bluuebunny/crossref_metadata_2025 huggingface dataset:
KOCHEN–SPECKER THEOREM AND EXPERIMENTAL TEST ON HIDDEN VARIABLES
Authors: CABELLO ADÁN
Published: August 2004

A recent proposal to experimentally test quantum mechanics against noncontextual hidden-variable theories [Phys. Rev. Lett.80, 1797 (1998)] is shown to be related with the smallest proof of the Kochen–Specker theorem currently known [Phys. Lett.A212, 183 (1996)]. This proof contains eighteen yes-no questions about a four-dimensional physical system, combined in nine mutually incompatible tests. When these tests are considered as tests about a two-part two-state system, then quantum mechanics and noncontextual hidden variables make the same predictions for eight of them, but make different predictions for the ninth. Therefore, this ninth test would allow us to discriminate between quantum mechanics and noncontextual hidden-variable theories in a (gedanken) single run experiment.
GRAVITOMAGNETIC MOMENTS OF THE FUNDAMENTAL FIELDS
Authors: ALDROVANDI R. , DE ANDRADE V. C. , PEREIRA J. G.
Published: August 2004

The quadratic form of the Dirac equation in a Riemann space–time yields a gravitational gyromagnetic ratio κS=2 for the interaction of a Dirac spinor with curvature. A gravitational gyromagnetic ratio κS=1 is also found for the interaction of a vector field with curvature. It is shown that the Dirac equation in a curved background can be obtained as the square-root of the corresponding vector field equation only if the gravitational gyromagnetic ratios are properly taken into account.
HYDROPHOBIC HYDRATION FROM CAR–PARRINELLO SIMULATIONS
Authors: KIRCHNER BARBARA , HUTTER JÜRG , KUO I.-FENG W. , MUNDY CHRISTOPHER J.
Published: August 2004

In this work we investigate the fast anomalous diffusion of hydrogen molecules in water using Car–Parrinello molecular dynamics simulations. We employ Voronoi polyhedra analysis to distinguish between void diffusion and void hopping. Our results indicate that a combination of both mechanism is sufficient to explain anomalous diffusion. Furthermore, we investigate the geometrical and electronical structure of the first solvation shell.
MESOSCOPIC TRANSPORT THROUGH A QUANTUM DOT–CARBON NANOTUBE SYSTEM IN AN APPLIED MICROWAVE FIELD
Authors: ZHAO LI-NA , ZHAO HONG-KANG
Published: August 2004

The coherent transport through a quantum-dot (QD) coupled with single-wall carbon nanotubes (SWCNs) is investigated by employing the nonequilibrium Green's function (NGF) technique. An external microwave field is applied to the central QD to induce side-bands in addition to the energy levels of the QD. The SWCNs act as quantum wires which open quantum channels for electron to transport through. The novel behaviors are obtained in differential conductance and tunneling current, which are strongly associated with the density of states (DOS) of leads. The hybrid system with a QD coupled to normal metal and SWCN is also investigated as a comparison. The armchair SWCN lead provides rich tunneling channels compared with that of a metal lead. The I–V characteristics is calculated to exhibit stair-like structures which correspond to the resonant peaks of differential conductance versus source–drain bias. The current resonance with the gate voltage is shown to exhibit the photon-assisted tunneling.
MAGNETIC FIELD AND TEMPERATURE DEPENDENCE OF THE SURFACE POLARON IN POLAR CRYSTALS
Authors: EERDUNCHAOLU  , XIAO WEI , XIAO JING LIN
Published: August 2004

There is weak bulk but strong surface coupling between electrons and phonons for many polar crystals. We investigate in this paper the effect of a magnetic field and temperature on the electron in polar crystals which is weakly coupled to the bulk longitudinal optical (LO) phonons while strongly coupled to the surface optical (SO) ones. The magnetic field and temperature dependences of the vibration frequency, the self-trapping energy, the induced potential and the effective interaction potential of the surface magnetopolaron were investigated by using a linear combination operator and variational method. The numerical calculation, taking AgCl crystal as an example, are performed.
ON THE THEORY OF PSEUDOGAP ANISOTROPY IN THE CUPRATE SUPERCONDUCTORS
Authors: LOKTEV V. M. , TURKOWSKI V.
Published: August 2004

We show by means of the theory of order parameter phase fluctuations that the temperature of the "closing" (or "opening") of the gap (and pseudogap) in the electron spectra of superconductors with anisotropic order parameter actually takes place within a finite temperature range. Every Fourier-component of the order parameter has its own critical temperature.
EXACTLY SOLVABLE MODELS THROUGH THE GENERALIZED EMPTY INTERVAL METHOD: MULTI-SPECIES AND MORE-THAN-TWO-SITE INTERACTIONS
Authors: AGHAMOHAMMADI AMIR , KHORRAMI MOHAMMAD
Published: August 2004

Multi-species reaction-diffusion systems, with more-than-two-site interaction on a one-dimensional lattice are considered. Necessary and sufficient constraints on the interaction rates are obtained, that guarantee the closure of the time evolution equation for [Formula: see text], the expectation value of the product of certain linear combination of the number operators on n consecutive sites at time t.
LIQUID–GAS PHASE TRANSITION TO FIRST ORDER OF AN ARGON-LIKE FLUID MODELED BY THE HARD-CORE SIMILAR SUTHERLAND POTENTIAL
Authors: TIAN JIANXIANG , GUI YUANXING
Published: August 2004

