bluuebunny/crossref_metadata_2025_split huggingface dataset:
Singularities Affect Dynamics of Learning in Neuromanifolds
Authors: Amari Shun-ichi , Park Hyeyoung , Ozeki Tomoko 
Published: May 2006

The parameter spaces of hierarchical systems such as multilayer perceptrons include singularities due to the symmetry and degeneration of hidden units. A parameter space forms a geometrical manifold, called the neuromanifold in the case of neural networks. Such a model is identified with a statistical model, and a Riemannian metric is given by the Fisher information matrix. However, the matrix degenerates at singularities. Such a singular structure is ubiquitous not only in multilayer perceptrons but also in the gaussian mixture probability densities, ARMA time-series model, and many other cases. The standard statistical paradigm of the Cramér-Rao theorem does not hold, and the singularity gives rise to strange behaviors in parameter estimation, hypothesis testing, Bayesian inference, model selection, and in particular, the dynamics of learning from examples. Prevailing theories so far have not paid much attention to the problem caused by singularity, relying only on ordinary statistical theories developed for regular (nonsingular) models. Only recently have researchers remarked on the effects of singularity, and theories are now being developed. This article gives an overview of the phenomena caused by the singularities of statistical manifolds related to multilayer perceptrons and gaussian mixtures. We demonstrate our recent results on these problems. Simple toy models are also used to show explicit solutions. We explain that the maximum likelihood estimator is no longer subject to the gaussian distribution even asymptotically, because the Fisher information matrix degenerates, that the model selection criteria such as AIC, BIC, and MDL fail to hold in these models, that a smooth Bayesian prior becomes singular in such models, and that the trajectories of dynamics of learning are strongly affected by the singularity, causing plateaus or slow manifolds in the parameter space. The natural gradient method is shown to perform well because it takes the singular geometrical structure into account. The generalization error and the training error are studied in some examples.
Analysis of Spike Statistics in Neuronal Systems with Continuous Attractors or Multiple, Discrete Attractor States
Authors: Miller Paul 
Published: May 2006

Attractor networks are likely to underlie working memory and integrator circuits in the brain. It is unknown whether continuous quantities are stored in an analog manner or discretized and stored in a set of discrete attractors. In order to investigate the important issue of how to differentiate the two systems, here we compare the neuronal spiking activity that arises from a continuous (line) attractor with that from a series of discrete attractors. Stochastic fluctuations cause the position of the system along its continuous attractor to vary as a random walk, whereas in a discrete attractor, noise causes spontaneous transitions to occur between discrete states at random intervals. We calculate the statistics of spike trains of neurons firing as a Poisson process with rates that vary according to the underlying attractor network. Since individual neurons fire spikes probabilistically and since the state of the network as a whole drifts randomly, the spike trains of individual neurons follow a doubly stochastic (Poisson) point process. We compare the series of spike trains from the two systems using the autocorrelation function, Fano factor, and interspike interval (ISI) distribution. Although the variation in rate can be dramatically different, especially for short time intervals, surprisingly both the autocorrelation functions and Fano factors are identical, given appropriate scaling of the noise terms. Since the range of firing rates is limited in neurons, we also investigate systems for which the variation in rate is bounded by either rigid limits or because of leak to a single attractor state, such as the Ornstein-Uhlenbeck process. In these cases, the time dependence of the variance in rate can be different between discrete and continuous systems, so that in principle, these processes can be distinguished using second-order spike statistics.
Representation and Timing in Theories of the Dopamine System
Authors: Daw Nathaniel D. , Courville Aaron C. , Touretzky David S. 
Published: May 2006

