bluuebunny/crossref_metadata_2025 huggingface dataset:
Accurate Haplotype Inference for Multiple Linked Single-Nucleotide Polymorphisms Using Sibship Data
Authors: Liu Peng-Yuan , Lu Yan , Deng Hong-Wen
Published: June 2006

Sibships are commonly used in genetic dissection of complex diseases, particularly for late-onset diseases. Haplotype-based association studies have been advocated as powerful tools for fine mapping and positional cloning of complex disease genes. Existing methods for haplotype inference using data from relatives were originally developed for pedigree data. In this study, we proposed a new statistical method for haplotype inference for multiple tightly linked single-nucleotide polymorphisms (SNPs), which is tailored for extensively accumulated sibship data. This new method was implemented via an expectation-maximization (EM) algorithm without the usual assumption of linkage equilibrium among markers. Our EM algorithm does not incur extra computational burden for haplotype inference using sibship data when compared with using unrelated parental data. Furthermore, its computational efficiency is not affected by increasing sibship size. We examined the robustness and statistical performance of our new method in simulated data created from an empirical haplotype data set of human growth hormone gene 1. The utility of our method was illustrated with an application to the analyses of haplotypes of three candidate genes for osteoporosis.
Microsatellite Length Differences Between Humans and Chimpanzees at Autosomal Loci Are Not Found at Equivalent Haploid Y Chromosomal Loci
Authors: Kayser Manfred , Vowles Edward J , Kappei Dennis , Amos William
Published: June 2006

When homologous microsatellites are compared between species, significant differences in mean length are often noted. A dominant cause of these length differences is ascertainment bias due to selection for maximum repeat number and repeat purity when the markers are being developed. However, even after ascertainment bias has been allowed for through reciprocal comparisons, significant length differences remain, suggesting that the average microsatellite mutation rate differs between species. Two classes of mechanism have been proposed: rapid evolution of enzymes involved in the generation and repair of slippage products (enzyme evolution model) and heterozygote instability, whereby interchromosomal events at heterozygous sites offer extra opportunities for mutations to occur (heterozygote instability model). To examine which of these hypotheses is most likely, we compared ascertainment bias and species length differences between humans and chimpanzees in autosomal and Y chromosomal microsatellites. We find that levels of ascertainment bias are indistinguishable, but that interspecies length differences are significantly greater for autosomal loci compared with haploid Y chromosomal loci. Such a pattern is consistent with predictions from the heterozygote instability model and is not expected under models of microsatellite evolution that do not include interchromosomal events such as the enzyme evolution model.
A Novel Method for Estimating Linkage Maps
Authors: Tan Yuan-De , Fu Yun-Xin
Published: June 2006

The goal of linkage mapping is to find the true order of loci from a chromosome. Since the number of possible orders is large even for a modest number of loci, the problem of finding the optimal solution is known as a NP-hard problem or traveling salesman problem (TSP). Although a number of algorithms are available, many either are low in the accuracy of recovering the true order of loci or require tremendous amounts of computational resources, thus making them difficult to use for reconstructing a large-scale map. We developed in this article a novel method called unidirectional growth (UG) to help solve this problem. The UG algorithm sequentially constructs the linkage map on the basis of novel results about additive distance. It not only is fast but also has a very high accuracy in recovering the true order of loci according to our simulation studies. Since the UG method requires n − 1 cycles to estimate the ordering of n loci, it is particularly useful for estimating linkage maps consisting of hundreds or even thousands of linked codominant loci on a chromosome.
TheSaccharomyces cerevisiae rev6-1Mutation, Which Inhibits Both the Lesion Bypass and the Recombination Mode of DNA Damage Tolerance, Is an Allele ofPOL30, Encoding Proliferating Cell Nuclear Antigen
Authors: Zhang Hengshan , Gibbs Peter E M , Lawrence Christopher W
Published: June 2006

The rev6-1 allele was isolated in a screen for mutants deficient for UV-induced reversion of the frameshift mutation his4-38. Preliminary testing showed that the rev6-1 mutant was substantially deficient for UV-induced reversion of arg4-17 and ilv1-92 and markedly UV sensitive. Unlike other REV genes, which encode DNA polymerases and an associated subunit, REV6 has been found to be identical to POL30, which encodes proliferating cell nuclear antigen (PCNA), the subunit of the homotrimeric sliding clamp, in which the rev6-1 mutation produces a G178S substitution. This substitution appears to abolish all DNA damage-tolerance activities normally carried out by the RAD6/RAD18 pathway, including translesion replication by DNA polymerase ζ/Rev1 and DNA polymerase η, and the error-free, recombination-dependent component of this pathway, but has little effect on the growth rate, suggesting that G178S may prevent ubiquitination of lysine 164 in PCNA. We also find that rev6-1 mutation can be fully complemented by a centromere-containing, low copy-number plasmid carrying POL30, despite the presumed occurrence in the mutant of sliding clamp assemblies that contain between one and three G178S PCNA monomers as well as the fully wild-type species.
Heritable Endosymbionts of Drosophila
Authors: Mateos Mariana , Castrezana Sergio J , Nankivell Becky J , Estes Anne M , Markow Therese A , Moran Nancy A
Published: June 2006

