bluuebunny/crossref_metadata_2025 huggingface dataset:
The Annexin 2/S100A10 Complex Controls the Distribution of Transferrin Receptor-containing Recycling Endosomes
Authors: Zobiack Nicole , Rescher Ursula , Ludwig Carsten , Zeuschner Dagmar , Gerke Volker
Published: September 2003

The Ca2+- and lipid-binding protein annexin 2, which resides in a tight heterotetrameric complex with the S100 protein S100A10 (p11), has been implicated in the structural organization and dynamics of endosomal membranes. To elucidate the function of annexin 2 and S100A10 in endosome organization and trafficking, we used RNA-mediated interference to specifically suppress annexin 2 and S100A10 expression. Down-regulation of both proteins perturbed the distribution of transferrin receptor- and rab11-positive recycling endosomes but did not affect uptake into sorting endosomes. The phenotype was highly specific and could be rescued by reexpression of the N-terminal annexin 2 domain or S100A10 in annexin 2- or S100A10-depleted cells, respectively. Whole-mount immunoelectron microscopy of the aberrantly localized recycling endosomes in annexin 2/S100A10 down-regulated cells revealed extensively bent tubules and an increased number of endosome-associated clathrin-positive buds. Despite these morphological alterations, the kinetics of transferrin uptake and recycling was not affected to a significant extent, indicating that the proper positioning of recycling endosomes is not a rate-limiting step in transferrin recycling. The phenotype generated by this transient loss-of-protein approach shows for the first time that the annexin 2/S100A10 complex functions in the intracellular positioning of recycling endosomes and that both subunits are required for this activity.
Importin α/β and Ran-GTP Regulate XCTK2 Microtubule Binding through a Bipartite Nuclear Localization Signal
Authors: Ems-McClung Stephanie C. , Zheng Yixian , Walczak Claire E.
Published: September 2003

The small GTPase Ran is essential for spindle assembly. Ran is proposed to act through its nuclear import receptors importin α and/or importin β to control the sequestration of proteins necessary for spindle assembly. To date, the molecular mechanisms by which the Ran pathway functions remain unclear. Using purified proteins, we have reconstituted Ran-regulated microtubule binding of the C-terminal kinesin XCTK2, a kinesin important for spindle assembly. We show that the tail of XCTK2 binds to microtubules and that this binding is inhibited in the presence of importin α and β (α/β) and restored by addition of Ran-GTP. The bipartite nuclear localization signal (NLS) in the tail of XCTK2 is essential to this process, because mutation of the NLS abolishes importin α/β-mediated regulation of XCTK2 microtubule binding. Our data show that importin α/β directly regulates the activity of XCTK2 and that one of the molecular mechanisms of Ran-regulated spindle assembly is identical to that used in classical NLS-driven nuclear transport.
TetrahymenaTelomerase Is Active as a Monomer
Authors: Bryan Tracy M. , Goodrich Karen J. , Cech Thomas R.
Published: September 2003

Telomerase is an enzyme that utilizes an internal RNA molecule as a template for the extension of chromosomal DNA ends. The catalytic core of telomerase consists of the RNA subunit and a protein reverse transcriptase subunit, known as telomerase reverse transcriptase (TERT). It has previously been shown that both yeast and human telomerase can form dimers or multimers in which one RNA in the complex can influence the activity of another. To test the proposal that dimerization might be essential for telomerase activity, we sought to determine whether Tetrahymena thermophila telomerase is active as a dimer or a monomer. Recombinant Tetrahymena telomerase eluted from a gel filtration column at the size of a monomeric complex (one RNA plus one TERT), and those fractions showed processive telomerase activity. We were unable to detect dimerization of Tetrahymena telomerase by coprecipitation experiments, by using tags on either the TERT protein or telomerase RNA. Therefore, a majority, if not all, of the recombinant Tetrahymena telomerase in our reconstitution system is present as a monomeric complex. We were also unable to detect dimerization of native telomerase from mating and vegetative Tetrahymena cell extracts. These results demonstrate that Tetrahymena telomerase does not need to dimerize to be active and processive.
Software algorithms in air data attitude heading reference systems
Authors: Greene Michael E. , Trent Victor
Published: September 2003

An introduction to air data attitude heading reference systems (ADAHRS) is presented along with the developments and discussion of software algorithms used in such systems. Both Kalman filtering and fuzzy logic adaptive signal processing are presented and discussed. Quaternions are used in this paper as the basis for the discussion of both algorithms. Flight results from Archangel Systems AHR150 ADAHRS are also presented and discussed.
Ensuring system safety is more efficient
Authors: Lunde Karin
Published: September 2003

