bluuebunny/crossref_metadata_2025 huggingface dataset:
Harmonic Response of a Bulk Superconductor MgB2
Authors: Güçlü N. , Kiliç A. , Askerzade I. N. , Gencer A.
Published: July 2003

Magnetic characterisation of an intermetallic bulk superconductor, MgB2, was carried out by use of odd-order harmonic susceptibility χn = χ′n - iχ″n (n is odd) at low fields. The simplified Kim model was found to be suitable to account for the main features of the experimental odd-order harmonic susceptibilities. Full penetration field is fitted to [Formula: see text] for temperature scaling. The experiments are in good agreement with theory.
The Effect of the Impulse IR Laser Radiation Upon the Mechanical Properties of Thick Films of C60
Authors: Rahvalov V. , Spoiala D. , Prilepov V.
Published: July 2003

The study of mechanical properties of crystals under exterior factors gives important information on the structure in the body of a crystal. So, for example, exterior magnetic field ~ 1–10 T brings about change in the plastic properties in dielectric crystals and polymers. The influence of pulsing magnetic field more than 10 ΔH on the change of a microhardness monocrystal C60 is also revealed. In the present work the influence of another type of exterior effect in the form of pulsing laser irradiation upon mechanical parameters is studied. The mechanical parameters, the microhardness and acoustic emission, are studied under microindentation. The study is done on thick films C60 on a quartz substrate; the thickness of the film C60 ~ 3 μm. In order to prevent photoboosted oxidizing, the measuring of a microhardness was performed in darkness with a red light filter on the PMT-3 device. The experiments for the study of the acoustic emission (Å) were also carried out with microindentation C60 and the dependences Å from the energy of laser bundle are received. An explanation is offered of a similar dependence of microhardness bound with the dislocation mechanism of plastic deformation.
Superconductivity and Localization in Nd2-xCexCuO4+δ
Authors: Ponomarev A. I. , Harus G. I. , Charikova T. B. , Ignatenkov A. N. , Sabirzjanova L. D. , Shelushinina N. G. , Tashlykov A. O. , Ivanov A. A.
Published: July 2003

The in-plane resistivity, Hall effect (T = 77 K ) and SC-transition for some Nd 1.85- Ce 0.15 CuO 4+δ single crystal films are investigated at different nonstoichiometric disorder (δ). It is shown that with increasing of δ the Hall-coefficient for the most of the samples differs no more than twice but the normal state resistivity increases by a factor of five. SC-transition temperature decreases with essential broadening of the transition region. The observed evolution from homogeneous metallic (and superconducting) Nd 1.85 Ce 0.15 CuO 4+δ system to inhomogeneous dielectric one is described as Anderson-type disorder-induced transition in a two-dimensional electron system.
Modern Approach to the Calculation of the Correlation Function in Superconductivity Models
Authors: Bogolubov N. N. , Bogolubova E. N. , Kruchinin S. P.
Published: July 2003

The superconductivity Hamiltonian model with attraction is investigated. An asymptotic relation for average calculation is constructed in the model and the approximating Hamiltonians are presented.
A Fast and Sensitive Algorithm for Aligning ESTs to the Human Genome
Authors: Ogasawara Jun , Morishita Shinichi
Published: July 2003

There is a pressing need to align the growing set of expressed sequence tags (ESTs) with the newly sequenced human genome. However, the problem is complicated by the exon/intron structure of eukaryotic genes, misread nucleotides in ESTs, and the millions of repetitive sequences in genomic sequences. To solve this problem, algorithms that use dynamic programming have been proposed. In reality, however, these algorithms require an enormous amount of processing time. In an effort to improve the computational efficiency of these classical DP algorithms, we developed software that fully utilizes lookup-tables to detect the start- and endpoints of an EST within a given DNA sequence efficiently, and subsequently promptly identify exons and introns. In addition, the locations of all splice sites must be calculated correctly with high sensitivity and accuracy, while retaining high computational efficiency. This goal is hard to accomplish in practice, due to misread nucleotides in ESTs and repetitive sequences in the genome. Nevertheless, we present two heuristics that effectively settle this issue. Experimental results confirm that our technique improves the overall computation time by orders of magnitude compared with common tools, such as SIM4 and BLAT, and simultaneously attains high sensitivity and accuracy against a clean dataset of documented genes.
Automated Identification of Single Nucleotide Polymorphisms from Sequencing Data
Authors: Takahashi Masazumi , Matsuda Fumihiko , Margetic Nino , Lathrop Mark
Published: July 2003

The single nucleotide polymorphism (SNP) is the difference of the DNA sequence between individuals and provides abundant information about genetic variation. Large scale discovery of high frequency SNPs is being undertaken using various methods. However, the publicly available SNP data sometimes need to be verified. If only a particular gene locus is concerned, locus-specific polymerase chain reaction amplification may be useful. Problem of this method is that the secondary peak has to be measured. We have analyzed trace data from conventional sequencing equipment and found an applicable rule to discern SNPs from noise. The rule is applied to multiply aligned sequences with a trace and the peak height of the traces are compared between samples. We have developed software that integrates this function to automatically identify SNPs. The software works accurately for high quality sequences and also can detect SNPs in low quality sequences. Further, it can determine allele frequency, display this information as a bar graph and assign corresponding nucleotide combinations. It is also designed for a person to verify and edit sequences easily on the screen. It is very useful for identifying de novo SNPs in a DNA fragment of interest.
Bayesian Network and Nonparametric Heteroscedastic Regression for Nonlinear Modeling of Genetic Network
Authors: Imoto Seiya , Kim Sunyong , Goto Takao , Aburatani Sachiyo , Tashiro Kousuke , Kuhara Satoru , Miyano Satoru
Published: July 2003

