bluuebunny/crossref_metadata_2025 huggingface dataset:
Horizontal pressure on barricades for backfilled stopes. Part II: Submerged conditions
Authors: Li Li , Aubertin Michel
Published: January 2009

This paper presents a method to calculate the pressure generated by submerged backfill on barricades (or bulkheads) located in drifts at the base of mine stopes. The paper complements Part I (see companion paper, this isue), which presents an analytical solution for the pressure on barricades when the backfill is in drained conditions (after the pore-water pressure has dissipated). The solution presented here applies shortly after backfill deposition, for undrained conditions. In this case, the effect of pore pressure cannot be neglected as it may be critical for the response of barricades. The solution is developed for totally or partly submerged backfill (with the water table at various elevations). Experimental testing and numerical modelling results are used to validate the proposed equations. Both numerical and analytical results show that the total pressure on barricades can be significantly increased by pore pressure, while the effective stress is decreased in the access drifts (compared to dry or drained conditions). The proposed solution provides a simple method to obtain a realistic estimate of the total and effective stresses, and can thus be used as a basis for barricade design.
Effects of turnover and internal variability of tree root systems on modelling coarse root architecture: comparing simulations for young Populus deltoides with field data
Authors: Nygren Pekka , Lu Miaoer , Ozier-Lafontaine Harry
Published: January 2009

The behaviour of the FracRoot model, which describes coarse-root architecture based on proximal root diameters using a recursive algorithm, was studied using field data on Populus deltoides Bartr. ex Marsh. in a short-rotation plantation. Roots were described as a branching, hierarchical network of connected links. Diameters of daughter links were estimated from the diameter of the mother link using scaling parameter p and allocation parameter q, which were based on sharing of the root cross-sectional area by daughter links. Parameters were estimated from complete root excavations. The length of each link and the vertical and horizontal branching angle distributions were recorded. Parameter p values were distributed log-normally, and q values followed a beta distribution both for the whole root system and within 5 mm link diameter classes. Including the variability of p and q in the model did not significantly improve root length estimates compared with the use of mean p and q values over all branching points. Including a coarse-root turnover factor based on field-observed evidence on root mortality improved the model fit to field data. Root length was more sensitive to parameter values and turnover factor than root mass. Field observations and the importance of the turnover factor to simulation accuracy suggest that coarse-root turnover should be considered in root research, at least under conditions of strong competition or other external stress.
Deadwood abundance in Labrador high-boreal black spruce forests
Authors: Hagemann Ulrike , Moroni Martin T. , Makeschin Franz
Published: January 2009

Deadwood (woody debris (WD), standing dead trees (snags), stumps, and buried deadwood) abundance was estimated in Labrador humid high-boreal black spruce (Picea mariana (Mill.) BSP) forests regrown following natural and anthropogenic disturbances. Aboveground deadwood (DW) abundance in Labrador was similar to values observed in other boreal forests experiencing drier or warmer climates. Clear-cut harvest generated large amounts of WD, which had almost completely decomposed 34–36 years following harvesting, with a fitted volume reduction rate of –0.058 year–1. Total WD in all harvested stands was composed of predominantly <10 cm pieces, which should be included in DW inventories of disturbed coniferous boreal forests. Postfire WD likely peaked ∼20 years following disturbance, as a result of the collapse of snags, and was dominated by large amounts of medium-sized logs (10.0–19.9 cm). Buried DW stocks considerably exceeded total aboveground DW stocks in old-growth, middle-aged, and older harvested stands. Old-growth stands contained 179.3 m3·ha–1 of buried DW, a vast amount indicative of long-term accumulation requiring significantly depressed rates of WD decomposition following burial. DW stocks could be significantly underestimated if buried DW is excluded from DW inventories in cool and moist coniferous forests with long fire-return intervals.
REGULAR BLACK HOLES IN AN ASYMPTOTICALLY DE SITTER UNIVERSE
Authors: MATYJASEK JERZY , TRYNIECKI DARIUSZ , KLIMEK MARIUSZ
Published: January 2009

A regular solution of the system of coupled equations of the nonlinear electrodynamics and gravity describing static and spherically-symmetric black holes in an asymptotically de Sitter universe is constructed and analyzed. Special emphasis is put on the degenerate configurations (when at least two horizons coincide) and their near horizon geometry. It is explicitly demonstrated that approximating the metric potentials in the region between the horizons by simple functions and making use of a limiting procedure one obtains the solutions constructed from maximally symmetric subspaces with different absolute values of radii. Topologically they are AdS2×S2 for the cold black hole, dS2×S2 when the event and cosmological horizon coincide, and the Plebański–Hacyan solution for the ultraextremal black hole. A physically interesting solution describing the lukewarm black holes is briefly analyzed.
GAUGE-INVARIANT LAGRANGIANS FOR FREE AND INTERACTING HIGHER SPIN FIELDS: A REVIEW OF THE BRST FORMULATION
Authors: FOTOPOULOS ANGELOS , TSULAIA MIRIAN
Published: January 2009

We give a detailed review of the construction of gauge-invariant Lagrangians for free and interacting higher spin fields using the BRST approach developed over the past few years.
IMPEDANCE SPECTROSCOPY STUDY OF NaCa2Nb5O15 CERAMICS
Authors: BEHERA BANARJI , NAYAK P. , CHOUDHARY R. N. P.
Published: January 2009

