bluuebunny/crossref_metadata_2025 huggingface dataset:
Spirituality in science education: studying the environment
Authors: Solomon Joan
Published: December 2003

The value of including a kindof spirituality in science education, and especially in environmental education, is taken as a given. The work on which the argument is based starts from the young child's use of the senses which are so acute at primary school age, but also stimulates the asking of ‘big questions’ which seem spiritual in a sense that is examined here. A fragmented historical exploration shows pre-enlightenment educators encouraging the use of the senses, whereas Descartes, Hume, and Locke all argued against it. Later Husserl and Merleau-Ponty took a phenomenological stance which sometimes saw wonder, based on perception, as seriously opposed to scientific curiosity or explanation. The paper ends with an attempt to reconcile the phenomenological with the scientific, suggesting a perception of play which includes curiosity, andof theenvironment basedon the sensory. A brief look at thedevelopment of environmental attitudes over the last century shows an increasing use of the affective along with the scientific. A closing consideration of spirituality in the Gaia hypothesis is illustrated by an extract from metaphysical poetry.
Inquiry and performance: analogies andidentities between the arts and the sciences
Authors: Crease Robert P.
Published: December 2003

The concept of performance can be used to explain and elaborate key aspects of various issues often neglected within traditional philosophy of science, including among others artistry, technique, and affective power. The word ‘performance’ has a spectrumof meanings, but one important sense in which it is applied, especially in the dramatic arts, is to the conception, production, and witnessing of material events the experience of which gives us something more than what we had before. When viewed in this way, the structure of performance is not a metaphor extended merely suggestively from the theatre arts into experimental science; it is the same in both. In both contexts, the representation (theory, language, script) used to programme the performance does not completely determine the outcome (product, work), but only assists in the encounter with the new. The world is wilder and richer than we can represent; what appears in performance can exceed the programme used to put it together, can even surprise and baffle us. An experiment planned and programmed on the basis of a certain theory can disclose things that trigger changes in that theory.
Privacy: what's different now?
Authors: Jones Karen Spärck
Published: December 2003

Modern computing technology makes it possible to record, preserve, collate, reconstruct, and use detailed facts about individuals on a scale and in a style quite different from the past. With this technology, data is voluminous, not sparse; is permanent, not transient; and is detached, not tied to the individual's own observation. How do these developments change the reality, or the perception, of privacy for the individual? How, in particular, do they change the reality or perception of privacy for daily life, not just in legal situations or in relations with authority? This paper examines the properties of current computing technology, illustrating their consequences for personal data, and argues that they have profound implications for personal privacy and autonomy.
Virtual objects: the endof the real?
Authors: Swade Doron
Published: December 2003

The central article of faith in museum life is the belief in the primacy of original objects. Traditional museums are part of an object centred culture. Physical artefacts, their acquisition, meanings, and care, dominate the psyche of the museum profession. Original artefacts are sanctified and prized above object surrogates – replicas, graphic depictions, holograms – for reasons that are not always easy to articulate. Yet there is a new genre of object in the museological landscape – the virtual object. By this I mean an electronic representation of a thing whether real or imagined. The creation and manipulation of computer based virtual objects is compellingly attractive to museum directors, exhibition designers, and educationalists. Virtual objects prompt a reexamination of the status and role of the original artefact, and agitate our assumptions about the status of the original. This article explores some of the respects in which the virtual object may be seen to challenge the primacy of the original in museum culture.
Theology and psychology: an essay review on Fraser Watts
Authors: Albright Carol Rausch
Published: December 2003

In his recent book Theology and Psychology, Fraser Watts explores an area of interdisciplinary dialogue that has become active on many fronts. He traces the main areas of engagement while limiting his purview mostly to psychological explorations of the formation of the human spirit and of religious experience, and theology directed to parallel concepts. Psychology is largely pursued within its subdisciplines pertaining to introspective psychologies, neuroscience, and social psychology. The theology is mostly within the Christian, and especially Anglican, tradition, yet the variety of voices here is also well known. Within these broad limits, and with impressive depth and breadth of scholarship, Watts addresses topics as diverse as evolutionary theory, the nature of consciousness, artificial intelligence, the foundations of morality, the soul, immortality, divine action, the doctrine of the Fall, eschatology, and the origin of belief. Although he provides fair representations of various views, he consistently rejects ‘greedy’ forms of ‘nothing buttery’, because he believes that the human person and religious experience are so multifaceted that they cannot be grasped from any single standpoint. In addition, as he points out, various reductionistic claims are simply inaccurate. It is suggested that Watts's thinking shows many parallels with theories developing within the new sciences of complexity. Further development of his work along these lines might have significance both for his own contribution and for the growing field of complexity studies.
Adult chronic idiopathic thrombocytopenic purpura (ITP) is the manifestation of a type-1 polarized immune response
Authors: Panitsas Fotios P. , Theodoropoulou Maria , Kouraklis Alexandra , Karakantza Marina , Theodorou Georgios L. , Zoumbos Nicholas C. , Maniatis Alice , Mouzaki Athanasia
Published: December 2003

