bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral findings in ankyloblepharon‐ectodermal dysplasia‐cleft lip/palate (AEC) syndrome
Authors: Farrington Frank , Lausten Leonard
Published: August 2009

This article outlines the dental conditions and treatment findings of individuals ranging in age from 4 months to 30 years of age diagnosed with ankyloblepharon‐ectodermal dysplasia‐cleft lip/palate (AEC) syndrome. The average number of permanent teeth present is 4.75 with a range of 0–12 teeth. The most frequently present permanent teeth are first molars, canines and maxillary incisors. The dentition of AEC‐affected individuals in our study is similar to reports in other ectodermal dysplasia syndromes. The dental treatment findings, including those necessitated by the cleft palate defect seen in the syndrome, are also similar to age appropriate treatment seen in other cases of ectodermal dysplasia syndromes. Only 22% of subjects had prosthetic replacement of missing teeth. History indicated that issues related to treatment of the palatal cleft and lack of recognition of the oral defects as a part of the underlying medical problem were factors in receiving comprehensive tooth replacement care. © 2009 Wiley‐Liss, Inc.
ΔNp63 knockdown mice: A mouse model for AEC syndrome
Authors: Koster Maranke I. , Marinari Barbara , Payne Aimee S. , Kantaputra Piranit N. , Costanzo Antonio , Roop Dennis R.
Published: August 2009

Dominant mutations in TP63 cause ankyloblepharon ectodermal dysplasia and clefting (AEC), an ectodermal dysplasia characterized by skin fragility. Since ΔNp63α is the predominantly expressed TP63 isoform in postnatal skin, we hypothesized that mutant ΔNp63α proteins are primarily responsible for skin fragility in AEC patients. We found that mutant ΔNp63α proteins expressed in AEC patients function as dominant‐negative molecules, suggesting that the human AEC skin phenotype could be mimicked in mouse skin by downregulating ΔNp63α. Indeed, downregulating ΔNp63 expression in mouse epidermis caused severe skin erosions, which resembled lesions that develop in AEC patients. In both cases, lesions were characterized by suprabasal epidermal proliferation, delayed terminal differentiation, and basement membrane abnormalities. By failing to provide structural stability to the epidermis, these defects likely contribute to the observed skin fragility. The development of a mouse model for AEC will allow us to further unravel the genetic pathways that are normally regulated by ΔNp63 and that may be perturbed in AEC patients. Ultimately, these studies will not only contribute to our understanding of the molecular mechanisms that cause skin fragility in AEC patients, but may also result in the identification of targets for novel therapeutic approaches aimed at treating skin erosions. © 2009 Wiley‐Liss, Inc.
Dermatologic findings of ankyloblepharon‐ectodermal defects‐cleft lip/palate (AEC) syndrome
Authors: Julapalli Meena R. , Scher Richard K. , Sybert Virginia P. , Siegfried Elaine C. , Bree Alanna F.
Published: August 2009

Hay–Wells syndrome, caused by mutations in the p63 gene, is an autosomal dominant ectodermal dysplasia with the main features of ankyloblepharon filiforme adnatum, ectodermal defects, and cleft lip/palate, from which the disorder's other name, AEC syndrome, is derived. The National Foundation for Ectodermal Dysplasias convened the International Research Symposium for AEC Syndrome on November 8–10, 2006, at Texas Children's Hospital/Baylor College of Medicine, Houston, TX with appropriate IRB approval. This multidisciplinary conference was the largest gathering of such patients to date and allowed us to further characterize dermatologic features of AEC syndrome, which included: sparse and wiry hair, nail changes, past or present scalp erosions, decreased sweat production, palmar/plantar changes, and unique pigmentary anomolies. Early recognition of the features of AEC syndrome and subsequent early diagnosis is important in minimizing invasive diagnostic studies, improving morbidity and mortality, and providing genetic counseling. Skin erosions, especially those of the scalp, were identified as the most challenging cutaneous aspect of this syndrome. Although the reasons for the skin erosions and poor healing are not known, mutations of p63 may lead to a diminished store of basal cells capable of replenishing the disrupted barrier. Therapeutic strategies currently under exploration include gene therapy, as well as epidermal stem cell therapy. Until then, gentle wound care and limiting further trauma seem to be the most prudent treatment modalities. © 2009 Wiley‐Liss, Inc.
Perspective on the classification of ectodermal dysplasia
Authors: Jorgenson Ronald J.
Published: August 2009

The need for revisiting the classification of ectodermal dysplasia syndromes has come. Prior to considering a new way to classify this group of disorders, however, thought should be given to some basic ideas about terminology and the process of classification. Consequently, this article reiterates the meanings of the words ectoderm, dysplasia, genetic and syndrome, and describes the process by which numeric taxonomists go about classification. In the process, a new family with the Jorgenson syndrome is described and the inheritance of the Schopf syndrome is clarified. Finally, the backgrounds of those with vested interests in the ectodermal dysplasia syndromes are described in order that all approaches to classification are covered. © 2009 Wiley‐Liss, Inc.
Molecular aspects of hypohidrotic ectodermal dysplasia
Authors: Mikkola Marja L.
Published: August 2009

