bluuebunny/crossref_metadata_2025 huggingface dataset:
Care at home for people with dementia: as in a total institution?
Authors: ASKHAM JANET , BRIGGS KATE , NORMAN IAN , REDFERN SALLY
Published: December 2006

This article examines three kinds of social relationship likely to be present when people with dementia are cared for at home by relatives or friends: custodial care, an intimate relationship, and home-life. Using Goffman's three defining aspects of custodial care – routinisation, surveillance and mortification of the self – the paper examines whether these characterised the care of people with dementia at home and, if so, whether they conflicted with the intimate relationship and with home-life. The study involved sustained observations and interviews with 20 people with dementia and their carers in and around London, and qualitative analysis of the data. It was found that all three aspects of custodial care were present although not fully realised, and that they led to difficulties, many of which were associated with the concurrent pursuit of an intimate relationship and home-life. In all cases, daily life was routinised partly to help accomplish care tasks but was found monotonous, while surveillance was usual but restrictive, and prevented both the carers and those with dementia from doing things that they wished to do. Those with dementia were distressed by the denial of their former identities, such as car-driver or home-maker, and by being treated like children. Both the carers and the people with dementia had various ways of balancing custodial care, their intimate relationships and home-life, such as combining routines with other activities, evading surveillance or carrying it out by indirect means, and there were many attempts to maintain some semblance of former identities.
Are different forms of care-management for older people in England associated with variations in case-mix, service use and care-managers' use of time?
Authors: CHALLIS DAVID , HUGHES JANE , JACOBS SALLY , STEWART KAREN , WEINER KATE
Published: December 2006

This paper reports one component of an evaluation of the different forms, types and models of local authority social services' care-management for older people that have emerged in England since 1993. It was undertaken at a time of a growing debate about whether care-management differentiated those with simple from complex needs, and whether for the latter a multi-disciplinary approach was required. A sample representative of different approaches to care-management was selected from a national survey of local authorities to explore the associations between types of care-management and case-mix, the services received by the clients, and the use of staff time. The paper addresses the categorisation of the types of care-management and the differences associated with these. The care-management teams were distinguished by whether they used a ‘targeted approach’, had ‘specialist older people's teams’, or used other arrangements. It was found that those with a targeted approach undertook more multi-disciplinary assessments, provided more assistance to older people with mental health problems, and that their staff spent significantly less time in direct contact with users and carers. Conversely, those with specialist older people's teams had more users in receipt of occupational therapy services. Further research is required to explore the influence of these different arrangements on the wellbeing of service users and their carers.
Older people and transport: coping without a car
Authors: DAVEY JUDITH A.
Published: December 2006

Much of the literature on ageing and transport has been concerned with older drivers, which underlines the importance of private transport in their everyday lives, but little has been written about how a lack of transport impacts on quality of life. A survey was commissioned by the Office for Senior Citizens of the New Zealand government, and face-to-face semi-structured interviews were conducted in 2004 with 28 couples and 43 single people (14 men and 29 women). The sample was identified through Volunteer Community Co-ordinators (VCCs) and drawn from metropolitan, urban, small-town and rural areas. The average age of the men was 84.5 years and of the women 81.4 years, and all had been without private transport for at least six months. The interviews sought the experiences and opinions of older people who were ‘coping without a car’, and asked how this affected their lifestyle and quality of life, and how they met their transport needs. The findings reveal variations by gender, health status and personal outlook, including views on independence and reciprocity. While ‘serious’ transport requirements may be provided for by alternative means, the ‘discretionary’ trips that contribute significantly to the quality of life may be lost when private transport is unavailable. The findings have implications for local and national policy and planning, extend well beyond the sphere of transport, and illuminate processes of social exclusion among older people.
The roles and functions of the informal support networks of older people who receive formal support: a Swedish qualitative study
Authors: DUNÉR ANNA , NORDSTRÖM MONICA
Published: December 2006

Several studies of frail older people have focused on the relationship between formal and informal care, while others have examined the character of inter-generational relationships. Yet knowledge of the significance of the informal-support networks of older people who receive formal care is still scarce. The aim of this paper was to explore how older Swedes who receive formal elder-care experienced their informal support networks. The findings presented emanate from a qualitative case study. The structural, interaction and functional dimensions of the support networks were the main analytical tools. In the study population, the size of the formal support network varied from one to 12 people (or categories of people), and the size of the informal support network varied from one to six people (or categories of people). The main results demonstrate the importance of informal support with reciprocal relationships, and the value of confidants and emotional support, both of which contribute to feelings of belonging, security and wellbeing. A well-functioning formal and informal support network allows individuals to maintain autonomy in old age, even when they have to depend on help from others.
Palliative care in old age
Authors: Lo Raymond SK , Woo Jean
Published: December 2006

With an aging population globally, and increasing numbers of older patients facing chronic illnesses, better palliative care in old age should be promoted.In this review we will

Highlight the pressing need for better palliative care for older people

Advocate the concept of palliative care as applied to geriatrics and gerontology

Review current end-of-life care for older people with chronic disease, both non-cancer and cancer

Discuss the palliative-care approaches to common physical symptoms and psychospiritual distress