With continuously shrinking time to market and ever increasing requirements regarding product quality and safety, efficiency is crucial in system development. In contrast to classical simulation tools, the model‐based simulation and diagnosis tool RODON supports a wide range of analyses based on a single product model. Besides the resultant considerable reduction of modeling effort, it helps to increase safety and efficiency by automating tasks which traditionally involve a substantial amount of manual labour, like failure modes and effects analysis (FMEA). Considering a model of a typical fly‐by‐wire system as example, this paper describes a few ways how the system engineer can benefit from RODON to enhance system safety and quality, from FMEA to model‐based diagnosis. The main focus of the study was the investigation of sensor tolerances and their impact both on the system behavior and on the fault detection by the system's monitoring functions.
Automatic scanning with multi‐frequency eddy current on multi‐layered structures
Authors: van den Bos Barend , Sahlén Stefan , Andersson Joakim
Published: September 2003

Eddy current testing is a frequently used NDT method at Saab/CSM but recently only single frequency testing has been used. The purpose of our work was to increase both testing speed and sensitivity by using multi‐frequency eddy current testing combined with a scanning system for corrosion detection in multi‐layered structures. The wing of the Saab 2000 aircraft was one specific example for which several samples were manufactured with both artificial (chemically etched) corrosion of various severity and cracks. Using previously determined optimal single frequency as a start, frequency combinations were determined to give increased detectability for the different structures and defects. The influence of different disturbing signals, e.g. signals from rivets, thickness variations, noise, and how to reduce them using the multi‐frequency technique was studied. Tests were also made in “field” conditions to evaluate the system.
A case study exploring the packaging design management process within a UK food retailer
Authors: Vazquez Delia , Bruce Margaret , Studd Rachel
Published: September 2003

Food retailers invest heavily in design expertise to create exciting packaging to entice customers to buy premium food products, and to strengthen their competitive edge. The process by which food retailers manage food packaging design has not been documented and this is an oversight in the design management and retailing literatures that this paper addresses. An in‐depth case study of one of the top four UK retailers is presented and their approach pack design management is analysed and discussed. The process outlined here was in place in 1997 at a time when the retailer had just moved from number three in the market place to number two and was aiming to be number one. The process documented is that of a dynamic growing food retailer working on improving its brand image through packaging design.
Creating growth for yourself as leader
Authors: Eales‐White Rupert
Published: September 2003

Before we can grow those we lead, we need to learn how to grow ourselves. This article focuses on how we achieve that through building our self‐confidence, using both affirmative statements and the ring of confidence; developing our awareness and ability to take constructive action; overcoming limiting beliefs though analysis and coaching and creating a written action plan to improve our performance in key areas of effective leadership where we are motivated to create effective change.
“Search disclosure”
Authors: Nicholas David , Huntington Paul , Williams Peter , Gunter Barrie
Published: September 2003

The authors propose a concept of “search disclosure” to assist in the understanding of the willingness of a user to moderate their digital information seeking behaviour as a result of the perceived anonymity afforded at the point of searching and information consumption. Differences in the way people search for health information on touch‐screen kiosks, the Internet and digital interactive television are thought to result partly from the anonymity of the place in which the search is conducted. Data have been drawn from 11 independent studies, involving questionnaire, interview and log analysis methods across the three digital information platforms. These studies were all funded by the Department of Health as part of the evaluation of the national roll‐out of digital information and advice services to the consumer. Search disclosure is important in not only providing an understanding of existing consumer search behaviour but also in helping to design personalised online services, such as the electronic patient record. The data presented are speculative in nature and further work is being conducted to gather more robust data.
The potential role of e‐books in remote document supply
Authors: Line Maurice B.
Published: September 2003

Presents an overview and evaluation of the technical options available for e‐books and their potential for document supply.
The relationship between strategic type and firm capabilities in Chinese firms
Authors: Di Benedetto C. Anthony , Song Michael
Published: September 2003

Proposes that firms of different Miles and Snow strategic types will have different bundles of firm‐level capabilities; that is, certain capabilities will be more important to certain strategic types. Specifically, proposes that prospectors have greater relative inside‐out capabilities and information technology capabilities, while defenders have greater relative outside‐in capabilities and marketing capabilities. Empirically tests, and finds support for, the propositions using a data set of 245 Chinese firms, comprised mostly of state‐owned enterprises. Understanding the Chinese business environment is of importance to businesses around the world as the Chinese economy undergoes rapid expansion and decentralization of strategic decision making to the level of the state‐owned enterprise. As the central government takes on a lesser role in the management of enterprises, and Chinese enterprise managers become more responsible for their own strategic decision making, a clear understanding of the enterprise's specific capabilities and advantages is required in order to achieve sustained competitive advantage. Concludes by discussing managerial implications.
The effect of FDI inflows and ICT infrastructure on exporting in ASEAN/AFTA countries
Authors: Suh Taewon , Khan Omar J.
Published: September 2003

