bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of the nuclease inhibitor aurintricarboxylic acid (ATA) for improved non‐viral intratumoral in vivo gene transfer by jet‐injection
Authors: Walther Wolfgang , Stein Ulrike , Siegel Robert , Fichtner Iduna , Schlag Peter M.
Published: November 2004

Background

Stability, integrity and retention of the DNA within the targeted tissue is decisive for efficient gene transfer using naked DNA. Pre‐clinical and clinical studies require reproducible transfection rates by preventing rapid degradation of naked DNA in the transduced tissue. Tumor tissues contain nuclease activity, which can affect DNA stability if naked DNA is used. Therefore, inhibition of nuclease‐mediated DNA degradation by the nuclease inhibitor aurintricarboxylic acid (ATA) might lead to improved gene transfer efficiency in tumor tissues.

Methods

For both, DNA‐degradation analysis and in vivo gene transfer experiments, the β‐galactosidase (LacZ)‐expressing pCMVβ and the cytosine deaminase (CD)‐expressing pCMV‐CD plasmid were used. Influence of the nuclease inhibitor ATA was determined in tumors, in which naked pCMVβ or pCMV‐CD DNA and ATA was co‐administered by jet‐injection. The nuclease activity and inhibition by ATA was analyzed using the DNase Alert detection system. The influence of ATA on LacZ expression was determined by specific ELISA and its effect on the therapeutic efficacy of CD gene transfer on tumor growth was determined in vivo.

Results

The screening of different human mammary and colon carcinoma models revealed strong nuclease activity rapidly degrading naked plasmid DNA. Co‐administration of ATA with pCMVβ or pCMV‐CD for in vivo jet‐injection of tumors prevented DNA from nuclease degradation associated with either increased LacZ gene expression or improved reduction in tumor growth.

Conclusions

Tumor‐associated nuclease activity is a notable hurdle in gene transfer of naked DNA and therefore inhibition of nucleolytic degradation of plasmid DNA facilitates intratumoral gene expression. Copyright © 2004 John Wiley & Sons, Ltd.
Analysis of the glucocerebrosidase gene in Parkinson's disease
Authors: Sato Christine , Morgan Angharad , Lang Anthony E. , Salehi‐Rad Shabnam , Kawarai Toshitaka , Meng Yan , Ray Peter N. , Farrer Lindsay A. , St George‐Hyslop Peter , Rogaeva Ekaterina
Published: November 2004

Parkinson's disease (PD) is a common progressive neurodegenerative disorder characterized clinically by a combination of motor symptoms. Identifying novel PD genetic risk factors is important for understanding its pathogenesis. A recent study suggested that up to 21% of subjects with PD may have mutations in the glucocerebrosidase (GBA) gene. We investigated the GBA gene for mutations in 88 PD cases and 122 normal controls and detected the presence of heterozygous GBA mutations in 5 PD cases and in 1 control. Sequencing of the entire open reading frame of the GBA gene in a subset of 25 cases with early‐onset PD (<50 years of age) uncovered no additional mutations. Our results demonstrate a marginally significant association of GBA mutations with PD and suggest that variations in the GBA gene may constitute a rare susceptibility factor for PD (P = 0.048). © 2004 Movement Disorder Society
Pre‐handover signalling for QoS aware mobility management
Authors: Chaouchi Hakima , Antunes Pedro Marques
Published: November 2004

In this paper we present a new approach to provide fast handover in Mobile IP. A new Pre‐Handover Signalling (PHS) protocol is proposed to allow the network to achieve accurate handover decisions considering different constraints such as QoS, load balancing in the base stations, the user profile, the mobile node service requirements, etc. In addition we propose to minimize the time discovery of the new base station in order to minimize the handover latency. We propose to start the PHS as soon as the mobile node crosses a predefined critical zone area in its current location, this signalling will provide a list of candidate cells to the mobile node with corresponding priorities; the mobile node will select the highest priority base station as soon as the layer two handover occurs. We propose in the current work to use an extension of COPS (Common Open Policy Service) to support the proposed PHS mechanism and overcome the blind handover decisions of Mobile IP and improve the handover performance. Copyright © 2004 John Wiley & Sons, Ltd.
Highly convergent dynamic models obtained by modal synthesis with application to short wave pulse propagation
Authors: Barauskas Rimantas , Barauskiene Ramute
Published: November 2004

A general approach for obtaining the matrices of a substructure ensuring minimum modal frequency errors of the whole structure is presented. The mass and stiffness matrices of a small component domain of selected dimension are obtained by applying the modal synthesis of a limited number of close‐to‐exact modes such that after assembling a larger joined domain model the modal convergence rate of the latter should be as high as possible. The goal is achieved by formulating the minimization problem for the penalty‐type target function representing the cumulative relative modal frequency error of the joined sample domain and by applying the gradient descent minimization method. After the optimum matrices of a component domain are obtained, they can be used in any structure as higher‐order elements or super‐elements. The well‐known generalized mass matrices obtained as a weighted sum of lumped and consistent components can be treated as a special case of the presented approach. The obtained dynamic models are used for modelling short transient waves and wave pulses propagating in elastic or acoustic environments by using a only a few nodal points per pulse length. Copyright © 2004 John Wiley & Sons, Ltd.
Design of frames using genetic algorithm, force method and graph theory
Authors: Kaveh A. , Abdietehrani A.
Published: November 2004

