bluuebunny/crossref_metadata_2025 huggingface dataset:
Constipation, polyps, or cancer? let PTEN predict your future
Authors: Eng Charis
Published: September 2003

The inherited hamartoma polyposis syndromes encompass several distinct clinical syndromes with different genetic bases, Cowden syndrome (CS), Bannayan–Riley–Ruvalcaba syndrome (BRRS), juvenile polyposis syndrome (JPS), and Peutz–Jeghers syndrome (PJS). Germline mutations in PTEN, encoding a tumor suppressor phosphatase on 10q23.3, is associated with 80% of CS and 60% of BRRS. JPS is caused by mutations in MADH4 and BMPR1A, encoding two members of the TGFB superfamily. Germline mutations in LKB1 (STK11) are associated with a subset of PJS. The number, distribution, and histologic type of polyps differ amongst these syndromes as do component cancer risks. While rare, usually asymptomatic, hamartomatous polyps are felt to be component to CS. Hamartomatous polyposis is usually prominent and symptomatic in BRRS. Polyposis, which can be quite symptomatic, is a cardinal component feature of PJS and JPS. Interestingly, glycogenic acanthosis of the esophagus is highly predictive of CS and the presence of PTEN mutation. PTEN mutation positive CS have been shown to be at increased risk of breast, thyroid, and endometrial cancer. PTEN mutation positive BRRS are at increased risk of at least breast cancer, possibly that of the thyroid as well. In contrast, JPS and PJS have increased risk of gastrointestinal cancers in particular. Thus, molecular‐based diagnoses to differentiate each of these syndromes are important for medical management. © 2003 Wiley‐Liss, Inc.
Biliary tract malformations
Authors: Knisely A.S.
Published: September 2003

The biliary tree extends from the canals of Hering at the margin of the most peripheral portal tracts to the ampulla of Vater. Malformations occur at every level of this structure. Phenotypic features dominate present understanding of these malformations and of the disorders with which they are associated. Classifications of disease will likely shift from a phenotypic basis to a genotypic basis as genes implicated in biliary tree development and function are identified. Involvement of such genes in biliary tree disorders now considered inflammatory, such as extrahepatic biliary atresia, awaits study. The concept of “feeble cholangiocytes” postnatally susceptible to the effects of “toxic bile” is presented. © 2003 Wiley‐Liss, Inc.
Persistent hyperinsulinemic hypoglycemia of infancy
Authors: Cohen, M. Michael
Published: September 2003

In persistent hyperinsulinemic hypoglycemia (PHHI) of infancy, secretion of insulin is unregulated, resulting in profound hypoglycemia. Two histopathologic forms are known: focal adenomatous islet‐cell hyperplasia and diffuse abnormalities of β‐cell hyperfunction. PHHI is caused by mutations in SUR1, which is a member of the ATP‐binding cassette superfamily, and in Kir6.2, which is a member of the inwardly rectifying family of potassium channels. © 2003 Wiley‐Liss, Inc.
Onset of dementia is associated with age at menopause in women with Down's syndrome
Authors: Schupf Nicole , Pang Deborah , Patel Bindu N. , Silverman Wayne , Schubert Romaine , Lai Florence , Kline Jennie K. , Stern Yaakov , Ferin Michel , Tycko Benjamin , Mayeux Richard
Published: September 2003

Women with Down's syndrome experience early onset of both menopause and Alzheimer's disease. This timing provides an opportunity to examine the influence of endogenous estrogen deficiency, indicated by age at menopause, on risk of Alzheimer's disease. A community‐based sample of 163 postmenopausal women with Down's syndrome, 40 to 60 years of age, was ascertained through the New York State Developmental Disability service system. Information from cognitive assessments, medical record review, neurological evaluation, and caregiver interviews was used to establish ages for onset of menopause and dementia. We used survival and multivariate regression analyses to determine the relation of age at menopause to age at onset of Alzheimer's disease, adjusting for age, level of mental retardation, body mass index, and history of hypothyroidism or depression. Women with early onset of menopause (46 years or younger) had earlier onset and increased risk of Alzheimer's disease (AD) compared with women with onset of menopause after 46 years (rate ratio, 2.7; 95% confidence interval [CI], 1.2–5.9). Demented women had higher mean serum sex hormone binding globulin levels than nondemented women (86.4 vs 56.6 nmol/L, p = 0.02), but similar levels of total estradiol, suggesting that bioavailable estradiol, rather than total estradiol, is associated with dementia. Our findings support the hypothesis that reductions in estrogens after menopause contribute to the cascade of pathological processes leading to AD.
Oligoclonal immunoglobulins in cerebrospinal fluid during varicella zoster virus (VZV) vasculopathy are directed against VZV
Authors: Burgoon Mark P. , Hammack Barbara N. , Owens Gregory P. , Maybach Amy L. , Eikelenboom M. Judith , Gilden Donald H.
Published: September 2003

Limited analyses of cerebrospinal fluid from patients with central nervous system infections have shown that the oligoclonal IgG is antibody directed against the agent that causes disease. Using a new method involving binding of IgG to beads coated with lysates prepared from candidate infectious antigens, we showed that the oligoclonal IgG in cerebrospinal fluid of a patient with chronic varicella zoster virus vasculopathy is directed against the causative virus. This approach holds promise in identifying and purifying the relevant oligoclonal IgGs in inflammatory central nervous system diseases of unknown cause.
Imaging‐guided convection‐enhanced delivery and gene therapy of glioblastoma
Authors: Voges Juergen , Reszka Regina , Gossmann Axel , Dittmar Claus , Richter Raphaela , Garlip Guido , Kracht Lutz , Coenen Heinz H. , Sturm Volker , Wienhard Karl , Heiss Wolf‐Dieter , Jacobs Andreas H.
Published: September 2003