Highlight advanced care planning and quality-of-life issues
ATP content and maturational/developmental ability of bovine oocytes with various cytoplasmic morphologies
Authors: Nagano Masashi , Katagiri Seiji , Takahashi Yoshiyuki
Published: December 2006

We examined the relationship among morphological appearance (six groups) of bovine oocytes, ATP content and maturational/developmental ability. Oocytes with a brown ooplasm (with or without a dark region) had intermediate levels of ATP at the germinal vesicle (GV) stage and showed higher rates of first polar body (PB) extrusion than the other groups. Oocytes with a low level of ATP (oocytes with a pale ooplasm without dark clusters) and oocytes with a high level of ATP (oocytes with a black ooplasm) showed lower rates of PB extrusion. During in vitro maturation, ATP levels in oocytes decreased at around GV breakdown and increased toward metaphase II (MII). MII oocytes having a brown ooplasm with a dark region, which had good developmental capacity, had a relatively high level of ATP. MII oocytes with a brown or pale ooplasm without dark clusters, which had poor developmental capacity, had low ATP levels. MII oocytes with a black ooplasm, which had poor developmental capacity, had an unusually high level of ATP. These results suggest that the morphological appearance of bovine oocytes is closely related to their ATP levels and that cytoplasmic morphology will give an advantage for the selection of oocytes with a high maturational and developmental ability.
Inhibition of boar sperm hyaluronidase activity by tannic acid reduces polyspermy duringin vitrofertilization of porcine oocytes
Authors: Tatemoto Hideki , Tokeshi Isao , Nakamura Satoshi , Muto Norio , Nakada Tadashi
Published: December 2006

The present study was conducted to examine the effects of three polyphenols (tannic acid, apigenin and quercetin) on hyaluronidase activity andin vitrofertilization (IVF) parameters. Among them, tannic acid showed by far the strongest potency for blocking hyaluronidase activity extracted from preincubated boar sperm, causing a dose-dependent inhibition over the range of 2–10 μg/ml. When cumulus-intact and cumulus-free oocytes were inseminated in IVF medium containing tannic acid, the penetration and the polyspermy rates were significantly decreased in the presence of 10 μg/ml tannic acid compared with those in the absence of tannic acid, and the addition of 5 μg/ml tannic acid significantly reduced the polyspermy rate (p< 0.05) compared with that of the control while maintaining the high penetration rate. However, apigenin and quercetin had no effect on the rate of polyspermy. Interestingly, the incidence of polyspermy was significantly reduced in oocytes inseminated with sperm pretreated with 5 μg/ml tannic acid (p< 0.05), although the pretreatment of oocytes had no effect against the polyspermy after insemination with untreated sperm. Treatment with tannic acid caused neither a protective proteolytic modification of the zona pellucida matrix before fertilization, nor a reduction of the proteolytic activity of acrosomal contents or the number of zona-bound spermatozoa. These data suggest that an appropriate concentration of tannic acid prevents polyspermy through the inhibition of sperm hyaluronidase activity during IVF of porcine oocytes.
The Kit ligand/c-Kit receptor system in goat ovaries: gene expression and protein localization
Authors: Silva J.R.V. , van den Hurk R. , van Tol H.T.A. , Roelen B.A.J. , Figueiredo J.R.
Published: December 2006

Relatively little information is available on the local factors that regulate folliculogenesis in goats. To examine the possibility that the Kit ligand (KL) system is expressed throughout the folliculogenesis, we studied the presence and distribution of KL and its receptor, c-Kit, in goat ovaries. Ovaries of goats were collected and either fixed in paraformaldehyde for immunohistochemical localization of KL and c-Kit proteins, or used for the isolation of follicles, luteal cells, surface epithelium and medullary samples to study mRNA expression for KL and c-Kit, using the reverse transcriptase polymerase chain reaction (RT-PCR). KL protein and mRNA were found in follicles at all stages of development, i.e. primordial, primary, secondary, small and large antral follicles, as well as in corpora lutea, surface epithelium and medullary tissue. Antral follicles expressed both KL-1 and KL-2 mRNAs, while earlier staged follicles expressed KL-1 transcript only. KL protein was demonstrated in granulosa cells from the primordial follicle onward. Its mRNA could be detected in granulosa cells isolated from antral follicles and occasionally in their theca cells. c-Kit mRNA was expressed in all antral follicular compartments and at all stages of follicular development. c-Kit protein was predominantly found in oocytes from the primordial follicle stage onwards, in theca cells of antral follicles, as well as in corpora lutea, surface epithelium and medullary tissue, particularly in the wall of blood vessels, which may indicate these cells as the main sites of action of KL. It is concluded that the KL/c-Kit system, in goat ovaries, is widespread and that it may be involved in the regulation of various local processes, including folliculogenesis and luteal activity.
Development of rat tetraploid and chimeric embryos aggregated with diploid cells
Authors: Shinozawa T. , Sugawara A. , Matsumoto A. , Han Y-J. , Tomioka I. , Inai K. , Sasada H. , Kobayashi E. , Matsumoto H. , Sato E.
Published: December 2006

