bluuebunny/crossref_metadata_2025 huggingface dataset:
CORRELATION BETWEEN STRUCTURAL STABILITY AND ELECTRONIC STRUCTURE OF UGa3 UP TO 30 GPa
Authors: KATHIRVEL V. , CHANDRA SHARAT , CHANDRA SHEKAR N. V. , SAHU P. CH. , RAJAGOPALAN M.
Published: April 2011

High-pressure angle-dispersive X-ray diffraction experiments were performed on UGa 3 up to 30 GPa within a diamond-anvil cell. UGa 3 remains in its cubic AuCu 3 type structure up to the maximum pressure studied and does not show any structural phase transition. To understand the structural stability of UGa 3, band structure calculations were performed as a function of reduced volume using the full-potential linear augmented plane wave (FP-LAPW) method. The results show that the Fermi level coincides with a deep valley in the density of states (DOS) curve in the antiferromagnetic state, whereas it lies near a valley (towards the bonding side) in the nonmagnetic state. At high pressures, the DOS near EF does not show much variation in both the cases. The experimental and theoretical equation of state, bulk modulus, and its pressure derivative values are also reported. The pressure dependence of magnetic moment shows a linear decrease at the rate of dμ/dP = -0.027 μ B / GPa .
PHOTONIC GAPS OF ALUMINIUM–NITRIDE FILM RELATED WITH STRUCTURE AND DEPOSITION
Authors: ESCAMILLA CONETT HUERTA , LARA FABIO CHALE , XIAO MUFEI
Published: April 2011

Work is reported on the characterizations of pulsed laser deposited aluminum–nitride thin films. The films were deposited on silicon substrate with a KrF 248 nm pulse laser operating in a Riber LDM-22 system. Optical reflection spectroscopy (400–900 nm) was carried out, which revealed that, under certain deposition conditions, the films could show strong periodic spectra with reflection gaps of about 50–100 nm in width. The microscopic structures, such as crystalline status and element composition, were also investigated with Auger electron spectroscopy, X-ray photoelectron spectroscopy, atomic force microscopy, scanning electron microscopy, and profilometry etc. Relations between the optical responses and the microscopic structures were established. The foundations underlying the relations were studied and discussed.
ANALOG HARDWARE IMPLEMENTATIONS OF ARTIFICIAL NEURAL NETWORKS
Authors: NEDJAH NADIA , DA SILVA RODRIGO MARTINS , MOURELLE LUIZA DE MACEDO
Published: April 2011

There are several possible implementations of artificial neural network that are based either on software or hardware systems. Software implementations are rather inefficient due to the fact that the intrinsic parallelism of the underlying computation is usually not taken advantage of in a mono-processor kind of computing system. Existing hardware implementations of ANNs are efficient as the dedicated datapath used is optimized and the hardware is usually parallel. Hardware implementations of ANNs may be either digital, analog, or even hybrid. Digital implementations of ANNs tend to be of high complexity, thus of high cost, and somehow imprecise due to the use of lookup table for the activation function. On the other hand, analog implementation of ANNs are generally very simple and much more precise. In this paper, we focus on possible analog implementations of ANNs. The neuron is based on a simple operational amplifier. The reviewed implementations allow for the use of both negative and positive synaptic weights. An alternative implementation permits the realization of the training process.
DYNAMIC RESOURCE ALLOCATION WITH FINITE RATE FEEDBACK FOR MULTIUSER MIMO-OFDM SYSTEMS
Authors: XU LEI , XU DAZHUAN , ZHANG XIAOFEI , XU SHUFANG , WANG JUNBO , LI YAPING
Published: April 2011

Tailored for the best effort service, the present paper deals with dynamic allocation of subcarriers, rate and power resources based on channel state information (CSI) for multiuser MIMO-OFDM systems with trellis code modulation (TCM). Users rely on adaptive modulation and power modes that they select in accordance with the finite-rate feedback (FRF) they receive from the base station (BS). The BS uses CSI to maximize a generic concave utility of average rates while adhering to power constraints imposed on every user. We utilize a stochastic approximation primal-dual algorithm for on-line scheduling and resource allocation. The resultant optimum resource allocation depends on the current channel realization and optimally calculates dual prices. The simulation results show that the system throughput of proposed algorithm is not only good but also can effectively reduce the feedback overhead and the adoption of TCM can improve the system throughput greatly comparing to uncoded system.
BANDWIDTH EXPANSION METHODS OF INDUCTANCE SIMULATOR CIRCUITS AND VOLTAGE-MODE BIQUADS
Authors: ALPASLAN HALIL , YUCE ERKAN
Published: April 2011

In this paper, novel low and high frequency performance improvement techniques are proposed. High frequency performance improvement method is based on the single pole effect reduction/completely elimination by creating a corresponding zero while a low one is based on reduction/elimination of Z terminal parasitic resistors. Therefore, two grounded capacitance multipliers, three grounded inductor simulators, a floating inductor and a voltage-mode (VM) universal filter using second-generation current conveyors (CCIIs) are used to explain the developed methods. One of the grounded inductor simulators, floating simulated inductor and VM biquad are novel. Further, both of the new simulated inductors use a grounded capacitor; accordingly, they are suitable for IC fabrication. However, all the proposed circuits need a single matching condition. A number of simulations through PSPICE program and experimental tests are accomplished to demonstrate the workability, performance and effectiveness.
FULLY CASCADABLE MIXED-MODE UNIVERSAL FILTER BIQUAD USING DDCCS AND GROUNDED PASSIVE COMPONENTS
Authors: LEE CHEN-NONG
Published: April 2011

