bluuebunny/crossref_metadata_2025 huggingface dataset:
Important but Neglected Ethical and Cultural Considerations in the Fight Against HIV/AIDS in Malawi
Authors: Muula Adamson S , Mfutso-Bengo Joseph M
Published: July 2004

Southern African countries have the highest HIV infection rates in the world. In most of the countries in the region, the rate among adults is at least 10%. The fight against HIV/AIDS has mostly been inadequate owing to the lack of proper consideration of ethical and cultural issues. In this article, the authors discuss the ethical and cultural dilemmas concerning HIV/AIDS, with Malawi as a case in point. It is argued that increasing financial resources alone, as exemplified by the Global Fund to Fight AIDS, Tuberculosis and Malaria initiative, without proper attention to ethical issues, morals and appropriate legal obligations, are unlikely to reduce the spread of HIV in southern Africa.
Truth-Telling in Clinical Practice and the Arguments for and Against: a review of the literature
Authors: Tuckett Anthony G
Published: July 2004

In general, most, but not necessarily all, patients want truthfulness about their health. Available evidence indicates that truth-telling practices and preferences are, to an extent, a cultural artefact. It is the case that practices among nurses and doctors have moved towards more honest and truthful disclosure to their patients. It is interesting that arguments both for and against truth-telling are established in terms of autonomy and physical and psychological harm. In the literature reviewed here, there is also the view that truth-telling is essential because it is an intrinsic good, while it is argued against on the grounds of the uncertainty principle. Based on this review, it is recommended that practitioners ought to ask patients and patients’ families what informational requirements are preferred, and research should continue into truth-telling in clinical practice, particularly to discover its very nature as a cultural artefact, and the other conditions and contexts in which truth-telling may not be preferred.
Patient Rights and Law: tobacco smoking in psychiatric wards and the Israeli Prevention of Smoking Act
Authors: Kagan Ilya , Kigli-Shemesh Ronit , Tabak Nili , Abramowitz Moshe Z , Margolin Jacob
Published: July 2004

In August 2001, the Israeli Ministry of Health issued its Limitation of Smoking in Public Places Order, categorically forbidding smoking in hospitals. This forced the mental health system to cope with the issue of smoking inside psychiatric hospitals. The main problem was smoking by compulsorily hospitalized psychiatric patients in closed wards. An attempt by a psychiatric hospital to implement the tobacco smoking restraint instruction by banning the sale of cigarettes inside the hospital led to the development of a black market and cases of patient exploitation in return for cigarettes. This article surveys the literature dealing with smoking among psychiatric patients, the role of smoking in patients and the moral dilemmas of taking steps to prevent smoking in psychiatric hospitals. It addresses the need for public discussion on professional caregivers’ dilemmas between their commitment to uphold the law and their duty to act as advocates for their patients’ rights and welfare.
Nursing and Midwifery Malpractice in Turkey Based on the Higher Health Council Records
Authors: Gündoğmuş Ümit N , Özkara Erdem , Mete Samiye
Published: July 2004

Medical malpractice has attracted the attention of people and the media all over the world. In Turkey, malpractice cases are tried according to both criminal and civil law. Nurses and midwives in Turkey fulfill important duties in the distribution of health services. The aim of this study was to reveal the legal procedures followed in malpractice allegations and malpractice lawsuits in which nurses and midwives were named as defendants. We reviewed 59 nursing and midwifery lawsuits reported to the Higher Health Council between 1993 and 1998. Health professionals were held liable in 59% of the lawsuits. Midwives had the highest percentage of malpractice liability (52%), followed by physicians (29%) and nurses (19%). To reduce potential liability, nurse education should be improved, a nursing malpractice law should be enacted, and instructions for nursing procedures should be formulated.
Evidence that Cocaine- and Amphetamine-Regulated Transcript Is a Novel Intraovarian Regulator of Follicular Atresia
Authors: Kobayashi Yasuhiro , Jimenez-Krassel Fermin , Li Qinglei , Yao Jianbo , Huang Ruiping , Ireland James J. , Coussens Paul M. , Smith George W.
Published: July 2004

We recently obtained evidence that cocaine- and amphetamine-regulated transcript (CART), a potent anorectic neuropeptide, is expressed in the bovine ovary. The objectives of this study were to characterize bovine ovarian CART and determine its localization, regulation, and regulatory role during follicular development. CART mRNA was detected in stroma of adult ovaries and in large follicles, but was undetectable in several peripheral tissues, fetal ovaries, and corpora lutea. Within the ovary, CART mRNA and peptide were localized to the granulosal layer of some, but not all, antral follicles, with low, but detectable, expression in oocytes and cumulus cells. CART mRNA was undetectable in granulosal cells of dominant ovulatory follicles collected before and after the preovulatory gonadotropin surge, but was detected in the granulosal layer of adjacent subordinate follicles. In addition, amounts of CART mRNA and follicular fluid concentrations of CART peptide were greater in subordinate follicles vs. dominant follicles of the first follicular wave. Furthermore, CART treatment inhibited basal estradiol production, but not progesterone production, by granulosal cells in a dose-dependent fashion, and the effect was dependent on stage of cell differentiation. We conclude that granulosal cell CART expression is temporally regulated and potentially associated with follicle health status, and CART can inhibit granulosal cell estradiol production. Thus, CART may be a novel local regulator of follicular atresia in the bovine ovary.
Cocaine- and Amphetamine-Regulated Transcript Activates the Hypothalamic-Pituitary-Adrenal Axis through a Corticotropin-Releasing Factor Receptor-Dependent Mechanism
Authors: Smith Sean M. , Vaughan Joan M. , Donaldson Cynthia J. , Rivier Jean , Li Chien , Chen Alon , Vale Wylie W.
Published: July 2004

