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other | The luminal surface of the epithelial cells of this segment of the nephron is covered with densely packed microvilli forming a border readily visible under the light microscope giving the brush border cell its name. | ||||||
other | The microvilli greatly increase the luminal surface area of the cells, presumably facilitating their reabsorptive function as well as putative flow sensing within the lumen. | ||||||
other | The cytoplasm of the cells is densely packed with mitochondria, which are largely found in the basal region within the infoldings of the basal plasma membrane. | ||||||
other | The high quantity of mitochondria gives the cells an acidophilic appearance. | ||||||
other | The mitochondria are needed in order to supply the energy for the active transport of sodium ions out of the cells to create a concentration gradient which allows more sodium ions to enter the cell from the luminal side. | ||||||
other | Water passively follows the sodium out of the cell along its concentration gradient. | ||||||
other | Cuboidal epithelial cells lining the proximal tubule have extensive lateral interdigitations between neighboring cells, which lend an appearance of having no discrete cell margins when viewed with a light microscope. | ||||||
other | Agonal resorption of the proximal tubular contents after interruption of circulation in the capillaries surrounding the tubule often leads to disturbance of the cellular morphology of the proximal tubule cells, including the ejection of cell nuclei into the tubule lumen. | ||||||
other | This has led some observers to describe the lumen of proximal tubules as occluded or "dirty-looking", in contrast to the "clean" appearance of distal tubules, which have quite different properties. | ||||||
other | The proximal tubule as a part of the nephron can be divided into two sections, "pars convoluta" and "pars recta". | ||||||
other | Differences in cell outlines exist between these segments, and therefore presumably in function too. | ||||||
other | Regarding ultrastructure, it can be divided into three segments, "oS1, S2, and S3": | ||||||
other | The pars convoluta (Latin "convoluted part") is the initial "convoluted portion". | ||||||
other | In relation to the morphology of the kidney as a whole, the convoluted segments of the proximal tubules are confined entirely to the renal cortex. | ||||||
other | Some investigators on the basis of particular functional differences have divided the convoluted part into two segments designated "S1" and "S2". | ||||||
other | The pars recta (Latin "straight part") is the following "straight (descending) portion. | ||||||
other | Straight segments descend into the outer medulla. | ||||||
other | They terminate at a remarkably uniform level and it is their line of termination that establishes the boundary between the inner and outer stripes of the outer zone of the renal medulla. | ||||||
other | As a logical extension of the nomenclature described above, this segment is sometimes designated as "S3". | ||||||
other | The proximal tubule efficiently regulates the pH of the filtrate by exchanging hydrogen ions in the interstitium for bicarbonate ions in the filtrate; it is also responsible for secreting organic acids, such as creatinine and other bases, into the filtrate. | ||||||
other | Fluid in the filtrate entering the proximal convoluted tubule is reabsorbed into the peritubular capillaries. | ||||||
other | This is driven by sodium transport from the lumen into the blood by the Na/K ATPase in the basolateral membrane of the epithelial cells. | ||||||
other | Sodium reabsorption is primarily driven by this P-type ATPase. | ||||||
other | 60-70% of the filtered sodium load is reabsorbed in the proximal tubule through active transport, solvent drag, and paracellular electrodiffusion. | ||||||
other | Active transport is mainly through the sodium/hydrogen antiporter NHE3. | ||||||
other | Paracellular transport increases transport efficiency, as determined by oxygen consumed per unit of Na reabsorbed, thus playing a part in maintaining renal oxygen homeostasis. | ||||||
other | Many types of medications are secreted in the proximal tubule. | ||||||
other | "Further reading: Table of medication secreted in kidney" | ||||||
other | Most of the ammonium that is excreted in the urine is formed in the proximal tubule via the breakdown of glutamine to alpha-ketoglutarate. | ||||||
other | This takes place in two steps, each of which generates an ammonium anion: the conversion of glutamine to glutamate and the conversion of glutamate to alpha-ketoglutarate. | ||||||
other | The alpha-ketoglutarate generated in this process is then further broken down to form two bicarbonate anions, which are pumped out of the basolateral portion of the tubule cell by co-transport with sodium ions. | ||||||
other | Proximal tubular epithelial cells (PTECs) have a pivotal role in kidney disease. | ||||||
other | Two mammalian cell lines are commonly used as models of the proximal tubule: porcine LLC-PK1 cells and marsupial OK cells. | ||||||
other | Most renal cell carcinoma, the most common form of kidney cancer, arises from the convoluted tubules. | ||||||
other | Acute tubular necrosis occurs when PTECs are directly damaged by toxins such as antibiotics (e.g., gentamicin), pigments (e.g., myoglobin) and sepsis (e.g., mediated by lipopolysaccharide from gram-negative bacteria). | ||||||