We propose a new statistical method for constructing a genetic network from microarray gene expression data by using a Bayesian network. An essential point of Bayesian network construction is the estimation of the conditional distribution of each random variable. We consider fitting nonparametric regression models with heterogeneous error variances to the microarray gene expression data to capture the nonlinear structures between genes. Selecting the optimal graph, which gives the best representation of the system among genes, is still a problem to be solved. We theoretically derive a new graph selection criterion from Bayes approach in general situations. The proposed method includes previous methods based on Bayesian networks. We demonstrate the effectiveness of the proposed method through the analysis of Saccharomyces cerevisiae gene expression data newly obtained by disrupting 100 genes.
Computational Assignment of Protein Backbone NMR Peaks by Efficient Bounding and Filtering
Authors: Lin Guohui , Xu Dong , Chen Zhi-Zhong , Jiang Tao , Wen Jianjun , Xu Ying
Published: July 2003

NMR resonance assignment is one of the key steps in solving an NMR protein structure. The assignment process links resonance peaks to individual residues of the target protein sequence, providing the prerequisite for establishing intra- and inter-residue spatial relationships between atoms. The assignment process is tedious and time-consuming, which could take many weeks. Though there exist a number of computer programs to assist the assignment process, many NMR labs are still doing the assignments manually to ensure quality. This paper presents a new computational method based on the combination of a suite of algorithms for automating the assignment process, particularly the process of backbone resonance peak assignment. We formulate the assignment problem as a constrained weighted bipartite matching problem. While the problem, in the most general situation, is NP-hard, we present an efficient solution based on a branch-and-bound algorithm with effective bounding techniques using two recently introduced approximation algorithms. We also devise a greedy filtering algorithm for reducing the search space. Our experimental results on 70 instances of (pseudo) real NMR data derived from 14 proteins demonstrate that the new solution runs much faster than a recently introduced (exhaustive) two-layer algorithm and recovers more correct peak assignments than the two-layer algorithm. Our result demonstrates that integrating different algorithms can achieve a good tradeoff between backbone assignment accuracy and computation time.
Constrained Multiple Sequence Alignment Tool Development and Its Application to RNase Family Alignment
Authors: Tang Chuan Yi , Lu Chin Lung , Chang Margaret Dah-Tsyr , Tsai Yin-Te , Sun Yuh-Ju , Chao Kun-Mao , Chang Jia-Ming , Chiou Yu-Han , Wu Chia-Mao , Chang Hao-Teng , Chou Wei-I
Published: July 2003

In this paper, we design a heuristic algorithm of computing a constrained multiple sequence alignment (CMSA for short) for guaranteeing that the generated alignment satisfies the user-specified constraints that some particular residues should be aligned together. If the number of residues needed to be aligned together is a constant α, then the time-complexity of our CMSA algorithm for aligning K sequences is O(αKn4), where n is the maximum of the lengths of sequences. In addition, we have built up such a CMSA software system and made several experiments on the RNase sequences, which mainly function in catalyzing the degradation of RNA molecules. The resulting alignments illustrate the practicability of our method.
Design and Implementation of a Domain Specific Language for Phylogenetic Inference
Authors: Pontelli Enrico , Ranjan Desh , Gupta Gopal , Milligan Brook
Published: July 2003

Domain experts think and reason at a high level of abstraction when they solve problems in their domain of expertise. We present the design and motivation behind a domain specific language, called ΦLOG, to enable biologists to program solutions to phylogenetic inference problems at a very high level of abstraction. The implementation infrastructure (interpreter, compiler, debugger) for the DSL is automatically obtained through a software engineering framework based on Denotational Semantics and Logic Programming.
Exploring Alternative Transcript Structure in the Human Genome Using BLOCKS and InterPro
Authors: Loraine Ann E. , Helt Gregg A. , Cline Melissa S. , Siani-Rose Michael A.
Published: July 2003

Understanding how alternative splicing affects gene function is an important challenge facing modern-day molecular biology. Using homology-based, protein sequence analysis methods, it should be possible to investigate how transcript diversity impacts protein function. To test this, high-quality exon-intron structures were deduced for over 8000 human genes, including over 1300 (17 percent) that produce multiple transcript variants. A data mining technique (DiffMotif) was developed to identify genes in which transcript variation coincides with changes in conserved motifs between variants. Applying this method, we found that 30 percent of the multi-variant genes in our test set exhibited a differential profile of conserved InterPro and/or BLOCKS motifs across different mRNA variants. To investigate these, a visualization tool (ProtAnnot) that displays amino acid motifs in the context of genomic sequence was developed. Using this tool, genes revealed by the DiffMotif method were analyzed, and when possible, hypotheses regarding the potential role of alternative transcript structure in modulating gene function were developed. Examples of these, including: MEOX1, a homeobox-containing protein; AIRE, involved in auto-immune disease; PLAT, tissue type plasminogen activator; and CD79b, a component of the B-cell receptor complex, are presented. These results demonstrate that amino acid motif databases like BLOCKS and InterPro are useful tools for investigating how alternative transcript structure affects gene function.
Fast Large Scale Oligonucleotide Selection Using the Longest Common Factor Approach
Authors: Rahmann Sven
Published: July 2003