In this paper, an argon-like canonical system is studied. We introduce five hypothesis to deal with the total potential of the system. Then the balanced liquid–gas coexistence phenomenon is analyzed. Good equations of state and phase diagram are given.
THE GREEN'S FUNCTIONS OF SPATIALLY CONFINED ORDER-DISORDER SYSTEMS
Authors: GARIĆ M. , OBADOVIĆ D. , TOŠIĆ B. , PANTIĆ M.
Published: August 2004

The theory of Green's functions (GF) for thin films was formulated, where site indices were different also along the direction of broken symmetry. This approach results in the layer dependence of correlation functions in films, which did not appear in the previous investigations of thin films. The magnetizations of three layer thin ferromagnetic (FM) and four layer thin ferroelectric (FE) films were investigated using the GFs found in this way. It was shown that the transition temperature varies from layer to layer, which is the obvious consequence of the generalization of the formalism of the GF calculation for films.
A NOTE ON QUANTUM OSCILLATORS COUPLED BY NONRESONANT INTERACTION: ENVIRONMENT MODIFYING DYNAMICS
Authors: DE ALMEIDA N. G. , AVELAR A. T. , BASEIA B.
Published: August 2004

We study the dynamics of a single fermionic system interacting non-resonantly with a single mode of a bosonic oscillator coupled to a reservoir. It is shown that the damping rates for both systems are modified when the action of their environments are frequency-dependent. The interest of such demand is discussed.
MODIFIED COMFORTABLE DRIVING MODEL FOR CONGESTED TRAFFIC FLOW
Authors: JIANG RUI , WU QING-SONG
Published: August 2004

In this paper, the concepts of "jammed status" and "jam headway" [X. B. Li, R. Jiang and Q. S. Wu, Phys. Rev.E68, 016117 (2003)] are introduced into the Modified Comfortable Driving (MCD) model [R. Jiang and Q. S. Wu, J. Phys.A36, 381 (2003)] to simulate the congested traffic flow including synchronized flow and wide moving jams. Using computer simulation, the fundamental diagram, the space–time plots, the time series of the density in the jams, the 1-min average data in the flow-density plane, the traffic patterns induced by red light are investigated. It is shown that the new model can describe both the synchronized flow and the sparse wide jams quite well.
THE INFLUENCE OF SPUTTERING TIME AND OXYGEN PARTIAL PRESSURE ON ELECTRICAL RESISTIVITY OF Bi:2201 THIN FILMS
Authors: POP AUREL , ILONCA GHEORGHE , DELTOUR ROBERT
Published: August 2004

By using different times of sputtering and different value of partial pressure of oxygen in sputtering gas, Bi 2.1 Sr 1.9 CuO y thin films ( Bi :2201) were deposited onto heated single crystal (100) MgO substrates. The temperature dependence of the in-plane resistivity measured on epitaxial c-axis thin films is strongly influenced by the thin films synthesis conditions. Electrical resistivity changes strongly from optimal doping superconducting state to underdoped insulator state with decreasing partial pressure in sputtering gas. The increase of electrical resistance near superconducting transition were analyzed by using some theoretical models.
DECISION TREE SIMPLIFICATION FOR CLASSIFIER ENSEMBLES
Authors: WINDEATT T. , ARDESHIR G.
Published: August 2004

The goal of designing an ensemble of simple classifiers is to improve the accuracy of a recognition system. However, the performance of ensemble methods is problem-dependent and the classifier learning algorithm has an important influence on ensemble performance. In particular, base classifiers that are too complex may result in overfitting. In this paper, the performance of Bagging, Boosting and Error-Correcting Output Code (ECOC) is compared for five decision tree pruning methods. A description is given for each of the pruning methods and the ensemble techniques. AdaBoost.OC which is a combination of Boosting and ECOC is compared with the pseudo-loss based version of Boosting, AdaBoost.M2 and the influence of pruning on the performance of the ensembles is studied. Motivated by the result that both pruned and unpruned ensembles made by AdaBoost.OC give similar accuracy, pruned ensembles are compared with ensembles of Decision Stumps. This leads to the hypothesis that ensembles of simple classifiers may give better performance for some problems. Using the application of face recognition, it is shown that an AdaBoost.OC ensemble of Decision Stumps outperforms an ensemble of pruned C4.5 trees for face identification, but is inferior for face verification. The implication is that in some real-world tasks to achieve best accuracy of an ensemble, it may be necessary to select base classifier complexity.
MULTICLASS CLASSIFIER FROM A COMBINATION OF LOCAL EXPERTS: TOWARD DISTRIBUTED COMPUTATION FOR REAL-PROBLEM CLASSIFIERS
Authors: KÖNIG CHRISTOPH , GINI GIUSEPPINA , CRACIUN MARIAN , BENFENATI EMILIO
Published: August 2004

