A biochemical logic gate using an enzyme and its inhibitor. Part II: The logic gate

Enzyme-Based Logic Gates (ENLOGs) are key components in bio-molecular systems for information processing. This report and the previous one in this series address the characterization of two bio-molecular switching elements, namely the alpha-chymotrypsin (alphaCT) derivative p-phenylazobenzoyl-alpha-chymotrypsin (PABalphaCT) and its inhibitor (proflavine), as well as their assembly into a logic gate.The experimental output of the proposed system is expressed in terms of enzymic activity and this was translated into logic output (i.e. "1" or "0") relative to a predetermined threshold value. We have found that an univalent link exists between the dominant isomers of PABalphaCT (cis or trans), the dominant form of either acridine (proflavine) or acridan and the logic output of the system. Thus, of all possible combinations, only the trans-PABalphaCT and the acridan lead to an enzymic activity that can be defined as logic output "1". The system operates under the rules of Boolean algebra and performs as an "AND" logic gate.     

Study of Metaphoric and Associative Thinking in Children of Different Age Groups and in Patients with Childhood Autism

The study was performed on 35 healthy children and 9 patients with childhood autism (Asperger's syndrome). It was shown that formation of metaphoric thinking in norm begins as early as at the age of 7–8 years, the ability to understand metaphors decreasing suddenly at the age of 13–15 years. In the patients with childhood autism the inability was revealed of understanding metaphors and idioms widely used in the verbal communication. It is suggested that the deficit of the metaphoric thinking is due to introduction of the logic, theoretical thinking and, hence, to the underlying increased activity of the left hemisphere, as well as to the deficit of the imaginative-metaphoric thinking and to the underlying decreased activity of the right hemisphere. The study of the associative process has shown that the healthy school children have a high degree of association between the words meaning the sensory world of objects. In the patients with autism there were revealed an attenuation of the object association and the predominance of the first names, which indicates the left-hemispheric type of the association process.     

Paradoxical Aspects of Human Thinking

The work is devoted to study of amazing peculiarities of two different (and, in a way, mutually excluding) forms of human thinking, which are often are opposed to each other as empirical and theoretical thinking. On the example of solution of simple syllogisms, it has been shown that at different states of the left and right hemispheres of the human brain the same person gives principally different answers to the posed question. At domination of the left hemisphere, the answers turn out to be strictly formal, regardless of the real knowledge (or ignorance) of the object. At domination of the right hemisphere, the answer is based on the person's own experience rather than on formal logic. Whereas the formal-logic thinking provides for the breakthrough of the thought to new spheres of knowledge, the empirical thinking controls correspondence of the thought and reality. The integrity of the thinking activity at the combined work of both hemispheres is emphasized. The possibilities and limitations of the empirical and theoretical thinking in various spheres of the human activity are discussed from the point of view of sign systems.     

A survey of affected-sibship statistics for nonparametric linkage analysis

We have compared the power of a large number of allele-sharing statistics for "nonparametric" linkage analysis with affected sibships. Our rationale was that there is an extensive literature comparing statistics for sibling pairs but that there has not been much guidance on how to choose statistics for studies that include sibships of various sizes. We concentrated on statistics that can be described as assigning scores to each identity-by-descent-sharing configuration that a pedigree might take on (Whittemore and Halpern 1994). We considered sibships of sizes two through five, 27 different genetic models, and varying recombination fractions between the marker and the trait locus. We tried to identify statistics whose power was robust over a wide variety of models. We found that the statistic that is probably used most often in such studies-S(all)-performs quite well, although it is not necessarily the best. We also found several other statistics (such as the R criterion, S(robdom), and the Sobel-and-Lange statistic C) that perform well in most situations, a few (such as S(-#geno) and the Feingold-and-Siegmund version of S(pairs)) that have high power only in very special situations, and a few (such as S(-#geno), the N criterion, and the Sobel-and-Lange statistic B) that seem to have low power for the majority of the trait models. For the most part, the same statistics performed well for all sibship sizes. We also used our results to give some suggestions regarding how to weight sibships of different sizes, in forming an overall statistic.     