In the present study, we examined the preimplantation and postimplantation development of rat tetraploid embryos produced by electrofusion of 2-cell-stage embryos. Developmental rate of tetraploid embryos to morula or blastocyst stage was 93% (56/60) and similar to that found in diploid embryos (95%, 55/58). After embryo transfer, rat tetraploid embryos showed implantation and survived until day 8 of pregnancy, however the conceptuses were aberrant on day 9. In mouse, tetraploid embryos have the ability to support the development of blastomeres that cannot develop independently. As shown in the present study, a pair of diploid blastomeres from the rat 8-cell-stage embryo degenerated immediately after implantation. Therefore, we examined whether rat tetraploid embryos have the ability to support the development of 2/8 blastomeres. We produced chimeric rat embryos in which a pair of diploid blastomeres from an 8-cell-stage green fluorescent protein negative (GFP−) embryo was aggregated with three tetraploid blastomeres from 4-cell GFP-positive (GFP+) embryos. The developmental rate of rat 2n(GFP−) ↔ 4n(GFP+) embryos to the morula or blastocyst stages was 93% (109/117) and was similar to that found for 2n(GFP−) ↔ 2n(GFP+) embryos (100%, 51/51). After embryo transfer, 2n(GFP−) ↔ 4n(GFP+) conceptuses were examined on day 14 of pregnancy, the developmental rate to fetus was quite low (4%, 4/109) and they were all aberrant and smaller than 2n(GFP−) ↔ 2n(GFP+) conceptuses, whereas immunohistochemical analysis showed no staining for GFP in fetuses. Our results suggest that rat tetraploid embryos are able to prolong the development of diploid blastomeres that cannot develop independently, although postimplantation development was incomplete.
PKA activation in concert with ARIS and asterosap induces the acrosome reaction in starfish
Authors: Islam M. Sadiqul , Kawase O. , Hase S. , Hoshi M. , Matsumoto M.
Published: December 2006

The acrosome reaction (AR) is a fundamental event for fertilization, which is induced in concert with acrosome reaction-inducing substance (ARIS) and asterosap, both of which are components of starfish egg jelly (EJ). During the AR, a spermatozoon undergoes a series of physiological changes, such as in intracellular cGMP concentration ([cGMP]i), pHiand intracellular Ca2+concentration ([Ca2+]i). Affinity purification of cGMP-binding protein resulted in the isolation of a regulatory subunit of the cAMP-dependent protein kinase A (PKA), suggesting the involvement of a cAMP-dependent pathway in the AR. By using a cAMP enzyme immunoassay, [cAMP]iwas found to increase in starfish spermatozoa when stimulated with ARIS and asterosap. ARIS could also increase the [cAMP]iin the presence of high pH seawater. Pretreatment of spermatozoa with two specific and cell-permeable PKA inhibitors, H89 and KT5720, prevented the induction of the AR in a concentration-dependent manner. These results suggest that PKA activity participates in the induction of the AR with ARIS and asterosap. To investigate this, we have cloned a gene that encodes a regulatory subunit of PKA that had been identified in starfish spermatozoa.
Connexin 43 expression in the testis of the frogRana esculenta
Authors: Izzo G. , d'Istria M. , Ferrara D. , Serino I. , Aniello F. , Minucci S.
Published: December 2006

Testicular cell-to-cell interactions play a key role in the regulation of spermatogenesis. In the testis, cell contacts are mediated through several mechanisms, including paracrine and direct contacts depending on gap junctional pathways. Gap junctions require connexin (Cx) channels and connexin-43 (Cx43) represent the most abundant Cx found in mammalian testis. Little is known about Cx expression in non-mammalian testis. Here we report the partial cloning of a Cx43 transcript of 381 bp fromRana esculentatestis. We also demonstrate that, in the frog testis, Cx43 transcript and protein show a parallel temporal and spatial pattern of expression throughout the reproductive annual cycle, with higher levels from September to January (when spermatogenesis is at a maximum level).In situhybridization, carried out on testis collected in October, indicated that Leydig cells (LC) and Sertoli cells express Cx43 transcript, while the hybridization signal was less intense in germ cells. To obtain more information on Cx43 expression in the frog testis, we have used ethane-dimethane sulphonate (EDS), a toxin that specifically destroys LC. RT-PCR analysis shows a progressive decrease in Cx43 expression in EDS-treated testis from day 1 to day 4 after the injection, associated with LC destruction. Moreover, Cx43 expression returns to normal on day 28, when a new population of LC reappear in the interstitium, indicating that Cx43 is mainly expressed by LC. Taken together our data provide evidence that Cx43 is present in the frog testis with an important role in spermatogenesis.
Interview with Salomón Lerner
Authors: Salmón Elizabeth
Published: December 2006

Salomón Lerner Febres was the President of the Truth and Reconciliation Commission of Peru from 2001 to 2003. After two decades of armed conflict, political violence and suffering due to an authoritarian regime, the Commission, created by the government of Peru, was established to face up to the factors which made violence possible, and to the consequences of destruction and of physical and moral suffering, especially in the most humble and impoverished sectors of Peruvian society. The Commission published its report on 28 April 2003. Salomón Lerner is now President of the Institute for Democracy and Human Rights at the Pontificia Universidad Católica del Perú, where he was Rector from 1994 to 2004. He was also President of the Union of Latin American Universities, where he had previously been Vice-President for universities in the Andean region. After studying law in Peru and obtaining a doctorate in philosophy from the Catholic University of Louvain (Belgium), Dr Lerner worked at a number of academic institutions and is currently a research associate at Tokyo University. In addition to several other awards, he was honoured as ‘Great Official of the Order of Merit of Peru’ by Peru's Ministry of Domestic Affairs in 2003.
The right to the truth in international law: fact or fiction?
Authors: Naqvi Yasmin
Published: December 2006

