Modeling the kinematics of the canine midcostal diaphragm

The hypotheses that the chest wall insertion (CW) is displaced laterally during inspiration and that this displacement is essential in maintaining muscle curvature of the costal diaphragmatic muscle fibers were tested. With the use of data from three dogs, caudal, lateral, and ventral displacements of CW during both quiet, spontaneous inspiration and during inspiratory efforts against an occluded airway were observed and recorded. We have developed a kinematic model of the diaphragm that incorporates these displacements. This model describes the motions of the muscle fibers and central tendon; the displacements of the midplane, muscle-tendon junction (MTJ), CW, and center of the muscle fiber-central tendon arcs are modeled as functions of muscle fiber length. In the model, the center of the fiber arcs and MTJ both move caudally parallel to the midplane during inspiration, whereas CW moves both caudally and laterally. The observed lateral displacement of CW and the observed caudal displacement of MTJ, as functions of muscle fiber length, both approximate well the theoretical displacements that would be necessary to maintain curvature of the fiber arcs. In confirming our hypotheses, we have found that lateral displacement of CW is a mechanism by which changes in the shape of the costal diaphragm, as described by its curvature, are limited.     

A comparison of test statistics for assessing the effects of concomitant variables in survival analysis

In data analysis involving the proportional-hazards regression model due to Cox (1972, Journal of the Royal Statistical Society, Series B 34, 187-220), the test criteria commonly used for assessing the partial contribution to survival of subsets of concomitant variables are the classical likelihood ratio (LR) and Wald statistics. This paper presents an investigation of three other test criteria with potentially major computational advantages over the classical tests, especially for stepwise variable selection in moderate to large data sets. The alternative criteria considered are Rao's efficient score statistic and two other score statistics. Under the Cox model, the performance of these tests is examined empirically and compared with the performance of the LR and Wald statistics. Rao's test performs comparably to the LR test in all the cases considered. The performance of the other criteria is competitive in many cases. The use of these statistics is illustrated in a study of coronary artery disease.     

Testing for Poisson Zero Inflation in Disease Mapping

When analyzing mortality data due to rare diseases in small areas, it is common to find several health zones with no mortality cases. In these circumstances, the classical homogeneous model based on the Poisson distribution used to estimate the relative risks within each area may encounter lack of fit due to a disproportionately large frequency of zeros. To cope with these zeros, the zero inflated Poisson model can be used. In this paper, we propose a test for detecting zero inflation in the context of disease mapping which is based on bootstrap techniques. The test is illustrated using male mortality data due to brain cancer in Navarra, Spain. In addition, comparisons with other tests for Poisson zero inflation such as the score test and the likelihood ratio test are carried out in terms of empirical power and size using the brain cancer scenario. The proposed bootstrap test has good power and size and works well when detecting the excess of zeros in small area data sets. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Issues regarding artificial neural network modeling for reactors and fermenters

In recent years researchers in many areas have used artificial neural networks (ANNs) to model a variety of physical relationships. While in many cases this selection appears sound and reasonable, one must remember than ANN modeling is an empirical modeling technique (based on data) and is subject to the limitations of such techniques. Poor prediction occurs when the training data set does not contain adequate "information" to model a dynamic process. Using data from a simulated continuous-stirred tank reactor, this paper illustrates four scenarios: (1) steady state, (2) large process time constant, (3) infrequent sampling, and (4) variable sampling rate. The first scenario is typical of simulation studies while the other three incorporate attributes found in real plant data. For the cases in which ANNs predicted well, linear regression (LR), one of the oldest empirical modeling techniques, predicted equally well, and when LR failed to accurately model/predict the data, ANNs predicted poorly. Since real plant data would resemble a combination of situations (2), (3), and (4), it is important to understand that empirical models are not necessarily appropriate for predictively modeling dynamic processes in practice.     

