bluuebunny/crossref_metadata_2025 huggingface dataset:
Directed Crystallisation of Synthetic Polymers by Low‐Molar‐Mass Self‐Assembled Templates
Authors: Nogales Aurora , Olley Robert H. , Mitchell Geoffrey R.
Published: June 2003

A novel and powerful method of microstructure control in polyolefins is presented. By dispersing tiny amounts of sorbitol derivatives in the polymer, the subsequent crystal growth can be controlled with modest prior flow‐fields; in particular high levels of preferred orientation are generated in the resultant crystals. Under shear flow, the additive forms highly extended crystals which lie parallel to the flow‐field and which serve to direct the crystallisation of the polymer leading to a massive amplification of the anisotropy present in the melt.

TEM image of a carbon replica taken from an etched surface of a PE sample containing 1% of DBS.

magnified image

TEM image of a carbon replica taken from an etched surface of a PE sample containing 1% of DBS.
Novel surface treatments for glass fillers
Authors: Boyles David A. , Kellar Jon J. , Cross William M.
Published: June 2003

Glass fillers were suface modified by direct formation of a silicon‐carbon non‐hydrolyzable linkage between glass and coupling agent. The grafted silane monolayer was evaluated by infrared spectroscopy. Samples were subjected to hydrolytic conditions to compare their surface treatment stability with traditional surface treatment hydrolytic stability. Composite specimens were fabricated and their mechanical properties were compared with traditional aminopropylsilane coupling agent treatment.
Multifunctional action of in situ formed Zn‐salt of monoallylmaleamic acid
Authors: Rzymski W.M. , Wolska B. , Balicki T.
Published: June 2003

Monoallylmaleamic acid (CH2=CH‐CH”2‐NH‐CO‐CH=CH‐CO‐OH; MAMA) when used in combination with zinc basic carbonate (ZBC) shows multifunctional action during processing and peroxide curing of hydrogenated nitrile rubber (HNBR). It follows from the lower viscosity, higher crosslinking degree and higher tensile strength of samples prepared from HNBR, MAMA, ZBC and peroxide, compared with the HNBR cured with the peroxide only. This kind of activity of the such system is connected with the in situ formation of very small particles of Zn‐MAMA salt dispersed in the rubber matrix and in part chemically bound to the rubber.
Adsorption of curatives and activity of silica toward elastomers
Authors: Kosmalska Anna , Zaborski Marian , Ślusarski Ludomir
Published: June 2003

To characterize an activity of silica toward elastomers usually the parameters of the filler structure and a possibility of its interactions with macromolecules of a matrix are taken into consideration [1,2,3]. As a rule, low molecular weight substances of different polarity are dissolved in a rubber mix (e.g. accelerators, activators, crosslinking substances, etc). They undergo adsorption on the surface of active fillers what exerts an effect on a structure of a network formed and influences mechanical properties of vulcanizates at the same time.
Modification of precipitated calcium carbonate to improve its activity toward elastomers
Authors: Lipińska M. , Zaborski M. , Ślusarski L.
Published: June 2003

Surface area of precipitated calcium carbonate was modified by using difuncional compounds f.e.: hydroxyacids, aminoacids, unsaturated acids, their derivatives and silanes. We observed the influence of the degree of surface coverage ratio of calcium carbonate on the properties of modified filler, particularly its surface free energy. As a result of the modification, the dispersive component of surface energy and its specific interactions parameter Sf decreased. The investigations showed that the modification of calcium carbonate with difuncional compounds increased the adsorption of dibutyl phthalate on its surface. The activity of modified fillers in ethylene‐propylene copolymer, butadiene‐acrylonitrile copolymer and carboxylated butadiene‐acrylonitrile copolymer was studied. We tried to modify CaCO3 by using hydroxyacids and proadhesive silanes substances so that interactions between fillers particles increased. As the result of these modifications the absorption of dibutyl phthalate increased what could indicate a higher tendency to create CaCO3 own structure.
Interaction of poly(hydromethyl siloxane) and cyclic Si‐H functional oligomers with metal hydroxides
Authors: Voliotis Anastasios , Liauw Christopher M. , Lees Graham C. , Rothon Roger N. , Thomas Bryan
Published: June 2003

The adsorption of oligomeric trimethyl terminated poly(methylhydrosiloxane) (M.D(H)75.M) (PMHS) and pentamethyl‐cyclopentasiloxane (D(H)5) onto aluminium hydroxide (A1(OH)3) and magnesium hydroxide (Mg(OH)2), from heptane, has been investigated. The filler isolated from adsorption flasks was analysed using diffuse reflectance Fourier Transform infrared spectroscopy (DRIFTS) and solid‐state 29Si NMR. Data from the above analytical methods indicate strong adsorption of these probes on to both fillers. Adsorption of both probes occurs via formation of metal‐O‐Si linkages. Self condensation of Si‐H groups of adsorbed PMHS was also evident. With Al(OH)3, the adsorption PMHS involved a greater proportion of the Si‐H groups, causing the adsorption density to be lower than with Mg(OH)2.
Structure‐electrical properties relationships of polymer composites filled with Fe‐powder
Authors: Zois Haralampos , Apekis Lazaros , Mamunya Yevgen P.
Published: June 2003

