bluuebunny/crossref_metadata_2025 huggingface dataset:
Replicable and recombinogenic RNAs
Authors: Chetverin Alexander B.
Published: April 2004

This paper summarizes results of the 40‐year studies on replication and recombination of RNA molecules in the cell‐free amplification system of bacteriophage Qβ. Special attention is paid to the molecular colony technique that has provided for the discovery of the nature of “spontaneous” RNA synthesis by Qβ replicase and of the ability of RNA molecules to spontaneously rearrange their sequences under physiological conditions. Also discussed is the impact of these data on the concept of RNA World and on the development of new in vitro cloning and diagnostic tools.
Guest Editor's Preface: International Conference on the
Frontiers of Plasma Physics and Technology
Authors: Desai Tara
Published: April 2004

The first International Conference on the Frontiers of Plasma Physics
and Technology was organized in Bangalore, India during December
9–14, 2002. More than 100 delegates from all the continents
participated in the conference and about half the delegates were from
overseas. This Forum specially encouraged the young researchers to
present their work and exchange ideas with experts. This conference
which was inter-disciplinary in nature, brought several plasma
physicists and technologists to a common platform to discuss the
research and applications useful for the advancement of the present
society.
Parametric exploration of intense positron beam–plasma
interactions
Authors: BLUE B.E. , CLAYTON C.E. , O'CONNELL C.L. , DECKER F.-J. , HOGAN M.J. , HUANG C. , IVERSON R. , JOSHI C. , KATSOULEAS T.C. , MARSH K.A. , MORI W.B. , WALZ D.
Published: April 2004

A systematic investigation of the longitudinal fields excited in a
plasma by a short, dense beam of positrons is carried out using
two-dimensional, cylindrical geometry, particle-in-cell code
simulations. In particular, we examine the behavior of the accelerating
and decelerating fields of the wakefield as a function of beam charge,
radius, length, and plasma density. The parameters are chosen to be
consistent with those employed in current and future experiments
designed to elucidate the physics of positron beam–plasma
interactions.
Effect of cross focusing of two laser beams on the growth of laser
ripple in plasma
Authors: PUROHIT GUNJAN , PANDEY H.D. , SHARMA R.P.
Published: April 2004

This article presents an effect of cross focusing of two laser beams
on the growth of a laser ripple in laser-produced plasmas. The
mechanism of nonlinearity is assumed to be ponderomotive force, arising
because of the Gaussian intensity distribution of the laser beams. The
dynamical equation governing the laser ripple intensity has been set up
and a numerical solution has been presented for typical laser plasma
parameters. It is found that the change in the intensity of the second
laser beam can affect the growth of the laser ripple significantly.
Theoretical investigation of high-energy ions produced from
laser-cluster interactions
Authors: ZHU PINPIN , LIU JIANSHENG , XU ZHIZHAN
Published: April 2004

By using an effective dielectric constant to modify the nanoplasma
model, the interactions of large Ar clusters with high-intensity
femtosecond laser pulses have been studied. It is shown that the
resonance absorption mechanism plays a predominant role in the
production of highly energetic argon ions, and the calculated mean
kinetic energy of Ar ions is in good agreement with our previous
experimental results. The scaling of mean kinetic energy and charge
states of Ar ions against cluster size and laser intensity has also
been analyzed. The results indicate the existence of optimum cluster
sizes and optimum laser intensities where the best coupling efficiency
of the laser energy can be obtained.
The principle of superposition in human prehension
Authors: Zatsiorsky Vladimir M. , Latash Mark L. , Gao Fan , Shim Jae Kun
Published: April 2004

The experimental evidence supports the validity of the principle of superposition for multi-finger prehension in humans. Forces and moments of individual digits are defined by two independent commands: “Grasp the object stronger/weaker to prevent slipping” and “Maintain the rotational equilibrium of the object”. The effects of the two commands are summed up.
Einflusskompetenz in Organisationen
Authors: Blickle Gerhard
Published: April 2004

Zusammenfassung. In diesem Beitrag soll ein Überblick über die neuere organisationspsychologische Einflussforschung in Bezug auf das Konstrukt der Einflusskompetenz in Organisationen gegeben werden. Einflusskompetenz bezeichnet diejenige Facette der sozialen Kompetenzen, die durch die erfolgreiche Beeinflussung anderer zum Realisieren von Zielen und Plänen einer Person im Handlungskontext einer Organisation beiträgt. Dazu wird zunächst ein theoretischer Überblick über die Wirkmechanismen der intraorganisationalen Einflusstaktiken gegeben. Dann wird über zwei Meta-Analysen zu den Effekten intraorganisationaler Einflussnahme berichtet. Im Anschluss wird dargestellt, durch welche Art von Förderung es zu einer gezielten Entwicklung der situationsspezifischen und situationsübergreifenden Einflusskompetenz von Personen in Organisationen kommen kann und inwiefern Persönlichkeitsmerkmale und kognitive Fähigkeiten dafür dienlich sind. Abschließend werden einschlägige Forschungsdefizite aufgezeigt.
Design Choices when Architecting Visualizations
Authors: Tang Diane , Stolte Chris , Bosch Robert
Published: April 2004

