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The scientific community is often asked to predict the future state of the environment and, to do so, the structure (biodiversity) and the functions (ecosystem functioning) of the investigated systems must be described and understood. In his "handful of feathers" metaphor, Charles Darwin explained the difference between simple and predictable systems, obeying definite laws, and complex (and unpredictable) systems, featured by innumerable components and interactions among them. In order not to waste efforts in impossible enterprises, it is crucial to ascertain if accurate predictions are possible in a given domain, and to what extent they might be reliable. Since ecology and evolution (together forming "natural history") deal with complex historical systems that are extremely sensitive to initial conditions and to contingencies or 'black swans', it is inherently impossible to accurately predict their future states. Notwithstanding this impossibility, policy makers are asking the community of ecological and evolutionary biologists to predict the future. The struggle for funding induces many supposed naturalists to do so, also because other types of scientists (from engineers to modellers) are keen to sell predictions (usually in form of solutions) to policy makers that are willing to pay for them. This paper is a plea for bio-ecological realism. The "mission" of ecologists and evolutionary biologists (natural historians) is not to predict the future state of inherently unpredictable systems, but to convince policy makers that we must live with uncertainties. Natural history, however, can provide knowledge-based wisdom to face the uncertainties about the future. Natural historians produce scenarios that are of great help in figuring out how to manage our relationship with the rest of nature. [ABSTRACT FROM AUTHOR]

• I briefly summarize Michael Savageau's "Biochemical Systems Analysis" papers, published in volumes 25 and 26 of the journal. • These papers kickstarted Biochemical Systems Theory, which originated many of the core concepts and tools of Systems Biology. • I identify the most relevant developments in Biochemical Systems Theory since 1969. Michael Savageau's Biochemical Systems Analysis I, II, III papers, published in volumes 25 and 26 of the journal, kickstarted a research programme that originated many of the core concepts and tools of Systems Biology. This article briefly summarizes these papers and discusses the most relevant developments in Biochemical Systems Theory since their publication. [ABSTRACT FROM AUTHOR]

Holothuria scabra is one of the most intensively studied holothuroids, or sea cucumbers (Echinodermata: Holothuroidea), having been discussed in the literature since the early 19th century. The species is important for several reasons: (1) it is widely distributed and historically abundant in several shallow soft-bottom habitats throughout the Indo-Pacific, (2) it has a high commercial value on the Asian markets, where it is mainly sold as a dried product (beche-de-mer) and (3) it is the only tropical holothuroid species that can currently be mass-produced in hatcheries. Over 20 years have elapsed since the last comprehensive review on H. scabra published in 2001. Research on H. scabra has continued to accumulate, fuelled by intense commercial exploitation, and further declines in wild stocks over the entire distribution range. This review compiles data from over 950 publications pertaining to the biology, ecology, physiology, biochemical composition, aquaculture, fishery, processing and trade of H. scabra, presenting the most complete synthesis to date, including scientific papers and material published by local institutions and/or in foreign languages. The main goal of this project was to summarize and critically discuss the abundant literature on this species, making it more readily accessible to all stakeholders aiming to conduct fundamental and applied research on H. scabra, or wishing to develop aquaculture, stock enhancement and management programs across its geographic range. [ABSTRACT FROM AUTHOR]

• I briefly describe the Boolean modeling approach to investigate gene regulatory networks (GRNs). • I discuss the foundational contributions by the three seminal manuscripts more than 15 years ago. • Finally, the applications of the Boolean modeling approach to the large-scale omics data is discussed. Boolean modeling is a mathematical modeling framework used for defining and studying gene-regulatory networks (GRNs). It serves as a means to develop mechanistic models, offering insights into the trajectories and dynamic properties of GRNs. In this review, I delve into seminal papers published in the Journal of Theoretical Biology that have spearheaded this field. Additionally, I explore the application of these modeling methods in the current era of data-intensive science. [ABSTRACT FROM AUTHOR]

In the recent work of Ullah et al. (2012a) , the authors developed an effective method to simplify reversible Markov chains by removal of states with low equilibrium occupancies. In this paper, we extend this result to irreversible Markov chains. We show that an irreversible chain can be simplified by removal of states with fast leaving rates. Moreover, we reveal that the irreversibility of the chain will always decrease after model simplification. This suggests that although model simplification can retain almost all the dynamic information of the chain, it will lose some thermodynamic information as a trade-off. Examples from biology are also given to illustrate the main results of this paper. [ABSTRACT FROM AUTHOR]

