Errors between sites in restriction site mapping

Restriction site mapping programs construct maps by generatingpermutations of fragments and checking for consistency. Unfortunatelymany consistent maps often are obtained within the experimentalerror bounds, even though there is only one actual map. A particularlyefficient algorithm is presented that aims to minimize errorbounds between restriction sites. The method is generalizedfor linear and circular maps. The time complexity is derivedand execution times are given for multiple enzymes and a rangeof error bounds. Received on July 17, 1987; accepted on November 3, 1987     

Construction of restriction maps

A computer program is described, which constructs maps of restrictionendonuclease cleavage sites in linear or circular DNA molecules,given the fragment lengths in single and double digestions withtwo enzymes. The algorithm is based upon a partition methodand a very simple rule to chain fragments. The program is writtenin Prolog II. Received on July 28, 1987; accepted on December 31, 1987     

Restriction map construction using a 'complete sentences compatibility' algorithm

We have developed a new algorithm ‘Complete sentencescompatibility’ (CSC) which uses single and double digestionfragments to rapidly determine restriction maps of circularDNA. From possible combinations of fragments of each simpledigestion, which we call ‘sentences of decomposition’,we construct a restriction map which combines the sentenceswhile taking into account compatibility rules. The algorithmcan also deal with experimental errors of fragment weight andcan suggest solutions that account for non-readable bands (fragmentsof zero length or multiple bands) on the gel. Because experimentsusing pairs of restrictive enzymes often result in multiplesolutions, a complementary algorithm tries to reduce the numberof proposed solutions by establishing consensus maps. The restrictionmap construction algorithm was tested on real cases, some containingmore than fifteen fragments. Execution times range from 1 –10 s on an IBM PC compatible microcomputer. Received on July 21, 1987; accepted on December 31, 1987     

A Comparison of Postmigration and Migration-Coupled Mismatch Correction Mechanisms for Branch Migration-Mediated Gene Conversion

We examine several models for nonreciprocal recombination based on the formation of heteroduplex DNA by bidirectional branch migration. We show that the consistency of genetic maps resulting from postmigration mismatch correction is disrupted by the presence of a favored site for initiation of strand exchange, with local inversion of the genetic and physical maps a predicted consequence. We also examine models that allow mismatch correction to take place concurrently with the process of strand exchange and show that the genetic maps resulting from such migration-coupled conversions are substantially free of the anomalies expected of postmigration conversions.     

Genome majority vote improves gene predictions

Recent studies have noted extensive inconsistencies in gene start sites among orthologous genes in related microbial genomes. Here we provide the first documented evidence that imposing gene start consistency improves the accuracy of gene start-site prediction. We applied an algorithm using a genome majority vote (GMV) scheme to increase the consistency of gene starts among orthologs. We used a set of validated Escherichia coli genes as a standard to quantify accuracy. Results showed that the GMV algorithm can correct hundreds of gene prediction errors in sets of five or ten genomes while introducing few errors. Using a conservative calculation, we project that GMV would resolve many inconsistencies and errors in publicly available microbial gene maps. Our simple and logical solution provides a notable advance toward accurate gene maps.     

Quantitative concept mapping in pulmonary physiology: comparison of student and faculty knowledge structures

Quantitative concept mapping, in contrast with qualitative approaches, is rigorous scientifically and permits statistical analyses of data about concept learning. This study extends past quantitative research on the structure of student concept learning in pulmonary physiology. Pathfinder scaling is used to derive concept maps for medical and veterinary students and their physiology instructors at Northwestern University and the University of Wisconsin, respectively. The concept maps are evaluated for coherence (internal consistency), student-instructor similarity, and correlation of similarity with final examination scores. Results show that student and instructor concept maps are coherent and that student concept maps become increasingly similar to instructors' concept maps from pre- to postinstruction, but that student-instructor concept map similarity does not correlate with examination performance. Research outcomes are discussed concerning possible sources of variation in student and faculty knowledge structures.     

Mapping of sequenced genes (700 kbp) in the restriction map of the Escherichia coli chromosome

This paper describes software (written in Pascal and running on Macintosh computers) allowing localization of unknown DNA fragments from the Escherichia coli chromosome on the restriction map established by Kohara et al. (1987). The program identifies the segment's map position using a restriction pattern analysis obtained with all, or some, of the eight enzymes used by Kohara et al. (1987). Therefore, the sequenced genes available in the EMBL library may be localized on the E. coli chromosome restriction map. This allowed correction of the map (mainly by introducing missing sites in the published maps) at the corresponding positions. Analysis of the data indicates that there is only a very low level of polymorphism, at the nucleotide level, between the E. coli K12 strains used by the various laboratories involved in DNA sequencing. The program is versatile enough to be used with other genomes.     