Polycrystalline sample of NaCa 2 Nb 5 O 15 was prepared by a high-temperature solid-state reaction technique. Preliminary X-ray structural analysis exhibits the orthorhombic crystal structure of the compound at room temperature. Detailed dielectric studies of NaCa 2 Nb 5 O 15 over a wide range of temperature (31–500°C) and frequency (102–106 Hz) did not show any dielectric anomaly (or ferroelectric phase transition) as observed in other members of the tungsten bronze structural family. However, the low loss tangent and dielectric constant increase with increasing temperature. Complex impedance and modulus plots (at different temperature and frequency) show the existence of non-Debye type of relaxation process in the compound. Complex modulus spectrum shows only grain contribution in the compound. Electric modulus analysis suggests that a possible hopping mechanism is evident for electrical transport processes in the system. Studies of AC conductivity with frequency suggest that the material obeys Jonscher's universal power law.
UNCONVENTIONAL BOSE–EINSTEIN CONDENSATIONS BEYOND THE "NO-NODE" THEOREM
Authors: WU CONGJUN
Published: January 2009

Feynman's "no-node" theorem states that the conventional many-body ground state wavefunctions of bosons in the coordinate representation are positive definite. This implies that time-reversal symmetry cannot be spontaneously broken. In this article, we review our progress in studying a class of new states of unconventional Bose–Einstein condensations beyond this paradigm. These states can either be the long-lived metastable states of ultracold bosons in high orbital bands in optical lattices as a result of the "orbital Hund's rule" interaction, or the ground states of spinful bosons with spin-orbit coupling linearly dependent on momentum. In both cases, Feynman's argument does not apply. The resultant many-body wavefunctions are complex-valued and thus break time-reversal symmetry spontaneously. Exotic phenomena in these states include the Bose–Einstein condensation at nonzero momentum, the ordering of orbital angular momentum moments, the half-quantum vortex, and the spin texture of skyrmions.
TWO-DIMENSIONAL ARRAY OF ION TRAPS ON A PLANAR CHIP
Authors: WAN JIN-YIN , WANG YU-ZHU , LIU LIANG
Published: January 2009

We investigate a planar ion chip design with a two-dimensional array of linear ion traps for the scalable quantum information processor. The segmented electrodes reside in a single plane on a substrate and a grounded metal plate, a combination of appropriate rf and DC potentials are applied to them for stable ion confinement, and the trap axes are located above the surface at a distance controlled by the electrodes' lateral extent and the substrate's height as discussed. The potential distributions are calculated using static electric field qualitatively. This architecture is conceptually simple and many current microfabrication techniques are feasible for the basic structure. It may provide a promising route for scalable quantum computers.
EOLSR: AN ENERGY EFFICIENT ROUTING PROTOCOL IN WIRELESS AD HOC AND SENSOR NETWORKS
Authors: MAHFOUDH SAOUCENE , MINET PASCALE
Published: January 2009

Energy efficiency is a key issue in wireless ad hoc and sensor networks. In order to maximize network lifetime, several directions have been explored, among them energy efficient routing. In this paper, we show how to extend the standardized OLSR routing protocol, in order to make it energy efficient. This extension selects the path minimizing the energy consumed in the end-to-end transmission of a flow packet and avoids nodes with low residual energy. As it has been shown that two-path routing is energy efficient, we compare this extension with a two-path source routing strategy (with different links or different nodes). Moreover, to take into account residual node energy, the native selection of multipoint relays of OLSR is changed. Three selection algorithms based on the minimum residual energy are evaluated. An extensive performance evaluation allows us to choose for EOLSR (Energy efficient OLSR) the best variant maximizing both network lifetime and delivery rate.
COMMUNICATION MODELING OF QoS-AWARE WORMHOLE-ROUTED NoCs
Authors: MOADELI MAHMOUD , VANDERBAUWHEDE WIM , SHAHRABI ALI
Published: January 2009

Network on-Chips (NoC) have emerged as an attractive communication architecture to address the increasing demand for communication in performance-sensitive applications. Employing differentiated services is a widely used approach to support QoS (Quality of Service) by relatively prioritizing traffic in the networks employing connection-less communication mechanisms. In this paper we present an analytical evaluation of the average message latency for wormhole-routed interconnect architectures exploiting a traffic prioritization mechanism to achieve differentiated services-based QoS. To verify the validity of the model we apply the method to the Spidergon NoC and compare the model against the results obtained from a discrete-event simulator developed using OMNET++.
MULTIFRACTAL CHARACTERIZATION OF SPATIAL INCOME CURDLING: THEORY AND APPLICATIONS
Authors: ROSALES FRANCISCO , POSADAS ADOLFO , QUIROZ ROBERTO
Published: January 2009

A spatial curdling index [Formula: see text] is presented for studying income concentration in two-dimensional fields originated by a cascade process, resembling resource allocation maps. Computational simulations of spatial distributions show that the relation between [Formula: see text] and measures of income inequality such as the Gini coefficient [Formula: see text] forms a concave area. Acknowledgment of this fact brings additional information for formulating geopolitical strategies for income inequality reduction, and for comparison purposes in a set of countries or across time within a country. With the aim of showing the importance of index [Formula: see text], a prototype of the empirical application is shown based on the Peruvian and Swedish income maps.
LEARNING, EVOLUTION AND POPULATION DYNAMICS
Authors: JOST JÜRGEN , LI WEI
Published: January 2009