Although heritable microorganisms are increasingly recognized as widespread in insects, no systematic screens for such symbionts have been conducted in Drosophila species (the primary insect genetic models for studies of evolution, development, and innate immunity). Previous efforts screened relatively few Drosophila lineages, mainly for Wolbachia. We conducted an extensive survey of potentially heritable endosymbionts from any bacterial lineage via PCR screens of mature ovaries in 181 recently collected fly strains representing 35 species from 11 species groups. Due to our fly sampling methods, however, we are likely to have missed fly strains infected with sex ratio-distorting endosymbionts. Only Wolbachia and Spiroplasma, both widespread in insects, were confirmed as symbionts. These findings indicate that in contrast to some other insect groups, other heritable symbionts are uncommon in Drosophila species, possibly reflecting a robust innate immune response that eliminates many bacteria. A more extensive survey targeted these two symbiont types through diagnostic PCR in 1225 strains representing 225 species from 32 species groups. Of these, 19 species were infected by Wolbachia while only 3 species had Spiroplasma. Several new strains of Wolbachia and Spiroplasma were discovered, including ones divergent from any reported to date. The phylogenetic distribution of Wolbachia and Spiroplasma in Drosophila is discussed.
Genetic Mapping in a Natural Population of Collared Flycatchers (Ficedula albicollis): Conserved Synteny but Gene Order Rearrangements on the Avian Z Chromosome
Authors: Backström Niclas , Brandström Mikael , Gustafsson Lars , Qvarnström Anna , Cheng Hans , Ellegren Hans
Published: June 2006

Data from completely sequenced genomes are likely to open the way for novel studies of the genetics of nonmodel organisms, in particular when it comes to the identification and analysis of genes responsible for traits that are under selection in natural populations. Here we use the draft sequence of the chicken genome as a starting point for linkage mapping in a wild bird species, the collared flycatcher—one of the most well-studied avian species in ecological and evolutionary research. A pedigree of 365 flycatchers was established and genotyped for single nucleotide polymorphisms in 23 genes selected from (and spread over most of) the chicken Z chromosome. All genes were also found to be located on the Z chromosome in the collared flycatcher, confirming conserved synteny at the level of gene content across distantly related avian lineages. This high degree of conservation mimics the situation seen for the mammalian X chromosome and may thus be a general feature in sex chromosome evolution, irrespective of whether there is male or female heterogamety. Alternatively, such unprecedented chromosomal conservation may be characteristic of most chromosomes in avian genome evolution. However, several internal rearrangements were observed, meaning that the transfer of map information from chicken to nonmodel bird species cannot always assume conserved gene orders. Interestingly, the rate of recombination on the Z chromosome of collared flycatchers was only ∼50% that of chicken, challenging the widely held view that birds generally have high recombination rates.
Connection Between the Rag4 Glucose Sensor and the KlRgt1 Repressor in Kluyveromyces lactis
Authors: Rolland Stéphane , Hnatova Martina , Lemaire Marc , Leal-Sanchez Juana , Wésolowski-Louvel Micheline
Published: June 2006

The RAG4 gene encodes for the sole transmembrane glucose sensor of Kluyveromyces lactis. A rag4 mutation leads to a fermentation-deficient phenotype (Rag− phenotype) and to a severe defect in the expression of the major glucose transporter gene RAG1. A recessive extragenic suppressor of the rag4 mutation has been identified. It encodes a protein (KlRgt1) 31% identical to the Saccharomyces cerevisiae Rgt1 regulator of the HXT genes (ScRgt1). The Klrgt1 null mutant displays abnormally high levels of RAG1 expression in the absence of glucose but still presents an induction of RAG1 expression in the presence of glucose. KlRgt1 is therefore only a repressor of RAG1. As described for ScRgt1, the KlRgt1 repressor function is controlled by phosphorylation in response to high glucose concentration and this phosphorylation is dependent on the sensor Rag4 and the casein kinase Rag8. However, contrary to that observed with ScRgt1, KlRgt1 is always bound to the RAG1 promoter. This article reveals that the key components of the glucose-signaling pathway are conserved between S. cerevisiae and K. lactis, but points out major differences in Rgt1 regulation and function that might reflect different carbon metabolism of these yeasts.
A Role for Sterol Levels in Oxygen Sensing in Saccharomyces cerevisiae
Authors: Davies Brandon S J , Rine Jasper
Published: June 2006

Upc2p and Ecm22p are a pair of transcription factors responsible for the basal and induced expression of genes encoding enzymes of ergosterol biosynthesis in yeast (ERG genes). Upc2p plays a second role as a regulator of hypoxically expressed genes. Both sterols and heme depend upon molecular oxygen for their synthesis, and thus the levels of both have the potential to act as indicators of the oxygen environment of cells. Hap1p is a heme-dependent transcription factor that both Upc2 and Ecm22p depend upon for basal level expression of ERG genes. However, induction of both ERG genes and the hypoxically expressed DAN/TIR genes by Upc2p and Ecm22p occurred in response to sterol depletion rather than to heme depletion. Indeed, upon sterol depletion, Upc2p no longer required Hap1p to activate ERG genes. Mot3p, a broadly acting repressor/activator protein, was previously shown to repress ERG gene expression, but the mechanism was unclear. We established that Mot3p bound directly to Ecm22p and repressed Ecm22p- but not Upc2p-mediated gene induction.
Nucleotide Variation and Haplotype Diversity in a 10-kb Noncoding Region in Three Continental Human Populations
Authors: Zhao Zhongming , Yu Ning , Fu Yun-Xin , Li Wen-Hsiung
Published: June 2006