In this paper, we focus on some of the key design decisions we faced during the process of architecting a visualization system and present some possible choices, with their associated advantages and disadvantages. We frame this discussion within the context of Rivet, our general visualization environment designed for rapidly prototyping interactive, exploratory visualization tools for analysis. As we designed increasingly sophisticated visualizations, we needed to refine Rivet in order to be able to create these richer displays for larger and more complex data sets. The design decisions we discuss in this paper include the internal data model, data access, semantic meta-data information the visualization can use to create effective visual encodings, the need for data transformations in a visualization tool, modular objects for flexibility, and the tradeoff between simplicity and expressiveness when providing methods for creating visualizations.
Nanometer-scale magnetic resonance imaging
Authors: Chao Shih-hui , Dougherty William M. , Garbini Joseph L. , Sidles John A.
Published: April 2004

Magnetic resonance force microscopy (MRFM) images the three-dimensional spatial distribution of resonant spins by mechanical force detection. Image reconstruction in MRFM is challenging because the resonance occurs in a strongly curved shell that extends beyond the scan range. In contrast with conventional magnetic resonance imaging, where Fourier techniques work well, the curved-shell resonant geometry inherent to MRFM requires novel reconstruction methods. Here, we show the application of iterative reconstruction in an electron spin resonance imaging experiment with 80 nm voxels. The reconstructed image has a total scan volume of 0.5 cubic micrometers, and was generated by a magnetic resonant shell with a curvature radius of 2.3 μm. The imaged object was a paramagnetically doped solid with an obliquely tilted surface. The reconstructed image correctly identified the location and orientation of the surface, and mapped the spin distribution within the solid. Applications of MRFM include three-dimensional nanometer-scale mapping of dopant distributions in semiconductors, studies of magnetism of thin films, and spin diffusion physics. An ultimate goal of MRFM is the direct observation of molecular structure at the atomic scale.
HLA-G1-expressing antigen-presenting cells induce immunosuppressive CD4+T cells
Authors: LeMaoult Joël , Krawice-Radanne Irène , Dausset Jean , Carosella Edgardo D.
Published: April 2004

We recently reported that HLA-G1-transfected antigen-presenting cells (HLA-G1+APCs) were capable of inhibiting alloproliferative responses. The aim of the present work was to further study the function and the mechanisms of action of HLA-G1+APCs. We show here that HLA-G1+APCs are immunoinhibitory cells that (i) inhibit the proliferation of CD4+T cells, (ii) shed HLA-G1 molecules that might provide extra, non-antigen-specific, inhibitory or proapoptotic signals, (iii) induce CD4+T cell anergy, or at least long-term unresponsiveness, and (iv) cause the differentiation of CD4+T cells into suppressive cells. Thus, HLA-G+APCs might (i) be involved in the direct suppression of immune responses and (ii) contribute to long-term efficient immune escape or tolerance.
Dietary approach to attenuate oxidative stress, hypertension, and inflammation in the cardiovascular system
Authors: Wu Lingyun , Ashraf M. Hossein Noyan , Facci Marina , Wang Rui , Paterson Phyllis G. , Ferrie Alison , Juurlink Bernhard H. J.
Published: April 2004

Imbalance between production and scavenging of superoxide anion results in hypertension by the inactivation of nitric oxide, and the increased oxidative stress from the resultant peroxynitrite that is produced promotes inflammatory processes such as atherosclerosis. Induction of phase 2 proteins promotes oxidant scavenging. We hypothesized that intake of dietary phase 2 protein inducers would ameliorate both hypertension and atherosclerotic changes in the spontaneously hypertensive stroke-prone rat. For 5 days/week for 14 weeks, we fed rats 200 mg/day of dried broccoli sprouts that contained glucoraphanin, which is metabolized into the phase 2 protein-inducer sulforaphane (Group A), sprouts in which most of the glucoraphanin was destroyed (Group B), or no sprouts (Group C). After 14 weeks of treatment, no significant differences were seen between rats in Groups B and C. Rats in Group A had significantly decreased oxidative stress in cardiovascular and kidney tissues, as shown by increased glutathione (GSH) content and decreased oxidized GSH, decreased protein nitrosylation, as well as increased GSH reductase and GSH peroxidase activities. Decreased oxidative stress correlated with better endothelial-dependent relaxation of the aorta and significantly lower (20 mm Hg) blood pressure. Tissues from Groups B and C had considerable numbers of infiltrating activated macrophages, indicative of inflammation, whereas animals in Group A had few detectable infiltrating macrophages. There is interest in dietary phase 2 protein inducers as means of reducing cancer incidence. We conclude that a diet containing phase 2 protein inducers also reduces the risk of developing cardiovascular problems of hypertension and atherosclerosis.
A role for fast rhythmic bursting neurons in cortical gamma oscillations
in vitro
Authors: Cunningham Mark O. , Whittington Miles A. , Bibbig Andrea , Roopun Anita , LeBeau Fiona E. N. , Vogt Angelika , Monyer Hannah , Buhl Eberhard H. , Traub Roger D.
Published: April 2004

