bluuebunny/crossref_metadata_2025 huggingface dataset:
Ginzburg–Landau Equations for a d-Wave Superconductor with Paramagnetic Impurities
Authors: Kim Wonkee , Ting C. S.
Published: June 2003

Ginzburg–Landau (GL) equations for a d-wave superconductor with a repulsive s-wave interaction between electrons in the presence of paramagnetic impurities are microscopically derived based on the Born approximation. The diagrammatic relationships for the impurity-averaged product of Green's functions are algebraically established. The effect of paramagnetic impurities on the transition temperature and the London penetration depth are discussed. GL equations for a superconductor with both s-wave and d-wave pairing interactions are also examined. We show that the transition temperature for a superconductor with an s-wave symmetry is suppressed twice as rapidly as that with a d-wave symmetry in the dilute impurity limit if the strength of the spin-non-flip scattering is much weaker than the spin-flip interaction.
Is Aharonov–Casher Effect Topological?
Authors: Lee Tae-Yeon
Published: June 2003

It is shown that the Aharonov–Casher effect and neutron scalar Aharonov–Bohm effect are topological in two dimension and this fact is not incompatible with the argument of Peshkin and Lipkin.
Current Developments in Antithrombotic Therapy: The Role of Antithrombin Agents
Authors: Breddin H.K.
Published: June 2003

Hirudin, the specific thrombin inhibitor from medicinal leeches, is now produced by recombinant technology. r-Hirudin and to a lesser extent polyethyleneglycol-coupled hirudin (PEG-hirudin) have been used in many clinical trials. Hirudin has been shown to be more effective than low molecular weight heparin in the prevention of deep venous thrombosis after total hip replacement. In (acute) coronary syndromes hirudin as well as a synthetic hirudin analogue bivalirudin have been studied in large clinical trials. Higher doses of hirudin were associated with an increased risk of bleeding. A large-scale study with bivalirudin in patients with acute MI (the HERO-2 trial) has not shown a reduction in mortality but a 30% reduction of reinfarction within 96 h. Hirudin and argatroban have been successfully used in patients with heparin-induced thrombocytopenia type II. Several orally active thrombin inhibitors are being developed. The combined use of subcutaneous and oral administration of melagatran in patients with hip or knee replacement has led to promising results. It is likely that in the future thrombin inhibitors will replace other forms of anticoagulation in a number of indications.
Development of Argatroban as an Anticoagulant and Antithrombin Agent in Japan
Authors: Ikoma Hidenobu
Published: June 2003

Argatroban is a synthetic direct thrombin inhibitor which has been used in Japan for three indications, namely, chronic arterial occlusion, acute cerebral thrombosis and hemodialysis in AT-deficient patients or in patients with decreased AT. In patients with chronic arterial occlusion, argatroban increased the skin temperature, reduced the size of skin ulcers, and decreased the thrombin-antithrombin complex. In patients with acute cerebral thrombosis, neuronal symptoms improved significantly compared with the placebo group, wherein activated partial thromboplastin time (aPTT) was prolonged by about 1.5-fold and fibrinopeptide A was reduced. In some patients in whom hemodialysis is difficult due to the generation of blood clots in the dialyzer, hemodialysis is now possible with the replacement of heparin by argatroban.
The Art of Fusion: From Penams and Cephems to Penems
Authors: Dalhoff Axel , Thomson Christopher J.
Published: June 2003

This synopsis of published literature summarises the key chemical and bacteriological characteristics of penicillins, i.e. penams, cephalosporins, i.e. cephems, and their hybrid structure, i.e. the penems. Consequently, the antibacterial spectrum of a typical penem, e.g. faropenem, encompasses gram-positive as well as gram-negative species. Dependent from the substituents at position 1 of the five-membered saturated ring fused to the beta-lactam ring oxa-, carba-, or thiopenems can be differentiated. A major determinant of their antibacterial activity and CNS-excitatory potential, however, is the C-2 side chain. The excitatory potential correlates with the basicity of the C-2 side chain as does their antibacterial activity against gram-negative species and non-fermenters like P. aeruginosa. Lipophilicity is a determinant for good in vitro activity against gram-positive bacteria. Several investigational penems exhibit interesting antibacterial spectra, encompassing methicillin resistant staphylococci, enterococci and even P. aeruginosa due to their improved binding affinity to both wild-type and modified low-affinity penicillin binding proteins. The development of these agents may offer therapeutic alternatives for the management of infections.
Effect of Varidase (Streptodornase) on Biofilm Formed by Pseudomonas aeruginosa
Authors: Nemoto Ken , Hirota Katsuhiko , Murakami Keiji , Taniguti Kazuko , Murata Hiromi , Viducic Darija , Miyake Yoichiro
Published: June 2003

The biofilm of Pseudomonas aeruginosa could be removed by Varidase (streptodornase) that was used as defibrinating drug. After cultivating the biofilm on a silicone chip in a modified alginate-producing medium in vitro, it was treated with Varidase or DNase I. In both treatments, the biofilm was removed depending on the concentration of the reagents. Varidase was apparently effective under the condition that the biofilm was exposed to more than 625 U/ml (a quarter of the concentration of the medical use) for 3 h, twice, at 37°C. The result of this experiment indicates that (a) the DNases, DNase I and Varidase, were effective in destroying the biofilm of P. aeruginosa in vitro, and (b) in a clinical field, Varidase could be useful for P. aeruginosa focal infection, such as urinary tract infection, by removing the biofilm.
Comparative Effects of Cidofovir and Cyclic HPMPC on Lethal Cowpox and Vaccinia Virus Respiratory Infections in Mice
Authors: Smee Donald F. , Bailey Kevin W. , Sidwell Robert W.
Published: June 2003