Noncoding regions are usually less subject to natural selection than coding regions and so may be more useful for studying human evolution. The recent surveys of worldwide DNA variation in four 10-kb noncoding regions revealed many interesting but also some incongruent patterns. Here we studied another 10-kb noncoding region, which is in 6p22. Sixty-six single-nucleotide polymorphisms were found among the 122 worldwide human sequences, resulting in 46 genotypes, from which 48 haplotypes were inferred. The distribution patterns of DNA variation, genotypes, and haplotypes suggest rapid population expansion in relatively recent times. The levels of polymorphism within human populations and divergence between humans and chimpanzees at this locus were generally similar to those for the other four noncoding regions. Fu and Li's tests rejected the neutrality assumption in the total sample and in the African sample but Tajima's test did not reject neutrality. A detailed examination of the contributions of various types of mutations to the parameters used in the neutrality tests clarified the discrepancy between these test results. The age estimates suggest a relatively young history in this region. Combining three autosomal noncoding regions, we estimated the long-term effective population size of humans to be 11,000 ± 2800 using Tajima's estimator and 17,600 ± 4700 using Watterson's estimator and the age of the most recent common ancestor to be 860,000 ± 258,000 years ago.
Assessment of Linkage Disequilibrium in Potato Genome With Single Nucleotide Polymorphism Markers
Authors: Simko Ivan , Haynes Kathleen G , Jones Richard W
Published: June 2006

The extent of linkage disequilibrium (LD) is an important factor in designing association mapping experiments. Unlike other plant species that have been analyzed so far for the extent of LD, cultivated potato (Solanum tuberosum L.), an outcrossing species, is a highly heterozygous autotetraploid. The favored genotypes of modern cultivars are maintained by vegetative propagation through tubers. As a first step in the LD analysis, we surveyed both coding and noncoding regions of 66 DNA fragments from 47 accessions for single nucleotide polymorphism (SNP). In the process, we combined information from the potato SNP database with experimental SNP detection. The total length of all analyzed fragments was >25 kb, and the number of screened sequence bases reached almost 1.4 million. Average nucleotide polymorphism (θ = 11.5 × 10−3) and diversity (π = 14.6 × 10−3) was high compared to the other plant species. The overall Tajima's D value (0.5) was not significant, but indicates a deficit of low-frequency alleles relative to expectation. To eliminate the possibility that an elevated D value occurs due to population subdivision, we assessed the population structure with probabilistic statistics. The analysis did not reveal any significant subdivision, indicating a relatively homogenous population structure. However, the analysis of individual fragments revealed the presence of subgroups in the fragment closely linked to the R1 resistance gene. Data pooled from all fragments show relatively fast decay of LD in the short range (r2 = 0.208 at 1 kb) but slow decay afterward (r2 = 0.137 at ∼70 kb). The estimate from our data indicates that LD in potato declines below 0.10 at a distance of ∼10 cM. We speculate that two conflicting factors play a vital role in shaping LD in potato: the outcrossing mating type and the very limited number of meiotic generations.
The Contributions of Protein Kinase A and Smoothened Phosphorylation to Hedgehog Signal Transduction in Drosophila melanogaster
Authors: Zhou Qianhe , Apionishev Sergey , Kalderon Daniel
Published: June 2006

Protein kinase A (PKA) silences the Hedgehog (Hh) pathway in Drosophila in the absence of ligand by phosphorylating the pathway's transcriptional effector, Cubitus interruptus (Ci). Smoothened (Smo) is essential for Hh signal transduction but loses activity if three specific PKA sites or adjacent PKA-primed casein kinase 1 (CK1) sites are replaced by alanine residues. Conversely, Smo becomes constitutively active if acidic residues replace those phosphorylation sites. These observations suggest an essential positive role for PKA in responding to Hh. However, direct manipulation of PKA activity has not provided strong evidence for positive effects of PKA, with the notable exception of a robust induction of Hh target genes by PKA hyperactivity in embryos. Here we show that the latter response is mediated principally by regulatory elements other than Ci binding sites and not by altered Smo phosphorylation. Also, the failure of PKA hyperactivity to induce Hh target genes strongly through Smo phosphorylation cannot be attributed to the coincident phosphorylation of PKA sites on Ci. Finally, we show that Smo containing acidic residues at PKA and CK1 sites can be stimulated further by Hh and acts through Hh pathways that both stabilize Ci-155 and use Fused kinase activity to increase the specific activity of Ci-155.
Septicemia in a young dog following treatment of patent ductus arteriosus via coil occlusion
Authors: Wood Anne C. , Fine Deborah M. , Spier Alan W. , Eyster George E.
Published: June 2006

Case Description—A 12-week-old female English Springer Spaniel was evaluated for lethargy, vomiting, and pyrexia 1 week after treatment of patent ductus arteriosus (PDA) via coil occlusion.

Clinical Findings—Test results were consistent with septicemia, and the assumption was made that the PDA occlusion coils were infected. Radiography revealed partial migration of the coil mass into the pulmonary artery and signs of congestive heart failure.

Treatment and Outcome—After successful treatment of the septicemia and heart failure, surgical removal of the coils and resection of the PDA were undertaken. Although the coil that embolized to the pulmonary vasculature was left in place, the dog's clinical signs resolved.