In a prospective phase I/II clinical study, we treated eight patients suffering from recurrent glioblastoma multiform with stereotactically guided intratumoral convection‐enhanced delivery of an HSV‐1‐tk gene–bearing liposomal vector and systemic ganciclovir. Noninvasive identification of target tissue together with assessment of vector‐distribution volume and the effects of gene therapy were achieved using magnetic resonance imaging and positron emission tomography. The treatment was tolerated well without major side effects. In two of eight patients, we observed a greater than 50% reduction of tumor volume and in six of eight patients focal treatment effects. Intracerebral infusion of contrast medium before vector application displayed substantial inhomogeneity of tissue staining indicating the need of test infusions to monitor the mechanical distribution of vectors. Visualization of therapeutic effects on tumor metabolism and documentation of gene expression using positron emission tomography indicated that molecular imaging technology appears to be essential for the further development of biological treatment strategies.
Chronic epilepsy and cognition: A longitudinal study in temporal lobe epilepsy
Authors: Helmstaedter Christoph , Kurthen Martin , Lux Silke , Reuber Markus , Elger Christian Erich
Published: September 2003

It remains unclear whether uncontrolled epilepsy causes mental decline. This longitudinal study contrasts change of memory and nonmemory functions in 147 surgically and 102 medically treated patients with temporal lobe epilepsy. All participants were evaluated at baseline (T1) and after 2 to 10 years (T3). Surgical patients underwent additional testing 1 year postoperatively (T2). Data were analyzed on an individual and group level. Sixty‐three percent of the surgical and 12% of the medically treated patients were seizure‐free at T3. Fifty percent of the medically treated and 60% of the surgical patients showed significant memory decline at T3 with little change in nonmemory functions (difference not significant). Surgery anticipated the decline seen in the medically treated group and exceeded it when surgery was performed on the left, or if seizures continued postoperatively. Seizure‐free surgical patients showed recovery of nonmemory functions at T2 (p< 0.001) and of memory functions at T3 (T3,p= 0.03). Multiple regression indicated retest interval, seizure control, and mental reserve capacity as predictors of performance changes. In addition, psychosocial outcome was better when seizures were controlled. In conclusion, chronic temporal lobe epilepsy is associated with progressive memory impairment. Surgery, particularly if unsuccessful, accelerates this decline. However, memory decline may be stopped and even reversed if seizures are fully controlled. Ann Neurol 2003;54:425–432
Microdysgenesis in mesial temporal lobe epilepsy: A clinicopathological study
Authors: Kasper Burkhard S. , Stefan Hermann , Paulus Werner
Published: September 2003

The interrelationship of mesial temporal lobe epilepsy (MTLE), hippocampal sclerosis, and febrile convulsions still remains an enigma. Additional microscopical cortical dysplasia or microdysgenesis has been suggested as pre‐existent susceptibility factor rendering the affected brain vulnerable to the development of MTLE after initial precipitating injuries such as febrile convulsions. Twenty‐four MTLE cases with histopathologically definite hippocampal sclerosis were examined for clearly defined features of microdysgenesis and further signs of neocortical dysplasia. Although unequivocal signs of dysplasia were absent, 29.2% of cases showed cortical neuronal clustering, 25.0% showed perivascular clustering, and 20.8% showed increased white matter neurons. The features of microdysgenesis studied here were not linked with each other and were not related to initial precipitating injuries, positive family history, or any other clinical parameter. Their suggested fundamental role as dysplastic factor within development of hippocampal sclerosis and MTLE is not confirmed. Ann Neurol 2003;54:501–506
Lack of paternal inheritance of muscle mitochondrial DNA in sporadic mitochondrial myopathies
Authors: Filosto Massimiliano , Mancuso Michelangelo , Vives‐Bauza Cristofol , Vilà Maya R. , Shanske Sara , Hirano Michio , Andreu Antoni L. , DiMauro Salvatore
Published: September 2003

In 2002, paternal inheritance of muscle mitochondrial DNA (mtDNA) was reported in a patient with exercise intolerance and a mitochondrial DNA (mtDNA) mutation restricted to skeletal muscle. To evaluate whether paternal inheritance is a common phenomenon, we studied 10 sporadic patients with skeletal muscle‐restricted mtDNA mutations: five harbored mtDNA point mutations in protein‐coding genes and five had single mtDNA deletions. We performed haplotype analysis and direct sequencing of the hypervariable regions 1 and 2 of the D‐loop in muscle and blood from the patients and, when available, in blood from their parents. We did not observe paternal inheritance in any of our patients.
Retrograde reactions of Clarke's nucleus neurons after human spinal cord injury
Authors: Schmitt Andreas B. , Breuer Sebastian , Polat Leyla , Pech Katrin , Kakulas Byran , Love Seth , Martin Didier , Schoenen Jean , Noth Johannes , Brook Gary A.
Published: September 2003

Successful axon regeneration depends on the expression of regeneration‐associated genes by axotomized neurons. Here, we demonstrate, for the first time to our knowledge, the expression of regeneration‐associated genes by axotomized human CNS neurons. In situ hybridization and immunohistochemistry showed a transient induction of GAP‐43 and c‐jun in Clarke's nucleus neurons caudal to traumatic human spinal cord injury. These results support experimental data that nonregenerating central nervous system neurons can temporarily upregulate regeneration‐associated genes, reflecting a transient regenerative capacity that fails over time. Ann Neurol 2003;54:534‐539
A diagnostic cycle test for McArdle's disease
Authors: Vissing John , Haller Ronald G.
Published: September 2003

