bluuebunny/crossref_metadata_2025 huggingface dataset:
Duck Hepatitis B Virus Virion Secretion Requires a Double-Stranded DNA Genome
Authors: Perlman David , Hu Jianming
Published: January 2003

Hepatitis B virus assembly begins with the packaging of an RNA pregenome into intracellular nucleocapsids, with subsequent reverse transcription within these nucleocapsids converting the RNA into a characteristic, partially double-stranded DNA, which, alone, is found in enveloped extracellular virions as the viral genome. Using a synchronized replication system for the duck hepatitis B virus, together with a stringent two-step assay for virion secretion, we demonstrate that this selective genome secretion results from an intrinsic secretion competence gained only by the nucleocapsids at the late stage of reverse transcription.
In Vitro RNA Replication Directed by Replicase Complexes Isolated from the Subgenomic Replicon Cells of Hepatitis C Virus
Authors: Lai Vicky C. H. , Dempsey Shannon , Lau Johnson Y. N. , Hong Zhi , Zhong Weidong
Published: January 2003

Replication of hepatitis C virus (HCV) RNA in virus-infected cells is believed to be catalyzed by viral replicase complexes (RCs), which may consist of various virally encoded nonstructural proteins and host factors. In this study, we characterized the RC activity of a crude membrane fraction isolated from HCV subgenomic replicon cells. The RC preparation was able to use endogenous replicon RNA as a template to synthesize both single-stranded (ss) and double-stranded (ds) RNA products. Divalent cations (Mg
2+
and Mn
2+
) showed different effects on RNA synthesis. Mg
2+
ions stimulated the synthesis of ss RNA but had little effect on the synthesis of ds RNA. In contrast, Mn
2+
ions enhanced primarily the synthesis of ds RNA. Interestingly, ss RNA could be synthesized under certain conditions in the absence of ds RNA, and vice versa, suggesting that the ss and ds RNA were derived either from different forms of replicative intermediates or from different RCs. Pulse-chase analysis showed that radioactivity incorporated into the ss RNA was chased into the ds RNA and other larger RNA species. This observation indicated that the newly synthesized ss RNA could serve as a template for a further round of RNA synthesis. Finally, 3′ deoxyribonucleoside triphosphates were able to inhibit RNA synthesis in this cell-free system, presumably through chain termination, with 3′ dGTP having the highest potency. Establishment of the replicase assay will facilitate the identification and evaluation of potential inhibitors that would act against the entire RC of HCV.
Phylogenetic analysis of North AmericanElymusand the monogenomic Triticeae (Poaceae) using three chloroplast DNA data sets
Authors: Mason-Gamer Roberta J , Orme Nancy L , Anderson Claire M
Published: January 2003

Although the monogenomic genera of the Triticeae have been analyzed in numerous biosystematic studies, the allopolyploid genera have not been as extensively studied within a phylogenetic framework. We focus on North American species of Elymus, which, under the current genomic system of classification, are almost all allotetraploid, combining the St genome of Pseudoroegneria with the H genome of Hordeum. We analyze new and previously published chloroplast DNA data from Elymus and from most of the monogenomic genera of the Triticeae in an attempt to identify the maternal genome donor of Elymus. We also present a cpDNA phylogeny for the monogenomic genera that includes more data than, and thus builds on, those previously published. The chloroplast DNA data indicate that Pseudoroegneria is the maternal genome donor to all but one of the Elymus individuals. There is little divergence among the Elymus and Pseudoroegneria chloroplast genomes, and as a group, they show little divergence from the rest of the Triticeae. Within the monogenomic Triticeae, the problematic group Thinopyrum is resolved as monophyletic on the chloroplast DNA tree. At the intergeneric level, the data reveal several deeper-level relationships that were not resolved by previous cpDNA trees.Key words: chloroplast genome, phylogeny, polyploidy, systematics.
Comparative linkage map of theSolanum lycopersicoidesandS. sitiensgenomes and their differentiation from tomato
Authors: Pertuzé Ricardo A , Ji Yuanfu , Chetelat Roger T
Published: January 2003

The wild nightshades Solanum lycopersicoides and Solanum sitiens are closely affiliated with the tomatoes (Lycopersicon spp.). Intergeneric hybridization with cultivated tomato (Lycopersicon esculentum) is impeded by strong reproductive barriers including hybrid sterility and suppressed recombination. Conservation of genome structure between these nightshades and tomato was studied by construction of a genetic map from F2S. sitiens × S. lycopersicoides and comparison with existing maps of tomato. Owing to self-incompatibility of the F1, two hybrid plants were crossed to obtain a population of 82 F2individuals. Using 166 previously mapped RFLP markers and 5 restriction enzymes, 101 loci polymorphic in the S. sitiens × S. lycopersicoides population were identified. Analysis of linkage between the markers resulted in a map with 12 linkage groups covering 1192 cM and one unlinked marker. Recombination rates were similar to those observed in tomato; however, significant segregation distortion was observed for markers on 7 out of the 12 chromosomes. All chromosomes were colinear with the tomato map, except for chromosome 10, where a paracentric inversion on the long arm was detected. In this region, S. sitiens and S. lycopersicoides share the same chromosomal configuration previously reported for potato (S. tuberosum) and pepper (Capsicum), suggesting that of tomato is derived. The 10L inversion explains the lack of recombination detected among homeologous chromosomes of intergeneric hybrids in this region. On this basis, we recognize two principle genomes, designated L for the Lycopersicon spp., and S for S. lycopersicoides and S. sitiens, the first examples of structural differentiation between tomato and its cross-compatible wild relatives.Key words: tomato, Solanum lycopersicoides, Solanum sitiens, RFLPs, comparative linkage maps.
Genetic diversity in three groups of barley germplasm assessed by simple sequence repeats
Authors: Matus I A , Hayes P M
Published: January 2003