Hypohidrotic (anhidrotic) ectodermal dysplasia (HED) is a congenital syndrome characterized by sparse hair, oligodontia, and reduced sweating. It is caused by mutations in any of the three Eda pathway genes: ectodysplasin (Eda), Edar, and Edaradd which encode a ligand, a receptor, and an intracellular signal mediator of a single linear pathway, respectively. In rare cases, HED is associated with immune deficiency caused by mutations in further downstream components of the Eda pathway that are necessary for the activation of the transcription factor NF‐κB. Here I present a brief research update on the molecular aspects of this evolutionarily conserved pathway. The developmental role of Eda will be discussed in light of loss‐ and gain‐of‐function mouse models with emphasis on the past few years. © 2009 Wiley‐Liss, Inc.
What the future holds for ectodermal dysplasias: Future research and treatment directions
Authors: Slavkin Harold C.
Published: August 2009

A contrarian view suggests that the ectodermal dysplasias, including more than 200 different disorders, represent clinical variability and molecular heterogeneity as well as complex multigene heritable conditions often characterized by dysmorphogenesis of derivatives of embryonic ectoderm and beyond. Controversy exists over which syndromes do or do not belong in the classification of the clinical features that characterize ectodermal dysplasias. For example, Ellis–van Creveld syndrome is characterized by abnormalities of the teeth and hair, as well as of the skeleton and the cardiovascular system. Precision in diagnosis often is a preamble for improved patient diagnosis, treatment and desired outcomes. In tandem, molecular studies of complex epithelial–mesenchymal interactions required for ectodermal derivatives (e.g., hair, nail, skin, teeth, and exocrine glands) continue to identify and explain many signal transduction pathways and networks related to ectodermal dysplasias. Meanwhile, major international investments in fundamental biomedical research continue to yield significant benefits to the larger society. The convergence of informatics, nanotechnology, genomics, and epigenetic studies with clinical medicine and dentistry promise major progress for special needs patients such as ectodermal dysplasias. For example, investments in the molecular biology of genes and their regulation and function now provide more than 30 candidates for specific biomarkers to improve diagnosis, prognosis, treatments, therapeutics, and biomaterials for ectodermal dysplasias. Innovations in high throughput genotyping, gene mapping, single nucleotide polymorphisms (SNPs), interference RNA treatments, bioimaging, tissue engineering and related biomimetic approaches to design and fabricate biomaterials, offer enormous promise for the future of ectodermal dysplasias. © 2009 Wiley‐Liss, Inc.
Ectodermal dysplasias: Clinical and molecular review
Authors: Visinoni Átila F. , Lisboa‐Costa Toni , Pagnan Nina A.B. , Chautard‐Freire‐Maia Eleidi A.
Published: August 2009

Ectodermal dysplasias (EDs) as defined by Freire‐Maia [Freire‐Maia (1971); Hum Hered 21: 309–312; Freire‐Maia (1977); Acta Genet Med Gemellol 26: 121–131] are congenital disorders characterized by alterations in two or more ectodermal structures, at least one of these involving alterations in hair, teeth, nails, or sweat glands. Suggestions for a new definition and, consequently, for a new classification of EDs have being proposed lately, mainly with the purpose of connecting clinical knowledge with recent discoveries of gene mutations responsible for about 30% of EDs. The aim of this review was to update the clinical classification of EDs with recent molecular (64 genes and 3 chromosome regions) and clinical data, mainly of EDs of the A group (N = 186), in order to contribute information for the evaluation of the ED definition proposed by Freire‐Maia. Our conclusion is that the combination of both procedures—clinical and molecular—only brings advantages for a deeper knowledge of EDs. First, it allows a rapid diagnosis that may become even more precise whenever DNA exams are available. Secondly, the comprehension of the biological mechanisms that cause EDs is needed for the design of efficient prevention and treatment approaches. © 2009 Wiley‐Liss, Inc.
Approach towards a new classification for ectodermal dysplasias: Integration of the clinical and molecular knowledge
Authors: DiGiovanna John J. , Priolo Manuela , Itin Peter
Published: August 2009

Rapid advances in new basic knowledge have led to a greater understanding of the genetic, embryologic, molecular biologic, and functional mechanisms underlying the ectodermal dysplasias. Scientists, researchers, and clinicians from diverse fields desire a classification that meets the needs of these rapidly changing concepts which, in addition to being clinically useful, can help further advances in understanding the basic underlying mechanisms, and can also spur the development of new therapies. The currently used classification was designed for clinical utility and has not easily integrated with the new concepts. Various users have suggested that a new classification should be based on underlying genetic and molecular abnormality, functional mechanism, embryology, or clinical features. The goal of this conference was to advance towards a consensus and this manuscript is a summary of a workshop focused on an approach towards the development of a classification that integrates the clinical and molecular knowledge. © 2009 Wiley‐Liss, Inc.
A novel missense mutation in SCYL1BP1 produces geroderma osteodysplastica phenotype indistinguishable from that caused by nullimorphic mutations
Authors: Al‐Dosari Mohammed , Alkuraya Fowzan S.
Published: August 2009

Effect of aging on decreased skin elasticity and bone mass is well known. Geroderma osteodysplastica (GO) is a very rare autosomal recessive disorder that recapitulates these two phenotypes at a much younger age. Using homozygosity mapping and linkage analysis in four Saudi families we have identified two mutations in SCYL1BP1, consistent with the very recent report by Hennies et al. [Hennies et al. (2008); Nat Genet 40: 1410–1412]. Interestingly, the missense mutation identified in our study is associated with an identical phenotype to that seen with the other null mutations including the other mutation in this study. Our study, therefore, supplements the limited available data on SCYL1BP1 and further establishes deficiency of this recently described golgin as the only known cause of GO. © 2009 Wiley‐Liss, Inc.
Catalytic CC, CN, and CO Ullmann‐Type Coupling Reactions
Authors: Monnier Florian , Taillefer Marc
Published: August 2009