We study a complementarity game as a systematic tool for the investigation of the interplay between individual optimization and population effects and for the comparison of different strategy and learning schemes. The game randomly pairs players from opposite populations. It is symmetric at the individual level, but has many equilibria that are more or less favorable to the members of the two populations. Which of these equilibria is then attained is decided by the dynamics at the population level. Players play repeatedly, but in each round with a new opponent. They can learn from their previous encounters and translate this into their actions in the present round on the basis of strategic schemes. The schemes can be quite simple, or very elaborate. We can then break the symmetry in the game and give the members of the two populations access to different strategy spaces. Typically, simpler strategy types have an advantage because they tend to go more quickly toward a favorable equilibrium which, once reached, the other population is forced to accept. Also, populations with bolder individuals that may not fare so well at the level of individual performance may obtain an advantage toward ones with more timid players. By checking the effects of parameters such as the generation length or the mutation rate, we are able to compare the relative contributions of individual learning and evolutionary adaptations.
A MULTI-OBJECTIVE HW–SW CO-SYNTHESIS ALGORITHM BASED ON QUANTUM-INSPIRED EVOLUTIONARY ALGORITHM
Authors: WEI WENLONG , LI BIN , ZOU YI , ZHANG WENCONG , ZHUANG ZHENQUAN
Published: January 2009

Hardware–Software (HW–SW) co-synthesis is one of the key steps in modern embedded system design. Generally, HW–SW co-synthesis is to optimally allocate processors, assign tasks to processors, and schedule the processing of tasks to achieve a good balance among performance, cost, power consumption, etc. Hence, it is a typical multi-objective optimization problem. In this paper, a new multi-objective HW–SW co-synthesis algorithm based on the quantum-inspired evolutionary algorithm (MQEAC) is proposed. MQEAC utilizes multiple quantum probability amplitude vectors to model the promising areas of solution space. Meanwhile, this paper presents a new crossover operator to accelerate the convergence to the Pareto front and introduces a PE slot-filling strategy to improve the efficiency of scheduling. Experimental results show that the proposed algorithm can solve the typical multi-objective co-synthesis problems effectively and efficiently.
ROTATED PROBLEMS AND ROTATIONALLY INVARIANT CROSSOVER IN EVOLUTIONARY MULTI-OBJECTIVE OPTIMIZATION
Authors: IORIO ANTONY , LI XIAODONG
Published: January 2009

Problems that are not aligned with the coordinate system can present difficulties to many optimization algorithms, including evolutionary algorithms, by trapping the search on a ridge. The ridge problem in single-objective optimization is understood, but until now little work has been done on understanding this issue in the multi-objective domain. Multi-objective problems with parameter interactions present difficulties to an optimization algorithm, which are not present in the single-objective domain. In this work, we have explained the nature of these difficulties, and investigated the behavior of the NSGA-II, which has difficulties with problems not aligned with the principle coordinate system. This study has investigated Simplex Crossover (SPX), Unimodal Normally Distributed Crossover (UNDX), Parent-Centric Crossover (PCX), and Differential Evolution (DE), as possible alternatives to the Simulated Binary Crossover (SBX) operator within the NSGA-II, on problems exhibiting parameter interactions through a rotation of the coordinate system. An analysis of these operators on three rotated bi-objective test problems, and a four-and eight-objective problem is provided. New observations on the behavior of rotationally invariant crossover operators in the multi-objective problem domain have been reported.
A HYBRID ESTIMATION OF DISTRIBUTION ALGORITHM FOR CDMA CELLULAR SYSTEM DESIGN
Authors: SUN JIANYONG , ZHANG QINGFU , LI JIN , YAO XIN
Published: January 2009

This paper proposes a hybrid estimation of distribution algorithm (HyEDA) to address the design problem of code division multiple access cellular system configuration. Given a service area, the problem is to find a set of optimal locations of base stations, associated with their corresponding powers and antenna heights in the area, in order to maximize call quality and service coverage, at the same time, to minimize the total cost of the system configuration. HyEDA is a two-stage hybrid approach which integrates an estimation of distribution algorithm, a K-means clustering method, and a simple local search algorithm. We have compared HyEDA with a simulated annealing method on a number of instances. Our simulation results have demonstrated that HyEDA outperforms the simulated annealing method in terms of the solution quality and computational cost.
EXPLICITLY SIMPLIFYING EVOLVED GENETIC PROGRAMS DURING EVOLUTION
Authors: ZHANG MENGJIE , WONG PHILLIP
Published: January 2009

The genetic programming (GP) evolutionary process typically introduces a large amount of redundancy and unnecessary complexity into evolved programs. Quick growth of redundant and functionally useless sections of programs can quickly overcome a GP system, exhausting system resources and causing premature termination of the system before an acceptable solution can be found. Rather than implicitly controlling the redundancy and code growth/bloat as in most of the existing approaches, this paper investigates an algebraic simplification algorithm for explicitly removing the redundancy from the genetic programs and simplifying these programs online during the evolutionary process. The new GP system with the simplification is examined and compared with a standard GP system on two regression and three classification problems of varying difficulties. The results show that the GP system employing a simplification component can achieve superior efficiency with comparable or slightly superior effectiveness to the standard GP system on these problems. The programs evolved by the new GP approach with the explicit simplification contain ``hidden patterns'' for a particular problem and are relatively simple and easy to interpret.
Selective mtDNA mutation accumulation results in β-cell apoptosis and diabetes development
Authors: Bensch Kenneth G. , Mott Justin L. , Chang Shin-Wen , Hansen Polly A. , Moxley Michael A. , Chambers Kari T. , de Graaf Wieke , Zassenhaus H. Peter , Corbett John A.
Published: January 2009

