bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanical Properties of a High‐Strength Al90Mn8Ce2 Alloy
Authors: Li J.C. , Zhao Z.K. , Jiang Q.
Published: March 2003

A lightweight alloy with excellent strength and wear resistance, Al90Mn8Ce2, has been manufactured in bulk by powder metallurgy. The best colligative mechanical properties of the alloy made by this technique are achieved by pressing at 753 K, where the porosity reaches a minimum, and the plasticity a maximum. The Figure juxtaposes SEM images of the alloy pressed at 473 K and 753 K.
Nanocrystallization in Al‐rich Metallic Glasses
Authors: Wilde G. , Boucharat N. , Hebert R.J. , Rösner H. , Tong W.S. , Perepezko J.H.
Published: March 2003

The most attractive material properties and performance among glassy alloys are derived from microstructures based upon a high number density of nanocrystals dispersed within an amorphous matrix. The generation mechanism of these nanocrystal dispersions is still not clear; the present analyses point out that a nearly balanced kinetic competition between crystallization and vitrification is essential but indicate also the involvement of further mechanisms.
Low‐Temperature and High‐Strain Rate Superplastic Zirconia
Authors: Sakka Y. , Matsumoto T. , Suzuki T.S. , Morita K. , Kim B.‐N. , Hiraga K. , Moriyoshi Y.
Published: March 2003

A superplastic ceramic with a strain rate comparable to metals based on 3% Y2O3‐doped tetragonal zirconia (3YTZ) was synthesized at relatively low temperature, based on the doping with MgO and TiO2. The desirable material properties result from both a refined preparation procedure for the zirconia, and from enhanced cation lattice diffusion due to the MgO and TiO2 doping.
Effect of Lubrication in Rapid Gas Forming of Aluminum Alloy
Authors: Yang Y.‐L. , Lee S. , Ou B.‐L.
Published: March 2003

Drastically reduced cycle times for gas forming of a workpiece made of a superplastic alloy (here, Al alloy 5083) are achieved by lubrication, to be applied not only between the workpiece and the die cavity, but also to the area under the railing. The method allows large volume production of such parts. The Figure shows a top view of a specimen with markings to show material flow and deformation.
Influence of Selected Manufacturing Parameters on the Fatigue Strength and the Damage Behavior of Aluminum Light Weight Structures for Automotive Series Production
Authors: Gerber A. , Schulze V. , Löhe D.
Published: March 2003

What can be done to minimize the rate of fatigue failures of aluminium lightweight structures? Generally speaking, the authors’ answer is: make the weak spots, i.e. weld seams and roots, stronger. In detail, they show how joint extrusion techniques, extrusion shape, modified welding sequences, and TIG dressing of seams can be beneficial for fatigue resistance. The Figure shows a typical fatigue failure initiating at the weld root due to pores.
Investigation of Dislocation Microstructures Formed in Heavily Deformed Metals Through the Combined Use of EBSD and TEM
Authors: Richard V. , Chiron R. , Gerber P. , Gaspérini M. , Bacroix B.
Published: March 2003

New applications of the electron back scattering diffraction (EBSD) technique for studying dislocation microstructures are presented. Examples from copper and steel samples are given to illustrate the links between crystallographic measurements and dislocation microstructure. The purpose of combining transmission electron microscopy (TEM) and EBSD is to obtain quantitative information about the evolution and heterogeneity of the dislocation microstructure, and how it depends on the texture of the material.
Conjugated Polymer Actuators for Biomedical Applications
Authors: Smela E.
Published: March 2003

Conjugated polymers are electroactive and have found applications as artificial muscles. Actuators that have been developed over the last decade have now reached the early stages of commercialization, particularly for use in biomedical devices. This article reviews the motivation for using this class of actuator, the types of devices that have been fabricated, and some of the biomedical applications that are being developed. Recommendations are presented for future work on understanding the actuation mechanisms, on actuator design, and on the measurement of metrics.
Meso‐Epitaxial Solution‐Growth of Self‐Organizing Discotic Liquid‐Crystalline Semiconductors
Authors: van de Craats A.M. , Stutzmann N. , Bunk O. , Nielsen M.M. , Watson M. , Müllen K. , Chanzy H.D. , Sirringhaus H. , Friend R.H.
Published: March 2003

Substituted hexabenzocoronenes (HBCs) form films with supramolecularly ordered columnar stacks that are uniaxially oriented onto poly(tetrafluoroethylene) alignment layers (see Figure). In field‐effect transistor (FET) tests, mobilities of up to 10–3 cm2 V–1 s–1 and high on–off ratios of more than 104 were derived for these aligned HBC films, characteristics superior to FETs prepared from isotropic HBC layers.
A Polychromic, Fast Response Metallopolymer Gel Photonic Crystal with Solvent and Redox Tunability: A Step Towards Photonic Ink (P‐Ink)
Authors: Arsenault A.C. , Míguez H. , Kitaev V. , Ozin G.A. , Manners I.
Published: March 2003

A broadly wavelength tunable polyferrocenylsilane–silica composite photonic crystal with a fast response is presented. Polychromic variation in the reflection wavelength is effected via the swelling by solvent of a crosslinked redox‐active metallopolymer gel network incorporated in the voids of a planarized silica colloidal crystal film. The Figure demonstrates the fast mechanical response of the composite photonic crystals.
Platinum Surface Modification of SBA‐15 by γ‐Radiation Treatment
Authors: Yamada T. , Zhou H.‐S. , Hiroishi D. , Tomita M. , Ueno Y. , Asai K. , Honma I.
Published: March 2003