other | Renal tubular acidosis (proximal type) (Fanconi syndrome) occurs when the PTECs are unable to properly reabsorb glomerular filtrate so that there is increased loss of bicarbonate, glucose, amino acids, and phosphate. | ||||||
other | PTECs also participate in the progression of tubulointerstitial injury due to glomerulonephritis, ischemia, interstitial nephritis, vascular injury, and diabetic nephropathy. | ||||||
other | In these situations, PTECs may be directly affected by protein (e.g., proteinuria in glomerulonephritis), glucose (in diabetes mellitus), or cytokines (e.g., interferon-γ and tumor necrosis factors). | ||||||
other | There are several ways in which PTECs may respond: producing cytokines, chemokines, and collagen; undergoing epithelial mesenchymal trans-differentiation; necrosis or apoptosis. | ||||||
other | Steve Furber | ||||||
other | Stephen Byram Furber (born 21 March 1953) is a British computer scientist, mathematician and hardware engineer, currently the ICL Professor of Computer Engineering in the Department of Computer Science at the University of Manchester, UK. | ||||||
other | After completing his education at the University of Cambridge (BA, MMath, PhD), he spent the 1980s at Acorn Computers, where he was a principal designer of the BBC Micro and the ARM 32-bit RISC microprocessor. | ||||||
other | , over 100 billion variants of the ARM processor have been manufactured, powering much of the world's mobile computing and embedded systems. | ||||||
other | In 1990, he moved to Manchester where he leads research into asynchronous systems, low-power electronics and neural engineering, where the Spiking Neural Network Architecture (SpiNNaker) project is delivering a computer incorporating a million ARM processors optimised for computational neuroscience. | ||||||
other | Furber was educated at Manchester Grammar School and represented the UK in the International Mathematical Olympiad in Hungary in 1970 winning a bronze medal. | ||||||
other | He went on to study the Mathematical Tripos as an undergraduate student of St John's College, Cambridge, receiving a Bachelor of Arts (BA) and Master of Mathematics (MMath - Part III of the Mathematical Tripos) degrees. | ||||||
other | In 1978, he was appointed a Rolls-Royce research fellow in aerodynamics at Emmanuel College, Cambridge and was awarded a PhD in 1980 for research on the fluid dynamics of the Weis-Fogh principle supervised by John Ffowcs Williams. | ||||||
other | During his PhD studies in the late 1970s, Furber worked on a voluntary basis for Hermann Hauser and Chris Curry within the fledging Acorn Computers (originally the Cambridge Processor Unit), on a number of projects; notably a microprocessor based fruit machine controller, and the "Proton" - the initial prototype versio... | ||||||
other | In 1980, following the completion of his PhD and the award of the BBC contract to Acorn, he formally joined the company where he was a Hardware Designer and then Design Manager. | ||||||
other | He led the final design and productionization of the BBC Micro and later, the Electron, and the ARM microprocessor. | ||||||
other | In August 1990 he moved to the University of Manchester to become the ICL Professor of Computer Engineering and established the AMULET microprocessor research group. | ||||||
other | Furber's main research interests are in Neural Networks, Networks on Chip and Microprocessors. | ||||||
other | In 2003, Furber was a member of the EPSRC research cluster in biologically-inspired novel computation. | ||||||
other | On 16 September 2004, he gave a speech on "Hardware Implementations of Large-scale Neural Networks" as part of the initiation activities of the Alan Turing Institute. | ||||||
other | Furber's most recent project SpiNNaker, is an attempt to build a new kind of computer that directly mimics the workings of the human brain. | ||||||
other | Spinnaker is an artificial neural network realised in hardware, a massively parallel processing system eventually designed to incorporate a million ARM processors. | ||||||
other | The finished Spinnaker will model 1 per cent of the human brain's capability, or around 1 billion neurons. | ||||||
other | The Spinnaker project aims amongst other things to investigate: | ||||||
other | Furber believes that "significant progress in "either" direction will represent a major scientific breakthrough". | ||||||
other | Furber's research interests include asynchronous systems, ultra-low-power processors for sensor networks, on-chip interconnect and globally asynchronous locally synchronous (GALS), and neural systems engineering. | ||||||
other | His research has been funded by the Engineering and Physical Sciences Research Council (EPSRC), Royal Society and European Research Council. | ||||||
other | In February 1997, Furber was elected a Fellow of the British Computer Society. | ||||||
other | In 1998, he became a member of the European Working Group on Asynchronous Circuit Design (ACiD-WG). | ||||||
other | He was elected a Fellow of the Royal Society (FRS) in 2002 and was Specialist Adviser to the House of Lords Science and Technology Select Committee inquiry into microprocessor technology. | ||||||
other | Furber was elected a Fellow of the Royal Academy of Engineering (FREng), the Institute of Electrical and Electronics Engineers (IEEE) in 2005 and a Fellow of the Institution of Engineering and Technology (FIET). | ||||||
other | He is a Chartered Engineer (CEng). | ||||||
other | In September 2007 he was awarded the Faraday Medal and in 2010 he gave the Pinkerton Lecture. | ||||||