The right to the truth has emerged as a legal concept at the national, regional and international levels, and relates to the obligation of the state to provide information to victims or to their families or even society as a whole about the circumstances surrounding serious violations of human rights. This article unpacks the notion of the right to the truth and tests the normative strength of the concept against the practice of states and international bodies. It also considers some of the practical implications of turning “truth” into a legal right, particularly from the criminal law perspective.
Dealing with the past and transitional justice: building peace through accountability
Authors: Sooka Yasmin
Published: December 2006

Based on her experience as a member of the South African and the Sierra Leonean truth and reconciliation commissions, the author formulates guiding principles and looks at the circumstances in which a truth and reconciliation commission constitutes an appropriate instrument to deal with transitional justice issues. The author also identifies possible contributions that truth and reconciliation commissions can make during a period of transition.
Reflections on international humanitarian law and transitional justice: lessons to be learnt from the Latin American experience
Authors: Salmón G. Elizabeth
Published: December 2006

Compliance with or violations of international humanitarian law during an armed conflict undoubtedly influence the conduct of the judiciary, the situations of the victims and the correlation of forces in the post-conflict society. This article seeks to determine the influence of international humanitarian law on the transitional justice process. The author examines the specific experience of certain Latin American states that have been deeply affected by serious violations of human rights and international humanitarian law.
The missing and transitional justice: the right to know and the fight against impunity
Authors: Crettol Monique , La Rosa Anne-Marie
Published: December 2006

Any body or institution dealing with the missing persons issue will interact in one way or another with transitional justice proceedings, if only to examine the possibility of sharing relevant information gathered. The question becomes even more acute when international tribunals intervene in the national context where transitional justice mechanisms are operating. The authors look at the ways in which transitional justice mechanisms may support the right of families to know the fate of their relatives, and how work to resolve the missing persons issue can be reconciled with an effective fight against impunity.
The principles of universal jurisdiction and complementarity: how do the two principles intermesh?
Authors: Philippe Xavier
Published: December 2006

This article addresses the relationships between the principles of universal jurisdiction and complementarity and the difficulties in their implementation. Even if the two principles are well known, there are still a number of obstacles – legal and non-legal – to proper and better implementation. Moreover, universality and complementarity are quite often to be applied in a difficult political environment, keeping in mind that these principles have to deal with international and national constraints. The number of obstacles is such that the two principles face many challenges. This article advocates that the principle of complementarity represents one aspect of the principle of universality and should rely on its general acceptance to further its efficiency and implementation. In conclusion, the article explores some possible ideas to be developed to reach this goal.
Fractional Factorial Design for Optimization of the SELDI Protocol for Human Adipose Tissue Culture Media
Authors: Szalowska Ewa , Van Hijum Sacha A.F.T. , Roelofsen Han , Hoek Annemiek , Vonk Roel J. , te Meerman Gerard J.
Published: December 2006

The early factors inducing insulin resistance are not known. Therefore, we are interested in studying the secretome of the human visceral adipose tissue as a potential source of unknown peptides and proteins inducing insulin resistance. Surface‐enhanced laser desorption/ionization time‐of‐flight (SELDI‐TOF) mass spectrometry is a high‐throughput proteomics technology to generate peptide and protein profiles (MS spectra). To obtain good quality and reproducible data from SELDI‐TOF, many factors in the sample pretreatment and SELDI protocol should be optimized. To identify the optimal combination of factors resulting in the best and the most reproducible spectra, we designed an experiment where factors were varied systematically according to a fractional factorial design. In this study, seven protein chip preparation protocol factors were tested in 32 experiments. The main effects of these factors and their interactions contributing to the best quality spectra were identified by ANOVA. To assess the reproducibility, in a subsequent experiment the eight protocols generating the highest quality spectra were applied to samples in quadruplicates on different chips. This approach resulted in the development of an improved chip protocol, yielding higher quality peaks and more reproducible spectra.
Forschungsinteresse bei praktizierenden Ärzten: Eine Umfrage
Authors: Rossi  , Zoller  , Steurer
Published: December 2006