Basic cellular and network mechanisms underlying gamma frequency oscillations (30–80 Hz) have been well characterized in the hippocampus and associated structures. In these regions, gamma rhythms are seen as an emergent property of networks of principal cells and fast-spiking interneurons. In contrast, in the neocortex a number of elegant studies have shown that specific types of principal neuron exist that are capable of generating powerful gamma frequency outputs on the basis of their intrinsic conductances alone. These fast rhythmic bursting (FRB) neurons (sometimes referred to as “chattering” cells) are activated by sensory stimuli and generate multiple action potentials per gamma period. Here, we demonstrate that FRB neurons may function by providing a large-scale input to an axon plexus consisting of gap-junctionally connected axons from both FRB neurons and their anatomically similar counterparts regular spiking neurons. The resulting network gamma oscillation shares all of the properties of gamma oscillations generated in the hippocampus but with the additional critical dependence on multiple spiking in FRB cells.
Time-dependent density-matrix renormalization-group using adaptive effective Hilbert
spaces
Authors: A J Daley  , C Kollath  , U Schollwöck  , G Vidal
Published: April 2004

An algorithm for the simulation of the evolution of slightly entangled quantum states has
been recently proposed as a tool to study time-dependent phenomena in one-dimensional
quantum systems. Its key feature is a time-evolving block-decimation (TEBD) procedure to
identify and dynamically update the relevant, conveniently small, subregion of the
otherwise exponentially large Hilbert space. Potential applications of the TEBD algorithm
are the simulation of time-dependent Hamiltonians, transport in quantum systems far from
equilibrium and dissipative quantum mechanics. In this paper we translate the TEBD
algorithm into the language of matrix product states in order to both highlight and exploit
its resemblances to the widely used density-matrix renormalization-group (DMRG)
algorithms. The TEBD algorithm, being based on updating a matrix product state in
time, is very accessible to the DMRG community and it can be enhanced by
using well-known DMRG techniques, for instance in the event of good quantum
numbers. More importantly, we show how it can be simply incorporated into existing
DMRG implementations to produce a remarkably effective and versatile ‘adaptive
time-dependent DMRG’ variant, that we also test and compare to previous proposals.
An apprenticeship in scientific communication: the early correspondence of Henry Oldenburg (1656-63)
Authors: Avramov I.
Published: April 2004

This paper examines how Henry Oldenburg became a man of scientific communication during the years 1656-1663. His interest in the new natural philosophy started in the mid-1650s when, while visiting England, he became acquainted with men like Robert Boyle and Samuel Hartlib. Embarking on a trip over Europe as tutor to Richard Jones, Boyle's nephew, he also began to practice merchandising in knowledge. His communication skills quickly developed, for he learned a great deal from his personal contacts with men of science and from his correspondence with Hartlib, Boyle, and others. His prolonged stay in Paris in the late 1650s was very important for there he acquired an experience of the intellectual life of the private scientific academies, and gained for himself a host of new correspondents. The paper concludes by looking at Oldenburg in his role as mediator in the Spinoza-Boyle debate of 1663. By that time, at the beginning of his career as Secretary of the Royal Society, he was already a well-rounded ‘philosophicall merchant’.
John Tyndall, the rhetorician of molecularity. Part one. Crossing the boundary towards the invisible
Authors: Yamalidou M.
Published: April 2004

This paper highlights the way in which Tyndall achieved his broad understanding of the molecular character of physical nature through an examination of the various molecular explanations he put forward in his papers and lectures, and argues that, in Tyndall's writings, one can find a most articulate version of nineteenth-century British molecular discourse. The exploration of those molecular conditions which underlay physical phenomena was central to his research throughout the years, and for this exploration he utilized his imagination, which he believed to be an innate faculty of the human mind. According to Tyndall, the imaginative dimension of science consisted of the creation of mental images of the unseen which enabled scientists to cross the boundary that separated the realm of phenomena from those of causal mechanisms. In his writings he expressed these mental images of the unseen in the distinctive molecular language of his age.
The discovery of microorganisms by Robert Hooke and Antoni van Leeuwenhoek, Fellows of The Royal Society
Authors: Gest H.
Published: April 2004

The existence of microscopic organisms was discovered during the period 1665–83 by two Fellows of The Royal Society, Robert Hooke and Antoni van Leeuwenhoek. In
Micrographia
(1665), Hooke presented the first published depiction of a microrganism, the microfungus
Mucor
. Later, Leeuwenhoek observed and described microscopic protozoa and bacteria. These important revelations were made possible by the ingenuity of Hooke and Leeuwenhoek in fabricating and using simple microscopes that magnified objects from about 25–fold to 250–fold. After a lapse of more than 150 years, microscopy became the backbone of our understanding of the roles of microbes in the causation of infectious diseases and the recycling of chemical elements in the biosphere.
The life and work of Charles Tomlinson FRS: a career in Victorian science and technology
Authors: Kurzer F.
Published: April 2004

Charles Tomlinson (1808–97) was an exceptionally versatile scientist of the Victorian era, who, in a long career as an educator, encyclopaedist and researcher contributed significantly to the advancement of science and technology. By his prolific authorship of some 50 books and 100 published papers and notes, he promoted the dissemination of scientific information, both to professionals and to a wider public that was beginning to appreciate the powerful influence of technology on the wealth and well-being of society. In his magnificent
Cyclopaedia of the useful arts
, he set a monument to the contemporary state of science, technology and the manufactures. His researches in the field of chemical physics, especially concerned with the phenomena of surface tension, supersaturation and meteorology, were recognized by his election as a Fellow of The Royal Society.
Parvovirus LuIII transducing vectors packaged by LuIII versus FPV capsid proteins: the VP1 N-terminal region is not a major determinant of human cell permissiveness
Authors: Maxwell Ian H. , Maxwell Françoise
Published: April 2004

