bluuebunny/crossref_metadata_2025 huggingface dataset:
Enzyme Replacement Therapy for Murine Hypophosphatasia
Authors: Millán José Luis , Narisawa Sonoko , Lemire Isabelle , Loisel Thomas P , Boileau Guy , Leonard Pierre , Gramatikova Svetlana , Terkeltaub Robert , Camacho Nancy Pleshko , McKee Marc D , Crine Philippe , Whyte Michael P
Published: December 2007

Introduction: Hypophosphatasia (HPP) is the inborn error of metabolism that features rickets or osteomalacia caused by loss-of-function mutation(s) within the gene that encodes the tissue-nonspecific isozyme of alkaline phosphatase (TNALP). Consequently, natural substrates for this ectoenzyme accumulate extracellulary including inorganic pyrophosphate (PPi), an inhibitor of mineralization, and pyridoxal 5′-phosphate (PLP), a co-factor form of vitamin B6. Babies with the infantile form of HPP often die with severe rickets and sometimes hypercalcemia and vitamin B6-dependent seizures. There is no established medical treatment.

Materials and Methods: Human TNALP was bioengineered with the C terminus extended by the Fc region of human IgG for one-step purification and a deca-aspartate sequence (D10) for targeting to mineralizing tissue (sALP-FcD10). TNALP-null mice (Akp2−/−), an excellent model for infantile HPP, were treated from birth using sALP-FcD10. Short-term and long-term efficacy studies consisted of once daily subcutaneous injections of 1, 2, or 8.2 mg/kg sALP-FcD10 for 15, 19, and 15 or 52 days, respectively. We assessed survival and growth rates, circulating levels of sALP-FcD10 activity, calcium, PPi, and pyridoxal, as well as skeletal and dental manifestations using radiography, μCT, and histomorphometry.

Results: Akp2 −/− mice receiving high-dose sALP-FcD10 grew normally and appeared well without skeletal or dental disease or epilepsy. Plasma calcium, PPi, and pyridoxal concentrations remained in their normal ranges. We found no evidence of significant skeletal or dental disease.

Conclusions: Enzyme replacement using a bone-targeted, recombinant form of human TNALP prevents infantile HPP in Akp2−/− mice.
MEMS-basierter piezoelektrischer Energiewandler (MEMS-based Piezoelectric Energy Converter)
Authors: Kühne Ingo , Eckstein Gerald , Seidel Helmut
Published: December 2007

Im vorliegenden Beitrag wird ein neuer Ansatz eines MEMS-basierten (Micro-Electro-Mechanical System) piezoelektrischen Energiewandlers vorgestellt. Dieser MEMS-Generator basiert im Wesentlichen auf einer massebeaufschlagten piezoelektrischen Membran, die in der Lage ist, umgebende mechanische Vibrationen in elektrische Energie zu wandeln. Im Folgenden wird ein entsprechender MEMS-Entwurf präsentiert, wobei im Speziellen auf die Optimierung der geometrischen Anordnung des Bauteils eingegangen wird. Darüber hinaus demonstrieren erste Experimente die Funktionsweise des Energiewandlers. Elektrische Messungen zeigen Abhängigkeiten bezüglich elektrischer Last, Schichtstress in der Membran und Elektrodenstruktur. Der typische Frequenzgang eines piezoelektrischen Mikrogenerators wird ebenso vorgestellt.
About the variable-counting-time techniques in powder diffraction data: their use in EXPO2004
Authors: da Silva Iván , González-Platas Javier , Giacovazzo Carmelo , Altomare Angela
Published: December 2007

High quality data are essential for crystal structure solution, particularly when Direct Methods instead of Global Optimization Techniques are used. In this work we study the performances of the variable-counting-time techniques in the two crucial steps of the phasing process: decomposition of the full diffraction pattern and direct phasing. The experimental data were collected by a conventional X-ray laboratory diffractometer: they were then submitted to the program EXPO2004 for assessing their usefulness in the phasing process. The results are compared with those obtained by using experimental diffraction data collected via the traditional fixed-counting-time technique under the same experimental conditions.
New insight into the pectolite – serandite series: a single crystal diffraction study of Na(Ca1.73Mn0.27)[HSi3O9] at 293 and 100 K
Authors: Arakcheeva Alla , Pattison Philip , Meisser Nicolas , Chapuis Gervais , Pekov Igor V. , Thélin Philippe
Published: December 2007

Using synchrotron radiation, a single crystal investigation has been performed at 293 and 100 K for the structural characterization of the manganoan pectolite, Na(Ca1.73Mn0.27)[Si3O8(OH)] (from the pegmatite at Mt. Koashva, Khibiny alkaline massif, Kola peninsula, Russia). The data obtained are compared with other members of the pectolite – serandite, Na(Ca2–xMnx)[Si3O8(OH)], series. The strong asymmetric hydrogen bond observed in the other members of the series has been confirmed at 293 K (O3–O4 = 2.473(3) Å; H–O3 = 0.97(4) Å, H … O4 = 1.50(4) Å ; O3–H … O4 = 178(4)°). This bond exhibits strengthening (O3–O4 = 2.458(2) Å) and becomes more symmetric at 100 K (H–O3 = 1.06(4) Å, H … O4 = 1.40(4) Å, O3–H … O4 177(4)°). The data obtained for 293 K confirm the previously hinted tendency: the higher the content of Mn, the more asymmetric the H-bond. The influence of the asymmetric position of the H-bond on the environment close to the bonded O3 and O4 atoms and the H–Na interaction are discussed. The alternative topological role of the hydrogen bond is considered in comparison to a similar structure Li2Mg2 [Si4O11].
Crystal and molecular structures of 4-substituted 3,4-dihydropyrimidin-2(1H)-ones studied by X-ray and AM1 and B3LYP calculations
Authors: Vega-Teijido Maurício , Zukerman-Schpector Julio , Macedo Nunes Fábio , Gatti Paula M. , Stefani Hélio Alexandre , Caracelli Ignez
Published: December 2007