Background: Cidofovir is approved for the treatment of cytomegalovirus retinitis in humans. Although highly effective, the drug can cause renal toxicity in patients. There is much interest in cidofovir as a potential treatment for smallpox, monkeypox and other orthopoxvirus infections. A cyclic phosphonate form of cidofovir, 1-[((S)-2-hydroxy-2-oxo-1,4,2-dioxaphosphorinan-5-yl)methyl]cytosine (cyclic HPMPC), was reported to be less nephrotoxic than cidofovir in animals. Thus, it was deemed important to directly compare the activities of cidofovir and cyclic HPMPC against poxvirus infections in mouse models. Methods: The compounds were evaluated by intraperitoneal and intranasal infection routes using multiple doses of each agent, with single doses of compound given 24 h after virus challenge. Results: By intraperitoneal route, cidofovir protected mice from mortality at 40, 80 and 160 mg/kg, whereas cyclic HPMPC was similarly protective only at 160 mg/kg. By intranasal route, cidofovir was active down to 5 mg/kg, compared to cyclic HPMPC efficacy at 20 and 40 mg/kg. Intraperitoneal doses of 40, 80 and 160 mg/kg cidofovir significantly reduced mortality from vaccinia virus infections, compared to doses of 80 and 160 mg/kg cyclic HPMPC. Intranasal treatment with cidofovir at 5–40 mg/kg was comparably effective to cyclic HPMPC doses of 20 and 40 mg/kg in vaccinia virus infections. Active doses significantly reduced lung virus titers and lung consolidation. Overall, the potency of cyclic HPMPC was about 4 times less than that of cidofovir. Conclusions: Although cyclic HPMPC is reported to exhibit reduced nephrotoxicity in vivo, it is also less potent than cidofovir against orthopoxvirus infections. For this reason, cyclic HPMPC may not offer any advantage over cidofovir in treating these infections in humans.
Genotoxic Action of Cycloplatam, a New Platinum Antitumor Drug, on Mammalian Cells in vivo and in vitro
Authors: Nersesyan Armen , Perrone Emanuela , Roggieri Paola , Bolognesi Claudia
Published: June 2003

Cycloplatam (CP), a new antitumor platinum compound of the second generation, was first synthesized in Russia. This drug shows less toxicity in vivo than the widely used cisplatin and carboplatin and a higher antitumor activity than carboplatin. CP is not nephrotoxic with respect to the platinum-based antitumor agents. CP is actually studied in clinical phase II trials in Russia and Armenia. Promising results were obtained in patients with lung, ovary, and prostate cancers. The aim of this work was to study the micronuclei (MN) inducing effect of CP in vivo in murine bone marrow cells and in human lymphocytes in vitro. The mutagenic activity of CP in bone marrow of mice was significantly lower than that of cisplatin at equitoxic doses. In human lymphocytes CP induced a dose-dependent increase of MN, beginning at a very low dose (0.1 µM). Our results showed that CP is much less toxic and MN inducing in vivo in murine bone marrow than cisplatin. In vitro data evidenced that CP is more toxic and genotoxic to human cells than cisplatin. The evidence of a MN-induced activity of an antitumor drug suggests a potential risk for long-time survivors.
Long-Term Survival in Acute Lymphoblastic Leukaemia in Adults Treated according to the LALA 87 Protocol
Authors: Čolović M. , Bogdanović A. , Janković G. , Kraguljac N. , Suvajdžić N.
Published: June 2003

Background: Between January 1989 and July 1995, a prospective study of the therapeutic efficacy of the LALA 87 protocol in adult acute lymphoblastic leukaemia (ALL) has been conducted. Methods: A total of hundred and twelve patients with ALL have been analysed. The median age of the patients was 40 years (range: 15–65), the gender ratio (M/F) was 66/46, and the morphologic FAB (French-American-British) profile was L1 in 30 (26.9%) patients, L2 in 71 (63.3%) and L3 morphology in 11 (9.8%) of the patients. The LALA 87 protocol includes five phases: induction, consolidation, reinforcement, maintenance and central nervous system (CNS) prophylaxis with intrathecal methotrexate and irradiation. The induction phase comprised daunorubicin 50 mg/m2 (days 1–3), cyclophosphamide 600 mg/m2 (days 1 and 8), vincristine 1.5 mg/m2 (on days 1, 8, 15 and 22) and daily oral prednisone on days 1–21. Maintenance therapy was given for 2 years and consisted of different drugs as reinforcement, daily 6-mercaptopurine and weekly methotrexate. Results: Complete remission (CR) was achieved in 81 (72.3%) of the patients. The causes of induction failure were partial response in 10 (8.9%), and hypoplastic death in 12 patients (10.7%), and 9 were non-responders (8.0%). Of the 81 patients who achieved CR, 62 relapsed (76%). Among the relapsed patients, 9 developed CNS disease in spite of CNS prophylaxis during induction chemotherapy. Median follow-up for the living patients was 110 months. Median disease-free survival (DFS) was 16 months; 19 patients are still in remission with an estimated 10-year DFS (24%). Adverse prognostic factors were >50 years of age, immunologic subtype and cytogenetic profile. Conclusion: The results support the strategy of applying more effort and other treatment modalities in the therapy of ALL.
A Phase II Trial of Gemcitabine in the Treatment of Advanced Bile Duct and Periampullary Carcinomas
Authors: Lin Ming-Hsien , Chen Jen-Shi , Chen Helen H.-W. , Su Wu-Chou
Published: June 2003

