Infrastructural expectations: exploring the promise of international large-scale induced pluripotent stem cell banks

This paper investigates the recent emergence of several major projects to bank and distribute large numbers of human induced pluripotent stem cells (hiPSCs) for translational research. The conceptual framework of the sociology of expectations is applied to interrogate the promise underpinning these developments. An analytic distinction is made between expectations associated with the field of hiPSC research more broadly and those specifically invested in cell banks as a form of scientific infrastructure, with the focus predominantly on the latter element. Empirical data for the analysis comes from qualitative interviews with stem cell scientists involved in a major European hiPSC banking project. In order to unpack these expectations, parallels to previous infrastructures of dissemination will be highlighted, with an emphasis on the functions of circulating and securing the quality of biological research materials.     

Classification of amine type G-protein coupled receptors with feature selection

G-protein coupled receptors (GPCRs) are involved in various physiological processes. Therefore, classification of amine type GPCRs is important for proper understanding of their functions. Though some effective methods have been developed, it still remains unknown how many and which features are essential for this task. Empirical studies show that feature selection might address this problem and provide us with some biologically useful knowledge. In this paper, a feature selection technique is introduced to identify those relevant features of proteins which are potentially important for the prediction of amine type GPCRs. The selected features are finally accepted to characterize proteins in a more compact form. High prediction accuracy is observed on two data sets with different sequence similarity by 5-fold cross-validation test. The comparison with a previous method demonstrates the efficiency and effectiveness of the proposed method.     

Thermodynamic investigations of proteins. I. Standard functions for proteins with lysozyme as an example.

A direct method is proposed for obtaining thermodynamic standard functions for native and denatured proteins using experimental data from scanning calorimetry, isothermal calorimetry and potentiometric titrations. The possibility of this approach is demonstrated on the example of lysozyme in the range of pH 1.5-7.0 and temperature 0-100 degrees C. Tests for the validity of the obtained functions of enthalpy and entropy are presented in the form of cyclic processes using experimental data obtained from thermodynamically different pathways. The Gibbs function is checked by comparison with results of an independent method. The methodic problems in determining and checking standard functions for proteins are discussed in detail.     

Analytic methods for the management of pesticide resistance.

In a previous paper a method was developed for deriving optimal pesticide strategies for multivoltine pests including the long-term costs of resistance. The present paper extends the mathematical techniques to cover a much more general ecological system, and allows different control costs for each pest brood. The control strategies in the new method are expressed in terms of a target pest population density after control. The previous results can also be expressed in this convenient form.     

Distance-dependent dielectric constants and their application to double-helical DNA

Detailed studies of structures of biological macromolecules, even in simplified models, involve many costly and time-consuming calculations. Any thorough methods require sampling of an extremely large conformation and momentum space. Calculations of electrostatic interactions, which depend on many physical factors, such as the details of solvent, solvent accessibility in macromolecules, and molecular polarizability, are always developed in a compromise between more rigorous, detailed models and the need for immediate application to complicated biological systems. In this paper, a middle ground is taken between the more exact theoretical models and the simplest constant values for the dielectric constant. The effects of solvent, counterions, and molecular polarizability are incorporated through a set of adjustable parameters that should be determined from experimental conditions. Several previous forms for the dielectric function are compared with the new ones. The present methods use Langevin functions to span the region of dielectric constant between bulk solvent and cavity values. Application of such dielectric models to double-helical DNA is important because base-stacking preferences were previously demonstrated [A. Sarai, J. Mazur, R. Nussinov, and R. L. Jernigan (1988) Biochemistry, vol. 27, pp. 8498-8502] to be sensitive to the electrostatic formulation. Here we find that poly(dG).poly(dC) can be A form for high screening and B form for low screening. By contrast, poly(dA).poly(dT) can only take the B form. Base stacking is more sensitive to the form of the dielectric function than are the sugar-phosphate backbone conformations. Also in B form, the backbone conformations are not so affected by the base types as in A form.     