To test the hypothesis that somatic mitochondrial (mt)DNA mutation accumulation predisposes mice to β-cell loss and diabetes development, transgenic mice expressing a proofreading-deficient mtDNA polymerase-γ under the control of the rat insulin-1 promoter were generated. At 6 wk of age, mtDNA mutations reached 0.01% (1.05 mutations/10,000 bp) in islets isolated from transgenic mice. This mutational burden is associated with impaired glucose tolerance and a diabetes prevalence of 52% in male transgenic mice. Female transgenic mice maintain slightly elevated fasting glucose levels, mild glucose intolerance, and a diabetes prevalence of 14%. Diabetes in transgenic animals is associated with insulin insufficiency that results from a significant reduction in β-cell mass. Importantly, apoptosis of β-cells is increased 7-fold in female and 11-fold in male transgenic mice compared with littermate controls. These results are consistent with a causative role of somatic mtDNA mutation accumulation in the loss of β-cell mass and diabetes development.
Three weeks of postweaning exercise in DIO rats produces prolonged increases in central leptin sensitivity and signaling
Authors: Patterson Christa M. , Bouret Sebastien G. , Dunn-Meynell Ambrose A. , Levin Barry E.
Published: January 2009

In rats selectively bred to develop diet-induced obesity (DIO) 3 wk of postweaning exercise reduces weight and adipose regain for 10 wk after exercise cessation, despite intake of 31% fat high-energy (HE) diet. To test the hypothesis that this effect is due to increased central leptin sensitivity, 4-wk-old DIO rats were fed the HE diet and left sedentary (Sed), exercised for 3 wk, and then remained sedentary for 10 additional weeks (Ex/Sed) or continued exercise for a full 13 wk (Ex). After 3 wk, leptin (5 mg/kg ip) induced a 36% decrease in 24-h food intake in Ex rats, while Sed rats had no change in 24-h intake. Ex rats also had 23% more leptin-induced phospho-STAT3 (pSTAT3)-expressing neurons in the arcuate nucleus (ARC) and 95% and 68% higher 125I-labeled leptin receptor binding in the ventromedial and dorsomedial nuclei than did Sed rats, respectively. At 7 wk after onset, leptin decreased 24-h intake by 20% in Ex and 24% in Ex/Sed rats without altering Sed intake. After a total of 13 wk, compared with Sed rats, Ex and Ex/Sed rats had 58% and 38% less fat, respectively, but leptin failed to decrease food intake in any group. Nevertheless, Ex, but not Ex/Sed rats, still had 32% more ARC leptin-induced pSTAT3-expressing neurons than Sed rats. These data suggest that brief postweaning exercise in DIO rats that are inherently leptin resistant causes a sustained resistance to obesity on HE diet, which is, in part, due to increased central leptin sensitivity.
T1R2 and T1R3 subunits are individually unnecessary for normal affective licking responses to polycose: implications for saccharide taste receptors in mice
Authors: Treesukosol Yada , Blonde Ginger D. , Spector Alan C.
Published: January 2009

The T1R2 and T1R3 proteins are expressed in taste receptor cells and form a heterodimer binding with compounds described as sweet by humans. We examined whether Polycose taste might be mediated through this heterodimer by testing T1R2 knockout (KO) and T1R3 KO mice and their wild-type (WT) littermate controls in a series of brief-access taste tests (25-min sessions with 5-s trials). Sucrose, Na-saccharin, and Polycose were each tested for three consecutive sessions with order of presentation varied among subgroups in a Latin-Square manner. Both KO groups displayed blunted licking responses and initiated significantly fewer trials of sucrose and Na-saccharin across a range of concentrations. KO mice tested after Polycose exposure demonstrated some degree of concentration-dependent licking of sucrose, likely attributable to learning related to prior postingestive experience. These results are consistent with prior findings in the literature, implicating the T1R2+3 heterodimer as the principal taste receptor for sweet-tasting ligands, and also provide support for the potential of postingestive experience to influence responding in the KO mice. In contrast, T1R2 KO and T1R3 KO mice displayed concentration-dependent licking responses to Polycose that tracked those of their WT controls and in some cases licked midrange concentrations more; the number of Polycose trials initiated overall did not differ between KO and WT mice. Thus, the T1R2 and T1R3 proteins are individually unnecessary for normal concentration-dependent licking of Polycose to be expressed in a brief-access test. Whether at least one of these T1R protein subunits is necessary for normal Polycose responsiveness remains untested. Alternatively, there may be a novel taste receptor(s) that mediates polysaccharide taste.
Galanin microinjection into rostral ventrolateral medulla of the rat is hypotensive and attenuates sympathetic chemoreflex
Authors: Abbott Stephen B. G. , Pilowsky Paul M.
Published: January 2009