This paper explores the impact of both the increase in foreign direct investment inflows and the increase in information and communication technology infrastructure investments on exporting in ASEAN nations (the trade bloc of which is known as AFTA) compared with two other major trade blocs: CEFTA and LAIA. The analyses are based on data from a cross section of countries (26 emerging markets from three trade blocs) over time (from 1995 to 2000). The results show that the increase of investments in ICT infrastructure yields positive and significant returns in the national exporting level only for the ASEAN/AFTA and CEFTA sample. Interestingly, the impact of the increase of FDI inflows on export is significant only in the CEFTA and LAIA samples. These results are discussed in the light of the different economic experiences of these trade blocs, noting that variations are typically present between individual countries. Overall, reflecting the results from this study, research concerned with the determinants of national exporting level should be conducted independently, along with regional and national characteristics.
Self‐stratifying coatings for industrial applications
Authors: Verkholantsev V.V.
Published: September 2003

This paper reviews the self‐stratifying coatings concept, which is a tool to formulate film‐forming compositions based on incompatible polymer blends capable of producing coatings having polymer/polymer composite structures and outstanding performance in a number of application fields. The self‐stratifying concept is applicable to waterborne, solvent‐based and powder coatings, requiring specific formulations and frequently also conditions of application and film formation. Micro‐heterogeneous and non‐homogeneous‐in‐layer (or ultimately double‐layer) film structures obtained by one‐coat application of a single coating composition render considerable enhancement in coatings properties (mechanical, protective etc.) particularly various surface/interfacial properties (e.g. scratch‐resistance, mar‐resistance and adhesion durability, etc.).
A vorticity method for the solution of natural convection flows in enclosures
Authors: Ingber Marc S.
Published: September 2003

Vorticity formulations for the incompressible Navier‐Stokes equations have certain advantages over primitive‐variable formulations including the fact that the number of equations to be solved is reduced through the elimination of the pressure variable, identical satisfaction of the incompressibility constraint and the continuity equation, and an implicitly higher‐order approximation of the velocity components. For the most part, vorticity methods have been used to solve exterior isothermal problems. In this research, a vorticity formulation is used to study the natural convection flows in differentially‐heated enclosures. The numerical algorithm is divided into three steps: two kinematic steps and one kinetic step. The kinematics are governed by the generalized Helmholtz decomposition (GHD) which is solved using a boundary element method (BEM) whereas the kinetics are governed by the vorticity equation which is solved using a finite element method (FEM). In the first kinematic step, vortex sheet strengths are determined from a novel Galerkin implementation of the GHD. These vortex sheet strengths are used to determine Neumann boundary conditions for the vorticity equation. (The thermal boundary conditions are already known.) In the second kinematic step, the interior velocity field is determined using the regular (non‐Galerkin) form of the GHD. This step, in a sense, linearizes the convective acceleration terms in both the vorticity and energy equations. In the third kinetic step, the coupled vorticity and energy equations are solved using a Galerkin FEM to determine the updated values of the vorticity and thermal fields. Two benchmark problems are considered to show the robustness and versatility of this formulation including natural convection in an 8×1 differentially‐heated enclosure at a near critical Rayleigh number.
No change from within: senior women managers’ response to gendered organizational structures
Authors: Rindfleish Jennifer , Sheridan Alison
Published: September 2003

The gendered nature of organizations has now been well established by feminist researchers. In particular, the most senior levels of management have been identified as sites of hegemonic masculinity; the causes of which are complex, socially reproduced inter‐relationships that are highly resistant to change. While it has been argued that these structures will become less problematic as more women enter the paid workforce and more move into senior management, in this paper this argument is challenged. Recent research by the authors concerning women in the most senior ranks of management in the private sector in Australia suggests that, while the majority of these women identify the need for change, they have not used their role in senior management as a means of challenging gendered structures. The implications of the findings are that it is invalid to assume that change will come about through increasing numbers of women in management. Other means of challenging gendered organizational structures must be implemented, if quantifiable change is to come about.
Knowledge and learning in female team‐managed firms adopting information communication technologies (ICTs)
Authors: Martin Lynn M. , Halstead Alison
Published: September 2003

This micro‐level view of information and communication technology (ICT)‐related decision‐making processes in particular female “knowledge” firms offers areas for further review, research and discussion. Internally focused, these firms reflect earlier studies recommending support for female networking to develop competitive advantage, since fewer sources of ideas, advice, and information may mean that options are limited when problems arise outside previous organisational experience. ICT adoption relied on family and friends rather than professional support. Similarly, Internet use to scope the market or source information was also limited. Further research is suggested to explore management practices within established female‐run firms, and in firms run by teams rather than single owners, to develop deeper understanding of the processes at work and how to support change and development in such firms.
Comparing online and traditional teaching – a different approach
Authors: Salter Graeme
Published: September 2003

Rather than attempt to measure the effectiveness of online teaching by comparison with some non‐existent traditional method, this paper attempts to determine the conditions that promote learning and examine if these can be provided in an online environment. In this case, learning is viewed as a path to wisdom rather than simply having knowledge or the ability to apply knowledge. After examining the role of technology related to conditions for learning, the paper suggests that technology has the potential to enhance and transform teaching, but it can also be used inappropriately or in ways that actually interfere with learning. The real question is not whether effective learning can occur online, but rather how this can be most appropriately achieved?
Prioritising information systems projects in higher education
Authors: Dutta R. , Burgess T.F.
Published: September 2003

