Components of episodic memory: the contribution of recollection and familiarity

The examination of recognition memory confidence judgements indicates that there are two separate components or processes underlying episodic memory. A model that accounts for these results is described in which a recollection process and a familiarity process are assumed to contribute to recognition memory performance. Recollection is assumed to reflect a threshold process whereby qualitative information about the study event is retrieved, whereas familiarity reflects a classical signal-detection process whereby items exceeding a familiarity response criterion are accepted as having been studied. Evidence from cognitive, neuropsychological and neuroimaging studies indicate that the model is in agreement with the existing recognition results, and indicate that recollection and familiarity are behaviourally, neurally and phenomenologically distinct memory retrieval processes.     

Diversity and Evolution of the Marsupial Mandibular Angular Process

A medial inflection of the mandibular angular process is present in most marsupials. The few living marsupials that lack this trait either are very specialized forms (e.g., Tarsipes) or show a medial inflection at some point in development that is lost in later ontogenetic stages (cf. Dactylopsila and Phascolarctos). A medially inflected angular process is not present in any known extant or extinct placental (including all Cretaceous taxa that preserve the back of the dentary bone). Some extant placentals with enlarged auditory bullae evolved a medial flange of the angular process as a strategy to increase gape, but this is not homologous to the marsupial condition. We conclude that the medially inflected angular process is a shared derived trait of extant and extinct marsupials. The significant diversity in the form of the medially inflected mandibular angular process in marsupials, documented here for 53 taxa, shows a general relation to dietary adaptations. Herbivores (with well-developed masseter and medial pterygoid muscles) tend to have a shelf-like angular process, while small, insectivorous marsupials generally have a rod-like angular process. A close connection between the angular process and the ectotympanic is maintained during early postnatal development in all marsupials examined, a relation not seen in the placentals examined. A previous hypothesis suggested that the angular process plays a role in hearing in pouch-young Monodelphis. Data on the maturation of the auditory system does not support this hypothesis. Currently there are no data on differences in muscular anatomy or mastication between marsupials and placentals that could serve as a causal explanation for the difference in adult form of the angular process between the two groups.     

Estimation of Clustering Parameters Using Gaussian Process Regression

We propose a method for estimating the clustering parameters in a Neyman-Scott Poisson process using Gaussian process regression. It is assumed that the underlying process has been observed within a number of quadrats, and from this sparse information the distribution is modelled as a Gaussian process. The clustering parameters are then estimated numerically by fitting to the covariance structure of the model. It is shown that the proposed method is resilient to any sampling regime. The method is applied to simulated two-dimensional clustered populations and the results are compared to a related method from the literature.     

Saturable and nonsaturable process of sugar uptake: effect of oncogenic transformation in transport and uptake of nutrients.

Uptake of sugars into cells by a saturable process increased enormously during and after transformation, and uptake by a nonsaturable process increased significantly but less remarkably compared to controls. The drastic change of uptake rates, observed at around 5 x 10(-3) M sugar during and after transformation, emphasizes the significant observation that transition of the sugar uptake system from a saturable to a nonsaturable process occurs near the physiological concentration of D-glucose normally seen in animal blood. At concentrations below higher than 5 x 10(-3) M, where a saturable process is barely involved, nonsaturable uptakes of D-glucose, D-mannose, D-galactose, 2-deoxy-D-glucose and 3-O-methyl-D-glucose proceed tens to hundreds fold faster than the rate of simple diffusion of L-glucose. These findings suggest that nonsaturable uptake of the sugars known to be substrates for the saturable transport carrier system may not be a physical process or simple diffusion, as observed for L-glucose uptake. Rather, the nonsaturable uptake might be part of the total physiological process which, along with the saturable process, is controlled by a membrane-coordination mechanism. A plausible mechanism is discussed in which negative cooperativity of nutrient uptake, such as that found in bacteria, is involved.     

Implementation of quality by design toward processing of food products

Quality by design (QbD) is a systematic approach that begins with predefined objectives and emphasizes product and process understanding and process control. It is an approach based on principles of sound science and quality risk management. As the food processing industry continues to embrace the idea of in-line, online, and/or at-line sensors and real-time characterization for process monitoring and control, the existing gaps with regard to our ability to monitor multiple parameters/variables associated with the manufacturing process will be alleviated over time. Investments made for development of tools and approaches that facilitate high-throughput analytical and process development, process analytical technology, design of experiments, risk analysis, knowledge management, and enhancement of process/product understanding would pave way for operational and economic benefits later in the commercialization process and across other product pipelines. This article aims to achieve two major objectives. First, to review the progress that has been made in the recent years on the topic of QbD implementation in processing of food products and second, present a case study that illustrates benefits of such QbD implementation.     