Derangement of cellular immunity is central in the pathophysiology of adult autoimmune/idiopathic thrombocytopenic purpura (ITP). Herein we investigated cytokine gene expression in peripheral blood mononuclear cells (PBMCs) of adult chronic ITP patients and attempted to correlate cytokine polarization with the degree of thrombocytopenia. We used semiquantitative reverse-transcriptase–polymerase chain reaction (RT-PCR) to measure the expression of type-1 (interleukin-2 [IL-2], interferon γ [IFN-γ]) and type-2 (IL-4, IL-5, IL-10, IL-3, IL-13) cytokines by PBMCs from 21 patients and 11 controls. Plasma transforming growth factor β1 (TGF-β1) levels were measured by enzyme-linked immunoassay (ELISA). T helper 1 (Th1)/Th2 ([IL-2 + IFN-γ]/[IL-4 + IL-5]) cytokine mRNA ratios, thought to reflect the Th deviation of the pathogenic disease-specific T cells, and type-1/type-2 mRNA ratios, thought to reflect the overall immune response polarization, were significantly increased in ITP patients. The Th1/Th2 ratio was inversely correlated with platelet counts. TGF-β1 levels appeared suppressed in patients with active disease, though not significantly. Our findings show a clear type-1 cytokine polarization of the autoimmune response in adult ITP that persists irrespective of disease status.
The quantity and duration of FcRγ signals determine mast cell degranulation and survival
Authors: Yamasaki Sho , Ishikawa Eri , Kohno Masayuki , Saito Takashi
Published: December 2003

Immunoglobulin E (IgE) bound to multivalent antigen (Ag) elicits mast cell degranulation but not survival; on the contrary, IgE in the absence of Ag (IgE(-Ag)) induces survival only but not degranulation. Although these distinct responses are mediated through the same receptor, FcϵRI, the molecular mechanism generating the divergence is largely unknown. We recently showed that the signals through FcRγ chain are essential for IgE(-Ag)–induced mast cell survival as well as IgE(+Ag)–induced degranulation. To determine whether the cellular output is regulated by the quantity of FcRγ signal, we expressed CD8/FcRγ chimeras (CD8/γ) in bone marrow–derived mast cells (BMMCs) from FcRγ-/- mice to manipulate the strength of FcRγ signals by anti-CD8 cross-linking. Cross-linking of CD8/γ induced mast cell survival and degranulation. Survival was induced by weaker stimulation than needed for degranulation in terms of anti-CD8 concentration and the valency of chimera. However, sustained extracellular signal-regulated kinase (Erk) activation seems to regulate survival even when the activation signal was strong enough to elicit degranulation. Generation of sustained Erk activation by active mitogen-activated protein kinase kinase (MEK) induced BMMC survival. These results suggest that the duration and the magnitude of FcRγ signals may determine mast cell survival and degranulation, respectively. (Blood. 2004;103:3093-3101)
Membrane type 1–matrix metalloproteinase (MT1-MMP) cooperates with sphingosine 1–phosphate to induce endothelial cell migration and morphogenic differentiation
Authors: Langlois Stéphanie , Gingras Denis , Béliveau Richard
Published: December 2003

Membrane type 1–matrix metalloproteinase (MT1-MMP) has been suggested to play an important role in angiogenesis, but the mechanisms involved remain incompletely understood. Using an in vitro model of angiogenesis in which cell migration of bovine aortic endothelial cells (BAECs) and their morphogenic differentiation into capillary-like structures on Matrigel are induced by overexpression of MT1-MMP, we show that the platelet-derived bioactive lipid sphingosine 1–phosphate (S1P) is the predominant serum factor essential for MT1-MMP–dependent migration and morphogenic differentiation activities. In the presence of S1P, MT1-MMP–dependent cell migration and morphogenic differentiation were inhibited by pertussis toxin, suggesting the involvement of Gi-protein–coupled receptor-mediated signaling. Accordingly, cotransfection of BAECs with MT1-MMP and a constitutively active Gαi2 (Q205L) mutant increased cell migration and morphogenic differentiation, whereas treatment of BAECs overexpressing MT1-MMP with antisense oligonucleotides directed against S1P1 and S1P3, the predominant S1P receptors, significantly inhibited both processes. These results demonstrate that MT1-MMP–induced migration and morphogenic differentiation involve the cooperation of the enzyme with platelet-derived bioactive lipids through S1P-mediated activation of Gαi-coupled S1P1 and S1P3 receptors. Given the important contribution of platelets to tumor angiogenesis, the stimulation of endothelial MT1-MMP function by S1P may thus constitute an important molecular event linking hemostasis to angiogenesis. (Blood. 2004;103:3020-3028)
Thrombopoietin cooperates with FLT3-ligand in the generation of plasmacytoid dendritic cell precursors from human hematopoietic progenitors
Authors: Chen Wei , Antonenko Svetlana , Sederstrom Joel M. , Liang Xueqing , Chan Anissa S. H. , Kanzler Holger , Blom Bianca , Blazar Bruce R. , Liu Yong-Jun
Published: December 2003

