bluuebunny/crossref_metadata_2025 huggingface dataset:
The Muse Pixeliope
Authors: Olson Scott Robert , Pollard Timothy
Published: August 2004

Most media literacy programs fail to take into account the dramatic nature of digitalization, focusing on analog-native media such as the newspaper or digital-native media such as computers and overlooking the process through which these forms are blending and converging. Those trends and ideas includenew digital aesthetics and new social effects caused by digitalization, both of which need to be taken into account in media literacy programs. The aesthetics of digitalization include prepurposing and repurposing content, virtual experience, sampling, interactivity, and manipulation. The new social effects include nonlinearity and content on demand. Digitalization will not immediately replace analog- and digital-oriented programs but needs to be considered as a part of thorough media literacy education.
Creating Reality Through Administrative Practice
Authors: McSwite O. C.
Published: August 2004

Camilla Stivers’book, Bureau Men, Settlement Women, is being misread as a feminist political tract and overlooked as the resource that it is for the field of public administration. A review of the current literature of feminism reveals that Stivers’work, a historical study of the New York Bureau of Municipal Research, cannot be described by any version of feminist theory. Rather, her central concern is how the male-dominated Bureau movement pushed the field away from the model of the city as “home”—which developed in the women’s reform movement—and toward the idea of the city as “business.” A Lacanian psychoanalytic reading reveals a critical implication of her research: The women’s movement carried the potential to bring a balance to public agency discourse, one adequate for the new realities that the social problems of the day required. The administration as business model denies the achievement of this balance.
Integrative Leadership in the Public Sector
Authors: Moynihan Donald P. , Ingraham Patricia Wallace
Published: August 2004

This article proposes a new model for understanding leadership in the public sector. The integrative approach to leadership focuses on how leaders choose, promote, institutionalize, and use public management systems, and reform those in time. Using data from a 50-state survey, this article explores the role of integrative leadership in one of the most popular reforms of government in recent years, managing for results. The findings suggest that leadership does indeed matter to the use of performance information in decision making and offer insights into how and when leadership matters.
The ETS family transcription factor PU.1 is necessary for the maintenance of fetal liver hematopoietic stem cells
Authors: Kim Hyung-Gyoon , de Guzman Cristina G. , Swindle C. Scott , Cotta Claudiu V. , Gartland Larry , Scott Edward W. , Klug Christopher A.
Published: August 2004

PU.1 is a member of the ETS family of transcription factors and is required for the development of multiple hematopoietic lineages. PU.1-/- mice die from hematopoietic failure at about embryonic day 18.5 (e18.5) and show a complete absence of B cells, mature T cells, and macrophages. This phenotype suggests that PU.1 may function at the level of the hematopoietic stem cell (HSC) or a multilineage progenitor. To investigate the role of PU.1 in the regulation of HSCs, PU.1-/- embryos were analyzed at various stages of embryonic development. The absolute number and frequency of HSCs were determined by flow cytometric analysis of c-Kit+Thy-1.1loLin-Sca-1+ (KTLS) cells. We found that KTLS cells were absent or severely reduced in PU.1-/- fetal liver from e12.5 to e15.5. Progenitor cells with a c-Kit+Lin-AA4.1+ and c-Kit+Lin-CD34+ phenotype were also severely reduced. In addition, PU.1-/- fetal liver at e14.5 lacked common myeloid progenitors (CMPs) and granulocyte-macrophage progenitors (GMPs) but retained megakaryocyteerythroid progenitors (MEPs). Consistent with the loss of HSC activity, a 10-fold reduction in erythroid progenitors (mature erythroid burst-forming units [BFUEs]) was observed between e14.5 and e16.5. These data suggest that PU.1 plays an important role in the maintenance or expansion of HSC number in murine fetal liver. (Blood. 2004;104:3894-3900)
LDL-receptor–related protein regulates β2-integrin–mediated leukocyte adhesion
Authors: Spijkers Patricia P. E. M. , da Costa Martins Paula , Westein Erik , Gahmberg Carl G. , Zwaginga Jaap J. , Lenting Peter J.
Published: August 2004

β2-Integrin clustering on activation is a key event in leukocyte adhesion to the endothelium during the inflammatory response. In the search for molecular mechanisms leading to this clustering, we have identified low-density lipoprotein (LDL) receptor–related protein (LRP) as a new partner for β2-integrins at the leukocyte surface. Immobilized recombinant LRP fragments served as an adhesive surface for blood-derived leukocytes and the U937 cell line. This adhesion was decreased up to 95% in the presence of antibodies against β2-integrins, pointing to these integrins as potential partners for LRP. Using purified proteins, LRP indeed associated with the αMβ2 complex and the αM and αL I-domains (Kd, app ≈ 0.5 μM). Immunoprecipitation experiments and confocal microscopy revealed that endogenously expressed LRP and αLβ2 colocalized in monocytes and U937 cells. Furthermore, activation of U937 cells resulted in clustering of αLβ2 and LRP to similar regions at the cell surface, indicating potential cooperation between both proteins. This was confirmed by the lack of αLβ2 clustering in U937 cells treated by antisense oligonucleotides to down-regulate LRP. In addition, the absence of LRP resulted in complete abrogation of β2-integrin–dependent adhesion to endothelial cells in a perfusion system, demonstrating the presence of a previously unrecognized link between LRP and leukocyte function.
Incorporation of CXCR4 into membrane lipid rafts primes homing-related responses of hematopoietic stem/progenitor cells to an SDF-1 gradient
Authors: Wysoczynski Marcin , Reca Ryan , Ratajczak Janina , Kucia Magda , Shirvaikar Neeta , Honczarenko Marek , Mills Michael , Wanzeck Jens , Janowska-Wieczorek Anna , Ratajczak Mariusz Z.
Published: August 2004

