bluuebunny/crossref_metadata_2025 huggingface dataset:
Suppressor of Cytokine Signaling 3 Is Induced by Angiotensin II in Heart and Isolated Cardiomyocytes, and Participates in Desensitization
Authors: Calegari Vivian C. , Bezerra Rosangela M. N. , Torsoni Márcio A. , Torsoni Adriana S. , Franchini Kleber G. , Saad Mário J. A. , Velloso Lício A.
Published: July 2003

Angiotensin II (Ang II) exerts a potent growth stimulus on the heart and vascular wall. Activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) intracellular signaling pathway by Ang II mediates at least some of the mitogenic responses to this hormone. In other signaling systems that use the JAK/STAT pathway, proteins of the suppressor of cytokine signaling (SOCS) family participate in signal regulation. In the present study it is demonstrated that SOCS3 is constitutively expressed at a low level in rat heart and neonatal rat ventricular myocytes. Ang II at a physiological concentration enhances the expression of SOCS3 mRNA and protein, mainly via AT1 receptors. After induction, SOCS3 associates with JAK2 and impairs further activation of the JAK2/STAT1 pathway. Pretreatment of rats with a specific phosphorthioate antisense oligonucleotide to SOCS3, reverses the desensitization to angiotensin signaling, as detected by a fall in c-Jun expression after repetitive infusions of the hormone. Thus, SOCS3 is induced by Ang II in rat heart and neonatal rat ventricular myocytes and participates in the modulation of the signal generated by this hormone.
Gonadotropin-Releasing Hormone-Desensitized LβT2 Gonadotrope Cells Are Refractory to Acute Protein Kinase C, Cyclic AMP, and Calcium-Dependent Signaling
Authors: Liu Fujun , Austin Darrell A. , Webster Nicholas J. G.
Published: July 2003

Sustained exposure of gonadotropes to GnRH causes a pronounced desensitization of gonadotropin release, but the mechanisms involved are poorly understood. It is known that desensitization is associated with decreased GnRH receptor and Gq/11 levels in αT3-1 cells, but it is not known whether downstream signaling is impaired. We have shown previously that chronic stimulation of signaling via expression of an active form of Gαq causes GnRH resistance in LβT2 cells. In this study we investigated whether chronic GnRH treatment could down-regulate protein kinase C (PKC), cAMP, or Ca2+-dependent signaling in LβT2 cells. We found that chronic GnRH treatment desensitizes cells to acute GnRH stimulation not only by reducing GnRH receptor and Gq/11 expression but also by down-regulating PKC, cAMP, and calcium-dependent signaling. Desensitization was observed for activation of ERK and p38 MAPK and induction of c-fos and LHβ protein expression. Activation of individual signaling pathways was able to partially mimic the desensitizing effect of GnRH on ERK, p38 MAPK, c-fos, and LHβ but not on Gq/11. Chronic stimulation with phorbol esters reduced GnRH receptor expression to the same extent as chronic GnRH. Sustained GnRH also desensitized PKC signaling by down-regulating the δ, ε, and θ isoforms of PKC. We further show that chronic GnRH treatment causes heterologous desensitization of other Gq-coupled receptors.
Hyperleptinemia, Visceral Adiposity, and Decreased Glucose Tolerance in Mice with a Targeted Disruption of the Histidine Decarboxylase Gene
Authors: Fülöp András K. , Földes Anna , Buzás Edit , Hegyi Krisztina , Miklós Ildikó H. , Romics László , Kleiber Monika , Nagy András , Falus András , Kovács Krisztina J.
Published: July 2003

Histamine has been referred to as an anorexic factor that decreases appetite and fat accumulation and affects feeding behavior. Tuberomammillary histaminergic neurons have been implicated in central mediation of peripheral metabolic signals such as leptin, and centrally released histamine inhibits ob gene expression. Here we have characterized the metabolic phenotype of mice that completely lack the ability to produce histamine because of targeted disruption of the key enzyme in histamine biosynthesis (histidine decarboxylase, HDC). Histochemical analyses confirmed the lack of HDC mRNA, histamine immunoreactivity, and histaminergic innervation throughout the brain of gene knockout mouse. Aged histamine-deficient (HDC−/−) mice are characterized by visceral adiposity, increased amount of brown adipose tissue, impaired glucose tolerance, hyperinsulinemia, and hyperleptinemia. Histamine-deficient animals are not hyperphagic but gain more weight and are calorically more efficient than wild-type controls. These metabolic changes presumably are due to the impaired regulatory loop between leptin and hypothalamic histamine that results in orexigenic dominance through decreased energy expenditure, attenuated ability to induce uncoupling protein-1 mRNA in the brown adipose tissue and defect in mobilizing energy stores. Our results further support the role of histamine in regulation of energy homeostasis.
Activin βC-Subunit Heterodimers Provide a New Mechanism of Regulating Activin Levels in the Prostate
Authors: Mellor Sally L. , Ball Emma M. A. , O’Connor Anne E. , Ethier Jean-François , Cranfield Mark , Schmitt Jacqueline F. , Phillips David J. , Groome Nigel P. , Risbridger Gail P.
Published: July 2003