A fully cascadable (i.e., low/high input impedance for current/voltage input signals and high/low output impedance for current/voltage output signals) mixed-mode (input and output signals can be voltage or current) universal filter biquad by using three differential difference current conveyors (DDCCs), three grounded resistors, and two grounded capacitors is presented in this paper. The proposed biquad can realize the inverting, non-inverting, and differential types universal filtering responses (lowpass, highpass, bandpass, notch, and allpass) from the voltage and current output terminals without changing the filter topology. The proposed circuit is suitable for cascading in all the four possible modes (i.e., voltage, current, transresistance, and transconductance modes). Moreover, the proposed mixed-mode biquad still enjoys (i) using only grounded passive components, (ii) no need of extra inverting and non-inverting amplifiers for special input signals, and (iii) low active and passive sensitivities. This paper also shows how analytical synthesis can be used to produce the proposed mixed-mode filter circuit. H-Spice simulation results confirm the theory.
VERSATILE VOLTAGE-MODE DDCC-BASED UNIVERSAL FILTER
Authors: CHEN HUA-PIN
Published: April 2011

A novel versatile three-input five-output universal voltage-mode filter employing two differential difference current conveyors, two grounded capacitors and three resistors is proposed. The proposed configuration can be used as either a single-input five-output or three-input two-output. Unlike the previously reported works, it can simultaneously realize five different generic signals: low-pass, band-pass, high-pass, notch and all-pass. Moreover, the proposed circuit still offers the following advantages: (i) the employment of two grounded capacitors, (ii) no need to employ inverting-type input signals, (iii) no need to impose component choice, (iv) orthogonal control of the resonance angular frequency ωo and the quality factor Q and (v) low active and passive sensitivity performances.
AN IMPROVEMENT OF REMOTE AUTHENTICATION AND KEY AGREEMENT SCHEMES
Authors: LEE CHENG-CHI , LI CHUN-TA , HUANG KUO-YOU , HUANG SHIOW-YUAN
Published: April 2011

Recently, Shieh et al. have pointed out that Juang's password authenticated key agreement scheme and Chien et al.'s remote authentication scheme are vulnerable to some attacks. Therefore, they presented a modified protocol to avoid those attacks. However, the authors of this article shall show that Shieh et al.'s scheme and Juang's scheme have two weaknesses, respectively. Therefore, we shall improve the weaknesses of their schemes.
IMPROVED MODIFIED FAT-TREE TOPOLOGY NETWORK-ON-CHIP
Authors: BOUHRAOUA ABDELHAFID , ELRABAA MUHAMMAD E. S.
Published: April 2011

C-based cycle-accurate simulations are used to evaluate the performance of a Network-on-Chip (NoC) based on an improved version of the modified Fat Tree topology. The modification simplifies routing further and guarantee orderly reception of packets without any loss of performance. Several traffic models have been used in these simulations; Bursty and non-bursty traffic with uniformly-distributed destination addresses and non-uniformly-distributed destination addresses. A simple new traffic model has been developed for generating non-uniformly-distributed destination addresses. This model is general enough to be used in developing new NoC architectures and captures universally accepted place-and-route methodologies. Simulation results are used to illustrate how the hardware resources of a modified Fat Tree NoC can be minimized without affecting the network performance. The performance of a NoC with regular Mesh topology was also evaluated for comparison with the modified Fat Tree topology.
SIMULATION AND DESIGN OF A CONSTANT-CURRENT-CONTROLLED SPOT WELDING INVERTER WITH THE FUZZY NEURAL NETWORK
Authors: ZHANG YONG , BAI HUA , CAI YONGQING , MA TIEJUN , XIE HONGXIA
Published: April 2011

Resistance spot welding is a major metal connecting method in vehicle and other domestic electronic domains. Among all the welding techniques, the spot welding inverter is an important direction at the present time. The high nonlinearity and strongly coupled multiple parameters in the resistance spot welding process challenge the classical control theory based on some specific conditions and ideal assumptions, which in real practice obstacle the high-quality welding. This paper put the fuzzy neural network into a constant-current-controlled spot welding inverter, where the welding current peak and its variation are adopted as the input parameters and the duty ratio of the switches is regarded as the output. Eventually a five-layer feed-forward network was constructed, back propagation (BP) algorithm was applied to revise the adjustable parameters in the network, and a mathematical model was established to obtain the training samples serving for the network. The ultimate precision could reach 1.75%, the relative control error is 2.28% with strong external disturbances, the overmodulation is 3.35%, and the total modulating period is seven switching period, which indicated that the proposed algorithm has good performance.
A FPGA-BASED RECONFIGURABLE PARALLEL ARCHITECTURE FOR HIGH-PERFORMANCE NUMERICAL COMPUTATION
Authors: FERLIN EDSON PEDRO , LOPES HEITOR SILVÉRIO , LIMA CARLOS R. ERIG , PERRETTO MAURÍCIO
Published: April 2011

Many real-world engineering problems require high computational power, especially regarding the processing time. Current parallel processing techniques play an important role in reducing the processing time. Recently, reconfigurable computation has gained large attention thanks to its ability to combine hardware performance and software flexibility. Also, the availability of high-density Field Programmable Gate Array devices and corresponding development systems allowed the popularization of reconfigurable computation, encouraging the development of very complex, compact, and powerful systems for custom applications. This work presents an architecture for parallel reconfigurable computation based on the dataflow concept. This architecture allows reconfigurability of the system for many problems and, particularly, for numerical computation. Several experiments were done analyzing the scalability of the architecture, as well as comparing its performance with other approaches. Overall results are relevant and promising. The developed architecture has performance and scalability suited for engineering problems that demand intensive numerical computation.
ARTIFICIAL MICRO-WORLDS PART I: A NEW APPROACH FOR STUDYING LIFE-LIKE PHENOMENA
Authors: BILOTTA ELEONORA , PANTANO PIETRO , VENA STEFANO
Published: April 2011