Copper‐catalyzed Ullmann condensations are key reactions for the formation of carbon–heteroatom and carbon–carbon bonds in organic synthesis. These reactions can lead to structural moieties that are prevalent in building blocks of active molecules in the life sciences and in many material precursors. An increasing number of publications have appeared concerning Ullmann‐type intermolecular reactions for the coupling of aryl and vinyl halides with N, O, and C nucleophiles, and this Minireview highlights recent and major developments in this topic since 2004.
Synthesis and characterization of novel photoactive polyamide derived from substituted fluorene by copper (I) catalyst
Authors: Ghaemy Mousa , Barghamadi Mohammad
Published: August 2009

A novel polyamide has been successfully prepared through the reaction of 2,7‐dibromo‐9,9‐dioctylfluorene with 2,5‐dipiperazinedione in the presence of CuI, N,N′‐dimethylethylene diamine (DMEDA) and K2CO3 as base mixture and as catalyst. The structures of the monomer and the resulting model compound, as well as the structure, solution viscosity, solubility, molecular weights, thermal behavior, thermal stability, and light absorption and emission spectra of the resulting polyamide were characterized by means of FTIR, elemental analysis, 1H‐NMR, 13C‐NMR, DSC, TGA, GPC and UV–visible absorption, and fluorescence emission spectrophotometers. The polyamide possesses excellent solubility in organic solvents such as tetrahydrofuran (THF), N‐methyl‐2‐pyrrolidone (NMP), N,N‐dimethylacetamide (DMAc), N,N‐dimethylformamide (DMF), ethylacetate, acetone, ethanol, pyridine, chloroform, and toluene at room temperature. The polyamide had inherent viscosity of 0.65 dL/g, and molecular weights of Mn= 4.25 × 104 and Mw= 5.99 × 104 g/mol. The polyamide had glass transition temperature (Tg) of 138°C, and 10% weight loss at 350°C in nitrogen. The polyamide showed strong UV absorption and blue emission in solution and in solid state. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Generation of polymer ultrafine fibers through solution (air‐) blowing
Authors: Zhang Lifeng , Kopperstad Perry , West Michael , Hedin Nyle , Fong Hao
Published: August 2009

Solution (air‐) blowing, an innovative technique for generation of ultrafine polymer fibers from solutions, was developed by feeding polymer solutions (instead of melts) to a die assembly similar to that used in the conventional melt (air‐) blowing process. Micro‐ to nano‐scaled polyvinylpyrrolidone (PVP) fibers were produced using PVP solutions with water, ethanol, and/or their mixtures as the solvents; and the morphologies of the fibers were examined by scanning electron microscopy. The processing variables, including PVP concentration, air‐blowing pressure, solution‐feeding pressure, and the volatility of the solvent system (the ratio of ethanol to water), were systematically investigated. The results indicated that solution (air‐) blowing was a viable technique to produce nonwoven fabrics consisting of ultrafine polymer fibers with diameters ranging from micrometers to nanometers. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Hydrolysis reaction of poly(ethylene terephthalate) using ionic liquids as solvent and catalyst
Authors: Liu Fusheng , Cui Xiao , Yu Shitao , Li Zhuo , Ge Xiaoping
Published: August 2009

The hydrolysis of poly(ethylene terephthalate) (PET) was studied using ionic liquid 1‐n‐butyl‐3‐methylimidazolium chloride ([Bmim][Cl]) as solvent and acid‐functionalized ionic liquid 1‐methyl‐3‐(3‐sulfopropyl)‐imidazolium hydrogen sulfate ([HSOpmim][HSO4]) as catalyst. The effects of temperature, time, and dosages of solvent and catalyst on hydrolysis results were examined. Under the optimum conditions of m(PET) : m(H2O) : m([Bmim][Cl]) : m([HSOpmim][HSO4]) = 3 : 4 : 6 : 0.6, reaction temperature 170°C and time 4.5 h, the conversion of PET and the yield of terephthalic acid (TPA) were almost 100% and ≥88%, respectively. After easily separated from the product, the ionic liquids could be reused eight times without obvious decrease in the conversion of PET and yield of TPA. Hence, an environmental friendly strategy for chemical recycling of PET was developed. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Biodegradation of blends of polyethylene‐octene elastomer with starches by fungi
Authors: Shang Xiao‐Ya , Fu Xiong , Chen Xu‐Dong , Yang Lian‐Sheng
Published: August 2009