Activins are formed by dimerization of β-subunits and, as members of the TGF-β superfamily, have diverse roles as potent growth and differentiation factors. As the biological function of the activin C homodimer (βC-βC) is unknown, we sought to compare activin A (βA-βA), B (βB-βB), and C homodimer bioactivities and to investigate the consequences of activin βC-subunit overexpression in prostate tumor cells. Exogenous activin A and B homodimers inhibited cell growth and activated activin-responsive promoters. In contrast, the activin C homodimer was unable to elicit these responses. We previously showed that the activin βC-subunit heterodimerized with activin βAin vitro to form activin AC. Therefore, we hypothesize that the activin βC-subunit regulates the levels of bioactive activin A by the formation of activin AC heterodimers. To test this hypothesis, we measured activin AC heterodimer production using a novel specific two-site ELISA that we developed for this purpose. In the PC3 human prostate tumor cell line, activin βC-subunit overexpression increased activin AC heterodimer levels, concomitantly reduced activin A levels, and decreased activin signaling. Overall, these data are consistent with a role for the activin βC-subunit as a regulatory mechanism to reduce activin A secretion via intracellular heterodimerization.
Autocrine/Paracrine Action of Pituitary Vasoactive Intestinal Peptide on Lactotroph Hyperplasia Induced by Estrogen
Authors: Gómez Oscar , Balsa José Antonio
Published: July 2003

Vasoactive intestinal polypeptide (VIP) content is increased in the hyperplastic pituitaries of estrogen (E)-treated rats, thus suggesting that this neuropeptide could mediate the E effect on lactotrophs. E also decreases pituitary TGF-β1 content, an autocrine/paracrine inhibitor of lactotroph proliferation, and induces pituitary angiogenesis. To elucidate the role of VIP in this context, lactotroph hyperplasia was induced in female Fisher 344 rats by implanting sc pellets of diethylstilbestrol (DES). Twenty-five days later, the rats were treated with three different increasing doses of a VIP receptor antagonist or the vehicle for 5 d. DES treatment resulted in a marked increase of serum prolactin (PRL), pituitary PRL content, PRL mRNA expression, pituitary weight, and pituitary proliferating cell nuclear antigen. DES treatment also increased pituitary VIP content and VIP mRNA levels, but not in the hypothalamus and cerebral cortex. Simultaneously, DES treatment decreased the pituitary TGF-β1 content and increased the pituitary content of vascular endothelial growth factor. VIP receptor antagonist partially reverted the effect of DES on serum PRL and pituitary PRL, proliferating cell nuclear antigen, TGF-β1, and vascular endothelial growth factor contents, as well as on pituitary weight, in a dose-dependent relation. These data suggest that pituitary VIP mediates the effect of E on lactotroph hyperplasia, pituitary TGF-β1, and angiogenesis.
Nuclear Factor-κB Translocation Mediates Double-Stranded Ribonucleic Acid-Induced NIT-1 β-Cell Apoptosis and Up-Regulates Caspase-12 and Tumor Necrosis Factor Receptor-Associated Ligand (TRAIL)
Authors: Robbins Marjorie A. , Maksumova Lola , Pocock Emma , Chantler Janet K.
Published: July 2003

The mechanism of induction of apoptosis by double-stranded RNA (dsRNA) is not fully characterized. The dsRNA is normally present in extremely low quantities in cells, but following infection with RNA viruses, large quantities of the dsRNA viral replicative intermediate may be produced triggering the antiviral response as well as cell death. In this report, transfection of polyinosinic-polycytidylic acid [poly(I:C)] into NIT 1 cells has been used as a model of intracellular dsRNA-induced β-cell apoptosis. At 18 h post transfection, 45% of the cells were apoptotic as indicated by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) staining, and this was accompanied by an increase in nuclear factor κB (NF-κB) p50/p65 nuclear translocation and cleavage of caspases 3 and 8. The NF-κB inhibitor peptide, SN50, significantly reduced caspase-3 activity and the percentage of TUNEL-positive cells, substantiating a role for NF-κB in inducing intracellular dsRNA-mediated apoptosis. Concomitantly, RNA-dependent protein kinase activity was observed at 3 h post transfection along with phosphorylation and degradation of inhibitory κB-α. Expression of TRAIL (TNF-related apoptosis-inducing ligand), Fas, IL-15, and caspase-12 mRNAs was up-regulated in the presence of poly(I:C) but not when SN50 was also added. In contrast, there was no change detected in Fas, Fas-associated death domain, Bcl-2, Bcl-xl, Bax, p53, or XIAP(X-linked inhibitor of apoptosis protein) expression up to 12 h after poly(I:C) transfection. In addition, caspase-12 was cleaved, and phosphorylation of eukaryotic initiation factor 2α occurred, suggesting that an endoplasmic reticulum stress pathway was involved in addition to NF-κB induction of an extrinsic pathway, possibly mediated by TNF-related apoptosis-inducing ligand.
Estrogen and Progesterone Up-Regulate Glucose Transporter Expression in ZR-75-1 Human Breast Cancer Cells
Authors: Medina Rodolfo A. , Meneses Ana Maria , Vera Juan Carlos , Guzman Catherine , Nualart Francisco , Astuya Allisson , de los Angeles García María , Kato Sumie , Carvajal Andrés , Pinto Mauricio , Owen Gareth I.
Published: July 2003

