Correlation between qualitatively distributed predicting variables and chemical terms in acridine derivatives using principal component analysis

When biological variables are not continuously distributed, the multiple and multivariate regression analysis cannot be used to correlate these variables against chemical regressors. As the employment of discriminant analysis requires the homogeneity of dispersion matrices and, that n_hp where n_h= degree of freedom of hypothesis, p =number of chemical terms, the reliability and validity of this method is highly questionable here. An alternative method is based on the principal component analysis where multicategory variables of drug responses can be classified into measures of inactive, slightly active, sufficiently active, and highly active drugs, for instance. The rules for classification are based on biological sources that can be expressed by chemical terms, too. An example adapted from antitumor action of acridine derivatives shows the working technique.     

The MASCA Approach Applied to Break Multicollinearities in Quantitative Structure-Activity Relationships

Since the regressors in multiple and multivariate regression analysis are intercorrelated, the coefficients of a regression of regressands on them are unreliable with respect to the predictive model power. Nonpredictive and predictive multicollinearity affect the ability to predict the biological activity (regressand) of novel drugs based on a function of physiochemical parameters (regressors), therefore. The nonpredictive multicollinearity can be broken by using the principal component regression analysis of the MASCA model. The working technique is exemplified on bispyridinium oxime antidotes, trimethoprim derivatives, and Taft's steric constant.     

合并与不合并：两个相似性聚类分析方法比较

以山西省4638种昆虫在7个地理小区的分布、内蒙古7766种昆虫在14个地理小区的分布和中国16804属昆虫在67个生态区域的分布3组数据为样本,用传统的层层合并的相似性聚类分析法(SCA)和新的不需合并的多元相似性聚类分析法(MSCA)进行运算分析,对比结果表明,不合并法都能得到既符合统计学逻辑,又符合地理学、生物学逻辑的结果;合并法在参与小区较少时,还能够得到与不合并法类似的结果,随着参与小区的增多,聚类结构发生变化,以致聚类功能彻底丧失.无论两种聚类结果差异大小,其性质都迥然不同:不合并法的相似性系数是固有的、互相独立的、同时存在的,聚类结果是所有小区之间关系亲疏、距离远近的状态;合并法的每个相似性系数都是合并的依据或结果,前一个系数是后一个系数产生的条件,后一个系数是前一个系数消亡的结果,严格按照顺序,当最后一个系数产生时,前面所有系数和所有小区都已不复存在,聚类结果只是记录不断合并、不断消亡的过程.因此在肯定合并法历史价值的同时,认为申效诚等创建的多元相似性系数公式及多元相似性聚类分析法摈弃合并降阶这一产生偏差和错误的根源,能够得出相对客观的聚类结果,是生物地理学研究领域有效的聚类分析工具,必将推动生物地理学定量研究迈入一个新阶段.     

Traditional melissopalynology integrated by multivariate analysis and sampling methods to improve botanical and geographical characterisation of honeys

Abstract

Melissopalynological analysis is the official test to determine the botanical and geographical origin of honey. Geographical characterisation is generally obtained by synthesising the pollen data of all available local honeys in a pollen spectrum interpreted according to palynological expertise. The subjective ability to interpret data is considered a limiting factor for this method and alternative tests are promoted. Nevertheless, melissopalynological analysis is still the most reliable test, and data, if properly exploited, could provide a large amount of information that is generally disregarded. The aim of our work was to apply a new experimental approach for honey sampling, and a statistical multivariate analysis of melissopalynological data. The study was conducted in the Sorrento-Amalfi Peninsula (southern Italy) where 36 hives were positioned in 12 experimental stations distributed in three main land-use types (citrus orchards, chestnut woods and Mediterranean maquis). The new approach proved to be useful for the comprehensive evaluation of honey variability across time and space, allowing objective identification of the pollen types as markers of a given geographical area.     

The Use of Multiple Outcomes Analysis in Neurotoxicity: An Example from the New Zealand Study of Offspring of Mothers Exposed to Methyl Mercury

Neurotoxicity has become an important area in the study of the risk to children of noncarcinogens. Many of the tests used to evaluate neurotoxic effects in neurotoxic studies are psychometric tests to assess cognitive, motor, and perceptual performance in individuals in order to determine the presence of psychological problems, impaired educational achievement, or neurological abnormalities. The underlying assumption of these procedures are that a test performance deficit is indicative of a neurological disability, and that such disability derives from the prenatal exposure to an offending substance. The usual analytic paradigm for discerning environmental impacts is to analyze the scores of a particular subtest in a battery taken separately as the dependent variable with regression analysis, which adjusts for cultural background, educational level, and socioeconomic status. The impact of this analysis is to determine the correlation of each of the psychometric test results to exposure. We show a statistical method to simultaneously analyze the multiple outcomes of many tests using General Estimating Equations (GEE) to determine if a correlation exists between the global measure of all these tests and exposure adjusted for covariates of interest and the correlation among the dependent psychometric variables. We show the application of this method to the results of children whose mothers were exposed to mercury during pregnancy.     