We investigated whether the second wind phenomenon (ie, a decrease in heart rate and perceived exertion during exercise) is pathognomonic for McArdle's disease. Twenty‐four patients with McArdle's disease, 17 healthy subjects, and 25 patients with other inborn errors of muscle metabolism cycled a constant workload for 15 minutes. In McArdle's disease patients, heart rate consistently decreased by 35 ± 3 beats per minute from the 7th to the 15th minute of exercise, whereas heart rate increased progressively with exercise in all 42 control subjects. The findings indicate that cycling at a moderate, constant workload provides a specific, sensitive, and simple diagnostic test for McArdle's disease. Ann Neurol 2003;54:539‐542
Retinal involvement in dementia with Lewy bodies: A clue to hallucinations?
Authors: Maurage Claude‐Alain , Ruchoux Marie‐Magdeleine , De Vos Rob , Surguchov Andrei , Destee Alain
Published: September 2003

Visual hallucinations are a core feature of dementia with Lewy bodies. Their pathophysiology is not well understood, because neither clinical nor histological data have shown their basic mechanisms. Here, we report the presence of pale inclusions in the outer plexiform layer of the retina in a patient with dementia with Lewy bodies. These inclusions are related to cytoskeletal disorganization of the cones at ultrastructural level and modifications of the immunohistochemical pattern of distribution of synucleins in the retina. These modifications may participate in the visual impairment in dementia with Lewy bodies. Ann Neurol 2003;54:542‐547
Beschreibung der Zusammensetzung und Struktur geordneter mikro‐ und mesoporöser Materialien mit anorganischen Wirtsystemen
Authors: Liebau Friedrich , Behrens, Hannover Peter
Published: September 2003

Es werden ein System von Begriffen, das zur Beschreibung geordneter mikro‐ und mesoporöser Materialien geeignet ist, sowie Regeln zur Erstellung einer standardisierten kristallchemischen Formel für solche Materialien vorgeschlagen. Die Vorschläge basieren sowohl auf üblichen Vorgehensweisen als auch auf einem systematischen Klassifizierungsschema. Die Nomenklatur wurde so gestaltet, dass sie alle anorganischen Materialien mit geordneten, zugänglichen Poren umfasst, die freie Durchmesser kleiner 50 nm haben. Die kristallchemische Formel beschreibt die chemische Zusammensetzung sowohl der Gastspezies als auch des Wirts, die Struktur des Wirts, die Struktur des Porensystems und die Symmetrie des Materials. Die Formel kann entsprechend den Bedürfnissen des Nutzers vereinfacht oder erweitert werden.
Relativistische Effekte in der Gasphasenchemie von Ionen aus experimenteller Sicht
Authors: Schwarz Helmut
Published: September 2003

Über den Nachweis der Existenz schwer fassbarer Moleküle hinaus dienen Gasphasenexperimente, in Verbindung mit Ergebnissen aus quantenchemischen Rechnungen, zur Aufklärung der entscheidenden Rolle relativistischer Effekte in etlichen Bereichen der Übergangsmetallchemie. Speziell die thermochemischen Daten von Goldhalogeniden in unterschiedlichen Ladungszuständen, die faszinierenden strukturellen Eigenschaften von Gold(I)‐Komplexen, die drastischen Effekte von Liganden auf die Ionisierungsenergie von Gold oder die Bindungssituation in kationischen Metallcarbenkomplexen werden hier als Beispiele behandelt. Des Weiteren soll der Chemie kationischer Metallcarbenkomplexe und ihrer Bedeutung für die Methanfunktionalisierung besondere Aufmerksamkeit zukommen. Es ist das Zusammenspiel von Experimenten an “isolierten” Molekülen unter wohldefinierten Bedingungen und zuverlässigen quantenchemischen Berechnungen elektronischer Strukturen, die unser Verständnis für relativistische Effekte in der Übergangsmetallchemie, Katalyse und darüber hinaus entscheidend vorangebracht haben.
Chemikaliensicherheit in einer verletzlichen Welt
Authors: Gärtner Sabine , Küllmer Jens , Schlottmann Ulrich
Published: September 2003

Der Titel dieses Beitrags ist das Motto des vierten zwischenstaatlichen Forums für Chemikaliensicherheit (Forum IV), das im November 2003 in Bangkok tagen wird. In den zehn Jahren des Bestehens dieses Forums hat die Sensibilität gegenüber den mit Chemikalien verbundenen Risiken in Politik, Wissenschaft und Öffentlichkeit zugenommen. Es entstanden völkerrechtliche Konventionen über Verbote und Beschränkungen gefährlicher Chemikalien sowie über einen besser kontrollierbaren Handel, die in Kürze völkerrechtlich verbindlich sein werden. Viele Menschen, die in Entwicklungsländern mit gefährlichen Chemikalien umgehen, sind Analphabeten oder haben eine geringe Schulbildung und daher häufig keine Chance zu verstehen, womit sie hantieren. Daher haben die Industrieländer die besondere Verpflichtung, Chemikaliensicherheit in die Entwicklungszusammenarbeit einzubinden. Prominente Chemiker, wie Carl Djerassi, wollen durch ihre Präsenz auf dem Forum IV unterstreichen, dass Gesundheits‐ und Umweltvorsorge nur durch internationale Kooperation zu erzielen sind. Diese Übersicht beschreibt die Entwicklungen auf dem Politikfeld “Chemikaliensicherheit”, stellt eine Auswahl des in der Europäischen Union geltenden Chemikalienrechts vor und bietet einen Einblick in die verflochtenen Strukturen der internationalen Zusammenarbeit sowohl auf politischer als auch auf fachlicher Ebene.
Die Verantwortung von Forschern: eine europäische Sicht
Authors: Ernst Richard R.
Published: September 2003