Hintergrund: Forschung in der Grundversorgung setzt die aktive Mitarbeit von Hausärzten voraus. In der Schweiz besteht wenig hausärztliche Forschungstradition und es hat sich noch kaum eine eigenständige Forschung in der Grundversorgung etabliert. Zweck: Diese Umfrage erhebt Informationen zur generellen Einstellung der Hausärzte zur Forschung in der Grundversorgung, ihren spezifischen Interessen und zu ihrer Bereitschaft zur aktiven Teilnahme an Forschungsprojekten. Methode: Es wurde ein für diese Studie entwickelter Fragebogen an 3044 Grundversorger (FMH Innere Med., FMH Allg. Med., Med. pract., FMH Pädiatrie, andere) im Einzugsgebiet der Universität Zürich (inklusiv Liechtenstein) geschickt. Resultate: 1596 (52%) der Grundversorger schickten den Fragebogen zurück. Trotz der geringen Erfahrung im Forschungsbereich, bekundet eine Mehrheit von 1450 (94%) der teilnehmenden Hausärzte ein generelles Interesse an der Forschung. 900 (60%) der Teilnehmenden sind bereit zur aktiven Teilnahme an Forschungsprojekten. Als Bedingungen der Grundversorger für eine Projektteilnahme nennen sie in erster Linie ein für die eigene Praxis relevantes Thema und die Anerkennung der Projektarbeit als Fortbildung. Die teilnehmenden Hausärzte sind bereit, durchschnittlich 15 Min/Tag für die Datenerhebung für ein Projekt aufzuwenden. Die Haupthinderungsgründe für eine Teilnahme sind zeitliche Zusatzbelastung, administrativer Zusatzaufwand und mangelnder Bezug zum Praxisalltag. Schlussfolgerung: Obwohl die Mehrheit der Grundversorger in der Schweiz die Wichtigkeit der Forschungsarbeit erkennt und zur aktiven Mitarbeit an Forschungsprojekten bereit ist, fehlen bis heute entsprechende Strukturen und Netzwerke, die das Etablieren einer erfolgreichen Forschungstradition ermöglichen. Diese Umfrage macht deutlich, dass der Wille zur aktiven Forschungsarbeit gegeben ist.
Differentialdiagnose eines unspezifischen Beschwerdebildes: Riesenzellarteriitis (Morbus Horton)
Authors: Vetter  , Bonél  , Burkhard  , Bielecki  , Müller
Published: December 2006

Die Symptome der Riesenzellarteriitis sind meist unspezifisch und gehen zum Teil mit polymyalgischen Beschwerden einher. Als Komplikationen der Riesenzellarteriitis sind Ischämien, Infarkte oder Rupturen gefürchtet. Wir berichten über eine 56-jährige Patientin, welche seit einem Jahr über einen Gewichtsverlust, progrediente Müdigkeit und Leistungsintoleranz sowie ein polymyalgisches Beschwerdebild klagte. Im Rahmen der Tumorsuche zeigte sowohl die durchgeführte Gastroskopie wie auch die Kolonoskopie einen Normalbefund. Die anschliessend veranlasste Computertomographie sowie die Magnetresonanztomographie des Abdomens ergaben eine Verdickung und Enhancement der Aortenwand, was zur Arbeitsdiagnose einer Riesenzellarteriitis führte, sodass umgehend eine Kortikoidtherapie eingeleitet wurde. Die im Verlauf vorgenommene Biopsie beider Arteriae temporales untermauerte die Diagnose einer Riesenzellarteriitis (Morbus Horton) histologisch.
36-jähriger Patient mit multiplen hypodensen Rundherden der Milz
Authors: Ozimek  , Chatterjee  , Stanga  , Cottagnoud  , Stucki
Published: December 2006

Der Anteil der abdominalen Tuberkulose an allen Tuberkulosefällen beträgt ungefähr 1–3%. Häufig befallene Organsysteme sind das Peritoneum und der Gastrointestinaltrakt. Ein isolierter Milzbefall ist bei immunkompetenten Patienten sehr selten. Die unspezifische Symptomatik mit Fieber, Bauchschmerzen und Aszites sowie das Versagen der üblichen Tuberkulosediagnostik führen häufig zu einer verzögerten Diagnosestellung oder zu Fehldiagnosen und damit unnötigen operativen Eingriffen. Diagnostische Methode der Wahl ist die PCR auf Mycobacterium-tuberculosis-Komplex aus Aszitesflüssigkeit. Bei frühzeitigem Therapiebeginn ist die Prognose sehr gut.
Managing E-learning Group Processes Using Teleological Enquiring Principles
Authors: Kawalek John Paul , Hart Diane
Published: December 2006

This paper is concerned with managing e-learning communities. It reports on the process and methods adopted in an EU project called MEDFORIST. The challenges of managing this project were considerable because there was significant social diversity amongst the e-leaning community members. The paper outlines some key principles derived from teleology (or, the ‘study of purpose’) that were used to structure some key aspects of the management of the e-learning group processes. These principles were developed and used, in order to structure enquiring activities to inform the design, monitoring and evaluation activities in the provision of e-learning group processes. The paper outlines the use of such enquiry as a foundation for the continued development of the application of e-learning in contexts in which divergent human groups come together in unstructured, non-prescriptive human learning activities. As such, the paper outlines some key methodological requirements for managing e-learning group processes.
The Diffusion of WOZ: Expanding the Topology of IS Innovations
Authors: Costello Gabriel J , Donnellan Brian
Published: December 2006