Five fungi including Aspergillus niger, Penicilium pinophilum, Chaetoomium globsum, Gliocladium virens and Aureobasium pullulans were used to investigate the biodegradation of starch‐based elastomers: polyethylene‐octene elastomer (POE)/starch and grafted POE‐g‐MAH/starch copolymer blends. The viability of the composite spore suspensions were measured before estimating the fungal growth on the surface of specimens. The weight loss, morphology and mechanical properties of the blended specimens were measured using scanning electron microscopy and a mechanical properties tester after 28 days of culturing. The spore suspension in the experiment showed good viability. Pure POE and POE‐g‐MAH did not allow significant fungal growth. Pure POE did not lose weight or have a change in tensile strength, but pure POE‐g‐MAH lost about 0.07% of its weight with a slight reduction in tensile strength during culture period. There was heavy growth on the surface of POE/starch and POE‐g‐MAH/starch blends after 28 days of culturing. The weight loss of POE/starch and POE‐g‐MAH/starch blends increased with increasing starch content. POE‐g‐MAH/starch blends tended to lose more weight than POE/starch blends. After biodegradation, the surface of POE/starch and POE‐g‐MAH/starch blends became rough with many holes and cracks, indicating that the films were eroded by the fungi. Tensile strength of POE/starch and POE‐g‐MAH/starch blends decreased after culturing because of microbial attack. On the contrary, elongation at break of POE‐g‐MAH/starch blends increased after biodegradation. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci 114:3574–3584, 2009
Role of PLLA plasma surface modification in the interaction with human marrow stromal cells
Authors: Armentano Ilaria , Ciapetti Gabriela , Pennacchi Manuela , Dottori Mariaserena , Devescovi Valentina , Granchi Donatella , Baldini Nicola , Olalde Beatriz , Jurado Maria Jesus , Alava Jose Inaki Marquinez , Kenny José M.
Published: August 2009

The effects of oxygen‐based radio frequency plasma enhanced chemical vapor deposition (rf PECVD) on the surface of poly(L‐lactide) (PLLA) polymers and the influence thereof on protein adsorption and on bone–cell behavior have been studied. Thin films and porous scaffolds based on PLLA polymer were developed, and the role of surface modifications were investigated extensively. PECVD surface treatments were used to alter surface functionality and modulate protein adsorption on the PLLA polymer matrix. In particular, Bovine Serum Albumine fluorescein isothiocyanate (fitc‐BSA) conjugate adsorption on patterned surfaces of treated PLLA was analyzed by fluorescence microscopy. Human marrow stromal cells (MSCs) were cultured on scaffolds and cell adhesion and morphology were assessed using fluorescence microscopy. The results indicated that the PLLA surface became hydrophilic and its roughness increased with the treatment time and it had a dominant influence on the adsorption process of the protein. The outcome of the plasma treatment of various PLLA surfaces has been shown to be the up‐regulator of the cell‐adhesive proteins expression and consequently the improvement of cell adhesion and growth. Oxygen‐treated PLLA promoted higher adhesion and proliferation of the MSCs in comparison to the untreated samples. It can be concluded that following plasma treatment, PLLA samples show enhanced affinity for osteoprogenitor cells. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Tracking control for switched linear systems with time‐delay: a state‐dependent switching method
Authors: Li Qing‐Kui , Zhao Jun , Dimirovski Georgi M. , Liu Xiang‐Jie
Published: August 2009

Tracking control for switched linear systems with time‐delay is investigated in this paper. Based on the state‐dependent switching method, sufficient conditions for the solvability of the tracking control problem are given. We use single Lyapunov function technique and a typical hysteresis switching law to design a tracking control law such that theH∞model reference tracking performance is satisfied. The controller design problem can be solved efficiently by using linear matrices inequalities. Since convex combination techniques are used to derive the delay independent criteria, some subsystems are allowed to be unstable. It is highly desirable that a non‐switched time‐delay system can not earn such property. Simulation example shows the feasibility and validity of the switching control law. Copyright © 2009 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society
Spatial contagion between financial markets: a copula‐based approach
Authors: Durante Fabrizio , Jaworski Piotr
Published: August 2009

A method is proposed for defining and investigating spatial contagion between two financial markets X and Y by using the information contained in their copula. A practical illustration of the introduced method is also given by examining the presence of contagion among two European stock indices (namely, FTSE 100 and DAX). Copyright © 2009 John Wiley & Sons, Ltd.
Idiopathic environmental intolerance attributed to electromagnetic fields (formerly ‘electromagnetic hypersensitivity’): An updated systematic review of provocation studies
Authors: Rubin G. James , Nieto‐Hernandez Rosa , Wessely Simon
Published: August 2009

Idiopathic Environmental Intolerance attributed to electromagnetic fields (IEI‐EMF; formerly ‘electromagetic hypersensitivity’) is a medically unexplained illness in which subjective symptoms are reported following exposure to electrical devices. In an earlier systematic review, we reported data from 31 blind provocation studies which had exposed IEI‐EMF volunteers to active or sham electromagnetic fields and assessed whether volunteers could detect these fields or whether they reported worse symptoms when exposed to them. In this article, we report an update to that review. An extensive literature search identified 15 new experiments. Including studies reported in our earlier review, 46 blind or double‐blind provocation studies in all, involving 1175 IEI‐EMF volunteers, have tested whether exposure to electromagnetic fields is responsible for triggering symptoms in IEI‐EMF. No robust evidence could be found to support this theory. However, the studies included in the review did support the role of the nocebo effect in triggering acute symptoms in IEI‐EMF sufferers. Despite the conviction of IEI‐EMF sufferers that their symptoms are triggered by exposure to electromagnetic fields, repeated experiments have been unable to replicate this phenomenon under controlled conditions. A narrow focus by clinicians or policy makers on bioelectromagnetic mechanisms is therefore, unlikely to help IEI‐EMF patients in the long‐term. Bioelectromagnetics 31:1–11, 2010. © 2009 Wiley‐Liss, Inc.
Acceleration of germination and early growth of wheat and bean seedlings grown under various magnetic field and osmotic conditions
Authors: Cakmak Turgay , Dumlupinar Rahmi , Erdal Serkan
Published: August 2009

