Erythropoietin production in kidney tubular cells

The erythropoietin gene has been cloned in three mammalian species including man and recombinant erythropoietin is now used to treat the anaemia of chronic renal failure. Despite the isolation of the gene the precise cellular location of erythropoietin synthesis remains controversial. We present studies which demonstrate erythropoietin production by kidney tubular cells. Erythropoietin gene expression (messenger RNA) was detected by in situ hybridization using an oligonucleotide gene probe and the translated protein product by immunohistochemistry employing antibodies raised to pure recombinant DNA derived erythropoietin.

The effect of hypobaric hypoxia on misonidazole binding in normal and tumour-bearing mice

The effect of hypobaric hypoxia on the in vivo binding of misonidazole was investigated in normal mice and mice bearing T50/80 or CA NT mammary carcinomas. After the intraperitoneal injection of radiolabelled misonidazole, mice were randomised to breathe either room air or air at 0.5 atmospheres. The distribution of misonidazole in liver, kidney, heart, spleen and tumour tissue, 24 h later, was studied by scintillation counting and by autoradiography. Significantly higher misonidazole binding occurred in the livers (x2.5), kidneys (x2.4), spleens (x2.9) and hearts (x1.8) of hypoxic mice compared to controls. Hypobaric hypoxia was associated with a greater than four-fold increase in misonidazole binding within T50/80 tumours. However, significantly higher binding was not demonstrated within CA NT tumours after exposure of tumour-bearing animals to hypoxic conditions. In autoradiographs of hypoxic liver, labelling was intense in regions near to hepatic veins but sparse in areas surrounding portal tracts. This pattern was striking and consistent. In hypoxic kidney, labelling was most intense over tubular cells, less intense over glomeruli and sparse in the renal medulla. It is likely that the hepatic and renal cortical distributions of misonidazole binding reflect local oxygen gradients.

Every Situation has its Rhythm: Acoustic Mimesis and Sonic Exoticism in Tambours Sur La Digue.

This article examines the soundscapes of Ariane Mnouchkine’s Tambours Sur La Digue and explores the concept of acoustic mimesis located in the performance as a dramaturgical strategy to create, aurally, an imagined Far East. In Tambours, mimesis is the performative principle exemplified by the presentation of the mise en scène, and most distinctly Mnouckine’s decision to adapt the Japanese performance tradition of Bunraku through a process of 'reversed' mimicry (in which human bodies simulate the wooden marionettes of the Japanese style). Mimesis pervades the acoustemologies of the performance as it is heard in the extracted sounds, styles, and rhythms of Asian musical modes and movements that consequently become dislocated from context; the sounds become imitated, iconicised and exoticised as sonic signatures as they reify the Orientalist spectacle. The 'oriental' soundscape, reverberating with exotic overtones, becomes the means by which the production creates an imaginary Orient – one in which the Orient Other is silenced, and is resounded only through the musical sensibilities of the Occidental Self.

A system lifeworld perspective on dying in long term care settings for older people:Contested states in contested places

In many Western countries, older people live and die in long-term institutional care settings. Habermas's concepts of lifeworld, system and communicative action are drawn upon to illuminate the experience of living and dying in this particular place. It is proposed that dying older adults, their family and care staff occupy different contested states and long term care settings are contested places, located in a wider system. This wider system, mediated through care homes, can colonise the life world experiences of dying individuals. The development of communicative space bridges the lifeworld and system and offers a way for the lifeworld of dying individuals, and those around them to be reintegrated into, and influence the wider system. © 2010 Elsevier Ltd.

Arching or Compressive Membrane Action in Reinforced Concrete Slabs

Arching or compressive membrane action (CMA) in reinforced concrete slabs occurs as a result of the great difference between the tensile and compressive strength of concrete. Cracking of the concrete causes a migration of the neutral axis which is accompanied by in-plane expansion of the slab at its boundaries. If this natural tendency to expand is restrained, the development of arching action enhances the strength of the slab. The term arching action is normally used to describe the arching phenomenon in one-way spanning slabs and compressive membrane action is normally used to describe the arching phenomenon in two-
way spanning slabs. This encyclopedic article presents the background to the discovery of the phenomenon of arching action and presents a factual history of the approaches to the treatment of arching action in the United Kingdom and North American bridge deck design codes. The article summarises the theoretical methodology used in the United Kingdom Design Manual for Roads and Bridges, BD81/02, which was based on the work by Kirkpatrick, Rankin & Long at Queen's University Belfast.

