bluuebunny/crossref_metadata_2025 huggingface dataset:
Fraser Syndrome: Affected Siblings Born to Nonconsanguineous Parents and Diagnosed at Autopsy
Authors: De Jong Ann , Warren Miranda , Rehrauer William , Harter Josephine , Baraboo Melissa , Chandra Sunita , Pauli Richard M. , Singer Don B. , Fritsch Michael K.
Published: June 2008

Fraser syndrome (MIM #219000) is a rare genetic disorder with major features including cryptophthalmos, syndactyly, and genital anomalies. We report 2 independently autopsied children of the same nonconsanguineous parents. The siblings exhibit similar clinical features, all of which are consistent with a diagnosis of Fraser syndrome. The gross and microscopic findings provide insight into the highly variable clinical presentation of Fraser syndrome. Molecular diagnostic studies of the index case failed to identify one of the known gene mutations in the FRAS1 and FREM2 genes associated with Fraser syndrome. This raises the possibility that other genes or undetected mutations in the FRAS1/FREM2 genes may cause Fraser syndrome.
Characterization of C4d Immunostaining Utilizing Paraffin-Embedded Tissue of Nonpresensitized Pediatric Heart Transplant Patients
Authors: Galambos Csaba , Feingold Brian , Webber Steven A.
Published: June 2008

Immunoperoxidase techniques for demonstration of complement split product C4d on paraffin-embedded endomyocardial biopsy samples have been used for the evaluation of humoral rejection mainly in adult heart transplantation. Interpretation of suspected humoral rejection in children requires knowledge of the pattern and frequency of C4d deposition in nonpresensitized pediatric heart transplantation patients. Paraffin-embedded endomyocardial biopsy samples of 65 patients with no rejection, acute cellular rejection (ACR), or early ischemic/reperfusion injury were studied. Six biopsies within each grade of ACR both early (<6 months) and late (>6 months) after heart transplantation were reviewed, as were 5 biopsies of ischemic/reperfusion injury. None of the subjects was sensitized prior to transplant. All slides were blindly evaluated for histologic features traditionally associated with humoral rejection. C4d staining was quantified by counting the number of positive capillaries in 10 random high-power fields (hpf). C4d positivity (C4d+) was defined as >10 capillaries/10 hpf. C4d+ was observed in 6 (9%) endomyocardial biopsy samples; 2 in the early and 4 in the late ACR groups. Four had ACR grades 1A/B, and 2 had grade 3B/4. Thirteen (20%) endomyocardial biopsy samples had histologic features suggestive of humoral rejection. Of these, only 2 were C4d+ and both had ACR grade 3B/4. No C4d+ staining was found in the ischemic/reperfusion injury group. C4d immunostaining was negative in endomyocardial biopsy samples of the majority of our patients (91%). Endomyocardial biopsy samples with C4d+ did not show consistent ACR grade or time specificity. Contrary to previously reported data, none of the ischemic/reperfusion injury endomyocardial biopsy samples was C4d+, and histologic features alone were poor predictors of C4d+.
Legitimisation and Proximisation Values in the Discourse of Historic Change
Authors: Wieczorek Anna
Published: June 2008

Legitimisation and Proximisation Values in the Discourse of Historic Change

This methodological-critical paper belongs to the field of pragmaticcognitive discourse analysis. It develops Cap's STA model of legitimisation (2005, 2006, 2008) and investigates various mechanisms legitimising the speaker's actions (or actions for which he bears responsibility) in political discourse of historic change. Proximisation as the salient feature of the model adds significantly to effectiveness of the speaker's continual attempt to convince the addressee of the rightness of political steps taken. It is a powerful and coercive tool "alerting the addressee [to] the proximity or imminence of phenomena which can be a ‘threat’ to the addressee" located in the deictic centre of a given event (Cap 2006:4) or a chain of events. The STA model accounts for the application of a three-dimensional pattern of the phenomenon in question, i.e. spatial, temporal, and axiological proximisation. However, the division does not exhaust the notion's potential, since properties of the dimensions mentioned enable us to classify them according to an extended taxonomic system in which they possess positive, negative, and neutral values (cf. Wieczorek 2008). Thus, the aim of this paper is to (a) analyse the interplay between a number of legitimisation strategies, (b) present the positive/negative/neutral classification of proximisation, and (c) comment on the nature of the interaction between and potency of the three dimensions and values. These can coexist within the body of one text, as well as within the body of one paragraph and their complementary character strengthens the overall goal of legitimisation providing various stimuli for the addressee to accept the speaker's stance, his decisions and actions, to comply with them, and to undertake actions intended by the speaker.
Evidence of a Differential Effect of Ability Grouping on the Reading Achievement Growth of Language-Minority Hispanics
Authors: Robinson Joseph P.
Published: June 2008

Ability grouping is sometimes thought to exacerbate inequality by increasing achievement gaps; however, ability grouping may in fact benefit a fast growing and often marginalized student population: children from non-English-speaking home environments. The level-appropriate, small-group instruction received in reading ability groups may be particularly beneficial to these language-minority children, who are not regularly exposed to English at home. Focusing on Hispanics, who make up the majority of language-minority students, the author examined this hypothesis through difference-in-differences estimation techniques in a hierarchical linear model framework. Ability grouping in reading during kindergarten was significantly associated with greater benefits for language-minority Hispanic students relative to other students. However, this benefit faded during the summer and first grade, unless grouping continued in first grade. These findings are robust to alternative specifications and suggest that differentiated instructional strategies upon school entry may be an effective, relatively low cost tool to combat the achievement gap faced by a fast growing segment of students.
Do Teacher Absences Impact Student Achievement? Longitudinal Evidence From One Urban School District
Authors: Miller Raegen T. , Murnane Richard J. , Willett John B.
Published: June 2008

