTION OF PARKINSON'S DISEASE TREMOR ONSET USING A RADIAL BASIS FUNCTION NEURAL NETWORK BASED ON PARTICLE SWARM OPTIMIZATION
Authors: WU DEFENG , WARWICK KEVIN , MA ZI , GASSON MARK N. , BURGESS JONATHAN G. , PAN SONG , AZIZ TIPU Z.
Published: April 2010

Deep Brain Stimulation (DBS) has been successfully used throughout the world for the treatment of Parkinson's disease symptoms. To control abnormal spontaneous electrical activity in target brain areas DBS utilizes a continuous stimulation signal. This continuous power draw means that its implanted battery power source needs to be replaced every 18–24 months. To prolong the life span of the battery, a technique to accurately recognize and predict the onset of the Parkinson's disease tremors in human subjects and thus implement an on-demand stimulator is discussed here. The approach is to use a radial basis function neural network (RBFNN) based on particle swarm optimization (PSO) and principal component analysis (PCA) with Local Field Potential (LFP) data recorded via the stimulation electrodes to predict activity related to tremor onset. To test this approach, LFPs from the subthalamic nucleus (STN) obtained through deep brain electrodes implanted in a Parkinson patient are used to train the network. To validate the network's performance, electromyographic (EMG) signals from the patient's forearm are recorded in parallel with the LFPs to accurately determine occurrences of tremor, and these are compared to the performance of the network. It has been found that detection accuracies of up to 89% are possible. Performance comparisons have also been made between a conventional RBFNN and an RBFNN based on PSO which show a marginal decrease in performance but with notable reduction in computational overhead.
IDENTIFICATION OF NONLINEAR OSCILLATORY ACTIVITY EMBEDDED IN BROADBAND NEURAL SIGNALS
Authors: VEJMELKA MARTIN , PALUŠ MILAN , ŠUŠMÁKOVÁ KRISTÍNA
Published: April 2010

Oscillatory phenomena in the brain activity and their synchronization are frequently studied using mathematical models and analytic tools derived from nonlinear dynamics. In many experimental situations, however, neural signals have a broadband character and if oscillatory activity is present, its dynamical origin is unknown. To cope with these problems, a framework for detecting nonlinear oscillatory activity in broadband time series is presented. First, a narrow-band oscillatory mode is extracted from a broadband background. Second, it is tested whether the extracted mode is significantly different from linearly filtered noise, modelled as a linear stochastic process possibly passed through a static nonlinear transformation. If a nonlinear oscillatory mode is positively detected, further analysis using nonlinear approaches such as the phase synchronization analysis can potentially bring new information. For linear processes, however, standard approaches such as the coherence analysis are more appropriate and provide sufficient description of underlying interactions with smaller computational effort. The method is illustrated in a numerical example and applied to analyze experimentally obtained human EEG time series from a sleeping subject.
INDIRECT ADAPTIVE CONTROL OF UNKNOWN MULTI VARIABLE NONLINEAR SYSTEMS WITH PARAMETRIC AND DYNAMIC UNCERTAINTIES USING A NEW NEURO-FUZZY SYSTEM DESCRIPTION
Authors: THEODORIDIS DIMITRIOS , BOUTALIS YIANNIS , CHRISTODOULOU MANOLIS
Published: April 2010

The indirect adaptive regulation of unknown nonlinear dynamical systems with multiple inputs and states (MIMS) under the presence of dynamic and parameter uncertainties, is considered in this paper. The method is based on a new neuro-fuzzy dynamical systems description, which uses the fuzzy partitioning of an underlying fuzzy systems outputs and high order neural networks (HONN's) associated with the centers of these partitions. Every high order neural network approximates a group of fuzzy rules associated with each center. The indirect regulation is achieved by first identifying the system around the current operation point, and then using its parameters to device the control law. Weight updating laws for the involved HONN's are provided, which guarantee that, under the presence of both parameter and dynamic uncertainties, both the identification error and the system states reach zero, while keeping all signals in the closed loop bounded. The control signal is constructed to be valid for both square and non square systems by using a pseudoinverse, in Moore-Penrose sense. The existence of the control signal is always assured by employing a novel method of parameter hopping instead of the conventional projection method. The applicability is tested on well known benchmarks.
A DISCRETE-TIME RECURRENT NEUROFUZZY NETWORK FOR BLACK-BOX MODELING OF INSULIN DYNAMICS IN DIABETIC TYPE-1 PATIENTS
Authors: GONZÁLEZ-OLVERA MARCOS A. , GALLARDO-HERNÁNDEZ ANA G. , TANG YU , REVILLA-MONSALVE MARIA CRISTINA , ISLAS-ANDRADE SERGIO
Published: April 2010

In this work we present a data-driven modeling of the insulin dynamics in different in silico patients using a recurrent neural network with output feedback. The inputs for the identification is the rate of insulin (μU / dl / min) applied to the patient, and blood glucose concentration. The output is insulin concentration (μU / ml) present in the blood stream. Once completed the off-line modeling, this model could be used for on-line monitoring of the insulin concentration for a better treatment. The learning law of the recurrent neural network is inspired by adaptive observer theory, and proven to be convergent in the parameters and stable in the Lyapunov sense, even with only 13 samples available. Simulation results are shown to validate the presented modeling.
CHAOTIC SYNCHRONIZATION OF HYBRID STATE ON COMPLEX NETWORKS
Authors: NIAN FUZHONG , WANG XINGYUAN
Published: April 2010

