A nation Under Attack essays

A nation Under Attack essays We are a nation under attack. No, I am not confused. I am not mixing us up with Iraq, which is systematically being attacked by the U.S. government. I mean we, a nation of American citizens who are systematically being attacked by the U.S. government. No bombs have been dropped yet but the soldiers have certainly been put on alert. Im not sure if this was George W.s plan all the time or if the light suddenly went on when he was granted the presidency by the Supreme Court, but somewhere along the line he decided the old rules of American government, including the built in checks and balance system of separate branches of government, were no longer needed and he would make up some new ones. And, boy, has he been busy. Since he took office, George W. has little by little beaten back our assumed, and always before guaranteed, civil rights. He has established what is known as the Bush Doctrine. It says, in essence: he, the leader of the United States, will be ever vigilant looking for countries that may someday develop into a threat and, pre-emptively, declare war on them. No, he will not need anyones approval, he assigned himself sovereign power. To be clear, this is a power given to a monarch or other supreme ruler. Yes, I am still talking about America, land of democracy. I read most of the Bush Doctrine and never did find who gets to keep an eye on us, in case we develop into a threatbecause right about now Id say that country is either loading the missiles or asleep on the job. He has signed into law the Patriot Act, which gives the government the right to arrest without charge and hold indefinitely anyone the government labels a threat. Well, two lines in to this editorial I became a threat to the new regime. One of the reasons we broke from England in 1776 was that they were arresting people without charge and holding them indefinitely. At the time we considered ...

Forieng Author Project Essay

Forieng Author Project Essay Forieng Author Project Essay Ellen Wiah English 12 March 22, 2013 Period 4th Octavio Paz was a renowned poet, essayist who won the Nobel Prize for Literature. He was recognized for being the first Mexican to win a Nobel Prize in literature. Using poetry combine with prose, Paz explored multifaceted and paradoxical forces in contemporary life, while revealing his love for Mexican history and customs as well as his interest in surreal literature, and some other literary movement of the 19th century (Octavio, Paz-biography). Octavio Paz was a spokesperson for 20th-century Mexico, a poet whose work today exceeds his native land to connect with the world. Influenced by surrealism, Paz wrote of contradictions; but in his work opposites are blended and seen as part of the whole. Paz always used his art to establish relationships among cultures, people, and time (Hamm16).Octavio Paz was born in Mexico City in 1914, his father, a journalist and lawyer, was serving as assistant to Emiliano Zapata, a leader of the 1911 revolution. Paz's mother was from a prominent family of Spanish descent (Hamm16). During the revolutionary turmoil of the decade of Octavio's birth, the Paz family and many others were forced to flee the country. After living in Los Angeles for a few years, Paz's family returned to Mexico City. Although the family was now poor; Paz had access in the Macao house to an expansive library and was taught by Marist brothers. He reported that he first learned the craft of writing by immersing himself in the classics of Spanish literature and the great writers of Latin America. Paz attended the National University of Mexico but left without obtaining a degree to concentrate on writing (Hamm18). Paz was already published when he began his university studies. Several poems and stories had been printed in small regional publications. He also began publishing his own literary magazine, Barandal, at 17. Later he helped launch several other magazines, including Vuelta, one of Mexico's most influential publications. Luna Silvestre (Forest Moon), Paz's first book of poetry, was published when he was 19 (Diamond18). At the encouragement of Chilean poet Pablo Neruda, Paz travelled to Spain to attend a meeting in 1937 of leftist writers. While there Paz became so involved in the Spanish civil war (1936–39) that for a period he joined a unit fighting against Francisco Franco. In 1944 Paz received a Guggenheim Fellowship that allowed him to study in the United States. There he continued his education in poetry, reading the works of Walt Whitman, T. S. Eliot, Ezra Pound, and William Carlos Williams (Hamm17). In 1950 Paz published one of his most influential works: a philosophical essay about the nature of the Mexican character. El laberinto de la Soledad (The Labyrinth of Solitude) is part autobiography, part Mexican history, and part philosophy, all played out against the background of the dual cultural heritage of Mexico. Paz's style is often experimental at the same time that it draws on tradition. The 1953 volume Piedra de sol (Sun Stone) is a lyrical poem following the circular structure of the ancient Aztec calendar. Written in one sentence of 584 lines, the poem explores love, myth, the art of writing, and time (Diamond17). Among his diverse literary activities, Paz was an expert translator fluent in several languages, and he used this skill to help introduce upcoming writers from Latin America to the modern world by translating their work. Paz died of cancer of the spine in 1998. He had become so much of a national figure that the public announcement of his death was made by the president of Mexico, Ernesto Zedillo (Hamm19). Octavio Paz is a poet and an essayist. His style of writing is inspired by his belief that poetry establishes "the secret religion of the modern age." His work displays an ever-deepening intelligence and complexity as it explores the connection of philosophy, religion, art, politics, and the role of the individual within our

