Variations of Dynamic Contrast-Enhanced Magnetic Resonance Imaging in Evaluation of Breast Cancer Therapy Response: A Multicenter Data Analysis Challenge

Pharmacokinetic analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) time-course data allows estimation of quantitative parameters such as K^trans (rate constant for plasma/interstitium contrast agent transfer), v_e (extravascular extracellular volume fraction), and v_p (plasma volume fraction). A plethora of factors in DCE-MRI data acquisition and analysis can affect accuracy and precision of these parameters and, consequently, the utility of quantitative DCE-MRI for assessing therapy response. In this multicenter data analysis challenge, DCE-MRI data acquired at one center from 10 patients with breast cancer before and after the first cycle of neoadjuvant chemotherapy were shared and processed with 12 software tools based on the Tofts model (TM), extended TM, and Shutter-Speed model. Inputs of tumor region of interest definition, pre-contrast T₁, and arterial input function were controlled to focus on the variations in parameter value and response prediction capability caused by differences in models and associated algorithms. Considerable parameter variations were observed with the within-subject coefficient of variation (wCV) values for K^trans and v_p being as high as 0.59 and 0.82, respectively. Parameter agreement improved when only algorithms based on the same model were compared, e.g., the K^trans intraclass correlation coefficient increased to as high as 0.84. Agreement in parameter percentage change was much better than that in absolute parameter value, e.g., the pairwise concordance correlation coefficient improved from 0.047 (for K^trans) to 0.92 (for K^trans percentage change) in comparing two TM algorithms. Nearly all algorithms provided good to excellent (univariate logistic regression c-statistic value ranging from 0.8 to 1.0) early prediction of therapy response using the metrics of mean tumor K^trans and k_ep (= K^trans/v_e, intravasation rate constant) after the first therapy cycle and the corresponding percentage changes. The results suggest that the interalgorithm parameter variations are largely systematic, which are not likely to significantly affect the utility of DCE-MRI for assessment of therapy response.     

三种回归分析方法在Hyperion影像LAI反演中的比较

借助GPS进行地面精确定位,利用LAI-2000冠层分析仅在攸县黄丰桥林场开展130个样地(60m×60m)的叶面积指数(Leaf Area Index,LAI)测量.采用FLAASH模块对Hyperion数据进行大气校正并与地面同步冠层观测数据进行拟合,通过研究地面实测LAI与Hyperion影像波段及其衍生的系列植被指数(NDVI、RVI等)的相关性,筛选出估算叶面积指数的植被指数因子.应用曲线估计、逐步回归及偏最小二乘三种回归分析技术分别建立叶面积指数的最优估算模型.结果表明:参与建模的因子中,比值植被指数(RVI)与LAI的相关性最大,敏感性最高,其次是SARVI0.1,NDVI705,NDVI,SARVI0.1,SARVI0.25;曲线估计、逐步回归分析和偏最小二乘回归三种分析方法所建的6个回归模型中,偏最小二乘回归的拟合效果最好,预测值与实测值的决定系数R2为0.84、曲线估计的拟合效果最低,预测值与实测值的决定系数R2为0.64;建模精度分析表明,选用5-6个自变量因子进行LAI建模是可靠的,以6个植被因子建立的偏最小二乘回归模型预测精度最高.     

Structural and spectroscopic studies of Mo 2Cl 4(PR 3) 4 compounds with phosphines of varied basicity

The influence of the π acidity of the PR ₃ ligands in Mo ₂Cl ₄(PR ₃) ₄ compounds on the strength of the Mo−Mo quadruple bond has been studied for twenty such compounds. The main result is that reasonable correlations exist between the δ → δ* transition energy (TE) and two accepted measures of π-acidity for phosphine ligands, namely Tolman's v̄(CO) IR criterion and Bodner's Δδ(CO) ¹³C NMR criterion. For a plot of TE versusv̄(CO) a correlation coefficient of −0.892 was obtained employing data for 15 compounds. For TE versus Δδ(CO), a correlation coefficient of 0.982 was obtained for 13 compounds (excluding three for which a steric factor may be important). An attempt to correlate the Mo−Mo bond lengths with π-acidity was unsuccessful since few compounds were obtained in satisfactory form for structure determination, and for the four compounds with known structure there was no correlation. In addition to the PMe ₃ compound whose structure was previously known, those of the PEt ₃, PMe ₂Ph and PHPh ₂ compounds have been determined and are reported here.     