Quantitative Structure-Activity Relationship Studies on Cyclic Urea-Based HIV Protease Inhibitors

Abstract

A quantitative structure-activity relationship (QSAR) study is described on some cyclic ureas that inhibit the enzyme HIV-I protease (HIV-I-PR) and exhibit antiviral potency. Both the enzyme inhibition activity and the antiviral potency were found to be primarily governed by the hydrophobic property of the substituents at the nitrogens (N2/N2′) of the urea. Adjacent to the nitrogens, the CI/CI -substituents are, however, found to affect the activity (inhibition) by their molecular size. The essential binding of the ureas with the receptor is, however, through multiple hydrogen bonding, where the substituents, too, can participate in such binding if they are capable of doing so. A schematic diagram of the overall interaction of the inhibitors with the receptor is presented.     

SPECIES DISCRIMINATION AND EVOLUTIONARY MODE OF BUCHIA (BIVALVIA: BUCHIIDAE) FROM UPPER JURASSIC–LOWER CRETACEOUS STRATA OF GRASSY ISLAND, BRITISH COLUMBIA, CANADA

Abstract: Buchiid bivalves are geographically widespread in Upper Jurassic and Lower Cretaceous strata of the Northern Hemisphere. They are often abundant and their short stratigraphic ranges make them ideal biostratigraphic index fossils; these characteristics also render them useful for study of evolutionary patterns. We used multivariate methods to determine if we could discriminate between species of Buchia and examine how morphological characters change through time within the genus. Using ten morphological characters to describe shell shape and size, we tested for taxonomic differences and morphologic change in populations of buchiids collected from a single stratigraphic section on Grassy Island, located along the west coast of Vancouver Island, British Columbia. Morphometric analysis utilized traditional morphological metrics and techniques, including linear and angular measurements as well as Fourier (outline shape) analyses. Phenetic discrimination revealed considerable overlap among the recognized species in the morphospace, as well as a fairly low discriminatory power between species when compared as a group using a step‐wise canonical variate analysis. Step‐wise discriminant analyses between species pairs gave rise to much higher classification rates, suggesting that different characters are important for distinguishing between different species pairs. Our results also indicate that single individuals and small sample sizes of Buchia specimens are insufficient for biostratigraphic discrimination (unless other rarely preserved features such as the hinge and bysuss ear are available) and that a number of previously described species variants may not be taxonomically valid. A biolog using the multivariate axis that best discriminates between species (CV1) and a random walk‐based test using a Hurst estimate analysis indicate a gradualistic evolutionary mode for the Buchia species of Grassy Island. Shell shape and size of buchiids do not appear to be closely tied to lithofacies changes over the c. 10 myr time interval, suggesting that ecophenotypic variation (as it relates to substrate changes) probably had minimal influence on morphology.     

A comparison of univariate and multivariate numerical and graphical techniques for determining inter- and intraspecific feeding relationships in estuarine fish

The advantages and disadvantages of various numerical and graphical techniques for the analysis of inter- and intraspecific feeding relationships of fishes were examined. All methods have been cited in the literature since 1988. The index of preponderance, the resultant index and graphical methods proposed by Costello and Tokeshi were used to illustrate the relative importance of prey species to an individual fish species with no differentiation between size classes. Inter- and intraspecific competition and niche overlap were determined from multivariate analysis [the ordination technique, detrended correspondence analysis, cluster analysis by the Bray-Curtis equation, per cent overlap and two-way indicator species analysis (TWINSPAN)]. The identity of the prey organisms are not lost in the comparisons, and the value of this is determined through comparison with techniques such as Shannon-Wiener which obscure these data. The Shannon-Wiener diversity index was combined with an analysis of 'evenness' to refine the technique further to assess niche breadth, as was the Levins index. The study shows that to give an estimate of competition within the community, it is important to assess the data with respect to seasonal and temporal patterns using multivariate analysis.     