Control of the AtMAP65-1 interaction with microtubules through the cell cycle

Cell division depends on the fine control of both microtubule dynamics and microtubule organisation. The microtubule bundling protein MAP65 is a 'midzone MAP' essential for the integrity of the anaphase spindle and cell division. Arabidopsis thaliana MAP65-1 (AtMAP65-1) binds and bundles microtubules by forming 25 nm cross-bridges. Moreover, as AtMAP65-1 bundles microtubules in interphase, anaphase and telophase but does not bind microtubules in prophase or metaphase, its activity through the cell cycle must be under tight control. Here we show that AtMAP65-1 is hyperphosphorylated during prometaphase and metaphase and that CDK and MAPK are involved in this phosphorylation. This phosphorylation inhibits AtMAP65-1 activity. Expression of nonphosphorylatable AtMAP65-1 has a negative effect on mitotic progression resulting in excessive accumulation of microtubules in the metaphase spindle midzone causing a delay in mitosis. We conclude that normal metaphase spindle organisation and the transition to anaphase is dependent on inactivation of AtMAP65-1.

The Arabidopsis microtubule-associated protein AtMAP65-1: Molecular analysis of its microtubule bundling activity

The 65-kD microtubule-associated protein (MAP65) family is a family of plant microtubule-bundling proteins. Functional analysis is complicated by the heterogeneity within this family: there are nine MAP65 genes in Arabidopsis thaliana, AtMAP65-1 to AtMAP65-9. To begin the functional dissection of the Arabidopsis MAP65 proteins, we have concentrated on a single isoform, AtMAP65-1, and examined its effect on the dynamics of mammalian microtubules. We show that recombinant AtMAP65-1 does not promote polymerization and does not stabilize microtubules against cold-induced microtubule depolymerization. However, we show that it does induce microtubule bundling in vitro and that this protein forms 25-nm cross-bridges between microtubules. We further demonstrate that the microtubule binding region resides in the C-terminal half of the protein and that Ala409 and Ala420 are essential for the interaction with microtubules. Ala420 is a conserved amino acid in the AtMAP65 family and is mutated to Val in the cytokinesis-defective mutant pleiade-4 of the AtMAP65-3/PLEIADE gene. We show that AtMAP65-1 can form dimers and that a region in the N terminus is responsible for this activity. Neither the microtubule binding region nor the dimerization region alone could induce microtubule bundling, strongly suggesting that dimerization is necessary to produce the microtubule cross-bridges. In vivo, AtMAP65-1 is ubiquitously expressed both during the cell cycle and in all plant organs and tissues with the exception of anthers and petals. Moreover, using an antiserum raised to AtMAP65-1, we show that AtMAP65-1 binds microtubules at specific stages of the cell cycle.

Cinematic Peripheries of Dublin

The term periphery is, most of the time, used with or in relation to the centre. The ‘zoning’ taken by granted by the architect is unlike the one portrayed by the director who frames the differences of places in a non-linear manner. Film offers a constructed urban experience, suggesting the city to be a local network composed of nodes and links, rather than a centre and the margin. It is possible to talk about the construction of a new kind of network in film through a temporal representation of space, of the distant as the close. In this way, film may be a tool to shift the gaze from the bird’s-eye view to the eye level to create ‘a unified perceptual image of the city’, in Christine Boyer’s words. The experienced surface of the city is two-dimensional neither in fiction nor in reality. In this chapter, the nodes of Dublin are examined through two Irish films, Goldfish Memory (Elizabeth Gill, 2003) and Adam and Paul (Leonard Abrahamson, 2004). Specific elements of the city of Dublin, including walls, houses, pubs, streets, bridges, and parks, are analysed to understand the nature of the network of the city composed of nodes and their connections.

Commissioning and Evaluation of a Fiber-Optic Sensor System for Bridge Monitoring

This paper describes the design, commissioning, and evaluation of a ?ber-optic strain sensor system for the structural health monitoring of a prestressed concrete posttensioned box girder railway bridge in Mumbai, India, which shows a number of well-documented structural problems. Preliminary laboratory trials to design the most appropriate sensor system that could be readily transported and used on site are described, followed by a description of load tests on the actual bridge undertaken in collaboration with Indian Railways and using locomotives of known weight. Results from the load tests using the optical system are compared with similar results obtained using electrical resistance strain gages. Conclusions are summarized concerning the integrity of the structure and for the future use of the sensor system for monitoring bridges of this type. Crack width measurements obtained during the load tests are also described.