In many real-world applications simple classifiers are too weak to have predictive power. Ensemble techniques, or mixture of experts, are a possible solution. We illustrate why mixture of experts are a natural choice in domains such as the prediction of environmental toxicity for chemicals, when a structural approach is pursued. The real data here used are derived from peer reviewed experiments, and are publicly available, but are difficult to model. We used them to predict aquatic toxicity for fish. Chemical information was coded into a set of about 160 descriptors; after reducing the dimensions of the feature vector through different techniques, we developed multivariate regression to build a model of the toxic effects of chemicals. Defining toxicity as a category, as in European Union (EU) regulations, we extended the study to predict toxicity class. Problems with poor predictive power of this simple approach have led us to reconsider the problem from a more theoretical angle. We have respected locality criterion to build different local classifiers, one for each chemical class, to achieve better results. Then we combined the classifiers to get a complete system to predict any chemical for the chemical classes studied.
ON DIFFERENT MODEL SELECTION CRITERIA IN A FORWARD AND BACKWARD REGRESSION HYBRID NETWORK
Authors: COHEN SHIMON , INTRATOR NATHAN
Published: August 2004

An assessment of the performance of a hybrid network with different model selection criteria is considered. These criteria are used in an automatic model selection algorithm for constructing a hybrid network of radial and perceptron hidden units for regression. A forward step builds the full hybrid network; a model selection criterion is used for controlling the network-size and another criterion is used for choosing the appropriate hidden unit for different regions of input space. This is followed by a conservative pruning step using Likelihood Ratio Test, Bayesian or Minimum Description Length, which leads to robust estimators with low variance. The result is a small architecture that performs well on difficult, realistic, benchmark data-sets of high dimensionality and small training size. Best results are obtained by using the Bayesian approach for the model selection.
A STUDY ON COMBINING IMAGE REPRESENTATIONS FOR IMAGE CLASSIFICATION AND RETRIEVAL
Authors: LAI CARMEN , TAX DAVID M. J. , DUIN ROBERT P. W. , PĘKALSKA ELŻBIETA , PACLÍK PAVEL
Published: August 2004

A flexible description of images is offered by a cloud of points in a feature space. In the context of image retrieval such clouds can be represented in a number of ways. Two approaches are here considered. The first approach is based on the assumption of a normal distribution, hence homogeneous clouds, while the second one focuses on the boundary description, which is more suitable for multimodal clouds. The images are then compared either by using the Mahalanobis distance or by the support vector data description (SVDD), respectively.

The paper investigates some possibilities of combining the image clouds based on the idea that responses of several cloud descriptions may convey a pattern, specific for semantically similar images. A ranking of image dissimilarities is used as a comparison for two image databases targeting image classification and retrieval problems. We show that combining of the SVDD descriptions improves the retrieval performance with respect to ranking, on the contrary to the Mahalanobis case. Surprisingly, it turns out that the ranking of the Mahalanobis distances works well also for inhomogeneous images.
A MULTICLASS EXTENSION TO THE BROWNBOOST ALGORITHM
Authors: MCDONALD ROSS A. , HAND DAVID J. , ECKLEY IDRIS A.
Published: August 2004

Brownboost is an adaptive, continuous time boosting algorithm based on the Boost-by-Majority (BBM) algorithm. Though it has been little studied at the time of writing, it is believed that it should prove especially robust with respect to noisy data sets. This would make it a very useful boosting algorithm for real-world applications. More familiar algorithms such as Adaboost, or its successor Logitboost, are known to be especially susceptible to overfitting the training data examples. This can lead to a poor generalization error in the presence of class noise, since weak hypotheses induced at later iterations to fit the noisy examples will tend to be given undue influence in the final combined hypothesis. Brownboost allows us to specify an expected base-line error rate in advance, corresponding to our prior beliefs about the proportion of noise in the training data, and thus avoid overfitting. The original derivation of Brownboost is restricted to binary classification problems. In this paper we propose a natural multiclass extension to the basic algorithm, incorporating error-correcting output codes and a multiclass gain measure. We test two-class and multiclass versions of the algorithm on a number of real and simulated data sets with artificial class noise, and show that Brownboost consistently outperforms Adaboost in these situations.
A MULTI-EXPERT SYSTEM FOR SHOT CHANGE DETECTION IN MPEG MOVIES
Authors: DE SANTO MASSIMO , PERCANNELLA GENNARO , SANSONE CARLO , VENTO MARIO
Published: August 2004

Shot Change Detection (SCD) in MPEG coded videos is a complex and still open research problem whose interest is growing up more and more due to the diffusion of Video Databases and Digital Libraries. Techniques providing fully satisfactory performances on complex video domains are not yet available even if a number of proposals exist; such proposals show very often to be complementary in their results. In this context, the Authors investigated the use of Multi-Expert Systems (MES) for approaching the SCD problem. In the present paper, we propose and discuss a strategy to select the SCD techniques to be combined and a method for choosing an effective combining rule. In order to assess the performance of the proposed MES, we set up a database that is significantly wider than the ones commonly used in the field. Experimental results demonstrate that the proposed system performs better than each of the single SCD technique considered.
HANDWRITTEN WORD RECOGNITION USING CLASSIFIER ENSEMBLES GENERATED FROM MULTIPLE PROTOTYPES
Authors: GÜNTER SIMON , BUNKE HORST
Published: August 2004