Modification of the mesoporous surface of SBA‐15 with platinum has been successfully carried out by means of γ‐radiation treatment. This novel treatment allows the selective growth of platinum in the SBA‐15 micropores (see Figure). This is in contrast to traditional temperature treatment, in which platinum particles or rods also grow in the mesopores.
Thermomechanical Lithography: Pattern Replication Using a Temperature Gradient Driven Instability
Authors: Schäffer E. , Harkema S. , Roerdink M. , Blossey R. , Steiner U.
Published: March 2003

A capillary surface instability caused by a high temperature gradient is used to replicate sub‐micrometer patterns (see Figure for an example). As opposed to convection effects, the film instability is driven by the diffusion of heat across the polymer film. By lateral modulation of the temperature gradient, this instability can be harnessed as a lithographic technique.
Chemically Amplified Positive Resists for Two‐Photon Three‐Dimensional Microfabrication
Authors: Yu T. , Ober C.K. , Kuebler S.M. , Zhou W. , Marder S.R. , Perry J.W.
Published: March 2003

A simple one‐step process to fabricate three‐ dimensional (3D) microstructures is reported. Based on two‐photon excited‐state chemistry, a chemically amplified positive tone photoresist has been developed and the lithographic process investigated. The results, as indicated by the fabricated material (see Figure) suggest that positive tone two‐photon 3D microfabrication may be a valuable route to precision microfluidic and microoptical devices.
Novel Oxides for Cycled Hydrogen Production from Methane and Water Using a Temperature Swing
Authors: Kang Z. , Wang Z.L.
Published: March 2003

A group of iron‐doped novel oxides of cerium, terbium, and praseodymium are reported to produce hydrogen at relatively low temperatures through a cycling two‐step reaction process without catalyst. Iron doping in the oxides not only stimulates surface activity, but also lowers the reduction temperature of water vapor (to ∼ 375 °C) while preserving efficient hydrogen production. The two‐step reactions eliminate the problem of catalyst deactivation due to coke. Thus the cycle can be carried out continuously without replacing oxide.
Quantum Confinement Observed in ZnO/ZnMgO Nanorod Heterostructures
Authors: Park W.I. , Yi G.‐C. , Kim M.Y. , Pennycook S.J.
Published: March 2003

Multiple quantum well nanorods have been fabricated via heteroepitaxial growth of ZnO and ZnMgO (see Figure and also cover). Simple yet accurate thickness control allows the realization of nanosized well structures in individual nanorods that are tunable through the effects of quantum confinement. This approach should be readily extendible to other heteroepitaxial semiconductor nanorods.
Stable Nanoporous Metallic Nickel Colloids
Authors: Hattori Y. , Konishi T. , Kanoh H. , Kawasaki S. , Kaneko K.
Published: March 2003

Nanoporous metallic nickel colloids (∼8.3 nm, see Figure) are produced by the thermal decomposition of nickel‐doped poly(vinyl alcohol) films. A small amount of carbon remaining on the surface protects the particles against further degradation. Adsorption isotherms indicate the colloids have both mesopores and micropores.
Spectroscopic Ellipsometric Evaluation of Gold Nanoparticle Thin Films Fabricated Using Layer‐by‐Layer Self‐Assembly
Authors: Zhang H.‐L. , Evans S.D. , Henderson J.R.
Published: March 2003

Uniform thin films of gold nanoparticles have been fabricated on gold substrates using a layer‐by‐layer self‐assembly approach (see Figure). The optical properties of these nanoparticle films were characterized using variable‐angle spectroscopic ellipsometry, and the data modeled using a Lorentz oscillator dispersion model. Both the thickness and refractive indices were evaluated simultaneously over a wide wavelength range.
Semiconductor Carbon Nanotubes as Ultrafast Switching Materials for Optical Telecommunications
Authors: Tatsuura S. , Furuki M. , Sato Y. , Iwasa I. , Tian M. , Mitsu H.
Published: March 2003

The third‐order nonlinear optical property χ(3)I of a film of single‐walled carbon nanotubes was studied in the infrared region. The film combines a high χ(3)I (–0.85 × 10–7 esu at resonant wavelength) with a rapid transmittance recovery (from differential transmission spectra, see Figure), making it suitable for highly efficient and ultrafast devices for optical telecommunications.
A Covalently Interconnected Phosphazene–Silicate Hybrid Network: Synthesis, Characterization, and Hydrogel Diffusion‐Related Application
Authors: Chang Y. , Allcock H.R.
Published: March 2003

Sol–gel precursors of poly[bis(methoxyethoxyethoxy)phosphazene] have been synthesized by incorporating triethoxysilane in the polymer side groups. Studies of the water‐swelling (see Figure, dry left, water‐swollen, right) behavior and dye‐release of the hybrid network indicate that the polyphosphazene–silicate network has potential as a biomaterial and for use in both passive and responsive membranes.
Fabrication of Organic Light‐Emitting Devices by Low‐Pressure Cold Welding
Authors: Kim C. , Forrest S.R.
Published: March 2003

Low‐pressure cold welding has been used to fabricate 200 μm diameter organic light‐emitting devices (OLEDs) (see Figure). The contacts are made by transferring a metal film from a patterned, soft elastomeric stamp onto unpatterned organic and metal layers on a substrate. The process does not adversely affect the OLED performance when compared with those fabricated by shadow mask patterning.
Exploring Chiral Space en route to DPC 963: A Personal Account
Authors: Nugent William A.
Published: March 2003