Background: Gemcitabine is a novel nucleoside analogue with clinical anticancer activity in several malignancies. From September 1998 to April 2000, we treated patients with advanced bile duct and periampullary carcinomas with gemcitabine alone. Methods: Gemcitabine 1,000 mg/m2/day was administered in 200 ml of normal saline as a 30-min intravenous infusion on day 1 weekly for 3 weeks, followed by a 1-week rest. Results: A total of 24 consecutive patients (15 men, 9 women), with a median age of 59.5 years (range 40–72 years), were enrolled. All patients were evaluable for response: 1 patient achieved complete remission (CR); 2 patients had partial remission (PR); 8 patients remained stable (SD), and 13 patients had progressive disease (PD). The overall response rate (CR + PR) was 12.5% with a 95% confidence interval (CI) of 2.7–32.4%. The median progression-free survival (PFS) was 2.5 months (95% CI 1.6–5.5 months), and the median overall survival (OS) was 7.2 months (95% CI 3.8–8.9 months). Patients with disease control (CR + PR + SD) had better PFS and OS than those with PD. There were no treatment-related deaths. Few patients encountered grade 3/4 toxicity. Conclusion: Chemotherapy with gemcitabine demonstrated notable activity and was associated with a well-tolerable toxicity profile in patients with advanced biliary tract malignancies.
Correlates of Sensitization to Blomia tropicalis and Dermatophagoides pteronyssinus in Asthma in Barbados
Authors: Manolio Teri A. , Barnes Kathleen C. , Naidu Raana P. , Levett Paul N. , Beaty Terri H. , Wilson Alexander F.
Published: June 2003

Background: Sensitivity to the mite Blomia tropicalis is related to asthma in tropical climates, but correlates of sensitivity to B. tropicalis and its relationship to Dermatophagoides pteronyssinus sensitivity have not been widely examined in families with asthma. The main objective of this study was to determine prevalence and correlates of sensitivity to these mites in families with asthma and characteristics of persons sensitized to both. Methods: Antibodies to major antigens (Blo t 5 and Der p 1) of these mites were measured by immunochemiluminescent assay in 481 members of 29 families from Barbados ascertained through two asthmatic siblings. Results: Blo t 5 sensitivity was present in 261 subjects (46%) and was associated with younger age, higher total serum IgE level, and more than a three-fold increased prevalence of asthma (42 vs. 13%). Der p 1 sensitivity was less common (27%) and showed similar associations with age, IgE, and asthma. Of the 261 subjects sensitized to Blo t 5, 116 were also sensitized to Der p 1; they were younger, had higher total and Blo t 5 specific IgE levels, and had more than twice the asthma prevalence as those sensitized to Blo t 5 alone (59 vs. 29%). Der p 1 sensitivity without Blo t 5 sensitivity was uncommon; 90% of those sensitized to Der p 1 were also sensitized to Blo t 5. Geometric mean total IgE levels were lowest in the 207 participants without any mite sensitization (102 U/ml), intermediate in 158 sensitized to either Blo t 5 or Der p 1 (609 U/ml), and highest in 116 sensitized to both (1,869 U/ml). Conclusions: Blo t 5 is the predominant sensitizing mite allergen in these Barbadian families with correlates similar to Der p 1. Concomitant sensitization to Der p 1 appears to identify a more reactive subgroup of individuals at a higher risk of asthma.
Distribution and Morphology of GFAP-Positive Astrocytes in the Human Fetal Brain at Second Trimester
Authors: Rezaie Payam , Ulfig Norbert , Male David
Published: June 2003

Background: Various studies have shown that a close physical and functional relationship exists between astrocytes and microglia during development. The maturation of astrocytes can be followed by their specific expression of glial fibrillary acidic protein (GFAP). Although there have been several reports on the expression of GFAP in the developing brain, these are mainly descriptive and have not defined clearly the regional distribution patterns of these cells during fetal development. Aim: This study set out to analyse the regional distribution and morphology of GFAP-expressing astrocytes during the latter half of the second trimester (19–23 gestational weeks) within five normal fetal brains, with a view towards comparing the findings with the microglial distribution and differentiation previously recorded throughout the same period. Results: A clear account of the morphology and regional distribution of GFAP-positive astrocytes is presented. Differentiating astrocytes (including radial glia and their processes) were found in the germinal layers, corpus callosum and cavum septum pellucidum, within neural tracts and surrounding the basal ganglia – areas known to be populated by microglia during the same period. The differentiation of astrocytes was predominant within the subplate and intermediate zone towards the end of the second trimester. Importantly, the differentiation of astrocytes within these regions followed a similar spatially interspersed pattern as reported for fetal microglia. However, astrocytes appeared to differentiate at a later stage within these regions than described for microglia. This will require further investigations for confirmation. Differentiated astrocytes were also found to associate with cortical blood vessels in a region-specific manner during the second trimester. Conclusions: These observations indicate that the differentiation and spatial distribution of astrocytes parallels those of microglia during the second trimester. It remains to be seen whether factors released by microglia can directly influence the differentiation of astrocytes in situ during development.
The Functional Organization of the Developing Human Brain in Relation to Motor Deficits, Cognitive Impairment and Psychotic States
Authors: Ulfig Norbert
Published: June 2003