Charge delocalization in proton channels, I: the aquaporin channels and proton blockage

The explicit contribution to the free energy barrier and proton conductance from the delocalized nature of the excess proton is examined in aquaporin channels using an accurate all-atom molecular dynamics computer simulation model. In particular, the channel permeation free energy profiles are calculated and compared for both a delocalized (fully Grotthuss shuttling) proton and a classical (nonshuttling) hydronium ion along two aquaporin channels, Aqp1 and GlpF. To elucidate the effects of the bipolar field thought to arise from two alpha-helical macrodipoles on proton blockage, free energy profiles were also calculated for computational mutants of the two channels where the bipolar field was eliminated by artificially discharging the backbone atoms. Comparison of the free energy profiles between the proton and hydronium cases indicates that the magnitude of the free energy barrier and position of the barrier peak for the fully delocalized and shuttling proton are somewhat different from the case of the (localized) classical hydronium. The proton conductance through the two aquaporin channels is also estimated using Poisson-Nernst-Planck theory for both the Grotthuss shuttling excess proton and the classical hydronium cation.     

Computer simulation of single-file transport

A stochastic model of single-file transport was developed as the Markov process in continuous time technique. The model was constructed using an EC-1060 computer. Unidirectional fluxes were investigated and populations of channels were correlated with flux fluctuations. The profiles of channel populations were shown to have nonlinear shapes even with the transport of nonelectrolyte (the classical diffusion approach gives linear profiles). The relationship between the paired correlation function F(AB) and the concentration of transported particles was examined. The F(AB) profile was shown to become flattened (or exponential for asymmetrical cases) at high concentrations. The concentration dependence jA/jA0 ratio were analyzed, where jA is a single-file unidirectional flux, jA0 is unidirectional flux for the case of free diffusion. An interesting "stack" phenomenon was observed for abnormal time correlations of single-file fluxes.     

Genetic analysis of thr mutations in Salmonella typhimurium

Previous workers divided threonine-requiring (Thr(-)) strains of Salmonella into three phenotypes with mutations in four complementation groups. The mutations were deemed to define four genes in the order thrD-C-A-B at minute zero on the Salmonella linkage map. In the present study 12 of these mutants were reexamined together with eight new Thr(-) strains. The three phenotypes were: homoserine-requiring (Hom(-)); Thr(-), feeders of Hom(-) strains; Thr(-), nonfeeders. Exact correlation between these phenotypic groups and three complementation groups was confirmed by abortive transduction. No evidence was found for intergenic complementation between mutations in Hom(-) strains. It is proposed that thr mutations define three genes rather than four and that these be renamed thrA (Hom(-)), thrB (Thr(-) feeders), and thrC (Thr(-) nonfeeders) to correspond with the sequence of reactions in threonine biosynthesis. Double mutant trpRthr strains were used in reciprocal three-point transduction tests to establish the order of thr mutation sites. Although revisions were made in the classification or location of several mutations, there was an overall correlation of complementation group, phenotype, and map position. The present data provide a basis for further correlation of threonine genes and biosynthetic enzymes, and analysis of cross regulation in aspartate amino acid biosynthesis in Salmonella.     

Compliances of the liquid-filled lungs and chest wall during development in fetal sheep.

Our aim was to measure the compliance of the liquid-filled lungs (CL), and the compliance of the chest wall (CW) in fetal sheep in utero. CL and CW were measured in 6 fetuses. The compliance of the lungs and chest wall combined (respiratory system, Crs) was measured in 9 fetuses. Pressure differences across the lungs (PL), chest wall (PW) and respiratory system (Prs) were measured while the lungs were deflated and inflated with liquid from their resting lung liquid volume (V1). V1 was measured using an indicator dilution technique. Specific compliance values were obtained by normalizing the values of CL, CW and Crs with respect to values of V1. From values obtained during stepwise inflation from V1, specific compliances (ml/cm H2O/ml of lung liquid) were: lungs, 0.22 +/- 0.02; chest wall, 0.41 +/- 0.07; respiratory system, 0.13 +/- 0.01. Specific compliances of the lungs, chest wall and respiratory system did not change significantly with advancing gestational age from 120 to 143 days. Our baseline data will be valuable in assessing the in utero progress of the structural development of the lungs following manipulations known to cause altered lung growth.     

Assessing the goodness-of-fit of hidden Markov models

In this article, we propose a graphical technique for assessing the goodness-of-fit of a stationary hidden Markov model (HMM). We show that plots of the estimated distribution against the empirical distribution detect lack of fit with high probability for large sample sizes. By considering plots of the univariate and multidimensional distributions, we are able to examine the fit of both the assumed marginal distribution and the correlation structure of the observed data. We provide general conditions for the convergence of the empirical distribution to the true distribution, and demonstrate that these conditions hold for a wide variety of time-series models. Thus, our method allows us to compare not only the fit of different HMMs, but also that of other models as well. We illustrate our technique using a multiple sclerosis data set.     