受损沙地生态系统景观变化分析——以内蒙古浑善达克沙地为例

生态系统变化会引起景观结构及格局的改变,而景观格局及其演化可以作为评价环境变化的指标。为了揭示浑善达克沙地生态系统变化特征,该文使用陆地卫星(Landsat 5、7)的TM/ETM⁺资料及地面调查数据来分析沙地景观变化特征。通过计算机监督分类,获得了研究区1987和2000年景观类型数据,研究区的景观类型有草地、固定沙地、半固定沙地、流动沙地、灌木林及水体。通过对两期景观数据的基本特征、变化检测及转移矩阵分析发现:1)从1987到2000年,草原、固定沙地、半固定沙地都在减少,斑块破碎,而流动沙地显著增加,成为主要景观类型,同时斑块相互联合形成两条流动沙带;2)类型转移上,草原转为沙地,固定沙地主要转为半固定沙地,半固定沙地以绝对优势转为流动沙地,水体转为流动沙地及草原;3)变化监测显示,流动沙地增加面积远远大于减少的面积,而草原、固定沙地、半固定沙地呈现相反趋势,变化区域的空间分布也不尽相同。结果表明研究区沙地生态系统已经退化比较严重,特别是流动沙带的出现,需要采取积极有效的防治措施,防止进一步扩大。     

Carbon-fate maps for metabolic reactions

MOTIVATION: Stable isotope labeling of small-molecule metabolites (e.g. (13)C-labeling of glucose) is a powerful tool for characterizing pathways and reaction fluxes in a metabolic network. Analysis of isotope labeling patterns requires knowledge of the fates of individual atoms and moieties in reactions, which can be difficult to collect in a useful form when considering a large number of enzymatic reactions. RESULTS: We report carbon-fate maps for 4605 enzyme-catalyzed reactions documented in the KEGG database. Every fate map has been manually checked for consistency with known reaction mechanisms. A map includes a standardized structure-based identifier for each reactant (namely, an InChI string); indices for carbon atoms that are uniquely derived from the metabolite identifiers; structural data, including an identification of homotopic and prochiral carbon atoms; and a bijective map relating the corresponding carbon atoms in substrates and products. Fate maps are defined using the BioNetGen language (BNGL), a formal model-specification language, which allows a set of maps to be automatically translated into isotopomer mass-balance equations. AVAILABILITY: The carbon-fate maps and software for visualizing the maps are freely available (http://cellsignaling.lanl.gov/FateMaps/).     

The effects of groundwater discharge,mowing and eutrophication on fen vegetation evaluated over half a century

Questions: Were continued groundwater discharge and mowing regimes sufficient for vegetation preservation from 1944 to 1993? Which has a stronger effect on vegetation development; groundwater discharge or mowing? What is the role of surface water eutrophication as driver of vegetation change? Location: Het Hol, The Netherlands (ca. 92 ha, 52°13′N, 5°05′E). Methods: Hydrology was simulated for the late 1940s, early 1960s and 1987. Vegetation maps (1944, 1960, 1975 and 1993) were compared for biotope cover. Vegetation recordings in 1944 and 1987 were compared. Surface water quality was compared between 1950 and 1987. Which sites were mown was reconstructed from an interview. Effects of periodic mowing and groundwater discharge on vegetation development were tested for correlation. Results: Biotope diversity reduced significantly through decrease of semi‐aquatic and tall‐herb biotopes, and expansion of forest. The quagfen terrestrialization sere nearly disappeared from 1987 recordings, while the reed sere did well concerning abundance and species richness. Several typical (rich) fen species disappeared from recordings, while new species were mostly field margin species. Periodic mowing and discharge combined are correlated with increasing species numbers. The P‐concentration in surface water increased while N‐concentration decreased. Conclusions: Preservation of the reed sere was successful, whereas preservation of the quagfen sere was not. Periodic mowing and discharge stimulate species richness, discharge more so than periodic mowing. But slight eutrophication likely induced a shift from P‐limitation to N‐limitation, which stimulated the reed sere at the expense of the quagfen sere.     