In the process of discrete‐sizing optimal design of frame structures by genetic algorithm, analysis should be performed several times. In this article, the force method is employed for the analysis using subminimal cycle basis of their graph models. The advantage of employing this method lies in the fact that the matrices corresponding to particular and complementary solutions are formed once and independently of the mechanical properties of members. These matrices are then used several times in the process of the sequential analyses, increasing the speed of optimization. Copyright © 2004 John Wiley & Sons, Ltd.
How Customer Satisfaction Improvement Works To Fuel Business Recovery at IBM
Authors: Schiff Larry
Published: November 2004

Back in 1995, IBM was in bad shape, economically and competitively. Its subsequent business turnaround was based on the simple‐sounding principle of thoroughly satisfying customers. Avoiding the trap of bureaucracy, it developed a disciplined and direct method of dealing with customers, worldwide, applying its own best practices for measurable behaviors of every customer‐touching employee. The strength of the system is the firm foundation set by top management and continually reinforced by other executives—and by a reward structure in which achieving customer satisfaction is a critical factor. © 2001 by John Wiley & Sons, Inc.
Nonverbal Communication: How To Read What's Plain as the Nose… or Eyelid… or Chin… on Their Faces
Authors: Fulfer Mac
Published: November 2004

For most people, “reading” others' nonverbal messages is an intuitive, “gut” process. But learning to do it consciously and deliberately can enhance understanding and thus greatly improve interpersonal relations in a wide variety of situations. At work, it can be a useful tool to facilitate decision making and ease work processes—for example, during interviews or at meetings. © 2001 John Wiley & Sons, Inc.
The Role of Change Management in Establishing a Shared Services Business Model at Air Products and Chemicals
Authors: Legare Thomas L. , Bechtel Rebecca L.
Published: November 2004

Under a shared services strategy, staff functions operate as an internal market‐place for their own services, with a business focus of service to customers. When Air Products and Chemicals' Controllership recognized the cost and effectiveness advantages to following this model, it began a transformation process that altered the human as well as the functional dynamics in the company. Its ultimate success resulted from the depth of its effort to implement change. © 2001 John Wiley & Sons, Inc.
Systemic versus Nonsystemic Approaches To Quality Improvement
Authors: Roth William , Capuano Terry
Published: November 2004

Despite the best of intentions, most quality improvement processes are not producing the desired results. This is frequently because those shaping the process do not understand that the quality improvement movement is simply the latest version of the systems approach, which has been around for about 40 years. © 2001 John Wiley & Sons, Inc.
PSS World Medical: Opening the Books Boosts Commitment and Performance
Authors: O'Reilly III Charles A. , Pfeffer Jeffrey
Published: November 2004

Running an open company, giving people authority and accountability, sharing the wealth, and having lots of leaders, not managers—these are the four central ideas behind the surprising success of PSS World Medical. Despite having been built on acquisitions and being in a low‐margin and extremely competitive industry, the company—a distributor of medical supplies—has thrived, with a strict customer focus defined and applied down to the smallest detail. © 2000 President and Fellows of Harvard College.
Pharmacovigilance‐related topics at the level of the International Conference on Harmonisation (ICH)
Authors: Bahri Priya , Tsintis Panos
Published: November 2004

Marketing authorisations for medicines need to be based on the universal criteria quality, safety and efficacy, whilst taking into account local public health needs. With view to using resources efficiently and avoiding delay in access to medicines, scientific standards for investigating quality, safety and efficacy should be universal too. A major step to achieve this was taken in 1990 when the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) was established between authorities and industry in the European Union (EU), Japan and the United States. Since then more than 50 ICH Guidelines have been published, out of which six are specific to pharmacovigilance. They refer to management and expedited reporting of individual adverse drug reaction (ADR) cases, including electronic formats, periodic reporting of worldwide data and planning of pharmacovigilance. Their development has to be seen in the context of initiatives taken in the three ICH Regions to strengthen pharmacovigilance. Most recently this involves making use of risk management concepts, reflecting new thinking of proactivity in pharmacovigilance. Moreover, consideration is given to regional and international cooperation beyond the ICH Regions. Copyright © 2004 John Wiley & Sons, Ltd.
In‐situ ultrasonic compatibilization of unvulcanized and dynamically vulcanized PP/EPDM blends
Authors: Feng Wenlai , Isayev A. I.
Published: November 2004

Dynamically vulcanized PP/EPDM blends were treated by high‐intensity ultrasonic waves during extrusion. These blends were compared with unvulcanized PP/EPDM blends that were treated by ultrasound during extrusion and then dynamically vulcanized. Die pressure and power consumption were measured. The effects of different gap sizes, ratio of components, and number of ultrasonic horns were investigated. The rheological properties, morphology and mechanical properties of the blends with and without ultrasonic treatment were compared. The results obtained indicated that ultrasonic treatment induced thermo‐mechanical degradation, causing enhanced molecular transport and chemical reactions at the interfaces, thus leading to in‐situ compatibilization, which is evident by the morphological and mechanical property studies. Processing conditions were established for enhanced in‐situ compatibilization of the PP/EPDM blends that were either originally dynamically vulcanized and then ultrasonically treated or first treated and then dynamically vulcanized. Polym. Eng. Sci. 44:2019–2028, 2004. © 2004 Society of Plastics Engineers.
Electroactive polymer patterns with metal incorporation on a polymeric substrate
Authors: Zhao Luping , Wang Jinggong , Neoh K. G. , Kang E. T.
Published: November 2004

