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Wnt Signaling Pathway in Tooth Development

Wnt Signaling Pathway in Tooth Development. Yu Jian [Abstract] Tooth development begins with reciprocal signaling interactions between the neural-crest-derived ectoderm epithelium and the ectomesenchyme cells. In recent two decades, a mass of signaling molecules and transcription factors which are crucial for these processes have been confirmed, among which Wnt signaling pathway plays a key role in the regulation of embryo tooth development. This article reviews the research advancements on the function of Wnt signaling pathway during the course of embryo and postnatal tooth development as well as relevant molecular biological mechanism, providing new inspiration for understanding the mechanism of tooth development and associated disease. [Key words] Tooth development, Wnt signaling pathway, Mechanism. Tooth development starts with reciprocal signaling interactions between the ectoderm epithelium and the ectomesenchyme cells derived from the neural crest[1]. The first sign of tooth development is acknowledged as the thickening of the oral epithelium, then the epithelium begins to invaginate into the underlying mesenchyme to form buds[2]. Central features of tooth morphogenesis are the generation of the epithelial placode, the budding of the epithelium, the condensation of mesenchyme around the bud and the folding and growth of the epithelium generating the shape of the tooth crown. The communication between the two tissues, the epithelium and the mesenchyme, is the key regulatory mechanism on governing tooth development. The language that cells use for communication is composed of mainly secreted signal molecules and growth factors. The most studied and universal signals are members of four conserved families, transforming growth factor beta (TGF-b, includes BMPs and activins), fibroblast growth factor (FGF), sonic hedgehog (Shh, in sonic hedgehog teeth only) and Wnt[1]. Wnt proteins mediate the transduction of at least three major signaling pathways that play central roles in many early and late developmental decisions[3]. Wnt genes regulate cell growth, development, migration and differentiation[4]. Wnt genes encode secreted glycoproteins, usually 350–400 amino acids in length. The degree of sequence identity in Wnt proteins is minimally 18%, including a conserved pattern of 23-24 cysteine residues, in addition to other invariant amino acids[4]. Wnt signals transduce many distinct pathways, three of which have been the most studied these past decades. Among these three major pathways, the first to be elucidated was the Wnt/β-catenin pathway, often called the “canonical” Wnt pathway. After that, several others called “non-canonical” Wnt pathways were discovered; these involve many of the same components used by the canonical pathway but with molecular relationships between these components that are altered relative to the canonical pathway, or they utilize different transducing molecules. The most studied of these non-canonical Wnt pathways are the planar cell polarity (PCP) pathway and the Wnt-calcium pathway[4, 5]. In this article, it will primarily focus on Wnt signaling pathway, paying particular attention to recent insights. Research advances on the function of Wnt signaling pathway during the course of embryo and postnatal tooth development as well as relevant molecular biological mechanism are reviewed, offering new principles for understanding the mechanism of tooth development and associated disease. 1. The role of Wnt signaling pathway in the initial stage of dental germ The early arrest of tooth development in Lef1 mutant mice suggested that Wnt signaling pathway may have an essential effect in early tooth development. Wnt10b was expressed especially in mesial cells of the molar dental epithelial thickening and not in the oral epithelium. Wnt5a exhibited the similar graded proximo-distal (P-D) increased in the expression in mandibular and maxillary mesenchymal expression as MFrzb1 and Mfrp2. Wnt4 transcripts together with the Wnt receptor MFz6 exhibited uniform expression in the oral, dental and head epithelium. Wnt3 and Wnt7b were expressed in the oral epithelium but were notably absent from the dental epithelium[6]. Fjeld K et al.[7] found that members of the Dickkopf (Dkk) family modulated the Wnt signaling pathway by binding to the Wnt receptor complex. Dkk1 was prominently expressed in the distal, incisor-bearing mesenchyme area of the mandibular process during the initial stages of tooth formation. Dkk2 was discovered in the dental papilla, whereas Dkk3 was specifically expressed in the putative epithelial signaling centers, the primary and secondary enamel knots. By performing tissue recombinant experiments and analyzing the effects of signaling molecules, Kettunen P found that in early oral and dental epithelia, which instructed tooth formation, and epithelial Wnt4 induced Sema3a expression in the presumptive dental mesenchyme before the arrival of the first dental nerve fibers. By analyzing Sema3a and its receptor Npn1 knockout mouse embryos, they found that Sema3a regulated dental trigeminal axon navigation and patterning, as well as the timing of the first mandibular molar innervation, and that the effects of Sema3a appeared to be mediated by Npn1 presented in the axons[8]. Wnt7b acted to repress Shh expression in oral ectoderm, thus maintained the boundaries between oral and dental ectodermal cells. Implantation of beads soaked in Shh protein into Wnt7b-infected explants resulted in complete rescue of tooth development, confirming that the repressive action of Wnt7b specifically affected Shh signaling[9]. 2. The role of Wnt signaling pathway in bug stage of dental germ Using nuclear localization of β-catenin, however, Wnt activity was found not only in the tooth bud epithelium but also the underlying mesenchyme[2]. Wnt/β-catenin signaling was active throughout tooth development. A gain of function mutation in epithelial β-catenin resulted in expanded expression of several key regulatory genes. Conversely, expression of these key dental regulators was disrupted when epithelial and mesenchymal Wnt/β-catenin signaling was inhibited soon after tooth initiation in Dkk1 expressing embryos, resulting in arrested development at the early bud stage[10]. These data indicated that Wnt/β-catenin signaling was required within dental epithelial cells for tooth development beyond the lamina-early bud stage. The mechanism underlying arrested development in Dkk1 expressing embryos appeared to involve loss of expression of Bmp4, Msx1, and Msx2. Consistent with this model, tooth development arrested at a similar stage in Msx1−/− Msx2−/− mice and Wnt-inhibited mice[11]. Lef1 and PITX2 function in the Wnt signaling pathway by recruiting and interacting with β-catenin to activate target genes. PITX2 isoforms regulated the Lef1 promoter, and β-catenin synergistically enhanced activation of the Lef1 promoter in combination with PITX2 and Lef1 isoforms. PITX2 enhanced endogenous expression of the full-length β-catenin-dependent Lef1 isoform (Lef-1 FL) while decreasing expression of the N-terminally truncated β-catenin-independent isoform[12]. Recombinations of epithelial and mesenchymal tissues from developing teeth of wild-type and Lef1−/− embryos showed that Lef1 was required only transiently in epithelium in a tissue-nonautonomous manner, which was rather unexpected for a component of a signal reception pathway[13]. In addition, Fgf4 beads induced rapidly the expression of Fgf3 in dental mesenchyme and that both epithelial and mesenchymal Fgf proteins induced the delayed expression of Shh in the epithelium. Taken together, these data indicated that a single target of Lef1 can account for the function of Lef1 in tooth development and for a relay of a Wnt signal reception to a cascade of Fgf signaling activities, allowing for a sequential and reciprocal communication between epithelium and mesenchyme[12]. 