Relative growth and size at onset of sexual maturity of the brown crab,Cancer pagurus in the Isle of Man,Irish Sea

In this study, the relative growth, size–weight relationships and size at onset of maturity of the brown crab Cancer pagurus were investigated in the Isle of Man. For the analyses of relative growth and size at onset of maturity, the samples were collected seasonally between autumn 2012 and spring 2013 using several methods: pot surveys, dredge and trawl surveys, market surveys and shore surveys. Results showed that allometric growth occurred in the chelipeds of males (n?=?87) and in the abdomen of females (n?=?222). Four different measures of maturity (behavioural, functional, morphometric and physiological) were examined. With respect to the behavioural maturity, the smallest female crab found with a sperm plug measured 110?mm CW, whereas in terms of functional maturity the smallest ovigerous female had a CW of 134?mm. Based on direct observations of gonad maturity, 50% of females were mature at 108?mm CW, whereas 50% of males were mature at 89?mm CW. The size at the onset of maturity measurements of female and male C. pagurus based on gonad development is smaller than the current minimum landing size (130?mm), and therefore this suggests that the current minimum landing size is an adequate management measure.     

Ozone inactivation of Cryptosporidium parvum in demand-free phosphate buffer determined by in vitro excystation and animal infectivity.

Inactivation of Cryptosporidium parvum oocysts by ozone was performed in ozone demand-free 0.05 M phosphate buffer (pH 6.9) in bench-scale batch reactors at 7 and 22 degrees C. Ozone was added to each trial from a concentrated stock solution for contact times ranging from 5 to 15 min. The viability of the control and treated oocysts was determined by using in vitro excystation and infection in neonatal CD-1 mice. It was found that excystation consistently underestimated inactivation when compared with animal infectivity (P < or = 0.05). As inactivations increased, the difference between excystation and infectivity also increased. The inactivation kinetics of C. parvum by ozone deviated from the simple first-order Chick-Watson model and was better described by a nonlinear Hom model. The use of the Hom model for predicting inactivation resulted in a family of unique concentration and time values for each inactivation level rather than the simple CT product of the Chick-Watson model.     

Characterization and performance of a near-infrared 2-deoxyglucose optical imaging agent for mouse cancer models

Malignant neoplasms exhibit an elevated rate of glycolysis over normal cells. This characteristic can be exploited for optical imaging of tumors in mice. A near-infrared fluorophore, IRDye 800CW, emission maximum 794 nm, was conjugated to 2-deoxyglucose (2-DG). An immunofluorescent cell-based assay was used to evaluate specificity and sensitivity of the conjugate in cultured cell monolayers. Dose-dependent uptake was established with increasing concentrations of IRDye 800CW 2-DG for epithelial and prostate carcinomas. IRDye 800CW 2-DG was specifically blocked by an antibody against GLUT1 glucose transporter, and by excess unlabeled 2-DG or d-glucose. Signal was increased by a phorbol ester activator of glucose transport. Fluorescence microscopy data confirmed localization of the conjugate in the cytoplasm. Subsequent in vivo studies optimized dose, clearance, and timing for signal capture in nude mouse xenografts. In all cases, tumors were clearly imaged with good signal-to-noise characteristics. These data indicate that IRDye 800CW 2-DG is a broadly applicable optical imaging agent for in vivo imaging of neoplasms in mice.     

结核杆菌可溶性细胞壁抗原与重组38Kd蛋白用于结核病血清学诊断的价值

目的探讨结核杆菌CW抗原和rTPA38蛋白用于结核病血清学诊断的价值。方法以CW和rTPA38蛋白为抗原,LAM为对照,用DICFA检测血清中的抗结核抗体。结果191例肺结核病人血清,用CW、rTPA38和LAM检测的敏感性分别为78．0％、65．5％和72．3％,特异性分别为95．9％、98．4％和95．9％。统计分析显示CW和rTPA38检测肺结核病人血清抗结核抗体的敏感性差异有非常显著性（χ^2=16．230,P〈0．01）。两者检测健康人和非结核组病人血清的特异性差异有显著性（χ^2=3．972,P〈0．05）。检测痰涂片阳性血清86例,发现CW和rTPA38与痰阳的一致率分别为84．9％和69．8％,CW抗原与痰涂片的阳性反应明显高于rTPA38。结论CW抗原有较好的敏感性和特异性,且与痰涂片有较高的符合率,有助于结核病的血清学诊断。     

Substitution of crude cell wall for neutral detergent fibre in the equations of the Cornell Net Carbohydrate and Protein System that predict carbohydrate fractions: application to sunflower ( Helianthus annuus L.)

