Coherent Infomax as a Computational Goal for Neural Systems

Signal processing in the cerebral cortex is thought to involve a common multi-purpose algorithm embodied in a canonical cortical micro-circuit that is replicated many times over both within and across cortical regions. Operation of this algorithm produces widely distributed but coherent and relevant patterns of activity. The theory of Coherent Infomax provides a formal specification of the objectives of such an algorithm. It also formally derives specifications for both the short-term processing dynamics and for the learning rules whereby the connection strengths between units in the network can be adapted to the environment in which the system finds itself. A central assumption of the theory is that the local processors can combine reliable signal coding with flexible use of those codes because they have two classes of synaptic connection: driving connections which specify the information content of the neural signals, and contextual connections which modulate that signal processing. Here, we make the biological relevance of this theory more explicit by putting more emphasis upon the contextual guidance of ongoing processing, by showing that Coherent Infomax is consistent with a particular Bayesian interpretation for the contextual guidance of learning and processing, by explicitly specifying rules for on-line learning, and by suggesting approximations by which the learning rules can be made computationally feasible within systems composed of very many local processors.     

Longitudinal Data Analysis with Event Time as a Covariate

We consider the estimation of a nonparametric smooth function of some event time in a semiparametric mixed effects model from repeatedly measured data when the event time is subject to right censoring. The within-subject correlation is captured by both cross-sectional and time-dependent random effects, where the latter is modeled by a nonhomogeneous Ornstein–Uhlenbeck stochastic process. When the censoring probability depends on other variables in the model, which often happens in practice, the event time data are not missing completely at random. Hence, the complete case analysis by eliminating all the censored observations may yield biased estimates of the regression parameters including the smooth function of the event time, and is less efficient. To remedy, we derive the likelihood function for the observed data by modeling the event time distribution given other covariates. We propose a two-stage pseudo-likelihood approach for the estimation of model parameters by first plugging an estimator of the conditional event time distribution into the likelihood and then maximizing the resulting pseudo-likelihood function. Empirical evaluation shows that the proposed method yields negligible biases while significantly reduces the estimation variability. This research is motivated by the project of hormone profile estimation around age at the final menstrual period for the cohort of women in the Michigan Bone Health and Metabolism Study.     

Conditions for Global Dynamic Stability of a Class of Resource-Bounded Model Ecosystems

This paper studies a class of dynamical systems that model multi-species ecosystems. These systems are ‘resource bounded’ in the sense that species compete to utilize an underlying limiting resource or substrate. This boundedness means that the relevant state space can be reduced to a simplex, with coordinates representing the proportions of substrate utilized by the various species. If the vector field is inward pointing on the boundary of the simplex, the state space is forward invariant under the system flow, a requirement that can be interpreted as the presence of non-zero exogenous recruitment. We consider conditions under which these model systems have a unique interior equilibrium that is globally asymptotically stable. The systems we consider generalize classical multi-species Lotka–Volterra systems, the behaviour of which is characterized by properties of the community (or interaction) matrix. However, the more general systems considered here are not characterized by a single matrix, but rather a family of matrices. We develop a set of ‘explicit conditions’ on the basis of a notion of ‘uniform diagonal dominance’ for such a family of matrices, that allows us to extract a set of sufficient conditions for global asymptotic stability based on properties of a single, derived matrix. Examples of these explicit conditions are discussed.     

Workload characterization in a high-energy data grid and impact on resource management

The analysis of data usage in a large set of real traces from a high-energy physics collaboration revealed the existence of an emergent grouping of files that we coined “filecules”. This paper presents the benefits of using this file grouping for prestaging data and compares it with previously proposed file grouping techniques along a range of performance metrics. Our experiments with real workloads demonstrate that filecule grouping is a reliable and useful abstraction for data management in science Grids; that preserving time locality for data prestaging is highly recommended; that job reordering with respect to data availability has significant impact on throughput; and finally, that a relatively short history of traces is a good predictor for filecule grouping. Our experimental results provide lessons for workload modeling and suggest design guidelines for data management in data-intensive resource-sharing environments.