Breast cancer incidence increases in women receiving combined estrogen and progesterone therapy. Breast tumors show increased expression of the glucose transporter GLUT1. We determined the effect of these hormones on GLUT1–4 expression and deoxyglucose transport in ZR-75-1 breast cancer cells. Immunoblotting, immunocytochemistry, flow cytometry, and RT-PCR showed that GLUT1 expression is up-regulated by progesterone and, to a greater degree, combined therapy. GLUT2 expression is unaffected by hormonal treatment. GLUT3 protein and RNA is up-regulated by progesterone and combined therapy, and GLUT4 protein expression is up-regulated by all hormonal treatments. Deoxyglucose transport studies revealed the presence of three transport components with characteristics corresponding to GLUT1/4, GLUT2, and GLUT3. 17β-Estradiol produced a slight increase in transport at the Michaelis constant (Km) corresponding to GLUT3. Progesterone produced a small increase in transport at the Km corresponding to GLUT1/4, and combined 17β-estradiol and progesterone produced a small increase in transport at the Km corresponding to GLUT3 and a large increase in transport at the Km corresponding to GLUT1/4. This indicates that 17β-estradiol and progesterone differentially regulate GLUT1–4 expression and that these changes correlate to changes in glucose uptake. We postulate that combined hormone replacement therapy provides a survival advantage to developing ZR-75 breast cancer cells.
Disruption of a Receptor-Mediated Mechanism for Intracellular Sorting of Proinsulin in Familial Hyperproinsulinemia
Authors: Dhanvantari Savita , Shen Fu-Sheng , Adams Tiffany , Snell Christopher R. , Zhang ChunFa , Mackin Robert B. , Morris Stephen J. , Loh Y. Peng
Published: July 2003

In familial hyperproinsulinemia, specific mutations in the proinsulin gene are linked with a profound increase in circulating plasma proinsulin levels. However, the molecular and cellular basis for this disease remains uncharacterized. Here we investigated how these mutations may disrupt the sorting signal required to target proinsulin to the secretory granules of the regulated secretory pathway, resulting in the unregulated release of proinsulin. Using a combination of molecular modeling and site-directed mutagenesis, we have identified structural molecular motifs in proinsulin that are necessary for correct sorting into secretory granules of endocrine cells. We show that membrane carboxypeptidase E (CPE), previously identified as a prohormone-sorting receptor, is essential for proinsulin sorting. This was demonstrated through short interfering RNA-mediated depletion of CPE and transfection with a dominant negative mutant of CPE in a β-cell line. Mutant proinsulins found in familial hyperproinsulinemia failed to bind to CPE and were not sorted efficiently. These findings provide evidence that the elevation of plasma proinsulin levels found in patients with familial hyperproinsulinemia is caused by the disruption of CPE-mediated sorting of mutant proinsulins to the regulated secretory pathway.
Effect of the distribution and clustering of the type I A BMP receptor(ALK3) with the type II BMP receptor on the activation of signalling pathways
Authors: Nohe Anja , Keating Eleonora , Underhill T. Michael , Knaus Petra , Petersen Nils O.
Published: July 2003

Bone morphogenetic proteins (BMPs) play an important role during embryonic development, especially in chondrogenesis, osteogenesis, neurogenesis and hematopoiesis. There are over 19 BMPs known in mammalians, but only three BMP-type-I receptors and three BMP-type-II receptors are known so far to mediate these responses. Previous reports provide evidence to support that oligomerisation of BMP receptors influences the activation of the downstream BMP signalling pathways, the Smad or the p38 MAPK pathway. To further explore the importance of BMP receptor clustering in signalling, image correlation spectroscopy has been used to investigate the clustering and distribution of BMP receptors at the surface of the cell membrane. Here we demonstrate that the co-expression of the BMP-type-II receptor (BRII) influences the aggregation and the distribution of the BMP-type-Ia receptor (BRIa) in COS7 cells and in A431 cells. We also demonstrate that BMP-2 stimulation of the cells leads to a rearrangement of receptor complexes at the cell surface. Using A431 cells and limb bud-derived mesenchymal cells, we show that co-expression of the BRII and a constitutive active BRIa-ca is necessary for the activation of the Smad pathway. Importantly using a kinase-inactive BRII the rearrangement of BRIa is blocked. Together, these findings suggest that rearrangement of the receptors at the cell surface prior to forming preformed ligand independent complexes plays a critical role in activation of the Smad pathway. It also suggests further that the kinase activity of BRII is needed for signalling beyond the activation of BRIa at the GS domain.
Exocrine specific expression of Connexin32 is dependent on the basic helix-loop-helix transcription factor Mist1
Authors: Rukstalis J. Michael , Kowalik Agnes , Zhu Liqin , Lidington Darcy , Pin Christopher L. , Konieczny Stephen F.
Published: July 2003