Summary Essay Example | Topics and Well Written Essays - 1000 words - 3

Summary - Essay Example Intruders try to gain control on the computer systems to access confidential information. Someone may place harmful programs in one’s computer. To challenge these eventualities, understanding technologies that govern the internet and introducing them into the system without delay is the answer. Some of the networking systems are Broadband, Cable Modem Access with â€Å"shared medium† topology and DSL Access. From the point of view of technology, broadband services are different from traditional dial-up services. In the latter case, computer connects to the Internet when it has something specific act to perform. As soon as the action is over, after the specified idle time, the computer will disconnect the call. A different IP address is assigned on each call, since the Internet connection is part of the pool system of the modems. An intruder finds it tough to break-in, into the data in this system. Since Broadband is â€Å"always-on† service, the intruder has the fixed target to attack. Large networks like corporate and government have protection systems by many layers of security, in the form of firewalls to encryption. The same may not be possible for an individual user of internet. Your ISP takes care about maintaining the services offered to you. The ultimate responsibility for operating the home network is with the concerned individual. Many protection systems are in use for safeguarding the operations and communications of the computers. Protocol, Internet Protocol, IP Addresses, static vs. dynamic addressing, NAT, TCP and UDP Ports, Software firewall - specialized software running on an individual computer, or Network firewall - a dedicated device designed to protect one or more computers. Antivirus software system is one of the important agents that guard one’s computer against viruses. They indicate the possible presence of viruses. New viruses are discovered daily and there is no fool-proof method to stop them altogether. Pr ofiles needs to be kept up-to-date, and appropriate solutions must be found to tackle the new viruses. The important information security areas are confidentiality, integrity and availability. These fundamental rules are applicable to individual users of networking system, as well as to the corporate and government networks. The user must be constantly on the lookout for new threats, and keep one’s knowledge up-to-date with the help of new technologies that are introduced for the protection of the networking community. Eternal vigilance and taking simple protective steps are assurances that the system will not be affected by the common threats. The risks in the networking field are both accidental and intentional. Intentional risks are the handiworks of the intruders, and this has to be challenged immediately, as no network user likes to reveal one’s information to others. Curtailing Information Security Vulnerabilities through Situational Crime Prevention Internet rev olution has engulfed and impacted majority of the segments of life of humankind. Information has taken over the center-stage of business activities, whether it is administration, production or marketing. Consequently, an unfortunate aspect of this positive development is the rapid increase in cyber-crimes. To counter this, many security systems meant to protect computer applications are on the anvil. The business houses and government departments have resolutely reacted to the exploitation of

From a Sole Proprietorship to a Corporation Essay

From a Sole Proprietorship to a Corporation - Essay Example A corporation is a distinct legal entity with a name and it also enjoys many legal powers like a natural person (Cillers, 24). Thus, it can be observed that when the company is formed, it automatically acquires the capacity and authority to have its own rights and duties (Gibson, 198). One major distinction between a corporation and a proprietorship is that corporations can acquire and exchange property and they can enter into contracts. In this case, the new company to be formed will be called Global Courier Services Inc. This company will be incorporated from a small business that has been specifically concerned with providing delivery services of small parcels to clients located in different parts of the local city. However, as a result of booming business, it has been underscored to expand the business into a large company called Global Courier Services Inc. This new company will be comprised of different shareholders and it will compete with other large companies that are involv ed in this particular business. Global Courier Services Inc will specialize in transporting parcels, light goods as well as mail among different clients. The corporation will cover the whole state and it will be headquartered in New York. However, the company will have offices in major towns and cities around the state. The company will operate a fleet of cars and bikes that will be used to deliver various goods to different clients across the whole state. The company will be publicly listed and it will be run by a board of directors that will be selected by the shareholders. It is also intended that the company will be comprised of various shareholders though it will initially hold a 55 % ownership of the organization. The company will offer 24 hour services to the clients and it will also be comprised of a complaints office that will deal with various customer queries and other related issues that may affect them in carrying out business. When this company has been fully incorpora ted, it is expected to employ more than 3Â  000 workers across the geographical area it would cover in its operations. Local people with the knowledge of geographical areas in their respective cities and towns would be given preference in terms of employment. The