This article exploits highly detailed data on teacher absences from a large urban school district in the northern United States to shed light on the determinants and effects of teacher absences. The topic is important because both school and district policies can influence teachers’ propensity to be absent. The authors estimate the impact of teacher absences on academic achievement of students matched to elementary school teachers. Models include fixed effects for teachers to control statistically for potential correlation between time-invariant levels of teachers’ skill and effort and their rates of absence. The authors estimate 10 additional days of teacher absence reduce mathematics achievement of fourth-grade students by 3.2% of a standard deviation. They employ an additional instrumental variables strategy to bolster the case for a causal interpretation of results. Instrumental variables results indicate the impact of unexpected teacher absences on student achievement is larger than the impact of anticipated absences.
ThermoCalc-based numerical computations for temperature, fraction of solid phase and composition couplings in alloy solidification
Authors: Zhao Guangwei , Xu Daming , Fu Hengzhi
Published: June 2008

The directional solidification transport behaviors in blade-like castings of Al – Cu and Fe – C alloys were simulated based on a multilength-scale continuum model for solidification transport processes. The simulations were closely coupled with the commercial ThermoCalc package via its TQ-interface codes, for instantaneous determination of the related thermodynamic data at each calculation time step. Comparisons were made between the simulation results obtained by the ThermoCalc-coupled modeling and the model using the regression functions for the solidification thermodynamic data. The present numerical investigations confirm the feasibility of a close linkage of ThermoCalc software/Databases to the solidification simulations, but indicate an urgent need to cut down significantly the CPU-time spent for accessing the ThermoCalc/Databases for an efficient coupled computation.
Phase equilibria of the Al–Ni–Zn system at 340°C
Authors: Xu Honghui , Du Yong , Zhou Yichun , Zheng Xuejun , Xiong Wei , Liu Shuhong , Su Xuping , Yin Fucheng
Published: June 2008

The phase equilibria at 340°C of the Al – Ni – Zn system were investigated by combining the diffusion couple technique with the equilibrated alloys method. The samples were examined by means of optical microscopy, X-ray diffraction, scanning electron microscopy, and electron probe microanalysis. Two ternary compounds (1 and 2) were found to exist at 340°C. The solubilities of Zn in AlNi, Al3Ni2 and Al3Ni were determined to be about 20, 2 and 1 at.% Zn, respectively. The solubilities of Al in β1-NiZn and in were measured to be about 11.5 and 1 at.% Al, respectively. The solubilities of Zn in both AlNi3 and Al3Ni5 are below 1 at.% Zn.
Construction of the Al–Ni–Si phase diagram over the whole composition and temperature ranges: thermodynamic modeling supported by key experiments and first-principles calculations
Authors: Xiong Wei , Du Yong , Hu Rong-Xiang , Wang Jiong , Zhang Wei-Wei , Nash Philip , Lu Xiao-Gang
Published: June 2008

An extensive thermodynamic investigation of the Al – Ni – Si system is carried out via an integrated approach of calculation of phase diagrams, first-principles calculations, and key experiments. Eighteen decisive alloys are prepared in order to verify the existence of the previously reported ternary compounds and to provide new phase equilibrium data. Phase compositions, microstructure, and phase transition temperatures are determined using the combined techniques of X-ray diffraction, scanning electron microscopy, energy dispersion X-ray analysis, and differential thermal analysis. The order/disorder transition between disordered bcc_A2 and ordered bcc_B2 phases as well as that between disordered fcc_A1 and ordered L12 phase are described using a two-sublattice model. A self-consistent parameter set is finally obtained by considering the huge amount of experimental data including 13 vertical sections and 5 isothermal sections from both the literature and the present experiments. Almost all of the reliable phase diagram data can be well described by the present modeling. The reliability of the calculated thermodynamic properties for ternary phases is verified through enthalpy measurement employing drop calorimetry and first-principles calculations. The thermodynamic parameters obtained can also successfully predict most of the thermodynamic properties and describe the solidification path for the selected as-cast alloy Al6Ni55Si39.
Phase equilibria in the Y–Ti–Si system at 773 K
Authors: Zhan Yongzhong , Yu Zhengwen , Li Chunhui , Guo Qinghua , Hu Zhaohua , Zhuang Yinghong
Published: June 2008

Physico-chemical analysis techniques, including X-ray powder diffraction, scanning electron microscopy, optical microscopy and differential thermal analysis were employed in constructing the isothermal section of the Y – Ti – Si system at 773 K. The isothermal section consists of 12 single phase regions, 21 binary phase regions and 10 ternary phase regions. No ternary compound is found in the work. None of the phases in this system reveals a remarkable homogeneity range at 773 K.
Thermodynamic description of the Ce-Mg-Y and Mg-Nd-Y systems
Authors: Guo Cuiping , Du Zhenmin , Li Changrong
Published: June 2008