We present a fast method that selects oligonucleotide probes (such as DNA 25-mers) for microarray experiments on a truly large scale. For example, reliable oligos for human genes can be found within four days, a speedup of one to two orders of magnitude compared to previous approaches. This speed is attained by using the longest common substring as a specificity measure for candidate oligos. We present a space- and time-efficient algorithm, based on a suffix array with additional information, to compute matching statistics (lengths of longest matches) between all candidate oligos and all remaining sequences. With the matching statistics available, we show how to incorporate constraints such as oligo length, melting temperature, and self-complementarity into the selection process at a postprocessing stage. As a result, we can now design custom oligos for any sequenced genome, just as the technology for on-site chip synthesis is becoming increasingly mature.
Identification of Biological Relationships from Text Documents Using Efficient Computational Methods
Authors: Palakal Mathew , Stephens Matthew , Mukhopadhyay Snehasis , Raje Rajeev , Rhodes Simon
Published: July 2003

The biological literature databases continue to grow rapidly with vital information that is important for conducting sound biomedical research and development. The current practices of manually searching for information and extracting pertinent knowledge are tedious, time-consuming tasks even for motivated biological researchers. Accurate and computationally efficient approaches in discovering relationships between biological objects from text documents are important for biologists to develop biological models. The term "object" refers to any biological entity such as a protein, gene, cell cycle, etc. and relationship refers to any dynamic action one object has on another, e.g. protein inhibiting another protein or one object belonging to another object such as, the cells composing an organ. This paper presents a novel approach to extract relationships between multiple biological objects that are present in a text document. The approach involves object identification, reference resolution, ontology and synonym discovery, and extracting object-object relationships. Hidden Markov Models (HMMs), dictionaries, and N-Gram models are used to set the framework to tackle the complex task of extracting object-object relationships. Experiments were carried out using a corpus of one thousand Medline abstracts. Intermediate results were obtained for the object identification process, synonym discovery, and finally the relationship extraction. For the thousand abstracts, 53 relationships were extracted of which 43 were correct, giving a specificity of 81 percent. These results are promising for multi-object identification and relationship finding from biological documents.
Prediction of Protein Coarse Contact Maps
Authors: Vullo Alessandro , Frasconi Paolo
Published: July 2003

Prediction of topological representations of proteins that are geometrically invariants can contribute towards the solution of fundamental open problems in structural genomics like folding. In this paper we focus on coarse grained protein contact maps, a representation that describes the spatial neighborhood relation between secondary structure elements such as helices, beta sheets, and random coils. Our methodology is based on searching the graph space. The search algorithm is guided by an adaptive evaluation function computed by a specialized noncausal recursive connectionist architecture. The neural network is trained using candidate graphs generated during examples of successful searches. Our results demonstrate the viability of the approach for predicting coarse contact maps.
Host resistance and tolerance to migratory plant-parasitic nematodes
Authors: Moens Maurice , Peng Yunliang
Published: July 2003

Plant-parasitic nematodes are divided according to their feeding strategy into three major groups: sedentary endoparasites, migratory endoparasites and ectoparasites. Compared to what is known about sedentary endoparasitic nematode species, resistant and tolerant relationships between the nematodes from the latter two groups and their hosts are much less documented. However, methods for screening and evaluation of the resistance and tolerance of plants to migratory plant-parasitic nematodes have been well developed and sources of resistance and tolerance to these nematodes have been found. Advances have been made in breeding resistance to migratory plant-parasitic nematodes in rice, alfalfa, banana, pine trees, grape, woody fruits and other crops. Although accessions immune to stem, leaf and bud nematodes are found quite frequently, host resistance to migratory root-parasitic nematodes has been detected less frequently and generally only partly reduces nematode multiplication. Host tolerance to migratory nematodes is important even for resistant varieties and therefore is gaining attention. An insufficient degree of resistance and tolerance, their variability with the environment, and their linkage to undesired agricultural or horticultural characters are commonly observed. Polygenic bases for plant resistance and tolerance to migratory nematodes have been demonstrated by genetic and biochemical observations and make breeding even more complicated than that for resistance to sedentary plant-parasitic nematodes. These factors, with the presence of different nematode species in the field and community and population differences in pathogenicity, hinder the availability of host resistance and tolerance and offer a big challenge.
Nematode soil faunal analysis of decomposition pathways in different ecosystems
Authors: Ruess Liliane
Published: July 2003

Carbon flow via decomposition of organic matter proceeds through different energy channels depending on the input and turnover rate of plant material. Generally, energy channels in grasslands are considered to be bacteria-dominated, whereas in forests the importance of fungal decomposition increases. Agroecosystems are regarded as intermediate. This hypothesis was tested using indices based on nematode faunal analysis that have been proposed as indicators of decomposition pathways. The ratio of fungal- to bacterial-feeding nematodes and the channel index (Ferris et al., 2001) were calculated from a range of studies, taking into account 131 different sites or sampling times. No distinct differences in the fungal- to bacterial-feeder ratio between grassland, field and forest were observed. However, the channel index indicated a fungal-based energy channel in coniferous forest sites. Generally, the results suggest that soil and climate affect nematode faunal indices more strongly than ecosystem type.
Cylindrocorpus inevectus sp. n. associated with the oil palm weevil, Elaeidobius kamerunicus (Faust) (Coleoptera: Curculionidae), with a synopsis of the family Cylindrocorporidae and establishment of Longibuccidae n. fam. (Diplogastroidea: Nematoda)
Authors: Poinar George , Jackson Trevor , Bell Nigel , Wahid Mohd
Published: July 2003

