Wednesday, August 26, 2020
Influence of Security and Trust in the Use of E-Commerce among Essay
Impact of Security and Trust in the Use of E-Commerce among Consumers in China - Essay Example M-com impacts the business exercises and buyer conduct. Be that as it may, in spite of these components, for example, usability and saw esteem, the Chinese purchasers have been delayed to receive this innovation. M-com is still in its early stages in China in spite of a high pace of cell phone clients (Zhou, 2010). While the e-com incomes are high in China, complex m-com applications are as yet restricted in spite of China having a portable endorser base of 461 million toward the finish of 2006 â⬠the most noteworthy on the planet (Xu, Yan and Zheng, 2008). M-com would keep on staying an enhancement to the conventional appropriation channel since organizations need to build up their m-com contributions to shoppers (Zhihao, 2011). In addition, few out of every odd customer likes to shop without visiting the genuine stores. Examinations on the reasons should be found out. Points and goals Several variables impact the utilization of m-com and these components may contrast across area s, countries and societies. With the mean to learn how security and trust concerns impact the expectations to utilize m-business, the goals of the investigation are: To assess the advantages of m-com over web shopping To assess the degree to which security and trust discourage buyers from utilizing m-trade To decide the degree to which Chinese customers use m-business for charge installments Literature Review Studies have been led on assessing the social reasons why Chinese purchasers have been delayed in embracing m-trade. The aims to utilize m-com have been resolved and Dai and Palvia (2009) found that apparent value and saw usability have huge impact on the Chinese consumersââ¬â¢ aim to utilize m-com. The examination in any case, didn't assess the reasons or factors that are liable for low expectations to utilize e-com in China. One of the potential reasons refered to by the creators is security and trust in m-com. Zhou (2010) finds that framework quality and the data quality impact the apparent worth and the apparent usability of the Chinese customers. Administration quality effects the degree of trust that customers have in utilizing m-business. Exchanging expenses and duty can likewise impact m-com which has not been explored. Utilizing cell phones for money related exchanges can carry numerous advantages to the financial division yet its use is restricted. It benefits the banks as well as the customers who can pay for remote buying however numerous frameworks must be shut down (Cognet, 2010). Hypothetical structure It in this way gives the idea that the goal to utilize depends to a huge degree on the framework quality, nature of the site and the substance. The nature of these elements decides the degree of trust that can impact the choice to utilize m-business. Subsequently the hypothetical structure for the investigation would be founded on the components of relationship promoting and the trust hypothesis. Relationship advertising includes social co ntracting and working organizations. Fruitful relationship promoting requires common trust and duty. This has gotten significant as associations understand that they need to work together to contend. Along these lines, how much the retailers have had the option to create trust among the shoppers would be found out in light of the fact that this decides the certainty they would have in participating in m-trade. Examination Design The adolescent are more
Saturday, August 22, 2020
Looking Deeper into Schizophrenia Essay Example
Looking Deeper into Schizophrenia Essay Schizophrenia is a ceaseless, tireless and immobilizing or rendering the cerebrum broken (National.., 2007). Roughly one percent of people living in the United States are influenced by Schizophrenia (National.., 2007). People who are analyzed to have schizophrenia are ordinarily frightful, pulled back, just as, fomented (National.., 2007). Such practices might be realized by the way that people enduring schizophrenia experience the accompanying: 1) hear voices however others don't; 2) conviction that others are guessing their thoughts; 3) sureness that others are controlling their brain; or 4) amazingly feel that someone needed to hurt them (National.., 2007). The previously mentioned are additionally the a portion of the reasons why: 1) on the off chance that you listen to them intently, nothing they state appear to bode well; 2) they can sit for a considerable length of time without moving or talking; or 3) show up okay that others will possibly see that there is something incorrec tly when they start to express their musings (National.., 2007). The previously mentioned realities affirm that endless people determined to have schizophrenia experience horrifying encounters remembering inconveniences for keeping their occupations, just as, and particularly, dealing with themselves (National.., 2007). This at that point influences the patients themselves, yet their families and the general public also (National.., 2007).Meanwhile, history has it that Schizophrenia previously developed in 2000 BC (Wikipedia,2007). In 1893, Schizophrenia has been recognized by Kraepelin as mental issue (Wikipedia, 2007).â The previously mentioned scatter got its name from Eugene Blueler who firmly accepts that there is an insufficiency of interface among discernment and mental procedures, accordingly he authored two Greek words which implied ââ¬Å"splitâ⬠and ââ¬Å"mindâ⬠or broke psyche (Wikipedia, 2007). Besides, even before the side effects has formally been express ed or pronounced, Eugene Blueler as of now has said that itââ¬â¢s indications are the accompanying: 1) ââ¬Å"flattened affectâ⬠; 2) chemical imbalance; 3) hindered relationship of thoughts; and 4) inner conflict (Wikipedia, 2007). Curiously, quite a while prior, schizophreniaââ¬â¢s just realized reason is that it is supposed to be a direct result of hereditary qualities or in light of the fact that it has been passed on from the original of the family to the succeeding ones (Wikipedia, 2007). Another amazingly eye catching actuality with respect to the historical backdrop of schizophrenia is that incalculable individuals were analyzed to experience the ill effects of it previously and that they were completely demolished in the Nazi program in fact alluded to as the ââ¬Å"Operation T-4â⬠(Wikipedia, 2007).Moreover, the principal focal point of this paper is on the reasons for schizophrenia whichincludes: 1) hereditary; 2) condition; 3) perinatal mental health; 4) y outh and juvenile turn of events; 5) grown-up cerebrum structure; 6) neuropsychology and mind work; 7) psychosocial components; and 8) immune system hypothesis (Wikipedia, 2007). Following that, the signs and side effects including the: 1) positive indications; 2) negative side effects; just as 3) subjective manifestations will be quickly talked about likewise (National.., 2007).â â Finally, treatment for schizophrenia will likewise be investigated (Wikipedia, 2007). Subjects for this class involve: 1) drug; 2) dietary enhancements; 3) neurological methods; and 4) mental and social mediations (Wikipedia, 2007).It is very certain that schizophrenia influences the patients themselves, their families, aswell as, the whole society, therefore, it is exceedingly imperative to reintroduce the causes, indications, just as, treatment for schizophrenia, which this paper expects to do so.Causes, Symptoms, and TreatmentThere are a few reasons for schizophrenia and a portion of these are the following:1) Genetic â⬠Experts guarantee that schizophrenia might be acquired (Wikipedia, 2007). This came about because of the examination results wherein it tends to be reasoned that there is a twenty eight percent chance for a twin to create schizophrenia if the other one previously obtained it (Wikipedia, 2007).2) Environment â⬠Researchers state that awful encounters, for example, physical maltreatment during youth causes schizophrenia (Wikipedia, 2007). Besides, negative medicines including, controlling disposition, hostility, absence of compassion and so on additionally triggers schizophrenia (Wikipedia, 2007). In addition, unpleasant encounters including loss of an occupation, deficiency of cash, segregation and so forth likewise prompts schizophrenia (Wikipedia, 2007).3) Perinatal mental health â⬠It is said that in the event that there are diseases that rose during the third trimester of pregnancy, at that point it is conceivable that later schizophrenia will cre ate (Wikipedia, 2007). Pre-birth adverse encounters including mental injury may likewise trigger schizophrenia (Wikipedia, 2007).4) Childhood and youthful improvement â⬠Experts state that since schizophrenia commonly creates during late youthfulness and early adulthood, it might then be said that when the phase of youth end, schizophrenia may effectively introduce itself (Wikipedia, 2007).5) Adult cerebrum structure â⬠It is said that there are sure size and structure of the districts of the mind that may cause the advancement of Schizophrenia (Wikipedia, 2007).6) Neuropsychology and cerebrum work â⬠Scientists state that practical incongruities at the top of the priority list movement impact the rise of schizophrenia (Wikipedia, 2007).7) Psychosocial factors â⬠Experts express that individuals who experience enthusiastic pressure, exceedingly confounding circumstances, despondency, feeling of inadequacy, challenges in concentrating/listening