Type 1 interferon–producing cells (IPCs), also known as plasmacytoid dendritic cell (DC) precursors, represent the key effectors in antiviral innate immunity and triggers for adaptive immune responses. IPCs play important roles in the pathogenesis of systemic lupus erythematosus (SLE) and in modulating immune responses after hematopoietic stem cell transplantation. Understanding IPC development from hematopoietic progenitor cells (HPCs) may provide critical information in controlling viral infection, autoimmune SLE, and graft-versus-host disease. FLT3-ligand (FLT3-L) represents a key IPC differentiation factor from HPCs. Although hematopoietic cytokines such as interleukin-3 (IL-3), IL-7, stem cell factor (SCF), macrophage–colony-stimulating factor (M-CSF), and granulocyte M-CSF (GM-CSF) promote the expansion of CD34+ HPCs in FLT3-L culture, they strongly inhibit HPC differentiation into IPCs. Here we show that thrombopoietin (TPO) cooperates with FLT3-L, inducing CD34+ HPCs to undergo a 400-fold expansion in cell numbers and to generate more than 6 × 106 IPCs per 106 CD34+ HPCs within 30 days in culture. IPCs derived from HPCs in FLT3-L/TPO cultures display blood IPC phenotype and have the capacity to produce large amounts of interferon-α (IFN-α) and to differentiate into mature DCs. This culture system, combined with the use of adult peripheral blood CD34+ HPCs purified from G-CSF–mobilized donors, permits the generation of more than 109 IPCs from a single blood donor.
HAMP as a modifier gene that increases the phenotypic expression of the HFE pC282Y homozygous genotype
Authors: Jacolot Sandrine , Le Gac Gerald , Scotet Virginie , Quere Isabelle , Mura Catherine , Ferec Claude
Published: December 2003

Hereditary hemochromatosis is a genetically heterogeneous disease of iron metabolism. The most common form of the disorder is an adult-onset form that has mainly been associated with the HFE pC282Y/pC282Y genotype. The phenotypic expression of this genotype is very heterogeneous and could be modulated by both environmental factors and modifier genes. The non-HFE hereditary hemochromatosis forms include a juvenile onset form associated with mutations in HAMP. From a cohort of 392 C282Y homozygous patients, we found 5 carriers of an additional HAMP mutation at the heterozygous state (pR59G, pG71D, or pR56X). We found that iron indices of these 5 patients were among the most elevated of the cohort. Moreover, we specified that the HAMP mutations were not detected in 300 control subjects. These results revealed that mutations in HAMP might increase the phenotypic expression of the pC282Y/pC282Y genotype. From a cohort of 31 patients with at least one chromosome lacking an HFE mutation, we further identified 4 males carrying a heterozygous HAMP mutation (pR59G or pG71D). Based on a digenic model of inheritance, these data suggest that the association of heterozygous mutations in the HFE and HAMP genes could lead, at least in some cases, to an adult-onset form of primary iron overload. (Blood. 2004;103:2835-2840)
Local antibodies against Pneumocystis carinii in bronchoalveolar lavage fluid
Authors: Laursen AL , Jensen BN , Andersen PL
Published: December 2003

Pneumocystis carinii pneumonia (PCP) is a frequent cause of pneumonia among human immunodeficiency virus (HIV)-infected patients. Little is known, however, about the role played by humoral immunity to control the infection. This study was undertaken to elucidate the role played by local antibodies. Bronchoalveolar lavage (BAL) fluids from 18 acquired immune deficiency syndrome (AIDS) patients with PCP, 20 HIV-antibody positive patients without PCP, and 20 lung cancer patients were examined for antibodies against P. carinii by the indirect immunofluorescence method. The ratio of albumin concentration in BAL fluid to serum was used to standardize the lavage fluids. Immunoglobulin G (IgG) antibodies against P. carinii occurred less frequently, and immunoglobulin M (IgM) antibodies more frequently, in PCP patients than in other groups. Immunoglobulin A (IgA) antibodies against pneumocysts were found with the same frequency in all three groups, although the median titre was lower among HIV-antibody positive patients without PCP, compared with the other groups. When indexed (antibody titre in BAL fluid x albumin concentration in serum/antibody titre in serum x albumin concentration in BAL fluid) to express locally produced antibodies, IgG indices were significantly higher in HIV-infected patients without PCP, whereas IgM and IgA indices were significantly higher in PCP patients. These findings suggest that the local IgG response is impaired in patients with PCP, whereas the local IgA and, to some extent, the IgM responses are preserved.
Effect of beclomethasone dipropionate on bone mineral content assessed by X-ray densitometry in asthmatic children: a longitudinal evaluation
Authors: Baraldi E , Bollini MC , De Marchi A , Zacchello F
Published: December 2003

There is little information on bone turnover in asthmatic children taking long-term treatment with inhaled steroids (ICS). The aim of this longitudinal study was to determine the effects of inhaled beclomethasone dipropionate (BDP) on bone mineral density (BMD), in asthmatic children treated over a period of six months. BMD and growth were studied in two age- and sex-matched groups of asthmatic children. These comprised: 14 asthmatic children (Group 1) who had taken BDP in a dosage of 300-400 micrograms daily through a 145 ml spacer device for at least 6 months (mean age 9.1 yrs); and a control group of 16 age- and sex-matched asthmatic patients (Group 2) not treated with ICS (mean age 9.5 yrs). Mean duration of asthma was 5.7 yrs in Group 1 and 5.5 yrs in Group 2. Vertebral BMD (L2-L4) was measured by dual energy X-ray absorptiometry (DEXA) at the beginning (baseline) of the study and 6 months later. There were no significant differences in the baseline bone mass (mean +/- SEM) between the two groups (0.63 +/- 0.03 and 0.64 +/- 0.02 g.cm-2 in Group 1 and 2, respectively). During the observation period, bone density increased, by 4% (95% confidence interval (95% CI) 2-6) in the control group and by 2.3% (95% CI 0.4-4.2) in the group under BDP treatment, showing no significant influence of the treatment. No difference was found in height velocity evaluated before starting BDP and after 6 months of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Arterial oxygenation does not predict the outcome of patients with acute respiratory failure needing mechanical ventilation
Authors: Jimenez P , Torres A , Roca J , Cobos A , Rodriguez-Roisin R
Published: December 2003