Human cell lines are permissive for LuIII, a member of the rodent group of autonomous parvoviruses. However, LuIII vectors pseudotyped with feline panleukopaenia virus (FPV) capsid proteins can transduce feline cells but not human cells. Feline transferrin receptor (FelTfR) functions as a receptor for FPV. Transfection of Rh18A, a human rhabdomyosarcoma cell line, with FelTfR enabled transduction by vector with FPV capsid. This was not true of other human lines, suggesting restriction at some additional, post-entry, level(s) in human cells other than Rh18A. It seemed a reasonable hypothesis that a second blockage might be in nuclear delivery mediated by the N-terminal region of the minor capsid protein, VP1. We therefore generated virions containing an LuIII–luciferase genome, packaged using chimaeric VP1 molecules (N-terminal region of LuIII VP1, fused with body of FPV, and vice versa) together with the major capsid protein, VP2, of FPV or LuIII. The virions were tested for ability to transduce feline and human cells. Our hypothesis predicted that the N-terminal region of LuIII VP1 should allow transduction of human cells expressing FelTfR, while the FPV N-terminal region should not allow transduction of human cells (except for Rh18A). The experimental results did not bear out either of these predictions. Therefore, the VP1 N-terminal region appears not to be a major determinant of permissiveness for LuIII, versus FPV, capsid in human cells.
In vitro transcription of Tomato spotted wilt virus is independent of translation
Authors: van Knippenberg Ingeborg , Goldbach Rob , Kormelink Richard
Published: April 2004

Ongoing transcriptionin vitroofTomato spotted wilt virus(TSWV) has previously been demonstrated to require the presence of reticulocyte lysate. This dependence was further investigated by testing the occurrence of transcription in the presence of two translation inhibitors: edeine, an inhibitor that still allows scanning of nascent mRNAs by the 40S ribosomal subunit, and cycloheximide, an inhibitor that completely blocks translation including ribosome scanning. Neither of these inhibitors blocked TSWV transcription initiation or elongationin vitro, as demonstrated byde novo-synthesized viral mRNAs with globin mRNA-derived leader sequences, suggesting that TSWV transcriptionin vitrorequires the presence of (a component within) reticulocyte lysate, rather than a viral protein resulting from translation.
Centre stage or just a supporting role? International interlending in the twenty‐first century – a UK perspective
Authors: Street Penelope
Published: April 2004

The world is fast becoming a smaller place and the same is true of the document delivery world. Rapid growth in resource discovery tools has led to a breaking down of barriers resulting in the international nature of resource sharing that now exists. Traditional methods of finding, requesting and delivery have radically altered and the “where” of the information object required is no longer of importance. Global availability of information has increased choice and expectation for the end‐user but, conversely, has created a new set of problems for the interlending community. One specific problem area of this global document delivery market is traditional interlending – the loan of returnables. This article considers how UK libraries are attempting to reconcile global demand with the unique problems of this particular area.
Interlending and document supply: a review of the recent literature – XLVII
Authors: McGrath Mike
Published: April 2004

Reviews more than 100 journals and some electronic lists and newsletters for issues and matters relevant to interlending and document supply. In particular, in this review, site licences, distance learning, providers of document supply, pricing, copyright, publishers, usage and open access are examined.
Observing experiences with the VSM
Authors: Schuhmann Werner
Published: April 2004

This paper offers a senior manager's reflections on experiences with the viable system model (VSM) in different situations of its application. These reflections are based on second‐order observation; that is on observing the forms of first‐order distinctions. Recently, systems thinking developed by Niklas Luhmann serves as an epistemological background. The VSM is recognized as a valuable tool to study and to change organizations, however, its “upgrade” is recommended in the light of insights, such as the protologic of distinctions or the more consistent realization of systems properties, such as operational closure and self‐reference.
Viability versus tribalism
Authors: Hilder Trevor
Published: April 2004

The viability of an organisation can be compromised by the tribal behaviour of its members. If this is not understood, attempts to reform it will be met with resistance, since the effort will be perceived as an attack against the norms of the organisation. The paper offers examples and evidence for this, suggests source materials for understanding the phenomenon, and practical techniques for overcoming it.
Observations on the development of cybernetic ideas in Colombia
Authors: Bula German
Published: April 2004

This paper is an account of management and organisational interventions in multiple institutions and enterprises in Colombia during the past 10 years, mainly influenced by Stafford Beer's ideas and work. It offers comments about the use of these ideas in three projects; particularly it focuses on an intervention in the National Controller's Office. These are accounts of failure and success. However, assessments of success and failure are tempered by difficulties in appreciating the complexity of social processes and our inability to see cause‐effect connections. The paper offers insights about concrete aspects of these interventions and the footprints they have left in the country.
The footprint of complexity: the embodiment of social systems
Authors: Espejo Raul
Published: April 2004

