Computational and statistical study on the molecular interaction between antigen and antibody

Monoclonal antibodies are one of the most successful bio-molecules utilized in the clinical scene of today. It is important to clarify general characteristics of the interaction between antigen and antibody and to draw a guide for enhancing their binding affinity in rational design of antibody drugs. In this study, we carried out molecular dynamics simulations for 20 kinds of antigen–antibody complexes. From the statistical analysis of the calculation results, the following findings were deduced. At complementarity determining regions (CDRs) of the antibodies, the rates for the presence of serine (Ser) and tyrosine (Tyr) are high. The amino residues involved in direct hydrogen bonds between antigens and antibodies were examined by counting the numbers of the hydrogen bonds from the respective residues. The contribution of Tyr to the direct hydrogen bonding was the highest and that of Ser was the fourth. Furthermore, the short-distance hydrogen bonds, which is assumed to be so-called “low-barrier hydrogen bond”, were observed at CDRs in three complexes. Interestingly, Ser is involved in the short-distance hydrogen bonding in two cases out of the three. This result suggests that these two unchanged polar amino acid residues play an important role for recognition of antigen. In almost all of the complexes (18/20), the contribution of the electrostatic energy (ΔE_ele) to the binding free energy was calculated to be larger than that of the van der Waals energy (ΔE_vdw). This dominance of the electrostatic energy is in contrast to the case that low molecular-weight compounds are bound to their targets. The findings of this study will be helpful to design an antibody with a high specificity and a high affinity to the antigen.     

A model of the interaction between mood and memory

This paper investigates a neural network model of the interaction between mood and memory. The model has two attractor networks that represent the inferior temporal cortex (IT), which stores representations of visual stimuli, and the amygdala, the activity of which reflects the mood state. The two attractor networks are coupled by forward and backward projections. The model is however generic, and is relevant to understanding the interaction between different pairs of modules in the brain, particularly, as is the case with moods and memories, when there are fewer states represented in one module than in the other. During learning, a large number of patterns are presented to the IT, each paired with one of two mood states represented in the amygdala. The recurrent connections within each module, the forward connections from the memory module to the amygdala, and the backward connections from the amygdala to the memory module, are associatively modified. It is shown how the mood state in the amygdala can influence which memory patterns are recalled in the memory module. Further, it is shown that if there is an existing mood state in the amygdala, it can be difficult to change it even when a retrieval cue is presented to the memory module that is associated with a different mood state. It is also shown that the backprojections from the amygdala to the memory module must be relatively weak if memory retrieval in the memory module is not to be disrupted. The results are relevant to understanding the interaction between structures important in mood and emotion (such as the amygdala and orbitofrontal cortex) and other brain areas involved in storing objects and faces (such as the inferior temporal visual cortex) and memories (such as the hippocampus).     

规则网络中的SIRS病毒局域控制建模与仿真*

提出一个带有局域控制的二维规则网络SIRS模型,理论分析和计算机仿真都表明局域控制能很好地抑制此模型中的病毒传播。研究发现系统状态随时间的演化最终会达到一个稳定状态;病毒的稳态感染比例与传播效率、被控制个体比例和免役个体失去免役能力的概率有关。只有当传播效率大于一个临界值时,病毒才能在网络中持续传播。     

Analysis of the effects of quantization in multilayer neuralnetworks using a statistical model

A statistical quantization model is used to analyze the effects of quantization when digital techniques are used to implement a real-valued feedforward multilayer neural network. In this process, a parameter called the effective nonlinearity coefficient, which is important in the studying of quantization effects, is introduced. General statistical formulations of the performance degradation of the neural network caused by quantization are developed as functions of the quantization parameters. The formulations predict that the network's performance degradation gets worse when the number of bits is decreased; that a change of the number of hidden units in a layer has no effect on the degradation; that for a constant effective nonlinearity coefficient and number of bits, an increase in the number of layers leads to worse performance degradation; and the number of bits in successive layers can be reduced if the neurons of the lower layer are nonlinear     

Fluid-structure interaction: A general method used in the ceasemt computer programs

This paper presents a general method to calculate the dynamic behaviour of coupled fluid-structure systems. It is shown how this method can be easily implemented in finite element computer codes. Some applications in the case of axisymetric and three dimensional structures are compared either with analytical or with experimental results. A reference is given for fluid-structure interaction in piping systems.     