Gap junctions are intercellular channels that provide direct passage of small molecules between adjacent cells. In pancreatic acini, the connexin26(Cx26) and connexin32 (Cx32) proteins form functional channels that coordinate the secretion of digestive enzymes. Although the function of Cx26/Cx32 gap junctions are well characterized, the regulatory circuits that control the spatial and temporal expression patterns of these connexin genes are not known. In an effort to identify the molecular pathways that regulate connexin gene expression, we examined Cx26 and Cx32 gene activities in mice lacking the basic helix-loop-helix transcription factor Mist1(Mist1KO). Mist1, Cx26 and Cx32 are co-expressed in most exocrine cell types, and acinar cells from Mist1KO mice exhibit a highly disorganized cellular architecture and an altered pattern of expression for several genes involved in regulated exocytosis. Analysis of Mist1KO mice revealed a dramatic decrease in both connexin proteins, albeit through different molecular mechanisms. Cx32 gene transcription was greatly reduced in all Mist1KO exocrine cells, while Cx26 gene expression remained unaffected. However, in the absence of Cx32 protein, Cx26 did not participate in gap junction formation, leading to a complete lack of intercellular communication among Mist1KO acinar cells. Additional studies testing Mist1 gene constructs in pancreatic exocrine cells confirmed that Mist1 transcriptionally regulates expression of the Cx32 gene. We conclude that Mist1 functions as a positive regulator of Cx32 gene expression and, in its absence, acinar cell gap junctions and intercellular communication pathways become disrupted.
The prostaglandin E2 analogue sulprostone antagonizes vasopressin-induced antidiuresis through activation of Rho
Authors: Tamma Grazia , Wiesner Burkhard , Furkert Jens , Hahm Daniel , Oksche Alexander , Schaefer Michael , Valenti Giovanna , Rosenthal Walter , Klussmann Enno
Published: July 2003

Arginine-vasopressin (AVP) facilitates water reabsorption in renal collecting duct principal cells by activation of vasopressin V2 receptors and the subsequent translocation of water channels (aquaporin-2, AQP2) from intracellular vesicles into the plasma membrane. Prostaglandin E2(PGE2) antagonizes AVP-induced water reabsorption; the signaling pathway underlying the diuretic response is not known. Using primary rat inner medullary collecting duct (IMCD) cells, we show that stimulation of prostaglandin EP3 receptors induced Rho activation and actin polymerization in resting IMCD cells, but did not modify the intracellular localization of AQP2. However, AVP-, dibutyryl cAMP- and forskolin-induced AQP2 translocation was strongly inhibited. This inhibitory effect was independent of increases in cAMP and cytosolic Ca2+. In addition,stimulation of EP3 receptors inhibited the AVP-induced Rho inactivation and the AVP-induced F-actin depolymerization. The data suggest that the signaling pathway underlying the diuretic effects of PGE2and probably those of other diuretic agents include cAMP- and Ca2+-independent Rho activation and F-actin formation.
Demonstration by FRET of BACE interaction with the amyloid precursor protein at the cell surface and in early endosomes
Authors: Kinoshita Ayae , Fukumoto Hiroaki , Shah Tejal , Whelan Christa M. , Irizarry Michael C. , Hyman Bradley T.
Published: July 2003

Amyloid-β peptide, which accumulates in senile plaques in Alzheimer's disease, is derived from the amyloid precursor protein (APP) by proteolytic processing. β-secretase (Asp2), which cleaves APP at the N-terminus of amyloid-β, has recently been identified to be the protease BACE. In the present study, we examined the subcellular localization of interactions between APP and BACE by using both double immunofluorescence and a fluorescence resonance energy transfer (FRET) approach. Cell surface APP and BACE, studied by using antibodies directed against their ectodomains in living H4 neuroglioma cells co-transfected with APP and BACE, showed exquisite co-localization and demonstrated a very close interaction by FRET analysis. The majority of cell surface APP and BACE were internalized after 15 minutes,but they remained strongly co-localized together in the early endosomal compartment, where FRET analysis demonstrated a continued close interaction. By contrast, at later timepoints, almost no co-localization or FRET was observed in lysosomal compartments. To determine whether the APP-BACE interaction on cell surface and endosomes contributed to amyloid-βsynthesis, we labeled cell surface APP and demonstrated detectable levels of labeled amyloid-β within 30 minutes. APP-Swedish mutant protein enhanced amyloid-β synthesis from cell surface APP, consistent with the observation that it is a better BACE substrate than wild-type APP. Taken together, these data confirm a close APP-BACE interaction in early endosomes,and highlight the cell surface as an additional potential site of APP-BACE interaction.
Dynamic behavior of Nuf2-Hec1 complex that localizes to the centrosome and centromere and is essential for mitotic progression in vertebrate cells
Authors: Hori Tetsuya , Haraguchi Tokuko , Hiraoka Yasushi , Kimura Hiroshi , Fukagawa Tatsuo
Published: July 2003

Nuf2 and Hec1 are evolutionarily conserved centromere proteins. To clarify the functions of these proteins in vertebrate cells, we characterized them in chicken DT40 cells. We generated GFP fusion constructs of Nuf2 and Hec1 to examine in detail the localization of these proteins during the cell cycle. We found that Nuf2 is associated with Hec1 throughout the cell cycle and that this complex is localized to the centrosomes during G1 and S phases and then moves through the nuclear membrane to the centromere in G2 phase. During mitosis, this complex is localized to the centromere.