Handwritten text recognition is one of the most difficult problems in the field of pattern recognition. In this paper, we describe our efforts towards improving the performance of state-of-the-art handwriting recognition systems through the use of classifier ensembles. There are many examples of classification problems in the literature where multiple classifier systems increase the performance over single classifiers. Normally one of the two following approaches is used to create a multiple classifier system. (1) Several classifiers are developed completely independent of each other and combined in a last step. (2) Several classifiers are created out of one prototype classifier by using so-called classifier ensemble creation methods. In this paper an algorithm which combines both approaches is introduced and it is used to increase the recognition rate of a hidden Markov model (HMM) based handwritten word recognizer.
A POSTERIORI ERROR ESTIMATION FOR THE STOKES PROBLEM: ANISOTROPIC AND ISOTROPIC DISCRETIZATIONS
Authors: CREUSÉ E. , NICAISE S. , KUNERT G.
Published: August 2004

The paper presents a posteriori error estimators for the stationary Stokes problem. We consider anisotropic finite element discretizations (i.e. elements with very large aspect ratio) where conventional, isotropic error estimators fail.

Our analysis covers two- and three-dimensional domains, conforming and non-conforming discretizations as well as different elements. This large variety of settings requires different approaches and results in different estimators. Furthermore many examples of finite element pairs that are covered by the analysis are presented.

Lower and upper error bounds form the main result with minimal assumptions on the elements. The lower error bound is uniform with respect to the mesh anisotropy with the exception of nonconforming 3D discretizations made of pentahedra or hexahedra. The upper error bound depends on a proper alignment of the anisotropy of the mesh which is a common feature of anisotropic error estimation.

In the special case of isotropic meshes, the results simplify, and upper and lower error bounds hold unconditionally. Some of the corresponding results seem to be novel (in particular for 3D domains), and cover element pairs of practical importance.

The numerical experiments confirm the theoretical predictions and show the usefulness of the anisotropic error estimators.
AN EXPLANATION OF NON-EQUILIBRIUM CURRENCY BID-ASK SPREADS
Authors: AFFUL KOFI B.
Published: August 2004

This paper proposes a theoretical model which is used to illustrate that transactions costs and a risk premium are not sufficient to explain the excess currency bid-ask spread. It illustrates that only in market structures that engender market power can foreign exchange dealers widen their currency bid-ask spread to exploit adverse economic forces and also exploit a relatively price inelastic demand for foreign exchange to charge higher-than-market-determined risk premiums thus charging an excess currency bid-ask spread.
A NEW MONTE CARLO METHOD FOR AMERICAN OPTIONS
Authors: MILSTEIN G. N. , REIß O. , SCHOENMAKERS J.
Published: August 2004

We introduce a new Monte Carlo method for constructing the exercise boundary of an American option in a generalized Black–Scholes framework. Based on a known exercise boundary, it is shown how to price and hedge the American option by Monte Carlo simulation of suitable probabilistic representations in connection with the respective parabolic boundary value problem. The method presented is supported by numerical experiments.
ESTIMATES OF THE SHORT-TERM RATE PROCESS IN AN ARBITRAGE-FREE FRAMEWORK
Authors: KAZEMI HOSSEIN , MAHDAVI MAHNAZ , SALAZAR BRETT
Published: August 2004

This paper uses a new restriction imposed by the no-arbitrage condition on interest rate processes to estimate the parameters of the short-term rates for US, France, UK and Germany. A general process that nests almost all previous one-factor models is estimated. The results show that the volatility structure of US short-term rate is similar to the processes suggested by Duffie and Kahn [9] or Chan et al. [4] depending on the proxy used for the short-term rate and the time period covered by the study. The volatility structures of the short-term rates in France and Germany do not have constant elasticity with respect to the short-term rate, while the elasticity of UK's short-term rate is constant and equal to 1.5.
GROWTH-OPTIMAL STRATEGIES WITH QUADRATIC FRICTION OVER FINITE-TIME INVESTMENT HORIZONS
Authors: AURELL ERIK , MURATORE-GINANNESCHI PAOLO
Published: August 2004

We investigate the growth optimal strategy over a finite time horizon for a stock and bond portfolio in an analytically solvable multiplicative Markovian market model. We show that the optimal strategy consists in holding the amount of capital invested in stocks within an interval around an ideal optimal investment. The size of the holding interval is determined by the intensity of the transaction costs and the time horizon.
ESTIMATING THE FRACTAL DIMENSION OF THE S&P 500 INDEX USING WAVELET ANALYSIS
Authors: BAYRAKTAR ERHAN , POOR H. VINCENT , SIRCAR K. RONNIE
Published: August 2004

S&P 500 index data sampled at one-minute intervals over the course of 11.5 years (January 1989–May 2000) is analyzed, and in particular the Hurst parameter over segments of stationarity (the time period over which the Hurst parameter is almost constant) is estimated. An asymptotically unbiased and efficient estimator using the log-scale spectrum is employed. The estimator is asymptotically Gaussian and the variance of the estimate that is obtained from a data segment of N points is of order [Formula: see text]. Wavelet analysis is tailor-made for the high frequency data set, since it has low computational complexity due to the pyramidal algorithm for computing the detail coefficients. This estimator is robust to additive non-stationarities, and here it is shown to exhibit some degree of robustness to multiplicative non-stationarities, such as seasonalities and volatility persistence, as well. This analysis suggests that the market became more efficient in the period 1997–2000.
A TWO-REGIME, STOCHASTIC-VOLATILITY EXTENSION OF THE LIBOR MARKET MODEL
Authors: REBONATO RICCARDO , KAINTH DHERMINDER
Published: August 2004