A computational model of the interaction between environmental dynamics and economic behavior

Environmental issues have been considered to be very important for a long time. We believe that they should be examined from an interdisciplinary view point in order to reach a solution, because they have arises as the consequence of complex interactions among various factors. This article proposes a new model termedColorChanger. By using this model, we aim to explore the nature of ecological issues beyond separate discussions on specific subjects, and make the acquired knowledge available to encourage the solution of environmental issues. This article also reports on the results of the preliminary experiments. This work was presented in part at the Sixth International Symposium on Artificial Life and Robotics, Tokyo, January 15–17, 2001     

User documentation and control language I: Evaluation and comparison of statistical computer packages

Procedures for comparing and evaluating aspects of the user interface of statistical computer packages are described. These procedures are implemented in a study of three packages. SPSS. BMDP and Minitab, by a class of 21 students with some statistical background. It was found that most participants exhibited consistent personal preferences among the packages. In selecting packages to solve specific problems, however, their choice was determined more by issues of good statistical practice than by personal preference for overall package features.     

Theoretical study of chlordecone and surface groups interaction in an activated carbon model under acidic and neutral conditions

Activated carbons (ACs) are widely used in the purification of drinking water without almost any knowledge about the adsorption mechanisms of the persistent organic pollutants. Chlordecone (CLD, Kepone) is an organochlorinated synthetic compound that has been used mainly as agricultural insecticide. CLD has been identified and listed as a persistent organic pollutant by the Stockholm Convention. The selection of the best suited AC for this type of contaminants is mainly an empirical and costly process. A theoretical study of the influence of AC surface groups (SGs) on CLD adsorption is done in order to help understanding the process. This may provide a first selection criteria for the preparation of AC with suitable surface properties. A model of AC consisting of a seven membered ring graphene sheet (coronene) with a functional group on the edge was used to evaluate the influence of the SGs over the adsorption. Multiple Minima Hypersurface methodology (MMH) coupled with PM7 semiempirical Hamiltonian was employed in order to study the interactions of the chlordecone with SGs (hydroxyl and carboxyl) at acidic and neutral pH and different hydration conditions. Selected structures were re-optimized using CAM-B3LYP to achieve a well-defined electron density to characterize the interactions by the Quantum Theory of Atoms in Molecules approach. The deprotonated form of surface carboxyl and hydroxyl groups of AC models show the strongest interactions, suggesting a chemical adsorption. An increase in carboxylic SGs content is proposed to enhance CLD adsorption onto AC at neutral pH conditions.     

Towards optimal allocation of computer resources: Trade-offs between uncertainty quantification,discretization and model reduction

The computational complexity of numerical models can be broken down into contributions ranging from spatial, temporal and stochastic resolution, e.g., spatial grid resolution, time step size and number of repeated simulations dedicated to quantify uncertainty. Controlling these resolutions allows keeping the computational cost at a tractable level whilst still aiming at accurate and robust predictions. The objective of this work is to introduce a framework that optimally allocates the available computational resources in order to achieve highest accuracy associated with a given prediction goal. Our analysis is based on the idea to jointly consider the discretization errors and computational costs of all individual model dimensions (physical space, time, parameter space). This yields a cost-to-error surface which serves to aid modelers in finding an optimal allocation of the computational resources (ORA). As a pragmatic way to proceed, we propose running small cost-efficient pre-investigations in order to estimate the joint cost-to-error surface, then fit underlying complexity and error models, decide upon a computational design for the full simulation, and finally to perform the designed simulation at near-optimal costs-to-accuracy ratio. We illustrate our approach with three examples from subsurface hydrogeology and show that the computational costs can be substantially reduced when allocating computational resources wisely and in a situation-specific and task-specific manner. We conclude that the ORA depends on a multitude of parameters, assumptions and problem-specific features and, hence, ORA needs to be determined carefully prior to each investigation.     