Stable generation of simple forms

It has been suggested by Thom that the mathematical theory of structural stability gives insight into the stable reproduction of form in biological systems. In this paper a process for the generation of some simple forms is described and it is shown that the forms produced are insensitive to perturbations in the production process. The reason for this stability is found in an analysis of the process in terms of the theory of structural stability and in particular in terms of “catastrophes”. Based on the example of our form generating process, we give a general definition of form and define the pattern recognition problem (which is inverse to the generation problem) in the context of that definition.     

Joint analysis of longitudinal data and recurrent episodes data with application to medical cost analysis

This paper discusses regression analysis of longitudinal data in which the observation process may be related to the longitudinal process of interest. Such data have recently attracted a great deal of attention and some methods have been developed. However, most of those methods treat the observation process as a recurrent event process, which assumes that one observation can immediately follow another. Sometimes, this is not the case, as there may be some delay or observation duration. Such a process is often referred to as a recurrent episode process. One example is the medical cost related to hospitalization, where each hospitalization serves as a single observation. For the problem, we present a joint analysis approach for regression analysis of both longitudinal and observation processes and a simulation study is conducted that assesses the finite sample performance of the approach. The asymptotic properties of the proposed estimates are also given and the method is applied to the medical cost data that motivated this study.     

The behavior of adaptive bone-remodeling simulation models

The process of adaptive bone remodeling can be described mathematically and simulated in a computer model, integrated with the finite element method. In the model discussed here, cortical and trabecular bone are described as continuous materials with variable density. The remodeling rule applied to simulate the remodeling process in each element individually is, in fact, an objective function for an optimization process, relative to the external load. Its purpose is to obtain a constant, preset value for the strain energy per unit bone mass, by adapting the density. If an element in the structure cannot achieve that, it either turns to its maximal density (cortical bone) or resorbs completely.

It is found that the solution obtained in generally a discontinuous patchwork. For a two-dimensional proximal femur model this patchwork shows a good resemblance with the density distribution of a real proximal femur.

It is shown that the discontinuous end configuration is dictated by the nature of the differential equations describing the remodeling process. This process can be considered as a nonlinear dynamical system with many degrees of freedom, which behaves divergent relative to the objective, leading to many possible solutions. The precise solution is dependent on the parameters in the remodeling rule, the load and the initial conditions. The feedback mechanism in the process is self-enhancing; denser bone attracts more strain energy, whereby the bone becomes even more dense. It is suggested that this positive feedback of the attractor state (the strain energy field) creates order in the end configuration. In addition, the process ensures that the discontinuous end configuration is a structure with a relatively low mass, perhaps a minimal-mass structure, although this is no explicit objective in the optimization process.

It is hypothesized that trabecular bone is a chaotically ordered structure which can be considered as a fractal with characteristics of optimal mechanical resistance and minimal mass, of which the actual morphology depends on the local (internal) loading characteristics, the sensor-cell density and the degree of mineralization.     

Design of a mathematical model of the formation of erythrocyte shape as an autowave process]

The phenomenological model of T. Teorell's "biomembrane generator" underlies the mathematical model of erythrocyte forms as an autowave process. For a distributed system the model is formulated as a differential equation of the second order in partial derivatives with a small parameter. It is stated that a substantial thing in the model is the presence of mass-transfer through a pore membrane determined by its electrostatic and hydrostatic permeabilities, as well as the fact that mass-transfer through the membrane results in a non-uniform distribution of the liquid current through it. It is suggested that as a consequence of this process there appears mechanical instability of the spherical membrane, which is the cause of the autowave process. Due to the membrane elasticity this process can be compared with the movement of "tank caterpillar".     