The growth and diffusion of self-service technology (SST) over the last decade has resulted in an increasing number of business and government transactions being completed without human assistance. One innovation in this area, the speech-enabled business system, is characterised by complex implementations that bring together language-processing technologies, applications development, and end-user psychology. A resulting secondary innovation, the Wizard-of-OZ (WOZ) experiment is a valuable technique for simulating and building human–machine prototypes to ensure successful deployment of the completed service. The objective of the paper is to examine these innovations in relation to the changing business landscape; the technology and innovation literature, and the population of likely adopters. The review is carried out by placing the authors’ former experience as practitioners within current theoretical research frameworks. The result is a number of suggestions relating to both IT technology research and IT innovation research. Firstly, it proposes the simplification and diffusion of the WOZ methodology to support the growth in demand for automated e-business transactions that is mindful of human and ethical challenges. Secondly, the paper argues that because SST and business extends the traditional boundaries of the customer service function, it now needs to be incorporated into Swanson's tri-core innovation typology. The paper concludes by presenting the suggested reorientation of information systems research that incorporates an outward facing perceptive as a conceptual model.
Order
N
algorithm for computation of electrostatic interactions in biomolecular systems
Authors: Lu Benzhuo , Cheng Xiaolin , Huang Jingfang , McCammon J. Andrew
Published: December 2006

Poisson–Boltzmann electrostatics is a well established model in biophysics; however, its application to large-scale biomolecular processes such as protein–protein encounter is still limited by the efficiency and memory constraints of existing numerical techniques. In this article, we present an efficient and accurate scheme that incorporates recently developed numerical techniques to enhance our computational ability. In particular, a boundary integral equation approach is applied to discretize the linearized Poisson–Boltzmann equation; the resulting integral formulas are well conditioned and are extended to systems with arbitrary numbers of biomolecules. The solution process is accelerated by Krylov subspace methods and a new version of the fast multipole method. In addition to the electrostatic energy, fast calculations of the forces and torques are made possible by using an interpolation procedure. Numerical experiments show that the implemented algorithm is asymptotically optimal
O
(
N
) in both CPU time and required memory, and application to the acetylcholinesterase–fasciculin complex is illustrated.
A system for quantifying dynamic protein interactions defines a role for Herceptin in modulating ErbB2 interactions
Authors: Wehrman T. S. , Raab W. J. , Casipit C. L. , Doyonnas R. , Pomerantz J. H. , Blau H. M.
Published: December 2006

The orphan receptor tyrosine kinase ErbB2 is activated by each of the EGFR family members upon ligand binding. However, difficulties monitoring the dynamic interactions of the membrane receptors have hindered the elucidation of the mechanism of ErbB2 activation. We have engineered a system to monitor protein–protein interactions in intact mammalian cells such that different sets of protein interactions can be quantitatively compared. Application of this system to the interactions of the EGFR family showed that ErbB2 interacts stably with the EGFR and ErbB3, but fails to spontaneously homooligomerize. The widely used anti-cancer antibody Herceptin was found to effectively inhibit the interaction of the EGFR and ErbB2 but not to interfere with the interaction of ErbB2–ErbB3. Treatment of cells expressing EGFR and ErbB2 with Herceptin results in increased EGFR homooligomerization in the presence of EGF and a subsequent rapid internalization and down-regulation of the EGFR. In summary, the protein interaction system described here enabled the characterization of ErbB2 interactions within the biological context of the plasma membrane and provides insight into the mechanism of Herceptin action on cells overexpressing ErbB2.
The
Arabidopsis
NRT1.1 transporter participates in the signaling pathway triggering root colonization of nitrate-rich patches
Authors: Remans Tony , Nacry Philippe , Pervent Marjorie , Filleur Sophie , Diatloff Eugene , Mounier Emmanuelle , Tillard Pascal , Forde Brian G. , Gojon Alain
Published: December 2006

Localized proliferation of lateral roots in NO
3
−
-rich patches is a striking example of the nutrient-induced plasticity of root development. In
Arabidopsis
, NO
3
−
stimulation of lateral root elongation is apparently under the control of a NO
3
−
-signaling pathway involving the ANR1 transcription factor. ANR1 is thought to transduce the NO
3
−
signal internally, but the upstream NO
3
−
sensing system is unknown. Here, we show that mutants of the NRT1.1 nitrate transporter display a strongly decreased root colonization of NO
3
−
-rich patches, resulting from reduced lateral root elongation. This phenotype is not due to lower specific NO
3
−
uptake activity in the mutants and is not suppressed when the NO
3
−
-rich patch is supplemented with an alternative N source but is associated with dramatically decreased
ANR1
expression. These results show that NRT1.1 promotes localized root proliferation independently of any nutritional effect and indicate a role in the ANR1-dependent NO
3
−
signaling pathway, either as a NO
3
−
sensor or as a facilitator of NO
3
−
influx into NO
3
−
-sensing cells. Consistent with this model, the
NRT1.1
and
ANR1
promoters both directed reporter gene expression in root primordia and root tips. The inability of NRT1.1-deficient mutants to promote increased lateral root proliferation in the NO
3
−
-rich zone impairs the efficient acquisition of NO
3
−
and leads to slower plant growth. We conclude that NRT1.1, which is localized at the forefront of soil exploration by the roots, is a key component of the NO
3
−
-sensing system that enables the plant to detect and exploit NO
3
−
-rich soil patches.
Regions of IκBα that are critical for its inhibition of NF-κB·DNA interaction fold upon binding to NF-κB
Authors: Truhlar Stephanie M. E. , Torpey Justin W. , Komives Elizabeth A.
Published: December 2006