Galanin is present in neurons in the brain that are important in the control of arterial pressure, and intracisternal administration of galanin evokes hypotension, but the site of action is unknown. In urethane-anesthetized, vagotomized mechanically ventilated Sprague-Dawley rats ( n = 34), we investigated the effects of microinjecting galanin (1 mM, 50 nl, 50 pmol) into the rostral ventrolateral medulla on resting splanchnic sympathetic nerve activity, arterial pressure, heart rate, and phrenic nerve activity. Second, we determined the effect of microinjecting galanin into the rostral ventrolateral medulla on the cardiovascular response to stimulation of central and peripheral chemoreceptors, arterial baroreceptors, and the somatosympathetic reflex. Galanin caused a prolonged reduction in resting splanchnic sympathetic nerve activity (−37.0 ± 7.2% of baseline), mean arterial pressure (−17.0 ± 3.5 mmHg), and heart rate (−25.0 ± 9.1 beats/min). Galanin increased the sympathoinhibitory response to aortic depressor nerve stimulation by 51.8%, had no effect on the somatosympathetic reflex, and markedly attenuated the effect of hypercapnia and hypoxia on arterial pressure (by 65% and 92.4% of control, respectively). These results suggest a role for galanin neurotransmission in the integration of the cardiovascular responses to hypoxia, hypercapnia, and the sympathetic baroreflex in the rostral ventrolateral medulla. The data suggest that galanin may be an important peptide in the homeostatic regulation of chemosensory reflexes.
Acupuncture and exercise restore adipose tissue expression of sympathetic markers and improve ovarian morphology in rats with dihydrotestosterone-induced PCOS
Authors: Mannerås Louise , Cajander Stefan , Lönn Malin , Stener-Victorin Elisabet
Published: January 2009

Altered activity of the sympathetic nervous system, which innervates adipose and ovarian tissue, may play a role in polycystic ovary syndrome (PCOS). We hypothesize that electro-acupuncture (EA) and physical exercise reduce sympathetic activity by stimulating ergoreceptors and somatic afferent pathways in muscles. Here we investigated the effects of low-frequency EA and physical exercise on mRNA expression of sympathetic markers in adipose tissue and on ovarian morphology in female rats that received dihydrotestosterone (DHT) continuously, starting before puberty, to induce PCOS. At age 11 wk, rats with DHT-induced PCOS were randomly divided into three groups: PCOS, PCOS plus EA, and PCOS plus exercise. The latter two groups received 2-Hz EA (evoking muscle twitches) three times/week or had free access to a running wheel for 4–5 wk. In mesenteric adipose tissue, expression of β3-adrenergic receptor (ADRB3), nerve growth factor (NGF), and neuropeptide Y (NPY) mRNA was higher in untreated PCOS rats than in controls. Low-frequency EA and exercise downregulated mRNA expression of NGF and NPY, and EA also downregulated expression of ADRB3, compared with untreated rats with DHT-induced PCOS. EA and exercise improved ovarian morphology, as reflected in a higher proportion of healthy antral follicles and a thinner theca interna cell layer than in untreated PCOS rats. These findings support the theory that increased sympathetic activity contributes to the development and maintenance of PCOS and that the effects of EA and exercise may be mediated by modulation of sympathetic outflow to the adipose tissue and ovaries.
Short-Term Temporal Discounting of Reward Value in Human Ventral Striatum
Authors: Gregorios-Pippas Lucy , Tobler Philippe N. , Schultz Wolfram
Published: January 2009

Delayed rewards lose their value for economic decisions and constitute weaker reinforcers for learning. Temporal discounting of reward value already occurs within a few seconds in animals, which allows investigations of the underlying neurophysiological mechanisms. However, it is difficult to relate these mechanisms to human discounting behavior, which is usually studied over days and months and may engage different brain processes. Our study aimed to bridge the gap by using very short delays and measuring human functional magnetic resonance responses in one of the key reward centers of the brain, the ventral striatum. We used psychometric methods to assess subjective timing and valuation of monetary rewards with delays of 4.0–13.5 s. We demonstrated hyperbolic and exponential decreases of striatal responses to reward predicting stimuli within this time range, irrespective of changes in reward rate. Lower reward magnitudes induced steeper behavioral and striatal discounting. By contrast, striatal responses following the delivery of reward reflected the uncertainty in subjective timing associated with delayed rewards rather than value discounting. These data suggest that delays of a few seconds affect the neural processing of predicted reward value in the ventral striatum and engage the temporal sensitivity of reward responses. Comparisons with electrophysiological animal data suggest that ventral striatal reward discounting may involve dopaminergic and orbitofrontal inputs.
Activation of Lumbar Spinal Wide-Dynamic Range Neurons by a Sanshool Derivative
Authors: Sawyer Carolyn M. , Carstens Mirela Iodi , Simons Christopher T. , Slack Jay , McCluskey T. Scott , Furrer Stefan , Carstens E.
Published: January 2009

The enigmatic sensation of tingle involves the activation of primary sensory neurons by hydroxy-α-sanshool, a tingly agent in Szechuan peppers, by inhibiting two-pore potassium channels. Central mechanisms mediating tingle sensation are unknown. We investigated whether a stable derivative of sanshool—isobutylalkenyl amide (IBA)—excites wide-dynamic range (WDR) spinal neurons that participate in transmission of chemesthetic information from the skin. In anesthetized rats, the majority of WDR and low-threshold units responded to intradermal injection of IBA in a dose-related manner over a >5-min time course and exhibited tachyphylaxis at higher concentrations (1 and 10%). Almost all WDR and low-threshold units additionally responded to the pungent agents mustard oil (allyl isothiocyanate) and/or capsaicin, prompting reclassification of the low-threshold cells as WDR. The results are discussed in terms of the functional role of WDR neurons in mediating tingle sensation.
Multidrug Resistance Decreases with Mutations of Melanosomal Regulatory Genes
Authors: Xie Tong , Nguyen Thuyen , Hupe Melanie , Wei Maria L.
Published: January 2009