The thermodynamic modeling and optimization of the Ce-Mg, Ce-Y, Mg-Nd, Nd-Y, Ce-Mg-Y and Mg-Nd-Y systems have been carried out by means of the CALPHAD technique. The solution phases, liquid, body-centered cubic, face-centered cubic, hexagonal close-packed and double hexagonal close-packed, were described by the substitutional solution model. The isostructural MgCe, MgNd and MgY phases with B2 structure form continuous range of solid solutions in the Ce-Mg-Y and Mg-Nd-Y ternary systems. The order-disorder transition between the solutions with A2 structure and compounds with B2 structure in the systems has been taken into account and thermodynamically modeled. The other compounds Mg2Y, Mg24Y5, Mg3R, Mg41R5, Mg2R and Mg12Ce (R = Ce and Nd) in the Mg-R-Y system exhibit different solubilities of the third component. A set of self-consistent thermodynamic descriptions of the Ce-Mg-Y and Mg-Nd-Y systems was obtained.
First-principles calculations of the thermodynamic and elastic properties of the L12-based Al3RE (RE = Sc, Y, La–Lu)
Authors: Tao Xiaoma , Ouyang Yifang , Liu Huashan , Feng Yuanping , Du Yong , Jin Zhanpeng
Published: June 2008

First-principles calculations of the total energy and elastic properties of the L12-based Al3RE (RE = Sc, Y, Lanthanide) at T = 0 K are performed by using the projector augmented-wave method within the generalized gradient approximation. The lattice constants, formation enthalpies, elastic constants and bulk modulus of the L12-based Al3RE are obtained. Young's modulus, shear modulus and Poisson's ratios are also estimated in the present work. By using the Debye – Grüneisen model, the Debye temperatures, Grüneisen constants and the sound velocity are obtained for the L12-based Al3RE. All the calculated results are in good agreement with experimental values and other theoretical calculations available.
Thermodynamic description of multi-component multi-phase alloys and its application to the solidification process
Authors: Jie Wanqi , Zhang Ruijie , He Zhi
Published: June 2008

Metallic materials in engineering applications are mostly multi-component and multi-phase alloys. The solidification principles of these materials still lack quantitative description. In this work, the solute partition behavior and its influence on the solidification process of multi-component alloys are studied based on CALPHAD.

A complete thermodynamic model for the accurate calculation of the partition coefficients in solidification is described. The model is applied to Al – Si – Mg ternary alloys, and the predicted partition coefficients are compared with some former experimental data. Good agreement between the calculation results and the experimental data demonstrates the validity of the present model.

The variation of solute partition coefficients of both Si and Mg is studied in dendritic solidification of Al – Si – Mg alloys. It is found that the partition coefficient changes greatly during solidification. By coupling CALPHAD with a micro-scale solidification model, the predicted solidification path for different composition and cooling rates and the off-eutectic fraction of Al – Si – Mg alloys agrees well with the experimental results.

The conventional theory of constrained dendrite growth for binary alloys is extended to multi-component alloys based on the CALPHAD method with consideration of the solute interactions, through which the primary dendrite spacing is estimated.
Phase-diagram-related problems in thermoelectric materials: Skutterudites as an example
Authors: Shi X. , Zhang W. , Chen L. D. , Uher C.
Published: June 2008

CoSb3 is a very promising thermoelectric semiconductor with narrow gap and good electrical transport properties. It is also a special compound with an intrinsically caged crystal structure. By taking void filling in the intrinsic cages and impurity substitution for Co in the skutterudites as examples, a few phase-diagram-related problems in thermoelectric materials are discussed. The first topic shows that the filling fraction limit for an impurity in the crystal voids could be taken as a phase-diagram-related issue to be solved by first-principles energetic calculations. But the partial void filling also reveals that the structural integrity of a compound with special structure is very sensitive to electron filling and its influence on chemical bonding, which needs further study. This is assumed to be a general problem linking with the group of compounds with special 2-D layered or 3-D caged structures, a focus of current thermoelectric research. The second topic relates to the solid solution problem when mixing CoSb3 with IrSb3 (or RhSb3) to realize new materials with random distribution of Ir or Rh at Co sites. By going through most of the currently state-of-the-art thermoelectric compounds including CoSb3/IrSb3, PbTe/(Ag,Sb)Te2, MgSi2/MgSn2/MgGe2, and ZrNiSn/HfNiSn, it is found that their mixing enthalpies are usually slightly positive, implying the possibility of mixing 2- or 3-similar compounds to realize nanocomposites with low internal strain for promising performance. Related experimental and theoretical issues on nanocomposite thermoelectrics are briefly discussed.
Tropical forest structure and diversity in relation to altitude and disturbance in a Biosphere Reserve in central India
Authors: Sahu P.K. , Sagar R. , Singh J.S.
Published: June 2008

Questions: Is species diversity affected in protected areas where human activities are permitted or tolerated? On plots of a fixed size, does stem density alone predict number of species? Are differences in density related to disturbance and altitude?

Location: Achanakmar‐Amarkantak Biosphere Reserve, central India.

Methods: 42 sites, each with three replicate 10‐m radius plots, were examined. All trees (≥ 30 cm GBH) in each plot were measured for girth at breast height. α‐diversity, species richness and evenness were calculated for each site. The sites were ordinated by Nonmetric Multidimensional Scaling (NMS) using relative importance values of component species. Correspondence Analysis was used to broadly delineate communities. Anthropogenic disturbances were recorded in terms of percentage of trees lopped, scale of lopping, number of domestic livestock dung piles and foot trails (both livestock and people) for each plot.