This paper deals with organisational complexity, seen from the perspective of its unfolding from global to local concerns. Historically, this unfolding has produced rigid social systems, where those in power positions have forced unfair constraints over the majorities at the local level, and often excluded them. There is a need to move towards flexible, fair, social systems, inclusive in character. This transformation requires an increasing appreciation of communication problems in society and the embodiment of effective social systems. This transformation is presented as a problem‐solving paradigm which requires social systems with capacity to create and produce their own meanings, with capacity to manage necessary structural couplings among existing social systems, thus making this management a heuristic to produce necessary social differentiation to overcome communication failures among existing self‐producing, operationally closed, social systems. A key construct used in this paper to practically produce this management is the viable system model, developed by Stafford Beer.
A framework for global IS outsourcing by application service providers
Authors: Soliman Khalid S.
Published: April 2004

The phenomenal growth of the Internet has persuaded many companies of its potential as a channel for outsourcing information systems applications. Application service providers (ASP) are firms that offer outsourcing application services to many organizations via the Internet. By contracting ASP, organizations are having information technology (IT) staff focusing their efforts on core competencies while, at the same time, capitalizing on the expertise of outsourcer. On the other hand, many ASP turn some of their projects to global outsourcer. The study develops a framework that identifies the critical factors influencing ASP' decision to outsource globally. These factors are product development costs, IT talent, product quality, communication technology, tax incentives, and cultural differences. The rest of the paper discusses the differences between different types of global outsourcing, explore the emerging trend and advantages of utilizing ASP, and recommend measures to ensure the success of projects to be developed globally. The framework developed in this paper represents a foundation for more rigorous empirical research to identify the significance of each influencing factor. The results can provide ASP managers with a road map that addresses issues of concern in global outsourcing.
A case analysis of business process outsourcing project failure profile and implementation problems in a large organisation of a developing nation
Authors: Khalfan Abdulwahed
Published: April 2004

As is the case for many developing economies, internationally published research on information systems (IS) practice in Kuwait is in short supply. The few reports of Kuwaiti IS/information technology (IT) practice highlighted in studies of Middle Eastern or Arab computing, have also largely discussed them in terms of these broader regional identities rather than their specific national context. Business process outsourcing (BPO) is becoming a widely‐accepted management practice throughout the world. In recent years, outsourcing of information services has become a pervasive phenomenon. Increasingly, organisations rely on external service providers for IS/IT services. Kuwait has been used as an example of a developing country where the data collection for this study was done there. This study employed case study methodology because the author was interested in answers for “how” and “why” questions and because the study was partly exploratory. The primary data on IS/IT outsourcing practices, obtained for the first time in Kuwait, were collected by means of semi‐structured interviews supported by organisational documentation. The case study discussed in this paper brought to the surface critical elements missing in the contract that led to the demise of the BPO project. Studying failure is preventive because it helps organisations reduce the probability of failure in the future. A central argument of this paper concerns the need to understand the complex cultural and political implications of outsourcing within a global context (perspectives), a policy that is becoming increasingly important. The case study findings are crucial as they provide a careful diagnosis of failed IT outsourcing project.
Determining Uses and Gratifications for the Internet
Authors: Stafford Thomas F. , Stafford Marla Royne , Schkade Lawrence L.
Published: April 2004

Uses and gratifications (U&G) is a media use paradigm from mass communications research that guides the assessment of consumer motivations for media usage and access. It has been used previously in research and decision making related to the promotion of emerging radio and television media. Recent adaptations of U&G research to the Internet are incomplete and have not identified important new Internet‐specific gratifications. This paper empirically derives dimensions of consumer Internet use and usage gratifications among customers of a prominent Internet Service Provider (ISP). Results describe three key dimensions related to consumer use of the Internet, including process and content gratifications as previously found in studies of television, as well as an entirely new social gratification that is unique to Internet use. All three dimensions of gratification are relevant to managing the Internet as a commercial medium, and measures developed from the gratification profiles identified here can serve as trait‐valid scales in future Internet and e‐commerce research.
Selecting Influential Business‐to‐Business Customers in New Product Development: Relational Embeddedness and Knowledge Heterogeneity Considerations
Authors: Bonner Joseph M. , Walker Orville C.
Published: April 2004

This study examines how the most influential business‐to‐business (B2B) customers, both existing and potential, involved in providing input to a new product development (NPD) project influence new product advantage. As the relational literature suggests, involving customers who have had close and embedded relationships with a firm's new product organization, such as a firm's largest customers, and customers who have been involved in past collaborative activities, should lead to the development of superior products. To the contrary, the innovation literature suggests that a firm may become too close to its large, embedded customers resulting in less innovation and in lower performing products. Also, the relationship between the heterogeneity of the knowledge of the most influential customers and new product advantage is examined. A contingency perspective is hypothesized such that the degree of product newness sought in the project moderates the effects of both relational embeddedness and knowledge heterogeneity on new product advantage.

Empirical findings from a sample of 137 NPD projects support this contingency view. For projects seeking to develop incremental products, where the product being developed is an extension or an enhancement to an existing product, new product advantage tended to be higher in projects using embedded or homogeneous customers. For incremental projects, projects using less‐embedded or heterogeneous customers tended to have lower product performance. For projects following a highly innovative product strategy, new product advantage tended to be higher in projects that involved heterogeneous customers. These heterogeneous customers provided NPD projects with a diversity of perspectives, competencies, and experiences that fostered significant product innovations.

