A Rule-Based Decision Support System for Critical Infrastructure Management

This article presents a new rule-based decision support system for critical infrastructure management based on the interdependencies among critical infrastructures. Unlike the conventional flood front prediction model, the new failure front prediction model consists of both physical parameters and interdependencies among infrastructures, which is represented by a multi-level complex network. This study employs advanced computation methods to build tools for better understanding emergent behavior of water security infrastructure systems for use in developing superior preparedness and response strategies. This study highlights the important role played by the interdependencies among the infrastructures in failure front prediction.     

Explaining Asian American achievement

ABSTRACT

Jennifer Lee and Min Zhou’s The Asian American Achievement Paradox is a remarkable analysis of the educational upward mobility of Chinese and Vietnamese Americans in Los Angeles. It also provides important insights about the status of contemporary Asian Americans more generally. While critical of the ‘model minority’ thesis, the authors take seriously the role of culture in fostering educational attainment. However, their emphasis on immigrant selectivity and individual psychology may be misplaced when it comes to understanding the achievement of second-generation groups.     

Regular systems of inbreeding

Regular systems of inbreeding with discrete, nonoverlapping generations and the same number of individuals and mating pattern in every generation are studied. The matrix Q that specifies the recursion relations satisfied by the probabilities of identity is expressed in terms of the matrix M that describes the mating system. Necessary and sufficient conditions for convergence to genetic uniformity are given, and it is determined which probabilities of identity approach one. If the mating system has certain symmetries and these are imposed initially, then a matrix R, of lower dimension than Q, specifies the recursion relations. For such a mating system, for generic initial conditions, the condensed matrix R suffices for determining whether convergence to uniformity occurs and which probabilities of identity approach one. If Q is irreducible, the maximal eigenvalue of R is the same as that of Q. If Q is also aperiodic, this implies that the asymptotic rate of convergence to homogeneity of the condensed system is the same as that of the complete one. The above results apply to autosomal loci in monoecious (with or without selfing) and dioecious populations and to X-linked loci. As an example, all the eigenvalues and right and left eigenvectors of Q for circular mating are found.Supported by National Science Foundation Grant BSR-8512844     

Comprehensive Logic Based Analyses of Toll-Like Receptor 4 Signal Transduction Pathway

Among the 13 TLRs in the vertebrate systems, only TLR4 utilizes both Myeloid differentiation factor 88 (MyD88) and Toll/Interleukin-1 receptor (TIR)-domain-containing adapter interferon-β-inducing Factor (TRIF) adaptors to transduce signals triggering host-protective immune responses. Earlier studies on the pathway combined various experimental data in the form of one comprehensive map of TLR signaling. But in the absence of adequate kinetic parameters quantitative mathematical models that reveal emerging systems level properties and dynamic inter-regulation among the kinases/phosphatases of the TLR4 network are not yet available. So, here we used reaction stoichiometry-based and parameter independent logical modeling formalism to build the TLR4 signaling network model that captured the feedback regulations, interdependencies between signaling kinases and phosphatases and the outcome of simulated infections. The analyses of the TLR4 signaling network revealed 360 feedback loops, 157 negative and 203 positive; of which, 334 loops had the phosphatase PP1 as an essential component. The network elements'' interdependency (positive or negative dependencies) in perturbation conditions such as the phosphatase knockout conditions revealed interdependencies between the dual-specific phosphatases MKP-1 and MKP-3 and the kinases in MAPK modules and the role of PP2A in the auto-regulation of Calmodulin kinase-II. Our simulations under the specific kinase or phosphatase gene-deficiency or inhibition conditions corroborated with several previously reported experimental data. The simulations to mimic Yersinia pestis and E. coli infections identified the key perturbation in the network and potential drug targets. Thus, our analyses of TLR4 signaling highlights the role of phosphatases as key regulatory factors in determining the global interdependencies among the network elements; uncovers novel signaling connections; identifies potential drug targets for infections.     

Structural Model of the Pre-pore Ring-like Structure of Panton-Valentine Leukocidin: Providing Dimensionality to Biophysical and Mutational Data

Abstract

Panton-Valentine leukocidin (PVL) is a bipartite toxin that plays an important role in the pathogenesis of methicillin-resistant Staphylococcus aureus. Recent clinical data suggest a correlation between PVL and severe cases of S. aureus pneumonia. A clear understanding of the structure and function of PVL is critical to the development of novel, effective treatments. Here, we report an all-atom model of the macromolecular structure of Panton-Valentine leukocidin in its octameric, pre-pore conformation that confirms and extends our understanding of the toxin's mechanism of action.     