DPC 961 and DPC 963 are non‐nucleoside reverse transcriptase inhibitors (NNRTIs) for the treatment of HIV. These drug candidates contain a chiral quaternary center, which can be installed via addition of lithium cyclopropylacetylide to an N‐acylketimine in the presence of a chiral moderator. This account describes our efforts to identify a cost‐effective moderator by rapidly preparing, screening, and optimizing libraries of enantiopure β‐amino alcohols. The result is a highly enantioselective process that has been used to produce these NNRTIs on a metric ton scale.
Lonza: 20 Years of Biotransformations
Authors: Shaw Nicholas M. , Robins Karen T. , Kiener Andreas
Published: March 2003

Biotransformations are an important tool in organic synthesis, especially for the production of chiral molecules, and where chemical reactions are not possible or inefficient. Lonza is a major custom manufacturer of intermediates for the life science industries, and uses biocatalysis in many of its processes. A synthetic route may have one or more biotransformation steps. This article gives a number of examples of syntheses that involve biotransformations for the production of both achiral and chiral intermediates, at development and production scales. For each example the reasons and advantages of using a biotransformation are given.
Industrialization of the Microbial Resolution of Chiral C3 and C4 Synthetic Units: From a Small Beginning to a Major Operation, a Personal Account
Authors: Kasai Naoya , Suzuki Toshio
Published: March 2003

This account describes the research and development of the microbial resolution of chiral C3 and C4 synthetic units through to the production stage. These chiral C3 and C4 synthetic units are mainly used for the production of various pharmaceuticals, new materials such as liquid crystals, chiral polymers, and natural compounds as well as in basic chemical research. The research started in 1983 and the industrial plant was built in 1994. The development is still ongoing and is being broadened to include C4 chiral units, chiral propylene glycol, and so on. This project started as simple research on the activated sludge from an epichlorohydrin plant and evolved through many events and much research to an industrial production. We describe the various implications and the flow of events in the research and development through to the production of these chiral C3 and C4 synthetic units.
Practical Heterogeneous Catalysts for Epoxide Production
Authors: De Vos Dirk E. , Sels Bert F. , Jacobs Pierre A.
Published: March 2003

An overview of heterogeneous epoxidation catalysts is given, with an emphasis on practical parameters such as catalyst productivity, turnover numbers and stereoselectivity. Special focus is directed towards catalysts that have resulted from research in the authors' group.
AgOTf‐Catalyzed Aza‐Diels–Alder Reactions of Danishefsky's Diene with Imines in Water
Authors: Loncaric Catherine , Manabe Kei , Kobayashi Shū
Published: March 2003

Aza‐Diels–Alder reactions of Danishefsky's diene with imines in water took place smoothly in the presence of a catalytic amount of silver triflate to afford dihydro‐4‐pyridones in high yields. The silver triflate‐catalyzed three‐component reactions starting from aldehydes, amines, and Danishefsky's diene were also performed efficiently. In the three‐component reactions with benzaldehyde, the addition of a non‐ionic surfactant was found to be effective.
Novel Reductive Amination of Nitriles: An Efficient Route to 5‐Hydroxypiperidone‐Derived N,N‐Acetals
Authors: Vink Mandy K. S. , Schortinghuis Christien A. , Mackova‐Zabelinskaja Antonina , Fechter Martin , Pöchlauer Peter , Castelijns A. Marianne C. F. , van Maarseveen Jan H. , Hiemstra Henk , Griengl Herfried , Schoemaker Hans E. , Rutjes Floris P. J. T.
Published: March 2003

5‐Hydroxypiperidin‐2‐one is a versatile building block for the preparation of potentially biologically active compounds. We detail an enantioselective biocatalytic approach towards its synthesis using (S)‐hydroxynitrile lyase (HNL)‐mediated cyanohydrin formation, followed by hydrogenation. By adjusting the conditions of the latter step, we were able to obtain 5‐hydroxypiperidinone‐derived (bicyclic) N,N‐acetals via an unprecedented reductive amination of the nitrile group, as well as form N‐alkylated 5‐hydroxypiperidinone in a single step from the same cyanohydrin intermediate.
Pd(0)‐Catalyzed Bismetallative Cyclization of Enynes in the Presence of Bu3SnSiMe3 Using N‐Heterocyclic Carbene as a Ligand
Authors: Sato Yoshihiro , Imakuni Noriko , Mori Miwako
Published: March 2003

It was found that a nucleophilic N‐heterocyclic carbene could be utilized as a ligand for Pd(0)‐catalyzed bismetallative cyclization of enynes in the presence of Bu3SnSiMe3. An imidazolium salt having a bulky alkyl group attached to both nitrogen atoms of its imidazol‐2‐ylidene skeleton or an imidazolinium salt is suitable as a ligand precursor. The cyclized products obtained from this cyclization have both a vinylsilane moiety and a homoallylstannane moiety, whose utility in synthetic organic chemistry has been proven by transformation into cyclopropanol derivatives.
Base‐Catalysed Hydrogenation of Sulphur‐Containing Aldehydes
Authors: Vu Thi‐Thu‐Ha , Kumbhar Pramod S. , Figueras François
Published: March 2003

The present work reports the first selective catalytic hydrogenation of bifunctional compounds containing a carbonyl and sulphur moieties, using hydrogen transfer from alcohols and a basic catalyst. The reaction was performed in batch at 371 K at atmospheric pressure with 3‐mercaptopropionaldehyde, thiophene‐2‐carboxaldehyde, 5‐bromothiophene‐2‐carboxaldehyde and 4‐methylthiobenzaldehyde. The only product of reaction was the alcohol, formed with yields >80%, except with 3‐mercaptopropionaldehyde which did not give the alcohol but rather afforded unidentified heavy products. 5‐Bromothiophenemethanol was obtained with 100% yield in 3 h. The reaction obeys a mechanism of competitive adsorption of the reactants, and the reaction rates are higher than those reported for supported rhodium catalysts.
Catalytic Conversions in Water. Part 22: Electronic Effects in the (Diimine)palladium(II)‐Catalysed Aerobic Oxidation of Alcohols
Authors: ten Brink Gerd‐Jan , Arends Isabel W. C. E. , Hoogenraad Marcel , Verspui Göran , Sheldon Roger A.
Published: March 2003