The study contributes to the literature by empirically testing relational and innovation theories in NPD projects and by providing evidence on the importance of relational embeddedness and knowledge heterogeneity in selecting influential customers in NPD projects.
Myogenesis contributes to functional electrical stimulation (fes)‐induced recovery of myofiber excitability and mass of human long‐term denervated muscles in spinal cord injury (SCI)
Authors: Kern H , Boncompagni S , Rossigni K , Mayr W , Protasi F , Carraro U
Published: April 2004

Many months after SCI, when an irreversible injury involves lower motoneurons, severe atrophy of human muscle is complicated by fibrosis and fat substitution (denervated, degenerated muscle, DDM). We will describe the effects of long‐term lower motoneuron denervation on human muscle and present the structural results of muscle trained using FES. Antibody for embryonic myosin demonstrates that sustained myogenesis occurs in human DDM. By electron microscopy we studied: a) the overall structure of fibers and myofibrils in long‐term DDM, including the effects of FES, and b) the structure and localization of calcium release units, or triads, the structure deputed to activate muscle contraction during excitation‐contraction coupling (ECC). The poor excitability of human long‐term DDM fibers during the first stages of FES training could be explained in terms of spatial disorder of both the ECC and contractile apparati. The structural studies are extremely encouraging since they demonstrate that FES training is effective in reverting long‐term DDM atrophy and in maintaining the trophic state of the recovered myofibers.
Frequency of clinically diagnosed small fiber neuropathy in a neuropathy population
Authors: Gemignani F , Brindani F , Zinno L , Allegri I , Alfieri S , Marbini A
Published: April 2004

We reviewed the files of outpatients with polyneuropathy or multiple mononeuropathy over a two‐year period (2002–2003), to assess the relative incidence of small fiber sensory neuropathy (SFSN), diagnosed with clinical criteria. The cohort included a total of 97 patients (41 men, 56 women), age 11–85 years (median 64), 91 with polyneuropathy and 6 with multiple mononeuropathy. Twenty‐seven patients with SFSN (27.8%) were identified (7 men, 20 women), age 11–76 years (median 62). SFSN was idiopathic in 8 cases, and secondary to other diseases in 19 cases, mainly diabetes or glucose intolerance (8 cases) and mixed cryoglobulinemia (6 cases). The most frequent manifestations of SFSN were burning feet (12 cases) and restless legs syndrome (12 cases). Duration of neuropathy was 2.2 + 2.06 years, whereas in the other patients with polyneuropathy was 9.02 + 13.6 (p = 0.011). Treatment with drugs for neuropathic pain was effective in 9 out of 16 cases (56.2%). In this series, SFSN diagnosed by minimal clinical criteria showed an unexpectedly high relative incidence among miscellaneous peripheral neuropathies. This can be due to overdiagnosis of SFSN, as we included patients diagnosed using minimal clinical criteria; on the other hand, the diagnostic sensitivity of additional tests (quantitative sensory examination and skin biopsy) is not definitive, thus diagnosis of SFSN is actually a frequent diagnostic challenge. The efficacy of treatment with drugs for neuropathic pain in many patients may provide further support for diagnosis.
Charcot‐marie‐tooth disease type 1: novel cases and novel mutations detected by DHPLC
Authors: Angiari C , Ferrarini M , Taioli F , Cavallaro T , Fabrizi GM , Rizzuto N
Published: April 2004

Background: Charcot‐Marie‐Tooth disease type 1 (CMT1) and related Dejerine‐Sottas syndrome (DSS) and Hereditary Neuropathy with liability to Pressure Palsy (HNPP) have a high degree of genetic heterogeneity; mutation analysis performed by direct nucleotide sequencing is highly sensitive but time‐consuming and expensive. Objective: To evaluate the sensitivity of denaturing high performance liquid chromatography (DHPLC), a recently developed technology for fast mutational analysis. Methods: Optimal conditions for analysing Cx32, P0 and PMP22 genes by DHPLC were developed on the basis of 39 mutations (Cx32 = 21; P0 = 10; PMP22 = 8) detected in the period 1997–2002. Patients: During 2003, 44 patients fitting the clinical and electrophysiological criteria of CMT1, DSS or HNPP who were negative for the 17p11.2 duplication/deletion were analysed either by nucleotide sequencing or by DHPLC. Results: In the last year we identified a total of 3 mutations in Cx32, 3 mutations in MP0 (2 novels mutations, one recessive) and 2 mutations in PMP22 (2 novels nonsense mutations). Conclusions: DHPLC was capable of detecting all mutations identified by sequencing, thus appearing as a reliable approach for the mutational analysis of CMT1.
Distal hereditary motor neuropathy (DHMN): a new locus for an autosomal recessive form
Authors: Mostacciuolo ML , Crestanello E , Boaretto F , Boscolo E , Liguori M , Tessarolo D , Vettori A , Vazza G
Published: April 2004