We propose a two-regime stochastic volatility extension of the LIBOR market model that preserves the positive features of the recently introduced (Joshi and Rebonato 2001) stochastic-volatility LIBOR market model (ease of calibration to caplets and swaptions, efficient pricing of complex derivatives, etc.) and overcomes most of its shortcomings. We show the improvements by analyzing empirically and theoretically the real and the model-produced change sin swaption implied volatility.
Letter to the Editor
Authors: Clarke David C.
Published: August 2004

The following is the abstract of the article discussed in the subsequent letter:

Silverthorn DU. Restoring physiology to the undergraduate biology curriculum: a call to action. Adv Physiol Educ 27:91–96, 2003.—The National Research Council-sponsored report, BIO 2010: Transforming Undergraduate Education for Future Research Biologists, describes a number of significant changes that should be made to the undergraduate biology curriculum if we are to adequately train students to become the researchers of the 21st century. What should be of concern to the physiology community is the lack of identifiable physiology in the proposed revisions. This article describes the report and suggests some steps that physiologists can take to enhance our discipline in the undergraduate biology curriculum.
What is the ultimate goal in neural regulation of cardiovascular function?
Authors: Prakash E. S. , Madanmohan  , Pal Gopal Krushna
Published: August 2004

We used the following multiple-choice question after a series of lectures in cardiovascular physiology in the first year of an undergraduate medical curriculum ( n = 66) to assess whether students had understood the neural regulation of cardiovascular function. In health, neural cardiovascular mechanisms are geared toward maintaining A) cardiac output, B) total peripheral resistance (TPR), C) arterial blood pressure (BP), D) tissue blood flow. The same question was administered to 275 graduates preparing for postgraduate exams (but not following the same series of lectures as the undergraduates). In both groups, we found a large proportion of incorrect answers (70% in undergraduates and 85% in graduates) and sorted this out by offering a step-by-step explanation and two examples and found it successful: 1) What happens to BP and heart rate (HR) when a person loses 500 ml of blood (∼10% of blood volume) in one minute? 2) What happens to your BP and HR as you get out of bed after a night’s sleep? Flow = perfusion pressure/resistance to flow; cardiac output = BP/TPR; BP = cardiac output × TPR = [stroke volume (SV) × HR] × TPR. In both examples, BP decreases and is rapidly brought into the normal range by the arterial baroreflex mechanism. TBF is regulated chiefly by varying local vascular resistance (autoregulation). In summary, the ultimate goal of all neural cardiovascular reflex mechanisms is to maintain arterial BP within a range in which tissues can regulate their own blood flows. Cardiovascular control during exercise was used as an example to emphasize these facts. A discussion of this kind triggered interest in the minds of students and graduates, helping them get rid of a major misconception in about 20–40 minutes.
Evolution of an educator: lessons learned and challenges ahead
Authors: Modell Harold I.
Published: August 2004

In selecting a Claude Bernard Distinguished Lecturer, the Teaching Section looks for an individual who has made major contributions to physiology education. Dr. Harold Modell has certainly earned this honor. Harold has an undergraduate degree from the University of Minnesota, a Masters in biomedical engineering from Iowa State, and, continuing the southern migration, a Ph.D. from the University of Mississippi Medical Center. After four years in Buffalo, first as a postdoctoral fellow and then as an assistant professor, Harold made the long trek to Seattle, WA, where he has been ever since. Harold Modell’s contributions to physiology education are many and varied. He was certainly one of the early developers of teaching software aimed at helping students learn physiology. His programs are widely used, but more importantly, he has been instrumental in bringing others into the field of computer-based education. The existence of the Teaching Section is in no small measure the result of Harold’s efforts to persuade APS that teaching was important to a great many of its members, and to the Society. Similarly, this journal, Advances in Physiology Education, came to life after a long campaign spearheaded by Harold. As the journal’s founding editor, he set the stage for the growing success that it is enjoying today. Finally, Harold is an educational researcher of note whose every project is aimed at helping the learner to learn. As a leading advocate of this attitude, Harold has helped physiology teachers at all levels adopt this approach to teaching.
An online tutorial for helping nonscience majors read primary research literature in biology
Authors: Gillen Christopher M. , Vaughan Jasmine , Lye Bethany R.
Published: August 2004

Using primary literature is an effective tool for promoting active learning and critical thinking in science classes. However, it can be challenging to use primary literature in large classes and in classes for nonscience majors. We describe the development and implementation of an online tutorial for helping nonscience majors learn to read primary literature in biology. The tutorial includes content about the scientific process and the structure of scientific papers and provides opportunities for students to practice reading primary literature. We describe the use of the tutorial in Biology of Exercise, a course for nonscience majors. Students used the tutorial outside of class to learn the basic principles involved in reading scientific papers, enabling class sessions to focus on active-learning activities and substantive class discussions.
Understanding lipoproteins as transporters of cholesterol and other lipids
Authors: Biggerstaff Kyle D. , Wooten Joshua S.
Published: August 2004