In real application, the measurable physical quantities always are hybrid states instead of the states itself. From the point of view of practice, the chaotic synchronization of hybrid state on complex networks was investigated in this paper. Compared with general synchronization method, a new error dynamic system was constructed. And the controller which is determined by the error of hybrid states and hybrid matrix was designed. The theoretical analysis and proof were given, as well as numerical simulations. The results indicate that our method is effective and feasible.
MASS RATIO OF W AND Z BOSONS IN SU(5) GAUGE-HIGGS UNIFICATION
Authors: UEKUSA NOBUHIRO
Published: April 2010

We study the mass ratio of W and Z bosons in an SU(5) gauge-Higgs unification model with the left–right symmetry remaining locally for boundary conditions and with no scalar fields except for the extra-dimensional component of gauge bosons. We find that there are a variety of boundary conditions to yield distinct values of the mass ratio.
QUASIPARTICLE LIFETIME OF A TWO-DIMENSIONAL ELECTRON GAS
Authors: ESMAILIAN A. , ABOLHASSANI M. R.
Published: April 2010

We calculate the inelastic scattering lifetime of an excited quasiparticle at low (or zero) temperature, due to electron-electron interaction for a clean two-dimensional (2D) electron gas within the random-phase approximation (RPA) and compare it with the lifetime measured from the tunnelling experiment. Our result obtained by direct numerical calculation increases the electron relaxation rate considerably, hence decreases the size of discrepancy (roughly by a factor of 4) between theory and experiment which exists in the literature. We also show that including local-field factors in the effective electron interaction yields small correction to the result calculated within the RPA for rs ~ 1, corresponding to electron density of the sample in the tunnelling experiment. This result suggests that the RPA is reasonably accurate for a 2D electron gas in weak coupling limit.
PHASE TRANSFORMATIONS DURING HEATING OF AMORPHOUS/NANOCRYSTALLINE Ni–Ti POWDERS
Authors: VERDIAN M. M. , SALEHI M. , RAEISSI K.
Published: April 2010

Amorphous/nanocrystalline 50 Ni –50 Ti powders were synthesized from elemental Ti and Ni powders by solid state synthesis utilizing low energy mechanical alloying with times up to 100 h. The produced powders were investigated by X-ray diffraction and differential scanning calorimetry to study phase transformations that occurred during heating in the calorimeter. It was found that at the first stage of the heating process, a disordered NiTi phase was formed at temperature of about 400°C. Further investigations indicated that this phase transformed into the Ni 3 Ti and Ti 2 Ni intermetallic compounds after heating at a temperature of about 800°C.
TWO-TEMPERATURE MODEL OF NONEQUILIBRIUM ELECTRON RELAXATION: A REVIEW
Authors: SINGH NAVINDER
Published: April 2010

The present paper is a review of the phenomena related to nonequilibrium electron relaxation in bulk and nano-scale metallic samples. The workable Two-Temperature Model (TTM) based on Boltzmann–Bloch–Peierls kinetic equation has been applied to study the ultra-fast (femto-second) electronic relaxation in various metallic systems. The advent of new ultra-fast (femto-second) laser technology and pump-probe spectroscopy has produced wealth of new results for micro- and nano-scale electronic technology. The aim of this paper is to clarify the TTM, conditions of its validity and nonvalidity, its modifications for nano-systems, to sum-up the progress, and to point out open problems in this field. We also give a phenomenological integro-differential equation for the kinetics of nondegenerate electrons that goes beyond the TTM.
RESONANT ULTRASOUND SPECTROSCOPY: OVERVIEW AND APPLICATIONS
Authors: DRYMIOTIS FIVOS R.
Published: April 2010

The study of mechanical resonances can provide a plethora of information concerning the physical behavior of a system, both at the macroscopic and microscopic level. Resonant ultrasound spectroscopy (RUS), through advances in electronics and computational power, has evolved into the premier method for the precise study of mechanical resonances of solids. The range of applications is diverse, and as the popularity of RUS continues to increase, so will its spectrum of applications. This article contains an overview of the method, a short discussion of elastic constants, elastic moduli, and a survey of some successful RUS applications.
GENERALIZED WATCHMAN ROUTE PROBLEM WITH DISCRETE VIEW COST
Authors: WANG PENGPENG , KRISHNAMURTI RAMESH , GUPTA KAMAL
Published: April 2010

In this paper, we introduce a generalized version of the Watchman Route Problem (WRP) where the objective is to plan a continuous closed route in a polygon (possibly with holes) and a set of discrete viewpoints on the planned route such that every point on the polygon boundary is visible from at least one viewpoint. Each planned viewpoint has some associated cost. The total cost to minimize is a weighted sum of the view cost, proportional to the number of viewpoints, and the travel cost, the total length of the route. We call this problem the Generalized Watchman Route Problem or the GWRP. We tackle a restricted nontrivial (it remains NP-hard and log-inapproximable) version of GWRP where each polygon edge is entirely visible from at least one planned viewpoint. We call it Whole Edge Covering GWRP. The algorithm we propose first constructs a graph that connects O(n12) number of sample viewpoints in the polygon, where n is the number of polygon vertices; and then solves the corresponding View Planning Problem with Combined View and Traveling Cost, using an LP-relaxation based algorithm we introduced in [27, 29]. We show that our algorithm has an approximation ratio in the order of either the view frequency, defined as the maximum number of sample viewpoints that cover a polygon edge, or a polynomial of log n, whichever is smaller.
FINDING ALL DOOR LOCATIONS THAT MAKE A ROOM SEARCHABLE
Authors: KAMEDA TSUNEHIKO , ZHANG JOHN Z.
Published: April 2010