In this paper, we present the k-totalistic class of Cellular Automata (CA), which we generate from evolutionary processes, giving rise to Artificial Micro-Worlds (AMW). Within these micro-worlds, we observe a huge range of self-replicators and an equally huge range of models of self-replicating structures that behave like biological species. On the basis of empirical observations, we propose a new way for studying artificial life-like phenomena through which we can apply methods similar to those used in Zoology, observing and classifying different species and investigating their population dynamics.
A NEW WAY OF GENERATING N-SCROLL ATTRACTORS VIA TRIGONOMETRIC FUNCTION
Authors: GÜNAY ENIS , KILIÇ RECAI
Published: April 2011

In this work, a way of generating n-scroll attractors in State Controlled-Cellular Neural Network (SC-CNN) using a trigonometric function is introduced. In spite of the studies on generation of n-scrolls cited in literature, there is no need to add break points in the nonlinear function of the system. Also, wide number of scrolls can be generated by modifying only one variable.
REGULAR AND CHAOTIC DYNAMICS IN BOUNCING BALL MODELS
Authors: VOGEL SEBASTIAN , LINZ STEFAN J.
Published: April 2011

One of the prime paradigms for complex temporal dynamics, the motion of an inelastic ball bouncing on a sinusoidally oscillating table, is revisited. Using extensive numerical simulations, we address the not yet conclusively settled problem of the occurrence of chaos in the partially elastic case. We systematically investigate the spectrum of long-time solutions as function of the initial conditions and system parameters. Subsequently, we generalize the bouncing ball system by taking the velocity dependence of the coefficient of restitution into account and exemplarily demonstrate the drastic impact of such a generalization on the overall dynamics.
LOCAL BIFURCATION BOUNDARY AND STEADY-STATE SECURITY BOUNDARY IN LARGE ELECTRIC POWER SYSTEMS: NUMERICAL STUDIES
Authors: ZHANG YI-SHAN , CHIANG HSIAO-DONG
Published: April 2011

The local bifurcation boundary and steady-state security boundary of parameter-dependent electric power system models are computed and studied. A computational procedure for numerically constructing the local bifurcation boundary and the steady-state security boundary is proposed. Then the proposed computational procedure is applied to large power systems to compute the local bifurcation boundary and steady-state security boundary. Numerical studies reveal the characteristics and the convexity properties of these boundaries. The impact of the physical limitation of the generator reactive capability on the local bifurcation boundary and the steady-state security boundary are also investigated.
4-ORDERED HAMILTONICITY FOR SOME CHORDAL RING GRAPHS
Authors: SHERMAN DAVID , TSAI MING , LIN CHENG-KUAN , LIPTÁK LÁSZLÓ , CHENG EDDIE , TAN JIMMY J. M. , HSU LIH-HSING
Published: April 2011

A graph G is k-ordered if for any sequence of k distinct vertices of G, there exists a cycle in G containing these k vertices in the specified order. It is k-ordered Hamiltonian if, in addition, the required cycle is Hamiltonian. The question of the existence of an infinite class of 3-regular 4-ordered Hamiltonian graphs was posed in 1997 by Ng and Schultz.13At the time, the only known examples were K4and K3,3. Some progress was made in 2008 by Mészáros,12when the Peterson graph was found to be 4-ordered and the Heawood graph was proved to be 4-ordered Hamiltonian; moreover, an infinite class of 3-regular 4-ordered graphs was found. In 2010 a subclass of generalized Petersen graphs was shown to be 4-ordered by Hsu et al.,10with an infinite subset of this subclass being 4-ordered Hamiltonian, thus answering the open question. In this paper we find another infinite class of 3-regular 4-ordered Hamiltonian graphs, part of a subclass of the chordal ring graphs. In addition, we classify precisely which of these graphs are 4-ordered Hamiltonian.
PERIODIC HOMOGENIZATION OF THE PRANDTL–REUSS MODEL WITH HARDENING
Authors: SCHWEIZER BEN , VENERONI MARCO
Published: April 2011

We study the n-dimensional wave equation with an elastoplastic nonlinear stress–strain relation. We investigate the case of heterogeneous materials, i.e., x-dependent parameters that are periodic at the scale η>0. We study the limit η→0 and derive the plasticity equations for the homogenized material. We prove the well-posedness for the original and the effective system with a finite-element approximation. The approximate solutions are also used in the homogenization proof which is based on oscillating test functions and an adapted version of the div-curl Lemma.
EXERGY ANALYSIS OF THE PERFORMANCE OF A VARIABLE REFRIGERANT FLOW (VRF) AIR CONDITIONING SYSTEM
Authors: PADILLA MIGUEL
Published: April 2011