Prediction of carbohydrate fractions using equations from the Cornell Net Carbohydrate and Protein System (CNCPS) is a valuable tool to assess the nutritional value of forages. In this paper, these carbohydrate fractions were predicted using data from three sunflower (Helianthus annuus L.) cultivars, fresh or as silage. The CNCPS equations for fractions B2 and C include measurement of ash and protein-free neutral detergent fibre (NDF) as one of their components. However, NDF lacks pectin and other non-starch polysaccharides that are found in the cell wall (CW) matrix, so this work compared the use of a crude CW preparation instead of NDF in the CNCPS equations. There were no differences in the estimates of fractions B1 and C when CW replaced NDF; however, there were differences in fractions A and B2. Some of the CNCPS equations could be simplified when using CW instead of NDF. Notably, lignin could be expressed as a proportion of DM, rather than on the basis of ash and protein-free NDF, when predicting CNCPS fraction C. The CNCPS fraction B1 (starch + pectin) values were lower than pectin determined through wet chemistry. This finding, along with the results obtained by the substitution of CW for NDF in the CNCPS equations, suggests that pectin was not part of fraction B1 but present in fraction A. We suggest that pectin and other non-starch polysaccharides that are dissolved by the neutral detergent solution be allocated to a specific fraction (B2) and that another fraction (B3) be adopted for the digestible cell wall carbohydrates.     

Network pharmacology combined with metabolomics approach to investigate the protective role and detoxification mechanism of Yunnan Baiyao formulation

BackgroundYunnan Baiyao (YNBY) is a traditional Chinese medicine formulae, which has the functions of hemostasis, activating blood circulation and removing blood stasis, anti-inflammation, etc. Although the presence of Caowu (CW, Aconiti Kusnezoffii Radix), the detoxification mechanism of YNBY is still unclear.PurposeIn current study, network pharmacology, toxicological methods and metabolomics technique were applied to explore YNBY in attenuating toxicity of CW.MethodsPrediction of targets and pathways of CW were carried out by commonly used network pharmacological method. Simultaneously, SD rats were orally administrated with CW, processed CW (ZCW), YNBY, and YNBY which lack of CW (QCW) for 15 days. Tissue samples were observed with histopathology. Urine samples were analyzed with ultra-performance liquid chromatography-mass spectrometry to screen differential metabolites and related metabolic pathways associated with toxicity of CW. Furthermore, by comparing the changes of the metabolite contents, focused the attenuated metabolic pathway. Finally, the network pharmacological and experimental data were integrated to investigate detoxification mechanism of YNBY.ResultsA total of 44 potential toxicity biomarkers were identified and 14 related pathways were involved in the toxicity of CW. Furthermore, 5 core toxicity biomarkers (2-keto-6-acetamidocaproate, γ-glutamylleucine, prostaglandin E₃, 4-hydroxy-5-(3’-hydroxyphenyl)-valeric acid-3’-O-sulphate, and 3,4-dihydroxy- phenylglycol O-sulfate) were regulated to normal condition in YNBY group. Lysine degradation was locked as the core metabolic pathway of detoxification of YNBY. Integrating the predicted results of network pharmacology, ACHE, SLC6A3, SLC6A4 might be the target of protective role of other herbs in YNBY.ConclusionNetwork pharmacology combined with metabolomics exhibited a powerful mean to investigate the herbal toxicity and probed into the detoxification mechanism of formulae, which contributes to its safety evaluation.     