We also created conditional loss-of-function mutants of Nuf2 and Hec1. In both mutants, the cell cycle arrested at prometaphase, suggesting that the Nuf2-Hec1 complex is essential for mitotic progression. The inner centromere proteins CENP-A, -C, and -H and checkpoint protein BubR1 were localized to chromosomes in the mutant cells arrested at prometaphase, but Mad2 localization was abolished. Furthermore, photobleaching experiments revealed that the Nuf2-Hec1 complex is stably associated with the centromere and that interaction of this complex with the centrosome is dynamic.
A Finite Element Method for the Dynamic Analysis of Automatic Transmission Gear Shifting with a Four-Degree-of-Freedom Planetary Gearset Element
Authors: Zhang N , Crowther A , Liu D K , Jeyakumaran J
Published: June 2003

A dynamic model of a passenger car automatic transmission and driveline is developed for simulating transient torsional vibration in gearshifts. A finite element method is proposed for presenting the transient dynamics of the parametric system, element matrices are defined and then global inertial, stiffness and damping matrices are formulated corresponding to the defined global coordinate vectors. A four-degree-of-freedom matrix element is developed that describes the rigid body dynamics of the planetary gear set and is then integrated with the driveline system; this element captures the parametric change while the transmission speed ratios vary over gearshifts. Free vibration analysis and a transient 2-3 upshift simulation are discussed and results presented.
Potential and Pitfalls in the Use of dual exhaust gas oxygen sensors for three-way catalyst monitoring and control
Authors: Peyton Jones J C , Jackson R A
Published: June 2003

Although it is known that exhaust gas oxygen (EGO) sensors are sensitive to gas composition, even at a constant air-fuel ratio (AFR), its significance in dual EGO sensor based catalyst control and on-board diagnostic systems has not been fully recognized. The (time varying) difference in gas composition across the catalyst gives rise to a dynamically changing bias component at the sensor output, which is not readily distinguishable from the oxygen storage and release effects the sensor is intended to monitor. Unless treated explicitly, this is likely to degrade the performance of dual EGO sensor based systems. However, the distortion itself also reflects catalyst activity and is strongly correlated with a reversible catalyst deactivation effect which dominates hydrocarbon and NO conversion efficiency under rich conditions. A method for exploiting the biased signal to obtain both improved estimates of the true AFR and an insight into the reversible deactivation effect is therefore outlined.
Engine Test Data Modelling by Evolutionary Radial Basis Function Networks
Authors: Lin W , Wu M H , Duan S
Published: June 2003

The engine test bed is introduced briefly and the importance of modelling for the engine test is discussed. The application of combining radial basis function (RBF) networks and a real-coded genetic algorithm (RCGA) to create the model is described for the engine test. Finally, the experimental results are analysed and it is shown that the proposed approach combining RCGA and RBF models is well suited for the engine test data modelling task.
Correlation of Ignitability with Injection Timing for Direct Injection Combustion Fuelled with Compressed Natural Gas and Gasoline
Authors: Huang Z , Shiga S , Ueda T , Nakamura H , Ishima T , Obokata T , Tsue M , Kono M
Published: June 2003

A study on the correlation of ignitability with fuel injection timing for direct injection combustion fuelled with natural gas and gasoline was carried out by using a rapid compression machine. The injection pressure of natural gas is 9 MPa and the injection pressure of gasoline is 7 MPa. The study results show that natural gas direct injection possesses higher momentum than that of gasoline, and this is beneficial to the combustion enhancement since a higher intensity of turbulence could be induced. Correlation of ignitability with injection timing shows better behaviour in natural gas direct injection, and this correlation is insensitive to injection modes in the case of natural gas. Thus, natural gas direct injection would have better engine applicability under cold-start conditions. The lean burn limits of natural gas and gasoline direct injection can extend to extremely low equivalence ratio when the ignitable stratified mixture exists around the spark electrode gap by optimizing the injection timing.
Review of current technologies for urinary incontinence: Strengths and limitations
Authors: Fader M
Published: July 2003

A wide range of continence products is available, and this paper focuses on products to prevent incontinence (such as urinals and commodes) and to contain or manage urinary incontinence (such as absorbent pads, penile sheaths and urethral catheters). Drawing on results from published clinical evaluations at the Continence Product Evaluation Network at UCL and at other centres, the strengths and limitations of the major categories of incontinence products currently on the market are reviewed. It is concluded that, although products for continence have improved considerably over the last 20 years, there is considerable scope for the designer and engineer to improve on current products.
Engineered structures for use in disposable incontinence products
Authors: White C F
Published: July 2003

The background and evolution of absorbent disposable hygiene products is discussed. The current technology used to produce disposable hygiene products such as baby diapers, feminine hygiene products and adult incontinence management products is shown to have a number of manufacturing and in-use problems. Alternative technologies, such as multilayer composite webs offer the opportunity to achieve better product weight control, and therefore better control over the other related properties, reduced raw material waste and improved functional characteristics. There are still problems to be resolved when using such composite materials, but the potential of these new technologies has now been established.
Mapping liquid distribution in absorbent incontinence products
Authors: Landeryou M A , Yerworth R J , Cottenden A M
Published: July 2003