We found that supernatants of leukapheresis products (SLPs) of patients mobilized with granulocyte–colony-stimulating factor (G-CSF) or the various components of SLPs (fibrinogen, fibronectin, soluble vascular cell adhesion molecule-1 [VCAM-1], intercellular adhesion molecule-1 [ICAM-1], and urokinase plasminogen activator receptor [uPAR]) increase the chemotactic responses of hematopoietic stem/progenitor cells (HSPCs) to stromal-derived factor-1 (SDF-1). However, alone they do not chemoattract HSPCs, but they do increase or prime the cells' chemotactic responses to a low or threshold dose of SDF-1. We observed that SLPs increased calcium flux, phosphorylation of mitogen-activated protein kinase (MAPK) p42/44 and AKT, secretion of matrix metalloproteinases, and adhesion to endothelium in CD34+ cells. Furthermore, SLPs increased SDF-dependent actin polymerization and significantly enhanced the homing of human cord blood (CB)– and bone marrow (BM)–derived CD34+ cells in a NOD/SCID mouse transplantation model. Moreover, the sensitization or priming of cell chemotaxis to an SDF-1 gradient was dependent on cholesterol content in the cell membrane and on the incorporation of the SDF-1 binding receptor CXCR4 and the small GTPase Rac-1 into membrane lipid rafts. This colocalization of CXCR4 and Rac-1 in lipid rafts facilitated guanosine triphosphate (GTP) binding/activation of Rac-1. Hence, we postulate that CXCR4 could be primed by various factors related to leukapheresis and mobilization that increase its association with membrane lipid rafts, allowing the HSPCs to better sense the SDF-1 gradient. This may partially explain why HSPCs from mobilized peripheral blood leukapheresis products engraft more quickly in patients than do those from BM or CB. Based on our findings, we suggest that the homing of HSPCs is optimal when CXCR4 is incorporated in membrane lipid rafts and that ex vivo priming of HSPCs with some of the SLP-related molecules before transplantation could increase their engraftment.
Influence of microarrays experiments missing values on the stability of gene groups by hierarchical clustering
Authors: de Brevern Alexandre G , Hazout Serge , Malpertuy Alain
Published: August 2004

Background

Microarray technologies produced large amount of data. The hierarchical clustering is commonly used to identify clusters of co-expressed genes. However, microarray datasets often contain missing values (MVs) representing a major drawback for the use of the clustering methods. Usually the MVs are not treated, or replaced by zero or estimated by the k-Nearest Neighbor (kNN) approach. The topic of the paper is to study the stability of gene clusters, defined by various hierarchical clustering algorithms, of microarrays experiments including or not MVs.

Results

In this study, we show that the MVs have important effects on the stability of the gene clusters. Moreover, the magnitude of the gene misallocations is depending on the aggregation algorithm. The most appropriate aggregation methods (e.g. complete-linkage and Ward) are highly sensitive to MVs, and surprisingly, for a very tiny proportion of MVs (e.g. 1%). In most of the case, the MVs must be replaced by expected values. The MVs replacement by the kNN approach clearly improves the identification of co-expressed gene clusters. Nevertheless, we observe that kNN approach is less suitable for the extreme values of gene expression.

Conclusion

The presence of MVs (even at a low rate) is a major factor of gene cluster instability. In addition, the impact depends on the hierarchical clustering algorithm used. Some methods should be used carefully. Nevertheless, the kNN approach constitutes one efficient method for restoring the missing expression gene values, with a low error level. Our study highlights the need of statistical treatments in microarray data to avoid misinterpretation.
Chloroplast DNA rearrangements in Campanulaceae: phylogenetic utility of highly rearranged genomes
Authors: Cosner Mary E , Raubeson Linda A , Jansen Robert K
Published: August 2004

Background

The Campanulaceae (the "hare bell" or "bellflower" family) is a derived angiosperm family comprised of about 600 species treated in 35 to 55 genera. Taxonomic treatments vary widely and little phylogenetic work has been done in the family. Gene order in the chloroplast genome usually varies little among vascular plants. However, chloroplast genomes of Campanulaceae represent an exception and phylogenetic analyses solely based on chloroplast rearrangement characters support a reasonably well-resolved tree.

Results

Chloroplast DNA physical maps were constructed for eighteen representatives of the family. So many gene order changes have occurred among the genomes that characterizing individual mutational events was not always possible. Therefore, we examined different, novel scoring methods to prepare data matrices for cladistic analysis. These approaches yielded largely congruent results but varied in amounts of resolution and homoplasy. The strongly supported nodes were common to all gene order analyses as well as to parallel analyses based on ITS and rbcL sequence data. The results suggest some interesting and unexpected intrafamilial relationships. For example fifteen of the taxa form a derived clade; whereas the remaining three taxa – Platycodon, Codonopsis, and Cyananthus – form the basal clade. This major subdivision of the family corresponds to the distribution of pollen morphology characteristics but is not compatible with previous taxonomic treatments.