Although the responses of dopamine neurons in the primate midbrain are well characterized as carrying a temporal difference (TD) error signal for reward prediction, existing theories do not offer a credible account of how the brain keeps track of past sensory events that may be relevant to predicting future reward. Empirically, these shortcomings of previous theories are particularly evident in their account of experiments in which animals were exposed to variation in the timing of events. The original theories mispredicted the results of such experiments due to their use of a representational device called a tapped delay line.Here we propose that a richer understanding of history representation and a better account of these experiments can be given by considering TD algorithms for a formal setting that incorporates two features not originally considered in theories of the dopaminergic response: partial observability (a distinction between the animal's sensory experience and the true underlying state of the world) and semi-Markov dynamics (an explicit account of variation in the intervals between events). The new theory situates the dopaminergic system in a richer functional and anatomical context, since it assumes (in accord with recent computational theories of cortex) that problems of partial observability and stimulus history are solved in sensory cortex using statistical modeling and inference and that the TD system predicts reward using the results of this inference rather than raw sensory data. It also accounts for a range of experimental data, including the experiments involving programmed temporal variability and other previously unmodeled dopaminergic response phenomena, which we suggest are related to subjective noise in animals' interval timing. Finally, it offers new experimental predictions and a rich theoretical framework for designing future experiments.
Enabling Scalability by Partitioning Virtual Environments Using Frontier Sets
Authors: Steed Anthony , Angus Cameron 
Published: May 2006

We present a class of partitioning scheme that we have called frontier sets. Frontier sets build on the notion of a potentially visible set (PVS). In a PVS, a world is subdivided into cells and for each cell all the other cells that can be seen are computed. In contrast, a frontier set considers pairs of cells, A and B. For each pair, it lists two sets of cells (two frontiers), FAB and FBA. By definition, from no cell in FAB is any cell in FBA visible and vice versa. Our initial use of frontier sets has been to enable scalability in distributed networking. This is possible because, for example, if at time t0 Player1 is in cell A and Player2 is in cell B, as long as they stay in their respective frontiers, they do not need to send update information to each other. In this paper we describe two strategies for building frontier sets. Both strategies are dynamic and compute frontiers only as necessary at runtime. The first is distance-based frontiers. This strategy requires precomputation of an enhanced potentially visible set. The second is greedy frontiers. This strategy is more expensive to compute at runtime, however it leads to larger and thus more efficient frontiers. Network simulations using code based on the Quake II engine show that frontiers have significant promise and may allow a new class of scalable peer-to-peer game infrastructures to emerge.
Higher urine 1-hydroxy pyrene glucuronide (1-OHPG) is associated with tobacco smoke exposure and drinking maté in healthy subjects from Rio Grande do Sul, Brazil
Authors: Fagundes Renato B , Abnet Christian C , Strickland Paul T , Kamangar Farin , Roth Mark J , Taylor Philip R , Dawsey Sanford M 
Published: May 2006

Abstract

Background
The highest rates of esophageal squamous cell carcinoma (ESCC) in Brazil occur in Rio Grande do Sul, the most southern state, which has incidence rates of 20.4/100,000/year for men and 6.5/100,000/year for women. Exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs) through tobacco smoke and other sources may increase the risk of ESCC. The aims of the current study were to investigate the degree and sources of PAH exposure of the inhabitants of this region of southern Brazil.

Methods
Two hundred healthy adults (half smokers, half non smokers, half male and half female) were recruited, given a standardized questionnaire, and asked to provide a urine sample for measurement of 1-hydroxypyrene glucuronide (1-OHPG), a PAH metabolite). Urine 1-OHPG concentrations were measured using immunoaffinity chromatography and synchronous fluorescence spectroscopy and urine cotinine was measured using a dipstick test. We examined factors associated with 1-OHPG concentration using Wilcoxon tests and multiple linear regression.

Results
Urine 1-hydroxypyrene glucuronide (1-OHPG) was successfully measured on 199 subjects. The median (interquartile range) of urine 1-OHPG in the 199 participants was 2.09 pmol/mL (0.51, 5.84). Tobacco smoke exposure and maté drinking were statistically significantly associated with higher urine 1-OHPG concentrations in the multivariate linear regression model.