3. The role of Wnt signaling pathway in cap stage of dental germ At the cap stage of dental germ the primary enamel knots were evident. Expression of Lef1, Wnt3, Wnt6, Wntl0 and MFz6 were seen exclusively in the primary enamel knots. Wnt5a and MFrzb1 showed strong expression in dental papilla mesenchyme[6]. At the cap stage Dkk1 and Dkk2 transcripts were observed in the cervical region of the mesenchymal dental papilla and in the dental follicle, respectively, whereas Dkk3 mRNAs were specifically expressed in the epithelial PEK, mostly at the buccal side[7]. 4. The role of Wnt signaling pathway in bell stage of dental germ Inducible Dkk1 expression after the cap stage caused formation of blunted molar cusps, downregulation of the enamel knot marker p21, and loss of restricted ectodin expression, revealing requirements for Wnt activity in maintaining secondary enamel knots[14]. The inhibitory effect of Wise on Wnt signaling was further examined by assaying secondary head induction, which could be induced by simultaneous inhibition of both BMP and Wnt signaling[10]. Ectodin, a secreted bone morphogenetic protein (BMP) inhibitor, is expressed as a ‘‘negative’’ image of mouse enamel knots. Furthermore, the ectodin-deficient mice have enlarged enamel knots, highly alters cusp patterns, and extra teeth. Unlike in normal teeth, excessive BMP accelerates patterning in ectodin-deficient teeth. The ectodin is critical for robust spatial delineation of enamel knots and cusps. These data placed Wnt/β-catenin signaling upstream of key morphogenetic signaling pathways at multiple stages of tooth development and indicated that tight regulation of this pathway was essential both for patterning tooth development in the dental lamina and controlling the shape of individual teeth[15]. At the early bell stage, Wnt reporter activity localized to the developing molar cusps and by the late bell stage was present asymmetrically in the epithelial enamel knots of developing molar cusps. Wnt/β-catenin signaling was active at multiple stages of tooth development. Mutation of β-catenin to a constitutively active formed in oral epithelium caused formation of large, misshapen tooth buds and ectopic teeth, and expanded expression of signaling molecules important for tooth development. Conversely, expression of key morphogenetic regulators including Bmp4, Msx1, and Msx2 was downregulated in embryos expressing the secreted Wnt inhibitor Dkk1, which blocked signaling in epithelial and underlying mesenchymal cells[16]. 5. The role of Wnt signaling pathway in secretory stage of dental germ Dspp and Wnt10a were co-localized in the differentiated odontoblasts. Wnt10a and cell to matrix interactions played an important role for odontoblast differentiation and that Wnt10a linked tooth morphogenesis and the differentiation of odontoblasts[17]. In addition to being expressed in the developing mandibular bone, Dkk1 was prominently up-regulated in the preodontoblasts and the expression continued in the secretory odontoblasts. In contrast, Dkk3 was transiently expressed in the ameloblasts before enamel matrix secretion. When comparing the Dkk1-Tg first molars with the age-matched controls, it was observed striking differences in the appearance of the dentin tubules, with the tubular processes being sharply reduced and disorganized. Analysis of quantitative data showed a significant reduction of dentinal tubule number in Dkk1-Tg mice[18]. 6. The role of Wnt signaling pathway in postnatal tooth development Hertwig’s epithelial root sheath (HERS) is very important for root development. Syndecan-1 is cell surface heparan sulfate proteoglycans (HSPGs) and it plays an important role for Wnt/β-catenin signaling pathway as a coreceptor[19]. Genetic data from humans and mice revealed that the formation of cementum was sensitive to intra- and extracellular phosphate/pyrophosphate distribution. Studies of the temporal effects of extracellular phosphate on global patterns of gene expression in a line of immortalized mouse cementoblasts indicated that extracellular phosphate altered the expression of genes comprising several gene ontology (GO) groups, including Wnt signaling. The analysis of existing data demonstrated a role for Wnt signaling in bone formation or remodeling and tooth development. In this regard, the ability of ePi to alter the expression pattern of genes involved in Wnt signaling is of interest. The expression of one secreted blocker of canonical Wnt signaling, Sfrp4, was enhanced, while that of another, Wif1, was depressed. Two Wnt signaling genes, Wnt10b and Wnt4, were diminished, as was the level of the membrane-bound inhibitor Dkk 3 (Dickkoff)[20]. Tumors associated with osteomalacia elaborated the novel factor(s), phosphatonin(s), which caused phosphaturia and hypophosphatemia by cAMP-independent pathways. Results showed that secreted frizzled-related protein-4 (sFRP-4), a protein highly expressed in such tumors, was a circulating phospha-turic factor that antagonized renal Wnt-signaling[21]. Studies using Wnt reporters have revealed discrepancies between nuclear B-catenin and Wnt reporter expression during tooth development, and so it was wished to clarify Wnt responsiveness using the Axin2 reporter during early stages of tooth development. Previous studies have also concentrated on molar development and so expression in the incisors was also investigated. In addition, because canonical Wnt activity has so far only been investigated up to the bell stage of dental germ, it was investigated expression at later stages of tooth development to gain an insight into the possible later roles of canonical Wnt signaling in tooth development[2]. Canonical Wnt activity was completely absent at all stages investigated in the developing ameloblasts in molars and incisors, while presented in areas of the epithelium where ameloblasts did not form (molars-enamel–free areas, incisors–lingual side and tip of tooth). This indicated that canonical Wnt activity did not play a role in the terminal differentiation of ameloblasts and may, in fact, act to keep epithelial cells in a proliferative state[22]. In conclusion, Wnt