Can Imaging Parameters Provide Information Regarding Histopathology in Head and Neck Squamous Cell Carcinoma? A Meta-Analysis

OBJECT: Our purpose was to provide data regarding relationships between different imaging and histopathological parameters in HNSCC. METHODS: MEDLINE library was screened for associations between different imaging parameters and histopathological features in HNSCC up to December 2017. Only papers containing correlation coefficients between different imaging parameters and histopathological findings were acquired for the analysis. RESULTS: Associations between ¹⁸F-FDG positron emission tomography (PET) and KI 67 were reported in 8 studies (236 patients). The pooled correlation coefficient was 0.20 (95% CI = [?0.04; 0.44]). Furthermore, in 4 studies (64 patients), associations between ¹⁸F-fluorothymidine PET and KI 67 were analyzed. The pooled correlation coefficient between SUV_max and KI 67 was 0.28 (95% CI = [?0.06; 0.94]). In 2 studies (23 patients), relationships between KI 67 and dynamic contrast-enhanced magnetic resonance imaging were reported. The pooled correlation coefficient between K_trans and KI 67 was ?0.68 (95% CI = [?0.91; ?0.44]). Two studies (31 patients) investigated correlation between apparent diffusion coefficient (ADC) and KI 67. The pooled correlation coefficient was ?0.61 (95% CI = [?0.84; ?0.38]). In 2 studies (117 patients), relationships between ¹⁸F-FDG PET and p53 were analyzed. The pooled correlation coefficient was 0.0 (95% CI = [?0.87; 0.88]). There were 3 studies (48 patients) that investigated associations between ADC and tumor cell count in HNSCC. The pooled correlation coefficient was ?0.53 (95% CI = [?0.74; ?0.32]). Associations between ¹⁸F-FDG PET and HIF-1α were investigated in 3 studies (72 patients). The pooled correlation coefficient was 0.44 (95% CI = [?0.20; 1.08]). CONCLUSIONS: ADC may predict cell count and proliferation activity, and SUV_max may predict expression of HIF-1α in HNSCC. SUV_max cannot be used as surrogate marker for expression of KI 67 and p53.     

Control of Respiration by Cytochrome c Oxidase in Intact Cells: ROLE OF THE MEMBRANE POTENTIAL*

Metabolic control analysis was applied to intact HepG2 cells. The effect on the control coefficient of cytochrome c oxidase (CcOX) over cell respiration of both the electrical (Δψ) and chemical (ΔpH) component of the mitochondrial transmembrane proton electrochemical gradient (Δμ_H⁺) was investigated. The overall O₂ consumption and specific CcOX activity of actively phosphorylating cells were titrated with cyanide under conditions in which Δψ and ΔpH were selectively modulated by addition of ionophores. In the absence of ionophores, CcOX displayed a high control coefficient (C_IV = 0.73), thus representing an important site of regulation of mitochondrial oxidative phosphorylation. A high control coefficient value (C_IV = 0.85) was also measured in the presence of nigericin, i.e. when Δψ is maximal, and in the presence of nigericin and valinomycin (C_IV = 0.77), when Δμ_H⁺ is abolished. In contrast, CcOX displayed a markedly lower control coefficient (C_IV = 0.30) upon addition of valinomycin, when Δψ is converted into ΔpH. These results show that Δψ is responsible for the tight control of CcOX over respiration in actively phosphorylating cells.     

A Novel Method for Measuring the Diffusion,Partition and Convective Mass Transfer Coefficients of Formaldehyde and VOC in Building Materials

The diffusion coefficient (D _m) and material/air partition coefficient (K) are two key parameters characterizing the formaldehyde and volatile organic compounds (VOC) sorption behavior in building materials. By virtue of the sorption process in airtight chamber, this paper proposes a novel method to measure the two key parameters, as well as the convective mass transfer coefficient (h _m). Compared to traditional methods, it has the following merits: (1) the K, D _m and h _m can be simultaneously obtained, thus is convenient to use; (2) it is time-saving, just one sorption process in airtight chamber is required; (3) the determination of h _m is based on the formaldehyde and VOC concentration data in the test chamber rather than the generally used empirical correlations obtained from the heat and mass transfer analogy, thus is more accurate and can be regarded as a significant improvement. The present method is applied to measure the three parameters by treating the experimental data in the literature, and good results are obtained, which validates the effectiveness of the method. Our new method also provides a potential pathway for measuring h _m of semi-volatile organic compounds (SVOC) by using that of VOC.     