One hundred and eighteen patients consecutively submitted to mechanical ventilation during a one year period, and admitted to the Respiratory Intensive Care Unit of the Hospital Clinic of Barcelona, were prospectively studied in order to define the importance of hypoxaemia as a predictor of mortality. Using a discriminant multivariate analysis, the following variables were selected as the best predictors of outcome: 1) the number of associated complications (NAC) on admission; 2) the simplified acute physiologic score (SAPS); 3) oxygenation index (PAO2-AaPO2)/PAO2 + 0.014 positive end-expiratory pressure (PEEP); and 4) the age of the patients. Using these predictors, 84% of the patients were accurately classified as survivors or as nonsurvivors. The partial contribution of each predictor to the model was also assessed using a logistic regression, by eliminating each single predictor and each possible pair of predictors. Using this means of analysis, the NAC and SAPS were the only predictors of mortality. The inclusion of short-term mechanically-ventilated patients did not bias the accuracy of prediction.
IVOX in ARDS: respiratory effects and serious complications
Authors: Gasche Y , Romand JA , Pretre R , Suter PM
Published: December 2003

We describe the beneficial effects of an intravenous oxygenator (IVOX) on ventilatory pressure requirement, and also several severe complications related to its use in a young trauma victim developing severe acute respiratory distress syndrome (ARDS). In this patient, adequate systemic oxygenation could not be maintained despite the use of fractional inspired oxygen of 1.0, high level positive end-expiratory pressure (PEEP), and nitric oxide inhalation (30 ppm). The introduction of an intravenous oxygenator improved arterial oxygenation and CO2 elimination, allowing a decrease in minute ventilation and airway pressure. However, hepatic cytolysis, acute renal dysfunction and iliac vein thrombosis developed concomitantly, in spite of full anticoagulation with heparin. These complications resolved rapidly after removal of the IVOX device and the patient made a good recovery.
In situ demonstration of dendritic cell migration from rat intestine to mesenteric lymph nodes: relationships to maturation and role of chemokines
Authors: Kobayashi Hisashi , Miura Soichiro , Nagata Hiroshi , Tsuzuki Yoshikazu , Hokari Ryota , Ogino Takashi , Watanabe Chikako , Azuma Toshifumi , Ishii Hiromasa
Published: December 2003

Dendritic cells (DCs) are continuously transported from the intestine to mesenteric lymph nodes (MLNs). The objective of this study was to determine the migration kinetics of DCs via intestinal lymph and to investigate regulatory factors affecting their migration in vivo. DCs were obtained from spleen or thoracic duct lymph of mesenteric lymphadenectomized rats. The DCs were fluorescently labeled and injected into the subserosa of the small intestine near the cecum, and their migration patterns into MLNs were determined. Isolated DCs from intestinal lymph express intercellular adhesion molecule-1 (ICAM-1), CD11b/c, CD80/86, and major histocompatibility complex class II but maintain their ability to phagocytize latex particles, suggesting the presence of immature DCs. The isolated DCs accumulated in MLNs in a time-dependent manner with maximal accumulation at 48 h. Cytokine-induced maturation of lymph DCs did not cause a change in cell number but accelerated their transport into MLNs with a maximum at 24 h. Splenic DCs showed an intermediate level of maturation and a migration pattern similar to mature DCs. Inhibition of ICAM-1 or CD11b/c did not affect DC migration. Migration of mature DCs to MLNs was specifically blocked by desensitization of CCR7 with CCL21. In contrast, freshly isolated lymph DCs were not chemotactic for CCL21, but their migration to MLNs was mainly inhibited by desensitization of CCR6 with CCL20. The migratory ability of DCs correlates well with their degree of maturation, and different chemokine/chemokine receptor use may be the main regulator of DC migration kinetics through intestinal lymph.
Phase I Trial Using a Time-to-Event Continual Reassessment Strategy for Dose Escalation of Cisplatin Combined With Gemcitabine and Radiation Therapy in Pancreatic Cancer
Authors: Muler Jeffrey H. , McGinn Cornelius J. , Normolle Daniel , Lawrence Theodore , Brown Diane , Hejna Gwen , Zalupski Mark M.
Published: December 2003

Purpose

The primary objective of this study was to determine the maximum-tolerated dose of cisplatin that could be added to full-dose gemcitabine and radiation therapy (RT) in patients with pancreatic cancer.

Patients and Methods

Nineteen patients were treated. Gemcitabine 1,000 mg/m2 was administered over 30 minutes on days 1, 8, and 15 of a 28-day cycle. Cisplatin followed gemcitabine on days 1 and 15. The initial dose level of cisplatin was 30 mg/m2, escalated to a targeted dose of 50 mg/m2 using Time-to-Event Continual Reassessment Method. RT was initiated on cycle 1, day 1, in 2.4 Gy fractions to a total dose of 36 Gy. A second cycle of chemotherapy was planned following a 1-week rest.