Structure‐properties relationships of composite materials, consisting of a polymer matrix and metal inclusions, is very important for designing new materials with desirable properties. In the present work the electrical and dielectric properties of several composites, consisting of a polymer matrix and iron (Fe) particles as filler, were investigated. Broadband dielectric relaxation spectroscopy measurements were carried out. The electrical behaviour of the composites is described in terms of the percolation theory. Percolation threshold values were calculated and the values of the dielectric permittivity critical exponent were found in good agreement with the theoretical ones. The influence of using different polymer matrices on the physical properties of the composites was also of particular interest. The results were related to the microstructure of the composites and a schematic model was proposed.
Treatment of fillers with organofunctional silanes, technology and applications
Authors: Guillet Antoine
Published: June 2003

The surface of mineral fillers and reinforcements can be modified by reaction with organofunctional silanes. When they are incorporated into polymers, four major consequences result from the chemical modification of the filler surface:

1. The filler‐polymer physical interactions are affected. This has a strong impact on rheology and can be used to improve processing.

2. The filler‐polymer chemical interactions are affected. The resulting interphase maybe designed to be chemically stable, to exhibit barrier properties or to have specific mechanical properties that may help transfering stresses from the matrix to the filler. Organofunctional silanes are preferred candidates for creating covalent bonds between the filler and the polymer.

3. The filler‐filler physical interactions are affected. This can be best observed in composite materials that are highly filled with fine particles. The effect is highlighted by a striking modification of dynamic properties at low strain.

4. The polymer structure close to the interphase can be modified through cure control agents or crosslinking agents. Silanes are moisture‐curable, environmentally stable molecules that can be used as accelerators, crosslinkers or co‐monomers.
A numerical tool for multiattribute ranking problems
Authors: Cardoso Domingos Moreira , de Sousa Jorge Freire
Published: June 2003

A large variety of techniques have been developed to solve or approximate the solution of multiattribute ranking problems. From such techniques, several implicit or explicit partial orders, defined on the same set of alternatives, are obtained (in many cases, by pairwise comparisons) with the goal of determining a linear order. Often, this goal is attained by assigning positive weights to each partial order relation. However, the imprecise judgments of the pairwise comparisons as well as other factors lead to inconsistencies which have been analyzed in an extensive literature devoted to this type of problem. In this paper, numerical results about linear extensions of weighted sum relations are applied to the recognition of pairwise imprecise judgments between alternatives as well as to the confirmation of a ranking solution as a linear extension of a quasi‐order defined by a weighted sum of binary preference relations. © 2003 Wiley Periodicals, Inc.
Trees, slices, and wheels: On the floorplan area minimization problem
Authors: De Almeida Ana Maria , Rodrigues Rosália
Published: June 2003

Hierarchical approaches to floorplan design usually use trees to represent hierarchical floorplans, defining topological relations between a set of components to be placed on a (circuit) board. This placement is then optimized to minimize chip area, perimeter, or other such cost measurements. This work places the problem of minimizing hierarchical floorplans of order k within the appropriate theoretical framework and presents an algorithm that uses exclusively the k‐ary representation tree to determine the best or minimal solution to a conflicting bicriteria problem. The algorithm does not need predefined partitioning schemes and determines the orientation of each individual component. It can deal both with five‐module wheels, as well as slices, and can handle an arbitrary number of realizations for each individual component. © 2003 Wiley Periodicals, Inc.
Punctuations and agendas: A new look at local government budget expenditures
Authors: Jordan Meagan M.
Published: June 2003

Punctuated equilibrium theory (PET) is an agenda‐based theory that offers a theoretical
foundation for large budget shifts. PET emphasizes that the static, incremental nature of agendas is
occasionally interrupted by punctuations. These punctuations indicate shifts in priority among the agenda items,
and with those agenda shifts come trade‐offs. This article expands the discussion of punctuated budgets
to the level of local government by determining that local government expenditures have the characteristics
espoused by the punctuated equilibrium theory. The article also determines the frequency of punctuations and the
probability for future punctuations. The findings show that some budget functions and policy types are more
prone to punctuations and, therefore, have a less stable agenda. The practical significance of extending PET to
local government budgeting is the implication on planning, forecasting, and the agenda‐setting process.
© 2003 by the Association for Public Policy Analysis and Management.
Deformation in lamellar and crystalline structures: in situ simultaneous small‐angle X‐ray scattering and wide‐angle X‐ray diffraction measurements on polyethylene terephthalate fibers
Authors: Murthy N. S. , Grubb D. T.
Published: June 2003

Changes in the lamellar and crystalline structures were followed as a function of applied stress to understand the influence of the interactions between the crystalline and amorphous domains on the fiber properties. We observed a reversible transformation from a structure giving a four‐point small‐angle pattern to a structure giving a two‐point pattern; these structures corresponded to the lamellae with oblique and normal lamellar surfaces, respectively. The characteristics of these two structures such as the stack diameter, stack height, and tilt angle were different and were determined by the processing conditions and did not change when the fiber was elastically deformed. The structure giving a two‐point pattern was probably the load‐carrying lamellar entity in these fibers. The diameter of the lamellar stacks, tilt angle of the lamellae, and the strain in the lamellar spacing appeared to have the most influence on properties such as tenacity and dimensional stability. The long‐spacing strain, which is about the same as the fiber strain, determined the modulus at low elongation as well as ultimate elongation. These indicate that the lamellar stacks have at least as much influence as the interfibrillar chains on fiber properties. Structural features that determine the performance in semicrystalline polymers were investigated by analyzing four generations of polyethylene terephthalate fibers. Some of the fiber properties correlate with changes in the crystalline domains such as the crystalline orientation, size, and unit cell dimensions. Fibers in which the crystalline strain was large because of their strong linkages to the amorphous chains, and better load transfer, had the highest modulus and lowest ultimate elongation. © 2003 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 1538–1553, 2003
Preparation and characterization of melt‐compounded polyethylene/vermiculite nanocomposites
Authors: Tjong S. C. , Meng Y. Z.
Published: June 2003