Solubility of gases and the temperature dependency of whole leaf affinities for carbon dioxide and oxygen: an alternative perspective

An analysis of the kinetics of simultaneous photosynthesis and photorespiration at the end of a diffusion path is applied to observed net photosynthetic rate as a function of O₂ and CO₂ concentrations. The data of Ku and Edwards (Plant Physiol. 59: 991-999, 1977) from wheat (Triticum aestivum L.) are analyzed in detail. Ku and Edwards, using an analysis that ignored diffusion resistance between the intercellular air space and fixation site, the competitive effect of CO₂ on photorespiration, and the actual concentrations of gases at the fixation site, concluded that: (a) the affinity coefficient of the leaf for CO₂ was approximately 3.5 to 5 micromolar; (b) this affinity coefficient is independent of temperature between 25 and 35 C; (c) the effect of O₂ was independent of temperature over this range; and (d) competition between CO₂ and O₂ is responsible for the major share of CO₂ loss from photosynthesis due to photorespiration. They suggest that using gas concentrations calculated as equilibium values in the liquid phase is very important in reaching these conclusions. By applying a more complete analysis to their data which includes diffusion in the cell, it is concluded that: (a) the affinity coefficient of the leaf for CO₂ is 0.1 to 1.1 micromolar; (b) the temperature dependence of this affinity coefficient cannot be determined from existing data, but there is no evidence to refute independent temperature effect on the two functions of ribulose-1,5-bisphosphate carboxylase-oxygenase being important in the regulation of whole leaf net photosynthesis; and (c) the competitive interplay of CO₂ and O₂ at ribulose-1,5-bisphosphate carboxylase may under certain conditions lead to a stimulation of fixation by the Calvin cycle because of photorespiration. These conclusions are reached whether CO₂ and O₂ are expressed as dissolved concentrations or as gas concentrations in the intercellular air space. The relative merits of these two expressions of concentration are discussed.     

Genetic differentiation of pink salmon Oncorhynchus gorbuscha Walbaum in the Asian part of the range

Genetic variation at 19 enzyme (including 11 polymorphic) and 10 microsatellite loci was examined in the population samples of odd-and even-broodline pink salmon from the southern part of Sakhalin Island, Southern Kuril Islands, and the northern coast of the Sea of Okhotsk. The estimates of relative interpopulation component of genetic variation for the allozyme loci, per broodline, were on average 0.43% (G _ST), while over the microsatellite loci it was 0.26% (the ?_ST coefficient, F-statistics based on the allele frequency variance), and 0.90% (the ρ_ST coefficient, R-statistics based on the allele size variance). The values of interlinear component constituted 2.34, 0.31, and 1.05% of the total variation, respectively. Using the allozyme loci, statistically significant intralinear heterogeneity was demonstrated among the regions, as well as among the populations of southern Sakhalin. Multidimensional scaling based on the allozyme data demonstrated regional clustering of the sample groups, representing certain populations during the spawning run or in different years. Most of the microsatellite loci examined were found to be highly polymorphic (mean heterozygosity > 0.880). The estimates of interlinear, interregional, and interpopulation variation over these loci in terms of ?_ST values were substantially lower than in terms of ρ_ST values. Regional genetic differentiation, mostly expressed at the allozyme loci between the populations from the northern Sea of Okhotsk and the Sakhalin and Kuril group of populations, was less expressed at the microsatellite loci. The differentiation between these regions observed can be considered as the evidence in favor of a large-scale isolation by distance characterizing Asian pink salmon. It is suggested that in pink salmon, low genetic differentiation at neutral microsatellite loci can be explained by extremely high heterozygosity of the loci themselves, as well as by the migration gene exchange among the populations (the estimate of the gene migration coefficient inferred from the “private” allele data constituted 2.6 to 3.4%), specifically, by the ancient migration exchange, which occurred during postglacial colonization of the range     

Structure--activity relationships of chemical inducers of carotenoid biosynthesis

Fifteen amines having a profound effect on carotenogenesis in Marsh seedless grapefruit are reported. The compounds fall into three series: Et₂N(CH₂)_nMe (n = 4–8), Et₂N(CH₂)_nPh (n = 1–5), and Et₂NCH₂CH₂OC₆H₄R (R=H, p-Me, p-Et, p-iso-Pr, p-tert-Bu), There was up to an 11-fold increase in the total carotene content. Lycopene, not normally accumulated, became a major pigment. The inducing ability of the amines on carotenoid biosynthesis is correlated with the octanol-water partition coefficient. The mode of action appears to be similar to that of 2-(4-chlorophenylthio)triethylamine hydrochloride.     