signaling pathway plays a vital role in the development of multiple ectodermal appendages including teeth. As the regulation of Wnt signaling pathway emerges during the course of embryo and postnatal tooth development, it is of great significance to study the exact molecular biological mechanism. Moreover, more efforts should be made so as to achieve a better understanding for tooth development and associated disease, and new strategies which utilized to activate this pathway for tooth regeneration are needed as well. References [1] Thesleff I. The genetic basis of tooth development and dental defects. Am J Med Genet A 2006, 140(23): 2530-2535. [2] Lohi M, Tucker AS, Sharpe PT. Expression of Axin2 indicates a role for canonical Wnt signaling in development of the crown and root during pre- and postnatal tooth development. Dev Dyn 2010, 239(1): 160-167. [3]Croce JC, McClay DR. Evolution of the Wnt pathways. Methods Mol Biol 2008, 469: 3-18. [4]Cadigan KM, Nusse R. Wnt signaling: a common theme in animal development. Genes Dev 1997, 11(24): 3286-3305. [5]Gordon MD, Nusse R. Wnt signaling: multiple pathways, multiple receptors, and multiple transcription factors. Journal Of Biological Chemistry 2006, 281(32): 22429-22433. [6]Sarkar L, Sharpe PT. Expression of Wnt signalling pathway genes during tooth development. Mech Dev 1999, 85(1-2): 197-200. [7]Fjeld K, Kettunen P, Furmanek T, et al. Dynamic expression of Wnt signaling-related Dickkopf1, -2, and -3 mRNAs in the developing mouse tooth. Dev Dyn 2005, 233(1): 161-166. [8]Kettunen P, Loes S, Furmanek T, et al. Coordination of trigeminal axon navigation and patterning with tooth organ formation: epithelial-mesenchymal interactions, and epithelial Wnt4 and Tgfbeta1 regulate semaphorin 3a expression in the dental mesenchyme. Development 2005, 132(2): 323-334. [9]Sarkar L, Cobourne M, Naylor S, et al. Wnt/Shh interactions regulate ectodermal boundary formation during mammalian tooth development. Proc Natl Acad Sci U S A 2000, 97(9): 4520-4524. [10]Liu F, Chu EY, Watt B, et al. Wnt/beta-catenin signaling directs multiple stages of tooth morphogenesis. Developmental Biology 2008, 313(1): 210-224. [11]Kuraguchi M, Wang XP, Bronson RT, et al. Adenomatous polyposis coli (APC) is required for normal development of skin and thymus. PLoS Genet 2006, 2(9): e146. [12]Amen M, Liu X, Vadlamudi U, et al. PITX2 and beta-catenin interactions regulate Lef-1 isoform expression. Molecular And Cellular Biology 2007, 27(21): 7560-7573. [13]Kratochwil K, Dull M, Farinas I, et al. Lef1 expression is activated by BMP-4 and regulates inductive tissue interactions in tooth and hair development. Genes Dev 1996, 10(11): 1382-1394. [14]Kassai Y, Munne P, Hotta Y, et al. Regulation of mammalian tooth cusp patterning by ectodin. Science 2005, 309(5743): 2067-2070. [15]Itasaki N, Jones CM, Mercurio S, et al. Wise, a context-dependent activator and inhibitor of Wnt signalling. Development 2003, 130(18): 4295-4305. [16]Sarkar L, Sharpe PT. Inhibition of Wnt signaling by exogenous Mfrzb1 protein affects molar tooth size. Journal Of Dental Research 2000, 79(4): 920-925. [17]Yamashiro T, Zheng L, Shitaku Y, et al. Wnt10a regulates dentin sialophosphoprotein mRNA expression and possibly links odontoblast differentiation and tooth morphogenesis. Differentiation 2007, 75(5): 452-462. [18]Han XL, Liu M, Voisey A, et al. Post-natal effect of overexpressed DKK1 on mandibular molar formation. Journal Of Dental Research 2011, 90(11): 1312-1317. [19]Liu BY, Kim YC, Leatherberry V, et al. Mammary gland development requires syndecan-1 to create a beta-catenin/TCF-responsive mammary epithelial subpopulation. Oncogene 2003, 22(58): 9243-9253. [20]Rutherford RB, Foster BL, Bammler T, et al. Extracellular phosphate alters cementoblast gene expression. Journal Of Dental Research 2006, 85(6): 505-509. [21]Berndt T, Craig TA, Bowe AE, et al. Secreted frizzled-related protein 4 is a potent tumor-derived phosphaturic agent. Journal Of Clinical Investigation 2003, 112(5): 785-794. [22]Kratochwil K, Galceran J, Tontsch S, et al. FGF4, a direct target of LEF1 and Wnt signaling, can rescue the arrest of tooth organogenesis in Lef1(-/-) mice. Genes Dev 2002, 16(24): 3173-3185. Wnt Signaling Pathway in Tooth Development

Designing A Creep Testing Machine Engineering Essay

A Creep Testing Machine is one that accurately measures the creep of a material under constant load and at elevated temperatures until final rupture. Basically, it demonstrates the effect of Temperature on Creep. Creep is defined as the time dependant deformation of a material under constant load at constant elevated temperature. The resulting strain is a function of applied stress, temperature and time. Creep is increasingly important in industry in many different applications ranging from turbine rotors, high pressure steam tubes, suspended cables, tightened bolts where materials are subjected to extremely high temperatures and stresses which may cause them to change size, shape and lead to rupture. So the main objective of a creep test is to measure how a given material will perform under constant loads and elevated temperatures to make sure they are ready for use in industry under such conditions. In a creep test, a tensile specimen is subjected to a constant load inside a furnace set to a specified temperature maintained at a constant high temperature. The material will go through 3 phases of creep; primary, secondary (steady state, lengthiest stage) and tertiary until it ruptures. The test may run on for days until eventually the specimen fails and the creep properties are recorded. Applications in industry Creep testing is increasingly important in large areas of industry. There are three types of high temperature industry applications. Displacement limited applications: where precise dimensions must be maintained, examples of which are in turbine rotors/aircraft turbine blades. Rupture limited applications: where fracture must be avoided, such as in steam tubes. Stress-relaxation limited applications: where initial tension relaxes with time such as in suspended cables and tightened bolts. Aims and Objectives: To fully design a Creep Testing Machine within a hard budget in the given time frame – by the end of the semester in week 13. The reason behind the project is to provide AUT Engineering School with its first working Creep Machine. It will provide an opportunity for materials to be tested for Creep under extremely high temperatures for research or educational purposes after the project is completed. The very high temperatures will allow for testing stronger more complex materials such as alloys with higher melting points. A fully detailed, clear and FEA tested 3D CAD drawing will be produced, effectively demonstrating the complete final design of the Creep Testing Machine in all of its dimensions and absolute properties. Deliverables: The machine will be designed to be cheap, practical, robust, reliable, easy to use, relatively lightweight, safe (to the touch), long lasting and professional looking. The project meets