Der Notwendigkeit, mehr Verantwortung für gesellschaftliche Belange zu übernehmen, können sich auch Naturwissenschaftler nicht länger entziehen. Dieser Essay ist ein Appell an Dozierende und Forschende im akademischen Umfeld, ihre Aktivitäten über ihr Spezialgebiet hinaus zu erweitern und sich auch den großen Fragen unserer Zeit zu stellen.
Titelbild: “Cascade‐Release Dendrimers” Liberate All End Groups upon a Single Triggering Event in the Dendritic Core / Self‐Immolative Dendrimers (Angew. Chem. 37/2003)
Authors: de Groot Franciscus M. H. , Albrecht Carsten , Koekkoek Ralph , Beusker Patrick H. , Scheeren Hans W. , Amir Roey J. , Pessah Neta , Shamis Marina , Shabat Doron
Published: September 2003

Dendrimere die sich selbst “opfern”, um aus ihren Endgruppen in einer selbstzerstörerischen Kaskadenreaktion funktionelle Moleküle freizusetzen, zeigt das Titelbild. Auf ein Signal hin zersetzen sich die Makromoleküle vollständig in ihre Bestandteile. F. M. H. de Groot et al. (auf S. 4628 ff.) und D. Shabat et al. (auf S. 4632 ff.) beschreiben in ihren Zuschriften diese Verbindungen, die neuartige Anwendungen für funktionelle Dendrimere, z. B. beim Wirkstofftransport, ermöglichen könnten.
Relativistic Effects in Gas‐Phase Ion Chemistry: An Experimentalist's View
Authors: Schwarz Helmut
Published: September 2003

Gas‐phase experiments provide information which, in conjunction with results from electronic structure calculations, help to unravel the critical role relativistic effects play in many areas of transition‐metal chemistry. Examples include the thermochemical data of gold halides in different oxidation states, the fascinating structural properties of gold(I) complexes, the dramatic effects of ligands on the ionization energy of gold, or the binding in cationic metal–carbene complexes. Furthermore, in the context of methane functionalization, special emphasis is paid to the chemistry of cationic metal–carbene complexes, and at uncovering the mechanistic details of important carbon–heteroatom coupling reactions. It is the interplay of conducting experiments of “isolated” molecules under well‐defined conditions with reliable electronic structure calculations that has considerably improved our understanding of the role relativistic effects play in the context of transition‐metal chemistry, catalysis, and beyond.
Chemical Safety in a Vulnerable World
Authors: Gärtner Sabine , Küllmer Jens , Schlottmann Ulrich
Published: September 2003

The title of this article is the motto of the fourth meeting of the Intergovernmental Forum on Chemical Safety (Forum IV), which is to be held in Bangkok in November 2003. The IFCS has been in existence for 10 years. During this period politicians, scientists, and the general public have become increasingly aware of the risks associated with chemicals. International conventions providing for prohibitions and restrictions of dangerous chemicals, and for better control of trade have been set up. These conventions will soon be binding under international law. In developing countries many people who handle or use hazardous chemicals are illiterate or poorly educated; they may not fully understand what they are handling. The industrialized countries therefore have a special duty to incorporate chemical safety in development cooperation measures. Through their presence at this year's forum, prominent chemists such as Carl Djerassi will seek to underline the fact that a long term preventive approach to healthcare and the environment is only possible through international cooperation. This overview describes current developments in the field of chemical safety policy and presents a selection of the legislation currently in force for chemicals in the European Union. It also provides an insight into the interwoven structure of international cooperation that takes place at both the political and the technical level.
The Responsibility of Scientists, a European View
Authors: Ernst Richard R.
Published: September 2003

The necessity to take on more responsibility for societal matters is something scientists can no longer avoid. This essay is an appeal to researchers and teachers in academia to extend their activities to transgress their own specialist fields and to face up to the important questions of our times.
Cover Picture: “Cascade‐Release Dendrimers” Liberate All End Groups upon a Single Triggering Event in the Dendritic Core / Self‐Immolative Dendrimers (Angew. Chem. Int. Ed. 37/2003)
Authors: de Groot Franciscus M. H. , Albrecht Carsten , Koekkoek Ralph , Beusker Patrick H. , Scheeren Hans W. , Amir Roey J. , Pessah Neta , Shamis Marina , Shabat Doron
Published: September 2003

Cascade‐release dendrimers or self‐immolative dendrimers, as shown in the cover picture, spontaneously release all the end‐group molecules following a single activation event. This triggering event induces a cascade of self‐eliminations which leads to complete dissociation of the dendrimer into its separate building blocks. As the research groups of both F. M. H. de Groot (on page 4490 ff) and D. Shabat (on page 4494 ff) describe, such functionally novel dendrimers open up new modes of application of dendrimers, for example, for drug delivery.
Synthesis and characterization of block copolymers from aromatic diols, fumaric acid, sebacic acid and PEG
Authors: Najafi Farhood , Sarbolouki Mohammad N.
Published: September 2003