Biological guidelines for freshwater sediment based on BEnthic Assessment of SedimenT (the BEAST) using a multivariate approach for predicting biological state

Abstract This paper describes the first results for an alternative approach to the development of sediment quality criteria in the nearshore areas of the Laurentian Great Lakes. The approach is derived from methods developed in the United Kingdom for establishing predictive relationships between macroinvertebrate fauna and the physico-chemistry of riverine environments. The technique involves a multivariate statistical approach using (i) data on the structure of benthic invertebrate communities, (ii) functional responses (survival, growth and reproduction) in four sediment toxicity tests (bioassays) with benthic invertebrates; and (iii) selected environmental variables at 96 reference (‘clean’) sites in the nearshore areas of all five Great Lakes (Lakes Superior, Huron, Erie, Ontario and Michigan). Two pattern recognition techniques (using the computer software package PATN) are employed in the analysis: cluster analysis and ordination. The ordination vector scores from the original axes of the pattern analysis are correlated (using CORR in SAS) with environmental variables which are anticipated to be least affected by anthropogenic activities (e. g. alkalinity, depth, silt, sodium etc.). Multiple discriminant analysis (MDA) is used to relate the site groupings from the pattern analysis to the environmental variables and to generate a model that can be used to predict community assemblages and functional responses at new sites with unknown but potential contamination. The predicted community assemblages and functional responses are then compared with the actual benthic communities and responses at a site, and the need for remedial action is determined. The predictive capability of the discriminant model was confirmed by performing several validation runs on subsets of the data. An example of the use of the model for sediment in Collingwood Bay (an area of concern designated by the IJC in Georgian Bay, Lake Huron) is presented and the technique is shown to be more precise in determining the need for remediation than the currently used provincial sediment quality criteria based on Screening Level Concentration (SLC) and laboratory toxicity tests. The ultimate goal of the study is the development of a method to determine the need for, and the success of, remedial action and to predict what benthic communities should look like at a site if it were clean and what responses of organisms in sediment toxicity tests constitute an acceptable end-point.     

INDIVIDUAL AND SPECIES-SPECIFIC SONG PATTERNS OF ROCK AND MEADOW PIPITS: PHYSICAL CHARACTERISTICS AND EXPERIMENTS

ABSTRACT

The songs of Anthus spinoletta littoralis and A. pratensis, in sympatric populations in SW Sweden were recorded, analysed in sound spectrographs and tested in the field. The purpose was to investigate: a) if the strophes are species specifically and individually distinct and, if so, whether pipits are able to make such distinctions; b) if the species-specific and individual-specific patterns are concentrated in different sections of the song and, if so, whether the species-specific section transmits individual-specific information and the individual-specific section transmits species-specific information as well.

The basic structure of the syllables in the terminating section of the strophe was found to be intraspecifically stereotyped, but varied between the two species. Replay experiments showed that territorial males could discriminate between con- and heterospecific strophes and this ability persisted when the terminating section of the strophe was replayed alone. The terminating part of the strophe did not seem to transmit individual-specific information to conspecific males. On the other hand, the basic structure of the syllables in the first section of the strophe was intraindividually stereotyped but varied between most conspecific males. Playback experiments showed that a territorial male could discriminate his neighbours' song patterns and this ability remained intact when the introductory phrase of the strophe was replayed alone. Both song pattern and position were necessary properties of the identifying signal in these pipits. But the introductory phrase of a total stranger did not seem to transmit unambiguous species-specific information to conspecific males.     

甘南玛曲植物群落的多元分析与环境解释

应用无偏对应分析（ＤＣＡ）及二岐指示种分析（ＴＷＩＮＳＰＡＮ）对玛曲１７８个植物群落样方资料进行了多斐邓和数量分类,并应用植物群落的排序值与环境参数的多元回归分析出各群类型的定量环境解释,探讨了该区植物群的基本类型生态梯度及其与环境因子的定量关系。结果表明,玛曲的植物群落类型及基分布主要取惟地热量和湿度,并可通过环境参数地数字表达式定量地确定。     

