bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy, Plasma Pharmacokinetics, and Safety of Icofungipen, an Inhibitor of
Candida
Isoleucyl-tRNA Synthetase, in Treatment of Experimental Disseminated Candidiasis in Persistently Neutropenic Rabbits
Authors: Petraitiene Ruta , Petraitis Vidmantas , Kelaher Amy M. , Sarafandi Alia A. , Mickiene Diana , Groll Andreas H. , Sein Tin , Bacher John , Walsh Thomas J.
Published: April 2005

Icofungipen (formerly PLD-118) is a synthetic derivative of the naturally occurring β-amino acid cispentacin that blocks isoleucyl-tRNA synthetase, resulting in the inhibition of protein synthesis and growth of fungal cells. We investigated the efficacy, plasma pharmacokinetics, and safety of icofungipen in escalating dosages for the treatment of experimental subacute disseminated candidiasis in persistently neutropenic rabbits. Icofungipen was administered for 10 days starting 24 h after the intravenous inoculation of 10
3
Candida albicans
blastoconidia. Study groups consisted of rabbits treated with icofungipen at 4 (ICO-4), 10 (ICO-10), and 25 (ICO-25) mg/kg of body weight/day in two divided dosages, rabbits treated with fluconazole at 10 mg/kg/day, rabbits treated with amphotericin B at 1 mg/kg/day, and untreated controls. Levels of icofungipen in plasma were derivatized by phthaldialdehyde and quantified by high-performance liquid chromatography with fluorescence detection. Rabbits treated with ICO-10 (
P
< 0.01) and ICO-25 (
P
< 0.001) showed significant dosage-dependent tissue clearance of
C. albicans
from the liver, spleen, kidney, brain, vitreous, vena cava, and lung in comparison to untreated controls. ICO-25 cleared
C. albicans
from all tissues and had activity comparable to that of amphotericin B versus untreated controls (
P
< 0.001). Pharmacokinetics of icofungipen in plasma approximated a dose-dependent relationship of the maximum concentration of drug in serum and the area under the concentration-time curve. There was no significant elevation of the levels of hepatic transaminases, alkaline phosphatase, bilirubin, urea nitrogen, or creatinine in icofungipen-treated rabbits. Icofungipen followed dose-dependent pharmacokinetics and was effective in the treatment of experimental disseminated candidiasis, including central nervous system infection, in persistently neutropenic rabbits.
Evaluation of Disk Diffusion Method for Determining Eberconazole Susceptibility of Dermatophytes and Influence of Culture Medium
Authors: Fernández-Torres Belkys , Inza Isabel , Guarro Josep
Published: April 2005

We have evaluated a disk diffusion method to determine the activity of eberconazole against 50 strains of dermatophytes by testing three culture media (RPMI, antibiotic medium 3, and high resolution). No differences were found among the results obtained with the three media. A significant correlation between disk diffusion and microdilution methods was observed with AM3.
COHERENT FOURIER COMPONENTS IN THE LISA MEASUREMENT BANDWIDTH FROM TEST MASS CHARGING: ESTIMATES AND SUPPRESSION
Authors: SHAUL DIANA N. A. , SUMNER TIM J. , ROCHESTER GEOFF K.
Published: April 2005

The success of LISA is dependent on the precision with which the test masses, the interferometer mirrors, can maintain pure geodesic motion. Their accumulation of charge from cosmic rays and solar wind particles can give rise to spurious Lorentz and Coulomb forces. Coherent Fourier components, which appear due to the time dependence of the amount of charge accrued, are estimated to exceed the acceleration noise target. The general forms of these signals are derived. It is shown that for typical parameter values, coherent signals with significant signal-to-noise ratios can result from Coulomb interactions, while the signal from Lorentz interactions is expected to fall below the instrumental noise target. In this description, the signals' peak magnitudes are shown to increase with decreasing frequency. Hence their impact may be greater for missions that aim to look for gravitational waves at frequencies below the nominal LISA band. It is expected that the accuracy with which these signals can be removed from the data will depend on deviations from the predictable temporal behavior of the parameters on which they are dependent. Methods to substantially decrease these signals for LISA are discussed.
CORE-ENVELOPE MODELS OF SUPERDENSE STAR WITH ANISOTROPIC ENVELOPE
Authors: THOMAS V. O. , RATANPAL B. S. , VINODKUMAR P. C.
Published: April 2005

A core-envelope model for superdense matter distribution with the feature — core consisting of isotropic fluid distribution and envelope with anisotropic fluid distribution — is studied on the background of pseudo-spheroidal spacetime. In the case of superdense stars core-envelope models, with isotropic pressure in the core and anisotropic pressure in the envelope, may not be unphysical. Physical plausibility of the models have been examined analytically and using numerical methods.
OBSERVATIONAL SIGNATURES OF AN ELECTROMAGNETIC OVERCRITICAL GRAVITATIONAL COLLAPSE
Authors: RUFFINI REMO , FRASCHETTI FEDERICO , VITAGLIANO LUCA , XUE SHE-SHENG
Published: April 2005

