Part 1: This week you learned about the importance of adopting a growth mindset vs. a fixed mindset. Describe a time in your life when you faced an important opportunity or challenge with a fixed mindset? What held you back? Were you concerned about your ability to succeed? Were you worried about other people’s perception of you? (Briefly describe the situation.)If you could go back in time and redo this situation with a growth mindset, how would that change your approach and the outcome?Part 2: Respond to Jerad EdwardsGood Afternoon Professor and Class,Growing up, I was raised to have high standards of myself and others. My father told me that people that commit criminal acts are those that do more harm to the world. I grew up thinking that people with a criminal history are not good people. I remember in 2014. I had to make a decision to either do wrestling training after graduating from high school or join the military. I remember than this one individual couldn’t really work because he had some type of domestic violence charge on his record. I decided that I rather go through to the military because of the way my father taught me on high standards. I believed that maintaining a high standard would get me from coming around certain people. But I had a best friend named Potter in the military. He told me about how bad he was before the military. In my head, I was wondering if he was truly presenting himself as himself not being fake or anything. So, I asked him so important questions. He looked a t me and said, “I know you are a goody two-shoes but hear me out”. When I gave my attention to him, he said that people are not perfect. your father raised you in the intent to be perfect. I realized that and apologized. Actions only defines the person in the moment. People change and they do not want the past to redirect their future. I was so upset at my father because I was judging based off of the past when I should look at them for who they are now. If I could go back in time, I would definitely have chosen wrestling no matter the past you have. i was so fixated on that, that I didn’t see the true potential growth of others. I was the one limited. When I outgrown my fathers teachings, I became open minded. I don’t want to be viewed as a judgmental person just because i was in a strict environment. Ever since my best friend potter, I never saw criminals as criminals but as human beings with emotions. I don’t know why or what they did but that is not a business I should revolve myself if my goal is to bring happiness to people.
JGR 100 Strayer University Fixed vs Growth Mindset Discussion
Discuss the process of infection, including the infection cycle and its components:
• Infectious agent
• Portal of exit
• Means of transmission
• Portal of entry
• Susceptible host
Review the stages of infection: (1) incubation period, (2) prodromal stage, (3) full stage of illness, and (4) convalescent period. Relate the process and stages of infection to the unique role of the infection preventionist in the hospital setting.
Discuss the process of infection, including the infection cycle and its components
Case Study EssayThis week, you will have an opportunity to apply the knowledge and strategies you explored during this term. You will gather information from a provided case study and use it to write an informative essay describing the helping process as it applies to the specific case.For this assignment, begin by reading the Case Study for Reggie and Todd. Then, use the Unit 8 Assignment Template to complete and submit your 2–3-page informative essay based on the case provided.Please address the following:Explain confidentiality and the times when a human service professional would have to break confidentiality.Be sure to refer to your state law and the NOHS Code of Ethics.Based on your readings and other credible sources you may find, discuss how personal values, beliefs, prejudices, and stereotypes can help or harm the helping process.Using the case study of Reggie and Todd, discuss the potential ethical and legal issues surrounding the case.What would your obligations be as professional regarding those issues? Please be sure to support your points with the NOHS Code of Ethics and your state law.What can a human service professional do to gain more insight if they are unclear on what to do in an ethical or legal situation with a client?APA Style. Do not copy essays from coursehero.