C-Terminal 23 kDa polypeptide of soybean Gly m Bd 28 K is a potential allergen

Gly m Bd 28 K is a major soybean (Glycine max Merr.) glycoprotein allergen. It was originally identified as a 28 kDa polypeptide in soybean seed flour. However, the full-length protein is encoded by an open reading frame (ORF) of 473 amino acids, and contains a 23 kDa C-terminal polypeptide of as yet unknown allergenic and structural characteristics. IgE-binding (allergenic potential) of the Gly m Bd 28 K protein including the 23 kDa C-terminal portion as well as shorter fragments derived from the full-length ORF were evaluated using sera from soy-sensitive adults. All of these sera contained IgE that efficiently recognized the C-terminal region. Epitope mapping demonstrated that a dominant linear C-terminal IgE binding epitope resides between residues S256 and A270. Alanine scanning of this dominant epitope indicated that five amino acids, Y260, D261, D262, K264 and D266, contribute most towards IgE-binding. A model based on the structure of the subunit of soybean -conglycinin revealed that Gly m Bd 28 K contains two cupin domains. The dominant epitope is on the edge of the first -sheet of the C-terminal cupin domain and is present on a potentially solvent-accessible loop connecting the two cupin domains. Thus, the C-terminal 23 kDa polypeptide of Gly m Bd 28 K present in soy products is allergenic and apparently contains at least one immunodominant epitope near the edge of a cupin domain. This knowledge could be helpful in the future breeding of hypoallergenic soybeans.Abbreviations Ara h 1 Arachis hypogaea allergen 1 - Ara h 3 Arachis hypogaea allergen 3 - BCA Bicinchoninic acid - Gly m Bd 28 K Glycine max band 28 kDa allergen - Gly m Bd 30 K Glycine max band 30 kDa allergen - Gly m Bd 68 K Glycine max band 68 kDa allergen - IgE Immunoglobulin E     

Diffusion as a Ruler: Modeling Kinesin Diffusion as a Length Sensor for Intraflagellar Transport

An important question in cell biology is whether cells are able to measure size, either whole cell size or organelle size. Perhaps cells have an internal chemical representation of size that can be used to precisely regulate growth, or perhaps size is just an accident that emerges due to constraint of nutrients. The eukaryotic flagellum is an ideal model for studying size sensing and control because its linear geometry makes it essentially one-dimensional, greatly simplifying mathematical modeling. The assembly of flagella is regulated by intraflagellar transport (IFT), in which kinesin motors carry cargo adaptors for flagellar proteins along the flagellum and then deposit them at the tip, lengthening the flagellum. The rate at which IFT motors are recruited to begin transport into the flagellum is anticorrelated with the flagellar length, implying some kind of communication between the base and the tip and possibly indicating that cells contain some mechanism for measuring flagellar length. Although it is possible to imagine many complex scenarios in which additional signaling molecules sense length and carry feedback signals to the cell body to control IFT, might the already-known components of the IFT system be sufficient to allow length dependence of IFT? Here we investigate a model in which the anterograde kinesin motors unbind after cargo delivery, diffuse back to the base, and are subsequently reused to power entry of new IFT trains into the flagellum. By mathematically modeling and simulating such a system, we are able to show that the diffusion time of the motors can in principle be sufficient to serve as a proxy for length measurement. We found that the diffusion model can not only achieve a stable steady-state length without the addition of any other signaling molecules or pathways, but also is able to produce the anticorrelation between length and IFT recruitment rate that has been observed in quantitative imaging studies.     

Spatiotemporal Dynamics of the Epidemic Transmission in a Predator-Prey System

Epidemic transmission is one of the critical density-dependent mechanisms that affect species viability and dynamics. In a predator-prey system, epidemic transmission can strongly affect the success probability of hunting, especially for social animals. Predators, therefore, will suffer from the positive density-dependence, i.e., Allee effect, due to epidemic transmission in the population. The rate of species contacting the epidemic, especially for those endangered or invasive, has largely increased due to the habitat destruction caused by anthropogenic disturbance. Using ordinary differential equations and cellular automata, we here explored the epidemic transmission in a predator-prey system. Results show that a moderate Allee effect will destabilize the dynamics, but it is not true for the extreme Allee effect (weak or strong). The predator-prey dynamics amazingly stabilize by the extreme Allee effect. Predators suffer the most from the epidemic disease at moderate transmission probability. Counter-intuitively, habitat destruction will benefit the control of the epidemic disease. The demographic stochasticity dramatically influences the spatial distribution of the system. The spatial distribution changes from oil-bubble-like (due to local interaction) to aggregated spatially scattered points (due to local interaction and demographic stochasticity). It indicates the possibility of using human disturbance in habitat as a potential epidemic-control method in conservation.     

Utilisation of cardiac pacemakers over a 20-year period: Results from a nationwide pacemaker registry

The implantation of cardiac pacemakers has become a well-established therapy for conduction disorders and sinus node dysfunction. In many countries pacemaker registries have been initiated in order to collect information on patient characteristics, trends in numbers and the types of pacemakers used, to identify problematic devices, and for safety monitoring. For this utilisation study the Central Pacemaker Patients Registration (CPPR) from the Netherlands Pacemaker Registry Foundation (CPPR-SPRN) containing data collected for more than 20 years was used. During this period nearly 97,000 first pacemakers were implanted. Analyses show an increase in the rate of implanted devices. The change in pacemaker type from VVI to DDD, followed by biventricular stimulation, is reflected by the number of simultaneously implanted leads, which is partly a consequence of cardiac resynchronisation therapy. Our data demonstrate that indications for implantation and type of pacemaker are comparable with other European countries.     