Cylindrocorpus inevectus sp. n. (Cylindrocorporidae: Nematoda) is described from oil palm flowers (Elaeis guineensis Jacquin) and from the under surface of the elytra of the oil palm weevil, Elaeidobius kamerunicus (Faust) (Coleoptera: Curculionidae) in Malaysia. Cylindrocorpus inevectus sp. n. differs from previously described species in the genus (as defined in the present study) by apparently having only eight pairs of genital papillae in contrast to nine or ten pairs. In addition, the male of the new species differs from C. macrolaimus (Schneider) and C. longistoma (Stefanski) by possessing a very short tail spine. The degree of stoma coverage by the pharyngeal sleeve is suggested as an important character and is 77% in C. longistoma but 91% in C. inevectus sp. n. In the male of C. erectus the bursa does not encircle the tail tip and the tail is much stouter than that of C. inevectus sp. n. In addition, there are only two pairs of pre-anal papillae and two pairs of dorso-lateral post-anal papillae in C. erectus but three pairs of pre-anal papillae and only one pair of dorso-lateral post-anal papillae in C. inevectus sp. n. From C. curzii the new species differs in having the bursal membrane continuing around the tail tip with only two pairs of pre-anal papillae reaching the bursal rim. A key to the genera of the Cylindrocorporidae is provided and Myctolaimus rifflei (Massey & Hinds, 1970) comb. n. is proposed. Because of their parasitic association with vertebrates and morphological characters distinct from those of the saprophagic Cylindrocorporidae, such as the corpus merging with the isthmus, the absence of a valve in the corpus, a posteriorly located vulva, the presence of lateral alae, a reduced number of genital papillae and ovoviviparous nature, members of the genus Longibucca, previously placed in the Cylindrocorporidae, are placed in the new family Longibuccidae fam. n.
Steinernema scarabaei n. sp. (Rhabditida: Steinernematidae), a natural pathogen of scarab beetle larvae (Coleoptera: Scarabaeidae) from New Jersey, USA
Authors: Koppenhöfer Albrecht , Stock S. Patricia
Published: July 2003

Steinernema scarabaei n. sp. (Rhabditida: Steinernematidae) is a new entomopathogenic nematode isolated from larvae of the scarab beetles Anomala(= Exomala)orientalis and Popillia japonica from turfgrass in New Jersey, USA. Morphology, hybridisation and molecular studies indicated the distinctness of S. scarabaei n. sp. from other Steinernema spp. Distinctive diagnostic characters include: the presence of a mucronated tail in both first generation adults; the presence of a ventrally bifurcated mucro in the first generation female tail; the size and shape of the spicules and gubernaculum and the arrangement of the genital papillae of the male; third-stage infective juvenile with total body length of 890-959 μm and lateral field with eight longitudinal ridges. RFLP analysis of the ITS region of rDNA showed S. scarabaei n. sp. to be distinct from 50 other Steinernema species and isolates. In addition, phylogenetic interpretation of sequence data from the LSU of rDNA provided further evidence for autapomorphies and separate species status for S. scarabaei n. sp.
Effect of plant lectins on the host-finding behaviour of Radopholus similis
Authors: Sági László , Swennen Rony , De Waele Dirk , Peumans Willy , Van Damme Els , Elsen Annemie , Wuyts Nathalie
Published: July 2003

The motility and the chemotactic response towards plant roots of Radopholus similis, after treatment with novel types of lectins, were examined in vitro by analysing movement tracks on agar plates. Six plant lectins belonging to five different lectin families and a banana thaumatin-like protein (BanTLP) were included in the experiment. A 1% concentration of Phaseolus vulgaris agglutinin (PHA) had an adverse effect on the motility of R. similis females: 63% showed no or very little movement on agar plates compared to an average of 33% for other lectins and 3% for the control treatment. A 0.05% concentration of PHA still reduced the motility of R. similis females by 75%. Concanavalin A and wheat germ agglutinin did not alter the chemotactic response towards plant roots, despite binding of both lectins to R. similis. In contrast, Galanthus nivalis agglutinin (GNA) reduced orientated movement of R. similis towards plant roots. Subsequently, secretions of R. similis were stained with Coomassie Brilliant Blue R. Nematodes treated with GNA produced secretions less abundantly compared to the control treatment and BanTLP. The other lectins in the experiment had variable effects on secretion.
Molecular cloning and life stage expression pattern of a new acetylcholinesterase gene from the plant-parasitic nematode Meloidogyne incognita
Authors: Laffaire Jean-Baptiste , Rosso Marie-Noëlle , Jaubert Stéphanie , Abad Pierre
Published: July 2003