and so on are will undoubte dly create schizophrenia (Wikipedia, 2007).8) Autoimmune hypothesis â⬠It is additionally said that autoimmunity causes schizophrenia (Wikipedia, 2007). This is the place the living being glitches and won't have the option to distinguish itself making it conflict with its own phones and tissues (Wikipedia, 2007).Of course, there are likewise various signs and side effects that might be spotted to know whether an individual experiences schizophrenia and a portion of these are the following:1) Positive side effects â⬠If an individual is seen to have fancies, fantasies, at that point he might be experiencing schizophrenia (National.., 2007). Notwithstanding that, if their musings are in extraordinary turmoil and their physical developments are in disorder too, at that point the person might be analyzed as having schizophrenia (National.., 2007).2) Negative manifestations â⬠If an individual who isn't essentially lethargic or isn't experiencing melancholy but then thinks that its hard to explain their feelings, find and pinpoint what will fulfill the person in question, and can't make arrangements on their ownâ then the person in question might be schizophrenic (National.., 2007).3) Cognitive indications â⬠If an individual have a trouble attempting to center, experience memoryEven however the previously mentioned causes and side effects are frightening, it is extremelyfortunate that there are approaches to oversee/treat the previously mentioned illness. A portion of these are the following:1) Medications, which are typically antipsychotic, including dopamine framework stabilizers or agonists (Wikipedia, 2007).2) Dietary enhancements like omega-3 unsaturated fats, alpha lipoic corrosive, d-sarcosine, glycine, folate, nutrient A, nutrient C, just as, nutrient E (Wikipedia, 2007).3) Neurological strategies like electroshock and psychosurgery (Wikipedia, 2007).4) Psychological and social mediations like subjective conduct treatment, intellectual remedi ation treatment, music treatment, mental instruction for the entire family and psychotherapy (Wikipedia, 2007).ConclusionThis paper means to reintroduce the causes, side effects, just as, treatment forSchizophrenia. It has been completed in light of the way that it influences the patients themselves, their families, and the entire of society.Furthermore, this paper is significant in light of the fact that it assumes a huge job in thereintroduction of the subjects on the essential data about schizophrenia. It won't just remind people yet will likewise assist them with acquainting themselves with the following:â First of all, schizophrenia is achieved by the accompanying: 1) hereditary; 2) condition; 3) perinatal mental health; 4) youth and pre-adult turn of events; 5) grown-up mind structure; 6) neuropsychology and cerebrum work; 7) psychosocial elements; and 8) immune system hypothesis (Wikipedia, 2007). Besides, the manifestations are known as: 1) positive; 2) negative; just as 3 ) intellectual (National.., 2007). At long last, that it might be dealt with/oversaw through: 1) medicine; 2) dietary enhancements; 3) neurological techniques; and 4) mental and social intercessions (Wikipedia, 2007).On a last note, it is additionally acceptable to referenced that there are likewise a few examines led that might be incredibly useful later on. A portion of these are the following:A) Acupuncture for schizophreniaDescription of Study: This specific examination entitled, ââ¬Å"Acupuncture for Schizophreniaâ⬠, investigates a treatment wherein incredibly flimsy needles are set just underneath the outside of the skin all through the body. It looks to give proof to clinicians, just as, patients with respect to the advantages of needle therapy in schizophrenia (Rathbone et. al., 2006).Methodology: autonomous extraction of information/randomized controlled trialTreatment Protocol: needle therapy/electro-needle therapy/laser-needle therapy/no treatment/antipsychotic drug sFindings/Results:The scientists presume that needle therapy can not be proposed and recommended for individuals experiencing schizophrenia on account of insufficient validation (Rathbone et. al., 2006).B) Amisulpride for SchizophreniaDescription of Study:This explore examines the specific dopamine rival, Amisulpride (Mota Neto et. al., 2002). It means to evaluate its belongings (Mota Neto et. al., 2002). It likewise means to contrast it and fake treatment, common, as
Monday, August 17, 2020
Seven Tips on How to Write an Expository Essay
Seven Tips on How to Write an Expository Essay Expository Essay Definition and Structure When writing an essay, your task is to explain an idea in a clear manner. With no personal subjective views or opinions, no emotions or feelings. Only bare facts and definitions. The language should be simple and plain. If you are asked to describe how the flower has grown, you donât have to write about its smell or appearance. Writing an expository paper is easy only at first glance. Are there any expository essay prompts? Well, you are lucky to come across this article that if full of helpful tips and recommendations. As far as the structure is concerned, it consists of five paragraphs. They are the intro, 3 main paragraphs that form the body of the paper, and the conclusion. Itâs good to know how to complete such essays as youâll be able to use this skill in your future profession. So mastering it while youâre studying is a great advantage of you when searching for a new job. Write your expository essay outline: its structure and some tips What is an expository essay? In other words, you should brainstorm hard and answer why anyone may want to read your paper and what value you can give to your readers. Letâs consider how to write an expository essay in more detail. A good beginning How to start your essay? Start your expository paper with an intriguing sentence that can grab the readerâs attention. Make it sound and look attractive for the reader. If you know well who is going to read the essay, you will easily find the necessary words. Put the main idea of the story in the first sentence and explain what youâre going to say about. Itâs a kind of a preview for the essay. You should mention the thesis in the last sentence of the first paragraph. A great context In the first paragraph, you should make sure that the readers know well what youâre writing about. Give them some background information. For example, you can write the name of the book and the name of the author. If youâre highlighting a historical event, it will be good to give more details about that specific day, etc. Find a perfect length The most popular expository essay format is five paragraphs. It doesnât mean that you are limited or you cannot write more. First of all, look up in the guideline or ask your tutor about the format and the exact amount of paragraphs. If there are no limits, make it look proportional. Add more information to every part of your paper. Start the paragraph with an idea It is good if the reader can get the idea of what is going to be highlighted in the paragraph in the first sentence. Of course, it should prove your thesis. We know that this rule may seem too complicated. And if your paper is challenging, feel free to get tips on how to cope with it in the final part of the article. Prove your expository essay ideas Prove your ideas in subsequent sentences. Itâs better to use cited quotes, summaries. Where can you take these things? You need to conduct the investigation in advance before you start composing your essay. You can also write about your personal experience. Try to give 2-5 proofs that support your idea. Conclude and make a transition Each paragraph should end with a little conclusion and logically take the reader to the next paragraph. If you donât do it, the logical chain in the mind can break and there will be a sense of misunderstanding between you and your audience. This is not what you want. A good ending When it comes to finishing expository essay, ideas usually donât come to the writerâs mind quickly. However, here are some helpful tips. Start your conclusion with paraphrasing your thesis. Make a summary of your ideas from each paragraph. End your essay with a final thought or provide a call to action phrase. Expository essays: 5 main types What are the most popular types of expository essay? Check it below and make your writing more effective: Comparison essay. As the name prompts you need to compare something or someone. You can compare differences and whatâs in common as well. Process essay. Itâs the most commonly used type of paper. Need an expository essay example? You can write about how to cook eggs or how to cut your hair, or anything else. Descriptive essay. This kind of paper gives you a lot of freedom. It means you can write as much as you want to attract the reader. Problem / Solution essay. Here you mention the problem that is usually stated in the first paragraph and you show the solutions to it. Cause and Effect essay. In this essay, you build up a logical chain in the minds of your readers about what happens as a result of this or that action. No time for completing your papers? If you have little time for composing your essays, thereâs nothing to worry about. There are experts and authors who are always ready to come and assist you. If writing is challenging for it, you should definitely try ordering an essay. It means you ask another person to help you, provide the topics for expository essay, check the result and pay some money. Nothing more. Now you can relax and take it easy.