Results: The NMS analysis exhibited a near linear arrangement of sites with no evidence of discrete vegetation zones. NMS axes were significantly related to altitude and disturbance scores. With increasing elevation, basal area increased but number of species, α‐diversity and its components declined monotonically. The number of species and indices of species diversity were positively associated with tree lopping and also with total disturbance. Number of species was controlled by stem density only in plots not dominated by Shorea robusta.

Conclusions: Recent levels of human disturbance are associated with higher species diversity in this biosphere reserve. There is some evidence that stands at all altitudes follow the same successional pattern to dominance by Shorea, a successional pattern that also results in decreased diversity without disturbance.
Land use designation and vegetation community structure in the Adirondack uplands (New York, USA)
Authors: Woodcock T. , Evans C. , Laxson C. , Tucker R. , Allen J. , Mihuc J. , Allen E. , Mihuc T.
Published: June 2008

Question: Does forest vegetation community structure reflect legislative land use designations?

Location: Adirondack Park, New York, USA.

Methods: The Adirondack Park, located in northern New York State, is a mixture of public and private lands, with state‐owned Forest Preserve lands comprising ca. 42% of the 2.4 million ha, on which timber harvesting and many other forms of anthropogenic disturbance are prohibited. A survey of vegetation communities was conducted in eighteen upland catchments with differing land use history (managed and Forest Preserve), including overstory, understory, and dead wood (snags and downed woody debris) using randomly placed plots.

Results: Mean overstory density and basal area were not significantly different between land uses, although mean overstory tree size was greater in Preserve catchments. Sapling densities were greater in managed catchments, while mean herb/shrub coverage was not affected by land use. Densities of 25% of common species were affected by land use, determined by GIS coverages constructed using an Inverse Distance Weighted estimation procedure. Discriminant Analysis of per‐plot plant community data correctly classified 89% of both managed and Preserve plots.

Conclusion: The success of the Discriminant Analysis in classifying land uses based on vegetation communities indicates its potential utility of this method in comparing forest vegetation to a reference condition in this and other areas. The analysis suggests that at least 85 years is required for Adirondack up‐land catchments to recover following harvesting. Uncertainty in classification was related to heterogenous management and disturbance patterns within catchments.
Roadside revegetation with native plants: Experimental seeding and transplanting of stem cuttings
Authors: Mallik Azim U. , Karim M.N.
Published: June 2008

Questions: Can we use local native plants for roadside revegetation? What cultural methods help enhance the process?

Location: Trans Canada Highway, Terra Nova National Park, Newfoundland.

Objectives: To (1) test stratification requirements for seed ger‐mination, (2) determine if germination, survival and growth of seedlings and stem cuttings of selected plants can be increased by mulching treatments and (3) identify native plants and cultural treatments useful for revegetation.

Methods: We tested seed germination of Kalmia angustifoliaIris versicolorJuncus effususEriophorum vaginatum, Clintonia borealis and Cornus canadensis in a greenhouse experiment. We conducted field experiments of roadside revegetation using seeds of K. angustifolia, I. versicolorJ. effusus and E. vaginatum, as well as seedlings of I. versicolor and rooted stem cuttings of Emptrum nigrum and Juniperus communis after hay‐mat mulch and organic matter mulch application.

Results: Stratified seeds of K. angustifoliaI. versicolor, J. effusus and E. vaginatum germinated successfully in the greenhouse, whereas C. borealis and C. canadensis seeds did not. Along roadsides, only I. versicolor seeds germinated. Iris versicolor cover increased significantly in organic matter mulch compared to hay‐mat mulch and control. Transplanted I. versicolor seedlings had high survival in all treatments but growth was reduced in organic matter mulch. Survival and growth of stem cuttings of E. nigrum and J. communis were significantly increased on hay‐mat mulch.

Application: Rooted stem cuttings of E. nigrum and J. communis planted on hay‐mat mulch can be used as a practical method of roadside revegetation. These shrubs have low structure, are evergreen, and exhibit stress‐tolerance properties, which make them ideal species for roadside revegetation. They are also non‐palatable to wildlife. Roadside ditches can be revegetated by seeds or seedlings of I. versicolor. Robust roots and rhizomes of this plant may provide soil stability and dark green leaves and attractive flowers create aesthetically pleasing vegetation cover.
HEDONIC ANALYSIS OF PRICE IN THE ISTANBUL HOUSING MARKET
Authors: Keskin Berna
Published: June 2008