Magnetic field (MF) can have different effects on plant metabolism depending on its application style, intensity, and environmental conditions. This study reports the effects of different intensities of static MF (4 or 7 mT) on seed germination and seedling growth of bean or wheat seeds in different media having 0, 2, 6, and 10 atmosphere (atm) osmotic pressure prepared with sucrose or salt. The germination percentages of the treated seeds were compared with untreated seeds germinated in different osmotic pressure during 7 days of incubation. The application of both MFs promoted the germination ratios of bean and wheat seeds, regardless of increasing osmotic pressure of sucrose or salt. Growth data measured on the 7th day showed that the treated plants grew faster than control. After 7 days of incubation, the mean length of treated seedlings was statistically higher than control plants in all the media. The greatest germination and growth rates in both plants were from the test groups exposed to 7 mT MF. Strikingly, effects of static MF on germination and growth increased positively with increasing osmotic pressure or salt stress compared to their respective controls. On the other hand, MF application caused an increase in dry biomass accumulation of root and shoots of both seedlings; however, this effect was found statistically important in all the conditions for wheat but not for bean, in general. Bioelectromagnetics 31:120–129, 2010. © 2009 Wiley‐Liss, Inc.
A Novel Multistep Mechanism for the Stereocontrolled Ring Opening of Hindered Sulfamidates: Mild, Green, and Efficient Reactivity with Alcohols
Authors: Jiménez‐Osés Gonzalo , Avenoza Alberto , Busto Jesús H. , Rodríguez Fernando , Peregrina Jesús M.
Published: August 2009

Cyclic hindered sulfamidates exhibited an outstanding performance in their ring‐opening reactions with alcohols and in the absence of any external activator. The mechanism of this unprecedented transformation was thoroughly studied both experimentally and theoretically. As a result, a nontrivial stepwise pathway involving solvent‐induced conversion of the sulfamidates to activated aziridinium and then to oxazolinium cations, which are finally opened at their 5‐position with inversion of configuration, is proposed. The presence of the SO3 moiety in the sulfamidate was revealed as a “built‐in activator”. In fact, the spontaneous SO3 cleavage takes place under the reaction conditions and avoids the subsequent step of hydrolysis after the ring opening of the sulfamidates. This is another important improvement of this methodology with respect to the standard basic conditions, allowing a greater compatibility with other functional groups. Furthermore, the carbamate group plays a key role in this mechanism. Briefly, a highly chemoselective and stereoespecific formal solvolysis of hindered sulfamidates with alcohols without further activation is described. This reaction takes place exclusively at the quaternary center with inversion of configuration, providing a new straightforward synthetic route to O‐substituted α‐methylisoserines.
Stereocontrolled and Versatile Total Synthesis of Bispyrrolidinoindoline Diketopiperazine Alkaloids: Structural Revision of the Fungal Isolate (+)‐Asperdimin
Authors: Pérez‐Balado Carlos , Rodríguez‐Graña Paula , de Lera Ángel R.
Published: August 2009

Homo‐ and heterodimeric bispyrrolidinoindoline diketopiperazine alkaloids have been synthesized following a concise, versatile, and stereoselective route. Highlights of the sequence are a diastereoselective construction of the C3a‐bromo‐hexahydropyrrolo[2,3‐b]indole nucleus, its CoI‐induced C3aC3a′ dimerization, and the twofold or sequential amide‐bond formation before cyclization to the diketopiperazine of the homo‐ or heterodimeric alkaloids, respectively. Stereochemical diversity is achieved through the choice of the appropriate amino acids combined with the base‐induced epimerization of the C2‐acyl‐hexahydropyrrolo[2,3‐b]indole at C2. According to this strategy, the natural products (+)‐WIN 64821 1, (+)‐WIN 64745 2 and (+)‐asperdimin 6 as well as analogues (5, 22, 32, 44) with different relative and absolute configuration have been efficiently synthesized. The flexibility of this synthetic methodology has facilitated the structural revision of the natural product (+)‐asperdimin, whose structure has been corrected to diastereomer 6.
Hydrogen–Deuterium Exchange Reactions of Aromatic Compounds and Heterocycles by NaBD4‐Activated Rhodium, Platinum and Palladium Catalysts
Authors: Derdau Volker , Atzrodt Jens , Zimmermann Jochen , Kroll Carsten , Brückner Francois
Published: August 2009

Conventional thermal and microwave conditions were compared for hydrogen–deuterium (H/D) exchange reactions of aminobenzoic acids catalysed by NaBD4‐activated Pd/C or RhCl3 with D2O as the deuterium source. We also investigated different NaBD4‐activated metal catalysts (including Pd/C, RhCl3 and Pt/C) under microwave conditions for an efficient H/D exchange of aromatic and heterocyclic compounds. Even higher deuterium incorporations were obtained for Pd/C and Pt/C catalyst mixtures due to the previously observed synergistic effect. Finally, we have applied these optimised conditions for one‐step syntheses of the MS standards of several pharmaceutically active compounds.
Synthesis, Structure, Photoluminescence and Photoreactivity of 2,3‐Diphenyl‐4‐neopentyl‐1‐silacyclobut‐2‐enes
Authors: Yan Duanchao , Thomson Mark D. , Backer Michael , Bolte Michael , Hahn Robert , Berger Robert , Fann Wunshain , Roskos Hartmut G. , Auner Norbert
Published: August 2009