Electroactive polymer patterns on a polymeric substrate were fabricated using either a UV lithographic approach or plasma polymerization method. For the lithographic patterning technique, photosensitive thin films comprising polyaniline (PANI) coatings on viologen‐grafted low‐density polyethylene (LDPE) substrates were first prepared. The composite film was subsequently exposed to UV irradiation through a mask. Under UV irradiation, reactions between PANI and viologen occurred, resulting in the conversion of the PANI to a doped state. The PANI micropatterns were developed by using N‐methylpyrrolidinone (NMP) to dissolve the soluble‐unexposed (and hence undoped) parts. The use of Ar plasma treatment of the composite film instead of UV irradiation was not successful in inducing the doping reaction between PANI and viologen. On the other hand, plasma polymerization was shown to be another convenient way for the selective surface deposition of aniline polymer on the surface of the LDPE substrate through a mask. The further incorporation of metal/metal ions in both the PANI‐viologen and plasma polymerized aniline system was successfully carried out on the micropatterns. Polym. Eng. Sci. 44:2061–2069, 2004. © 2004 Society of Plastics Engineers.
The structure and properties of PA6/MMT nanocomposites prepared by melt compounding
Authors: Shishan Wu , Dingjun Jiang , Xiaodong Ouyang , Fen Wu , Jian Shen
Published: November 2004

Polyamide 6 (PA6)/organo‐montmorillonite nanocomposites prepared by melt compounding using a co‐rotating twin‐screw extruder were intercalated nanocomposites. The modulus, bending strength and heat distortion temperature of these nanocomposites increased with increasing clay content, and tensile strength increased up to 4.3 wt% and then decreased with further increases in montmorillonite content. The notched Izod impact strength decreased slightly with montmorillonite content. Nanocomposites based on the higher‐molecular‐weight PA6 yielded higher moduli, tensile strengths, and heat distortion temperatures at the same montmorillonite content. Polym. Eng. Sci. 44:2070–2074, 2004. © 2004 Society of Plastics Engineers.
Effects of oxidation and particle shape on critical volume fractions of silver‐coated copper powders in conductive adhesives for microelectronic applications
Authors: Lin Yung‐Sen , Chiu Sheng‐Shiang
Published: November 2004

The effects of oxidation and particle shape on critical volume fractions of silver‐coated copper powders in conductive adhesives are investigated. Silver‐coated copper powders with spherical and flake‐shaped particles were oxidized at temperatures of 30°C, 175°C and 240°C for two hours and dispersed in an epoxy matrix. As silver‐coated copper powders are oxidized at 30°C and 175°C, the critical volume fractions of the conductive adhesives are slightly affected by oxidation and particle shape at these temperatures. As the oxidation temperature approaches 240°C, the critical volume fractions of the conductive adhesives are strongly affected by oxidation temperature and particle shape, owing to the formation of oxides such as Cu2O on the surface of silver‐coated copper powder—Cu diffuses from the interior to the surface of silver‐coated copper powder and reacts with the oxygen in the air. Silver‐coated copper powder with flake‐shaped particles shows lower critical volume fractions in conductive adhesives than silver‐coated copper powder with spherically shaped particles. Polym. Eng. Sci. 44:2075–2082, 2004. © 2004 Society of Plastics Engineers.
Strain hardening in polypropylenes and its role in extrusion foaming
Authors: Spitael Pieter , Macosko Christopher W.
Published: November 2004

Extensional viscosity of several polypropylene polymers and their blends was measured and the foam processing of these blends using carbon dioxide blowing agent was studied. Foaming was carried out on a co‐rotating twin‐screw extrusion line, with a gear pump to build pressure. A linear isotactic polypropylene and two branched polypropylenes were considered. The uniaxial extensional viscosity was quantified and the foam characterized based on bulk density, cell size, and cell concentration. The linear polymer exhibits no strain hardening, while both branched polymers show pronounced strain hardening. Blends of low concentrations of branched polymer in the linear polypropylene show significant strain hardening down to 10‐wt% branched polypropylene. Strain hardening is expected to prevent cell coalescence and lead to higher cell concentrations. The branched polymers were found to have a lower cell concentration than the linear polymer. Yet blends of linear and branched polypropylenes attained a cell concentration higher than either of the neat polymers. This suggests that even small amounts of branched polypropylene blended in linear polypropylene can improve the foaming process. Polym. Eng. Sci. 44:2090–2100, 2004. © 2004 Society of Plastics Engineers.
Characteristics of antiplasticized thermosets: Effects of network architecture and additive chemistry on mechanical fortification
Authors: Zerda Adam S. , Lesser Alan J.
Published: November 2004

A new class of molecular additives is investigated for epoxy‐based crosslinked polymers. These additives are shown to increase modulus and yield stress in the cured networks. In order to elucidate the mechanisms for reinforcement of epoxy thermosets, the effects of additive chemistry and network architecture are considered. Both model and commercial epoxy networks are studied, thereby probing the effect of molecular weight between crosslinks, Mc, on reinforcement. Additionally, the family of phosphates being studied ranges in molecular weight, solubility parameter and density. These parameters are demonstrated to strongly influence the degree of reinforcement and correlate with the ability of the additive to reduce mobility of the polymer network. Mechanisms of reinforcement are discussed. Polym. Eng. Sci. 44:2125–2133, 2004. © 2004 Society of Plastics Engineers.
Structure development in melt‐spinning syndiotactic polystyrene and comparison to atactic polystyrene
Authors: Hong Myeong‐Ho , White James L.
Published: November 2004