Results

Four of eight patients experienced acute dose limiting toxicity at the 50 mg/m2 cisplatin dose level. Patients treated at 30 and 40 mg/m2 cisplatin dose level tolerated therapy without dose-limiting toxicity. Median survival was 10.7 months (95% CI, 5.4 to 18.2) for all patients, and 12.9 months (95% CI, 7.4 to 21.2) for those without metastasis.

Conclusion

Cisplatin at doses up to 40 mg/m2 may be safely added to full-dose gemcitabine and conformal RT. The Time-to-Event Continual Reassessment Method trial design allowed rapid completion of the study and confidence in the conclusion about the maximum tolerated dose, but accrued more patients to a dose level above the maximum tolerated dose than the typical phase I design. Local and systemic disease control and survival in this study cohort supports further investigation of gemcitabine-based RT and combination chemotherapy in this disease.
Sphingolipid-Cholesterol Domains (Lipid Rafts) in Normal Human and Dog Thyroid Follicular Cells Are Not Involved in Thyrotropin Receptor Signaling
Authors: Costa M. J. , Song Y. , Macours P. , Massart C. , Many M. C. , Costagliola S. , Dumont J. E. , Van Sande J. , Vanvooren V.
Published: December 2003

Partition of signaling molecules in sphingolipid-cholesterol-enriched membrane domains, among which are the caveolae, may contribute to signal transduction efficiency. In normal thyroid, nothing is known about a putative TSH/cAMP cascade compartmentation in caveolae or other sphingolipid-cholesterol-enriched membrane domains. In this study we show for the first time that caveolae are present in the apical membrane of dog and human thyrocytes: caveolin-1 mRNA presence is demonstrated by Northern blotting in primary cultures and that of the caveolin-1 protein by immunohistochemistry performed on human thyroid tissue. The TSH receptor located in the basal membrane can therefore not be located in caveolae. We demonstrate for the first time by biochemical methods the existence of sphingolipid-cholesterol-enriched domains in human and dog thyroid follicular cells that contain caveolin, flotillin-2, and the insulin receptor. We assessed a possible sphingolipid-cholesterol-enriched domains compartmentation of the TSH receptor and the α- subunit of the heterotrimeric Gs and Gq proteins using two approaches: Western blotting on detergent-resistant membranes isolated from thyrocytes in primary cultures and the influence of 10 mm methyl-β-cyclodextrin, a cholesterol chelator, on basal and stimulated cAMP accumulation in intact thyrocytes. The results from both types of experiments strongly suggest that the TSH/cAMP cascade in thyroid cells is not associated with sphingolipid-cholesterol-enriched membrane domains.
Hyzic, theHydrahomolog of thezic/odd-pairedgene, is involved in the early specification of the sensory nematocytes
Authors: Lindgens Dirk , Holstein Thomas W. , Technau Ulrich
Published: December 2003

Cnidaria are the first class of organisms in animal evolution with a nervous system. The cnidarian Hydra has two types of neuronal cell,nerve cells and nematocytes. Both differentiate from the same pool of pluripotent stem cells. Yet, the molecular regulation of neural differentiation in Hydra is largely unknown. Here, we report the identification of Hyzic, a homolog of the Zn-finger transcription factor gene zic/odd-paired, which acts as an early neural effector gene in vertebrates. We show, that Hyzic is expressed in the early nematocyte differentiation pathway, starting at the level of interstitial stem cells. Expression of Hyzic is restricted to the proliferative stages of nematoblasts. Hyzic acts before and possibly directly upstream of Cnash, a homolog of the proneural bHLH transcription factor gene achaete-scute, and of Nowa, an early nematocyte differentiation marker gene. Hyzic may determine stem cells to differentiate into nematocytes. Our data are consistent with a role of Hyzic in inhibiting nematocyte differentiation, by keeping committed nematoblast cells in the cell cycle. A similar role has been demonstrated for Zic genes in vertebrates. Our results suggest, that genetic cascades of neural development may be conserved from Hydra to vertebrates, indicating that the molecular regulation of neural development evolved only once.
Genome-wide germline-enriched and sex-biased expression profiles in Caenorhabditis elegans
Authors: Reinke Valerie , Gil Inigo San , Ward Samuel , Kazmer Keith
Published: December 2003

We performed a genome-wide analysis of gene expression in C. elegans to identify germline- and sex-regulated genes. Using mutants that cause defects in germ cell proliferation or gametogenesis, we identified sets of genes with germline-enriched expression in either hermaphrodites or males,or in both sexes. Additionally, we compared gene expression profiles between males and hermaphrodites lacking germline tissue to define genes with sex-biased expression in terminally differentiated somatic tissues. Cross-referencing hermaphrodite germline and somatic gene sets with in situ hybridization data demonstrates that the vast majority of these genes have appropriate spatial expression patterns. Additionally, we examined gene expression at multiple times during wild-type germline development to define temporal expression profiles for these genes. Sex- and germline-regulated genes have a non-random distribution in the genome, with especially strong biases for and against the X chromosome. Comparison with data from large-scale RNAi screens demonstrates that genes expressed in the oogenic germline display visible phenotypes more frequently than expected.
Lachesin is a component of a septate junction-based mechanism that controls tube size and epithelial integrity in theDrosophilatracheal system
Authors: Llimargas Marta , Strigini Maura , Katidou Markella , Karagogeos Domna , Casanova Jordi
Published: December 2003