The electronic effects in the (diimine)Pd(II)‐catalysed aerobic oxidation of alcohols were investigated from the viewpoint of both the catalyst and the alcohol. A ‘push–pull' mechanism is operative, where both electron‐donating substituents on the benzyl alcohol (ρ=−0.58) and electron‐withdrawing groups on the 4,4′‐disubstituted‐2,2′‐bipyridine ligand (ρ=+0.18) increase the reaction rate. The results indicate partial reduction of the palladium centre in the transition state of the rate‐limiting step.
Enantioselective [4+2] Cycloaddition of Buta‐1,3‐dienes to Alkyl Glyoxylates Catalyzed by the Chiral (Salen)Chromium(III) Complex
Authors: Kwiatkowski Piotr , Asztemborska Monika , Caille Jean‐Claude , Jurczak Janusz
Published: March 2003

Thermal and high‐pressure [4+2] cycloadditions of buta‐1,3‐diene (3), cyclohexa‐1,3‐diene (5), and 2,3‐dimethylbuta‐1,3‐diene (6) to alkyl glyoxylates of type 2 ( Rn‐Bu, i‐Pr, t‐Bu), catalyzed by chromium complex (R,R)‐1, leading to the corresponding cycloadducts 4, 7 and 8 with relatively high enantioselectivity, are described.
Selective Oxidation of Alcohols to Carbonyl Compounds and Carboxylic Acids with Platinum Group Metal Catalysts
Authors: Anderson Ross , Griffin Ken , Johnston Peter , Alsters Paul L.
Published: March 2003

The use of platinum group metal (PGM) catalysts for the selective oxidation of various primary and secondary alcohols under mild conditions is described. High throughput screening (HTS) techniques have been used to identify trends in catalyst activity and product selectivity. Using air as oxidant and water as solvent 5% Pt, 1% Bi/C has been identified as an efficient catalyst for the transformation of 2‐octanol to 2‐octanone and 1‐octanol to octanoic acid. To improve aldehyde selectivity the promotion of Pt/Al2O3and Ru/C catalysts has been investigated. The use of H2O2as oxidant has been demonstrated as a suitable alternative to air.
Automated Enzyme Screening Methods for the Preparation of Enantiopure Pharmaceutical Intermediates
Authors: Yazbeck Daniel R. , Tao Junhua , Martinez Carlos A. , Kline Billie J. , Hu Shanghui
Published: March 2003

In a pharmaceutical environment, the need for efficient and practical screening techniques has become vital in the search for ideal enzymes that can be used in the preparation of drug intermediates. This paper describes a general high throughput screening (HTS) protocol that has been validated by a number of global projects within Pfizer. It outlines the procedures for the preparation of screening kits, as well as protocols for reaction set‐up, optimization and analysis. The need for such protocols in routinely evaluating the use of solvent engineering in enzymatic hydrolysis reactions is also outlined, with several examples provided. The advantages and disadvantages of a number of complementary analytical tools that are being used in the analysis of enzymatic reactions are also discussed.
An Expeditious Synthesis of 1‐(4‐Chlorophenyl)‐3,3‐dimethyl‐2‐butanone by a Ligand‐Free Palladium‐Catalyzed α‐Arylation of Pinacolone: Scale‐Up and Effect of Base Concentration
Authors: Prashad Mahavir , Liu Yugang , Repič Oljan
Published: March 2003

An efficient and large‐scale synthesis of 1‐(4‐chlorophenyl)‐3,3‐dimethyl‐2‐butanone (1) by an α‐arylation of pinacolone (2) with 1‐bromo‐4‐chlorobenzene (3) in the presence of palladium acetate and sodium t‐butoxide in toluene is described. An increase in the concentration of sodium t‐butoxide to 2.5–3.0 equivalents suppressed the formation of over‐arylated products. These ligand‐free conditions afforded a yield of 1 that was comparable to those obtained by using a ligand.
Effects ofMECP2mutation type, location and X‐inactivation in modulating Rett syndrome phenotype
Authors: Weaving Linda S. , Williamson Sarah L. , Bennetts Bruce , Davis Mark , Ellaway Carolyn J. , Leonard Helen , Thong Meow‐Keong , Delatycki Martin , Thompson Elizabeth M. , Laing Nigel , Christodoulou John
Published: March 2003

Rett syndrome (RTT) is a clinically defined disorder that describes a subset of patients with mutations in the X‐linkedMECP2gene. However, there is a high degree of variability in the clinical phenotypes produced by mutations inMECP2, even amongst classical RTT patients. In a large‐scale screening project, this variability has been examined by looking at the effects of mutation type, functional domain affected and X‐inactivation. Mutations have been identified in 60% of RTT patients in this study (25% of whom were atypical), including 23 novel mutations and polymorphisms. More mutations were found in classical patients (63%) compared to atypical patients (44%). All of the pathogenic mutations were de novo in patients for whom parent DNA was available for screening. A composite phenotype score was developed, based on the recommendations for reporting clinical features in RTT of an international collaborative group. This score proved useful for summarising phenotypic severity, but did not correlate with mutation type, domain affected or X‐inactivation, probably due to complex interactions between all three. Other correlations suggested that truncating mutations and mutations affecting the methyl‐CpG‐binding domain tend to lead to a more severe phenotype. Skewed X‐inactivation was found in a large proportion (43%) of our patients, particularly in those with truncating mutations and mutations affecting the MBD. It is therefore likely that X‐inactivation does modulate the phenotype in RTT. © 2003 Wiley‐Liss, Inc.
Self‐injurious behavior in young boys with fragile X syndrome
Authors: Symons Frank J. , Clark Renee D. , Hatton Deborah D. , Skinner Martie , Bailey Donald B.
Published: March 2003