This paper reviews methods available for mapping the distribution of fluid in incontinence pad materials to assist with evaluating existing products and developing new ones, and to provide data for building and validating predictive models. Specifically, the following technologies are considered and their strengths and limitations described: discrete sensors based on conductance, temperature or optical measurements, optical imaging, gravimetric methods, X-ray imaging and magnetic resonance imaging. It is suggested that the ideal method would enable fluid distribution to be mapped in three dimensions with good spatial and time resolution in single materials and composite structures of simple and complex geometries under static and dynamic mechanical loading. It would also allow liquid to be mapped in products when worn by users. It is concluded that, although each existing method meets some of these requirements, and each requirement is met, at least reasonably well, by at least one method, improved techniques are needed. The particular need for methods that can provide some measurement of liquid saturation within absorbent products, both in the laboratory and in real use, is highlighted. In many cases, simple methods used appropriately are sufficient to elicit the important aspects of liquid transport and storage within absorbent products.
Experimental and theoretical study of the spread of fluid from a point source on an inclined incontinence bed-pad
Authors: Eames I , Small I , Frampton A , Cottenden A M
Published: July 2003

The spread of fluid from a localized source on to a flat fibrous sheet is studied. The sheet is inclined at an angle, α, to the horizontal, and the areal flux of the fluid released is Qa. A new experimental study is described where the dimensions of the wetted region are measured as a function of time t, Qa and α (>0). The down-slope length, Y, grows according to Y ∼ ( Qa t)2/3(sin α)1/3; for high discharge rates and low angles of inclination, the cross-slope width, X, grows as ∼ ( Qa t)1/2, while for low discharge rates or high angles of inclination, the cross-slope transport is dominated by infiltration and X ∼ 2(2 KsΦ∗ t)1/2, where Ks is the saturated permeability and Φ∗ is the characteristic value of capillary pressure. A scaling analysis of the underlying non-linear advection diffusion equation describing the infiltration process confirms many of the salient features of the flow observed. Good agreement is observed between the collapse of the numerical solutions and experimental results. The broader implications of these results for incontinence bed-pad research are briefly discussed.
Wetting between parallel fibres; column-unduloid and column disintegration transitions
Authors: Lukáš D , Chaloupek J
Published: July 2003

Wetting phenomena are studied for a fibre bundle consisting of three parallel cylinders of radius b. Two types of long liquid column (a disintegrated and a channel-filling column) and a state akin to the unduloid can form, depending on whether the cylinder-cylinder separation, 2 d, is larger or smaller than certain critical values. The dimensionless threshold values d/b have been calculated, when gravity can be neglected and the liquid-fibre contact angle is zero. The threshold value for the morphological transition between disintegrated columns and channel-filling columns occurs for ( d/b)tr1 = 0.07869, and the transition between channel-filling column and unduloid sets in when ( d/b)tr2 = 2.85337. The existence of the first type of morphological transition is validated by computer simulation based on the Ising model and the Monte Carlo method, as well as by experiments carried out with steel cylinders and epoxy resin.
Polymer surface properties and their effect on the adhesion of Proteus mirabilis
Authors: Downer A , Morris N , Feast W J , Stickler D
Published: July 2003

A problem encountered in patients undergoing long-term catheterization of the urinary tract is that of encrustation and blockage of the catheter by crystalline bacterial biofilms. This is principally caused by the action of the urease-producing pathogen Proteus mirabilis. A major aim of this work is to develop materials resistant to encrustation. Here, the effects of polymer surface properties on the adhesion of P. mirabilis are examined. Spin-coated polymer films were characterized through contact angle measurements to give the Lifschitz-van der Waals, electron acceptor and electron donor terms of the surface free energy, γsLW, γs+ and γs− respectively. A parallel-plate flow cell was used to assess adhesion to these polymer films of P. mirabilis suspended in an aqueous phosphate buffer, pH 7.4, ionic strength 0.26 mol/kg. P. mirabilis was found to adhere significantly less ( p<0.02) to films of agarose, poly(2-hydroxyethylmethacrylate) and cross-linked poly(vinyl alcohol) than to more hydrophobic materials. These polymer films were found to be strongly electron donating, i.e. possessing large γs−. Films examined using scanning electron microscopy mostly showed no evidence of roughness down to a scale of 1–10 μm. The better performance is thought to be due to a repulsive interaction with the bacterial surface caused by acid/base-type interactions.
The further development of the active urine collection device: A novel continence management system
Authors: Tinnion E , Jowitt F , Clarke-O'Neill S , Cottenden A M , Fader M , Sutherland I
Published: July 2003

Continence difficulties affect the lives of a substantial minority of the population. Women are far more likely than men to be affected by urinary incontinence but the range of management options for them is limited. There has been considerable interest in developing an external urine collection system for women but without success to date. This paper describes the development and preliminary clinical testing of an active urine collection device (AUCD), which could provide a solution for sufferers. The device uses stored vacuum, protected by a high bubble point filter, to remove urine as quickly as it is produced. This allows a small battery-operated pump to provide the required vacuum, enabling the device to be portable.

Two different types of non-invasive patient/device interface were developed, and tested by volunteers: urinal and small pad. The slimline urinal was popular with users although liquid noise was a problem. The pad interface was successful on occasions but further work is necessary to produce a reliable pad.