This paper focuses on solving the problem faced by higher education institutions (HEIs) when prioritising information systems (IS) projects. In many instances HEIs face many more potential IS projects than they can cope with. Making good decisions as to which projects should be supported becomes a complex but crucial issue. In practice, managers may resort to simple heuristics or rules of thumb to decide on projects that should be evaluated against competing objectives. In such complex situations structured approaches exist such as multi‐criteria decision making. The case study reported here explores the application of such a technique, simple multi‐attribute rating technique (SMART), to support the IS Department of Leeds University when prioritising IS projects.
The online education market
Authors: Eisenbarth Greg
Published: September 2003

The online degree and education market represents a crossroad for Higher Education. Outlines some issues the HE community must now face and several factors to success for their online degree programs. Universities have played an important role in the formation of the Internet and application of online education. The question remains, will universities actively participate and lead this market or sit on the sidelines and watch an opportunity for education slip away? Universities must act now.
Job commitment, job satisfaction and gender as predictors of mentoring in the Nigeria Police
Authors: Oyesoji Aremu A. , Adeola Adeyoju C.
Published: September 2003

This study investigates the effect of mentoring on commitment to job, job satisfaction and gender in the Nigeria Police. The participants, numbering 592, were recruited for the study from three out of six geo‐political zones in Nigeria using a cluster quota random sampling method. They comprised 396 (66.9 per cent) males and 196 (33.1 per cent) females, 179 (30.2 per cent) officers (senior officers) and 413 (69.8 per cent) junior staff. Two hypotheses and two research questions were tested and answered at 0.05 margin of error using Z score and analysis of variance statistics. Results showed that mentored male police are more committed to their job. The mentored female police showed more satisfaction with their job than the mentored male police. Mentoring was also found to predict commitment to job of the police. The implications of these findings are discussed.
CRM and customer‐centric knowledge management: an empirical research
Authors: Stefanou Constantinos J. , Sarmaniotis Christos , Stafyla Amalia
Published: September 2003

Current competitive challenges induced by globalization and advances in information technology have forced companies to focus on managing customer relationships, and in particular customer satisfaction, in order to efficiently maximize revenues. This paper reports exploratory research based on a mail survey addressed to the largest 1,000 Greek organizations. The objectives of the research were: to investigate the extent of the usage of customer‐ and market‐related knowledge management (KM) instruments and customer relationship management (CRM) systems by Greek organizations and their relationship with demographic and organizational variables; to investigate whether enterprises systematically carry out customer satisfaction and complaining behavior research; and to examine the impact of the type of the information system used and managers’ attitudes towards customer KM practices. In addition, a conceptual model of CRM development stages is proposed. The findings of the survey show that about half of the organizations of the sample do not adopt any CRM philosophy. The remaining organizations employ instruments to conduct customer satisfaction and other customer‐related research. However, according to the proposed model, they are positioned in the first, the preliminary CRM development stage. The findings also suggest that managers hold positive attitudes towards CRM and that there is no significant relationship between the type of the transactional information system used and the extent to which customer satisfaction research is performed by the organizations. The paper concludes by discussing the survey findings and proposing future research.
A knowledge processing method for intelligent systems based on inclusion degree
Authors: Qiu Guo Fang , Li Huai Zu , Xu Li Da , Zhang Wen Xiu
Published: September 2003

The probability reasoning method, fuzzy reasoning method, evidential reasoning method and other reasoning methods are main techniques employed in intelligent systems for processing uncertain and vague information. The concept of inclusion degree was proposed earlier and it has been proved that the methods mentioned above are examples of inclusion degrees. In this paper, we introduce type S1 and type S2 inclusion degrees, discuss the relationship between them, and further propose inclusion degrees on interval numbers, divisions, vectors and set vectors. This paper addresses an uncertainty analysis method with different inclusion degrees for intelligent systems and other systems such as fuzzy relational databases.
A Report on the Development of a Research Agenda for the Product Development and Management Association
Authors: Burger Philip C.
Published: September 2003

One of the most critical steps in the development of a professional field is the development of a research tradition. The Product Development and Management Association has long been committed to the stimulation of quality research efforts in the field of new products management. Accordingly, to begin the development of a research agenda, PDMA sponsored a colloquium of academic and practitioner researchers. Philip C. Burger, then serving as PDMA's Vice President of Research, organized the meeting and reports on the results of a two and a half day discussion. Some of the topics emphasized include organizational behavior and leadership, dissemination of good practice and the importance of a benchmark study of new product success and failure as starting points.
Positioning of Financial Services for Competitive Advantage
Authors: Easingwood Christopher J. , Mahajan Vijay
Published: September 2003

The financial services sector is becoming increasingly competitive. Deregulation allows formerly nonoverlapping financial institutions to compete. To survive and succeed, financial institutions must develop strong positions. A position summarizes the distinctive competence that a company seeks to convey to the marketplace to establish its competitive advantage. In this article, Christopher Easingwood and Vijay Mahajan describe a number of positioning attempts in the financial services sector. They are guided by two central objectives.