the academic requirements of my qualification as it will require a great deal of knowledge I have obtained from papers such as: material science, manufacturing technology, CAD/solidworks engineering design, quantitative techniques, thermodynamics, solid mechanics and heat transfer papers. Potential Industry organisations involved: Steel suppliers high temperature material suppliers high temperature measuring/control device distributers electronic and electrical control distributers insulation material suppliers Resources (likely required): Solidworks/CAD design programs, matlab/computer programming programs, Microsoft excel, electrical/electronic equipment. Workshop machines: milling, lathe, drilling, soldering, welding machines and more. Project Plan Plan/chart will be subject to refinement throughout the duration of the project. Project Information This project is supposed to be carried on through until the end of the 4th year industrial project. From now until the end of the semester we will be designing the Creep Testing Machine completely, putting the designs through numerous tests and immense scrutiny until it is certain that the design will be achievable and the project a total success. Our supervisor, Tim, informed us with the estimated budget for this project of around $5,000NZ. This is a hard budget and we are not to exceed it under any circumstances. Therefore an important goal of this project is to stay under budget (by a decent sized margin if possible) and design a relatively cheap Creep Testing Machine that can be delivered realistically for the 4th year industrial project (where the machine should be produced). The Creep machine consists of several main components that fit into three categories; Heat, mechanics and control. The components are as follows: Frame, Furnace, Control, Electronics Data acquisition, Strain measurement device (extra), Emergency shut off, Temperature measurement device, Grip system, Timer, On/Off switch and Loading mechanism. The furnace should be designed to reach exceedingly high temperatures of up to 800C so that it may be suitable for creep testing on a wide range of specimen materials (high T alloys etc) for research and educational purposes at the AUT Engineering department. During our first group meeting after the first formal meeting with our supervisor, we (the project team) assigned several components to each of us to carry out detailed research and gather our findings before the next meeting with Tim. The larger, more complex components namely the furnace and loading mechanism were both shared between me and Ramez, Steven and John-Paul respectively. The full details are illustrated in my logbook. Literature review So the components assigned to me for research were the Furnace, strain measuring device and the frame. I began dissecting the furnace into its individual components and features. A standard muffle furnace consists of insulation, the body, heating element, temperature measurement/controller and door with locking mechanism, compartments for other components (load train, measuring apparatus), mounting kit and air vents. After I completed some general research I developed a good and original idea of what our Creep testing machine will consist of: Furnace insulation will either consist of two different materials namely refractory firebrick and refractory ceramic fibre blanket or solely just ceramic fibre blanket/wool. These are highly heat resistance materials (one that has especially low thermal conductivity value – k). Fire brick; would be the first line of insulation and the main barrier to heat loss from the furnace chamber with a k value of ~ 0.21 (@800C). Ceramic fibre; would be the surrounding/main layer of insulation and will be put around the fire brick and on the inner door surface. It has a k value of ~ 0.22 (@800C). There are several types of suitable fibre and one will be chosen based on its cost and thermal properties. The reason that firebrick is being considered as a layer of insulation is because of the ease of fitting it with heating elements. However they are more bulky and considerably heavier than ceramic blankets. The insulation choices will be theoretically tested for suitability using standard thermal resistance equations: Qtransfer = ∆T/Rth Rth = (1/hiA) (L/kA) (1/hoA) Where; L is the minimum thickness of insulation, k is its thermal conductivity, h is the convection heat transfer coefficient and Rth is the total heat resistance. Choice and list of possible heating elements why chosen. Take into accnt start up hting time The minimum insulation thickness required is found as follows; Properties: Power in: 1.6kW heating element ∆T = TMAX – TAMB Insulation, Ceramic fibre: k = 0.22W/m2K hi = 10W/mK, ho = 40W/mK Rth = (1/hiA) (L/kA) (1/hoA) Rth = (1/10*0.35*0.15) (L/0.22*0.35*0.15) (1/40*0.35*0.15) L = 21.87mm L Specimen HC H WC WW Body Chamber Initial Dimensions: Specimen ASTM: Round dog bone: Length, L = 127mm Flat dog bone: Length, L = 101mm Gripping mechanism: Length, L ~ 40mm Only round dog bone specimens will tested – ASTM creep/fatigue specimens. Full dimensions below: (( gripping mechanism size)) The bottom pull rod will be fixed in place but the top pull rod will be adjustable such that the specimen can be placed into the gripping mechanisms. Therefore this will be considered when estimating the height of the furnace and its chamber. Preferably, the chamber should be small in size such that it can be heated up quicker and use up less energy thereby increasing the efficiency of the furnace. Therefore, Chamber width, WC = 150mm Chamber Length, LC = 150mm Chamber Height, HC = 350mm As the minimum insulation thickness ranges from 21 to27mm (depending on the heating element’s power rating) therefore, it will be necessary to have two layers of 25mm thick insulation around the chamber. So the outer body dimensions will be about: Width, W = 250mm Length, L = 200mm Height, H = 450mm The main body will almost certainly be made from mild steel due to its relatively low cost and robust, tough nature. The heating element will have to be either kanthal A1 or Nichrome most probably in wire form so that it may be easily routed into specially made grooves in the firebrick. With temperature ranges up to 1800C and relatively low cost kanthal A1 may be more suitable in this case. The time for the furnace to reach its required temperature will also be taken into account and the choice of heating element (power rating, shape and material) will be based on the time it takes to heat the chamber to a stable working temperature and the thickness of insulation required to work at such energy inputs. Also whether or not the heating element can be fitted into the insulation material will be a factor. Temperature measurement and control device will most probably be a standard high temperature thermocouple. There are many different types, shapes and sizes but most are relatively cheap and affordable regarding the project budget. The thermocouple will give the give the reading and control the temperature in the chamber (keeping