We present theoretical predictions for the spectral, temporal and intensity signatures of the electromagnetic radiation emitted during the process of the gravitational collapse of a stellar core to a black hole, during which electromagnetic field strengths rise over the critical value for e+e- pair creation. The last phases of this gravitational collapse are studied, leading to the formation of a black hole with a subcritical electromagnetic field, likely with zero charge, and an outgoing pulse of initially optically thick e+e--photon plasma. Such a pulse reaches transparency at Lorentz gamma factors of 102–104. We find a clear signature in the outgoing electromagnetic signal, drifting from a soft to a hard spectrum, on very precise time-scales and with a very specific intensity modulation. The relevance of these theoretical results for the understanding of short gamma-ray bursts is outlined.
Randomized distributed access to mutually exclusive resources
Authors: Dror Moshe , Hartman Bruce , Knotts Gary , Zeng Daniel
Published: April 2005

Many systems consist of a set of agents which must acquire exclusive access to resources from a shared pool. Coordination of agents in such systems is often implemented in the form of a centralized mechanism. The intervention of this type of
mechanism, however, typically introduces significant computational overhead and reduces the amount of concurrent activity. Alternatives to centralized mechanisms exist, but
they generally suffer from the need for extensive interagent communication. In this paper, we develop a randomized approach to make multiagent resource-allocation decisions with the objective of maximizing expected concurrency measured by the number of the active agents. This approach does not assume a centralized mechanism and has no need for interagent communication. Compared to existing autonomous-decentralized-decision-making (ADDM)-based approaches for resource-allocation, our work emphasizes achieving the highest degree of agent autonomy and is able to handle more general resource requirements.
Approximating distribution functions by iterated function systems
Authors: Iacus Stefano Maria , La Torre Davide
Published: April 2005

An iterated function system (IFS) on the space of distribution functions is built with the aim of proposing a new class of distribution function estimators. One IFS estimator and its asymptotic properties are studied in detail. We also propose a density estimator derived from the IFS distribution function estimator by using Fourier
analysis. Relative efficiencies of both estimators, for small and moderate sample sizes, are presented via Monte Carlo analysis.
A two-stage procedure on comparing several experimental treatments
and a control—the common and unknown variance case
Authors: Zhang John , Chen Pinyuen , Fang Yue
Published: April 2005

This paper introduces a two-stage selection rule to compare several experimental treatments with a control when the variances are common and unknown. The selection rule integrates the indifference zone approach and the subset selection approach in multiple-decision theory. Two mutually exclusive subsets of the parameter space are defined, one is called the preference zone (PZ) and the other, the indifference zone (IZ). The best experimental treatment is defined to be the experimental treatment with the largest population mean. The selection procedure opts to select only the experimental treatment which corresponds to the largest sample mean when the parameters are in the PZ, and selects a subset of the experimental treatments and the control when the
parameters fall in the IZ. The concept of a correct decision is defined differently in these two zones. A correct decision in the preference zone (CD1) is defined to be the event that the best experimental treatment is selected. In the indifference zone, a selection is called correct (CD2) if the selected subset contains the best experimental treatment. Theoretical results on the lower bounds for P(CD1) in PZ and P(CD2) in IZ are developed. A table is computed for the implementation of the selection procedure.
Tissue-Type Plasminogen Activator Crosses the Intact Blood-Brain Barrier by Low-Density Lipoprotein Receptor–Related Protein-Mediated Transcytosis
Authors: Benchenane Karim , Berezowski Vincent , Ali Carine , Fernández-Monreal Mónica , López-Atalaya José P. , Brillault Julien , Chuquet Julien , Nouvelot André , MacKenzie Eric T. , Bu Guojun , Cecchelli Roméo , Touzani Omar , Vivien Denis
Published: April 2005

Background—

Accumulating evidence demonstrates a critical involvement of tissue-type plasminogen activator (tPA) in pathological and physiological brain conditions. Determining whether and how vascular tPA can cross the blood-brain barrier (BBB) to enter the brain is thus important, not only during stroke but also in physiological conditions.

Methods and Results—

In the present work, we provide evidence in vivo that intravenous injection of tPA increases NMDA-induced striatal lesion in the absence of BBB leakage. Accordingly, we show that tPA crosses the BBB both after excitotoxic lesion and in control conditions. Indeed, vascular injected tPA can be detected within the brain parenchyma and in the cerebrospinal fluid. By using an in vitro model of BBB, we have confirmed that tPA can cross the intact BBB. Its passage was blocked at 4°C, was saturable, and was independent of its proteolytic activity. We have shown that tPA crosses the BBB by transcytosis, mediated by a member of the LDL receptor–related protein family.

Conclusions—

We demonstrate that blood-derived tPA can reach the brain parenchyma without alteration of the BBB. The molecular mechanism of the passage of tPA from blood to brain described here could represent an interesting target to improve thrombolysis in stroke
Persistent Cardiac Aldosterone Synthesis in Angiotensin II Type 1A Receptor–Knockout Mice After Myocardial Infarction
Authors: Katada Jun , Meguro Tomomi , Saito Hitomi , Ohashi Akira , Anzai Toshihisa , Ogawa Satoshi , Yoshikawa Tsutomu
Published: April 2005

Background—

The renin-angiotensin-aldosterone system is implicated in the pathogenesis of heart failure. Pharmacological blockade of angiotensin II (Ang II)–dependent signaling is clinically effective in reducing cardiovascular events after myocardial infarction (MI) but still fails to completely prevent remodeling. The molecular basis underlying this Ang II–independent remodeling is unclear.