Whereas resistance to chemotherapy has long impeded effective treatment of metastatic melanoma, the mechanistic basis of this resistance remains unknown. One possible mechanism of drug resistance is alteration of intracellular drug distribution either by drug efflux or sequestration into intracellular organelles. Melanomas, as well as primary melanocytes from which they arise, have intracellular organelles, called melanosomes, wherein the synthesis and storage of the pigment melanin takes place. In this study, comparisons of congenic cells with and without functional molecules regulating melanosome formation show that sensitivity to the chemotherapeutic agent cis-diaminedichloroplatinum II (cis-platin) significantly increases with the mutation of genes regulating melanosome formation, concomitant disruption of melanosome morphology, and loss of mature melanosomes. Absence of the melanosomal structural protein gp100/Pmel17 causes increased cis-platin sensitivity. Independent mutations in three separate genes that regulate melanosome biogenesis (Dtnbp1, Pldn, Vps33a) also result in increased cis-platin sensitivity. In addition, a mutation of the gene encoding the integral melanosomal protein tyrosinase, resulting in aberrant melanosome formation, also causes increased cis-platin sensitivity. Furthermore, sensitivity to agents in other chemotherapeutic classes (e.g., vinblastine and etoposide) also increased with the mutation of Pldn. In contrast, a mutation in another melanosomal regulatory gene, Hps1, minimally affects melanosome biogenesis, preserves the formation of mature melanosomes, and has no effect on cis-platin or vinblastine response. Together, these data provide the first direct evidence that melanosomal regulatory genes influence drug sensitivity and that the presence of mature melanosomes likely contributes to melanoma resistance to therapy. [Cancer Res 2009;69(3):992–9]
A Requirement for Cyclin-Dependent Kinase 6 in Thymocyte Development and Tumorigenesis
Authors: Hu Miaofen G. , Deshpande Amit , Enos Miriam , Mao Daqin , Hinds Elisabeth A. , Hu Guo-fu , Chang Rui , Guo Zhuyan , Dose Marei , Mao Changchuin , Tsichlis Philip N. , Gounari Fotini , Hinds Philip W.
Published: January 2009

Cyclin-dependent kinase 6 (CDK6) promotes cell cycle progression and is overexpressed in human lymphoid malignancies. To determine the role of CDK6 in development and tumorigenesis, we generated and analyzed knockout mice. Cdk6-deficient mice show pronounced thymic atrophy due to reduced proliferative fractions and concomitant transitional blocks in the double-negative stages. Using the OP9-DL1 system to deliver temporally controlled Notch receptor–dependent signaling, we show that CDK6 is required for Notch-dependent survival, proliferation, and differentiation. Furthermore, CDK6-deficient mice were resistant to lymphomagenesis induced by active Akt, a downstream target of Notch signaling. These results show a critical requirement for CDK6 in Notch/Akt-dependent T-cell development and tumorigenesis and strongly support CDK6 as a specific therapeutic target in human lymphoid malignancies. [Cancer Res 2009;69(3):810–8]
IFN Regulatory Factor 8 Sensitizes Soft Tissue Sarcoma Cells to Death Receptor–Initiated Apoptosis via Repression of FLICE-like Protein Expression
Authors: Yang Dafeng , Wang Suizhao , Brooks Craig , Dong Zheng , Schoenlein Patricia V. , Kumar Vijay , Ouyang Xinshou , Xiong Huabao , Lahat Guy , Hayes-Jordan Andrea , Lazar Alexander , Pollock Raphael , Lev Dina , Liu Kebin
Published: January 2009

IFN regulatory factor 8 (IRF8) has been shown to suppress tumor development at least partly through regulating apoptosis of tumor cells; however, the molecular mechanisms underlying IRF8 regulation of apoptosis are still not fully understood. Here, we showed that disrupting IRF8 function resulted in inhibition of cytochrome c release, caspase-9 and caspase-3 activation, and poly(ADP-ribose) polymerase cleavage in soft tissue sarcoma (STS) cells. Inhibition of the mitochondrion-dependent apoptosis signaling cascade is apparently due to blockage of caspase-8 and Bid activation. Analysis of signaling events upstream of caspase-8 revealed that disrupting IRF8 function dramatically increases FLIP mRNA stability, resulting in increased IRF8 protein level. Furthermore, primary myeloid cells isolated from IRF8-null mice also exhibited increased FLIP protein level, suggesting that IRF8 might be a general repressor of FLIP. Nuclear IRF8 protein was absent in 92% (55 of 60) of human STS specimens, and 99% (59 of 60) of human STS specimens exhibited FLIP expression, suggesting that the nuclear IRF8 protein level is inversely correlated with FLIP level in vivo. Silencing FLIP expression significantly increased human sarcoma cells to both FasL-induced and tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)–induced apoptosis, and ectopic expression of IRF8 also significantly increased the sensitivity of these human sarcoma cells to FasL- and TRAIL-induced apoptosis. Taken together, our data suggest that IRF8 mediates FLIP expression level to regulate apoptosis and targeting IRF8 expression is a potentially effective therapeutic strategy to sensitize apoptosis-resistant human STS to apoptosis, thereby possibly overcoming chemoresistance of STS, currently a major obstacle in human STS therapy. [Cancer Res 2009;69(3):1080–8]
Large-Scale Profiling of Archival Lymph Nodes Reveals Pervasive Remodeling of the Follicular Lymphoma Methylome
Authors: Killian J. Keith , Bilke Sven , Davis Sean , Walker Robert L. , Killian M. Scott , Jaeger Erich B. , Chen Yidong , Hipp Jason , Pittaluga Stefania , Raffeld Mark , Cornelison Robert , Smith, William I. , Bibikova Marina , Fan Jian-Bing , Emmert-Buck Michael R. , Jaffe Elaine S. , Meltzer Paul S.
Published: January 2009