Modelling microalgal productivity in a High Rate Algal Pond based on wavelength dependent optical properties

A model is presented to predict algal biomass concentration and productivity in a High Rate Algal Pond (HRAP) at all possible combinations of incident photon flux density (PFD), pond depth and hydraulic retention time (HRT). The total extinction coefficientk _t and the absorption coefficient k_a of algal biomass were measured at 1 nm intervals. Thek _t values were used to calculate the underwater light climate, which included the spectral narrowing of the photon flux density with increasing depth. The number of quanta absorbed (QA) from the photosynthetic available radiation (PAR) was calculated using thek _a /k _t ratio and incident PFD at 1 nm intervals. Algal oxygen production is related to QA by the quantum requirement (QR), which was determined fromk _a ,and the slope of the photosynthesis versus irradiance curve (α). Based on this calculation we propose a new concept: the compensating absorption rate (CAR), which represents the rate of photon absorption necessary to balance oxygen consuming processes. The model calculated productivities using literature data on HRT, pond depth and incident PFD, that compared well with the actual measured productivities. To achieve optimal HRAP productivities under fluctuating climatological conditions, we propose a pond management strategy based on model simulations.     

Analyse des courbes de survie de nématodes phytoparasites selon le modèle de Teissier

Four survival curves of plant parasitic nematodes are analysed with Teissier's model. The model is based upon the assumption of an exponential decrease with time of the life expectancy, E(t) = E₀ exp(−αt), with E₀ the life expectancy at time 0 and α a decay coefficient. By integrating this formula we obtain an expression for the number of survivors at time t, S(t), as a function of the time, t, and S₀, the number of individuals at time 0, and the parameters E₀ and α: S(t) = S₀exp[αt −(exp(αt) −1)/αE₀. S₀ is a scaling parameter, related to the initial number of individuals in the population, thus the form of the curve depends only on the parameters E₀ and α, which are readily understandable in a biological model. These parameters E₀ and α are estimated by fitting the model to experimental data using a non-linear regression based on a least squares procedure. The results show a highly significant fit of the model to the data indicating the ability of the model to describe the plant parasitic nematodes survival curve. Results are discussed and the hypothesis of Teissier is compared with other related hypotheses.     

Modeling the performance of upflow anaerobic filters treating paper-mill wastewater using gene-expression programming

This study investigates the predictive ability of gene-expression programming (GEP) in the estimation of methane yield (Y_m) and effluent substrate (S_e) produced by two anaerobic filters. The modeling study was carried out using the data obtained from two upflow anaerobic filters - one mesophilic (35 °C) and one thermophilic (55 °C) - operated for the treatment of paper-mill wastewater under varying organic loadings. The GEP model was composed of three inputs, hydraulic retention time (T_hr), organic loading rate (R_ol), and influent substrate (S_i), and one output, either S_e or Y_m. The Stover-Kincannon model was also used for data analysis and to evaluate the prediction ability. Three statistical criteria, root mean square error (RMSE), determination coefficient (R²), and Akaike's information criteria (AIC), were the means used for comparison. The results showed that the GEP approach predicted the performance of both anaerobic filters much better than the Stover-Kincannon model.     

Evidence for the allosteric regulation of bacterial glycogen synthesis in vivo

In stationary-phase cultures of either Escherichia coli W4597(K) or G34 in various nutrient conditions there is a 10-fold range of steady-state rates of glycogen synthesis with an essentially constant steady-state level of ATP, presumably reflecting an essentially constant energy charge. The steady-state level of fructose-1,6-diphosphate in these cultures varies from experiment to experiment as a function of the observed rate of glycogen synthesis. These data were fitted to the Hill equation using an assumed Hill coefficient of 2: a plot of [Fru-P₂]²/rate of glycogen synthesis versus [Fru-P₂]² is linear with a correlation coefficient greater than 0.999, indicating a causal relationship between the concentration of Fru-P₂ and the rate of glycogen synthesis. These data provide further evidence that allosteric effects observed in vitro function in vivo.     

A comparison of approaches to estimate the inbreeding coefficient and pairwise relatedness using genomic and pedigree data in a sheep population

Genome-wide SNP data provide a powerful tool to estimate pairwise relatedness among individuals and individual inbreeding coefficient. The aim of this study was to compare methods for estimating the two parameters in a Finnsheep population based on genome-wide SNPs and genealogies, separately. This study included ninety-nine Finnsheep in Finland that differed in coat colours (white, black, brown, grey, and black/white spotted) and were from a large pedigree comprising 319 119 animals. All the individuals were genotyped with the Illumina Ovine SNP50K BeadChip by the International Sheep Genomics Consortium. We identified three genetic subpopulations that corresponded approximately with the coat colours (grey, white, and black and brown) of the sheep. We detected a significant subdivision among the colour types (F _ST = 5.4%, P<0.05). We applied robust algorithms for the genomic estimation of individual inbreeding (F _SNP) and pairwise relatedness (Φ _SNP) as implemented in the programs KING and PLINK, respectively. Estimates of the two parameters from pedigrees (F _PED and Φ _PED) were computed using the RelaX2 program. Values of the two parameters estimated from genomic and genealogical data were mostly consistent, in particular for the highly inbred animals (e.g. inbreeding coefficient F>0.0625) and pairs of closely related animals (e.g. the full- or half-sibs). Nevertheless, we also detected differences in the two parameters between the approaches, particularly with respect to the grey Finnsheep. This could be due to the smaller sample size and relative incompleteness of the pedigree for them.We conclude that the genome-wide genomic data will provide useful information on a per sample or pairwise-samples basis in cases of complex genealogies or in the absence of genealogical data.     