Distal hereditary motor neuropathy (dHMN), also known as the spinal form of Charcot‐Marie‐Tooth (spinal CMT) disease or as distal spinal muscular atrophy (dSMA), is an exclusively motor disorder of the peripheral nervous system. Seven different variants of distal HMN have been clinically identified and 5 loci have so far been mapped, of which two for the recessive forms (HMN type 3 and type 6). We collected the DNA of a family in which some cases of HMN have been clinically diagnosed. This family lives in a small and geographically isolated village of southern Italy. Due to the presence of a high frequency of inbreeding evident from several consanguinity loops, an autosomal recessive inheritance has been postulated and the involvement of a single gene responsible can be assumed. To exclude possible involvement of genes causing similar pathological phenotypes, a preliminary mutational screening for the genes PMP22 and P0, involved in CMT1, and SMN1 gene, responsible for the SMA, has been carried out: no mutations were found. Furthermore, a linkage analysis has been made for the HMN 3 and 6, obtaining negative LOD score values (less than ‐2). On the bases of such data and considering the high informativity of this pedigree (simulated max LOD score = 4.24 at a recombination frequency of 0.0), we performed a genomewide analysis using 483 fluorescent‐labelled microsatellite markers. Preliminary results allow us to identify a critical region cosegregating with the disease in the affected subjects on chromosome 11p.
THalidomide sensory neurotoxicity: results of a collaborative clinical and neurophysiolgical study
Authors: Cavaletti G , Beronio A , Reni L , Ghiglione E , Schenone A , Briani C , Zara G , Cocito D , Isoardo G , Ciaramitaro P , Plasmati R , Pastorelli F , Frigo M , Piatti M , Carpo M
Published: April 2004

Despite long‐lasting use, several features of thalidomide neurotoxicity have yet to be resolved. A more detailed knowledge of thalidomide‐induced sensory neurotoxicity is desirable, particularly in view of the future use of thalidomide derivatives which are currently under investigation. Our study demonstrates that thalidomide sensory neurotoxicity is cumulative dose‐dependent, but this effect is evident only when the dose is relatively high (in our study >20 g). In fact, the risk of developing sensory neuropathy is low (around 10%) below this threshold, while it steadily increases with increasing cumulative doses. In our series, a discrepancy between clinical and neurophysiological results was frequent when a low cumulative dose of thalidomide was administered. Regarding the need for thalidomide withdrawal at the onset of any evidence of peripheral neuropathy, we followed up the course of seven patients who were clinically and neurophysiologically normal at baseline, but had treatment‐induced neurotoxicity and a very severe change in their SAPs. In all these cases the thalidomide dose was reduced and no clinically‐relevant worsening was observed despite a further marked reduction in their SAPs. This finding suggests that thalidomide withdrawal is not mandatory even in the presence of marked abnormalities in sensory neurophysiological parameters, provided that an accurate clinical follow‐up is guaranteed and the dose is adjusted.
Pro‐inflammatory cytokines induce differentiation in cultured schwann cells
Authors: Conti G , Baron PL , Scarpini E , Bresolin E , De Pol A
Published: April 2004

During cell‐mediated demyelination of the peripheral nervous system (PNS), pro‐inflammatory cytokines have a predictable pattern of expression and appear to be involved in damaging the myelin sheath and the axon. However, the role of these molecules regarding Schwann cell life and death is still controversial. In fact, some pro‐inflammatory cytokines act synergistically to kill PNS glial cells, but besides Schwann cell death they can induce cell proliferation, and both processes are related to cytokine dosage and time of exposure. In this preliminary study we stimulated Schwann cell cultures with 10 U/ml interleukin‐1 beta and 50 U/ml interferon‐gamma for 24, 48 and 72 hours. As previously reported we observed the peak of cell death and proliferation by 24 hours with both cytokines. At this time point, interestingly, in few Schwann cells belonging to the cytokine treated cultures and not to the untreated control cultures, we observed by electron microscopy analysis a cellular differentiation towards a myelin forming phenotype, even though our cultures were axon free as we have detected by immunocytochemical analysis with neurofilament antibody. In conclusion, we think that pro‐inflammatory cytokines besides promoting Schwann cell death and proliferation might be involved in the processes of cellular differentiation.
Immunologic profile in chronic inflammatory polyneuropathies associated or not associated with MGUS
Authors: Santuccio G , Sanvito L , Speciale L , Merlino L , Sgandurra M , Ceresa L , Ferrante P , Nemni R
Published: April 2004

Chronic inflammatory polyneuropathies (CIP) may be associated with monoclonal gammopathies (MGUS) directed or not against neuropathy‐related antigens. We analysed peripheral T and B cell subsets and cytokine network in 13 patients with CIP without MGUS (CIP), 10 with CIP with MGUS anti‐MAG (CIP‐MAG) and 5 with CIP with MGUS without anti‐MAG activity (CIP‐MGUS). We evaluated, by flow cytometry, CD3+, CD3 + DRII+, CD4+, CD8+, CD16+ and CD19+ cells subset distribution, and intracellular IL2, INFg, IL1, IL6, IL10 and TNFa production by CD4+, CD8+ and CD14+ cells. Results were compared with age‐matched healthy controls (HC); statistical analysis was performed. Compared to HC, CIP patients had a significant decrease of CD3+ and B cells, CIP‐MAG patients had an increase of CD3+ and NK and a decrease of CD3 + DRII+ and B cells. Comparing the different subgroups, we found a decrease of CD3 + DRII+ and B cells in CIP‐MAG versus CIP, and an increase of CD4+ in CIP‐MGUS versus CIP. Compared to HC, CIP showed an increase of INFg in CD4+ and of IL6 in CD14+. CIP‐MAG showed an increase of IL10 in CD4+, IL1 and IL10 in CD8+, and IL1 in CD14+, versus HC and other subgroups. Our results suggest that in CIP‐MAG patients it is possible to identify a distinct immunological profle.
Phrenic nerve conduction study in CIDP
Authors: Ciaramitaro P , Poglio F , Tavella A , Rota E , Prolasso I , Isoardo G , Baldi S , Cocito D
Published: April 2004

