Diseases among Elderly People Essay Example | Topics and Well Written Essays - 2000 words

Illnesses among Elderly People - Essay Example thromboxane A2 that advances a course of occasions driving at last to cluster arrangement. Expanded homocysteine levels influence the internal coating of the blood vessel divider, and in this way have since quite a while ago been involved in the causation of apoplexy (Scott, J. also, Weir, D., 1996). In reality, expanded homocysetine levels related with condition of homocysteinuria are recognized to be a reason for intravascular apoplexy. It has been seen that plasma homocysteine is regularly changed over to methionine co-considered by folic corrosive relates in the body. At the point when this response is disabled because of lack of cobalamine; since cobalamine controls folate digestion, it is unhinged prompting raised homocysteine levels (Mayer, E.L., Jacobsen, D.W., and Robinson, K., 1996). High plasma homocysteine, consequently, will incline to expanded apoplexy, in spite of the fact that it isn't yet known regardless of whether hyperhomocysteinaemia due to folic corrosive insufficiency inclines to apoplexy or on the other hand adjusts its reaction to treatment (Welch, G.N. what's more, Loscalzo, J., 1998). This proposition means to examine the impact of folic corrosive on the old as far as danger of coronary corridor sickness as applicable to avoidance of apoplexy in prior atherosclerotic heart sickness regarding frequency of myocardial dead tissue (Bots, M.L. et al., 1999).Increasingly, human services is centering towards anticipation of sickness as opposed to rewarding it after the disaster occurs. Coronary conduit malady showed by intense myocardial infraction is one of the most well-known analyses in created nations all through the world. The death pace of the infection is 30% with over a large portion of the patients terminating even before they can arrive at the clinic. Endurance from a heart...Research attendants will screen the clinical records and avoid patients who have a background marked by coronary heart infections or patients who are consuming medications known to meddle with folic corrosive, or taking nutrient enhancements containing folic corrosive. Patients will be qualified for consideration whenever matured 65 years or more and if their clinical narratives incorporate at least two of the accompanying conditions: diabetes, hypertension, hyperlipidemia, stoutness or smoking. Every single qualified individual will get a letter from the emergency clinic clarifying the examination, trailed by a call welcoming them to go to the main visit and training them to quick from 12 PM the night prior to the visit. At the main visit, all standard estimations will be taken. Exploration medical caretakers will take general data, for example, name, age, sex, telephone number, address, smoking history, conjugal status, financial components, and the names and telephone quantities of a few companions or family members who consistently realize how to arrive at the members. Medications history including headache medicine or different anticoagulants, antihypertensive, against angina, and lipid-bringing down medications will be surveyed. Study techniques will be disclosed to all subjects. Subjects who are probably not going to finish follow-up because of plans to move or because of ailment prone to be lethal inside 4 years, or reluctant to partake will be avoided from the examination. Morals: All subjects will be clarified the investigation convention, and a composed educated assent will

The Prioress And Women Of Chaucers Time English Literature Essay Essay Example

The Prioress And Women Of Chaucers Time English Literature Essay Geoffrey Chaucer s The Canterbury Tales is a prank bit of writing which tells the account of a gathering of voyagers who are on an explorers venture. The General Prologue to The Canterbury Tales is a long progress wherein Chaucer depicts the characters. The characters cultural height and general businesss fluctuate incredibly and it is obvious to the peruser that there are some who Chaucer significantly appreciates and other people who he expects to a scoff of. In making in this way, he other than appoints sexual orientation generalizations, which can be found in his ideal likeness of the Knight character and extremely horrible picture of the Prioress character. By looking at the Prioress and Knight s portrayals in the General Prologue, the peruser can express this to be valid. We will compose a custom article test on The Prioress And Women Of Chaucers Time English Literature Essay explicitly for you for just $16.38 $13.9/page Request now We will compose a custom exposition test on The Prioress And Women Of Chaucers Time English Literature Essay explicitly for you FOR ONLY $16.38 $13.9/page Recruit Writer We will compose a custom paper test on The Prioress And Women Of Chaucers Time English Literature Essay explicitly for you FOR ONLY $16.38 $13.9/page Recruit Writer Upon first perusing Chaucer s Prioress portrayal it would look that she is a positive figure in his eyes: Ther was other than a Nonne, a Prioress/That of hir grin was ful basic and hesitant./Hir gretteste ooth was yet by sainte euphoria! ( lines 118-120 ) . This presently goes to a wry tone and we perceive how Chaucer utilizes the Prioress to delineate his situations on grown-up females all in all: reef, unfaithful and needing wealth/higher cultural position. The Prioress is portrayed as a cloister adherent yet Chaucer stresses her blue mode and open picture. The Prioress is trying to move as though she were in a higher cultural height than she genuinely is. Her endeavors to pretend she is something that she is non is Chaucer s way to demo her triviality ( and his debasing situation towards grown-up females when all is said in done ) . Similarly troublesome as she may try to hide them, Chaucer calls attention to her imperfections. The Abbess parades her guidance and perception of Fre nch as though she had gone at that place for a drawn-out time of clasp and was a common voyager. At the point when the narrator says, And Frenssh she spak ful faire and fetishly,/After the scole of Stratford at the Bowe-/For Frenssh of Paris was to connect with unknowe ( lines 124-126 ) , it is Chaucer s way of expressing the peruser that she does non cognize her Gallic from her movements, rather from books and tutoring. Her endeavors to hoax herself as modern just cause her character to appear to be even shallower. This structure proceeds with when the narrator comments on her social graces At allot wel ytaught was she withalle:/She leet no piece from hir lippes falle,/Ne wette hir fingers in hir sauce deepe ;/wel coude she carye a piece, and wel keepe/That no drope ne fille upon hir Brest ( lines 127-131 ) and again two lines in this way including Hir over-lippe cleaned she so clene/That in hir coppe ther was no firthing seene ( lines 133-134 ) . This was obviously intended to be taken as incongruity rather than a decent quality on the grounds that no 1 needs to be recollected or depicted for their social graces. For this ground the peruser can find that Chaucer is using the narrator to slander the Prioress character and grown-up females by and large. At the clasp Chaucer composed this, a grown-up female of the Prioress height, a religious woman, should act and move a specific way. That is to state, she should move in a mode that the Church would O.K. of. The narrator depicts her in a couple of ways as the antonym, which would be unmistakably known to any peruser of the twenty-four hours. The first being the point at which the narrator is delineating her propose of golde ful sheene ( lines 160 ) which is engraved with the adherents, Cupid vincit omni. The propose is a bit of adornments, and the lettering on a very basic level means love vanquishes all. Since the Prioress is a religious recluse, she ought to non hold a propose made of gold. She is non expected to hold anything kind ; rather, she ought to populate an existence of basic offices. She has purportedly made this committedness to the congregation. Love overcomes everything is ordinarily utilized as a look between an adoration shared by a grown-up male and a grown-up femal e. As a cloister adherent, the Prioress should hold no comprehension of this kind of affection and to the individuals and Church of the twenty-four hours this would be viewed as disrespectful. Last ( in regard to the Prioress insufficiency of following her Church committednesss ) , the narrator describers her headgear known as a wimple But sikerly she hadde a faire forheed:/It was about a spanne brood ( lines 154-155 ) . Interpreted this implies her forehead is demoing through her headgear when only her face ought to be. The peruser can assume that she does this so as to do herself progressively lovely. Joined, these activities show the Prioresses disregard for the Church, for in the event that she really minded, none of these future present. Towards the terminal of the Prioress portrayal, the narrator leaves the peruser with and tormented recruit to countrefete cheere/Of council, and to been statlich of manere ( lines 139-140 ) . This essentially summarizes the Priores, s and Chauc er s position of grown-up females: falsification. The Prioress efficiently neglects to move in similarity with the Churches guidelines in spite of the fact that she is a pious devotee, and professes to be a genuine socialite and common figure when she is nil in excess of a student and a picture of individual she wishes to really be. When contrasted with the Prioress, the male Knight is portrayed rather well as a legit character. Chaucer s Knight is the genuine model of an officer. Orchestrating to the narrators depiction, he has murdered many work powers and has ventured to every part of the universe, including Russia, Spain, Prussia, Lithuania, Africa and numerous other topographic focuses. Chaucer s depiction of the Knight has non one negative feature. For this ground, it is evident that Chaucer is demoing the peruser the entirety of the great characteristics work powers have rather than the characteristics females inadequacy. The Knight s characteristics incorporate honor, boldness, devotedness to his territories, and honestness. This is appeared all through the narrator s depiction of the Knight, including when he states he adored chivalrye. /Troughe and respect, opportunity and curteisye ( lines 45-46 ) , He nevere yet no vilainye ne saide ( line 70 ) and a verray, parfit, gentil knight ( line 72 ) . Fittin g to the narrator, he has been on a greater number of missions than any other person, and no 1 can analyze in footings of notoriety. The accompanying concentrate from the General Prologue shows this obviously: At Alisander he was whan it was wonne ; Influenza ofte cut he hadde the broord bigonne Aboven alle nacious in Pruce ; In Lettou had he resised, and in Ruce, No Christian grown-up male so ofte of his evaluation ; In Grenade at the sege eek hadde he b Of Algezir, and ridden in Bekamarye ; At Lyeis was he, and at Satalye, Whan they were wonne ( lines 51-59 ) Contrasted with Chaucer s imperfect Prioress, the Knight has voyage everywhere throughout the universe, and in the event that he had realized how to talk Gallic it would be on the grounds that he had visited the land and gained as a matter of fact. The way that the Knight went on such huge numbers of missions ( crusades ) and is held in such high regard by his state demonstrates his commitment to his state, or what he should make ( it is his obligation to make this as a solider ) . Since the Prioress should follow the rules of the Church yet deliberately does non, she is inverse from the Knight as such. This angle is distinctly coordinated by Chaucer intentionally to raise the picture of work powers much higher from grown-up females. He does his obligation regardless of the risks he may faces, since just work powers could work their state ; Chaucer is using this aspect of the Knights character in a twofold way to separate work powers and grown-up females. The finishing up contrasting between the Prioress and Knight can be appeared in footings of mainstream possessions and visual angles. Both a knight and religious recluse should hold little in footings of articles of clothing and proprietorships. As expressed aforesaid the Prioress has a longing for kind focuses and endeavors to do herself all the more truly engaging. In footings of proprietorships and appearances the Knight is portrayed by the narrator in the undermentioned footings: His hors were goode, yet he was non lively. /Of fustian he wered a gipoun/All bismotered with his haubergoun ( line 74-76 ) , meaning the Knight is non truly dressed to keep up with current inclinations, even his protective layer is worn. This is the means by which it ought to be for a grown-up male of his height. The solitary possession the Knight holds is his Equus caballus: he would be nil without it. This is a lowering trademark that is other than needed by the Prioresses character. An investigation of Chaucer s work uncovers obtuse contrasts between his promise image of male ( the Knight ) and female ( the Prioress ) characters. Chaucer attributes various characteristics moving various intensions to the two sexual orientations. While Chaucer uncovered the Prioress as beguiling and narrow minded, the Knight is depicted in considerably more legitimate footings, truly manifesting nobility and connection to obligation. All through Chaucer s The Canterbury Tales, the peruser finds that the narrators portrayals of the characters are comparative, in that the guys appear to hold a higher level of character when contrasted with the female characters. The entirety of the female characters are depicted as deceptive, shallow, missing religion, and just thinking about themselves. For this ground, the peruser can see that Chaucer s genuine sentiments towards every sexual orientation are spoken to all through The Canterbury Tales. Truth be told, many have said that when the n arrator s

Work Projects Administration

Work Projects Administration Work Projects Administration (WPA), former U.S. government agency, established in 1935 by executive order of President Franklin Delano Roosevelt as the Works Progress Administration; it was renamed the Work Projects Administration in 1939, when it was made part of the Federal Works Agency. Created when unemployment was widespread, the WPAâ€"headed by Harry L. Hopkins until 1938â€"was designed to increase the purchasing power of persons on relief by employing them on useful projects. WPA's building program included the construction of 116,000 buildings, 78,000 bridges, and 651,000 mi (1,047,000 km) of road and the improvement of 800 airports. Also a part of WPA's diversified activities were the Federal Art Project, the Federal Writers' Project, and the Federal Theatre Project. Close to 10,000 drawings, paintings, and sculptured works were produced through WPA, and many public buildings (especially post offices) were decorated with murals. The experiments in theatrical productions wer e highly praised and introduced many fresh ideas. Musical performances under the project averaged 4,000 a month. The most notable product of writers in WPA was a valuable series of state and regional guidebooks. WPA also conducted an education program and supervised the activities of the National Youth Administration . At its peak WPA had about 3.5 million persons on its payrolls. Altogether WPA employed a total of 8.5 million persons, and total federal appropriations for the program amounted to almost $11 billion. There was sharp criticism of the WPA in a Senate committee report in 1939; the same year the WPA appropriation was cut, several projects were abolished, and others were curtailed. A strike of thousands of WPA workers to prevent a cut in wages on building projects was unsuccessful. Steadily increasing employment in the private sector, much speeded just before and during World War II, caused further drastic cuts in WPA appropriations and payrolls. In June, 1943, the agency officially went out of existence. See D. S. Howard, WPA and Federal Relief Policy (1943). The Columbia Electronic Encyclopedia, 6th ed. Copyright © 2012, Columbia University Press. All rights reserved. See more Encyclopedia articles on: U.S. History