A clear picture of lipoprotein metabolism is essential for understanding the pathophysiology of atherosclerosis. Many students are taught that low-density lipoprotein-cholesterol is “bad” and high-density lipoprotein-cholesterol is “good.” This misconception leads to students thinking that lipoproteins are types of cholesterol rather than transporters of lipid. Describing lipoproteins as particles that are composed of lipid and protein and illustrating the variation in particle density that is determined by the constantly changing lipid and protein composition clarifies the metabolic pathway and physiological function of lipoproteins as lipid transporters. Such a description will also suggest the critical role played by apolipoproteins in lipid transport. The clarification of lipoproteins as particles that change density will help students understand the nomenclature used to classify lipoproteins as well.
Involvement of ryanodine receptors in muscarinic receptor-mediated membrane current oscillation in urinary bladder smooth muscle
Authors: Kajioka Shunichi , Nakayama Shinsuke , Asano Haruhiko , Brading Alison F.
Published: August 2004

The urinary bladder pressure during micturition consists of two components: an initial, phasic component and a subsequent, sustained component. To investigate the excitation mechanisms underlying the sustained pressure, we recorded from membranes of isolated detrusor cells from the pig, which can be used as a model for human micturition. Parasympathomimetic agents promptly evoke a large transient inward current, and subsequently during its continuous presence, oscillating inward currents of relatively small amplitudes are observed. The two types of inward current are considered to cause the phasic and sustained pressure rises, respectively. Ionic substitution and applications of channel blockers revealed that Ca2+-activated Cl− channels were responsible for the large transient and oscillating inward currents. Furthermore, the inclusion of guanosine 5′- O-(2-thiodiphosphate) in the patch pipette indicates that both inward currents involve G proteins. However, applications of heparin in the patch pipette and of xestospongin C in the bathing solution suggest a signaling pathway other than inositol 1,4,5-trisphosphate (IP3) operating in the inward current oscillations, unlike the initial transient inward current. This IP3-independent inward current oscillation system required both sustained Ca2+ influx from the extracellular space and Ca2+ release from the intracellular stores. These two requirements are presumably SKF-96365-sensitive cation channels and ryanodine receptors, respectively. Experiments with various Ca2+ concentrations suggested that Ca2+ influx from the extracellular space plays a major role in pacing the oscillatory rhythm. The fact that distinct mechanisms underlie the two types of inward current may help in development of clinical treatments of, for example, urinary incontinence and residual urine volume control.
Na+/Ca2+ exchange activity in neonatal rabbit ventricular myocytes
Authors: Huang Jingbo , Hove-Madsen Leif , Tibbits Glen F.
Published: August 2004

Much less is known about the contributions of the Na+/Ca2+ exchanger (NCX) and sarcoplasmic reticulum (SR) Ca2+ pump to cell relaxation in neonatal compared with adult mammalian ventricular myocytes. Based on both biochemical and molecular studies, there is evidence of a much higher density of NCX at birth that subsequently decreases during the next 2 wk of development. It has been hypothesized, therefore, that NCX plays a relatively more important role for cytosolic Ca2+ decline in neonates as well as, perhaps, a role in excitation-contraction coupling in reverse mode. We isolated neonatal ventricular myocytes from rabbits in four different age groups: 3, 6, 10, and 20 days of age. Using an amphotericin-perforated patch-clamp technique in fluo-3-loaded myocytes, we measured the caffeine-induced inward NCX current ( INCX) and the Ca2+ transient. We found that the integral of INCX, an indicator of SR Ca2+ content, was greatest in myocytes from younger age groups when normalized by cell surface area and that it decreased with age. The velocity of Ca2+ extrusion by NCX ( VNCX) was linear with [Ca2+] and did not indicate saturation kinetics until [Ca2+] reached 1–3 μM for each age group. There was a significantly greater time delay between the peaks of INCX and the Ca2+ transient in myocytes from the youngest age groups. This observation could be related to structural differences in the subsarcolemmal microdomains as a function of age.
Renal blood flow in heart failure patients during exercise
Authors: Momen Afsana , Bower Douglas , Boehmer John , Kunselman Allen R. , Leuenberger Urs A. , Sinoway Lawrence I.
Published: August 2004

During exercise, reflex renal vasoconstriction maintains blood pressure and helps in redistributing blood flow to the contracting muscle. Exercise intolerance in heart failure (HF) is thought to involve diminished perfusion in active muscle. We studied the temporal relationship between static handgrip (HG) and renal blood flow velocity (RBV; duplex ultrasound) in 10 HF and in 9 matched controls during 3 muscle contraction paradigms. Fatiguing HG ( protocol 1) at 40% of maximum voluntary contraction led to a greater reduction in RBV in HF compared with controls (group main effect: P < 0.05). The reduction in RBV early in HG tended to be more prominent during the early phases of protocol 1. Similar RBV was observed in the two groups during post-HG circulatory arrest (isolating muscle metaboreflex). Short bouts (15 s) of HG at graded intensities ( protocol 2; engages muscle mechanoreflex and/or central command) led to greater reductions in RBV in HF than controls ( P < 0.03). Protocol 3, voluntary and involuntary biceps contraction (eliminates central command), led to similar increases in renal vasoconstriction in HF ( n = 4). Greater reductions in RBV were found in HF than in controls during the early phases of exercise. This effect was not likely due to a metaboreflex or central command. Thus our data suggest that muscle mechanoreflex activity is enhanced in HF and serves to vigorously vasoconstrict the kidney. We believe this compensatory mechanism helps preserve blood flow to exercising muscle in HF.
Functional Properties of Electrical Synapses Between Inhibitory Interneurons of Neocortical Layer 4
Authors: Gibson Jay R. , Beierlein Michael , Connors Barry W.
Published: August 2004