The human developing brain displays transient architectonic features, i.e. prominent structures which are involved in fetal neuronal circuitries. The latter play a pivotal role in the establishment of mature projections. In the first part of this review, data are summarized that the ganglionic eminence (a conspicuous part of the telencephalic proliferative zone) serves as an intermediate target for growing axons. Bleedings occurring in the ganglionic eminence could therefore lead to subtle alterations in mature connectivities, which may account for cognitive deficits. Subtle alterations of neuronal morphology in fetal hydrocephalus are demonstrated and discussed to account for mental impairment. In the second part, data are presented which demonstrate the complex modes of neuronal migration, such as tangential and ventricle-directed migration. It is hypothesized that a disturbance of a certain mechanism of migration may be involved in the developmental origin of schizophrenia. In the third part, the putative role of a transient projection of the red nucleus in periventricular leukomalacia is shown. It is speculated that a continuous reduction of this (rubrospinal) projection is related to the delayed and gradual occurrence of spastic diplegia in infants with periventricular leukomalacia. On the whole, this review emphasizes that certain clinical observations and symptoms may be associated with transitory neuronal circuitries in the developing brain. Moreover, it is pointed out that the application of current concepts in neuronal migration may contribute to a better understanding of neuropathological alterations in schizophrenia.
8-Iso-Prostaglandin F2α, a Product of Noise Exposure, Reduces Inner Ear Blood Flow
Authors: Miller Josef M. , Brown J. Nadine , Schacht Jochen
Published: June 2003

Noise exposure induces the formation in the cochlea of 8-isoprostaglandin F2α (8-iso-PGF2α), a marker for reactive oxygen species [Ohinata et al., 2000a] and a potent vasoconstrictor, raising the possibility that 8-iso-PGF2α may be responsible for noise-induced reductions in cochlear blood flow (CBF). To test this hypothesis, CBF was assessed in the guinea pig in response to ‘local’ (via the anterior inferior cerebellar artery) and systemic (i.v.) delivery of 8-iso-PGF2α using laser Doppler flowmetry. Local 8-iso-PGF2α induced a clear reduction in CBF. With systemic infusion, vascular conductance (VC), the ratio of CBF to systemic blood pressure, decreased in a dose-dependent manner up to 30%, consistent with an 8-iso-PGF2α-induced constriction of the cochlear vasculature. Infusion of SQ29548, a specific antagonist of 8-iso-PGF2α, appropriately blocked an 8-iso-PGF2α-induced CBF response. Similarly, noise-induced changes in CBF and VC were prevented by infusion of SQ29548 during noise exposure or by antioxidant treatment (glutathione monoethyl ester) prior to exposure. Prevention of isoprostane-mediated vasoconstriction may have clinical utility in the protection from noise-induced hearing loss.
UV-Absorbing Compounds in the Aqueous Humor from Aquatic Mammals and Various Non-Mammalian Vertebrates
Authors: Ringvold Amund , Anderssen Erlend , Jellum Egil , Bjerkås Ellen , Sonerud Geir A. , Haaland Peder J. , Devor Tone Pahle , Kjønniksen Inge
Published: June 2003

Objective: To evaluate the absorbance of ultraviolet radiation (UVR) in the aqueous humor of various animal species in relation to the ambient radiation of their respective habitats, and to identify substances responsible for this absorbance. Representatives of all five classes (fish, amphibian, reptile, bird, and mammal) have been tested. Methods: Absorbance was recorded using a spectrophotometer. The ascorbic and uric acid concentrations were determined by HPLC, and the amino acid profiles with an automatic analyzer. Screening for potential UV-absorbing substances was performed by HPLC and a total of 12 species were examined, 7 of them birds. Results: UV-absorbing substances in the aqueous humor were proteins, tryptophan, tyrosine and ascorbic and uric acid. In addition, an unknown UV-absorbing component present in bird aqueous humor caused a high, red-shifted UV-absorbance spectrum, particularly in tentatively heavily exposed species such as goose when migrating at 10,000 m altitude. By comparison, the UV absorbance above the 288-nm wavelength was low in the aqueous humor of fish, frogs, aquatic mammals and two ground-living birds. The crocodile, whose aqueous humor contained significant amounts of both ascorbic and uric acid, revealed a concentration mechanism for ascorbic acid. Conclusions: The UV absorbance of aqueous humor varies considerably from one species to the next, and independent of class. It is noteworthy that the species being at highest risk for high-dose UV exposure, the migrating goose, showed the most red-shifted spectrum.
A Review of Positive and Bipolar Lightning Discharges
Authors: Rakov V. A.
Published: June 2003