Methods and Results—

Acute MI was induced by coronary ligation in wild-type (WT) and angiotensin II type IA receptor–knockout (AT
1A
-KO) mice. Left ventricular (LV) geometry, hemodynamics, and cardiac gene expression were evaluated on day 28. Severe LV remodeling and resultant cardiac dysfunction were observed in WT mice, whereas less marked, but still significant, LV remodeling and cardiac dysfunction were induced in AT
1A
-KO mice. Gene expression levels of aldosterone synthase and the cardiac aldosterone content were both elevated in the MI hearts, even in AT
1A
-KO mice. In AT
1A
-KO mice treated with spironolactone (20 mg/kg per day), LV remodeling, cardiac dysfunction, and cardiac gene expression of collagens and natriuretic peptides were almost normalized.

Conclusions—

Our results indicate that genetic blockade of AT
1A
signaling fails to arrest aldosterone production in cardiac tissues and that cardiac aldosterone plays a critical role in post-MI LV remodeling. The results suggest that spironolactone could be potentially effective in patients with MI, when used in combination with renin-angiotensin system blockade, by blocking the actions of aldosterone produced by Ang II–independent mechanisms.
Functional Ephrin-B2 Expression for Promotive Interaction Between Arterial and Venous Vessels in Postnatal Neovascularization
Authors: Hayashi Shin-ichiro , Asahara Takayuki , Masuda Haruchika , Isner Jeffrey M. , Losordo Douglas W.
Published: April 2005

Background—

Ephrin-B2, one of the transmembrane ligands, is a genetic marker of arterial endothelial cells (ECs) at embryonic stages and is essential for cardiovascular development, but its roles in ischemic cardiovascular disease are not well understood. In this study, we focused on the function of ephrin-B2 in postnatal neovascularization.

Methods and Results—

We found that ephrin-B2 is exclusively expressed and significantly upregulated in the arterial vasculature after the initial angiogenic responses in tissue ischemia. Upregulation of ephrin-B2 is also observed in EC cordlike formation in vitro. Interestingly, ephrin-B2 expression on ECs was enhanced by promotive angiogenic growth factors, such as vascular endothelial growth factor, basic fibroblast growth factor, and hepatocyte growth factor, whereas it was attenuated by angiopoietin-1, a factor for blood vessel maturation. Moreover, an ephrin-B2–rich environment was shown to induce neovascularization mainly through venous angiogenesis in an in vivo cornea micropocket assay.

Conclusions—

Our study indicates that the ephrin-B2 ligand is likely to have functional expression on angiogenic arterial ECs and induce a subsequent promotive effect on venous vessels during postnatal neovascularization.
Inflammation and Carotid Artery—Risk for Atherosclerosis Study (ICARAS)
Authors: Schillinger Martin , Exner Markus , Mlekusch Wolfgang , Sabeti Schila , Amighi Jasmin , Nikowitsch Robert , Timmel Ewald , Kickinger Bernhard , Minar Christoph , Pones Matthias , Lalouschek Wolfgang , Rumpold Helmut , Maurer Gerald , Wagner Oswald , Minar Erich
Published: April 2005

Background—

Compelling evidence suggests that inflammation is fundamentally involved in the pathogenesis of atherosclerosis; however, temporal correlation between inflammation and morphological features of atherosclerosis progression has not been demonstrated unequivocally.

Methods and Results—

We prospectively studied 1268 consecutive patients who were initially asymptomatic with respect to carotid artery disease. Patients underwent serial carotid ultrasound investigations at baseline and after a follow-up interval of a median of 7.5 months (range 6 to 9 months), with measurement of carotid flow velocities and categorization of carotid arteries as 0% to 29%, 30% to 49%, 50% to 69%, 70% to 89%, or 90% to 99% stenosed or occluded. High-sensitivity C-reactive protein (hs-CRP) and serum amyloid A (SAA) were measured at baseline and follow-up. Progression of carotid atherosclerosis was found in 103 (8.1%) of 1268 patients. Hs-CRP and SAA, respectively, at baseline (
P
=0.004 and
P
=0.014) and follow-up (
P
<0.001 and
P
<0.001) and the change from baseline to follow-up (
P
<0.001 and
P
<0.001) were significantly associated with progressive atherosclerosis. Adjusted ORs (95% CI) for atherosclerosis progression with increasing quintiles of baseline hs-CRP were 1.65 (0.71 to 3.84), 1.87 (0.8 to 4.37), 3.32 (1.49 to 7.39), and 3.65 (1.65 to 8.08), and with increasing quintiles of baseline SAA, they were 0.86 (0.38 to 1.92), 0.99 (0.49 to 1.99), 1.72 (0.91 to 3.28), and 2.28 (1.24 to 4.20), respectively, compared with the lowest quintiles.