Dielectric characterization of neutralized and nonneutralized chitosan upon drying

Isothermal dielectric loss spectra of neutralized and nonneutralized chitosan were acquired in successive runs from -130 degrees C up to increasing final temperatures, in a frequency range between 20 Hz and 1 MHz. Essentially, three relaxation processes were detected in the temperature range covered: (i) a beta-wet process, detected when the sample has a higher water content that vanishes after heating to 150 degrees C; (ii) a beta process, which is located at temperatures below 0 degrees C, becoming better defined and maintaining its location after annealing at 150 degrees C independently of the protonation state of the amino side group; and (iii) a sigma process that deviates to higher temperatures with drying, being more mobile in the nonneutralized form. Moreover, in dried neutralized chitosan, a fourth process was detected in the low frequency side of the secondary beta process that diminishes after annealing. Whether this process is a distinct relaxation of the dried polymer or a deviated beta-wet process due to the loss of water residues achieved by annealing is not straightforward. Only beta and sigma processes persist after annealing at 150 degrees C. The changes in molecular mobility upon drying of these two relaxation processes were evaluated.     

Regulation of the terminal event in cellular differentiation: biological mechanisms of the loss of proliferative potential

Human plasma has been demonstrated to contain factors that induce the sequential expression of nonterminal and terminal adipocyte differentiation in 3T3 T mesenchymal stem cells. We now report the development of methods for the isolation of purified populations of nonterminally differentiated cells and terminally differentiated cells, and we show that it is possible to experimentally induce transition from the nonterminal to the terminal state of differentiation. With this model system it is therefore now possible to examine the biological and molecular processes associated with the terminal event in differentiation, i.e., the irreversible loss of proliferative potential. In this regard, we demonstrate that transition from the nonterminal to terminal state of differentiation is a complex metabolic process that consists of at least two steps and that this process can be triggered by pulse exposure to an inducer for approximately 12 h but that approximately 24-48 h is required for the process to be completed. The data also establish that induction of the terminal event in differentiation requires protein synthesis but not RNA and DNA synthesis. These and additional results suggest that loss of proliferative potential associated with the terminal event in cellular differentiation is a distinct regulatory process, and we suggest that defects in this regulatory process may be of etiological significance in the pathogenesis of specific human diseases, especially cancer.     

Effect of nonindependent substitution on phylogenetic accuracy

All current phylogenetic methods assume that DNA substitutions are independent among sites. However, ample empirical evidence suggests that the process of substitution is not independent but is, in fact, temporally and spatially correlated. The robustness of several commonly used phylogenetic methods to the assumption of independent substitution is examined. A compound Poisson process is used to model DNA substitution. This model assumes that substitution events are Poisson-distributed in time and that the number of substitutions associated with each event is geometrically distributed. The asymptotic properties of phylogenetic methods do not appear to change under a compound Poisson process of DNA substitution. Moreover, the rank order of the performance of different methods does not change. However, all phylogenetic methods become less efficient when substitution follows a compound Poisson process.     

Development of a robust, versatile, and scalable inoculum train for the production of a DNA vaccine

For many microbial fermentation processes, the inoculum train can have a substantial impact on process performance in terms of productivity, profitability, and process control. In general, it is understood that a well-characterized and flexible inoculum train is essential for future scale-up and implementation of the process in a pilot plant or manufacturing setting. A fermentation process utilizing E. coli DH5 for the production of plasmid DNA carrying the HIV gag gene for use as a vaccine is currently under development in our laboratory. As part of the development effort, we evaluated inoculum train schemes that incorporate one, two, or three stages. In addition, we investigated the effect of inoculum viable-cell concentrations, either thawed or actively growing, over a wide range (from 2.5 x 10(4) to 1.0 x 10(8) viable cells/mL or approximately 0.001% to 4% of final working volume). The various inoculum trains were evaluated in terms of final plasmid yield, process time, reproducibility, robustness, and feasibility at large scale. The results of these studies show that final plasmid yield remained in the desired range, despite the number of stages or inoculation viable-cell concentrations comprising the inoculum train. On the basis of these observations and because it established a large database, the first part of these investigations supports an exceptional flexibility in the design of scalable inoculum trains for this DNA vaccine process. This work also highlighted that a slightly higher level of process reproducibility, as measured by the time for the culture to reach mid-exponential growth, was observed when using actively growing versus frozen cells. It also demonstrated the existence of a viable-cell concentration threshold for the one-stage process, since we observed that inoculation of the production stage with very low amounts of viable cells from a frozen source could lead to increased process sensitivity to external factors such as variation in the quality of the raw materials used in the medium formulation. However, our analysis indicates that, despite this slight disadvantage, a one-stage inoculum train was a viable option in many situations, especially if the inoculation viable-cell concentration was kept above 4.8 x 10(6) viable cells/mL. Because it leads to a reduction in process steps and eliminates some capital investments (i.e., inoculum fermenter), when feasible a one-stage process configuration will positively impact process economics.     