Repeatability and precision of a weighted centroid method for estimating dynamic in vivo tibiofemoral surface interactions in sheep

Persistent changes in joint biomechanics resulting from knee injury are thought to contribute to progressive cartilage damage and post-traumatic osteoarthritis (PTOA). The identification and quantification of in vivo tibiofemoral surface interactions are critical to understanding them, particularly abnormal interactions that are damaging to articular cartilage and other structures of the knee. In this study, we describe an approach for understanding such potential interactions by using a weighted centroid derived from in vivo stifle kinematics in sheep. Collectively, repeatability and sensitivity analyses indicate that the magnitude of the changes in tibiofemoral centroid location resulting from combined ligament transection is greater than the repeatability and precision of the current weighted centroid approach, making this method useful for describing the changes in dynamic surface interactions that may be relevant in the pathogenesis of PTOA in this stifle injury model.     

Using a zebrafish Danio rerio model system to study NOTCH1‐induced T‐cell leukaemia

Notch receptors are a family of cell‐surface proteins that regulate cell fate decisions and growth control. Human NOTCH1 gain‐of‐function mutations–deletions have been found in c. 60% of patients with T‐cell acute lymphoblastic leukaemia (T‐ALL). Therefore, understanding the molecular mechanisms by which dysregulated Notch‐signalling induces leukaemia is of importance and may reveal novel targets for the development of more effective therapies. Zebrafish, Danio rerio, is an ideal model system to use for forward genetic screens to uncover pathways critical for transformation. Danio rerio also have the capacity for small molecule screening for drug discovery. rag2‐ICN1‐EGFP transgenic fish have been created that develop a T‐cell leukaemia, and these fish are now being used in genetic modifier screens.     

Comparative analysis of <Emphasis Type="Italic">iol</Emphasis> clusters in <Emphasis Type="Italic">Lactobacillus casei</Emphasis> strains

The present study was designed to expand genetic knowledge of myo -inositol (MI) metabolism in Lactobacillus casei. Twenty-four L. casei isolates of dairy origin were tested for the presence of iol cluster. PCR screening revealed eight strains encoded functions involved in MI utilization, of which one strain was able to use MI as carbon source. To gain a deeper understanding of the function of iol genes, four of the eight observed iol clusters were subjected to the full sequencing procedure. The results showed that the iol cluster was not a common feature among dairy L. casei strains. In addition, the four iol clusters were highly similar to one another in terms of sequence similarity and operon architecture. However, abundant polymorphisms that comprised a majority of synonymous mutations were detected throughout the full sequences. Three of them distributed among iolB, iolC, and iolT genes were found in linkage to MI-negative phenotype. Compared with other bacterial iol clusters, the iol cluster of L. casei showed a high similarity with that of Bacillus subtilis.     

Cancer risk among young men with weight gain after smoking cessation: A population-based cohort study

BackgroundSmoking cessation may help the current smokers to reduce cancer risk. However, weight gain following smoking cessation may attenuate the protective association of cessation with cancer.Patients and methodsOur study included 1,278,794 men who were aged 20–39 years and underwent two consecutive health examinations by the National Health Insurance Service, without previous diagnosis of cancer. Participants were categorized into continual smokers, quitters with different degree of body weight change, and never smokers based on the biennial national health screening program (2002–2003 and 2004–2005) and were followed from January 1, 2006 to December 31, 2015. Cox proportional hazard models and restricted cubic spline model was used to evaluate the association of post-cessation weight change and cancer risk after adjustment for potential confounders.ResultsDuring the 10 years of follow-up, the analyses included 1,278,794 men with 21,494 cancer incidences. Compared to continual smokers, quitters without weight gain of 2.0 kg had significantly lower risk of obesity-related cancer (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.79-0.97), smoking-related cancer (HR, 0.90; 95% CI, 0.83 to 0.98), and gastrointestinal cancer (HR, 89; 95% CI, 0.80 to 0.98). Weight gain among quitters attenuated the risk reduction of cancer compared to continual smoking. Among quitters, weight gain up to 5.0 kg with smoking cessation showed protective association with cancer risk among quitters without weight gain.ConclusionExcessive weight gain with smoking cessation among quitters was not associated with reduced risk of several cancer types. This association should be taken into account when recommending smoking cessation to prevent cancer     

Assessing the effects of multiple infections and long latency in the dynamics of tuberculosis

In order to achieve a better understanding of multiple infections and long latency in the dynamics of Mycobacterium tuberculosis infection, we analyze a simple model. Since backward bifurcation is well documented in the literature with respect to the model we are considering, our aim is to illustrate this behavior in terms of the range of variations of the model's parameters. We show that backward bifurcation disappears (and forward bifurcation occurs) if: (a) the latent period is shortened below a critical value; and (b) the rates of super-infection and re-infection are decreased. This result shows that among immunosuppressed individuals, super-infection and/or changes in the latent period could act to facilitate the onset of tuberculosis. When we decrease the incubation period below the critical value, we obtain the curve of the incidence of tuberculosis following forward bifurcation; however, this curve envelops that obtained from the backward bifurcation diagram.     