HN 205 Purdue University Global HSP Actions in Unclear Ethical Situations Case Study
Development of Chapel Design
Development of Chapel Design. Stage 0 – Strategic Definition Traditionally religion has inspired people to create beautiful pieces of architecture, on a grand scale, from the cathedrals that stretch as cross Europe, Mosques across Arabia and Temples of the Far East, Bishop Edward King Chapel achieves this ethereal idea on a more muted human scale. However this beautiful chapel is set in a declining religious western Europe and Christianity in particular the UK has been on the decline for 30 years according to research conducted by the British Social Attitudes survey, in 1983 31% classified themselves as not belong to a religion, whereas in 2015 50% now see themselves as not religious . The largest decline has been seen by the Church of England, which has halved since 1983 from 40% to 20% it still equates to the largest religious group in the UK 20% belonging to the Church of England. Of those brought up in a religious setting or identifying as belong to a religion 56% never attend religious services and only 14% attend on a weekly basis. There is also a generation gap with nearly 64% of 18–24 not being religious, in contrast to the 28% of those aged 65 and above. This is set in a wider decline across Europe where the European social survey found that there we falling religious views amongst 16- to 29-year-olds with Czechs being the least religious, with 91% of that age group saying they have no religious affiliation. Estonia, Netherlands and Sweden had between 70% and 80% of young adults classifying themselves as non-religious. Stage 1 – Preparation and Brief The Chapel in Cuddesdon Oxfordshire was born out of a RIBA Competition commissioned in 2009 by the Ripon Theological College and the Sisters of Begbroke a small community of nuns’ that reside in the grounds of the college to replace an existing smaller chapel on the campus. A total of 126 architects from all over the world submitted concepts for the competition, with the winning entry being designed by the London based architects Niall McLaughlin. After an 18 months construction phase with a cost in the region of £2.6m the Chapel opened for prays and services in February 2013, the entire process was funded through the sale of the Sisters of Begbroke’s pervious convent. Bishop Edward King Chapel was nominated for the 2013 RIBA Sterling Prize and finishing as runner up to Astley Castle. Stage 2 – Concept Design The chapel is sited around two very contrasting concepts, firstly the idea of a being grounded and sheltered by a gentle hollow or depression in the earth with the impression of a sheltered gathering area for the community. Secondly is a of focus towards the light and the skies above which reaches through the surrounding trees creating a warm uplifting ethereal atmosphere and offers the idea of rising towards the light. Trees play an important role in the siting of the Chapel they surround it, they frame and fill the views from every window and their dappled light an animated take on stained glass. “The idea that you are grounded and yet lifted up was extremely profound for us. It shows a very implicit understanding of what we wanted.” The Idea of the church nave which is the long central hall or aisle of a traditional cruciform church, which runs traditionally from west to east with its loaded etymology and connotations, was the starting point for designs initial concept. The word nave, has developed from the Latin word ‘Navis’, which means ` ship, ‘ as the church is perceived as an ark or refuge for its followers but it offers further ideas to explore as the nave is also the centre of a turning wheel. Looking to the East the word nave also has roots in the Sanskrit word ‘Nabhis’ which describes a hollow a theme key to the siting of the Chapel. The word navel also has its origins in nave and suggests ideas of the umbilical cords and a place of origin. The concept of the Nave and the Ark have been explored in many Cathedrals, Churches, and Chapel we can see explicit examples such as Maya Lin ‘s 2003 Riggio – Lynch Chapel in Clinton, Tennessee explicitly uses the idea of an ark through an elliptical layout and the ark-like form of the chapel is reinforced by its setting by a pond. The chapel’s wooden structure, with its beamed roof, forces the idea as metaphorical ship at every turn of the head. The chapel has no windows along its arching walls and is lit in day only by skylights, which gives its curving, slatted, timber interior and warm, womb-like feel. Peter Zumthor ‘s 1988 St Bernard’s Chapel in Sumvitg, Switzerland openly uses the idea of an ark more subtly with an elliptical layout and the ark-like form of the. The chapel’s wooden construction, with its beamed roof, echoes the notion of the ark with its windows high up it forces the worshipper up and out towards the sky, the simplicity in its timber interior offers a warm, meditative space. Bishop Edward King Chapel builds more upon the refined ideas of Zumthors Chapel with a more subtle message through its shape and use of materials, however its ‘heavier’ choice of exterior materials and siting amongst the trees roots the Chapel into its context leaving it looking more of a permanent lasting place of worship. All great Christian churches have been ships of the soul, with their naves – from “navis”, meaning ship – symbolising the voyage of a community of souls. “Much like when people come out of the cinema and it feels like they’ve been immersed in one world and are coming out into another, that’s what I wanted from the chapel,” says McLaughlin. “I wanted people to come out underneath the protective canopy of the beech.” Stage 3 – developed design The new chapel is placed in a clearing on a traditional east west axis at the very heart of the college open to nature and the elements dancing around it. The Chapel siting within the campus puts the existing college with many of its buildings design in the late 19th century by George Edmund Street firmly behind it and looks out through the trees across the valley towards Garsington. Approaching from the east and the campus the Chapel is instantly recognisable both jarring and complimenting the traditional buildings in its context. It’s curving elliptical form jars with the traditional geometric 19th century surroundings yet feels like it belongs as its materials echo and reflects its context. Looking at its form it can be considered jarring as it context offers little in the way of curves or ellipses or contrast in height, however looking closer there are the layers of history of religious architecture with the ideas of the basilica and the subtle features of the baroque. In a basilica a common feature is that the central nave extends to one or two storeys more than the lateral aisles, and it has upper windows much like the Chapel with its elliptical nave being much taller than the ancillary buildings attached to it along with the top portion adorned with tall windows. The idea of the baroque style comes through the use of the oval or ellipse which is common in many baroque churches throughout Western Europe. Moving around the exterior of the chapel it provides numerous contrasts and almost contradictions the pure elliptical nave is set next to and features very geometric shapes and features, towards the west is a geometric projection that thrusts out providing a very concentrated and framed view across the valley whilst the ancillary space are housed in a very simple geometric box to the south. The materials provide a big but subtle contrast, looking at the chapel there appears to be three distinct strata firstly the lower strata comprised of smooth facing stone on top of this sits arguably the chapels most distinguishing feature or at least externally the dogtooth laid stone providing a stark contrast with its very angular protruding pattern in even in this each stone provides a rough/smooth contrast side to side and above and below, whilst providing a contrast in light and dark with the shadowing it creates. Upon these two heavy and dense layers sits a ring of slender glazing like a crown of thorns offering more contrast between the heavy dense stone below and the transparent glass which floods the chapel with light The entrance was aligned with the trunk of a large copper beech tree; sadly however this has since been removed. This was an intentional decision by the design team as they wanted to provide a striking departure from the chapel not just a striking entrance. At the entrance of the Chapel is a doorway that contrasts with the feel of the chapel in that the wooden door is heavy and almost a foot thick invoking a defensive gate to a fort protecting the hollow and the congregation. Entering the chapel through the heavy door into a dark hallway and descending down three steps into the ‘hollow’ on to the smooth concrete floor, much like Tadao Ando’s Church of light there is an entrance on the right hand wall which draws people into the main prayer space. The Chapel is organised around a pure ellipse with a collection of more intimate spaces for smaller group or individual pray attached to the main space. A narrow ring much like a cloister separates the internal structure and external leaf of the building; it is possible to walk unimpeded around the ellipse feeling compelled to walk it completely before breaking into the into the naturally light centre something which is present in the earliest churches building on this with the contrast of the shadows to the light is an allegory used for centuries to imply conversion as described by Richard Sennet in his description of the Palatine Church in Aachen. The Chapel borrows many ideas from the Baroque when we look at churches designed in that style the use of the oval is very prevalent in its layout but concealed in a traditional cruciform structure whereas our Chapel is explicit in its use. Baroque churches used contrast between light and dark to great effect to reinforced the idea of salvation and redemption in part designed through high naves and small isles allowing light to flood in from the top of the space, something which has been used in a simpler more refined manner by the The Chapel with its shadowy oval walkway around the bright central nave. Many factors influence the design of a church or chapel for example abbey and collegiate churches tend to be more complex in design whereas a church under the patronage of a Bishop will have a more refined style as they could afford a competent architect compared to parochial churches. Bishop Edward King Chapel for a chapel has a simple layout and materiality however the complexity of the lattice work and the skill of the dogtooth brick work show this was