Analysis of complex physiological systems by information flow: a time scale-specific complexity assessment.

In the last two decades conventional linear methods for biosignal analysis have been substantially extended by non-stationary, non-linear, and complexity approaches. So far, complexity is usually assessed with regard to one single time scale, disregarding complex physiology organised on different time scales. This shortcoming was overcome and medically evaluated by information flow functions developed in our research group in collaboration with several theoretical, experimental, and clinical partners. In the present work, the information flow is introduced and typical information flow characteristics are demonstrated. The prognostic value of autonomic information flow (AIF), which reflects communication in the cardiovascular system, was shown in patients with multiple organ dysfunction syndrome and in patients with heart failure. Gait information flow (GIF), which reflects communication in the motor control system during walking, was introduced to discriminate between controls and elderly patients suffering from low back pain. The applications presented for the theoretically based approach of information flow confirm its value for the identification of complex physiological systems. The medical relevance has to be confirmed by comprehensive clinical studies. These information flow measures substantially extend the established linear and complexity measures in biosignal analysis.     

Electrogenetic signaling and information propagation for controlling microbial consortia via programmed lysis

To probe signal propagation and genetic actuation in microbial consortia, we have coopted the components of both redox and quorum sensing (QS) signaling into a communication network for guiding composition by “programming” cell lysis. Here, we use an electrode to generate hydrogen peroxide as a redox cue that determines consortia composition. The oxidative stress regulon of Escherichia coli, OxyR, is employed to receive and transform this signal into a QS signal that coordinates the lysis of a subpopulation of cells. We examine a suite of information transfer modalities including “monoculture” and “transmitter-receiver” models, as well as a series of genetic circuits that introduce time-delays for altering information relay, thereby expanding design space. A simple mathematical model aids in developing communication schemes that accommodate the transient nature of redox signals and the “collective” attributes of QS signals. We suggest this platform methodology will be useful in understanding and controlling synthetic microbial consortia for a variety of applications, including biomanufacturing and biocontainment.     

Potential for unintended consequences of environmental enrichment for laboratory animals and research results

Many aspects of the research animal's housing environment are controlled for quality and/or standardization. Of recent interest is the potential for environmental enrichment to have unexpected consequences such as unintended harm to the animal, or the introduction of variability into a study that may confound the experimental data. The effects of enrichment provided to nonhuman primates, rodents, and rabbits are described to illustrate that the effects can be numerous and may vary by strain and/or species. Examples of parameters measured where no change is detected are also included because this information provides an important counterpoint to studies that demonstrate an effect. In addition, this review of effects and noneffects serves as a reminder that the provision of enrichment should be evaluated in the context of the health of the animal and research goals on a case-by-case basis. It should also be kept in mind that the effects produced by enrichment are similar to those of other components of the animal's environment. Although it is unlikely that every possible environmental variable can be controlled both within and among research institutions, more detailed disclosure of the living environment of the subject animals in publications will allow for a better comparison of the findings and contribute to the broader knowledge base of the effects of enrichment.     

EphA2 induction of fibronectin creates a permissive microenvironment for malignant cells

Normal and metastatic cells continuously exchange information with the surrounding tissue environment, and this communication governs many aspects of cell behavior. In particular, the physical placement or adhesions of cells within their environment are increasingly understood to facilitate this communication. Classically, cell-cell and cell-extracellular matrix adhesions have been viewed as separable events that are independently controlled. This simple view is changing, as evidence emerges of coordinated regulation of cellular adhesions. Here, we show that the EphA2 tyrosine kinase, which is overexpressed in many aggressive cancers, regulates a fine balance of cell-cell and cell-extracellular matrix adhesions in epithelial cells. EphA2 selectively inhibits cell-cell adhesions by increasing cell attachment and up-regulating the extracellular matrix protein fibronectin. We also show that fibronectin can contribute to important aspects of malignant character. Antibody-based targeting of EphA2 inhibits malignant cell growth by decreasing fibronectin and thereby inducing apoptotic death. Our findings strengthen a concept that cancer progression is regulated by a bidirectional communication between tumor cells and their surrounding microenvironment.     

Voluntary emergence and water detection in a newly recognized amphibious fish

Galaxias ‘nebula’, a small fish which has adaptations for air‐breathing but is not known to be amphibious, voluntarily emerged from water and, in an unfamiliar environment, moved preferentially towards an alternative water source. Nebula may thus be considered one of the few truly amphibious fishes, and their ability to detect water provides a selective advantage which aids their survival in unpredictable natural environments.     