Clinical Relevance—This case highlights the fact that as PDA coil occlusion devices become more widely used in dogs, practitioners must be prepared to treat implant infections aggressively, with both medical and surgical interventions if necessary.
Metal Bioavailability: How Does its Significance Change in the Time?
Authors: Calace Nicoletta , Petronio Bianca Maria , Pietroletti Marco
Published: June 2006

The significance of terms “metal bioavailability” and “bioavailable metal fraction” is evolved in the time, passing from a very simple concept to a complex concept bound to abiotic and biotic aspects. At the beginning metal toxicity was related to metal fraction present in water phase, than only free metal ion activity was considered and the free ion activity model (FIAM) was proposed. Successively, due to the exceptions observed and to the consciousness that metal bioavailability could be considered as dynamic characteristic the concept of metal bioavailability became very complex, depending on physical, chemical and biological factors.
Tracer measurements in groyne fields for the quantification of mean hydraulic residence times and of the exchange with the stream
Authors: Kozerski Hans‐Peter , Schwartz René , Hintze Thomas
Published: June 2006

Tracer experiments were carried out in groyne fields (GF) of the river Elbe near Havelberg (Germany) in order to estimate the hydraulic connectivity with the river channel. The characteristic times of the five groyne fields, which were estimated from the exponentially declining tracer curves in 43 runs, ranged between 15 min and 69 min and did not correlate with the water level. Methodological investigations show that single point injection and two measurements (in the outflowing water and in the dominant region) are sufficient to provide robust in‐situ tracer curves. Using simplified mathematical simulations with connected stirred tanks, the conditions are investigated for the development of breaks in tracer curves and for the occurrence of significant errors in the estimation of intrinsic residence times. It was shown that an initial uniform dye distribution is not mandatory for the estimation during steady states. In special cases, point injections are more advisable. Moreover, the mean hydraulic residence time was found to be not equivalent to the estimated characteristic time. In fact, it is mostly overestimated by tracer experiments. The degree of overestimation depends on mixing and the volumetric proportions between the different parts of the GF and can be calculated from measured dye concentration differences. For example, an overestimation of 32% was calculated for a groyne field with a commonly found circulation flow pattern.
Tetanus antibody titers and duration of immunity to clinical tetanus infections in free‐ranging rhesus monkeys (Macaca mulatta)
Authors: Kessler Matthew J. , Berard John D. , Rawlins Richard G. , Bercovitch Fred B. , Gerald Melissa S. , Laudenslager Mark L. , Gonzalez‐Martinez Janis
Published: June 2006

Prior to 1985 tetanus was a major cause of mortality in the free‐ranging colony of rhesus monkeys on Cayo Santiago, accounting for almost a quarter of annual deaths. In 1985 and 1986 all animals (except infants) received primary and booster doses, respectively, of tetanus toxoid. In subsequent years primary immunizations were given to all yearlings, and boosters were administered to all 2‐year‐old animals during the annual capture of the colony. The main objectives of the tetanus immunization program were to reduce the pain and suffering caused by tetanus infections and to decrease mortality in the colony. Other objectives were to evaluate the efficacy of the two‐dose tetanus toxoid immunization protocol and to determine whether additional boosters might be required to provide adequate long‐term protection against tetanus infections. The immediate effect of the mass immunization program was the elimination of clinical tetanus infections in the population and a 42.2% reduction in the overall mortality rate. Since the immunization program began, no cases of tetanus have been observed in the colony, except in two unimmunized infants, and it has not been necessary to give tertiary injections of tetanus toxoid to maintain protection against infection. A sample collected in 2004 of the original cohort of monkeys immunized in 1985 and 1986 showed that 93.3% (14/15) had protective tetanus antibody titers (>0.01 IU/ml) at the ages of 20–23 years, which is close to the life expectancy of the Cayo Santiago rhesus macaques. Two intramuscular doses of tetanus toxoid provided long‐term, if not lifelong, protection against tetanus for rhesus monkeys living in a tropical clime where tetanus is enzootic and the risk of infection is great. Am. J. Primatol. 68:725–731, 2006.© 2006 Wiley‐Liss, Inc.
Bed‐building in captive chimpanzees (Pan troglodytes): the importance of early rearing
Authors: Videan Elaine N.
Published: June 2006

In the wild, great apes sleep in beds they make by successively bending branches into an interwoven platform. These beds are functionally more closely related to human beds than they are to the nests and tree‐holes used by other primate species. The idea that bed‐building by great apes is learned behavior that is dependent on appropriate early experiences has been proposed but never fully tested. In the present study this hypothesis was indirectly tested in 73 captive adult chimpanzees (Pan troglodytes; 27 wild‐born and 46 captive‐born). Bed‐building and use were tested experimentally by the introduction of three sets of bedding materials. Over 200 hr of scan‐sampling data were collected during 45‐min observations following introduction of the bedding material. The wild‐born subjects built and used beds significantly more often than the captive‐born subjects. Also, wild‐born subjects used more complex techniques during construction. Captive‐born subjects that were mother‐reared through early adolescence spent more time building and using beds than their nursery‐reared counterparts. These differences remained consistent even when previous adult experience with bedding (measured as naturalistic vs. traditional housing) was accounted for. These results suggest that bed‐building is a learned behavior that requires early experience and practice for acquisition. Am. J. Primatol. 68:745–751, 2006. © 2006 Wiley‐Liss, Inc.
New approach to antibacterial treatment of cotton fabric with silver nanoparticle–doped silica using sol–gel process
Authors: Tarimala Sowmitri , Kothari Neha , Abidi Noureddine , Hequet Eric , Fralick Joe , Dai Lenore L.
Published: June 2006