Teaching critical thinking in a developmental biology course at an American liberal arts college

We all expect our students to learn facts and concepts, but more importantly, we want them to learn how to evaluate new information from an educated and skeptical perspective; that is, we want them to become critical thinkers. For many of us who are scientists and teachers, critical thought is either intuitive or we learned it so long ago that it is not at all obvious how to pass on the skills to our students. Explicitly discussing the logic that underlies the experimental basis of developmental biology is an easy and very successful way to teach critical thinking skills. Here, I describe some simple changes to a lecture course that turn the practice of critical thinking into the centerpiece of the learning process. My starting point is the "Evidence and Antibodies" sidelight in Gilbert's Developmental Biology (2000), which I use as an introduction to the ideas of correlation, necessity and sufficiency, and to the kinds of experiments required to gather each type of evidence: observation ("show it"), loss of function ("block it") and gain of function ("move it"). Thereafter, every experiment can be understood quickly by the class and discussed intelligently with a common vocabulary. Both verbal and written reinforcement of these ideas dramatically improve the students' ability to evaluate new information. In particular, they are able to evaluate claims about cause and effect; they become experts at distinguishing between correlation and causation. Because the intellectual techniques are so powerful and the logic so satisfying, the students come to view the critical assessment of knowledge as a fun puzzle and the rigorous thinking behind formulating a question as an exciting challenge.     

Word learning,phonological short-term memory,phonotactic probability and long-term memory: towards an integrated framework

Word learning is studied in a multitude of ways, and it is often not clear what the relationship is between different phenomena. In this article, we begin by outlining a very simple functional framework that despite its simplicity can serve as a useful organizing scheme for thinking about various types of studies of word learning. We then review a number of themes that in recent years have emerged as important topics in the study of word learning, and relate them to the functional framework, noting nevertheless that these topics have tended to be somewhat separate areas of study. In the third part of the article, we describe a recent computational model and discuss how it offers a framework that can integrate and relate these various topics in word learning to each other. We conclude that issues that have typically been studied as separate topics can perhaps more fruitfully be thought of as closely integrated, with the present framework offering several suggestions about the nature of such integration.     

Querying quantitative logic models (Q2LM) to study intracellular signaling networks and cell-cytokine interactions

Mathematical models have substantially improved our ability to predict the response of a complex biological system to perturbation, but their use is typically limited by difficulties in specifying model topology and parameter values. Additionally, incorporating entities across different biological scales ranging from molecular to organismal in the same model is not trivial. Here, we present a framework called "querying quantitative logic models" (Q2LM) for building and asking questions of constrained fuzzy logic (cFL) models. cFL is a recently developed modeling formalism that uses logic gates to describe influences among entities, with transfer functions to describe quantitative dependencies. Q2LM does not rely on dedicated data to train the parameters of the transfer functions, and it permits straight-forward incorporation of entities at multiple biological scales. The Q2LM framework can be employed to ask questions such as: Which therapeutic perturbations accomplish a designated goal, and under what environmental conditions will these perturbations be effective? We demonstrate the utility of this framework for generating testable hypotheses in two examples: (i) a intracellular signaling network model; and (ii) a model for pharmacokinetics and pharmacodynamics of cell-cytokine interactions; in the latter, we validate hypotheses concerning molecular design of granulocyte colony stimulating factor.     

Informal Exchange Networks in Formal Systems: A Theoretical Model

Studies of the informal economy in the Third World have evolved toward defining the informal sector in relationship to the state. This article analyzes some activities that escape the control of the state, with special attention to centrally planned economies. Informal exchanges include bureaucratic favors ("connections"), clientelism, different forms of corruption, and the "parallel" system of production and marketing. I show that economic laws are not sufficient to understand the logic of these economies.     