Conclusions

Our use of gene order data in the Campanulaceae provides the most highly resolved phylogeny as yet developed for a plant family using only cpDNA rearrangements. The gene order data showed markedly less homoplasy than sequence data for the same taxa but did not resolve quite as many nodes. The rearrangement characters, though relatively few in number, support robust and meaningful phylogenetic hypotheses and provide new insights into evolutionary relationships within the Campanulaceae.
In situ transduction of stromal cells and thymocytes upon intrathymic injection of lentiviral vectors
Authors: Marodon Gilles , Klatzmann David
Published: August 2004

Background

The thymus is the primary site for T-cell development and induction of self-tolerance. Previous approaches towards manipulation of T-cell differentiation have used intrathymic injection of antigens, as proteins, cells or adenoviruses, leading to transient expression of the foreign protein. Lentiviral vectors, due to their unique ability to integrate into the genome of quiescent cells, may be best suited for long-term expression of a transgene in the thymus.

Results

Young adult mice were injected in the thymus with lentiviral vectors expressing eGFP or the hemaglutinin of the Influenza virus under the control of the ubiquitous phospho glycerate kinase promoter. Thymi were examined 5 to 90 days thereafter directly under a UV-light microscope and by flow cytometry. Intrathymic injection of lentiviral vectors predominantly results in infection of stromal cells that could be detected for at least 3 months. Importantly, hemaglutinin expression by thymic stromal cells mediated negative selection of thymocytes expressing the cognate T-cell receptor. In addition and despite the low multiplicity of infection, transduced thymocytes were also detected, even 30 days after injection.

Conclusions

Our results demonstrate that intrathymic delivery of a lentiviral vector is an efficient means for stable expression of a foreign gene in the thymus. This new method of gene delivery may prove useful for induction of tolerance to a specific antigen and for gene therapy of severe combined immunodeficiencies.
Evaluation of safety and efficacy of gefitinib ('iressa', zd1839) as monotherapy in a series of Chinese patients with advanced non-small-cell lung cancer: experience from a compassionate-use programme
Authors: Mu Xin-Lin , Li Long-Yun , Zhang Xiao-Tong , Wang Shu-Lan , Wang Meng-Zhao
Published: August 2004

Background

The gefitinib compassionate-use programme has enabled >39,000 patients worldwide to receive gefitinib ('Iressa', ZD1839) treatment. This paper reports the outcome of gefitinib treatment in Chinese patients who enrolled into the 'Iressa' Expanded Access Programme (EAP) at the Peking Union Medical College Hospital.

Methods

Thirty-one patients with advanced or metastatic non-small-cell lung cancer (NSCLC) that had progressed after prior systemic chemotherapy were eligible to receive oral gefitinib 250 mg/day as part of the EAP. Treatment was continued until disease progression or unacceptable toxicity occurred. The impact of treatment on disease-related symptoms and quality of life (QoL) was evaluated with the Chinese versions of European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ-C30 and QLQ-LC13).

Results

Gefitinib was well tolerated. Adverse events (AEs) were generally mild (grade1 and 2) and reversible. The most frequent AEs were acneform rash and diarrhoea. Only one patient withdrew from the study due to a drug-related AE. The objective tumour response rate was 35.5% (95% confidence interval [CI]: 18.6–52.3); median progression-free survival was 5.5 months (95% CI, 1.6 to 9.4); median overall survival was 11.5 months (95% CI, 5.6 to 17.3). The QoL response rates for five functioning scales and global QoL varied from 56–88%. The main symptom response rates varied from 44–84%. QoL and symptom response were correlated with objective tumour response.

Conclusion

Gefitinib demonstrated safety and efficacy as monotherapy in this series of Chinese patients with advanced NSCLC and was also associated with remarkable symptom relief and improvement in QoL. Although clinical trials are needed to confirm these positive findings, the data suggest that treatment with gefitinib may be beneficial for some Chinese patients who do not respond to chemotherapy and have poor prognosis.
The impact of surgery and mild hyperthermia on tumor response and angioneogenesis of malignant melanoma in a rat perfusion model
Authors: Pelz Joerg , Mollwitz Marco , Stremmel Christian , Goehl Jonas , Dimmler Arno , Hohenberger Werner , Meyer Thomas
Published: August 2004

Background

The aim of this experimental study was to determine the effect of mild hyperthermia on tumor response and angioneogenesis in an isolated limb perfusion model with a human melanoma xenograft.

Methods

A human melanoma xenograft was implanted into the hindlimbs of 30 athymic nude rats. The animals were randomized into five groups: group I: control, group II: sham group, group III: external hyperthermia with a tissue temperature of 41.5°C for 30 minutes without ILP, group IV: normothermic ILP (tissue temperature 37°C for 30 minutes, group V: hyperthermic ILP (tissue temperature 41.5°C for 30 minutes). Tumor response was evaluated by tumor size determination and immunohistochemical analysis 6 weeks postoperatively. Tissue sections were investigated for expression of CD34 and basic fibroblast growth factor (bFGF).