Emerging technologies allow broad profiling of the cancer genome for differential DNA methylation relative to benign cells. Herein, bisulfite-modified DNA from lymph nodes with either reactive hyperplasia or follicular lymphoma (FL) were analyzed using a commercial C/UpG genotyping assay. Two hundred fifty-nine differentially methylated targets (DMT) distributed among 183 unique genes were identified in FL. Comparison of matched formalin-fixed, paraffin-embedded and frozen surgical pathology replicates showed the complete preservation of the cancer methylome among differently archived tissue specimens. Analysis of the DMT profile is consistent with a pervasive epigenomic remodeling process in FL that affects predominantly nonlymphoid genes. [Cancer Res 2009;69(3):758–64]
In-Depth Proteomics to Define the Cell Surface and Secretome of Ovarian Cancer Cells and Processes of Protein Shedding
Authors: Faça Vitor M. , Hanash Samir M.
Published: January 2009

Current proteomics technologies allow substantial depth of analysis of cellular and subcellular proteomes as shown in the proteomic profiling of ovarian cancer cells. This in-depth analysis has elucidated the repertoire of proteins expressed on the cell surface and proteins released into the extracellular milieu, uncovering extensive shedding of extracellular domains of cell adhesion proteins and a highly dynamic protein secretion process. The protein sets identified provide a rich resource of potential circulating markers and targets for imaging and therapeutics for ovarian cancer. [Cancer Res 2009;69(3):728–30
The Transcriptional Corepressor CtBP: A Foe of Multiple Tumor Suppressors
Authors: Chinnadurai G.
Published: January 2009

CtBP1 and CtBP2 are closely related and evolutionarily conserved transcriptional corepressors. There is strong evidence linking CtBPs to tumorigenesis and tumor progression. CtBPs promote epithelial-mesenchymal transition and function as apoptosis antagonists. Also, CtBPs mediate repression of several tumor suppressor genes. Certain tumor suppressors also target CtBPs to restrain their tumor-promoting activity. Down-regulation of CtBPs mediated by some tumor suppressors results in p53-independent apoptosis and reduced tumor cell migration and invasion. The role of CtBPs in modulating the activities of different tumor suppressors is reviewed here. The results discussed here suggest that CtBPs may constitute a novel p53-independent anticancer target. [Cancer Res 2009;69(3):731–4]
Human Postmeiotic Segregation 2 Exhibits Biased Repair at Tetranucleotide Microsatellite Sequences
Authors: Shah Sandeep N. , Eckert Kristin A.
Published: January 2009

The mismatch repair (MMR) system plays a major role in removing DNA polymerization errors, and loss of this pathway results in hereditary cancers characterized by microsatellite instability. We investigated microsatellite stability during DNA replication within human postmeiotic segregation 2 (hPMS2)–deficient and proficient human lymphoblastoid cell lines. Using a shuttle vector assay, we measured mutation rates at reporter cassettes containing defined mononucleotide, dinucleotide, and tetranucleotide microsatellite sequences. A mutator phenotype was observed in the hPMS2-deficient cell line. The mutation rate of vectors containing [G/C]10 or [GT/CA]10 alleles was elevated 20-fold to 40-fold in hPMS2-deficient cells, relative to an hPMS2-expressing cell line. We observed a 6-fold and 12-fold relative increase in mutation rate of [TTTC/AAAG]9 and [TTCC/AAGG]9 sequences, respectively, in hPMS2-deficient cells. Mutational specificity analyses suggested that repair by hPMS2 is biased. In the absence of hPMS2, a greater number of microsatellite expansion versus deletion mutations was observed, and expansion rates of the tetranucleotide alleles were similar. In the presence of hPMS2, we observed a 29-fold decrease in the [TTCC/AAGG]9 expansion rate but only a 6-fold decrease for the [TTTC/AAAG]9 allele. Our data indicate that hPMS2 is more protective of tetranucleotide expansions than deletions and that hPMS2 displays a sequence bias, wherein [TTCC/AAGG] sequences are stabilized to a greater extent than [TTTC/AAAG]. Our results allow for greater accuracy during identification of MMR defects by providing a mutational signature characteristic of hPMS2 defect. This study also provides clues to possible mechanisms of repair by hPMS2 in the context of the MMR system. [Cancer Res 2009;69(3):1143–9]
Emerging Paradigms in Cancer Genetics: Some Important Findings from High-Density Single Nucleotide Polymorphism Array Studies
Authors: Bacolod Manny D. , Schemmann Gunter S. , Giardina Sarah F. , Paty Philip , Notterman Daniel A. , Barany Francis
Published: January 2009

High-density single nucleotide polymorphism (SNP) mapping arrays have identified chromosomal features whose importance to cancer predisposition and progression is not yet clearly defined. Of interest is that the genomes of normal somatic cells (reflecting the combined parental germ-line contributions) often contain long homozygous stretches. These chromosomal segments may be explained by the common ancestry of the individual's parents and thus may also be called autozygous. Several studies link consanguinity to higher rates of cancer, suggesting that autozygosity (a genomic consequence of consanguinity) may be a factor in cancer predisposition. SNP array analysis has also identified chromosomal regions of somatic uniparental disomy (UPD) in cancer genomes. These are chromosomal segments characterized by loss of heterozygosity (LOH) and a normal copy number (two) but which are not autozygous in the germ-line or normal somatic cell genome. In this review, we will also discuss a model [cancer gene activity model (CGAM)] that may explain how autozygosity influences cancer predisposition. CGAM can also explain how the occurrence of certain chromosomal aberrations (copy number gain, LOH, and somatic UPDs) during carcinogenesis may be dependent on the germ-line genotypes of important cancer-related genes (oncogenes and tumor suppressors) found in those chromosomal regions. [Cancer Res 2009;69(3):723–7]
Our 21-Year Experience with the Thiersch-Duplay Technique following Surgical Correction of Penoscrotal Transposition
Authors: Sunay Melih , Emir Levent , Karabulut Ayhan , Erol Demokan
Published: January 2009