The existence of electrical synapses between GABAergic inhibitory interneurons in neocortex is well established, but their functional properties have not been described in detail. We made whole cell recordings from pairs of electrically coupled fast-spiking (FS) or low threshold–spiking (LTS) neurons, and filled some cells with biocytin for morphological reconstruction. Data were used to create compartmental cable models and to guide mathematical analysis. We analyzed the time course and amplitude of electrical postsynaptic potentials (ePSPs), the subthreshold events generated by presynaptic action potentials, in both FS and LTS neurons. The results imply that the generation of ePSPs is predominantly a linear process in both cell types for presynaptic firing of both single and repetitive spikes. Nonlinearities shape ePSPs near spike threshold, but our data suggest that the underlying synaptic current is still a linear process. Cell-to-cell electrical signaling on longer timescales also appears to be linear. Cable models of electrically coupled FS and LTS neurons imply that the analyzed electrical synapses are, on average, within 50 μm of the soma. Finally, we show that electrical coupling between 2 inhibitory cells promotes synchrony at all spiking frequencies. This contrasts with the effect of reciprocal inhibitory postsynaptic potentials (IPSPs) evoked by the same cells, which promote antisynchronous firing at frequencies less than about 100 Hz. Electrical coupling counteracts the antisynchronous behavior induced by IPSPs and facilitates spiking synchrony. Our results suggest that electrical synapses among inhibitory interneurons are most readily described as low-pass linear filters that promote firing synchrony.
Quantitative Characterization and Classification of Leech Behavior
Authors: Mazzoni Alberto , Garcia-Perez Elizabeth , Zoccolan Davide , Graziosi Sergio , Torre Vincent
Published: August 2004

This paper describes an automatic system for the analysis and classification of leech behavior. Three colored beads were attached to the dorsal side of a free moving or pinned leech, and color CCD camera images were taken of the animal. The leech was restrained to moving in a small tank or petri dish, where the water level can be varied. An automatic system based on color processing tracked the colored beads over time, allowing real-time monitoring of the leech motion for several hours. At the end of each experimental session, six time series (2 for each bead) describing the leech body motion were obtained. A statistical analysis based on the speed and frequency content of bead motion indicated the existence of several stereotypical patterns of motion, corresponding to different leech behaviors. The identified patterns corresponded to swimming, pseudo-swimming, crawling, exploratory behavior, stationary states, abrupt movements, and combinations of these behaviors. The automatic characterization of leech behavior demonstrated here represents an important step toward understanding leech behavior and its properties. This method can be used to characterize the behavior of other invertebrates and also for some small vertebrates.
Can Delay-Period Activity Explain Working Memory?
Authors: Sobotka Stanislaw , Diltz Mark D. , Ringo James L.
Published: August 2004

Working-memory tasks often lead to elevated delay-period discharge rates in cortical neurons. When this altered neuronal discharge rate, called delay activity, shows stimulus specificity, it is a good candidate for a neuronal mechanism of working memory. If the delay activity is indeed the carrier of memory, then experimental manipulation during the delay period that disrupts delay activity should also disrupt behavioral performance. We tested this hypothesis in two macaque monkeys with a delayed matching-to-sample task (delay time: 8 or 10 s) in which only two visual images were used. In each trial, one of the images was randomly chosen as the sample. In control trials (without disruptive stimulation), the monkeys performed at the level of 74.3% correct recognition. Three electrical stimulation levels (mild: a 0.25-s train of electrical pulses; medium: 1-s train; strong: 4 s), delivered to the hippocampal formation or to the orbito-frontal and inferotemporal cortices during delay period, decreased the performance to 71.4, 66.8, and 58.0% respectively (all are significantly less than control performance, P < 0.05 for mild stimulation and P < 0.0001 for other stimulation levels). Three hundred and thirty-four cells were recorded from inferotemporal (211 cells) and prefrontal (123 cells) cortices. Significant ( P < 0.05) stimulus-specific delay activity was found in about one-third of recorded cells. For these cells in control trials, the mean difference in delay-period spike rates between preferred and nonpreferred images was 26%. The electrical stimulation reduced this difference to 20% (not a statistically significant reduction) in trials with mild stimulation, to 14% ( P < 0.05) with medium stimulation, and just to 4% ( P < 0.0005) with strong stimulation. These results, that increasing electrical stimulation reduced neuronal selectivity and at the same time reduced behavioral performance, directly support the hypothesis that delay activity is the carrier of memory through the delay period.
Imatinib and pegylated human recombinant interferon-α2b in early chronic-phase chronic myeloid leukemia
Authors: Baccarani Michele , Martinelli Giovanni , Rosti Gianantonio , Trabacchi Elena , Testoni Nicoletta , Bassi Simona , Amabile Marilina , Soverini Simona , Castagnetti Fausto , Cilloni Daniela , Izzo Barbara , de Vivo Antonio , Messa Emanuela , Bonifazi Francesca , Poerio Angela , Luatti Simona , Giugliano Emilia , Alberti Daniele , Fincato Gianluca , Russo Domenico , Pane Fabrizio , Saglio Giuseppe ,   for the GIMEMA Working Party on Chronic Myeloid Leukemia
Published: August 2004

