Knowledge acquisition, semantic text mining, and security risks in health and biomedical informatics

Computational techniques have been adopted in medi-cal and biological systems for a long time. There is no doubt that the development and application of computational methods will render great help in better understanding biomedical and biological functions. Large amounts of datasets have been produced by biomedical and biological experiments and simulations. In order for researchers to gain knowledge from origi- nal data, nontrivial transformation is necessary, which is regarded as a critical link in the chain of knowledge acquisition, sharing, and reuse. Challenges that have been encountered include: how to efficiently and effectively represent human knowledge in formal computing models, how to take advantage of semantic text mining techniques rather than traditional syntactic text mining, and how to handle security issues during the knowledge sharing and reuse. This paper summarizes the state-of-the-art in these research directions. We aim to provide readers with an introduction of major computing themes to be applied to the medical and biological research.     

PKC-induced stiffening of hyaluronan/CD44 linkage; local force measurements on glioma cells

Interaction of cells with hyaluronan (HA) rich extracellular matrix involves the membrane receptor CD44. HA-CD44 interactions are particularly important in the development of glioma pathogenesis for its implication in tumor cells spreading. Highly motile states rely on the spaciotemporal regulation of HA-CD44 interactions occurring in specific cytoskeletal-supported membrane organization such as microvilli or the leading edge observed in migrating cell. We used AFM-based force measurement to probe the HA-CD44 interaction at localized regions at the surface of living glioma cells expressing high level of the CD44 standard isoform. We show that unstimulated cells interact with HA over their entire surfaces and are highly deformable when force is exerted on individual HA molecules bound to membrane CD44 receptors. Conversely, in PKC-activated cells the probed interactions are concentrated at the leading edge of the cells with reduced membrane deformability. Taken together, our results show that PKC-enhanced motility in glioma cells is associated with a redistribution of CD44 receptors at the leading edges concomitant with a stiffer anchoring of CD44 to the cell surface involving the actin cytoskeleton.     

Reduction of neuromuscular redundancy for postural force generation using an intrinsic stability criterion

Postural control requires the coordination of multiple muscles to achieve both endpoint force production and postural stability. Multiple muscle activation patterns can produce the required force for standing, but the mechanical stability associated with any given pattern may vary, and has implications for the degree of delayed neural feedback necessary for postural stability. We hypothesized that muscular redundancy is reduced when muscle activation patterns are chosen with respect to intrinsic musculoskeletal stability as well as endpoint force production. We used a three-dimensional musculoskeletal model of the cat hindlimb with 31 muscles to determine the possible contributions of intrinsic muscle properties to limb stability during isometric force generation. Using dynamic stability analysis we demonstrate that within the large set of activation patterns that satisfy the force requirement for posture, only a reduced subset produce a mechanically stable limb configuration. Greater stability in the frontal-plane suggests that neural control mechanisms are more highly active for sagittal-plane and for ankle joint control. Even when the limb was unstable, the time-constants of instability were sufficiently great to allow long-latency neural feedback mechanisms to intervene, which may be preferential for movements requiring maneuverability versus stability. Local joint stiffness of muscles was determined by the stabilizing or destabilizing effects of moment-arm versus joint angle relationships. By preferentially activating muscles with high local stiffness, muscle activation patterns with feedforward stabilizing properties could be selected. Such a strategy may increase intrinsic postural stability without co-contraction, and may be useful criteria in the force-sharing problem.     

生物多样性数据集成模式初探

本文以生物多样性研究发展现状的分析为基础,为生物多样性保护政策的制定提供可靠的数据支持为目标,通过对国内外几个著名的生物多样性数据库建设情况的分析,从相关学者的需求出发,提出了设计一个多层次多角度并带有一定人工智能的生物多样性集成数据库的构想。该系统基于都柏林核心(Dublin Core)的数据规范,并符合基于开放文献预研的元数据互操作协议(The Open Archixles Initiative Protocol for Metadata Hatvesting,OAIPMH)的标准,是一个集文字、图件、图片、声音、影像为一体的,能够在网上和硬件载体(如光盘)上同时进行发布的分布式数据库平台。其网上数据库系统的子系统之间以及子系统和硬件载体之间可以通过元数据获取的开放档案倡议协议互相交换数据。     

Interspecific Pollen Transfer: Magnitude,Prevalence and Consequences for Plant Fitness

Interspecific pollen transfer (IPT) is one of the mechanisms underlying potential competition among plants for pollinators, and it refers to movement of pollen between different plant species by pollinators that visit their flowers simultaneously. Two components of IPT, related to each other, are distinguished: (a) heterospecific pollen deposition (HPD) on conspecific stigmas, which may interfere with fertilization by conspecific pollen; and (b) conspecific pollen loss (CPL) on heterospecific flowers, which may reduce the amount of pollen transferred between conspecific flowers. Thus, IPT may lead to reciprocal losses for male and female functions of the plant, with potentially important ecological and evolutionary consequences. In this review, we explore the magnitude and prevalence of IPT, examining documented mechanisms and evaluating such potential ecological and evolutionary consequences. We compiled existing evidence of interspecific pollinator sharing and interspecific pollinator switching between flowers of different species in natural communities. We evaluated the relative importance of both HPD and CPL from studies comparing these variables in pure vs. mixed floral neighborhoods, analyzing evidence for the claim that IPT is an evolutionary force promoting character displacement in habitat affinity, flowering times, and floral morphology. We also examined the findings of hand-pollination experiments carried out to reveal different mechanisms by which heterospecific pollen can affect performance of native pollen. Finally, we review evidence for impacts of alien plant species on native species' reproduction, and briefly comment on risks of crop-to-wild gene flow imposed by the release of genetically modified (transgenic) crops through IPT.     