The Logic of Misplaced Concreteness: Paiela Body Counting and the Nature of the Primitive Mind

The paper has two goals: to demonstrate ethnographically the connection between "structure" and communication, which Lévi-Strauss has consistently alleged to exist, and to challenge the thesis of Hallpike's book , The Foundations of Primitive Thought, that primitive thought reflects an "incomplete," unsophisticated logic .
The paper focuses on the counting system of the Paiela, a highland Papua New Guinea group. It argues that Paiela counting behavior is best analyzed as an element in a complex communication process. The logic of Paiela counting behavior is then the logic of the encompassing process: a communicational logic founded on concepts such as information and pattern. According to some theorists, the relationship between this logic and the logic that informs Western science is metalogical and dualistic. Paiela thought is thus revealed to be based on a complete and sophisticated alternative logic, a science among sciences. [Papua New Guinea, counting behavior, communication]     

The tobacco mouse and its relatives: a "tail" of coat colors, chromosomes, hybridization and speciation

The article reviews over 30 years' study of the chromosomal variation of the western house mice (Mus musculus domesticus) from the neighboring valleys of Poschiavo and Valtellina on the Swiss-Italian border. This is done in the context of the social and political history of this area, on the grounds that mice, as commensals, are influenced by human history. The chromosomal study of mice in this area was initiated because their unusual black coat color led a 19th century naturalist to describe the "tobacco mice" from Val Poschiavo as a separate species (Mus poschiavinus). The special coloration of the Val Poschiavo mice is matched by their chromosomes: they have 26 chromosomes instead of the usual 40. The Val Poschiavo mice are not a separate species according to the Biological Species Concept; instead they constitute a chromosome race (the "Poschiavo", POS) that is related to other races with reduced chromosome numbers that occur in N Italy (of which only those races in Val Poschiavo and Upper Valtellina have black coats). A phylogenetic analysis of mitochondrial DNA sequences suggests that the lineage of chromosome races found in N Italy was not formed during an extreme population bottleneck, although such bottlenecks have apparently occurred during the origin of individual races and certainly have influenced single populations. In one small, isolated population in Valtellina (Migiondo), two chromosome races (the POS and the "Upper Valtellina", UV, 2n = 24) became reproductively isolated from each other. In another small population (Sernio) bottlenecking led to fixation of a hybrid form with the UV karyotype and coat color, but with allozyme and microsatellite alleles characteristic of mice with the standard 40-chromosome karyotype. Two of the chromosome races in Valtellina (the UV and the "Mid Valtellina", MV, 2n = 24) also appear to be the product of hybridization. The dynamic history and patchy distribution of the house mouse chromosome races in Val Poschiavo and Valtellina in part reflects extinction-recolonization events; the formation of the UV and MV races and the introduction of the pale brown Standard race mice are believed to reflect such events. Dynamism in the chromosomal constitution of single populations is also evident from 25 years of data on the population in Migiondo. Due to change in agricultural practices, house mice in Valtellina and Val Poschiavo are becoming rarer, which is likely to have further impacts on the distribution and characteristics of the chromosome races in this area.     

Cell cycle Start is coupled to entry into the yeast metabolic cycle across diverse strains and growth rates

Cells have evolved oscillators with different frequencies to coordinate periodic processes. Here we studied the interaction of two oscillators, the cell division cycle (CDC) and the yeast metabolic cycle (YMC), in budding yeast. Previous work suggested that the CDC and YMC interact to separate high oxygen consumption (HOC) from DNA replication to prevent genetic damage. To test this hypothesis, we grew diverse strains in chemostat and measured DNA replication and oxygen consumption with high temporal resolution at different growth rates. Our data showed that HOC is not strictly separated from DNA replication; rather, cell cycle Start is coupled with the initiation of HOC and catabolism of storage carbohydrates. The logic of this YMC–CDC coupling may be to ensure that DNA replication and cell division occur only when sufficient cellular energy reserves have accumulated. Our results also uncovered a quantitative relationship between CDC period and YMC period across different strains. More generally, our approach shows how studies in genetically diverse strains efficiently identify robust phenotypes and steer the experimentalist away from strain-specific idiosyncrasies.     