(1) C13H13N3O5, Mr = 291.26, P-1, a = 7.4629(9), b = 7.9203(9), c = 12.126(2) Å, α = 86.804(5), β = 78.471(7), γ = 69.401(8)°, V = 657.3(2) Å3, Z = 2, R
1 = 0.0454; (2) C11H12N2O4, Mr = 236.23, Pbca, a = 7.2713(9), b = 14.234(1), c = 20.848(3) Å, V = 2157.8(4) Å3, Z = 8, R
1 = 0.0504; (3) C13H13N2O3Cl, Mr = 280.70, P2/n, a = 17.344(2), b = 9.237(1), c = 18.398(2) Å; β = 92.61(2)°, V = 2944.4(6) Å3, Z = 8, R
1 = 0.0714. The conformational features of three 4-substituted-3-4-dihydropyrimidin-2(1H)-ones were investigated by computational and single crystal X-ray crystallographic studies. The geometries were optimized using semiempirical (AM1) and first principle calculations (B3LYP/6-31G**) methods, the rotational barriers for important functional groups were studied. In all structures the pyrimidinone rings are in a more or less distorted boat conformation. The phenyl and the furane rings are almost perpendicular to the best least-squares plane through the dihydropyrimidinone ring.
Consumo de cafeína entre gestantes e a prevalência do baixo peso ao nascer e da prematuridade: uma revisão sistemática
Authors: Pacheco Alice Helena de Resende Nóra , Barreiros Nathália Silva Raposo , Santos Iná S. , Kac Gilberto
Published: December 2007

Realizou-se revisão sistemática sobre o consumo de cafeína em gestantes na ocorrência de baixo peso ao nascer e prematuridade, enfocando métodos para quantificação deste consumo e confundimentos controlados na análise. A revisão consistiu na busca de artigos publicados de 1996 a 2006 nas bases MEDLINE, LILACS e PubMed, utilizando-se as palavras-chave: "caffeine", "coffee", "low birth weight", "birth weight", "preterm", "premature" e "prematurity". Dez artigos foram selecionados. Os métodos utilizados para quantificar o consumo de cafeína foram: questionário de freqüência alimentar semiquantitativo - da dieta ou apenas de produtos cafeinados, sendo um do tipo auto-aplicado; recordatório alimentar; perguntas sobre tipo e modo de preparo; análise de amostras; e dosagens urinária e plasmática. Em três estudos revisados, o consumo elevado de cafeína associou-se com baixo peso ao nascer e/ou prematuridade. Contradições nos achados devem-se a dificuldades na mensuração do consumo de cafeína; às fontes abordadas; a variações no preparo e na quantidade consumida; e ao tamanho amostral. Não foi demonstrada associação entre ingestão moderada de cafeína e crescimento fetal, sendo necessária uma avaliação mais precisa do consumo dessa substância.
Tendência do campo de avaliação de intervenções públicas de alimentação e nutrição em programas de pós-graduação no Brasil: 1980-2004
Authors: Henrique Flávia Conceição dos Santos , Lira Pedro Israel Cabral , Santos Sandra Maria Chaves dos , Andrade Sonia Lucia Lucena Sousa de
Published: December 2007

A avaliação de políticas públicas no Brasil vem, nas últimas décadas, emergindo como ferramenta estratégica para melhoria da performance da ação pública, capaz esta de contribuir efetivamente para o bem-estar social. Em que pese esse reconhecimento, essa prática não tem sido incorporada ao "ciclo de vida" de programas, sobretudo aqueles da área social. Dentre as ações que se ressentem de uma prática avaliativa significativa, estão aquelas da área de alimentação e nutrição. Diante destas questões, esse artigo teve como objetivo caracterizar o campo da avaliação de intervenções públicas de alimentação e nutrição em programas de pós-graduação no Brasil. Utilizou-se como objeto central de análise a produção bibliográfica, especificamente teses e dissertações, defendidas no período de 1980 a 2004. No que se refere aos achados desse estudo foi possível observar que a produção tem convergido para o processo de funcionamento das intervenções com predomínio da pesquisa documental e estudos de caso. Do ponto de vista analítico as categorias temáticas privilegiadas nos trabalhos vêm sendo modificadas migrando de padrão mais próximo à dimensão biológica para outro, situado numa dimensão sócio-política.
Alimentação institucionalizada e suas representações sociais entre moradores de instituições de longa permanência para idosos em São Paulo, Brasil
Authors: Santelle Odete , Lefèvre Ana Maria Cavalcanti , Cervato Ana Maria
Published: December 2007

Foram analisadas representações sociais sobre alimentação entre moradores de instituições de longa permanência para idosos, para identificar condicionantes do comportamento alimentar que podem interferir no estado nutricional destes indivíduos. Realizada pesquisa qualitativa e exploratória em cinco asilos de São Paulo, Brasil. Participaram quarenta idosos de ambos os gêneros, sem distúrbios cognitivos, residentes nas instituições há seis meses ou mais. Foram selecionados vinte sujeitos desnutridos ou em risco de desnutrição e vinte sem risco de desnutrição. Foram utilizadas entrevistas com roteiro semi-estruturado e os dados analisados pela técnica do Discurso do Sujeito Coletivo. Os resultados apontaram que, na percepção dos idosos, a rotina alimentar institucionalizada, os cardápios rotineiros e a oferta insuficiente de hortaliças e frutas interferem negativamente no processo de alimentação. Os idosos reconhecem que a alimentação equilibrada melhora a saúde e a qualidade de vida. Revelam que a inapetência de alguns está relacionada a comidas que não agradam ao paladar, problemas de saúde e à assistência inadequada durante as refeições. Este estudo contribuiu para identificar fatores psicológicos e sociais que podem concorrer para a maior freqüência de desnutrição entre idosos institucionalizados.
A violência na Venezuela: renda petroleira e crise política
Authors: Briceño-León Roberto
Published: December 2007