A Dynamical Study of a Cellular Automata Model of the Spread of HIV in a Lymph Node

We conduct a mathematical study of a cellular automata model of the spread of the HIV virus in a lymph node. The model was proposed by Zorzenon dos Santos and Coutinho and captures the unique time scale of the viral spread. We give some rigorous mathematical results about the time scales and other dynamical aspects of the model as well as discuss parameter and model changes and their consequences.     

In vitro separation of a rose chimera

“Fairmount 1 thorny” (“FM1 thorny”) (a Rosa multiflora Thunb ex. J. Murr.) and a thornless sport of “FM1 thorny” (“Fairmount 1” (“FM1”)) were established in vitro to investigate chimeral segregation under various levels of BA and to obtain a pure thornless rose. While the chimeral thornless sport was expected to segregate in vitro and yield both thorny and thornless plantlets, “FM1 thorny” was to yield only thorny plants. “FM1” segregated in vitro into its constituent genotypes and yielded thorny and thornless plantlets, suggesting that “FM1” is chimeral. “FM1 thorny” produced only thorny plants in vitro. These results indicate that the “FM1 thorny” clone was not chimeral (pure thorny) and that the thornless regenerates of “FM1” did not develop via somaclonal variation. There was a significant linear relationship between increasing BA concentration and the percentage of thorny plants. Among a population of 690 tissue culture derived plants from all the BA experiments, 6 plants were classified as pure thornless plants 1 year later.     

Turing Pattern Formation with Two Kinds of Cells and a Diffusive Chemical

We study a three-variable Turing system with two kinds of cells and a diffusive chemical, considering the formation and maintenance of fish skin patterns with multiple pigment cells. The two types of cells are produced from undifferentiated cells. They inhibit the supply rate of the other cell type, forming local clusters of the same cell type. In addition, the cells of one type can be maintained only in the presence of a diffusive chemical produced by the other cell type, resulting in the coexistence of two cell types in heterogeneous spatial patterns. We assume linear interaction among cells and the chemical, and cell supply rates constrained to be positive or zero. We derive the condition for diffusion-driven instability. In one-dimensional model, we examine how the wavelength of the periodic pattern depends on parameters. In the two-dimensional model, we study the condition for spot, stripe or reversed spot pattern to emerge (pattern selection). We discuss heuristic criteria for the pattern selection.     

Visual system: prostriata - a visual area off the beaten path

Recent work establishes that Prostriata, a little-studied area of the visual cortex neighboring V1, has distinct but hybrid visual properties which are suggestive of an unsuspected role in the rapid analysis and integration of peripheral visual stimuli.     

Male-sterile mutation alters Zea m 1 (β-expansin 1) accumulation in a maize mutant

gaMS-2 is a gametophytic male-sterile mutant of maize, with sterile pollen grains developmentally blocked at the binucleate stage. To characterise differentially expressed proteins in gaMS-2 pollen, we compared protein profiles of anthers and mature pollen from heterozygous GaMS-2/gaMS-2 plants and wild type (wt) plants by two-dimensional electrophoresis (2-DE). A basic protein present at a greatly reduced level in GaMS-2/gaMS-2 anthers was subsequently identified by tandem mass spectrometry as Zea m 1 (a glycoprotein of 31 kDa), the major group-1 allergen of maize pollen and a member of the -expansin 1 family. Moreover, we show that Zea m 1 can be deglycosylated by peptide N-glycosidase F. After deglycosylation, four major isoforms—Zea m 1a (more acetic), Zea m 1b, Zea m1c and Zea m 1d (more basic)—can be discriminated in wt anther in 2-DE immunoblots probed with a monoclonal antibody against the group-1 pollen allergen, whereas all the isoforms, especially Zea m 1a, exist at reduced levels in GaMS-2/gaMS-2 anthers. Furthermore, the reduced Zea m 1 accumulation in the mutant appears to occur in immature pollen but not in anther sporophytic tissues. Finally, we separated sterile pollen grains (at the mononucleate stage) from fertile ones using 42% Percoll solution, and found that Zea m 1 is barely detectable in sterile pollen grains. Together, our results indicate that a reduced Zea m 1 level is associated with the sterile phenotype of gaMS-2.W. Wang and M. Scali contributed equally to this study     

Calcineurin ensures a link between the DNA replication checkpoint and microtubule-dependent polarized growth