A team-teaching model for practicing project-based learning in high school: Collaboration between computer and subject teachers

Project-based learning (PBL) is a highly effective means of motivating students to learn independently. However, training or encouraging teachers to practice PBL in their classrooms is challenging, especially if the educational system does not accommodate creative teaching practices. In particular, in a test-driven educational system, time constraints and an excess of teaching content makes it difficult to practice PBL at the high school level. This work presents a novel team-teaching model that is based on collaboration between subject teachers and the computer teacher to facilitate PBL in the classroom. A two-year experiment was conducted to study the feasibility of the proposed model, in which the school computer teacher conducts PBL with the 10th grade students in the first year, and subject teachers conduct PBL with the 11th grade students in the second year. Experimental results indicate that the proposed model is feasible in the given educational setting. No class time was lost, and the subject teacher successfully conducted PBL activities. Furthermore, a follow-up survey indicated that the students enjoyed the PBL activities in both classes.     

Calculation of survival curves and statistical comparison of two censored populations: a computer program in BASIC

In experimental aging research the handling of censored data imposes a serious problem in the calculation of survival curves of partly censored populations and the statistical comparison of such populations. The presented computer program combines a method to calculate a corrected survival curve and a test to compare two censored populations. In both methods, the proportion of the animals that survive or die during an interval and the number at risk at the start of that interval is used in the calculation of relative survival or death during that interval. The program is written in an elementary BASIC and will run on practically every computer programmable in BASIC. The presented method can be used for testing the difference between survival characteristics of two animal populations but might also be employed in evaluating the effect of a medical treatment.     

From rooms to Cyberspace: models of interaction in large virtual computer spaces

Room metaphors have become increasingly popular as a basis for CSCW systems. The paper describes how such metaphors might be extended to support large scale communication through the introduction of a spatial model for mediating conversations in virtual computer spaces. The model is described in terms of an abstract mathematical framework and the paper then outlines how this might be applied to various kinds of CSCW system. As a next step, the combination of rooms into larger virtual structures is considered and this results in proposals for structuring, navigating and mapping a large virtual Cyberspace for cooperation. Finally, the paper describes a current prototype application and reflects on some of the architectural issues involved in its realisation as a distributed system.     

Non-extensive statistical analysis of seismicity in the area of Javakheti, Georgia

The distribution of earthquake magnitudes in the Javakheti highlands was analyzed using a non-extensive statistical approach. The earthquakes occurring from 1960 to 2008 in this seismically active area of Southern Caucasus were investigated. The seismic catalog was studied using different threshold magnitude values. Analyses of the whole time period of observations as well as of sub-catalogs of consecutive 10-year span time windows were performed. In every case non-extensive parameter q and value a, the physical quantity characterizing energy density, were calculated from the modified frequency–magnitude relationship. According to our analysis the magnitude sequence in the Javakheti area for the whole period of observation is characterized by a non-extensivity parameter q=1.81, in the upper limit of values reported elsewhere. While calculated non-extensivity parameters for consecutive 10-year windows fall within the range 1.6–1.7 reported worldwide. A significant increase of parameter q was identified in those 10-year sub-catalogs that included the strongest earthquakes within the period of observation. We suppose that this increase may be related to a more correlated behavior within the system of ‘fault fragments’ when a strong earthquake strikes or immediately after; during aftershock activity. Concurrently, smaller values of non-extensivity parameters q_i, found during seismically relatively quiet times, could be associated to the decreased correlations within the system during the earthquake generation stage, under an essentially decreased tectonic stress. The behavior of the energy density characteristic a almost mirrors the variation of parameter q: increases for seismically quiet periods in the Javakheti area and decreases in periods when strong earthquakes occur. We suggest that decreases of energy density characteristic a may point to a prevalent contribution of large size fragments to fragment–asperity interaction under the influence of a rapidly released stress, as opposed to relatively quiet periods when accumulated stress energy is supposedly released through the relative movement of smaller fragments.     