De schakelaars van de celcyclus exit - Free Essay Example

Sample details Pages: 21 Words: 6154 Downloads: 2 Date added: 2017/06/26 Category Statistics Essay Did you like this example? Hoofdstuk 1: Inleiding Om als organisme te kunnen groeien is er celdeling nodig. Deze celdeling wordt gereguleerd door middel van de celcyclus en zal hier kort uitlegd worden. De celcyclus is in twee delen opgedeeld. Don’t waste time! Our writers will create an original "De schakelaars van de celcyclus exit" essay for you Create order De interfase en de M-fase. Tijdens de interfase groeit de cel en verdubbelt het zijn chromosomen. De interfase is ook weer opgedeeld in 3 delen, Gap fase 1 (G1), Synthese (S) en Gap fase 2 (G2) (zie figuur 1). In de G1 groeit de cel en bereidt het zich voor op de S-fase. In de S-fase wordt het genoom verdubbeld waarna het naar de G2 fase gaat waar de cel verder gaat met groeien tot het klaar is om te delen. Na de interfase komt de mitose of M-fase waar de cel uiteindelijk een nucleaire deling en en cytoplasmatische deling ondergaat. Wanneer de M-fase is afgerond zijn er twee cellen ontstaan die weer de celcyclus kunnen ingaan vanaf de G1 fase. Afhankelijk van de omgevings- en ontwikkelingssignalen kunnen cellen in G1 tijdelijk of permanent de celcyclus verlaten. De cellen komen dan in een rust fase van de celcyclus waar de cellen niet delen. Deze fase wordt ook wel de G0 genoemd. De meeste cellen in het lichaam van een volwassen vertebraat delen weinig en bevinden zich het grootste deel van de tijd in de G0 fase. Wanneer een cel uit de celcyclus gaat naar de G0 fase wordt dit meestal cel cyclus exit genoemd. Er zijn drie soorten van tijdelijke of definitieve rust fase na cel cyclus exit te onderscheiden. De eerste is quiescence, een niet delende conditie waarin de cel terug kan keren naar de celcyclus. Quiescence komt vaak voor bij cellen met DNA schade of cellen die niet de juiste benodigdheden voor proliferatie hebben. Wanneer DNA uit de cel beschadigd is maar niet te repareren is zal deze vaak in apoptose, celdood, gaan. Een tweede is terminale differentiatie, waarin de cel zich blijvend in een postmitotische staat bevind. De derde vorm van G0 fase is proliferatieve senescence, een andere vorm van permanente posmitotische staat. De beslissing van een cel om te delen wordt gemaakt in de G1-fase. Deze beslissing wordt gemaakt na afwezigheid van verwarring, schade, of stres in de cel, volgens een zeer gecoÃÆ' ¶rdineerd maar automatisch proces. [sherr 99] Het punt waarop deze beslissing wordt gemaakt is een checkpoint die hier restrictiepunt wordt genoemd. Intracellulaire en extracellulaire signalen kunnen de celcyclus op deze checkpoints blokkeren. Wanneer er daarna weer goede condities aanwezig zijn, zoals voldoende nutriÃÆ' «nten en groeifactoren en er geen inhibitie factoren zijn, zal een cel in quiescente staat terug de celcyclus in gaan. Er zijn meerdere checkpoints in de celcyclus aanwezig. Zo is er aan het einde van de G2 fase een checkpoint voor controle of de omgevings condities nog steeds voordelig zijn en al het DNA verdubbeld is en is er een checkpoint aan het einde van de M fase of alle chromosomen wel aan de spoel gehecht zijn voordat de cel gaat delen. Wanneer een cel gaat delen moeten beid e van de chromatide van een chromosoom namelijk eerst aan de spoelen aan weerzijden van de cel gehecht zijn. De chromosomen kunnen hierdoor gelijk gesplitst worden doordat ze uit elkaar worden getrokken richting beide polen. Dit levert twee gelijkwaardige cellen op. In dit essay zijn de laatste twee checkpoints verder niet van belang. De gehele celcyclus wordt gereguleerd door de activatie of inactivatie van verschillende cycline-afhankelijke kinasen (Cyclin-Dependent Kinases, CDKs). CDKs zijn kleine eiwit kinasen die associatie met een cycline subunit nodig hebben voor activatie [vd Heuvel 05]. Bij elke fase van de celcyclus zijn verschillende cycline/CDK complexen actief en de regulatie van de activiteit wordt geregeld via de cyclines. Tijdens elke cel cyclus ondergaan cyclines een cyclus van synthese waarna de CDKs complexen vormen met passende cyclines om vervolgens afgebroken te worden. De CDK-cycline complexen katalyseren de aanhechting van een fosfaat groep aan specifieke serine of threonine aminozuren in een doel eiwit. De fosfaat groepen veranderen eigenschappen van de doel eiwitten, zoals de interactie met andere eiwitten. CDKs worden daarom ook wel serine/threonine kinasen genoemd. De G1 wordt gereguleerd door meerdere cyclines waaronder Cycline D1, D2, D3 en E. De belangrijkste G1 CDKs zijn CDK4 en CDK6, die aan de D-type cyclines binden, en CDK2, die voornamelijk aan cycline E en cycline A bind [Sherr 04]. In figuur 2 wordt een overzicht gegeven van de cyclines en CDKs die tijdens de celcyclus een rol spelen. Omdat er in dit essay vooral wordt gekeken naar de exit van de celcyclus tijdens de G1 en S fase worden de andere cyclines en CDKs niet besproken. Ontregeling van de celcyclus speelt een grote rol in de ontwikkeling van kankercellen. Overexpressie van eiwitten die de celcyclus progressie regelen zoals CDKs en cyclines, en remming van eiwitten die de celcyclus stoppen kan leiden tot ongecontroleerde cel proliferatie. In menselijke tumoren zijn vooral de genen die coderen voor eiwitten die de overgang van G1 naar de S fase regelen veranderd. Het begrijpen van de gehele celcyclus en daarmee ook vooral het gedeelte van de celcyclus exit is daarom erg belangrijk. Organismen moeten genoeg cellen kunnen vormen door deling maar wanneer ze niet bijtijds stoppen met delen kan dit leiden tot kankercellen. Kanker onderzoek richt zich dan ook vaak op het uitschakelen van de celcyclus regulatie. Dit proces is eveneens belangrijk in de regeneratie van cellen voor onderzoek naar degeneratie ziektes, waarbij bepaalde type cellen hun functie verliezen of verloren gaan. In regeneratie onderzoek wordt er op twee manieren geprobeerd de weefsels weer functionele cellen te geven. Zo wordt er onderzoek gedaan om de cellen terug te brengen naar de staat waarin ze nog niet ge-dedifferentieerd zijn maar wel weer delen. Een tweede onderzoek is gebaseerd op cel herprogrammering waarbij de cellen volledig worden ge-dedifferentieerd. Het probleem hierbij is dat ze wel tijdig moeten stoppen met delen om geen kankervorming te krijgen. Het begrijpen ho e een cel de celcyclus uitgaat is dus voor veel onderzoeken van belang. Om de celcyclus exit verder te begrijpen staat daarom in dit essay de vraag wat zijn de regulatie mechanismen van de celcyclus exit? centraal. Deze vraag zal worden uitgelicht door gebruik te maken van eerder gepubliceerde artikelen en zal om nader uitgelegde redenen vooral bekeken worden in het modelorganisme Drosophila melanogaster. Hoofdstuk 2: de celcyclus exit bepalende componenten modelorganisme Om een duidelijk beeld van de regulatie mechanismen van de celcyclus exit te krijgen is er hier gekozen om dit te bekijken in het modelorganisme Drosophila melanogaster. Dit omdat D. melanogaster een veel voorkomend modelorganisme in de genetica is. Het genoom is bekend en veel van de genen zijn al beschreven. Het heeft een snelle reproductie tijd waardoor er snel nakomelingen geproduceerd kunnen worden en er snel over veel organismen te beschikken is. Hiernaast is D. melanogaster erg klein en heeft het weinig voedingsstoffen en geen ingewikkelde leefomstandigheden nodig om te overleven. Dit maakt D. melanogaster een handig dier om in het laboratorium mee te werken. Naast deze voordelen is dit modeldier ook gemakkelijk in in vivo systemen te gebruiken. De meest belangrijke reden waarom D. melanogaster hier gebruikt wordt als model organisme is dat het dezelfde componenten in de celcyclus exit heeft als zoogdieren maar minder varianten van deze componenten heeft waardoor het systeem g emakkelijker te bestuderen is. Aan het einde van dit hoofdstuk zal er een vergelijking met andere modelorganismen gemaakt worden. Retinoblastoma eiwit familie Een van de belangrijkste componenten in de celcyclus exit wordt gecodeerd door het retinoblastoma gen. Het retinoblastoma gen is het eerste tumor onderdrukkende gen dat is geÃÆ' ¯dentificeerd en werd gevonden in 1986. Het gen was eerder gekloneerd als resultaat van een zeldzame oog tumor bij kinderen, retinoblastoma kanker. Waarom deze oog tumor ontstaat door een gen die zich in het hele lichaam bevind is niet bekend. Het retinoblastoma gen codeert voor een aminozuur fosfoproteÃÆ' ¯ne, het Rb eiwit. Het Rb eiwit is een tumor onderdrukkend eiwit en is defect in de meeste vormen van kanker. Rb remt cellen in de G1 fase naar de S fase te gaan tot dat de cel klaar is om te delen[Harbour 00] (zie figuur 3). Buitensporige cel groei wordt hierdoor tegen gegaan. Er kan hierdoor gezegd worden dat Rb een negatieve regulatie op de cel cyclus heeft en daardoor de cel cyclus exit stimuleert. Rb heeft meerdere functionele delen die samen de centrale pocket van het eiwit vormen. Rb behoort daarom tot de pocket eiwitten. Het bestaat uit twee geconserveerde delen, een A en B domein (zie figuur 4), die verantwoordelijk zijn voor de meeste eiwit-eiwit interacties. D. melanogaster bevat twee RB familie leden, RBF en RBF2. RBF2 is echter niet een essentieel gen. Rbf2 mutant vliegen vertonen namelijk geen duidelijk fenotypen [Stevaux 05]. Hier in tegen, voldoet RBF aan alle cel cyclus gerelateerde functies van een Rb eiwit familie in Drosophila. De regulatie van RBF op een cel om te stoppen in G1 of door te gaan naar de S fase wordt gereguleerd door cycline/cdk complexen. Een van de belangrijkste taken van deze complexen is het fosforyleren en defosforyleren van RBF tijdens de celcyclus. De RBF eiwit familie bevat hiervoor meerdere fosforylatie punten die gefosforyleerd kunnen worden. Bij de G1 fase zijn het de cyclineD/cdk4 complexen en bij de G1/S fase zijn het de cyclineE/cdk2 en cyclineA/cdk2 complexen die RBF fosforyleren. De hyper-gefosforyleerde vorm, wat de inactieve vorm is, is dominant in prolifererende cellen. De hypogefosryleerde vorm, wat de actieve vorm is, komt meestal voor in quiescente cellen of differentiÃÆ' «rende cellen. [Du 06] E2F transcriptie factoren De biologische functie van RBF bestaat uit tumor onderdrukking, regulatie van de cel cyclus, differentiatie en apoptose. Deze functies van RBF worden allemaal gereguleerd in combinatie met een heleboel cellulaire eiwitten. Een van die eiwitten die interactie met RBF aangaat is E2F. In de begin dagen stond E2F bekend als DRTF1/E2F. E2F was ontdekt als een cellulaire factor nodig voor de vroege regio 1A (E1A)-transformatie eiwit van het adenovirus om de transcriptie activatie van een viraal E2A promoter te reguleren [Nevins 92]. DRTF1 was eerder geÃÆ' ¯dentificeerd als een transcriptie factor waarvan de DNA bindings activiteit verlaagd werd tijdens de differentiatie van F9 embryonale carcinoma stam cellen [la Thangue 87]. De consensus DNA bindings site voor DRTF1 en E2F waren gelijk net als andere observaties. Dit suggereerde dat DRTF1 en E2F verwant waren. Interesse in E2F nam toe doordat, door studies van cellulaire targets van virale oncoproteÃÆ' ¯nes, het ontdekt was dat E2F belangrijk was voor de functie van RBF [Nevins 92]. E2F behoort tot de E2F familie van DNA-bindende transcriptie factoren. De meeste E2F eiwitten worden geassocieerd met een dimerisatie partner (DP) eiwit en vormen een heterodimeer complex dat aan DNA bind in een sequentie specifieke manier. Beide E2Fs en dDP hebben hiervoor een DNA-bindings domein (DBD) en een dimerisatie domein (Dim) (zie figuur 5). De D. melanogaster E2F familie leden kunnen in tweeÃÆ' «n worden gesplitst. dE2F1 functioneert voornamelijk als een transcriptie activator en dE2F2 functioneert voornamelijk als een actieve onderdrukker van transcriptie. Cel cyclus exit door onderdrukking van transcriptie De cel kan door meerdere modellen van RBF-E2F in cel cyclus exit gaan. Een hiervan is het mechanismen waarbij E2F geregelde transcriptie door retinoblastoma familie leden wordt onderdrukt. Dit kan op drie manieren gebeuren. Bij de eerste manier bind RBF aan de E2F transcriptie factoren en blokkeert hiermee hun mogelijkheid tot het activeren van gentranscriptie. Cycline-cdk complexen kunnen RBF fosforyleren, zoals eerder beschreven, waardoor het E2F-DP complex vrij komt te liggen en er weer transcriptie plaats kan vinden en een cel de cel cyclus weer kan vervolgen (zie figuur 6). Bij een tweede manier blokkeert RBF het vormen van pre-initiatie complexen waardoor aangrenzende transcriptie factoren worden onderdrukt. Bij een derde manier gebruikt RBF een eiwit interactie domein die afgescheiden is van zijn E2F-bindings plaats om geassocieerd te worden met complexen die chromatine structuren veranderen [Frolov 04]. Over deze manieren zal in het volgende hoofdstuk meer volgen. Cdk remming Cdk activiteit is gereguleerd door cycline afhankelijke kinase onderdrukkers (Cyclin dependent kinase inhibitors, CKIs). De Cip/Kip familie behoort tot deze CKIs. De Cip/Kip onderdrukker in D. melanogaster is Dacapo, die homoloog is aan p21/p27 van het zoogdier. De Cip/Kip moleculen zijn in staat tot het binden van alle soorten cyclines en cdks en ze daardoor