Cocaine- and amphetamine-regulated transcript (CART) is a highly expressed hypothalamic transcript that is concentrated in areas associated with the stress response. There is evidence for a role of CART in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. However, it is not clear whether CART regulates activity of the HPA axis by directly stimulating ACTH release from pituitary corticotropes or through interaction with hypothalamic factors. To address this issue, the effects of central and peripheral administration of CART on the HPA axis were compared. Central administration of CART(55–102) (1 μg) significantly increased circulating levels of ACTH (481 ± 122 vs. 93 ± 14 pg/ml; CART vs. vehicle) and corticosterone (460 ± 29 vs. 179 ± 62 ng/ml; CART vs. vehicle). In contrast, iv injection of CART(55–102) (0.09-9.0 nmol/kg) did not significantly affect circulating levels of ACTH or corticosterone. The corticotropin-releasing factor (CRF) receptor antagonist Astressin B was used to determine whether CART(55–102) elicits ACTH secretion via a CRF receptor-dependent mechanism. Injection of Astressin B (50 μg/kg, iv) inhibited CART(55–102)-induced ACTH and corticosterone responses. The effects of CART(55–102) on CRF and arginine vasopressin (AVP) expression were also examined in static hypothalamic explants. RT-PCR analysis revealed a significant up-regulation of CRF and AVP mRNA levels after CART(55–102) (10 nm and 1 μm) treatment. Last, the effects of CART(55–102) on CRF- and AVP-mediated ACTH release was investigated in dispersed rat anterior pituitary cells. Incubation of CART(55–102) (10–100 nm) did not significantly affect ACTH release from anterior pituitary cells. Findings from the present study suggest that CART regulates activity of the HPA axis through a CRF-dependent central mechanism and not by means of direct interaction with pituitary corticotropes.
Region-Specific Leptin Resistance within the Hypothalamus of Diet-Induced Obese Mice
Authors: Münzberg Heike , Flier Jeffrey S. , Bjørbæk Christian
Published: July 2004

Leptin resistance in diet-induced obese (DIO) mice is characterized by elevated serum leptin and a decreased response to exogenous leptin and is caused by unknown defects in the central nervous system. Leptin normally acts on several brain nuclei, but a detailed description of leptin resistance within individual brain regions has not been reported. We first mapped leptin-responsive cells in brains from DIO mice using phospho-signal transducer and activator of transcription (P-STAT3) immunohistochemistry. After 16 wk of high-fat-diet feeding, leptin-activated P-STAT3 staining within the arcuate nucleus (ARC) was dramatically decreased. In contrast, other hypothalamic and extrahypothalamic nuclei remained leptin sensitive. Reduced leptin-induced P-STAT3 in the ARC could also be detected after 4 wk and as early as 6 d of a high-fat diet. To examine potential mechanisms for leptin-resistant STAT3 activation in the ARC of DIO mice, we measured mRNA levels of candidate signaling molecules in the leptin receptor-STAT3 pathway. We found that the level of suppressor of cytokine signaling 3 (SOCS-3), an inhibitor of leptin signaling, is specifically increased in the ARC of DIO mice. The study suggests that the ARC is selectively leptin resistant in DIO mice and that this may be caused by elevated suppressor of cytokine signaling 3 in this hypothalamic nucleus. Defects in leptin action in the ARC may play a role in the pathogenesis of leptin-resistant obesity.
A Possible Mechanism for the Action of Adrenomedullin in Brain to Stimulate Stress Hormone Secretion
Authors: Taylor Meghan M. , Samson Willis K.
Published: July 2004

Adrenomedullin (AM) has been reported to have actions at each level of the hypothalamo-pituitary-adrenal (HPA) axis, suggesting that the peptide plays a role in the organization of the neuroendocrine responses to stress. We examined the mechanism by which AM regulates the central nervous system branch of the HPA axis as well as the possible role of AM in the modulation of the releases of two other hormones, prolactin and GH, whose secretions also are altered by stress. Intracerebroventricular administration of AM led to elevated plasma corticosterone levels in unrestrained, conscious male rats. This effect was abrogated by pretreatment with a CRH antagonist, suggesting that AM activates the HPA axis by causing the release of CRH into hypophyseal portal vessels. In addition, AM given intracerebroventricularly stimulated the release of prolactin but did not alter the secretion of GH. We propose that AM produced in the brain may be an important neuromodulator of the hormonal stress response.
Chick Dach1 interacts with the Smad complex and Sin3a to control AER formation and limb development along the proximodistal axis
Authors: Kida Yasuyuki , Maeda Yukiko , Shiraishi Tomoki , Suzuki Takayuki , Ogura Toshihiko
Published: July 2004