Allocation procedure in multi-output process: an illustration of ISO 14041

Allocation results for a multi-output process in a life cycle assessment study depend on the definition of the unit process which can vary with the depth of a study. The unit process may be a manufacturing site, a sub-process, or an operational unit (e.g. distillation column or reactor). There are three different approaches to define a unit process: macroscopic approach, quasi-microscopic approach, and microscopic approach. In the macroscopic approach, a unit process is the manufacturing site, while a unit process in the quasi-microscopic approach is a sub-process of the manufacturing site. An operational unit becomes the unit process in the microscopic approach. In the quasi-microscopic and the microscopic approaches, a process can be subdivided into a joint process, a physically separated process which is physically apart from other processes, and a fully separated process. Each type can be a unit process. Therefore, the multi-output process in the quasi-microscopic and the microscopic approaches can be subdivided among two or more unit processes depending on the actual operations. The allocation in the fully separated process can be avoided because this process fulfills one function. In the joint process and the physically separated process, which deliver two or more functions, allocation is still required. Ammonia manufacturing, where carbon dioxide is formed as a byproduct is given to show a specific detailed example of the allocation procedure by subdivision in ISO 14041. It is shown that the quasi-microscopic and the microscopic approaches can reduce the multi-output allocation of a given chemical product. Furthermore, the quasi-microscopic and the microscopic approaches are very useful in identifying key pollution prevention issues related with one product or function.     

The density of the extinction probability of a time homogeneous linear birth and death process under the influence of randomly occurring disasters

Under the influence of randomly occurring disasters, the eventual extinction probability, q, of a birth and death process, Z, is a random variable. In this paper, we obtain an integral expression for the probability density function g(x) of q under the assumption that the population process Z is a time homogeneous linear birth and death process and the disasters occur according to an arbitrary renewal process so that its interarrival times have a density. An example is provided to demonstrate how to evaluate the integral numerically.     

Origin and biology of cancer metastasis

Metastasis, the spread of cells from a primary neoplasm to distant sites where they grow, contributes to the death of most cancer patients. The process of metastasis is not random. Rather, the process consists of a series of linked, sequential steps that must be completed by tumor cells if a metastasis is to develop. Thus, metastatic cells must succeed in invasion and embolization, survive in the circulation, arrest in a distant capillary bed, and extravasate into and multiply in organ parenchyma. Although some of the steps in this process contain stochastic elements, as a whole metastasis favors the survival and growth of a few subpopulations of cells that preexist within the parent neoplasm. Moreover, metastases can have a clonal origin, and different metastases can originate from the proliferation of single cells. The outcome of metastasis depends on the interaction of metastatic cells with different organ environments. Organ-specific metastases have been demonstrated in a variety of experimental tumor systems, and even within one organ, site-specific tumor growth can be found. The conclusion that metastasis is a highly selective process that is influenced by both the intrinsic properties of tumor cells and by host factors is optimistic. A selective process is regulated and therefore can be studied and then manipulated.     

Mixing rate of phosphate between plasma and interstitial body fluid of cows

Radiophosphate was injected into the left jugular vein of dairy cows. Blood samples were taken frequently from the right jugular vein during the first hour after injection. Between 20 minutes and 1 hour after injection, the decrease in plasma radioactivity could be formulated as a first order process, designated as "process 3," with a turnover time of 50 minutes. From 5 to 20 minutes after injection the decrease in plasma activity could be interpreted as the result of mixing plasma phosphate with another phosphate pool, designated as the second pool. The capacity of this second pool was derived as a constant in a kinetic equation, so chosen that the resulting mixing rates were independent of time. For two cows the capacity of the second pool was 5 and 8 times, respectively. the phosphate content of the plasma. This result led to the working hypothesis that the major part of the second pool was the phosphate in the interstitial tissue fluid. The turnover time of the plasma phosphate in the mixing process with the second pool amounted to an average of 14 minutes for 5 lactating cows, and an average of 21 minutes for 2 dry cows. This result was obtained under the assumption that the slow first order process 3 is parallel to the mixing process. The assumption that the slower first order process is in series with the mixing process reduces the resulting mixing time to about four-fifths of that reported above. The calculation of process 2 which deviates from first order may be applicable to numerous turnover processes in which both exchange pools have a limited capacity.