Syndiotactic polystyrene (s‐PS) and atactic polystyrene (a‐PS) were melt‐spun into filaments. The s‐PS filaments exhibited increasing amounts of crystallinity and orientation with increasing drawdown ratio and spinline stress. The a‐PS filaments were amorphous but exhibited birefringence. The birefringence and Hermans orientation factors for a‐PS were proportional to this spinline stress. In ice water and at low drawdown ratios, the s‐PS is glassy or mesomorphic. At higher drawdown ratios and spinline stresses, it crystallized. The crystalline form was the zigzag TTTT hexagonal α‐form. The birefringence and orientation factors of the s‐PS filaments were higher than those of the a‐PS filaments and the difference of the birefringence increased with increasing spinline stress. Mechanical testing results showed that the Young's modulus and tensile strength generally increased with increasing spinline drawdown ratio for both a‐PS and s‐PS filaments. The elongation to break was enhanced for both materials by increased chain orientation. Polym. Eng. Sci. 44:2141–2147, 2004. © 2004 Society of Plastics Engineers.
Origin of directional tear in blown films of ethylene/methacrylic acid copolymers and ionomers
Authors: Lee Li‐Bong W. , Register Richard A. , Dean David M.
Published: November 2004

Blown films of ethylene/methacrylic acid copolymers and ionomers can exhibit pronounced directional tear, meaning that a tear can propagate with much less resistance in a particular direction. However, films blown from the same resin can exhibit different preferred tear directions, which depend on the process conditions. Through wide‐ and small‐angle X‐ray scattering, we demonstrate that this directional tear behavior is a direct result of the orientation of the lamellar polyethylene crystallites in these films; tears propagate more readily between lamellae than through lamellae, as previously recognized for low‐density polyethylene homopolymer. Unlike polyethylene homopolymer, however, an increase in the blowup ratio during the film processing of ethylene/methacrylic acid copolymers and ionomers leads to a 90° rotation of the lamellae that form upon subsequent crystallization. The lamellar rotation arises from a change in the orientation of the row nuclei that form after the melt is inflated and produces a consequent rotation of the preferred tear direction. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 97–106, 2005
Critical strains in tensile deformed polyamide 6 and 6/66 copolymer
Authors: Men Yongfeng , Rieger Jens , Hong Ke
Published: November 2004

The recovery properties of dry and water saturated polyamide 6 (PA6) and its copolymer PA6/66 (ratio 4:1 by mol) were studied at elevated temperatures above the glass‐transition temperature in uniaxial tensile tests. The data yield critical points along the true stress–strain curves at which the differential compliance and the recovery property change. These critical points include the onset of the plastic deformation (point A), the yield point (B), and the point where the elasticity of the samples reaches a plateau value (C). The strains at points A and B remain constant, whereas the strain at point C varies with temperature. The invariance of the critical strains at points A and B is assumed to be the result of the homogeneous strain distribution in the system and the general activation of the intralamellar block slip mechanism at low deformations. The strain at point C, being related to the properties of the entangled network, varies because the effective entanglement density of the network changes due to the change in the hydrogen bond number with temperature. With the Gaussian model of Haward and Thackray, we calculated the network moduli. From these data, we derived that the network stress remains constant at point C. At point C, the deformation mechanism starts to change from the block slip mechanism to a stress‐induced melting–recrystallization process. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 87–96, 2005
Binding of glutamine to glutamine‐binding protein from Escherichia coli induces changes in protein structure and increases protein stability
Authors: D'Auria Sabato , Scirè Andrea , Varriale Antonio , Scognamiglio Viviana , Staiano Maria , Ausili Alessio , Marabotti Anna , Rossi Mosè , Tanfani Fabio
Published: November 2004

Glutamine‐binding protein (GlnBP) from Escherichia coli is a monomeric protein localized in the periplasmic space of the bacterium. It is responsible for the first step in the active transport of L‐glutamine across the cytoplasmic membrane. The protein consists of two similar globular domains linked by two peptide hinges, and X‐ray crystallographic data indicate that the two domains undergo large movements upon ligand binding. Fourier transform infrared spectroscopy (FTIR) was used to analyze the structure and thermal stability of the protein in detail. The data indicate that glutamine binding induces small changes in the secondary structure of the protein and that it renders the structure more thermostable and less flexible. Detailed analyses of IR spectra show a lower thermal sensitivity of α‐helices than β‐sheets in the protein both in the absence and in the presence of glutamine. Generalized two‐dimensional (2D) analyses of IR spectra reveal the same sequence of unfolding events in the protein in the absence and in the presence of glutamine, indicating that the amino acid does not affect the unfolding pathway of the protein. The data give new insight into the structural characteristics of GlnBP that are useful for both basic knowledge and biotechnological applications. Proteins 2005. © 2004 Wiley‐Liss, Inc.
Fragmentation study of short‐chain products derived from oxidation of diacylphosphatidylcholines by electrospray tandem mass spectrometry: identification of novel short‐chain products
Authors: Reis A. , Domingues P. , Ferrer‐Correia A. J. V. , Domingues M. R. M.
Published: November 2004