In this study, we distributed surveys to 67 families of young boys with fragile X syndrome to determine the prevalence, onset, form, function, location, and correlates of self‐injurious behavior. Fifty‐five surveys were completed (82%). The mean age of the boys at the time of the survey was 80 months (range = 20–144). Self‐injurious behavior (SIB) was reported for 58% of the participants with a mean age of onset of 31 months. The mean number of forms of self‐injury was 2 per participant. Biting was the most commonly reported form of self‐injury with the fingers and back of the hand disproportionately targeted as the most prevalent self‐injury body site. There was no linear increase in risk of SIB with age past 25 months. SIB was reported as most likely to occur following the presentation of difficult task demands or changes in routine. Significant group differences were found between overall ratings of problem behavior for boys with self‐injury compared to those without self‐injury. Groups did not differ on measures of fragile X mental retardation protein (FMRP), autism status, adaptive behavior, or age first medicated. Results are discussed in terms of future research designed to further elucidate the behavioral phenotype of fragile X syndrome. © 2003 Wiley‐Liss, Inc.
Relationship of deficits of FMR1 gene specific protein with physical phenotype of fragile X males and females in pedigrees: A new perspective
Authors: Loesch D.Z. , Huggins R.M. , Bui Q. M. , Taylor A. K. , Hagerman R. J.
Published: March 2003

The effect of deficit of the FMR1‐gene product (FMRP) on physical phenotype was investigated using a robust modification of the maximum likelihood estimators for pedigree data. The approach is a powerful method of examining genotype–phenotype relationships because it adjusts for intra‐familial variation, and the robust modification allows violation of distributional assumptions in the data to be overcome by objectively down‐weighting unusual observations. The data on 19 age‐ or height‐adjusted physical measures including head, trunk and limb measures and height and weight from 110 extended fragile X families (including 185 fragile X males and females and 120 normal relatives) were related to the FMRP levels assessed in peripheral blood lymphocytes. A significant interaction between FMRP and age was also included in the models for some measures. The results have demonstrated a linear effect of progressively reducing levels of FMRP on the values of a majority of physical measures considered in the study. The most evident effect of FMRP deficit in sexes combined was in decreasing body height and limb length, and in increasing head height and the degree of connective tissue involvement (measured by the middle finger extension angle). Heritability estimated from the complex FMRP models showed the highest values for height and limb length, and the lowest for weight, finger extension angle and some facial measures. On the basis of the present data, a possible mechanism by which the FMRP deficit impacts physical phenotype is discussed. © 2003 Wiley‐Liss, Inc.
Mutation screening of FOXP2 in individuals diagnosed with autistic disorder
Authors: Gauthier Julie , Joober Ridha , Mottron Laurent , Laurent Sandra , Fuchs Marketa , De Kimpe Violaine , Rouleau Guy A.
Published: March 2003

Although it is well established that genetic factors play an important role in the etiology of autistic disorder (AD), no specific genes have as yet been implicated. Genetic epidemiological data, particularly the sharp fall in concordance rates from monozygotic to dizygotic twins, indicate that the mode of transmission of this disorder is complex and may involve several genes. The 7q31 locus has been repeatedly linked to AD, suggesting that this chromosomal region is likely to harbor a susceptibility gene for AD. Recently, variations in the FOXP2 gene were reported to be responsible for a severe speech and language disorder. Because of the chromosomal location of FOXP2 (7q31) and the putative implication of the 7q31 region both in autistic and in language disorders (a feature of AD), it has been hypothesized that FOXP2 may be implicated in the pathophysiology of AD. To test this hypothesis, we screened the FOXP2 gene coding sequence for mutations in subjects diagnosed with AD and in normal controls. We identified four silent polymorphisms that were equally distributed between patients and controls. Using an intra‐family association design, we identified no transmission disequilibrium in any of the four identified alleles, suggesting that the FOXP2 gene does not play a significant role in AD. © 2003 Wiley‐Liss, Inc.
Developing culturally sensitive cancer genetics communication aids for African Americans
Authors: Baty Bonnie Jeanne , Kinney Anita Yeomans , Ellis Sara Marie
Published: March 2003

The goal of this project was to develop educational materials to communicate genetic health information in a culturally sensitive manner. These materials were designed to communicate information about cancer risk, genetic testing options, and health management options in an African American kindred with a knownBRCA1mutation. Educational materials were pilot‐tested in four African American focus groups varying in socioeconomic status and gender. The audiotaped focus groups consisted of presentation of the educational materials, followed by a feedback session led by an African American facilitator. Qualitative analysis of the focus group transcripts identified important themes and the educational materials were revised in response to the participants' suggestions. The products included a booklet and a flip chart for use in educational sessions. Focus group participants recommended a substantial reduction in technical detail, and recommended that information be personalized and made relevant to the lives of the target population. Other critical themes included the importance of building trust in the medical system and avoiding words and images that have strong negative associations in the African American community. Strategies that were successful included nontechnical images to explain genetic concepts, clip art images to energize and personalize word slides, vibrant color, identifiably African American figures, and the development of themes relevant to many African Americans. The use of these materials in an ongoing study offeringBRCA1counseling and testing to a large, rural Louisiana‐based kindred will provide additional feedback about the effectiveness of the culturally tailored genetic education and counseling materials. © 2003 Wiley‐Liss, Inc.
Famous people and genetic disorders: From monarchs to geniuses—A portrait of their genetic illnesses
Authors: Ho Nicola C. , Park Susan S. , Maragh Kevin D. , Gutter Emily M.
Published: March 2003