it at a constant working temperature) by clicking the relay on and off when necessary. The furnace body will have to be made from a hard, tough and relatively thick material. This is why I think that mild steel sheets should be purchased and formed to the desired shape. Processes such as bending and cutting can be undertaken at the mechanical engineering workshop at AUT. Mild steel plates/sheets prices per quantity list of possible materials, choose most suitable. An idea that I have deemed suitable for the furnace is that a simple solid, robust steel filing cabinet could be converted into a furnace body. Simple tools and workshop resources available at AUT can be used to machine the necessary features to make it work as a muffle furnace. This could potentially save a great deal of investment that could be used in other areas where it is needed more (concerning the project). The strain measuring device will have to be one that works efficiently under the high temperatures experienced with muffle furnaces. I have narrowed it down to either a high temperature extensometer or an LVDT. The most suitable device is the high temperature extensometer as they are specifically suited to such elevated temperatures and give an extremely accurate strain/displacement measurement beyond ASTM standards. They can also be attached easily to standard creep testing furnaces. However, a strain measuring device is an optional extra as the specimen displacement can be accurately measured after the specimen ruptures and simple calculations can be used to determine the strain experienced. A strain measuring device would be for convenience purposes only. List of strain measuring devices, filter to high temp use devices, then the only suitable model prices and deem if actually suitable. Speak with Wassim. Extensometer or LVDT. Resources Introduction to Engineering Design, Andrew Samuel and John Weir Manufacturing Engineering and Technology, Serope Kalpakjian Heat and Mass Transfer a practical approach, Yunus A Cengel Thermodynamics an Engineering approach, Cengel and Boles Materials Science and Engineering an Introduction, William D Callister Jr

Earth’s Natural Resources

essay help online Earth’s Natural Resources.

QUESTION 1Coal deposits were formed when ancient plants died and were buried in sediment layers. After burial in sediment layers, what happened next to change them to coal?addition of water to form hydrocarbon moleculescompression by extreme pressure over millions of yearsreaction with acids in the environment3 points QUESTION 2Many experts predict that our oil supplies will run out in the next few decades. Describe two factors that may extend our world oil supplies and two factors that may more rapidly deplete our world oil supplies.– Font family –Andale MonoArialArial BlackBook AntiquaComic Sans MSCourier NewGeorgiaHelveticaImpactSymbolTahomaTerminalTimes New RomanTrebuchet MSVerdanaWebdingsWingdings– Font size –1 (8pt)2 (10pt)3 (12pt)4 (14pt)5 (18pt)6 (24pt)7 (36pt)– Format –HeadingSub Heading 1Sub Heading 2ParagraphFormatted Code– Font family —- Font size –Path: pWords:05 points QUESTION 3The largest exporter of oil in the world isSaudi ArabiaJapanKuwait3 points QUESTION 4Describe what oil shale is and explain the advantages and disadvantages associated with its use and extraction.Path: pWords:04 points QUESTION 5Why can lignite only be used close to the area in which it is found?It has such a low energy content that transporting it is not worth it.It has toxic metals in it that prevent it from being legal to ship.It is too heavy to transport out of the area from which it is mined.3 points QUESTION 6Coal is burned to produce steam in an electrical power plant. The steam is then used toturn a motor called a turbineconvert mechanical energy to electrical energyextract atoms from the coal3 points QUESTION 7Which of the following gases is the major byproduct of fossil fuel combustion?water vapormethanecarbon dioxide3 points QUESTION 8Fossil fuel combustion removes deeply stored carbon from the land and releases it to the atmosphere. True False2 points QUESTION 9Of the two nuclear processes, fusion and fission, which one is used to generate commercial nuclear power? Why is the other one not used?Path: pWords:04 points QUESTION 10What happens to a uranium-235 atom when it is bombarded with neutrons? How is this process used to generate nuclear power?Path: pWords:04 points QUESTION 11After uranium is mined from the ground, it is leached to produce a substance called ______.yellowcakeuranium hexafluoridereactor fuel3 points QUESTION 12The process that increases the amount of fissionable uranium-235 in nuclear fuel is calledampingleachingenrichment3 points QUESTION 13Control rods can be taken away from a nuclear reactor to make the fission reactiontake place at lower temperaturesconvert to a fusion reactiongo faster3 points QUESTION 14The part of a nuclear reactor that spins because of exposure to heat energy in steam is thecontrol rodturbinegenerator3 points QUESTION 15What happens during the process of decommissioning a nuclear power plant?Path: pWords:05 points QUESTION 16Using nuclear fuel emits less sulfur and mercury into the environment than does using fossil fuels. True False2 points QUESTION 17What is the difference between renewable and non-renewable energy? Give two examples of each.Path: pWords:04 points QUESTION 18Wind farms are ideally located in areas withsteady winds at a speed of about 13 mphintermittent winds with speeds well over 50 mphsteady but slow winds less than 10 mph3 points QUESTION 19The worldwide leading source of renewable energy iswind powersolar powerhydropower3 points QUESTION 20Energy derived from hot fluids and rocks beneath Earth’s surface is calledhydropowersolar powergeothermal power3 points QUESTION 21Wind power is most practical when wind speeds are over 55 mph. True False2 points QUESTION 22Describe two advantages and two disadvantages associated with the use of geothermal power.Path: pWords:05 points QUESTION 23As long as wind turbines are manufactured correctly, they do not generally pose a threat to birds. True False2 points QUESTION 24An ore is a rock thatcontains enough of a mineral resource to be economically profitablecontains any amount of a mineral resourcecontains no waste materials, but is made entirely of a pure mineral substance3 points QUESTION 25Most mining deaths take place inopen pit minesstrip minessubsurface mines3 points QUESTION 26In _______, the mineral ore is taken out of a surface hole layer by layer, and the hole just keeps getting bigger and pit miningmountaintop removaldrift mining3 points QUESTION 27What type of mining is commonly used to extract coal from the Appalachian area of the United States?shaft miningmountaintop removalopen pit3 points QUESTION 28What type of subsurface mining involves digging deep underground tunnels and then sending workers down in cages?shaft mininghard rock miningdrift mining3 points QUESTION 29Acid mine drainage can develop when rainwater seeps throughmine tailingsmineral oreoverburden3 points QUESTION 30Acid mine drainage forms when water reacts with _____ in discarded mining materials.nitrogenmercurysulfur3 points QUESTION 31Acid mine drainage contains sulfuric acid, which can kill or harm wildlife. True False2 points QUESTION 32Collapsing underground mines can fracture natural gas pipelines. True False