In this study, cotton fabric was successfully modified to have an antibacterial property through use of the sol–gel process. Dodecanethiol‐capped silver nanoparticles, which have powerful antibacterial activity, were incorporated in silica sol. The starting materials were silver nitrate, tetraoctylammonium bromide, sodium borohydride, chloroform, 1‐dodecanethiol, ethanol, tetraethylorthosilicate, and water. The cotton fabric was padded with dodecanethiol‐capped silver nanoparticle–doped sol, dried at 60°C, and cured at 150°C. Scanning electron microscopy showed a uniform and continuous layer of doped sol on the fiber surface. The antibacterial effects of the treated cotton fabric against Escherichia coli were examined and found to be excellent. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101:2938–2943, 2006
Morphology of polyvinylidene fluoride and its blend in thermally induced phase separation process
Authors: Li Xianfeng , Lu Xiaolong
Published: June 2006

Polyvinylidene fluoride (PVDF) and its blend films were prepared by melt‐blending the binary mixture of PVDF/dibutyl phthalate (DBP) and the ternary mixture of PVDF/CaCO3/DBP in combination of TIPS. Their morphologies were characterized by scanning electron microscope depended on preparation condition, such as the diluent and CaCO3 weight fraction, and the cooling rate, and the crystallization information was also investigated by DSC. The results showed that CaCO3 influenced the morphology of PVDF in the TIPS process regardless of the cooling conditions, and the formation of the spherulitic morphology can be disturbed by CaCO3 at the quenching condition. The effect of CaCO3 weight fraction on the tensile strength of PVDF was measured, which indicated CaCO3 had a negative effect on PVDF tensile strength. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 2944–2952, 2006
Study on the rheological behavior of the hydrophobically modified hydroxyethyl cellulose with 1,2‐epoxyhexadecane*
Authors: Ye Lin , Li Qin , Huang Ronghua
Published: June 2006

Through the macromolecule reaction method, the hydrophobically modified hydroxyethyl cellulose (EP16–HAHEC) was synthesized using 1, 2‐epoxyhexadecane as the hydrophobic monomer. The solution properties of EP16–HAHEC were comprehensively investigated, which showed that the polymer with enhanced; viscosification property, thermal stability, shear resistance, and salt resistance was obtained. Amphiphilic structure of EP16–HAHEC molecules contributed to the surface activity of the polymer. By forming complex solution with surfactants or carboxylmethyl cellulose (CMC), the viscosification property of EP16–HAHEC could be enhanced through the interactions of hydrophobic groups and hydrogen bonds. The viscosity‐enhancing mechanism of HAHEC was studied by the environment scan electronic microscope (ESEM) and the fluorescence spectrum measurements, which demonstrated that the formation of the supramolecular aggregation networks was coincident with the increase of the apparent viscosity of HAHEC. With the gradual formation of the complete polymer molecule networks, the apparent viscosity rised dramatically, and the associating aggregations of the polymer molecules appeared far before the great change of the macroproperty of the polymer. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 2953–2959, 2006
HEMA‐grafted chitosan for dialysis membrane applications
Authors: Radhakumary C. , Nair Prabha D. , Mathew Suresh , Nair C. P. Reghunadhan
Published: June 2006

Chitosan was graft copolymerized with HEMA (2‐Hydroxyethylmethacrylate) for the development of blood‐compatible dialysis membranes. The permeation characteristics of HEMA‐grafted chitosan films for four different solutes creatinine, urea, glucose, and albumin was studied in vitro at 37°C for assessment of the suitability as dialysis membranes. The grafted film CH‐12.5 composition (425% grafting) showed very high permeation to creatinine by reaching the equilibrium within 45 min. The compositions CH‐7.5 and CH‐12.5 showed excellent permeation to glucose when compared to virgin chitosan films. In the case of urea permeation, all the grafted compositions exhibited higher percent permeation than the virgin chitosan films. The copolymer films CH‐7.5 and CH‐12.5 showed enhanced permeability for the high molecular weight solute, albumin. The other grafted copolymer compositions followed almost the same trend as that of chitosan for the low molecular weight solutes as well as the high molecular weight solute. The copolymer films were also found to be highly blood compatible, noncytotoxic, and biodegradable. Hence, the need for developing blood‐compatible chitosan membranes with desirable permeability properties is achieved by the graft copolymerization of HEMA onto chitosan. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 2960–2966, 2006
Poly(methacrylamide‐co‐acrylic acid) hydrogels for gastrointestinal delivery of theophylline. I. Swelling characterization
Authors: Dubey Seema , Bajpai S. K.
Published: June 2006

pH sensitive copolymeric hydrogels have been synthesized by free‐radical polymerization of methacrylamide and acrylic acid in aqueous medium. The gels were characterized by FTIR spectroscopy, thermogravimetric analysis, and swelling measurements. To determine the suitability of theses hydrogels for gastrointestinal oral delivery of model drug theophylline, their swelling behavior was investigated as a function of pH and various structural parameters such as the average molecular weight between crosslinks, crosslink density, and mesh size were calculated. Likewise initial, average and late time diffusion coefficients were also evaluated in simulating intestinal fluid of pH 6.8 at 37°C. The gel underwent sharp volume phase transition in the vicinity of pH 5.8. The mesh sizes of the hydrogel were between 8.4 and 9.2 Å in the collapsed state (pH range 1–2; SGF) and between 514 and 524 Å in the swollen state (pH range 7–8; SIF). The experimental data was found to fit well to Beren‐Hopfenberg equation thus suggesting that later part of swelling was chain relaxation controlled. The activation energy, as determined from Arrhenius equation was found to be 13.71 kJ mol−1. Likewise, enthalpy of mixing was also evaluated using Gibbs‐Helmholtz equation. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 2995–3008, 2006
Functionalization of low‐molecular‐weight oligomer dienes and olefins with sulfur‐ and oxygen‐containing compounds
Authors: Biglova R. Z. , Galimzyanova A. U. , Dokichev V. A. , Konesev G. V. , Zaikov G. E. , Talipov R. F.
Published: June 2006

