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2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference.

OBJECTIVE: In 1991, the American College of Chest Physicians (ACCP) and the Society of Critical Care Medicine (SCCM) convened a "Consensus Conference," the goals of which were "to provide a conceptual and a practical framework to define the systemic inflammatory response to infection, which is a progressive injurious process that falls under the generalized term 'sepsis' and includes sepsis-associated organ dysfunction as well." The general definitions introduced as a result of that conference have been widely used in practice and have served as the foundation for inclusion criteria for numerous clinical trials of therapeutic interventions. Nevertheless, there has been an impetus from experts in the field to modify these definitions to reflect our current understanding of the pathophysiology of these syndromes. DESIGN: Several North American and European intensive care societies agreed to revisit the definitions for sepsis and related conditions. This conference was sponsored by the SCCM, The European Society of Intensive Care Medicine (ESICM), The American College of Chest Physicians (ACCP), the American Thoracic Society (ATS), and the Surgical Infection Society (SIS). METHODS: The conference was attended by 29 participants from Europe and North America. In advance of the conference, five subgroups were formed to evaluate the following areas: signs and symptoms of sepsis, cell markers, cytokines, microbiologic data, and coagulation parameters. The subgroups corresponded electronically before the conference and met in person during the conference. A spokesperson for each group presented the deliberation of each group to all conference participants during a plenary session. A writing committee was formed at the conference and developed the current article based on executive summary documents generated by each group and the plenary group presentations. The present article serves as the final report of the 2001 International Sepsis Definitions Conference. CONCLUSION: This document reflects a process whereby a group of experts and opinion leaders revisited the 1992 sepsis guidelines and found that apart from expanding the list of signs and symptoms of sepsis to reflect clinical bedside experience, no evidence exists to support a change to the definitions. This lack of evidence serves to underscore the challenge still present in diagnosing sepsis in 2003 for clinicians and researchers and also provides the basis for introducing PIRO as a hypothesis-generating model for future research.

Humans↗

Identifying the structure in cuttlefish visual signals.

The common cuttlefish (Sepia officinalis) communicates and camouflages itself by changing its skin colour and texture. Hanlon and Messenger (1988 Phil. Trans. R. Soc. Lond. B 320, 437-487) classified these visual displays, recognizing 13 distinct body patterns. Although this conclusion is based on extensive observations, a quantitative method for analysing complex patterning has obvious advantages. We formally define a body pattern in terms of the probabilities that various skin features are expressed, and use Bayesian statistical methods to estimate the number of distinct body patterns and their visual characteristics. For the dataset of cuttlefish coloration patterns recorded in our laboratory, this statistical method identifies 12-14 different patterns, a number consistent with the 13 found by Hanlon and Messenger. If used for signalling these would give a channel capacity of 3.4 bits per pattern. Bayesian generative models might be useful for objectively describing the structure in other complex biological signalling systems.

Animal Communication↗

Chord-distribution functions of three-dimensional random media: approximate first-passage times of Gaussian processes.

The main result of this paper is a semianalytic approximation for the chord-distribution functions of three-dimensional models of microstructure derived from Gaussian random fields. In the simplest case the chord functions are equivalent to a standard first-passage time problem, i.e., the probability density governing the time taken by a Gaussian random process to first exceed a threshold. We obtain an approximation based on the assumption that successive chords are independent. The result is a generalization of the independent interval approximation recently used to determine the exponent of persistence time decay in coarsening. The approximation is easily extended to more general models based on the intersection and union sets of models generated from the isosurfaces of random fields. The chord-distribution functions play an important role in the characterization of random composite and porous materials. Our results are compared with experimental data obtained from a three-dimensional image of a porous Fontainebleau sandstone and a two-dimensional image of a tungsten-silver composite alloy.

Journal Article↗

Model for striped growth.

We introduce a model for describing the defected growth of striped patterns. This model, while roughly related to the Swift-Hohenberg model, generates a quite different mixture of defects during phase ordering. We find two characteristic lengths in the system: the scaling length L(t), and the average width of the domain walls. The growth law exponent is larger than the value of 1/2 found in typical point defect systems.

Journal Article↗

Exactly solvable model of continuous stationary 1/f noise.

An exactly solvable model generating a continuous random process with a 1/f power spectrum is presented. Examples of such processes include the angular (phase) speed of trajectories near stable equilibrium points in two-dimensional dynamical systems perturbed by colored Gaussian noise. An exact formula giving the correlation function of the 1/f noise in terms of the correlation of the perturbing colored noises is derived, and used to show that the 1/f spectrum is found in a wide variety of cases. The 1/f noise is non-Gaussian, as demonstrated by calculating its one-time probability distribution function. Numerical simulations confirm and extend the theoretical results.