ANNA: A new prediction method for bioassessment programs

1. Cluster analysis of reference sites with similar biota is the initial step in creating River Invertebrate Prediction and Classification System (RIVPACS) and similar river bioassessment models such as Australian River Assessment System (AUSRIVAS). This paper describes and tests an alternative prediction method, Assessment by Nearest Neighbour Analysis (ANNA), based on the same philosophy as RIVPACS and AUSRIVAS but without the grouping step that some people view as artificial. 2. The steps in creating ANNA models are: (i) weighting the predictor variables using a multivariate approach analogous to principal axis correlations, (ii) calculating the weighted Euclidian distance from a test site to the reference sites based on the environmental predictors, (iii) predicting the faunal composition based on the nearest reference sites and (iv) calculating an observed/expected (O/E) analogous to RIVPACS/AUSRIVAS. 3. The paper compares AUSRIVAS and ANNA models on 17 datasets representing a variety of habitats and seasons. First, it examines each model's regressions for Observed versus Expected number of taxa, including the r², intercept and slope. Second, the two models’ assessments of 79 test sites in New Zealand are compared. Third, the models are compared on test and presumed reference sites along a known trace metal gradient. Fourth, ANNA models are evaluated for western Australia, a geographically distinct region of Australia. The comparisons demonstrate that ANNA and AUSRIVAS are generally equivalent in performance, although ANNA turns out to be potentially more robust for the O versus E regressions and is potentially more accurate on the trace metal gradient sites. 4. The ANNA method is recommended for use in bioassessment of rivers, at least for corroborating the results of the well established AUSRIVAS‐ and RIVPACS‐type models, if not to replace them.     

The Genus Uroleucon Mordvilko (Insecta, Aphidoidea) in South America, with a key and descriptions of four new species

Uroleucon is one of only two genera of Aphidinae to have undergone significant speciation in South America, with a group of about 14 endemic, morphologically similar species feeding on native Compositae, especially Baccharis . Multivariate morphometrics (canonical variates analysis, CVA) was used to discriminate between these species and compare them with the North American subgenus Lambersius , in which most of them have hitherto been placed. It is concluded that they probably form a separate monophyletic group. Four new species are described in this group— brevisiphon, essigi, petrohuense and pseudomuennosum— and five names are placed in synonymy. Of the other species of Uroleucon in South America, U. lizerianum is widespread and feeds on many species of native and introduced Compositae; it is morphometrically inseparable from the North American species U. ambrosiae and is probably an introduced form of that species, but has consistently fewer secondary rhinaria. A key is provided to the 19 available species of Uroleucon recorded from South America.     

Exploring the relationship between entheseal changes and physical activity: A multivariate study

Analyses of entheseal changes (EC) in identified skeletal samples employ a common research strategy based on the comparison between occupations grouped on the basis of shared biomechanical and/or social characteristics. Results from this approach are often ambiguous, with some studies that point to differences in EC between occupational samples and others failing to provide evidence of behavioral effects on EC. Here we investigate patterns of EC among documented occupations by means of a multivariate analysis of robusticity scores in nine postcranial entheses from a large (N = 372) contemporary skeletal sample including specimens from one Italian and two Portuguese identified collections. Data on entheseal robusticity, analyzed by pooled sides as well by separated sides and levels of asymmetry, are converted in binary scores and then analyzed through nonlinear principal component analysis and hierarchical cluster analysis. Results of these analyses are then used for the classification of occupations. Differences between occupational classes are tested by MANOVA and pairwise Hotelling's test. Results evidence three classes which separate occupations related to farming, physically demanding but generalized occupation, and physically undemanding occupations, with the more consistent differences between the first and the last classes. Our results are consistent with differences in biomechanical behavior between the occupations included in each class, and point to the physical and social specificity of farming activities. On the other hand, our study exemplifies the usefulness of alternative analytical protocols for the investigation of EC, and the value of research designs devoid of a priori assumptions for the test of biocultural hypotheses. Am J Phys Anthropol 156:215–223, 2015. © 2014 Wiley Periodicals, Inc.     

Multivariate Extensions of the Mixed Model for Quantitative Traits

The mixed model for complex segregation analysis of quantitative data from three-generational nuclear families is extended to the multivariate case. Likelihood functions for hypothesis testing are derived for two types of conditional analysis of multiple traits: first when entry to the study depends on the index case's values of all the quantitative traits that are of interest, and second when entry depends on only one trait, but other correlated traits are to be studied simultaneously. Using direct products of covariance matrices, these functions are seen to be direct multivariate equivalence of the univariate functions.     

Medicinal Chemistry Perspectives on Recent Advances in Src Kinase Inhibitors as a Potential Target for the Development of Anticancer Agents: Biological Profile,Selectivity, Structure-Activity Relationship