A new cDNA, named Mi-ace-2, encoding an acetylcholinesterase, was isolated from Meloidogyne incognita. The full-length cDNA, carrying the trans-spliced SL1 leader sequence, was 2122 bp long with an open reading frame of 2058 bp. The predicted protein shared 32.3% identity with the previously identified MI ACHE and 49.1% identity with the C. elegans ACE-2. The conserved motifs involved in the catalytic triad, the choline binding site and 11 aromatic residues lining the catalytic gorge were present in the MI-ACE-2 deduced protein. RT-PCR analysis showed that Mi-ace-2 is transcribed in second stage juveniles before and after hatching, in females and in males. Phylogenetic analysis showed that MI-ACE-2 and ACE-2 were clustered in a distinct group closely related to the acetylcholinesterases secreted by animal-parasitic nematodes.
Comparison of the production and mobility of hatching activity towards the potato cyst nematodes, Globodera rostochiensis and G. pallida within soil planted with a host potato crop
Authors: Devine Ken , Jones Peter
Published: July 2003

Soil core samples were taken from a commercial potato field before emergence of the potato crop, during crop development and after harvesting. Leachates from the cores were analysed in an in vitro hatching assay in the laboratory for activity towards the potato cyst nematodes (PCN), Globodera rostochiensis and G. pallida. Hatching activity in the soil increased rapidly after plant emergence and peaked between 2 and 5 weeks after emergence; thereafter, at about the onset of flowering, hatching factor activity decreased markedly. The soil cores collected in the first 2 weeks after plant emergence contained significantly greater hatching activity towards G. pallida than G. rostochiensis, indicating that G. pallida-selective hatching factors were produced by the host crop earlier than G. rostochiensis-selective hatching factors. Soil cores collected from the potato ridge and the furrows at various depths and distances from the host plants differed in the distribution of G. pallida-selective and G. rostochiensis-selective hatching activity within the soil profile. Globodera pallida-selective hatching activity had greater vertical and horizontal mobility in the soil profile and elicited significantly greater hatching responses than G. rostochiensis beyond the region of the rhizosphere. Significant levels of hatching factor activity could be detected in the field 90 days after harvesting of the potato crop.
New citrus selections from Cleopatra mandarin × Poncirus trifoliata with resistance to Tylenchulus semipenetrans Cobb
Authors: Ornat César , Sorribas F. Javier , Forner Juan , Galeano Magda , Alcaide Antonio , Verdejo-Lucas Soledad
Published: July 2003

The response of four resistant selections of Cleopatra mandarin × Poncirus trifoliata to increasing inoculum densities of a population of the Mediterranean biotype of Tylenchulus semipenetrans was determined in microplots established at two sites. One-yearold trees of the resistant selections and of a susceptible Carrizo citrange were inoculated with 0, 1, 5 or 10 × 104 eggs per plant (Pi). Nematode reproduction on the resistant selections was consistently less than on Carrizo citrange. Increasing initial inoculum densities had no effect on the relative resistance in three selections (03.01.42, 03.01.5 and 03.01.16). Selection 03.01.42 was highly resistant (no females and eggs per g fresh root), and 03.01.5 and 03.01.16 both had good resistance (≤15% as many females and eggs per g fresh root as on Carrizo citrange). The fourth selection (03.01.18) expressed resistance at Pi 1 and 5 × 104 eggs per plant but was moderately susceptible at 10× 104 eggs per plant (>15% females and eggs per g fresh root). Deposits of a lignin or suberin-like material were more abundant in resistant selections 03.01.5 and 03.01.18 than in susceptible Carrizo citrange. The proportional increase in trunk diameter of inoculated and uninoculated trees of each rootstock was similar at both sites.
In vitro systems for studying the interaction of root-knot nematode with grapevine
Authors: Savocchia Sandra , Franks Tricia , Van Heeswijck Robyn
Published: July 2003

A simple system for in vitro dual culture of grapevine (Vitis spp.) plantlets and root-knot nematode (Meloidogyne javanica (Treub) Chitwood) is described. Based on the presence or absence of mature females, or the total number of nematodes in the roots after 36-day co-culture, the system reliably discriminated resistant (cv. Ramsey) and susceptible (cv. Chardonnay) grapevines. The system was sensitive enough to differentiate between infestation levels of cvs Börner and Chardonnay, both susceptible in the in vitro conditions. A modification of the system to use plantlets from rooted petioles has reduced labour and space requirements and would suit mass screening of grapevine genotypes in traditional or genetic engineering-based breeding programmes. In both systems, nematodes in roots of cv. Ramsey tended to be associated with brown tissue and, compared with those in roots of cv. Chardonnay, were more likely to be confined to tips rather than be distributed along the root after co-culture for 11 or 36 days.
Nematodes of the order Rhabditida from Andalucía Oriental, Spain. The genus Chiloplacus Thorne, 1937, with description of C. maginensis sp. n. and a key to species
Authors: Peña-Santiago Reyes , Abolafia Joaquín
Published: July 2003