Results

Average tumor volumes of the controls (I) increased from 105 mm3 to 1388 mm3. In the sham operated group (II) tumor volumes were significantly larger than in group I. Tumor volumes in group IV were significantly smaller than in group I and lowest in group V. There were no significant differences in size between group I and group III after six weeks. In group III and IV each, 5 animals showed tumor progression and one had a partial tumor response. In group V only 2 animals showed tumor progression. Immunhistochemical analysis of the tissue sections demonstrated that angioneogenesis was more pronounced in group II than in group I and less pronounced in group IV and V compared with group I.

Conclusions

Our results suggest that even a surgical manipulation such as a skin incision promotes tumor growth, probably by induction of growth factors like bFGF.

External hyperthermia of 41.5°C tissue temperature for 30 minutes only has no impact on tumor growth and angioneogenesis in vivo.
An unusual presentation of anetoderma: a case report
Authors: Aghaei Shahin , Sodaifi Manouchehr , Aslani Fatemeh Sari , Mazharinia Nazila
Published: August 2004

Background

Anetoderma is a benign condition with focal loss of dermal elastic tissue resulting in localized areas of flaccid or herniated saclike skin. Currently, anetoderma is classified as either primary (idiopathic), or secondary anetoderma (which is associated with a variety of skin conditions, penicillamine use, or neonatal prematurity). Lesions appear on the upper arms, trunk, and thighs.

Case presentation

We report a 14-year-old boy, which was noticed to have had multiple, white, non-pruritic areas on the acral sites of upper and lower extremities for two years. In physical examination, the patient had normal mental development. Skin lesions consisted of scattered, white to skin-colored papules, less than 1 cm in diameter, and with central protrusion, with distribution on dorsal part of the index finger, forearms, distal portion of thighs and calves. Lesions were detected neither on the trunk nor the proximal areas of extremities. There are no sensory changes associated with the lesions. Otherwise, his general health was good. He did not have any medication consumption history. Family history was negative. Laboratory examinations were within normal limits. Skin biopsy from one of his lesions was done, that confirmed the diagnosis of anetoderma.

Conclusions

In summary, we report a case of anetoderma on unusual sites of the skin. We could not find similar reports of anetoderma developing on distal extremities without involvement of the upper trunk and proximal arms, in the medical literature.
Short-term delay of Fas-stimulated apoptosis by GM-CSF as a result of temporary suppression of FADD recruitment in neutrophils: evidence implicating phosphatidylinositol 3-kinase and MEK1-ERK1/2 pathways downstream of classical protein kinase C
Authors: Kotone-Miyahara Yasuko , Yamashita Kouhei , Lee Kyung-Kwon , Yonehara Shin , Uchiyama Takashi , Sasada Masataka , Takahashi Atsushi
Published: August 2004

Granulocyte/macrophage colony-stimulating factor (GM-CSF) inhibits Fas-induced apoptosis of neutrophils. However, the exact step in the apoptotic pathway blocked by GM-CSF remained unclear. Here, we found that pretreatment of neutrophils with GM-CSF inhibits the recruitment of Fas-associated protein with death domain (FADD) to Fas, abolishing the formation of the death-inducing signaling complex required for Fas-induced apoptosis. Two-dimensional electrophoresis revealed that GM-CSF modifies the ratio of FADD subspecies. These GM-CSF-triggered changes were abrogated, and Fas-induced apoptosis was restored by an inhibitor of classical protein kinase C (PKC), Gö6976, and by the combination of a phosphatidylinositol 3-kinase (PI-3K) inhibitor, LY294002, and an inhibitor of mitogen-activated protein kinase kinase (MEK)1, PD98059. Gö6976 blocked GM-CSF-elicited phosphorylation of Akt/PKB and extracellular signal-regulated kinase (ERK)1/2. These results indicated that GM-CSF suppresses Fas-induced neutrophil apoptosis by inhibiting FADD binding to Fas, through redundant actions of PI-3K and MEK1-ERK1/2 pathways downstream of classical PKC.
Chemostratigraphy and vegetation in two boreal mires during the Holocene
Authors: Jauhiainen Sinikka , Pitkainen Aki , Vasanderl Harri
Published: August 2004

Two peatlands, a fen and a bog in southern Finland, were studied for peat and carbon accumulation rates, chemical and physical properties of the peat profile, and past vegetation, to assess what stage of succession these peatlands were at the time of human impacts, drainage and restoration. Paludification started at both sites soon after the glacial retreat around 9000 radiocarbon years BP. Peat accumulated at the fen site at an average rate of 0.28mm yr-1 (range 0.16-0.58mm yr-) during development. The peat was composed mostly of Carex with remains of Pin,us sylvestris and Betula spp. The bog site had an average accumulation rate of 0.47mm yr(range 0.25-1.19mm yr-1), and a minerotrophic sedge stage of about 2000 years in its early development, after which the peat was composed mostly of Sphagna. The long-term rates of carbon accumulation (LORCA) varied from 6.6 to 15.3 g m-2 yr '(average 1l.1 g m-2 yr-') for the fen and from 6.1 to 21.1 g m-2 yr-(average 13.2g m-2 yr-') for the bog. The main trend in peat chemistry of both mires was the change from higher to lower nutrient levels with an increased acidity towards the surface peat. The main changes in peat chemistry occurred between 4600 and 4200 BP, simultaneously with the spread of Picea abies in the area. This period was preceded by a large-scale climatic change at the boundary between Atlantic and Subboreal chronozones. Drainage during the twentieth century caused compaction in the uppermost peat of the fen, whereas evidence of drainage was hardly noticeable in the bog stratigraphy.
Interaction of fire, climate and vegetation change at a large landscape scale in the Big Woods of Minnesota, USA
Authors: Umbanhowar Charles E.
Published: August 2004