Genetic diversity can be measured by several criteria, including phenotype, pedigree, allelic diversity at marker loci, and allelic diversity at loci controlling phenotypes of interest. Abundance, high level of polymorphism, and ease of genotyping make simple sequence repeats (SSRs) an excellent molecular marker system for genetics diversity analyses. In this study, we used a set of mapped SSRs to survey three representative groups of barley germplasm: a sample of crop progenitor (Hordeum vulgare subsp. spontaneum) accessions, a group of mapping population parents, and a group of varieties and elite breeding lines. The objectives were to determine (i) how informative SSRs are in these three sets of barley germplasm resources and (ii) the utility of SSRs in classifying barley germplasm. A total of 687 alleles were identified at 42 SSR loci in 147 genotypes. The number of alleles per locus ranged from 4 to 31, with an average of 16.3. Crop progenitors averaged 10.3 alleles per SSR locus, mapping population parents 8.3 alleles per SSR locus, and elite breeding lines 5.8 alleles per SSR locus. There were many exclusive (unique) alleles. The polymorphism information content values for the SSRs ranged from 0.08 to 0.94. The cluster analysis indicates a high level of diversity within the crop progenitors accessions and within the mapping population parents. It also shows a lower level of diversity within the elite breeding germplasm. Our results demonstrate that this set of SSRs was highly informative and was useful in generating a meaningful classification of the germplasm that we sampled. Our long-term goal is to determine the utility of molecular marker diversity as a tool for gene discovery and efficient use of germplasm.Key words: Hordeum vulgare subsp. vulgare, Hordeum vulgare subsp. spontaneum, SSR, genetic diversity, germplasm.
Mosaic microecological differential stress causes adaptive microsatellite divergence in wild barley,Hordeum spontaneum, at Neve Yaar, Israel
Authors: Huang Qingyang , Beharav Alex , Li Youchun , Kirzhner Valery , Nevo Eviatar
Published: January 2003

Genetic diversity at 38 microsatellite (short sequence repeats (SSRs)) loci was studied in a sample of 54 plants representing a natural population of wild barley, Hordeum spontaneum, at the Neve Yaar microsite in Israel. Wild barley at the microsite was organized in a mosaic pattern over an area of 3180 m2in the open Tabor oak forest, which was subdivided into four microniches: (i) sunrock (11 genotypes), (ii) sunsoil (18 genotypes), (iii) shadesoil (11 genotypes), and (iv) shaderock (14 genotypes). Fifty-four genotypes were tested for ecologicalgenetic microniche correlates. Analysis of 36 loci showed that allele distributions at SSR loci were nonrandom but structured by ecological stresses (climatic and edaphic). Sixteen (45.7%) of 35 polymorphic loci varied significantly (p < 0.05) in allele frequencies among the microniches. Significant genetic divergence and diversity were found among the four subpopulations. The soil and shade subpopulations showed higher genetic diversities at SSR loci than the rock and sun subpopulations, and the lowest genetic diversity was observed in the sunrock subpopulation, in contrast with the previous allozyme and RAPD studies. On average, of 36 loci, 88.75% of the total genetic diversity exists within the four microniches, while 11.25% exists between the microniches. In a permutation test, GSTwas lower for 4999 out of 5000 randomized data sets (p < 0.001) when compared with real data (0.1125). The highest genetic distance was between shade-soil and sunrock (D = 0.222). Our results suggest that diversifying natural selection may act upon some regulatory regions, resulting in adaptive SSR divergence. Fixation of some loci (GMS61, GMS1, and EBMAC824) at a specific microniche seems to suggest directional selection. The pattern of other SSR loci suggests the operation of balancing selection. SSRs may be either direct targets of selection or markers of selected haplotypes (selective sweep).Key words: natural selection, genetic diversity, microsatellites, adaptation, Hordeum spontaneum, wild barley, microsite divergence.
Synaptic behaviour and morphological modifications of the X and Y chromosomes during pachytene in three species ofCtenomys(Rodentia, Caviomorpha, Ctenomyidae)
Authors: Lanzone C , Bidau C J , Giménez M D , Santos J L
Published: January 2003

Synaptic behaviour and the progression of morphological differentiation of the XY chromosome pair during pachytene was studied for the first time in three species of the South American subterranean rodents of the genus Ctenomys (tuco-tucos). In general, synapsis progression in the sex pair could be subdivided into four substages: (i) initial partial synapsis of the X and Y chromosome axes and beginning of the differentiation of the unsynapsed regions; (ii) complete or almost complete synapsis of the Y axis accompanied with morphological differentiation of the unsynapsed region of the X chromosome; (iii) a novel stage exclusive to Ctenomys perrensi consisting in a retraction of the free X axis, associated with the formation of a homogeneous and dense structure along the synaptic region, which leads to the achievement of full synapsis between sex chromosomes; or (iv) an increase in morphological complexity involving extreme splitting of the XY pair. The implications of the peculiar synaptic behaviour displayed by sex chromosomes in C. perrensi, a species complex highly polymorphic for Robertsonian translocations, are discussed in relation to both the triggering of the pachytene checkpoint and the avoidance of non-homologous associations between sex chromosomes and the asynaptic pericentromeric regions of trivalents in translocation heterozygotes.Key words: Ctenomys, meiosis, Robertsonian translocations, sex chromosomes, synapsis.
Fluorescence in situ hybridization mapping of Avena sativa L. cv. SunII and its monosomic lines using cloned repetitive DNA sequences
Authors: Irigoyen M L , Linares C , Ferrer E , Fominaya A
Published: January 2003