Earth’s Natural Resources

Supply Chain Management In Emirates Airline Commerce Essay

The aviation industry is the fastest growing sector worldwide that has enhanced the travelling experience of passengers across the globe. With breakthrough inventions happening in the aviation industry, the business environment has become tough and competitive for the airlines operating in present times (Shieh, 1740). Recently, the emergence of low-cost airlines has severely impacted the businesses of those airlines that have been leading the aviation industry for decades. However, these new entrants still lag behind in the development of an effective Supply Chain Management (SCM) system. In the last few years, the organization structures of many airline companies have undergone drastic transformations to incorporate the challenges encountered during the tough economic time that have been prevailing since 2008. Since the aviation industry has become dynamic and competitive, every player in the market has to ensure that it meets the demands of its target market effectively (Bolstorff and Robert, 40). In the airline industry, only those companies can survive that have a competitive edge in their SCM process which will ensure that they are providing premium quality services at competitive rates to their customers. Emirates Airline is among those companies that entered the market with the aim of becoming the leader in the aviation industry worldwide. It is among the top-ranked airlines available in the market which has been providing excellent range of services to its customers ranging from leisure to business travelling packages. Emirates Airline was the pioneer in introducing the concept of online booking and e-check-in system in United Arab Emirates (UAE). In order to exceed the expectations of its customers, the management team has developed a separate division ‘Emirates Engineering’ for developing an effective SCM framework (About Emirates Engineering, 3). Presently, Emirates Airline has a well-designed and strategically developed SCM system but there are some areas that need to be addressed by the Procurement and Operations department of the organization to effectively manage the prospective challenges in the aviation industry. Background of Emirates Airline Emirates Airline also known as Emirates is the top-ranked airline that is based at Dubai International Airport in Dubai, UAE. It is considered to be the largest airline in the Middle Eastern region that has been operating about 2,500 flights on weekly basis from Terminal 3 which is its central hub. Emirates is offering its services in 122 cities that are spread in 74 countries; it is the chief subsidiary of the Emirates Group and employs more than fifty thousand employees. The airline is owned by the Government of Dubai and its cargo activities are performed by the Emirates SkyCargo division of the Emirates Group (The Emirates Story, 4). The primary aim of this airline since its inception is to provide high quality services to the customers; quantity is never an important factor for performance evaluation of the airline. From regional travel destinations, Emirates Airline has evolved into an international airline that carries millions of passengers to various destinations on yearly basis. Emirates has divided its airline businesses into three broad categories i.e. international cargo division, airline IT developer and full-fledged travel and tourism destination management division (The Emirates Story, 23). Emirates has an exclusive range of wide-bodied aircraft fleet that comprises of three main aircraft families i.e. Boeing 777, Airbus A380, and Airbus A330/A340. It has set a policy that it will always keep a young fleet which stands as 6.7 years on average and it ensures that the fleet is renewed frequently (About Emirates Engineering, 30). In order to have effective operational facilities for its aircrafts, Emirates has developed an entire new division ‘Emirates Engineering’ where all the matters related to quality assurance, maintenance and repair of the fleet is performed. Currently, it has passenger aircraft fleet of 175 and nineteen aircraft are still on order (Engineering Procurement Aircraft, 34). SCM structure of Emirates Airline SCM has evolved to become an integral part of all organizations and it is the pre-requisite of every airline that wants to maintain a competitive position in the market. Initially, Emirates had a Procurement and Operations department that had the responsibility of managing the information and materials data and its main focus was on developing a strong internal value chain. The primary focal point of the department was to be a supplier’s supplier to the customer’s customer. When Emirates faced problems in the functioning of its aircraft in 2004, the management team decided to restructure the complete procurement, operations and logistics aspects of the business (Storey, Caroline, Janet and Alan, 756). The Procurement and Operations department was divested from the other functions and Emirates Engineering was established as a separate group. Under this new section, SCM was defined as “combining the impacts of all companies that are involved in the production, distribution and sales of the airline goods and services i.e. from suppliers to the manufacturers to the distributors to the final consumers.” According to this new approach, every stakeholder involved in the production and operation network is part of the supply chain (Kannan and Keih, 153). Emirates Engineering is viewed as the best and highly technologically advanced facility for aircraft repair, maintenance and servicing. In order to provide adequate engineering support to the entire fleet of Emirates, the department has outsourced the maintenance contracts to third parties. In order to meet the industry benchmarks, all aspects of Engineering, Quality, Planning, Logistics and Maintenance are effectively managed and implemented by highly skilled and well-experienced professionals who have ample knowledge about the particularities of SCM process (Engineering Materials Management, 35). There is a Procurement section in the Emirates Engineering division that provides support to the airline operations by undertaking all contracting and outsourcing contracts of every commodity of aircraft that comprise of fleet, equipment, spares, power plants, catering services and many more. There are four broad categories in the procurement department classified as power plans, airframe systems, cabin and avionics. The entire team is implementing a precise process approach by working as a cross-functional team; in such teams, the experts of all divisions are included to ensure that the supply chain requirements of the business are met at optimum level (Bhardawaj