The functionalization of piperylene fractions, oligodienes, and oligo‐olefins by elemental sulfur and phenols was carried out. The functionalized compounds were shown to be multipurpose additives, exhibiting high antiwear and antiscuff properties and simultaneously antioxidant and viscous properties. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 3097–3105, 2006
Effects of metallic monomer powders on the mechanical properties of hardened polyester and acrylic polymer concrete
Authors: Ahn Namshik
Published: June 2006

To investigate the effects of three metallic monomer powders on polyester‐ and acrylic‐hardened polymer concretes, polymer concretes incorporating different levels of these materials were investigated for the properties of hardened polymer concrete. The mix design was made and optimized for workability and strength, depending on the resin viscosity, the intended use, and the additional quantities of these polymeric materials. The investigated properties included the compressive strength, flexural strength, and bond strength of hardened polymer concrete. It was concluded that these polymeric materials offer the possibility of improving the properties of polyester‐ and acrylic‐hardened polymer concretes. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 3106–3113, 2006
Self‐assembled honeycomb polyurethane nanofibers
Authors: Thandavamoorthy S. , Gopinath N. , Ramkumar S. S.
Published: June 2006

Electrospinning uses a high voltage electric field to produce fine fibers. A new phenomenon of self‐assembly in the electrospinning of polyurethane nanofibers is observed. This report is the first known self‐assembling phenomenon in polyurethane electrospun nanofibers. Electrospun polyurethane nanofibers self‐assemble into unique honeycomb patterns on the collector surface. This novel observation opens up new and interesting opportunities for electrospun fibers in the areas of drug delivery devices, protective clothing, filters, and tissue scaffolds. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 3121–3124, 2006
A Glycosylated Nitric Oxide Donor, β‐Gal‐NONOate, and its Site‐specific Antitumor Activity
Authors: Chen Chang , Shi Yanqiu , Li Song , Qi Qingsheng , Gu Li , Song Jing , Wang Peng George
Published: June 2006

So far, nitric oxide (NO) donors have been applied to various aspects of antitumor therapy. To selectively sensitize tumor cells and avoid unwanted side effects, we recently synthesized a β‐galactosidase‐activatable NO‐releasing compound, β‐galactosyl‐pyrrolidinyl diazeniumdiolate (β‐Gal‐NONOate). In this study, we first verified its superiority over its parent diazeniumdiolate (NONOate) in terms of targeted intracellular NO‐releasing and antitumor activity with 9L/LacZ cells (rat glioma cell line 9L with transformed LacZ gene) in vitro. β‐Gal‐NONOate only released NO when hydrolyzed by induced β‐galactosidase in 9L/LacZ cells, which led to its more powerful cytotoxicity than that of NONOate. The results showed that β‐Gal‐NONOate produced higher NO levels than NONOate in 9L/LacZ cells at equal concentration, and hence induced optimal NO levels for antitumor activity. However, in 9L cells, β‐Gal‐NONOate showed less toxicity than NONOate. Therefore, it is demonstrated that β‐Gal‐NONOate is a site‐specific prodrug for targeting NO intracellularly as a β‐galactosidase‐sensitive NO donor, and it is also expected to be a promising probe in numerous experimental settings and a potential therapeutic drug for antitumor treatment.
Synthesis of β‐Hydroxypropanoic Acid Derivatives as Potential Anti‐inflammatory, Analgesic and Antimicrobial Agents
Authors: Abdel‐Rahman Hamdy M. , Hussein Mostafa A.
Published: June 2006

A series of new 3‐(substituted) 3‐hydroxy‐propanoic acid ethyl esters 1a–c, hydrazides 2a–c, thiosemicarbazides 3a–f, and semicarbazides 3g, 3h has been synthesized. Cyclization of compounds 3a–d in basic medium yielded 1,2,4‐triazole‐5‐thiones 4a–d. On the other hand, reaction of hydrazides 2a–c with CS2 in basic medium afforded 1,3,4‐oxadiazole‐5‐thiones 5a–c. All the synthesized compounds were characterized by their physical and spectral analyses data. The newly synthesized compounds were evaluated for their anti‐inflammatory, analgesic, and antimicrobial activities. Compounds 1c, 3g, 4a, 4b, 4c, and 5c exhibited comparable anti‐inflammatory activity to that of indomethacin and compounds 1c, 4c, and 5c were more analgesics than acetyl salicylic acid. Compounds 4b, 4c, and 5c showed superior GI safety profile (33.3%, 33.3% and 50.0% ulceration) than that of indomethacin (100% ulceration) at 100 mg/kg oral dose. Compounds 4b, 4c, and 5c were also non‐toxic with a median lethal dose (LD50) up to 200 mg/kg. The antibacterial and antifungal screenings identified compounds 3c, 4b, 4d, 5a, and 5b as the most effective against a variety of tested microorganisms.
A priori step size adaptation for the simulation of non‐smooth systems
Authors: Pfau Ralf Uwe
Published: June 2006