Conclusions—

These findings supply evidence for a close temporal correlation between inflammation and morphological features of rapidly progressive carotid atherosclerosis, which suggests that elevation or increase of the inflammatory biomarkers hs-CRP and SAA identifies the presence of active atherosclerotic disease.
Coronary Circulatory Dysfunction in Insulin Resistance, Impaired Glucose Tolerance, and Type 2 Diabetes Mellitus
Authors: Prior John O. , Quiñones Manuel J. , Hernandez-Pampaloni Miguel , Facta Alvaro D. , Schindler Thomas H. , Sayre James W. , Hsueh Willa A. , Schelbert Heinrich R.
Published: April 2005

Background—

Abnormal coronary endothelial reactivity has been demonstrated in diabetes and is associated with an increased rate of cardiovascular events. Our objectives were to investigate the presence of functional coronary circulatory abnormalities over the full spectrum of insulin resistance and to determine whether these would differ in severity with more advanced states of insulin resistance.

Methods and Results—

Myocardial blood flow (MBF) was measured with positron emission tomography and
13
N-ammonia to characterize coronary circulatory function in states of insulin resistance without carbohydrate intolerance (IR), impaired glucose tolerance (IGT), and normotensive and hypertensive type 2 diabetes mellitus (DM) compared with insulin-sensitive (IS) individuals. Indices of coronary function were total vasodilator capacity (mostly vascular smooth muscle–mediated) during pharmacological vasodilation and the nitric oxide–mediated, endothelium-dependent vasomotion in response to cold pressor testing. Total vasodilator capacity was similar in normoglycemic individuals (IS, IR, and IGT), whereas it was significantly decreased in normotensive (−17%) and hypertensive (−34%) DM patients. Compared with IS, endothelium-dependent coronary vasomotion was significantly diminished in IR (−56%), as well as in IGT and normotensive and hypertensive diabetic patients (−85%, −91%, and −120%, respectively).

Conclusions—

Progressively worsening functional coronary circulatory abnormalities of nitric oxide–mediated, endothelium-dependent vasomotion occur with increasing severity of insulin-resistance and carbohydrate intolerance. Attenuated total vasodilator capacity accompanies the more clinically evident metabolic abnormalities in diabetes.
Four-Year Angiographic and Intravascular Ultrasound Follow-Up of Patients Treated With Sirolimus-Eluting Stents
Authors: Sousa J. Eduardo , Costa Marco A. , Abizaid Alexandre , Feres Fausto , Seixas Ana C. , Tanajura Luiz F. , Mattos Luiz A. , Falotico Robert , Jaeger Judith , Popma Jeffrey J. , Serruys Patrick W. , Sousa Amanda G.M.R.
Published: April 2005

Background—

Despite the proven superiority of sirolimus-eluting stents (SESs) compared with bare stents in the first year after implantation, long-term outcomes of patients treated with these novel devices remain unknown. Our goal was to evaluate the clinical, angiographic, and intravascular ultrasound (IVUS) outcomes of patients treated with SESs 4 years after implantation.

Methods and Results—

The study included 30 patients treated with sirolimus-eluting Bx Velocity stenting (slow release [SR; n=15] and fast release [FR; n=15]). Twenty-six patients underwent 4-year angiographic and IVUS follow-up and had matched assessments at all time points (index and 4-, 12-, 24-, and 48-month follow-up). One death occurred during the study period in a patient with a patent SES. There were no target-vessel revascularizations or thromboses between 2- and 4-year follow-up examinations. There was no stent thrombosis, target-lesion revascularization, death, or myocardial infarction in the SR group up to 4 years. Cumulative event-free survival rate was 87% for the total population (80% in the FR group and 93% in the SR group). In-stent late loss was slightly greater in the FR group (0.41±0.49 mm) than the SR group (0.09±0.23) after 4 years. One patient in the FR group had a 52% in-stent restenosis lesion. Percent neointimal hyperplasia volume, as detected by IVUS, remained minimal after 4 years (FR=9.1% and SR=5.7%).

Conclusions—

This study confirms the longevity of the optimal outcomes observed in patients treated with sirolimus-eluting Bx Velocity stents 4 years after implantation. In-stent lumen dimensions remained essentially unchanged at 4-year follow-up, particularly in the population treated with the currently available SES (SR formulation).
Hypertension Management in the Elderly Has Improved
Authors: Tu Karen , Campbell Norman R.C. , Duong-Hua Minh , McAlister Finlay A.
Published: April 2005