A room is a simple polygon with a prespecified point, called the door, on its boundary. Search starts at the door, in order to detect any intruder who was in the room at the time it started. Search may be conducted by two guards on the boundary who can detect any intruder that crosses the line connecting them, or by a single searcher with a flashlight, moving on the boundary. A room may or may not be searchable, depending on where the door is placed or no matter where the door is placed. The main contribution of this paper is an O(n log n) time algorithm for finding all intervals on the polygon boundary, if any, where the door can be placed for the resulting room to be searchable, where n is the number of sides of the given polygon.
DISSECTIONS OF POLYGONS INTO CONVEX POLYGONS
Authors: ŻAK ANDRZEJ
Published: April 2010

In this paper we present purely combinatorial conditions that allow us to recognize the topological equivalence (or non-equivalence) of two given dissections. Using a computer program based on this result, we are able to generate a set which contains all topologically non-equivalent dissections of a p0-gon into convex pi-gons, i = 1…n, where n, p0,…,pn are integers such that n ≥ 2, pi ≥ 3. By analyzing generated structures, we are able to find all (up to similarity) dissections of a given type. Since the number of topologically non-equivalent dissections is huge even when the number of parts is small, it is necessary to find additional combinatorial conditions depending on the type of sought dissections, which will allow us to exclude the majority of generated structures. We present such conditions for some special dissections of a triangle into triangles. Finally we prove two new results concerning perfect dissections of a triangle into similar triangles.
Role ofN-linked glycosylation in biosynthesis, trafficking, and function of the human glucagon-like peptide 1 receptor
Authors: Chen Quan , Miller Laurence J. , Dong Maoqing
Published: April 2010

The family B G protein-coupled glucagon-like peptide 1 (GLP-1) receptor is an important drug target for treatment of type 2 diabetes. Like other family members, the GLP-1 receptor is a glycosylated membrane protein that contains three potential sites for N-linked glycosylation within the functionally important extracellular amino-terminal domain. However, the roles for each potential site of glycosylation in receptor biosynthesis, trafficking, and function are not known. In this work, we demonstrated that tunicamycin inhibition of glycosylation of the GLP-1 receptor expressed in CHO cells interfered with biosynthesis and intracellular trafficking, thereby eliminating natural ligand binding. To further investigate the roles of each of the glycosylation sites, site-directed mutagenesis was performed to eliminate these sites individually and in aggregate. Our results showed that mutation of each of the glycosylation sites individually did not interfere with receptor expression on the cell surface, ligand binding, and biological activity. However, simultaneous mutation of two or three glycosylation sites resulted in almost complete loss of GLP-1 binding and severely impaired biological activity. Immunostaining studies demonstrated receptor biosynthesis but aberrant trafficking, with most of the receptor trapped in the endoplasmic reticulum and golgi compartments and little of the receptor expressed on the cell surface. Interestingly, surface expression, ligand binding, and biological activity of these mutants improved significantly when biosynthesis was slowed using low temperature (30°C). These data suggest that N-linked glycosylation of the GLP-1 receptor is important for its normal folding and trafficking to the cell surface.
Glutamine: precursor or nitrogen donor for citrulline synthesis?
Authors: Marini Juan C. , Didelija Inka Cajo , Castillo Leticia , Lee Brendan
Published: April 2010

Although glutamine is considered the main precursor for citrulline synthesis, the current literature does not differentiate between the contribution of glutamine carbon skeleton vs. nonspecific nitrogen (i.e., ammonia) and carbon derived from glutamine oxidation. To elucidate the role of glutamine and nonspecific nitrogen in the synthesis of citrulline, l-[2-15N]- and l-[5-15N]glutamine and15N-ammonium acetate were infused intragastrically in mice. The amino group of glutamine labeled the three nitrogen groups of citrulline almost equally. The amido group and ammonium acetate labeled the ureido and amino groups of citrulline, but not the δ-nitrogen. D5-glutamine also infused in this arm of the study, which traces the carbon skeleton of glutamine, was utilized poorly, accounting for only 0.2–0.4% of the circulating citrulline. Dietary glutamine nitrogen (both N groups) incorporation was 25-fold higher than the incorporation of its carbon skeleton into citrulline. To investigate the relative contributions of the carbon skeleton and nonspecific carbon of glutamine, arginine, and proline to citrulline synthesis, U-13Cntracers of these amino acids were infused intragastrically. Dietary arginine was the main precursor for citrulline synthesis, accounting for ∼40% of the circulating citrulline. Proline contribution was minor (3.4%), and glutamine was negligible (0.4%). However, the glutamine tracer resulted in a higher enrichment in the ureido group, indicating incorporation of nonspecific carbon from glutamine oxidation into carbamylphosphate used for citrulline synthesis. In conclusion, dietary glutamine is a poor carbon skeleton precursor for the synthesis of citrulline, although it contributes both nonspecific nitrogen and carbon to citrulline synthesis.
The many facets of PPARγ: novel insights for the skeleton
Authors: Kawai Masanobu , Sousa Kyle M. , MacDougald Ormond A. , Rosen Clifford J.
Published: April 2010