This study has successfully demonstrated that a prototype AUCD liquid handling system can remove urine at clinically relevant flowrates. While further development is required, volunteer tests have shown that the AUCD could be a useful advance in continence management.
Developing alternative devices to the long-term urinary catheter for draining urine from the bladder
Authors: Feneley R C L , Parkin J , Scanlan J , Woolley M
Published: July 2003

The self-retaining urinary catheter is used for long-term drainage of urine from the bladder only as a last resort because of serious associated complications, yet it remains a routine method for managing older and disabled patients with loss of bladder control. Blockage of the catheter from calcified deposits within its lumen is a common occurrence, obstructing the passage of urine and causing an urgent, unpredictable problem for patients, carers and the nursing staff. The need for further research on the subject has been recognized for many years. The SuPort Project aimed to develop an alternative suprapubic urine collection system. This report outlines the approach adopted towards the design and selection of the novel device, the production problems that ensued and the small clinical trial of a modified prototype.
A system for logging incontinence events using a simple disposable sensor
Authors: Cusick G , Birkett A , Clarke-O'Neill S , Fader M , Cottenden A M
Published: July 2003

Many elderly people entering residential or nursing care are already incontinent to some degree, relying on incontinence pads to deal with the consequences. A proportion of these people have been shown to exhibit a regular pattern in their incontinence, which opens up the possibility of mitigating the problem by instituting an individual toileting regime for the person. This can reduce their reliance on incontinence pads, both improving their quality of life, and reducing the cost of care. This paper covers the development and evaluation of a sensor for detecting incontinence events, suitable for use in this setting, and describes the design of an associated electronic logger. The devices form part of an assessment system intended to identify a pattern in incontinence where it exists, and to help with the design of the toilet regime for an individual. The requirement is that the system must reliably record incontinence events, and present the information describing them in a manner appropriate to the users of the devices, who are likely to be non-technical and non-specialist.
Bladder reconstruction—from cells to materials
Authors: Southgate J , Cross W , Eardley I , Thomas D F M , Trejdosiewicz L K
Published: July 2003

Surgical reconstruction of the urinary bladder is performed on patients of all ages for a diverse range of conditions, including congenital abnormalities, bladder dysfunction, trauma and cancer. The most common material utilized to augment or replace the bladder during these procedures is a segment of the patient's own intestine. However, this procedure (‘enterocytoplasty’) is associated with significant clinical complications that arise due to the exposure of the epithelial lining of the intestine to urine. A number of alternative approaches are being actively developed to find a practical and functional substitute for native bladder tissue. These range from ‘composite enterocystoplasty’, where the de-epithelialized intestine wall is lined with bladder epithelial cells that have been propagated in vitro, to augmenting the urinary system with natural or synthetic biomaterials that may incorporate in vitro-propagated cells. However, if tissue-engineered products are to have therapeutic application in bladder reconstruction, a number of issues remain to be addressed; these issues are discussed briefly below.
A new device for the treatment of female stress urinary incontinence
Authors: van Veggel L , Morrell M , Harris C , Dormans-Linssen M
Published: July 2003

Treatment for stress urinary incontinence (SUI) comprises a broad range of possible interventions. Non-surgical options include absorbent pads, vaginal weights and cones, biofeedback and minimally invasive techniques such as urethral bulking agents (UBAs). Surgical interventions range in complexity from sling surgery and suspension techniques to more major surgeries such as burch colposuspension. Each option has its challenges and limitations. This paper will focus on UBAs, which are implantable materials whose purpose is to augment urethral tissue function and restore continence. The characteristics required of such materials, and the challenges to be overcome when incorporating them in a successful product design, will be described and discussed. Particular attention will be given to the latest developments in the administration of polydimethylsiloxane elastomer UBA.
A One-pot Synthesis of Cyclic Pyrido[1,2-a]quinoxaline Phosphate, a New Molecule of Biological Importance from a Quinoxaline Derivative of Sugar
Authors: Goswami Shyamaprosad , Adak Avijit Kumar
Published: July 2003

A five membered cyclic pyrido[1,2-a]quinoxaline phosphate has been first synthesized in one step in a good yield by phosphorylation of the quinoxaline derivative of sugar 1a with (PhO)P(O)Cl2. Phosphorylation of the tetrols (1a and 1b) and the diol acetals with other phosphorylating agents, however, affords a dehydration product 2-(2-furyl)quinoxaline.
Affinity Capillary Electrophoresis in a Poly(dimethylsiloxane)-glass Hybrid Microchip
Authors: Ito Toshiyuki , Inoue Akira , Sato Kae , Hosokawa Kazuo , Maeda Mizuo
Published: July 2003

Affinity capillary electrophoresis of DNA was conducted in a poly(dimethylsiloxane)-glass hybrid microchip with a 100 μm (width) × 130 μm (height) microchannel containing poly(N,N-dimethylacrylamide)-DNA conjugate. By this method, sample 12-mer oligonucleotide composed of c-K-ras codon 10-13 was separated from its single-base substituted mutant within 2 min.
The sensitivity of tropical squall lines to surface fluxes: Three‐dimensional cloud‐resolving model simulations
Authors: Wang Yansen , Tao Wei‐Kuo , Simpson Joanne , Lang Stephen
Published: July 2003