and Mitra, 60; Huan, Sunil and Ge, 24). This department bears the responsibility of managing cordial relations with suppliers for ensuring 100% satisfaction with the delivery and performance of the goods and services provided by them. In the airlines, quality of the aircraft is the utmost priority (Harrison and Remko, 140; Gunasekaran and E., 585) and Emirates Engineering section ensures that this area is never overlooked by the experts of the division. There is a distinctive management team for warranty and product support that is responsible for carrying out an array of activities such as contracts management, compliance with digital recording of documents, ensuring presence of a safe and secured storage area for every contractual documentation and appropriate administration of warranty and guarantees (Engineering Materials Management, 50). SCM Network of Emirates Airline The present Supply Chain network of Emirates Airline (Refer to Appendix I) can be divided primarily into three main chains that are inter-linked: Emirates Engineering that is providing top quality aircraft and facilities within the fleet to the Emirates Group so that it can meet the requirements of its customers who are the passengers. Product Support Agreements (PSAs) are signed between the Procurement Department and supplier of the division who ensure that the airline is provided aircrafts in accordance with the specifications. The suppliers then have agreements with their suppliers named as ‘direct suppliers’ who ensure that the finest raw materials are provided for manufacturing the fleet with precision. Value Chain Analysis of Emirates Airline In order to have effective management of procurement, operations and logistics department, it is vital for every organization to conducts its value chain analysis on an ongoing basis (Sisco and Joyce, 60). With the proper utilization of value chain analysis of entire SCM process, Emirates’ management team ensures that it properly allocates its resources for efficient management of inventory while adhering to the high quality standards required in the aviation industry (About Emirates Engineering, 34). The value chain analysis of Emirates Airline is explained below to briefly describe its activities as highlighted in Appendix II: The product development section of marketing department conducts market research on frequent basis to generate ideas for new products and services and work on its feasibility policy to decide about the cost requirements in accordance with the service standards of the industry. The material management team, component management team and procurement team work with the suppliers to ensure there is effective co-ordination among the teams and ensuring that right suppliers are included in the PSAs and proper measures are taken in developing healthy relationships with them. The flight and ground operations department of component management teams ensure that the inputs are effectively transformed into products of high quality that will add value to the airline’s operational activities. Customer Relations department which is an integral part of the after-sales service ensures that the passengers having any problem with their flights or baggage are properly handled. The personnel are trained in providing the superb service to the passengers both in-flight and on ground so that they have an excellent travelling experience. Human Resource department ensures that all employees are provided detailed information about the company’s policies, strategies and rules so that they ensure compliance with the work standards. The employees are given sufficient training so that they can exceed the expectations of the customers. IT department has the main responsibility of ensuring that a well-developed SCM system is implemented and managed to allow efficient flow of information that will ease decision making processes for various departments of the airline. Finance department is responsible for controlling the costs of managing the operations along with ensuring maintenance of effective auditing procedures so that everything is conducted within the legal boundaries. Product Life Cycle Management at Emirates As the business environment is becoming competitive and challenging for the organizations, it has become vital for them to continuously upgrade and introduce new and innovative their product and service offerings to proficiently fulfill the changing demands of the customers (Handfield, Robert and Steven, 6; Subhramain et al., 5). In airlines, product life cycle management is become a pre-requisite for maintaining the competitive edge in the market. Similarly, Emirates has created a separate division ‘Engineering Projects’ that assists the airline in employing the expertise of the professionals working in this department for evaluation, specification and negotiation of unique and new products and services. The entire process of product life cycle management is effectively monitored and the team guarantees that each and every step from generation of idea to the final delivery and acceptance are evaluated; any problems identified are addressed instantly to avoid any issues after complete development of the product. Within the department, there are two teams that are working on the development of its service offerings; one is Inflight Entertainment (IFE) team and other is Cabin Interior team (Engineering Projects, 3). The project team of IFE comprises of the specialists of products and professionals of IFE systems engineering. All team members are carefully selected to ensure that they have in-depth knowledge about IFE so that they can properly define, create and install an array of highly advanced and sophisticated inflight entertainment systems. A general product development process followed by IFE team is as follows: First of all, the experts work closely with the Original Equipment Manufacturers (OEMs) like Boeing and Airbus, product marketing and inflight services departments to develop a detailed list of the IFE system requirements. After the preparation of the list, the product vision is established so that everyone has an idea about the product that they perceive to be ideal for the end consumers. In the design and testing process, development milestones are set and they are coordinated and monitored in a group form by seeking opinion from the seat manufactures, third party suppliers, IFE suppliers and OEMs so that the process is carried out properly. The Buyer Furnished Equipment (BFE) list definition is referred for close monitoring of the IFE product specifications so that IFE system can support the new product installation process. The team provides follow up and support in the installation and integration activities of IFE system. IFE product development specifications are verified to ensure compliance with the requirements of the system. Inspection of the acceptance process of IFE system is done to ensure that support is provided for the existing IFE process. Before gaining entrance into the service, the spare parts list is prepared for the spares procurement