company would also be comprised of a board of directors since it would be publicly owned and listed on the stock exchange in New York. All the major decisions in the company will be approved by the board of directors as well as the number of shares that can be made available to the willing shareholders. The board will also be responsible for hiring and firing executives when consultations have been made among different stakeholders involved in this particular business. The other important aspect about the operations of the company is that all appointments would be based on merit. Only suitably qualified people would lend executive positions. Since the initial aim of the new company is to incorporate it as a public company, the finding for the start-up organization will mainly come from different sources. Part of the capital will be carried over from the small company that used to over transport services which is now being incorporated into a large company. The other source of start-up capital will come from private investors who may be interested in this particular business. Stockbrokers will be approached in order to convince them to provide funding for this promising

How is Cannery Row like a tidepool Essay Example | Topics and Well Written Essays - 1000 words - 3

How is Cannery Row like a tidepool - Essay Example The waves dislodge mussels and drive them to the ocean. The starfish prey on mussels whereas gulls break open the sea urchins and feed on the starfish. The black bears also sometimes feed on the intertidal creatures when the tides are low. However, as much as the organisms must avoid the strong currents, wave, sun and predators to survive, they also rely on the constant changes in the pools for food. The creatures that thrive in the tide pool cannot survive on their own. There is some kind of interdependence among the various organisms, where each relies on the other for survival according to Halpern (23). This way of life in the tide pools have attracted special attention of philosophical writers such as John Steinbeck, marine biologists and naturalists. In his novel Cannery Row, John Steinbeck relates life culture, values and class of the people in the town of Cannery to the structures of the tidal pools. Cannery Row is a story about a group of poor friends (Mack and his friends) who try to raise money to buy beer and throw their friend (Doc) a second party after the first one went out of control and ruined his lab. The story is set in the later hours of the day when the Cannery had closed and all the workers had gone and only the inhabitants of the street were left. Just as within the tidal pools, when the tides and the waves move back, the tidal pools are filled with life and the remnants are left behind. The life structures in the tide pools directly relate to the social structures of the Cannery Row. The mussels and limpets occupy the lowest status at the bottom of the pool whereas the starfish that prey on them and the eels that hide in crevices occupy a status above them. Hermit crabs who are always on the look out for empty shells that might be bigger than the ones they have also occupy the bottom of the sea. However, this structure is often silenced when the tides come back in but begin all over again when the tides

Regulation of Human Skin Pigmentation

Regulation of Human Skin Pigmentation Introduction In the human body, the skin is the largest organ, with it being a complicated epithelial and mesenchymal tissue. It consists of an epidermis which is multilayered as well as structures such as sebaceous and sweat glands, hair follicles, a dermis consisting of elastic and collagen fibres. There is also a layer of subcutaneous fat. There has been a discovery of over 1000 disease entities involved with the skin such as eczema, psoriasis, melanoma and urticaria. Around 15% of a human adults total body weight is accounted for by the skin with a surface area of approximately 2m2. The skin consists of three layers; the epidermis, the dermis and the hypodermis. The outer layer of the skin is known as the epidermis, which is a stratified squamous epithelium , where 95% of its cells are keratinocytes. The remaining cells in the epidermis are the melanocytes, merkel and langerhans cells. The role of the epidermis is to provide a defence barrier against environments of an inhospitable nature. The epidermis can be divided into four layers, in order from outer layer to deepest layer; stratum corneum (the cornified layer), stratum lucidum (the clear/translucent layer), stratum granulosum (the granular layer), stratum spinosum (the spinous layer) and the stratum basale (the basal layer) . There is a single layer of keratinocytes in the basal layer, where daughter cells can be produced by them to terminal differentiation via proliferation, resulting in the forming of the cornified layer , which can take around 40 days, however this can be shorter in various diseases, such psoriasis. About ten layers of corneocytes that are flattened make up the cornified layer . From the neural crest, dendritic cells can be derived which are known as melanocytes, which are also found in the basal layer. Melanosomes, which are subcellular organelles, transport melanin, which are synthesised by melanocytes, to the neighbouring basal keratinocytes. In order to prevent harm to the nuclei of the basal keratinocytes from ultraviolet radiation, a melanin cap is formed by the melanosomes. Melanosome size and number, as well as melanins nature determine skin colour or pigmentation. Langerhans cells are derived from the bone marrow and are antigen presenting dendritic cells founds in the epidermis. Sensory information is transmitted from the skin to the sensory nerves by merkel cells found in the epidermis . The dermis is the layer beneath the epidermis, and its thickness depends on the area of the body. For example, on the eyelid, the dermis is thin, whilst the dermis