Polyethylene (PE)‐layered vermiculite (VMT) nanocomposites were fabricated via direct melt compounding in a twin‐screw extruder followed by injection molding. Exfoliated PE/VMT nanocomposites were readily prepared via in situ melt mixing of maleic anhydride modified VMT with PE. Maleic anhydride acts as either the intercalation agent for VMT or as a compatibilizer for the PE and VMT phases. X‐ray diffraction and transmission electron microscopic observations revealed the formation of exfoliated PE/VMT nanocomposites. The experimental results showed that the storage modulus and strength of nanocomposites tend to increase with an increasing VMT content. Nearly 25.35% increment in the tensile strength and 50% increment in the storage modulus were achieved by incorporating 4 wt % VMT into PE. The thermal properties of the nanocomposites were investigated by dynamic mechanical analysis and differential scanning calorimetry. The glass‐transition temperature of PE/VMT nanocomposites appeared to increase upon the introduction of VMT into the PE matrix. The effects of maleic anhydride addition on the formation of the PE/VMT nanocomposites are discussed. © 2003 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 1476–1484, 2003
Surlyn®/silicate nanocomposite materials via a polymer in situ sol–gel process: Morphology
Authors: Start P. R. , Mauritz K. A.
Published: June 2003

Surlyn®/silicate hybrid materials were produced via diffusion‐controlled polymer in situ sol–gel reactions for tetraethylorthosilicate. The heterogeneous morphologies of these materials were inspected with transmission electron (TEM), atomic force (AFM), and environmental scanning electron microscopic methods. The silicate uptake was highly dependent on the water affinity of the particular Surlyn® form (acid or ionic) rather than on the affinity of the solvent. The morphology consisted of silicate particles with diameters that were on the order of tens of nanometers. Hence, these materials can be classified as nanocomposites. The particle size distributions in both the TEM and AFM images for all composites appeared to be narrow, with un‐neutralized Surlyn® exhibiting a broader distribution. Larger particles were found near the film surfaces, and the silicon elemental distribution across the film thickness indicated higher concentrations near the surfaces, which is most likely due to the fact that the sol–gel reaction is diffusion controlled in these polymeric media. © 2003 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 1563–1571, 2003
Molecular orientation of aromatic polycarbonates containing fluorene side chains by polarized infrared spectroscopy and birefringence analysis
Authors: Uchiyama Akihiko , Yatabe Toshiaki
Published: June 2003

The molecular orientation of an aromatic polycarbonate containing fluorene side chains was investigated by polarized infrared spectroscopy and birefringence analyses. The copolymers were synthesized from 2,2‐bis(4‐hydroxyphenyl)propane (BPA), 9,9‐bis(4‐hydroxy‐3‐methylpheny)fluorene (BMPF), and phosgene by interfacial polycondensation. The 1449‐cm−1 band of the uniaxially oriented films, stretched at the glass‐transition temperature (Tg) plus 5 °C, was assigned to various combinations of CC stretching and CH in‐plane bending vibrations in the fluorene ring, and the transition moment angle was estimated to be 90°. The intrinsic birefringence of aromatic polycarbonate films with BMPF molar ratios ranging from 0.5 to 1 was obtained with the 1449‐cm−1 band. The copolymer was estimated to show zero intrinsic birefringence at the BMPF molar ratio of 0.75, and the BMPF homopolymer showed negative intrinsic birefringence. A linear relationship between the volume fraction of BMPF units and the intrinsic birefringence indicated that the two monomer units of BPA and BMPF in each copolymer were not independent, and an intrinsic birefringence could be defined even in the copolymer. The sign of the photoelastic coefficient in the homopolymer with BMPF units was positive. The different signs of the photoelastic coefficient and the intrinsic birefringence suggest that the fluorene side‐chain orientation induced by stress in the glass state is quite different from the orientation of the uniaxially oriented films stretched at Tg + 5 °C. © 2003 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 1554–1562, 2003
Effect of pressure and temperature history on volume relaxation of amorphous polystyrene
Authors: Pantani R. , Titomanlio G.
Published: June 2003

Control of volume changes with time has a critical industrial relevance for the production of objects made of thermoplastic materials (obtained, e.g., by injection molding), but this phenomenon is completely disregarded by commercial codes for simulation of processes. In this work, attention is focused on the relevance of thermomechanical history on volume relaxation at room conditions of an amorphous polystyrene. A set of data of volume relaxation of samples obtained in an extremely wide range of thermomechanical treatments was collected. Data were analyzed with the aim of applying a simplified model on the basis of the well‐known KAHR model, which describes the postprocessing volume relaxation of amorphous polymers by adopting a minimum number of material parameters. Despite the fact that only two relaxation times are considered, the model satisfactorily describes volume evolution (either contraction or expansion) at room conditions after a given thermomechanical treatment if an appropriate partition of free volume into two fractions is provided. Furthermore, in its present form that neglects the effect of pressure on volume relaxation, the model satisfactorily describes the effect of a given thermal treatment (at room pressure), starting from the melt, on both specific volume and its relaxation rate after treatment. © 2003 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 1526–1537, 2003
C3H4: Density functional study of interconversion of isomers
Authors: Kakkar Rita
Published: June 2003