Journal Article↗

Generalized local-world models for weighted networks.

Based on the weighted scale-free network model proposed by Barrat, Barthélemy, and Vespignani [Phys. Rev. Lett. 92, 228701 (2004)] and enlightened by our local-world concept [Li and Chen, Physica A 328, 274 (2003)], we propose two generalized local-world (GLW) models for weighted complex networks. Theoretical analysis and numerical simulations show that the GLW models generate weighted networks as a crossover between exponential and scale-free weighted networks, and exhibit an alteration from assortative networks to disassortative networks.

Journal Article↗

Two-membered silicon rings on the dehydroxylated surface of silica

We present extensive modeling of the amorphous silica surface, aimed at connecting its structural and chemical features. beta-cristobalite surfaces are initially studied to model the hydroxylated surfaces. A model reconstruction of the (111) surface is used to define a path leading to the formation of two-membered silicon rings upon dehydroxylation. Subsequently, a realistic model of the amorphous dehydroxylated (dry) surface is produced, by full ab initio annealing of an initial model generated by classical simulation. The presence of surface two-membered silicon rings emerges naturally. A calculation of IR activity yields an associated peak doublet in agreement with experimental data.

Journal Article↗

Periodic knolls and valleys: coexistence of solid and liquid states in granular suspensions.

We report the spontaneous emergence of a doubly periodic train of sedimented knolls in a dense suspension. These solidified knolls rise out of, and coexist alongside, a sea of freely flowing liquid in a slowly rotating horizontal bottle. We apply a variable viscosity model that permits simultaneous analysis of fluidlike and solidlike behaviors that are ubiquitous in a variety of sedimenting flows. The model generates qualitative agreement with experiments, and produces new insights into mechanisms by which sedimented structures form.

Journal Article↗

A large complement of the predicted Arabidopsis ARM repeat proteins are members of the U-box E3 ubiquitin ligase family.

The Arabidopsis genome was searched to identify predicted proteins containing armadillo (ARM) repeats, a motif known to mediate protein-protein interactions in a number of different animal proteins. Using domain database predictions and models generated in this study, 108 Arabidopsis proteins were identified that contained a minimum of two ARM repeats with the majority of proteins containing four to eight ARM repeats. Clustering analysis showed that the 108 predicted Arabidopsis ARM repeat proteins could be divided into multiple groups with wide differences in their domain compositions and organizations. Interestingly, 41 of the 108 Arabidopsis ARM repeat proteins contained a U-box, a motif present in a family of E3 ligases, and these proteins represented the largest class of Arabidopsis ARM repeat proteins. In 14 of these U-box/ARM repeat proteins, there was also a novel conserved domain identified in the N-terminal region. Based on the phylogenetic tree, representative U-box/ARM repeat proteins were selected for further study. RNA-blot analyses revealed that these U-box/ARM proteins are expressed in a variety of tissues in Arabidopsis. In addition, the selected U-box/ARM proteins were found to be functional E3 ubiquitin ligases. Thus, these U-box/ARM proteins represent a new family of E3 ligases in Arabidopsis.

Amino Acid Motifs↗

Diffusion mechanism for phyllotaxis: theoretical physico-chemical and computer study.

The mechanism for leaf position determination by the diffusion of an inhibitor has been studied in relation to the geometry of leaf positions. A computer model has been constructed for the inhibitor-diffusion process on a cellular cylindrical surface. The behavior of the model has been analyzed mathematically. The main results are: (a) that our model generates most of the phyllotactic patterns observed in nature; and (b) that restraints have been found for permissible values of diffusion rates and decay rates of the hypothetical inhibitor.

Journal Article↗

Generalizing Swendsen-Wang to sampling arbitrary posterior probabilities.