inactiveren. In figuur 7 is te zien dat Dacapo eiwit, dap, cycline-cdk complexen in vitro kan remmen. Om dit te testen zijn wild-type en mutant eiwitten vergeleken in de mogelijkheid tot inhibitie van kinase activiteit van gezuiverde eiwit complexen. Bacterieel tot expressie gekomen Dacapo kon histon H1 kinase activiteit van het humaan cyclineE-cdk2 remmen. De twee mutant eiwitten met onderbrekingen in de bindings regio van cycline konden dit niet.Ook is er in ditzelfde onderzoek aangetoond dat overexpressie van dap celcyclus progressie in vivo kan remmen en dat expressie van dap gecorreleerd is met de exit van de cel cyclus [de Nooij 96]. CKIs kunnen de cyclines en cdks apart binden maar hebben meer affiniteit voor de heterodimere complexen. Hierdoor kunnen ze een regulerende functie hebben in alle fasen van de cel cyclus. Omdat cycline-cdk complexen een remmende werking op RBF hebben en CKIs een remmende werking op cycline-cdks stimuleren CKIs RBF als het ware via een negatief-negatieve pathway (zie figuur 3). CKIs zijn daarom naast RBF remmers van de cel cyclus en daarmee stimulansen van de cel cyclus exit. APC/C Zoals eerder besproken is cdk activiteit een belangrijke factor voor de progressie van de cel cyclus. Cdk speelt hier echter maar een rol tot de metafase. Voortgang in de anafase wordt namelijk door een ander regulatie component gereguleerd. Een ubiquitine-eiwit ligase die anafase-promoting complex (APC) of cyclosoom wordt genoemd speelt hier deze rol. Het ubiquitineert verschillende regulatie eiwitten en richt deze daarbij naar het proteasoom voor afbraak. De APC/C activiteit schommelt in reactie op veranderingen in de samenkomst van het APC met de activerende subunits Cdc20 of Cdh1 [Sullivan 07] (zie figuur 8). Associatie van het APC met Cdc20 in het middelste deel van de mitose lijdt tot de initiatie van de anafase. Associatie van het APC met Cdh1 in het late deel van de mitose onderhoudt het APC activiteit door de G1 fase. Een belangrijk doelwit van het APC is securine. Securine is normaal gehecht aan separase wat het inactief maakt. Wanneer securine wordt afgebroken komt separas e vrij en initieert het chromosoom splitsing. Het APC ubiquitineert ook mitotische cycline. De afbraak van deze cyclines inactiveert de cdks en staat fosfatases toe om de cdk substraten in de cel te defosforyleren. Defosforylatie van cdk substraten is nodig voor normale chromosoom en spoel beweging in de anafase zoals in eerder beschreven. Het is ook belangrijk voor de gebeurtenissen die hierop volgen in de telofase waarin de spoel uiteen valt, de kern opnieuw wordt gevormd en het chromatine wordt gedecondenseert [Sullivan 07]. De laatste delen van de mitose worden dus gereguleerd door defosforylatie van cdk substraten en ubiquitinatie van APC substraten. APC/C heeft hiernaast ook een rol in de cel cyclus blokkades die lijden tot quiescence. Ook Skp-Cullin-F-box (SCF) ubiquitine ligase complexen spelen hier een rol in [Buttita 07]. Naast de eerder genoemde degradaties van substraten in de mitose heeft APC/C ook een degraderende rol voor Skp2. De degradatie van de degradatie machine is gekoppeld aan de cel cyclus exit pathway. Hypogefosforyleert RBF kan namelijk worden geassocieerd met het APC/C, voornamelijk wanneer het geactiveerd wordt door Cdh1 [Binne 07]. Dit stimuleert degradatie van Skp2, een component van het SCFskp2 complex die verantwoordelijk is voor degradatie van p27 en p21. De RBF/APC/C interactie resulteert dus in de tot stand houding van p27 en p21. RBF kan hierdoor in een tweede, E2F onafhankelijke manier, de cel cyclus tegen houden (zie figuur 3) [Buttita 07]. Wanneer een gemuteerd RBF wordt genomen, die niet aan Cdh1 kan binden, kan gedemonstreerd worden dat de RBF/APC/C interactie nodig is voor RBF om de cel cyclus in prolifererende cellen tegen te houden [Binne 07]. Uit verschillende APC/C en SCF mutant studies in vivo is echter gebleken dat de cel cyclus maar tijdelijk wordt vertraagd. Dit wijst erop dat de eiwit degradatie machine en rol speelt in de cel cyclus exit maar dat er meerdere mechanismen nodig zijn om uiteindelijk een cel cyclus exit te krijgen [Buttita 07]. Prospero Het laatste component die een rol speelt in de cel cyclus exit is prospero (Pros) (zie figuur 3). Pros is een homeobox transcriptie factor die naast cel cyclus exit ook terminale differentiatie coÃÆ' ¶rdineert. In neuroblasten is Pros asymmetrisch gelokaliseerd op het cytoplasmisch membraan. Tijdens het delen van de cel wordt Pros geÃÆ' «rfd door ÃÆ' ©ÃƒÆ' ©n dochter cel, de ganglion moeder cel (GMC). Hier zal Pros de nucleus ingaan en terminale differentiatie aansporen. In meerdere studies van Pros in het Drosophila embryo werd er aangetoond dat Pros de transcriptie van cycline E en String tegenhield [Li 00]. Het bleef echter onduidelijk of dit een indirect effect van Pros was op differentiatie of een meer direct effect op deze cel cyclus genen [Buttita 07]. Uit later onderzoek waarin de genoom-wijde binding van Pros op chromatine werd onderzocht bleek dat Pros een directe rol had in het transcriptioneel tegen houden van meerdere sleutel cel cyclus genen waaronder, naast cycline E en string, ook e2f1. Pros heeft hiernaast ook een directe rol in het activeren van een aantal terminale differentiatie genen in neuronen wat het een dubbel functioneel signaal maakt [Choksi 06]. Pros expressie wordt in bepaalde type cellen erg onderdrukt. Hierdoor is het niet waarschijnlijk dat Pros een universele rol in de cel cyclus exit speelt. Uit onderzoek in de darmen van Drosophila is een stam cel differentiatie pathway gevonden waarin eenzelfde asymmetrisch delings patroon is gevonden gevolgd door differentiatie zonder tussen komst van mitose. Pros komt precies tot uiting in een van de resulterende postmitotische cel types waar het waarschijnlijk de terminale differentiatie van de celcyclus exit coÃÆ' ¶rdineert. Andere Homeobox eiwitten zouden eenzelfde rol kunnen spelen in andere cel types. Er blijft daarom nog veel onderzoek naar dubbel-functionele transcriptie factoren [Buttita 07]. Celcyclus regulatie van C. elegans en zoogdieren Twee andere model organismen waarin er veel onderzoek is gedaan naar de celcyclus exit zijn Caenorhabditis elegans en zoogdieren. Het voornaamste verschil tussen deze model organismen is het verschil in Rb en E2F-familie leden (zie tabel 1). Het zoogdier heeft namelijk acht E2F familie leden (E2f1-E2F8) en drie Rb familie leden (pRb, p107 en p130) waar D. melanogaster er van beide families maar twee heeft en C. elegans er drie E2F familie leden (Efl-1, Efl-2 en F49E12.6) en slechts ÃÆ' ©ÃƒÆ' ©n Rb familie lid (Lin-35) heeft. In het zoogdier is de verdeling van de E2F familie leden hetzelfde als in D. melanogaste (zie figuur 9). De E2F familie is opgedeeld in activatoren (E2F1-E2F3a) en onderdrukkers (E2F3b-E2F8). E2F1-E2F6 bevatten net als dE2F-1 en dE2F-2 van D. melanogaster dimerisatie domeinen en vormen DNA-bindings heterodimeren met eiwitten van de differentiatie-regulatie transcriptie factor-1 polypeptide (DP) familie. E2F6 vormt complexen met polycomb-groep (PcG) eiwitten. E2F7 en E2F8 hebben deze DP-bindings domeinen niet maar bevatten tandem repeats van een E2F DNA-bindings domein. E2F1-E2F5 bevatten C-terminale domeinden waarmee ze interactie aangaan met de pocket domeinen van de Rb familie leden. De drie familie leden associÃÆ' «ren met verschillende E2F eiwitten. Zo heeft pRB de voorkeur voor E2F1-E2F3a en E2F3b-E2F5 en hebben p107 en p130 de voorkeur voor associatie met E2F3b-E2F5. De pRB familie leden van zoogdieren worden net als die van D. melanogaster gereguleerd door fosforylatie van cycline-cdk complexen. [vd Heuvel 08] Het C. elegans eiwit product van het Rb gen gerelateerde gen cell lineage-abnormal-35 (lin-35) vertoont de meeste homologie met p107 en p130. Het C. elegans gen bevat ÃÆ' ©ÃƒÆ' ©n DP-achtig gen, dpl-1. Van de drie potentiÃÆ' «le homologen aan de zoogdier E2F transcriptie factoren (E2F-like-1 (efl-1), efl-2 en F49E12.6) is efl-1 het enige E2F gerelateerde gen met een duidelijk loss-of-function fenotype. De fenotypes van efl-1, dpl-1 en lin-35 mutanten hebben veel overeenkomsten en hun producten functioneren waarschijnlijk in een co-onderdrukkings complex. [vd Heuvel 08] Naast de verschillen in Rb en E2F familie leden zijn er ook verschillen in cycline afhankelijke kinase remmers, CKIs (zie tabel 1). Zoogdieren hebben net als D. melanogaster Cip/Kip type CKIs. Ze hebben drie verschillende eiwitten van deze familie, p21Cip1, p27Kip1 en p57Kip2. Naast de Cip/Kip type CKIs hebben zoogdieren ook nog Ink4 type CKIs. Deze Ink4 type CKIs familie bevat vier leden, p15, p16, p18 en p19, vernoemd naar hun moleculaire omvang. Ink4 remmers binden, in tegen stelling tot Cip/Kip type CKIs die aan alle cdks en cyclines binden, alleen aan cdk4 en cdk6 waardoor ze associatie met D cyclines voorkomen [Pajalunga 07]. C. elegans heeft twee CKI familie leden, CKI-1 en CKI-2. Beide eiwitten lijken erg op de Cip/Kip types p21 en p27 in de aminozuur sequentie maar alleen CKI-1 functioneert op dezelfde wijze in de celcyclus.[vd Heuvel 05] In deze vergelijkingen is te zien dat D. melanogaster meer op het zoogdier lijkt op het niveau van regulatie van de celcyclus dan C. elegans. Ook is op te merken dat het zoogdier door zijn vele leden van de Rb, E2F transcriptie factor en CKI families veel complexer is dan D. melanogaster wat deze vlieg tot een geschikt model organisme maakt in onderzoek naar de celcyclus exit. Hoofdstuk 3: regulatie van de celcyclus exit componenten Welke componenten de cel cyclus exit bepalen is grotendeels bekend (weergegeven in figuur 3). Waar nog een heleboel vraagtekens liggen is hoe deze componenten op hun beurt weer worden gereguleerd. In dit hoofdstuk zal zover er tot nu toe bekend is hier een antwoord op worden gegeven. Er zal worden gekeken welke signalen er aangrijpen op de celcyclus remmende componenten RBF en CKI. Hiernaast zal er verder ingegaan worden op dE2F target genen en de regulatie hiervan. Retinoblastoma regulatie Zoals eerder beschreven wordt de activatie en inactivatie van RBF gereguleerd door fosforylatie. Het fosforyleren van RBF door CDKs wordt geÃÆ' ¯nhibeerd door CKIs wat zorgt voor celcyclus exit. Dit lijdt tot gehypofosforyleerde RBF die een complex vormen met dE2F en zo celcyclus gen expressie blokkeert. Een volgende vraag is dan hoe gehypofosforyleerde RBF ontstaan wanneer CKIs afwezig zijn of wanneer cycline-cdk activiteit niet daalt. Om dit uit te zoeken wordt er onderzoek gedaan naar fosfatases die werken op RBF. Uit eerder onderzoek werd Protein Phosphatase 1 (PP1) als een potentiÃÆ' «le fosfatase geÃÆ' ¯dentificeerd. Een RBF-specifieke fosfatase, gevoelig voor concentraties van fosfatase remmer, is namelijk gevonden in mitotische extracten van cellen [Nelson 97]. Hiernaast is ook een PP1 katalytisch subunit geÃÆ' ¯soleerd door zijn mogelijkheid om interactie aan te gaan met pRb, homoloog van RBF (zie figuur 10) [Vietri 06]. Uit latere studies in D. melanogaster bleek echter dat PP1 niet nodig is voor de regulatie van RBF [Swanhart 07]. Hoe RBF fosforylatie gereguleerd zou kunnen worden door differentiatie signalen is ook nog niet duidelijk [Buttita 07]. Deze connectie zal in de toekomst verder onderzocht moeten worden. Chromatine remodellering Naast de fosforylatie van RBF voor het reguleren van de celcyclus exit speelt RBF zelf een rol in chromatine remodellering wat een rol speelt bij dE2F afhankelijke gen repressie. De basis van chromatine is een nucleosoom die bestaat uit DNA gewikkeld om een histon octameer. Elke histon bevat een bolvormige regio, een histon-vouw domein en een minder gestructureerde N-terminale staart die naar buiten steekt. Deze staarten zijn het doelwit van meerdere post-translationele modificaties zoals acetylatie, ubiquitylatie, fosforylatie, methylatie en meer. Deze veranderingen spelen een rol in regulatie van gen expressie. Histonen zijn in het algemeen gehyperacetyleerd bij de promoter van actief afgeschreven genen en gehypoacetyleerd bij momenteel inactieve genen. Veel transcriptie regulators gebruiken histon acetyltransferase (HAT) en histon deacetylase (HDAC) activiteiten (zie figuur 11). Acetylatie van histon staarten maakt de DNA histon contacten losser waardoor chromatine minder compact wordt. Hierdoor kan een SWI/SNF ATP afhankelijke chromatine remodellerings complex binden en transcriptie gestimuleerd worden. Bij gedeacetyleerde chromatine is het DNA histon contact strakker en is het minder toegankelijk voor transcriptie factoren en daarmee transcriptie. Methylatie van de histonen door histon methyltransferase (HMT) complexen in combinatie met deacetylatie zorgt voor structuren waar geen transcriptie plaats vind zoals in heterochromatine. Dit zou op een mechanisme waarbij E2F afhankelijke celcyclus genen onderdrukt kunnen worden door de Rb familie in celcyclus exit kunnen duiden. Het is echter nog niet duidelijk welke associaties er functioneel relevant zijn voor onderdrukking van celcyclus genen in terminale differentiatie [Buttita 07]. dE2F kan door RBF geremd worden door gebruik van chromatine remodellerings enzymen zoals HDAC en HAT (zie figuur 12). HDAC geassocieerd met