Abstract Throughout the last decade, we have seen much progress towards characterising and computing the minimum hybridisation number for a set P of rooted phylogenetic trees. Roughly speaking, this minimum quantifies the number of hybridisation events needed to explain a set of phylogenetic trees by simultaneously embedding them into a phylogenetic network. From a mathematical viewpoint, the notion of agreement forests is the underpinning concept for almost all results that are related to calculating the minimum hybridisation number for when | P | = 2. However, despite various attempts, characterising this number in terms of agreement forests for | P | > 2 remains elusive. In this paper, we characterise the minimum hybridisation number for when P is of arbitrary size and consists of not necessarily binary trees. Building on our previous work on cherry-picking sequences, we first establish a new characterisation to compute the minimum hybridisation number in the space of tree-child networks. Subsequently, we show how this characterisation extends to the space of all rooted phylogenetic networks. Moreover, we establish a particular hardness result that gives new insight into some of the limitations of agreement forests. [ABSTRACT FROM AUTHOR]

Abstract: The chronic exposure of humans through consumption of high levels of inorganic arsenic (iAs)-contaminated drinking water is associated with skin lesions, peripheral vascular disease, hypertension, and cancers. Additionally, humans are exposed to organic arsenicals when used as pesticides and herbicides (e.g., monomethylarsonic acid, dimethylarsinic acid (DMAV) also known as cacodylic acid). Extensive research has been conducted to characterize the adverse health effects that result from exposure to iAs and its metabolites to describe the biological pathway(s) that lead to adverse health effects. To further this effort, on May 31, 2006, the United States Environmental Protection Agency (USEPA) sponsored a meeting entitled “Workshop on Arsenic Research and Risk Assessment”. The invited participants from government agencies, academia, independent research organizations and consultants were asked to present their current research. The overall focus of these research efforts has been to determine the potential human health risks due to environmental exposures to arsenicals. Pursuant in these efforts is the elucidation of a mode of action for arsenicals. This paper provides a brief overview of the workshop goals, regulatory context for arsenical research, mode of action (MOA) analysis in human health risk assessment, and the application of MOA analysis for iAs and DMAV. Subsequent papers within this issue will present the research discussed at the workshop, ensuing discussions, and conclusions of the workshop. [Copyright &y& Elsevier]

Abstract: Hamilton''s famous rule was presented in 1964 in a paper called “The genetical theory of social behaviour (I and II)”, Journal of Theoretical Biology 7, 1–16, 17–32. The paper contains a mathematical genetical model from which the rule supposedly follows, but it does not provide a link between the paper''s central result, which states that selection dynamics take the population to a state where mean inclusive fitness is maximized, and the rule, which states that selection will lead to maximization of individual inclusive fitness. This note provides a condition under which Hamilton''s rule does follow from his central result. [Copyright &y& Elsevier]

Abstract: In this paper we study permanence, extinction and periodic solution of periodic predator–prey system with Beddington–DeAngelis functional response. We provide a sufficient and necessary condition to guarantee the predator and prey species to be permanent. In addition, sufficient condition is derived for the existence of positive periodic solution. This paper improves some main results obtained by Fan and Kuang [M. Fan, Y. Kuang, Dynamics of nonautonomous predator–prey system with the Beddington–DeAngelis functional response, J. Math. Anal. Appl. 295 (2004) 15–39]. [Copyright &y& Elsevier]

Abstract: Prompted by contemporary concerns in the West over a global vision of nature and society at risk, this paper builds on recent studies of expertise within a broader public culture. By focusing on earlier episodes of social and political uncertainty, the paper argues that there is scope to extend such analysis in terms of historical geographies of specialist knowledge. The paper examines the formative years of British ecology, a discipline which from its beginnings in the wake of urban industrialism more than a century ago, was centrally concerned with the relations of human well-being and the environment. In exploring when, where and how an ecological expertise became defined, it shifts the focus from familiar milestones in the discipline''s public recognition. By tracing the discursive and material practices of those who sought to identify and define ecology as a specialism, the paper illustrates the importance of groupings within and beyond accredited expertise in giving it meaning and purpose. In doing so it highlights the fragility and fluidity of the boundaries around ‘expertise’, and the significance of geographical context and connections in shaping its conduct and content. In terms of broader historical geographies, the paper suggests that while ‘expert’ cultures may be projected as giving greater public reassurance, the sense of certainty that this implies disguises complex processes in which the boundaries are imprecise between specialist and lay knowledge and between scientific and public spaces. [Copyright &y& Elsevier]

• Overview of the discovery and preliminary characterisation of CXCL17. • Discussion of contradictory reports regarding the chemotactic activity of CXCL17. • Discussion of contradictory reports regarding the proteolytic processing of CXCL17. • Discussion of contradictory reports regarding the adoption of a chemokine fold by CXCL17. • Concluding remarks. Chemotactic cytokines (chemokines) are a group of around 40 small proteins which share a similar protein fold and are well known for their ability to direct the migration of leukocytes to a variety of tissue locations. CXCL17 was the last member of the chemokine family to be assigned and was admitted to the family based on theoretical modelling of the CXCL17 structure and chemotactic activity for monocytes and dendritic cells. Of Interest, CXCL17 expression appears to be restricted to mucosal tissues such as the tongue, stomach and lung, suggestive of specific roles at these locations. A putative CXCL17 receptor, GPR35 was reportedly identified and mice deficient in CXCL17 were generated and characterised. More recently, however, some apparent contradictions regarding aspects of CXCL17 biology have been raised by ourselves and others. Notably, GPR35 appears to be a receptor for the serotonin metabolite 5-hydroxyindoleacetic acid rather than for CXCL17 and modelling of CXCL17 using a variety of platforms fails to identify a chemokine-like fold. In this article, we summarize the discovery of CXCL17 and discuss key papers describing the subsequent characterisation of this protein. Ultimately, we pose the question, 'What defines a chemokine?' (185 words) [ABSTRACT FROM AUTHOR]