Microtubules are central to eukaryotic cell morphogenesis. Microtubule plus-end tracking proteins (+TIPs) transport polarity factors to the cell cortex, thereby playing a key role in both microtubule dynamics and cell polarity. However, the signalling pathway linking +TIPs to cell polarity control remains elusive. Here we show that the fission yeast checkpoint kinase Cds1 (Chk2 homologue) delays the transition of growth polarity from monopolar to bipolar (termed NETO; new-end take-off). The +TIPs CLIP170 homologue Tip1 and kinesin Tea2 are responsible for this delay, which is accompanied by a reduction in microtubule dynamics at the cell tip. Remarkably, microtubule stabilization occurs asymmetrically, prominently at the non-growing cell end, which induces abnormal accumulation of the polarity factor Tea1. Importantly, NETO delay requires activation of calcineurin, which is carried out by Cds1, resulting in Tip1 dephosphorylation. Thus, our study establishes a critical link between calcineurin and checkpoint-dependent cell morphogenesis.     

The Evolution of Virulence in RNA Viruses under a Competition–Colonization Trade-Off

RNA viruses exist in large intra-host populations which display great genotypic and phenotypic diversity. We analyze a model of viral competition between two viruses infecting a constantly replenished cell pool. We assume a trade-off between the ability of the virus to colonize new cells (cell killing rate or virulence) and its local competitiveness (replicative success within coinfected cells). We characterize the conditions that allow for viral spread by means of the basic reproductive number and show that a local coexistence equilibrium exists, which is asymptotically stable. At this equilibrium, the less virulent competitor has a reproductive advantage over the more virulent colonizer reflected by a larger equilibrium population size of the competitor. The equilibria at which one virus outcompetes the other one are unstable, i.e., a second virus is always able to permanently invade. We generalize the two-virus model to multiple viral strains, each displaying a different virulence. To account for the large phenotypic diversity in viral populations, we consider a continuous spectrum of virulences and present a continuum limit of this multiple viral strains model that describes the time evolution of an initial continuous distribution of virulence without mutations. We provide a proof of the existence of solutions of the model equations, analytically assess the properties of stationary solutions, and present numerical approximations of solutions for different initial distributions. Our simulations suggest that initial continuous distributions of virulence evolve toward a distribution that is extremely skewed in favor of competitors. At equilibrium, only the least virulent part of the population survives. The discrepancy of this finding in the continuum limit with the two-virus model is attributed to the skewed equilibrium subpopulation sizes and to the transition to a continuum. Consequently, in viral quasispecies with high virulence diversity, the model predicts collective virulence attenuation. This result may contribute to understanding virulence attenuation, which has been reported in several experimental studies.     

Advanced backcross QTL analysis of a hard winter wheat × synthetic wheat population

Advanced backcross quantitative trait locus (AB-QTL) analysis was used to identify QTLs for yield and yield components in a backcross population developed from a cross between hard red winter wheat (Triticum aestivum L.) variety Karl 92 and the synthetic wheat line TA 4152-4. Phenotypic data were collected for agronomic traits including heading date, plant height, kernels per spike, kernel weight, tiller number, biomass, harvest index, test weight, grain yield, protein content, and kernel hardness on 190 BC₂F_2:4 lines grown in three replications in two Kansas environments. Severity of wheat soilborne mosaic virus (WSBMV) reaction was evaluated at one location. The population was genotyped using 151 microsatellite markers. Of the ten putative QTLs identified, seven were located on homoeologous group 2 and group 3 chromosomes. The favorable allele was contributed by cultivated parent Karl 92 at seven QTLs including a major one for WSBMV resistance, and by the synthetic parent at three QTLs: for grain hardness, kernels per spike, and tiller number. Mention of trade names or commercial products in this publication is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the U.S. Department of Agriculture.     

Searching for Spatial Patterns in a Pollinator–Plant–Herbivore Mathematical Model

This paper deals with the spatio-temporal dynamics of a pollinator–plant–herbivore mathematical model. The full model consists of three nonlinear reaction–diffusion–advection equations defined on a rectangular region. In view of analyzing the full model, we firstly consider the temporal dynamics of three homogeneous cases. The first one is a model for a mutualistic interaction (pollinator–plant), later on a sort of predator–prey (plant–herbivore) interaction model is studied. In both cases, the interaction term is described by a Holling response of type II. Finally, by considering that the plant population is the unique feeding source for the herbivores, a mathematical model for the three interacting populations is considered. By incorporating a constant diffusion term into the equations for the pollinators and herbivores, we numerically study the spatiotemporal dynamics of the first two mentioned models. For the full model, a constant diffusion and advection terms are included in the equation for the pollinators. For the resulting model, we sketch the proof of the existence, positiveness, and boundedness of solution for an initial and boundary values problem. In order to see the separated effect of the diffusion and advection terms on the final population distributions, a set of numerical simulations are included. We used homogeneous Dirichlet and Neumann boundary conditions.