O presente artigo analisa as mudanças na violência ocorridas na Venezuela nos últimos quarenta anos, relacionadas com os altos e baixos da renda petroleira e com a crise política no país, fatos que contribuíram para um aumento nas taxas de homicídios: de 7 por cem mil habitantes em 1970 a 12 em 1990; 19 em 1998; e 50 no ano de 2003. O artigo caracteriza a Venezuela como sociedade rentista e, a partir daí, faz uma retrospecção cobrindo desde a violência rural até os inícios da violência urbana, o movimento guerrilheiro dos anos 60, a criminalidade resultando da abundância dos recursos petroleiros e a violência em decorrência da revolta popular e dos saques ocorridos em 1989 em Caracas. Em seguida são analisados os golpes de Estado de 1992 e o impacto que a violência política exerceu sobre a violência criminal. Descrevemos as mudanças políticas e partidárias no país e sua influência sobre a estabilização das taxas de homicídios em meados dos anos 90, assim como seu considerável aumento durante o governo Chávez. O artigo conclui com uma análise da situação atual, fala sobre a proibição de publicar dados estatísticos sobre homicídios e faz uma reflexão sobre a perspectiva de ainda mais violência na Venezuela.
A inclusão da violência na agenda da saúde: trajetória histórica
Authors: Minayo Maria Cecília de Souza
Published: December 2007

Neste texto, busco sistematizar e registrar a trajetória histórica de legitimação do tema dos acidentes e da violência na área da saúde. Mostro que se trata de um processo inconcluso, que ocorre pela pressão de atores e pela força dos acontecimentos. Inicialmente o tema se inclui de forma reduzida, por meio dos conceitos de "acidentes, lesões e traumas". Já a partir da segunda metade do século 20, há a incorporação da pauta de direitos de vários sujeitos sociais, que vai desde a entrada da observação e notificação da violência contra crianças, mulheres e idosos, até a discussão da violência social, no seu sentido mais amplo, afetando a saúde das populações. No Brasil, esse processo, sem dúvida lento e intermitente, tem alguns logros e pioneirismos encenados pelo Ministério da Saúde, com a colaboração e a pressão de movimentos sociais, acadêmicos e profissionais: um documento de diagnóstico da situação de morbimortalidade por todos os tipos de violência; documento de uma Política Nacional de Redução de Acidentes e Violências e um Plano de Ação Nacional.
O impacto do suicídio sobre a morbimortalidade da população de Itabira
Authors: Souza Edinilsa Ramos de , Minayo Maria Cecília de Souza , Cavalcante Fátima Gonçalves
Published: December 2007

As taxas de suicídio em Itabira, município com cerca de 100. 000 habitantes, são mais elevadas do que as da população brasileira. Para entender esse fenômeno, investigou-se a morbimortalidade da população por meio de estudo epidemiológico descritivo, com ênfase nas causas externas e subgrupos específicos, destacando-se o suicídio, segundo características das vítimas e dos eventos, no período de 1990 a 2001 com base no Sistema de Informações sobre Mortalidade; e internações, por meio das Autorizações de Internações Hospitalares para 2000. Fez-se busca ativa das informações sobre suicídios no cartório e no batalhão de polícia militar locais, no período de 1996 a 2001, segundo sexo, idade e ocupação da vítima, mês de ocorrência e meio usado no suicídio consumado e nas tentativas. Calcularam-se proporções, taxas e médias referentes a esses dados. As populações usadas no cálculo das taxas foram extraídas do site do Datasus. Os resultados apontam para tendência de aumento de suicídios entre homens, coincidindo com a reestruturação produtiva que ocorreu nesta cidade monocultora da mineração de ferro. As tentativas são crescentes para donas de casa, domésticas e estudantes. Os suicídios se dão principalmente por enforcamento e armas de fogo. Nas tentativas são relevantes substâncias não-medicinais, drogas e medicamentos.
Troubled conception
Authors: May Marian
Published: December 2007

In the context of low fertility and Australia’s ageing population, a national longitudinal telephone survey,Negotiating the Life Course(NLC), asks women about their childbearing intentions. This paper uses conversation analysis (CA) to examine interaction between an interviewer and respondents on one NLC question about the likelihood of having children, Question 165. The analysis focuses on excerpts from troubled interviews, making transparent the task of negotiating responses acceptable to the interviewer and shedding light on problems inherent in the question for older women and women for whom prediction is difficult. Analysis shows the trouble to result from lack of congruence in the purposes of the researcher and the respondent: the researcher asks about likelihood, whereas the respondent tells her own story.
Effects of psychopathy traits on unprovoked aggression
Authors: Reidy Dennis E. , Zeichner Amos , Martinez Marc A.
Published: December 2007