Peroxisome proliferator-activated receptor-γ (PPARγ) is a nuclear receptor that functions as a master transcriptional regulator of adipocyte conversion. During PPARγ transactivation, multiple signaling pathways interact with one another, leading to the differentiation of both white and brown adipose tissue. Ligand activation of the PPARγ-RXR heterodimer complex also enhances insulin sensitivity, and this property has been heavily exploited to develop effective pharmacotherapies for the treatment of type 2 diabetes mellitus. PPARγ is also expressed in stem cells and plays a critical role in mesenchymal stromal cell differentiation and lineage determination events. The many facets of PPARγ activity within the bone marrow niche where adipocytes, osteoblasts, and hematopoietic cells reside make this molecule an attractive target for pharmacological investigation. Additional findings that osteoblasts can alter energy metabolism by influencing adiposity and insulin sensitivity, and observations of decreased bone turnover in diabetic subjects, underscore the contribution of the skeleton to systemic energy requirements. Studies into the role of PPARγ in skeletal acquisition and maintenance may lead to a better understanding of the molecular mechanisms governing stromal cell differentiation in the mesenchyme compartment and whether PPARγ activity can be manipulated to benefit skeletal remodeling events and energy metabolism.
LATS1 phosphorylates forkhead L2 and regulates its transcriptional activity
Authors: Pisarska Margareta D. , Kuo Fang-Ting , Bentsi-Barnes Ikuko K. , Khan Salma , Barlow Gillian M.
Published: April 2010

Forkhead L2 (FOXL2) is expressed in the ovary and acts as a transcriptional repressor of the steroidogenic acute regulatory (StAR) gene, a marker of granulosa cell differentiation. Human FOXL2 mutations that produce truncated proteins lacking the COOH terminus result in blepharophimosis/ptosis/epicanthus inversus (BPES) syndrome type I, which is associated with premature ovarian failure (POF). In this study, we investigated whether FOXL2's activity as a transcriptional repressor is regulated by phosphorylation. We found that FOXL2 is phosphorylated at a serine residue and, using yeast two-hybrid screening, identified LATS1 as a potential FOXL2-interacting protein. LATS1 is a serine/threonine kinase whose deletion in mice results in an ovarian phenotype similar to POF. Using coimmunoprecipitation and kinase assays, we confirmed that LATS1 binds to FOXL2 and demonstrated that LATS1 phosphorylates FOXL2 at a serine residue. Moreover, we found that FOXL2 and LATS1 are coexpressed in developing mouse gonads and in granulosa cells of small and medium follicles in the mouse ovary. Last, we demonstrated that coexpression with LATS1 enhances FOXL2's activity as a repressor of the StAR promoter, and this results from the kinase activity of LATS1. These results provide novel evidence that FOXL2 is phosphorylated by LATS1 and that this phosphorylation enhances the transcriptional repression of the StAR gene, a marker of granulosa cell differentiation. These data support our hypothesis that phosphorylation of FOXL2 may be a control mechanism regulating the rate of granulosa cell differentiation and hence, follicle maturation, and its dysregulation may contribute to accelerated follicular development and POF in BPES type I.
Dose-response downregulation within the span of single interpulse intervals
Authors: Keenan Daniel M. , Roelfsema Ferdinand , Veldhuis Johannes D.
Published: April 2010

Pituitary ACTH drives adrenal glucocorticoid (cortisol) pulses via a time-delayed asymptotic dose-response process. To test the postulate that ACTH stimulates cortisol secretion dynamically (unequally during the initiation and termination of a cortisol secretory burst), a mathematical formalism was developed in which dose-response hysteretic shifts were allowed, but not required, within the time evolution of ACTH-cortisol pulse pairs. A dual-waveform deconvolution model was used to quantify cortisol secretion rates and reconstruct ACTH concentration profiles in 28 healthy adults previously sampled every 10 min for 24 h in the unstressed state (8,120 measurements). ACTH concentration-cortisol secretion dose-response functions were then estimated in each subject 1) without hysteresis (base model) and with allowances for possible hysteresis in 2) ACTH potency, 3) adrenal sensitivity, and 4) ACTH efficacy. Model residual error was 40% lower in the potency and sensitivity models and 20% lower in the efficacy model than in the base model ( P < 0.001). Mean time shifts for inferable hysteretic inflection were model-independent, i.e., grand mean (95% confidence interval) 22 (12–39) min after the onset of a cortisol secretory burst. Half-maximally effective ACTH concentrations (EC50) differed before and after hysteretic inflection within individual pulses: 1) 9.4 and 54 ng/l in the potency model ( P < 0.001) and 2) 8.9 and 123 ng/l in the sensitivity model ( P < 0.001) compared with 16 ng/l in the no-hysteresis model ( P < 0.001). In the efficacy-shift model, estimated maximal ACTH drive varied by 17-fold within cortisol secretory bursts (from 22 to 1.3 nmol·l−1·min cortisol secretion−1, P < 0.001). The collective results introduce the basis for modeling the dynamics of rapid, reversible physiological downregulation within the span of single interpulse intervals in vivo. This construct should have utility in parsing mechanisms of physiological regulation in other integrative systems.
Removal of Movement Artifact From High-Density EEG Recorded During Walking and Running
Authors: Gwin Joseph T. , Gramann Klaus , Makeig Scott , Ferris Daniel P.
Published: April 2010