Conclusion
Tobacco smoke and maté both contribute to high levels of benzo[a]pyrene exposure in the people of southern Brazil. This high PAH exposure may contribute to the high rates of ESCC observed in this population. The increased urine 1-OHPG concentrations associated with maté suggest that contaminants, not just thermal injury, may help explain the increased risk of ESCC previously reported for maté consumption.
A placebo-controlled pilot study of intensification of antiretroviral therapy with mycophenolate mofetil
Authors: Kaur Rupinderjeet , Bedimo Roger , Kvanli Mary Beth , Turner Diana , Shaw Leslie , Margolis David 
Published: May 2006

Abstract

Purpose
We studied the safety, tolerability, virologic, and immunologic effects of mycophenolate mofetil (MMF) added to a stable antiretroviral therapy (ART) in the setting of low-level viremia.

Methods
MMF 500 mg BID or placebo was given to patients thought to be adherent on stable ART with plasma viremia between 200 and 4000 copies/mL. At week 4 unblinding was performed and patients on placebo were offered open-label MMF.

Results
Six patients were enrolled. At entry mean plasma HIV-1 RNA (VL) was 2.98 log10 copies/mL; mean CD4 count was 523. All subjects randomized to placebo elected to cross over to open label MMF. No significant adverse events were observed during MMF therapy. Three patients on MMF achieved VL < 50 copies/mL by week 4; a fourth had VL decline of > 0.5 log. Two patients on placebo had declines of VL. One of these had further decline on open label MMF. Cell surface markers of apoptosis, activation, and proliferation on CD4+ and CD8+ cells declined modestly or remained low. CD4 counts were stable at week 24. All but one subject had rebound of viremia by week 24, universally associated with missed doses of medication by pill count.

Conclusion
MMF appears to be safe, and its administration lead to decreased T cell activation. During periods of adherence to therapy, the use of MMF was correlated with declines in viremia, but this small pilot study could not prove this association. Further study of MMF in patients with viremia should be considered for whom additional or alternative antiretrovirals are impractical.
Evaluation of cell wall preparations for proteomics: a new procedure for purifying cell walls from Arabidopsis hypocotyls
Authors: Feiz Leila , Irshad Muhammad , F Pont-Lezica Rafael , Canut Hervé , Jamet Elisabeth 
Published: May 2006

Abstract

Background
The ultimate goal of proteomic analysis of a cell compartment should be the exhaustive identification of resident proteins; excluding proteins from other cell compartments. Reaching such a goal closely depends on the reliability of the isolation procedure for the cell compartment of interest. Plant cell walls possess specific difficulties: (i) the lack of a surrounding membrane may result in the loss of cell wall proteins (CWP) during the isolation procedure, (ii) polysaccharide networks of cellulose, hemicelluloses and pectins form potential traps for contaminants such as intracellular proteins. Several reported procedures to isolate cell walls for proteomic analyses led to the isolation of a high proportion (more than 50%) of predicted intracellular proteins. Since isolated cell walls should hold secreted proteins, one can imagine alternative procedures to prepare cell walls containing a lower proportion of contaminant proteins.

Results
The rationales of several published procedures to isolate cell walls for proteomics were analyzed, with regard to the bioinformatic-predicted subcellular localization of the identified proteins. Critical steps were revealed: (i) homogenization in low ionic strength acid buffer to retain CWP, (ii) purification through increasing density cushions, (iii) extensive washes with a low ionic strength acid buffer to retain CWP while removing as many cytosolic proteins as possible, and (iv) absence of detergents. A new procedure was developed to prepare cell walls from etiolated hypocotyls of Arabidopsis thaliana. After salt extraction, a high proportion of proteins predicted to be secreted was released (73%), belonging to the same functional classes as proteins identified using previously described protocols. Finally, removal of intracellular proteins was obtained using detergents, but their amount represented less than 3% in mass of the total protein extract, based on protein quantification.