Commercial multiple evaporators variable refrigerant flow (VRF) HVAC systems present many advantages such as being energy saving and the capability of adjusting refrigerant mass flow rate according to the change of high rises occurrence. This paper deals with an experimental control volume exergy analysis in a VRF air conditioning system. The experimental results show that the brunt of the total exergy destroyed in the whole system occurs in the outdoor unit, where the exergy destroyed in the condenser is more important. The values of coefficient of performance (COP) obtained for the tests increase as the system reaches operational conditions imposed in every indoor unit zone. The VRF system analyzed is highly sensitive to the action of the constant speed compressor. The use of an inverter compressor improves the system performance by adjusting the power consumption according to the cooling load in the evaporators.
CAPACITY ASSESSMENT OF A WINDOW AIR-CONDITIONER RETROFITTED WITH A REFRIGERANT MIXTURE
Authors: RAJ M. HERBERT , LAL D. MOHAN , JABARAJ D. B.
Published: April 2011

R22 being a HCFC is to be phased out soon as per the Montreal protocol. This paper presents the experimental performance study of an air-conditioner retrofitted with M20 (a refrigerant mixture of R407C, R600a and R290 in the mass fraction 80:10.96:9.04 respectively). M20 is considered as a substitute for R22 in window air-conditioners with mineral oil as the compressor lubricant. Previously, the performance of the same mixture has been reported with 19% extra condenser length as compared to that in the R22 system. In this study, experiments were conducted in a 5.25 kW window airconditioner to assess the potential of M20 as a retrofit refrigerant without making any system alteration other than changing the capillary. The system performance study was carried out with R22 and later with the M20 charge in a psychrometric test facility as per BIS and ASHRAE standards. Experimental results showed that with the M20, the system had 4.18% to 7.47% lower cooling capacity with respect to that of R22. The COP for the M20 refrigerant was lower, in the range of 0.58% to 7.78% than that of R22. Hence, M20 can be used as a drop- in-substitute for R22 in window air-conditioners but with a marginal reduction in cooling capacity.
Stock and Option Proportions in Executive Compensation
Authors: Boyle Phelim P. , Jha Ranjini , Kennedy Shannon , Tian Weidong
Published: April 2011

There is controversy about the relative merits of stock and options in executive compensation. Some observers contend that stock is a more efficient mechanism, while others reach the opposite conclusion. We focus on the manager's risk-taking incentives and derive an optimal compensation contract by using the concept of a comparable benchmark and imposing a volatility constraint in a principal-agent framework. We demonstrate a joint role for both stock and options in the optimal contract. We show that firms with higher volatility should use more options in compensating their executives and provide empirical evidence supporting this testable implication.
Chemical Mechanical Planarization Mechanism for Nitrogen-Doped Polycrystalline Ge2Sb2Te5 Film Using Nitric Acidic Slurry Added with Hydrogen Peroxide
Authors: Cui Hao , Cho Jong-Young , Park Jin-Hyung , Park Hyung Soon , Park Jea-Gun
Published: April 2011

We investigated the chemical mechanical planarization (CMP) mechanism of nitrogen-doped polycrystalline Ge2Sb2Te5 (pc-GST) using nitric acid slurry without or with 1.0 wt % hydrogen peroxide (H2O2). Without H2O2, the pc-GST film surface undergoes selective corrosion of Ge and Sb, resulting in pitting corrosion. Otherwise, with H2O2, the pc-GST film surface produces a Ge, Sb, Te oxide layer, thereby introducing a cyclic polishing process such as chemical oxidation, chemical and mechanical polishing, and sequential chemical oxidation. As a result, the polishing rate increased up to ∼1000 Å/min and the surface roughness decreased to 0.858 nm.
Differences in acute lung response to elastase instillation in two rodent species may determine differences in severity of emphysema development
Authors: Vecchiola Andrea , de la Llera Juan Francisco , Ramírez Rodrigo , Olmos Pablo , Herrera Cristobal I. , Borzone Gisella
Published: April 2011

Elastase intratracheal instillation induces early emphysema in rodents. However, Syrian Golden hamsters develop more severe emphysema than Sprague-Dawley rats. We have reported species differences in oxidant/antioxidant balance modulating antiprotease function early after instillation. We now hypothesize that other components of the initial lung response to elastase might also be species-dependent. Sprague-Dawley rats and Syrian Golden hamsters received a single dose of pancreatic elastase (0.55 U/100 g body wt) to study acute lung injury biomarkers. Using serum, lung, and bronchoalveolar lavage fluid (BALF) samples, we evaluated changes in alveolar-capillary permeability, alpha 1-antitrypsin (α1-AT) concentration and activity, glutathione content, and proinflammatory cytokines. Rats showed a large increase in alveolar-capillary permeability and few hemorrhagic changes, whereas hamsters exhibited large hemorrhagic changes ( P < 0.01) and mild transendothelial passage of proteins. Western blots showed a 30-fold increase in BALF α1-AT concentration in rats and only a 7-fold increase in hamsters ( P < 0.001), with [α1-AT-elastase] complexes only in rats, suggesting differences in antiprotease function. This was confirmed by the α1-AT bioassay showing 20-fold increase in α1-AT activity in rats and only twofold increase in hamsters ( P < 0.001). In rats, results were preceded by a 3-, 60-, and 20-fold increase in IL-6, IL-1β, and TNF-α respectively ( P < 0.001). In hamsters, only IL-1β and TNF-α showed mild increases. All parameters studied were back to baseline by 4 days. In conclusion, several components of the initial lung response showed species differences. Cytokine release pattern and functional inhibition of α1-AT were the most significant components differing among species and could account for differences in susceptibility to elastase.
Experimental Study of Heat Flux Distribution of Arc Driven by AC Magnetic Field
Authors: Matsumoto Naomi , Yamamoto Takeo , Sugimoto Masaya , Takeda Koichi
Published: April 2011