RBF-dE2F stimuleert nucleosoom vorming aan de promoter. Hierdoor wordt de toegang van het transcriptie mechanisme geblokkeerd. dE2F activiteit kan ook worden geremd door deacetylatie van het eiwit waardoor het niet meer aan het DNA kan binden. HAT activiteit geassocieerd met dE2F kan binding van dE2F aan de promoter stimuleren en het kan nucleosoom formatie juist remmen waardoor er wel transcriptie van het E2F target gen plaats zou kunnen vinden. [Harbour 00] E2F target genen E2F target genen werden als eerste gevonden bij onderzoek naar promoters van genen die bekend stonden om aangeschakeld te worden bij de G1/S fase overgang voor E2F bindingsplaatsen. Deze studies identificeerde E2F target genen die of celcyclus regulatoren (zoals cyclines E, A en B) of DNA replicatie factoren (zoals PCNA, dihydrofolate reductase (DHFR) en thymidine kinase) waren [Du 06]. Later zijn er meerdere evolutionair behouden complexen betrokken in de regulatie van E2F target genen gevonden. Deze complexen worden dREAM (Drosophila RBF, E2F en Myb-interacterende eiwitten) of Myb/MuvB genoemd en bevatten Rb/E2F complexen, Myb en Myb interacterende eiwitten. dREAM-Myb/MuvB is betrokken in transcriptionele onderdrukking maar bevat geen chromatine modificerende enzymen. Uit onderzoek [Korenjak 04] is gebleken dat het dREAM complex alleen bindt aan gedeacetyleerde histon H4 staarten en niet aan geacetyleerd histon H4 staarten (zie figuur 13). Dit duidt waarschijnlijk op een mechanisme waarbij dREAM acetylatie van target gen promoters voorkomt en ze in een onderdrukte staat houdt. Uit het onderzoek van Korenjak kwamen ook resultaten dat het dREAM complex nodig is om de genen arp53D, CG17142 enCG3505 (groep E genen) in S2 cellen stil te leggen. Deze genen zijn permanent onderdrukt in S2 cellen en geven een seks- of weefsel-specifiek expressie patroon. Hiernaast werd er in dit onderzoek aangetoond dat de dREAM subunits dE2F2 en Mip130/TWIT, in vivo, fysiek geassocieerd kunnen worden met deze groep E genen. Dit wijst erop dat dREAM complexen assembleren bij de genen arp53D, CG17142 enCG3505 en effect hebben op hun permanente onderdrukking in prolifererende cellen. Dit onderdrukkende effect blijkt echter specifiek te zijn voor genen die betrokken zijn in ontwikkelings- of seks-specifieke expressie patronen. Mogelijk is er een nog ander dE2F-RBF complex nodig voor de onderdrukking van celcyclus genen of onderdrukt het dREAM-Myb/MuvB complex de celcyclus controle targets onder andere condities. [Blais 07]. Regulatie van CKI In D. melanogaster embryos wordt de celcyclus exit gekarakteriseerd door een abrupte downregulatie van Cycline E en een korte piek van Dacapo expressie. In dap mutant embryos falen de meeste cellen in de epidermis en het perifere zenuwstelsel om op het juiste moment uit de mitotische cyclus te gaan en ondergaan een extra mitotische deling. Tijdens deze extra cyclus gaan de mutant cellen wel in mitotische rust wat erop wijst dat er meerdere mechanismen betrokken zijn in de exit van de mitotische cyclus. Waarschijnlijk functioneert downregulatie van de positieve cel cyclus regulator Cycline E in combinatie met de activatie van dap expressie voor celcyclus exit [de Nooij 00]. In figuur 14 is te zien dat in Cycline E mutant embryos een verlaging van Dacapo is. Cycline E is dus nodig voor Dacapo expressie. Uit eerdere onderzoeken was echter gebleken dat dap expressie geÃÆ' ¯nitieerd werd wanneer Cycline E niveaus daalde. Er waren ook resultaten dat er juist erg hoge Cycline E niveaus waren maar dat Dacapo niet geÃÆ' ¯nduceerd werd. Deze resultaten hebben tot het regulatie model in figuur 15 geleidt. Voordat de cel naar de celcyclus exit gaat en er precursor cellen worden ontwikkeld voorkomen ontwikkelings signalen de expressie van Dacapo ondanks de aanwezigheid van Cycline E. De remming van Dap expressie komt mogelijk door het gebrek aan essentiÃÆ' «le transcriptie activatoren of door de activiteit van transcriptie onderdrukkers. Vlak voordat de cellen klaar zijn met delen en differentiÃÆ' «ren worden ontwikkelingsremmers vrijgelaten en is Cycline E in staat tot het induceren van dap expressie. Dap translatie wordt gepromoot waardoor een snelle accumulatie van Dap ontstaat. Een hoge Cycline E activiteit promoot hiernaast de degradatie van Dap. Dit zorgt ervoor dat het Dap n iveau snel mee daalt wanneer het Cycline E niveau weer zal gaan dalen volgens het golvende model. Dap expressie zal na het volledig dalen ven het Cycline E niveau niet meer geÃÆ' ¯nduceerd worden. Uit de data van het onderzoek van de Nooij et al. blijkt dat Cycline E dap reguleert op transcriptioneel en post-transcriptioneel niveau. Ook blijkt uit de gegevens dat dap ook door andere signalen dan Cycline E wordt gereguleerd. Differentiatie signalen kunnen CKIs ook transcriptioneel reguleren zodat ze cellen aanzetten om in celcyclus exit te gaan. De Cip/Kip type CKIs worden onder andere gereguleerd door basic Helix Loop Helix (bHLH) transcriptie factoren. Hiernaast zetten groei-inhibitie signalen Kip type CKI aan tot accumulatie of activatie. Deze groei-remmende cytokines zoals morfogenen van de TGF-ÃŽÂ ² superfamilie en interferonen, en cel-cel contact induceren de synthese van de Cip/Kip CKIs [Mittnacht 98]. Ook condities van cellulaire stress zoals DNA schade of replicatie remming kunnen CKI synthese stimuleren. Er zijn dus meerdere factoren die de componenten van de celcyclus exit reguleren en veel hierover moet nog verder onderzocht worden. Hoofdstuk 4: conclusie In de laatste twintig jaar is er veel ontdekt over het mechanisme achter de celcyclus exit. Dit begon allemaal met de ontdekking van het eerste tumoronderdrukkende gen Rb. Ook E2F speelt een centrale rol in het coÃÆ' ¶rdineren van celcyclus progressie bij de G1 naar S fase of G0 overgang. De regulatie van specifieke target genen door Rb/E2F hangt echter niet alleen af van de aanwezigheid van specifieke Rb en E2F familie leden. Hun post-translationele modificaties en andere inter-acterende factoren spelen ook een belangrijke rol. Cyclines, cycline afhankelijke kinases en CDK inhibitoren spelen eveneens een belangrijke rol bij de celcyclus regulatie. Ondanks dat er al veel bekend is, blijven er ook een heleboel vraagtekens over de fysiologische rollen van Rb en E2F en het specifieke actie mechanisme dat deze rollen weer aanstuurt. Modelorganismen helpen bij het onderzoeken, van deze rollen en van gen functies, in verschillende fysiologische contexten. Vragen die overblijven en meer onderzoek nodig hebben zijn bijvoorbeeld: Hoe is de RB-familie en CKI activiteit gecoÃÆ' ¶rdineerd in het proces van terminale differentiatie? Zijn RBs en CKIs de enige cel cyclus remmers? En hoe grijpen de signalen aan op deze en mogelijk andere cel cyclus remmers? Een vraag die naar een ander pad van de celcyclus exit leidt is hoe de celcyclus exit behouden blijft in gedifferentieerde weefsel en niet weer gaat delen? Alleen quiescente cellen kunnen van nature de celcyclus exit verlaten en weer aan de celcyclus mee doen. Ze doen dit in de aanwezigheid van proliferatie-inducerende condities. Quiescente cellen kunnen in afwezigheid van groeifactoren geÃÆ' ¯nduceerd worden tot proliferatie door het weghalen van CKIs [Pajalunga 08]. Groeifactoren zijn dus waarschijnlijk voornamelijk nodig om de balans van positieve tegen negatieve celcyclus regulatoren te veranderen. Terminale differentiatie en senescente cellen kunnen niet van nature terug de celcyclus in gaan. Ze kunnen hier echter wel toe gestimuleerd worden. Verschillende soorten terminale differentiatie cellen kunnen door expressie van DNA-tumor-virus oncogenen, zoals SV40 LT of adenovirus E1A, gedwongen worden de celcyclus weer in te gaan [Pajalunga 08]. De verschillende groeiremmende mech anismen en moleculen hierachter zijn nog niet helemaal bekend en begrepen en er zal hier dus ook meer onderzoek naar gedaan moeten worden. Terminale differentiatie cellen kunnen ook door reactivatie van cdk4/6 kinase door overexpressie van cdk4/6 en cycline D1 weer terug de celcyclus ingaan. Ze kunnen hierbij weer skelet spier myotubes, adipocyten, enkele neuronen en cardiomyocyten vormen. Dit laat zien dat de voornaamste reden waarom terminale differentiatie cellen nooit spontaan de cel cyclus weer ingaan de negatieve controle van de cdk4/6 kinase is [Pajalunga 08]. Ook senescente cellen kunnen van nature niet terug de celcyclus in gaan. Ze kunnen wel weer geactiveerd worden en prolifereren door het weghalen van de CKIs p21 of p16 [Pajalunga 08]. In senescente cellen komt een hoog niveau van CKI complexen voor. De senescente cellen worden dus net als terminale differentiatie cellen in de celcyclus exit gehouden door hoge niveaus van remmers. De wetenschap dat de celcyclus weer geactiveerd kan worden door het weg halen van CKIs kan een belangrijke rol spelen voor omstandigheden waar de proliferatie zwak is zoals bij weefsel repair, cel vervangingstherapie, en regeneratie. De ontdekkingen in celcyclus regulatie helpen bij het beter begrijpen van kwaadaardige cel transformatie en bij de ontwikkeling van nieuwe therapieÃÆ' «n tegen kanker. Het is verder moeilijk om te beantwoorden welke componenten in het mechanisme van de celcyclus er nog missen. Een compleet antwoord op de vraag wat de regulatie mechanismen van de celcyclus exit zijn is er dus nog niet. Hopelijk leidt meer onderzoek uiteindelijk tot het volledig begrijpen van dit mechanisme. Referenties: Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., Walter, P. Molecular biology of the cell. Vierde editie. New York: Garland Science, Taylor and Francis group, 2002.p. 985. Fig 17-3. Bardin, A. J. Amon, A.Men and sin: whats the difference?Nat. Rev. Mol. Cell Biol.2, 815-826 (2001) Binne, U. K.et al. Retinoblastoma protein and anaphase-promoting complex physically interact and functionally cooperate during cell-cycle exit.Nat. Cell Biol.9, 225-232 (2007). Blais, A. Dynlacht, B. D.E2F-associated chromatin modifiers and cell cycle control.Curr. Opin. Cell Biol.19, 658-662 (2007). Buttitta, L. A. Edgar, B. A.Mechanisms controlling cell cycle exit upon terminal differentiation.Curr. Opin. Cell Biol.19, 697-704 (2007). Choksi, S. P.et al. Prospero acts as a binary switch between self-renewal and differentiation in Drosophila neural stem cells.Dev. Cell.11, 775-789 (2006). de Nooij, J. C., Graber, K. H. Hariharan, I. K.Expression of the cyclin-dependent kinase inhibitor Dacapo is regulated by cyclin E.Mech. Dev.97, 73-83 (2000). de Nooij, J. C., Letendre, M. A. Hariharan, I. K.A Cyclin-Dependent Kinase Inhibitor, Dacapo, Is Necessary for Timely Exit from the Cell Cycle during Drosophila Embryogenesis.Cell87, 1237-1247 (1996). Du, W. Pogoriler, J.Retinoblastoma family genes.Oncogene25, 5190-5200 (2006). Frolov, M. V. Dyson, N. J.Molecular mechanisms of E2F-dependent activation and pRB-mediated repression.J. Cell. Sci.117, 2173-2181 (2004). Harbour, J. W. Dean, D. C.The Rb/E2F pathway: expanding roles and emerging paradigms.Genes Dev.14, 2393-2409 (2000). Korenjak, M.et al. Native E2F/RBF complexes contain Myb-interacting proteins and repress transcription of developmentally controlled E2F target genes.Cell119, 181-193 (2004). La Thangue, N. B. Rigby, P. W.An adenovirus E1A-like transcription factor is regulated during the differentiation of murine embryonal carcinoma stem cells.Cell49, 507-513 (1987). Li, L. Vaessin, H.Pan-neural Prospero terminates cell proliferation during Drosophila neurogenesis.Genes Dev.14, 147-151 (2000). Mittnacht, S.Control of pRB phosphorylation.Curr. Opin. Genet. Dev.8, 21-27 (1998). Nelson, D. A., Krucher, N. A. Ludlow, J. W.High molecular weight protein phosphatase type 1 dephosphorylates the retinoblastoma protein.J. Biol. Chem.272, 4528-4535 (1997). Nevins, J. R.E2F: a link between the Rb tumor suppressor protein and viral oncoproteins.Science258, 424-429 (1992). Pajalunga, D., Mazzola, A., Franchitto, A., Puggioni, E. Crescenzi, M.The logic and regulation of cell cycle exit and reentry.Cell Mol. Life Sci.65, 8-15 (2008). Sherr, C. J. Roberts, J. M.Living with or without cyclins and cyclin-dependent kinases.Genes Dev.18, 2699-2711 (2004). Sherr, C. J. Roberts, J. M.CDK inhibitors: positive and negative regulators of G1-phase progression.Genes Dev.13, 1501-1512 (1999). Stevaux, O.et al. Retinoblastoma family 2 is required in vivo for the tissue-specific repression of dE2F2 target genes.Cell. Cycle4, 1272-1280 (2005). Sullivan, M. Morgan, D. O.Finishing mitosis, one step at a time.Nature Reviews Molecular Cell Biology8, 894-903 (2007). Swanhart, L. M., Sanders, A. N. Duronio, R. J.Normal regulation of Rbf1/E2f1 target genes in Drosophila type 1 protein phosphatase mutants.Developmental Dynamics236, 2567-2577 (2007). Trimarchi, J. M. Lees, J. A.Sibling rivalry in the E2F family.Nat. Rev. Mol. Cell Biol.3, 11-20 (2002). van den Heuvel, S.Cell-cycle regulation.WormBook, 1-16 (2005). van den Heuvel, S. Dyson, N. J.Conserved functions of the pRB and E2F families.Nat. Rev. Mol. Cell Biol.9, 713-724 (2008). Vietri, M., Bianchi, M., Ludlow, J. W., Mittnacht, S. Villa-Moruzzi, E.Direct interaction between the catalytic subunit of Protein Phosphatase 1 and pRb.Cancer. Cell. Int.6, 3 (2006).