Conclusion
The new cell wall preparation described in this paper gives the lowest proportion of proteins predicted to be intracellular when compared to available protocols. The application of its principles should lead to a more realistic view of the cell wall proteome, at least for the weakly bound CWP extractable by salts. In addition, it offers a clean cell wall preparation for subsequent extraction of strongly bound CWP.
Live Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis activate the inflammatory response through Toll-like receptors 2, 4, and 9 in species-specific patterns
Authors: Mogensen Trine H , Paludan Søren R , Kilian Mogens , Østergaard Lars 
Published: May 2006

Abstract
Toll-like receptors (TLRs) are pattern recognition receptors (PRR) that recognize molecular structures on pathogens and activate host defenses. Although much is known about specific bacterial components that activate TLRs, few studies have addressed the question of which TLRs are involved in immune activation by live bacteria. Here, we demonstrate that live Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis, the three principal causes of bacterial meningitis, use distinct sets of TLRs to trigger the inflammatory response. Using human embryonic kidney 293 cell lines, each overexpressing one type of TLR, we found that S. pneumoniae triggered activation of the transcription factor nuclear factor-κB and expression of interleukin-8, only in cells expressing TLR2 or -9. The same response was evoked by H. influenzae in cells expressing TLR2 or -4 and by N. meningitidis in cells expressing TLR2, -4, or -9. It is interesting that the ability of S. pneumoniae and N. meningitidis to activate TLR9 was severely attenuated when bacteria had been heat-inactivated prior to stimulation of the cells. In human peripheral blood mononuclear cells, we blocked TLR2, -4, or -9 and confirmed the essential role of these TLRs and also identified differential functions of TLRs in activation of the inflammatory response. Collectively, we here demonstrate that S. pneumoniae, H. influenzae, and N. meningitidis each activate several TLRs in species-specific patterns and show that infection with live pathogens may lead to activation of PRR not targeted by inactivated bacteria.
ICAM-1-dependent pathways regulate colonic eosinophilic inflammation
Authors: Forbes Elizabeth , Hulett Mark , Ahrens Richard , Wagner Norbert , Smart Vanessa , Matthaei Klaus I , Brandt Eric B , Dent Lindsay A , Rothenberg Marc E , Tang Mimi , Foster Paul S , Hogan Simon P 
Published: May 2006

AbstractEosinophilic inflammation is a common feature of numerous eosinophil-associated gastrointestinal (EGID) diseases. Central to eosinophil migration into the gastrointestinal tract are the integrin-mediated interactions with adhesion molecules. Although the mechanisms regulating eosinophil homing into the small intestine have begun to be elucidated, the adhesion pathways responsible for eosinophil trafficking into the large intestine are unknown. We investigated the role of adhesion pathways in eosinophil recruitment into the large intestine during homeostasis and disease. First, using a hapten-induced colonic injury model, we demonstrate that in contrast to the small intestine, eosinophil recruitment into the colon is regulated by a β7-integrin addressin cell adhesion molecule-1-independent pathway. Characterization of integrin expression on colonic eosinophils by flow cytometry analysis revealed that colonic CC chemokine receptor 3+ eosinophils express the intercellular adhesion molecule-1 (ICAM-1) counter-receptor integrins αL, αM, and β2. Using ICAM-1-deficient mice and anti-ICAM-1 neutralizing antibodies, we show that hapten-induced colonic eosinophilic inflammation is critically dependent on ICAM-1. These studies demonstrate that β2-integrin/ICAM-1-dependent pathways are integral to eosinophil recruitment into the colon during GI inflammation associated with colonic injury.
The factor structure of test task characteristics and examinee performance
Authors: Carr Nathan T. 
Published: May 2006