refined and design like a chapel under an important Bishop or Cardinal. Once in the space your eyes don’t spend long in the chapel but are drawn through the intricate lattice work towards the high windows and the light soft muted by the surrounding trees. Cast aside the formal religious aspect of this building it still evokes and radiates a warm otherness through its materials and space The large sweeping glulam arches spring up towards the light like saplings supporting the ceiling of the building. These arches are highly symbolic in that they are the trees of the site, a soft voice of the ship notion and the arches of the Gothic inspired churches of the past. This notion of the Gothic ribbed arches such as those at the Church of St Peter and St Paul, Bath allows for an architecturally stunning roof but also a light structure with barely any walls, which allows for the Nave to be flooded with copious amounts of light inside, The Chapel looks to pay homage to these ideas with its intricate lattice work playing with the idea of the ribbed fans and light glulam structure allowing light to flood in. Building upon its historical roots the glulam columns which create the tall oval nave echo that of the regularly spaced columns you would find creating the tall nave space in a baroque basilica. The roof makes reference to this idea of ship and its keel through its v shape which has historical reference with many 13th century Venetian carinated churches constructed by boat builders from the Arsenale. The ideas of having a lattice structure as an integral concept of the roof design is an idea that has been explored in several mid-19th century churches such as the Notre dame du chêne viroflay built in 1966 by Frères Sainsaulieu’s and the 1957 St Remy church by-Nicholas Kasiz to varying affect. St Remy has a very flat and angular roof which gives the tall central space a heavy engineered feel, Notre dame du chêne viroflay on the other hand provides a very light woven feel, Our chapel executes the graces of a light air lattice work structure with a nod to the engineering complexities that a roof of this intricacy provide. Unlike traditional churches with their rows of pews here there is an antiphonal seating arrangement; this bow arrangement provides a more communal discussion with the pulpit at the heart of the space rather than the traditional row by row format which offers a preached too atmosphere. This idea of having a pulpit in the centre of the space stems from the reformation and the idea that the word of god and the sermon was the most important part of mass placing the speaker in a visible space where all could hear the spoken word, an idea that is clear evident in the chapel. Following on from the idea of the pulpit and the reformation, the chapel has a stripped back and paired down design when it comes to ornamentation and decoration a concept that was prevalent in Protestantism focusing the worshipper on the word of god and not the intricate statues and carvings found in Catholicism. The chapel achieves this simpler style much like Zumthor’s St Bernard’s chapel using warm woods and tall glazing this is stark contrast to Zumthor’s Bruder Klaus Chapel and Ando’s Chapel of light which use harsh concrete and the stark contrast of the light and dark to focus the persons mind towards God. Maya Lin speaks about the quality light has to offer in the Riggio-Lynch Chapel, which is elegantly used and moderated, giving it a quiet and calming presence where the light is gently animated on the walls like stain glass. Bishop Edward King Chapel much like Lin’s has in it’s with its simple form and raw structure cultivates a feeling of spirituality and peace. Stage 4 – Technical Design The Chapel as a place of worship was exempt from Part L of the building regulations yet an explicit request from the Sisters and the College, to make the chapel ‘an example of forward looking liturgical design’ was taken up by the architects. From the outset the chapel was deliberately designed to make complete use of passive solar principles and sort to sourced responsibly managed local natural materials. The external stone materials were sourced responsibly and have a low embodied energy whilst the main Glulam structure was manufactured off site to cut down on construction time and wastage this also allowed for greater recycling of waste materials. The although on a traditional east west orientation the shape of the chapel allowed for a long façade to face south together with the stone walls and screed floor gives the chapel a good thermal mass helping to store the natural heat available. Along with the Chapel being twice as well insulated and three times more airtight than required by a modern building this aids in storing and mitigating heat loss stored in its thermal mass. The Chapel is designed to achieve natural ventilation with automated louvers and actuators instead of using a mechanical ventilation system this helps to keep the chapel at a comfortable level throughout the year. From the design and layout of the Chapel to the choice of materials contribute to the chapel having low Nitrogen Oxide emissions and Carbon Dioxide emissions in the region of 20kg per m2 which is below what is expected by modern well insulated buildings by half. The idea that the Chapel could be a vessel for spiritual good as well as environmentally friendly is not