Measuring Functional Diversity in Plant Communities with MixedLife Forms: A Problem of Hardand Soft Attributes

This paper examines the functional relationships among species in an Australian rangeland community with mixed life forms. It follows a previous study (Walker and others 1999) that explored the role of dominant and minor species in maintaining functional diversity and resilience in a rangeland ecosystem. Unlike our previous results, which were based on estimates of five plant functional attributes, the dominant species in this second community apparently are functionally no more dissimilar to each other than to all other species. We suggest that the lack of clear results in mixed life form communities represents a confounding of the relationships between the “hard” attributes that actually govern how a plant performs in an ecosystem and the “soft” attributes that we use as surrogates. There are very few data on the hard functional attributes of plant species and consequently little information on precisely how the (soft) measurable traits are related to their imputed functions. What evidence there is shows that although the relationships are strong within life forms, they differ between life forms. This poses a problem for the development of research relating plant biodiversity to ecosystem function. Until such a database is developed, it will be very difficult to advance our understanding and measurement of functional diversity in mixed life form communities. Received 30 April 2001; Accepted 23 January 2002.     

Zn- and Cu-thioneins: a functional classification for metallothioneins?

This report intends to provide the reader with a deeper insight in the chemical, and extensively biological, characteristics of the metallothionein (MT) system. We have devoted nearly 20 years to the study of MTs and this has allowed us to form what we believe is a more complete picture of this peculiar family of metalloproteins. At the beginning of the 1990s, the landscape of this field was quite different from the overall picture we have now. Many researchers have contributed to the readjustment of this part of scientific knowledge. In our case, we implemented a unified method for obtaining MTs, for characterizing their metal-binding features, and for applying a unified research rationale. All this has helped to enlarge the initial picture that was mainly dominated by mammalian MT1/MT2 and yeast Cup1, by introducing approximately 20 new MTs. It has also allowed some characteristics to be clarified and examined in more detail, such as the cooperativity or the coexistence of multiple species in the metal-substitution reactions, the availability of Ag(I) or Cd(II) for use as respective probes for the Cu(I) and Zn(II) binding sites, the participation of chloride or sulfide ligands in the metal coordination spheres, and the feasibility of using in vitro data as representative of in vivo scenarios. Overall, the results yield enough data to consider new criteria for a proposal of classification of MTs based on MT metal-binding features, which complements the previous classifications, and that can shed light on the still controversial physiological functions of this peculiar superfamily of metalloproteins.     

Small variations in multiple parameters account for wide variations in HIV-1 set-points: a novel modelling approach

Steady-state levels of HIV-1 viraemia in the plasma vary more than a 1,000-fold between HIV-positive patients and are thought to be influenced by several different host and viral factors such as host target cell availability, host anti-HIV immune response and the virulence of the virus. Previous mathematical models have taken the form of classical ecological food-chain models and are unable to account for this multifactorial nature of the disease. These models suggest that the steady-state viral load (i.e. the set-point) is determined by immune response parameters only. We have devised a generalized consensus model in which the conventional parameters are replaced by so-called 'process functions'. This very general approach yields results that are insensitive to the precise form of the mathematical model. Here we applied the approach to HIV-1 infections by estimating the steady-state values of several process functions from published patient data. Importantly, these estimates are generic because they are independent of the precise form of the underlying processes. We recorded the variation in the estimated steady-state values of the process functions in a group of HIV-1 patients. We developed a novel model by providing explicit expressions for the process functions having the highest patient-to-patient variation in their estimated values. Small variations from patient to patient for several parameters of the new model collectively accounted for the large variations observed in the steady-state viral burden. The novel model remains in full agreement with previous models and data.     

Order‐Restricted Semiparametric Inference for the Power Bias Model

Summary The power bias model, a generalization of length‐biased sampling, is introduced and investigated in detail. In particular, attention is focused on order‐restricted inference. We show that the power bias model is an example of the density ratio model, or in other words, it is a semiparametric model that is specified by assuming that the ratio of several unknown probability density functions has a parametric form. Estimation and testing procedures under constraints are developed in detail. It is shown that the power bias model can be used for testing for, or against, the likelihood ratio ordering among multiple populations without resorting to any parametric assumptions. Examples and real data analysis demonstrate the usefulness of this approach.     

Importance of molecular studies on major blood groups--intercellular adhesion molecule-4, a blood group antigen involved in multiple cellular interactions

Several blood groups, including the LW-blood group were discovered in the first part of last century, but their biochemical characteristics and cellular functions have only more recently been elucidated. The LW-blood group, renamed ICAM-4 (CD242), is red cell specific and belongs to the intercellular adhesion molecule family. ICAM-4 binds to several integrin receptors on blood and endothelial cells and is thus able to form large cellular complexes containing red cells. Its physiological function(s) has remained incompletely understood, but recent work shows that macrophage integrins can bind red cells through this ligand. In this article we discuss molecular properties of major blood group antigens, describe ICAM-4 in more detail, and show that phagocytosis of senescent red cells is in part ICAM-4/beta(2)-integrin dependent.     