Background: Alterations of the phrenic nerve (FN), as well as of the pulmonary function tests (PFTs), have been described in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Objective: Our study was aimed at assessing the relationship between FN conduction study and respiratory function in 24 CIDP patients without clinical signs of respiratory failure. Material and Methods: Bilateral FN and right median nerve conduction studies were accomplished, along with emogasanalysis (EGA) and PFTs: maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), forced vital capacity (FVC) and partial CO2 pressure. Results: The amplitude of the compound muscle action potential (CMAP) of the FN was altered in 19 (79%) of our 24 patients, the latency in 22 (92%). Eighteen patients (75%) showed at least one PFT or the pCO2 abnormal. FN alterations showed a low sensitivity and specificity with respect to PFTs or pCO2. Discussion: Our results demonstrated electrophysiological alterations of the FN in a high percentage of CIDP patients. No significant correlation was observed between FN and PFTs alterations.
Is clinical variability in CMT1A related to epigenetic factors?
Authors: Benedetti L , Zuccarino R , Grandis M , Fiocchi I , Beronio A , Ghiglione E , Bellone E , Mandich P , Abruzzese M , Mancardi GL , Lamba Doria L , Schenone A
Published: April 2004

CMT1A patients bear the same genetic defect but often present with a wide range of clinical disability. Knowing the relationship between the phenotypic variability and other parameters, such as electrophysiological findings, age, gender, disease duration and environmental factors may be important for understanding the pathogenetic mechanisms underlying CMT1A. We studied 15 families and 7 sporadic cases affected by CMT1A (27 adults and 9 children) from the clinical, neurophysiological and genetic standpoint. A detailed patient history included: disease onset and progression, distribution of weakness, additional symptoms, life habits, genealogical tree, exposure to toxic substances, geographic provenance, instruction grade, job, use of drugs, and concurrent diseases. A questionnaire about diet was administered. The disability was evaluated by modified Rankin scale, deambulation index, functional independence measure and Barthel index. As previously reported, disease onset was in the first decade in 50% of cases and before the age of 20 years in 70% of cases. Severe disability was rarely observed, only 2 patients walking with a cane. No clear influence of gender over clinical severity was observed. Interestingly, genetic anticipation was observed in all the families. Data on the influence of environmental factors will also be presented.
Genotype–phenotype correlation in some autosomal recessive hereditary spastic paraplegias
Authors: Manganelli F , Criscuolo C , Scarano V , Perretti A , De Michele G , Filla A , Santoro L
Published: April 2004

Hereditary spastic paraplegias (HSPs) are a group of clinically and genetically inherited disorders. Spastic paraparesis (SP), the main clinical feature of all HSPs can occur in relative isolation in the “pure” form or in combination with other neurological deficits in “complicated” forms. Autosomal dominant, autosomal recessive (AR) and X‐linked recessive inheritance pattern of HSPs have been reported. At present, among AR‐HSPs, three genes, paraplegin (SPG7), spartin (SPG20 – Troyer syndrome) and maspardin (SPG21) have been identified and six genetic loci have been mapped (SPG5, SPG11, SPG14, SPG15, SPG24, SPG25). We have evaluated 11 patients belonging to six AR‐HSP families genetically identified as SPG5, SPG7, SPG11 and SPG15. In all patients electromyography, nerve conduction velocity studies, visual (VEPs), somatosensory (SSEPs), brainstem auditory (BAEPs) and magnetic motor (MMEPs) evoked potentials were performed. All 4 SPG5 patients, affected by a pure form of SP, showed abnormalities of both MMEPs and SSEPs, and two of them also VEP alterations. In the two SPG7 patients with complicated SP, MMEP abnormalities only were discovered. Among the three SPG11 patients affected by SP, complicated by mental retardation and thin corpus callosum, electrophysiological studies revealed MMEP abnormalities and signs of motor neuropathy in one of them. Finally, in the SPG15 family, presenting with SP associated with mental retardation and neurosensorial deafness, MMEP and BAEP alterations were found.
Solution structure and domain architecture of the divisome protein FtsN
Authors: Yang Ji‐Chun , Van Den Ent Fusinita , Neuhaus David , Brevier Julian , Löwe Jan
Published: April 2004

Prokaryotic cell division occurs through the formation of a septum, which in Escherichia coli requires coordination of the invagination of the inner membrane, biosynthesis of peptidoglycan and constriction of the outer membrane. FtsN is an essential cell division protein and forms part of the divisome, a putative complex of proteins located in the cytoplasmic membrane. Structural analyses of FtsN by nuclear magnetic resonance (NMR) reveals an RNP‐like fold at the C‐terminus (comprising residues 243–319), which has significant sequence homology to a peptidoglycan‐binding domain. Sequential deletion mutagenesis in combination with NMR shows that the remaining of the periplasmic region of FtsN is unfolded, with the exception of three short, only partially formed helices following the trans‐membrane helix. Based on these findings we propose a model in which FtsN, anchored in the inner membrane, bridges over to the peptidoglycan layer, thereby enabling the coordination of the divisome and the murein‐shaping machinery in the periplasm.