Training Rats to Voluntarily Dive Underwater: Investigations of the Mammalian Diving Response

Underwater submergence produces autonomic changes that are observed in virtually all diving animals. This reflexly-induced response consists of apnea, a parasympathetically-induced bradycardia and a sympathetically-induced alteration of vascular resistance that maintains blood flow to the heart, brain and exercising muscles. While many of the metabolic and cardiorespiratory aspects of the diving response have been studied in marine animals, investigations of the central integrative aspects of this brainstem reflex have been relatively lacking. Because the physiology and neuroanatomy of the rat are well characterized, the rat can be used to help ascertain the central pathways of the mammalian diving response. Detailed instructions are provided on how to train rats to swim and voluntarily dive underwater through a 5 m long Plexiglas maze. Considerations regarding tank design and procedure room requirements are also given. The behavioral training is conducted in such a way as to reduce the stressfulness that could otherwise be associated with forced underwater submergence, thus minimizing activation of central stress pathways. The training procedures are not technically difficult, but they can be time-consuming. Since behavioral training of animals can only provide a model to be used with other experimental techniques, examples of how voluntarily diving rats have been used in conjunction with other physiological and neuroanatomical research techniques, and how the basic training procedures may need to be modified to accommodate these techniques, are also provided. These experiments show that voluntarily diving rats exhibit the same cardiorespiratory changes typically seen in other diving animals. The ease with which rats can be trained to voluntarily dive underwater, and the already available data from rats collected in other neurophysiological studies, makes voluntarily diving rats a good behavioral model to be used in studies investigating the central aspects of the mammalian diving response.     

A video digitizer for analysis of trunk deformity in scoliosis

Scoliosis is a deformity characterized by lateral curvature of the spine and accompanied by axial rotation of the vertebrae; it often causes varying degrees of trunk deformity. Research has indicated that topographic techniques can be used to describe the disorder and monitor its progression. A video image acquisition system has been designed which reduces the time required to quantify topographic details of the trunk and aids in the diagnosis, monitoring and research of scoliosis. This system integrates the capability of large, expensive grey-scale image acquisition equipment into a small, low-cost diagnostic imaging tool using current technologies and design techniques. The video digitizer accepts a standard NTSC monochromatic video signal as input and the unit is connected to a computer via an EEE-488 bus from which the ditigizer is controlled. The digitizer samples the video signal in real time using a high-speed flash converter controlled by an application-specific integrated circuit; the digital samples are stored in memory until the host computer requests that the information be transferred.     

Role of Utility and Inference in the Evolution of Functional Information

Functional information means an encoded network of functions in living organisms from molecular signaling pathways to an organism’s behavior. It is represented by two components: code and an interpretation system, which together form a self-sustaining semantic closure. Semantic closure allows some freedom between components because small variations of the code are still interpretable. The interpretation system consists of inference rules that control the correspondence between the code and the function (phenotype) and determines the shape of the fitness landscape. The utility factor operates at multiple time scales: short-term selection drives evolution towards higher survival and reproduction rate within a given fitness landscape, and long-term selection favors those fitness landscapes that support adaptability and lead to evolutionary expansion of certain lineages. Inference rules make short-term selection possible by shaping the fitness landscape and defining possible directions of evolution, but they are under control of the long-term selection of lineages. Communication normally occurs within a set of agents with compatible interpretation systems, which I call communication system. Functional information cannot be directly transferred between communication systems with incompatible inference rules. Each biological species is a genetic communication system that carries unique functional information together with inference rules that determine evolutionary directions and constraints. This view of the relation between utility and inference can resolve the conflict between realism/positivism and pragmatism. Realism overemphasizes the role of inference in evolution of human knowledge because it assumes that logic is embedded in reality. Pragmatism substitutes usefulness for truth and therefore ignores the advantage of inference. The proposed concept of evolutionary pragmatism rejects the idea that logic is embedded in reality; instead, inference rules are constructed within each communication system to represent reality, and they evolve towards higher adaptability on a long time scale.     

The distribution of completion times for random communication in a task-oriented group

The task-oriented groups considered here consist of a number of individuals, each having initially one piece of information which must be transmitted to all the others to complete the task. Interest is centered on the communication net which restricts the possible channels for messages. At every sending time each individual sends all the information he has acquired to one other individual; the major assumption here is that this recipient is chosen at random from the possibilities given by the communication net. The information state is defined as a matrix which shows where the initial information has spread. These matrices can be considered as the states of a Markov chain, and in this way the distribution of completion times for the task is obtained. Some special cases are worked out and generalizations are indicated. A proof is given of the formula for the shortest possible completion time in any net when a fixed number of messages is sent by each individual at each sending time.     