Mitosis-specific phosphorylation of histone H3 initiates primarily within pericentromeric heterochromatin during G2 and spreads in an ordered fashion coincident with mitotic chromosome condensation

We have generated and characterized a novel site-specific antibody highly specific for the phosphorylated form of the amino-terminus of histone H3 (Ser10). In this study, we used this antibody to examine in detail the relationship between H3 phosphorylation and mitotic chromosome condensation in mammalian cells. Our results extend previous biochemical studies by demonstrating that mitotic phosphorylation of H3 initiates nonrandomly in pericentromeric heterochromatin in late G2 interphase cells. Following initiation, H3 phosphorylation appears to spread throughout the condensing chromatin and is complete in most cell lines just prior to the formation of prophase chromosomes, in which a phosphorylated, but nonmitotic, chromosomal organization is observed. In general, there is a precise spatial and temporal correlation between H3 phosphorylation and initial stages of chromatin condensation. Dephosphorylation of H3 begins in anaphase and is complete immediately prior to detectable chromosome decondensation in telophase cells. We propose that the singular phosphorylation of the amino-terminus of histone H3 may be involved in facilitating two key functions during mitosis: (1) regulate protein-protein interactions to promote binding of trans-acting factors that “drive” chromatin condensation as cells enter M-phase and (2) coordinate chromatin decondensation associated with M-phase. Received: 4 September 1997; in revised form: 14 September 1997 /Accepted: 14 September 1997     

A geometric synthesis method to realize a switching function

Frequently in threshold logic it is necessary to realize a switching function f of n variables in a two or more stages realization, both because it is not possible to realize f in a single gate and for reliability considerations. This means that the given function must be decomposed into a certain number of threshold functions, each of them having a number of variables less than n. When a geometric representation of switching functions is considered, the problem is equivalent to that of looking for functions whose patterns (on-sets) cover, in an adequate way, the on-set of the function f to be realized. In this paper a heuristic covering approach has been introduced which provides a manageable method for searching for a two stage realization of f. Furthermore a class of switching functions whose patterns possess a particular geometric shape (shell structure) has been considered. It has been proved that such functions (shell functions) are linearly separable and that one of their separating systems strictly depends on the centre and on the diameter of the shell structure. Gates implementing shell functions have been considered and their use has been revealed more convenient than that of majority gates in the solution of the problem of network synthesis. To clarify this advantage an example has been discussed in detail.     

Modeling the electrical behavior of anatomically complex neurons using a network analysis program: Excitable membrane

We present methods for using the generalpurpose network analysis program, SPICE, to construct computer models of excitable membrane displaying Hodgkin-Huxley-like kinetics. The four non-linear partial differential equations of Hodgkin and Huxley (H-H; 1952) are implemented using electrical circuit elements. The H-H rate constants, and , are approximated by polynomial functions rather than exponential functions, since the former are handled more efficiently by SPICE. The process of developing code to implement the H-H sodium conductance is described in detail. The Appendix contains a complete listing of the code required to simulate an H-H action potential. The behavior of models so constructed is validated by comparison with the space-clamped and propagating action potentials of Hodgkin and Huxley. SPICE models of multiply branched axons were tested and found to behave as predicted by previous numerical solutions for propagation in inhomogeneous axons. New results are presented for two cases. First, a detailed, anatomically based model is constructed of group Ia input to an -motoneuron with an excitable soma, a myelinated axon and passive dendrites. Second, we simulate interactions among clusters of mixed excitable and passive dendritic spines on an idealized neuron. The methods presented in this paper and its companion (Segev et al. 1985) should permit neurobiologists to construct and explore models which simulate much more closely the real morphological and physiological characteristics of nerve cells.     