The first is to show how the special characteristics of services give rise to eight different positioning possibilities for financial services organizations. These positions present a range of potential options from which the manager may choose. For instance, an “extra service” position is one option, a “performance” position is another.

The second objective is to demonstrate the use of the positioning framework, with examples taken from the insurance sector to provide illustrations rather than a complete picture of insurance positioning.

The article concludes with a number of recommendations. For instance, financial institutions should avoid overcrowded positions and occupy underexploited positions. If accepted, these recommendations should help the financial services executive develop a competitive positioning strategy.
Leadership Differences in New Product Development Teams
Authors: Barczak Gloria , Wilemon David
Published: September 2003

Innovativeness is unlikely without skilled leaders to guide the teams which develop new products and technologies. Although the importance of leadership to innovation success is often discussed, the specific practices of effective team leaders are not. In this study, Gloria Barczak and David Wilemon focus on the roles, functions and methods employed by leaders of operating and innovating types of new product development teams. Operating teams are part of the daily activities of the firm, are involved with current markets and develop products similar to current product offerings. Innovating teams do not routinely engage in day‐to‐day activities. They pursue new markets and develop products quite different from existing ones. The results suggest that successful leaders of both types of teams perform similar roles and functions. However, the methods they use to achieve them vary by the type of new product development team.
Redesigning Product Lines with Conjoint Analysis: A Comment
Authors: Wittink Dick R.
Published: September 2003

In a recent article, Page and Rosenbaum [Journal of Product Innovation Management 4; 120–137 (June 1987)] discuss the use of conjoint analysis at Sunbeam Corporation. Their article provides a nice illustration of a conjoint application to food processor appliance redesign decisions. In this note, Dick Wittink compares characteristics of Sunbeam's approach to both established and more recent results reported in the conjoint literature.
Managing Technologically Innovative Team Efforts Toward New Product Success
Authors: Thamhain Hans J.
Published: September 2003

Based on his two‐year field study of 360 new product managers in 52 high technology companies, Hans Thamhain reports on the characteristics of innovative product teams. He identifies both drivers and barriers to innovative performance. Further, he presents a simple input‐output framework for organizing and analyzing the variables that influence team performance, and provides specific guidelines to help new products managers become more effective.
Entry Strategies and Market Performance Causal Modeling of a Business Simulation
Authors: Green Donna H. , Ryans Adrian B.
Published: September 2003

A key decision faced by marketing managers is the development of entry strategies for new markets. In addition to selecting which product market to enter, the manager must make decisions about the entry strategy itself. The entry strategy, whether managed actively or passively, affects the entrant's performance. In this article, Donna Green and Adrian Ryans discuss the three major components of an entry strategy: the timing of entry, the magnitude and areas of investment and the basis for competitive emphasis. They report that very little empirical research has focused on relationships between entry strategy and eventual product performance.
An Information Transfer Model for Integrating Marketing and R&D Personnel in New Product Development Projects
Authors: Moenaert Rudy K. , Souder William E.
Published: September 2003

Marketing and R&D personnel are key actors in the development of new product innovations. Interdependence between the marketing and the R&D functions necessitates integration. Rudy Moenaert and William Souder feel that task specification, structural design and climate orientation are the major integration mechanisms advocated in the literature. Supported by an extensive literature review, they propose a nomological network which interrelates integration mechanisms, interfunctional information transfer, uncertainty reduction and new product innovation success. They develop a causal framework to describe the determinants of successful information transfer between marketing and R&D in the development of technologically new products.
Characteristics of Innovative Firms in the Brazilian Computer Industry
Authors: da Rocha Angela , Christensen Carl H. , Paim Newton A.
Published: September 2003

A number of studies have reported characteristics of innovative firms; however, these studies have typically been conducted in freely competitive markets. Angela da Rocha, Carl Christensen and Newton Paim have studied firms within the Brazilian computer industry. The Brazilian government regulates the entrance of foreign competitors to this market. Thus, the authors are able to ask whether the characteristics of innovative firms in a protected market differ from characteristics previously reported in competitive markets. With only a few minor exceptions, the reported profiles of innovative firms are quite similar. These results suggest that characteristics of innovative firms are generalizable across certain industry and environmental conditions, including protected markets.
Marketing/R&D Interaction in New Product Development: Implications for New Product Success Rates
Authors: Hise Richard T. , O'Neal Larry , Parasuraman A. , McNeal James U.
Published: September 2003