Based on recent data, a new view is emerging that vertebrate Dachshund(Dach) proteins are components of Six1/6 transcription factor-dependent signaling cascades. Although Drosophila data strongly suggest a tight link between Dpp signaling and the Dachshund gene, a functional relationship between vertebrate Dach and BMP signaling remains undemonstrated. We report that chick Dach1 interacts with the Smad complex and the corepressor mouse Sin3a, thereby acting as a repressor of BMP-mediated transcriptional control. In the limb, this antagonistic action regulates the formation of the apical ectodermal ridge (AER) in both the mesenchyme and the AER itself, and also controls pattern formation along the proximodistal axis of the limb. Our data introduce a new paradigm of BMP antagonism during limb development mediated by Dach1, which is now proven to function in different signaling cascades with distinct interacting partners.
Notch inhibits Ptf1 function and acinar cell differentiation in developing mouse and zebrafish pancreas
Authors: Esni Farzad , Ghosh Bidyut , Biankin Andrew V. , Lin John W. , Albert Megan A. , Yu Xiaobing , MacDonald Raymond J. , Civin Curt I. , Real Francisco X. , Pack Michael A. , Ball Douglas W. , Leach Steven D.
Published: July 2004

Notch signaling regulates cell fate decisions in a variety of adult and embryonic tissues, and represents a characteristic feature of exocrine pancreatic cancer. In developing mouse pancreas, targeted inactivation of Notch pathway components has defined a role for Notch in regulating early endocrine differentiation, but has been less informative with respect to a possible role for Notch in regulating subsequent exocrine differentiation events. Here, we show that activated Notch and Notch target genes actively repress completion of an acinar cell differentiation program in developing mouse and zebrafish pancreas. In developing mouse pancreas, the Notch target gene Hes1 is co-expressed with Ptf1-P48 in exocrine precursor cells, but not in differentiated amylase-positive acinar cells. Using lentiviral delivery systems to induce ectopic Notch pathway activation in explant cultures of E10.5 mouse dorsal pancreatic buds, we found that both Hes1 and Notch1-IC repress acinar cell differentiation, but not Ptf1-P48 expression, in a cell-autonomous manner. Ectopic Notch activation also delays acinar cell differentiation in developing zebrafish pancreas. Further evidence of a role for endogenous Notch in regulating exocrine pancreatic differentiation was provided by examination of zebrafish embryos with homozygous mindbomb mutations, in which Notch signaling is disrupted. mindbomb-deficient embryos display accelerated differentiation of exocrine pancreas relative to wild-type clutchmate controls. A similar phenotype was induced by expression of a dominant-negative Suppressor of Hairless [Su(H)] construct, confirming that Notch actively represses acinar cell differentiation during zebrafish pancreatic development. Using transient transfection assays involving a Ptf1-responsive reporter gene, we further demonstrate that Notch and Notch/Su(H) target genes directly inhibit Ptf1 activity, independent of changes in expression of Ptf1 component proteins. These results define a normal inhibitory role for Notch in the regulation of exocrine pancreatic differentiation.
Bmp7 regulates branching morphogenesis of the lacrimal gland by promoting mesenchymal proliferation and condensation
Authors: Dean Charlotte , Ito Masataka , Makarenkova Helen P. , Faber Sonya C. , Lang Richard A.
Published: July 2004

The lacrimal gland provides an excellent model with which to study the epithelial-mesenchymal interactions that are crucial to the process of branching morphogenesis. In the current study, we show that bone morphogenetic protein 7 (Bmp7) is expressed with a complex pattern in the developing gland and has an important role in regulating branching. In loss-of-function analyses, we find that Bmp7-null mice have distinctive reductions in lacrimal gland branch number, and that inhibition of Bmp activity in gland explant cultures has a very similar consequence. Consistent with this,exposure of whole-gland explants to recombinant Bmp7 results in increased branch number. In determining which cells of the gland respond directly to Bmp7, we have tested isolated mesenchyme and epithelium. We find that, as expected, Bmp4 can suppress bud extension in isolated epithelium stimulated by Fgf10, but interestingly, Bmp7 has no discernible effect. Bmp7 does, however,stimulate a distinct response in mesenchymal cells. This manifests as a promotion of cell division and formation of aggregates, and upregulation of cadherin adhesion molecules, the junctional protein connexin 43 and ofα-smooth muscle actin. These data suggest that in this branching system,mesenchyme is the primary target of Bmp7 and that formation of mesenchymal condensations characteristic of signaling centers may be enhanced by Bmp7. Based on the activity of Bmp7 in promoting branching, we also propose a model suggesting that a discrete region of Bmp7-expressing head mesenchyme may be crucial in determining the location of the exorbital lobe of the gland.
Differential cytoplasmic mRNA localisation adjusts pair-rule transcription factor activity to cytoarchitecture in dipteran evolution
Authors: Bullock Simon L. , Stauber Michael , Prell Alexander , Hughes Julian R. , Ish-Horowicz David , Schmidt-Ott Urs
Published: July 2004