new Maya Lin’s Riggio-Lynch Chapel was sighted next to a pond not only to reinforce the notion of the ark but the pond also acts as a natural heat-exchanger to keep heating and cooling costs low, and environmentally sound. Stage 5 – Construction The materials used in the chapel all come from a similar earthly brown tonal palette and although offer little in colourful contrast provide a varied composition from soft woods to a rough stone and under the sun deliver a warm calming feel. The chapel is constructed of three simple traditional main materials stone, wood and glass. The external leaf of the chapel is constructed from Ashlar and Clipsham stone which bonds it to the existing campus buildings, the lower third uses Ashlar stone in a traditional dressing form with a smooth surface, the middle third offers one of the most distinguishing features of the chapel in the where a dogtooth pattern is used, a conscious design decision was made to laid stone with alternating rough and smooth edges facing outwards continuing the chapel contrasts. Looking at Zumthors use of material in the St Bernard’s Church we can see a use of simple natural materials from a similar earthly brown palette much like Bishop Edward King all with the same intent of using traditional materials in a modern way to fit and be sympathetic to their respective contexts. As with dogtooth pattern outside the large glulam arches and lattice work provide a striking modern interpretation of a traditional church feature the ribbed vaulted arches that are common throughout ecclesiastical architecture, because they are constructed of wood they ground the building in its context and the tie in with the trees on the site. The use of Larch and Ash woods in the furniture and beams, again offer delicate variations in tone and tie the chapel with its interior. These arches form the intricate lattice work above the main service space which holds the V shaped roof like a floating ship. The connections of the lattice and arches are held gather with invisible metal joints which leave the wood unspoilt by nuts and bolts. The interior walls and ceiling are rendered using a traditional lime plaster, and show like the materials palette an intelligent variation in textures and shade. The roof floats on a ring of tall slender panes of glass which give this chapel its warm and its contrast, it draws your attention up through the chapel and out pass the trees to the sky like an animated stain glass window. On one side the chapel opposite the entrance sits a window protruding precisely between two trees, gifting the only undisturbed view across the valley. Its floors are made from smooth and polished concrete, its furniture wooden and simple, like Ando’s Church of Light there is no decoration, or distracting adornment simply a space of focused contemplation. This is a building that takes architecture back to its roots, as a form of shelter, and as a vessel that connects us to old gods, and to spirituality The use of wood is significant in post reformation protestant Christianity ideology in that Christ died upon a wooden cross and having the alter made from wood and other furnishings made from wood it allows the follower to become closer to Christ and his struggle and therefore closer to God. The chapels structure the very essence of this building holding the ark like roof is constructed from wood one could argue that any idea with a religious connotation has been crafted from wood. is this a coincidence or a conscious idea that has been subtlety and quietly woven into the narrative of this Chapel? Stage 6 – Hand over and close out Stage 7 – In Use Bishop Edward King Chapel may be a chapel in name but it isn’t in its conventional use. A chapel or church has a its main use on traditional days and holidays usually Sundays where mass and prayers are conducted, the chapels settings are rooted in a monastic educational setting where those attending the college seeking to become ordained into the Church which makes this building take on a blended everyday use between reflection and pray to that of education and preparation “For the chapel to be foremost a place for the cultivation of personal prayer as well as of public worship. We knew that what was needed was not just a building but a work of art which would touch the spirit.” Cuddesdon Sisters, Conclusion Set against a background of declining religious affiliation and attendance the Bishop Edward King Chapel is a seminal piece of architecture it takes traditional themes and ideas and puts modern interpretation on them. The concept of the nave as a ship sets the tone for this building and is followed through in all aspects of the design from its elliptical floor plan to the glulam beams and lattice work Modern contemporary Unlike most churches which are focal points for villages, towns and cities this chapel pays sympathetic homage and blends into surroundings through its placement amongst the trees and the materials which tie it into existing campus. Harks back to traditional concepts The idea of the nave as a ship or an Ark is an idea that has been explored Ribbed Arches Contrast of light and shadow The Chapel uses the same materials which you could see on many churches across the land in stone, wood and glass but they are used in contemporary ways. The dogtooth brick work offers an interesting use of a traditional material, the