Sunday, May 24, 2020
The Persian Empire of Ancient Iran
Irans history as a nation of people speaking an Indo-European language did not begin until the middle of the second millennium B.C. Before then, Iran was occupied by peoples with a variety of cultures. There are numerous artifacts attesting to settled agriculture, permanent sun-dried- brick dwellings, and pottery-making from the sixth millennium B.C. The most advanced area technologically was ancient Susiana, present-day Khuzestan Province. By the fourth millennium, the inhabitants of Susiana, the Elamites, were using semipictographic writing, probably learned from the highly advanced civilization of Sumer in Mesopotamia (ancient name for much of the area now known as Iraq), to the west. Sumerian influence in art, literature, and religion also became particularly strong when the Elamites were occupied by, or at least came under the domination of, two Mesopotamian cultures, those of Akkad and Ur, during the middle of the third millennium. By 2000 B.C. the Elamites had become sufficiently unified to destroy the city of Ur. Elamite civilization developed rapidly from that point, and, by the fourteenth century B.C., its art was at its most impressive. Immigration of the Medes and the Persians Small groups of nomadic, horse-riding peoples speaking Indo-European languages began moving into the Iranian cultural area from Central Asia near the end of the second millennium B.C. Population pressures, overgrazing in their home area, and hostile neighbors may have prompted these migrations. Some of the groups settled in eastern Iran, but others, those who were to leave significant historical records, pushed farther west toward the Zagros Mountains. Three major groups are identifiable--the Scythians, the Medes (the Amadai or Mada), and the Persians (also known as the Parsua or Parsa). The Scythians established themselves in the northern Zagros Mountains and clung to a seminomadic existence in which raiding was the chief form of economic enterprise. The Medes settled over a huge area, reaching as far as modern Tabriz in the north and Esfahan in the south. They had their capital at Ecbatana (present-day Hamadan) and annually paid tribute to the Assyrians. The Persians were established in three areas: to the south of Lake Urmia (the tradional name, also cited as Lake Orumiyeh, to which it has reverted after being called Lake Rezaiyeh under the Pahlavis), on the northern border of the kingdom of the Elamites; and in the environs of modern Shiraz, which would be their eventual settling place and to which they would give the name Parsa (what is roughly present-day Fars Province). During the seventh century B.C., the Persians were led by Hakamanish (Achaemenes, in Greek), ancestor of the Achaemenid dynasty. A descendant, Cyrus II (also known as Cyrus the Great or Cyrus the Elder), led the combined forces of the Medes and the Persians to establish the most extensive empire known in the ancient world. By 546 B.C., Cyrus had defeated Croesus*, the Lydian king of fabled wealth, and had secured control of the Aegean coast of Asia Minor, Armenia, and theà Greek coloniesà along the Levant. Moving east, he took Parthia (land of the Arsacids, not to be confused with Parsa, which was to the southwest), Chorasmis, and Bactria. He besieged and captured Babylon in 539 and released the Jews who had been held captive there, thus earning his immortalization in the Book of Isaiah. When he died in 529**, Cyruss kingdom extended as far east as the Hindu Kush in present-day Afghanistan. His successors were less successful. Cyruss unstable son, Cambyses II, conquered Egypt but later committed suicide during a revolt led by a priest, Gaumata, who usurped the throne until overthrown in 522 by a member of a lateral branch of the Achaemenid family, Darius I (also known as Darayarahush or Darius the Great). Darius attacked the Greek mainland, which had supported rebellious Greek colonies under his aegis, but as a result of his defeat at theà Battle of Marathon in 490à was forced to retract the limits of the empire toà Asia Minor. The Achaemenids thereafter consolidated areas firmly under their control. It was Cyrus and Darius who, by sound and farsighted administrative planning, brilliant military maneuvering, and a humanistic worldview, established the greatness of the Achaemenids and in less than thirty years raised them from an obscure tribe to a world power. The quality of the Achaemenids as rulers began to disintegrate, however, after the death of Darius in 486. His son and successor, Xerxes, was chiefly occupied with suppressing revolts in Egypt and Babylonia. He also attempted to conquer the Greek Peloponnesus, but encouraged by a victory at Thermopylae, he overextended his forces and suffered overwhelming defeats at Salamis and Plataea. By the time his successor, Artaxerxes I, died in 424, the imperial court was beset by factionalism among the lateral family branches, a condition that persisted until the death in 330 of the last of the Achaemenids, Darius III, at the hands of his own subjects. The Achaemenids were enlightened despots who allowed a certain amount of regional autonomy in the form of the satrapy system. A satrapy was an administrative unit, usually organized on a geographical basis. A satrap (governor) administered the region, a general supervised military recruitment and ensured order, and a state secretary kept official records. The general and the state secretary reported directly to the central government. The twenty satrapies were linked by a 2,500-kilometer highway, the most impressive stretch being theà royal roadà from Susa to Sardis, built by command of Darius. Relays of mounted couriers could reach the most remote areas in fifteen days. Despite the relative local independence afforded by the satrapy system, however, royal inspectors, the eyes and ears of the king, toured the empire and reported on local conditions, and the king maintained a personal bodyguard of 10,000 men, called the Immortals. The language in greatest use in the empire was Aramaic. Old Persian was the official language of the empire but was used only for inscriptions and royal proclamations. Darius revolutionized the economy by placing it on a silver and gold coinage system. Trade was extensive, and under theà Achaemenidsà there was an efficient infrastructure that facilitated the exchange of commodities among the far reaches of the empire. As a result of this commercial activity, Persian words for typical items of trade became prevalent throughout theà Middle Eastà and eventually entered the English language; examples are, bazaar, shawl, sash, turquoise, tiara, orange, lemon, melon, peach, spinach, and asparagus. Trade was one of the