is thick on a persons back. The dermis consists of two layers; the papillary dermis and the reticular dermis. The papillary dermis is in contact with the basement membrane zone, which provides adhesion between the epidermis and dermis, where skin blistering can occur due to defects. Blood vessels as well as sensory nerve endings are richly supplied to the papillary dermis. The reticular dermis is in contact with the hypodermis and is the main component of the dermis. Interstitial components, such as elastic and collagen fibres, and cellular components, such as fibroblasts and plasma and mast cells, are what make up the composition of the dermis. Collagen accounts for around 70% of the dermis dry weight , where types I and III are predominant. The predominant cell type, however, is fibroblasts in the dermis, which are derived from the mesenchyme. The hypodermis is the deepest layer of the skin consisting of lipocytes. The function of the hypodermis is to connect the skin to the bone and muscle, thus supplying the bone with nerves and blood vessels. The arrangement of these is in fat lobules, where the fibrous septae separates one from another. The connection between the dermis and the hypodermis is strengthened by fibre bundles originally from the dermis. Around 80% of the entire body fat is found within the hypodermis in those individuals who are not obese . As very briefly mentioned previously, melanocytes function is dependent upon for pigmentation. These cells from melanoblasts during embryological development. Each basal melanocyte is connected functionally to the dermal fibroblasts as well as to the basal keratinocytes. These three cell types interact and communicate with each other in order to regulate the skins phenotype and function through the secreted factors and receptors in addition to cell to cell contact . Stem cell keratinocytes and basal melanocytes has a slow proliferation rate in normal circumstances, however the upper basal keratinocytes have a much rapid proliferation rate, which carries them towards the skins surface alongside the ingested melanin thus forming a barrier. Therefore the skins colour is not personified by only the melanin found in melanocytes, but also in a conjunction with pigment found in the superficial layers of the skin . Currently, pigmentation is known to be regulated in a direct or indirect fashion by over 125 different genes, with this number potentially rising 150-200 in less than another 100 years. Out of them genes, the ones whose function is understood, a lot of them affect processes that are involved in development which are critical for melanoblasts. Some genes regulate melanocytes differentiation and survival whilst others control processes affecting pigmentation. Melanosomes functions or biogenesis is affected by more than 25 of the genes. Some critical enzymes involved in the control of pigmentation include tyrosinase, tyrosinase related protein 1 (TRP-1) and DCT (DOPAchrometautomerase). If these enzymes are mutated, melanins which are synthesis could be affected in terms of their quantity and quality. Some critical structural proteins required for the melanosomes to mature structurally include Pmel17 and MART1. Mutations in proteins that are involved in the sorting of melanosome proteins can result inherited disorders of hypopigmentary nature . This critical appraisal will look at in further detail the different types of pigmentation, constitutive and facultative, and how they are regulated, including the roles of MC-1R, cyclic AMP (cAMP) pathway Agouti Signalling Protein, MITF and ultraviolet radiation. Also covered in this piece of work is CRHs and ÃŽÂ ²-endorphins roles in regulation of human skin pigmentation. Melanin Within the melanosomes, melanins are synthesises via the previously mentioned enzymes. The reaction which limits the melanogenesis rate becomes catalysed by tyrosinase, as is tyrosinases hydroxylation resulting in 3,4-dihydroxyphenylalanine (DOPA), along with DOPA oxidising into DOPAquinone. The oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) take place in mice due to TRP-1, however this same activity doesnt take place in humans. DOPAchrome is isomerised into DHICA by DCT. In human, there is productions of two types of melanin, eumelanin which is black or brown and pheomelanin which is yellow or red. Tyrosinase is essential for the synthesis of both types of melanin, whilst TRP1 and DCT more for the synthesis of eumelanin . With regards to skin pigmentation, there are two types; Constitutive pigmentation and Facultative pigmentation. Regulation of Constitutive Pigmentation Depending upon the racial and ethnic background of the person, the colour of human skin varies from extremely light to extremely dark. Several major chaperones, melanin, oxyhaemoglobin and deoxyhaemoglobin and carotenoids determine the colour of human skin. In 1954, the first observation was made with regards to the pigmentary system of the skin by Szabo when an immunohistochemical technique was used to test tyrosinases enzymatic activity via staining of tissues , where Caucasian skin was examined at first followed by other colours of skin. Along with various other studies as well as Szabos it was shown that in different human skin types had similar melanocytes densities as well as distribution in similar body areas. They also found that there is less melanin content in lighter skin, with melanosomes which are pigmented poorly being clustered above the nuclei within keratinocytes. There is more melanin present in darker skin, with the distribution of melanosomes that are pigmented heavily being individual in keratinocytes rather than clustered, which increases light absorption. The density of melanocytes is different in distinct parts of the body. For example, the skin on an individuals palms or soles is lighter in comparison to others parts of the body. Environmental factors can affect the density of constitutive