• I briefly summarize two classic papers by W. D. Hamilton, published in Volume 7 of the journal (in 1964). • In this work Hamilton introduced 'inclusive fitness' and I explain why the concept was transformative. • I identify three key developments in inclusive-fitness theory since 1964, and I suggest there is scope to develop the theory further. [ABSTRACT FROM AUTHOR]

Environmental stochasticity is known to be a destabilizing factor, increasing abundance fluctuations and extinction rates of populations. However, the stability of a community may benefit from the differential response of species to environmental variations due to the storage effect. This paper provides a systematic and comprehensive discussion of these two contradicting tendencies, using the metacommunity version of the recently proposed time-average neutral model of biodiversity which incorporates environmental stochasticity and demographic noise and allows for extinction and speciation. We show that the incorporation of demographic noise into the model is essential to its applicability, yielding realistic behavior of the system when fitness variations are relatively weak. The dependence of species richness on the strength of environmental stochasticity changes sign when the correlation time of the environmental variations increases. This transition marks the point at which the storage effect no longer succeeds in stabilizing the community. [ABSTRACT FROM AUTHOR]

Admissible measures of diversity allow specification of the number of types (species, alleles, etc.) that are “effectively” involved in producing the diversity (the “diversity effective number”, also referred to as “true diversity”) of a community or population. In metacommunities, effective numbers additionally serve in partitioning the total diversity (symbolized by γ ) into one component summarizing the diversity within communities (symbolized by α ) and an independent component summarizing the differences between communities (symbolized by β ). There is growing consensus that the β -component should be treated in terms of an effective number of “distinct” communities in the metacommunity. Yet, the notion of distinctness is shown in the present paper to remain conceptually ambiguous at least with respect to the diversity within the “distinct” communities. To overcome this ambiguity and to provide the means for designing further desirable effective numbers, a new approach is taken that involves a generalized concept of effective number. The approach relies on first specifying the distributional characteristics of partitioning diversity among communities (among which are differentiation, where the same types tend to occur in the same communities, and apportionment, where different types tend to occur in different communities), then developing the indices which measure these characteristics, and finally inferring the effective numbers from these indices. Major results: (1) The β -component reflects apportionment characteristics of metacommunity structure and is quantified by the “apportionment effective number” of communities (number of effectively monomorphic communities). Since differentiation between communities arises only as a side effect of apportionment, the common interpretation of the β -component in terms of differentiation is unwarranted. (2) Multiplicative as well as additive methods of partitioning the total type diversity ( γ ) involve apportionment effective numbers of communities that are based on different apportionment indices. (3) “Differentiation effective numbers” of communities exist but do not conform with the classical concept of partitioning total type diversity into components within and between communities. (4) Differentiation characteristics are measured as effective numbers of distinct types (rather than communities) from the dual perspective, in which the roles of type and community membership are exchanged. This is relevant e.g. in studies of endemism and competitive exclusion. (5) For Shannon-Wiener diversity, all of the differentiation and apportionment effective numbers are equal, with the exception of those representing additive partitioning. (6) Under either perspective, that is dual or non-dual, measures of compositional differentiation (as originally suggested for the assessment of β -diversity) do not figure in the partitioning of total diversity into components, since they do not build on the intrinsic concept of diversity. [ABSTRACT FROM AUTHOR]

This commentary describes a highly-cited paper by John Gutteridge and myself that appeared in Arch. Biochem. Biophys. It is dedicated to the memory of John Gutteridge, my frequent co-author and a lifelong friend, who sadly passed away on July 5, 2021. [ABSTRACT FROM AUTHOR]

Abstract: Reliable functioning is crucial for the survival and development of the genetic regulatory networks in living cells and organisms. This functional reliability is an important feature of the networks and reflects the structural features that have been embedded in the regulatory networks by evolution. In this paper, we integrate this reliability into network reconstruction. We introduce the concept of dependency probability to measure the dependency of functional reliability on network edges. We also propose a method to estimate the dependency probability and select edges with high contributions to functional reliability. We use two real examples, the regulatory network of the cell cycle of the budding yeast and that of the fission yeast, to demonstrate that the proposed method improves network reconstruction. In addition, the dependency probability is robust in calculation and can be easily implemented in practice. [Copyright &y& Elsevier]