Fluorescent in situ hybridization (FISH) employing multiple probes was used with mitotic or meiotic chromosome spreads of Avena sativa L. cv. SunII and its monosomic lines to produce physical chromosome maps. The probes used were Avena strigosa pAs120a (which hybridizes exclusively to A-genome chromosomes), Avena murphyi pAm1 (which hybridizes exclusively to C-genome chromosomes), A. strigosa pAs121 (which hybridizes exclusively to A- and D-genome chromosomes), and the wheat rDNA probes pTa71 and pTa794. Simultaneous and sequential FISH employing two-by-two combinations of these probes allowed the unequivocal identification and genome assignation of all chromosomes. Ten pairs were found carrying intergenomic translocations: (i) between the A and C genomes (chromosome pair 5A); (ii) between the C and D genomes (pairs 1C, 2C, 4C, 10C, and 16C); and (iii) between the D and C genomes (pairs 9D, 11D, 13D, and 14D). The existence of a reciprocal intergenomic translocation (10C14D) is also proposed. Comparing these results with those of other hexaploids, three intergenomic translocations (10C, 9D, and 14D) were found to be unique to A. sativa cv. SunII, supporting the view that 'SunII' is genetically distinct from other hexaploid Avena species and from cultivars of the A. sativa species. FISH mapping using meiotic and mitotic metaphases facilitated the genomic and chromosomal identification of the aneuploid chromosome in each monosomic line. Of the 18 analyzed, only 11 distinct monosomic lines were actually found, corresponding to 5 lines of the A genome, 2 lines of the C genome, and 4 lines of the D genome. The presence or absence of the 10C14D interchange was also monitored in these lines.Key words: Avena sativa, monosomics, FISH mapping, genomic identification, intergenomic translocations.
Microsatellite DNA fingerprinting, differentiation, and genetic relationships of clones, cultivars, and varieties of six poplar species from three sections of the genus Populus
Authors: Rahman Muhammad H , Rajora Om P
Published: January 2003

Accurate identification of Populus clones and cultivars is essential for effective selection, breeding, and genetic resource management programs. The unit of cultivation and breeding in poplars is a clone, and individual cultivars are normally represented by a single clone. Microsatellite DNA markers of 10 simple sequence repeat loci were used for genetic fingerprinting and differentiation of 96 clones/cultivars and varieties belonging to six Populus species (P. deltoides, P. nigra, P. balsamifera, P. trichocarpa, P. grandidentata, and P. maximowiczii) from three sections of the genus. All 96 clones/cultivars could be uniquely fingerprinted based on their single- or multilocus microsatellite genotypes. The five P. grandidentata clones could be differentiated based on their single-locus genotypes, while six clones of P. trichocarpa and 11 clones of P. maximowiczii could be identified by their two-locus genotypes. Twenty clones of P. deltoides and 25 clones of P. nigra could be differentiated by their multilocus genotypes employing three loci, and 29 clones of P. balsamifera required the use of multilocus genotypes at five loci for their genetic fingerprinting and differentiation. The loci PTR3, PTR5, and PTR7 were found to be the most informative for genetic fingerprinting and differentiation of the clones. The mean number of alleles per locus ranged from 2.9 in P. trichocarpa or P. grandidentata to 6.0 in P. balsamifera and 11.2 in 96 clones of the six species. The mean number of observed genotypes per locus ranged from 2.4 in P. grandidentata to 7.4 in P. balsamifera and 19.6 in 96 clones of the six species. The mean number of unique genotypes per locus ranged from 1.3 in P. grandidentata to 3.9 in P. deltoides and 8.8 in 96 clones of the six species. The power of discrimination of the microsatellite DNA markers in the 96 clones ranged from 0.726 for PTR4 to 0.939 for PTR7, with a mean of 0.832 over the 10 simple sequence repeat loci. Clones/cultivars from the same species showed higher microsatellite DNA similarities than the clones from the different species. A UPGMA cluster plot constructed from the microsatellite genotypic similarities separated the 96 clones into six major groups corresponding to their species. Populus nigra var. italica clones were genetically differentiated from the P. nigra var. nigra clones. Microsatellite DNA markers could be useful in genetic fingerprinting, identification, classification, certification, and registration of clones, clultivars, and varieties as well as genetic resource management and protection of plant breeders' rights in Populus.Key words: Populus, simple sequence repeat markers, clonal identification, genetic fingerprinting, clonecultivar relationships.
The relationship between the dominantAdditionalveinmutant inDrosophila melanogasterandengrailed
Authors: Srivastava Ajay , Heise Christina , Garg Ankush , Bell John B
Published: January 2003