Controlling a system with redundant degrees of freedom. I. Torque distribution in still standing stick insects

The question is investigated as to how a stick insect solves the task of distributing its body weight onto its six legs, i.e., how are the torques coordinated that are produced by the 18 joints (3 per leg). Three-dimensional force measurements of ground reaction forces have been used to calculate the torques developed by each of the 18 joints. Torques were found to change considerably although the body and the legs of the animal did not move. This result implies a tight cooperation between the 18 joint controllers. Indeed, in each individual experiment, strong correlations could be observed between specific pairs of joints. However, in spite of thorough analysis, no general correlation rules between torques could be detected. The only common attribute found for all experiments was that high absolute torques observed at the beginning of the experiment tend to converge to some minimum over time. Thus, the insects tend to decrease the torques while standing still, but do not use fixed rules. Rather they appear to exploit their extra degrees of freedom and produce time courses that can strongly vary between experiments. Possible mechanisms underlying this behaviour are discussed in a companion paper [Lévy and Cruse (2008) Controlling a system with redundant degrees of freedom: ii. solution of the force distribution problem without a body model, submitted].     

Simulation system of spinal cord motor nuclei and associated nerves and muscles,in a Web-based architecture

A Web-based simulation system of the spinal cord circuitry responsible for muscle control is described. The simulator employs two-compartment motoneuron models for S, FR and FF types, with synaptic inputs acting through conductance variations. Four motoneuron pools with their associated interneurons are represented in the simulator, with the possibility of inclusion of more than 2,000 neurons and 2,000,000 synapses. Each motoneuron action potential is followed, after a conduction delay, by a motor unit potential and a motor unit twitch. The sums of all motor unit potentials and twitches result in the electromyogram (EMG), and the muscle force, respectively. Inputs to the motoneuron pool come from populations of interneurons (Ia reciprocal inhibitory interneurons, Ib interneurons, and Renshaw cells) and from stochastic point processes associated with descending tracts. To simulate human electrophysiological experiments, the simulator incorporates external nerve stimulation with orthodromic and antidromic propagation. This provides the mechanisms for reflex generation and activation of spinal neuronal circuits that modulate the activity of another motoneuron pool (e.g., by reciprocal inhibition). The generation of the H-reflex by the Ia-motoneuron pool system and its modulation by spinal cord interneurons is included in the simulation system. Studies with the simulator may include the statistics of individual motoneuron or interneuron spike trains or the collective effect of a motor nucleus on the dynamics of muscle force control. Properties associated with motor-unit recruitment, motor-unit synchronization, recurrent inhibition and reciprocal inhibition may be investigated.     

Modeling residual force enhancement with generic cross-bridge models

The interaction of actin and myosin through cross-bridges explains much of muscle behavior. However, some properties of muscle, such as residual force enhancement, cannot be explained by current cross-bridge models. There is ongoing debate whether conceptual cross-bridge models, as pioneered by Huxley (A.F. Huxley, Muscle structure and theories of contraction, Prog. Biophys. Biophys. Chem. 7 (1957) 255) could, if suitably modified, fit experimental data showing residual force enhancement. Here we prove that there are only two ways to explain residual force enhancement with these ‘traditional’ cross-bridge models: the first requires cross-bridges to become stuck on actin (the stuck cross-bridge model) while the second requires that cross-bridges that are pulled off beyond a critical strain enter a ‘new’ unbound state that leads to a new force-producing cycle (the multi-cycle model). Stuck cross-bridge models cannot fit the velocity and stretch amplitude dependence of residual force enhancement, while the multi-cycle models can. The results of this theoretical analysis demonstrate that current kinetic models of cross-bridge action cannot explain the experimentally observed residual force enhancement. Either cross-bridges in the force-enhanced state follow a different kinetic cycle than cross-bridges in a ‘normal’ force state, or the assumptions underlying traditional cross-bridge models must be violated during experiments that show residual force enhancement.     

Adaptive Sector Grouping to Reduce False Sharing in Distributed RAID

Distributed redundant array of inexpensive disks (RAID) is often embedded in a cluster architecture. In a centralized RAID subsystem, the false sharing problem does not exist, because the disk array allows only mutually exclusive access by one user at a time. However, the problem does exist in a distributed RAID architecture, because multiple accesses may occur simultaneously in a distributed environment. This problem will seriously limit the effectiveness of collective I/O operations in network-based, cluster computing. Traditional accesses to disks in a RAID are done at block level. The block granularity is large, say 32 KB, often resulting in false sharing among fragments in the block. The false sharing problem becomes worse when the block size or the stripe unit becomes too large. To solve this problem, we propose an adaptive sector grouping approach to accessing a distributed RAID. Each sector has a fine grain of 512 B. Multiple sectors are grouped together to match with the data block size. The grouped sector has a variable size that can be adaptively adjusted by software. Benchmark experiments reveal the positive effects of this adaptive access scheme on the performance of a RAID. Our scheme can reduce the collective I/O access time without increasing the buffer size. Both theoretical analysis and experimental results demonstrate the performance gain in using grouped sectors for fast access of distributed RAID.