Lineloyl‐palmitoyl (PLPC) and arachidonoyl‐palmitoyl (PAPC) phosphatidylcholine were oxidized under Fenton reaction conditions (H2O2 and Fe2+), and the short‐chain products formed were identified by electrospray ionization mass spectrometry (ESI‐MS). The short‐chain products resulted from β‐cleavage of oxygen‐centered radicals and comprised aldehydes, hydroxyaldehydes and dicarboxylic acids that yielded both [MH]+ and [MNa]+ ions. The fragmentation of the [MH]+ and [MNa]+ ions of the peroxidation products was studied by tandem mass spectrometry (MS/MS). The MS/MS spectra of both ions showed ions resulting from characteristic losses of glycerophosphatidylcholine. Other product ions, resulting from CC cleavages occurring in the vicinity of the functional group, and fragmentations involving the hydroxy groups, were the most informative since they allowed us to obtain structural information relating to the sn‐2 acyl residue. Both fragmentation pathways are due to charge‐remote fragmentation occurring by a 1,4‐hydrogen elimination mechanism and/or by homolytic cleavage. Furthermore, the fragmentation pathway of some ions observed in the ESI‐MS spectrum was not consistent with the fragmentation behavior expected for some of the short‐chain species identified in the literature and allowed the reassignment of the ions as different structures. Isobaric ions were observed in the ESI‐MS spectra of both oxidized phospholipids, and were differentiated based on distinct fragmentation. The detailed knowledge of lipid peroxidation degradation products is of major importance and should be very valuable in providing new markers for oxidative stress signaling and for disease states monitoring. Copyright © 2004 John Wiley & Sons, Ltd.
Stable carbon and oxygen isotopic determination of sub‐microgram quantities of CaCO3 to analyze individual foraminiferal shells
Authors: Ishimura Toyoho , Tsunogai Urumu , Gamo Toshitaka
Published: November 2004

We have developed an analytical system to determine stable isotopic compositions (δ13C and δ18O) of sub‐microgram quantities of CaCO3 for the purpose of analyzing individual foraminiferal shells, using continuous‐flow isotope ratio mass spectrometry (CF‐IRMS). The system consists of a micro‐volume CaCO3 decomposition tube, stainless steel CO2 purification vacuum line with a quantity‐regulating unit, helium‐purged CO2 purification line, gas chromatograph, and a CF‐IRMS system. By using this system, we can determine stable carbon and oxygen isotopic compositions as low as 0.2 μg of CaCO3, with standard deviations of ±0.10‰ for δ13C and ±0.18‰ for δ18O within a 4‐h reaction time and 30‐min analysis period. Copyright © 2004 John Wiley & Sons, Ltd.
A software test process stochastic control model based on CMM characterization
Authors: Cangussu João W.
Published: November 2004

The state variable model of the software test process has shown to be a promising approach for the control of the system test phase of the software test process. However, the presence of unforeseen perturbations and noise in the data collection process impacts the accuracy of the predictions of the model and motivates the application of a stochastic control approach.

This article explores a stochastic model construct upon the deterministic state variable model of the software test process. The Capability Maturity Model is used to identify levels of disturbance and noise that can be associated with the maturity level of processes. Simulation results are presented as an indication of the applicability of the stochastic state model. Copyright © 2004 John Wiley & Sons, Ltd.
Guided support for collaborative modeling, enactment and simulation of software development processes
Authors: Fernández Alejandro , Garzaldeen Badie , Grützner Ines , Münch Jürgen
Published: November 2004

Recently, the awareness of the importance of distributed software development has been growing in the software engineering community. Economic constraints, more and more outsourcing of development activities, and the increasing geographical distribution of companies come along with challenges of how to organize distributed development.

In this article, we reason that a common process understanding is mandatory for successful distributed development. Integrated process planning, guidance and enactment are seen as enabling technologies for achieving a unique process view.

We present an overview of the software process modeling environment SPEARMINT and the XCHIPS system for web‐based process support. SPEARMINT offers extensive capabilities for multi‐view modeling and analysis of software development processes. XCHIPS provides capabilities for distributed modeling and offers enactment and simulation functionalities. This article describes the integration of both approaches. The resulting environment provides planners and developers with collaborative planning and enactment support and advanced process guidance via electronic process guides (EPGs). Additionally, experience with the integrated environment is described. We describe, in particular, the usage of this integrated environment in the context of a case study for the development of a learning system. Finally, an overview of related work is given and future research directions are sketched. Copyright © 2004 John Wiley & Sons, Ltd.
Decoding the reading of history: An example of the process
Authors: Pace David
Published: November 2004

In most disciplines, professors ask students to “read” without specifying what this operation means for their particular field. This chapter traces the path laid out in a cultural history class, where reading entails identifying the essential elements of a text.
Decoding genetics and molecular biology: Sharing the movies in our heads
Authors: Zolan Miriam , Strome Susan , Innes Roger
Published: November 2004

For three biology professors, visualizing molecular processes is central to thinking in their discipline. This chapter reports their attempts at getting students to make this same cognitive move and the results of their assessments.
Decoding astronomical concepts
Authors: Durisen Richard H. , Pilachowski Catherine A.
Published: November 2004

Two astronomy professors, using the Decoding the Disciplines process, help their students use abstract theories to analyze light and to visualize the enormous scale of astronomical concepts.
Decoding the humanities
Authors: Ardizzone Tony , Breithaupt Fritz , Gutjahr Paul C.
Published: November 2004