Substance Abuse And Alcohol Abuse - 3037 Words

Substance abuse is use of a substance (drug) or alcohol in which the person consumes the substance/alcohol in amounts or with different methods which are harmful for themselves or others. Substance abuse and addictions are run in families. Alcohol drinking can be defined in many types as following- Social drinking is defined as occasional drinking in a social setting without an intention to get drunk. Binge drinking is defined as consumption of alcohol in excess of which is socially acceptable, with primary intention of becoming intoxicated by heavy episodic alcohol intake during a short period of time. Binge drinking is a problem among adolescents young adults particularly. The National Institute on Alcohol Abuse and Alcoholism [NIAAA]†¦show more content†¦Source:- Wikimedia Commons ( Mikael Haggstrom diagrams,2009). According to DSM-IV Criteria, Alcohol dependence is an abnormal adaptation of substance use, causing a significant impairment or distress clinically , as manifested by 3 (or more) of the following occurring at any time in the same 12 months duration :----- 1) Tolerance, can be defined by any of the following ----- *They require markedly excess amounts of the alcohol to achieve intoxication or desired effect or *Markedly decreasing effect with continued use of the same amount of alcohol. 2) Withdrawal, as manifested with any of the following------ *The specific withdrawal syndrome for the alcohol or *The same (or closely similar) substance is consumed to relieve or avoid these withdrawal symptoms. 3) The substance is often consumed in excess amount or over a longer duration than was intended. 4) Patient has a persistent desire or unsuccessful effort to cut down on or control alcohol use. 5) Large time is spent in activities to obtain the alcohol, use of alcohol or recover from its effects. 6) Important recreational, occupational or social activities are given up or reduced because of alcohol use. 7) Patient has continued consumption of alcohol despite knowledge of

Your Trusted Friends Analysis Free Essays

Have you ever been watching television and right in the middle of your show been flooded with an endless amount of commercials? If you answered yes, I’m willing to bet that one of those advertisements were for one of the many fast food companies in the United States. In our country, fast food corporations have a dominating grasp on the consumer and the market as to which they are tackling. Some are calling it a pandemic, the next tobacco, and even a deadly drug that is being given to us willingly without any restrictions. We will write a custom essay sample on Your Trusted Friends Analysis or any similar topic only for you Order Now Society has come to see this so called viable source of food as a quick, convenient way of getting the nutrition needed during our everyday lives. The only reason as to which we have been able to convince our minds that what is being offered is ok is due to the intense advertising campaigns, which these multi-million dollar fast food companies run. With ads directed at adults showing how a quick burger can be convenient on the go to a full blown marketing campaign directed at kids from ages three to thirteen, fast food companies have been able to brainwash most of America without any real restrictions. To ensure the health and well being of our countries youth, fast food companies must take more responsibility and be required to have restrictions on their marketing campaigns. Toys, Play place’s, clowns and kid’s club are only a few of the many marketing ploys which giant fast food companies have enacted to grab the youth demographic and capitalize on it. What kid is going to deny a fun finger food like french-fries, a cheeseburger, and on top of all that a toy! It’s like the big brother stealing candy from his younger sibling. In America, we have determined that the age of 18 is when one is considered an adult and liable for his own actions. Yet we allow major companies, which are detrimental to our overall health, to spend billions of dollars on marketing tactics that our directed solely at our countries youth. How can we expect these young children to make decision about poor food choices and living a healthy lifestyle when there is a toy involved? Schlosser touches on the growing problems with marketing that is aimed directly at the youth. He admits that studies don’t by the FTC show that young children cannot tell the difference between advertisements and actual television shows (192). This gives these companies a huge advantage over their target market. The child’s brain is under constant development and when they are exposed to so many advertisements daily for these fun, exciting foods that come with toys and feelings of fun, they are bound to give in do to their sheer mental capacity. In Eric Schlossers article â€Å"Your Trusted Friends† he states, â€Å"The typical American child now spends about twenty-one hours a week watching television- roughly one and a half months of TV a year† (193). This being said, children are seeing hundreds of these brainwashing commercials a week. Fast food corporations are pretty much stealing from the helpless with out any repercussions. Without any restrictions theses billion dollar empires are going to continue to target the heart of America, which will inevitably leading to a completely unhealthy nation who is blinded by the advertisements. It is time someone steps in and makes a change to benefit those who are suffering the most from this outrageous marketing scheme, our nations youth. That someone I speak of is the government. We need stricter policies on advertisements and target audiences. It’s one thing for an adult male to make a decision to eat the unhealthy food offered by these companies. Being an adult he should be able to understand the consequences of eating fast food. It’s the eight-year-old child who does not. If fast food companies are going to base their marketing campaigns around children they should be inclined to help support positive programs for theses children such as schools physical education, summer programs and other activities that will teach kids to become active. The government needs to formulate a plan that would implement strict tax laws on marketing campaigns directed at younger audiences we could use these tax dollars for these types of programs that would counter the effects these companies products are having on the kid. I doubt parents would feel as bad giving McDonalds their money for non-nutritious food if they new a few pennies out of the cost of a cheeseburger would be going to her child’s elementary school P. E. fund. Kids will always love toys, fun foods and a happy time and these companies know that. There is no stopping the marketing that will be pushed at these kids. But what we can do is hold the companies responsible and demand that they give back. Our country over the past decade has been through everything from wars to recessions and the last thing we need is to only worsen the poor health of our country due to fast food. Our most impressionable citizens, our youth, are being flooded every day by the intense marketing schemes from fast food companies daily. These empires that have been built on our bad eating habits and poor decisions are only going to get worse and effect our children as well grandchildren if we don’t start finding solutions to counteract what these companies our doing to us. And I say counteract because we cannot bring these companies down. What we can do is hold them accountable and demand that they give a fraction of what they put into these giant marketing campaigns back to our nation’s children and the programs that are needed to keep them healthy. If we are going to make certain that our country lasts we must make fast food companies more responsible for the elaborate schemes they direct at our children. With some push and demanding of change from our government concerning this issue we can ensure the future health of our country. How to cite Your Trusted Friends Analysis, Papers