Establishment of segmental pattern in the Drosophila syncytial blastoderm embryo depends on pair-rule transcriptional regulators. mRNA transcripts of pair-rule genes localise to the apical cytoplasm of the blastoderm via a selective dynein-based transport system and signals within their 3′-untranslated regions. However, the functional and evolutionary significance of this process remains unknown. We have analysed subcellular localisation of mRNAs from multiple dipteran species both in situ and by injection into Drosophila embryos. We find that although localisation of wingless transcripts is conserved in Diptera, localisation of even-skipped and hairy pair-rule transcripts is evolutionarily labile and correlates with taxon-specific changes in positioning of nuclei. We show in Drosophila that localised pair-rule transcripts target their proteins in close proximity to the nuclei and increase the reliability of the segmentation process by augmenting gene activity. Our data suggest that mRNA localisation signals in pair-rule transcripts affect nuclear protein uptake and thereby adjust gene activity to a variety of dipteran blastoderm cytoarchitectures.
The development of semicircular canals in the inner ear: role of FGFs in sensory cristae
Authors: Chang Weise , Brigande John V. , Fekete Donna M. , Wu Doris K.
Published: July 2004

In the vertebrate inner ear, the ability to detect angular head movements lies in the three semicircular canals and their sensory tissues, the cristae. The molecular mechanisms underlying the formation of the three canals are largely unknown. Malformations of this vestibular apparatus found in zebrafish and mice usually involve both canals and cristae. Although there are examples of mutants with only defective canals, few mutants have normal canals without some prior sensory tissue specification, suggesting that the sensory tissues,cristae, might induce the formation of their non-sensory components, the semicircular canals. We fate-mapped the vertical canal pouch in chicken that gives rise to the anterior and posterior canals, using a fluorescent,lipophilic dye (DiI), and identified a canal genesis zone adjacent to each prospective crista that corresponds to the Bone morphogenetic protein 2 (Bmp2)-positive domain in the canal pouch. Using retroviruses or beads to increase Fibroblast Growth Factors (FGFs) for gain-of-function and beads soaked with the FGF inhibitor SU5402 for loss-of-function experiments,we show that FGFs in the crista promote canal development by upregulating Bmp2. We postulate that FGFs in the cristae induce a canal genesis zone by inducing/upregulating Bmp2 expression. Ectopic FGF treatments convert some of the cells in the canal pouch from the prospective common crus to a canal-like fate. Thus, we provide the first molecular evidence whereby sensory organs direct the development of the associated non-sensory components, the semicircular canals, in vertebrate inner ears.
Compromised generation of GABAergic interneurons in the brains ofVax1-/- mice
Authors: Taglialatela Paola , Soria José Miguel , Caironi Veronica , Moiana Alessia , Bertuzzi Stefano
Published: July 2004

The subcortical telencephalon is the major source of GABAergic interneurons that, during development, tangentially migrate to the cerebral cortex, where they modulate the glutamatergic excitatory action of pyramidal cells. The transcription factor Vax1, an intracellular mediator of both Shh and Fgf signaling, is expressed at high levels in the medial and lateral ganglionic eminences (MGE and LGE, respectively), in the septal area (SA), in the anterior entopeduncular area (AEP) and in the preoptic area (POA). We show that Vax1 expression in the neuroepithelium is graded: low in the ventricular zone (VZ) and high in the subventricular zone (SVZ), in a pattern that closely reproduces that of several members of the Dlx and Gsh family of homeobox transcription factors. We provide evidence that Vax1 plays an important role in proliferation and differentiation of MGE, POA/AEP and septum, and that the last structure is completely absent in Vax1-/- mice. We show that the absence of Vax1 causes a severe depletion of GABAergic neurons in the neocortex, ranging from 30% to 44%, depending on the cortical areas considered. Taken together, our data indicate that a loss of function mutation in the Vax1 gene generates abnormalities in basal ganglia subventricular zone development and that it prevents the formation of the septum, impairing GABAergic interneuron generation.
The co-repressor hairless has a role in epithelial cell differentiation in the skin
Authors: Zarach Joanna M. , Beaudoin Gerard M. J. , Coulombe Pierre A. , Thompson Catherine C.
Published: July 2004

Although mutations in the mammalian hairless (Hr) gene result in congenital hair loss disorders in both mice and humans, the precise role of Hr in skin biology remains unknown. We have shown that the protein encoded by Hr (HR) functions as a nuclear receptor co-repressor. To address the role of HR in vivo, we generated a loss-of-function (Hr-/-) mouse model. The Hr-/- phenotype includes both hair loss and severe wrinkling of the skin. Wrinkling is correlated with increased cell proliferation in the epidermis and the presence of dermal cysts. In addition,a normally undifferentiated region, the infundibulum, is transformed into a morphologically distinct structure (utricle) that maintains epidermal function. Analysis of gene expression revealed upregulation of keratinocyte terminal differentiation markers and a novel caspase in Hr-/- skin, substantiating HR action as a co-repressor in vivo. Differences in gene expression occur prior to morphological changes in vivo, as well as in cultured keratinocytes, indicating that aberrant transcriptional regulation contributes to the Hr-/-phenotype. The properties of the cell types present in Hr-/- skin suggest that the normal balance of cell proliferation and differentiation is disrupted, supporting a model in which HR regulates the timing of epithelial cell differentiation in both the epidermis and hair follicle.
Survivin dynamics increases at centromeres during G2/M phase transition and is regulated by microtubule-attachment and Aurora B kinase activity
Authors: Beardmore Victoria A. , Ahonen Leena J. , Gorbsky Gary J. , Kallio Marko J.
Published: July 2004