The B3LYP density functional has been used to calculate the reaction paths for the interconversion of the three stable isomers of C3H4, namely, propyne, allene, and cyclopropene, and the results compared with experimental data. It is found that the trans nonplanar isomer of vinylmethylene plays a central role in the interconversions. Other thermochemical parameters, like the entropies of reaction and activation, have also been calculated. The rate constants of the various competing reactions have been calculated using the Rice–Ramsperger–Kassel–Marcus theory. Kinetic isotope effects for the reactions have also been investigated to gain an insight into their mechanisms. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2003
Rumer's transformation, in biology, as the negation, in classical logic
Authors: Négadi Tidjani
Published: June 2003

In this article, we make a connection between the Rumer transformation, used in the study of the genetic code‐doublets, and the negation of classic logic. A unified classification is given, relying on two Klein's 4‐groups describing the symmetries of the 16 doublets of nitrogenous bases and those of the 16 binary connectives of classic logic, both groups being subgroups of a larger noncommutative group with eight elements we identify as the dihedral group D4. Also, some connections with other works are briefly considered. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2003
DFT study of 1‐D Li6Gd(BO3)3
Authors: Rivas‐Silva J.F. , Flores‐Riveros A. , Berrondo M.
Published: June 2003

Solid‐state calculations were performed with the program CASTEP to analyze some electronic structure features of the crystal compound Li6Gd(BO3)3 (LIGDBO), which is known to be an efficient gamma radiation detector, in particular when doped with rare‐earth ions. The structure of this material displays a clear 1‐D preference, where chains of atoms are formed along one of the crystalline axes. These quasilinear chains are responsible for the energy transfer occurring in the system prior to the actual detection. To elucidate on some aspects of the former process, calculations based on a few cluster models were also carried out by means of the molecular program JAGUAR. One of our results corresponds to a theoretical absorption energy value close to that experimentally obtained. In our calculation, the absorption process seems to be associated with the formation of an excitonic magnon state. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2003
Coping with incest: The relationship between recollections of childhood coping and adult functioning in female survivors of incest
Authors: Brand Bethany L. , Alexander Pamela C.
Published: June 2003

One hundred and one adult female survivors' recollections of coping with childhood incest, abuse characteristics, and current functioning in adulthood were studied. Analyses controlling for characteristics of the trauma indicated that recollections of using avoidance coping and seeking social support were related to poor adult functioning whereas recollections of using distancing coping were related to better functioning. As a set of variables, abuse characteristics also predicted a significant amount of variance in adult functioning. Implications for future research were discussed.
Psychiatric medication use among Manhattan residents following the World Trade Center disaster
Authors: Boscarino Joseph A. , Galea Sandro , Ahern Jennifer , Resnick Heidi , Vlahov David
Published: June 2003

To assess medication use in New York after the September 11th attacks, a telephone survey was conducted in October 2001 (N = 1,008). The prevalence of psychiatric medication use 30 days before the disaster was 8.9 and 11.6% 30 days after, a small but significant increase. The most important factor predicting postdisaster use was predisaster use—92% of those who used medications postdisaster used them predisaster. In addition, 3.3% used psychiatric medications 30 days postdisaster, but not 30 days before. Those who had panic attacks, posttraumatic stress disorder (PTSD), and insurance coverage, were the most likely medicated (26.5%). However, among those who used postdisaster medications (n = 129), new users tended to be those with panic attacks (44.1%) and those with panic attacks and PTSD (69.2%).
Predictors of acute distress among young adults injured by community violence
Authors: Jaycox Lisa H. , Marshall Grant N. , Orlando Maria
Published: June 2003

Acute reactions to trauma are examined in 267 individuals severely injured via community violence. Respondents were interviewed about pretrauma, peritraumatic, and acute posttraumatic factors. A series of bivariate and multivariate analyses were conducted. We found few factors related to peritraumatic dissociation (PD): only injury severity and neuroticism emerged as multivariate predictors and the effects were small. PD was strongly related to acute PTSD symptoms, and partially mediated the relationship between other factors and acute PTSD and general distress symptoms. Different patterns of predictors emerged for acute PTSD symptoms vis‐à‐vis general distress symptoms. Future research on predictors of PD is indicated to develop prevention and early intervention programs.
Assessment of response style in combat veterans seeking compensation for posttraumatic stress disorder
Authors: Franklin C. Laurel , Repasky Stephanie A. , Thompson Karin E. , Shelton Shannon A. , Uddo Madeline
Published: June 2003

This study examined response styles of veterans seeking compensation for PTSD (N = 204). Veterans were classified as having a valid or overreporting response style based on their scores on three MMPI‐2 validity scales that measure overreporting F, F(p), F‐K. Sixteen percent of veterans had valid scores on all three scales. The number of veterans classified as having an overreporting response style differed depending on which scale was used. This finding highlights the importance of using multiple validity scales to measure response style. Veterans who were and were not classified as overreporters were compared on measures of combat exposure, PTSD, and depression.
Perceptions of sexuality as related to sexual functioning and sexual risk in women with different types of childhood abuse histories
Authors: Schloredt Kelly A. , Heiman Julia R.
Published: June 2003