Human Physical Appearance and Inner Beauty free essay sample

Beauty is an aspect, an attribute or characteristic that a person has which can be defined as anything that appeals the other individual. It could be ones looks personality or even habits that would be attractive to other people. It is really very hard to enumerate these features because they vary from one person to the next and are also very many. Physical beauty could refer to someones outer attributes such as elegance, complexion or figure while inner beauty is more concerned with someones traits such as a sense of humor, character or good general behavior, kind heart, empathy, always helping nature. This definition changes depending on how an individual perceives beauty. Science has alluded that one can be said to be beautiful if they possess facial features that are nearly symmetrical. This again is a very subjective issue that is yet to be fully proven. Inner beauty on the other hand is of the intellect and mostly refers to people with good intentions to pleasing others. It is therefore true to say that inner beauty is something that has to be psychologically or mentally perceived. Many argue that beauty of the inside is far better and more preferable than physical beauty. This is because, despite having any good looks, bad behavior is likely to tarnish ones attractiveness to others to an extent that the superficial attributes do not even matter anymore. One may be the personification of physical beauty but what matters at the end of the day is their inner beauty. Purity within outshines what is on the face and it will always show no matter what he physical looks are. Another key difference between outer beauty and inner beauty is that, while physical beauty is mostly given naturally through birth, one can however work toward attaining true inner beauty by simply changing their characters to match what is attractive to the people around them. The obsession with the search for only physical beauty neglects the inner beauty which could be the most important aspect in a human being. It is the aura that we bring about in our lives and even the spiritual aspect of our livelihoods. Attraction to physical matter can also be said as to be driven by subject matter while that of inner beauty is considered as being objective. Objectivity is about understanding the inside first, liking it and then liking the outside next. It is rather unfair to discriminate against physical beauty because the subject mostly has no say on how they would want to look from the outside but people can choose to be nice and well behaved, which turns out to be a very pleasant characteristic to possess for an individual. The demand for physical attractiveness is also short-lived as compared to the quest for inner beauty. People that are thought to be physically attractive could later seem not so appealing to them if they start to behave in an unpleasant manner. However, if someone is always well mannered and has a love and kindness to people, they will forever be perceived to possess inner beauty that cannot be taken away from them. Inner beauty is also about how you feel about yourself. When you feel beautiful, that is inner beauty. On the other hand physical beauty is left for the judgment of the onlooker. Inner beauty in this way is about how we feel and treat each other. We should also note that physical beauty changes everyday according to what the society reflects on us through television, movie, media, the role models around us religion and many other social factors. This therefore means that what looks beautiful today might not be regarded as beautiful in the future. This is unlike inner beauty whose fundamental principles can stand the test of time. Attributes such as kindness, love, helping others and many more have been considered as excellent inner beauty attributes for generations as well as across different sections of the society such as race and religion. I conclusion, we can say that inner beauty has a higher meaning on how we look at what is attractive. We should be more interested in the inner beauty first before seeking what is on the outside. This is however yet to be realized as most people are blinded by what they see on the outside only to later realize that the people they were attracted to are not as beautiful on the inside. As long as this happens, many will not fully enjoy the gift of people that are beautiful inside but rather be driven by an obsession to like what looks beautiful on the outside. Many have heard the old proverb â€Å"beauty is in the eye of the beholder† and how true these words are. One may see a person and find them attractive, while another sees nothing attractive in that particular person. Outer and inner beauty plays a major role in life, which leads to the fulfillment each one seeks. Both are needed but if one is magnified than the other, discrimination from others will be a problem. Whether it’s from looks or the beauty that lies within, it will be seen and sensed. Beauty is an asset to life which is needed, and both inner and outer are important. Being able to balance them both will enhance opportunities that will attribute to each one’s uniqueness and goals. Inner beauty by itself cannot always stand alone, just like outer beauty can’t as well, but it will always outshine outer beauty in the long run. Knowing the characteristics, how they attract others, and the healthy choices that are made are to be considered in finding true beauty that lies within each and every one of us. There are many characteristics to beauty, and both inner and outer play a role in what matters. As perceived, beauty depends on the one looking in, on what they think is beautiful. Inner beauty relates to one’s personality traits, habits, or even sense of humor. A person who has inner beauty is caring, understanding, helps when help is needed, and believes when all fail to believe. Standing up for what is just, and defending those who have no defender is a rare but powerful characteristic found in the hearts of those who possess inner beauty. However, outer beauty defines the elegance, features, figure, or complexion of one. But when it stands alone, outer beauty is nothing but selfish, greedy, and arrogant pride, mixed with good looks. A person may acquire physical traits of beauty, and have all the features and figure that come in the package, but if they have it alone one, action could cast all the. I define inner beauty as a beauty that someone has inside and they help you and are not judgmental. I define outer beauty as the beauty that is good to look at, but only in a physical sense. Beauty is defined in the Merriam-Webster dictionary as the quality or aggregate of qualities in a person or thing that gives pleasure to the senses or pleasurably exalts the mind or spirit. An even better explanation of beauty is Physical beauty is good, and it is definitely something that should be cultivated. However, there is a higher beauty than this mere physical type of beauty. This higher beauty is the beauty that we see when we observe people helping and serving others especially those in need. Although physical beauty is very valuable and good, this higher beauty is something that should be sought out even more. http://www. beauty007. com/art_phil_what_is_beauty. html Both inner beauty and outer beauty are great but only inner beauty can stand-alone. It would be a great thing for a person to possess both inner and outer beauty and some do. Not everyone looks at him or herself and think about their inner beauty. They only look and think they are not beautiful by looking at the outside. Its amazing the damage someone can do to someone by judging based on outer beauty only.

6 Tips for Writing Good Website Copy Blog

6 Tips for Writing Good Website Copy Blog 6 Tips for Writing Good Website Copy The internet is a big place, with a lot of websites competing for attention. How, then, can you make sure that your website stands out from the crowd? 1. Get to the Point! People have busy lives. If they’re looking for information online, they want it quickly. As such, each page on your site should clearly state what it is about. If you are writing copy for a pizza restaurant, for example, you would want to say what kind of food it sells and where the restaurant is first, as these are the most important details. An appetizing image will go a long way, too! Should you have more to say, you can save it for further down the page! 2. Keep It Short Short paragraphs are much easier to read, especially on screen. And since you’re not limited by page size with website copy, there is no reason to pack a lot of text into a small space. The ideal length of a paragraph on paper is typically around 100-200 words. But even this is too long for online copy, where paragraphs shouldn’t be more than two or three sentences long. You can even use single-sentence paragraphs, like this one! 3. Use Simple Language There is a place for long, fancy words on the internet (especially in online Scrabble). But your website copy needs to be easy to read and you should keep your writing simple. This may include: Using clear, concise sentences Avoiding jargon and technical language Using the active voice Using shorter words where possible For example, if you were selling lawnmowers, you could boast of offering â€Å"contraptions for the accelerated and efficacious reduction of Poa pratensis.† But it would be much better for everyone involved if you simply said â€Å"machines for fast and effective lawn care† instead. 4. Format for Skimmers How you format your copy is almost as important as what you write. In particular, you need to format your writing to catch the attention of skim readers. This means using: Subheadings to break up the text Bold fonts or other emphasis to highlight key words Bullet points and numbered lists Images and/or videos alongside the text If your reader can spot key information thanks to formatting, this will keep them on the site. 5. Think SEO When writing website copy, you’re not just writing for human readers. You’re also writing for search engines, as this is one way that people will find your site. This is where search engine optimization (SEO) comes in. We won’t go into any depth about SEO here, as it is a complicated subject. But the basic idea involves: Identifying key words for each page on the site (i.e. what people will search for to find it) Working these naturally into your website copy If you do not have key words yet, do a little research online to find the right ones for your site. 6. Proofread Everything The internet is a Wild West for writing, with the rules of grammar, spelling, and punctuation often ignored. But typos on your website will look unprofessional. And if you don’t care about your website copy, people might think you don’t care about your business either! As such, getting your website copy proofread before it goes online is essential.

Owning A Coffe Shop

Owning A Coffe Shop Free Online Research Papers In considering my future, I have decided that I want to own and manage a coffee shop. I love to sample and drink different varieties and forms of coffee beverages. I enjoy the chilled atmosphere and the people that frequent coffee shops. After thinking about my career choices for the past year, I have decided to pursue a coffee shop entrepreneurship or franchise. A review of the nature of the job, the required education, the job outlook, and the sources of education for this field will help to develop a plan to reach this dream. Business managers take full responsibility of the daily routine of their business. They must plan, direct, and coordinate the business so it can run smoothly and efficiently. Businesses haves goals, and its goal is to make profit. To meet this goal, they must most importantly make sales, have the necessary materials, correct budget, and have potential employees (Morkes 3). Managers must look after the inventory while checking up on the maintenance for the upkeep. They must schedule hours for their employees. When running a food service, Managers are responsible for the correct food preparation that has been ordered and the consumers satisfactory (Nature of the Work www.cfnc.org) Managers May hire or be an executive chef who is responsible foe all food orders, running the kitchen, plan the menu, and having quality food (Nature of Work www.cfnc.org). Managers may also hire Assistant managers to look over a specific department (Walsh 3). Managers should communicate well with others. In some cases; in different languages. They should be laid back, flexible and can handle high tension situations without too much stress. They should be able to keep their cool stay professional when they are dealing with mad, annoying customers and uncooperative employees (Nature of the Work www.cfnc.org) It’s also important to keep a positive mind to keep you going (Foot). Its generally easy to become a manager with a degree in foods and nutrition. It’s also possible to become a manager with a degree in any other field because it shows that you are determined and motivated in your work which is as good as having a 4-year degree in foods and nutrition. A bachelors degree in restaurant and food service is a great preparation for this occupation. For those who are not interested in a 4-year degree can get an associate degree at a community college. Community colleges also offer a 2-year and a 4-year programs that has subjects closely relative to this field (Training, Other Qualifications, and Advancement www.cfnc.org) The salary for a food service manager may vary from restaurant to restaurant due to consumers interest in your food you prepare and competition with other fellow restaurant. The average yearly income in this service is about 38,710 (Walsh 4). The Business itself makes much more money than this, but you must consider the cost of the business such as facilities, resources, employees payroll, and upkeep. Some food service manager, generally in full-service restaurants, can get bonuses based on the businesses sales or revenue (Earnings www.cfnc.org) Opportunities continue to grow. Businesses are always look for replacements for managers who might have transferred to another job site or just decided to quit. Applicants with a 2-year degree will have a good chance to be hires. Applicants with a higher level will have the best advantages. Other opportunities happen through advancements. Start off as a waiter or waitress and show high responsibility and the ability to handle the job greatly. Then it is possible to be advanced to assistant manager, then if the business is in need of a manager, it is possible to be advanced to manager (Training, Other Qualifications, and Advancement www.cfnc.org). When advanced to manager, you are able to partake in educational programs, generally paid by a organization or the business (Walsh 5). Wayne Community College is just fine for my preparation in this occupation. Here, I will earn my bachelors degree. My major will be foods and nutrition and minor in communications. The tuition is $632.00, activity fees are $16.00 equaling it up to $648.00. My payment method is quit easy, my parent and I already agreed that they will pay for my tuition if I live with them during these two years for tax break reasons. Doing these studies, I have more knowledge about this occupation and how it works. There is a lot more to it than my first original thought. The schooling is not too much to handle. Though the job is a lot of work, I still would like to do this job. Research Papers on Owning A Coffe ShopThe Project Managment Office SystemMarketing of Lifeboy Soap A Unilever ProductNever Been Kicked Out of a Place This NiceAnalysis of Ebay Expanding into AsiaOpen Architechture a white paperResearch Process Part OneGenetic EngineeringThe Effects of Illegal ImmigrationThe Hockey GameTwilight of the UAW

Use r(which is a software) stata or excel to do the assignment - 1

Use r(which is a software) stata or excel to do the - Assignment Example This supports the model, which supposes that education is a factor of labor production The scatter plot assumes a downhill pattern as we move from left to right. As the values in the horizontal axis increase, those in the vertical axis decrease. The trend line drawn also depicts a negative linear association with outliers on either side. The data are scattered all over indicating a t-statistics of less than 0.5 hence weak correlation detected. From the analysis, showing the strong correlation and positive relationship, one can conclude that there is a possible association between education and labor production in any country. This supports the model, which supposes that education is a factor of labor production. The analysis supports the theory that level of education is not a factor for infant mortality. In which case, education only serves as a growth factor and not as a factor which can reduce the number of infants’ deaths. From the scatter plot, the pattern depicted assumes an uphill pattern as we move from left to right. As the values in the horizontal axis increase so do those in the vertical axis. The trend line drawn also depicts a linear association with outliers on either side. Consequently, the aspects show a linear association between the two variables. The cluster also insinuates a t-statistics of more than 5 hence the strong correlation detected. This analysis supports the theory that there is a possibility of relationship between higher levels of education and domestic saving rates. The scatter plots drawn above, shows that levels of education act as one of the major factors influencing growth in a country. First, the possibility of its relation to domestic savings rate shows that a country with greater level of education is likely to witness growth. This is because the increased savings put a country in a better place for exploiting every opportunity that proves beneficial towards growth. Further,

Organization Attractiveness Assignment Example | Topics and Well Written Essays - 250 words

Organization Attractiveness - Assignment Example In the general workforce, the two mentioned attributes can be said to be highly applicable to recruiting talent. This is because in a well motivated organization, there is very little for employees to look outside for (Greenberg & Sweeney, 2010). Because employees get all that they require by way of salary, allowances and other forms of remuneration, chances that they will be looking elsewhere after settling for a new job are less. Meanwhile, the longer employees try their hands on one thing, the better they become with their talents (Silzer & Dowell, 2010). Engagement is also necessary in recruiting talent because it is the only way by which employees can have a feeling that their talents are being respected and being put to use (Felps et al., 2009). As far as talented people are concerned, there are other attributes that contribute to their selection of one organization other the other. A working environment that encourages growth is one such attribute. This is because every talented person wants to work in an environment where original talent will not only be utilized but also nurtured to grow (Greenberg & Sweeney, 2010). Finally, competition is crucial for talented people because it forces them to always look out for more in terms of making use of what they already have. Felps, W., Mitchell, T. R., Hekman, D. R., Lee, T. W., Holtom, B. C., & Harman, W. S. (2009). Turnover contagion: How coworkers job embeddedness and job search behaviors influence quitting. Academy of Management Journal, 52(3),