A series of six 2,3‐diphenyl‐4‐neopentyl‐1‐silacyclobut‐2‐enes with different 1,1‐substituents has been prepared and characterized by single‐crystal X‐ray crystallography. These compounds possess a cis‐stilbene‐like chromophore involving also the four‐membered ring, and exhibit a photophysical behavior similar to that of previously reported 1,2‐diphenyl‐cycloalkenes. This chromophore system is confirmed by a theoretical investigation of the electronic structure and excitation spectra. The absorption and photoluminescence of selected derivatives were studied in solution, as solid powder samples, and in doped‐polymer thin films. In well‐dissolved solution, the silacyclobutenes show only very weak fluorescence emission (quantum yield ∼0.1 %), due to competition with photochemical and non‐radiative photophysical relaxation. When the solubility is degraded in a poor (aqueous) solvent, the formation of nanoscale aggregates leads to a significant enhancement factor in the emission intensity, due to the suppression of the photoreactivity in the more rigid molecular environment, although the quantum yield still remains below a few percent. In the solid‐state, however, photoreactivity is completely suppressed leading to fluorescence quantum efficiencies of 8–23 % depending on the 1,1‐substituents, which demonstrates these compounds’ potential as chromophores for condensed‐phase luminescence applications. Two dominant competing photochemical reactions have been identified in solution (for excitation in the lowest‐energy absorption band, >260 nm), which are analogous to related (sila‐)cyclobutenes and stilbenoids. The first involves ring‐opening due to cleavage of the 1,4‐SiC bond to form metastable silabutadienes, which was confirmed by isolating the stereospecifically formed allylsilane which results from a secondary reaction with trapping agents such as methanol or water. The second photochemical reaction involves ring closure of the 2,3‐diphenyl substructure to form a dihydrophenanthrene analogue, which was confirmed by isolating the phenanthrene derivative that results following subsequent hydrogen abstraction in the presence of oxygen. Measurements of the silacyclobutenes in doped‐polymer thin films reveal a spectroscopic behavior ranging from that in solution to the nano‐aggregate case as the silacyclobutene dopant concentration is increased.
Visualizing massively multithreaded applications with ThreadScope
Authors: Wheeler Kyle B. , Thain Douglas
Published: August 2009

As highly parallel multicore machines become commonplace, programs must exhibit more concurrency to exploit the available hardware. Many multithreaded programming models already encourage programmers to create hundreds or thousands of short‐lived threads that interact in complex ways. Programmers need to be able to analyze, tune, and troubleshoot these large‐scale multithreaded programs. To address this problem, we present ThreadScope: a tool for tracing, visualizing, and analyzing massively multithreaded programs. ThreadScope extracts the machine‐independent program structure from execution trace data from a variety of tracing tools and displays it as a graph of dependent execution blocks and memory objects, enabling identification of synchronization and structural problems, even if they did not occur in the traced run. It also uses graph‐based analysis to identify potential problems. We demonstrate the use of ThreadScope to view program structure, memory access patterns, and synchronization problems in three programming environments and seven applications. Copyright © 2009 John Wiley & Sons, Ltd.
Abnormal glucose tolerance is associated with diminished postload change in leptin levels in women
Authors: Madarász Eszter , Tabák Ádám Gy. , Speer Gábor , Lakatos Péter , Kerényi Zsuzsa , Tamás Gyula
Published: August 2009

Background

It is generally accepted that the metabolic effects of leptin are diminished in the obese due to leptin resistance. Hormone resistance may develop if diurnal (including meal‐related) changes in hormone levels are disrupted. We sought to describe leptin changes after a 75g oral glucose tolerance test (OGTT) in women with a prior diagnosis of gestational diabetes mellitus (a high risk group for the metabolic syndrome) compared to that in healthy controls.

Methods

In 2000 a retrospective cohort study was performed on women who had been diagnosed with gestational diabetes mellitus (WHO criteria 1985, n = 57) between 1996 and 1998 and on a healthy control female group (n = 36) all of whom had had a prior pregnancy without any diagnosis of diabetes. All the women underwent a standard 75g OGTT. Serum leptin was measured by radioimmunoassay before and 90 min after the OGTT.

Results

Using multilevel models of change, fasting leptin levels were shown to be associated with body mass index; 10.1% (95% CI 8.1–12.1%) increase per 1 kg/m2 increase in body mass index), homeostasis model assessment insulin sensitivity; 0.4% (95% CI 0.2–0.7%) decrease per 1% increase in insulin sensitivity); abnormal glucose tolerance (24% decrease, 95% CI 8–37%); and smoking (31% decrease, 95% CI 16–44%). Postload (90 min) leptin levels decreased significantly in women with normal glucose tolerance by 13% (95% CI 8–18%), while no significant change in postload leptin level was apparent in women with abnormal glucose tolerance (3% increase, 95% CI −4% to 29%).

Conclusions

Disturbed leptin changes were found following an OGTT in women with abnormal glucose tolerance that might be either a cause or a consequence of leptin resistance. Copyright © 2009 John Wiley & Sons, Ltd.
Targeted deletion of Dicer disrupts lens morphogenesis, corneal epithelium stratification, and whole eye development
Authors: Li Yan , Piatigorsky Joram
Published: August 2009