glass although not stained glass the use has been thought of as animated stain glass windows. Finally glulam wood offers modern engineered shapes and helps to tie the concept with reality. Can see evolution of ideas from previous churches and chapel Bibliography The “no religion” population of Britain (Recent data from the British Social Attitudes Survey (2015) and the European Social Survey (2014)) Stephen Bullivant British Social Attitudes Survey 28 (2015) European Social Survey (2014-16) Stephen Bullivant Seamus Heaney (1992). ‘Lightning viii’, Seeing Things. London: Faber and Faber Philip Larkin (1989). ‘Church Going’, Collected Poems. Ed. Anthony Thwaite. New York: Farrar, Straus, And Giroux: 97-98 Rudolf Schwarz (1958). The Church Incarnate, The Sacred function of Christain Architecture: Henry Regnery Company Gottfried semper (2004). Style in the Technical and tectonic Arts; or, Practical Aesthetics. Los Angles: Getty Publications Peter Salter (2011)’Architect Peter Salter records the English innovation of the fan vault, a pragmatic and romantic alternative to the gothic arch that has challenged his thoughts on contemporary skins’. Architectural Review 299. 1367: 70-75 Richard Sennett (1994). Flesh and Stone, the body and the City in Western Civilisation. London: Faber and Faber Krautheimer, Richard (1992). Early Christian and Byzantine architecture. New Haven: The Yale University Press. ISBN 0-300-05294-4 James Ackerman (), The Villa George Perec () Species of Spaces Conrad Rudolph (2006) A companion to medieval art : Romanesque and Gothic in Northern Europe, Malden, MA ; Oxford : Blackwell Journels B. KNAPP-FISHER ENGLISH CHURCH ARCHITECTURE. Journal of the Royal Society of Arts, Vol. 103, No. 4960 (16TH SEPTEMBER, 1955), pp. 747-762 Newspaper Articles P117, Rowan Moore, ‘The answer to their prayers’. Observer Magazine (28 April 2013):31. P118-121, Rowan Moore, ‘Bishop Edward King Chapel, Ripon College- Review’. The Observer (28 April 2013) https://www.theguardian.com/artanddesign/2013/apr/28/ripon-college-chapel-niall-mclaughlin P116, Rowan Moore, ‘Talking the bling out of building…’ Observer Magazine (21 July 2013):31. Online Reviews Lucy Townsend,’ Stirling Prize: Bishop Edward King Chapel’ BBC Magazine (16 September 2013) https://www.bbc.co.uk/news/magazine-24045643 Amy Fearson, ’Bishop Edward King Chapel by Niall McLaughlin Architects‘ Dezeen Magazine (19 June 2013) https://www.dezeen.com/2013/06/19/bishop-edward-king-chapel-by-niall-mclaughlin-architects/ http://www.naaro.com/bishop-edward-king-chapel/ic39hojde1u1fffly4z0iggk9j8atq https://www.ajbuildingslibrary.co.uk/projects/display/id/6655 https://www.architecture.com/awards-and-competitions-landing-page/competitions-landing-page/bishop-edward-king-chapel https://www.durhamworldheritagesite.com/architecture/cathedral/architectural-importance Bishop Edward King Chapel / Niall McLaughlin Architects” 23 Mar 2015. ArchDaily. Accessed 26 Feb 2019. ISSN 0719-8884 Development of Chapel Design
Jack Welch at General Electric Case Study
order essay cheap Jack Welch at General Electric Case Study.
Read the case study on Jack Welch at General Electric and answer the following questions:1. Corporate social responsibility is defined in Chapter 5 as the corporate duty to create wealth by using means that avoid harm to, protect, or enhance social assets. Did GE in the Welch era fulfill this duty? Could it have done better? What should it have done?2. Does GE under Welch illustrate a narrower view of corporate social responsibility closer to Friedman’s view that the only social responsibility is to increase profits while obeying the last law? 3. How well did GE conform with the “General Principles of Corporate Social Responsibility” set forth in the section of the title in the chapter? (I have attached the 8 principles below, you need to talk about each one of them briefly.)4. What are pros and cons of ranking shareholders over employees and other stakeholders? It is wrong to see employees as costs of production? Should GE have rebalanced its priorities? 5. Was GE more socially responsible corporation in the Welch era or the Immelt aftermath? In which era dud it give the most benefit to society? What lesson(s) can be learned from the differences?The case study needs to be 4.5 – 5 PAGES, double spaced
Jack Welch at General Electric Case Study
The Strength of Diversity Programs
The Strength of Diversity Programs.
The Strength of Diversity ProgramsMost governmental organizations and many private companies have diversity programs. Author a case study (from the Internet or published article & CITE/Reference) about a diversity program and explain its plus and minuses about addressing diversity.In your book there is a self-assessment in Chapter 10. Pick out 5 of the assessment items (show a subheading on this part or you paper) and comment on why they should be important and addressed in your case study.Here is an example of a Diversity Program posted on the web (DO NOT USE THIS ONE)http://www.northropgrumman.com/CorporateResponsibility/Diversity/Pages/DiversityPrograms.aspx
Submission: Follow the instructions below.IMPORTANT: You must write (NO Copy/Paste) a 3-page minimum document in Microsoft Word using the M-APA format as provided in the attached document. Use citations and references when needed.Submit the Word.Docx file using the Assignment Attachment in Blackboard.