This commentary describes a highly-cited paper by John Gutteridge and myself that appeared in Arch. Biochem. Biophys. It is dedicated to the memory of John Gutteridge, my frequent co-author and a lifelong friend, who sadly passed away on July 5, 2021. [ABSTRACT FROM AUTHOR]

Abstract: This paper examines the role of other-regarding behavior as a mechanism for the establishment and maintenance of cooperation in resource use under variable social and environmental conditions. By coupling resource stock dynamics with social dynamics concerning compliance to a social norm prescribing non-excessive resource extraction in a common pool resource, we show that when reputational considerations matter and a sufficient level of social stigma affects the violators of a norm, sustainable outcomes are achieved. We find large parameter regions where norm-observing and norm-violating types coexist, and analyze to what extent such coexistence depends on the environment. [Copyright &y& Elsevier]

Abstract: Humans become infected with Toxoplasma gondii mainly by ingesting uncooked meat containing viable tissue cysts or by ingesting food or water contaminated with oocysts from the feces of infected cats. Circumstantial evidence suggests that oocyst-induced infections in humans are clinically more severe than tissue cyst-acquired infections. Until recently, waterborne transmission of T. gondii was considered uncommon, but a large human outbreak linked to contamination of a municipal water reservoir in Canada by wild felids and the widespread infection of marine mammals in the USA provided reasons to question this view. The present paper examines the possible importance of T. gondii transmission by water. [Copyright &y& Elsevier]

Abstract: Microwell array cytometry is a novel high-throughput experimental technique that makes it possible to correlate pre-stress cell phenotypes and post-stress outcomes with single cell resolution. Because the cells are seeded in a high density grid of cell-sized microwells, thousands of individual cells can be tracked and imaged through manipulations as extreme as freezing or drying. Unlike flow cytometry, measurements can be made at multiple time points for the same set of cells. Unlike conventional image cytometry, image analysis is greatly simplified by arranging the cells in a spatially defined pattern and physically separating them from one another. To demonstrate the utility of microwell array cytometry in the field of biopreservation, we have used it to investigate the role of mitochondrial membrane potential in the cryopreservation of primary hepatocytes. Even with optimized cryopreservation protocols, the stress of freezing almost always leads to dysfunction or death in part of the cell population. To a large extent, cell fate is dominated by the stochastic nature of ice crystal nucleation, membrane rupture, and other biophysical processes, but natural variation in the initial cell population almost certainly plays an important and under-studied role. Understanding why some cells in a population are more likely to survive preservation will be invaluable for the development of new approaches to improve preservation yields. For this paper, primary hepatocytes were seeded in microwell array devices, imaged using the mitochondrial dyes Rh123 or JC-1, cryopreserved for up to a week, rapidly thawed, and checked for viability after a short recovery period. Cells with a high mitochondrial membrane potential before freezing were significantly less likely to survive the freezing process, though the difference in short term viability was fairly small. The results demonstrate that intrinsic cell factors do play an important role in cryopreservation survival, even in the short term where extrinsic biophysical factors would be expected to dominate. We believe that microwell array cytometry will be an important tool for a wide range of studies in biopreservation and stress biology. [Copyright &y& Elsevier]

Abstract: The flux-summation theorem (FST) is a central principle of metabolic control analysis. It describes how the control of flux through any metabolic pathway of arbitrary complexity is distributed among the component reaction steps. Two issues concerning the FST are discussed in this paper. First, it has been suggested that the theorem could, in principle, be inapplicable under certain conditions, i.e. the sum of the control coefficients of all the enzymes supporting a pathway could exceed unity. Such conditions have not been found in any species so far studied, so in practice the FST is always applicable. I argue that applicability of the FST is a precondition for phenotypic robustness and therefore for survival. Second, the FST provides a basis for explaining dominance that renders Fisher''s ‘modifier genes’ hypothesis otiose. Some recent misunderstandings of metabolic control analysis have led to the claim that this explanation is flawed and therefore that Fisher''s hypothesis can and should be reinstated. Here, these suggestions are refuted. [Copyright &y& Elsevier]

Abstract: This paper develops connections between objective Bayesian epistemology—which holds that the strengths of an agent''s beliefs should be representable by probabilities, should be calibrated with evidence of empirical probability, and should otherwise be equivocal—and probabilistic logic. After introducing objective Bayesian epistemology over propositional languages, the formalism is extended to handle predicate languages. A rather general probabilistic logic is formulated and then given a natural semantics in terms of objective Bayesian epistemology. The machinery of objective Bayesian nets and objective credal nets is introduced and this machinery is applied to provide a calculus for probabilistic logic that meshes with the objective Bayesian semantics. [Copyright &y& Elsevier]