Interfacing human and computer with wireless body area sensor networks: the WiMoCA solution

Wireless Body Area Sensor Networks (WBASN) are an emerging technology enabling the design of natural human–computer interfaces (HCI). Automatic recognition of human motion, gestures, and activities is studied in several contexts. For example, mobile computing technology is being considered as a replacement of traditional input systems. Moreover, body posture and activity monitoring can be used for entertainment and health-care applications. However, until now, little work has been done to develop flexible and efficient WBASN solutions suitable for a wide range of applications. Their requirements pose new challenges for sensor network designs, such as optimizing traditional solutions for use as environmental monitoring-like applications and developing on-the-field stress tests. In this paper, we demonstrate the flexibility of a custom-designed WBASN called WiMoCA with respect to a wide range of posture and activity recognition applications by means of practical implementation and on-the-field testing. Nodes of the network mounted on different parts of the human body exploit tri-axial accelerometers to detect its movements. The advanced digital Micro-electro-mechanical system (MEMS) based inertial sensor has been chosen for WiMoCA because it demonstrated high flexibility of use in many different situations, providing the chance to exploit both static and dynamic acceleration components for different purposes. Furthermore, the sensibility and accuracy of the sensing element is perfectly adequate for monitoring human movement, while keeping cost low and size compact, thus meeting our requirements. We implemented three types of applications, stressing the WBASN in many aspects. In fact, they are characterized by different requirements in terms of accuracy, timeliness, and computation distributed on sensing nodes. For each application, we describe its implementation, and we discuss results about performance and power consumption.

A learning environment for the conservation of area and its measurement: a computer microworld

In this paper, we present the design and implementation of a microworld as a possible learning environment for the concept of conservation of area and its measurement. This microworld is the result of the synthesis of three models. The first is the model of the subject matter. The second is a model of children's sensory-motor actions while they face specific measurement tasks. The third is a model of learning viewed as an active, subjective and constructive process. All these models are enriched by the features of the electronic media which have an impact on the children's cognitive development. The modelling is the result of the study of past research in the above areas but also reflects the designers' beliefs about the nature of mathematics, its teaching and learning, and about the ways that computers can be used in the teaching and learning of mathematics. The requirements for the design of the software emerged from the educational requirements defined as a result of the modelling. The aim of this microworld is to provide the students with a set of tools to create their own objects (shapes) and transform or compare them using measurement or conservation concepts. The rationale of the design of this computer environment and an analysis of its main features are presented. Finally, the design of the pilot study of evaluation of the microworld is presented and the results of this study are discussed.     

Qualitative differences in computer experience,computer anxiety,and students' use of computers: A path model

Biographical information (age and gender) was obtained on 180 first year psychology students along with self-report measures relating to computer use. The measures were: age of initial introduction to computers; qualitative aspects of early computer experience (how relaxed and unpressured the experience was and the extent to which the individual had felt ‘in control’ and competent during the experience); level of computer anxiety; current and anticipated future frequency of use of computers. A path model linking the above variables was proposed and tested. Apart from gender, all of the predictor variables exerted direct and/or indirect influences on use made (and expected to be made) of computers. In particular, an early introduction to computers was generally associated with a more favourable quality of initial experience, leading to lower anxiety and greater readiness of students to use computers.     

Qualitative differences in computer experience, computer anxiety, and students' use of computers: A path model

Biographical information (age and gender) was obtained on 180 first year psychology students along with self-report measures relating to computer use. The measures were: age of initial introduction to computers; qualitative aspects of early computer experience (how relaxed and unpressured the experience was and the extent to which the individual had felt ‘in control’ and competent during the experience); level of computer anxiety; current and anticipated future frequency of use of computers. A path model linking the above variables was proposed and tested. Apart from gender, all of the predictor variables exerted direct and/or indirect influences on use made (and expected to be made) of computers. In particular, an early introduction to computers was generally associated with a more favourable quality of initial experience, leading to lower anxiety and greater readiness of students to use computers.     

Three-dimensional computer model of the heart: fibrillation induced by extrastimulation

We present a three-dimensional (3D) computer model that simulates electrical activity in the heart during fibrillation. A real dog heart is discretized to form 1473 interconnected cubic elements. The model exhibits normal activation and recovery from pacing. Five or more extrastimuli induce a self-sustaining tachyarrhythmia that soon degenerates into a fibrillatory rhythm. The extrastimuli increase the excitability of the myocardial cell population. The result is a rapid re-excitation of cells that allows for only a partial recovery of cell action potential. This suggests that a dispersion of refractory states of the cell population is the cause of fibrillation in this computer model.