Characteristics of lightning discharges that transport either positive charge or both positive and negative charges to the ground are reviewed. These are termed positive and bipolar lightning discharges, respectively. Different types of positive and bipolar lightning are discussed. Although positive lightning discharges account for 10% or less of global cloud-to-ground lightning activity, there are five situations that appear to be conducive to the more frequent occurrence of positive lightning. These situations include 1) the dissipating stage of an individual thunderstorm, 2) winter thunderstorms, 3) trailing stratiform regions of mesoscale convective systems, 4) some severe storms, and 5) thunderclouds formed over forest fires or contaminated by smoke. The highest directly measured lightning currents (near 300 kA) and the largest charge transfers (hundreds of coulombs or more) are thought to be associated with positive lightning. Two types of impulsive positive current waveforms have been observed. One type is characterized by rise times of the order of 10 μs, comparable to those for first strokes in negative lightning, and the other type is characterized by considerably longer rise times, up to hundreds of microseconds. The latter waveforms are apparently associated with very long, 1–2 km, upward negative connecting leaders. The positive return-stroke speed is of the order of 108 m s−1. Positive flashes are usually composed of a single stroke. Positive return strokes often appear to be preceded by significant in-cloud discharge activity, then followed by continuing currents, and involve long horizontal channels. In contrast to negative leaders, which are always optically stepped when they propagate in virgin air, positive leaders seem to be able to move either continuously or in a stepped fashion. The reported percentage of bipolar flashes in summer storms ranges from 6% to 14% and from 5% to 33% in winter storms. Bipolar lightning discharges are usually initiated by upward leaders from tall objects. It appears that positive and negative charge sources in the cloud are tapped by different upward branches of the bipolar-lightning channel.
Case studies in Bayesian segmentation applied to CD control
Authors: Taylor A.R. , Duncan S.R.
Published: June 2003

Identifying step changes in historical process and controller output variables can lead to improved process understanding and fault resolution in control system performance analysis. This paper describes an application of Bayesian methods in the search for statistically significant temporal segmentations in the data collected by a cross directional (CD) control system in an industrial web forming process. CD control systems give rise to vector observations which are often transformed through orthogonal bases for control and performance analysis. In this paper two models which exploit basis function representations of vector times series data are segmented. The first of these is a power spectrum model based on the asymptotic Chi‐squared approximation which allows large data sets to be processed. The second approach, more capable of detecting small changes, but as a result is more computationally demanding, is a special case of the multivariate linear model. Given the statistical model of the data, inference regarding the number and location of the change‐points is based on numerical Bayesian methods known as Markov chain Monte Carlo (MCMC). The methods are applied to real data and the resulting segmentation relates to real process events. Copyright © 2003 John Wiley & Sons, Ltd.
Poly(2‐) and (3‐aminobenzoic acids) and their copolymers with aniline: Synthesis, characterization, and properties
Authors: Rivas B. L. , Sánchez C. O.
Published: June 2003

Poly(2‐aminobenzoic acid) and poly(3‐aminobenzoic acid) were synthesized by chemical polymerization of the respective monomers with aqueous 1M hydrochloric acid and 0.49M sodium hydroxide, using ammonium persulfate as an oxidizing agent. In addition, polymerization in an acid medium was carried out in the presence of metal ions, such as Cu(II), Ni(II), and Co(II). Poly(2‐aminobenzoic acid‐co‐aniline) and poly(3‐aminobenzoic acid‐co‐aniline) were synthesized by chemical copolymerization of aniline with 2‐ and 3‐aminobenzoic acids, respectively, in aqueous 1M hydrochloric acid. The copolymers were synthesized at several mole fractions of aniline in the feed and characterized by UV–visible and FTIR spectroscopy, the thermal stability, and the electrical conductivity. Metal ions, such as Cu(II), Ni(II), and Co(II), were incorporated into homo‐ and copolymers by the batch method. The percentage of metal ions in the polymers was higher in the copolymers than in the homopolymers. The thermal stability of the copolymers increased as the feed mole fraction of aniline decreased and varied with the incorporation of metal ions in the polymers. The electrical conductivity of the homo‐ and copolymers was measured, which ranged between 10−3 and 10−10 S cm−1. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 2641–2648, 2003
Physical and mechanical behavior of single‐walled carbon nanotube/polypropylene/ethylene–propylene–diene rubber nanocomposites
Authors: Valentini L. , Biagiotti J. , Kenny J. M. , López Manchado M. A.
Published: June 2003

The effects of the incorporation of single‐walled carbon nanotubes (SWNTs) on the physical and mechanical properties of thermoplastic elastomers based on blends of isotactic polypropylene (iPP) and ethylene–propylene–diene rubber (EPDM) are described. A marked decrease of the half‐time of PP–EPDM crystallization and a sensible increase of the overall crystallization rate were observed in the presence of SWNTs. These results confirmed the expected nucleant effect of nanotubes on the crystallization of polypropylene. This effect was not linearly dependent on the SWNTs' content, showing a saturation of the nucleant effect at high nanotube concentrations. Dynamic mechanical analysis results showed a significant and controversial change of the mechanical behavior of the PP–EPDM/SWNT composites depending on the nanotube content. In particular, the storage modulus increased at the lowest incorporation of SWNTs, whereas a further increase of nanotubes led to a reduction of the storage modulus with respect to the pristine polymer matrix. Raman spectroscopy and scanning electron microscopy were successfully applied to demonstrate that in the composite films, the changes in the crystallization kinetics and mechanical properties could be explained in terms of the changes of the distance between nanotubes in bundles after a different intercalation of the polymer matrix. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 2657–2663, 2003
Study of the fine crystalline structure of polyethylenes via annealing and thermal fractionation
Authors: Xie Yunchuan , Zhang Qian , Fan Xiaodong
Published: June 2003

The fine crystalline structures of two polyethylenes have been investigated with annealing and fractionation techniques via modulated differential scanning calorimetry. The molecular structure and polydispersity of both high‐density polyethylene and low‐density polyethylene have been characterized by multiple‐step annealing and successive self‐nucleation/annealing thermal fractionation methods. The effects of annealing on the crystallinity and mechanical properties and the possible mechanism of the formation of the different fine crystalline structures related to the macromolecular chain motion for the two polyethylenes have also been studied and analyzed according to detailed annealing and fractionation processes. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 2686–2691, 2003
Synthesis and characterization of chiral side‐chain liquid‐crystalline polymer containing menthol ester
Authors: Jiang Tong‐Ying , Zhang Bao‐Yan , Tian Mei , Wang Ying
Published: June 2003