Research has demonstrated that risk of violent behavior is high in individuals who display psychopathic traits. However, prediction of general aggression, and in particular unprovoked aggression, in nonforensic men who possess such traits has received little experimental attention to date. This study examined the role of psychopathic traits in the prediction of unprovoked aggression in a nonforensic sample. One hundred and five men completed the Levenson Self‐Report Psychopathy Scales and competed in a sham aggression paradigm. These men were identified as unprovoked aggressors, provoked aggressors, and provoked nonaggressors contingent on their responses to the experimental paradigm. Findings indicated that men with high levels of psychopathic traits had a 30% greater probability of becoming aggressive in the absence of provocation relative to those with lower psychopathic traits. Results also indicated that unprovoked aggressors evinced more general aggression when provocation was initiated. Findings are discussed in terms of the importance of trait‐based risk factors in the prediction of seemingly random, unprovoked aggression. Aggr. Behav. 34:319–328, 2008. © 2007 Wiley‐Liss, Inc.
Synthesis and application of a novel epoxy grafted thermosetting acrylic resin
Authors: Zheng Yian , Zhou Lei , Yang Ying , Gao Yaping
Published: December 2007

A novel manufacturing process for high performance metallic can coating was carried out based on an epoxy‐grafted acrylic resin. Firstly, the epoxy resin was reacted with acrylic amide forming a ring opened product epoxy‐amide resin, and then the product obtained copolymerized with all other monomers, such as acrylic acid (AA), butyl acrylate (BA), hydroxypropyl acrylate (HPA), 2‐ethylhexyl acrylate (2‐EHA), methyl methacrylate (MMA), styrene (St), using free radical solvent polymerization in the presence of BPO. The resins prepared present the transparent appearance, and the target resin coating based on these resins exhibits excellent boiling resistance and chemicals resistance and can be applied as the protective coating for metallic can. The effects on the coating properties, such as amount of acrylic acid, 2‐EHA wt % between 2‐EHA and BA, amount of amino resin, amount of catalyst, and so forth, were investigated. In addition, the influences of polymerization time on the conversion ratio of monomers were also studied. Results show that under the optimal conditions, the target resin coating provides excellent physical and mechanical properties. The various properties tests for this coating have been performed in accordance with the standards of ASTM. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Involvement of the Klotho Protein in Dentin Formation and Mineralization
Authors: Suzuki Hironobu , Amizuka Norio , Oda Kimimitsu , Noda Masaki , Ohshima Hayato , Maeda Takeyasu
Published: December 2007

Klotho‐deficient mice exhibit multiple pathological conditions resembling human aging. Our previous study showed alterations in the distribution of osteocytes and in the bone matrix synthesis in klotho‐deficient mice. Although the bone and tooth share morphological features such as mineralization processes and components of the extracellular matrix, little information is available on how klotho deletion influences tooth formation. The present study aimed to elucidate the altered histology of incisors of klotho‐deficient mice–comparing the findings with those from their wild‐type littermates, by using immunohistochemistry for alkaline phosphatase (ALP), osteopontin, and dentin matrix protein‐1 (DMP‐1), terminal deoxynucleotidyl transferase‐mediated deoxyuridinetriphosphate nick end‐labeling (TUNEL) detection for apoptosis, and electron probe microanalyzer (EPMA) analysis on calcium (Ca), phosphate (P), and magnesium (Mg). Klotho‐deficient incisors exhibited disturbed layers of odontoblasts, predentin, and dentin, resulting in an obscure dentin‐predentinal border at the labial region. Several odontoblast‐like cells without ALP activity were embedded in the labial dentin matrix, and immunopositivity for DMP‐1 and osteopontin was discernible in the matrix surrounding these embedded odontoblast‐like cells. TUNEL detection demonstrated an apoptotic reaction in the embedded odontoblast‐like cells and pulpal cells in the klotho‐deficient mice. EPMA revealed lower concentrations of Ca, P, and Mg in the klotho‐deficient dentin, except for the dentin around abnormal odontoblast‐like cells. These findings suggest the involvement of the klotho gene in dentinogenesis and its mineralization. Anat Rec, 2007. © 2008 Wiley‐Liss, Inc.
Connexin 43 Expression Delineates Two Discrete Pathways in the Human Atrioventricular Junction
Authors: Hucker William J. , Mccain Megan L. , Laughner Jacob I. , Iaizzo Paul A. , Efimov Igor R.
Published: December 2007

Gap junction expression has been studied in the atrioventricular junction (AVJ) of many species, however, their distribution in the human AVJ is unknown. The AVJ expression of the gap junction protein connexin 43 (Cx43) is species dependent; therefore we investigated its distribution in the human AVJ. Using Masson trichrome histology, we reconstructed the AVJ of three normal human hearts and one with dilated cardiomyopathy in three dimensions. Cx43 was immunolabeled with vimentin and α‐actinin to determine the cellular origin of Cx43 and was quantified in the following structures: interatrial septum (IAS), His bundle, compact node (CN), lower nodal bundle (LNB), leftward and rightward nodal extensions (LE and RE), and inferior, endocardial, and left‐sided transitional cells. Histology revealed two nodal extensions in three of four hearts. Cx43 was found in the myocytes, but not fibroblasts, of the AVJ. LE and CN Cx43 was lower than the IAS (P < 0.05) and the RE, LNB, and His all expressed Cx43 similarly, with approximately half of IAS expression (RE: 44 ± 36%; LNB: 50 ± 26%; His: 48 ± 12%, P = NS compared with IAS). Cx43 levels in transitional cells were similar to the IAS (P = not significant). Cx43 was found in myocytes of the human AVJ, and its expression pattern delineates two separate continuous structures: one consists of the LE and CN with little Cx43, and the other consists of the His, LNB, and RE expressing approximately half the Cx43 of the IAS. The differential Cx43 expression may provide each structure with unique conduction properties, contributing to arrhythmias arising from the AVJ. Anat Rec, 2007. © 2007 Wiley‐Liss, Inc.
Effect of Enamel Prism Decussation and Chemical Composition on the Biomechanical Behavior of Dental Tissue: A Theoretical Approach to Determine the Loading Conditions to Which Modern Human Teeth are Adapted
Authors: Shimizu Daisuke , Macho Gabriele A.
Published: December 2007