Determination of the drag coefficient of a toroidal plasma vortex in air

Forces acting on toroidal vortices in an unbounded medium (plasma vortices in air and vortex rings in air and water) are investigated. A solution to the equations describing such votrices is obtained. It is shown that this solution satisfactorily agrees with experiment. Based on the experimental results and the solution obtained, the drag coefficient C _x of such vortices is found. For the same Reynolds numbers, the value of C _x may be much less than the drag coefficient of a drop-shaped axisymmetric body (0.045), which is known to be the best streamlined object.     

Effect of nitrogen deficiency on the ion-exchange properties of cell wall polymers from wheat roots

The ion-exchange properties of cell wall polymers isolated from the roots of wheat (Triticum aestivum L.) plants grown on either nitrate-free (N-deficient) or nitrate-containing (+N) hydroponic nutrient medium have been investigated. Irrespective of the nitrogen nutrition regimen, the studied cell walls contained four types of ion-exchange groups: primary amino groups of structural proteins (pK_a < 3), carboxyl groups of polygalacturonic acid in pectin (pK _a ~4.7), carboxyl groups of hydroxycinnamic acids (pK _a ~7.3), and phenolic OH-groups of lignin (pK_a ~10.2). The quantitative ratio between these types of ion-exchange groups, the mass fraction of cell walls in the dry weight of roots, and the swelling coefficient of cell walls depended on the nitrate presence in the growing medium. Compared to the +N variant, the N-deficient variant was characterized by a 2.4 times higher content of phenolic OH-groups in cell walls and 1.24 times higher mass fraction of cell walls; at the same time, the swelling coefficient for this variant was lower by 10%. The obtained data indicate that nitrogen deficiency results in a formation of thicker root cell walls with a higher degree of polymer cross-linking that may be caused by the increased lignin content.     

基于形态及分子标记的濒危植物夏蜡梅自然居群的遗传变异研究

比较了濒危植物夏蜡梅(Sinocalycanthus chinensis)大明山、大雷山、龙须山3个居群的果实与种子的形态变异,采用ISSR分子标记技术分析DNA序列的变异,综合评价夏蜡梅3个居群的遗传变异。结果如下:果实性状中,果柄长、果实长、果实重、每果种子数等指标均以大明山居群最大、大雷山居群次之、龙须山居群最小,它们之间差异显著(P<0.05)。种子重、种子长、种子宽、种子厚等指标均以大雷山居群最大,与大明山居群和龙须山居群差异显著(P<0.05)。基于果实形态特征的表型分化系数(VST)在0.5518—0.9750之间,平均为0.8930,所有果实形态指标的变异大部分存在于居群间。基于种子形态特征的VST在0.1669—0.8678之间,平均为0.6240,除种子长外,其他种子形态指标的变异也大部分存在于居群间。ISSR分析表明,3个居群的多态位点百分率、Shannon信息指数、Nei基因多样性均是大明山居群最高、龙须山居群次之、大雷山居群最低。居群间的遗传分化系数(GST)为0.6050。基于ISSR分子标记数据的聚类结果显示大明山居群先与龙须山居群聚在一起,再与大雷山居群相聚,这与基于种子性状特征的聚类结果相似,而与基于果实性状特征的聚类结果不同。3个居群的种子形态特征变异系数与遗传多样性水平具有显著的正相关,且基于果实形态特征估算的VST要高于GST,而基于种子形态特征估算的VST仅略高于GST,表明夏蜡梅不同居群间的种子形态变异主要由遗传变异所造成的,而环境因子在果实形态变异中起了重要作用。Mantel检验显示3个居群基于分子标记数据的遗传距离矩阵和基于果实及种子形态特征的欧氏距离矩阵之间的相关性不显著,表明果实与种子在居群间出现的表型分化除了受遗传因素影响外,还受到其它环境因子的强烈影响。