The synthesis of new chiral side‐chain liquid‐crystalline polysiloxanes containing p‐(allyoxy)benzoxy‐p‐chlorophenyl (ABCH) as mesogenic units and undecylenic acid menthol ester (UM) as chiral nonmesogenic units is presented. The chemical structures of monomers and polymers are confirmed by IR spectroscopy. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) are used to measure thermal properties of those polymers. Mesogenic properties are characterized by polarized optical microscope (POM), DSC, and small‐angle X‐ray diffraction. Analytic results revealed that polymers P0–P6 are thermotropic liquid‐crystalline polymers with low glass transition; Polymers P2–P6 exhibit chiral smectic liquid‐crystalline properties with marble texture, optical rotation, and a sharp reflection at low angles in X‐ray diffraction; polymers P0, P1 only exhibit smectic liquid‐crystalline properties without chirality; and P7 only exhibits chirality without liquid‐crystalline properties. All the polymers exhibit good thermal stability with temperature of 5% mass loss over 297°C. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 2845–2851, 2003
Preparation and properties of APPSSQ‐like/polyimide hybrid composites
Authors: Hsueh Huai‐Bin , Chen Chuh‐Yung , Wang Cheng‐Chien , Chu Tzong‐Jeng
Published: June 2003

Hydrolysis and condensation proceeded to generate 3‐aminopropyl polysilsesquioxane‐like (APPSSQ‐like) particles from 3‐aminopropyl triethoxysilane. An APPSSQ‐like particle includes two domains: crosslinking SiOSi networks inside and 3‐aminopropyl groups outside the particle. The APPSSQ‐like/polyimide (APPSSQ‐like/PI) hybrid composites were prepared from a solution of poly(amic acid) (PAA, polyimide precursor) and APPSSQ‐like particles using N,N‐dimethylacetamide as a solvent. Scanning electron microscopy (SEM) showed that the APPSSQ particle sizes were about 100 nm, and there was no obvious phase separation between the APPSSQ‐like particles and the PI matrix in the fracture surfaces of the hybrid films. Owing to the highly crosslinked SiOSi networks inside the APPSSQ‐like particles, the APPSSQ‐like/PI hybrid composites possessed desired properties such as improved thermal resistance and reduced coefficients of thermal expansion (CTE). The presence of covalent bonds between the APPSSQ‐like particles and the PI molecules improved the compatibility between these two components. Thus, the tensile strength increased with the APPSSQ‐like content, and the elongation at break also slightly increased with the APPSSQ‐like content. The initial tensile and storage moduli of the APPSSQ‐like/PI hybrid composites increased with the APPSSQ‐like content, which indicates that the mechanical properties of these hybrid composites were enhanced by the incorporation of the APPSSQ‐like content in the PI matrix. Furthermore, the glass transition temperatures of these composites increased with the APPSSQ‐like content because the adhesion between the APPSSQ‐like particles and the PI molecules restricts the PI chains' mobility. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 2865–2874, 2003
NKG2D engagement of colorectal cancer‐specific T cells strengthens TCR‐mediated antigen stimulation and elicits TCR independent anti‐tumor activity
Authors: Maccalli Cristina , Pende Daniela , Castelli Chiara , Mingari Maria Cristina , Robbins Paul F. , Parmiani Giorgio
Published: June 2003

The NKG2D receptor is expressed by human NK, γ δ T and α/β T lymphocytes and its engagement results in the stimulation of effector cells. We evaluated the role of NKG2D receptor in anti‐colorectal cancer (CRC) immune response. The cell surface expression of stress‐inducible NKG2D ligands MICA/B (MHC class I‐related chain molecules A/B) and ULBP (UL16 binding protein) by apanel of CRC lines was evaluated by flow cytometry. MICA and ULBP2/3 were widely expressed by the analyzed lines, with a minority of them being also ULBP‐1+, whereas MICB was undetectable.CD8+ and CD4+ HLA‐restricted anti‐tumor T cell clones of a CRC patient were used to evaluate whether NKG2D engagement could mediate tumor recognition. Three out of four CD8+ T cell clones recognized the autologous tumor with a marginal NKG2D engagement, a finding that was correlated with the weak expression of NKG2D ligands by the autologous tumor. On the contrary, NKG2D triggering of these CD8+ T cell clones induced recognition of allogeneic CRC lines showing high expression of MICA and ULBP. A costimulatory role of NKG2D was observed with one CD4+/NKG2D+ T cell clone when stimulated by tumors sharing the HLA class II alleles and expressing NKG2D ligands. Taken together these data indicate that the engagement of NKG2D, depending on the expression of its ligands by target cells, can influence the pattern of anti‐tumor reactivity by T lymphocytes.
Suitability of oligonucleotide‐mediated cystic fibrosis gene repair in airway epithelial cells
Authors: de Semir David , Nadal Marga , González Juan R. , Larriba Sara , Avinyó Anna , Nunes Virginia , Casals Teresa , Estivill Xavier , Aran Josep M.
Published: June 2003

Background

Non‐viral vector‐mediated targeted gene repair could become a useful alternative to classical gene addition strategies. The methodology guarantees a physiologically regulated and persistent expression of the repaired gene, with reported gene conversion and phenotypic correction efficiencies approaching 40–50% in some in vitro and in vivo models of disease. This is particularly important for cystic fibrosis (CF) because of its complex pathophysiology and the cellular heterogeneity of the cystic fibrosis transmembrane conductance regulator (CFTR) gene expression and function in the lung.