Additional vein (Adv) is a dominant mutation that affects the first wing vein in Drosophila. It also manifests a recessive lethal phenotype and is associated with a large inversion. Using a combination of genetic and cytogenetic techniques, we show that Adv interacts with engrailed (en), likely because one of the inversion breakpoints interferes with en function. Genetic interaction studies reveal that Adv is lethal in trans with various lethal alleles of en and gives an engrailed-like wing phenotype with weak alleles of en. In situ hybridization to polytene chromosomes using en cDNA demonstrates that one of the inversion breakpoints lies within the en coding region. Although the cause of the wing phenotype is not determined herein, it likely is caused by the other inversion breakpoint interfering with a different function. The characterization of this mutation could expedite studies to understand what molecular events result in the Adv phenotype and thereby provide insight into the development of the first wing vein in Drosophila.Key words: wing vein, dominant mutation, engrailed.
Mapping of quantitative trait loci controlling broomrape (Orobanche crenataForsk.) resistance in faba bean (Vicia fabaL.)
Authors: Román Belén , Torres Ana M , Rubiales Diego , Cubero Jose Ignacio , Satovic Zlatko
Published: January 2003

Orobanche crenata Forsk. is a root parasite that produces devastating effects on many crop legumes and has become a limiting factor for faba bean production in the Mediterranean region. The efficacy of available control methods is minimal and breeding for broomrape resistance remains the most promising method of control. Resistance seems to be scarce and complex in nature, being a quantitative characteristic difficult to manage in breeding programmes. To identify and map the QTLs (quantitative trait loci) controlling the trait, 196 F2plants derived from the cross between a susceptible and a resistant parent were analysed using isozymes, RAPD, seed protein genes, and microsatellites. F2- derived F3lines were studied for broomrape resistance under field conditions. Of the 130 marker loci segregating in the F2population, 121 could be mapped into 16 linkage groups. Simple interval mapping (SIM) and composite interval mapping (CIM) were performed using QTL Cartographer. Composite interval mapping using the maximum number of markers as cofactors was clearly the most efficient way to locate putative QTLs. Three QTLs for broomrape resistance were detected. One of the three QTLs explained more than 35% of the phenotypic variance, whereas the others accounted for 11.2 and 25.5%, respectively. This result suggests that broomrape resistance in faba bean can be considered a polygenic trait with major effects of a few single genes.Key words: Orobanche crenata, Vicia faba, QTL, broomrape resistance.
Genetic diversity in bambara groundnut (Vigna subterranea (L.) Verdc) landraces revealed by AFLP markers
Authors: Massawe F J , Dickinson M , Roberts J A , Azam-Ali S N
Published: January 2003

Bambara groundnut (Vigna subterranea (L.) Verdc), an African indigenous legume, is popular in most parts of Africa. The present study was undertaken to establish genetic relationships among 16 cultivated bambara groundnut landraces using fluorescence-based amplified fragment length polymorphism (AFLP) markers. Seven selective primer combinations generated 504 amplification products, ranging from 50 to 400 bp. Several landrace-specific products were identified that could be effectively used to produce landrace-specific markers for identification purposes. On average, each primer combination generated 72 amplified products that were detectable by an ABI Prism 310 DNA sequencer. The polymorphisms obtained ranged from 68.0 to 98.0%, with an average of 84.0%. The primer pairs M-ACA + P-GCC and M-ACA + P-GGA produced more polymorphic fragments than any other primer pairs and were better at differentiating landraces. The dendrogram generated by the UPGMA (unweighted pair-group method with arithmetic averaging) grouped 16 landraces into 3 clusters, mainly according to their place of collection or geographic origin. DipC1995 and Malawi5 were the most genetically related landraces. AFLP analysis provided sufficient polymorphism to determine the amount of genetic diversity and to establish genetic relationships in bambara groundnut landraces. The results will help in the formulation of marker-assisted breeding in bambara groundnut.Key words: under-utilized, African legume, molecular markers.
ELECTRICAL CONDUCTANCE OF ZIGZAG NANOGRAPHITE RIBBONS WITH LOCALLY APPLIED GATE VOLTAGE
Authors: WAKABAYASHI KATSUNORI , AOKI TAKASHI
Published: January 2003

The electric conductance of the graphite ribbon with locally applied gate voltage has been studied in terms of the Landauer approach. In the low-energy region, nano-graphite ribbon with zigzag boundaries exhibits the single electronic transport channel due to the edge states. The chemical potential dependence of the electric conductance shows qualitatively different behavior, depending on whether the magnitude of the potential barrier (gate voltage bias) Vg is larger than the energy gap Δ of the single channel region of the zigzag ribbon. For positive Vg with Vg < Δ, the zero-conductance resonances appear for 0 ≤ E ≤ Vg, and average transmission probability is quite small in this region. However the transmission probability is almost one, i.e. perfect transmission, for E > Vg. This step-function-like behavior of the conductance shows that it is possible to fabricate a nano-graphite-based switching device by the application of weak gate voltage bias.
ULTRASONIC PROPERTIES AND ELECTRON-PHONON COUPLING CONSTANT IN TlSr2(M1 - xYx)Cu2O7 (M = Ca, Sr) SUPERCONDUCTOR
Authors: HASSAN Z. R. , ABD-SHUKOR R. , ALWI H. A.
Published: January 2003