Drug Profile of Tizanidine HCl

Drug Profile of Tizanidine HCl Structure: Categories: Analgesics, Anticonvulsants, Parasympatholytics, Muscle Relaxants, Central, Adrenergic aipha-2 Receptor Agonists, Neuromuscular Agents, Muscle relaxant , Skeletal Weight: Average: 253.711 Monoisotopic: 253.018893678 Chemical Formula: C9H8ClN5S IUPAC Name: 5-Chloro-N-(4, 5-dihydro-1H-imidazol-2, 1, 3-benzothiadiazol-4-amine Taxonomy: Kingdom: Organic Compounds Superclass: Heterocyclic Compounds Class: Benzothiadiazoles Direct parent: Benzothiadiazoles Alternative parents: Chlorobenzenes:Thiadiazoles; Polyamines; Aryl Chlorides; Guanidines; Organochlorides. Substituents: Chlorobenzene: Aryl chloride; Aryl halide; Thiadiazole; Guanidine; Azole; Organochloride; Organohalogen; Polyamine; Organonitrogen compound; Amine. Classification: These belong to Heterocyclic. This compound belongs to the benzothiadiazoles. Description: Aromatic compound containing a benzene ring fused to a thiadiazole ring. Pharmacology: Indication: To manage increased muscle tone associated with spasticity. For the management of spasticity Tizanidine is a short- acting drug. It is a agonist at a2-adrenergic receptor sites and by increasing presynaptic inhibition of motor neurons presumably decreases spasticity. Pharmacodynamics: Tizanidine has no direct effect on neuromuscular junction or skeletal muscle fibers and in monosynaptic spinal reflexes there is no major effect, in animal models. On polysynaptic pathways the effects of Tizanidine are more. To reduce the facilitation of spinal motor neurons the overall effect of these actions are thought. Mechanism of action: By increasing the presynaptic inhibition of motor neurons reduces Tizanidine spasticity through agonist action at a2-adrenergic receptor sites. Volume of distribution: 2.4L/kg Protein binding: 30% Route of elimination: Approximately 95% of an administered dose is metabolized. Half life: 2.5 hours Affected organisms: Humans and other mammals Drug interactions: Amlodipine: Amlodipine may decrease the clearance and metabolism of Tizanidine During co-administration considers alternate use caution or Therapy. Benazepril: With ACE inhibitor Tizanidine increases the risk of hypotension. Captopril: With ACE inhibitor Tizanidine increases the risk of hypotension. Solubility: Storage: cool dry place and in well-closed container. 4.3. EXCIPIENT PROFILE: Pharmaceutical excipients are substances, alternative than the pharmacologically effective drug or prodrug, that are indicated in the manufacturing process are hold in the final pharmaceutical compound dosage form. Excipients bring enhance practicability to the pharmaceuticals, advancement the alterations in the drug development and aid to advance patent life as well. Excipients arrange the products also practical at lower cost, they use a lot aim by the pharmaceutical industry which is overflow with pressure to reduce cost. Excipients show a comprehensive change of useful in pharmaceutical dosage forms, along with: The bioavailability and solubility of active pharmaceutical ingredients (APIs) have been modulated. In dosage forms stability of the active ingredients have been increased. Preferred polymorphic conformations or forms are maintained by helping active ingredients. Maintaining the pH and/or osmolality of liquid productions. Acting as emulsifying agents, antioxidants, tablet binders, aerosol propellants, and as a tablet disintegrate. Preventing dissociation or aggregation (e.g., polysaccharide and actives protein). Immunogenic responses of active ingredients are modulated (e.g., adjuvant). Polymers: Hydroxypropyl methylcellulose Synonyms: Hydroxypropyl methyl ether, HPMC, Methocel. Methylcellulose propylene glycol ether, Methyl hydroxypropyl methyl ether [9004-65-3]. Non- proprietary name: BP:Hypromellose USP:Hydroxypropyl methylcellulose Functional Category: Coating agent, viscosity- increasing agent, tablet binder. Description: HPMC is tasteless and an odorless, white fibrous or granular powder, white or creamy. Alkalinity /acidity: pH 5.5-8.0 for a 1%w/w aqueous solution. Melting point: Browns at 190-200 °C, chars at 225-230 °C, glass transition temperature is 170-180 °C. Moisture content: Hydroxypropyl methyl cellulose consume moisture from the atmosphere, the quantity of water consumed based on the moisture content and relative humidity and temperature of the surrounding air. Solubility: Soluble in forming a viscous colloidal solution, cold water, practically insoluble in ethanol (95%), chloroform, and either, but soluble in mixtures of dichloromethane and ethanol and mixtures of dichloromethane and methanol, and mixtures of alcohol and water. Methocel productUSP 28 DesignationNormal Viscosity (cps) Methoel K4M Premium 22084000 Methocel K100M Premium2208100000 Methocel K15M Premium220815000 Most influential factors is drug solubility for designing a drug release pattern. Require higher amounts of HPMC in the tablet because they are highly water soluble drugs. Suitable types of HPMC are the methocel K100M and methocel K4M grades, which have a characteristics of quick hydration and gel formation. The higher amount of HPMC or viscosity of HPMC can decrease the drug release rate in the tablet. Generally, maximum contended of methocel in the tablet is less 20%. If the contended is below 20%, there is a danger for excess dissolution in the 1st stage or initial erosion. Application in pharmaceutical formulation or technology: Hypromellose is mostly used in oral and pharmaceutical formulation. Hypromellose is most primarily used as a binder in tablet for oral products, as an extended release tablet matrix and in film coating. Depending upon the viscosity grade, concentration of 2-20% w/w are used in film coating tablets as film-forming solutions. In aqueous film-coating solutions Lower-viscosity grades are used. While in organic solvents higher-viscosity grades are used. Hypromellose at concentration between 0.45-1.0% w/w are may be used for eye drops and artificial tear solution as a thickening agent to vehicles. Also, used as suspending agent, an emulsifier, and stabilizing agent in topical ointments and gels. In addition, for manufacture of capsule hyprmellose is used, for hard contact lenses as a wetting agent and as an adhesive in plastic bandages. Also mostly used in food products and cosmetics. Stability and storage Conditions: HPMC powder is balanced material, although it is hygroscopic after drying. HPMC powder should be stored in a in a cool, dry place and in well- closed container. Incompatibilities: With some oxidizing agents HPMC is incompatible. HPMC will not complex with ionic organic or metallic salts to form insoluble precipitates since it is non-ionic. Safety: It is generally considered as a non-irritant and nontoxic material although oral consumption may have a laxative effect39. Sodium bicarbonate Non-proprietary names: BP/EP: sodium bicarbonate Synonym: Baking soda, e-500, and monosodium carbonate. Chemical name: carbonic acid, monosodium salt, monosodium carbonate. Empirical formula: NaHCO3 Molecular weight: 84.01 Category: alkalizing agent, therapeutic agent. Description: it is an odorless, white crystalline powder with slight alkaline taste. Acidity/ alkalinity: pH 8.3 for freshly prepared 0.1m aqueous solution at 250C. Density: 2.159 g/cm3 Solubility: Practically insoluble in ethanol and soluble in water,. Stability and storage: Sodium bicarbonate is balanced in dry air but still slowly disintegrates in moist air and should accordingly be reserved in a cool dry place and in well-closed container. Safety: sodium bicarbonate balance gastric acid with the change of carbon dioxide orally ingested and that may cause stomach cramps and flatulence. Applications: Employed as a cause of carbon dioxide in effervescent tablets and granules. Also used to buffer the drug molecules that are weak acids. Used in solutions as buffering agent. Also used as freeze-drying stabilizer. As a gas forming agent40. Magnesium stearate Nonproprietary names: BP: Magnesium Stearate, IP: Magnesium Stearate, PhEur: Magnesiistearas, USPNF: Magnesium Stearate. Synonyms: Magnesium octadecananoate; Octadecanoic acid; Magnesium salt; stearic acid magnesium salt. Empirical formula: C36H70MgO4 Chemical name: Octadecanoic acid magnesium salt Molecular weight: 591.34 Structural Formula: Fig 13. Structure of Magnesium Sterate Functional category: Capsule and tablet lubricant. Applications in Pharmaceutical Technology: Magnesium stearate is mostly used in pharmaceutical formulations food and cosmetics. Most primarily at the time of tablet and capsule manufacturing used as a lubricant with concentrations between 0.25% and 0.5% w/w. And also used in barrier creams. Description: Magnesium stearate is actual accomplished milled or precipitated, light white, impalable powder of less bulk density, having faint smell of stearic acid and a quality taste. The powder readily be attached to the skin and greasy to touch. Solubility: Practically insoluble in ether, ethanol (95%), ethanol, ether and water, slightly. Soluble in warm ethanol (95%) and warm benzene41. . Microcrystalline cellulose Synonyms: Microcrystalline cellulose, Avicel, Crystalline cellulose, emocel, vivacel, Cellulosum microcrystallinum. Chemical Name: Cellulose Empirical Formula: (C6H10O5)n where n ≈ 220. Structural formula: Fig 14: Structure of microcrystalline cellulose Functional category: suspending agent, Adsorbent, tablet disintegrant, tablet and capsule diluent. Applications in pharmaceutical formulation or technology: It is primarily used as a diluent/ binder in oral tablet and capsule formulation in both wet granulation processes and direct compression. It has also got some lubricant, antiadherent, and disintegrating properties, which is useful in tableting. Microcrystalline cellulose is used in food products and cosmetics. Description: It occurs as a white, tasteless, odourless crystalline powder keeping of porous particles. It is commercially applicable in different applications and properties. Solubility: Slightly soluble in 5% w/v sodium hydroxide solution; insoluble in most organic solvents, water and dilute acids. GradeNominal mean particle size ( µm)Moisture content Avicel pH -10150≠¤5.0 Avicel pH -102100≠¤5.0 Uses of microcrystalline cellulose Density (bulk): 0.28-0.32 g/cm3 for Avicel PH 102 and 0.29-0.36 g/cm3 for Avicel PH 200 pH: 5.5-7 Flowability: 1.41 g/s Melting point: 260–270 °C. Moisture content: Typically less than 5% w/w. Solubility: Insoluble in dilute acids and water, slightly soluble in 5% w/v sodium hydroxide solution. Specific surface area: 1.21–1.30 m2/g for Avicel pH-102, 0.78–1.18 m2/g for Avicel pH-200. Stability: Microcrystalline cellulose is a stable though hygroscopic material. Storage Conditions: Storeatambientconditions.Keepcontainers sealed; material is very hygroscopic. Incompatibilities: Incompatible with strong oxidizing agents43. Xanthum gum Synonyms: Bacterial Polysaccharide, Corn Sugar Gum, Xanthan, Gomme desucre de mais, Polysaccharide Xanthane, Gomme Xanthane, Polysaccharide Bactà ©rien, Xanthane, Goma Xantana, Xanthomonas campestris. Gomme de Xanthane, Description: Xanthan gum is a sugar-like compound prepared by blending aged (fermented) sugars with assured kind of bacteria. It is used to make medicine. It is used in making some medications and foods. In these products it has different effects. It can keep textures from changing, add thickness, and hold ingredients in place. In many types of medicines Xanthan gum is found. These include: Tablets which slowly break down in the body Liquid drops for the eyes Xanthan gum is formed by heating a carbohydrate (a substance which consists of sugar) withXanthomonas campestrisbacteria, then processing it. Uses: Use as a bulk-forming laxative to treatconstipation. In people with diabetes it lowers blood sugar. In people with diabetes it lowers cholesterollevels. For dry mouth used as a saliva substitute. Side effects: Xanthan gum assume to cause some side effects. A 1987 study, in that five men who are healthy ate roughly 10 to 13gm daily, has commence no adverse effects. It may cause gas. Risks.The FDA has warned against for giving simply thick to premature infants. It has been combined to a danger digestive problem called necrotizing enterocolitis in neonate born prematurely. Interactions: Medications for diabetes (Antidiabetes drugs) interrelates with XANTHAN GUM. By decreasing the absorption of sugars in food Xanthan gum might lower blood sugar. To lower blood sugar Diabetes medications are also used. Blood sugar to be too low may cause by taking xanthan gum with diabetes medications. Guide your blood sugar nearly. The dose of your diabetes medication may need to change. Some medications used for diabetes be composed of glimepiride (Amaryl), chlorpropamide (Diabinese), glyburide, glipizide (Glucotrol), (Micronase, Dia Beta, Pres Tab, Glynase), pioglitazone (Actos), insulin, rosiglitazone (Avandia), tolbutamide (Orinase), and others. Dosing: In scientific research the following doses have been studied. Bymouth: The World Health Organization (WHO) has agreed the maximum pleasing intake for xanthan gum as a laxative of 15 grams per day and as a food additive of 10 mg/kg /day. Xanthan gum require extra fluids for effectiveness and safety, bulk laxatives such as. For diabetes: As an ingredient in muffins a typical dose is 12grams per day44. Aerosil IUPAC Name: Silicon dioxide Synonyms: Quartz, Silicic oxide, Silica, Crystalline silica, Silicon (IV) oxide, Description: Silicon dioxide, also known assilica (from the  Latinsilex), is a  chemical compound  that is an  oxide  of  silicon  with  chemical formulaSiO2. It has been known since ancient times. Silica is most usually found in nature as  quartz or sand, and also in the  cell   walls  of  diatoms  (frustule). Silica is prepared in many forms including fused quartz,  crystal,  fumed silica  (or pyrogenic silica), aerogel,  colloidal silica, and silica gel49.