empires main sources of revenue, along with agriculture and tribute. Other accomplishments of Dariuss reign included codification of the data, a universal legal system upon which much of later Iranian law would be based, and construction of a new capital at Persepolis, where vassal states would offer their yearly tribute at the festival celebrating the spring equinox. In its art and architecture, Persepolis reflected Dariuss percept ion of himself as the leader of conglomerates of people to whom he had given a new and single identity. The Achaemenid art and architecture found there is at once distinctive and also highly eclectic. The Achaemenids took the art forms and the cultural and religious traditions of many of the ancient Middle Eastern peoples and combined them into a single form. This Achaemenid artistic style is evident in the iconography of Persepolis, which celebrates the king and the office of the monarch. Envisioning a new world empire based on a fusion of Greek and Iranian culture andà ideals,à ââ¬â¹Alexander the Greatà of Macedon accelerated the disintegration of the Achaemenid Empire. He was first accepted as leader by the fractious Greeks in 336 B.C. and by 334 had advanced to Asia Minor, an Iranian satrapy. In quickà succession,à he took Egypt, Babylonia, and then, over the course of two years, the heart of theà Achaemenid Empire--Susa, Ecbatana, and Persepolis--the last of which he burned. Alexander married Roxana (Roshanak), the daughter of the most powerful of the Bactrian chiefs (Oxyartes, who revolted in present-day Tadzhikistan), and in 324 commanded his officers and 10,000 of his soldiers to marry Iranian women. The mass wedding, held at Susa, was a model of Alexanders desire to consummate the union of the Greek and Iranian peoples. These plans ended in 323 B.C., however, when Alexander was struck with fever and died in Babylon, leaving no heir. His empire w as divided among four of his generals. Seleucus, one of these generals, who became ruler of Babylon in 312, gradually reconquered most of Iran. Under Seleucuss son, Antiochus I, many Greeks entered Iran, and Hellenistic motifs in art, architecture, and urban planning became prevalent. Although the Seleucids faced challenges from theà Ptolemies of Egyptà and from the growing power of Rome, the main threat came from the province of Fars (Partha to the Greeks). Arsaces (of the seminomadic Parni tribe), whose name was used by all subsequent Parthian kings, revolted against the Seleucid governor in 247 B.C. and established a dynasty, the Arsacids, or Parthians. During the second century, the Parthians were able to extend their rule to Bactria, Babylonia, Susiana, and Media, and, under Mithradates II (123-87 B.C.), Parthian conquests stretched from India to Armenia. After the victories of Mithradates II, the Parthians began to claim descent from both the Greeks and the Achaemenids. They spoke a language similar to that of the Achaemenids, used the Pahlavi script, and established an administrative system based on Achaemenid precedents. Meanwhile, Ardeshir, son of the priest Papak, who claimed descent from the legendary hero Sasan, had become the Parthian governor in the Achaemenid home province of Persis (Fars). In A.D. 224 he overthrew the last Parthian king and established the Sassanid dynasty, which was to last 400 years. The Sassanids established an empire roughly within the frontiers achieved by the Achaemenidsà [c, 550-330 B.C.;à with the capital at Ctesiphon. The Sassanids consciously sought to resuscitate Iranian traditions and to obliterate Greek cultural influence. Their rule was characterized by considerable centralization, ambitious urban planning, agricultural development, and technological improvements. Sassanid rulers adopted the title of shahanshah (king of kings), as sovereigns over numerous petty rulers, known asà shahrdars. Historians believe that society was divided into four classes: the priests, warriors, secretaries, and commoners. The royal princes, petty rulers, great landlords, and priests together constituted a privileged stratum, and the social system appears to have been fairly rigid. Sassanid rule and the system of social stratification were reinforced by Zoroastrianism, which became the state religion. The Zoroastrian priesthood became immensely powerful. The head of the priestly class, theà mobadanà mobad, along with the military commander, theà eranà spahbod, and the head of the bureaucracy, were among the great men of the state. Rome, with its capital atà Constantinople, had replaced Greece as Irans principal Western enemy, and hostilities between the two empires were frequent. Shahpur I (241-72), son and successor of Ardeshir, waged successful campaigns against the Romans and in 260 even took the emperor Valerian prisoner. Chosroes I (531-79), also known as Anushirvan the Just, is the most celebrated of the Sassanid rulers. He reformed the tax system and reorganized the army and the bureaucracy, tying the army more closely to the central government than to local lords. His reign witnessed the rise of theà dihqansà (literally, village lords), the petty landholding nobility who were the backbone of later Sassanid provincial administration and the tax collection system. Chosroes was a great builder, embellishing his capital, founding new towns, and constructing new buildings. Under his auspices, too, many books were brought from India and translated into Pahlavi. Some of these later found their way into the literature of the Islamic world. The reign of Chosroes II (591-628) was characterized by the wasteful splendor and lavishness of the court. Toward the end of hisà reignà Chosroes IIs power declined. In renewed fighting with the Byzantines, he enjoyed initial successes, captured Damascus, and seized the Holy Cross in Jerusalem. But counterattacks by the Byzantine emperor Heraclius brought enemy forces deep into Sassanid territory. Years of warfare exhausted both the Byzantines and the Iranians. The later Sassanids were further weakened by economic decline, heavy taxation, religious unrest, rigid social stratification, the increasing power of the provincial landholders, and a rapid turnover of rulers. These factors facilitated the Arab invasion in the seventh century. Data as of December 1987Source: Library of Congress Country Studies Corrections *Jona Lenderingà points out that a 547/546 date for the fall of Croesus is based on theà Nabonidus Chronicleà whose reading is uncertain. Rather thanà Croesusà it may have been the ruler of Uratu. Lendering says the fall of Lydia should be listed as the 540s. **He also advises that cuneiform sources start to mention Cambyses as sole ruler in August 530, so the date of his death the following year is wrong.