Perceptions of one's sexuality, self‐reported sexual functioning, and sexual risk were examined in a community sample of 148 women with histories of either childhood sexual abuse (n = 26), both childhood sexual and physical abuse (n = 44), and neither form of abuse (n = 78). Controlling for depression and anxiety, the groups did not differ on sexual desire, arousal/orgasm, sexual pain, or masturbation. Women with abuse histories reported more negative affect during sexual arousal and reported more lifetime vaginal intercourse partners than nonabused women. In addition, the abuse samples reported more negative perceptions of their sexuality in their worst psychological states using the Structural Analysis of Social Behavior (SASB) method than did women with no abuse history. An interpersonal focus and more precise abuse labeling are recommended, potentially revising our assumptions about symptom clusters and treatment.
Effects of CS-US Interval on Unconditioned Response Diminution in Human Heart Rate Classical Conditioning
Authors: Redondo Jaime , Marcos José L.
Published: June 2003

Abstract This experiment studies the role of the conditioned response (CR) in explaining the unconditioned response (UR) diminution phenomenon in heart rate (HR) classical conditioning. In order to analyze the implication of the different CR components on UR diminution, the interstimulus interval (ISI) was varied. Sixty volunteer subjects received discrimination training with an interval between conditioned stimulus (CS) and unconditioned stimulus (US; aversive white noise) of 8 s. After the discrimination training phase, subjects were randomized into three different groups according to an ISI of 1, 5, or 8 s. The subjects of each group were then tested with five presentations of CS+/US. The results showed that UR amplitude as well as the deceleration immediately before this response (pre-UR deceleration) were significantly lower in the 5 s and 8 s ISI groups than in the 1 s ISI group. In addition, UR amplitude and pre-UR deceleration were statistically the same in the 5 s and 8 s ISI groups. These findings are discussed in terms of the adaptative role of the CR in classical conditioning.
Evidence that the Cys282Tyr mutation of the HFE gene originated from a population in Southern Scandinavia and spread with the Vikings
Authors: Milman N , Pedersen P
Published: June 2003

Hereditary hemochromatosis has been recognized as a clinical disorder for more than 100 years. The common form of the disorder is caused by the Cys282Tyr mutation (C282Y) of the HFE gene. Hereditary hemochromatosis affects predominantly people of Northern European origin. The C282Y mutation probably occurred on a single chromosome carrying the ancestral hemochromatosis haplotype, which subsequently was spread by emigration and the founder effect. It has been estimated that the C282Y mutation appeared 60–70 generations ago. It was initially suggested that the ancestral C282Y mutation occurred within the Celtic group of peoples. However, we hypothesize that the distribution of the C282Y mutation in Europe is more consistent with an origin among the Germanic Iron Age population in Southern Scandinavia. From this area, the mutation could later be spread by the migratory activities of the Vikings. The aim of the present study was to evaluate the validity of these two hypotheses. Several arguments are in favor of the ‘Viking hypothesis’: first, the highest frequencies (5.1–9.7%) of the C282Y mutation are observed in populations in the Northern part of Europe, i.e. Denmark, Norway, Sweden, Faeroe Islands, Iceland, Eastern part of England (Danelaw) and the Dublin area, all Viking homelands and settlements. Second, the highest allele frequencies are reported among populations living along the coastlines. Third, the frequencies of the C282Y mutation decline from Northern to Southern Europe. Intermediate allele frequencies (3.1–4.8%) are seen in the populations in Central Europe, which is the original Celtic homeland. Low allele frequencies (0–3.1%) are recognized in populations in Southern Europe and the Mediterranean.
A cluster of autosomal recessive spondylocostal dysostosis caused by three newly identified DLL3 mutations segregating in a small village
Authors: Bonafé L , Giunta C , Gassner M , Steinmann B , Superti‐Furga A
Published: June 2003

In 1982, one of us reported a cluster of eight individuals affected by spondylocostal dysostosis (SD, MIM 277300) in four nuclear families indigenous to a village from eastern Switzerland. We tested the hypothesis that the molecular basis for this cluster was segregation of a single mutation in the DLL3 gene, recently linked to SD. Marker haplotypes around the DLL3 locus contradicted this hypothesis as three different haplotypes were seen in affected individuals, but sequence analysis showed that three unreported DLL3 mutations were segregating: a duplication of 17 bp in exon 8 (c.1285–1301dup), a single‐nucleotide deletion in exon 5 (c.615delC), and a R238X nonsense mutation in exon 6. Contrary to our initial assumption of a single allele segregating in this small community, three different pathogenic alleles were observed, with a putative founder mutation occurring at the homozygous state but also compounding with, and thus revealing, two other independent mutations. As all three mutations predict truncation of the DLL3 protein and loss of the membrane‐attaching domain, the results confirm that autosomal recessive spondylocostal dysostosis represents the null phenotype of DLL3, with remarkable phenotypic consistency across families.
Tremor, ataxia and dementia in older men may indicate a carrier of the fragile X syndrome
Authors: Rogers C , Partington MW , Turner GM
Published: June 2003

Recently it has been reported that late‐onset tremor, gait unsteadiness and dementia can be associated with brain atrophy in males of normal intelligence and the pre‐mutation carrier state of the fragile X syndrome. We have shown, by means of a telephone survey, that this association is probably causal rather than coincidental. These findings have uncovered another testable cause of late‐onset neurological symptoms in males, which also has serious genetic implications for their daughters who are at risk of having sons with full mutations causing mental handicap – the fragile X syndrome.
Association of the myocilin mt.1 promoter variant with the worsening of glaucomatous disease over time
Authors: Polansky JR , Juster RP , Spaeth GL
Published: June 2003