The Big Woods region of Minnesota is on the prairie-forest border and is a much studied model for the interaction of climate, fire and vegetation. The purpose of this study was (a) to document the extent and timing of changes in vegetation and fire over the past 2000 years and (b) to examine the link between charcoal influx and vegetation during the eighteenth and early nineteenth centuries. To reconstruct changes in vegetation, fire and climate, sieve charcoal (120 gm), pollen, environmental magnetism and loss-on-ignition were used. Charcoal deposition at prairie lakes was 3-4 times greater than for woodland or forest lakes, consistent with current understanding of the fire dependence of prairies, but charcoal influxes to forests were considerably higher than reported elsewhere, suggesting that ground fires were more common than assumed. Regionally, charcoal deposition at a subset of 17 lakes began to change at cal. AD 1100, dating to the period of the ‘Mediaeval Climate Anomaly’ (MCA; cal. AD 900-1250) but preceding the ‘Little Ice Age’ (LIA; cal. AD 1250). For seven of 14 lakes the MCA was characterized by a significant increase in charcoal deposition. This was followed by a decrease with the onset of the LIA, which for most sites continued into the nineteenth century. Relative timing of changes in charcoal and pollen and the other proxies differed from site to site, suggesting no one single response to climatic change. This variation most likely derives from local differences in fuels and topography, as compounded by strong positive feedbacks between fuels and fire.
Aeolian sediment in raised bog deposits, Halland, SW Sweden: a new proxy record of Holocene winter storminess variation in southern Scandinavia?
Authors: Björckl Svante , Clemmensen Lars B.
Published: August 2004

Cores of peat taken from two raised bogs in the near-coastal part of Halland, SW Sweden, were examined for their content of wind-transported clastic material. The Boarps Mosse core has a length of 262 cm and covers the last 2850 years (age model based on three radiocarbon dates), while the Hyltemossen core has a length of 347 cm and records the last 7000 years (age model based on eight radiocarbon dates). The peat contains aeolian quartz silt and sand (from trace amount to more than 10 weight /% of the dry peat sample), and the grain-size composition of the minerogenic sediment indicates that the material is composed of both far-travelled dust and local wind-eroded silt and sand. Grains larger than 0.2mm are present in many intervals and probably record niveo-aeolian transport in connection with severe snowstorms. A systematic count of quartz grains between 0.2-0.35mm and larger than 0.35mm was carried out to determine variations in aeolian sand influx (ASI) and winter wind climate with time. The Boarps Mosse site is situated in a hilly terrain and is primarily open to southerly and northerly winds, while the Hyltemossen site is situated in a more flat landscape open to winds from most directions. Furthermore, at Boarps Mosse dense forest stands seem to have protected the site from significant aeolian sand influx until about AD 1000, while aeolian sand influx apparently was less influenced by local forest development at Hyltemossen. However, using periods with low ASI values as marker horizons it is possible to identify a number of periods of high ASI values during the last 2500 years. These periods, which probably record high winter storminess, are dated to 130, 300, 400, 475, (700), 900, (1000), (1100), (1150), (1350), (1450), 1675, (1800), 1875, 1950-2000, (2050), 2150, 2225 and (2300) cal. yr BP. In addition, the Hyltemossen site documents peak storminess at 2450, 2725, 2850-3050, 3275, 3675, 4100-4200, 4550, 4900, 5100-5200 and 5450-5700 cal. yr BP. Most of the aeolian activity phases in Halland correlate with well-known cold periods in northwest Europe, suggesting a link between winter storminess in southern Scandinavia and expansion of the polar vortex.
Holocene shelf-sea seasonal stratification dynamics: a dinoflagellate cyst record from the Celtic Sea, NW European shelf
Authors: Marretj Fabienne , Scourse James , Austin William
Published: August 2004

Published records of the Holocene evolution of seasonal stratification in the Celtic Sea (NW European shelf) have been based on benthic proxies, notably benthic foraminifera and associated stable isotopic data. We have investigated organic-walled dinoflagellate cyst assemblages from a well-dated Holocene sequence from the central Celtic Sea in order to assess the signal from this planktonic proxy and to reconstruct paired bottom-and surface-water conditions through time. This sequence has, on the basis of the benthic proxies, been interpreted previously as a record of the replacement of tidally mixed water by stratified water associated with tidal-front migration during the early Holocene. Interpretation of the dinocyst record has been facilitated by a parallel study of the distribution of cysts from Celtic Sea surface sediments and their relationship with seasonal water masses. The dinocyst stratigraphy indicates mixed-water conditions during the early Holocene consistent with reduced water depths (hence lowered sea level) over the core site. The first significant change in the dinocyst assemblages is recorded at around 6650 cal. years BP and indicates a transition from mixed-frontal conditions to seasonal stratification. This interpretation of frontal migration is consistent with changes in the benthic foraminiferal assemblages and associated stable isotopes at the same core depth. From 6650 to 3600cal. years BP, the significant occurrence of Bitectatodinium tepikiense accompanied by SpiniJferites elongatus is attributed to strong seasonality, with winter sea-surface temperatures possibly below 5C. Another transition at 3600cal. years BP is attributed to a reduction in seasonality generated by milder winter conditions linked to a stronger influence of the thermohaline circulation over the studied area. This transition is not recorded by the benthic proxies and is attributed to climate forcing rather than to any change in tidal dynamics. It is notable that many mires in western Britain record distinct wet shifts contemporary with this change.
Motivational interviewing
Authors: Treasure Janet
Published: August 2004