melanocytes in the skin, including ultraviolet radiation (UVR), where the density can be increase by 3 or 4 times of the norm. Another environmental factor that can increase the density are toxic compounds, for example hydroquinone, resulting in the destruction of melanocytes. In increase of decreased melanocyte densities, pigmentary disorders which are inherited can result, for example freckles or vitiligo respectively . Due to Bcl2s high expression, epidermal keratinocytes are resistant to apoptosis as they have a slow proliferation rate in normal circumstances. It has been shown that the palms and soles dermis have a high level of Dickkopf-1 (DKK1) secretion which causes the Wnt/ÃŽÂ ²-catenin signalling pathway to become inhibited via the suppression of the growth function of melanocytes, thus inhibiting the melanogenic pathway. This can have effects on some transcriptional regulators, for example microphthalmia transcription factor (MITF), to some downstream melanogenic proteins. Epidermal Keratinocytes also become affected by DKK1 as melanin uptake is diminished, resulting in a skin phenotype which is a lot thicker with less pigmentation . Melanocortin 1 Receptor (MC-1R), which is domain receptor of seven transmembranes which binds to pro-opiomelanocortin peptides due to it being coupled with ÃŽÂ ±s G-protein , is a major skin pigment phenotype determinant. It regulated the quality and quantity of melanin production. Two agonists regulate MC-1R function, which are ÃŽÂ ± melanocyte stimulating hormone (ÃŽÂ ±-MSH) and adrenocorticotropic hormone (ACTH). An antagonist called Agouti signalling protein (ASP) also regulates MC-1R function. When ÃŽÂ ±-MSH or ACTH activate MC-1R, melanogenic cascade expression is stimulated, resulting in stimulation of eumelanin synthesis. This can be reversed by ASP, resulting in stimulation of pheomelanin production. MC-1R gene expression can be upregulated by ÃŽÂ ±-MSH and ACTH, which act in a positive feedback loop . Melanogenesis Melanogenesis can be defined as the biosynthetic pathway of melanin in living cells, which is a complex process with multiple steps which involves substrates, specific enzymes already mentioned and various cofactors commencing with phenylalanine and/or tyrosinase resulting in melanin deposition on the melanosomes protein matrix. The understanding of melanogenesis was greatly increased in the 1950s onwards by Fitzpatrick et al . During the cycle of hair growth in Agouti mice, melanogensis regulation occurs quantitatively as well as qualitatively. Pheomelanins are produced instead of eumelanins in the anagen phase, a switch incurred by the melanocytes in the hair follicles, causing a yellow band on top of a brown background. The regulation of this switch involves extension and agouti loci products that encode MC-1R and ASP respectively. When a ligand binds to MC-1R it activates, resulting in activation of adenylyl cyclase by the ÃŽÂ ±s G-protein, causing an increase in the intracellular cAMP significantly. If the extension locus incurs any mutations, the MC-1R reception will become non functional, therefore adenylate cyclase will remain inactive in ÃŽÂ ±-MSH presence, meaning mice will have a yellow coat colour. The MC-1R receptor is bound by ASP, which results in the ÃŽÂ ±-MSH effects being antagonised, which includes the adenylate cyclase activation caused by the ÃŽÂ ±-MSH . There is lots of evidence which shows that ÃŽÂ ±-MSH, ACTH and cAMP have key roles in skin pigmentation regulation in humans. For example, ÃŽÂ ±-MSH hypersecretrion has been reported to cause skin hyperpigmentation. Patients with severe obesity and hair pigmentation which is red have been shown to have pro opiomelanocortin gene mutations . In human melanocytes that have been cultured, dendricity and melanogenesis are upregulated by the pro opiomelanocortin peptides. Pharmalogical cAMP can also mimic these effects. All of this clearly suggests that ÃŽÂ ±-MSH, ACTH and cAMP have a vital role in melanogenesis regulation. Role of cAMP It is suggested that cAMP has a pivotal role in melanogenic enzymes activity / expression regulation. This is because the enzyme activity of melanogenesis is diminished much more than TRP-1 and DCT. The melanogenic effects of the pro opiomelanocortin peptides seem to be mediated via the cAMP pathway upregulation through the activation of MC-1R as well as adenylate cyclase. Within the cell, cAMP binds to protein kinase A (PKA), enabling activation of the catalytic subunit. PKA phosphorylates its substrates, then translocating to the nucleus, phosphorylating cAMP responsive element binding protein (CREB) transcription factors family. Specific genes have their expression activated by this family of proteins, which contains consensus cAMP responsive element (CRE) sequences within their promoters. CREB-binding protein is also phosphorylated by PKA, where PKA dependent gene expression is required in order for the interaction with the family of CREB proteins . MITF, which is a helix loop helix transcription factor has been shown to be encoded by the mi locus. This is due to mice which have the mi mutation have a coat colour which is diluted, have white spots, or entire pigmentation loss. They can also have a microphthalmic phenotype caused by ocular development defects. Within melanocytes, mast cells, pigment cells in the retina and osteoclasts, MITF has been found to be expressed. Also, the lack of melanocytes seems to be the cause of the defective pigmentation in mi mice. It has been established that in the development and survival of melanocytes, MITF plays a key role, which is confirmed by the cloning of the MITF homologue within humans. Patients who have type II Waardenburg syndrome have been known to have mutations in MITF present, where there is defective pigmentation in the skin, hair and eyes, as well as hearing alterations . It was shown by Bertolotto et al that there is some sort of connection