The inhibitor of apoptosis protein survivin is implicated in two key biological events: in the control of cell proliferation and in the regulation of cell lifespan. Although the details of mitotic roles of survivin are unclear, the protein appears to modulate microtubule function and might participate in regulating the spindle checkpoint. Survivin physically associates with Aurora B, a serine-threonine kinase involved in microtubule attachment to centromeres and regulation of chromosome segregation. Here we have examined the dynamics and localization of a survivin-GFP chimera using high-resolution fluorescence microscopy and photobleaching. Survivin forms a bi-partite structure at the inner centromere that undergoes significant stretching during mitosis. Photobleaching experiments revealed marked changes in rates of survivin turnover at centromeres. These were regulated by stage of the cell cycle, microtubule attachment, and Aurora B kinase activity. We hypothesize that changes in the turnover of survivin at centromeres influence the stability of kinetochore-microtubule attachment and signaling of the spindle checkpoint.
Compartment-specific perturbation of protein handling activates genes encoding mitochondrial chaperones
Authors: Yoneda Takunari , Benedetti Cristina , Urano Fumihiko , Clark Scott G. , Harding Heather P. , Ron David
Published: July 2004

Protein folding in the mitochondria is assisted by nuclear-encoded compartment-specific chaperones but regulation of the expression of their encoding genes is poorly understood. We found that the mitochondrial matrix HSP70 and HSP60 chaperones, encoded by the Caenorhabditis elegans hsp-6 and hsp-60 genes, were selectively activated by perturbations that impair assembly of multi-subunit mitochondrial complexes or by RNAi of genes encoding mitochondrial chaperones or proteases, which lead to defective protein folding and processing in the organelle. hsp-6 and hsp-60 induction was specific to perturbed mitochondrial protein handling, as neither heat-shock nor endoplasmic reticulum stress nor manipulations that impair mitochondrial steps in intermediary metabolism or ATP synthesis activated the mitochondrial chaperone genes. These observations support the existence of a mitochondrial unfolded protein response that couples mitochondrial chaperone gene expression to changes in the protein handling environment in the organelle.
α3β1 integrin promotes keratinocyte cell survival through activation of a MEK/ERK signaling pathway
Authors: Manohar Asha , Shome Swati Ghosh , Lamar John , Stirling Lee , Iyer Vandana , Pumiglia Kevin , DiPersio C. Michael
Published: July 2004

Inadequate or inappropriate adhesion of epithelial cells to extracellular matrix leads to a form of apoptosis known as anoikis. During various tissue remodelling events, such as wound healing or carcinoma invasion, changes in the physical properties, and/or composition of the extracellular matrix, can lead to anoikis of epithelial cells that lack appropriate receptor-matrix interactions. Laminin-5 is the major ligand for keratinocyte adhesion in the epidermis, and it also promotes keratinocyte survival in vivo and in vitro. Integrins α3β1 and α6β4 are the major receptors for laminin-5; however, specific roles for these integrins in keratinocyte survival have not been determined. In the current study, we exploited keratinocyte cell lines derived from wild-type or α3 integrin knockout mice to reveal a critical role for α3β1 in protecting keratinocytes from apoptosis upon serum withdrawal. We show that α3β1-mediated adhesion to laminin-5 extracellular matrix inhibits proteolytic activation of caspase-3 and TUNEL-staining, both hallmarks of apoptosis. We also show that α3β1-mediated adhesion activates focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK), and that inhibition of either FAK or ERK signaling leads to apoptosis of keratinocytes attached to laminin-5. α6β4-mediated adhesion to laminin-5 only partially protects cells from apoptosis in the absence of α3β1, and α6β4 is not necessary for cell survival in the presence of α3β1. These results suggest that α3β1 is necessary and sufficient for maximal keratinocyte survival on laminin-5. We propose a model to address the potential importance of α3β1-mediated survival for migrating keratinocytes at the leading edge of a cutaneous wound.
Coordination of cell growth and cell division: a mathematical modeling study
Authors: Qu Zhilin , Weiss James N. , MacLellan W. Robb
Published: July 2004

Although there is general agreement that cell growth and division are functionally coordinated, the mechanisms that link the two processes are poorly understood. In this study, we have developed a mathematical model based on current biological concepts of the signaling transduction pathways involved in cell growth, which predicts that cell growth rate is proportional to cell surface area at birth. To investigate the relationship between growth control and cell division, we then applied our mathematical model to three classic experiments measuring cycle time versus cell birth size in fission yeast and Xenopus laevis, and the cell cycle delay in mammalian cells after serum withdrawal. When coupled to a cell cycle exhibiting `sizer' and `timer' phases, we show that a simple model in which growth rate is proportional to the cell surface area immediately after division reproduces the experimental observations including the relationship between cycle time and birth size in fission yeast and Xenopus laevis. The model also accounts for the cell cycle delay seen in restriction point experiments performed in HeLa cells.
The performance envelope of forming shoulders and implications for design and manufacture
Authors: McPherson C. J. , Mullineux G , Berry C , Hicks B. J. , Medland A. J.
Published: July 2004

The production of packaging machinery is a highly competitive global market driven by the ever-increasing demands of customers and legislation. The fundamental design principles of many packaging machines are the result of incremental improvements made over the last few decades. This paper looks at the underlying theory for forming shoulders and, starting with previously published results, determines the performance envelope relating to certain critical parameters. The findings are discussed in the light of their relevance for the creation of new designs.
An attribute management approach to concurrent engineering
Authors: Mileham A. R. , Morgan E. J. , Chatting I
Published: July 2004