The syntheses of two linear unsaturated aromatic oligoesters, poly(hydroquinone fumarate‐co‐sebacate) (PHFS) and poly(resorcinol fumarate‐co‐sebacate) (PRFS), are described. PHFS, PRFS and poly(ethylene glycol) (PEG) are then used to prepare di‐ and tri‐block copolymers. Products thus obtained are investigated in terms of molecular weight, composition, structure and thermal properties by gel permeation chromatography (GPC), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and NMR and FTIR spectroscopies. A number of design parameters including the molecular weights of PHFS, PRFS and PEG and the ratios of PEG to PPFS or to PEFS are varied in order to assess their effects on product yields and properties. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 2358–2363, 2003
Enhancement of uranyl ion uptake by the prestructuring of poly(2‐hydroxyethyl methacrylate itaconic acid) hydrogels in the presence of lead and cadmium ions/polarographic determination
Authors: Özyürek Cengiz , Çaykara Tuncer , İnam Recai
Published: September 2003

Poly(2‐hydroxyethyl methacrylate/itaconic acid) [P(HEMA/IA)] hydrogels were prepared by the γ‐ray irradiation of aqueous solutions. In the presence of lead and cadmium ions, the UO ion uptake on P(HEMA/IA) hydrogels was investigated with two types of hydrogel systems prepared by nonprestructuring and prestructuring methods. A differential pulse polarographic technique was used for the determination of trace quantities of uptake elements by the measurement of the reduction peak currents at −200, −410, and −580 mV for UO, Pb(II), and Cd(II) ions, respectively. Hydrogels prestructured with UO ions took up approximately 45% more UO ions than hydrogels prepared by the usual procedure. The UO ion uptake capacity of the hydrogels increased with an increasing percentage of itaconic acid in the hydrogel systems and an increasing concentration of UO ions in the presence of Pb(II) and Cd(II) ions. Uptake studies showed that other stimuli, such as the temperature and ionic strength of the solutions, also influenced the UO ion uptake capacity of the P(HEMA/IA) hydrogels. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 2385–2390, 2003
Effect of anhydride‐modified ethylene–propylene–diene rubber and ethylene–vinyl acetate copolymers on the compatibilization of nitrile rubber/ethylene–propylene–diene rubber blends
Authors: Oliveira Marcia G. , Soares Bluma G.
Published: September 2003

The effects of maleic anhydride modified ethylene–propylene–diene rubber (EPDMMA) and maleic anhydride modified ethylene–vinyl acetate (EVAMA) on the compatibilization of nitrile rubber (NBR)/ethylene–propylene–diene rubber (70:30 w/w) blends vulcanized with a sulfur system were investigated. The presence of EPDMMA and EVAMA resulted in improvements of the tensile properties, whereas no substantial change was detected in the degree of crosslinking. The blend systems were also analyzed with scanning electron microscopy and dynamic mechanical thermal analysis. The presence of EVAMA resulted in a blend with a more homogeneous morphology. The compatibilizing effect of this functional copolymer was also detected with dynamic mechanical analysis. A shift of the glass‐transition temperature of the NBR phase toward lower values was observed. The presence of EPDMMA and EVAMA also increased the thermal stability, as indicated by an improvement in the retention of the mechanical properties after aging in an air‐circulating oven. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 2408–2414, 2003
Plasma‐graft polymerization of a monomer with double bonds onto the surface of carbon fiber and its adhesion to a vinyl ester resin
Authors: Yamada Kenji , Yamane Hirokazu , Kumada Kiyoshi , Tanabe Seiji , Kajiyama Tisato
Published: September 2003

Double bonds reactive with active radical species were introduced onto the surface of carbon yarn by the plasma‐graft polymerization of adipic acid divinyl ester and ethylene glycol dimethacrylate monomers to increase the adhesive strength in the interface between the carbon yarn and a vinyl ester resin. The degree of grafting increased with increasing polymerization time and polymerization temperature. The degree of grafting depended on both the solvent and the monomer species used in the polymerization, and a high degree was obtained with ethylene glycol dimethacrylate as the conjugated monomer and in a mixture of methyl isobutyrate and water. The grafted yarn, whose surface layer contained double bonds, was reacted with a vinyl ester resin containing benzoyl peroxide and N,N‐dimethylaniline. The pull‐out force of the yarn embedded in the resin increased with increasing degree of grafting. The failure in pulling out the yarn was cohesive. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 2415–2419, 2003
Study on the thermoplastic vulcanizate using ultrasonically treated rubber powder
Authors: Kim Jin Kuk , Lee Sung Hyo , Hwang Sung Hyuk
Published: September 2003

Nowadays, waste EPDM (ethylene propylene diene monomer) increasingly has been causing significant environmental problems with increasing numbers of vehicles. From the perspective of the environment and economics, recycling is the best method to treat waste materials. This study investigated waste EPDM/PP (polypropylene) blends with waste EPDM. Waste EPDM powders were treated ultrasonically, which physically modifies the rubber particles to confer good mechanical properties. Also investigated were the relevance of the mass percentage of the dispersed phase, the influence of the geometry and rotation speeds of the screw used in extrusion, and the melting temperature of PP materials on the morphology and mechanical properties of the blend. The purpose of this study was to develop a valuable thermoplastic elastomer from waste EPDM. This study concentrated on determining the optimum conditions for producing a blend by extrusion, including parameters of screw geometry, screw rotational speed, and operating temperature. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 2503–2507, 2003
Crosslinking reaction of poly(vinyl alcohol) with poly(acrylic acid) (PAA) by heat treatment: Effect of neutralization of PAA
Authors: Kumeta K. , Nagashima I. , S. Matsui  , K. Mizoguchi
Published: September 2003