The authors earlier developed a model to predict the heat flux distribution in an arc driven by an AC magnetic field. That theoretical model implied that the heat flux distribution depended on waveforms of the imposed AC magnetic field. Experiments were conducted in this study to validate that theoretical prediction. Theoretical calculations of heat flux distribution in the arc driven by AC magnetic field were conducted using the heat flux profile in the arc root obtained from the measurement under no magnetic field. The heat flux distributions in arcs driven by AC magnetic fields were measured by imposing two AC magnetic fields with sinusoidal and rectangular waveforms. Agreement between experimental and theoretical heat flux distributions was good. Results confirm that heat flux profiles of various types are producible by controlling the imposed magnetic flux density and its waveform.
A General Iterative Algorithm for Generalized Mixed Equilibrium Problems and Variational Inclusions Approach to Variational Inequalities
Authors: Jitpeera Thanyarat , Kumam Poom
Published: April 2011

We introduce a new general iterative method for finding a common element
of the set of solutions of fixed point for nonexpansive mappings, the set of solution of generalized
mixed equilibrium problems, and the set of solutions of the variational inclusion for a β‐inverse‐strongly
monotone mapping in a real Hilbert space. We prove that the sequence converges strongly
to a common element of the above three sets under some mild conditions. Our results improve and
extend the corresponding results of Marino and Xu (2006), Su et al. (2008), Klin‐eam and Suantai
(2009), Tan and Chang (2011), and some other authors.
Referral to an Electronic Screening and Brief Alcohol Intervention in Primary Health Care in Sweden: Impact of Staff Referral to the Computer
Authors: Bendtsen Preben , Stark Ekman Diana , Johansson AnneLie , Carlfjord Siw , Andersson Agneta , Leijon Matti , Johansson Kjell , Nilsen Per
Published: April 2011

The aim of this paper was to evaluate whether primary health care staff's referral of patients to perform an electronic screening and brief intervention (e-SBI) for alcohol use had a greater impact on change in alcohol consumption after 3 month, compared to patients who performed the test on their own initiative. Staff-referred responders reported reduced weekly alcohol consumption with an average decrease of 8.4 grams. In contrast, self-referred responders reported an average increase in weekly alcohol consumption of 2.4 grams. Staff-referred responders reported a 49% reduction of average number of heavy episodic drinking (HED) occasions per month. The corresponding reduction for self-referred responders was 62%. The differences between staff- and self-referred patient groups in the number who moved from risky drinking to nonrisky drinking at the followup were not statistically significant. Our results indicate that standalone computers with touchscreens that provide e-SBIs for risky drinking have the same effect on drinking behaviour in both staff-referred patients and self-referred patients.
Evaluation of the Reconfiguration of the Data Acquisition System for 3D USCT
Authors: Birk Matthias , Hagner Clemens , Balzer Matthias , Ruiter Nicole V. , Hübner Michael , Becker Jürgen
Published: April 2011

As today's standard screening methods often fail to diagnose breast cancer before metastases have developed, an earlier breast cancer diagnosis is still a major challenge. To improve this situation, we are currently developing a fully three-dimensional ultrasound computer tomography (3D USCT) system, promising high-quality volume images of the breast. For obtaining these images, a time-consuming reconstruction has to be performed. As this is currently done on a PC, parallel processing in reconfigurable hardware could accelerate both signal and image processing. In this work, we investigated the suitability of an existing data acquisition (DAQ) system for further computation tasks. The reconfiguration features of the embedded FPGAs have been exploited to enhance the systems functionality. We have adapted the DAQ system to allow for bidirectional communication and to provide an overall process control. Our results show that the studied system can be applied for data processing.
In vivoInhibition of Human CD19-Targeted Effector T Cells by Natural T Regulatory Cells in a Xenotransplant Murine Model of B Cell Malignancy
Authors: Lee James C. , Hayman Erik , Pegram Hollie J. , Santos Elmer , Heller Glenn , Sadelain Michel , Brentjens Renier
Published: April 2011

Human T cells genetically modified to express chimeric antigen receptors (CAR) specific to the B cell tumor antigen CD19 can successfully eradicate systemic human CD19+ tumors in immunocompromised SCID (severe combined immunodeficient)-Beige mice. However, in the clinical setting, CD4+ CD25hi T regulatory cells (Treg) present within the tumor microenvironment may be potent suppressors of tumor-targeted effector T cells. In order to assess the impact of Tregs on CAR-modified T cells in the SCID-Beige xenotransplant model, we isolated, genetically targeted and expanded natural T regulatory cells (nTreg). In vitro nTregs modified to express CD19-targeted CARs efficiently inhibited the proliferation of activated human T cells, as well as the capacity of CD19-targeted 19-28z+ effector T cells to lyse CD19+ Raji tumor cells. Intravenous infusion of CD19-targeted nTregs into SCID-Beige mice with systemic Raji tumors traffic to sites of tumor and recapitulate a clinically relevant hostile tumor microenvironment. Antitumor efficacy of subsequently infused 19-28z+ effector T cells was fully abrogated as assessed by long-term survival of treated mice. Optimal suppression by genetically targeted nTregs was dependent on nTreg to effector T-cell ratios and in vivo nTreg activation. Prior infusion of cyclophosphamide in the setting of this nTreg-mediated hostile microenvironment was able to restore the antitumor activity of subsequently infused 19-28z+ effector T cells through the eradication of tumor-targeted nTregs. These findings have significant implications for the design of future clinical trials utilizing CAR-based adoptive T-cell therapies of cancer. Cancer Res; 71(8); 2871–81. ©2011 AACR.
Inhibition of NEDD8-Activating Enzyme Induces Rereplication and Apoptosis in Human Tumor Cells Consistent with Deregulating CDT1 Turnover
Authors: Milhollen Michael A. , Narayanan Usha , Soucy Teresa A. , Veiby Petter O. , Smith Peter G. , Amidon Benjamin
Published: April 2011