A new approach for achieving increased concurrency in the new product development process (PDP) is discussed. It is termed an ‘attribute management’ approach and is based on the release of information to the next stage of the PDP on an attribute-by-attribute basis, with concurrency taking place within the development of the attribute rather than a part. For this process, an attribute is defined as a specified part or process feature that can be identified as an entity and used independently in the development or manufacture of the part. In order to validate this new approach, it has been tested in industry for the introduction of two major aerospace products, which form the basis of case studies for this paper. The results of this action research have then been compared with metrics considered typical for the introduction of these new products using a conventional concurrent engineering (CE) approach. The use of the attribute management approach, for the two cases presented, has been shown to provide significant improvements in development lead-time, development time input, recurring product cost and post-PDP design changes.
Remote Access Toolkit for industrial robots
Authors: Rajapakse B , Hildreth N
Published: July 2004

This paper describes the development of a toolkit for LabVIEW, allowing remote communication and programming of ABB industrial robots from a standard PC. The toolkit facilitates remote robot control over Ethernet and can be readily applied to numerous industrial applications for remote administration and control, and real-time data logging. The toolkit enables robot programs to be loaded, started and stopped from LabVIEW. Robot variables may be monitored and modified on-line, plus file transfer and logging capabilities are also available. Context help is available for the toolkit together with a detailed user reference within the LabVIEW help environment. When errors occur in the robot domain, they are interpreted and expressed in plain English. A custom, cross-platform C library underpins the toolkit and therefore makes it accessible to many applications and programming languages.
Investigation into sheet hydroforming based on hydromechanical deep drawing with uniform pressure on the blank
Authors: Lang L , Danckert J , Nielsen K. B.
Published: July 2004

Sheet hydroforming has gained increasing interest in the automotive and aerospace industries because of its many advantages such as a higher forming limitation, good quality of the formed parts, the capability of forming complicated parts, etc. Based on the proposed hydromechanical deep drawing (HDD) with uniform pressure on the blank, some characteristics of sheet hydroforming, including the drawing ratio improvement, the quality of the formed parts, the thickness distributions of the formed parts and the process window, are investigated in detail. The effect of the process parameters on the features and ways to improve the sheet formability are discussed both in experiment and simulation. With consideration of the forming limit diagram (FLD), the forming process was studied in simulation. The results from a simulation were in reasonable agreement with those from an experiment.
The Use of Activated and Non-Activated Tar Sands as Adsorbents for Copper Ion Removal
Authors: Zeatoun Lua'y , Yousef Shadi
Published: July 2004

Jordanian tar sands were used as an adsorbent for the removal of copper ions from aqueous solutions. Experimental results showed that the adsorption of Cu2+ ions onto tar sands was pH- and temperature-dependent. Copper ion uptake increased with increasing pH, temperature and initial adsorbate concentration, but decreased with adsorbent concentration. An increase of ca. 40% in the uptake was noted when the tar sands were activated physically with CO2. The presence of NaCl salt in the adsorption process influenced the uptake of Cu2+ ions by the adsorbent studied. The adsorption process was very fast with equilibrium being achieved in about 2 min. The experimental data were well represented by both the Langmuir and Freundlich isotherm models.
Adsorption of Basic Dyes onto Natural Clay
Authors: Guiza S. , Bagane M. , Al-Soudani A.H. , Amore H. Ben
Published: July 2004

The adsorption ability of natural clay towards the removal of basic dyes from aqueous textile solutions was investigated. The equilibrium isotherms were measured and analyzed using the Langmuir model and the experimental results compared with the theoretical data. The adsorbent exhibited considerable adsorption capacities of 567, 526, 427 and 300 mg/g towards Neutral Red, Methyl Violet, Methyl Green and Methylene Blue, respectively. Thus, the clay may be used as a cost-effective industrial adsorbent for the removal of basic dyes from industrial effluents.
Adsorption Capacities of Activated Carbons Derived from Rice Straw and Water Hyacinth in the Removal of Organic Pollutants from Water
Authors: Rashwan Wafaa E. , Girgis Badie S.
Published: July 2004

Two activated carbons were prepared from unconventional raw materials, i.e. rice straw (RS) and water hyacinth (WH), using the same activation scheme, i.e. impregnation with 50 vol% H3PO4 followed by pyrolysis at 500°C. The porosity characteristics of the samples were determined via nitrogen adsorption studies at −196°C from which the various parameters were evaluated. WH carbon showed a more developed porosity relative to RS, although both carbons were apparently of low quality. The capacities of both samples towards the removal from aqueous solution of five organic sorbates were tested. These were phenol (P), p-nitrophenol (PNP), p-nitroaniline (PNA), Methylene Blue (MB) and Congo Red (CR). The adsorption of the two dyes (MB and CR) was a function of the pore dimensions, whereas phenol uptake was greatly reduced because of the acidic oxygen functional groups on the carbon surface. The amount of PNP taken up corresponded exactly with the specific surface area as estimated from nitrogen isotherm measurements. The surface abundances (as μmol/m2) of PNP, P and PNA were found to be independent of the porosity characteristics of the active carbon and followed the general sequence PNP > P > PNA > MB > CR. The observed removal capacities were comparable to that of a commercial carbon produced by Prolabo whose porosity was much more developed.
Sorption Equilibrium Studies of Toxic Nitro-Substituted Phenols on Fly Ash
Authors: Singh B.K. , Nayak Preeti Sagar
Published: July 2004