Many vision tasks can be formulated as graph partition problems that minimize energy functions. For such problems, the Gibbs sampler provides a general solution but is very slow, while other methods, such as Ncut and graph cuts are computationally effective but only work for specific energy forms and are not generally applicable. In this paper, we present a new inference algorithm that generalizes the Swendsen-Wang method to arbitrary probabilities defined on graph partitions. We begin by computing graph edge weights, based on local image features. Then, the algorithm iterates two steps. 1) Graph clustering: It forms connected components by cutting the edges probabilistically based on their weights. 2) Graph relabeling: It selects one connected component and flips probabilistically, the coloring of all vertices in the component simultaneously. Thus, it realizes the split, merge, and regrouping of a "chunk" of the graph, in contrast to Gibbs sampler that flips a single vertex. We prove that this algorithm simulates ergodic and reversible Markov chain jumps in the space of graph partitions and is applicable to arbitrary posterior probabilities or energy functions defined on graphs. We demonstrate the algorithm on two typical problems in computer vision--image segmentation and stereo vision. Experimentally, we show that it is 100-400 times faster in CPU time than the classical Gibbs sampler and 20-40 times faster then the DDMCMC segmentation algorithm. For stereo, we compare performance with graph cuts and belief propagation. We also show that our algorithm can automatically infer generative models and obtain satisfactory results (better than the graphic cuts or belief propagation) in the same amount of time.

Algorithms↗

Dynamic Trees for unsupervised segmentation and matching of image regions.

We present a probabilistic framework--namely, multiscale generative models known as Dynamic Trees (DT)--for unsupervised image segmentation and subsequent matching of segmented regions in a given set of images. Beyond these novel applications of DTs, we propose important additions for this modeling paradigm. First, we introduce a novel DT architecture, where multilayered observable data are incorporated at all scales of the model. Second, we derive a novel probabilistic inference algorithm for DTs--Structured Variational Approximation (SVA)--which explicitly accounts for the statistical dependence of node positions and model structure in the approximate posterior distribution, thereby relaxing poorly justified independence assumptions in previous work. Finally, we propose a similarity measure for matching dynamic-tree models, representing segmented image regions, across images. Our results for several data sets show that DTs are capable of capturing important component-subcomponent relationships among objects and their parts, and that DTs perform well in segmenting images into plausible pixel clusters. We demonstrate the significantly improved properties of the SVA algorithm--both in terms of substantially faster convergence rates and larger approximate posteriors for the inferred models--when compared with competing inference algorithms. Furthermore, results on unsupervised object recognition demonstrate the viability of the proposed similarity measure for matching dynamic-structure statistical models.

Algorithms↗

Ca2+-induced structural changes in phosphorylase kinase detected by small-angle X-ray scattering.

Phosphorylase kinase (PhK), a 1.3-MDa (alphabetagammadelta)(4) hexadecameric complex, is a Ca(2+)-dependent regulatory enzyme in the cascade activation of glycogenolysis. PhK comprises two arched (alphabetagammadelta)(2) octameric lobes that are oriented back-to-back with overall D(2) symmetry and joined by connecting bridges. From chemical cross-linking and electron microscopy, it is known that the binding of Ca(2+) by PhK perturbs the structure of all its subunits and promotes redistribution of density throughout both its lobes and bridges; however, little is known concerning the interrelationship of these effects. To measure structural changes induced by Ca(2+) in the PhK complex in solution, small-angle X-ray scattering was performed on nonactivated and Ca(2+)-activated PhK. Although the overall dimensions of the complex were not affected by Ca(2+), the cation did promote a shift in the distribution of the scattering density within the hydrated volume occupied by the PhK molecule, indicating a Ca(2+)-induced conformational change. Computer-generated models, based on elements of the known structure of PhK from electron microscopy, were constructed to aid in the interpretation of the scattering data. Models containing two ellipsoids and four cylinders to represent, respectively, the lobes and bridges of the PhK complex provided theoretical scattering profiles that accurately fit the experimental data. Structural differences between the models representing the nonactivated and Ca(2+)-activated conformers of PhK are consistent with Ca(2+)-induced conformational changes in both the lobes and the interlobal bridges.

Animals↗

Socially mediated speciation.

We employ a simple model to show that social selection can lead to prezygotic reproductive isolation. The evolution of social discrimination causes the congealing of phenotypically similar individuals into different, spatially distinct tribes. However, tribal formation is only obtained for certain types of social behavior: altruistic and selfish acts can produce tribes, whereas spiteful and mutualistic behaviors never do. Moreover, reduced hybrid fitness at tribal borders leads to the selection of mating preferences, which then spread to the core areas of the respective tribes. Unlike models of resource competition, our model generates reproductive isolation in an ecologically homogeneous environment. We elaborate on how altruistic acts can lead to reproductive isolation, but also predict that certain types of competition can lead to the speciation effect. Our theory provides a framework for how individual-level interactions mold lineage diversification, with parapatric speciation as a possible end product.

Social Behavior↗

The discrete-time kinetic model analysis of DNA content distributions in experimental tumour cells.