Loss of NEDD8-activating enzyme (NAE) function by siRNA knockdown or inhibition by the small molecule NAE inhibitor MLN4924 leads to increased steady-state levels of direct Cullin-RING ligase (CRL) substrates by preventing their ubiquitination and proteasome-dependent degradation. Many of these CRL substrates are involved in cell cycle progression, including a critical DNA replication licensing factor CDT1. Cell cycle analysis of asynchronous and synchronous cultures after NAE inhibition revealed effects on cell cycle distribution and activation of DNA break repair signaling pathways similar to that reported for CDT1 overexpression. The siRNA knockdown of cullins critical for the turnover of CDT1 recapitulated the aberrant rereplication phenotype while CDT1 knockdown was suppressing. Although NAE inhibition leads to deregulation of many CRL substrates, these data demonstrate that CDT1 accumulation mediates the DNA rereplication phenotype resulting from loss of NAE function. DNA rereplication is an unrecoverable cellular insult and the small molecule inhibitor MLN4924, currently in phase I trials, represents an unprecedented opportunity to explore this mechanism of cytotoxicity for the treatment of cancer. Cancer Res; 71(8); 3042–51. ©2011 AACR.
IRF8 Regulates Acid Ceramidase Expression to Mediate Apoptosis and Suppresses Myelogeneous Leukemia
Authors: Hu Xiaolin , Yang Dafeng , Zimmerman Mary , Liu Feiyan , Yang Jine , Kannan Swati , Burchert Andreas , Szulc Zdzislaw , Bielawska Alicja , Ozato Keiko , Bhalla Kapil , Liu Kebin
Published: April 2011

IFN regulatory factor 8 (IRF8) is a key transcription factor for myeloid cell differentiation and its expression is frequently lost in hematopoietic cells of human myeloid leukemia patients. IRF8-deficient mice exhibit uncontrolled clonal expansion of undifferentiated myeloid cells that can progress to a fatal blast crisis, thereby resembling human chronic myelogeneous leukemia (CML). Therefore, IRF8 is a myeloid leukemia suppressor. Whereas the understanding of IRF8 function in CML has recently improved, the molecular mechanisms underlying IRF8 function in CML are still largely unknown. In this study, we identified acid ceramidase (A-CDase) as a general transcription target of IRF8. We demonstrated that IRF8 expression is regulated by IRF8 promoter DNA methylation in myeloid leukemia cells. Restoration of IRF8 expression repressed A-CDase expression, resulting in C16 ceramide accumulation and increased sensitivity of CML cells to FasL-induced apoptosis. In myeloid cells derived from IRF8-deficient mice, A-CDase protein level was dramatically increased. Furthermore, we demonstrated that IRF8 directly binds to the A-CDase promoter. At the functional level, inhibition of A-CDase activity, silencing A-CDase expression, or application of exogenous C16 ceramide sensitized CML cells to FasL-induced apoptosis, whereas overexpression of A-CDase decreased CML cells' sensitivity to FasL-induced apoptosis. Consequently, restoration of IRF8 expression suppressed CML development in vivo at least partially through a Fas-dependent mechanism. In summary, our findings determine the mechanism of IRF8 downregulation in CML cells and they determine a primary pathway of resistance to Fas-mediated apoptosis and disease progression. Cancer Res; 71(8); 2882–91. ©2011 AACR.
The Two Faces of Capsaicin
Authors: Bode Ann M. , Dong Zigang
Published: April 2011

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is the principal pungent component in hot peppers, including red chili peppers, jalapeños, and habaneros. Consumed worldwide, capsaicin has a long and convoluted history of controversy about whether its consumption or topical application is entirely safe. Conflicting epidemiologic data and basic research study results suggest that capsaicin can act as a carcinogen or as a cancer preventive agent. Capsaicin is unique among naturally occurring irritant compounds because the initial neuronal excitation evoked is followed by a long-lasting refractory period, during which the previously excited neurons are no longer responsive to a broad range of stimuli. This process is referred to as desensitization and has been exploited for its therapeutic potential. Capsaicin-containing creams have been in clinical use for many years to relieve a variety of painful conditions. However, their effectiveness in pain relief is also highly debated and some adverse side effects have been reported. We have found that chronic, long-term topical application of capsaicin increased skin carcinogenesis in mice treated with a tumor promoter. These results might imply that caution should be exercised when using capsaicin-containing topical applications in the presence of a tumor promoter, such as, for example, sunlight. Cancer Res; 71(8); 2809–14. ©2011 AACR.
Treatment of Posttraumatic Embitterment Disorder with Cognitive Behaviour Therapy Based on Wisdom Psychology and Hedonia Strategies
Authors: Linden Michael , Baumann Kai , Lieberei Barbara , Lorenz Constanze , Rotter Max
Published: April 2011