Motivational interviewing is a style of patient-centred counselling developed to facilitate change in health-related behaviours. The core principle of the approach is negotiation rather than conflict. In this article I review the historical development of motivational interviewing and give some of the theoretical underpinnings of the approach. I summarise the available evidence on its usefulness and discuss practical details of its implementation, using vignettes to illustrate particular techniques.
Critical psychiatry in practice
Authors: Thomas Philip , Bracken Patrick
Published: August 2004

The ideas of critical psychiatry are influencing a growing number of psychiatrists in Britain and elsewhere. In this article we examine the origins and development of critical psychiatry over the past 25 years, through the work of philosophers such as Foucault and of critical social theorists such as Ingleby, Miller and Rose. We outline the important differences between critical psychiatry and anti-psychiatry. Finally, we examine the current status of critical psychiatry, and what is called postpsychiatry. We regard both as an attempt by practising psychiatrists to engage with service users' concerns about psychiatry, with government policies that stress democracy, citizenship and the importance of social and cultural contexts in health care, and with what might broadly be described as postmodernism.
Psychological treatment for personality disorders
Authors: Bateman Anthony W. , Tyrer Peter
Published: August 2004

There is encouraging evidence that some patients with personality disorder are treatable. Psychotherapeutic interventions show promise, although interpretation of the literature is problematic: the number of patients in most trials is small, outcome measures are questionable, follow-up is limited, and treatments are multifaceted, complex interventions in which the effective components are unclear. The evidence base can be assessed according to efficacy and generalisability, and when both are taken into account the best verification is for psychodynamic therapy. However, there is inadequate evidence to make specific recommendations for any particular therapy.
Area and individual circumstances and mood disorder prevalence
Authors: Wainwright Nicholas W. J. , Surtees Paul G.
Published: August 2004

Background

Associations have been demonstrated between contextual (area level) factors and a range of physical health outcomes, but their relationship with mental health outcomes is less well understood.

Aims

To investigate the relative strength of association between individual and area-level demographic and socioeconomic factors and mood disorder prevalence in the UK.

Method

Cross-sectional data from 19 687 participants from the European Prospective Investigation into Cancer and Nutrition in Norfolk.

Results

Area deprivation was associated with current (12-month) mood disorders after adjusting for individual-level socio-economic status (OR for top v. bottom quartile of deprivation scores 1.29, 95% C11.1–1.5, P < 0.001). However, this association was small relative to those observed for individual marital and employment status. Significant residual area-level variation in current mood disorders (representing 3.6% of total variation, P=0.04) was largely accounted for by individual-level factors.

Conclusions

The magnitude of the association between socio-economic status and mood disorders is greater at the individual level than at the area level.
Audit of psychiatric discharge summaries: completing the cycle
Authors: Crossan Isabelle , Curtis David , Ong Yong-Lok
Published: August 2004

Aims and Method

To examine and attempt to improve the recording of information within psychiatric discharge summaries in an adult psychiatry department, by means of audit and feedback. Psychiatric discharge summaries from an acute adult psychiatric department were examined to determine the recording of ten selected items. Following feedback and discussion, the audit was repeated after 6 months.

Results

Fifty-one discharge summaries were examined on the first occasion and 53 on the second. There was considerable variability in the standard of recording across the selected items, but the patterns of recording were similar at both stages. No improvement was found in the recording of information at the second audit.

Clinical Implications

Audit and feedback alone may have little effect in changing clinical practice. This study examines the experience of undertaking clinical audit from a trainee's perspective, illustrates barriers to change and highlights the possible limitations of audit as a clinical tool.
Phylogenetic conservation of disulfide-linked, dimeric acetylcholine receptor pentamers in southern ocean electric rays
Authors: Tierney M. L. , Osborn K. E. , Milburn P. J. , Stowell M. H. B. , Howitt S. M.
Published: August 2004

Intact acetylcholine receptors have been purified on a novel affinity resin from three electric fish endemic to Australian waters. Their binding properties and morphology are compared with those of their northern hemisphere homolog, Torpedo marmorata. All four exhibit apparent dissociation constants, Kd, in the nanomolar range for the snake neurotoxin α-bungarotoxin and have a distinctive rosette-like appearance when viewed in negative stain under the electron microscope. Furthermore,these rosettes are paired, indicating that acetylcholine receptors from southern ocean electric fish exist as dimers, in the same fashion as their northern hemisphere counterparts. The cDNAs of the receptor's four subunits were sequenced from Hypnos monopterigium and the northern hemisphere counterpart, Torpedo marmorata, while cDNAs from only two subunits,α and δ, were able to be sequenced from Narcine tasmaniensis. The penultimate amino acid in the δ subunit of each of the newly sequenced fish species is a cysteine residue. Its conservation suggests that the mechanism for the observed dimerization of acetylcholine receptors is disulfide bond formation between the δ subunit of adjacent receptors, analogous to acetylcholine receptor dimers observed in other electric fish. It appears that this mechanism for receptor clustering is unique to acetylcholine receptors packed and organized in the specialized organs of electric fish. Alignment of the deduced protein sequences with the equivalent sequences from Torpedo californica and humans reveals a high degree of homology.
Experimental investigation of axial fan erosion and performance degradation
Authors: Ghenaiet A , Tan S C , Elder R L
Published: August 2004