Honest signalling through chemicals by elephants with applications for care and conservation

Chemical signals are difficult to fake because they are often directly associated with phenotype and physiological condition, and hence likely to be honest signals for intraspecific communication. Chemical signals may be modified after release by the sender or by the environment. The proximate and ultimate signal meanings are dependent not only on the condition of the sender, but also on the physiological status of the receiver. Understanding the relationships and linkage among signal modality, signal function and receiver response is an essential first step before using natural signals for animal care and conservation. Our studies on chemical communication in Asian and African elephants combine observational and experimental work in captive and wild settings to further this understanding. Recent discoveries of pheromones in Asian elephants and the biochemistry of these compounds provide strong evidence that such chemical signals are honest indicators of reproductive status. Chemically identifying the signals and verifying their functional context with statistically robust behavioural studies are essential aspects for understanding the communication system. Additionally, the investigative process of discovering, identifying and verifying the function of chemical signals among captive elephants offers safe and stimulating enrichments. The knowledge garnered from such studies has potential conservation benefits for managing wild elephant populations. A firm foundation of scientific information is required for successful behavioural investigations and applied conservation and enrichment components.     

Small photoactivatable molecules for controlled fluorescence activation in living cells

The search for chemical probes which allow a controlled fluorescence activation in living cells represent a major challenge in chemical biology. To be useful, such probes have to be specifically targeted to cellular proteins allowing thereof the analysis of dynamic aspects of this protein in its cellular environment. The present paper describes different methods which have been developed to control cellular fluorescence activation emphasizing the photochemical activation methods known to be orthogonal to most cellular components and, in addition, allowing a spatio-temporal controlled triggering of the fluorescent signal.     

Communication aids in patients with motor neurone disease.

The study aimed at determining the main factors responsible for the speech and communication problems in motor neurone disease to try to assess the suitability of commercially available aids. Sixteen patients suffering from motor neurone disease with communication problems had their speech assessed by using the Frenchay dysarthria assessment. It was found essential to offer a choice of aids to the patient since suitability of a particular aid could not be evaluated without the patient practising with it.     

Internet: a major resource for toxicologists

Use of the Internet in developing countries is now growing faster. Internet has created a new conduit not only for communication but also in the access, sharing and exchange of information among scientists. The Internet is now viewed as the world's biggest library where retrieval of scientific literature and other information resources are possible within seconds. Large volumes of toxicological information resources are available on the Internet. This review outlines some sites that may be of great importance and useful to the toxicologist.     

Communication and complexity in a GRN-based multicellular system for graph colouring

Artificial Genetic Regulatory Networks (GRNs) are interesting control models through their simplicity and versatility. They can be easily implemented, evolved and modified, and their similarity to their biological counterparts makes them interesting for simulations of life-like systems as well. These aspects suggest they may be perfect control systems for distributed computing in diverse situations, but to be usable for such applications the computational power and evolvability of GRNs need to be studied. In this research we propose a simple distributed system implementing GRNs to solve the well known NP-complete graph colouring problem. Every node (cell) of the graph to be coloured is controlled by an instance of the same GRN. All the cells communicate directly with their immediate neighbours in the graph so as to set up a good colouring. The quality of this colouring directs the evolution of the GRNs using a genetic algorithm. We then observe the quality of the colouring for two different graphs according to different communication protocols and the number of different proteins in the cell (a measure for the possible complexity of a GRN). Those two points, being the main scalability issues that any computational paradigm raises, will then be discussed.     

Biology Needs Information Theory

Communication is an important feature of the living world that mainstream biology fails to adequately deal with. Applying two main disciplines can be contemplated to fill in this gap: semiotics and information theory. Semiotics is a philosophical discipline mainly concerned with meaning; applying it to life already originated in biosemiotics. Information theory is a mathematical discipline coming from engineering which has literal communication as purpose. Biosemiotics and information theory are thus concerned with distinct and complementary possible meanings of the word ‘communication’. Since literal communication needs to be secured so as to enable semantics being communicated, information theory is a necessary prerequisite to biosemiotics. Moreover, heredity is a purely literal communication process of capital importance fully relevant to literal communication, hence to information theory. A short introduction to discrete information theory is proposed, which is centred on the concept of redundancy and its use in order to make sequences resilient to errors. Information theory has been an extremely active and fruitful domain of researches and the motor of the tremendous progress of communication engineering in the last decades. Its possible connections with semantics and linguistics are briefly considered. Its applications to biology are suggested especially as regards error-correcting codes which are mandatory for securing the conservation of genomes. Biology needs information theory so biologists and communication engineers should closely collaborate.     

Basic module for an adaptive control system based on neurone information processing

The design of such devices as robotic aids for handicapped people, powered prostheses and manipulative aids such as page turners would benefit from the use of an adaptive control system. Much recent work on adaptive networks has been based on simplified models of the information processing capabilities of neurones. Neurones are now known to be capable of association learning and memory and this study incorporates these features in a neurone model. A single neuronal input system, the NMDA-type glutamate receptor, is modelled by deriving finite difference equations from its reaction dynamics so that the concentration of several molecules in the receptor can be plotted as a function of time. The model shows association learning taking place at the glutamate receptor. A whole neurone with ten glutamate receptor regions is also modelled and shows that a neurone should be capable of recognizing patterns of inputs. As the neurone model is complicated and slow to run, a much simplified form of the model is described which embodies the basic features of neurone information processing in a simple algorithm.     