Polarized Sphingolipid Transport from the Subapical Compartment: Evidence for Distinct Sphingolipid Domains

In polarized HepG2 cells, the sphingolipids glucosylceramide and sphingomyelin (SM), transported along the reverse transcytotic pathway, are sorted in subapical compartments (SACs), and subsequently targeted to either apical or basolateral plasma membrane domains, respectively. In the present study, evidence is provided that demonstrates that these sphingolipids constitute separate membrane domains at the luminal side of the SAC membrane. Furthermore, as revealed by the use of various modulators of membrane trafficking, such as calmodulin antagonists and dibutyryl-cAMP, it is shown that the fate of these separate sphingolipid domains is regulated by different signals, including those that govern cell polarity development. Thus under conditions that stimulate apical plasma membrane biogenesis, SM is rerouted from a SAC-to-basolateral to a SAC-to-apical pathway. The latter pathway represents the final leg in the transcytotic pathway, followed by the transcytotic pIgR-dIgA protein complex. Interestingly, this pathway is clearly different from the apical recycling pathway followed by glucosylceramide, further indicating that randomization of these pathways, which are both bound for the apical membrane, does not occur. The consequence of the potential coexistence of separate sphingolipid domains within the same compartment in terms of "raft" formation and apical targeting is discussed.     

Quantitative characterization of the regulation of iron metabolism in glioblastoma stem-like cells using magnetophoresis

This study focuses on different iron regulation mechanisms of glioblastoma (GBM) cancer stem-like cells (CSCs) and non-stem tumor cells (NSTCs) using multiple approaches: cell viability, density, and magnetophoresis. GBM CSCs and NSTCs were exposed to elevated iron concentration, and their magnetic susceptibility was measured using single cell magnetophoresis (SCM), which tracks the magnetic and settling velocities of thousands of individual cells passing through the magnetic field with a constant energy gradient. Our results consistently demonstrate that GBM NSTCs have higher magnetic susceptibility distribution at increased iron concentration compared with CSCs, and we speculate that it is because CSCs have the ability to store a high amount of iron in ferritin, whereas the free iron ions inside the NSTCs lead to higher magnetic susceptibility and reduced cell viability and growth. Further, their difference in magnetic susceptibility has led us to pursue a separate experiment using a quadrupole magnetic separator (QMS), a novel microfluidic device that uses a concentric channel and permanent magnets in a special configuration to separate samples based on their magnetic susceptibilities. GBM CSCs and NSTCs were exposed to elevated iron concentration, stained with two different trackers, mixed and introduced into QMS; subsequently, the separated fractions were analyzed by fluorescent microscopy. The separation results portray a successful label-less magnetic separation of the two populations.     

A biokinetic model to describe consequences of inhibition/stimulation in DNA-proofreading and repair-1. Development of the model

A biokinetic model is described which deals with the mathematical consequences of the inhibition or stimulation of DNA proofreading. It demonstrates the development of the number of DNA mismatch-dependent cells (e.g. cells with a malignant phenotype), where such mismatches arise by the in situ interaction of various substances with nucleotides of the DNA. The model can test for consequences by a logic gating on an "if-then" type of analysis in relation to the separate and consecutive processes of proofreading and repair. In particular, the consequences are considered in cases where either (i) the efficacy of proofreading and repair are reduced/prevented (inhibited) or (ii) are increased by some form of stimulation. On the chosen kinetic parameters, the model is accessible to manipulation as new data arising from further investigations become available and are introduced. The model is based on recently published data which show that an increased "mutant fraction" (see note on terms) arises in DNA replication when intracellular nucleotide pools show "asymmetries" (see note on terms). Extraordinarily high mutant fractions can be predicted/have been recorded in the presence of proofreading inhibitors. The model expresses data in mathematical terms of the competition between the development of mismatch-dependent cells and those with authentic genetic information. (Feedback and metastasis-effects and those of wild-type replicates are included.) A computerized (numerical) integration of the corresponding set of differential equations is offered. (A diskette with the program CANCER.xls is available upon request.)     

Construction in chimpanzees

Chimpanzees with the help of reconstruction and the "step-by-step" analysis of a figure--sample can plan a circuit of actions, forming an image of an end result. Ability to such actions proves at them an opportunity of cogitative operations, allowing to collect multielement figures on a sample. Generalization of concrete operations with concrete elements creates the precondition for the generalized understanding of a principle of actions--knowledge--in general to collect separate elements in complex designs. In it the powerful conceptual potential chimpanzees is covered. It allows to use chimpanzees as model preverbal a level of thinking.     