Organ morphogenesis requires the coordinated activity of many mechanisms involved in cell rearrangements, size control, cell proliferation and organ integrity. Here we report that Lachesin (Lac), a cell surface protein, is required for the proper morphogenesis of the Drosophila tracheal system. Homozygous embryos for Lac mutations, which we find fail to complement the previous identified bulbous (bulb) mutation, display convoluted tracheal tubes and tube breaks. At the cellular level, we can detect enlarged cells, suggesting that Lac regulates organ size by influencing cell length rather than cell number, and cell detachments,indicating a role for Lac in cell adhesion. Results from an in vitro assay further support that Lac behaves as a homophilic cell adhesion molecule. Lac co-localizes with Septate Junction (SJ) proteins, and ultrastructural analysis confirms that it accumulates specifically at this type of cellular junction. In Lac mutant embryos, previously characterized components of the SJs are mislocalized, indicating that the proper organization of SJs requires Lac function. In addition, mutations in genes encoding other components of the SJs produce a similar tracheal phenotype. These results point out a new role of the SJs in morphogenesis regulating cell adhesion and cell size.
Skeletal development is regulated by fibroblast growth factor receptor 1 signalling dynamics
Authors: Hajihosseini Mohammad K. , Lalioti Maria D. , Arthaud Sandrine , Burgar Helen R. , Brown Jill M. , Twigg Stephen R. F. , Wilkie Andrew O. M. , Heath John K.
Published: December 2003

Ligand-dependent signalling pathways have been characterised as having morphogen properties where there is a quantitative relationship between receptor activation and response, or threshold characteristics in which there is a binary switch in response at a fixed level of receptor activation. Here we report the use of a bacterial artificial chromosome (BAC)-based transgenic system in which a hypermorphic mutation has been introduced into the murine Fgfr1 gene. These mice exhibit cranial suture and sternal fusions that are exacerbated when the BAC copy number is increased. Surprisingly,increasing mutant BAC copy number also leads to the de novo appearance of digit I polydactyly in the hind limb and transformations of the vertebrae. Polydactyly is accompanied by a reduction of programmed cell death in the developing hind limb. Candidate gene analysis reveals downregulation of Dkk1 in the digit I field and upregulation of Wnt5a and Hoxd13. These findings show that Fgfr1-mediated developmental pathways exhibit differing signalling dynamics, whereby development of the cranial sutures and sternum follows a morphogen mode, whereas development of the vertebral column and the hind limbs has threshold signalling properties.
A domain-specific usherin/collagen IV interaction may be required for stable integration into the basement membrane superstructure
Authors: Bhattacharya Gautam , Kalluri Raghu , Orten Dana J. , Kimberling William J. , Cosgrove Dominic
Published: December 2003

Usherin is a basement membrane protein encoded by the gene associated with Usher syndrome type IIa, the most common deaf/blind disorder. This report demonstrates a specific interaction between type IV collagen and usherin in the basement membrane, with a 1:1 stoichiometry for binding. Genetic and biochemical approaches were used to explore the role of type IV collagen binding in usherin function. We demonstrate binding occurs between the LE domain of usherin and the 7S domain of type IV collagen. A purified fusion peptide comprising the first four LE modules was shown to compete with full-length recombinant usherin for type IV collagen binding. However, synonymous fusion peptides with single amino acid substitutions resulting from missense mutations that were known to cause Usher syndrome type IIa in humans, failed to compete. Only mutations in loop b of the LE domain abolished binding activity. Co-immunoprecipitation and western blot analysis of testicular basement membranes from the Alport mouse model show a 70% reduction in type IV collagen is associated with a similar reduction in usherin, suggesting the usherin/collagen (IV) interaction stabilizes usherin in the basement membrane. Thus, the domain-specific interaction between usherin and type IV collagen appears essential to usherin stability in vivo, and loss of this interaction may result in Usher pathology in humans.
Localisation of histone macroH2A1.2 to the XY-body is not a response to the presence of asynapsed chromosome axes
Authors: Hoyer-Fender Sigrid , Czirr Eva , Radde Rebecca , Turner James M. A. , Mahadevaiah Shantha K. , Pehrson John R. , Burgoyne Paul S.
Published: December 2003

Histone macroH2A1.2 and the murine heterochromatin protein 1, HP1β, have both been implicated in meiotic sex chromosome inactivation (MSCI) and the formation of the XY-body in male meiosis. In order to get a closer insight into the function of histone macroH2A1.2 we have investigated the localisation of macroH2A1.2 in surface spread spermatocytes from normal male mice and in oocytes of XX and XYTdym1 mice. Oocytes of XYTdym1 mice have no XY-body or MSCI despite having an XY chromosome constitution, so the presence or absence of `XY-body' proteins in association with the X and/or Y chromosome of these oocytes enables some discrimination between potential functions of XY-body located proteins. We demonstrate here that macroH2A1.2 localises to the X and Y chromatin of spermatocytes as they condense to form the XY-body but is not associated with the X and Y chromatin of XYTdym1 early pachytene oocytes. MacroH2A1.2 and HP1β co-localise to autosomal pericentromeric heterochromatin in spermatocytes. However, the two proteins show temporally and spatially distinct patterns of association to X and Y chromatin.
GTPases and reactive oxygen species: switches for killing and signaling
Authors: Werner Erica
Published: December 2003