Although human cognition often occurs during dynamic motor actions, most studies of human brain dynamics examine subjects in static seated or prone conditions. EEG signals have historically been considered to be too noise prone to allow recording of brain dynamics during human locomotion. Here we applied a channel-based artifact template regression procedure and a subsequent spatial filtering approach to remove gait-related movement artifact from EEG signals recorded during walking and running. We first used stride time warping to remove gait artifact from high-density EEG recorded during a visual oddball discrimination task performed while walking and running. Next, we applied infomax independent component analysis (ICA) to parse the channel-based noise reduced EEG signals into maximally independent components (ICs) and then performed component-based template regression. Applying channel-based or channel-based plus component-based artifact rejection significantly reduced EEG spectral power in the 1.5- to 8.5-Hz frequency range during walking and running. In walking conditions, gait-related artifact was insubstantial: event-related potentials (ERPs), which were nearly identical to visual oddball discrimination events while standing, were visible before and after applying noise reduction. In the running condition, gait-related artifact severely compromised the EEG signals: stable average ERP time-courses of IC processes were only detectable after artifact removal. These findings show that high-density EEG can be used to study brain dynamics during whole body movements and that mechanical artifact from rhythmic gait events may be minimized using a template regression procedure.
Lack of carotid stiffening associated with MTHFR 677TT genotype in cardiorespiratory fit adults
Authors: Iemitsu Motoyuki , Murakami Haruka , Sanada Kiyoshi , Yamamoto Kenta , Kawano Hiroshi , Gando Yuko , Miyachi Motohiko
Published: April 2010

The TT genotype of C677T polymorphism in 5,10-methylenetetrahydrofolate reductase (MTHFR) induces elevation of homocysteine level and leads to atherosclerosis and arterial stiffening. Furthermore, cardiorespiratory fitness level is also associated with arterial stiffness. In the present study, a cross-sectional investigation of 763 Japanese men and women (18–70 yr old) was performed to clarify the effects of cardiorespiratory fitness on the relationship between arterial stiffness and MTHFR C677T gene polymorphism. Arterial stiffness was assessed by carotid β-stiffness with ultrasonography and tonometry. The study subjects were divided into high-cardiorespiratory fitness (High-Fit) and low-cardiorespiratory fitness (Low-Fit) groups based on the median value of peak oxygen uptake in each sex and decade. The plasma homocysteine level was higher in the TT genotype of MTHFR C677T polymorphism compared with CC and CT genotype individuals. MTHFR C677T polymorphism showed no effect on carotid β-stiffness, but there was a significant interaction effect between fitness and MTHFR C677T polymorphism on carotid β-stiffness ( P = 0.0017). In the Low-Fit subjects, carotid β-stiffness was significantly higher in individuals with the TT genotype than the CC and CT genotypes. However, there were no such differences in High-Fit subjects. In addition, β-stiffness and plasma homocysteine levels were positively correlated in Low-Fit subjects with the TT genotype ( r = 0.71, P < 0.0001), but no such correlations were observed in High-Fit subjects. In CC and CT genotype individuals, there were also no such correlations in either fitness level. These results suggest that the higher cardiorespiratory fitness may attenuate central artery stiffening associated with MTHFR C677T polymorphism.
Certain Subclasses of Starlike Functions of Complex Order Involving Generalized Hypergeometric Functions
Authors: Murugusundaramoorthy G. , Magesh N.
Published: April 2010

Making use of the generalized hypergeometric functions, we define a new subclass
of uniformly convex functions and a corresponding subclass of starlike functions with negative
coefficients and obtain coefficient estimates, extreme points, the radii of close‐to‐convexity, starlikeness
and convexity, and neighborhood results for the class . In particular, we
obtain integral means inequalities for the function f that belongs to the class in the unit disc.
Design and Lyapunov Stability Analysis of a Fuzzy Logic Controller for Autonomous Road Following
Authors: Fu Yi , Li Howard , Kaye Mary
Published: April 2010

Autonomous road following is one of the major goals in intelligent vehicle applications. The development of an autonomous road following embedded system for intelligent vehicles is the focus of this paper. A fuzzy logic controller (FLC) is designed for vision‐based autonomous road following. The stability analysis of this control system is addressed. Lyapunov′s direct method is utilized to formulate a class of control laws that guarantee the convergence of the steering error. Certain requirements for the control laws are presented for designers to choose a suitable rule base for the fuzzy controller in order to make the system stable. Stability of the proposed fuzzy controller is guaranteed theoretically and also demonstrated by simulation studies and experiments. Simulations using the model of the four degree of freedom nonholonomic robotic vehicle are conducted to investigate the performance of the fuzzy controller. The proposed fuzzy controller can achieve the desired steering angle and make the robotic vehicle follow the road successfully. Experiments show that the developed intelligent vehicle is able to follow a mocked road autonomously.
Prolonged Unilateral Disuse Osteopenia 14 Years Post External Fixator Removal: A Case History and Critical Review
Authors: Knapp Karen M. , Rowlands Ann V. , Welsman Joanne R. , MacLeod Kenneth M.
Published: April 2010