department so that the recommendation of the experts can be taken. In-house training along with IFE service readiness activities are organized so that adequate support can be provided for the new system. After developing the personnel, the product development team works with the Supplemental Type Certificate (STC) certification houses, airline base maintenance and installation teams so that retrofit processes can be effectively coordinated. After the complete development of new IFE service, a maintenance and troubleshooting manual is developed along with software; all of these elements are designed, developed and delivered directly from the suppliers before the aircraft completely introduces the new service. The cabin interiors team undertakes various activities to ensure that the passengers have exceptional travelling experience by exceeding their expectations. This team has responsibility of performing a diverse range of activities which are as follows: Introducing unique and innovative features and amenities to enhance the comfort level of passengers. Developing the specifications for latest BFE products. Evaluation and selection of the best suppliers for BFE products. Coordinating the technology and managing the program required for management of the items of BFE. Providing support to other department for facilitating smooth introduction of contemporary aircrafts that have been added to its fleet. Role of Information Technology (IT) in SCM An effective SCM is one which has a strong IT system that will provide support to the organization in managing its operations effectively and productively (Blanchard, 80; Gaudenzi and Antonio, 116). With the help of an efficient IT system, the inventory and warehousing costs are reduced to a great extent; efficiency of the production process is enhanced; and inflight services are upgraded on constant basis to ensure that passengers are provided an extraordinary appealing and thrilling travelling experience. In order to have a highly productive SCM system, Emirates has installed an Electronic Data Interchange (EDI) system that is operated primarily by the Engineering Materials Management section; the experts are responsible for developing the policies, processes and procedures for optimization of the inventory and earning high Return on Investment (ROI). The system is responsible for material provisioning, forecasting the demand of customers, planning of procurement, reviewing the stock level, storing and usage of materials, repairing and replacement of parts and disposal of materials (Christopher, 250). The team responsible for material provisioning has to perform four major functions i.e. establishment of optimum levels for re-ordering and safety maintenance, increase the number of requests required for timely purchases to ensure that items are available on time, data is accurately stored and high standards of safety and quality policies are followed that are set by the agencies of the aviation industry. Similarly, the component management team deals with the high value and rotable assets of aircraft components so that initial provisioning and re-provisioning can be easily done. By ensuring the best SCM best practices, Emirates is maintaining the top quality standards of service levels in a cost-effective manner. Key issues and challenges of SCM After analysis and assessment of the SCM process implemented at Emirates, it can be concluded that it has an efficient and well-designed system that ensures that it has adequate stock of supplies and product development process is effective for managing the product life cycle of its product and service offerings (Deveshwar and Rupa, 194). The key challenges and issues that can be faced in SCM of Emirates are as follows: Globalization – With the advent of globalization, the IT infrastructure needs to be compatible with the requirements of the corporations that will ensure that all variations encountered are effectively handled. Since Emirates is a global airline, it has to ensure that it has effective SCM system on all of its destinations so that there is proper management of its fleet; the repair and maintenance services should be constant everywhere so that top quality of services is provided to every customer. Supply Chain disruption – As SCM systems are based on IT infrastructure, there are chances that the system can get disrupted by any of unforeseen events such as interruption of IT system, improper functioning of the system, trouble in the airline systems that can affect the customer database and flight scheduling can be severely impacted and many more. If Emirates does not have a contingency plan for dealing with severe problem in SCM system, then it can effectively impact the Mitigation of damage – When SCM system is implemented in the organization, it is vital for the professionals to keep some manual records and avail the insurance policy option so that damage can be mitigated. Emirates has bought insurance policies to minimize any loss that can be encountered when supplies are either damaged or are not compatible with the quality standards of the aviation industry. Conclusion and Recommendations For every organization, it is important to have a well-integrated SCM system that will ensure that its supply chain strategy is complementing the business strategy. With the help of an effective SCM system, Emirates Airline and its consumers and partners can have quicker and on-time orders, production planning and inventory management is effectively done, high rate of order fulfillment rate is observed, forecasting is efficiently completed and performance of the company can be easily monitored. An organization strives to be the leader in its industry by following a well-designed strategy that incorporates the company’s mission, vision, values, goals and objectives so that it can attain its long-term competitive position in the market. Emirates has ensured that its SCM strategy is properly aligned with the business strategy. Every strategy in the SCM comprises of the plan that the company will implement for achieving its goal of capturing the target market and enhancing the satisfaction level of end consumers. The SCM strategy ensures that the logistics of the company are planned out in advance so that there is an adequate supply of raw materials, minimum level of inventory is maintained and the supply chain operations’ cost is reduced; all of these measures ensure that Emirates Airline is able to generate an appropriate amount of profit and maintain its strong position in the industry.

Santa Monica College Prime Numbers Average Java Program

Santa Monica College Prime Numbers Average Java Program.

1. finding the prime numbers from 0 to n where n is the input.2.finding factorials. Do this using loops, and recursive functions.3.find the average of all prime numbers between 0 to n.4.finding the total of all doubles (or cubes…) between a range 0 to n.requirements:code in c ONLY.use proper syntax.programs must be able to run.Use proper terms.
Santa Monica College Prime Numbers Average Java Program