Contextual conditioning. A comparison of eastern and western views

Eastern and Western interpretations of contextual control of phasic conditional responses (transswitching) are contrasted. The Eastern (Asratyan, 1965) approach emphasizes the role of the tonic conditional stimulus and the (hypothetical) tonic response it evokes. The Western (Lachnit, 1986) approach emphasizes the role of compound conditional stimuli. Although Lachnit showed that transswitching-like results can be obtained without a tonic stimulus, attempts to simulate transswitching experiments using a computer model of the Rescorla-Wagner theory (Kimmel and Lachnit, 1988) have shown that predictions from the theory approximate empirical results in human classical conditioning only when the tonic stimulus is given far greater weight than the phasic stimulus. In other words, only when the Rescorla-Wagner theory is made more like Asratyan's theory, can the compound conditional stimulus approach account for real empirical transswitching data.     

Low Incidence of Chest Wall Pain with a Risk-Adapted Lung Stereotactic Body Radiation Therapy Approach Using Three or Five Fractions Based on Chest Wall Dosimetry

Purpose

To examine the frequency and potential of dose-volume predictors for chest wall (CW) toxicity (pain and/or rib fracture) for patients receiving lung stereotactic body radiotherapy (SBRT) using treatment planning methods to minimize CW dose and a risk-adapted fractionation scheme.

Methods

We reviewed data from 72 treatment plans, from 69 lung SBRT patients with at least one year of follow-up or CW toxicity, who were treated at our center between 2010 and 2013. Treatment plans were optimized to reduce CW dose and patients received a risk-adapted fractionation of 18 Gy×3 fractions (54 Gy total) if the CW V30 was less than 30 mL or 10–12 Gy×5 fractions (50–60 Gy total) otherwise. The association between CW toxicity and patient characteristics, treatment parameters and dose metrics, including biologically equivalent dose, were analyzed using logistic regression.

Results

With a median follow-up of 20 months, 6 (8.3%) patients developed CW pain including three (4.2%) grade 1, two (2.8%) grade 2 and one (1.4%) grade 3. Five (6.9%) patients developed rib fractures, one of which was symptomatic. No significant associations between CW toxicity and patient and dosimetric variables were identified on univariate nor multivariate analysis.

Conclusions

Optimization of treatment plans to reduce CW dose and a risk-adapted fractionation strategy of three or five fractions based on the CW V30 resulted in a low incidence of CW toxicity. Under these conditions, none of the patient characteristics or dose metrics we examined appeared to be predictive of CW pain.     

SRAP Polymorphisms Associated to Cell Wall Degradability in Lignified Stems of Alfalfa

The identification of DNA polymorphisms associated to increased cell wall (CW) degradability could accelerate the development of alfalfa (Medicago sativa L.) cultivars with superior ethanol conversion yields. Genotypes with high (D+) or low (D?) CW degradability were recently identified within a biomass-type and three winter-hardy-type populations using near-infrared reflectance spectroscopy (NIRS) prediction of CW glucose released by enzyme saccharification. In this report, we used sequence-related amplified polymorphism to search for DNA variations associated to differences in enzyme-released glucose. A bulk segregant analysis (BSA) of pooled DNA samples (20 plants/bulk) from D+, D?, and randomly chosen genotypes uncovered polymorphisms associated to CW degradability. Polymorphisms that increase or decrease in intensity between D+ and D? bulks indicated the presence of genomic regions with either positive or negative effects on CW degradability. A primer pair (Me4-R14) generated a fragment, which increased in intensity in the D+ bulk of the biomass-type population. Conversely, the amplification of that fragment declined in the D+ bulks of the winter-hardy-type populations. Interestingly, these populations differ in their degradability. Assessment of the genotypic occurrence of this fragment confirmed that polymorphism detected with BSA reflects changes in the frequency of occurrence within populations. Sequence analysis of the Me4-R14 fragment revealed homologies with sequences from Medicago truncatula, a model species for legumes with documented synteny with M. sativa. Our results show that genomic regions associated to CW degradability can be identified using the combination of BSA of genotypes with contrasted degradability and a PCR-based amplification technique.     

微嗜酸寡养单胞菌中的漆酶对黄曲霉毒素B1降解脱毒的生物活性

[目的]探究微嗜酸寡养单胞菌中的漆酶对AFB1的降解活性,并确定漆酶在菌株CW117降解代谢AFB1过程中的贡献.[方法]从微嗜酸寡养单胞菌基因组中,共筛选到两个漆酶基因lc1和lc2,并用大肠杆菌BL21外源表达蛋白rLC1和rLC2,在体外检测其对AFB1的降解活性.同时参考前人报道,研究了氧化性辅剂对漆酶AFB1...