This theoretical study explored whether the directions of loads to which modern human molars are commonly subjected to are reflected in the biomechanical behavior of the tissue itself. A detailed finite element model of a piece of decussating enamel (M3 paracone) was created, taking into account differences in crystal orientation between the prism head and the interprismatic matrix, and was tested under differently angled mediolateral loads (i.e., mimicking various stages of the chewing cycle). Second, although teeth are highly mineralized, they also contain organic material and water, while in modern humans, there are systematic differences in chemical composition from the outer enamel surface to the dentinoenamel junction. To test the biomechanical effects of this gradient in mineralization a second set of models with gradually changing properties was created and subjected to the same loads. Chemically heterogeneous enamel yielded overall lower stress levels than homogenous enamel, especially at extreme loading angles. However, the general trends regarding the increase in tensile stresses at more oblique angles, and the number of nodes exhibiting tension, were comparable between the different set‐ups. The findings support suggestions that (a) the biomechanical behavior of dental tissue is the combined result of micromorphology and chemical composition and (b) that the range of loading directions, to which teeth are normally subjected to, can be inferred from dental microanatomy. For (palaeo)biological applications, the findings suggest that the absolute strength of teeth (e.g., bite force) cannot be predicted with certainty, whereas kinematic parameters of the masticatory apparatus can. Anat Rec, 2007. © 2008 Wiley‐Liss, Inc.
Pretreatment: the key to unlocking low‐cost cellulosic ethanol
Authors: Yang Bin , Wyman Charles E.
Published: December 2007

New transportation fuels are badly needed to reduce our heavy dependence on imported oil and to reduce the release of greenhouse gases that cause global climate change; cellulosic biomass is the only inexpensive resource that can be used for sustainable production of the large volumes of liquid fuels that our transportation sector has historically favored. Furthermore, biological conversion of cellulosic biomass can take advantage of the power of biotechnology to take huge strides toward making biofuels cost competitive. Ethanol production is particularly well suited to marrying this combination of need, resource, and technology. In fact, major advances have already been realized to competitively position cellulosic ethanol with corn ethanol. However, although biotechnology presents important opportunities to achieve very low costs, pretreatment of naturally resistant cellulosic materials is essential if we are to achieve high yields from biological operations; this operation is projected to be the single, most expensive processing step, representing about 20% of the total cost. In addition, pretreatment has pervasive impacts on all other major operations in the overall conversion scheme from choice of feedstock through to size reduction, hydrolysis, and fermentation, and on to product recovery, residue processing, and co‐product potential. A number of different pretreatments involving biological, chemical, physical, and thermal approaches have been investigated over the years, but only those that employ chemicals currently offer the high yields and low costs vital to economic success. Among the most promising are pretreatments using dilute acid, sulfur dioxide, near‐neutral pH control, ammonia expansion, aqueous ammonia, and lime, with significant differences among the sugar‐release patterns. Although projected costs for these options are similar when applied to corn stover, a key need now is to dramatically improve our knowledge of these systems with the goal of advancing pretreatment to substantially reduce costs and to accelerate commercial applications. © 2007 Society of Chemical Industry and John Wiley & Sons, Ltd
Molecular characterization and comparative localization of the mRNAs encoding two glutamic acid decarboxylases (GAD65 and GAD67) in the brain of the african lungfish, Protopterus annectens
Authors: Trabucchi Michele , Trudeau Vance L. , Drouin Guy , Tostivint Hervé , Ihrmann Isabelle , Vallarino Mauro , Vaudry Hubert
Published: December 2007

The existence of two distinct genes encoding two isoforms of glutamic acid decarboxylase (GAD65 and GAD67) has been demonstrated in most vertebrate classes, yet little is known about their differential distributions and functions in the central nervous system in nonmammalian vertebrates. In the present study, we have partially sequenced the cDNAs encoding GAD65 and GAD67 in the lungfish Protopterus annectens and determined their relative distributions in the adult brain by in situ hybridization histochemistry. The expression patterns of the GAD65 and GAD67 mRNAs were globally similar; the highest expression levels being observed in the granular layer of the olfactory bulb, the pallium, the subpallium, the anterior preoptic area, the thalamus, the hindbrain central gray, and the rhombencephalic visceral areas. However, striking differential expression was noticed in several structures. Very high to high concentrations of GAD67 mRNA were seen in the dorsal and ventral aspects of the anterior olfactory nucleus, which is in marked contrast to the very low expression of GAD65 in this region. Similarly, high levels of GAD67 mRNA were observed in the intermediate and ventral parts of the medial pallium that were virtually devoid of GAD65 mRNA. In contrast, GAD65 mRNA was found in the periaqueductal gray that did not express GAD67 mRNA. The differential expression of GAD65 and GAD67 mRNAs in these regions of the lungfish CNS indicates that the two GAD isoforms can be differentially regulated and that they may have distinct physiological roles. J. Comp. Neurol. 506:979–988, 2008. © 2007 Wiley‐Liss, Inc.
Cellulose Aerogels from Aqueous Alkali Hydroxide–Urea Solution
Authors: Cai Jie , Kimura Satoshi , Wada Masahisa , Kuga Shigenori , Zhang Lina
Published: December 2007