A major variant of myocilin (MYOC) [TIGR/MYOC mt.1 (−1000 C/G)], present in the gene's promoter, is found to be associated with more rapid progression of the glaucoma disease state. Time‐to‐event analyses using the Cox proportional hazards model produced substantial statistical evidence that this TIGR/MYOC mt.1(+) variant accelerates worsening for both optic disc and visual field measures of disease progression. These analyses were based on evaluations of 147 patients with primary open‐angle glaucoma (POAG) over 35 years of age with an average follow‐up of approximately 15 years. Our analyses showed that there are independent effects of the variant on disease progression, taking into account other relevant disease‐related baseline risk factors, including age, family history, initial drug treatment, initial surgical treatment, diabetes, gender, myopia, and initial disease severity. The finding that a TIGR/MYOC mt.1(+) determination provided a strong marker for glaucoma progression, above and beyond the other baseline risk factors, suggests a clinical utility in testing for this promoter genotype.
Gaucher's disease: identification of novel mutant alleles and genotype–phenotype relationships
Authors: Zhao H , Keddache M , Bailey L , Arnold Gl , Grabowski G
Published: June 2003

A sequencing protocol for the acid β‐glucosidase (GCase) gene (GBA) was developed using a long‐range PCR template. This protocol has an advantage of greater DNA yields over similar strategies. Seven Gaucher's disease patients had four novel and five other rare alleles. A non‐pseudogene in‐frame deletion (g.2600–2602delTAC) and a new complex mutation (null allele) were identified in Gaucher's disease type 1, i.e. the g.2600‐2602delTAC deletion is associated with the non‐neuronopathic variant. An F251L allele was found in a baby with the collodion skin phenotype. Three mutant alleles were identified in a single primary family with type 3. The patients' father at 45 years is healthy and is heteroallelic for the G202R and E326K alleles. Family studies indicated that E326K is in trans to G202R and L444P, and that isolated E326K is non‐pathogenic in this family. A rare mutation R257Q was identified in a type 2 patient, providing an association with neuronopathic disease. A genotype L444P/L444P was noted in a 22‐year‐old non‐neuronopathic patient. Complete gene sequencing showed a new complex allele consisting of L444P and g.7741T > C in the 3′ UTR. Three additional complex alleles also involved the 3′ UTR. Complete gene characterization in Gaucher's disease should allow greater insights into the correlation of specific alleles with phenotype.
Frequencies of gap‐ and tight‐junction mutations in Turkish families with autosomal‐recessive non‐syndromic hearing loss
Authors: Uyguner O , Emiroglu M , Uzumcu A , Hafiz G , Ghanbari A , Baserer N , Yuksel‐Apak M , Wollnik B
Published: June 2003

Mutations in genes encoding gap‐ and tight‐junction proteins have been shown to cause distinct forms of hearing loss. We have now determined the GJB2[connexin 26 (Cx26)] mutation spectrum in 60 index patients from mostly large Turkish families with autosomal‐recessive inherited non‐syndromic sensorineural hearing loss (NSSHL). GJB2 mutations were found in 31.7% of the families, and the GJB2–35delG mutation accounted for 73.6% of all GJB2 mutations. The carrier frequency of GJB2–35delG in the normal Turkish population was found to be 1.17% (five in 429). In addition to the described W24X, 233delC, 120delE and R127H mutations, we also identified a novel mutation, Q80R, in the GJB2 gene. Interestingly, the Q80R allele was inherited on the same haplotype as V27I and E114G polymorphisms. As little is known about the mutation frequencies of most other recently identified gap‐ and tight‐junction genes as a cause for hearing loss, we further screened our patients for mutations in GJB3 (Cx31), GJA1 (Cx43), ΔGJB6–D13S1830 (Cx30) and the gene encoding the tight‐junction protein, claudin 14 (CLDN14). Several novel polymorphisms, but no disease‐associated mutations, were identified in the CLND14 and GJA1 genes, and we were unable to detect the ΔGJB6–D13S1830 deletion. A novel putative mutation, P223T, was found in the GJB3 gene in heterozygous form in a family with two affected children. Our data shows that the frequency of GJB2 mutations in Turkish patients with autosomal‐recessive NSSHL and the carrier rate of the GJB2–35delG mutation in the Turkish population, is much lower than described for other Mediterranean countries. Furthermore, mutations in other gap‐ and tight‐junction proteins are not a frequent cause of hearing loss in Turkey.
XL PCR for the detection of large trinucleotide expansions in juvenile Huntington's disease
Authors: Milunsky JM , Maher TA , Loose BA , Darras BT , Ito M
Published: June 2003

Juvenile Huntington's disease (HD) becomes clinically manifest before 20 years of age. The diagnosis of HD is based on family history, characteristic clinical findings, and the detection of an expansion of a CAG polyglutamine tract in the Huntingtin gene. Juvenile HD is characterized by paternal anticipation and large CAG expansions that may be missed using routine molecular analysis. We have developed an easy, rapid, and reliable modified PCR method using XL (Extra Long) PCR that allowed us to diagnose one of the youngest children reported with juvenile HD. Without this innovation we would not have been able to demonstrate the large CAG expansion. This assay could become part of a standard protocol for HD testing in molecular diagnostic laboratories.
Diagnostic delay in women with pain and endometriosis
Authors: Husby Gunhild Kalleberg , Haugen Ragnhild Skipnes , Moen Mette Haase
Published: June 2003

Background.  Women with endometriosis claim that delayed diagnosis is a problem. Anglo‐American studies have shown a delay from 3 to 11 years between the onset of pain symptoms and the final diagnosis of endometriosis. The aim of this study was to find the time difference between the onset of pelvic pain symptoms and the final diagnosis of endometriosis among Norwegian patients.