The present study focuses on the task characteristics of reading passages and key sentences in a test of second language reading. Using a new methodological approach to describe variation in test task characteristics and explore how differences in these characteristics might relate to examinee performance, it posed the two following research questions: First, how do the characteristics of the texts used in a high-stakes test of English for Academic Purposes reading vary? Second, what relationships exist between its text characteristics and examinee performance? An expanded test task characteristics instrument was constructed, following Freedle and Kostin (1993) and Bachman et al. (1996), and adding a large number of syntactic features (Celce-Murcia and Larsen-Freeman, 1999). Ratings and numerical counts were compiled for three forms of the Test of English as a Foreign Language (TOEFL) Reading Comprehension Section. Taking items as the object of measurement, the results were then used in a series of exploratory and confirmatory factor analyses, along with IRT (item response theory) parameter estimates for the items in question.
Activities of daily living and social activities in people with multiple sclerosis in Stockholm County
Authors: Einarsson U , Gottberg K , Fredrikson S , von Koch L , Holmqvist L Widén 
Published: May 2006

Objective: To describe independence in personal and instrumental activities of daily living (ADL), and frequency of social/lifestyle activities in a population-based sample of people with multiple sclerosis in Stockholm. Design: Population-based survey. Setting: Data collection in home environment. Subjects: One hundred and sixty-six people with multiple sclerosis. Interventions: Data were collected using measurements and structured interviews. Main measures: Independence in ADL was assessed by the Barthel Index; independence in personal and instrumental ADL by the Katz Extended ADL Index; and frequency of social/lifestyle activities by the Frenchay Activities Index. Results: The mean age was 519 ± 12 years in the included 166 people with multiple sclerosis, of whom 71% ( n = 118) were women. Fifty-two per cent ( n = 85) were independent in personal ADL, 30% ( n = 50) in instrumental ADL, and 35% ( n = 57) had normal frequency of social/lifestyle activities. Most frequently affected ADL items were cleaning indoors and outdoors transportation (62%, n = 102) and the social/lifestyle items of household maintenance (59%, n = 97), walking outside (59%, n = 97), heavy housework (61%, n = 100), and gardening (68%, n = 112). Conclusions: ADL and social/lifestyle activities were affected in two-thirds of people with multiple sclerosis in Stockholm. The most affected items were items that could be classified as mobility-related and physically demanding, underlining the importance of developing and using evidence-based exercise treatments and rehabilitation to increase independence in people with multiple sclerosis in Stockholm.
Strength training in adolescent learners with cerebral palsy: a randomized controlled trial
Authors: Unger Marianne , Faure Mary , Frieg Annette 
Published: May 2006

Objective: To evaluate the impact of an eight-week strength training program targeting multiple muscle groups using basic inexpensive free weights and resistance devices, on gait and perceptions of body image and functional competence. Design: A randomized control trial. Setting: A school for children with special needs in a disadvantaged suburb in Cape Town. Subjects: Thirty-one independently ambulant senior learners with spastic cerebral palsy (19 males, 12 females; aged 13-18 years; 15 diplegics and 16 hemiplegics). Intervention: Eight-week strength training programme in circuit format executed during school hours, one to three times per week for 40-60 min per session. Programmes were individually designed and included 8-12 exercises selected from a 28-station circuit to target upper and lower limbs and trunk. Twenty-one subjects took part in the strength training programme and were compared with 10 control subjects. Main outcome measures: Three-dimensional gait analysis and a questionnaire were used to evaluate the various parameters of gait and perceptions of body image and functional competence respectively. Results were analysed using repeated measures ANOVA and bootstrap analysis. Results: The experimental group differed significantly from the control group for measure of crouch gait (sum of the ankle, knee and hip angles at midstance) (P = 0.05) and perceptions of body image (P = 0.01). Walking velocity, cadence and stride length as well as perceptions of functional ability did not change significantly after training. Conclusion: Participation in a school-based strength training programme targeting multiple muscle groups can lead to improved degree of crouch gait and improve perception of body image.