Nuclear factor κB (NF-κB) transcription factors regulate genes responsible for critical cellular processes. IκBα, -β, and -ε bind to NF-κBs and inhibit their transcriptional activity. The NF-κB-binding domains of IκBs contain six ankyrin repeats (ARs), which adopt a β-hairpin/α-helix/loop/α-helix/loop architecture. IκBα appears compactly folded in the IκBα·NF-κB crystal structure, but biophysical studies suggested that IκBα might be flexible even when bound to NF-κB. Amide H/
2
H exchange in free IκBα suggests that ARs 2–4 are compact, but ARs 1, 5, and 6 are conformationally flexible. Amide H/
2
H exchange is one of few techniques able to experimentally identify regions that fold upon binding. Comparison of amide H/
2
H exchange in free and NF-κB-bound IκBα reveals that the β-hairpins in ARs 5 and 6 fold upon binding to NF-κB, but AR 1 remains highly solvent accessible. These regions are implicated in various aspects of NF-κB regulation, such as controlling degradation of IκBα, enabling high-affinity interaction with different NF-κB dimers, and preventing NF-κB from binding to its target DNA. Thus, IκBα conformational flexibility and regions of IκBα folding upon binding to NF-κB are important attributes for its regulation of NF-κB transcriptional activity.
Correction of hemophilia as a proof of concept for treatment of monogenic diseases by fetal spleen transplantation
Authors: Aronovich Anna , Tchorsh Dalit , Katchman Helena , Eventov-Friedman Smadar , Shezen Elias , Martinowitz Uri , Blazar Bruce R. , Cohen Sivan , Tal Orna , Reisner Yair
Published: December 2006

Previous clinical attempts to correct genetic deficiencies such as hemophilia or Gaucher disease by transplantation of allogeneic spleen were associated with aggressive graft versus host disease, mediated by mature T cells derived from the donor spleen. We show that a fetal pig spleen harvested at the embryonic day 42 stage, before the appearance of T cells, exhibited optimal growth potential upon transplantation into SCID mice, and the growing tissue expressed factor VIII. Transplantation of embryonic day 42 spleen tissue into hemophilic SCID mice led to complete alleviation of hemophilia within 2–3 months after transplant, as demonstrated by tail bleeding and by assays for factor VIII blood levels. These results provide a proof of principle to the concept that transplantation of a fetal spleen, obtained from a developmental stage before the appearance of T cells, could provide a novel treatment modality for genetic deficiencies of an enzyme or a factor that can be replaced by the growing spleen tissue.
Notch activity permits retinal cells to progress through multiple progenitor states and acquire a stem cell property
Authors: Jadhav Ashutosh P. , Cho Seo-Hee , Cepko Constance L.
Published: December 2006

Signaling through the Notch pathway regulates multiple aspects of development. The vertebrate retina allows an investigation of the basis for these various effects, because the major cell types of the retina arise from a common progenitor that expresses
Notch1
. The Notch pathway was constitutively activated in distinct populations of retinal cells during development. Prolonged Notch activity in progenitor cells maintained cells in the progenitor state without perturbing temporal identity, promoting early progenitor characteristics early in development and late progenitor characteristics later in development. Eventually, constitutive Notch activation led these cells to acquire characteristics of glial and stem cells. In contrast, reactivating the Notch pathway in newly postmitotic retinal cells promoted mature glial cell formation in a subset of cells. These data suggest that prolonged Notch activity does not disrupt the normal progression of progenitor temporal states, and that down-regulating or overcoming Notch activity is required for proper formation of both neuronal and glial cell fates.
Legionella pneumophila
type II secretome reveals unique exoproteins and a chitinase that promotes bacterial persistence in the lung
Authors: DebRoy Sruti , Dao Jenny , Söderberg Maria , Rossier Ombeline , Cianciotto Nicholas P.
Published: December 2006

Type II protein secretion is critical for
Legionella pneumophila
infection of amoebae, macrophages, and mice. Previously, we found several enzymes to be secreted by this (Lsp) secretory pathway. To better define the
L. pneumophila
type II secretome, a 2D electrophoresis proteomic approach was used to compare proteins in wild-type and type II mutant supernatants. We identified 20 proteins that are type II-dependent, including aminopeptidases, an RNase, and chitinase, as well as proteins with no homology to known proteins. Because a chitinase had not been previously reported in
Legionella
, we determined that wild type secretes activity against both
p
-nitrophenyl triacetyl chitotriose and glycol chitin. An
lsp
mutant had a 70–75% reduction in activity, confirming the type II dependency of the secreted chitinase. Newly constructed chitinase (
chiA
) mutants also had ≈75% less activity, and reintroduction of
chiA
restored the mutants to normal levels of activity. Although
chiA
mutants were not impaired for
in vitro
intracellular infection, they were defective upon intratracheal inoculation into the lungs of A/J mice, and antibodies against ChiA were detectable in infected animals. In contrast, mutants lacking a secreted phosphatase, protease, or one of several lipolytic enzymes were not defective
in vivo
. In sum, this study shows that the output of type II secretion is greater in magnitude than previously appreciated and includes previously undescribed proteins. Our data also indicate that an enzyme with chitinase activity can promote infection of a mammalian host.
Adhesion and friction in gecko toe attachment and detachment
Authors: Tian Yu , Pesika Noshir , Zeng Hongbo , Rosenberg Kenny , Zhao Boxin , McGuiggan Patricia , Autumn Kellar , Israelachvili Jacob
Published: December 2006