Material and methods.  Questionnaires were sent to 400 women, of whom 313 were members of the Norwegian Endometriosis Association and 87 were patients with endometriosis being hospitalized at St Olav's Hospital, Trondheim, in recent years. The response rate was 89%. Among the 356 questionnaires returned, 95 were excluded as not fulfilling the inclusion criterion of surgically verified symptomatic endometriosis or incomplete questionnaires. Data were analyzed from 261 women, of whom 223 were members of the Norwegian Endometriosis Association. In all included patients, pain was an indication for diagnostic surgery.

Results.  The mean delay in diagnosis was 6.7 ± 6.2 years and the median delay was 5.0 years for the two groups in total. There was no statistically significant difference in delay between the two recruitment groups. Mean delay in diagnosis had not changed significantly with time. Women reporting infertility in addition to pain did not have a significantly shorter delay.

Conclusion.  In Norway there is a considerable delay in the diagnosis of endometriosis, with figures comparable to results from Anglo‐American studies. A greater awareness of symptoms of endometriosis and a more rapid investigation should thus be encouraged.
Periconceptional use of folic acid supplements in Oslo
Authors: Braekke Kristin , Staff Anne Cathrine
Published: June 2003

Background.  Periconceptional supplementation with folic acid has been shown to decrease the occurrence of neural tube defects (NTD). A daily supplement of 400 µg folic acid from the month before pregnancy and the first 2 to 3 months of pregnancy is recommended in Norway. We wanted to evaluate the use of folic acid supplements among pregnant women in Oslo, and to explore demographic factors that were associated with periconceptional intake.

Methods.  All women attending antenatal ultrasound screening at the two main obstetric departments in Oslo during 3 months in 2001 were invited to answer questions regarding folic acid supplementation before and during their present pregnancy.

Results.  A total of 1541 women (91, 5%) participated in the study, of which 26% were nonwestern immigrants. Only 17% of all women had started the folic acid supplementation preconceptionally (22% of the nonimmigrant vs. 2% of the immigrant population). Folic acid had been used by 58% at some time during the present pregnancy (73% of the nonimmigrant vs. 19% of the immigrant population). Regression analysis demonstrated that the difference in periconceptional use of folic acid between the two population groups could not be explained by registered demographic factors other than immigrant status.

Conclusions.  Most pregnant women in Oslo do not use folic acid as recommended and a dramatically low usage is seen among the immigrant population, indicating that more widespread information is necessary. Furthermore, fortification of cereals with folic acid should be considered to secure a sufficient intake of folic acid in all fertile women.
Correlation between estrogen receptor α expression, collagen content and stiffness in human uterine arteries
Authors: Lydrup Marie‐Louise , Fernö Mårten
Published: June 2003

Aim of the study.  To investigate the relationship between estrogen receptor α expression, collagen content and distensibility of the human uterine artery.

Study design.  Uterine arteries (n = 13) obtained from women undergoing hysterectomy were mounted for length–tension relations and thereafter frozen for later determination of collagen and estrogen receptor α contents.

Results.  A negative correlation between estrogen receptor α content and collagen content (r = −0.76, n = 13) and a positive correlation between collagen content and passive tension at 1.4 Lo (r = 0.72, n = 13) in the uterine artery were detected. No difference was found between pre‐ and postmenopausal women concerning the estrogen receptor α content, the collagen content or maximal active force.

Conclusions.  Our data show a functional correlate to the expression of estrogen receptors α, as a high content of estrogen receptor α correlates with a lower collagen concentration, indicating that estrogen through activation of estrogen receptor α protects against vascular collagen accumulation making the vessel more distensible.
A3 adenosine and CB1 receptors activate a PKC‐sensitive Cl− current in human nonpigmented ciliary epithelial cells via a Gβγ‐coupled MAPK signaling pathway
Authors: Shi Chanjuan , Szczesniak Anna , Mao Lucy , Jollimore Christine , Coca‐Prados Miguel , Hung Orlando , Kelly Melanie E M
Published: June 2003

We examined A3 adenosine and CB1 cannabinoid receptor‐coupled signaling pathways regulating Cl− current in a human nonpigmented ciliary epithelial (NPCE) cell line.

Whole‐cell patch‐clamp recordings demonstrated that the A3 receptor agonist, IB‐MECA, activates an outwardly rectifying Cl−current (ICl,Aden) in NPCE cells, which was inhibited by the adenosine receptor antagonist, CGS‐15943 or by the protein kinase C (PKC) activator, phorbol 12,13 dibutyrate (PDBu).

Treatment of NPCE cells with pertussis‐toxin (PTX), or transfection with the COOH‐terminus of β‐adrenergic receptor kinase (ct‐βARK), inhibited ICl,Aden. The phosphatidyl inositol 3‐kinase (PI3K) inhibitor, wortmannin, had no effect on ICl,Aden; however, the mitogen‐activated protein kinase kinase (MEK) inhibitor, PD98059, inhibited ICl,Aden.