between the cAMP pathway with MITF. In normal melanocytes and B16 melanoma cells, MITF expression was shown to be increased by cAMP. Tyrosinase expression stimulation that is induced by cAMP requires MITF as shown by a MITF missing the transactivation domain by a dominant negative mutation . PKA becomes activated by cAMP. PKA then goes on to phosphorylate and activate CREB. CREB binds to CRE after it is activated. The CRE is in the microphthalmia promoter, which upregulates its transcription. Microphthalmia expression is therefore increased, which leads to amplified binding of microphthalmia to the M box motif found in the tyrosinase promoter. Tyrosinase expression is increased, as is the upregulation of the synthesis of melanin. Agouti Signalling Protein In cultured human melanocytes, eumelanin synthesis and the activity of tyrosinase is inhibited by ASP. TRP-1 and the expression of tyrosinase is also reduced by ASP. Because of tyrosinases slightest inhibition of activity as well as to the near loss of the expression of TRP-1 and DCT, ASP decreases eumelanin synthesis. It has been found that genes were downregulated by ASP founds in tyrosinase and DCT, as well as upregulated genes which have some association with a basic helix loop helix transcription factor (ITF2). This shows that ITF2 may have a role in melanogenesis regulation, particularly in the previously mentioned switch of eumelanin to pheomelanin. Regulation of Facultative Pigmentation Physiological regulation that causes an increase in skin colour can be defined as facultative skin pigmentation. There are lots of factors that regulated facultative skin colour, including ultraviolet (UV) which is also known as the tanning reaction which occurs in fish as well as humans. The skins response to UV radiation is kinetically complex causing tanning of the skin over a period of several weeks . The effects of UVR can be divided into acute and chronic effects. The acute effects include erythema (sunburn), tanning and immunosuppression. The skins visible pigmentation is added to by UV causing erythema of the skin itself. There are three different stages of tanning, two of which occur rapidly, immediate and persistent tanning, and one that takes time in order for it to develop, delayed tanning. Immunosuppression can result in a decreased number and function of antigen presenting langerhans cells, as well morphological changes. The chronic effects of UVR include photoaging and photocarcinogenesis. In photoaging, wrinkles and freckles start to appear on the skin, where there is a leather type appearance. Photocarcinogenesis can be caused due to the indirect damage of DNA by reactive oxygen species generation. There are three types of UVR: UVA which is 320 400nm long. Its the longest wave from all the types of UVR and can penetrate deeply into the dermis. UBV is 280 320nm long. It can penetrate the epidermis and is 100 fold more energetic and mutagenic. UVC is 200 280nm long but does not reach the surface of Earth. Immediate Persistent Tanning The reaction of immediate tanning can occur almost instantaneously, within a few minutes after being exposed to UV, where it still persists several hours later. Persistent tanning is a separate second stage of the tanning reaction whereupon it occurs within a few hours after being exposed to UV, with it still being persistent several days later. Melanin and/or melanogenic precursors oxidation and polymerisation is thought to be behind both immediate and persistent tanning. The responses of both these types of tanning are greater to UVA than to UVB. Immediate tanning has a colour of gray to black whilst persistent tanning appears brown.It has been shown that one week after being exposed to UV, there is very little production of more melanin . Reported in 1986 was that immediate tanning can be educed by UVA in epidermal sheets. Honigsmanns results suggested that existing melanin or melanin precursors chemical oxidation is reflected upon by immediate tanning rather than pigment granules physiological movement. Reactive oxygen species are able to cause the oxidation of tyrosine as well as DOPA to melanin which occurs in immediate tanning. Also, pigmentations UVA induction is dependent upon melanin which is soluble and there are two different types of melanin absorption which are involved in UVA photoxidation. Delayed Tanning The reaction of delayed tanning has a developmental time of more than several days. Skin tanning appears to peak one week after being exposed to UV, after which tanning appears to diminish for the next ten weeks, but doesnt return to the constitutive level after that time. Within the same time frame, Asian skin pigmentation increase is relatively small. Therefore there is a higher level of hyperplasia in skin that contains smaller levels of constitutive pigment, playing somewhat of a protective role in the response to UV than did the increased pigmentation the skin types that are lighter. Skin pigmentation increase over a long term caused by UV are due to lots of physiological facts being regulated by UV, affecting the growth and / or differentiation of melanocytes. Pigmentation is also stimulated by DNA damage caused by UV exposure . The levels of eumelanin and pheomelanin slowly increase together after being exposed to UV on human skin. This shows that by UV, they are not regulated separately. In various ethnic origins skin pigmentation, there are around two fold differences in melanins chemical content and the melanosomes distribution and size of the particle are important to the visible colour of skin. In comparison with skin which is protected to skin which is constantly radiated with UV, there is only less than a two-fold increase again. All of this shows that aside from the quantity of melanin, other factors are necessary for skin pigmentation. An increase in their expression of ÃŽÂ ±-MSH and ACTH is a response by epidermal keratinocytes and