The purpose of this paper is to explore the factors that affect housing prices in Istanbul. A hedonic price model is employed in order to examine housing price determinants with respect to property characteristics, socio‐economic characteristics, neighbourhood quality characteristics, and locational factors. The results reveal that housing prices are affected by these factors: living area size, being in a low storey building, being in a secured site (with swimming pool and garage), and age of the building. In addition to these determinants, the length of time the inhabitants have lived in Istanbul, the average income of the household, neighbour satisfaction and earthquake risk of the area have effects on the residential prices in Istanbul. Further research is suggested by constructing a second model that includes neighbourhood dummy variables as a proxy for submarkets, and a multi‐level modelling framework will be employed in order to analyse the urban housing submarket system. Santrauka Šiame darbe siekiama išnagrinėti veiksnius, kurie daro įtaką būsto kainoms Stambule. Pa si tel kus hedoninį kainų modelį, tyrinėjami būsto kainas lemiantys veiksniai, atsižvelgiant į nekilnojamojo turto charakteristikas, socialinius-ekonominius veiksnius, apylinkių kokybės bruožus ir vietos veiksnius. Rezultatai rodo, kad būsto kainoms įtaką daro tokie veiksniai: gy ve namosios teritorijos dydis, pastato aukštingumas, buvimas sklype ir pastato amžius. Be šių veiksnių, būsto kainas Stambule veikia ir laikas gyventas mieste, vidutinės namų ūkio pajamos, patinkantys kaimynai bei žemės drebėjimų rizika toje terito ri jo je. Siūloma atlikti tolesnius tyrimus, suformuojant antrą fi ktyviuosius apylinkių kintamuosius apimantį modelį, kuris bus taikomas kaip subrinkų pakaitalas, o naudojant daugialypę modeliavimo struktūrą bus siekiama išanalizuoti miesto būsto subrinkos sistemą.
DETERMINANTS OF COMMERCIAL MORTGAGE‐BACKED SECURITIES CREDIT RATINGS: AUSTRALIAN EVIDENCE
Authors: Chikolwa Bwembya , Chan Felix
Published: June 2008

Using artificial neural networks (ANN) and ordinal regression (OR) as alternative methods to predict Commercial Mortgage‐backed Securities (CMBS) credit ratings, we examine the role that various financial and industry‐based variables have on CMBS credit ratings issued by Standard and Poor's from 1999–2005. Our OR results show that rating agencies use only a subset of variables they describe or indicate as important to CMBS credit rating as some of the variables they use were statistically insignificant. Overall, ANN show superior results to OR in predicting CMBS credit ratings. Santrauka Sisteminant komercine hipoteka užtikrintų vertybinių popierių prekybos sandorius, svarbiausias tikslas – gauti aukštą kredito reitingą, nes tai daro poveikį pelningumui ir emitento sėkmei. Kredito reitingų agentūros teigia, kad jų vertinimai išreiškia kiekvienos agentūros nuomonę apie potencialią emitento nemokumo riziką ir daugiausia remiasi emitento gebėjimo bei noro grąžinti savo skolą analize, kurią atlieka komitetas, taigi tyrinėtojams jų reitingų kiekybiškai replikuoti nepavyktų. Tačiau tyrinėtojai replikavo obligacijų reitingus, remdamiesi prielaida, kad finansiniai koefi cientai turi daug informacijos apie įmonės kredito riziką. Prognozuodami komercine hipoteka užtikrintų vertybinių popierių reitingus, kaip alternatyvius metodus naudojame dirbtinius neuroninius tinklus ir ranginę regresiją. Ranginės regresijos rezultatai rodo, kad reitingų agentūros naudoja tik tą kintamųjų poaibį, kuriuos jos apibūdina arba nurodo kaip svarbius komercine hipoteka užtikrintų vertybinių popierių reitingui, nes kai kurie iš naudojamų kintamųjų statistiškai nereikšmingi. Apskritai dirbtinių neuroninių tinklų rezultatai, prognozuojant komercine hipoteka užtikrintų vertybinių popierių reitingus, geresni nei ranginės regresijos.
Numerical characterization of three‐dimensional serpentine micromixers
Authors: Park Jang Min , Kwon Tai Hun
Published: June 2008

Three‐dimensional serpentine micromixer (TSM) has been well known to be an attractive design because of its simple fabrication and efficient mixing performance, but its basic characteristics have not been fully investigated notwithstanding several reports in the past. The present article comprehensively investigates flow and mixing characteristics of TSM. Three major mixing mechanisms are identified, namely rotation, lamination, and chaotic advection. The mixing performance of TSM is analyzed and compared in terms of the three mechanisms by means of numerical analysis with three representative types as examples of TSM: (1) serpentine type C; (2) serpentine type L; (3) improved serpentine laminating micromixer. Numerical analysis system based on a finite element method and a colored particle tracking method enables not only flow visualization but also computation of Poincaré section and Lyapunov exponent for a dynamical system analysis of TSM. © 2008 American Institute of Chemical Engineers AIChE J, 2008
Clinical and genetic heterogeneity in patients with mosaic variegated aneuploidy: Delineation of clinical subtypes
Authors: García‐Castillo Herbert , Vásquez‐Velásquez Ana Isabel , Rivera Horacio , Barros‐Núñez Patricio
Published: June 2008

Mosaic variegated aneuploidy (MVA) is a rare autosomal recessive syndrome related to BUB1B gene mutations and characterized by multiple mosaic aneuploidies, cancer predisposition, and a distinct phenotype. We report on two mildly affected sibs with MVA syndrome but without BUB1B mutation. Both patients exhibited growth retardation, frontal bossing, triangular face and micrognathia but not microcephaly or cancer. Aneuploidies were assessed both in G‐banded metaphases from lymphocyte cultures and in interphase nuclei from buccal cells by FISH. Screening of 23 exons and intron–exon boundaries of BUB1B was also carried out. These patients were then compared with other 19 MVA patients screened for BUB1B mutations. Around one half of the cultured lymphocytes from our patients had aneuploidies ranging from nullisomies to heptasomies; the most frequent abnormalities were trisomies (42%) and monosomies (28%). FISH results demonstrated more chromosomal losses than gains. Screening of BUB1B in our two patients failed to identify any mutation. A review of the 21/35 patients screened for BUB1B demonstrated three clinical pictures. Patients with monoallelic BUB1B mutations were severely affected with Dandy‐Walker complex (7/8), cataracts (6/6), and Wilms' tumor (7/8); premature chromatid separation (PCS) was observed in 8/8 propositi and 7/7 carrier parents. Patients without BUB1B mutations were mildly affected with no evidence of cancer, Dandy‐Walker malformation or cataract, and rarely (1/7) showed PCS. Finally, patients with biallelic BUB1B mutations showed a moderate phenotype. The distinct MVA clinical groups delineated here point to involvement of at least another mitotic spindle checkpoint gene in addition to the BUB1B gene. © 2008 Wiley‐Liss, Inc.
Novel thermally and mechanically stable hydrogel for enzyme immobilization of penicillin G acylase via covalent technique
Authors: Elnashar Magdy M. M. , Yassin Mohamed A. , Kahil Tarek
Published: June 2008