Abstract: Eye development is a complex process that involves the formation of the retina and the lens, collectively called the eyeball, as well as the formation of auxiliary eye structures such as the eyelid, lacrimal gland, cornea and conjunctiva. The developmental requirements for the formation of each individual structure are only partially understood. We have shown previously that the homeobox-containing gene Rx is a key component in eye formation, as retinal structures do not develop and retina-specific gene expression is not observed in Rx-deficient mice. In addition, Rx−/− embryos do not develop any lens structure, despite the fact that Rx is not expressed in the lens. This demonstrates that during normal mammalian development, retina-specific gene expression is necessary for lens formation. In this paper we show that lens formation can be restored in Rx-deficient embryos experimentally, by the elimination of β-catenin expression in the head surface ectoderm. This suggests that β-catenin is involved in lens specification either through Wnt signaling or through its function in cell adhesion. In contrast to lens formation, we demonstrate that the development of auxiliary eye structures does not depend on retina-specific gene expression or retinal morphogenesis. These results point to the existence of two separate developmental processes involved in the formation of the eye and its associated structures. One involved in the formation of the eyeball and the second involved in the formation of the auxiliary eye structures. [Copyright &y& Elsevier]

Abstract: It has recently been proposed [Dediu, D., Ladd, D.R., 2007. Linguistic tone is related to the population frequency of the adaptive haplogroups of two brain size genes, ASPM and Microcephalin. Proc. Natl Acad. Sci. USA 104(26), 10944–10949] that genetically coded linguistic biases can influence the trajectory of language change. However, the nature of such biases and the conditions under which they can become manifest have remained vague. The present paper explores computationally two plausible types of linguistic acquisition biases in a population of agents implementing realistic genetic, linguistic and demographic processes. One type of bias represents an innate asymmetric initial state (initial expectation bias) while the other an innate asymmetric facility of acquisition (rate of learning bias). It was found that only the second type of bias produces detectable effects on language through cultural transmission across generations and that such effects are produced even by weak biases present at low frequencies in the population. This suggests that learning preference asymmetries, very small at the individual level and not very frequent at the population level, can bias the trajectory of language change through the process of cultural transmission. [Copyright &y& Elsevier]

Abstract: DEBtox (Dynamic Energy Budget in toxicology) models have been designed to analyse various results from classic tests in ecotoxicology. They consist of a set of mechanistic models describing how organisms manage their energy, when they are exposed to a contaminant. Until now, such a biology-based modeling approach has not been used within the regulatory context. However, these methods have been promoted and discussed in recent guidance documents on the statistical analysis of ecotoxicity data. Indeed, they help us to understand the underlying mechanisms. In this paper, we focused on the 21 day Daphnia magna reproduction test. We first aimed to clarify and detail the model building process leading to DEBtox models. Equations were rederived step by step, and for some of them we obtained results different from the published ones. Then, we statistically evaluated the estimation process quality when using a least squares approach. Using both experimental and simulated data, our analyses highlighted several statistical issues related to the fitting of DEBtox models on OECD-type reproduction data. In this case, particular attention had to be paid to parameter estimates and the interpretation of their confidence intervals. [Copyright &y& Elsevier]

Abstract: The complexity–stability relation is a central issue in ecology. In this paper, we show how the sampling method most often used to parameterize an ecological community, can affect the conclusions about whether or not complexity promotes stability and we suggest a sampling algorithm that overcomes the problem. We also illustrate the importance of treating feasibility separately from stability when constructing model communities. Using model Lotka–Volterra competition communities we found that probability of feasibility decreases with increasing interaction strength and number of species in the community. However, for feasible systems we found that local stability probability and resilience do not significantly differ between communities with few or many species, in contrast with earlier studies that, did not account for feasibility and concluded that species-poor communities had higher probability of being locally stable than species-rich communities. [Copyright &y& Elsevier]

Abstract: Energy supply and use is of fundamental importance to society. Although the interactions between energy and environment were originally local in character, they have now widened to cover regional and global issues, such as acid rain and the greenhouse effect. It is for this reason that there is a need for covering the direct and indirect economic and environmental impacts of energy acquisition, transport, production and use. In this paper, particular attention is directed to ways of resolving conflict between economic and environmental goals by encouraging a power plant to consider co-firing biomass and refuse-derived fuel (RDF) with coal simultaneously. It aims at reducing the emission level of sulfur dioxide (SO2) in an uncertain environment, using the power plant in Michigan City, Indiana as an example. To assess the uncertainty by a comparative way both deterministic and grey nonlinear mixed integer programming (MIP) models were developed to minimize the net operating cost with respect to possible fuel combinations. It aims at generating the optimal portfolio of alternative fuels while maintaining the same electricity generation simultaneously. To ease the solution procedure stepwise relaxation algorithm was developed for solving the grey nonlinear MIP model. Breakeven alternative fuel value can be identified in the post-optimization stage for decision-making. Research findings show that the inclusion of RDF does not exhibit comparative advantage in terms of the net cost, albeit relatively lower air pollution impact. Yet it can be sustained by a charge system, subsidy program, or emission credit as the price of coal increases over time. [Copyright &y& Elsevier]