Five known and one new species of the genus Chiloplacus Thorne, 1937 are studied from natural ecosystems in the SE Iberian Peninsula: C.demani (Thorne, 1925) Thorne, 1937, C. maginensis sp. n., C. minimus (Thorne, 1925) Andrássy, 1959, C. magnus Rashid & Heyns, 1990, C. tenuis Rashid & Heyns, 1990 and C. trilineatus Steiner, 1940. Chiloplacus maginensis sp. n. is characterised by a female body length of 272-345 μm, lateral field starting far anterior near the labial region and with five incisures, lip region with bifurcate labial probolae bearing short prongs, pharyngeal corpus 2.5-3.6 times isthmus length, ovary without flexures posterior to vulva, spermatheca 8-17 μm long, postuterine sac 0.2-0.5 of corresponding body diam. long, female tail conical with rounded terminus (12-20 μm; c´ = 15.0-26.6; c′ = 1.1-1.5), phasmid at 39-48% of tail length. Descriptions, measurements and illustrations, including SEM photographs, are provided for the six species recorded. The diagnosis of Chiloplacus is emended, the nominal species listed and a key provided to those nominal species currently regarded as valid.
Histological studies on the anatomy of the parasitic stages of Australonema sp. (Nematoda: Marimermithida)
Authors: Miljutin Dmitry
Published: July 2003

Parasitic stages (7-122 mm long) of Australonema sp. (Marimermithida, Enoplia) found in deep-sea polychaetes and in an echiurid from the Southern and Northern Atlantic, were studied histologically. The cephalic sensilla of the anterior end comprise six labial papillae and ten short cephalic papillae. The amphidial apertures are pore-like. Numerous tiny sensilla are distributed throughout the lateral regions of the body and there are eight hypodermal chords. A mouth opening, rectum and anus are all present. The pharynx is long and muscular with a triradial internal lumen, the pharyngeal glands opening almost at the apical part of the labia. The cardia is small with a triradial lumen. The midgut has a spacious lumen. The cervical excretory gland is two-cellular. The female genital system is amphidelphic, the germinal zone extending the length of the ovary (i.e., hologonic).
Comparative morpho-anatomical studies of the female gonoduct within the Pratylenchidae (Nematoda: Tylenchina)
Authors: Borgonie Gaëtan , Bert Wim , Van Gansbeke Ruben , Geraert Etienne , Claeys Myriam
Published: July 2003

The cellular morphology of the gonoduct of six Pratylenchus species, three Pratylenchoides species, Radopholus similis, Zygotylenchus guevarai, Hirschmanniella loofi and Nacobbus aberrans was revealed by dissection and light microscopy. Except for Nacobbus aberrans, all studied species show an overall similarity in gonoduct construction, i.e., an ovary often ending with a ring of cells, an oviduct formed from two rows of four cells and a 12-celled spermatheca followed by a tricolumella containing 16-24 cells. Pratylenchoides magnicauda and Z. guevarai did not diverge from the other Pratylenchidae in this respect, although their gonoduct differs from that of Amplimerlinius and Meloidogyne, both formerly postulated as related genera. The spermatheca structure observed in N. aberrans has not been reported elsewhere in the Nematoda, although the uterus is similar to that reported within the Heteroderinae and Meloidogyninae and the uterus comprises more than 300 cells, enlarging from a tricolumella to a polycolumella. Transmission electron microscopy of Z. guevarai revealed details of the cytoplasmatic contact between epithelial cells and the germ cells; a finger-like ovarian wall cell extension was found penetrating the oocyte. The oviduct lacks a preformed lumen and comprises eight cells with highly plicated cell membranes. The spermatheca is constructed from flattened wall cells and is followed by columnar uterus cells where evidence of eggshell formation was demonstrated.
Ultrastructure of the attachment and feeding sites of Gracilacus latescens Raski, 1976 in timber bamboo roots and selected anatomical details of the female stylet
Authors: Achor Dianne , Duncan Larry , Inserra Renato , Troccoli Alberto
Published: July 2003

Mature female Gracilacus latescens are sedentary and remain attached by the stylet to the surface of timber bamboo roots (Phyllostachys bambusoides) for their entire life. Observations by transmission electron microscopy (TEM) of the anatomy of the anterior portion of the female body showed the stylet shaft surrounded by a thick stomatal wall sensu Endo (1983) and by large protractor muscles. Cross sections of the root at the site of nematode attachment showed accumulation of electron-opaque material between the nematode body and the epidermal wall penetrated by the stylet. Electron-dense material enwrapped the stylet from the point of its insertion in an epidermal cell wall until its end in the lumen of a sclerenchymal or cortical cell. Two to three cells are penetrated by the stylet. The electron-dense material appeared to originate from the walls of epidermal, cortical parenchymal and sclerenchymal cells perforated by the stylet. The thickness of this material increased with the number of sclerenchyma cell walls penetrated by the stylet. Cross sections of the enwrapped stylet showed it tightly encased in the electron-dense material, which appeared to anchor the stylet and consequently the nematode body to the root surface. A syncytium originates from the innermost cell reached by the enwrapped stylet and expands into the inner cortex and stele. Cell wall dissolution and pit fields are characteristics of the syncytium.
Effect of Metoprolol and Verapamil Administered Separately and Concurrently after Single Doses on Liver Blood Flow and Drug Disposition
Authors: Bauer Larry A. , Horn John R. , Maxon M. Scot , Easterling Thomas R. , Shen Danny D. , Strandness D. E.
Published: July 2003