κ‐Carrageenan hydrogel crosslinked with protonated polyethyleneimine (PEI+) and glutaraldehyde (GA) was prepared and evaluated as a novel biocatalytic support for covalent immobilization of penicillin G acylase (PGA). The method of modification of the carrageenan biopolymer is clearly illustrated using a schematic diagram and was verified by FTIR, elemental analysis, DSC, and INSTRON using the compression mode. Results showed that the gels' mechanical strength was greatly enhanced from 3.9 kg/cm2 to 16.8 kg/cm2 with an outstanding improvement in the gels thermal stability. It was proven that, the control gels were completely dissolved at 35°C, whereas the modified gels remained intact at 90°C. The DSC thermogram revealed a shift in the endothermic band of water from 62 to 93°C showing more gel‐crosslinking. FTIR revealed the presence of the new functionality, aldehydic carbonyl group, at 1710 cm−1 for covalent PGA immobilization. PGA was successfully immobilized as a model industrial enzyme retaining 71% of its activity. The enzyme loading increased from 2.2 U/g (control gel) to 10 U/g using the covalent technique. The operational stability showed no loss of activity after 20 cycles. The present support could be a good candidate for the immobilization of industrial enzymes rich in amino groups, especially the thermophilic ones. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Preparation of modified polystyrene with maleic anhydride in the presence of different solvents
Authors: Sayed Wafaa M.
Published: June 2008

Polystyrenes (PS's) with different molecular weights were chemically modified with maleic anhydride (MA) with of benzoyl peroxide as an initiator or with a cationic catalyst such as FeCl3 in chloroform. The effect of the solvents (i.e.; chloroform, benzene, toluene, xylene, and tetrahydrofuran), PS and MA concentration, molecular weight of PS, and type of catalyst used in the chemical modification was studied. The rate of the reaction was different with different solvents because of chain transfer to the solvent. The IR spectra of the modified polystyrene (MPS) existing at the end of the chemical modification were taken to show the presence of a carboxyl group fixed to the aromatic ring of PS. The kinetics of the reaction of MPS with MA were also studied. MPS samples containing COCHCH COOH fragments inside chains were crosslinked, as proven by differential thermal analysis. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Use of methacrylic acid grafted poly(ethylene terephthalate) fibers for the removal of basic dyes from aqueous solutions
Authors: Arslan Metin , Yiğitoğlu Mustafa
Published: June 2008

A reactive fibrous adsorbent was prepared through the grafting of a methacrylic acid monomer onto poly(ethylene terephthalate) fibers for the removal of basic dyes such as methylene blue and basic red 9 from aqueous solutions through a batch adsorption method. Effects of various parameters such as the grafting yield, pH, treatment time, initial dye concentration, and adsorption temperature on the amount of dye adsorbed onto reactive fibers were investigated. The adsorption amounts of basic dyes increased with increases in the grafting yield, pH, treatment time, initial dye concentration, and adsorption temperature. The rates of adsorption conformed to pseudo‐second‐order kinetics with a good correlation. The equilibrium data for methylene blue and basic red 9 adsorption fit the Langmuir equation, with maximum adsorption capacities of 200 and 250 mg/g, respectively. The adsorption rates of two basic dyes were much higher on the grafted poly(ethylene terephthalate) fiber than on the ungrafted poly(ethylene terephthalate) fiber. Within 45 min, about 99% of the cationic dyes was removed from the solutions (400 mg/L) by methacrylic acid‐graft‐poly (ethylene terephthalate) fibers. The highest desorption amounts for methylene blue and basic red 9 were 62 and 84%, respectively. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Formation of new thermosets by the reaction of cyanates with thiophenols
Authors: Bauer Monika , Bauer Jörg
Published: June 2008