Percolation Transition in the Parallel Hard-cube Model Fluid

Abstract

Pressure and self-diffusion calculations for a model fluid system of parallel hard cubes are reported. When viewed alongside equations of state incorporating the known coefficients in the virial expansion (b ₂ to b ₇), a weak phase change is postulated around 1/4 close-packing. Changes in behaviour are also seen at the same density for the self-diffusion coefficient and an associated single-particle free volume. It is conjectured that a transition may be identifiable with the low-density percolation transition that occurs in all hard-core fluids when the single particle configurational volume becomes extensive. If the hard-sphere model were to behave similarly, the observations may have implications for the general development of liquid-state theory.     

A note on the mathematical biology of automobile driving

It is pointed out that the three different stimuli for a corrective turn, namely the distance from the edge of the lane, the rate of approach to the edge, and the angle between the direction of the car and the direction of the lane (Bull. Math. Biophysics,28, 645–654, 1966,29, 181–186, 1967) may act all three simultaneously. It is found that in that case the tracking curve of the car is stable below a critical speed and becomes unstable above it.     

江西省县级综合医院基础设施和收支现状分析

目的 了解江西省县级综合医院的基础设施和收支现状,为今后卫生行政部门合理配置卫生资源提供科学依据。方法 采用普查方法对2007年江西省11个地级市的90家县级综合医院进行调查。结果 江西省县级综合医院的基础设施总体情况尚可,但重点设备的配置率较低;财政补助比重小,收支不平衡。结论 对尚未达到标准的基础设施进行合理配置,加大对县级综合医院的财政投入。     

Marker-based adjustment of the additive relationship matrix for estimation of genetic parameters��an example using Eucalyptus cladocalyx

The effects of adjusting additive (numerator) relationship matrices (A) for inbreeding estimates taken from molecular markers were investigated using a small, model population of Eucalyptus cladocalyx. A number of individual-tree, mixed-models were compared, incorporating estimates of population- and family-level selfing and ancestral inbreeding applied either as average values to the entire population or as variable estimates for subpopulation and family groups. The consequences of ignoring inbreeding were inflated additive genetic variance estimates and underestimation of residual variance, with resulting inflation of heritability. We found models that correct for differential inbreeding at the subpopulation level give similar results to more complex ones including family-level estimates. Our analysis indicates that the commonly applied coefficient of relationship for first-generation eucalypt progeny of ρ = 1/2.5 appears to be quite suitable for correcting variance component and heritability estimates. However, if inbreeding is not specifically corrected for by adjustment of A, some minor rank changes of individual breeding values can occur, especially where levels of inbreeding vary among families, and some suboptimal selections and loss of genetic gain may ensue.     

An overview of mechanistic modeling of liquid chromatography

Abstract

Liquid chromatography is considered to be the bottleneck for purification of therapeutic proteins. Development and optimization of chromatography process is a cumbersome activity due to the increasing complexities in the types and content of impurities present in the high product titer cell culture harvest obtained from the upstream processing. Further, regulatory expectations are continuously rising with the recent initiatives of quality by design and process analytical technology expecting the manufacturer to have a deeper understanding of the process and the product. Mechanistic modeling is one approach to gain this deeper understanding of a process step. It involves modeling of the underlying physicochemical processes. A well calibrated model with acceptable predictability can be very effective in both process optimization and process characterization activities. In this paper we provide an overview of mechanistic modeling of liquid chromatography. We discuss the various components that such a model entails and also presents the status quo of this area.     

Using concept maps to characterise cellular respiration knowledge in undergraduate students

ABSTRACT

Meaningful learning occurs by relating new information to and revising prior knowledge, making it essential to understand student knowledge before helping them move toward a more scientific understanding. In this study, we characterise prior knowledge about cellular respiration in undergraduate students enrolled in introductory biology by analysing student-constructed concept maps (N = 182) and interviews (N = 9). Students were instructed to create concept maps from a bank of 20 concepts with the purpose of interconnecting the processes of cellular respiration, showing how pools of ATP are generated and used, and identifying where the events of cellular respiration occur. Student maps were analysed for content, quality and organisation of knowledge. Interviews were used to corroborate inferences made from concept maps. Students had a simplified understanding of cellular respiration and its processes as evident by cognitive structures with limited quantities of schemas that were vaguely connected and linearly organised. Furthermore, students had a better understanding of glycolysis than fermentation. Instructors can use these findings to help students build better knowledge of cellular respiration by focusing on incorporating relevant schemas, creating quality connections among schemas, and organising their knowledge of cellular respiration to reflect biological complexity.