The crosslinking reaction of poly(vinyl alcohol) (PVA) by esterification using poly(acrylic acid) (PAA) as a crosslinking reagent was investigated to obtain highly insoluble PVA materials. Blend films of PVA and PAA (PVA/PAA = 8/2) were prepared to examine the effect of degree of neutralization (DN) in PAA and heat‐treatment conditions on the degree of crosslinking reaction. The degree of crosslinking reaction varied significantly when the DN of PAA changed. The optimum DN for the crosslinking reaction was in the range of 5 to 10 mol %. In the case of unneutralized PAA, the degree of crosslinking reaction was at most 15 mol % by heat treatment for 20 min at 200°C. Applying partially neutralized PAA (DN = 10 mol %) raised the degree to about 40 mol % under the same heat‐treatment conditions. FTIR analysis revealed that the hydroxyl group of PVA in the film blended with unneutralized PAA was degraded to a greater degree than that with partially neutralized PAA as a result of heat treatment. It was found that heat treatment at a low pH condition enhances the degradation of the hydroxyl group of PVA, resulting in a decrease of the number of crosslinking sites by esterification. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 2420–2427, 2003
Phase behavior of N‐isopropylacrylamide/acrylic acid copolymer hydrogels prepared with ultrasound
Authors: Seida Yoshimi , Takeshita Kenji , Nakano Yoshio
Published: September 2003

N‐Isopropylacrylamide/acrylic acid copolymer hydrogels were synthesized with ultrasound. The thermoresponsive phase behaviors of gels synthesized with ultrasound (US gels) were investigated and compared with those of gels synthesized in the absence of ultrasound (FR gels). The US gels showed thermoresponsive swelling behavior with a large hysteresis over a wide range of temperatures around its phase‐transition temperature. The hysteresis became larger with an increasing copolymerized acrylic acid content. The US gels were also characterized from the viewpoint of chemical, hydration, and macroscopic physical structures. Little difference was observed in the chemical and hydration structures of the FR gels and US gels. The macroscopic physical structure of the US gels was, however, distinct from that of the FR gels. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 2449–2452, 2003
Influence of untreated and novel electron‐beam‐modified surface‐coated silica filler on the thermorheological properties of ethylene–octene copolymer
Authors: Ray Sudip , Bhowmick Anil K. , Swayajith S.
Published: September 2003

We developed surface‐modified silica fillers by coating these with an acrylate monomer, trimethylolpropane triacrylate, or a silane coupling agent, triethoxyvinyl silane, followed by electron‐beam irradiation at room temperature. These were incorporated in an ethylene–octene copolymer rubber. Thermorheological studies of the unvulcanized ethylene–octene copolymer and its untreated and modified silica‐filled composites were done with a shear dynamic oscillating rheometer. Modification of the silica filler, especially via the silanization process followed by electron beam treatment, significantly reduced filler–filler networking as revealed from the log–log plots of storage modulus and complex shear viscosity, and its real component. The rheological complexity of the compositions was analyzed from a double logarithmic plot of the storage modulus and loss modulus. The results obtained from the master curves constructed on the basis of the time–temperature superposition principle and the activation energy calculated from the Arrhenius equation for the flow of above these compounds further supported these findings. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 2453–2459, 2003
Molecular cloning and characterization of a cDNA encoding cytochrome c oxidase subunit Va from the lesser grain borer, Rhyzopertha dominica (F.) (Coleoptera: Bostrichidae)
Authors: Ayala Jorge , Dowdy Alan K. , Beeman Richard W. , Zhu Kun Yan
Published: September 2003

A cDNA encoding subunit Va of cytochrome c oxidase (EC 1.9.3.1) was cloned and characterized from a lesser grain borer (Rhyzopertha dominica) cDNA library. The complete cDNA consists of 693‐bp and contains an open reading frame of 450‐bp that encodes 150 amino acid residues. The sequence includes a 28‐bp putative N‐terminal and a 122‐bp putative mature protein. The estimated molecular weight and pI for the predicted mature protein are 13,962 and 4.60, respectively. The cDNA‐deduced amino acid sequence of the mature protein shows 73% identity to that of a corresponding subunit of African malaria mosquito (Anopheles gambiae) and 59% identity to that of the fruit fly (Drosophila melanogaster). In addition, 31% of all amino acid residues are conserved among six different animal species. Evolutionary distance analysis suggests that cytochrome c oxidase subunit Va from R. dominica is most similar to the corresponding subunit from the malaria mosquito. Northern analysis revealed a single 4.9‐kb transcript that is much larger than that found in mammalian species. Arch. Insect Biochem. Physiol. 54:47–54, 2003. © 2003 Wiley‐Liss, Inc.
A continuous spectrophotometric assay for the determination of diamondback moth esterase activity
Authors: He Xiaodun
Published: September 2003

Conventional methods to determine esterase activity from insects are composed of a three‐step process where the enzyme is allowed to hydrolyze a 1‐naphthyl acetate substrate, that reaction is quenched by a SDS detergent, and then a Fast Blue B dye complex is formed with 1‐naphthol, the product of 1‐naphthyl acetate hydrolysis. These methods measure dye‐product complex rather than the product, 1‐naphthol. A new assay is presented that continuously monitors the formation of 1‐naphthol with the hydrolysis of an esterase substrate. The esterase activity was determined as the slope of the linear regression change in absorbance over time at 320 nm. The continuous assay provides a simple, rapid, and sensitive method for measuring esterases extracted from a single diamondback moth in 1–10 min. The detection limit of the assay is approximately 0.6 μM 1‐naphthol. The 1‐naphthol product from the esterase reaction was confirmed by HPLC analysis. According to the assay, the Km and Vmax values of the esterase were 28 ± 2 μM and 6.0 ± 0.1 μM/min, respectively, at 37°C for 1‐naphthyl acetate. The Ki value was 9 ± 2 μM using azadirachtin, an insecticide from neem tree, Azadirachta indica (A.Juss). Azadirachtin was a reversible competitive inhibitor of the esterase activity. Arch Insect Biochem Physiol 54:68–76, 2003. Published 2003 Wiley‐Liss, Inc.
The ken and barbie gene encoding a putative transcription factor with a BTB domain and three zinc finger motifs functions in terminalia development of Drosophila
Authors: Lukacsovich Tamas , Yuge Kazuya , Awano Wakae , Asztalos Zoltan , Kondo Shunzo , Juni Naoto , Yamamoto Daisuke
Published: September 2003