Nine healthy males participated in a double‐blind, placebo‐controlled, randomized, crossover study to determine the effects of verapamil and metoprolol administered alone and concurrently on blood flow through the hepatic artery and portal and hepatic veins and to detect a possible drug interaction between the two agents. Single oral doses of placebo/placebo, metoprolol (50 mg)/placebo, verapamil (80 mg)/placebo, or verapamil/metoprolol were separated by at least 14 days. Liver blood flow through individual hepatic vessels was measured up to 8 hours after dosage administration using a duplex Doppler ultrasound technique. Cardiac output, heart rate, blood pressure, stroke volume, and total peripheral resistance were measured for 3 hours after drug doses were given. In 5 subjects, pharmacokinetic parameters for total drug as well as S‐ and R‐enantiomers were also measured. Verapamil given alone caused a rapid and intense increase in liver blood flow (hepatic artery = 50%, portal vein = 42%, hepatic vein = 55%) 0.75 to 1 hour after administration because of a decrease in total peripheral resistance and an increase in heart rate, stroke volume, and cardiac output. Metoprolol given alone caused a slow but prolonged decrease in liver blood flow (maximum decrease: hepatic artery = −54%, portal vein = −21%, hepatic vein = −27%) 4 hours after administration because of a decrease in heart rate and cardiac output. When the two agents were given together, a composite of the changes noted after separate administration was noted: a brief peak increase in liver blood flow at 0.33 to 1 hour followed by a slow, prolonged decrease that reached its maximum decline 4 to 5 hours postdose. During the combined phase, metoprolol and its enantiomers had an increased AUC and Cmax, while verapamil and its enantiomers had an increased AUC and t1/2 These pharmacokinetic changes were consistent with the magnitude and time course of liver blood flow changes through the hepatic artery and portal or hepatic veins.
An Evolution of Drug Development and Clinical Pharmacology during the 20th Century
Authors: Heath Gene , Colburn Wayne A.
Published: July 2003

The current state of clinical pharmacology and drug development did not just happen. Clinical pharmacology and the drug development process were born, evolved, and have come to the fore during the past 100 years. The past century has been one of accelerating progress in science and medicine. The progress has not been a straight line but rather more like a sidewinder moving across the desert. Drug development has moved from small experiments with concoctions, extracts, and potions along with the manufacturing and promotion of the purported remedies to processes that exploited unknowing patients to a process that now requires concept generation, discovery, research, planning, and development with many checks and balances for the protection of human subjects. The factors that contributed to this progression from inappropriate use of potions, concoctions, and snake oil to the highly regulated drug development process of today is described in some detail.
Evaluation of CYP2D6 Oxidation of Dextromethorphan and Propafenone in a Chinese Population with Atrial Fibrillation
Authors: Chow Moses S. S. , White C. Michael , Lau Chu‐Pak , Fan Chengde , Tang Man‐Oi
Published: July 2003

The objective of this study was to determine the percentage of patients with paroxysmal atrial fibrillation who were poor metabolizers of CYP2D6 in a Chinese population from Hong Kong and to assess the relationship between the dextromethorphan/dextrorphan ratio and the propafenone/5‐hydroxypropafenone ratio or the steady‐state propafenone concentration. Patients (n = 60) were recruited from the Arrhythmia Clinic at the University of Hong Kong and given dextromethorphan 30 mg. The dextromethorphan and dextrorphan concentrations in urine over the next 8 hours were used to determine metabolizer status. If the metabolic ratio was greater than 0.3, the patient was determined to be a poor metabolizer. In phase 2, patients (n = 38) were given propafenone 150 mg twice daily, and at steady state, the propafenone and 5‐OH propafenone plasma concentrations were determined. It was found that 15% of the patients were poor metabolizers of dextromethorphan. There was a significant correlation between the metabolic ratios of dextromethorphan/dextrorphan and propafenone/5‐OH propafenone (r = 0.49, p = 0.0019) and between the dextromethorphan/dextrorphan ratio and the concentration of propafenone (r = 0.32, p = 0.05). No correlations were found in the extensive or poor metabolizer subgroups. It was concluded that the percentage of poor metabolizers in atrial fibrillation patients from Hong Kong was much larger than in previous studies of Chinese patients who were not from Hong Kong. The ability to metabolize dextromethorphan to dextrorphan is related to the ability to metabolize propafenone to 5‐hydroxypropafenone.
Sevelamer Hydrochloride (Renagel®), a Phosphate‐Binding Polymer, Does Not Alter the Pharmacokinetics of Two Commonly Used Antihypertensives in Healthy Volunteers
Authors: Burke Steven K. , Amin Naseem S. , Incerti Carlo , Plone Melissa A. , Lee Jean W.
Published: July 2003

Sevelamer hydrochloride (Renagel®) is a nonabsorbed phosphate‐binding polymer approved for the treatment of hyperphosphatemia in adult hemodialysis patients. The authors studied the potential effect of sevelamer on the pharmacokinetics of two antihypertensive drugs, enalapril (20 mg) and metoprolol (100 mg), commonly used in end‐stage renal disease patients. Two studies were conducted. Both were single dose, crossover design with or without a 2.4 g dose of sevelamer in healthy volunteers. Within each study, there was a 7‐day washout interval between the two dose administrations. There were 28 volunteers in the enalapril study and 32 in the metoprolol study. The mean plasma concentrations versus time profiles of enalapril, enalaprilat, and metoprolol were not altered by the simultaneous administration of sevelamer. Values for the ratio of ln[AUC(0‐∞)], ln[AUC(0‐t)], and ln[Cmax] with and without sevelamer were approximately 100%, and the 90% confidence intervals for the ratios of these parameters with and without sevelamer were within the 80% to 125% range in all cases except for the ln[Cmax] of enalapril, which had an upper confidence bound of 125.4%. The authors conclude that sevelamer does not interfere with the absorption and elimination of enalapril and metoprolol.
The Influence of Food on the Bioavailability of a Twice‐Daily Controlled Release Carbamazepine Formulation
Authors: McLean Angus , Browne Susan , Zhang Yuxin , Slaughter Elizabeth , Halstenson Charles , Couch Richard
Published: July 2003