Sulfur‐containing aromatic thermosets, mainly consisting of aryloxy‐ and arylthio‐substituted 1,3,5‐triazines, have been prepared through the reaction of difunctional cyanates with mono‐ and difunctional aromatic thiols. A straightforward three‐step reaction scheme is proposed and verified by the identification of key substances: (1) the addition of thiol and cyanate groups, (2) the stepwise addition of (thio)imino carbonic esters with one another, and (3) the ring closure of chain‐extended (thio)imino carbonic esters to form 1,3,5‐triazines. Reactions of types 2 and 3 are associated with an abstraction of phenol or thiophenol, which can enter into reaction 1 again. Characterization of the curing behavior of dicyanate of bisphenol A with thiophenol as well as dimercaptodiphenyl sulfide by differential scanning calorimetry shows that the reaction rates are significantly enhanced by the admixture of thiols to the cyanate. Dynamic mechanical analysis of resulting thermosets showed that large amounts of comonomers can be incorporated into the network resulting in a decrease of glass temperature but increase of fracture toughness. Finally, the fully cured thermosets resulting from the reaction of dicyanate of bisphenol A with different admixtures of dimercaptodiphenyl sulfide were characterized by cone calorimetry to get information about flame retardancy. The flame retardancy is influenced by incorporation of dimercaptodiphenyl sulfide into the triazine network only slightly. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Synthesis and properties of aliphatic polycarbonates derived from carbon dioxide, propylene oxide and maleic anhydride
Authors: Song P. F. , Xiao M. , Du F. G. , Wang S. J. , Gan L. Q. , Liu G. Q. , Meng Y. Z.
Published: June 2008

Terpolymerization of carbon dioxide (CO2) with propylene oxide (PO) and maleic anhydride (MA) was successfully carried out using supported zinc glutarate catalyst. Consequently giving high molecular weight poly(propylene carbonate maleate) (PPCMA) in a very high yield (72.5 g polymer/g catalyst). The resulting terpolymers were fully characterized by FTIR, 1H NMR, 13C NMR, and wide‐angle X‐ray diffraction (WAXD) techniques. NMR measurements showed that PPCMA had an almost alternating structure for the components of carbon dioxide and PO. The influence of molecular weight and MA content on the properties of PPCMA was also investigated. Differential scanning calorimetry (DSC) measurements revealed that the glass transition temperature (Tg) of PPCMA increased with increasing molecular weight. Thermogravimetric analysis (TGA) indicated that PPCMA51 exhibited a very high decomposition temperature (263°C) due to the introduction of the double bond of MA into the backbone of terpolymer. The terpolymers with double bonds can be readily subjected to crosslinking reaction in high temperature to give a slightly crosslinked PPCMA, which exhibit superior thermal stability. Tensile tests also showed that the mechanical properties of PPCMA increased with increasing molecular weight. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Effects of the functionality of polyol in rigid polyurethane foams
Authors: Lim Ho , Kim Sung Hee , Kim Byung Kyu
Published: June 2008

Rigid polyurethane foams (RPUFs) have been fabricated from crude MDI (CMDI) and polypropylene glycols (PPGs) of various functionalities (f) with HFC 365mfc as a blowing agent. Foam density increased, cell size and density distribution decreased with increasing f while the closed cell content was kept constant over 92%. The gel time, tack‐free time, volume change, and the thermal conductivity of the foam showed a minimum with f = 5, and the existence of minimum has been explained in terms of a large mixture viscosity and cell wall resistance. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Back‐calculation of the die swell phenomenon of rubber compounds by means of torsional rheometry
Authors: Müllner Herbert W. , Ernst Gerald , Eberhardsteiner Josef
Published: June 2008

The die swell phenomenon of capillary experiments with various ratios of length to diameter of capillary dies is investigated. This knowledge is important for the design of injection heads for the extrusion of rubber profiles. To predict the die swell of capillary experiments, additional tests with a torsional rheometer has been performed. For polymers, the combination of such rheological data is possible under usage of the empirical relationship by Cox and Merz. With the introduction of a scaling factor this rule is also applicable for rubber compounds. With the relationship of Laun and the new scaling factor a back‐calculation of the first normal stress difference is done. Finally, the die swell of arbitrary capillary experiments for industry‐used rubber compounds can be computed without introduction of new material parameters. For this task a relationship of Tanner is used, which connects the die swell and the first normal stress difference. An adaptation of the capillary viscometer allows the experimental investigation of the die swell and, thus, a validation of the presented approach. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Morphological aspects of rubber fracture and wear
Authors: Bieliński D. M. , Dobrowolski O. , Przybytniak G.
Published: June 2008

Morphology of carbon black (CB)‐filled rubber was studied with AFM and SEM and the classification of filler agglomerates, based on their internal structure and filler–matrix interactions, has been proposed. It varies according to the activity of CB and the kind of rubber. It has been shown that fracture of rubber starts either inside filler agglomerates (de‐cohesion) or in a filler–matrix interphase (de‐adhesion) initiating wear of the material. Microscopic observations correlate well with TGA and EPR data of wear debris collected during friction of rubber. The increase of thermal stability of CB and the appearance of additional spin signals, respectively, for elongated samples or debris, are proposed to be associated with de‐cohesion or de‐adhesion of the agglomerates. New approach to the fracture of rubber called “fatal agglomerate concept” is presented. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Nonclinical pharmacokinetics of BMS‐292655, a water‐soluble prodrug of the antifungal ravuconazole
Authors: Knipe Jay O. , Mosure Kathleen W.
Published: June 2008