Abstract: The dynamic stability of a submerged cantilever pipe conveying fluid from the free end to the fixed one is considered as one of the unresolved issues in the area of fluid–structure interaction. There is a contradiction between theoretical predictions and experiments. Reported experiments did not show any instability, while theory predicts instability beyond a critical fluid velocity. Recently, several papers appeared, improving the theoretical modelling of pipe dynamics. All theories predict instability, either oscillatory or static, referred to here as flutter and divergence, respectively. A new test set-up was designed to investigate the hypothesis that previous experimental set-ups could not allow observations of pipe instability or the pipe aspirating water is unconditionally stable. In this new test set-up, the fluid velocity could exceed the theoretically predicted critical velocities. A cantilever pipe of about 5m length was partly submerged in water. The free open end of the pipe was in the water, whereas the fixed end was above the waterline. The experiments clearly showed that the cantilever pipe aspirating water is unstable beyond a critical velocity of water convection through the pipe. Below this velocity the pipe is stable, whereas above it the pipe shows a complex motion that consists of two alternating phases. The first phase is a nearly periodic orbital motion with maximum amplitude of a few pipe diameters, whereas the second one is a noise-like vibration with very small amplitudes. Increasing the internal fluid velocity results in a larger amplitude of the orbital motion, but does not change the pipe motion qualitatively. [Copyright &y& Elsevier]

Abstract: This paper is concerned with the “isolation with migration” model, where a panmictic ancestral population gave rise to a symmetric -island model, time ago. Explicit analytical expressions are derived for the probability density function of the coalescence time of a pair of genes sampled at random from the same subpopulation or from different subpopulations, and for the probability distribution of the number of pairwise nucleotide differences. [Copyright &y& Elsevier]

Abstract: This paper presents an asynchronous integration scheme with local time stepping for transport problems. The concept consists in associating refresh time tags to the interface fluxes between cells and to the source terms within the cells rather than to the cell themselves. This scheme is less diffusive numerically than its synchronous equivalent. This method is very effective in terms of computation time for problems with localized sharp minima in the CFL condition. The method is then applied to dielectric barrier discharges for aerodynamic flow control. [Copyright &y& Elsevier]

Abstract: In this paper we report the thermal behavior of a new approach for vitrification. Thermal performance of traditional open pulled straws is compared with a new technique based on the combined use of quartz capillaries with slush nitrogen. This new method of vitrification achieved ultrafast cooling rates of 250,000°C/min. As a result, a much lower concentration of cryoprotectant was needed to reach vitrification. In fact, a cryoprotectant solution typically used in oocyte slow freezing protocols was shown to remain transparent after cooling to liquid nitrogen temperatures indicating apparent “vitrification”. This approach offers a new and very promising technique for vitrification of cells using low levels of cryoprotectants. [Copyright &y& Elsevier]

Abstract: Human and animal trails on steep hillsides often exhibit dramatic switchbacks and shortcuts. Helbing et al. have recently examined the emergence of human trail systems on flat terrains while Minetti and Margaria established the effect of gradients on human metabolic efficiency. In this paper we use these ideas to develop a semi-quantitative theoretical model of the behaviour of humans moving on a terrain with relief. The model determines the direction of movement by minimising metabolic cost per unit of distance in a desired direction. The structure of the theory resembles the Landau Theory of Phase Transitions, much used in theoretical physics. We find that both hairpin bends (switchbacks) and shortcuts appear as efficient strategies for downhill walkers, while uphill walkers retain switchbacks. For weakly inclined slopes, the best strategy involves walking directly uphill or downhill. For sufficiently steep slopes, however, we find that the best strategy should undergo a transition to a broken symmetry solution corresponding to the switchback trail patterns typical of rugged environments. The critical slope at which this transition takes place should be less steep for uphill and downhill walkers. The theory should be amenable to empirical investigation. Amongst other applications, this model will enable us to generalize the work of previous authors to real landscapes, eventually permitting the reconstruction of ancient patterns of movement in archaeological landscapes. [Copyright &y& Elsevier]