A growing body of literature has evolved which deals with the interaction between marketing and R&D in new product development. Much of this research, unfortunately, fails to associate various variables with new product success levels. Thus, it cannot suggest consensus guidelines for marketing's involvement to increase the performance levels of new products in the market place. Richard Hise, Larry O'Neal, A. Parasuraman and James McNeal report results of their analysis of the new product development procedures of 252 large manufacturing companies. The authors conclude that collaborative efforts between marketing and R&D during the actual designing of new products appear to be a key factor in explaining the success levels of new products, that management effort should focus on the design stage of the new product development process rather than on the earlier and later stages and that R&D's contributions cannot be ignored while decisions are made about marketing's role in developing new consumer and industrial products.
Project Team Communication and Cross‐Functional Cooperation in New Program Development
Authors: Pinto Mary Beth , Pinto Jeffrey K.
Published: September 2003

The importance of communication for the successful development of new projects, particularly within the R&D laboratory setting, has been well documented. Yet researchers have seldom examined the relationship between patterns of communication and cross‐functional cooperation in the development and management of new programs. In this article Mary Beth and Jeffrey Pinto report on the results of a research study that assessed the relationship of two aspects of project team communication (formal versus informal modes and reason for communication) with the level of cross‐functional cooperation actually achieved within a hospital project team charged with developing a new program. A total of 262 team members were surveyed from 72 hospital project teams. The results demonstrated that high cooperation teams differed from low cooperation teams both in terms of their increased use of informal methods for communication as well as their reasons for communicating. Finally, cross‐functional cooperation was found to be a strong predictor of certain project outcomes.
Book Reviews
Authors: Rosenau Milton D.
Published: September 2003

This issue's review looks at a recent book written by Milton D. Rosenau, Jr., a two‐time contributor to this journal. The review is written by Randy Englund, R&D project development manager for Hewlett‐Packard in Cupertino, California. Previously, he served as a computer systems program manager.

Englund's favorable review mentions a number of points that will be of interest to JPIM's readers:

the book emphasizes speed in development

it stresses a team‐based, phased development approach

it establishes the need for clear specifications

useful summaries and implementation guidelines are included throughout the text

the issues treated are of major importance to new product managers
Downregulation of renal AQP2 water channel and NKCC2 in mice lacking the apical Na+‐H+ exchanger NHE3
Authors: Amlal Hassane , Ledoussal Clara , Sheriff Sulaiman , Shull Gary E. , Soleimani Manoocher
Published: September 2003

The apical Na+‐H+ exchanger NHE3 plays an important role in fluid reabsorption in the proximal tubule. However, whether its deletion alters the salt and water transport in the distal nephron remains unknown. To answer these questions, wild‐type (Nhe3+/+) and NHE3 null mice (Nhe3−/−) were placed in metabolic cages and their water balance and urine osmolality were examined. Nhe3−/− mice demonstrated a significant polydipsia (P < 0.03) and polyuria (P < 0.04), with a lower urine osmolality (P < 0.003) as compared to Nhe3+/+ mice. Northern hybridization and immunoblotting studies indicated that the mRNA expression and protein abundance of the collecting duct (CD) water channel AQP2 decreased by 52 % (P < 0.0003) and 73 % (P < 0.003) in the cortex, and by 53 % and 54 % (P < 0.002) in the inner medulla (IM) of Nhe3−/− vs. Nhe3+/+ mice. The expression of AQP2 in the outer medulla (OM) remained unchanged. Further, the mRNA expression and protein abundance of the medullary thick ascending limb (mTAL) apical Na+‐K+‐2Cl− cotransporter (NKCC2) decreased by 52 % (P < 0.02) and 44 % (P < 0.01), respectively, in the OM of Nhe3−/− vs. Nhe3+/+ mice. The circulating plasma levels of vasopressin as well as the mRNA expression of vasopressin prohormone were significantly increased in Nhe3−/− vs. Nhe3+/+ mice (P < 0.05). Studies in mice treated with acetazolamide indicated that increased bicarbonate and fluid delivery to distal nephron did not alter the expression of NKCC2 in mTAL and decreased AQP2 protein only in OM but not in the cortex or IM. In conclusion, mice lacking the apical NHE3 have impairment in their water balance and urine osmolality, which correlates with the downregulation of AQP2 expression. These defects occur despite increased circulating levels of vasopressin. We propose that an ADH‐independent mechanism is responsible for the downregulation of AQP2 and the resulting polyuria in NHE3 null mice.
The Mouse That Roared
Authors: Chen Ingfei
Published: September 2003

Physiologist Andrzej Bartke, of Southern Illinois University School of Medicine in Springfield, made his official debut in biogerontology in 1996 with the discovery that the growth-hormone-deficient Ames dwarf mouse has an extended life span. At that time, Bartke already had 30 years of successes in endocrinology research under his belt, including work that elucidated the role of the hormone prolactin in male reproduction. Born in Poland, Bartke studied zoology at Krakow's Jagiellonian University and conducted research for a year in Vietnam before obtaining a Ph.D. from the University of Kansas, Lawrence. His interest in aging arose from endocrinology studies, done in the early 1990s, of giant mutant mice that overproduce growth hormone and seem to grow old prematurely. Since then Bartke has become a leading expert on the physiology of how growth hormone influences aging and life span.
Ubiquitin, Proteasomes, and the Aging Brain
Authors: Gray Douglas A. , Tsirigotis Maria , Woulfe John
Published: September 2003