The simulation of technical system include systems with discontinuities, jumps, discrete variables, slip–stick‐changes and similar. The solution of those systems with standard ODE solvers normally leads to a break‐down in the efficiency due to the changes in the systems which causes the step size selection rule to perform poorly. We present a strategy how to modify the standard step size selection with a priori information from the system to react on the upcoming change. This improves the efficiency and accuracy of the solution.Copyright © 2006 John Wiley & Sons, Ltd.
IGHV gene insertions and deletions in chronic lymphocytic leukemia: “CLL‐biased” deletions in a subset of cases with stereotyped receptors
Authors: Belessi Chrysoula J. , Davi Frédéric B. , Stamatopoulos Kostas E. , Degano Massimo , Andreou Thanassis M. , Moreno Carol , Merle‐Béral Hélène , Crespo Marta , Laoutaris Nikolaos P. , Montserrat Emili , Caligaris‐Cappio Federico , Anagnostopoulos Achilles Z. , Ghia Paolo
Published: June 2006

Nucleotide insertions/duplications or deletions in immunoglobulin heavy chain genes have been found in 24/760 patients (3.15%) with chronic lymphocytic leukemia (CLL). In 21/24 cases, the inserted/duplicated or lost nucleotides occurred in multiples of 3; therefore, the original reading frame was maintained and a potentially intact receptor was coded. The pattern and location of insertions/duplications or deletions in CLL and their restriction to mutated IGHV rearranged genes strongly suggests that they resulted from somatic hypermutation. Their incidence in CLL is consistent with previous reports in normal, auto‐reactive and neoplastic human B cells, thus seemingly indicating that these modifications generally arise without any particular disease‐specific associations. A striking exception to this rule was identified in CLL IGHV3‐21‐expressing cases: one amino acid was deleted from the CDR2 region in 16/63 (25.4%) mutated CLL IGHV3‐21 sequences (including public database‐derived IGHV3‐21 CLL cases + the present series) vs. only 2/257 (0.78%) public database‐derived mutated non‐CLL IGHV3‐21 sequences; 15/16 CLL IGHV3‐21 sequences carrying this deletion belonged to a subset with unique, shared HCDR3 and light chain CDR3 motifs. This finding further supports the idea of selective antigenic pressures playing a pathogenetic role in some CLL cases.
Plasmacytoid dendritic cell activation by foot‐and‐mouth disease virus requires immune complexes
Authors: Guzylack‐Piriou Laurence , Bergamin Fabio , Gerber Markus , McCullough Kenneth C. , Summerfield Artur
Published: June 2006

Natural IFN‐producing cells (NIPC), also called plasmacytoid dendritic cells, represent an essential component of the innate immune defense against infection. Despite this, not much is known about the pathways involved in their activation by non‐enveloped viruses. The present study demonstrates that the non‐enveloped foot‐and‐mouth disease virus (FMDV) cannot stimulate IFN‐α responses in NIPC, unless complexed with FMDV‐specific immunoglobulins. Stimulation of NIPC with such immune complexes employs FcγRII ligation, leading to strong secretion of IFN‐α. In contrast to the stimulation of NIPC by many enveloped viruses, FMDV induction of IFN‐α production requires live virus. It is necessary for the virus to initiate its replicative cycle. Moreover, it is an abortive replication, as witnessed by the decrease of dsRNA levels and viral titers with time post infection. Sensitivity of the NIPC stimulation to wortmannin and chloroquin, but not leupeptin, indicates an essential role for the pre‐lysosomal stage endosomal compartment. In conclusion, the present study demonstrates that immune complexes provide the means for a non‐interferogenic virus to induce IFN‐α responses by NIPC. This indicates an important link between NIPC and antibodies in immune responses against non‐enveloped viruses such as FMDV.
Anti‐coreceptor antibodies profoundly affect staining with peptide‐MHC class I and class II tetramers
Authors: Wooldridge Linda , Scriba Thomas J. , Milicic Anita , Laugel Bruno , Gostick Emma , Price David A. , Phillips Rodney E. , Sewell Andrew K.
Published: June 2006

The T cell coreceptors CD8 and CD4 bind to invariable regions of peptide‐MHC class I (pMHCI) and class II (pMHCII) molecules, respectively, and facilitate antigen recognition by a number of mechanisms. It is established that some antibodies (Ab) specific for the CD8 molecule, which stabilizes TCR/pMHCI interactions, can alter the binding of pMHCI tetramers to cell surface TCR. In contrast, the extremely weak pMHCII/CD4 interaction does not stabilize TCR/pMHCII interactions or contribute to cognate tetramer binding; consequently, it is assumed that anti‐CD4 Ab do not affect pMHCII binding. Here, we used a panel of point‐mutated HLA A2 molecules with a range of affinities for CD8 spanning over three orders of magnitude to demonstrate that anti‐CD8 Ab‐mediated inhibition of pMHCI tetramer binding and cognate T cell activation correlates directly with the strength of the pMHCI/CD8 interaction. Further, some anti‐CD4 Ab were found to block pMHCII tetramer binding; these effects were also paralleled in T cell activation assays. In sum, these data challenge the assertion that anti‐coreceptor Ab exert their effects on T cell activation and pMHC binding solely by blocking pMHC/coreceptor interactions.
Fluoromethyl Cations and Group XIV Congeners AHnF3 – n+ (A = Si, Ge, Sn, Pb; n = 0–2): From Covalent Structures to Ion‐Molecule Complexes
Authors: Antoniotti Paola , Borocci Stefano , Bronzolino Nicoletta , Giordani Maria , Grandinetti Felice
Published: June 2006