An experimental investigation was conducted to study the effects of sand ingestion on an axial fan with an upstream guide vane (contra-whirl). The experimental work was divided into two types of testing. Firstly, local injection tests were carried out to generate qualitative erosion patterns in order to validate a trajectory code. Secondly, global sand injection tests were carried out in order to assess the geometry deterioration and the subsequent degradation in the axial fan aerodynamic characteristics. Two types of particle were used; a narrow size bandwidth sand (150–300 μm) and MIL-E5007E sand (0–1000 μm). In all sand injection tests the fan operated near design point at a constant speed of rotation.
Multiobjective optimization of a journal bearing using the Pareto optimality concept
Authors: Hirani H
Published: August 2004

This paper deals with multiobjective optimization (minimization of temperature rise, minimization of oil feed flow, minimization of power loss) and discrete design variables (lubricant viscosity, radial clearance, length-diameter ratio) related to the design of a journal bearing. The aim of this paper is to show the sensitivity of radial clearance, oil viscosity and length-diameter ratio on bearing power loss and oil flow. The paper attempts to remove the difficulty of selecting the weighting factor in multiobjective journal bearing optimization problems.

The optimization model is based on a hybrid solution scheme for journal bearings. The objective of bearing optimization is to minimize a linear combination (weighted sum) of power loss and oil flow. Constraints are imposed on the maximum fluid film pressure, minimum film thickness, maximum temperature rise and critical speed. A generic algorithm is used as the optimization tool with a penalty to those solutions that violate constraints. The three-level Taguchi method is used to measure the effect of design variables on the optimum solution. The Pareto-optimal set approach is adapted to segregate the superior design vectors.

The results of power loss, oil flow, temperature rise, maximum pressure and minimum film thickness are presented in tabular and graphical form for comparative study. Three journal bearing design examples are included, demonstrating the effectiveness of the proposed method.
The formation of zinc dithiophosphate antiwear films
Authors: Fujita H , Spikes H. A.
Published: August 2004

In situ spacer layer interferometry has been used to monitor and compare the formation of both tribo- and thermal zinc dialkyldithiophosphate (ZDDP) films on steel surfaces. For the ZDDP solution studied, negligible thermal film formation takes place below a temperature of 110°C, but a ZDDP tribofilm is generated on rubbed surfaces even at room temperature. The ZDDP tribofilm formation is critically dependent on the extent of direct solid solid contact during rubbing and does not take place if the elastohydrodynamic film thickness is significantly greater than the surface roughness. Tests at different slide-roll ratios indicate that the rate of ZDDP tribofilm formation is proportional to the product of sliding distance and rubbing time. Based on the results, it is not possible to explain ZDDP tribofilm formation in terms of a response to contact pressure or flash temperature. It is likely that the tribofilm reaction is either strongly catalysed by species released during rubbing, such as soluble FeII or FeIII, or is triggered by triboelectronic processes such as exoelectron emission.
A Novel Enantioselective Reaction. Palladium-catalyzed Enantiodistinctive Reaction of Bicyclic Allylic Compounds
Authors: Daimon Hisashi , Ogawa Ryohei , Itagaki Shuichi , Shimizu Isao
Published: August 2004

Reaction of (±)-2β-acetoxy-4aβ-methyl-2,3,4,4a,5,6,7,8-octahydronaphthalene (4) with dimethyl malonate anion in the presence of a catalytic amount of [(1-Me-allyl)PdCl]2 and (S)-(−)-BINAP proceeded enantiodistinctively to give both the nucleophilic substituted product (2S,4aS)-5 and the diene (R)-6 as the elimination product in considerable enantiomeric excesses.
Trans-splicing and polyadenylation of let-7 microRNA primary transcripts
Authors: BRACHT JOHN , HUNTER SHAUN , EACHUS RACHEL , WEEKS PHILLIP , PASQUINELLI AMY E.
Published: August 2004

Members of the microRNA (miRNA) class of 22-nucleotide RNAs regulate the expression of target genes that contain sequences of antisense complementarity. Maturation of miRNAs involves cleavage of longer primary transcripts, but little is yet understood about how miRNA genes are transcribed and enter the processing pathway. We find that relatively long, polyadenylated transcripts encoded by the Caenorhabditis elegans let-7 gene undergo trans-splicing to the spliced leader 1 (SL1) RNA. Deletions, including removal of the trans-splice site, upstream of mature let-7 sequence result in stable accumulation of primary transcripts and compromised production of mature let-7 RNA in vivo. Our data show that multiple steps of let-7 miRNA biogenesis can be uncoupled, allowing for complex regulation in the production of a functional miRNA. Finally, the observation that let-7 primary transcripts undergo splicing highlights the importance of identifying the sequence of endogenous pri-miRNA substrates recognized by the cellular processing machinery.
Tethering of human Ago proteins to mRNA mimics the miRNA-mediated repression of protein synthesis
Authors: PILLAI RAMESH S. , ARTUS CAROLINE G. , FILIPOWICZ WITOLD
Published: August 2004