Since interferon-α and imatinib (IM; STI571, Glivec, Gleevec) are effective for the treatment of chronic myeloid leukemia (CML), and their mechanisms of action are different, we designed an exploratory study investigating the effects of a standard IM dose (400 mg/d) and a variable pegylated interferon-α (PegIFN) dose (50 μg/wk, 100 μg/wk, and 150 μg/wk). The criteria for dose adjustment were designed so as to ensure the delivery of the IM dose and to protect life quality. There were 76 patients with previously untreated Philadelphia (Ph)–positive CML enrolled in the study. There were 3 patients who discontinued IM and 45 patients who discontinued PegIFN. The severity of adverse events increased with increasing PegIFN dose. The IM dose could be administered to the patients who were assigned to receive 50 μg/wk or 100 μg/wk PegIFN but not to those who were assigned to receive 150 μg/wk. The median administered dose of PegIFN ranged between 32 μg/wk and 36 μg/wk. The cytogenetic response was 70% complete (Ph-neg 100%) and 83% major (Ph-neg > 65%). The BCR/ABL transcript was reduced by at least 3 logs in 68% of complete cytogenetic responders. These data of toxicity, compliance, and efficacy may assist in the design and preparation of prospective studies.
Growth retardation and dyslymphopoiesis accompanied by G2/M arrest in APEX2-null mice
Authors: Ide Yasuhito , Tsuchimoto Daisuke , Tominaga Yohei , Nakashima Manabu , Watanabe Takeshi , Sakumi Kunihiko , Ohno Mizuki , Nakabeppu Yusaku
Published: August 2004

APEX2/APE2 is a secondary mammalian apurinic/apyrimidinic endonuclease that associates with proliferating cell nuclear antigen (PCNA), and the progression of S phase of the cell cycle is accompanied by its expression. To determine the biologic significance of APEX2, we established APEX2-null mice. These mice were about 80% the size of their wild-type littermates and exhibited a moderate dyshematopoiesis and a relatively severe defect in lymphopoiesis. A significant accumulation of both thymocytes and mitogen-stimulated splenocytes in G2/M phase was seen in APEX2-null mice compared with the wild type, indicating that APEX2 is required for proper cell cycle progression of proliferating lymphocytes. Although APEX2-null mice exhibited an attenuated immune response against ovalbumin in comparison with wild-type mice, they produced both antiovalbumin immunoglobulin M (IgM) and IgG, indicating that class switch recombination can occur even in the absence of APEX2. (Blood. 2004;104: 4097-4103)
The use of retroviral vectors for gene therapy-what are the risks? A review of retroviral pathogenesis and its relevance to retroviral vector-mediated gene delivery
Authors: Anson Donald S
Published: August 2004

Retroviral vector-mediated gene transfer has been central to the development of gene therapy. Retroviruses have several distinct advantages over other vectors, especially when permanent gene transfer is the preferred outcome. The most important advantage that retroviral vectors offer is their ability to transform their single stranded RNA genome into a double stranded DNA molecule that stably integrates into the target cell genome. This means that retroviral vectors can be used to permanently modify the host cell nuclear genome. Recently, retroviral vector-mediated gene transfer, as well as the broader gene therapy field, has been re-invigorated with the development of a new class of retroviral vectors which are derived from lentiviruses. These have the unique ability amongst retroviruses of being able to infect non-cycling cells. Vectors derived from lentiviruses have provided a quantum leap in technology and seemingly offer the means to achieve significant levels of gene transfer in vivo.

The ability of retroviruses to integrate into the host cell chromosome also raises the possibility of insertional mutagenesis and oncogene activation. Both these phenomena are well known in the interactions of certain types of wild-type retroviruses with their hosts. However, until recently they had not been observed in replication defective retroviral vector-mediated gene transfer, either in animal models or in clinical trials. This has meant the potential disadvantages of retroviral mediated gene therapy have, until recently, been seen as largely, if not entirely, hypothetical. The recent clinical trial of γc mediated gene therapy for X-linked severe combined immunodeficiency (X-SCID) has proven the potential of retroviral mediated gene transfer for the treatment of inherited metabolic disease. However, it has also illustrated the potential dangers involved, with 2 out of 10 patients developing T cell leukemia as a consequence of the treatment. A considered review of retroviral induced pathogenesis suggests these events were qualitatively, if not quantitatively, predictable. In addition, it is clear that the probability of such events can be greatly reduced by relatively simple vector modifications, such as the use of self-inactivating vectors and vectors derived from non-oncogenic retroviruses. However, these approaches remain to be fully developed and validated. This review also suggests that, in all likelihood, there are no other major retroviral pathogenetic mechanisms that are of general relevance to replication defective retroviral vectors. These are important conclusions as they suggest that, by careful design and engineering of retroviral vectors, we can continue to use this gene transfer technology with confidence.