Geckos can run rapidly on walls and ceilings, requiring high friction forces (on walls) and adhesion forces (on ceilings), with typical step intervals of ≈20 ms. The rapid switching between gecko foot attachment and detachment is analyzed theoretically based on a tape model that incorporates the adhesion and friction forces originating from the van der Waals forces between the submicron-sized spatulae and the substrate, which are controlled by the (macroscopic) actions of the gecko toes. The pulling force of a spatula along its shaft with an angle θ between 0 and 90° to the substrate, has a “normal adhesion force” contribution, produced at the spatula-substrate bifurcation zone, and a “lateral friction force” contribution from the part of spatula still in contact with the substrate. High net friction and adhesion forces on the whole gecko are obtained by rolling down and gripping the toes inward to realize small pulling angles θ between the large number of spatulae in contact with the substrate. To detach, the high adhesion/friction is rapidly reduced to a very low value by rolling the toes upward and backward, which, mediated by the lever function of the setal shaft, peels the spatulae off perpendicularly from the substrates. By these mechanisms, both the adhesion and friction forces of geckos can be changed over three orders of magnitude, allowing for the swift attachment and detachment during gecko motion. The results have obvious implications for the fabrication of dry adhesives and robotic systems inspired by the gecko's locomotion mechanism.
Antibiotics as intermicrobial signaling agents instead of weapons
Authors: Linares J. F. , Gustafsson I. , Baquero F. , Martinez J. L.
Published: December 2006

It has been widely assumed that the ecological function of antibiotics in nature is fighting against competitors. This made them a good example of the Darwinian struggle-for-life in the microbial world. Based on this idea, it also has been believed that antibiotics, even at subinhibitory concentrations, reduce virulence of bacterial pathogens. Herein, using a combination of genomic and functional assays, we demonstrate that specific antibiotics (namely tobramycin, tetracycline, and norfloxacin) at subinhibitory concentrations trigger expression of determinants influencing the virulence of the major opportunistic bacterial pathogen
Pseudomonas aeruginosa
. All three antibiotics induce biofilm formation; tobramycin increases bacterial motility, and tetracycline triggers expression of
P. aeruginosa
type III secretion system and consequently bacterial cytotoxicity. Besides their relevance in the infection process, those determinants are relevant for the ecological behavior of this bacterial species in natural, nonclinical environments, either by favoring colonization of surfaces (biofilm, motility) or for fighting against eukaryotic predators (cytotoxicity). Our results support the notion that antibiotics are not only bacterial weapons for fighting competitors but also signaling molecules that may regulate the homeostasis of microbial communities. At low concentrations, they can even be beneficial for the behavior of susceptible bacteria in natural environments. This is a complete change on our vision on the ecological function of antibiotics with clear implications both for the treatment of infectious diseases and for the understanding of the microbial relationships in the biosphere.
Rapid decay of tree-community composition in Amazonian forest fragments
Authors: Laurance William F. , Nascimento Henrique E. M. , Laurance Susan G. , Andrade Ana , Ribeiro José E. L. S. , Giraldo Juan Pablo , Lovejoy Thomas E. , Condit Richard , Chave Jerome , Harms Kyle E. , D'Angelo Sammya
Published: December 2006

Forest fragmentation is considered a greater threat to vertebrates than to tree communities because individual trees are typically long-lived and require only small areas for survival. Here we show that forest fragmentation provokes surprisingly rapid and profound alterations in Amazonian tree-community composition. Results were derived from a 22-year study of exceptionally diverse tree communities in 40 1-ha plots in fragmented and intact forests, which were sampled repeatedly before and after fragment isolation. Within these plots, trajectories of change in abundance were assessed for 267 genera and 1,162 tree species. Abrupt shifts in floristic composition were driven by sharply accelerated tree mortality and recruitment within ≈100 m of fragment margins, causing rapid species turnover and population declines or local extinctions of many large-seeded, slow-growing, and old-growth taxa; a striking increase in a smaller set of disturbance-adapted and abiotically dispersed species; and significant shifts in tree size distributions. Even among old-growth trees, species composition in fragments is being restructured substantially, with subcanopy species that rely on animal seed-dispersers and have obligate outbreeding being the most strongly disadvantaged. These diverse changes in tree communities are likely to have wide-ranging impacts on forest architecture, canopy-gap dynamics, plant–animal interactions, and forest carbon storage.
Compartmentalization of protein kinase A signaling by the heterotrimeric G protein G
o
Authors: Ghil Sungho , Choi Jung-Mi , Kim Sung-Soo , Lee Young-Don , Liao Yanhong , Birnbaumer Lutz , Suh-Kim Haeyoung
Published: December 2006

G
o
, a member of the G
o
/
i
family, is the most abundant heterotrimeric G protein in brain. Most functions of G
o
are mediated by the G
βγ
dimer; effector(s) for its α-subunit have not been clearly defined. Here we report that G
oα
interacts directly with cAMP-dependent protein kinase (PKA) through its GTPase domain. This interaction did not inhibit the kinase function of PKA but interfered with nuclear translocation of PKA while sparing its cytosolic function. This regulatory mechanism by which G
o
bifurcates PKA signaling may provide insights into how G
o
regulates complex processes such as neuritogenesis, synaptic plasticity, and cell transformation.