To examine whether the treatment of elderly hypertensives had become more aggressive over the past decade, we evaluated: (1) the frequency of new prescriptions for hypertension treatment, adjusted by age and gender; (2) the frequency with which multiple antihypertensives were prescribed concurrently within 2 years of initial diagnosis; and (3) discontinuation rates for antihypertensive therapy. We linked 4 administrative databases and a province-wide clinical database in Ontario, Canada, to derive a cohort of patients ≥66 years of age who were newly started on an antihypertensive agent between July 1, 1994, and March 31, 2002, without another indication for the agent (all patients were followed for 2 years after their initial antihypertensive prescription). Our cohort consisted of 196 451 people newly started on antihypertensive therapy, 30 433 of whom also had diabetes mellitus. The population-adjusted rate of new antihypertensive prescriptions increased by 30% between 1994 and 2002. Whereas 21% of patients newly diagnosed with hypertension in 1994 were prescribed multiple antihypertensives concurrently within 2 years of diagnosis, this proportion had increased to 40% by 2002 (
P
<0.0001). In the cohort of patients first prescribed an antihypertensive in 1994, 36% were not taking any antihypertensive within 2 years; only 21% of patients first prescribed an antihypertensive in 2002 had discontinued all therapy within 2 years (
P
<0.0001). Our data provide evidence that the physician management of hypertension in elderly Canadians became more aggressive between 1994 and 2002.
Perspectives on Aesthetic Computing
Authors: Fishwick Paul , Diehl Stephan , Prophet Jane , Löwgren Jonas
Published: April 2005

The authors present an introduction to the new interdisciplinary area of aesthetic computing and proceed to define this area with examples from each of their own disciplines, practices and research. While several decades of publication and work have resulted in significant advancements in art as implemented through technology, less emphasis has been placed on studying the converse issue of art's effect on computing, or “aesthetic computing.” The authors present their individual work in this area and then follow with brief criticism of one another's work to elucidate different perspectives on the idea. By approaching the topic of aesthetic computing in this manner, the paper serves as an introduction to and survey and analysis of the field.
Pulse of an Ocean: Sonification of Ocean Buoy Data
Authors: Sturm Bob L.
Published: April 2005

The author presents his work in sonifying ocean buoy data for scientific, pedagogical and compositional purposes. Mapping the spectral buoy data to audible frequencies creates interesting and illuminating sonifications of ocean wave dynamics. Several phenomena can be heard, including both those visible and those invisible in graphical representations of the data. The author has worked extensively with this data to compose music and to produce Music from the Ocean, a multi-media CD-ROM demonstrating the data, the phenomena and the sonification. After a brief introduction to physical oceanography, many examples are presented and a composition and installation created from the sonifications are discussed.
Mikhail Matyushin's Contribution to Synthetic Art
Authors: Galeyev Bulat
Published: April 2005

The author explores the pioneering ideas and experiments that the Russian musician and artist Mikhail Matyushin (1861–1934) contributed to the theory and practice of synthetic art. Special emphasis is placed on light art, light music and Matyushin's reflections on analogies between visual and performance art and on synesthesia. The article adduces some new facts, taken mainly from Russian sources not readily accessible to Western researchers. Although Matyushin did not make a significant contribution to the cause of actual lightmusical synthesis, he did make interesting forecasts in this area, which still have value for the modern reader.
A New Approach to Spatial Covariance Modeling of Functional Brain Imaging Data: Ordinal Trend Analysis
Authors: Habeck Christian , Krakauer John W. , Ghez Claude , Sackeim Harold A. , Eidelberg David , Stern Yaakov , Moeller James R.
Published: April 2005

In neuroimaging studies of human cognitive abilities, brain activation patterns that include regions that are strongly interactive in response to experimental task demands are of particular interest. Among the existing network analyses, partial least squares (PLS; McIntosh, 1999; McIntosh, Bookstein, Haxby, & Grady, 1996) has been highly successful, particu-larly in identifying group differences in regional functional connectivity, including differences as diverse as those associated with states of aware-ness and normal aging. However, we address the need for a within-group model that identifies patterns of regional functional connectivity that ex-hibit sustained activity across graduated changes in task parameters. For example, predictions of sustained connectivity are commonplace in stud-ies of cognition that involve a series of tasks over which task difficulty increases (Baddeley, 2003). We designed ordinal trend analysis (OrT) to identify activation patterns that increase monotonically in their expres-sion as the experimental task parameter increases, while the correlative relationships between brain regions remain constant. Of specific interest are patterns that express positive ordinal trends on a subject-by-subject basis. A unique feature of OrT is that it recovers information about func-tional connectivity based solely on experimental design variables. In par-ticular, there is no requirement by OrT to provide either a quantitative model of the uncertain relationship between functional brain circuitry and subject variables (e.g., task performance and IQ) or partial informa-tion about the regions that are functionally connected. In this letter, we provide a step-by-step recipe of the computations performed in the new OrT analysis, including a description of the inferential statistical meth-ods applied. Second, we describe applications of OrT to an event-related fMRI study of verbal working memory and H2 15 O-PET study of visuo-motor learning. In sum, OrT has potential applications to not only studies of young adults and their cognitive abilities, but also studies of normal aging and neurological and psychiatric disease.
Asymptotic Theory of Information-Theoretic Experimental Design
Authors: Paninski Liam
Published: April 2005