In neutrophils and other phagocytic cells, the small GTPase Rac is an essential regulator of a multi-component NADPH oxidase that produces high levels of superoxide, which kills invading pathogens. In many other cell types, Rac and newly discovered relatives of the neutrophil burst oxidase and its subunits have been found associated with production of reactive oxygen species, implicating superoxide production in a wide range of cellular processes not related to host defense. Although the precise role played by Rac in the regulation of these novel oxidases is not known, Rac does control the cellular redox state. Through these pro-oxidant mechanisms, Rac and the novel oxidases modify gene expression, cell proliferation, adhesion and many cell-specific functions.
A multicriteria model for cutting fluid evaluation
Authors: Axinte D , Axinte M , Tannock J D T
Published: December 2003

This paper describes the results of a comprehensive evaluation programme for cutting fluid efficiency, when machining the aerospace ‘superalloy’, Inconel 718. The machining methods used were milling, drilling, tapping and VIPER grinding. Results from three cutting fluids were evaluated: a water-based semi-synthetic, a water-based synthetic and a high-oil emulsion fluid. Cutting forces, torque and spindle power were acquired during machining, while geometrical accuracy, surface texture and surface integrity of the workpiece were analysed afterwards. The experimental results demonstrate the difficulty of identifying the ‘best’ cutting fluid, especially when several different machining methods are to be employed on the same machine tool. It is unlikely that a single fluid will show the best performance on all machining trials and output measures. Therefore, prioritization of the output measures and specification of the relative importance of each machining operation becomes essential, in order to evaluate and rank the cutting fluid efficiencies. A flexible multicriteria model for the evaluation of cutting fluid efficiency, relative to the performance of a benchmark fluid, is proposed and described. The advantage of the model consists in its flexibility and capability to compare the efficiency of cutting fluids across different machining methods and output criteria. An application of the evaluation model is provided, using results from the tested cutting fluids.
A study on the numerical analysis of magnetic flux density by a solenoid for magnetically impelled arc butt welding
Authors: Kim J-W , Choi D-H
Published: December 2003

The magnetically impelled arc butt (MIAB) welding process uses a rotating arc as its heat source and is known as an efficient method for pipe butt welding. The arc in the gap of the pipe butt joints is rotated along the circumferential weld line by the electromagnetic force resulting from the interaction of the arc current and the magnetic field in the gap. The electromagnetic force is determined by the magnetic flux density in the gap, the arc current and the arc length (i.e. gap size). In particular, the radial magnetic flux density is an important factor in arc rotation and weld quality.

This paper proposes a two-dimensional finite element model for the analysis of magnetic flux density distributions in the MIAB welding process. The magnetic flux density is mainly dependent on the gap size between two pipes, the position of the exciting coil that generates the magnetic field, the exciting current in the coil, and the relative permeability of the pipes. Thus, the relations between the magnetic flux density and the above main factors were investigated through experiments and analyses. Experiments were performed on the steel pipes (outer diameter 48.1mm and thickness 2.0mm). From the analyses and experiments, it was revealed that the magnetic flux density in the gap between the pipes increases when there is an increasing exciting current and relative permeability, and a decreasing distance from the gap centre to the coil and gap size. It is considered that the numerical analysis model proposed in this study can be used as a useful means when designing an electromagnetic system for the MIAB welding machine.
A simple technique to characterize the role of work hardness in hard part machining
Authors: Koshy P , Dumitrescu P
Published: December 2003

An experimental technique that employs a Jominy end quench test specimen for rapid characterization of the machining response of a steel with reference to its bulk hardness is presented. Employed widely by metallurgists to appraise the hardenability of a steel, the Jominy test entails the quenching of a standard cylindrical specimen from one end, on having heated it to the austenitizing temperature. The cooling rate at any transverse section of the specimen is therefore dependent on the distance of the section from the quenched end, which brings about a continuous variation of material hardness along its length. The use of such a specimen as the workpiece to investigate the machining response of the steel with respect to its hardness significantly reduces the time, effort and cost involved in reliably optimizing a hard part machining application. Cutting force and surface finish data are presented to demonstrate this simple, innovative concept.
Establishing valid AIDS monitoring and research in countries with generalized epidemics
Authors: Brody Stuart , Potterat John J
Published: December 2003

The authors present guidelines for valid HIV/AIDS surveillance and epidemiologic research, and for clarification of uncertainties in transmission dynamics, particularly in countries with generalized epidemics. The consensus assumption that most HIV/AIDS cases in many developing regions, particularly sub-Saharan Africa, are explained by 'heterosexual' transmission (interpreted, by default, to mean penile-vaginal intercourse) has been challenged by recent reviews demonstrating an important contribution from unsafe health care practices. Resolution of existing uncertainties about the proportions of HIV transmission accounted for by specific parenteral exposures and sexual practices (e.g., vaginal and anal intercourse, considered separately) is crucial for the design and implementation of efficacious prevention strategies. Accurate risk-factor information is the best foundation upon which people living in countries with generalized epidemics can learn to protect themselves and their families. Multimethod approaches for developing sound HIV/AIDS research are presented.
The global burden of disease attributable to contaminated injections given in health care settings
Authors: Hauri Anja M , Armstrong Gregory L , Hutin Yvan J F
Published: December 2003