The physiological Src proto-oncogene is a protein tyrosine kinase receptor that served as the essential signaling pathway in different types of cancer. Src kinase receptor is divided into different domains: a unique domain, an SH3 domain, an SH2 domain, a protein tyrosine kinase domain, and a regulatory tail, which runs from the N-terminus to the C-terminus. Src kinase inhibitors bind in the kinase domain and are activated by phosphorylation. The etiology of cancer involved various signaling pathways and Src signaling pathways are also involved in those clusters. Although the dysregulation of Src kinase resulted in cancer being discovered in the late 19^th century it is still considered a cult pathway because it is not much explored by different medicinal chemists and oncologists. The Src kinase regulated through different kinase pathways (MAPK, PI3K/Akt/mTOR, JAK/STAT3, Hippo kinase, PEAK1, and Rho/ROCK pathways) and proceeded downstream signaling to conduct cell proliferation, angiogenesis, migration, invasion, and metastasis of cancer cells. There are numerous FDA-approved drugs flooded the market but still, there is a huge demand for the creation of novel anticancer drugs. As the existing drugs are accompanied by several adverse effects and drug resistance due to rapid mutation in proteins. In this review, we have elaborated about the structure and activation of Src kinase, as well as the development of Src kinase inhibitors. Our group also provided a comprehensive overview of Src inhibitors throughout the last two decades, including their biological activity, structure-activity relationship, and Src kinase selectivity. The Src binding pocket has been investigated in detail to better comprehend the interaction of Src inhibitors with amino acid residues. We have strengthened the literature with our contribution in terms of molecular docking and ADMET studies of top compounds. We hope that the current analysis will be a useful resource for researchers and provide glimpse of direction toward the design and development of more specific, selective, and potent Src kinase inhibitors.     

Assessment of near-infrared spectral information for rapid monitoring of bioprocess quality.

Access to real-time process information is desirable for consistent and efficient operation of bioprocesses. Near-infrared spectroscopy (NIRS) is known to have potential for providing real-time information on the quantitative levels of important bioprocess variables. However, given the fact that a typical NIR spectrum encompasses information regarding almost all the constituents of the sample matrix, there are few case studies that have investigated the spectral details for applications in bioprocess quality assessment or qualitative bioprocess monitoring. Such information would be invaluable in providing operator-level assistance on the progress of a bioprocess in industrial-scale productions. We investigated this aspect and report the results of our investigation. Near-infrared spectral information derived from scanning unprocessed culture fluid (broth) samples from a complex antibiotic production process was assessed for a data set that incorporated bioprocess variations. Principal component analysis was applied to the spectral data and the loadings and scores of the principal components studied. Changes in the spectral information that corresponded to variations in the bioprocess could be deciphered. Despite the complexity of the matrix, near-infrared spectra of the culture broth are shown to have valuable information that can be deconvoluted with the help of factor analysis techniques such as principal component analysis (PCA). Although complex to interpret, the loadings and score plots are shown to offer potential in process diagnosis that could be of value in the rapid assessment of process quality, and in data assessment prior to quantitative model development.     

A novel computer modeling approach to the structures of small bioactive peptides: The structure of gonadotropin releasing hormone

A novel computer modeling approach suitable for the structure analysis of small bioactive peptides has been developed. This approach involves identification of conformational patterns in protein structure data bank based on the sequence homology with the bioactive peptide. The models built on the basis of this homology and having common conformational patterns are analyzed under the structural constraints derived from the activity data of various synthetic analogs of the peptide. Application of this procedure to the gonadotropin releasing hormone (GnRH) resulted in a library of possible structures for GnRH, 9 among which shared a common β-turn. Further analysis of the structures containing the β-turn motif, in the context of the structure–activity data, led to a model for the active conformation of GnRH. The topology of the putative receptor binding site of the hormone is defined by a contiguous surface formed through an appropriate juxtaposition of the N-terminal pGlu¹ the guanidyl group of Arg⁸, aromatic side chain of Trp³, and the Gly¹⁰-NH₂ at the C-terminal end. ©Wiley-Liss, Inc.     

Typology of macrofaunal assemblages: a tool for the management of running waters in The Netherlands

A survey was carried out at 156 sites, situated in streams in the province of Overijssel (The Netherlands), to describe the macroinvertebrate assemblages and their environments. Fifty-six environmental variables were measured once at each sampling site. The main aim was to describe a typology of stream for this region.Different multivariate analysis techniques (clustering and ordination) were used in combination with ecological information on individual taxa to derive and describe site groups in terms of taxonomic composition and mean environmental conditions. The resulting site groups were termed cenotypes.Eleven cenotypes were distinguished. Differences between cenotypes were attributed to (combinations of) environmental key factors, namely, dimensions (width and depth), morphological (profile shape) and hydraulic stream characteristics, duration of drought and load of organic material.The typology offers a basis to be used for regional stream management and nature conservation. Efforts to improve stream ecosystems should be directed at the physical and hydraulic conditions.Typological studies are needed (especially in semi-natural landscapes) if we are to better understand, manage and conserve freshwater biota.