Ultrasonic properties of bulk TlSr 2 ( M 1 - x Y x) Cu 2 O 7( M = Ca , Sr ) high temperature superconductors have been measured between 80 and 280 K. Sound velocity measurements show that all samples exhibit an overall stiffening trend with decreasing temperature. The longitudinal sound velocity shows a pronounced slope change and attenuation peak around 200 K. The results were explained in terms of phase transition and distortion of Tl and O atoms associated with local oxygen ordering. The calculated acoustic Debye temperature does not show strong correlation with the transition temperature. The electron-phonon coupling constant was calculated using the weak and strong limit of the BCS theory as well as the van Hove scenario.
EFFECT OF LIGHT-FIELD SCREENING ON THE OPTICAL TRANSITIONS IN AROMATIC MOLECULES
Authors: TAKESHIMA MASUMI
Published: January 2003

A big discrepancy was found between the calculated transition dipole length and the experimental one for the anthracene crystal. The cause of the discrepancy is ascribed to the screening of the light electric field by the internal field within the molecule due to the induced dipole charges. It is indicated that this screening effect is important in big molecules like aromatic molecules and that this effect is not important in atoms having small sizes.
MAGNETIC MOMENT OF 2-DIMENSIONAL AND 3-DIMENSIONAL MANY-ELECTRON SYSTEMS EXAMINED WITH DEPENDENCE ON A COMMON SIZE PARAMETER
Authors: OLSZEWSKI S.
Published: January 2003

The orbital magnetic moments induced by a constant magnetic field in a two-dimensional (2D) and three-dimensional (3D) electron gas are calculated on the same footing independent of the conventional method based on statistical thermodynamics. The dependence of the moment on a common size parameter — defined as the cubic root of the volume occupied by one electron in a 3D gas — is found to be a similar monotonic function for both kinds of electron gas. This monotonic dependence is compared with the oscillating function of the size parameter obtained for the magnetic moment calculated in the case of a 2D slice of the tightly-bound s-electron states in a simple-cubic, or body-centred cubic, lattice.
GENERALIZED FIBONACCI NUMBERS AND DIMER STATISTICS
Authors: LU W. T. , WU F. Y.
Published: January 2003

We establish new product identities involving the q-analogue of the Fibonacci numbers. We show that the identities lead to alternate expressions of generating functions for close-packed dimers on non-orientable surfaces.
HISTOPHYSICS: A NEW DISCIPLINE
Authors: LAM LUI
Published: January 2003

History is the most important discipline of study. The system investigated in history is a many-body system consisting of biological material bodies, Homo sapiens, and hence can be studied scientifically. The unique role physicists can play in advancing the science of human history is presented. We will discuss the methods of study in history; worldviews; modeling history as a complex, dynamical system; predicting the future and retrodicting the past; and artificial history. In particular, active walk is shown to provide the foundation for a new worldview, and found to be widely applicable in modeling history, as illustrated by three examples from economic, evolutionary and social histories, respectively.
AB INITIOCALCULATIONS OF THE ELECTRONIC STRUCTURES AND BIOLOGICAL FUNCTIONS OF PROTEIN MOLECULES
Authors: ZHENG HAOPING
Published: January 2003

The self-consistent cluster-embedding (SCCE) calculation method reduces the computational effort from M3to about M1(M is the number of atoms in the system) with precise calculations. Thus the ab initio, all-electron calculation of the electronic structure and biological function of protein molecule has become a reality, which will promote new proteomics considerably. The calculated results of two real protein molecules, the trypsin inhibitor from the seeds of squash Cucurbita maxima (CMTI-I, 436 atoms) and the ascaris trypsin inhibitor (912 atoms, two three-dimensional structures), will be presented in this paper. The reactive sites of the inhibitors are determined and explained. The accuracy of structure determination of the inhibitors are tested theoretically.
MONOTONE APPROXIMATION OF AGGREGATION OPERATORS USING LEAST SQUARES SPLINES
Authors: BELIAKOV G.
Published: January 2003

The need for monotone approximation of scattered data often arises in many problems of regression, when the monotonicity is semantically important. One such domain is fuzzy set theory, where membership functions and aggregation operators are order preserving. Least squares polynomial splines provide great flexbility when modeling non-linear functions, but may fail to be monotone. Linear restrictions on spline coefficients provide necessary and sufficient conditions for spline monotonicity. The basis for splines is selected in such a way that these restrictions take an especially simple form. The resulting non-negative least squares problem can be solved by a variety of standard proven techniques. Additional interpolation requirements can also be imposed in the same framework. The method is applied to fuzzy systems, where membership functions and aggregation operators are constructed from empirical data.
A METHOD FOR IMPROVING THE CONSISTENCY OF JUDGEMENTS
Authors: LAMATA M. T. , PELAEZ J. I.
Published: January 2003

The Analytic Hierarchy Process provides the decision maker with a method for improving the consistency of pairwise comparison matrices. Although it is one of the most commonly used method it presents some disadvantages related generally with the consistency problem. The purpose of this paper is to provide an alternative method for improving consistency and show how it can be applied to pairwise comparison matrices. The contribution to this method and also its limitations are shown at the end.
Classical physics and the Church--Turing Thesis
Authors: Yao Andrew Chi-Chih
Published: January 2003