Abstract: Functioning as an “address tag” that directs nascent proteins to their proper cellular and extracellular locations, signal peptides have become a crucial tool in finding new drugs or reprogramming cells for gene therapy. To effectively and timely use such a tool, however, the first important thing is to develop an automated method for rapidly and accurately identifying the signal peptide for a given nascent protein. With the avalanche of new protein sequences generated in the post-genomic era, the challenge has become even more urgent and critical. In this paper, we have developed a novel method for predicting signal peptide sequences and their cleavage sites in human, plant, animal, eukaryotic, Gram-positive, and Gram-negative protein sequences, respectively. The new predictor is called Signal-3L that consists of three prediction engines working, respectively, for the following three progressively deepening layers: (1) identifying a query protein as secretory or non-secretory by an ensemble classifier formed by fusing many individual OET-KNN (optimized evidence-theoretic K nearest neighbor) classifiers operated in various dimensions of PseAA (pseudo amino acid) composition spaces; (2) selecting a set of candidates for the possible signal peptide cleavage sites of a query secretory protein by a subsite-coupled discrimination algorithm; (3) determining the final cleavage site by fusing the global sequence alignment outcome for each of the aforementioned candidates through a voting system. Signal-3L is featured by high success prediction rates with short computational time, and hence is particularly useful for the analysis of large-scale datasets. Signal-3L is freely available as a web-server at http://chou.med.harvard.edu/bioinf/Signal-3L/ or http://202.120.37.186/bioinf/Signal-3L, where, to further support the demand of the related areas, the signal peptides identified by Signal-3L for all the protein entries in Swiss-Prot databank that do not have signal peptide annotations or are annotated with uncertain terms but are classified by Signal-3L as secretory proteins are provided in a downloadable file. The large-scale file is prepared with Microsoft Excel and named “Tab-Signal-3L.xls”, and will be updated once a year to include new protein entries and reflect the continuous development of Signal-3L. [Copyright &y& Elsevier]

Abstract: The stability of a folded single-stranded nucleic acid depends on the composition and order of its constituent bases and may be assessed by taking into account the pairing energies of its constituent dinucleotides. To assess the possible biological significance of a computed structure, Maizel and coworkers in the 1980s compared the energy of folding of a natural single-stranded RNA sequence with the energies of several versions of the same sequence produced by shuffling base order. However, in the 2000s many took as self-evident the view that shuffling at the mononucleotide level (single bases) was conceptual wrong and should be replaced by shuffling at the level of dinucleotides (retaining pairs of adjacent bases). Folding energies then became indistinguishable from those of corresponding shuffled sequences and doubt was cast on the importance of secondary structures. Nevertheless, some continued productively to employ the single base shuffling approach, the justification for which is the topic of this paper. Because dinucleotide pairing energies are needed to calculate structure, it does not follow that shuffling should not disrupt dinucleotides. Base shuffling allows determination of the relative contributions of base composition and base order to total folding energy. The potential for secondary structure arises from pressures acting at both DNA and RNA levels, and is abundant throughout genomes—with a probable primary role in recombination. Within a gene the potential can often be accommodated, and base order and composition work together (values have the same negative sign) in contributing to total folding energy. But sometimes protein-coding pressure on base order conflicts with the pressure for secondary structure and the values have opposite signs. Total folding energy can be deemed of potential biological significance when the average of several readings is significantly less than zero. [Copyright &y& Elsevier]

Abstract: This paper is concerned with the asymptotic behavior of the regularized minimizer of an energy functional when , where is a bounded domain. The author proves convergence of minimizers to the map , where is an n-harmonic map. In addition, the author also gives the relation between the zeros of and the singularities of qualitatively. [Copyright &y& Elsevier]

Abstract: RNA interference (RNAi) is the most exciting insight in biology in past decades, which provided new perspectives into the genome-wide surveys of gene function by targeted degradation of mRNA with the introduction of small interfering RNAs (siRNAs) or small hairpin RNAs (shRNAs) in a large variety of organisms, and turned out to be a more efficient and convenient method compared with the traditional knockout pathway. What’s more, as the enhancement of its stability and improvement of its delivery vehicles, RNAi is bound to be a practical tool in determine gene function first in vitro and then in vivo. In this paper, we will focus on the recent achievements of RNAi and also depict the development of RNAi as a potentially powerful tool in studying bone-related diseases. [Copyright &y& Elsevier]

Abstract: In this paper, we performed phylogenetic analyses of Mesotriton alpestris populations from the entire range of species distribution, using fragments of two mtDNA genes, cytochrome b (309bp) and 16S rRNA (∼500bp). Sequence diversity patterns and phylogenetic analyses reveal the existence of a relict lineage (Clade A) of late Miocene origin, comprising populations from south-eastern Serbia. This lineage is proposed to be ancestor to a western and an eastern lineage, which diverged during the middle Pliocene. The western lineage is further divided in two clades (Clades B, C) of middle Pliocene origin that represent populations from Italy (B) and populations from central Europe and Iberia (C). Further subdivision, dated back to the middle-late Pliocene, was found within the eastern lineage, representing southern (Clade D) and central-northern (Clade E) Balkan populations, respectively. Extensive sequence divergence, implying greater isolation in multiple refugia, is found within eastern clades, while the western clades seem to have been involved in the colonization of central, western and north-eastern Europe from a hypothetical refugium in central Europe. The extent of divergence does not support the current taxonomy indicating cryptic speciation in the Balkans, while paedomorphic lineages were found to have been evolved during early-middle Pleistocene probably as a response to the ongoing dramatic climatic oscillations. [Copyright &y& Elsevier]