Methods

A cell‐free biochemical assay was applied to assess the ability of CF airway epithelial cells to support chimeraplast‐mediated repair. In addition, a methodology allowing the relative quantification of the percentage of W1282X mutation repair in a heterozygous background using the PCR/oligonucleotide ligation assay (PCR/OLA) was developed. The performance of different chimeraplast and short single‐stranded oligonucleotide structures delivered by non‐viral vectors and electroporation was evaluated.

Results

Chimeraplast‐mediated repair competency was corroborated in CF airway epithelial cells. However, their repair activity was about 5‐fold lower than that found in liver cells. Moreover, regardless of the corrector oligonucleotide structure applied to our CF bronchial epithelial cells, of compound heterozygous genotype (F508del/W1282X), the percentage of their resulting wild‐type allele in the W1282X (exon 20) locus of the CFTR gene was not significantly different from that of the control untreated cells by our PCR/OLA assay (confidence interval at 95% ± 4 allele wild‐type).

Conclusions

Oligonucleotide‐mediated CFTR gene repair is an inefficient process in CF airway epithelial cells. Further improvements in oligonucleotide structure, nuclear delivery and/or the capability for mismatch repair stimulation will be necessary to achieve therapeutic levels of mutation correction in these cells. Copyright © 2003 John Wiley & Sons, Ltd.
A tetracycline‐regulated adenoviral expression system for in vivo delivery of transgenes to lung and liver
Authors: Tietge Uwe J. F. , Kozarsky Karen F. , Donahee Mary H. , Rader Daniel J.
Published: June 2003

Background

Recombinant adenoviruses are an established tool for somatic gene transfer to multiple cell types in animals as well as in tissue culture. However, generation of adenoviruses expressing transgenes that are potentially toxic to the host cell line represents a practical problem. The aim of this study was to construct an adenoviral expression system that prevents transgene expression during the generation and propagation of the virus, and allows efficient gene transfer to lung and liver, major target organs of gene therapy.

Methods

Using the tet‐off system we constructed tetracycline (tet) regulatable recombinant adenoviruses expressing the marker gene LacZ (Adtet‐off.LacZ) as well as a secretory protein, human group IIA secretory phospholipase A2 (Adtet‐off.hsPLA2). Expression (Western blot, activity assay) was tested in vitro (HeLa cells), and in vivo by gene transfer to lung and liver.

Results

Without addition of tetracycline we demonstrated expression of LacZ (Adtet‐off.LacZ) and sPLA2 (Adtet‐off.hsPLA2) in HeLa cells. Providing additional tet‐transactivator (tTA) protein either by stable transfection or coinfection with a tTA‐expressing adenovirus resulted in a further increase of LacZ and sPLA2 expression. Transgene expression in vitro was eliminated by the addition of tetracycline to the culture medium. Adtet‐off.LacZ and Adtet‐off.hsPLA2 allowed successful gene transfer in vivo to lung and liver. While the expression was highly efficient within the lungs, however, additional tTA was necessary to achieve high‐level expression within liver.

Conclusions

Tet‐regulatable adenoviral expression systems may facilitate the construction of recombinant adenoviruses encoding potentially toxic transgenes and permit regulated transgene expression. Copyright © 2003 John Wiley & Sons, Ltd.
Adenoviral VEGF‐A gene transfer induces angiogenesis and promotes bone formation in healing osseous tissues
Authors: Tarkka Tatu , Sipola Annina , Jämsä Timo , Soini Ylermi , Ylä‐Herttuala Seppo , Tuukkanen Juha , Hautala Timo
Published: June 2003

Background

Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis. VEGF has been safely and efficiently applied to stimulate neovascularization in ischemic tissues in atherosclerotic patients. VEGF has an important role in bone repair by promoting angiogenesis and by stimulating major skeletal cell populations, chondrocytes, osteoblasts and osteoclasts.

Methods

We studied the effect of VEGF‐A on the recovery of bone drilling defects in rat femur delivered with first‐generation adenoviral vector. The virus was injected into the muscle layer surrounding the bone defect made by drilling and the healing was followed for 1, 2, and 4 weeks.

Results

The VEGF effect was first demonstrated with an increased number of FVIII‐related antigen‐positive blood vessels in the defect area 1 week after the procedure. The proportional area of remaining reparative tissue was significantly reduced in the VEGF‐treated animals 2 weeks after the injury suggesting favorable effect on bone healing. Increased periosteal cartilage was seen at the early phases of healing suggesting endochondral ossification. VEGF overexpression, however, completed the endochondral phase earlier compared with the control condition. Bone mineral content was enhanced in the VEGF‐treated femurs measured with peripheral quantitative computed tomography at a 2‐week time point.