Ab initio calculations at the MP2 and CCSD(T) level of theory (triple‐zeta quality basis sets for Si and Ge and effective core potentials plus DZ valence basis sets for tin and lead) have been performed to investigate the geometries, harmonic frequencies and relative stabilities of the (Si,H,F)+, (Ge,H,F)+, (Si,F3)+, (Ge,F3)+ and (A,Hn,F3 – n)+ (A = Si, Ge, Sn, Pb; n = 1 and 2) isomeric ions. While the H–Si–F+, F–SiH2+, H–SiF2+ and SiF3+ covalent structures are invariably predicted as the most stable isomers, the Ge+–(HF), FA+–(H2) and FA+–(HF) complexes (A = Ge, Sn, Pb) are the global minima on the potential energy surfaces, more stable than the corresponding covalent structures by up to some tens of kilocalories per mole. For tin and lead, the HA+–(HF) isomeric ions are also significantly more stable than F–AH2+ (A = Sn and Pb). Compared with the parent group XIV hydrides (A,H3)+, investigated so far by Schleyer and co‐workers (J. Am. Chem. Soc. 1996, 118, 12154–12158) and found to possess, for A = Sn and Pb, energetically favoured HA+–(H2) connectivities, the structural switch from covalent structures to ion‐dipole complexes occurs, therefore, even earlier. This suggests that the “regular” covalent connectivity of even the simplest AH2X+ or AHX2+ cations of group XIV cannot be taken for granted, and, especially for germanium, tin and lead, the role of ion‐molecule complexes must be carefully investigated. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Triple‐Decker Transition‐Metal Complexes (CnHn)M(B6C)M(CnHn) (M = Fe, Ru, Mn, Re; n = 5, 6) Containing Planar Hexacoordinate Carbon Atoms (Eur. J. Inorg. Chem. 13/2006)
Authors: Li Si‐Dian , Miao Chang‐Qing , Ren Guang‐Ming , Guo Jin‐Chang
Published: June 2006

The cover picture shows the structure and IR spectrum of a novel triple‐decker complex (C5H5)Fe(B6C)Fe(C5H5) obtained by density functional calculations. Similar results on a series of (CnHn)M(B6X)M(CnHn) (M = Fe, Ru, Mn, Re; X = B, C, N; n = 5, 6) complexes containing planar hexacoordinate carbon or other nonmetal atoms at the centers of the B6X middle‐deckers were also obtained. Natural orbital analyses indicate that the nonmetal centers X follow the octet rule in these complexes, and effective d–π coordination interactions exist between the partially filled Fe 3d orbitals and the delocalized π orbitals of the three parallel ligands. This work provides strong theoretical evidence to facilitate future experimental characterization of the long‐sought planar hexacoordinate carbon atom and expands the structural domain of traditional sandwich‐type transition‐metal complexes. Details are discussed in the article by S.‐D. Li et al. on p. 2567 ff.
Complete Chiral Induction from Enantiopure 1,2‐Diamines to Benzophenone‐Based Achiral Bisphosphane Ligands in Noyori‐Type RuII Catalysts
Authors: Jing Qing , Sandoval Christian A. , Wang Zheng , Ding Kuiling
Published: June 2006

We report the design and synthesis of a novel class of RuII catalysts (3) composed of achiral benzophenone‐based bisphosphane ligands and enantiopure 1,2‐diamines for the asymmetric hydrogenation of aryl ketones. The developed catalysts show excellent enantioselectivities (up to 97 % ee) and activities (up to S/C = 10,000) in the hydrogenation of a variety of aromatic ketones.Complete chiral induction from the enantiopure 1,2‐diamine to the achiral bisphosphane ligand was observed. The coordination of the C=O moiety in 3 to the cationic RuII center is considered to be of key importance in providing a higher thermodynamic and kinetic rotation barrier for the flexible bisphosphane ligand, resulting in the preferential formation of only one diastereomer, and thus explaining the high enantioselectivity of the catalyst. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
New Proton‐Sponge‐Like Macrocyclic Compound: Synergistic Hydrogen Bonds of Aminopyridine
Authors: Kanbara Takaki , Suzuki Yutaka , Yamamoto Takakazu
Published: June 2006

N,N′,N″‐Tris(p‐tolyl)azacalix[3](2,6)pyridine (1) that shows a high proton affinity (pKBH+ = 23.1 in CD3CN) has been classified as a new type of proton‐sponge‐like compound. X‐ray crystallography reveals that 1 is ideal for accommodating a single proton in its cavity. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Micellar electrokinetic capillary chromatographic method for the separation and quantitation of multiple amino acids as naphthoxy derivatives in pharmaceutical formulations
Authors: Ho Yu‐Hsiang , Wu Hsin‐Lung
Published: June 2006

The MEKC method is described for the quantitative analysis of 17 amino acids (AA) in pharmaceutical products. The method is based on simply derivatizing the AA with (2‐naphthoxy)acetyl chloride under mild conditions. The resulting derivatives were separated by MEKC with borate buffer (35 mM; pH 9.50) including 150 mM SDS at the applied voltage of 25 kV in an uncoated capillary (effective length, 40 cm) and monitored by UV at 230 nm. The detection limits of the amino acid derivatives were in the range of 3.0–8.0 µM (S/N = 3, injection 5.0 s, 6 895 Pa). The precision (RSD) and accuracy (relative error) of the method for intra‐ and interday analyses of the analytes are all below 5.2%. The amino acid derivatives are stable at room temperature for 33 h studied and the molar absorptivity of the alanine derivative (used as a model) is stable over a wide pH range of 3.00–12.00. This is favorable for monitoring the derivatives in various pH by CE or LC. Application of the method to the analysis of multiple AA in a liquid injection formulation proved satisfactory.