Highly porous and strong cellulose aerogels were prepared by gelation of cellulose from aqueous alkali hydroxide/urea solution, followed by drying with supercritical CO2. Their morphology, pore structure, and physical properties were characterized by scanning and transmission electron microscopy, X‐ray diffraction, nitrogen adsorption measurements, UV/Vis spectrometry, and tensile tests. The cellulose hydrogel was composed of interconnected fibrils of about 20 nm wide. By using supercritical CO2 drying, the network structure in the hydrogel was well preserved in the aerogel. The results are preliminary but demonstrate the ability of this method to give cellulose aerogels of large surface areas (400–500 m2 g−1) which may be useful as adsorbents, heat/sound insulators, filters, catalyst supports, or carbon aerogel precursors.
Toward a neuro‐developmental account of the development of declarative memory
Authors: Bauer Patricia J.
Published: December 2007

The study of the biological bases of memory has a long history. Based on research with patients with specific lesions and disease, animal models, and neuroimaging studies, the neural substrate that supports declarative memory in adults has been relatively well articulated. By contrast, studies of the neural bases of memory in development is in its infancy. Yet joint consideration of the processes involved in building a memory trace, and of the time course of development of the neural structures involved, has contributed to the generation of specific predictions regarding the sources of age‐related change. Specifically, there are suggestions that in infancy and very early childhood, encoding and consolidation processes account for substantial age‐related variance in long‐term declarative memory. With development, the locus of age‐related variability in the vulnerability of memory traces shifts to the later‐stage processes of memory storage and retrieval. These insights are afforded by consideration of multiple levels of analysis, from the biological to the behavioral. © 2007 Wiley Periodicals, Inc. Dev Psychobiol 50: 19–31, 2008.
Inhibitory deficits in tourette's syndrome
Authors: Stern Emily R. , Blair Clancy , Peterson Bradley S.
Published: December 2007

A developmental approach to the study of psychopathology can broaden understanding of a wide variety of complex psychological disorders. This article reviews research on Tourette's syndrome (TS), a developmental disorder characterized by unwanted motor and vocal tics. Over the past decade, knowledge of the neurobiology and pathophysiology of TS has progressed rapidly. The application of brain imaging techniques, primarily magnetic resonance imaging, to the study of Tourette's has increased knowledge of structural and functional deficits in brain areas associated with behavioral and psychological disturbances in the disorder. By reviewing some of this work, we will describe one way in which knowledge of brain function in TS has both informed and been informed by a developmental science approach. In particular, we will consider the extent to which the cognitive and emotional development of persons with TS may be affected by specific neurobiological characteristics of the disorder. © 2007 Wiley Periodicals, Inc. Dev Psychobiol 50: 9–18, 2008.
Developmental differences in infants' use of an object's shape to grasp it securely
Authors: Barrett Tracy M. , Needham Amy
Published: December 2007

This study examined twenty two 11‐ and 13‐month‐old infants' approach and grasp of two objects—one symmetric and one asymmetric—in an effort to understand infants' use of shape information to plan motor action. At first contact, all infants grasped the asymmetrical object further from its center of mass than the symmetrical object. In addition, results highlighted developmental differences in infants' abilities to correct for less stable hand placements, to maintain control of the objects without dropping, strategies used to obtain the objects, and latencies to grasp the objects. Older infants showed more effective skills in each of the aforementioned areas. Implications for our understanding of the development of processing of visual information for action are discussed. © 2007 Wiley Periodicals, Inc. Dev Psychobiol 50: 97–106, 2008.
BCL‐2 counteracts Doppel‐induced apoptosis of prion‐protein‐deficient Purkinje cells in the Ngsk Prnp0/0 mouse
Authors: Heitz S. , Gautheron V. , Lutz Y. , Rodeau J.‐L. , Zanjani H.S. , Sugihara I. , Bombarde G. , Richard F. , Fuchs J.‐P. , Vogel M.W. , Mariani J. , Bailly Y.
Published: December 2007

The pro‐apoptotic factor BAX has recently been shown to contribute to Purkinje cell (PC) apoptosis induced by the neurotoxic prion‐like protein Doppel (Dpl) in the prion‐protein‐deficient Ngsk Prnp0/0 (NP0/0) mouse. In view of cellular prion protein (PrPc) ability to counteract Dpl neurotoxicity and favor neuronal survival like BCL‐2, we investigated the effects of the anti‐apoptotic factor BCL‐2 on Dpl neurotoxicity by studying the progression of PC death in aging NP0/0‐Hu‐bcl‐2 double mutant mice overexpressing human BCL‐2 (Hu‐bcl‐2). Quantitative analysis showed that significantly more PCs survived in NP0/0‐Hu‐bcl‐2 double mutants compared with the NP0/0 mutants. However, number of PCs remained inferior to wild‐type levels and to the increased number of PCs observed in Hu‐bcl‐2 mutants. In the NP0/0 mutants, Dpl‐induced PC death occurred preferentially in the aldolase C‐negative parasagittal compartments of the cerebellar cortex. Activation of glial cells exclusively in these compartments, which was abolished by the expression of Hu‐bcl‐2 in the double mutants, suggested that chronic inflammation is an indirect consequence of Dpl‐induced PC death. This partial rescue of NP0/0 PCs by Hu‐bcl‐2 expression was similar to that observed in NP0/0:Bax−/− double mutants with bax deletion. Taken together, these data strongly support the involvement of BCL‐2 family‐dependent apoptotic pathways in Dpl neurotoxicity. The capacity of BCL‐2 to compensate PrPc deficiency by rescuing PCs from Dpl‐induced death suggests that the BCL‐2‐like property of PrPc may impair Dpl‐like neurotoxic pathways in wild‐type neurons. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2008
A displaced PAG enhances proximal signaling and SDF‐1‐induced T cell migration
Authors: Posevitz‐Fejfár Anita , Šmída Michal , Kliche Stefanie , Hartig Roland , Schraven Burkhart , Lindquist Jonathan A.
Published: December 2007