CoMFA and CoMSIA 3D-QSAR analysis of diaryloxy-methano-phenanthrene derivatives as anti-tubercular agents

Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) based on three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were conducted on a series (44 compounds) of diaryloxy-methano-phenanthrene derivatives as potent antitubercular agents. The best predictions were obtained with a CoMFA standard model (q (2)=0.625, r (2)=0.994) and with CoMSIA combined steric, electrostatic, and hydrophobic fields (q (2)=0.486, r (2)=0.986). Both models were validated by a test set of seven compounds and gave satisfactory predictive r (2) values of 0.999 and 0.745, respectively. CoMFA and CoMSIA contour maps were used to analyze the structural features of the ligands to account for the activity in terms of positively contributing physicochemical properties: steric, electrostatic, and hydrophobic fields. The information obtained from CoMFA and CoMSIA 3-D contour maps can be used for further design of phenanthrene-based analogs as anti-TB agents. The resulting contour maps, produced by the best CoMFA and CoMSIA models, were used to identify the structural features relevant to the biological activity in this series of analogs. Further analysis of these interaction-field contour maps also showed a high level of internal consistency. This study suggests that introduction of bulky and highly electronegative groups on the basic amino side chain along with decreasing steric bulk and electronegativity on the phenanthrene ring might be suitable for designing better antitubercular agents.     

Design-based mapping of tree attributes by 3P sampling

The estimation of individual values (marks) in a finite population of units (e.g., trees) scattered onto a survey region is considered under 3P sampling. For each unit, the mark is estimated by means of an inverse distance weighting interpolator. Conditions ensuring the design-based consistency of maps are considered under 3P sampling. A computationally simple mean squared error estimator is adopted. Because 3P sampling involves the prediction of marks for each unit in the population, prediction errors rather than marks can be interpolated. Then, marks are estimated by the predictions plus the interpolated errors. If predictions are good, prediction errors are more smoothed than raw marks so that the procedure is likely to better meet consistency requirements. The purpose of this paper is to provide theoretical and empirical evidence on the effectiveness of the interpolation based on prediction errors to prove that the proposed strategy is a tool of general validity for mapping forest stands.     

A program for drawing evolutionary trees

From the measures of evolutionary distance between pairs ofsequences in a set, it is possible to infer the genetic treeor trees which best fit these known data. DENDRON is a new program,written in FORTRAN 66, which computes an initial tree from thebottom-up, then searches among increasingly divergent treesfor a better fit. As a check on the consistency of the measures,the program tests all triplets for the triangle inequality.DENDRON also calculates a single ‘top-down’ tree,progressing from the trunk to the twigs, for comparison withthe ‘bottom-up’ trees. Received on August 17, 1987; accepted on June 1, 1988     

基于边界特征的山地森林景观碎裂化研究

景观边界特征与景观碎裂化过程之间的相互关系研究已经引起了广泛的关注。利用 1 987年和 1 997年两个时段遥感景观资料 ,编制了卧龙自然保护区的景观类型图 ,以验证景观碎裂化过程导致边界数量 ,特别是短边界数量增加这一假说。研究工作包括 4个方面的内容 :(1 )利用每年的 2 0个 2 0 0× 2 0 0像元的正方形样地 ,分析工作区内景观边界的一般特征 ;(2 )对每个样地边界数量的长度谱分布特征进行拟合 ,确定能够反映边界属性特征的拟合方程参数 ;(3 )将边界属性特征参数与样地的景观碎裂化指数进行比较研究 ,建立景观边界特征与景观碎裂化程度之间的量化关系模型 ;(4 )利用每个时段的 1 0个验证样地来检验关系模型的有效性。研究结果表明 ,所有样地边界数量的长度谱分布特征可以使用对数方程 y=bln(x) +c进行拟合。景观的碎裂化过程将同时导致拟合方程参数 b的绝对值和 c值线性增加 ,景观碎裂化水平的增加将导致景观边界数量和短边界数量均呈指数增长方式。从研究的结果中还可以推断出 ,生境碎裂化水平对于生物多样性的影响也将呈现出明显的放大效应。     

A program for the graphic representation and manipulation of DNA sequences

We have developed a program for the graphic representation andmanipulation of DNA sequences. The program (named CARTE fromthe French for ‘map’) is intended as a tool in theplanning and analysis of recombinant DNA experiments. DNA sequencesare represented as standard restriction maps, using any desiredcombination of restriction enzymes. Features of interest, suchas promoters or coding sequences, can be highlighted. The sequencecan be manipulated to mimic cloning, using deletions, insertionsor replacements at specified sites. This process is facilitatedby the simultaneous display of a graphic map of the entire sequence,a detailed picture of the work in progress, and a menu of functions. Received on November 17, 1986; accepted on March 12, 1987     