The potential of fly ash, a low cost and abundantly available material with good sorption properties, for removing phenols was investigated. Nitro-substituted phenols, i.e. o-nitrophenol, m-nitrophenol and p-nitrophenol, were selected for the studies. The effect of various factors such as adsorbent particle size, pH, phenol concentration and temperature on the sorption capacity was investigated. The removal of nitro-substituted phenols increased with decreasing adsorbent particle size, pH and increasing concentration and temperature. Langmuir adsorption isotherm constants were calculated and it was shown that the adsorption data for phenols onto fly ash fitted the Langmuir model well. The adsorption of the nitrophenols studied followed first-order rate kinetics. Thermodynamic studies were also undertaken and the values of the standard free energy (ΔG0), enthalpy (ΔH0) and entropy (ΔS0) changes calculated.
Adsorption of Biologically Active Compounds from Aqueous Solutions on to Commercial Unmodified Activated Carbons. Part VI. The Mechanism of the Physical and Chemical Adsorption of Acetanilide
Authors: Terzyk Artur P.
Published: July 2004

The new correlations recently suggested between the properties of the carbon surface and the constants characterizing the process of acetanilide adsorption were extended from data that had been measured initially for six carbons. It was shown that the mechanism of acetanilide adsorption on carbons was mixed between micropore filling and adsorption on active surface sites. The latter depended strongly on the concentration of surface carboxylic, phenol and basic groups. In acidic pH, the process was irreversible due to the chemisorption of acetanilide molecules on the nucleophilic carbon sites. The rate of adsorption of acetanilide increased at acidic pH levels. Diffusion was mainly a surface process with the energy of diffusion depending on the chemical composition of the carbon surface and its polarity.
Cationized Lignocelluloses as Scavengers for Anionic Surfactants. II. Hydrophobic Interactions
Authors: Zghida Haïfa , Gauthier Robert , Helal Ahmed
Published: July 2004

As reported in Part I of this study, anionic surfactants are rapidly adsorbed and strongly retained on cationized lignocellulosic materials as a result of ionic interactions. Consequently, the initially hydrophilic surface of the sorbent is strongly modified by the adsorbed surfactant molecules. Hydrophobic interactions with this modified surface allow a second layer of surfactant molecules to be adsorbed via their alkyl chains. Many combinations are possible with different kinds of surfactants, with the highest adsorption capacity being obtained when zwitterionic surfactants are involved in the second step.
Case Study: Comparison between the Acoustic Performance of a Mixed Building Technology Building and a Conventional Building
Authors: Bragança Luís , Patrício Jorge
Published: July 2004

The objective of this work is to compare the acoustical performance of MBT (Mixed Building Technology) constructions and conventional buildings. The sound insulation performance of a MBT construction was assessed by tests done in situ. The results were compared with similar data from earlier measurements undertaken by the Building Physics Laboratory of the University of Minho in Portugal, and from simplified prediction methods.

The building where this comparison was done is a 3-storey building. The first 2 storeys were refurbished using conventional construction methods, but the 3rd storey was built using MBT methods, characterised by using lightweight materials, with high thermal insulation, and large fenestration areas. Based on the work undertaken, some conclusions and proposals for further work are presented.
Invited Review Paper: The Physics of Reverberation
Authors: Pan Jie
Published: July 2004

Reverberation time is an important measure of speech intelligibility and acoustical quality in enclosures. The pursuit of a basic understanding of how the reverberation time is related to the physical properties of the enclosure boundaries has involved many acousticians for more than a century. This paper reviews some of these understandings.
Isolation of Buildings from Ground-Borne Noise Using a Sand Stratum
Authors: Hassan O. A. B.
Published: July 2004

The effect of an elastic stratum in reducing ground-borne sound transmission in buildings to be built above railway tunnels is investigated, by considering a sand layer between the bedrock and load bearing elements of the building. It is assumed that the initial vibrational energy that propagates from the foundation is in the form of quasi-longitudinal waves. The complete model as presented by the author in a previous paper is considered. Calculated results are compared with previous results for a typical building and it is shown that a sand layer can considerably reduce upward sound transmission in the building. The results of a parametric study to investigate the influence of the type of load-bearing elements and the thickness of the layer, on transmission of structure-borne sound in the building, are presented.
On the Accuracy of Direct Noise Calculations Based on the Euler Model
Authors: Abalakin Ilya V. , Dervieux Alain , Kozubskaya Tatyana K.
Published: July 2004

The paper reviews a class of Direct Noise Calculation (DNC) models based on the compressible Euler equations and analyses their computational accuracy considering the combination of model completeness, scheme accuracy and stability to round off errors. It is shown that a form of the Nonlinear Disturbance Equations (NLDE) is sensitive to the round off errors. An NLDE formulation with Roe average matrix (NLDE/Roe) for minimizing the round off errors is proposed. (The NLDE/Roe is identical to Direct Numerical Simulation (DNS) at rather large solutions and converges to the Linearised Euler Equations (LEE) at the small solutions NLDE/Roe thus accurately treats the signals including both large and small scales of disturbances). A version of NLDE in the case of disturbance decomposition is given in the general form. While studying the DNC model efficiency, a new measure of the total model accuracy is introduced. It is proposed to test all the models and schemes available by comparing the output numerical result with the exact solution of the complete model, that is, with the Euler equations.
Simulation of Multiple Pass Perforated Tube Silencers Based on the Method of Characteristics
Authors: El-Rahman Ahmed I. Abd , Sabry Ashraf S. , Mobarak Amin M.
Published: July 2004