The phosphate ester, BMS‐292655, was developed as a water‐soluble prodrug of the antifungal agent, ravuconazole (BMS‐207147). BMS‐292655 was comparatively stable in rat, beagle dog, cynomolgus monkey and human plasma, but was hydrolysed upon incubation with liver S9 preparations from all species. The major product in rat, monkey and human S9 was BMS‐207147, while in dog S9, the intermediate ester, BMS‐300043, predominated. BMS‐300043 itself was more stable in dog S9 than in S9 preparations from the other species. Intravenous administration of BMS‐292655 to rats, beagle dogs and cynomolgus monkeys indicated species differences in the extent of formation of BMS‐207147 (monkeys>rats>dogs). The lower overall generation of BMS‐207147 in dogs was consistent with the presence of circulating plasma levels of BMS‐300043. BMS‐300043 was present in monkey plasma but not detectable in rat plasma. The conversion of BMS‐292655 to BMS‐207147 in the presence of human S9 indicated the potential for BMS‐292655 to function as a BMS‐207147 prodrug in humans. The similarity in the hydrolysis of BMS‐292655 when incubated with human and monkey S9 in vitro, coupled with the effective release of BMS‐207147 from BMS‐292655 upon i.v. administration to monkeys, is consistent with this conclusion. Copyright © 2008 John Wiley & Sons, Ltd.
Pharmacokinetics of glycyrrhizin in normal and albumin‐deficient rats
Authors: Koga Kenjiro , Tomoyama Michiko , Ohyanagi Kazuo , Takada Kanji
Published: June 2008

The pharmacokinetics of glycyrrhizin (GZ) was compared in albumin‐deficient rats (NAR) and normal rats (SDR) after intravenous administration. The study sought to clarify the relationship between GZ concentration and its elimination rate in serum, liver and bile when the serum protein binding of GZ decreased. Serum protein binding in SDR and NAR, respectively, was 99.7% and 68.2% for a GZ concentration of 2.5 µg/ml. At steady‐state conditions after i.v. infusion of GZ (0.5–2.0 mg/h), the relationship between the GZ concentration in serum and liver was linear in the SDR but nonlinear in the NAR. For both NAR and SDR, the GZ liver level and the elimination rate was nonlinear, indicating that the elimination of GZ from liver into bile was the rate‐limiting step regardless of serum protein binding, and that the liver GZ level was extremely high when serum protein binding was decreased. It is concluded that a typical dose of GZ in chronic hepatitis patients whose serum albumin level is low will not cause a decrease of therapeutic effect compared with patients with a normal serum albumin level. Copyright © 2008 John Wiley & Sons, Ltd.
Case study and application of process analytical technology (PAT) towards bioprocessing: II. Use of ultra‐performance liquid chromatography (UPLC) for making real‐time pooling decisions for process chromatography
Authors: Rathore Anurag S. , Wood Rebecca , Sharma Ashutosh , Dermawan Shinta
Published: June 2008

Process analytical technology (PAT) has been gaining a lot of momentum in the biopharmaceutical community due to the potential for continuous real‐time quality assurance resulting in improved operational control and compliance. Two of the key goals that have been outlined for PAT are “variability is managed by the process” and “product quality attributes can be accurately and reliably predicted over the design space established for materials used, process parameters, manufacturing, environmental, and other conditions”. Recently, we have been examining the feasibility of applying different analytical tools for designing PAT applications for bioprocessing. We have previously shown that a commercially available online high performance liquid chromatography (HPLC) system can be used for analysis that can facilitate real‐time decisions for column pooling based on product quality attributes (Rathore et al., 2008). In this article we test the feasibility of using a commercially available ultra‐ performance liquid chromatography (UPLC) system for real‐time pooling of process chromatography columns. It is demonstrated that the UPLC system offers a feasible approach and meets the requirements of a PAT application. While the application presented here is of a reversed phase assay, the approach and the hardware can be easily applied to other modes of liquid chromatography. Biotechnol. Bioeng. 2008;101: 1366–1374. © 2008 Wiley Periodicals, Inc.
Stabilization of α‐chymotrypsin upon PEGylation correlates with reduced structural dynamics
Authors: Rodríguez‐Martínez José A. , Solá Ricardo J. , Castillo Betzaida , Cintrón‐Colón Héctor R. , Rivera‐Rivera Izarys , Barletta Gabriel , Griebenow Kai
Published: June 2008

Protein stability remains one of the main factors limiting the realization of the full potential of protein therapeutics. Poly(ethylene glycol) (PEG) conjugation to proteins has evolved into an important tool to overcome instability issues associated with proteins. The observed increase in thermodynamic stability of several proteins upon PEGylation has been hypothesized to arise from reduced protein structural dynamics, although experimental evidence for this hypothesis is currently missing. To test this hypothesis, the model protein α‐chymotrypsin (α‐CT) was covalently modified with PEGs with molecular weights (MW) of 700, 2,000 and 5,000 and the degree of modification was systematically varied. The procedure did not cause significant tertiary structure changes. Thermodynamic unfolding experiments revealed that PEGylation increased the thermal transition temperature (Tm) of α‐CT by up to 6°C and the free energy of unfolding [ΔGU (25°C)] by up to 5 kcal/mol. The increase in stability was found to be independent of the PEG MW and it leveled off after an average of four PEG molecules were bound to α‐CT. Fourier‐transformed infrared (FTIR) H/D exchange experiments were conducted to characterize the conformational dynamics of the PEG‐conjugates. It was found that the magnitude of thermodynamic stabilization correlates with a reduction in protein structural dynamics and was independent of the PEG MW. Thus, the initial hypothesis proved positive. Similar to the thermodynamic stabilization of proteins by covalent modification with glycans, PEG thermodynamically stabilizes α‐CT by reducing protein structural dynamics. These results provide guidance for the future development of stable protein formulations. Biotechnol. Bioeng. © 2008 Wiley Periodicals, Inc.