Serum erythropoietic activity in acute anemia--an animal model

Serum erythropoietic activity and reticulocyte response to anemia were investigated using a rabbit model. In hemolytic anemia, induced by injections of phenylhydrazine on Day 0 the hemoglobin reached a nadir (mean, 6.23 g/dl) on Day 4 when SEA was maximal (mean, 765 mU/ml). In animals venesected on Day 0 and Day 1 to produce anemia of equal severity, the SEA was maximal (mean 235 mU/ml) on Day 2. In both groups the reticulocyte response peaked on Day 7--at 34% for the hemolytic group and 21% for the venesected group. The 2,3-diphosphoglycerate, measured on Day 4, was significantly reduced in the PHZ-treated group. In the venesected group the 2,3-DPG increased between Day 0 and Day 4. There were no concurrent changes in acid-base balance. These results imply that the degree of anemia is only one of the factors which influence the level of circulating SEA.

Comparison of the mouse spleen cell assay and a radioimmunoassay for the measurement of serum erythropoietin

The mouse spleen cell assay (MSCA) has been compared with a radioimmunoassay for the measurement of serum erythropoietin (Ep). In 20 normal subjects the serum values ranged from 15 to 73 mU/ml for the MSCA compared with 5-30 mU/ml for the RIA. For normal sera there was no correlation between the results of the two assays. In 37 patients with anaemias of differing aetiologies and at various stages of treatment values ranged from 10 to 3645 mU/ml for the MSCA and 13-10,000 mU/ml for the RIA. Although patient values from the two assays were highly correlated (r = 0.98, P less than 0.001), the MSCA results were generally lower. These discrepancies can be largely accounted for by two factors. Firstly the MSCA is sensitive to non-specific matrix effects. Secondly, heat inactivation of serum, a prerequisite for the MSCA, but not for the RIA, destroys a variable and unpredictable proportion of the Ep in the test sera leading to an underestimation of Ep in the MSCA. We conclude that the RIA is more reliable than the MSCA which, in its present form, cannot be recommended for the accurate measurement of serum erythropoietin.

Erythropoietic response to hypobaric hypoxia in rabbits

Animals subjected to hypoxia become hypocapnic and after some hours show an increase in circulating erythropoietin. The steps involved in the increased production of erythropoietin in response to hypoxia are not fully understood, although it has been postulated that changes in coincident variables such as acid-base balance may contribute to the mechanism of increased erythropoietin production. A rabbit model has been used to determine the physiological changes which occur in short-term hypobaric hypoxia. After 1 h, no changes were found in pCO2, pH, P50, base excess, standard bicarbonate or serum erythropoietic activity (SEA). After 3 h the pCO2, pH, base excess and standard bicarbonate had decreased while the P50 and SEA had increased. After 6 h, although the pCO2 was still significantly reduced, the pH, base excess and standard bicarbonate had returned to the initial levels and maximal SEA values. 20-fold greater than the pre-hypoxia values were found. Overall the data are consistent with the view that the magnitude of the erythropoietic response to hypoxia is modified by changes in acid-base balance.

An investigation of the changes in the natural frequency of a Pile affected by Scour

Scour around bridge foundations is one of the leading causes of bridge failure. Up until recently, the monitoring of this phenomenon was primarily based around using underwater instrumentation to monitor the progression of scour holes as they develop around foundation systems. Vibration-based damage detection techniques have been used to detect damage in bridge beams. The application of these vibration based methods to the detection of scour has come to the fore in research in recent years. This paper examines the effect that scour has on the frequency response of a driven pile foundation system, similar to those used to support road and rail bridges. The effect of scour on the vibration characteristics of the pile is examined using laboratory and field testing. It is clear that there is a very clear reduction in the natural frequency of the pile as the severity of scour increases. It is shown that by combining state-of-the-art geotechnical techniques with relatively simple finite element modelling approaches, it is possible to accurately predict the natural frequency of the pile for a given scour depth. Therefore, the paper proposes a method that would allow the estimation of scour depth for a given observed pile frequency.

A bridge-monitoring tool based on bridge and vehicle accelerations

Previous research on damage detection based on the response of a structure to a moving load has reported decay in accuracy with increasing load speed. Using a 3D vehicle – bridge interaction model, this paper shows that the area under the filtered acceleration response of the bridge increases with increasing damage, even at highway load speeds. Once a datum reading is established, the area under subsequent readings can be monitored and compared with the baseline reading, if an increase is observed it may indicate the presence of damage. The sensitivity of the proposed approach to road roughness and noise is tested in several damage scenarios. The possibility of identifying damage in the bridge by analysing the acceleration response of the vehicle traversing it is also investigated. While vehicle acceleration is shown to be more sensitive to road roughness and noise and therefore less reliable than direct bridge measurements, damage is successfully identified in favourable scenarios.