Famous people with genetic disorders have always been a subject of interest because such news feeds the curiosity the public has for celebrities. It gives further insight into their lives and provides a medical basis for any unexplained or idiosyncratic feature or behavior they exhibit. It draws admiration from society of those who excel in their specialized fields despite the impositions of their genetic illnesses and also elicits sympathy even in the most casual observer. Such news certainly catapults a rare genetic disorder into the realm of public awareness. We hereby present six famous figures: King George III, Toulouse‐Lautrec, Queen Victoria, Nicolo Paganini, Abraham Lincoln, and Vincent van Gogh, all of whom made a huge indelible mark in either the history of politics or that of the arts. © 2003 Wiley‐Liss, Inc.
Clinical and epidemiological studies of amniotic deformity, adhesion, and mutilation (ADAM) sequence in a South American (ECLAMC) population
Authors: Orioli Iêda M. , Ribeiro Márcia G. , Castilla Eduardo E.
Published: March 2003

Amniotic deformity, adhesion, and mutilation (ADAM) sequence is a heterogeneous condition, with a broad spectrum of anomalies, where intrinsic causes, as defect of germ plasm, vascular disruption, and disturbance of threshold boundaries of morphogens during early gastrulation, alternate with extrinsic causes as amniotic band rupture to explain the condition. This study aimed to identify which phenotypes could be considered as ADAM sequence, determine the prevalence rate, and disclose risk factors for this sequence. We identified 270 cases defined as having some skin evidence of constriction band, plus those having limb defects suggestive of ADAM sequence, among 3,020,896 live and stillborns in the years 1982 to 1998 in ECLAMC (Latin American Collaborative Study of Congenital Malformations). Half of the cases presented mutilation (reduction), and deformity (ring constriction) affecting distal parts of fingers or toes bilaterally, without associated defects. Acrania, cephalocele, typical or atypical facial clefts, eyelid coloboma, and celosomia were also observed being significantly associated with the skin lesion. One affected infant in every 11,200 births, was found with stable trends during the last 17 years. There was an excess of cases in populations living at high altitude, stillborns, and neonatal infant dead. Among ADAM cases there was an excess of mothers with a prenatal history of febrile acute illness, medication drug use, or vaginal bleeding during the first trimester of pregnancy. Higher than expected frequencies of first‐born child, premature birth, low birth weight for gestational length, and non‐cephalic fetal presentation were also found. The observed geographic difference in birth prevalence could be a useful indication to study specific genetic and environmental candidate factors to ADAM susceptibility. © 2003 Wiley‐Liss, Inc.
Yeast‐like symbiotes as a sterol source in anobiid beetles (Coleoptera, Anobiidae): Possible metabolic pathways from fungal sterols to 7‐dehydrocholesterol
Authors: Nasir Habib , Noda Hiroaki
Published: March 2003

Insects are unable to synthesize sterols and require exogenous sterol sources for their normal development and reproduction. A few exceptions are insects associated with symbiotic yeasts or fungi. We analyzed sterols by GC‐MS in two anobiid beetles (Lasioderma serricorne and Stegobium paniceum), their intracellular yeast‐like symbiotes (YLS), and their diets in order to clarify the sterols synthesized by YLS and the metabolic pathways of the sterols in the beetles. Several C27, C28, and C29 saturated and unsaturated sterols were identified; the predominant sterols were cholesterol and 7‐dehydrocholesterol in the anobiid beetles and ergosterol in the YLS. Most sterols detected in YLS were those known in the late pathway of the ergosterol biosynthesis in yeasts and most of the sterols in the beetles appear to be intermediate metabolites from YLS sterols to 7‐dehydrocholesterol. The anobiid beetles appear to use ergosterol and 5‐dihydroergosterol as sources for 7‐dehydrocholesterol. Arch. Insect Biochem. Physiol. 52:175–182, 2003. © 2003 Wiley‐Liss, Inc.
Effects of silkworm paralytic peptide on in vitro hematopoiesis and plasmatocyte spreading
Authors: Nakahara Yuichi , Kanamori Yasushi , Kiuchi Makoto , Kamimura Manabu
Published: March 2003

Bombyx mori paralytic peptide (BmPP), a multifunctional cytokine‐like molecule, is expressed in the hematopoietic organ‐wing imaginal disc complex, suggesting that BmPP is involved in both immune response and the hematopoietic process. We studied the effects of BmPP on plasmatocytes and hematopoietic organs of the silkworm. BmPP (1 µM) stimulated spreading of circulating plasmatocytes, but the percentage of spread plasmatocytes was only 20%. Over 10 nM of BmPP, however, elicited prominent spreading in 70% of young plasmatocytes discharged from cultured hematopoietic organs. Cells in hematopoietic organs that were enzymatically dispersed did not spread even after adding 100 nM of BmPP, indicating that plasmatocytes acquired BmPP‐sensitivity immediately after discharge. When cultured in a medium containing larval plasma, hematopoietic organs grew markedly and discharged a large number of hemocytes, over 95% of which were morphologically plasmatocytes. The hemocyte discharge was blocked in the medium containing BmPP dose‐dependently, although hematopoietic organ growth was not suppressed. These results suggest that BmPP plays important roles both in hematopoietic regulation and in the hemocyte immune reaction of the silkworm. Arch. Insect Biochem. Physiol. 52:163–174, 2003. © 2003 Wiley‐Liss, Inc.
Eicosanoid involvement in the regulation of behavioral fever in the desert locust, Schistocerca gregaria
Authors: Bundey S. , Raymond S. , Dean P. , Roberts S.K. , Dillon R.J. , Charnley A.K.
Published: March 2003