Ecological and Historic-Zoogeographic Influences on Concepts of the Genus as Demonstrated in Certain Chrysomelidae (Coleoptera)

It is proposed that taxonomists make more frequent use of the hierarchic category "subgenus" for classifying infra-generic groups of species of common phylogenic origin and which share characters in common, rather than to over-rank such species-groups as separate genera through unwarranted splitting. Reality of the genus as a biological entity is demonstrated via considerations of geologic, paleoclimatic, and associated ecological phenomena. Geologic events of the Tertiary are used to explain the origin of many of our genera. Examples are given of certain Chrysomelidae (Coleoptera) which have evolved at different times and under different circumstances.     

Un modele ondulatoire en biologie

Many complex systems, like biologic ones, cannot be understood with reductionist and analytic methods which are based upon an aristotelian logic with two values, false and true; in the past, mathematicians and philosophers have developed alternative logics, and the philosopher Stéphane Lupasco proposed a dynamic logic named logic of contradictory statements, with three values, potential, actual, and T which represents a mediate position between actual state and potential state, moreover, dynamics is introduced in form of a logical movement from potential to actual, which can be reversed; last but not least, this logic presents a correlation with metaphysical concepts like involution/evolution dualism proposed by Aurobindo, implicate/explicate order proposed by the physician David Bohm, and hegelian synthesis.In this paper, we propose to describe biological systems with a general model derived from this logic, and propose that dynamics of such systems can be represented by use of (i) discontinuities which propagate, and (ii) organizing centres, so, two kinds of propagation can be involved; we propose to name actualization waves the discontinuities which propagate from centers toward periphery, and potentialization waves the ones which propagate from periphery toward centers (see fig. 1 and 2).So, it is evident that organizing centers are involved in organisation and integration of these two opposite movements in biological systems and we propose that centers are involved in autonomy and organisational closure postulated by Francisco Varela; moreover, we described interaction between two systems, a subject and an object, by use of this conception, and introduce a new concept to explain how these two systems are coupled and interact, and propose to describe this interaction as a reduction/exchange of wave packets, and postulate that cognitive and memorisation processes are associated with this mechanism which is controlled by organizing centres.Finally, we propose to describe these centres as composed of recursively interacting elements (see fig. 3), with topological concentric organisation composed of central elements, and peripheric elements associated to form an interface involved in resonance process between waves; and postulate that this configuration is involved in space-time organisation and regulation of dynamical process in biological systems; experimental evidences of these conception are showed, and we prove an analogy between (i) neuronal cognitive processes described with interfacial resonance between internal prerepresentation forms, and external application forms (Dehaene, 1987), and (ii) physical processes in which resonant particles are conceptualized as events which mediate interaction between observed and observing systems (Stapp, 1971).

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Cet article à pour but de résumer et compléter une étude générale présentée par ailleurs sur la structure et la dynamique des systèmes (Dugué, 1991); il en présente les principales conclusions.     

The Study of Visual Thinking

Man perceives the world not only as it really is but also as it might be. In other words, perception is productive as well as reproductive, and the visual system contains mechanisms that generate new images. A study of these mechanisms and the principles of image generation is the subject of a special field in psychology which has recently been given the name "visual thinking" (1).     

一种棉铃虫多角体病毒的纯化与鉴定

对一株纯化的棉铃虫多角体病毒进行电镜观察,形态呈不规则型,直径约2 μm,命名为棉铃虫多角体-B(Helicoverpa armigera nucleocapsid nucleopolyhedrovirus-B,HaNPV-B),它对东方粘虫有较好的感染性,与棉铃虫单核型多角体病毒(Helicoverpa armigera single nucleocapsid NPV,HaSNPV)有不同的宿主域.通过半补齐法建立HaNPV-B基因组文库,拼接了一个6 035 bp的核苷酸片段,推测包含6个ORF,其包含基因内容及基因结构与HaSNPV不同,分析表明两者是不同种病毒,这为杆状病毒与宿主的相互作用及共同进化提供了信息.