We discuss an idea for collecting data in a relatively efficient manner. Our point of view is Bayesian and information-theoretic: on any given trial, we want to adaptively choose the input in such a way that the mutual information between the (unknown) state of the system and the (stochastic) output is maximal, given any prior information (including data collected on any previous trials). We prove a theorem that quantifies the effectiveness of this strategy and give a few illustrative examples comparing the performance of this adaptive technique to that of the more usual nonadaptive experimental design. In particular, we calculate the asymptotic efficiency of the information-maximization strategy and demonstrate that this method is in a well-defined sense never less efficient—and is generically more efficient—than the nonadaptive strategy. For example, we are able to explicitly calculate the asymptotic relative efficiency of the staircase method widely employed in psychophysics research and to demonstrate the dependence of this efficiency on the form of the psychometric function underlying the output responses.
Estimating Entropy Rates with Bayesian Confidence Intervals
Authors: Kennel Matthew B. , Shlens Jonathon , Abarbanel Henry D. I. , Chichilnisky E. J.
Published: April 2005

The entropy rate quantifies the amount of uncertainty or disorder produced by any dynamical system. In a spiking neuron, this uncertainty translates into the amount of information potentially encoded and thus the subject of intense theoretical and experimental investigation. Estimating this quantity in observed, experimental data is difficult and requires a judicious selection of probabilistic models, balancing between two opposing biases. We use a model weighting principle originally developed for lossless data compression, following the minimum description length principle. This weighting yields a direct estimator of the entropy rate, which, compared to existing methods, exhibits significantly less bias and converges faster in simulation. With Monte Carlo techinques, we estimate a Bayesian confidence interval for the entropy rate. In related work, weap-ply these ideas to estimate the information rates between sensory stimuli and neural responses in experimental data (Shlens, Kennel, Abarbanel, & Chichilnisky, in preparation).
Maximum Likelihood Set for Estimating a Probability Mass Function
Authors: Jedynak Bruno M. , Khudanpur Sanjeev
Published: April 2005

We propose a new method for estimating the probability mass function (pmf) of a discrete and finite random variable from a small sample. We focus on the observed counts—the number of times each value appears in the sample—and define the maximum likelihood set (MLS) as the set of pmfs that put more mass on the observed counts than on any other set of counts possible for the same sample size. We characterize the MLS in detail in this article. We show that the MLS is a diamond-shaped subset of the probability simplex [0, 1]k bounded by at most k × (k − 1) hyper-planes, where k is the number of possible values of the random variable. The MLS always contains the empirical distribution, as well as a family of Bayesian estimators based on a Dirichlet prior, particularly the well-known Laplace estimator. We propose to select from the MLS the pmf that is closest to a fixed pmf that encodes prior knowledge. When using Kullback-Leibler distance for this selection, the optimization problem comprises finding the minimum of a convex function over a domain defined by linear inequalities, for which standard numerical procedures are available. We apply this estimate to language modeling using Zipf's law to encode prior knowledge and show that this method permits obtaining state-of-the-art results while being conceptually simpler than most competing methods.
Categorization of Neural Excitability Using Threshold Models
Authors: Tonnelier A.
Published: April 2005

A classification of spiking neurons according to the transition from quiescence to periodic firing of action potentials is commonly used. Nonbursting neurons are classified into two types, type I and type II excitability. We use simple phenomenological spiking neuron models to derive a criterion for the determination of the neural excitability based on the after potential following a spike. The crucial characteristic is the existence for type II model of a positive overshoot, that is, a delayed after depolarization, during the recovery process of the membrane potential. Our prediction is numerically tested using well-known type I and type II models including the Connor, Walter, & McKown (1977) model and the Hodgkin-Huxley (1952) model.
Case Study of an Intense African Easterly Wave
Authors: Berry Gareth J. , Thorncroft Chris
Published: April 2005

The life cycle of an intense African easterly wave (AEW) over the African continent is examined using European Centre for Medium-Range Weather Forecasts (ECMWF) operational analyses, Meteosat satellite images, and synoptic observations. This system, the strongest AEW of 2000, can be tracked from central North Africa into the eastern Atlantic Ocean, where it is associated with the genesis of Hurricane Alberto. Synoptic analysis of the kinematic and thermodynamic fields is supplemented by analysis of potential vorticity (PV), allowing exploration at the role of multiple scales in the evolution of this AEW.

The authors’ analysis promotes the division of the AEW life cycle into three distinctive phases. (i) Initiation: The AEW development is preceded by a large convective event composed of several mesoscale convective systems over elevated terrain in Sudan. This convection provides a forcing on the baroclinically and barotropically unstable state that exists over tropical North Africa. (ii) Baroclinic growth: A low-level warm anomaly, generated close to the initial convection, interacts with a midtropospheric strip of high PV that exists on the cyclonic shear side of the African easterly jet, which is consistent with baroclinic growth. This interaction is reinforced by the generation of subsynoptic-scale PV anomalies by deep convection that is embedded within the baroclinic AEW structure. (iii) West coast development: Near the West African coast, the baroclinic structure weakens, but convection is maintained. The midtropospheric PV anomalies embedded within the AEW merge with one another and with PV anomalies that are generated by convection over topography ahead of the system. These mergers result in the production of a significant PV feature that leaves the West African coast and rapidly undergoes tropical cyclogenesis.
The Accuracy of Solar Irradiance Calculations Used in Mesoscale Numerical Weather Prediction
Authors: Zamora Robert J. , Dutton Ellsworth G. , Trainer Michael , McKeen Stuart A. , Wilczak James M. , Hou Yu-Tai
Published: April 2005