other | Furber was appointed Commander of the Order of the British Empire (CBE) in the 2008 New Year Honours and was elected as one of the three laureates of Millennium Technology Prize in 2010 (with Richard Friend and Michael Grätzel), for development of ARM processor. | ||||||
other | In 2012, Furber was made a Fellow of the Computer History Museum "for his work, with Sophie Wilson, on the BBC Micro computer and the ARM processor architecture." | ||||||
other | In 2004 he was awarded a Royal Society Wolfson Research Merit Award. | ||||||
other | In 2014, he was made a Distinguished Fellow at the British Computer Society (DFBCS) recognising his contribution to the IT profession and industry. | ||||||
other | Furber's nomination for the Royal Society reads: | ||||||
other | Furber was played by actor Sam Philips in the BBC Four documentary drama Micro Men, first aired on 8 October 2009. | ||||||
other | Furber is married to Valerie Elliot with two daughters and plays 6-string and bass guitar. | ||||||
other | Department of Computer Science, University of Manchester | ||||||
other | The Department of Computer Science at the University of Manchester is the longest established department of Computer Science in the United Kingdom and one of the largest. | ||||||
other | It is located in the Kilburn building (and the attached IT Building) on the Oxford Road and currently has over 800 students taking a wide range of undergraduate and postgraduate courses and 60 full-time academic staff. | ||||||
other | The School currently offers a wide range of undergraduate courses from Bachelor of Science (BSc), Bachelor of Engineering (BEng) and Master of Engineering (MEng). | ||||||
other | These are available as single honours or as joint honours degrees within the themes of Artificial Intelligence, Computer Science, Computer systems engineering, Software engineering, Mathematics, Internet Computing, Business applications and Management. | ||||||
other | Industrial placements are offered with all undergraduate courses. | ||||||
other | At postgraduate level the department offers taught Master of Science (MSc) degrees, at an advanced level and also through a foundation route. | ||||||
other | Research degrees, Doctor of Philosophy (PhD) and Master of Philosophy (MPhil) are available as three and four year programmes through the Doctoral Training Centre in Computer Science, the first of its kind in the UK. | ||||||
other | Notable academic staff include: | ||||||
other | The School is organised into nine different research groups which received funding from a wide range of sources including the European Union, Engineering and Physical Sciences Research Council and Biotechnology and Biological Sciences Research Council. | ||||||
other | The Advanced Processor Technologies (APT) group researches advanced and novel approaches to processing and computation and is led by Professor Steve Furber. | ||||||
other | New projects include SpiNNaker, Transactional Memory, and TERAFLUX. | ||||||
other | Academic staff in the group include Dr Nick Filer, Dr Jim Garside, Dr David Lester, Dr , Dr John V Woods, Dr Javier Navaridas, Dr Vasilis Pavlidis, Dr Dirk Koch, Dr Antoniu Pop and Emeritus Professor Ian Watson, visiting Professor Alasdair Rawsthorne and Fellow Barry Cheetham. | ||||||
other | Past research projects include Jamaica, AMULET microprocessor, Network On Chip, Asynchronous Digital signal processors and System on a chip. | ||||||
other | The Bio-Health Informatics Group (BHIG) conducts research in Bioinformatics and Health informatics ranging from the applications in molecular biology through to clinical e-science and healthcare applications. | ||||||
other | Academic staff in the group include Emeritus Professor Alan Rector, Professor Andy Brass and Robert Stevens. | ||||||
other | The Formal Methods group has a very broad span of interests, ranging from developing the new mathematics of computational behaviour, to the study and development of system design and verification methods. | ||||||
other | There is a large group dedicated to the automation of logic including world-champion Vampire. | ||||||
other | The group is led by Professor Allan Ramsay and includes Professor Peter Aczel, Professor Andrei Voronkov, Professor Howard Barringer amongst more than a dozen staff and a large number of research students. | ||||||
other | The Information Management Group (IMG) conducts basic and applied into the design, development and use of data and knowledge management systems. | ||||||
other | Such research activities are broad in nature as well as scope, including basic research on models and languages that underpins activities on algorithms, technologies and architectures. | ||||||
other | Challenging applications motivate and validate this research, in particular the Semantic Web and e-Science. | ||||||
other | Examples of recent research include Protégé, Utopia Documents, myGrid, Taverna workbench, myExperiment, Open PHACTS. | ||||||
other | Academic staff in group include Professor Carole Goble CBE, Professor Norman Paton, Professor Ulrike Sattler, Professor Robert Stevens, Sean Bechhofer, Suzanne Embury, Alvaro A. | ||||||
other | A. Fernandes, Simon Harper, Bijan Parsia, Rizos Sakelloirou, Sandra Sampaio and Ning Zhang. | ||||||
other | The Machine learning and Optimisation (MLO) group conduct world-leading research into a wide range of techniques and applications of machine learning, optimization, data mining, probabilistic modelling, pattern recognition and machine perception. |
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