Putting information back into biological communication

At the heart of many debates on communication is the concept of information. There is an intuitive sense in which communication implies the transfer of some kind of information, probably the reason why information is an essential ingredient in most definitions of communication. However, information has also been an endless source of misunderstandings, and recent accounts have proposed that information should be dropped from a formal definition of communication. In this article, we re‐evaluate the merits and the internal logic of information‐based vs. information‐free approaches and conclude that information‐free approaches are conceptually incomplete and operationally hindered. Instead, we propose a functional notion of information that follows logically from previous adaptationist accounts. The ensuing definition of communication provides a wider, more inclusive theoretical scope that reflects more accurately the evolutionary scenario shaping animal signals. Additionally, it is a definition better equipped to deal with the extraordinary diversity of animal signals, facilitates the distinction of honest and deceptive signals at a proximate level and accommodates a number of conceptual and practical issues (e.g. redundancy, alerting components) that are lost when we fail to acknowledge the informative content of animal signals.     

The challenge of including social and ethical aspects in the development of nanobiotechnology

Nanotechnology as an enabling technology for many future medical applications touches on issues such as sensitivity of genetic information, the gap between diagnosis and therapy, health care resources and tensions between holistic and functional medicine. On the other hand nanotechnology will add a new dimension to the bio (human) and non-bio (machine) interface such as brain chips or implants, which eventually might raise new ethical issues specific to NanoMedicine. This requires careful analysis of ethical aspect in view of existing standards and regulations by ethics committees at the European scale. At the same time new nanomedical inventions have to be evaluated for new ethical aspects by Ethical, Legal and Social Aspects — specialists. The most crucial point in this regard is an early proactive analysis of new technological developments to identify and discuss possible issues as soon as possible. This requires a close collaboration and co-learning of technology developers and ethics specialists assisted by communication experts to ensure open and efficient information of the public about ethical aspects (old or new) related to nanomedicine. This co-evolution will ensure a socially and ethically accepted development of innovative diagnostic and therapeutic tools in NanoMedicine.     

探究早期现代人的南方扩散路线

本文从扩散时间、扩散路径、主要争论以及考古学证据等方面,对早期现代人南方扩散路线的研究现状进行梳理,对相关问题进行了探究。越来越多的证据显示,使用旧石器中期石器技术的早期现代人在晚更新世早期（MIS 5阶段）已经开始沿南方路线扩散,但学术界对于此次扩散的范围和影响程度仍存在争议。在距今约5万年以后,南方扩散路线上的早期现代人出现诸如使用赭石颜料、制作串珠和骨质工具、创作岩画艺术等行为,同时也独立发展出一些区域性适应行为。石器研究显示,南亚地区在5-3万年前逐渐出现了细石器技术及相关产品（细石叶、修背工具等）,而东南亚和大洋洲地区表现出以生产细小石片为主的权宜性石器技术体系,一些细小石片曾被用来加工有机质工具或作为复合型工具使用。中国南方地区紧邻东南亚和印度半岛,无论是从地理位置还是从生态环境来看,都可以纳入南方扩散路线的研究范围。建议从旧石器中期石制品组合和旧石器晚期细小石制品组合两方面入手,开展跨区域比较研究,为探索中国南方地区早期现代人的出现和演化提供重要考古学证据。     

Prenatal screening for cystic fibrosis carriers: an economic evaluation.

The cloning of the CFTR gene has made it technically possible to avert the unwanted birth of a child with cystic fibrosis (CF). Several large trials offering prenatal CF carrier screening suggest that such screening is practical and that identified carriers generally use the information obtained. Therefore, a critical question is whether the cost of such screening is justified. Decision analysis was performed that used information about choices that pregnant women were observed to make at each stage in the Rochester prenatal carrier-screening trial. The cost of screening per CF birth voluntarily averted was estimated to be $1,320,000-$1,400,000. However, the lifetime medical cost of the care of a CF child in today's dollars was estimated to be slightly>$1,000,000. Therefore, despite both the high cost of carrier testing and the relative infrequency of CF conceptions in the general population, the averted medical-care cost resulting from choices freely made are estimated to offset approximately 74%-78% of the costs of a screening program. At present, if it is assumed that a pregnancy terminated because of CF is replaced, the marginal cost for prenatal CF carrier screening is estimated to be $8,290 per quality-adjusted life-year. This value compares favorably with that of many accepted medical services. The cost of prenatal CF carrier screening could fall to equal the averted costs of CF patient care if the cost of carrier testing were to fall to $100.