Disuse osteopenia is a complication of immobilisation, with reversal generally noted upon remobilisation. This case report focuses on a patient who was seen 18 years following a road traffic collision when multiple fractures were sustained. The patient had an external fixator fitted for a tibia and fibula fracture, which remained in situ for a period of 4 years. Following removal, the patient was mobilised but, still required a single crutch to aid walking. Fourteen years post removal of the fixator, the patient had a DXA scan which, demonstrated a T-score 2.5 SD lower on the affected hip. This places the patient at an increased risk of hip fracture on this side, which requires monitoring. There appear to be no current studies investigating prolonged disuse-osteopenia in patients following removal of long-term external fixators. Further research is required to quantify unilateral long-term effects to bone health and fracture risk in this population.
A Universal Hurricane Frequency Function
Authors: Ehrlich Robert
Published: April 2010

Evidence is provided that the global distribution of tropical hurricanes is principally determined by a universal function H of a single variable z that in turn is expressible in terms of the local sea surface temperature and latitude. The data‐driven model presented here carries stark implications for the large increased numbers of hurricanes which it predicts for a warmer world. Moreover, the rise in recent decades in the numbers of hurricanes in the Atlantic, but not the Pacific basin, is shown to have a simple explanation in terms of the specific form of H(z), which yields larger percentage increases when a fixed increase in sea surface temperature occurs at higher latitudes and lower temperatures.
Expression of CYLD and NF-κB in Human Cholesteatoma Epithelium
Authors: Byun Jae Yong , Yune Tae Young , Lee Jee Youn , Yeo Seung Geun , Park Moon Suh
Published: April 2010

The tumor suppressor CYLD is a deubiquitinating enzyme that inhibits activation of the NF-κB, which has key roles in inflammation and apoptosis. We hypothesized that CYLD may regulate the NF-κB signaling pathway in cholesteatoma. We conducted immunohistochemistry to examine the expression of CYLD and NF-κB in 16 cases of cholesteatoma and paired cases of retroauricular (RA) skin. In cholesteatoma epithelium, activated NF-κB expression was significantly higher than in RA skin, whereas CYLD expression was significantly lower in cholesteatoma epithelium than in RA skin (P<.05). Furthermore, a significant inverse correlation was detected between CYLD and activated NF-κB expression in cholesteatoma epithelium (r=-0.630). We found that CYLD reduced and activated increased NF-κB in cholesteatoma epithelium in comparison to RA skin. The inverse correlation between CYLD and activated NF-κB in cholesteatoma may be involved in cholesteatoma epithelial hyperplasia.
In situ Vaccination Combined with Androgen Ablation and Regulatory T-Cell Depletion Reduces Castration-Resistant Tumor Burden in Prostate-Specific Pten Knockout Mice
Authors: Akins Elizabeth J. , Moore Miranda L. , Tang Shuai , Willingham Mark C. , Tooze Janet A. , Dubey Purnima
Published: April 2010

There is no effective treatment for prostate cancer arising after androgen ablation. Previous studies have analyzed the short-term effects of androgen ablation on the immune system and suggest an abatement of immune suppression by hormone removal. Because castration-resistant disease can arise years after treatment, it is crucial to determine the duration of immune potentiation by castration. Because immunotherapeutic efficacy is determined by the balance of immune cell subsets and their location within the tumor, we assessed the acute and chronic effect of androgen ablation on the localization of T-cell subsets within castration-resistant murine prostate cancer. We observed a transient increase in CD4+ and CD8+ T-cell numbers at the residual tumor after androgen ablation. More than 2 months later, regulatory T cells (Treg) were increasingly found within prostate epithelium, whereas CTLs, which were evenly distributed before androgen ablation, became sequestered within stroma. Anti-CD25 antibody administration along with castration enhanced CTL access to cancerous glands but did not increase effector function. Intraprostatic injection of LIGHT-expressing tumor cells increased the proportion of CD8+ T cells with functional capacity within the cancerous gland. In addition, Treg depletion within the tumor was enhanced. Together, these manipulations significantly reduced castration-resistant tumor burden. Thus, our results indicate that immune modulations, which prevent Treg accumulation and augment effector cell infiltration of prostatic epithelium, may be effective in reducing tumor burden or preventing tumor recurrence after androgen ablation therapy. Cancer Res; 70(9); 3473–82. ©2010 AACR.
Hypoxia Induces Trimethylated H3 Lysine 4 by Inhibition of JARID1A Demethylase
Authors: Zhou Xue , Sun Hong , Chen Haobin , Zavadil Jiri , Kluz Thomas , Arita Adriana , Costa Max
Published: April 2010