The desert locust Schistocerca gregaria behaviorally thermoregulates in order to try and maintain a favoured “set point” body temperature. Locusts infected with the deuteromycete fungal pathogen Metarhizium anisopliae var acridumchoose a significantly elevated temperature. This “behavioral fever” greatly delays the progress of mycosis. We have confirmed this phenomenon and shown that desert locusts also fever when infected with the bacterial pathogen Serratia marcescens. Elevation in the prefered environmental temperature occurs also upon injection with laminarin and lipopolysaccharide (microbial cell wall components). Since such treatments also stimulate the immune system it would appear that “behavioral fever” is probably a feature of the immune response. The eicosanoid biosynthesis inhibitor dexamethasone prevented laminarin invoked fever. This effect was reversable by arachidonic acid. Therefore in common with the febrile response in mammals behavioral fever in insects may be mediated locally by circulating eicosanoids. Arch. Insect Biochem. Physiol. 52:183–192, 2003. © 2003 Wiley‐Liss, Inc.
Transcriptional silencing and translational control: key features of early germline development
Authors: Leatherman Judith L. , Jongens Thomas A.
Published: March 2003

The germ lineage has been studied for a long time because of its crucial role in the propagation and survival of a species. While this lineage, in contrast to the soma, is clearly unique in its totipotent ability to produce a new organism, it has now been found also to have specific features at the cellular level. One feature, a period of transcriptional quiescence in the early germ cell precursors, has been observed in both Drosophila and C. elegans, where it is essential for the formation and the survival of the germline. In addition, there are numerous instances where these early germ cells are reliant on translational regulation, especially in Drosophila. The genes that are important for these two functions, the mechanisms of their action, and studies in vertebrate organisms that reveal similarities as well as some potential differences in early germ cell development are discussed. BioEssays 25:326–335, 2003. © 2003 Wiley Periodicals, Inc.
The intracrine hypothesis and intracellular peptide hormone action
Authors: Re Richard N.
Published: March 2003

There is evidence that many peptide growth factors and hormones act in the intracellular space after either internalization or retention in their cells of synthesis. These factors, commonly called intracrines, are structurally diverse while sharing some common functional features. Reports of intracellular peptide hormone binding and action are reviewed here. Also, this laboratory has made proposals regarding the origin and actions of intracrines and these areas are further explored. Intracrine interactions and the relationship of intracrines to transcription factors are discussed. The intracellular/intracrine renin–angiotensin system (iRAS) is reviewed to illustrate the intracrine analogue of a well‐established physiological system. The role of intracrine action in metazoan development is also considered. BioEssays 25:401–409, 2003. © 2003 Wiley Periodicals, Inc.
Neurofilaments and neurological disease
Authors: Al‐Chalabi Ammar , Miller Christopher C. J.
Published: March 2003

Neurofilaments are one of the major components of the neuronal cytoskeleton and are responsible for maintaining the calibre of axons. They are modified by post‐translational changes that are regulated in complex fashions including by the interaction with neighbouring glial cells. Neurofilament accumulations are seen in several neurological diseases and neurofilament mutations have now been associated with Charcot‐Marie‐Tooth disease, Parkinson's disease and amyotrophic lateral sclerosis. In this review, we discuss the structure, normal function and molecular pathology of neurofilaments. BioEssays 25:346–355, 2003. © 2003 Wiley Periodicals, Inc.
Evolution of adrenal and sex steroid action in vertebrates: a ligand‐based mechanism for complexity
Authors: Baker Michael E.
Published: March 2003

Various explanations have been proposed to account for complex differentiation and development in humans, despite the human genome containing only two to three times the number of genes in invertebrates. Ignored are the actions of adrenal and sex steroids—androgens, estrogens, glucocorticoids, mineralocorticoids, and progestins—which act through receptors that arose from an ancestral nuclear receptor in a protochordate. This ligand‐based mechanism is unique to vertebrates and was integrated into the already robust network of transcription factors in invertebrates. Adrenal and sex steroids influence almost all aspects of vertebrate differentiation and development. I propose that evolution of this ligand‐based mechanism in a primitive vertebrate was an important contribution to vertebrate complexity. Sequencing of genomes from a cephalochordate, such as amphioxus, and from hagfish and lamprey will establish early events in the evolution of steroid hormone signaling, and also allow genetic studies to elucidate how vertebrate complexity depends on steroid hormones. BioEssays 25:396–400, 2003. © 2003 Wiley Periodicals, Inc.
Enzymes and auxiliary factors for GPI lipid anchor biosynthesis and post‐translational transfer to proteins
Authors: Eisenhaber Birgit , Maurer‐Stroh Sebastian , Novatchkova Maria , Schneider Georg , Eisenhaber Frank
Published: March 2003