Mutations in the ken and barbie locus are accompanied by the malformation of terminalia in adult Drosophila. Male and female genitalia often remain inside the body, and the same portions of genitalia and analia are missing in a fraction of homozygous flies. Rotated and/or duplicated terminalia are also observed. Terminalia phenotypes are enhanced by mutations in the gap gene tailless, the homeobox gene caudal, and the decapentaplegic gene that encodes a TGFβ‐like morphogen. The ken and barbie gene encodes a protein with three CCHH‐type zinc finger motifs that are conserved in several transcription factors such as Krüppel and BCL‐6. All defects in ken and barbie mutants are fully rescued by the expression of a wild‐type genomic construct, which establishes the causality between phenotypes and the gene. Arch. Insect Biochem. Physiol. 54:77–94, 2003. © 2003 Wiley‐Liss, Inc.
Cloning of a putative Bombyx mori TFIIB‐related factor (BRF)
Authors: Martinez M. Juanita , Sprague Karen U.
Published: September 2003

To identify the protein domains responsible for its conserved and specialized functions, putative TFIIB‐Related Factor (BRF) from the silkworm (Bombyx mori) was compared with BRFs from other organisms. The Bombyx BRF coding region was assembled from three separate and overlapping cDNA fragments. Fragments encoding the middle portion and the 3′ end were discovered in the Bombyx mori Genome Project “Silkbase” collection through sequence homology with human BRF1, and the fragment encoding the N‐terminus was isolated in our laboratory using the 5′ RACE method. Southern analysis showed that silkworm BRF is encoded by a single‐copy gene. Bombyx BRF contains the following domains that have been noted in all other BRFs, and that are likely, therefore, to provide highly conserved functions: a zinc finger domain, an imperfect repeat, three “BRF Homology” domains, and an acidic domain at the C‐terminus. As expected from the evolutionary relationships among insects and mammals, Bombyx BRF is more similar overall to Drosophila BRF (55% identical) than to human BRF1 (42% identical). Detailed examination of individual domains reveals a remarkable exception, however. Domain II of Bombyx BRF is more similar to its human counterpart than to Drosophila Domain II. This result indicates that Domain II has undergone unusual divergence in Drosophila, and suggests a structural basis for Drosophila BRF's unique pattern of interaction with other transcription factors. Arch. Insect Biochem. Physiol. 54:55–67, 2003. © 2003 Wiley‐Liss, Inc.
Pharmacokinetics and pharmacodynamics of azosemide
Authors: Suh Ok K. , Kim So H. , Lee Myung G.
Published: September 2003

Azosemide is used in the treatment of oedematous states and hypertension. The exact mechanism of action is not fully understood, but it mainly acts on both the medullary and cortical segments of the thick ascending limb of the loop of Henle. Delayed tolerance was demonstrated in humans by homeostatic mechanisms (principally an increase in aldosterone secretion and perhaps also an increase in the reabsorption of solute in the proximal tubule). After oral administration to healthy humans in the fasting state, the plasma concentration of azosemide reached its peak at 3–4 h with an absorption lag time of approximately 1 h and a terminal half‐life of 2–3 h. The estimated extent of absolute oral bioavailability in humans was approximately 20.4%. After oral administration of the same dose of azosemide and furosemide, the diuretic effect was similar between the two drugs, but after intravenous administration, the effect of azosemide was 5.5–8 times greater than that in furosemide. This could be due to the considerable first‐pass effect of azosemide. The protein binding to 4% human serum albumin was greater than 95% at azosemide concentrations ranging from 10 to 100 μg/ml using an equilibrium dialysis technique. The poor affinity of human tissues to azosemide was supported by the relatively small value of the apparent post‐pseudodistribution volume of distribution (Vdβ), 0.262 l/kg. Eleven metabolites (including degraded products) of azosemide including M1, glucuronide conjugates of both M1 and azosemide, thiophenemethanol, thiophencarboxylic acid and its glycine conjugate were obtained in rats. Only azosemide and its glucuronide were detected in humans. In humans, total body clearance, renal clearance and terminal half‐life of azosemide were 112 ml/min, 41.6 ml/min and 2.03 h, respectively. Azosemide is actively secreted in the renal proximal tubule possibly via nonspecific organic acid secretory pathway in humans. Thus, the amount of azosemide that reaches its site of action could be significantly modified by changes in the capacity of this transport system. This capacity, in turn, could be predictably changed in disease states, resulting in decreased delivery of the diuretic to the transport site, as well as in the presence of other organic acids such as nonsteroidal anti‐inflammatory drugs which could compete for active transport of azosemide. The urinary excretion rate of azosemide could be correlated well to its diuretic effects since the receptors are located in the loop of Henle. The diuretic effects of azosemide were dependent on the rate and composition of fluid replacement in rabbits; therefore, this factor should be considered in the evaluation of bioequivalence assessment. Copyright © 2003 John Wiley & Sons, Ltd.
Convergence in peptide folding simulation: Multiple trajectories of a potential AIDS pharmacophore
Authors: Mihailescu Dan , Reed Jennifer , Smith Jeremy C.
Published: September 2003