Histone H3 lysine 4 (H3K4) trimethylation (H3K4me3) at the promoter region of genes has been linked to transcriptional activation. In the present study, we found that hypoxia (1% oxygen) increased H3K4me3 in both normal human bronchial epithelial Beas-2B cells and human lung carcinoma A549 cells. The increase of H3K4me3 from hypoxia was likely caused by the inhibition of H3K4 demethylating activity, as hypoxia still increased H3K4me3 in methionine-deficient medium. Furthermore, an in vitro histone demethylation assay showed that 1% oxygen decreased the activity of H3K4 demethylases in Beas-2B nuclear extracts because ambient oxygen tensions were required for the demethylation reaction to proceed. Hypoxia only minimally increased H3K4me3 in the BEAS-2B cells with knockdown of JARID1A, which is the major histone H3K4 demethylase in this cell line. However, the mRNA and protein levels of JARID1A were not affected by hypoxia. GeneChip and pathway analysis in JARID1A knockdown Beas-2B cells revealed that JARID1A regulates the expression of hundreds of genes involved in different cellular functions, including tumorigenesis. Knocking down of JARID1A increased H3K4me3 at the promoters of HMOX1 and DAF genes. Thus, these results indicate that hypoxia might target JARID1A activity, which in turn increases H3K4me3 at both the global and gene-specific levels, leading to the altered programs of gene expression and tumor progression. Cancer Res; 70(10); 4214–21. ©2010 AACR.
Anti–Vascular Endothelial Growth Factor Therapies as a Novel Therapeutic Approach to Treating Neurofibromatosis-Related Tumors
Authors: Wong Hon Kit , Lahdenranta Johanna , Kamoun Walid S. , Chan Annie W. , McClatchey Andrea I. , Plotkin Scott R. , Jain Rakesh K. , di Tomaso Emmanuelle
Published: April 2010

Patients with bilateral vestibular schwannomas associated with neurofibromatosis type 2 (NF2) experience significant morbidity such as complete hearing loss. We have recently shown that treatment with bevacizumab provided tumor stabilization and hearing recovery in a subset of NF2 patients with progressive disease. In the current study, we used two animal models to identify the mechanism of action of anti–vascular endothelial growth factor (VEGF) therapy in schwannomas. The human HEI193 and murine Nf2−/− cell lines were implanted between the pia and arachnoid meninges as well as in the sciatic nerve to mimic central and peripheral schwannomas. Mice were treated with bevacizumab (10 mg/kg/wk i.v.) or vandetanib (50 mg/kg/d orally) to block the VEGF pathway. Using intravital and confocal microscopy, together with whole-body imaging, we measured tumor growth delay, survival rate, as well as blood vessel structure and function at regular intervals. In both models, tumor vessel diameter, length/surface area density, and permeability were significantly reduced after treatment. After 2 weeks of treatment, necrosis in HEI193 tumors and apoptosis in Nf2−/− tumors were significantly increased, and the tumor growth rate decreased by an average of 50%. The survival of mice bearing intracranial schwannomas was extended by at least 50%. This study shows that anti-VEGF therapy normalizes the vasculature of schwannoma xenografts in nude mice and successfully controls the tumor growth, probably by reestablishing a natural balance between VEGF and semaphorin 3 signaling. Cancer Res; 70(9); 3483–93. ©2010 AACR.
The Tumor-Suppressive Function of Connexin43 in Keratinocytes Is Mediated in Part via Interaction with Caveolin-1
Authors: Langlois Stéphanie , Cowan Kyle N. , Shao Qing , Cowan Bryce J. , Laird Dale W.
Published: April 2010

Connexin43 (Cx43) is known to have tumor-suppressive effects, but the underlying mechanisms are still poorly understood. In keratinocytes, we previously showed that the COOH-terminal domain of Cx43 directly interacts with the tumor suppressor Cav-1. We now show that rat epidermal keratinocytes (REK) that are reduced in Cx43 present features of epithelial-to-mesenchymal transition and are more invasive than their control counterparts, whereas overexpression of Cx43 inhibited the 12-O-tetradecanoyl-phorbol-13-acetate (TPA)– and epidermal growth factor (EGF)–induced invasive properties. Carbenoxolone did not alter the inhibitory effect of Cx43 against TPA- and EGF-induced cell invasion, indicating the involvement of a gap junctional intercellular communication–independent mechanism. Interestingly, the association of Cx43 with Cav-1 was found to be reduced after TPA and EGF treatment. Accordingly, the colocalization of Cx43 with Cav-1 was diminished in cells from a human epidermal squamous cell carcinoma, as well as in sections from human keratinocyte tumors, suggesting that Cx43/Cav-1 interaction plays a protective role against keratinocyte transformation. As opposed to cells that overexpress Cx43-GFP, invasion could be induced in rat epidermal keratinocytes that overexpressed a GFP-tagged truncated mutant of Cx43 (Δ244-GFP) that we previously showed not to interact with Cav-1, as well as in cells that overexpressed Cx43-GFP but were reduced in Cav-1. Our data show that Cx43 possesses tumor-suppressive properties in keratinocytes and provide the first evidence that the Cx43/Cav-1 interaction is altered in keratinocyte transformation processes, as well as in human keratinocyte tumors, and that this association might play a role in Cx43-mediated tumor suppression. Cancer Res; 70(10); 4222–32. ©2010 AACR.
Molecular Target Class Is Predictive of In vitro Response Profile
Authors: Greshock Joel , Bachman Kurtis E. , Degenhardt Yan Y. , Jing Junping , Wen Yuan H. , Eastman Stephen , McNeil Elizabeth , Moy Christopher , Wegrzyn Ronald , Auger Kurt , Hardwicke Mary Ann , Wooster Richard
Published: April 2010