Reverse transcription–polymerase chain reaction experiments and immunocytochemistry confirmed mRNA and protein expression for the CB1 receptor in NPCE cells, and the CB1 receptor agonist, Win 55,212‐2, activated a PDBu‐sensitive Cl− current (ICl,Win).

Transfection of NPCE cells with the human CB1 (hCB1) receptor, increased ICl,Win, consistent with increased receptor expression, and ICl,Win in hCB1 receptor‐transfected cells was decreased after application of a CB1 receptor inverse agonist, SR 141716.

Constitutive activity for CB1 receptors was not significant in NPCE cells as transfection with hCB1 receptors did not increase basal Cl− current, nor was basal current inhibited by SR 141716.

ICl,Win was inhibited by PTX preincubation, by transfection with ct‐βARK and by the MEK inhibitor, PD98059, but unaffected by the PI3K inhibitor, wortmannin.

We conclude that both A3 and CB1 receptors activate a PKC‐sensitive Cl− current in human NPCE cells via a Gi/o/Gβγ signaling pathway, in a manner independent of PI3K but involving MAPK.

British Journal of Pharmacology (2003) 139, 475–486. doi:10.1038/sj.bjp.0705266
Vascular endothelial growth factor increases heme oxygenase‐1 protein expression in the chick embryo chorioallantoic membrane
Authors: Fernandez Mercedes , Bonkovsky Herbert L
Published: June 2003

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. It has been recently suggested that the inducible heme oxygenase (HO‐1) isoform may play a role in angiogenesis.

The aims of this study were to determine, in chicken embryo chorioallantoic membranes (CAM), whether VEGF increases HO‐1 protein expression, and, if so, by which molecular mechanism, and whether HO‐1 activity is required for VEGF‐induced angiogenesis.

Treatment of CAMs with VEGF for 48 h caused a significant increase in HO‐1 protein expression, simultaneously with angiogenesis.

VEGF‐stimulated angiogenesis in CAMs was markedly attenuated by the HO inhibitor zinc mesoporphyrin (ZnMP). This inhibitory effect of ZnMP was not observed with copper mesoporphyrin (CuMP), a metalloporphyrin that has a similar structure to ZnMP but does not inhibit HO enzymatic activity.

Overexpression of HO‐1 protein elicited by VEGF in CAMs was significantly attenuated by the intracellular calcium chelator 1,2‐bis(2‐aminophenoxy)ethane‐N,N,N′,N′‐tetraacetic acid‐acetoxymethyl ester (BAPTA‐AM). The effects of BAPTA‐AM were, in turn, compensated by the calcium ionophore A‐23187.

In addition, the protein kinase C inhibitor staurosporine significantly attenuated, in a dose‐dependent manner, the VEGF‐stimulated HO‐1 induction observed in CAMs.

These results demonstrate, for the first time, that VEGF upregulates HO‐1 protein expression in vivo in CAMs by a mechanism dependent on an increase in cytosolic calcium levels and activation of protein kinase C. Our findings also suggest that HO‐1 activity is necessary for VEGF‐induced angiogenesis in CAMs.

British Journal of Pharmacology (2003) 139, 634–640. doi:10.1038/sj.bjp.0705272
A specific taurine recognition site in the rabbit brain is responsible for taurine effects on thermoregulation
Authors: Frosini Maria , Sesti Casilde , Saponara Simona , Ricci Lorenzo , Valoti Massimo , Palmi Mitri , Machetti Fabrizio , Sgaragli Giampietro
Published: June 2003

Taurine and GABA are recognized as endogenous cryogens. In a previous study, some structural analogues of taurine, namely 6‐aminomethyl‐3‐methyl‐4H‐1,2,4‐benzothiadiazine 1,1‐dioxide (TAG), 2‐aminoethylarsonic (AEA), 2‐hydroxyethanesulfonic (ISE) and (±)cis‐2‐aminocyclohexane sulfonic acids (CAHS) have been shown to displace [3H]taurine binding from rabbit brain synaptic membrane preparations, without interacting either with GABA‐ergic systems, nor with taurine uptake mechanism, thus behaving like direct taurinergic agents.

To answer the question whether the role of taurine as an endogenous cryogen depends on the activation of GABA receptors or that of specific taurine receptor(s), taurine or the above structural analogues were injected intracerebroventricularly in conscious, restrained rabbits singularly or in combination and their effects on rectal (RT)‐ and ear–skin temperature and gross motor behavior (GMB) were monitored.

Taurine (1.2 × 10−6–4.8 × 10−5 mol) induced a dose‐related hypothermia, vasodilation at ear vascular bed and inhibition of GMB. CAHS, at the highest dose tested (4.8 × 10−5 mol) induced a taurine‐like effect either on RT or GMB. On the contrary ISE, injected at the same doses of taurine, induced a dose‐related hyperthermia, vasoconstriction and excitation of GMB. AEA and TAG caused a dose‐related hyperthermia, but at doses higher than 1.2 × 10−7 mol caused death within 24 h after treatment.

CAHS (4.8 × 10−5 mol) antagonized the hyperthermic effect induced by TAG (1.2 × 10−6 mol), AEA (1.2 × 10−8 mol) or ISE (4.8 × 10−5 mol).

In conclusion, these findings may indicate the existence of a recognition site specific for taurine, responsible for its effects on thermoregulation.

British Journal of Pharmacology (2003) 139, 487–494. doi:10.1038/sj.bjp.0705274