The Strength of Diversity Programs
Cytomegalovirus History, Biology and Treatment
Cytomegalovirus History, Biology and Treatment. Historical Aspect Human CMV (HCMV) is a very common human DNA virus. Since the beginning of human life; it has co-evolved with its host (McGeoch et al., 1995). Although being a part of humankind, not everybody is infected (Alford et al., 1990). It was first isolated in 1956 by Smith where two strains were isolated from the salivary gland and kidney of two dying infants. Cytomegalic inclusion bodies had been found in both tissues. In 1957, Weller and colleagues isolated three strains of CMV from adenoid tissues of three asymptomatic children after surgical removal. Also in 1970, they isolated three other strains from liver biopsy and urine of three congenitally infected infants with CMV (Ho, 2008). In 1881, Ribbert was the first who observed the characteristic cells in the kidney of a stillborn infant but without interpretation of these observations and that was the first description of histologic features of infection (Naraqi, 1991). The first histopathological evidenve of CMV infection was identified in 1904 by Ribbert in tissues from a congenitally infected infant. Mistakenly the large inclusion-bearing cells observed at autopsy was assumed to be from protozoa. As a result, these cells were called protozoa like cells and many workers thought that they were protozoa. After that, the similiraties between these cells and those infected by Varicella-Zoster virus and Herpes simplex virus raised the suspicion of a viral cause. In 1920, Good pasture hypothesized the viral cause of such inclusions (Ho, 2008). The first name proposed for CMV was salivary gland virus or salivary gland inclusion disease virus. In 1921, Good pasture and Talbot used the word cytomegalia to describe the huge enlargement and alterations of infected cells. Such word was the origin of the term cytomegalovirus initially proposed by Weller and colleagues in 1960 (Weller and Hanshaw, 1962). The role of the virus as an important pathogen with different clinical manifestations was significantly identified during the 1970s and 1980s. The molecular biology, immunology, and antiviral therapeutic agents had been characterized. However, establishment of preventive strategies of CMV infection and determining the role of certain genes in viral pathogenesis still need more efforts (Sung and Schleiss, 2010). Classification Human CMV, designated as HHV5, is a member of the Herpesviridae family of viruses. It is one of the 8 human herpesviruses (HHV) (Schleiss, 2009). The Herpesviridae family is divided into three subfamilies designated Î±, Î², and Î³. The classification into these subfamilies is based on the features of host range, duration of reproductive cycle, cytopathology and characteristics of latent infection. DNA sequence analysis, guanine and cytosine (G C) content snd serologic reactivity of gene products are the main criteria for subdivision of each subfamily into genera (Hanley and Bollard, 2014). The Î± subfamily includes herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) and varicella-zoster virus (VZV); the Î² subfamily includes cytomegalovirus (CMV) and the roseolaviruses, human herpes viruses 6 and 7, which are responsible for the clinical syndrome of exanthem subitum (roseola infantum) in young children, and the Î³ subfamily includes Epstein-Barr virus and human herpes virus 8. All of these viruses share similarities in virion morphology and genome organization (Schleiss, 2009). Human herpesvirus classification is represented in table ( ) (Ryan and Ray, 2004). Table (1): Humah haerpesvirus (HHV) classificstion Type Synonym Subfamily Primary Target Cell Pathophysiology Site of Latency Means of Spread HHV-1 Herpes simplex virus-1 (HSV-1) Î± (Alpha) Mucoepithelial Oral and/or genital herpes (predominantly orofacial), as well as other herpes simplex infections Neuron Close contact (oral or sexually transmitted infection) HHV-2 Herpes simplex virus-2 (HSV-2) Î± Mucoepithelial Oral and/or genital herpes (predominantly genital), as well as other herpes simplex infections Neuron Close contact (sexually transmitted disease) HHV-3 Varicella zoster virus (VZV) Î± Mucoepithelial Chickenpox and shingles Neuron Respiratory and close contact HHV-4 Epstein-Barr virus (EBV), lymphocryptovirus