An efficient two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis method for simultaneous peptide mapping of protein contained in a mixture

A method for simultaneous peptide mapping of polypeptides contained in a mixture is presented. The polypeptides were first separated by conventional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The strip of gel containing these unstained polypeptide bands was subsequently embedded perpendicular to the direction of electrophoresis in the stacking gel of a second gel. The proteolytic enzymes, loaded on top of the second gel, were brought in contact with the substrates through moving boundary electrophoresis. The peptides thus generated were then resolved by electrophoresis in a gradient gel. A polychromatic silver staining method added an extra dimension to the identification and characterization of the peptides in the maps obtained in that specific peptides got specific colors. Moreover, the sensitivity of this method was illustrated by the demonstration that original quantities in the submicrogram range of nonradioactive proteins (exemplified here by the structural proteins of densonucleosis virus) largely sufficed for satisfactory maps. Other advantages of this procedure over current methods included (i) the elimination of the purification step (and consequently virtually no loss or contamination), (ii) that only the strict minimum of material (necessary for the ultimate visualization of the maps) had to be used, (iii) that no special two-dimensional electrophoresis equipment was needed, and (iv) the consistency, speed, and simplicity of the method.     

Pharmacophore-based 3D-QSAR as a predictive method for the QSAR analysis on a series of potent and selective inhibitors for three kinases of RTK family

For targets belonging to the same family of receptors, inhibitors often act at more than one biological target and produce a synergistic effect. Separate pharmacophore-based comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models were developed from our data-set for the kinase insert domain-containing receptor (KDR), cKit and Flt1 inhibitors. These models showed excellent internal predictability and consistency; validation using test-set compounds yielded a good predictive power for the pIC₅₀-value. The field contour maps (CoMFA and CoMSIA) corresponding to the KDR, cKit and Flt1 kinase subtypes reflected the characteristic similarities and differences between these types. These maps provided valuable information to facilitate structural modifications of the inhibitor to increase selectivity of the KDR over cKit and Flt1.     

Fine needle aspiration cytology of granulomatous prostatitis

The fine needle aspiration (FNA) cytologic findings are presented for 18 cases of granulomatous prostatitis (12 nonspecific, 5 tuberculous and 1 eosinophilic cases). These cases represented 19% of all prostatitis cases and 2% of all prostatic aspirates examined from January 1986 to December 1987. The cytomorphologic differences between the three types of granulomatous prostatitis are described, with emphasis on the differentiation between the nonspecific and specific varieties. The differential diagnostic features between reactive changes and well-differentiated adenocarcinomas of the prostate are also presented. The findings in these cases indicate that FNA cytology is a reliable procedure for the morphologic diagnosis of granulomatous prostatitis, which can clinically mimic prostatic carcinoma when it presents as a diffuse or nodular enlargement with increased consistency.     

A study of the evolution of coxsackievirus A24 variant in Ghana by viral RNA fingerprinting analysis

An epidemic of acute haemorrhagic conjunctivities (AHC) caused by coxsackievirus A24 variant (CA24v) was reported in Accra, Ghana in May 1987. We studied 7 of the viral strains collected from May to November, 1987, by RNA genome fingerprinting. Pairwise comparisons of the oligonucleotide maps showed that genetic similarity among them ranged from between 60.0 to 84.7 %.Using base sequence variations deduced from genetic similarity among the isolates, isolation time of the strains and the rate of nucleotide substitution (estimated in a previous paper, Miyamura et al., 1990), we calculated divergence times and constructed a phylogenetic tree. This tree indicated that all the 7 strains had diverged from each other from 11 to 26 months before the AHC epidemic in Accra. CA24v may have been introduced into the country or the neighbouring area, at least, more than two years earlier, i. e. in the early half of 1985.     

Evidence for genetic heterogeneity in tuberous sclerosis: one locus on chromosome 9 and at least one locus elsewhere.

Linkage of tuberous sclerosis complex (TSC), an autosomal dominant disorder, to markers on chromosome 9 was reported first in 1987. This assignment was confirmed by an international collaborative study that suggested more than one locus may be responsible for the phenotype. We studied 14 multigenerational TSC families (13 previously unreported) with markers for nine loci in the linked region of chromosome 9q32-q34. Our results confirm the previous reports that the genetic locus in one-third to one-half of families maps to chromosome 9. Comparison of clinical findings in the chromosome 9-linked families with those in the chromosome 9-unlinked families reveals only a higher incidence of ungual fibromata in the chromosome 9-linked families.