Universal Microcontroller (Mcu) Trainer

CHAPTER I INTRODUCTION AND ITS BACKGROUND This section begins with a discussion of the role and importance of Microcontroller in everyday life. As we all know, Microcontrollers are considered as a major discovery in terms of science and technology. Just like the other major advances, it can control system and devices which can make people’s lives better and easier. Based on â€Å"The Microcontroller Idea Book† by Jan Axelson, Microcontroller is a computer-on-a-chip, or a single chip computer.It is said to be a single-chip computer because it contains memory and Input or Output interfaces in addition to the Central Processing Unit (CPU). Micro, as its name implies, advised that the device is small and Controller, however, tells that the device might be used to control objects as well as processes. Moreover, MCU has been described as an embedded controller, because the Microcontroller and its support circuits are often built into, or embedded in, the devices that they con trol.Basically, any product that interacts with its user has a microcontroller inside. The field of Microcontroller (MCU) beginning is due to the development of integrated circuits. It enabled the storing of hundreds of thousands of transistors into one chip which was later used in the manufacturing of Microcontrollers. Nowadays, we can find Microcontrollers in almost all kinds of things. Most of those things and devices are well-known to utilize for measuring, storing, calculating, controlling, and displaying of information.One of the largest applications of Microcontroller is in automobiles as it includes at least one MCU for engine control. In test equipment, microcontrollers make it easy to add features such as the ability to store measurements, to create and store user routines, and to display messages. In a desktop computer, MCU is founded inside keyboards, modems, printers, and other peripherals. Furthermore, products that we are fond of using like cameras, video recorders, c ompact-disk players, and ovens also use Microcontrollers. Background of the StudyMicrocontrollers have only been with us for a few decades but its impact on our lives is intense. Most of the microcontroller parts can be found in all electronic devices; it can be found on products which we use in our home like microwave ovens, alarm clock, washing machines, toys, and stereo equipment. Other common devices such as cash register, weighing scales, typewriters, photocopiers, elevators, industrial automation device, safety system, cars and traffic signals are some examples of microcontroller application.Numerous types of microcontrollers were designed and they quickly became man's invisible companion. It is also regarded as a powerful tool that allows a designer in creating his own design. Some of the crucial influence in the microcontroller development and success are powerful and carefully chosen electronics such as switches, push buttons, sensors, LCD displays, and relays, cheap automa tic devices and its power was widely spread prior to the knowledge in programming.With the necessity of making our MCU experience learning more enjoyable and helping us to do our jobs easier and safer, e- Gizmo decided to develop and launched the first Universal MCU Trainer. Unlike some of those mainstream MCU training kits, the e- Gizmo Training Kit is not attached to any particular type of microcontroller. It is known to be compatible with current MCU boards that include gizDuino, Zilog Encore, AVR ATMEGA8L, and Peripheral Interface Controller (PIC).In this project, the researchers should have the knowledge in programming, training experiments, as well as they should have the manipulation for the kits’ on board peripherals such as Relay and Motor Expander, Analog Voltage Sources, LM34 Temperature Sensor, 3 adjustable Voltage Sources, Digital to Analog DAC circuit, Switch Devices, Rotary Encoder Switch, 2 push button switches, 4 x 3 Keypad Matrix, Input and Output Expander, LED monitor, 2 Digit 7 segment LED display, Buzzer Circuit, Real Time Clock RTC, Alphanumeric LCD Display Unit, RS232 Interface Circuit, Power Supply Entry, Microcontroller Board Docking Port, and Breadboard.Project Objectives The main objective of this e- Gizmo Universal MCU kit is to test and learn the different kinds of application and peripherals on board. Moreover, the development of this microcontroller kit requires attaining the following: 1. ) To learn the programming languages use in microcontroller 2. ) To learn how to use the software through PC to the microcontroller 3. ) To learn the basic connection of the microcontroller to the MCU kit. 4. ) To study and familiarize the functions of the specific application use in the microcontroller 5. To learn how to connect or to know the relationship between the Input- Output or the application through the microcontroller Conceptual Framework The interrelation among the components of the microcontroller kit was shown as illustrate d in Figure 1. It represents the process on how the application and peripherals used in the trainer board works. In this kit, the researchers have used a microcontroller in gathering input from various applications, processing the input into a set of actions, and using the output mechanisms on the microcontroller to do something useful.The concept of the microcontroller kit was based on the need of creating convenient hardware designed for having knowledge and critical thinking for microcontroller widen. The diagram started with the input, followed by the process and the output. OUTPUT INPUT PROCESS RS 232 C INTERFACE 2 x 16 LCD DISPLAY BUZZER LED DRIVER OUTPUT EXPANDER RELAY STEPPER MOTOR DRIVER MICROCONTROLLER GIZDUINO AND PINGUINO 2 x 16 LCD DISPLAY REAL TIME CLOCK (RTC) INPUT EXPANDER 4 x 3 SWITCH EXPANDER PUSH BUTTON SWITCH ANALOG VOLTAGE OUTPUT TEMPERATURE SENSOR PROCESS GIZDUINO (USB CABLE) PINGUINO (UART MODE/USB CABLE)PERSONAL COMPUTER Figure 1. Conceptual Framework of e- G izmo Universal MCU Trainer The INPUT is comprises of 2 x 16 LCD Display, Real Time Clock (RTC), Input Expander, 4 x 3 Switch Matrix, Push Button Switch, Analog Voltage Output, and Temperature Sensor. LCD Display Module is tremendously popular low cost display device that can show user generated message in 2 lines x 16 alphanumeric format. Aside from 2 lines by 16 characters format, LCD modules are also available in 4 lines by 20 characters. A Real Time Clock (RTC) circuit serves as an electronic subsystem that keeps an accurate time and calendar.In addition, the next input is the Input Expander which has data out, since the host controller will be reading from U3 input port JP22. Furthermore, 4 x 3 Keypad matrix is also recognized as one of the input. The keypad used in this trainer consists of 12 push switches. The keypad switches are wired in 4 rows x 3 column arrangement. The Push Button Switches in the kit, which are S1 and S2, are held to logic 1 state by R2 and R3 when not pre ssed. There is also a well known device which is LM34 Temperature sensor U5 which gives an ambient temperature reading in analog Fahrenheit scale.After the Input, the figure shows the PROCESS which is comprises of Microcontroller Gizduino and Pinguino. Gizduino is ideal for beginner programmers and hobbyists because of its simplicity compared to other platforms. It is a multiplatform environment; it can run on Windows, Macintosh, and Linux. However, Pinguino is an Arduino for PIC user. Pinguino is also an Integrated Development Environment (IDE) which enables anyone to easily make an application on learning the program. Additionally, the program for both Gizduino and Pinguino is loaded to the Personal Computer which is also a major part of the process.Gizduino is programmable via USB (Universal Serial Bus) cable which makes it more accessible and allows communication to the computer. Pinguino, however uses UART mode through serial communication to PC. In addition, the OUTPUT include s RS 232 C Interface, 2 x 16 LCD Display, Buzzer, LED Driver, Output Expander, Relay, and Stepper Motor Driver. The RS 232 Interface allows the MCU UART to interface with RS 232 enabled devices. The function of the 2 x 16 LCD Display here in the output is the same as the input. For the 3rd output, the buzzer is used to indicate a warning or an alarm, a key closure or a machine function.The buzzer used in this trainer is essentially a small loudspeaker. With regards to the Output Expander, this trainer can have 8 outputs more using 5 or 6 MCU I/O. The Stepper Motor Drive subsection in the trainer can also be used to study and control stepper motor operations via user code. Significance of the Study The e- Gizmo Universal Microcontroller (MCU) Trainer was designed specifically for the benefits of the following: Electronic Designers. This trainer is intended for artists, designers, hobbyists, and anyone interested in prototyping and programming a microcontroller.The Students. This kit aspires for the students to acquire basic knowledge on how microcontroller works and also aims for students to be familiar with prototyping platform based on easy to use hardware and software. The Academe. Professors on higher education can use this trainer to introduce the college students on how to program and manage microcontroller the fast and easy way. The Researchers. With the help of this MCU kit, the researchers were able to have background about the major component details of both Gizduino and Pinguino platform, its features, and manual application.They were able to manipulate peripherals on board through programming familiarity. Future Researchers. This can serve as a guide to those who wants to delve into microcontroller relevance, and those who wanted to have comparisons among the MCU trainers that has been developed. The study also provides the data and guiding material about the universal trainer function. Scope and Limitation Scope The e- Gizmo Universal MCU trainer r equires an external well regulated +5V to power the whole trainer board. Unlike any other microcontroller trainers, this is unique since it does not assign to any single microcontroller.With this trainer, we can use available boards such as gizDuino itself (atmega 168 or atmega 328 versions), AVR atmega8L experimenter board, Zilog z8F042A MCU board, PIC18F2550, and STM32F100C8 ARM Cortex M3 MCU board. The gizDuino’s platform kit that has been executed in this trainer is a single board AVR microcontroller platform based on highly popular Arduino design. It is a multiplatform environment as it can run on Macintosh, Linux and Windows. It is also programmable via USB (Universal Serial Bus) cable as mentioned earlier.Gizduino’s User Interface is USB Port, DC Jack, Reset Button, ICSP Port, and Shield Connection Port. The external Power Input ranges from 8V- 12 V while it needed 5 V for USB. The DC Power Output is at 3. 3 V with a frequency of 16 MHz and 12 MHz. It is being p rogrammed using Integrated Development Environment (IDE). Additionally, PIC18F2550 platform which has also been programmed has an Arduino compatible layout. It works on Arduino like software development platform based on open source Pinguino project. The e- Gizmo’s Pinguino is also compatible with gizDuino line of shields and has an external power supply of 8V- 12V.Its communication medium is UART mode, serial communication to PC. Different applications are also placed on this trainer such as Relay and Motor Expander, Analog Voltage Sources, LM34 Temperature Sensor, 3 adjustable Voltage Sources, Digital to Analog DAC circuit, Switch Devices, Rotary Encoder Switch, 2 push button switches, 4 x 3 Keypad Matrix, Input and Output Expander, LED monitor, 2 Digit 7 segment LED display, Buzzer Circuit, Real Time Clock RTC, Alphanumeric LCD Display Unit, RS232 Interface Circuit, Power Supply Entry, Microcontroller Board Docking Port, s well as Breadboard. Limitation Since +5V is employ ed to power the trainer board, using unqualified +5V power source may cause damage to the trainer. Most components on this kit, especially the microcontrollers are known to be sensitive to Electrostatic discharge (ESD). With this, ESD may damage the trainer if not handled properly. As discussed, Microcontroller Board Docking is where the MCU board is installed. This accepts gizDuino style MCU board. However, since Arduino boards do not have extended connectors, it disallows any shields from being installed on it.Herewith, a suitable adapter is required for us to be able to use the Arduino with the Universal MCU Trainer. It should also be noted that each microcontroller family has its own software development kit (SDK) and some may require a separate programming cable. Definition of Terms Microcontroller (MCU). It is a small computer on a single integrated circuit containing a processor core, memory, and programmable input/output peripherals. Gizduino. It is an open source computing platform based on a simple input/output (I/O) board and use of standard programming language and is a tool for implementing specific design.Pinguino. It is also an Arduino compatible platform which works on Arduino like software development platform. Arduino. A popular open-source single-board microcontroller, descendant of the open-source wiring platform, designed to make the process of using electronics in multidisciplinary projects more accessible. AtMega 328. This is the microcontroller that powers the gizDuino. Integrated Development Environment (IDE). This is a software application that provides comprehensive facilities to computer programmers for software development. Zilog Encore.This system-on-a-chip includes an integrated memory controller, interfaces such as Universal Serial Bus (USB), Liquid Crystal Display (LCD) and Serial Peripheral Interface (SPI). RS232 Interface. It’s a RS232C Transistor Transistor Logic (TTL) level converter. LCD Display Module. A tremendous ly popular low cost display device that can show user generated messages in 2 lines x 16 alphanumeric characters format. Breadboard. It is used to easily build small circuits to work on in addition to the trainer module. Real Time Clock (RTC). Is an electronic subsystem that keeps an accurate time and calendar.Buzzer. It is an annunciator which provides cost effective audible feedback between the machine and the user. Light Emitting Diode (LED). Is a semiconductor diode that emits light when conducting current and is used in electrical equipment. Liquid Crystal Display (LCD). It is a flat panel display, electronic visual display or video display that uses the light modulating properties of liquid crystals. Multiplexing. A method used to rapidly switch two or more digits in synchronization with their corresponding segment drives (a-b-c-d-e-f-g). Input/Output Expander.This is used to serve 8 inputs and 8 outputs more using 5 or 6 microcontroller I/O. 4 x 3 Keypad Matrix. It is a small group of keys used to manually enter a data or a command while the microcontroller is running. Encoder Switch. Also known as rotary quadrature encoder switch, is a pure digital device that has the feel of an analog potentiometer. Push Button. An electrical switch operated by pressing a button, which closes or opens a circuit. Digital to Analog Converter (DAC). It is an interface device that will allow outputting an analog voltage based on a digital value.Analog Voltage Source. It provides both simulated and real analog voltage source which is used in Digital to Analog Converter. Stepper Motor Drive. This section in the trainer is used to control stepper motor operations via user code. Relay. Is an electrically operated switch, use an electromagnet to operate a switching mechanism mechanically and they are used where it is necessary to control a circuit by a low power signal. Universal Asynchronous Receiver/Transmitter (UART). It is the microchip with programming that controls a com puter's interface to its attached serial devices.