Carbatrol®, a new dosage form of carbamazepine (CBZ), was developed consisting of three different types of pellets (immediate release, controlled release, and enteric release). The objective of this study was to explore the influence of food on absorption of CBZ. This was a randomized, open‐label, single‐dose crossover study conducted in 12 healthy volunteers. Treatments were 2 × 200 mg Carbatrol with a high‐fat meal, fasted, or sprinkled over applesauce (but otherwise fasted). Each subject received one dose of each treatment separated by a washout period of at least 2 weeks. CBZ bioequivalence was established based on the equivalence of AUC (extent of absorption) in all three conditions. Carbatrol may be taken with or without food or the capsule opened and sprinkled on food.
Dichloroacetate: Population Pharmacokinetics with a Pharmacodynamic Sequential Link Model
Authors: Williams Paul J. , Lane James R. , Turkel Catherine C. , Capparelli Edmund V. , Dziewanowska Zofia , Fox Anthony W.
Published: July 2003

Dichloroacetate (DCA) is a small molecule that reduces ambient concentrations of lactate in man. It was the purpose of this study to develop pharmacokinetic and pharmacodynamic models for determination of a dose for a pivotal Phase III clinical trial of DCA in patients with traumatic brain injury (TBI). Population pharmacokinetic and pharmacodynamic models were developed for DCA using NONMEM® software. The pharmacokinetic data were fit to a physiologic two‐compartment model, and the pharmacodynamic data were fit to an indirect physiologic response model. Simulations were employed to evaluate various dosing strategies for consideration in a pivotal Phase III clinical trial of DCA. For the pharmacokinetic model, it was discovered that the clearance of DCA decreased on multiple dosing from 4.82 L/h to 1.07 L/h and that the pharmacokinetics and pharmacodynamics in TBI patients could not be predicted from normal volunteers. Population pharmacokinetic modeling and simulation of the expected effects of several dosing strategies were useful procedures for designing a Phase III trial.
Effect of Grapefruit Juice on Pharmacokinetics of Microemulsion Cyclosporine in African American Subjects Compared with Caucasian Subjects: Does Ethnic Difference Matter?
Authors: Lee Miyoung , Min David I. , Ku Yi‐Min , Flanigan Michael
Published: July 2003

This study aims to determine the effect of grapefruit juice (GJ) on microemulsion cyclosporine (CsA) in 11 African American subjects, and it was compared to those in 11 Caucasian subjects. Each subject received two oral doses of CsA with water (W) or GJ as well as IV CsA. Regardless of race, GJ significantly increased the peak concentration (Cmax) and area under the time‐curve (AUC) of CsA; however, the magnitude of GJ effects was different between African American subjects and Caucasian subjects(p =0.0003). GJ increased peak concentration of CsA by 39% in African American subjects, while the difference in Caucasian subjects was only 8%(p >0.05). GJ also increased AUC of CsA in African American subjects by 60%, while GJ increased that in Caucasian subjects by 44%(p =0.0001). The absolute bioavailability of CsA was 21% lower in African American subjects compared with Caucasian subjects when it was given with water(p =0.048), but these differences disappeared when it was given with GJ(p =0.6). These findings suggest that concurrent administration of GJ increases the bioavailability of CsA in African American subjects in greater magnitude compared with Caucasian subjects.
Effect of Alosetron on the Pharmacokinetics of Alprazolam
Authors: D'Souza Doreen L. , Levasseur Laurence M. , Nezamis James , Robbins Doris K. , Simms Lorinda , Koch Kevin M.
Published: July 2003

Lotronex® (alosetron hydrochloride) is a 5‐HT3 receptor antagonist indicated for the treatment of irritable bowel syndrome (IBS) in females whose predominant bowel habit is diarrhea. Alosetron is extensively metabolized by multiple cytochrome P450 (CYP) enzymes, including CYP 2C9 and 3A4. Alprazolam is a short‐acting benzodiazepine commonly prescribed for the treatment of anxiety disorders and a potential comedication in patients with IBS. Alprazolam is extensively metabolized by CYP3A4. This clinical study was conducted to assess the potential for a metabolic drug interaction between these two CYP3A4 substrates. This was an open‐label, randomized, two‐period, crossover study in 12 healthy female and male volunteers to determine the effect of concomitant administration of alosetron at the recommended dose of 1 mg PO bid on the pharmacokinetics of alprazolam following a single oral 1 mg dose. The results showed no effect of alosetron on the pharmacokinetics of alprazolam. Mean alprazolam AUC was 210 and 202 ng•h/mL in the absence and the presence of alosetron, respectively. Therefore, alprazolam may be safely coadministered with alosetron without the need for dosage adjustment.