Would physical laws permit the construction of computing machines that are capable of solving some problems much faster than the standard computational model? Recent evidence suggests that this might be the case in the quantum world. But the question is of great interest even in the realm of classical physics. In this article, we observe that there is fundamental tension between the Extended Church--Turing Thesis and the existence of numerous seemingly intractable computational problems arising from classical physics. Efforts to resolve this incompatibility could both advance our knowledge of the theory of computation, as well as serve the needs of scientific computing.
Genetic Privacy
Authors: Sankar Pamela
Published: January 2003

During the past 10 years, the number of genetic tests performed more than tripled, and public concern about genetic privacy emerged. The majority of states and the U.S. government have passed regulations protecting genetic information. However, research has shown that concerns about genetic privacy are disproportionate to known instances of information misuse. Beliefs in genetic determinacy explain some of the heightened concern about genetic privacy. Discussion of the debate over genetic testing within families illustrates the most recent response to genetic privacy concerns.
Anti-Integrin Therapy
Authors: Hamm Christian W.
Published: January 2003

The glycoprotein IIb/IIIa integrin receptor binds fibrinogen and is therefore a final common pathway responsible for platelet aggregation. One antibody (abciximab) and two synthetic compounds (tirofiban and eptifibatide) are clinically available to antagonize the function of this receptor. Several large-scale studies have documented the benefit of these compounds in acute coronary syndromes and during percutaneous interventions. Current data suggest that abciximab is the preferred drug in the catheterization laboratory, whereas the other compounds reduce risk for patients with unstable angina before coronary interventions are performed. The highest benefit is achieved in diabetic patients and in patients with elevated troponins. Adverse reactions are rare, and bleeding complications are minor when weight-adjusted heparin is given. Oral compounds have been associated with excess mortality, precluding their clinical use.
New Concepts in Chronic Obstructive Pulmonary Disease
Authors: Barnes Peter J.
Published: January 2003

Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability but has only recently been explored from a cellular and molecular perspective. In COPD, chronic inflammation leads to fixed narrowing of small airways and alveolar wall destruction (emphysema). This is characterized by increased numbers of alveolar macrophages, neutrophils, and cytotoxic T lymphocytes, and the release of multiple inflammatory mediators (lipids, chemokines, cytokines, growth factors). There is also a high level of oxidative stress, which may amplify this inflammation. There is increased elastolysis and probable involvement of matrix metalloproteinases. The inflammation and proteolysis in COPD is an amplification of the normal inflammatory response to cigarette smoke. Unlike asthma, this inflammation appears to be resistant to corticosteroids, prompting a search for novel anti-inflammatory therapies that may prevent the relentless progression of the disease.
Erectile Dysfunction
Authors: Shabsigh Ridwan , Anastasiadis Aristotelis G.
Published: January 2003

Erectile dysfunction (ED) is a highly prevalent and often undertreated condition. It may be a symptom of underlying, chronic illness and can have a negative impact on quality of life, psychosocial health, and relationships. The aging of the population, as well as the introduction of new treatment options, such as sildenafil, has led to increased public awareness of this disorder. New oral therapeutic agents are on the horizon. This article provides an overview of the physiology of erection, the pathophysiology of ED, and modern patient evaluation. Management options, including traditional therapeutic approaches as well as the new generation of oral agents, are also presented.
Update in Palliative Medicine and End-of-Life Care
Authors: Abrahm Janet L.
Published: January 2003

Palliative medicine includes clinical palliative care, education, and research that focus on the quality of life of patients with advanced disease and their families. The domain of palliative medicine is the relief of suffering: physical, psychological, social, and spiritual. Palliative medicine and care for patients at the end of life and their families include the following key components: compassionate communication; exploration of patient and family values and goals of care; expert attention to relief of suffering; management of pain, depression, delirium, and other symptoms; awareness of the manifestations of grief; and sensitivity to the concerns of bereaved survivors.
Diagnosis and Prevention of Bovine Spongiform Encephalopathy and Variant Creutzfeldt-Jakob Disease
Authors: Irani David N. , Johnson Richard T.
Published: January 2003

An outbreak of bovine spongiform encephalopathy (BSE) arose in the United Kingdom as a result of prions entering and being recycled through the ruminant food chain. Humans have since developed a variant form of Creutzfeldt-Jakob disease (vCJD), also mostly in the United Kingdom, that occurs in younger individuals and causes prominent psychiatric and/or behavioral manifestations early in disease. Laboratory studies now provide strong evidence that the causative agent of BSE in cattle and vCJD in humans share a common origin. Because of a lack of information regarding the incubation period of vCJD and the number of people who may have been exposed, the future scope of this disease remains unknown. Control of the current and any future outbreaks in cattle requires strict measures to prevent contamination of the animal food chain with prions of any species. Prevention of human exposure mandates the avoidance of neural tissue in all human foods.
Pathogenesis and Treatment of Graft-Versus-Host Disease After Bone Marrow Transplant
Authors: Vogelsang Georgia B. , Lee Linda , Bensen-Kennedy Debra M.
Published: January 2003

Stem cell transplantation is being used to treat a number of hematologic malignancies as well as hematologic and immune deficiency states. The ages of patients being offered this therapy and the donor marrow sources have been expanded. One persistent problem has been graft-versus-host disease (GVHD). This article reviews the basic biology of GVHD, clinical manifestations of acute and chronic GVHD, prophylaxis and treatment of acute GVHD, and treatment of chronic GVHD.
Pharmacogenetics in Cancer Treatment
Authors: Nagasubramanian R. , Innocenti F. , Ratain M. J.
Published: January 2003