Î³ (Gamma) B cells and epithelial cells Infectious mononucleosis, Burkitt’ lymphoma, CNS lymphoma in AIDS patients, post-transplant lymphoproliferative syndrome (PTLD), nasopharyngeal carcinoma, HIV-associated hairy leucoplakia B cell Close contact, transfusions, tissue transplant, and congenital HHV-5 Cytomegalovirus (CMV) Î²(Beta) Monocyte, lymphocyte, and epithelial cells Infectious mononucleosis-like syndrome, retinitis, etc. Monocyte, lymphocyte, and? Saliva, urine, breast milk, etc HHV-6A and 6B Roseolavirus, Herpes lymphotropic virus Î² T cells and ? Sixth disease (roseola infantum or exanthema subitum) T cell and ? Respiratory and close contact HHV-7 Pityriasis Rosea Î² T cells and ? ? (roseola infantum or exanthema subitum) T cell and ? ? HHV-8 Kaposi’s sarcoma -associated herpesvirus (KSHV), a type of rhadinovirus Î³ Lymphocyte, and other cells Kaposi’sarcoma, primary effusion lymphoma, some types of multicentric Castleman’s disease B cell Close contact (sexual), saliva? Quoted from (Ryan and Ray , 2004). Biology of Cytomegalovirus Morphology: Cytomegalovirus is an enveloped virus with a double-stranded DNA genome. The three distinct regions of the CMV virus particle include: an icosahedral capsid; the tegument layer; and an outer lipid envelope. The morphology of CMV is demonstrated in the electron microscopy (EM) studies shown in Fig. (). The capsid, which comprises 162 capsomere subunits arranged in an icosahedral symmetry, houses the viral genome, and is classically highly electron-dense when imaged by EM (Schleiss, 2011). In the virus particle, the capsid is surrounded by the tegument, a protein-rich layer containing several of the dominant targets of the T-lymphocyte response to infection, including a 65-kilodalton (kDa) phosphoprotein (pp) referred to as pp65 (Kern etal., 2002). Surrounding the tegument is the envelope layer which contains several virally-encoded glycoproteins (g), including protein complexes designated as the gB complex, the gM/gN complex, and the gH/gL/gO complex. CMV-seropositive individuals mount an immune response characterized by neutralizing antibodies that target these glycoproteins (Bernstein, 2011). In addition to serving as targets of the humoral immune response, these glycoproteins also play a central role in the binding and entry of CMV into cells (Ryckman etal., 2006). As a result of the variability in the thickness of the tegument, the complete virion varies in size from 150 to 200 nm in diameter. The genome is about 64 nm in diameter with a molecular weight of 100 x 106 to 150 x 106. The capsid is 110 nm in diameter (Subhendu et al., 2007). During the process of viral replication, a variety of types of CMV particles are generated. In cell culture, CMV infection leads to the assembly and release of, in addition to infectious virions, non-infectious defective particles termed “dense bodies” (DB), so designated because of their characteristic highly electron-dense appearance when imaged by EM. Another type of body, designated as a “noninfectious enveloped particle” (NIEP), is also generated during viral replication as designated in Fig. () (Pepperl etal., 2000). The structure and protein composition of NIEPs are comparable to those of virions, but they lack DNA and are therefore not infectious (Schleiss, 2011). DBs are enveloped spherical structures that lack capsid proteins and DNA (Pepperl etal., 2000). They consist mainly of viral tegument proteins and glycoproteins. In cell culture, the biology of DBs mimics that of infectious virus, since DBs enter cells efficiently and deliver their protein components intracellularly (Mersseman etal., 2008). In principle, DBs could induce a broad range of humoral and cellular immune responses (Schleiss, 2011). Cytomegalovirus particles exhibit additional levels of complexity. Using CMV gene array technology, a class of viral RNA transcripts, termed virion RNAs, has been identified in infectious virions (Bresnahan and Shenk, 2000). These RNAs, which are packaged during virion assembly, are delivered to the host cell immediately on infection, potentially allowing viral gene products to be expressed in an infected cell before any viral transcription or host immune response occurs. The role of virion Cytomegalovirus History, Biology and Treatment
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