Ubiquitinated proteinaceous inclusions are the hallmark of many neurodegenerative diseases. Inefficient proteolysis might lead to the accumulation and ultimate deposition of potentially toxic entities as inclusions within neurons or glial cells. This hypothesis is supported by genetic evidence both from patient populations and from engineered mutations in genes that encode ubiquitin/proteasome components in mice. The appearance of similar inclusions in the brains of elderly individuals of normal and subclinical conditions begs the question of whether there is a general age-related decline in the ability of the ubiquitin/proteasome pathway (UPP) to recognize and eliminate abnormal proteins, and whether such a decline would be reflected by changes in the abundance or activity of some or all components of the UPP. Here we describe alterations in the aging mammalian brain that correlate with a decline in the function of the UPP and review the evidence for age-related changes in specific UPP components. These alterations are discussed within the context of prevalent theories of aging.
Stimulated to Death
Authors: Leslie Mitch
Published: September 2003

Listening to your teenager's stereo blaring the same song all day only seems like it's destroying your brain. However, some kinds of overstimulation can wreck neurons, according to a new study. Brain cells kill themselves after incessant prodding by the neurotransmitter dopamine. The work uncovers a new mechanism of neural degeneration and might explain what triggers one of the most common side effects of Parkinson's disease (PD) treatment.
Novel Plasmid-Borne Gene
qacJ
Mediates Resistance to Quaternary Ammonium Compounds in Equine
Staphylococcus aureus
,
Staphylococcus simulans
, and
Staphylococcus intermedius
Authors: Bjorland Jostein , Steinum Terje , Sunde Marianne , Waage Steinar , Heir Even
Published: September 2003

We identified a novel plasmid-borne gene (designated
qacJ
) encoding resistance to quaternary ammonium compounds (QACs) in three staphylococcal species associated with chronic infections in four horses.
qacJ
was located on a 2,650-bp plasmid (designated pNVH01), a new member of the pC194 family of rolling-circle replication plasmids. The 107-amino-acid protein, QacJ, showed similarities to known proteins of the small multidrug resistance family: Smr/QacC (72.5%), QacG (82.6%), and QacH (73.4%). The benzalkonium chloride MIC for a
qacJ
-containing recombinant was higher than those for otherwise isogenic recombinants expressing Smr, QacG, or QacH. Molecular epidemiological analyses by pulsed-field gel electrophoresis suggested both the clonal spread of a
qacJ
-harboring
Staphylococcus aureus
strain and the horizontal transfer of pNVH01 within and between different equine staphylococcal species. The presence of pNVH01 of identical nucleotide sequence in different staphylococcal species suggests that recent transfer has occurred. In three of the horses, a skin preparation containing cetyltrimethylammonium bromide had been used extensively for several years; this might explain the selection of staphylococci harboring the novel QAC resistance gene.
In Vitro Activities of Three Licensed Antifungal Agents against Spanish Clinical Isolates of
Aspergillus
spp
Authors: Gomez-Lopez Alicia , Garcia-Effron Guillermo , Mellado Emilia , Monzon Araceli , Rodriguez-Tudela Juan L. , Cuenca-Estrella Manuel
Published: September 2003

The aim of the present study was to identify retrospectively trends in the species distributions and the susceptibility patterns of
Aspergillus
species causing fungal infections in Spanish medical centers from 2000 to 2002. The susceptibilities of 338 isolates to amphotericin B, itraconazole, and voriconazole were tested.
Aspergillus fumigatus
was the most common species (54.7%), followed by
Aspergillus terreus
(14.8%) and
Aspergillus flavus
(13.9%). Non-
A. fumigatus
species were encountered in 45.3% of the samples studied. The majority of
Aspergillus
isolates were obtained from respiratory tract specimens, followed by ear and skin samples. The geometric mean (GM) MIC of amphotericin B was 0.56 μg/ml, and the amphotericin B MIC was >2 μg/ml for 16 isolates (4.7%). Nine of them were
A. terreus
. The GM MIC of itraconazole was 0.37, and the itraconazole MIC was >4 μg/ml for 12 (3.5%) isolates. The voriconazole MICs were also high for 8 of the 12 strains for which itraconazole MICs were high (voriconazole MIC range, 2 to 8 μg/ml).
Penetration of Moxifloxacin into Healthy and Inflamed Subcutaneous Adipose Tissues in Humans
Authors: Joukhadar Christian , Stass Heino , Müller-Zellenberg Ulrike , Lackner Edith , Kovar Florian , Minar Erich , Müller Markus
Published: September 2003