To teach students particular ways of thinking in the humanities, three faculty in literature and creative writing discover how to conceptualize these approaches for students and model them or have students model them in the classroom, and they assess the results on student learning.
Using collaborative learning teams to decode disciplines: Physiology and history
Authors: Schlegel Whitney M. , Pace David
Published: November 2004

This chapter addresses the logistical considerations for the use of collaborative learning in the Decoding the Disciplines model and presents twelve principles for successfully using teamwork in the classroom and several assessments of the efficacy of the group process.
Facilitating a faculty learning community using the decoding the disciplines model
Authors: Middendorf Joan
Published: November 2004

This chapter explains how to plan a faculty learning community that engages a disciplinary inquiry of teaching and learning. It concludes with a five‐level assessment of the Indiana University Faculty Learning Community.
Phenotypical variation in a toxic strain of the phytoplankter, Cylindrospermopsis raciborskii (nostocales, cyanophyceae) during batch culture
Authors: Hawkins Peter R. , Putt Elizabeth , Falconer Ian , Humpage Andrew
Published: November 2004

A nonaxenic strain of Cylindrospermopsis raciborskii Woloszynska (AWT 205) was grown in batch culture, with and without nitrate as the primary N source. Rapid log‐phase growth with nitrate was 1.0 doubling/day versus 0.3 doubling/day without nitrate. Cylindrospermopsin (CYN) production was measured by HPLC. The rate of intracellular CYN production matched cell division rate for both the diazotrophies at cell densities less than 107 cell/ml. At cell density >107 cell/ml, additional resource limitation in batch culture slowed log‐phase growth to 0.04 division/day and cell division and CYN production decoupled. Intracellular CYN concentration increased at a rate of 0.08 doubling/day, twice the cell division rate.

Extracellular CYN as a proportion of the total CYN increased from 20% during the rapid growth phase, to 50% during the slow growth phase. The total CYN yield from cultures grown out to stationary phase (55 days) exceeded 2 mg CYN/l.

C. raciborskii cells in log‐phase growth, exposed to 1 ppm copper (as copper sulphate), lysed within 24 hours. After copper treatment, all CYN was in the filterable fraction. These findings imply that in naturally occurring blooms of C. raciborskii, the movement of intracellular CYN into solution will be the greatest during stationary phase, when intracellular concentrations are highest and cell lysis is more frequent. The application of algicides that promote cell lysis will exacerbate this effect. © 2001 John Wiley & Sons, Inc. Environ Toxicol 16: 460–467, 2001
Presence ofPlanktothrixsp. and cyanobacterial toxins in Lake Ammersee, Germany and their impact on whitefish (Coregonus lavaretusL.)
Authors: Ernst Bernhard , Hitzfeld Bettina , Dietrich Daniel
Published: November 2004

Due to the increasing oligotrophy of Lake Ammersee, southern Germany, metalimnicPlanktothrixhave become one of the dominant planktonic species causing regular blooms. Whitefish (Coregonus lavaretus) is the dominant local fish species with great importance for the fishing industry. Recently, whole age groups of this fish species have disappeared and since 1991, average body‐weight has decreased. The causes for this remain unclear.Planktothrixspecies produce the cyclic peptide toxin desmethyl microcystin‐RR, which inhibits glycogen metabolism and has detrimental effects on the development of aquatic organisms. During blooms, gut contents of whitefish displayed a blue discoloration, possibly representing phycobiliproteins typical for cyanobacteria. This study aimed to elucidate the impact ofPlanktothrixblooms on fish population dynamics.Planktothrixcell counts, performed by epifluorescence microscopy, showed blooms to contain up to 80,000 cells/ml. Microcystin levels of 1−5μg/mg dry weight inPlanktothrixextracts and 0.08μg/l in water samples, were determined via HPLC and protein‐phosphatase inhibition assay.Planktothrixfilaments were detected in gut contents of whitefish. In addition, microcystins could be detected in gut contents via ELISA. Similarly, immunoprobing with microcystin‐antibodies demonstrated microcystin‐protein adducts in liver homogenates of whitefish caught duringPlanktothrixblooms. Furthermore,Planktothrixextracts proved cytotoxic to trout hepatocytes as determined by MTT reduction. Whitefish eggs and larvae, obtained during blooms in winter 1998 and 2000 in a Lake Ammersee hatchery, were studied for developmental progress. Malformations typical for cyanobacterial toxin exposure were observed. © 2001 John Wiley & Sons, Inc. Environ Toxicol 16: 483–488, 2001
The effects of the ciliate Paramecium cf. caudatum Ehrenberg on toxin producing Cylindrospermopsis isolated from the Fitzroy River, Australia
Authors: Fabbro Larelle , Baker Melanie , Duivenvoorden Leo , Pegg Graham , Shiel Russ
Published: November 2004

The large ciliate Paramecium cf. caudatum Ehrenberg was found to be a successful grazer of toxin producing Cylindrospermopsis in the laboratory. The feeding rate increased with increasing cell concentration to 1367 cell animal hr−1 at 4.1×105 cells mL−1 but declined slightly at cell concentrations greater than this. Preliminary studies on the effects of this grazing on toxin concentrations in cultures of both straight and coiled forms of Cylindrospermopsis resulted in the production of different amounts of the toxin cylindrospermopsin in the different isolates. Differences in toxin production were also found between cultured and field populations from the lower Fitzroy River indicating that toxin production may be influenced by a suite of genetic and environmental factors. The proven ability of this ciliate to graze toxic Cylindrospermopsis provides some insight into interactions that may be able to control some toxic blooms in semiarid Australian conditions. © 2001 John Wiley & Sons, Inc. Environ Toxicol, 16: 489–497, 2001
Distribution of 14C cylindrospermopsin in vivo in the mouse
Authors: Norris R. L. G. , Seawright A. A. , Shaw G. R. , Smith M. J. , Chiswell R. K. , Moore M. R.
Published: November 2004