In this paper, solar irradiance forecasts made by mesoscale numerical weather prediction models are compared with observations taken during three air-quality experiments in various parts of the United States. The authors evaluated the fifth-generation Pennsylvania State University–National Center for Atmospheric Research (PSU–NCAR) Mesoscale Model (MM5) and the National Centers for Environmental Prediction (NCEP) Eta Model. The observations were taken during the 2000 Texas Air Quality Experiment (TexAQS), the 2000 Central California Ozone Study (CCOS), and the New England Air Quality Study (NEAQS) 2002. The accuracy of the model forecast irradiances show a strong dependence on the aerosol optical depth. Model errors on the order of 100 W m−2 are possible when the aerosol optical depth exceeds 0.1. For smaller aerosol optical depths, the climatological attenuation used in the models yields solar irradiance estimates that are in good agreement with the observations.
Initialization and Numerical Forecasting of a Supercell Storm Observed during STEPS
Authors: Sun Juanzhen
Published: April 2005

The feasibility of initializing a numerical cloud model with single-Doppler observations and predicting the evolution of thunderstorms has been tested using an observed case of a supercell storm during the Severe Thunderstorm Electrification and Precipitation Study (STEPS). Single-Doppler observations from the Weather Surveillance Radar-1988 Doppler (WSR-88D) at Goodland, Kansas, are assimilated into a cloud-scale numerical model using a four-dimensional variational data assimilation (4DVAR) scheme. A number of assimilation and short-range numerical prediction experiments are conducted. Both the assimilation and prediction results are compared with those of a dual-Doppler synthesis. The prediction results are also verified with reflectivity observations. It is shown that the analysis of the wind field captures the major structure of the storm as revealed by the dual-Doppler synthesis. Thermodynamical and microphysical features retrieved through the dynamical model show consistency with expectations for a deep convective storm. The predicted storm evolution represented by the reflectivity field correlates well with the observations for a 2-h prediction period. The relative importance of the initial fields on the subsequent prediction of the storm evolution is examined by alternately removing the perturbation in each of the initial fields. It is shown that the prediction is most sensitive to the initialization of wind, water vapor, and temperature perturbations.

A number of sensitivity experiments for initialization are conducted to show how the initial analysis depends on the application of a cycling procedure, the weights of the smoothness constraint, and the relative importance between the radial velocity and the reflectivity observations. It is found that the application of the cycling procedure improves the analysis and the subsequent forecast. Greater smoothness coefficients of the penalty term in the cost function result in a larger rms difference in the wind analysis, but help spread the information out and improve the forecast slightly. The radial velocity observations play a more important role than the reflectivity in terms of the wind analysis and the subsequent precipitation forecast.
Development of an Automated Classification Procedure for Rainfall Systems
Authors: Baldwin Michael E. , Kain John S. , Lakshmivarahan S.
Published: April 2005

An automated procedure for classifying rainfall systems (meso-α scale and larger) was developed using an operational analysis of hourly precipitation estimates from radar and rain gauge data. The development process followed two main phases: a training phase and a testing phase. First, 48 hand-selected cases were used to create a training dataset, from which a set of attributes related to morphological aspects of rainfall systems were extracted. A hierarchy of classes for rainfall systems, in which the systems are separated into general convective (heavy rain) and nonconvective (light rain) classes, was envisioned. At the next level of classification hierarchy, convective events are divided into linear and cellular subclasses, and nonconvective events belong to the stratiform subclass. Essential attributes of precipitating systems, related to the rainfall intensity and degree of linear organization, were determined during the training phase. The attributes related to the rainfall intensity were chosen to be the parameters of the gamma probability distribution fit to observed rainfall amount frequency distributions using the generalized method of moments. Attributes related to the degree of spatial continuity of each rainfall system were acquired from correlogram analysis. Rainfall systems were categorized using hierarchical cluster analysis experiments with various combinations of these attributes. The combination of attributes that resulted in the best match between cluster analysis results and an expert classification were used as the basis for an automated classification procedure.

The development process shifted into the testing phase, where automated procedures for identifying and classifying rainfall systems were used to analyze every rainfall system in the contiguous 48 states during 2002. To allow for a feasible validation, a testing dataset was extracted from the 2002 data. The testing dataset consisted of 100 randomly selected rainfall systems larger than 40 000 km2 as identified by an automated identification system. This subset was shown to be representative of the full 2002 dataset. Finally, the automated classification procedure classified the testing dataset into stratiform, linear, and cellular classes with 85% accuracy, as compared to an expert classification.
An Implicitly Balanced Hurricane Model with Physics-Based Preconditioning
Authors: Reisner J. M. , Mousseau A. , Wyszogrodzki A. A. , Knoll D. A.
Published: April 2005