The present study addressed the ability of moxifloxacin to penetrate into healthy and inflamed subcutaneous adipose tissues in 12 patients with soft tissue infections (STIs). Penetration of moxifloxacin into the interstitial space fluid of healthy and inflamed subcutaneous adipose tissues was measured by use of in vivo microdialysis following administration of a single intravenous dosage of 400 mg in six diabetic and six nondiabetic patients with STIs. For the entire study population, the mean time-concentration profile of free moxifloxacin in plasma was identical to the time-concentration profile of free moxifloxacin in tissue (Pwas not significant). For healthy and inflamed adipose tissues for the diabetic subgroup, the mean moxifloxacin areas under the concentration-time curves (AUCs) from 0 to 8 h (AUC0-8s) were 8.1 ± 7.1 and 3.7 ± 1.9 mg·h/liter, respectively (Pwas not significant). The ratios of the mean AUC0-8for inflamed tissue/AUC0-8for free moxifloxacin in plasma were 0.5 ± 0.4 for diabetic patients and 1.2 ± 0.8 for nondiabetic patients (Pwas not significant). The ratios of the AUCs from 0 to 24 h for free moxifloxacin in plasma/MIC at which 90% of isolates are inhibited were >58 and 121 h forStreptococcusspecies and methicillin-sensitiveStaphylococcus aureus, respectively. Concentrations of moxifloxacin effective against clinically relevant bacterial strains are reached in plasma and in inflamed and healthy adipose tissues. Thus, the pharmacokinetics of moxifloxacin in tissue and plasma support its use for the treatment of STIs in diabetic and nondiabetic patients.
Fluoroquinolone-Containing Third-Line Regimen against
Mycobacterium tuberculosis
In Vivo
Authors: Veziris Nicolas , Truffot-Pernot Chantal , Aubry Alexandra , Jarlier Vincent , Lounis Nacer
Published: September 2003

The objective of the present study was to compare the activities of a third-line regimen recommended by the World Health Organization (WHO) and two derivatives of that regimen with the activity of the standard combination of isoniazid, rifampin, and pyrazinamide as a positive control against
Mycobacterium tuberculosis
in a murine model. The WHO regimen combines ofloxacin (OFX), ethionamide, amikacin, and pyrazinamide; in the two derivatives of this regimen, OFX was replaced by levofloxacin (LVX) or moxifloxacin (MXF). The four drugs, a fluoroquinolone (either OFX, LVX, or MXF), ethionamide, pyrazinamide, and amikacin, were administered for the first 2 months (initial phase); and two drugs, a fluoroquinolone (either OFX, LVX, or MXF) and ethionamide, were administered for the following 10 months (continuation phase). After 6 months of treatment, only the spleens and lungs of mice treated with the standard regimen became culture negative. From 9 months onward, all of the organs of mice treated with the MXF-containing third-line regimen were culture negative. The majority of organs from mice treated with the OFX-containing regimen continued to be culture positive, and the mean CFU counts remained unchanged for as long as 12 months. The results for mice treated with the LVX-containing regimen fell between those for the groups receiving the MXF- and OFX-containing regimens. In conclusion, the activity of the OFX-containing third-line regimen against
M. tuberculosis
was rather weak in vivo, whereas when OFX was replaced by MXF, 9 months of treatment with a modified third-line regimen displayed bactericidal activity comparable to that of 6 months of treatment with the standard regimen in mice. The MXF-containing third-line regimen seems to be a powerful alternative for the treatment of tuberculosis (TB) when isoniazid and rifampin cannot be used, which is the main feature of multidrug-resistant TB.
Population Pharmacokinetics of Ciprofloxacin in Pediatric and Adolescent Patients with Acute Infections
Authors: Payen S. , Serreau R. , Munck A. , Aujard Y. , Aigrain Y. , Bressolle F. , Jacqz-Aigrain E.
Published: September 2003

The aim of the present study was to characterize the population pharmacokinetics of ciprofloxacin in patients with and without cystic fibrosis ranging in age from 1 day to 24 years and to propose a limited sampling strategy to estimate individual pharmacokinetic parameters. Patients were divided into four groups according to the treatment schedule. They received ciprofloxacin by intravenous infusion (30 min) or by the oral route. The number of samples collected from each patient ranged from 1 to 12. The population parameters were computed for an initial group of 37 patients. The data were analyzed by nonlinear mixed-effect modeling by use of a two-compartment structural model. The interindividual variability in clearance (CL) was partially explained by a dependence on age and the patient's clinical status. In addition, a significant relationship was found between weight and the initial volume of distribution. Eighteen additional patients were used for model validation and evaluation of limited sampling strategies. When ciprofloxacin was administered intravenously, sampling at a single point (12 h after the start of infusion) allowed the precise and accurate estimation of CL and the elimination half-life, as well as the ciprofloxacin concentration at the end of the infusion. It should be noted that to take into account the presence of a lag time after oral administration, a schedule based on two sampling times of 1 and 12 h is needed. The results of this study combine relationships between ciprofloxacin pharmacokinetic parameters and patient covariates that may be useful for dose adjustment and a convenient sampling procedure that can be used for further studies.