Conclusions

Our data confirm the important role of VEGF in bone healing. We show for the first time that adenoviral VEGF‐A gene transfer may modify bone defect healing in a rodent model. Copyright © 2003 John Wiley & Sons, Ltd.
Elastic properties of model basaltic melt compositions at high temperatures
Authors: Schilling Frank R. , Sinogeikin Stanislav V. , Hauser Markus , Bass Jay D.
Published: June 2003

To constrain the effect of composition and temperature on the elasticity of glasses and super‐cooled liquids, acoustic velocities of samples in the pseudoternary system anorthite‐diopside‐forsterite (An‐Di‐Fo) were measured by Brillouin spectroscopy. Both the longitudinal and shear wave velocities were measured in the glassy state and into the region of super‐cooled liquids. The glass transformation temperatures (Tg) inferred from the Brillouin measurements are equal to those obtained by earlier viscosity and thermal expansion measurements on the same samples, within the limits of experimental uncertainties. The variation of the elastic properties with temperature is approximately linear, both for the glassy state (below Tg) and in the super‐cooled liquid state (above Tg). The temperature derivative of vibrational contributions to Young's (E), bulk (KS), and shear (G) modulus is approximately 6–12 times greater for super‐cooled liquids than for glasses. In the glassy state the elastic moduli and their temperature derivatives are described by ideal mixing of molar properties of oxides. The pronounced variations with composition in the elastic and anelastic properties above the glass transformation can be related to changes in configurational contributions. The configurational contribution for chemically complex glasses (mixtures of the An‐Di‐Fo end‐members) does not affect the overall compressibility at lower temperatures, whereas at higher temperatures they dominate the temperature derivatives of the moduli. In the super‐cooled liquid state the temperature dependence of the vibrational elastic moduli for simple end‐member compositions (An, Di) is much higher than for complex compositions. On the other hand, the configurational contribution to compressibility is higher for complex compositions than extrapolated from end‐member compositions. Therefore the density and elastic properties of complex melts in the basaltic anorthite‐diopside‐forsterite‐system cannot be easily approximated from the behavior of pure anorthite or diopside samples. Our results indicate that with increasing temperature, configurations with a higher bond strength were preferentially occupied. Isothermal relaxation times, varying between ≈0.01 and ≈1 s at 950°C, show a minimum for intermediate anorthite‐diopside‐compositions and are related to the maximum in configurational entropy.
Atmospheric iron delivery and surface ocean biological activity in the Southern Ocean and Patagonian region
Authors: Erickson David J. , Hernandez Jose L. , Ginoux P. , Gregg W. W. , McClain C. , Christian J.
Published: June 2003

Iron is a limiting nutrient for biologic activity in much of the world ocean. We present a method to quantitatively address the response of surface ocean biology to inputs of atmospheric Fe associated with atmospheric dust. We merge two enabling technologies, global models of Earth system processes and satellite derived chlorophyll concentrations to assess the importance of Fe in oceanic biogeochemistry. We present an objective correlation analysis to elucidate the spatial response of chlorophyll to iron flux considering the ocean surface meridional center of mass in areas with high correlation. Several regions between 40°S and 60°S show correlations from 0.6 to 0.95, significant at the 0.05 level, particularly the Patagonian region. Surface chlorophyll and iron flux follow similar patterns, however chlorophyll may be displaced to different latitudes than where Fe input occurs due to meridional ocean transport.
Clinicopathological evaluation of renal allografts of four patients by 20‐year protocol biopsies
Authors: Okamoto Masahiko , Nobori Shuji , Higuchi Atsushi , Kadotani Yayoi , Ushigome Hidetaka , Nakamura Kenji , Akioka Kiyokazu , Omori Yoshihiro , Yoshimura Norio
Published: June 2003

Abstract: Twenty‐year protocol biopsies were performed in four cases of renal transplant recipients with grafts that had survived 20 years or more. All four recipients received transplants from their parents, and never had episodes of acute rejection. They were maintained with the conventional immunosuppressive protocol including azathioprine, mizoribine, and prednisolone. Three of them had past history of malignant diseases such as breast cancer and tongue cancer. In spite of fair graft function, the microscopic findings of 20‐year protocol biopsy showed various degrees of histological damage; e.g. obsolescence of the glomeruli, glomerulosclerosis, arteriole wall thickening, interstitial fibrosis and tubular atrophy. Although two of the four grafts were functioning with low serum creatinine levels (1.3–1.4 mg dL−1) at 24 years and 26 years following transplantation, respectively, the function of the other two grafts had decreased more than 20 years after transplantation. In the two grafts with decreased function, glomerulosclerosis and arteriole wall thickening tended to be more severe (Banff classification of chronic allograft nephropathy [CAN] grade II and III) at the 20‐year protocol biopsy compared with the two well‐functioning grafts (CAN grade I and II). We conclude that the protocol biopsies even at 20 years can contribute to predict the fate of renal allografts.
A case report of a renal transplant recipient developing chronic glomerular rejection with a weak antibody against anti‐donor T‐cell, only detected by flow‐cytometry crossmatch
Authors: Takeda Asami , Uchida Kazuharu , Haba Toshihito , Tominaga Yoshihiro , Katayama Akio , Gotoh Norihiko , Otsuka Yasuhiro , Fukuda Michio , Horike Keiji , Shimano Yasunobu , Takeuchi Oki , Yoshida Atsuhiro , Oikawa Tadashi , Morozumi Kunio
Published: June 2003

Abstract:  The pathogenesis of antibody‐mediated rejection has been investigated, but the precise mechanism of chronic glomerular rejection remains unclear. We have followed the clinicopathological course of a patient with pre‐existing anti‐donor antibody only detected by flow‐cytometry crossmatch for over 3 years. Glomerular endothelial injuries and peculiar glomerular lesions were noted in biopsy specimen of postoperative year 3; however, both typical chronic vascular rejection lesions and peritubular capillary multilayered lesions were not revealed. We consider that the presence of weak anti‐donor antibody leading early onset of acute humoral rejection played a role in the pathogenesis of early onset of chronic transplant glomerulopathy.