As part of the 2000 Global Burden of Disease study, we quantified the death and disability from injection-associated infections with hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV). We modelled the fraction of incident infections attributable to health care injections in the year 2000 on the basis of the annual number of injections, the proportion of injections administered with reused equipment, the probability of transmission following percutaneous exposure, the prevalence of active infection, the prevalence of immunity and the total incidence. Infections in 2000 were converted into disability-adjusted life years (DALYs) in 2000–2030 using natural history parameters, background mortality, duration of disease, disability weights, age weights and a 3% discount rate. Four Global Burden of Disease regions where reuse of injection equipment in the absence of sterilization was negligible were excluded from the analysis. In the remaining 10 regions, in 2000, persons received an average of 3.4 injections per year, 39.3% of which were given with reused equipment. In 2000, contaminated injections caused an estimated 21 million HBV infections, two million HCV infections and 260,000 HIV infections, accounting for 32%, 40% and 5%, respectively, of new infections for a burden of 9,177,679 DALYs between 2000 and 2030. Injection overuse and unsafe practices account for a substantial burden of death and disability worldwide. There is a need for policies and plans for the safe and appropriate use of injections in countries where practices are poor.
5% Imiquimod cream for external anogenital warts in HIV-infected patients under HAART therapy
Authors: Cusini M , Salmaso F , Zerboni R , Carminati G , Vernaci C , Franchi C , Locatelli A , Alessi E
Published: December 2003

The efficacy of imiquimod in the treatment of external genital warts in HIV positive subjects was compared to a group of patients with normal immune function. Imiquimod 5% cream was applied by patients three times a week until resolution for a maximum of 16 weeks. Assessment for response and the occurrence of side effects was performed every four weeks.

Thirty-one per cent of 75 HIV positive patients achieved a complete clearance, a partial response was obtained in 24% of subjects while in 45% we observed no clinical response. In the control group a total clearance was obtained in 62% of subjects, a partial response in 24% and no response in 14%. Recurrences occurred in 4/23 HIV patients and 2/31 immunocompetent patients within three months of follow-up. Side effects were minor to moderate.

We conclude that imiquimod 5% cream has an acceptable efficacy and safety on HIV patients.
Mycoplasma genitalium in chronic non-gonococcal urethritis
Authors: Taylor-Robinson D , Gilroy C B , Thomas B J , Hay P E
Published: December 2003

Seventy-eight men with a history of chronic urethritis were referred for investigation. Of 52 men diagnosed as having persistent or recurrent non-gonococcal urethritis (NGU) at the time of referral, 11 (21%) were infected with Mycoplasma genitalium and three with Chlamydia trachomatis. Men who were M. genitalium-positive had not previously received less antibiotic, in terms of treatment duration, than those who were M. genitalium-negative, suggesting a possible resistance to the antibiotics given.

In the current investigation, of 11 M. genitalium-positive men with persistent or recurrent NGU who were treated for four to six weeks with erythromycin, 500mg four times daily, nine (82%) responded clinically and microbiologically, but later six relapsed without M. genitalium being detected. The results of observing and investigating a patient for about one year, the only one to have concurrent chlamydial and mycoplasmal infections, is presented, a feature being the intermittent persistence of the mycoplasma.
A survey of study leave entitlement in 2002 amongst non-consultant career grade doctors in genitourinary medicine
Authors: Chandramani Shamala , Challenor Rachel , Mehta Som
Published: December 2003

Non-consultant career grade (NCCG) doctors perform a significant proportion of the clinical work in genitourinary medicine (GUM) and it is essential that their training and educational needs are met. Seven hundred questionnaires were posted to NCCGs in the UK to investigate whether employing trusts supported the educational needs of NCCG doctors by granting/funding study leave. A summary of the 220 replies (31% response) is presented. One hundred and twenty (55%) were not granted study leave to attend the 2002 national GUM NCCG conference. Study leave was less likely to be granted to those who held posts as clinical assistant or hospital practitioner and to those doctors who were working three or fewer sessions per week in GUM. It appears from our survey that many NCCG doctors who are seeing a significant proportion of the clinical workload in GUM are not supported by their employing trusts to keep up to date.
Following-up for HIV test results: what limits return in an STD clinic population?
Authors: Erbelding E J , Chung S , Zenilman J M
Published: December 2003

HIV testing is routinely performed in sexually transmitted disease (STD) clinics, but many tested do not follow up for results. We analysed data on STD clinic patients undergoing HIV testing between 1994-1998 who tested HIV-negative to describe characteristics associated with 'non-return' for results. Among 31,777 patients testing HIV-negative, male gender (odds ratio [OR] 1.25, 95% confidence interval [CI] 1.19, 1.33), age <30 years (OR 1.72, 95% CI 1.43, 1.82), and a diagnosis of gonorrhoea at the testing visit (OR 1.72, 95% CI 1.43, 1.82) were all independently associated with 'non-return.' Presentation to clinic specifically for HIV testing (OR 0.70, 95% CI 0.63, 0.77) or reporting a partner with HIV (OR 0.63, 95% CI 0.53, 0.74) were factors independently protective against 'non-return.' Operational changes to improve test results notification, or enhanced counselling at the initial test visit, particularly focusing on young men with gonorrhoea, may optimize prevention outcomes in this high risk population.