Two tropical oceanic squall lines, from the Tropical Ocean–Global Atmosphere Coupled Ocean–Atmosphere Response Experiment (TOGA COARE) and the Global Atmospheric Research Program Atlantic Tropical Experiment (GATE), that developed over the west Pacific and east Atlantic, respectively, are simulated using a three‐dimensional cloud‐resolving model to examine the impact of surface fluxes on tropical squall line development and associated precipitation processes. The important question of how convective available potential energy (CAPE) is maintained in clear and cloudy areas in the tropics is investigated. The boundary‐layer structure and evolution in the clear inflow area are also discussed. Although the cloud structure and precipitation intensity are different between the TOGA COARE and GATE squall line cases, the effects of the surface fluxes on the amount of rainfall and on the cloud development processes are quite similar. The area where surface fluxes originated was categorized into clear and cloudy regions according to whether there was cloud in the vertical column. The model results indicated that the surface fluxes from the large clear‐air environment are the dominant moisture source for tropical squall line development, even though the surface fluxes in the cloud region display a large peak. The high‐energy air from the boundary layer in the clear area is what feeds the convection, while the CAPE is removed by the convection. Trajectory and water budget analyses also indicate that most of the moisture (90%) is from the boundary layer of the clear‐air environment. Copyright © 2003 Royal Meteorological Society
Terrain influences on the dynamics of heat lows
Authors: Reichmann Zsuzsanna , Smith Roger K.
Published: June 2003

The hydrostatic primitive‐equation numerical model we used earlier to study the basic dynamics of heat lows in an idealized flow configuration is extended to investigate the effects of orography. Calculations are carried out over a heated land mass with an elevated plateau for the case with no surrounding sea, as well as with the sea present. We investigate the effect of the shape of the terrain on the mature heat low. In the presence of orography the mixed layer over land becomes deeper than without orography and the induced flow is stronger also. The width of the plateau influences, among other things, the relative‐vorticity distribution and the nocturnal jet development. The flow behaviour in the presence of orography provides an explanation for the different vertical profiles of vertical velocity in heat lows discussed in the literature. Copyright © 2003 Royal Meteorological Society
Validation and intercomparison of three mesoscale models on three FASTEX cloud systems: comparison with coarse‐resolution simulations
Authors: Lopez Philippe , Finkele Klara , Clark Peter , Mascart Patrick
Published: June 2003

Taking advantage of the observations collected during the Fronts and Atlantic Storm‐Track EXperiment (FASTEX), three FASTEX midlatitude cloud systems are simulated with three state‐of‐the‐art, mesoscale, limited‐area models (the Met Office's Unified Model (UM), Met Éireann's High Resolution Limited Area Model (HIRLAM), and the French Laboratoire d'Aérologie research modèle de Méso‐échelle Non‐Hydrostatique (Méso‐NH)), at an 11 km horizontal resolution and with about 50 vertical levels. The dynamical, thermodynamic, cloud and precipitation fields obtained from these numerical integrations are then intercompared and validated against various observational sources, including radio‐ and dropsondes, satellite radiometer, and rain‐gauges. The similarities and the deficiencies of the three models are summarized in the paper. After this validation work, the mesoscale fields are degraded in resolution, so that they can be directly compared with the outputs of 300 km resolution simulations, run with Météo‐France's atmospheric general‐circulation model (AGCM) Action de Recherche Petite Echelle et Grande Echelle (ARPEGE). The deviations between the upscaled mesoscale models and the coarse AGCM turn out to be significant and highly dependent on the location relative to the storm, with, in particular, a large contrast between the trailing cold region and the warm sector with thick layer clouds, suggesting the existence of some deficiencies in the AGCM. Copyright © Royal Meteorological Society, 2003. Peter Clark's contribution is Crown copyright.
A modelling study of ice‐spectrum modes in deep frontal clouds
Authors: Cardwell J. , Field P. R. , Choularton T. W.
Published: June 2003

Results from a one‐dimensional mixed‐layer model with explicit microphysics and a discrete ice‐spectrum were compared to in situ data provided by the Met Office C‐130 aircraft. Bimodal ice‐spectra were observed. The first mode was found at diameters near the lower limit of the instrumentation resolution (25 µm) at a roughly constant concentration. The second mode was found initially at diameters exceeding 200 µm but it shifted to larger sizes and smaller peak concentrations as depths below the cloud top increased.

The objectives of the paper are threefold: validation of the model with real cloud data; an analysis of parameters controlling the rate of aggregation, and to show that a secondary ice‐production process is needed to maintain the first mode and produce a second mode which is sensible.

A reasonable first mode could only be maintained by producing a constant supply of small ice particles at a rate of at least 10 m−3s−1. Primary nucleation was unable to supply this rate of ice‐particle production at temperatures above −20°C. In the model, it was achieved by invoking a secondary ice‐particle production process, such as the break‐up of evaporating ice crystals. The rate of production required is in broad agreement with laboratory investigations of secondary ice‐particle production during evaporation.

The relative importance of the processes of aggregation, deposition and sedimentation to the production of the bimodal spectra is also studied. While it is possible to grow ice particles to large sizes by deposition alone, the number concentration observed in these clouds produces so much competition for water vapour that deposition growth is very limited. The aggregation process is the strongest mechanism for the production of the larger ice‐particles, which then precipitate. Consequently, its strength controls the rate of small ice‐particle production needed, and so is mainly responsible for the second mode. Copyright © Royal Meteorological Society, 2003. P. R. Field's contribution is Crown copyright.