Objectives: To assess surgical techniques applied after surgical correction of penoscrotal transposition and their complications. Methods: The medical records of 64 patients with a mean age of 4.1 years (range 1–24) who underwent surgical correction for penoscrotal transposition and subsequent Thiersch-Duplay urethroplasty in the last 21 years were evaluated retrospectively. Results: All cases underwent Thiersch-Duplay urethroplasty following reconstruction of penoscrotal transposition after a minimum interval of 6 months. Following Thiersch urethroplasty, 41 (64%) cases with successful outcomes had glandular meatuses. Of the remaining 23 (36%) patients 15, 7 and 1 patients underwent second operations for urethrocutaneous fistulas, meatal regressions and urethral diverticulum, respectively. Eleven of 15 patients underwent primary fistula repair and 4 patients, turnover fistula repair. These patients had glandular meatuses following fistula repair. Seven cases with meatal regression and breakdown of the neourethra were reoperated on by using double-face urethroplasty, onlay island flap urethroplasty and free-tube urethroplasty techniques. Finally, all patients had glandular meatuses. One patient with urethral diverticulum underwent successful diverticulum excision and meatoplasty. Conclusions: Thierch uretroplasty is the most commonly performed technique after surgical correction of penoscrotal transposition; however, additional procedures are needed for the management of its complications.
Hydronephrosis Promotes Expression of Hypoxia-Inducible Factor 1α
Authors: Stravodimos Konstantinos G. , Koritsiadis Georgios , Lazaris Andreas C. , Agrogiannis Georgios , Koutalellis Georgios , Constantinides Constantinos , Patsouris Efstratios , Kapetanakis Theodoros , Zervas Anastasios
Published: January 2009

Background: Obstructive uropathy is argued to involve an ischemia-type tissue injury. Further, hypoxia-inducible factor 1α (HIF-1α) constitutes a nuclear transcription factor normally upregulated under hypoxic conditions. We hypothesized that HIF-1α is expressed in the hydronephrotic renal pelvis, as a result of tissue hypoxia. Patients and Methods: Renal pelvis tissue specimens were obtained from 2 patient groups. Group 1 (controls, n = 10) consisted of patients who underwent nephrectomy due to nonobstructive renal malignancy. Group 2 (n = 18) consisted of patients who underwent open procedures due to intractable hydronephrosis, not amenable to conservative measures. HIF-1α detection was conducted via immunohistochemical techniques, while histological alterations in both groups were also recorded. Results: Smooth muscle hypertrophy and urothelial hyperplasia were major findings in group 2. HIF-1α-positive cells (fibroblasts and occasionally macrophages), mainly localized in the stroma, were also found to a greater extent in group 2 (p = 0.0066). Conclusion: We conclude that HIF-1α is mainly expressed in stroma fibroblasts of the hydronephrotic renal pelvis, implying the presence of significant tissue hypoxia at the dilated upper urinary tract.
Influence of High Bladder Pressure on Vesicoureteral Reflux and Its Resolution
Authors: Acar Banu , Arıkan F. İnci , Germiyanoğlu Cankon , Dallar Yıldız
Published: January 2009

Objectives: Voiding dysfunction may result in lower urinary tract symptoms in children and is associated with urinary tract infection, renal damage and vesicoureteral reflux (VUR). The aim of this study was to assess the relationship between detrusor pressure, VUR and abnormal renal scintigraphy findings in children with dysfunctional voiding. Patients and Methods: Between 2004 and 2007, 30 children with VUR and voiding dysfunction, 22 girls and 8 boys, median age 8.2 years, were evaluated. Urodynamic study, renal scan and voiding cystourethrography were performed in all patients. Results: The degree of the renal scarring was found to be associated with the detrusor pressures (p = 0.018). The highest detrusor pressure was shown in the group of urge syndrome. The degree of the VUR was found to be correlated with the detrusor pressures (p = 0.038). In our study group, VUR had resolved in 11 (37%) patients, had improved in grade in 10 (33%) patients and remained unchanged in 9 (30%) patients after anticholinergic therapy. No significant relationship was found between the duration of therapy and the voiding patterns (p = 0.389). Conclusion: Every child with VUR should undergo a careful evaluation of its bladder function. The patients who have high detrusor pressures should be evaluated carefully for the presence of VUR and renal damage.
Mucoepidermoid Lung Tumor Appearing as an Abscess on the Scrotum
Authors: Szendrői Attila , Majoros Attila , Székely Eszter , Szűcs Miklós , Romics Imre
Published: January 2009

The authors present the case of a 52-year-old man who had recurring scrotal abscesses resulting in oncotomy being carried out seven times within 2 years. Eventually, it was dissected out totally. Histology proved anaplastic cancer metastasis. The primary tumor was detected in the bronchia; moreover, metastases were found in other organs as well. The patient died 6 weeks after the first diagnosis. We intended to draw attention to frequently occurring scrotal inflammation and thus the underlying diseases. We emphasize the importance of histology examinations.