melanocytes to UV exposure. This MC-1Rs function and expression to become upregulated, increasing the response of melanocytes to melanocortins. The weakly functioning MC-1R variants can be located in people with fair skin with red hair who have more pheomelanin with an inability to get a tan. The expression of Endothelin-1 by keratinocytes is enhanced by UV, thus enhancing MC-1Rs expression also, but endothelin-1 works via its own receptor on the melanocytes. The secretion of interleukin-1 by keratinocytes is also caused by UV, stimulating endothelin-1, ÃŽÂ ±-MSH and ACTH secretion by keratinocytes. In keratinocytes, p53s stimulation by the exposure to UV causes increased POMC gene expression resulting in an increase in ÃŽÂ ±-MSH secretion as well as MC-1R function stimulation in the neighbouring melanocytes . ÃŽÂ ²-endorphin/ÂÂ µ-opiate receptor It was reported for the first time by Kauser et al that ÃŽÂ ²-endorphin and the ÂÂ µ-opiate receptor system is expressed in epidermal melanocytes, theyre associated closely with melanosomes, and that in melanocyte biology regulation, this system is active due to its pigmentation, dendricity and proliferation upregulating ability. In the epidermal melanocytes and keratinocytes, the presence of both aforementioned ligand and receptor gives a platform for both autocrine and paracrine mechanisms for the regulation of melanocyte behaviour. ÃŽÂ ²-endorphin and ÃŽÂ ²-lipotropic levels are raised being exposed to UVR , further suggesting that ÃŽÂ ²-endorphin has a role in epidermal melanocytes. Kauser et al also showed that ÃŽÂ ²-endorphin that has been supplied exogenously can cause an increase in melanogenesis and proliferation in epidermal melanocyte cultures. ÃŽÂ ²-endorphin also has an association with melanosomes suggesting that melanogenesis might be regulated l ocally in the secretory granule. Corticotropin Releasing Hormone It has been established that Corticotropin Releasing Hormone (CRH) does have some sort of role in pigmentation. MC-1R action as well as the ÂÂ µ-opiate receptor moderates melanocytes behaviour in hair follicles where there is complete expression of the pro opiomelanocortin system within the pigmentary unit. The expression of CRH is low is different melanogenic zones, whilst there is differentiated distribution of melanocytes in the same area. CRH Receptor 1 seems to be more important in follicular melanocytes for the stimulation of melanogenesis, proliferation and dendricity. However, the role of CRH is in skin pigmentation is not 100% full established, and is an area that definitely required further research in order to gain some clarification. Aging As people get older, pigmentation continues to increase until adolescence or adulthood. Once theyve reached this point, pigmented lesions often begin to appear, and the hair starts to turn gray. It was found in 1979 that the quantity of melanocytes was decreased by about 10% with each decade the age went up by. This was confirmed by two other researches , where one was carried out on darker skin also. Another study compared very fair skin with Caucasian skin, finding that melanocyte density was greatly enhanced following continuous exposure to sunlight in the darker skin, however langerhans cell densities were decreased in the same time frame in both skin types after being exposed to UV.. It was proposed by Stierner et al that being exposed to UV might have some role in the development of melanoma in both exposed and protected skin, as well as being exposed to aberrant UV profoundly can be a lot more harmful than normal exposure , which has since been confirmed by various other studi es . Disruption of Regulation From time to time, different types of pigmentary disorders can occur due to disturbance of the normal regulation of skin pigmentation. Tyrosine function regulation lays importance on intracellular pH as catalytic functions are affected by the intramelanosomal pH as well as melanosomal protein delivery requiring the sorting pathway to have the right pH gradient. It is also considered that pigment production is regulating in some part by intracellular pH in different types of skin depending upon the racial or ethnic origin . Every single form of albinism is caused by tyrosine dysfunction or other types of melanogenic proteins, which can cause skin pigmentation to be blemished. Another pigmentary disorder is Hermansky Pudlak syndrome. This disorder have pleiotropic clinical effects . Pigmentary disorders which are caused by the acquiring of melanin involve the skin becoming lighter or darker. Skin colour which reduced is normally caused from epidermal melanin content declining. The skin may become darker due to an extremely large number of melanin being produced due to there being a an enhanced quantity of melanocytes, however it can also be due to melanin distribution becoming abnormal. Conclusion To summarise, in different skin colours and racial backgrounds, the density of melanocytes is near identical. The quantity and distribution of melanin is largely dependent upon for constitutive skin pigmentation. Less DNA damage occurs to melanocytes present in darker skin than those present in lighter skin. The activity of melanogenesis increases in darker skin in a more efficient manner than in lighter skin. The determination of constitutive skin pigmentation is achieved by: Melanoblasts migration during development Melanoblasts differentiation and survival to melanocytes Melanocyte density Melanosomal enzymes and their structural components expression and function Eumelanin and pheomelanin synthesis Melanosome transport to the dendrites Melanosomes being transferred into keratinocytes Melanin distribution in the skins suprabasal layers. MITF seems to respond to UV pretty quickly, with a response after 1 to 2 days. Some melanosomal proteins respond slower, such as tyrosinase, TRP-1 and DCT, with a response being elicited after about 1 week, where 3 