Interindividual variability in the efficacy and toxicity of drug therapy is associated with polymorphisms in genes encoding drug-metabolizing enzymes, transporters, or drug targets. Pharmacogenetics aims to identify individuals predisposed to high risk of toxicity from conventional doses of cancer chemotherapeutic agents. We review the role of genetic polymorphisms in UGT1A1 and TPMT, as well as mutations in DPD, in influencing drug disposition and toxicity. Recent studies show that pharmacogenetic determinants may also influence treatment outcomes. We discuss the clinical significance of polymorphisms in TS, MTHFR, and FCGR3A, as well as the polymorphic DNA repair genes XPD and XRCC1, in influencing reponse to chemotherapy and survival outcomes. Finally, the potential implications of transporter pharmacogenetics in influencing drug bioavailability are addressed.
Angiogenesis Ischemic and Neoplastic Disorders
Authors: Semenza Gregg L.
Published: January 2003

Vascular development involves vasculogenesis, in which endothelial cells form a primary tubular network, as well as angiogenesis, in which vessel size and structure are modified based upon flow and branching occurs to insure that all cells receive adequate O2 delivery. In adults, angiogenesis occurs in response to tissue hypoxia/ischemia and plays an important role in determining the progression of ischemic heart disease and cancer. A critical molecular pathway induced by hypoxia/ischemia is the activation of hypoxia-inducible factor 1, a transcriptional activator of genes encoding vascular endothelial growth factor and other important mediators of angiogenesis. Novel therapeutic approaches that involve stimulating angiogenesis in ischemic tissue and inhibiting angiogenesis in neoplastic tissue are currently being evaluated in clinical trials.
The Hypereosinophilic Syndrome Revisited
Authors: Roufosse Florence , Cogan Elie , Goldman Michel
Published: January 2003

Clinical and biological features of patients with the idiopathic hypereosinophilic syndrome (HES) are heterogeneous. Recent evidence suggests at least two distinct underlying hematological disorders involving myeloid and lymphoid cells, respectively. We therefore suggest that the term idiopathic should be abandoned in the classification of HES. This review defines the “myeloproliferative” and “lymphocytic” variants of the HES and addresses the management of each variant, focusing on diagnosis and treatment of the newly identified lymphocytic variant.
Pathophysiological-Based Approaches to Treatment of Sickle Cell Disease
Authors: Steinberg Martin H. , Brugnara Carlo
Published: January 2003

Sickle hemoglobin (HbS), as a result of its polymer-related and oxidant effects, damages the sickle erythrocyte, provokes inflammation, and causes endothelial injury. All these elements cause the phenotype of sickle cell disease. Novel treatments inhibit HbS polymerization by inducing fetal hemoglobin expression, prevent or repair erythrocyte dehydration by slowing cellular potassium and water loss, and replace HbS-producing erythroid progenitors by stem cell transplantation. Future treatment prospects include gene therapy, interruption of the interaction of sickle cells with the endothelium, inhibition of oxidative damage, and protection of an injured endothelium.
Monoclonal Antibody Therapy for Cancer
Authors: Mehren Margaret von , Adams Gregory P. , Weiner Louis M.
Published: January 2003

Monoclonal antibody therapy has emerged as an important therapeutic modality for cancer. Unconjugated antibodies show significant efficacy in the treatment of breast cancer, non-Hodgkin's lymphoma, and chronic lymphocytic leukemia. Promising new targets for unconjugated antibody therapy include cellular growth factor receptors, receptors or mediators of tumor-driven angiogenesis, and B cell surface antigens other than CD20. Immunoconjugates composed of antibodies conjugated to radionuclides or toxins show efficacy in non-Hodgkin's lymphoma. One immunoconjugate containing an antibody and a chemotherapy agent exhibits clinically meaningful antitumor activity in acute myeloid leukemia. Numerous efforts to exploit the ability of antibodies to focus the activities of toxic payloads at tumor sites are under way and show early promise. The ability to create essentially human antibody structures has reduced the likelihood of host-protective immune responses that otherwise limit the duration of therapy. Antibody structures now can be readily manipulated to facilitate selective interaction with host immune effectors. Other structural manipulations that improve the selective targeting properties and rapid systemic clearance of immunoconjugates should lead to the design of effective new treatments, particularly for solid tumors.
The Current Status of Hematopoietic Cell Transplantation
Authors: Appelbaum Frederick R.
Published: January 2003

Hematopoietic cell transplantation is the preferred therapy for a substantial proportion of patients with life-threatening diseases of the lymphohematopoietic system. Recent advances in donor identification, disease eradication, and supportive care measures have broadened the application of transplantation and improved outcomes. This article provides a brief review of the major clinical principles of transplantation and results achieved to date.
Technology-Driven Triage of Abdominal Trauma: The Emerging Era of Nonoperative Management
Authors: Demetriades D. , Velmahos G.
Published: January 2003