Preclinical cellular response profiling of tumor models has become a cornerstone in the development of novel cancer therapeutics. As efforts to predict clinical efficacy using cohorts of in vitro tumor models have been successful, expansive panels of tumor-derived cell lines can recapitulate an “all comers” efficacy trial, thereby identifying which tumors are most likely to benefit from treatment. The response profile of a therapy is most often studied in isolation; however, drug treatment effect patterns in tumor models across a diverse panel of compounds can help determine the value of unique molecular target classes in specific tumor cohorts. To this end, a panel of 19 compounds was evaluated against a diverse group of cancer cell lines (n = 311). The primary oncogenic targets were a key determinant of concentration-dependent proliferation response, as a total of five of six, four of four, and five of five phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway, insulin-like growth factor-I receptor (IGF-IR), and mitotic inhibitors, respectively, clustered with others of that common target class. In addition, molecular target class was correlated with increased responsiveness in certain histologies. A cohort of PI3K/AKT/mTOR inhibitors was more efficacious in breast cancers compared with other tumor types, whereas IGF-IR inhibitors more selectively inhibited growth in colon cancer lines. Finally, specific phenotypes play an important role in cellular response profiles. For example, luminal breast cancer cells (nine of nine; 100%) segregated from basal cells (six of seven; 86%). The convergence of a common cellular response profile for different molecules targeting the same oncogenic pathway substantiates a rational clinical path for patient populations most likely to benefit from treatment. Cancer Res; 70(9); 3677–86. ©2010 AACR.
FOXC1 Is a Potential Prognostic Biomarker with Functional Significance in Basal-like Breast Cancer
Authors: Ray Partha S. , Wang Jinhua , Qu Ying , Sim Myung-Shin , Shamonki Jaime , Bagaria Sanjay P. , Ye Xing , Liu Bingya , Elashoff David , Hoon Dave S. , Walter Michael A. , Martens John W. , Richardson Andrea L. , Giuliano Armando E. , Cui Xiaojiang
Published: April 2010

Gene expression signatures for a basal-like breast cancer (BLBC) subtype have been associated with poor clinical outcomes, but a molecular basis for this disease remains unclear. Here, we report overexpression of the transcription factor FOXC1 as a consistent feature of BLBC compared with other molecular subtypes of breast cancer. Elevated FOXC1 expression predicted poor overall survival in BLBC (P = 0.0001), independently of other clinicopathologic prognostic factors including lymph node status, along with a higher incidence of brain metastasis (P = 0.02) and a shorter brain metastasis–free survival in lymph node–negative patients (P < 0.0001). Ectopic overexpression of FOXC1 in breast cancer cells increased cell proliferation, migration, and invasion, whereas shRNA-mediated FOXC1 knockdown yielded opposite effects. Our findings identify FOXC1 as a theranostic biomarker that is specific for BLBC, offering not only a potential prognostic candidate but also a potential molecular therapeutic target in this breast cancer subtype. Cancer Res; 70(10); 3870–6. ©2010 AACR.
Attenuation of Tumor Growth by Formation of Antiproliferative Glycosaminoglycans Correlates with Low Acetylation of Histone H3
Authors: Nilsson Ulrika , Johnsson Richard , Fransson Lars-Åke , Ellervik Ulf , Mani Katrin
Published: April 2010

Glycosaminoglycan (GAG) chains anchored to core proteins form proteoglycans, widely distributed cell-surface macromolecules with multiple functions, such as regulation of growth factor and cytokine signaling, cell-cell interactions, and uptake of biomolecules. The biosynthesis of GAG can be manipulated by xylosides attached to various hydrophobic groups, and we have earlier reported that a naphthoxyloside, 2-(6-hydroxynaphthyl) β-d-xylopyranoside (XylNapOH), which serves as a primer for GAG synthesis, reduces tumor load up to 97% in vivo, despite lower efficiency in vitro. Here we show, using radiolabeled xylosides and coculture experiments, that XylNapOH-treated bladder and breast carcinoma cells secrete antiproliferative GAG chains that are taken up by both normal and cancer cells and transported to the cell nuclei where they induce an antiproliferative effect, accompanied by apoptosis. We also show that XylNapOH treatment lowers the level of histone H3 acetylation selectively in bladder and breast carcinoma cells without affecting expression of histone H3. However, XylNapOH-primed GAG chains from normal cells are not internalized and do not cause growth retardation. Using in vitro and in vivo C6 glioma cell and tumor models, we show that XylNapOH is much more effective in vivo than in vitro. We propose that, in vivo, the antiproliferative XylNapOH-primed GAG chains produced by tumor cells inhibit tumor growth in an autocrine fashion by formation of antiproliferative GAG chains on the xyloside prodrug, whereas no antiproliferative GAG chains are produced by surrounding normal cells. This is a novel mechanism for targeting tumor cells, making these xylosides promising drug candidates for antitumor therapy. Cancer Res; 70(9); 3771–9. ©2010 AACR.