Wednesday, May 13, 2020
The Overcrowding Of Prison And Massachusetts - 1261 Words
After exploring options of which states had the most overcrowding in prisons, the best option to go with was California because states like Alabama and Massachusetts did not have current statistics. If anything, their statistics were from 2016 or 2013, making data harder to collect. Therefore, according to the California Department of Corrections and Rehabilitation website, the most recent report they have of the total population is as of midnight February 8, 2017. The total population is 180,885, with four of them being civil addict. Total in-custody is of 129,284 inmates, parole is 44,721, non-CDC jurisdiction is 1,022 and lastly other population #6 inmates with 5,854 (ââ¬Å"Weekly Report of Populationâ⬠, 2017). Once again looking at a weeklyâ⬠¦show more contentâ⬠¦This law increased the population rate in prison because not only did it affect serious crimes, it also affected those that committed petty crimes. Later on, after the prisons were so overcrowded, California ââ¬â¢s Proposition 36 changed the way ââ¬Å"Three Strikes ââ¬Å" law was. Proposition 36 allowed those to only get life sentence if their new felony conviction was serious or violent (ââ¬Å"California Propositionâ⬠, 2017). Not only that, Martinez states that the state was then under pressure from a three-judge federal court. In 2011, the federal court ordered the state to reduce its population to 137.5 % by December 31st or be held in contempt. The judges determined that in order to meet the medical and mental health care of inmates, the only way to resolve this was to reduce prison overcrowding (ââ¬Å"California to Challengeâ⬠, 2013). Another addition to the changes in the prison population was Californiaââ¬â¢s Public Safety Realignment Act of 2011, this allowed certain offenders to serve their sentence in jail rather than prison (ââ¬Å"Realignment Reportâ⬠, 2013). Before 1998, Californiaââ¬â¢s state prisons were designed to house 66,000 inmates, that m eant one inmate per prison cell. Around the time of September of 1998, there were 120,000 inmates resulting in an overcrowding level of 182 %. Construction plans after 1998 were for new prisons to hold 80,000 inmates (ââ¬Å"Accommodatingâ⬠, 1995). Referring back to the 137.5% reduction that needed to be met by three-judge panel, that would mean that it wouldShow MoreRelatedThe Unconstitutional Horrors Of Prison Overcrowding934 Words à |à 4 PagesUNCONSTITUTIONAL HORRORS OF PRISON OVERCROWDING. The article is preceded with an illustration of a jail cell in Texas where a prisoner would wait to be executed. The author starts her article off with a hypothetical scenario involving convicts being executed entirely based on their healthiness. She went on to reference the 2011 Supreme Course Brown v. Plata. Mayeux mentions how the most functional of prisons have a difficult time employing certified medical staff. This prison in California was builtRead MoreThe Overcrowding Of The C orrectional Facilities1730 Words à |à 7 Pagesthreat to maintaining this balance is the overcrowding of prisons. In 2011, the United States Supreme Court ruled that massive overcrowding of California prisons violates its prisonerââ¬â¢s eighth amendment right protecting them from cruel and unusual punishment (Boylan, 2015, p. 558). At the time Californiaââ¬â¢s correctional institutions were at double their capacity, housing over 155, 500 prisoners in only 33 institutions (Specter, 2010, p. 194). The overcrowding of correctional facilities is one of theRead MoreThe Death Penalty Should Be Abolished1645 Words à |à 7 PagesThere have been recent debates over the methods used for putting people to death and over the abolishment of the death penalty. Despite its controversial nature, the death penalty must be in effect to diminish the rate of crime, regulate the overcrowding in prisons and for the solemn purpose of incapacitation. The death penalty was not just put into effect in recent years, but has been around for a long time. The death penalty dates back to the colonial time period (Smith 3). According to the articleRead MoreJust Mercy By Bryan Stevenson Essay1730 Words à |à 7 Pagesmurdered his stepfather because he was abusive with his mom and left her unconscious on the floor. Charlie was sentenced to an adult prison because his stepfather was an ex-police officer. When Steven heard about Charlieââ¬â¢s case he ran to the prison to go see him and the first thing that Charlie tells Stevenson is how every night he would get sexually abused in prison by so many men ,and how they would do really awful things to him. ââ¬Å"Florida is one of a few states that allows the prosecutor to decideRead MoreCapital Punishment Research Study1288 Words à |à 6 Pagesfour each from California and Louisiana, three each from Nevada and Massachusetts, two each from Missouri, Florida, Tennessee, and Georgia, and one each from Oklahoma, New York, West Virginia, and Maryland. According to The Death Penalty Information center, Alabama, Nevada, Florida, California, Oklahoma, Missouri, Texas, Tennessee, South Carolina, Louisiana, and Georgia support the death penalty. Maryland, West Virginia, Massachusetts, and New York have abolished the death penalty (States With and WithoutRead More Benefits of the Death Penalty Essay1545 Words à |à 7 Pageskilled someone you know? He should receive the death penalty! Murderers and rapists should be punished for the crimes they have committed and should pay the price for their wrongdoing. Having the death penalty in our society is humane; it helps the overcrowding problem and gives relief to the families of the victims, who had to go through an event such as murder. Without the death penalty, criminals would be more inclined to commit additional violent crimes. Fear of death discourages people from committingRead MoreThe Death Of The Devon County Pauper Lun atic Asylum876 Words à |à 4 Pagesill with better living conditions, sunny rooms and the ability to roam around the grounds. Though some things have improved, mistreatment in other asylums persisted. In the 1840s U.S. reformer Dorothea Dix observed that mentally ill people in Massachusetts were still mistreated. ââ¬Å"Timeline: Treatments for Mental Illnessâ⬠continues, ââ¬Å"they were incarcerated with criminals and left unclothed and in darkness and without hear or bathrooms. Many are chained and beaten.â⬠Over the next 40 years Dix establishesRead MoreThe Crime Of The American Criminal Justice System1898 Words à |à 8 Pages Over the last few decades, the American criminal justice system has seen an increase in the amount of drug offenses being committed. While the number of drug offenses have increased, the amount of resources for addicts who are in prison have not. Although it has been made clear that drug abuse and crime are linked, the justice system has co ntinued to punish offenders, rather than allowing them treatment. The lack of resources provided to prisoners who have issues with addiction has contributedRead MoreSlavery In The River Of Dark Dreams By Walter Johnson1745 Words à |à 7 Pagesthe North dictated the price placed on slaves, and the cotton produced in the South was shipped North to create textiles in Northern factories (Baptist 198). This network of wealth traveled all around the nation, linking Mississippi planters to Massachusetts manufactures and uniting the entire countryââ¬â¢s dependence on and profit from slave labor (Johnson 11). While we can now see how slavery embodied and shaped modern American capitalism from analysis of Baptist and Johnsonââ¬â¢s texts, it is even moreRead MoreThe Prison Industrial Complex Within The U.s. Essay2151 Words à |à 9 Pagesof the Prison Industrial Complex within the U.S. Following the privatisation of the prison industry in the 1970ââ¬â¢s, the prison population of the U.S. has increased by an estimated 500%. Despite this, statistics suggests that overall reported crime rates have remained relatively stable. (Fortner, 2013). A question is raised then, as to why incarceration rates would be on the rise despite little change in crime. This essay will attempt to answer this question and to make sense of the Prison Industrial
Wednesday, May 6, 2020
etitioner Leegin Creative Leather Products Free Essays
Petitioner Leegin Creative Leather Products, a manufacturer of womenââ¬â¢s accessories under the brand name Brighton, entered into a vertical minimum price agreements with its retailer, which includes herein respondent, PSKS, Inc. Petitioner avers that such price agreements intend to encourage competition among retailers in the areas of customer service and product promotion. However, herein respondent discounted Leegin products below their prescribed minimum price. We will write a custom essay sample on etitioner Leegin Creative Leather Products or any similar topic only for you Order Now After being dropped by Leegin as one of its retailers, PSKS filed a lawsuit, arguing that Leegin violates Section 1 of the Sherman Act by engaging in anticompetitive price fixing. The District Court decided in favor of PSKS citing Dr. Miles Medical Co. v. John D. Park Sons Co. , which held that mandatory price agreements are per se illegal under the Sherman Act. Petitioner, in an appeal to the U. S. Court of Appeals for the Fifth Circuit, argued that this rule was based on outdated economics and contended that a the ââ¬Å"rule of reasonâ⬠is a better legal analysis. Petitioner further claimed that price minimums will only be held illegal when proven to be anticompetitive. The appellate court ruled in favor of the district court hence, this petition for certiorari. ISSUE: Is it per se illegal for a manufacturer to set mandatory minimum prices for its products? RULE: No, it is not illegal for a manufacturer to set mandatory minimum prices for its products. Section 1 of the Sherman Act prohibits ââ¬Å"[e]very contract, combination in the form of trust or otherwise, or conspiracy, in restraint of trade or commerce among the several States. â⬠This provision only prohibits unreasonable restraints in trade or commerce. REASONING: The Court reasoned that Section 1 of said Act outlaws only unreasonable restraints. It further ruled that the Dr. Miles case should be overruled and that vertical price restraints are to be judged by the rule of reason. The Court, through economic literature, averred that vertical minimum price agreements are rarely anticompetitive and can often function to increase inter-brand competition. The Court further argued that instances where the price agreements are abused for anticompetitive reasons can be judged on a case-to-case basis under the rule of reason. In overruling the Dr. Miles case, the Court held that the Sherman Act must be treated as a common law statute, which should be allowed to evolve in courts as economic circumstances change. DECISION: The Supreme Court ruled for Leegin Creative Leather Products, Inc. The Supreme Court overruled the decision in the Dr. Miles case. It further ruled that in cases where vertical price restraints are involved, the rule of reason should be applied. I agree with the decision of the Supreme Court favoring Leegin Creative Leather Products, Inc. The decision in Dr. Miles was based on reasoning and economic assumptions that predate and conflict with modern economic theory. It was never shown in court that setting retail price minimums is anticompetitive. Further, retail price minimums have no absolute economic effect. In order to assess the anticompetitive tendencies of price minimums, the rule of reason must be employed. The Supreme Court, in the case at bar, employed the rule of reason in order to determine whether the actions taken by Leegin Creative Leather Products, Inc would hurt the economy. Hence, vertical price restraints should be judged by the rule of reason. How to cite etitioner Leegin Creative Leather Products, Papers
Monday, May 4, 2020
What are the discoveries of Dr. Maria Montessori free essay sample
Dr. Maria Montessori, internationally renowned child educator, was originally a medical doctor who brought the scientific methods of observation, experimentation, and research to the study of children, their development and education. As a doctor, Montessori came to believe that many of the problems of the children she was working with were educational rather than medical. In examining education she felt that children were not achieving their potential because education was not based upon science. Her first step, then, was to attempt to abandon preconceived ideas about education and to begin to study children, their development and the process of learning through scientific methods of observation and experimentation. In doing so, she made what she considered to be a number of startling discoveries. Through her research, she discovered that children possessed different and high qualities than those we usually attribute to them. Among these qualities are: a) Amazing Mental Concentration: Previously it was believed that children had short attention spans. Dr. Montessori was amazed to observe the length of time that very young children would choose to attend to tasks which interested them. When spontaneous repetition of an activity is done with interest the natural result is concentration. But concentration is not the end product of education, itââ¬â¢s only the beginning. Any true learning happens only with concentration. The children reveal that they can work with concentration when they find the right conditions. b) Love of Repetition: On their own, children would choose to practice things they were trying to master over and over again. When something answers an inner need meets with the inner urge the spontaneous interest is kindled. When this interest finds suitable conditions to work spontaneous repetition is resulted. When this spontaneous repetition of an activity is done with interest the natural result is concentration. For example, once a child decides to learn how to tie shoes, the child may tie and untie shoes many times, continuing the repetition until the task is mastered. c) Love of order: Whereas we normally think of children as messy, Dr. Montessori found that children have a natural inclination for organization and orderliness. This natural inclination can be helped and developed if provision is made to foster it. This order need not be only with things in the environment but also with values, functions and other human activities. The child needs to experience human values like ââ¬Å"telling the truthâ⬠being practised. If not so, the child gets confused and this can create a warp in his development. A contrary instruction about behaviour muddles his decision. We need to remember that the young child is in process of building his personality which lasts his lifetime. He needs consistency in everything in his environment. It takes a while for him to understand that things also can be different. d) Freedom of choice: Children like to choose things they do. If materials are set out for children so that they have easy access to them, children will choose, take and replace them with without the need of assistance from an adult. Dr. Montessori found out that the child is capable of choosing the type of activity that satisfies his inner urge and offers challenge. When an environment provides many options in developmental activities, the children choose activities according to their capacities. This further helps them to enhance their abilities and developmental attributes. The adult needs to be the instigators but only have to provide the necessary conditions. Total development results only when the child can work in the various fields of human activity. e) Children Prefer Work to Play: One of the greatest surprises for Dr. Montessori was the discovery that children preferred work to play. Sometimes adults tend to think children only want to play and not to work. However, Dr. Montessori found that play was a substitute for what the children really wanted to do, but couldnââ¬â¢t. For example, children like to play ââ¬Å"houseâ⬠. They may pretend to cook, to bake pies, to clean house, etc. however, if given a choice, the children prefer to be in the real kitchen with their mother (or father) learning how to prepare ââ¬Å"realâ⬠food. The introduction of exercise of practical life as developmental activities was Dr. Montessoriââ¬â¢s contribution to education. She found out how the children needed to perform the activities in daily life because they brought the intelligence, will and voluntary movements together. This co-ordination brought about integration of the personality. f) No Need for Reward and Punishment: Montessori discovered that children are intrinsically motivated to work. No one wants to be problem. So, they do not need external rewards and punishments. What they do need is help. The adult can help the child by showing the child how to do what he or she is trying to accomplish. Accomplishment, competence, and being a contributing member of a society are rewarding in themselves, and it is reward enough. There are many instances in Dr. Montessoriââ¬â¢s work where she explains why she ââ¬Å"eventuallyâ⬠¦gave up either punishing or rewarding the childrenâ⬠. She explains that this method is ââ¬Å"always a form of repressionâ⬠, and is based upon our ââ¬â in her opinion tragically erroneous ââ¬â belief that children ââ¬Å"come into the world bad and full of naughtiness. â⬠She found, after careful observation, that both punishment and reward were equally ineffective tools for supporting the type of development that she felt was important (i. e. the normalization of the individual and the valorisation of mankind). In fact she observed that children were disinterested in both of these methods and often could not even tell the difference between them. g) The Children Refuse Sweets: Children often show an indifference to the allurements of sweets when placed in conflict with the interest of the mind. Children love to work purposefully. If it corresponds with the inner development need they work until they reach their goal, in this any external stimulant effects negligibly. The inner drive is sufficient to show them the right path. h) Lovers of Silence: Whereas it is easy to think of children as noisy, Montessori discovered that children enjoy finding out how quiet they can be. The children like to listen to silence and to soft sounds. It is like a game to see if they can move a chair without making a sound. i) Sense of Personal Dignity: Children have a deep sense of personal dignity just as adults do. They want to be capable and held in high regard. They want to be able to do things for themselves. They can get embarrassed and can feel ashamed. A child would rather tie his own shoes than have tied for him. j) Desire to Read and Write: In the beginning, Dr. Montessori didnââ¬â¢t believe that young children of four and five years of age should be involved in reading and writing. However, the children showed such interest that she provided some beginning materials. She was astonished by how the children seeped to ââ¬Å"burst spontaneouslyâ⬠into writing and then reading if provided with the right materials. Dr. Montessori discovered that the children are often seen to behave in a certain manner; destructive, disorderly, stubborn, disobedient etc. But in specially prepared environments and with specially trained adults they show orderly, responsible, loving behaviour, both are seemingly real. As a reason of contradiction, Dr. Montessori explains that the second instance is the real one and they very common behaviour is the result of the child not finding the right conditions for development. This discovery was possible because she could witness this grandeur of human normality. It is well known that human life is a series of steps in gaining independence and credit would go to Dr. Montessori who pointed that this is true in childââ¬â¢s life also. All the help we offer should lead the child to independence in his individual and social life. We might conclude by saying Dr. Montessori calls upon every adult human being to develop the humility to learn from the children in order to help the child create a healthy human being.