Importance of molecular studies on major blood groups—Intercellular adhesion molecule-4, a blood group antigen involved in multiple cellular interactions

Several blood groups, including the LW-blood group were discovered in the first part of last century, but their biochemical characteristics and cellular functions have only more recently been elucidated. The LW-blood group, renamed ICAM-4 (CD242), is red cell specific and belongs to the intercellular adhesion molecule family. ICAM-4 binds to several integrin receptors on blood and endothelial cells and is thus able to form large cellular complexes containing red cells. Its physiological function(s) has remained incompletely understood, but recent work shows that macrophage integrins can bind red cells through this ligand. In this article we discuss molecular properties of major blood group antigens, describe ICAM-4 in more detail, and show that phagocytosis of senescent red cells is in part ICAM-4/β₂-integrin dependent.     

Synaptic integration of NMDA and non-NMDA receptors in large neuronal network models solved by means of differential equations

Alpha functions are commonly used to describe different receptor channel kinetics (non-NMDA, GABA_A and GABA_B). In this paper we show that they may be represented as solutions to simple ordinary differential equations. This alternative method is compared with the commonly used direct summation of the alpha function conductances in a high-level neuronal circuit model. A parametric study shows that the differential equation method greatly speeds up the previous summation method. The forward Euler method used to solve this differential equation is shown to be accurate for this type of simulation. The modelling of NMDA receptor channel kinetics is also discussed. Received: 18 December 1992/Accepted in revised form: 28 June 1993     

Studies in the mathematical biophysics of discrimination and conditioning II: Special case: Errors,trials, and number of possible responses

A special case of a problem discussed in a previous paper is treated in greater detail. An equation in the three variables, errors, trials and number of possible choices, is developed and compared with the results of an experiment performed under conditions closely approximating those required for the development of the equation. The agreement is excellent.     

Some quantitative aspects of history

In a previous paper, in which a possible mathematical approach to history was outlined, it was shown that urbanization plays an important part in the propagation of new ideas. The rate of such propagation influences the rate of historical developments. The present paper deals in more detail with possible mechanisms of formation of earliest cities. Equations are derived which give the limiting size of such cities and their rate of growth. Of particular importance for the spread of new ideas is the spread of information. The latter largely depends on the fraction of individuals who travel between city and country. Expressions for this quantity are derived. An approach is outlined to the mathematical study of the earliest social classes, which may have been formed as a result of military, religious, or economic stratifications.     

Social inequality and signaling in a costly ritual

Evolutionary perspectives suggest that participation in collective rituals may serve important communicative functions by signaling practitioners' commitment to the community and its values. While previous research has examined the effects of ritual signals at the individual and collective level, there has been limited attention directed to the impact of socio-environmental factors on the quality of ritual signaling. We examined this impact in the context of the Thaipusam Kavadi, a collective ritual performed by Tamil Hindus worldwide that involves body piercings and other costly activities. We show that participants' relative position in the social hierarchy systematically affects the form of ritual signaling. Specifically, we found that low-status participants are more likely to engage in signaling modalities that require somatic and opportunity costs in the form of body piercings and cumulative effort, while high-status individuals are more likely to use financial capital, in the form of more elaborate material offerings to the deity. Moreover, signaling in each particular modality is stronger among individuals who participate in more public (but not private) rituals, corresponding to their long-term commitment to the community. In sum, our results demonstrate that social hierarchies exact unequal requirements on ritual participants, who in turn modify their signaling strategies accordingly.     

The Application of Enterprise Modeling for Aerospace Manufacturing System Integration

The objective of enterprise modeling is to develop a repository regarding organizational elements and functions that maps information objectives with business functions. This is accomplished through an exhaustive process that analyzes and models the business to a level of detail sufficient to enable selection of appropriate technologies and the design of specific information systems. In this paper, enterprise modeling is utilized to provide a baseline reference for the successful integration of an FMS in an aerospace electronics manufacturing facility.     

哺乳类两大嗅觉系统功能的研究进展

近年来对于嗅觉系统的研究已成为动物学研究的热点之一,本文通过对以往关于哺乳类两大嗅觉系统功能的研究进行总结和回顾,对目前犁鼻器系统(VOE-AOB)和主嗅觉系统(MOE-MOB)功能结论上的争议做了初步探讨。通过概括和总结,发现目前对两大嗅觉系统功能还存在争议,其原因可能有以下几点:以前的研究方法上可能有不完善之处;不同的研究采用的物种不同,结论上的争议也许与不同物种间存在种间差异有关;动物的社会经验对研究结论可能也有一定影响。希望通过本文能进一步促进今后此方面的研究。