PAG, the phosphoprotein associated with glycosphingolipid‐enriched microdomains (GEM), negatively regulates Src family kinases by recruiting C‐terminal Src kinase (Csk) to the membrane, where Csk phosphorylates the inhibitory tyrosine of the Src kinases. S‐acylation of a CxxC motif juxtaposed to the transmembrane domain within PAG has been proposed to be responsible for targeting PAG to the lipid rafts. Here, we present the characterization of a mutant PAG molecule lacking the palmitoylation motif. We demonstrate that the mutant protein is expressed at the plasma membrane, but does not localize within the GEM. Despite being displaced, the mutant PAG molecule still binds the Src kinase Fyn and the cytoskeletal adaptor ezrin‐radixin‐moesin‐binding phosphoprotein of 50 kDa, becomes tyrosine‐phosphorylated, and recruits Csk to the membrane. Functional characterization of the mutant shows that, unlike WT PAG, it does not block proximal TCR signaling, and surprisingly enhances stromal cell‐derived factor 1 (CXCL12)‐induced migration. The mutant functions by depleting Csk from the GEM fractions, as apparent by changes in the phosphorylation of the inhibitory tyrosines within the Src kinases. Indeed this mechanism is supported by RNA interference of PAG, which results in enhanced migration and Src kinase activity. Our results therefore support a functional role for the compartmentalization of Src kinases within the membrane.
The orally‐active and selective c‐Fms tyrosine kinase inhibitor Ki20227 inhibits disease progression in a collagen‐induced arthritis mouse model
Authors: Ohno Hiroaki , Uemura Yasunori , Murooka Hideko , Takanashi Hiromi , Tokieda Takemi , Ohzeki Yumiko , Kubo Kazuo , Serizawa Isao
Published: December 2007

Macrophage colony‐stimulating factor (M‐CSF) is important in the development of macrophages and osteoclasts. Previous studies have also shown that CD11b+ myeloblasts and osteoclasts play key roles during inflammation and bone destruction in arthritic lesions. In this study, we investigated whether N‐{4‐[(6,7‐dimethoxy‐4‐quinolyl)oxy]‐2‐methoxyphenyl}‐N′‐[1‐(1,3‐thiazole‐2‐yl)ethyl] urea (Ki20227), an inhibitor of the M‐CSF receptor (c‐Fms), suppressed disease progression in a type II collagen (CII)‐induced arthritis (CIA) mouse model. We found that Ki20227 inhibited M‐CSF‐dependent reactions, such as lipopolysaccharide‐induced tumor necrosis factor‐α production, which were enhanced by M‐CSF in vitro. Oral administration of Ki20227 in vivo prevented inflammatory cell infiltration and bone destruction, and consequently suppressed disease progression. In addition, the number of CD11b+, Gr‐1+, and Ly‐6G+ cells in the spleen decreased in the Ki20227‐treated mice, and the CII‐induced cytokine production in splenocytes isolated from the Ki20227‐treated arthritic mice was also reduced. These observations indicate that Ki20227 might exert its therapeutic effects in the CIA mouse model by suppressing the M‐CSF‐dependent accumulation of both inflammatory and osteoclast cells, as well as by inhibiting inflammatory cytokine production. Hence, inhibitors of the c‐Fms tyrosine kinase might act as anti‐inflammatory or anti‐osteolytic agents against arthritis.
Retinoid receptor‐activating ligands are produced within the mouse thymus during postnatal development
Authors: Kiss Ildikó , Rühl Ralph , Szegezdi Éva , Fritzsche Britta , Tóth Beáta , Pongrácz Judit , Perlmann Thomas , Fésüs László , Szondy Zsuzsa
Published: December 2007

Vitamin A deficiency is known to be accompanied with immune deficiency and susceptibility to a wide range of infectious diseases. Experimental evidence suggests that the active metabolites of vitamin A that mediate its effects on the immune system are the retinoic acids (RA), which are ligands for the nuclear RA receptor (RAR) family. RA were previously shown both to promote proliferation and to regulate apoptosis of thymocytes. In this study we detected the age‐dependent mRNA expression of retinaldehyde dehydrogenases (RALDH1 and 2), cellular RA binding protein‐II and CYP26A, proteins responsible for the synthesis, nuclear transport and degradation of RA in the postnatally developing thymus. RALDH1 was located in thymic epithelial cells. However, the amount of all‐trans RA in thymic homogenates was close to the detection limit, suggesting that in this tissue all‐trans RA is not the main RAR‐regulating product of retinol metabolism. At the same time, by measuring the induction of a RAR‐responsive transgene in two independent transgenic mouse strains, we demonstrated the production of an RAR‐activating ligand, which was age and RALDH dependent. Our data provide evidence for the existence of endogenous retinoid synthesis in the thymus and suggest that retinoids similar to glucocorticoids might indeed be involved in the regulation of thymic proliferation and selection processes by being present in the thymus in functionally effective amounts.
RIP2 contributes to Nod signaling but is not essential for T cell proliferation, T helper differentiation or TLR responses
Authors: Hall Håkan T. L. , Wilhelm Margareta T. , Saibil Samuel D. , Mak Tak W. , Flavell Richard A. , Ohashi Pamela S.
Published: December 2007