Monday, March 30, 2020
Capacity Management free essay sample
Customer Demands DEMAND MANAGEMENT Costs: â⬠¢ building plants â⬠¢ operating plants Tactics Technological Change: â⬠¢ rate (including breakthroughs) â⬠¢ direction Control 2 à © Wallace J. Hopp, Mark L. Spearman, 1996, 2000 5 http://factory -physics. com à © Wallace J. Hopp, Mark L. Spearman, 1996, 2000 http://factory -physics. com Capacity Management Issues Volume: â⬠¢ relative to demand â⬠¢ safety capacity Predictions and Assumptions (cont. ) Competition: â⬠¢ likely behavior â⬠¢ anticipated reactions Timing: â⬠¢ lead or follow demand â⬠¢ relative to process technology changes Suppliers: â⬠¢ costs â⬠¢ availability â⬠¢ partnering/contracts Configuration: â⬠¢ spatial distribution â⬠¢ vendoring â⬠¢ layout Flexibility: â⬠¢ volume (scalability) â⬠¢ mix (flexibility) à © Wallace J. Hopp, Mark L. Spearman, 1996, 2000 3 http://factory -physics. com à © Wallace J. Hopp, Mark L. Spearman, 1996, 2000 6 http://factory -physics. com 1 Strategic Capacity Planning Market Share: â⬠¢ how much of total market to aim for? â⬠¢ effect on competitors Market Share Calculation (cont. ) Example: Suppose capacity costs $1/yr for each unit of productive capacity and lost sales result in $3 per unit. Then Timing: â⬠¢ lead â⬠¢ match â⬠¢ follow cs ? c o 3 ? 1 = = 0. 67 cs 3 So we should choose capacity slightly above the mean forecast (which would correspond to the ratio 0. We will write a custom essay sample on Capacity Management or any similar topic specifically for you Do Not WasteYour Time HIRE WRITER Only 13.90 / page 5) Increments: â⬠¢ â⬠¢ â⬠¢ â⬠¢ process considerations economies of scale exposure to risk defensive value 7 à © Wallace J. Hopp, Mark L. Spearman, 1996, 2000 Note: This is very rough, since cs and co may change based on how much capacity is installed (e. g. , economies of scale) and may be influenced by the future (e. g. , failure to meet demand now may affect future sales). But it gives a rough idea of whether we should aim for a large or small capacity cushion. 10 à © Wallace J. Hopp, Mark L. Spearman, 1996, 2000 http://factory -physics. com http://factory -physics. com Strategic Capacity Planning (cont. ) Type: â⬠¢ matching technology to market â⬠¢ flexibility Market Share Example Situation: In 1966 Zenith faced â⬠¢ Industry sales for color TVââ¬â¢s had doubled each year for 3 years. â⬠¢ Total demand greater than 5 million annually by 1966. â⬠¢ â⬠¢ â⬠¢ â⬠¢ â⬠¢ Zenith had maintained a 20% market share. Capacity of 1 million/year (4,000/day) was stretched to limit. Industry demand expected to increase to 7 -10 million in next 2 years. Selling price of $370/unit. After tax profit rate of 7% of sales. Location: â⬠¢ make or buy? â⬠¢ expansion or new facility? â⬠¢ global strategy Proposal: expand 2 existing plants and add new plant to bring capacity to 7,300 per day. New plant would cost $6 million and would have capacity of 2,100 per day. 8 à © Wallace J. Hopp, Mark L. Spearman, 1996, 2000 11 à © Wallace J. Hopp, Mark L. Spearman, 1996, 2000 http://factory -physics. com http://factory -physics. com Market Share Calculation Notation: â⬠¢ cs = cost per unit short (e. g. , lost sales) â⬠¢ co = cost per unit over (e. g. , wasted capacity) Market Share Example (cont. ) Analysis: cs = 2,100 ? $370 ? 250 ? 0. 07 = $13,597,500 per year annual profit from new plant annual cost of new plant co = $6,000,000 ? Capacity should be added to have roughly 90% probability of being able to meet 1968 demand. This means capacity of something over 9,000 sets per day. So, proposed increase and then some would ap pear to make sense. Problem: implicitly assumes uniform distribution of demand. Fails to consider competition. 9 à © Wallace J. Hopp, Mark L. Spearman, 1996, 2000 12 à © Wallace J. Hopp, Mark L. Spearman, 1996, 2000 http://factory -physics. Capacity Timing Lead Demand: â⬠¢ create ââ¬Å"capacity cushionâ⬠planned underutilization â⬠¢ accommodate surges in demand â⬠¢ attract new business take market share from competitors â⬠¢ likelihood of falling short roughly equal to likelihood of having too much capacity â⬠¢ could require OT, extra shifts, scrambling, etc. to make up difference â⬠¢ â⬠¢ â⬠¢ â⬠¢ negative capacity cushion conservative with regard to forecast assures high utilization, higher return on investment But, can lead to erosion of market share http://factory -physics. com capacity capacity capacity Developing a Capacity Strategy Caveat: modeling/analysis can help, but can only be part of the picture, since we cannot forecast the future. time Basic Strategies: 1. Peak: donââ¬â¢t build until need develops. â⬠¢ ââ¬Å"safeâ⬠strategy â⬠¢ but can cause synchronization with competition and high costs/risks 2. Countercyclical: add at lower point in business cycle when firm and competitors have excess capacity. â⬠¢ riskier? â⬠¢ reduced costs but can backfire Meet Demand: time Lag Demand: time 13 à © Wallace J. Hopp, Mark L. Spearman, 1996, 2000 16 http://factory -physics. com à © Wallace J. Hopp, Mark L. Spearman, 1996, 2000 Economies of Scale Short-Term: In short-term, almost everything (labor, equipment, insurance, etc. ) is fixed: Developing a Capacity Strategy (cont. ) 3. Long Haul: match or lag demand, but on average not for short-term. â⬠¢ easier to be right over long haul than in near term â⬠¢ better planning 4. Follow the Leader:build when they build. â⬠¢ prevents competition from gaining an advantage â⬠¢ can backfire (e. g. , oil tanker purchases in 1970ââ¬â¢s, 1973 war ? price increases ? conservation, falling demand). fixed cost + variable cost Unit cost = throughput fixed cost = + variable unit cost throughput so, short-term unit costs decrease with throughput. Intermediate-Term: In the intermediate-term, utilization of a resource depends on run lengths, so given changeover cost and run length of a particular product, unit cost can be expressed as: Unit cost = changeovercost + runningcost per unit units per run which is increasing in setup cost and decreasing in run length. 14 à © Wallace J. Hopp, Mark L. Spearman, 1996, 2000 17 à © Wallace J. Hopp, Mark L. Spearman, 1996, 2000 http://factory -physics. com http://factory -physics. com Economies of Scale (cont. ) Long -Term: are functions of plant equipment. Equipment cost as a function o f the capacity can be approximated by Causes of Overbuilding Manufacturing Capacity Technological Factors: â⬠¢ â⬠¢ â⬠¢ â⬠¢ â⬠¢ adding capacity in large increments economies of scale long lead times in adding capacity min efficient scale increasing over time changes in production technology Competitive Factors: â⬠¢ â⬠¢ â⬠¢ â⬠¢ large number of firms lack of credible market leaders entry of new competitors advantages of being an early mover K (C) = aC b where b is typically between 0. 6 and 1. Thus, cost per unit is: K( C) = aC b? 1 C Since b is usually less than one, this implies that unit cost tends to decrease with capacity. That is, larger plants are more efficien t than small ones. However, there are diseconomies of scale, such as material handling, communication, risk. Unit cost = Information Flow Factors: â⬠¢ â⬠¢ â⬠¢ â⬠¢ â⬠¢ inflation of future expectations divergent assumptions or perceptions breakdown of market signaling structural change financial community pressures Structural Factors: â⬠¢ â⬠¢ â⬠¢ â⬠¢ â⬠¢ â⬠¢ significant exit barriers motivation from suppliers building credibility with customers integrated competitors effect of capacity share on market share effect of age/type of capacity on demand Governmental Factors: â⬠¢ perverse tax incentives â⬠¢ desire for indigenous industry â⬠¢ pressures to increase/maintain employment Managerial Factors: 15 à © Wallace J. Hopp, Mark L. Spearman, 1996, 2000 â⬠¢ mgmt background and industry exp â⬠¢ attitude toward different types of risk à © Wallace J. Hopp, Mark L. Spearman, 1996, 2000 18 http://factory -physics. com http://factory -physics. com 3 Integrating with Business Strategy Capacity as Strategic Weapon: â⬠¢ supply can create demand (ââ¬Å"invest and growâ⬠) â⬠¢ preemptive weapon (prevent smaller competitors from adding capacity) Traditional Approach Formulation: min cost capacity feasible solution min Total Equipment Cost subject to: r e(i) ? TH, for all stations i Location Decisions: â⬠¢ move into geographic market â⬠¢ transportation costs â⬠¢ attractive locales to recruit talent Details: re (i) = m(i) ? TH te (i) m( i) ? TH ? t e( i) Leadtime Dimension: â⬠¢ competing on quality/responsiveness requires capacity cushion 19 à © Wallace J. Hopp, Mark L. Spearman, 1996, 2000 22 à © Wallace J. Hopp, Mark L. Spearman, 1996, 2000 http://factory -physics. com http://factory -physics. com Traditional vs. Modern View of Capacity 100 % Traditional Approach (cont. Provide basis for better optimization approach. Add machine at i* . 