A numerical framework for simulating hurricanes based upon solving a nonlinear equation set with an implicitly balanced solution procedure is described in this paper. The physical model is the Navier–Stokes equations plus a highly simplified and differentiable microphysics parameterization package. Because the method is fully implicit, the approach is able to employ time steps that result in Courant–Friedrichs–Lewy (CFL) numbers greater than one for advection, gravity, and sound waves; however, the dynamical time scale of the problem must still be respected for accuracy. The physical model is solved via the Jacobian-free Newton–Krylov (JFNK) method. The JFNK approach typically requires the approximate solution of a large linear system several times per time step. To increase the efficiency of the linear system solves, a physics-based preconditioner has been employed. To quantify the accuracy and efficiency of the new approach against traditional approaches, the implicitly balanced solver was first compared against semi-implicit approaches for the simulation of a precipitating moist bubble. The moist-bubble simulations demonstrated the ability of the implicitly balanced approach to achieve a given level of accuracy in a more efficient manner than either a first-order semi-implicit approach or a traditional leapfrog semi-implicit approach. This behavior is further illustrated in first-of-a-kind three-dimensional implicitly balanced hurricane simulations that reveal the first-order-in-time semi-implicit algorithm needs to take a time step at least 60 times smaller than the implicitly balanced algorithm to produce a comparable accuracy.
Hi5+: Systematic Development of a Family Intervention to Increase Fruit and Vegetable Intake
Authors: Davies Susan L. , Harrington Kathleen , Franklin Frank A. , Shewchuk Richard M. , Feese Michelle L. , Windle Michael
Published: April 2005

This article describes the development of a peer-led home-based intervention to increase fruit and vegetable (FV) intake and family interaction among fourth graders and their families. Hi5+ intervention content and delivery strategies were developed using two complementary processes: cognitive mapping (CM), a consumerbased approach to identifying salient issues, and intervention mapping (IM), a comprehensive planning model. Step 1 involved creating plans to guide the design, implementation, and evaluation of Hi5+. We delineated our performance objectives and then prioritized those determinants we felt were most salient and changeable. Step 2 involved selecting and utilizing cognitive and behavioral theory constructs to develop intervention methods and strategies. Step 3 involved designing and pilot testing the instructional materials and other intervention components. Step 4 entailed developing plans for program adoption and implementation, while the final step (Step 5) involved creating a comprehensive evaluation plan. Implications of this multistep approach to intervention development are discussed.
Localization of ADAMTS13 to the stellate cells of human liver
Authors: Uemura Masahito , Tatsumi Kouko , Matsumoto Masanori , Fujimoto Masao , Matsuyama Tomomi , Ishikawa Masatoshi , Iwamoto Taka-aki , Mori Toshio , Wanaka Akio , Fukui Hiroshi , Fujimura Yoshihiro
Published: April 2005

Although the chromosomal localization (9q34) of the gene encoding the human form of ADAMTS13 (a disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13) and its exclusive expression in the liver have been established, the cells that produce this enzyme are yet to be determined. We investigated the expression of ADAMTS13 mRNA and protein in fresh frozen specimens obtained during liver biopsies of 8 patients with liver diseases. In situ hybridizations to localize ADAMTS13 mRNA showed positive signals exclusively in perisinusoidal cells with irregularly elongated dendritic processes extending between hepatocytes. Furthermore, ADAMTS13 was detected immunohistochemically in perisinusoidal cells, whereas no staining was observed in hepatocytes. The positive cells varied in shape from unipolar to dendritic with irregularly elongated cytoplasmic processes, features common to hepatic stellate cells (HSCs). Double-labeling experiments revealed that the ADAMTS13-positive cells also expressed α-smooth muscle actin, confirming that these cells were activated HSCs. These results suggest that HSCs may be major cells producing ADAMTS13 in human liver.
Validation of a brief telephone battery for neurocognitive assessment of patients with pulmonary arterial hypertension
Authors: Taichman Darren B , Christie Jason , Biester Rosette , Mortensen Jennifer , White Joanne , Kaplan Sandra , Hansen-Flaschen John , Palevsky Harold I , Elliott C Gregory , Hopkins Ramona O
Published: April 2005

Background

The effects of pulmonary arterial hypertension on brain function are not understood, despite patients' frequent complaints of cognitive difficulties. Using clinical instruments normally administered during standard in-person assessment of neurocognitive function in adults, we assembled a battery of tests designed for administration over the telephone. The purpose was to improve patient participation, facilitate repeated test administration, and reduce the cost of research on the neuropsychological consequences of acute and chronic cardiorespiratory diseases. We undertook this study to validate telephone administration of the tests.

Methods

23 adults with pulmonary arterial hypertension underwent neurocognitive assessment using both standard in-person and telephone test administration, and the results of the two methods compared using interclass correlations.

Results

For most of the tests in the battery, scores from the telephone assessment correlated strongly with those obtained by in-person administration of the same tests. Interclass correlations between 0.5 and 0.8 were observed for tests that assessed attention, memory, concentration/working memory, reasoning, and language/crystallized intelligence (p ≤ 0.05 for each). Interclass correlations for the Hayling Sentence Completion test of executive function approached significance (p = 0.09). All telephone tests were completed within one hour.

Conclusion

Administration of this neurocognitive test battery by telephone should facilitate assessment of neuropsychological deficits among patients with pulmonary arterial hypertension living across broad geographical areas, and may be useful for monitoring changes in neurocognitive function in response to PAH-specific therapy or disease progression.