To examine the conformational properties in aqueous solution of a 15‐residue peptide that is a potential pharmacophore for AIDS vaccine development, molecular dynamics simulations were performed in water starting from structures determined experimentally in three different organic solvents. Convergence characteristics of the simulation are examined in Cartesian and conformational spaces. In addition, novel analysis tools are employed including a multidimensional scaling method to represent the distance between trajectory frames. As these methods are based on a variety of physical parameters, they provide a useful cross‐check on the structural convergence. Theoretical two‐dimensional (2D) 1H‐NMR spectra are also generated. These are superficially quite different in appearance, demonstrating that backbone similarities difficult to identify by visual inspection of 2D NMR data can be revealed using the methods described here. © 2003 Wiley Periodicals, Inc. Biopolymers 70: 121–133, 2003
Molecular dynamics studies of alanine racemase: A structural model for drug design
Authors: Mustata Gabriela Iurcu , Soares Thereza A. , Briggs James M.
Published: September 2003

Alanine racemase (AlaR) is a bacterial enzyme that catalyzes the interconversion of L‐ and D‐alanine, which is an essential constituent of the peptidoglycan layer of the bacterial cell wall and requires pyridoxal 5′–phosphate (PLP) as a cofactor. The enzyme is universal to bacteria, including mycobacteria, making it an attractive target for drug design. To investigate the effects of flexibility on the binding modes of the substrate and an inhibitor and to analyze how the active site is affected by the presence of the substrate versus inhibitor, a molecular dynamics simulation on the full AlaR dimer from Bacillus stearothermophilus (pdb code: 1SFT) with a D‐alanine molecule in one active site and the noncovalent inhibitor, propionate, in the second site has been carried out. Within the time scale of the simulation, we show that the active site becomes more stabilized in the presence of substrate versus inhibitor. The results of this simulation are in agreement with the proposed mechanism of alanine racemase reaction in which the substrate carboxyl group directly participates in the catalysis by acting cooperatively with Tyr 265′ and Lys 39. A structural water molecule in contact with both substrate and inhibitor (i.e., in both active sites) and bridging residues in both active sites was identified. It shows a remarkably low mobility and does not exchange with bulk water. This water molecule can be taken into account for the design of specific AlaR inhibitors by either utilizing it as a bridging group or displacing it with an inhibitor atom. The results presented here provide insights into the dynamics of the alanine racemase in the presence of substrate/inhibitor, which will be used for the rational design of novel inhibitors. © 2003 Wiley Periodicals, Inc. Biopolymers 70: 186–200, 2003
Interaction of angiotensin II with the C‐terminal 300–320 fragment of the rat angiotensin II receptor AT1a monitored by NMR
Authors: D'Amelio Nicola , Gaggelli Elena , Gaggelli Nicola , Lozzi Luisa , Neri Paolo , Valensin Daniela , Valensin Gianni
Published: September 2003

Interaction between angiotensin II (Ang II) and the fragment peptide 300–320 (fCT300–320) of the rat angiotensin II receptor AT1a was demonstrated by relaxation measurements, NOE effects, chemical shift variations, and CD measurements. The correlation times modulating dipolar interactions for the bound and free forms of Ang II were estimated by the ratio of the nonselective and single‐selective longitudinal relaxation rates. The intermolecular NOEs observed in NOESY spectra between HN protons of 9LysfCT and 6Hisang, 10PhefCT and 8Pheang, HN proton of 3TyrfCT and Hα of 4Tyrang, 5PhefCTHδ and Hα of 4Tyrang indicated that Ang II aromatic residues are directly involved in the interaction, as also verified by relaxation data. Some fCT300–320 backbone features were inferred by the CSI method and CD experiments revealing that the presence of Ang II enhances the existential probability of helical conformations in the fCT fragment. Restrained molecular dynamics using the simulated annealing protocol was performed with intermolecular NOEs as constraints, imposing an α‐helix backbone structure to fCT300–320 fragment. In the built model, one strongly preferred interaction was found that allows intermolecular stacking between aromatic rings and forces the peptide to wrap around the 6Leu side chain of the receptor fragment. © 2003 Wiley Periodicals, Inc. Biopolymers 70: 134–144, 2003
Molecular weight effects on the glass transition of gelatin/cosolute mixtures
Authors: Kasapis Stefan , Al‐Marhoobi Insaf M. , Mitchell John R.
Published: September 2003

The structural properties of four gelatin fractions in mixture with sucrose and glucose syrup have been investigated extensively using small deformation dynamic oscillation. The total level of solids was 80%, the number average molecular weight of the protein ranged from 29.2 to 68 kD, and the temperatures were between 60 and −60°C. Remarkably, the nature of the time and temperature dependence on the viscoelastic functions of all samples could be reduced to master curves using horizontal shift factors. The construction of master curves indicates a common mechanism of structure formation, which, in accordance with the synthetic polymer literature, comprises the rubbery zone, glass transition region, and glassy state. Application of Ferry's free‐volume formalism and Rouse theory suggests that there is no change in the thermodynamic state of materials during vitrification, with changes in molecular weight simply introducing shifts in the time scale and temperature range of contributions to viscoelasticity. The thermorheological simplicity allowed development of the concept of “rheological” Tg. This was defined as the point between free‐volume phenomena of the polymeric backbone occurring in the glass transition region and an energetic barrier to rotation required for local chain rearrangements in the glassy state. Mechanical relaxation and retardation distribution functions were calculated, thus obtaining values for the effective friction coefficient per monomer unit of the protein. It appears that the local friction coefficient is governed by a linear relationship between fractional free volume and the decreasing molecular weight of the protein, which introduces additional voids due to molecular ends. © 2003 Wiley Periodicals, Inc. Biopolymers 70: 169–185, 2003