Receptor‐interacting protein 2 (RIP2), also known as CARDIAK and RICK, has been reported to play a role in both adaptive T cell responses and innate immunity as a mediator in TLR signaling and nucleotide‐binding oligomerization domain (Nod) signaling. Because initial reports remain controversial, we have further examined both innate and adaptive immune responses in RIP2‐deficient mice on the C57BL/6 background. Despite the up‐regulation of RIP2 after T cell activation, we could not detect any defect in T cell proliferation or Th1/Th2 responses in RIP2‐KO mice. Furthermore, we found that TLR responses in RIP2‐deficient macrophages were normal. However, our analysis showed that Nod signaling was impaired in macrophages from RIP2‐deficient mice. In conclusion, our data demonstrate a critical role for RIP2 in Nod signaling, while T cell proliferation, T helper differentiation and TLR responses were unaffected by the absence of RIP2.
Apoptosis differentially regulates mesenteric and subcutaneous lymph node immune responses to Trypanosoma cruzi
Authors: de Meis Juliana , Ferreira Lidia M. S. , Guillermo Landi V. C. , Silva Elisabeth M. , DosReis George A. , Lopes Marcela F.
Published: December 2007

Infection with Trypanosoma cruzi causes expansion of subcutaneous (SLN) and atrophy of mesenteric (MLN) lymph nodes. Here we show that excision of MLN increased parasitemia in T. cruzi‐infected mice. We then studied how apoptosis of MLN cells affects immune responses to infection. T cell apoptosis increased in the MLN compared to SLN in T. cruzi‐infected mice. Absolute numbers of naïve T cells decreased, and activated T cells failed to accumulate in MLN during infection. In addition, activated T cells from MLN produced less IL‐2, IFN‐γ, IL‐4, and IL‐10 than T cells from SLN. Treatment with IL‐4 or with caspase‐9 inhibitor increased the recovery of viable T cells in vitro. Treatment with caspase‐9 inhibitor also increased the production of cytokines by MLN T cells from infected mice. Moreover, injection of a pan caspase inhibitor prevented MLN atrophy during T. cruzi infection. Caspase‐9, but not caspase‐8, inhibitor also reduced MLN atrophy and increased the recovery of naïve and activated T cells from MLN. These findings indicate that caspase‐mediated apoptosis and defective cytokine production are implicated in MLN atrophy and affect immune responses to T. cruzi infection.
Design and Synthesis of 1‐Benzazepine Derivatives by Strategic Utilization of Suzuki–Miyaura Cross‐Coupling, Aza‐Claisen Rearrangement and Ring‐Closing Metathesis
Authors: Kotha Sambasivarao , Shah Vrajesh R.
Published: December 2007

A new and simple methodology has been realized for the synthesis of 7‐substituted 2,3,4,5‐tetrahydro‐1‐benzazepine derivatives with Suzuki–Miyaura cross‐coupling, aza‐Claisen rearrangement and ring‐closing metathesis (RCM) the key steps. Here,o‐allylacetanilide derivatives were obtained by Suzuki–Miyaura cross‐coupling of the correspondingo‐iodoacetanilides. Theo‐allylacetanilides, onN‐allylation under phase‐transfter catalysis conditions, provided diallyl derivatives as suitable precursors for RCM. These diallyl derivatives, on treatment with Grubbs' second‐generation catalyst, gave the 1‐benzazepine derivatives in moderate‐to‐good yields. These RCM products were found to be unstable and so they were hydrogenated to provide stable tetahydro‐1‐benzazepine derivatives25–28. 1H‐1‐Benzazepin‐2‐one derivatives44and45were synthesized following a similar sequence. In addition, the aza‐Claisen rearrangement was utilized as a key step in the preparation of RCM precursor17. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Response surface examination of the relationship between experimental conditions and product distribution in electrophoretically mediated microanalysis
Authors: Montes Ruth E. , Gomez Frank A. , Hanrahan Grady
Published: December 2007

This work presents the first known use of response surface methodology (RSM) in electrophoretically mediated microanalysis. This concept is demonstrated by examining the optimization of reaction conditions for the conversion of nicotinamide adenine dinucleotide to nicotinamide adenine dinucleotide, reduced form by glucose‐6‐phosphate dehydrogenase (G6PDH, EC 1.1.1.49) in the conversion of glucose‐6‐phosphate to 6‐phosphogluconate. Experimental factors including voltage, enzyme concentration, and mixing time of reaction at the applied voltage were selected at three levels and tested in a Box–Behnken response surface design. Upon migration in a capillary under CE conditions, plugs of substrate and enzyme are injected separately in buffer and allowed to react at variable conditions. Extent of reaction and product ratios were subsequently determined by CE. The model predicted results are shown to be in good agreement (7.1% discrepancy difference) with experimental data. The use of chemometric RSM provides a direct relationship between electrophoretic conditions and product distribution of microscale reactions using CE, thereby offering a new and versatile approach to optimizing enzymatic experimental conditions.
A comparison of preconditioners for incompressible Navier–Stokes solvers
Authors: ur Rehman M. , Vuik C. , Segal G.
Published: December 2007

We consider solution methods for large systems of linear equations that arise from the finite element discretization of the incompressible Navier–Stokes equations. These systems are of the so‐called saddle point type, which means that there is a large block of zeros on the main diagonal. To solve these types of systems efficiently, several block preconditioners have been published. These types of preconditioners require adaptation of standard finite element packages. The alternative is to apply a standard ILU preconditioner in combination with a suitable renumbering of unknowns. We introduce a reordering technique for the degrees of freedom that makes the application of ILU relatively fast. We compare the performance of this technique with some block preconditioners. The performance appears to depend on grid size, Reynolds number and quality of the mesh. For medium‐sized problems, which are of practical interest, we show that the reordering technique is competitive with the block preconditioners. Its simple implementation makes it worthwhile to implement it in the standard finite element method software. Copyright © 2007 John Wiley & Sons, Ltd.