Selective nonoperative management of blunt or penetrating abdominal trauma is safe, has eliminated the complications associated with nontherapeutic laparotomies, and is cost-effective. Appropriately selected investigations, such as focused abdominal sonography for trauma, diagnostic peritoneal lavage, spiral computed tomography (CT) scan, diagnostic laparoscopy, or thoracoscopy and angiography, play a critical role in the triage of patients. Future technological advances, such as improvement of the ultrasonic hardware and software that provide automated interpretation and the availability of portable CT scan machines in the emergency room, may improve the speed and accuracy of the initial evaluation. Improvement of the optical system of minilaparoscopes may allow reliable bedside laparoscopy for suspected diaphragmatic injuries.
Randomized Trial Comparing Six Versus Three Cycles of Epirubicin-Based Adjuvant Chemotherapy in Premenopausal, Node-Positive Breast Cancer Patients: 10-Year Follow-Up Results of the French Adjuvant Study Group 01 Trial
Authors: Fumoleau Pierre , Kerbrat Pierre , Romestaing Pascale , Fargeot Pierre , Brémond Alain , Namer Moïse , Schraub Simon , Goudier Marie-Jo , Mihura Jeanne , Monnier Alain , Clavère Pierre , Serin Daniel , Seffert Philippe , Pourny Christiane , Facchini Thomas , Jacquin Jean-Philippe , Sztermer Jean-François , Datchary Jean , Ramos René , Luporsi Elisabeth
Published: January 2003

Purpose: To evaluate the duration and dose intensity of epirubicin-based regimens in premenopausal patients with lymph node-positive breast cancer.

Patients and Methods: Between 1986 and 1990, 621 patients with operable breast cancer were randomly assigned to receive fluorouracil (Roche SA, Basel, Switzerland) 500 mg/m2, epirubicin (Pharmacia SA, Milan, Italy) 50 mg/m2, and cyclophosphamide (Asta Medica AG, Frankfurt, Germany) 500 mg/m2 every 21 days (FEC 50) for six cycles (6 FEC 50); FEC 50 for three cycles (3 FEC 50); or the same regimen with epirubicin 75 mg/m2 (FEC 75) for three cycles (3 FEC 75). All patients in the three arms received chest wall irradiation at the end of the third cycle.

Results: After a 131-month median follow-up, the 10-year disease-free survival (DFS) was 53.4%, 42.5%, and 43.6% (P = .05) in the three arms, respectively. Pairwise comparisons demonstrate that 6 FEC 50 was superior both to 3 FEC 50 (P = .02) and to 3 FEC 75 (P = .05). The 10-year overall survival (OS) for the 6 FEC 50 arm was 64.3%, for the 3 FEC 50 arm it was 56.6%, and for the 3 FEC 75 arm, it was 59.7% (P = .25), respectively. Pairwise comparisons demonstrate that 6 FEC 50 was more effective than 3 FEC 50 (P = .10). Cox regression analysis demonstrates that OS was significantly better in the 6 FEC 50 than in the 3 FEC 50 arm (P = .046). No severe infections (grade 3 to 4), acute cardiac toxicity, or deaths from toxicity have been observed. Only five patients developed delayed cardiac dysfunctions, and three patients developed acute myeloblastic leukemia.

Conclusion: After a long-term follow-up in an adjuvant setting, the benefit of six cycles of FEC 50 compared with three cycles, whatever the dose, is highly significant in terms of DFS. As regards OS, the group receiving six cycles of FEC 50 has significantly better results than the group receiving three cycles of FEC 50.
Weekly Carboplatin and Paclitaxel Followed by Concomitant Paclitaxel, Fluorouracil, and Hydroxyurea Chemoradiotherapy: Curative and Organ-Preserving Therapy for Advanced Head and Neck Cancer
Authors: Vokes Everett E. , Stenson Kerstin , Rosen Fred R. , Kies Merrill S. , Rademaker Alfred W. , Witt Mary Ellyn , Brockstein Bruce E. , List Marcy A. , Fung Bing Bing , Portugal Louis , Mittal Bharat B. , Pelzer Harold , Weichselbaum Ralph R. , Haraf Daniel J.
Published: January 2003

Purpose: The paclitaxel, fluorouracil, and hydroxyurea regimen of paclitaxel, infusional fluorouracil, hydroxyurea, and twice-daily radiation therapy (TFHX) administered every other week has resulted in 3-year survival rates of 60% of stage IV patients. Locoregional and distant failure rates were 13% and 23%, respectively. To reduce distant failure rates, we added a brief course of induction chemotherapy to TFHX.

Patients and Methods: Sixty-nine patients received six weekly doses of carboplatin (AUC2) and paclitaxel (135 mg/m2) followed by five cycles of TFHX.

Results: Ninety-six percent had stage IV disease. Response to induction chemotherapy was partial response 52% and complete response (CR) 35%. Symptomatically, there was a significant reduction in mouth and throat pain. The most common grade 3 or 4 toxicity was neutropenia (36%). Best response following completion of TFHX was CR in 83%. Toxicities of TFHX consisted of grade 3 or 4 mucositis (74% and 2%) and dermatitis (47% and 14%). At a median follow-up of 28 months, locoregional or systemic disease progression were each noted in five patients. The overall 3-year progression-free survival was 80% (95% confidence interval [CI], 71% to 90%), and the 2- and 3-year overall survival rates were 77% (95% CI, 66% to 87%) and 70% (95% CI, 59% to 82%), respectively. At 12 months, five patients were completely feeding-tube dependent.

Conclusion: Administration of carboplatin and paclitaxel before TFHX chemoradiotherapy results in high response activity and may decrease distant failure rates. Overall survival, progression, and organ preservation/functional outcome data support definitive evaluation of this approach.