weeks later an increase in the synthesis in melanin can be observed, whereas melanocyte density is increased around 4 to 5 weeks. Cyclic AMP causes the complex induction of intracellular processes which seem to be interconnected. The sub-pathway where PKA is activated, MITF is upregulated as is some of the enzymes involved in melanogenesis, causes melanogenesis stimulation. A cAMP activated pathway, through ERK activation inducing the degradation and phosphorylation of MITF, regulated melanogenesis negatively, where PKA is independent upon. The skins melanin distribution plays a key role in pigmentation that is visible. After around 1 week, the existing pigments migration towards the epidermal surface is increased, after which newly synthesis melanin restores the balance in the distribution of pigment around 4 to 5 weeks later. It is also apparent that when the distribution in the content of melanin undergoes minor changes, it can result in major changes in visible pigmentation, affecting constitutive pigmentation as well as facultative pigmentation or the responses to being exposed to UV. After reading through the literature to carry out this critical appraisal, it is evident that lots of studies have opposing and conflicting results as well as conclusions which may be incoherent, where the same group of authors may diverge from something which they have previously stated. This is most probably due to lots of variants when conducting these types of in vivo and in situ physiological studies. These variants most definitely include: UV source types How much dose amount and frequency that has been applied The sites which have been exposed and their locations The point in time which is assessed after being exposed to UV The history of the subjects, and whether they have been exposed to the same / higher levels of UV conducted in the experiments previously The capacity of an individual DNA repairing Very importantly, the racial and / or ethnic origin of the subjects. There are many areas which require clarification in field, which are definite area of potential future research. For example; Is melanocyte function affected eumelanin against pheomelanin production? As facultative pigmentation is increased, is there further protection against damage caused by UV? Does DNA repair have a role in reducing the skins long term damage? Also, photocarcinogenesis understanding needs to be enhanced, some of the parameters that are critical to it, and some strategies on how to reduce its risks. Research into which pathways participate in melanogenesis induced by UV and MSH still seems to be under way. Any advances could help in discovery of new potential ways of treating certain pigmentary disorders. The regulating mechanisms in the synthesis on melanin arent understood as clearly as required, where its been speculate that research into this may lead to topical melanogens discovery that can cause the production of melanin when UV irradiation is absent, which causes photo aging as well as some skin cancers. Further studies are necessary regarding the pigmentary role of ÃŽÂ ²-endorphin, which seems to be the forgotten melanocortin with regards to pigmentation. Similarly, the role of CRH in pigmentation also needs to be enhanced further. It is also shown that some hormones play a role in regulation of pigmentation including some oestrogens and androgens, which are areas that could used for further research to increase our understanding.

The Italian Wars :: History

The Italian Wars Italy was the background for outside powers between the French invasion of 1494 and the accession of Francis 1 in 1515 for different reasons. Between these years, the States of Italy were invaded on a number occasions by armies from France, Spain and other countries. At this time, the Italian States were very vulnerable; there were conflicts in Italy itself, they had out of date military equipment and Italy had insecure frontiers and unreliable allies – â€Å"That Italy failed to organise herself against invaders was due to the selfish policies.† This gave outside powers reason to use Italy as their battleground. Italy was a very wealthy country, showing this wealth, a Florentine Historian, Guicciardini said â€Å"Italy has never enjoyed such prosperity or known so favourable a situation† Also, because the Pope lived in Italy, it gave enemies more incentive to fight in Italy as opposed to any other country. Another reason for Italy being the battleground was that foreign powers felt they had dynastic claims to certain states and therefore felt obliged to fight for them. I feel the most important reason why outside powers chose Italy to fight in was basically because they ‘could.’ Italy was divided, unstable and disunited; there were even civil disputes e.g. when Venice and its neighbour Ferrara went to war. It was hard to keep foreign powers out of their country because they weren’t working together; each state was not strong enough to protect Italy on its own. The Papacy also didn’t help in keeping enemies out – â€Å"there was always scope for dissension between them (Orsini and Colonna); and while they remained armed before the very eyes of the pontiff, they kept the papacy weak and insecure.† Also, it was playing its usual game of self interest. Pope Leo X in 1513 set about promoting the interests of himself and his family. He was prepared to negotiate for French aid to further his ambitions – this lead to more foreign powers (especially France), being able to easily use Italy as the main battleground. It can be disputed that the most important reason for Italy being the battle ground was that it was wealthy, but I feel that even though it was wealthy, there were certainly other wealthy states which could have been the battleground, had Italy not been such an easy target, with certain assets other countries did not have. This leads me to the next important reason why Italy was the battle ground; wealth.