Dicer, a ribonuclease essential for miRNA processing, is expressed abundantly in developing mouse cornea and lens. We studied the roles of Dicer and miRNAs in eye development by conditionally deleting the Dicer gene in the mouse lens and corneal epithelium. Adult Dicer conditional null (DicerCN) mice had severe microphthalmia with no discernible lens and a poorly stratified corneal epithelium. Targeted deletion of Dicer effectively inhibited miRNA processing in the developing lens at 12.5 day of embryogenesis (E12.5). Lens development initiated normally but underwent progressive dystrophy between E14.5 and E18.5. Microarray analysis revealed activation of P53 signaling in DicerCN lenses at E13.5, consistent with increased apoptosis and reduced cell proliferation between E12.5 and E14.5. Expression of Pax6 and other lens developmental transcription factors were not greatly affected between E12.5 and E14.5 but decreased as the lens degenerated. Our data indicated an indispensible role for Dicer and miRNAs in lens and corneal development. Developmental Dynamics 238:2388–2400, 2009. © 2009 Wiley‐Liss, Inc.
Acheate‐scute like 1 (Ascl1) is required for normal delta‐like (Dll) gene expression and notch signaling during retinal development
Authors: Nelson Branden R. , Hartman Byron H. , Ray Catherine A. , Hayashi Toshinori , Bermingham‐McDonough Olivia , Reh Thomas A.
Published: August 2009

Retinascape: Multiphoton microscopy was used to look deep into the retina, at the dawn of neurogenesis in the embryonic mouse eye: mitotic progenitors (anti‐phosphohistone H3, green) and newborn neurons (beta‐III tubulin Tuj1, red). View is of new neurons originating in the central neurogenic domain of the embryonic day 12 (E12) retina surrounded by mitotic progenitors, viewed from within an older E14.5 retina. New data from Nelson and colleagues (pages 2163–2178, this issue) reveals that in addition to Notch and Ascl1, mammalian retinal progenitors also express multiple Delta‐like genes, and that a conserved Ascl1/Delta‐like/Notch/Hes molecular circuitry operates between progenitors themselves to coordincate retinal histogenesis. From Nelson et al., Developmental Dynamics 238:2163–2178, 2009. © 2009 Wiley‐Liss, Inc.
Soluble TNF‐α but not transmembrane TNF‐α sensitizes T cells for enhanced activation‐induced cell death
Authors: Müller Stefan , Rihs Silvia , Dayer Schneider Johanna M. , Paredes Bruno E. , Seibold Ingeborg , Brunner Thomas , Mueller Christoph
Published: August 2009

In addition to its proinflammatory effects, TNF‐α exhibits immunosuppression. Here, we compared the capacities of transmembrane TNF‐α (tmTNF) and soluble TNF‐α (sTNF) in regulating expansion of activated T cells by apoptosis. Splenic CD4+ T cells from wtTNF, TNF‐α‐deficient (TNF−/−) and TNF−/− mice expressing a non‐cleavable mutant tmTNF showed comparable proliferation rates upon TCR‐mediated stimulation. Activation‐induced cell death (AICD), however, was significantly attenuated in tmTNF and TNF−/−, compared with wtTNF CD4+ T cells. Addition of sTNF during initial priming was sufficient to enhance susceptibility to AICD in tmTNF and TNF−/− CD4+ T cells to levels seen in wtTNF CD4+ T cells, whereas addition of sTNF only during restimulation failed to enhance AICD. sTNF‐induced, enhanced susceptibility to AICD was dependent on both TNF receptors. The reduced susceptibility of tmTNF CD4+ T cells for AICD was also evident in an in vivo model of adoptively transferred CD4+ T‐cell‐mediated colonic inflammation. Hence, the presence of sTNF during T‐cell priming may represent an important mechanism to sensitize activated T cells for apoptosis, thereby attenuating the extent and duration of T‐cell reactivities and subsequent T‐cell‐mediated, excessive inflammation.
Shifting therapeutic attention in MS to osteopontin, type 1 and type 2 IFN
Authors: Steinman Lawrence
Published: August 2009

It is widely debated whether MS is mediated solely by Th1, or solely by Th17, whether it might be mediated by both pathways, or perhaps by neither pathway. We must integrate the following four facts: first, MS lesions have a signature of IL‐6‐, IL‐17‐, osteopontin‐ and IFN‐driven transcriptional activity. Second, MS is worsened with administration of IFN‐γ, the quintessential type 2 IFN and Th1 cytokine. Third, blockade of TNF‐α worsened MS in clinical trials. Fourth, inhibiting the main driver of Th17, IL‐23, failed to modulate relapsing‐remitting MS (RRMS). Against this backdrop, standing outside the framework of the Th1 and Th17 pathways are the type 1 IFN, notably IFN‐β, the most widely used approved therapy for RRMS. A paper in this issue of the European Journal of Immunology demonstrates that IFN‐β suppresses production in CD4+ T cells of both osteopontin and IL‐17. In this commentary, the roles of these two molecules, i.e. osteopontin and IL‐17, are discussed in relation to the pathogenesis of MS. Osteopontin may be more important than Th1 or Th17 in the pathogenesis of RRMS. Trials targeting this small integrin‐binding protein ought to be pursued in RRMS.
Synthesis of Furanosyl C‐1 Glycals through Palladium‐Catalyzed Reactions of a Furanosyl 2,3‐Anhydro‐exo‐glycal
Authors: Gómez Ana M. , Pedregosa Ana , Barrio Aitor , Valverde Serafín , López J. Cristóbal
Published: August 2009