A method was developed to analyse and characterize FMF measurements of DNA content distribution, utilizing the discrete time kinetic (DTK) model for cell kinetics analysis. The DTK model determines the time sequence of the cell age distribution during the proliferation of a tumor cell population and simulates the distribution pattern of the DNA content of cells in each age compartment of the cell cycle. The cells in one age compartment are distributed and spread into several compartments of the DNA content distribution to allow for different rates of DNA synthesis and instrument dispersion effects. It is assumed that the DNA content of cells in each age compartment has a Gaussian distribution. Thus, for a given cell age distribution the DNA content distribution depends on two parameters of the cells in each age compartment: the average DNA content and its coefficient of variation. As the DTK model generates the best fit DNA content distribution to the FMF measurement data, it enables one to estimate specific values of these two parameters in each stage of the cell cycle and to determine the fraction of cells in each cycle phase. The method was utilized to fit FMf measurements of DNA content distributions and to analyse their relationship tothe cell kinetic parameters, namely cell loss rate, cell cycle times and grwoth graction of exponentially growing Chinese hamster ovary cells in vitro and, also, with a wide range of coeffficients of variation, of the L1210 ascites tumour during the growth period.

Cell Cycle↗

Relationship between thermotolerance and hydrophobin-like proteins in aerial conidia of Beauveria bassiana and Paecilomyces fumosoroseus as fungal biocontrol agents.

AIMS: This study was to illustrate the relationship between the thermotolerance and the contents of hydrophobin-like or formic-acid-extractable (FAE) proteins in aerial conidia of Beauveria bassiana and Paecilomyces fumosoroseus produced on rice-based substrate. METHODS AND RESULTS: Survival indices of 11 isolates were separately assessed as a ratio of the viability of conidia after 3-150 min thermal stress at 48 degrees C over that of unstressed conidia and fitted well to a survival model (r(2) >/= 0.97). For a given isolate, the fitted model generated an LT(50), the time for 50% viability loss under the stress. The LT(50)s of six B. bassiana isolates (10.1-61.9 min) and five P. fumosoroseus isolates (2.8-6.2 min) were correlated (r(2) = 0.81) with FAE protein contents (6.9-23.4 microg mg(-1)). The survival indices of a fixed B. bassiana isolate after 45-min thermal stress at 48 degrees C were also correlated to the FAE protein contents from conidia produced on glucose-, sucrose-, or starch-based substrate (0.79 </= r(2) </= 0.86). Three bands of 12.0, 15.0 and 17.5 kDa were recognized from SDS-PAGE profiles of protein extracts from different isolates or from the fixed isolate grown on the three carbon sources, but the 12 kDa was less likely related to the thermotolerance. CONCLUSIONS: Approximately 80% of variability in conidial thermotolerance was attributed to either 15.0- or 17.5-kDa FAE protein or both. SIGNIFICANCE AND IMPACT OF THE STUDY: The relationship between conidial thermotolerance and FAE protein contents implicates a new way to search for fungal biocontrol agents with more thermotolerance and environmental persistence.

Colony Count, Microbial↗

Stabilities of leucine zipper dimers estimated by an empirical free energy method.

The leucine zipper motif is a characteristic amino acid sequence found in dimeric DNA-binding proteins. Computer-generated models for leucine zippers were constructed as alpha-helical coiled dimers with leucine repeated every seventh residue. An empirical Gibbs free energy, delta G, function which incorporates hydrophobic force, electrostatic interactions, and conformational entropy loss as the major intermolecular interactions was used to estimate the delta G of dimer formation in fos, jun, and GCN4 zipper sequences. The calculations showed that complexes known to form stable homo- or heterodimers have favorable (negative) delta G, while other less stable complexes have unfavorable (positive) delta G. Leucines in position d of the coiled coil contribute large hydrophobic stabilization energies while residues in the a position contribute less to dimer stability. Hydrophobic contributions show little sequence specificity, however, and do not contribute significantly to homo/heterodimer preference. Charged residues in the e and g positions, on the other hand, determine homo/heterodimer specificity. In GCN4 homodimers, residues GLU el, Glu b2, Lys g2, and Lys e4 greatly contribute to dimer stability. The preferential stability of fos-jun heterodimer over the jun-jun and fos-fos homodimers is primarily due to the side chains Asp b1, Glu g1, Asp b2, Glu e2, Glu g2, Glu g3, and Lys a5 of the fos helix, and Arg c1, Lys g1, Lys b2, Lys e2, Arg e4, and Glu g4 of the jun helix.

Leucine Zippers↗