Based on the method of characteristics, a time domain non-linear model for unsteady compressible flow is used to simulate the flow in multi-pass perforated tube silencers. In the present work, the flow in both two and three pass anechoically terminated silencers will be simulated for low sound pressure level excitation. The temporal solution is first transferred into the frequency domain using FFT, and then processed by the two-microphone technique in order to evaluate the transmission loss. Derivation of necessary one-dimensional equations, which are used to implement the method of characteristics along with the mathematical formulation of length corrections and different boundary conditions, are presented. Resorting to the white noise excitation, a significant reduction in the computational effort is achieved compared to the step-by-step frequency excitation. The paper uses data from previously published experimental and numerical work for the sake of comparison. A good agreement is verified for the frequency range where the one-dimensional assumption is justified.
Cavity Mode Excitation by Vortex Shedding from a Cross-Beam
Authors: Winslow A. , Howe M. S.
Published: July 2004

An analysis is made of the tonal acoustic radiation produced by nominally steady, low Mach number flow past a shallow, rectangular wall cavity in the presence of a cross-beam in the flow adjacent to the cavity. At ‘lock-on’ the frequency of vortex shedding from the beam is equal to one of the resonant frequencies of the cavity. The sound produced by this vorticity is augmented by the presence of the cavity and is calculated for the lowest order resonance frequency of the cavity by using a Green's function derived by Howe ( International Journal of Aeroacoustics2, 347 – 365, 2003). Except for beams of very small cross-section, the efficiency of the aeroacoustic coupling between the beam and the cavity depends on the position of the beam above the cavity. Our results indicate that the coupling is strongest when the beam lies above the cavity mouth between the cavity leading edge and the centre of the mouth. The analysis makes use of two alternative models of vortex shedding, involving either an array of discrete, rectilinear vortices or a continuous, time-harmonic vortex sheet in the wake of the beam. At lock-on each of these models supplies essentially identical predictions of the acoustic sound power radiated directly away from the cavity.
High-affinity binding site for a group II intron-encoded reverse transcriptase/maturase within a stem–loop structure in the intron RNA
Authors: WATANABE KAZUO , LAMBOWITZ ALAN M.
Published: July 2004

Mobile group II introns encode proteins that have reverse transcriptase and maturase activities and bind specifically to the intron RNA to promote both RNA splicing and intron mobility. Previous studies with the Lactococcus lactis Ll.LtrB intron showed that the intron-encoded protein (LtrA) has a high-affinity binding site in intron subdomain DIVa, an idiosyncratic structure containing the translation initiation region of the LtrA open reading frame, and that this binding site consists of a small stem–loop emanating from a purine-rich internal loop. The binding of LtrA to DIVa is important for translational regulation, RNA splicing, and intron mobility. Here, we show by in vitro selection that part of the purine-rich internal loop can be closed by base pairing, enabling the LtrA binding site to be represented as an extended stem–loop structure with a bulged A (A556) required for tight binding of LtrA. The deletion or pairing of A556 has relatively little effect on maturase-promoted RNA splicing, but significantly inhibits intron mobility. The wild-type DIVa structure has a second bulged A (A553), which is selected against in tightly binding variants. As expected from the selection, the deletion or pairing of A553 results in tighter binding of LtrA, but surprisingly, also inhibits intron mobility. These findings suggest that the binding of LtrA to DIVa is delicately balanced, so that either too weak or too tight binding can be deleterious. The nature of the maturase/DIVa interaction and its role in translational regulation are reminiscent of the coat protein/RNA hairpin interactions of single-stranded RNA phages.
Potential Interaction Between Telithromycin and Warfarin
Authors: Kolilekas Likurgos , Anagnostopoulos George K , Lampaditis Ioannis , Eleftheriadis Iordanis
Published: July 2004

OBJECTIVE:

To report a case of warfarin—telithromycin interaction resulting in an elevated international normalized ratio (INR) and hemoptysis.

CASE SUMMARY:

A 73-year-old white man developed an elevated INR and mild hemoptysis as a result of an interaction between warfarin and telithromycin 800 mg/day. The INR increased from 3.1 before telithromycin was started to 11 after 5 days of telithromycin therapy. The INR returned to the therapeutic range 4 days after telithromycin was discontinued.

DISCUSSION:

Telithromycin is the first member of the macrolide subclass of ketolides and offers potential advantages over traditional macrolides/azalides for community-acquired respiratory tract infections caused by macrolide-resistant pathogens. As of July 16, 2004, bleeding complications and an increased INR as a result of an interaction between warfarin and telithromycin have not been described. Although the mechanism for this interaction remains unknown, it is suspected that it is a result of the inhibition of the metabolism of the R-isomer of warfarin, which is metabolized predominantly by CYP1A2 and less by CYP3A4. Further research is required to elucidate this issue. An objective causality assessment revealed that this adverse drug event as a result of the warfarin and telithromycin interaction was probable.

CONCLUSIONS:

We recommend close monitoring of INR levels in patients on warfarin who receive telithromycin therapy in an effort to control and prevent bleeding complications.