A furanose‐derived 2,3‐anhydro‐exo‐glycal, readily available from D‐mannose in four steps, has proven to be a useful substrate in the preparation of a variety of highly functionalized C‐1 glycals. Upon treatment with Pd0 it affords a π‐allyl palladium complex that can react with nucleophiles such as amines, ethyl malonate, or vinylstannanes. On the other hand, umpolung of the π‐allyl palladium complex with Et2Zn facilitates its reaction with electrophilic aldehydes and ketones.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Microwave‐Assisted 1,3‐Dipolar Cycloaddition: an Eco‐Friendly Approach to Five‐Membered Heterocycles
Authors: Pineiro Marta , Pinho e Melo Teresa M. V. D.
Published: August 2009

The review describes the use of microwave technology to carry out 1,3‐dipolar cycloaddition reactions, an important tool for the construction of five‐membered heterocycles. Microwave methodology can be applied to generate 1,3‐dipoles (nitrones, nitrile oxides, azomethine ylides, azomethineimines, nitrile imines, azides, carbonyl ylides) and to promote the subsequent cycloaddition and usually avoids harsh reaction conditions. This nonconventional energy source is able to reduce chemical reaction times and to increase yields and in some cases can lead to different outcomes from those obtained with conventional heating. The review highlights the more recent developments in the area with particular emphasis on aspects related to efficiency and to regio‐ and stereoselectivity. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
NACE‐ESI‐TOF MS to reveal phenolic compounds from olive oil: Introducing enriched olive oil directly inside capillary
Authors: Gómez‐Caravaca Ana María , Carrasco‐Pancorbo Alegría , Segura‐Carretero Antonio , Fernández‐Gutiérrez Alberto
Published: August 2009

Most CE methods for the analysis of phenols from olive oil use an aqueous electrolyte separation medium, although the importance of NACE is obvious, as this kind of CE seems to be more compatible with the hydrophobic olive oil matrix and could facilitate its direct injection. In the current work we develop a method involving SPE and NACE coupled to ESI‐TOF MS. All the CE and ESI‐TOF MS parameters were optimized in order to maximize the number of phenolic compounds detected and the sensitivity in their determination. Electrophoretic separation was carried out using a CE buffer system consisting of 25 mM NH4OAc/AcH in methanol/ACN (1/1 v/v) at an apparent pH value of 5.0. We studied in depth the effect of the nature and concentration of different electrolytes dissolved in different organic solvents and other experimental and instrumental CE variables. The results were compared with those obtained by CZE (with aqueous buffers) coupled to ESI‐TOF MS; both methods offered to the analyst the chance to study phenolic compounds of different families (such as phenolic alcohols, lignans, complex phenols, flavonoids, etc.) from virgin olive oil by injecting methanolic extracts with efficient and fast CE separations. In the case of NACE method, we also studied the direct injection of the investigated matrix introducing a plug of olive oil directly into the capillary.
CE separation approaches for combinations of anthracyclines and taxanes
Authors: Shakalisava Yuliya , Regan Fiona
Published: August 2009

For the first time the versatility of CE is demonstrated for the separation of different types of anticancer drugs – anthracyclines and taxanes simultaneously. The use of these drugs in combination therapy for cancer has sparked interest in the development of methods for potential application. The simultaneous analysis of anthracyclines and taxanes can significantly increase a sample throughput of a clinical laboratory. The study shows the potential of CE for such a challenge: anthracyclines and taxanes were separated by CZE, MEKC and MEEKC. The MEEKC method was successfully applied to these compounds for the first time and was characterised by very short separation time, high efficiencies of peaks and was proven to be generic for the separation of different combinations of anthracyclines and taxanes. This separation approach could be highly beneficial for clinical analysis if applied with a sensitive detection system. MEKC and high‐speed MEEKC methods were proven to show good potential in their application to plasma samples.
Quality control in fast pyrolysis bio‐oil production and use
Authors: Oasmaa A. , Elliott D.C. , Müller S.
Published: August 2009

Introducing a new fuel, fast pyrolysis bio‐oil, into the market is not without its challenges. Fast pyrolysis bio‐oil is different from conventional liquid fuels, and therefore must overcome both technical and marketing hurdles. To standardize the bio‐oil quality on the market, specifications are needed and in order to promote its acceptance as a fuel, the methodology should be as similar to that for mineral oils as possible. In the EU a new chemical regulation system is being implemented. The regulation applies to substances manufactured in or imported to the EU in annual quantities of one tonne or more per company.

This article will focus on norms and standards for fast pyrolysis bio‐oils. It will include the present status and address what still has to be done on bio‐oil specifications and relevant test methods. The article will address industrial needs in commercialization of the fuel oil use of bio‐oil, including the registration application to the REACH program, as well as development of a standard within ASTM. The article will discuss the most important properties of bio‐oil and the variation in these properties. It will address the issue of quality follow‐up in bio‐oil production, including the properties to be followed and the laboratory and on‐line monitoring methods. The article will provide a state of the art of fuel oil specifications, test methods, and testing procedures as they are applied to bio‐oil. It will review the effort in support of the implementation of an ASTM standard including the methods validation work. © 2009 American Institute of Chemical Engineers Environ Prog, 2009
A multi‐energy‐level lattice Boltzmann model for two‐dimensional wave equation
Authors: Shi Xiubo , Yan Guangwu , Zhang Jianying
Published: August 2009

A lattice Boltzmann model for two‐dimensional wave equation is presented. In this model, we used higher‐order moment method, multi‐scale technique and Chapman–Enskog expansion, and multi‐energy‐level to obtain wave equation and energy conservation equation. As numerical examples, the interference and diffraction of wave are simulated. The numerical results show this model can be used to simulate two‐dimensional wave propagation. Copyright © 2009 John Wiley & Sons, Ltd.