Background: Posttraumatic embitterment disorder (PTED) is a reaction to unjust or humiliating life events, including embitterment and impairment of mood, somatoform complaints, reduction in drive, withdrawal from social contacts, and even suicide and murder suicide. Patients have been shown to be nonresponders to many treatments. This paper gives an outline of cognitive behaviour therapy based on wisdom psychology and reports first data on treatment effects. Method: In a first pilot study on psychotherapy for PTED, a cohort of 25 PTED inpatients was treated with routine multidimensional cognitive behaviour therapy. A second consecutive cohort of 28 patients was treated with PTED-specific cognitive behaviour therapy, which is based on wisdom psychology (wisdom psychotherapy) and another 29 patients with cognitive behaviour therapy based on wisdom psychology together with additional hedonia strategies (wisdom and hedonia psychotherapy). Treatment integrity was measured with special modules of the Behaviour Therapy Competency Checklist. The outcomes were measured in all 3 groups with the SCL-90 and a global clinical rating of patients and therapists on treatment outcome. Results: There were significant and clinically meaningful reductions in the SCL score after wisdom therapy, as compared to routine treatment. In clinical ratings by therapists and patients, both specific treatments were judged as more effective than treatment as usual. Additional hedonia strategies did not lead to better treatment effects. Conclusions: The results of this pilot study suggest that wisdom psychology offers an approach to treat PTED and justify further randomized controlled outcome studies.
Waking and Sleep Electroencephalogram Variables as Human Sleep Homeostatic Process Biomarkers after Drug Administration
Authors: Giménez Sandra , Romero Sergio , Mañanas Miguel Angel , Barbanoj Manuel-José
Published: April 2011

Background/Aims: The correlation between theta activity during wakefulness and slow-wave activity (SWA) during sleep observed after sleep deprivation suggests such patterns can be used as electroencephalogram (EEG) biomarkers of the sleep homeostasis process. Since these EEG components would be very useful objective measures to assess CNS drug effects, we investigated whether the relationship between sleep homeostatic EEG biomarkers could be reproduced after an experimental pharmacological intervention. Methods: Seventeen healthy volunteers took part in a phase I randomized, double-blind, crossover design study. To increase sleep propensity, all participants received a single morning oral dose of olanzapine (5 mg) and placebo. Quantitative EEG analysis was done by power spectra calculations: theta activity (3.5–7.5 Hz) during wakefulness and SWA (0.5–4.0 Hz) during sleep. The relationship between the 2 EEG parameters was assessed by correlating the rise rate (percent/hour) of theta activity in wakefulness and the increase (percent) of SWA in the first non-REM sleep episode. Results: Following olanzapine administration we observed increases in theta activity during wakefulness, and increases in total sleep time, sleep efficiency and slow-wave sleep time during sleep. However, a weak and unreliable correlation was observed between the increases in theta activity and changes in sleep SWA. Conclusions: From these results, we cannot affirm that these waking and sleep EEG variables behave as biomarkers of human sleep homeostasis after drug administration. It is possible that these EEG biomarkers reflect different physiological mechanisms if they are assessed during drug CNS effects.
Gastric Cancer Surveillance in a High-Risk Population in Tuscany (Central Italy): Preliminary Results
Authors: Filomena A. , Saieva C. , Lucchetti V. , Santacroce F. , Falorni P. , Francini V. , Carrieri P. , Zini E. , Ridolfi B. , Belli P. , Orsini B. , Mandi P. , Palli D. , Scheggi S.
Published: April 2011

Background/Aims: The surveillance of subjects at high risk for developing gastric cancer (GC) may represent an effective strategy for reducing specific morbidity and mortality. The aim of this study was to identify GC at its initial phase and to identify precancerous lesions in a group of GC high-risk subjects. Methods: We enrolled first-degree relatives of patients affected by GC who resided in a GC high-risk area (Tuscany, Central Italy). The study’s protocol included the collection of several individual measurements, including a blood sample for the determination of specific biomarkers, an upper digestive tract endoscopy with detailed gastric biopsies and Helicobacter pylori (Hp) treatment followed by a specific check. Results: We enrolled 167 subjects who were members of 128 different familial groups with GC history. We identified 1 case of initial-phase GC, 1 gastric dysplasia type II, 32 intestinal metaplasia, 10 gastric atrophy, and 21 atrophic chronic gastritis. 81 subjects were Hp-positive and underwent eradication therapy. Conclusion: This study of a GC high-risk Italian population reveals positive results in terms of population compliance, the identification of specific gastric lesions requiring close follow-up and successful therapy for Hp infection. To define future surveillance strategies, a longer follow-up of these patients is necessary.
Effectiveness of Unilateral Pallidotomy for Meige Syndrome Confirmed by Motion Analysis
Authors: Valálik István , Jobbágy Ákos , Bognár László , Csókay András
Published: April 2011

Background: We report the case of a 64-year-old woman with bilateral manifestation of Meige syndrome (MS) successfully treated with left-side unilateral ventroposterolateral pallidotomy. Methods: Symptoms were evaluated according to the Burke-Fahn-Marsden dystonia rating scale. Head tremor, blepharospasm and orofacial dyskinesia were measured with an infrared, video-based, computerized, real-time passive marker-based analyzer of motions (RTPAM). Results: The Burke-Fahn-Marsden score showed a 90.2% reduction (from 25.5 to 2.5) at 6 months, and an 88.2% long-lasting benefit (to 3.0) at the 3-year follow-up with good bilateral control of the blepharospasm and orofacial movements. The RTPAM showed a substantial regression of acceleration for all markers, and abolishment of the 4.8-Hz head tremor. The correlation between symmetrical markers, and between markers within the right and left sides, was significantly decreased. Conclusions: Pallidotomy with staged procedure is recommended for the treatment of MS in patients on whom deep brain stimulation could not be performed. In case of good bilateral benefits from the unilateral procedure, contralateral surgery is not needed. The RTPAM is a useful tool for the mapping of facial involuntary movements.
Nutritional Modulation of the Inflammatory Bowel Response
Authors: Ioannidis Orestis , Varnalidis Ioannis , Paraskevas George , Botsios Dimitrios
Published: April 2011