MicroRNAs (miRNAs) are ~21-nt-long RNAs involved in regulating development, differentiation, and other processes in eukaryotes. In metazoa, nearly all miRNAs control gene expression by imperfectly base-pairing with the 3′slated region (3′f target mRNAs and repressing protein synthesis by an unknown mechanism. It is also unknown whether miRNA–mRNA duplexes containing mismatches and bulges provide specific features that are recognized by factors mediating the repression. miRNAs form part of ribonucleoprotein complexes, miRNPs, that contain Argonaute (Ago) and other proteins. Here we demonstrate that effects of miRNAs on translation can be mimicked in human HeLa cells by the miRNA-independent tethering of Ago proteins to the 3′ a reporter mRNA. Inhibition of protein synthesis occurred without a change in the reporter mRNA level and was dependent on the number, but not the position, of the hairpins tethering hAgo2 to the 3′hese findings indicate that a primary function of miRNAs is to guide their associated proteins to the mRNA.
Recruitment of the Puf3 protein to its mRNA target for regulation of mRNA decay in yeast
Authors: JACKSON JOHN S. , HOUSHMANDI S. SEAN , LOPEZ LEBAN FLORENCIA , OLIVAS WENDY M.
Published: August 2004

The Puf family of RNA-binding proteins regulates mRNA translation and decay via interactions with 3′ untranslated regions (3′ UTRs) of target mRNAs. In yeast, Puf3p binds the 3′ UTR of COX17 mRNA and promotes rapid deadenylation and decay. We have investigated the sequences required for Puf3p recruitment to this 3′ UTR and have identified two separate binding sites. These sites are specific for Puf3p, as they cannot bind another Puf protein, Puf5p. Both sites use a conserved UGUANAUA sequence, whereas one site contains additional sequences that enhance binding affinity. In vivo, presence of either site partially stimulates COX17 mRNA decay, but full decay regulation requires the presence of both sites. No other sequences outside the 3′ UTR are required to mediate this decay regulation. The Puf repeat domain of Puf3p is sufficient not only for in vitro binding to the 3′ UTR, but also in vivo stimulation of COX17 mRNA decay. These experiments indicate that the essential residues involved in mRNA decay regulation are wholly contained within this RNA-binding domain.
On a New Collection of Stochastic Linear Programming Test Problems
Authors: Ariyawansa K. A. , Felt Andrew J.
Published: August 2004

The purpose of this paper is to introduce a new test-problem collection for stochastic linear programming that the authors have recently begun to assemble. While there are existing stochastic programming test-problem collections, our new collection has three features that distinguish it from existing collections. First, our collection is web-based with free public access, and we intend to enrich it as new test problems become available. Indeed, we encourage submissions of new test problems. Second, along with the collection we provide documentation of the problems, so that researchers can quickly find information about each family without reading through the original source. Third, all of the data in our collection are provided in SMPS (Birge et al. 1987, Gassmann and Schweitzer 2001) format. In this paper, we provide an introduction to the stochastic linear program, give a brief description of each problem family currently in the test-problem collection, and describe the documentation that accompanies the collection.
The Pht/Pht/∞ Queueing System: Part I—The Single Node
Authors: Nelson Barry L. , Taaffe Michael R.
Published: August 2004

We develop a numerically exact method for evaluating the time-dependent mean, variance, and higher-order moments of the number of entities in a Pht/Pht/∞ queueing system. We also develop a numerically exact method for evaluating the distribution function and moments of the virtual sojourn time for any time t; in our setting, the virtual sojourn time is equivalent to the service time for virtual entities arriving to the system at that time t. We include several examples using software that we have developed and have put in downloadable form in the Online Supplement to this paper on the journal's website.
On the Existence of Moments for the Busy Period in a Single-Server Queue
Authors: Foss S. , Sapozhnikov A.
Published: August 2004

We obtain sufficient conditions for the finiteness of the moments of the single-server queue busy period in discrete and continuous time. In the cases of power and exponential moments, the conditions found coincide with the known necessary ones.
Optimal Bankruptcy Time and Consumption/Investment Policies on an Infinite Horizon with a Continuous Debt Repayment Until Bankruptcy
Authors: Jeanblanc Monique , Lakner Peter , Kadam Ashay
Published: August 2004

In this paper we consider the optimization problem of an agent who wants to maximize the total expected discounted utility from consumption over an infinite horizon. The agent is under obligation to pay a debt at a fixed rate until he/she declares bankruptcy. At that point, after paying a fixed cost, the agent will be able to keep a certain fraction of the present wealth, and the debt will be forgiven. The selection of the bankruptcy time is taken to be at the discretion of the agent. The novelty of this paper is that at the time of bankruptcy the wealth process has a discontinuity, and that the agent continues to invest and consume after bankruptcy. We show that the solution of a free boundary problem satisfying some additional conditions is the value function of the above optimization problem. Particular examples such as the logarithmic and the power utility functions will be provided, and in these cases explicit forms will be given for the optimal bankruptcy time, investment and consumption processes.