GPI lipid anchoring is an important post‐translational modification of eukaryote proteins in the endoplasmic reticulum. In total, 19 genes have been directly implicated in the anchor synthesis and the substrate protein modification pathway. Here, the molecular functions of the respective proteins and their evolution are analyzed in the context of reported literature data and sequence analysis studies for the complete pathway (http://mendel.imp.univie.ac.at/SEQUENCES/gpi‐biosynthesis/) and questions for future experimental investigation are discussed. Studies of two of these proteins have provided new mechanistic insights. The cytosolic part of PIG‐A/GPI3 has a two‐domain α/β/α‐layered structure; it is suggested that its C‐terminal subsegment binds UDP‐GlcNAc whereas the N‐terminal domain interacts with the phosphatidylinositol moiety. The lumenal part of PIG‐T/GPI16 apparently consists of a β‐propeller with a central hole that regulates the access of substrate protein C termini to the active site of the cysteine protease PIG‐K/GPI8 (gating mechanism) as well as of a polypeptide hook that embraces PIG‐K/GPI8. This structural proposal would explain the paradoxical properties of the GPI lipid anchor signal motif and of PIG‐K/GPI8 orthologs without membrane insertion regions in some species. BioEssays 25:367–385, 2003. © 2003 Wiley Periodicals, Inc.
Wnt–frizzled signaling in the induction and differentiation of the neural crest
Authors: Yanfeng Wang , Saint‐Jeannet Jean‐Pierre , Klein Peter S.
Published: March 2003

The neural crest is a transient population of multipotent progenitors arising at the lateral edge of the neural plate in vertebrate embryos. After delamination and migration from the neuroepithelium, these cells contribute to a diverse array of tissues including neurons, smooth muscle, craniofacial cartilage, bone cells, endocrine cells and pigment cells. Considerable progress in recent years has furthered our understanding at a molecular level of how this important group of cells is generated and how they are assigned to specific lineages. Here we review a number of recent studies supporting a role for Wnt signaling in neural crest induction, differentiation, and apoptosis. We also summarize the timing of expression of a number of Wnt ligands and receptors with respect to neural crest induction. BioEssays 25:317–325, 2003. © 2003 Wiley Periodicals, Inc.
The MID1/PP2A complex: a key to the pathogenesis of Opitz BBB/G syndrome
Authors: Schweiger Susann , Schneider Rainer
Published: March 2003

Opitz BBB/G syndrome is a monogenic disorder that is characterized by malformations of the ventral midline. Investigations into the underlying genetic defects and the pathobiochemistry of this syndrome have already shed light on the mechanisms of both the physiological and the pathological development of the ventral midline, a complicated multistep process. Moreover, these studies have revealed the ubiquitin‐dependent regulation of microtubule‐associated phosphatase 2A, a central mechanism in many cellular processes. In this review, we summarize recent findings and speculate upon their implications for both medical and general research. BioEssays 25:356–366, 2003. © 2003 Wiley Periodicals, Inc.
Actin‐based motility: from molecules to movement
Authors: Carlier Marie‐France , Clainche Christophe Le , Wiesner Sebastian , Pantaloni Dominique
Published: March 2003

Extensive progress has been made recently in understanding the mechanism by which cells move and extend protrusions using site‐directed polymerization of actin in response to signalling. Insights into the molecular mechanism of production of force and movement by actin polymerization have been provided by a crosstalk between several disciplines, including biochemistry, biomimetic approaches and computational studies. This review focuses on the biochemical properties of the proteins involved in actin‐based motility and shows how these properties are used to generate models of force production, how the predictions of different theoretical models are tested using a biochemically controlled reconstituted motility assay and how the changes in motility resulting from changes to the concentrations of components of the assay can help understand diverse aspects of the motile behavior of living cells. BioEssays 25:336–345, 2003. © 2003 Wiley Periodicals, Inc.
Eyespot placement and assembly in the green alga Chlamydomonas
Authors: Dieckmann Carol L.
Published: March 2003

The eyespot organelle of the green alga Chlamydomonas allows the cell to phototax toward (or away) from light to maximize the light intensity for photosynthesis and minimize photo‐damage. At cytokinesis, the eyespot is resorbed at the cleavage furrow and two new eyespots form in the daughter cells 180° from each other. The eyespots are positioned asymmetrically with respect to the microtubule cytoskeleton. Eyespots are assembled from all three chloroplast membranes and carotenoid‐filled granules, which form a sandwich structure overlaid by the tightly apposed plasma membrane. This review describes (1) my interest in cellular asymmetry and organelle biology, (2) isolation of mutations that describe four genes governing eyespot placement and assembly, (3) the characterization of the EYE2 gene, which encodes a thioredoxin superfamily member, and (4) the characterization of the MIN1 gene, which is required for the layered organization of granules and membranes in the eyespot. BioEssays 25:410–416, 2003. © 2003 Wiley Periodicals, Inc.
Block to DNA replication in meiotic maturation: a unified view for a robust arrest of cell cycle in oocytes and somatic cells
Authors: Kubota Yumiko , Takisawa Haruhiko
Published: March 2003

Under certain conditions, the cell cycle can be arrested for a long period of time. Vertebrate oocytes are arrested at G2 phase, while somatic cells arrest at G0 phase. In both cells, nuclei have lost the ability to initiate DNA synthesis. In a pair of recently published papers,1,2 Méchali and colleagues and Coué and colleagues have clarified how frog oocytes prevent untimely DNA synthesis during the long G2 arrest. Intriguingly, they found only Cdc6 is responsible for the inability of immature oocytes to replicate DNA. Cdc6 is a key component for replication licensing, and for G0 cells to re‐enter the proliferative stage. Strikingly similar strategies for preventing the untimely replication in both cells suggest that the suppression of replication licensing is a universal mechanism for securing the prolonged arrest of the cell cycle. BioEssays 25:313–316, 2003. © 2003 Wiley Periodicals, Inc.