Radiolabelled 14C cylindrospermopsin (CYN) has been prepared and used to investigate the distribution and excretion of CYN in vivo in male Quackenbush mice. At a dose of 0.2 mg/kg (i.e., approx. median lethal dose) the following mean (SD) urinary and faecal recoveries (cumulative) were obtained, respectively: (0–6 hours, n=4) 48.2 (29.3)%, 11.9 (21.4)%; (0–12 hours, n=12) 66.0 (27.1)%, 5.7 (5.6)%; (0–24 hours, n=12) 68.4 (26.7)%, 8.5 (8.1)%. Mean (SD) recoveries from livers at 6 hours were 20.6 (6.4)% (n=4), at 48 hours 13.1 (7.7)% (n=8), and 5–7 days were 2.1 (2.1)% (n=8). A substantial amount (up to 23%) can be retained in the liver for up to 48 hours with a lesser amount retained in the kidneys. The excretion patterns show substantial interindividual variability between predominantly faecal or urinary excretion, but these patterns are not related in any simple manner to the outcome in terms of toxicity. There is at least one methanol‐extractable metabolite as well as a nonmethanol‐extractable metabolite in the liver. The methanol‐extractable metabolite was not found in the kidney and is more hydrophilic than CYN itself on reverse phase. © 2001 John Wiley & Sons, Inc. Environ Toxicol 16: 498–505, 2001
Identification of cyanobacteria and their toxigenicity in environmental samples by rapid molecular analysis
Authors: Baker Judith A. , Neilan Brett A. , Entsch Barrie , Mckay David B.
Published: November 2004

We report molecular analyses which identify cyanobacterial strains present in environmental samples. These analyses do not require the isolation and culture of strains. Identification of cyanobacteria used the polymerase chain reaction (PCR), based on the phycocyanin operon. Differentiation was either by restriction endonuclease digestion (restriction fragment length polymorphisms) or sequencing of the PCR products. Identification was based on sequence homology of the intergenic spacer region (IGS) between the β‐ and α‐phycocyanin subunits (PC‐IGS) with database records. We have found that the length and sequence of the PC‐IGS is capable of predicting the genus accurately, but not the species. Toxigenicity was determined with oligonucleotide probes for key steps in the microcystin toxin synthesis pathway. We have shown that it is possible to easily and routinely obtain PCR amplification products and differentiate the strains in bloom samples. The methods can detect even minor components in bloom samples, which may not be apparent on microscopic examination. Genetic probes for microcystin toxigenicity are effective on environmental samples, eliminating the need for isolation and culture of the organisms. The use of a suite of tests described here will allow water managers to determine the presence and the type of cyanobacteria and their microcystin toxigenicity. © 2001 John Wiley & Sons, Inc. Environ Toxicol 16: 472–482, 2001
Sublethal effects of chronic exposure to an organochlorine compound on northern leopard frog (Rana pipiens) tadpoles
Authors: Glennemeier Karen A. , Denver Robert J.
Published: November 2004

Global contamination with organochlorine compounds (OCs) has posed developmental and reproductive problems in wildlife worldwide. However, little is known about the impact of OCs or other pollutants on amphibians, despite mounting concerns about amphibian population declines and developmental deformities in the wild. Wildlife populations may be affected critically by sublethal impacts of anthropogenic disturbances, yet little research has focused on such effects in amphibians. In the current study, northern leopard frog (Rana pipiens) tadpoles were chronically exposed to a polychlorinated biphenyl (PCB) congener, 77‐TCB, and effects on behavior, morphology, competitive performance, and corticosterone content were determined. R. pipiens activity levels and feeding rates were decreased by 77‐TCB exposure, but morphology of mouthparts and body proportions were unaffected. 77‐TCB enhanced growth and altered competitive interactions between R. pipiens and wood frog (Rana sylvatica) tadpoles. R. pipiens tadpoles exposed to 77‐TCB showed decreased whole‐body corticosterone content compared to controls both before and after injection with adrenocorticotropic hormone (ACTH). All of the factors examined in the current study play critical roles in tadpole development, growth, survivorship, and eventual reproductive success, suggesting negative population‐level consequences for amphibians in PCB‐contaminated habitats. © 2001 John Wiley & Sons, Inc. Environ Toxicol 16: 287–297, 2001
Prenatal diagnosis of Shone's syndrome: parental counseling and clinical outcome
Authors: Zucker N. , Levitas A. , Zalzstein E.
Published: November 2004

Objective

To describe a series of fetuses diagnosed as having Shone's syndrome, which includes four cardiac defects and for which there is a wide variety of clinical presentations, surgical treatments and outcomes, and to discuss the counseling strategy.

Methods

We reviewed retrospectively the records of four babies who were suspected prenatally to have Shone's syndrome.