Abstract: The aim of this paper is the study of the long-term behavior of population communities described by piecewise smooth models (known as Filippov systems). Models of this kind are often used to describe populations with selective switching between alternative habitats or diets or to mimic the evolution of an exploited resource where harvesting is forbidden when the resource is below a prescribed threshold. The analysis is carried out by performing the bifurcation analysis of the model with respect to two parameters. A relatively simple method, called the puzzle method, is proposed to construct the complete bifurcation diagram step-by-step. The method is illustrated through four examples concerning the exploitation and protection of interacting populations. [Copyright &y& Elsevier]

Abstract: This paper aims to illustrate how combining multiple approaches can inform us about the neurobiology of ADHD. Converging evidence from genetic, psychopharmacological and functional neuroimaging studies has implicated dopaminergic fronto-striatal circuitry in ADHD. However, while the observation of converging evidence from multiple vantage points is convincing, it does not necessarily inform us on how these observations fit together. How does a polymorphism in a (dopamine) risk-gene for ADHD translate into a neurobiological substrate and result in behaviors that warrant a diagnosis of ADHD in a developing child? To illustrate how integrating multiple methods may help address this issue, we discuss studies combining genetics, neuropsychopharmacology and neuroimaging approaches. We show how investigators are using these approaches to map the effects of ADHD risk-genes, and common ADHD-treatments on neurobiological measures. Given its central role in both ADHD and in stimulant treatment, the dopamine transporter gene is frequently discussed as an example. The studies discussed here demonstrate that a converging methods approach is a potentially powerful tool in unraveling the neurobiology of ADHD. These approaches may suggest new avenues for research, as well as point out new directions for the development of targeted treatments for this disorder. [Copyright &y& Elsevier]

Abstract: This paper studies the molecular organization, neuronal distribution and cellular differentiation dynamics of the giant fibrillar centers (GFCs) of nucleoli in rat sensory ganglia neurons. The GFC appeared as a round nucleolar domain (1–2μm in diameter) partially surrounded by the dense fibrillar component and accompanied by numerous small FCs. By immunocytochemistry, the GFC concentrated the upstream binding factor, which may serve as a marker of this structure, and also contain RNA polymerase I, DNA topoisomerase I, SUMO-1 and Ubc9. However, they lack ubiquitin–proteasome conjugates and 20S proteasome. Transcription assay with 5′-fluorouridine incorporation revealed the presence of nascent RNA on the dense fibrillar component of the neuronal nucleolus, but not within the low electron-density area of the GFC. The formation of GFCs is neuronal size dependent: they were found in 58%, 30% and 0% of the large, medium and small neurons, respectively. GFCs first appeared during the postnatal period, concomitantly with a stage of neuronal growth, myelination and bioelectrical maturation. GFCs were not observed in segregated nucleoli induced by severe inhibition of RNA synthesis. We suggest that the formation of GFCs is associated with a high rate of ribosome biogenesis of the transcriptionally more active large-size neurons. [Copyright &y& Elsevier]

Abstract: The study of dynamics of gene regulatory networks is of increasing interest in systems biology. A useful approach to the study of these complex systems is to view them as decomposed into feedback loops around open loop monotone systems. Key features of the dynamics of the original system are then deduced from the input–output characteristics of the open loop system and the sign of the feedback. This paper extends these results, showing how to use the same framework of input–output systems in order to prove existence of oscillations, if the slowly varying strength of the feedback depends on the state of the system. [Copyright &y& Elsevier]

Abstract: Cancer risk assessments for inorganic arsenic have been based on human epidemiological data, assuming a linear dose response below the range of observation of tumors. Part of the reason for the continued use of the linear approach in arsenic risk assessments is the lack of an adequate biologically based dose response (BBDR) model that could provide a quantitative basis for an alternative nonlinear approach. This paper describes elements of an ongoing collaborative research effort between the CIIT Centers for Health Research, the U.S. Environmental Protection Agency, ENVIRON International, and EPRI to develop BBDR modeling approaches that could be used to inform a nonlinear cancer dose response assessment for inorganic arsenic. These efforts are focused on: (1) the refinement of physiologically based pharmacokinetic (PBPK) models of the kinetics of inorganic arsenic and its metabolites in the mouse and human; (2) the investigation of mathematical solutions for multi-stage cancer models involving multiple pathways of cell transformation; (3) the review and evaluation of the literature on the dose response for the genomic effects of arsenic; and (4) the collection of data on the dose response for genomic changes in the urinary bladder (a human target tissue for arsenic carcinogenesis) associated with in vivo drinking water exposures in the mouse as well as in vitro exposures of both mouse and human cells. An approach is proposed for conducting a biologically based margin of exposure risk assessment for inorganic arsenic using the in vitro dose response for the expression of genes associated with the obligatory precursor events for arsenic tumorigenesis. [Copyright &y& Elsevier]