Crohn’s disease and ulcerative colitis represent distinct phenotypic forms of inflammatory bowel disease and continue to be a common cause of morbidity. The corticosteroids and the immunomodulatory drugs, which are the basis of treatment for the inflammatory bowel diseases, do not assure always satisfactory outcomes. Nutrition has been used in order to modify the inflammatory response of various chronic inflammatory diseases, including Crohn’s disease and ulcerative colitis. In the pathogenesis of inflammatory bowel diseases, the intestinal microflora and the intestinal mucosal disorders play a crucial role. Also, the release of reactive oxygen species is a significant factor of initiation and preservation of the inflammatory reaction in these diseases. The advantages of the nutritional treatment derive from the sequestration of intraluminal agents which may promote the inflammatory bowel response or, alternatively, nutrition is able to modify the immune response, reducing the uncontrolled inflammatory reaction. Furthermore, nutrition can enhance the mucosal barrier function and consists a significant source of antioxidants. This review focuses on certain nutritional components that modulate the inflammatory response of the bowel and aims to present a rational thesis regarding the use of nutritional agents in the management of inflammatory bowel diseases.
Inherited Aneuploidy: Germline Mosaicism
Authors: Delhanty J.D.A.
Published: April 2011

Germline mosaicism has been thought to be a rare cause of aneuploidy in the human population. Recent evidence from cytological and population studies suggests otherwise. Approximately 5% of young couples with a Down syndrome child show evidence of germinal mosaicism. Molecular cytogenetic analysis of oocytes has proved germinal or gonadal mosaicism for trisomies of chromosomes 13 and 21 in several studies involving both oocytes and first polar bodies. Most recently direct analysis of fetal ovarian pre-meiotic, meiotic, and stromal cells proved low level trisomy 21 mosaicism in every sample tested. Based upon this evidence, germinal or gonadal mosaicism is likely to make a significant contribution to aneuploidy in the human population, particularly where younger women are concerned.
Maxillary Sinus Floor Elevation Using a Tissue-Engineered Bone with rhBMP-2-Loaded Porous Calcium Phosphate Cement Scaffold and Bone Marrow Stromal Cells in Rabbits
Authors: Xia Lunguo , Xu Yuanjin , Wei Jie , Zeng Deliang , Ye Dongxia , Liu Changsheng , Zhang Zhiyuan , Jiang Xinquan
Published: April 2011

The aim of this study was to evaluate the effects of maxillary sinus floor elevation by a tissue-engineered bone complex with recombinant human bone morphogenetic protein-2 (rhBMP-2)-loaded porous calcium phosphate cement (CPC) scaffold and bone marrow stromal cells (bMSCs) in rabbits. bMSCs were cultured and osteogenically induced. The osteoblastic differentiation of expanded bMSCs was detected by alkaline phosphatase activity, and calcium deposits in vitro. Thirty-six rabbits were randomly allocated into week 2, 4 and 8 observation groups. At each time point, 24 maxillary sinus floor elevation surgeries in 12 rabbits were performed bilaterally and randomly implanted by (1) CPC materials alone (group A, n = 6), (2) rhBMP-2/CPC composite materials alone (group B, n = 6), (3) CPC/bMSCs complex (group C, n = 6) and (4) rhBMP-2/CPC/bMSCs complex (group D, n = 6). As for maxillary sinus floor elevation, rhBMP-2-loaded CPC could promote new bone formation as compared to CPC, while addition of bMSCs could further enhance its new bone formation and maturity significantly, as detected by histological findings, and fluorochrome labeling. Our data suggested that rhBMP-2/CPC possessed excellent osteoinductive ability, while combining with bMSCs could further promote new bone formation and maturation in maxillary sinus elevation.
Systematic Review of the Epidemiology of Complicated Peptic Ulcer Disease: Incidence, Recurrence, Risk Factors and Mortality
Authors: Lau James Y. , Sung Joseph , Hill Catherine , Henderson Catherine , Howden Colin W. , Metz David C.
Published: April 2011

Background/Aims: The incidence of uncomplicated peptic ulcer has decreased in recent years. It is unclear what the impact of this has been on the epidemiology of peptic ulcer complications. This systematic review aimed to determine the incidence, recurrence and mortality of complicated peptic ulcer and the risk factors associated with these events. Methods: Systematic PubMed searches. Results: Overall, 93 studies were identified. Annual incidence estimates of peptic ulcer hemorrhage and perforation were 19.4–57.0 and 3.8–14 per 100,000 individuals, respectively. The average 7-day recurrence of hemorrhage was 13.9% (95% CI: 8.4–19.4), and the average long-term recurrence of perforation was 12.2% (95% CI: 2.5–21.9). Risk factors for peptic ulcer complications and their recurrence included nonsteroidal anti-inflammatory drug and/or acetylsalicylic acid use, Helicobacter pylori infection and ulcer size ≧1 cm. Proton pump inhibitor use reduced the risk of peptic ulcer hemorrhage. Average 30-day mortality was 8.6% (95% CI: 5.8–11.4) after hemorrhage and 23.5% (95% CI: 15.5–31.0) after perforation. Older age, comorbidity, shock and delayed treatment were associated with increased mortality. Conclusions: Complicated peptic ulcer remains a substantial healthcare problem which places patients at a high risk of recurrent complications and death.