Results

The mean age at diagnosis was 27.5 (range, 22–35) weeks. A small left ventricle, mitral and aortic annulus and ascending aorta were detected in three cases. In three fetuses there was an abnormal mitral valve apparatus and in two fetuses a sub‐aortic membrane was detected. Coarctation of the aorta was an impending diagnosis in three babies. Following counseling, all parents decided to continue the pregnancy to term. Echocardiographic evaluation was performed soon after birth. The mean mitral valve annulus diameter was 8.2 (range, 7–10) mm, and that of the aortic valve annulus was 6 (range, 5–7) mm. The aortic valve was bicuspid in all babies with an additional sub‐aortic membrane in two babies. Doppler ultrasound examination revealed high‐velocity flow through the mitral valve in three babies; two of them had a parachute mitral valve. Coarctation repair was performed in two babies during the first week of life. One patient underwent mitral valvuloplasty followed by later mitral valve replacement. All patients were alive after a mean of 7.8 (range, 3.3–10.5) years' follow‐up.

Conclusion

When counseling families regarding fetal Shone's syndrome, it is important to emphasize the wide variety of clinical presentations and possible outcomes. Differentiation between hypoplastic left ventricle and Shone's complex is crucial and may influence the physician's attitude, the presentation of the case to the family and the family's final decision. Copyright © 2004 ISUOG. Published by John Wiley & Sons, Ltd.
An anatomical fetal brain structure and a normal variant mimicking anomalies on routine neurosonographic imaging: report of two cases
Authors: Correa F. F. , Lara C. , Bellver J. , Remohí J. , Pellicer A. , Serra V.
Published: November 2004

We present two cases in which an anatomical structure, the calcar avis, and a normal variant, a bifid choroid plexus, mimicked abnormalities on routine prenatal ultrasound examination. To the best of our knowledge these pitfalls have only been described in neonates. A familiarity with these false images is important to avoid erroneous diagnoses. Copyright © 2004 ISUOG. Published by John Wiley & Sons, Ltd.
Modulation of botulinum neurotoxin A catalytic domain stability by tyrosine phosphorylation
Authors: Ibañez Cristina , Blanes-Mira Clara , Fernández-Ballester Gregorio , Planells-Cases Rosa , Ferrer-Montiel Antonio
Published: November 2004

Botulinum neurotoxin A (BoNT A) is a substrate of the Src family of tyrosine kinases. Here, we report that the BoNT A light chain (LC) is phosphorylated in the tyrosine‐71 located at N‐terminus. Covalent modification of this residue notably increases the thermal stability of the endopeptidase activity, without affecting its catalytic efficacy. Similarly, mutation of this residue specifically affected the protein stability but not its endopeptidase function. Fusion of the Tat‐translocating domain to the N‐terminus of the enzyme produced a cell permeable, functional enzyme, as evidenced by immunocytochemistry and by the cleavage of cytosolic SNAP25 in intact PC12 cells. Noteworthy, truncation of cellular SNAP25 was reduced in cells when the Src kinase activity was inhibited with a specific antagonist, implying that tyrosine phosphorylation of BoNT A LC modulates the in vivo proteolytic activity of the neurotoxin. Taken together, these findings substantiate the tenet that tyrosine phosphorylation of BoNT A LC could be an important modulatory strategy of the neurotoxin stability and suggest that the phosphorylated neurotoxin may be a relevant molecule in vivo.
The cytoskeleton of mammalian spermatozoa
Authors: Fouquet Jean‐Pierre , Kann Marie‐Louise
Published: November 2004

Summary— The mammalian spermatozoa are endowed with a unique cytoskeleton which consists both of ubiquitous and specific proteins, some of them arising from a gene haploid transcription. In the head, a dense perinuclear layer is made of basic proteins (calicin, cylicin, etc) associated with calmodulin and actin remnants. In the flagellum, the axonemal microtubules are mainly composed of glutamylated tubulin isoforms; the periaxonemal outer dense fibers and fibrous sheath are considered as related cytoskeletal structures on the basis of some common polypeptides.
Characterization of aminopeptidase N from Torpedo marmorata kidney
Authors: O'Callaghan Barbara , Synguelakis Monique , La Salle Gildas Le Gal , Morel Nicolas
Published: November 2004

Summary— A major antigen of the brush border membrane of Torpedo marmorata kidney was identified and purified by immunoprecipitation. The sequence of its 18 N terminal amino acids was determined and found to be very similar to that of mammalian aminopeptidase N (EC 3.4.11.2). Indeed aminopeptidase N activity was efficiently immunoprecipitated by monoclonal antibody 180K1. The purified antigen gives a broad band at 180 kDa after SDS‐gel electrophoresis, which, after treatment by endoglycosidase F, is converted to a thinner band at 140 kDa. This antigen is therefore heavily glycosylated. Depending on solubilization conditions, both the antigen and peptidase activity were recovered either as a broad peak with a sedimentation coefficient of 18S (2% CHAPS) or as a single peak of 7.8S (1% CHAPS plus 0.2 % C12E9), showing that Torpedo aminopeptidase N behaves as an oligomer stabilized by hydrophobic interactions, easily converted into a 160 kDa monomer. The antigen is highly concentrated in the apical membrane of proximal tubule epithelial cells (600 gold particles/μm2 of brush border membrane) whereas no labeling could be detected in other cell types or in other membranes of the same cells (basolatéral membranes, vacuoles or vesicles). Monoclonal antibodies prepared here will be useful tools for further functional and structural studies of Torpedo kidney aminopeptidase N.