3. If CT feasible, stop. Else go to (2). 25 à © Wallace J. Hopp, Mark L. Spearman, 1996, 2000 28 à © Wallace J. Hopp, Mark L. Spearman, 1996, 2000 http://factory -physics. com http://factory -physics. com Other Capacity Dimensions Law (Buffering): Any manufacturing system with variability will have buffers in some combination of the following forms: 1. Inventory (and CT) 2. Capacity (low utilization, lost sales) 3. Time (long lead times) Implications: There are other ways to improve CT performance of a system.
Saturday, March 7, 2020
Product Dumping and Its Effect on Foreign Markets
Product Dumping and Its Effect on Foreign Markets Dumping is an informal name for the practice of selling a product in a foreign country for less than either the price in the domestic country or the cost of making the product. It is illegal in some countries to dump certain products into them because they want to protect their own industries from such competition, especially because dumping can result in a disparity in the domestic gross domestic products of impacted countries, such was the case with Australia until they passed a ââ¬â¹tariffà on certain goods entering the country. Bureaucracy and International Dumping Under the World Trade Organization (WTO) dumping is a frowned upon international business practices, especially in the case of causing material loss to an industry in the importing country of the goods being dumped. Although not expressly prohibited, the practice is considered bad business and often seen as a method to drive out the competition for goods produced in a particular market. The General Agreement on Tariffs and Trade and the Anti-Dumping Agreement (both WTO documents) allow for countries to protect themselves against dumping by allowing tariffs in cases where that tariff would normalize the price of the good once its sold domestically.à One such example of a dispute over international dumping comes between neighboring nations the United States and Canada in a conflict that came to be known as the ââ¬â¹Ã¢â¬â¹Softwood Lumber Dispute. The dispute began in the 1980s with a question of Canadian exports of lumber to the United States. Since Canadian softwood lumber was not regulated on private land as much of the United States lumber was, the prices were exponentially lower to produce. Because of this, the U.S. government claimed the lower prices constituted as a Canadian subsidy, which would make that lumber subject to trade remedy laws that fought such subsidies. Canada protested, and the fight continues to this day.à ââ¬â¹Ã¢â¬â¹ Effects on Labor Workers advocates argue that product dumping hurts the local economy for workers, especially as it applies to competition. They hold that safeguarding against these targeted cost practices will help detract the consequences of such practices between varied stages of local economies. Oftentimes such dumping practices result in increased favoritism of competition between workers, a sort of social dumping that results from making a monopoly of a certain product. One such example of this on a local level was when an oil company in Cincinnati attempted to sell below-cost oil to diminish profits of competitors, thereby forcing them out of the market. The plan worked, resulting in a local monopoly of oil as the other distributor was forced to sell to a different market. Because of this, oil workers from the company who outsold the other were given preference in hiring in the area.
Thursday, February 20, 2020
Why Is It Difficult to Create a Psychological Portrait of a Typical Te Coursework
Why Is It Difficult to Create a Psychological Portrait of a Typical Terrorist - Coursework Example In history, terrorism has always been an effective tactic of the weaker side in a conflict. It is especially true when the conflict is asymmetrical in term of the balance of power. Probably this characteristic of terrorism explains the recent resurgence of terrorism. It is argued that terrorism is one of the results of globalization, as it escalates ethnic conflicts in an attempt to secure oneââ¬â¢s identity.à Hence it will be present in some form or other in our lifetime and in the lives of our children. This paper aims at studying the nature, characteristics, and causes of terrorism. What makes a person become a terrorist? Does psychopathology provide any help in understanding and preventing terrorism? It will also identify the vulnerabilities of the terrorist groups. The nature and causes of terrorism are varied and diversified. People become terrorists in different ways in different roles and for different reasons. Although it can be helpful to identify the reason for joining, staying with a terrorist organization and leaving it no generic formula can be developed. The most common causes of terrorism are perceived injustices and the need for identity and belonging. Nature of terrorism has changed over the years. If we compare the terrorist groups and terrorists of the 1970s with the terrorists of the early 1990s an emerging new trend can be observed. Religious fundamentalism is growing and these new religious groups use weapons of mass destruction. Earlier it was presumed that terrorists do not use weapons of mass destruction because it will alienate them from the public and they will have to face harsh retaliation. The key extremist religious groups are Hizballah, Al ââ¬âQaida and Aum Shinrikyo. According to Post, the most dangerous terrori sts are religious terrorists. Political and social terrorist have a defined mission that can be measured in terms of their objective and government reaction, media reaction etc. whereas the religious terrorist can justify the most heinous crime.
Tuesday, February 4, 2020
4.How convincing is Porters model of national competitive advantage in Essay
4.How convincing is Porters model of national competitive advantage in explaining the characteristics and performance of the business systems of major economies - Essay Example However, irrespective of the individual firms, some countries as a whole have achieved a higher competitive position than the others (Baker, 2007). This paper will shed some light on how the nations achieve competitive advantage by using Porterââ¬â¢s Diamond model. This model focuses on the determining factors of national competitive advantage. The paper will discuss about the issues and loop holes of the Porterââ¬â¢s diamond Model and how they fail to answer certain circumstantial problems. Porter (1990) explained the competitiveness of a nation based on the four different parameters, which are factor conditions, demand conditions, supporting or related industries and firmsââ¬â¢ strategy, structure and rivalry. Factor Conditions: The factor conditions include the production factors of a nation, like human resources and human capital, physical resources, knowledge base, financial strength. The quantity and quality of the available human resources determine the national production capabilities. Demand Conditions: The demand conditions explain the level of demands of products in the home country. The higher level of demand influences the pace of product innovation and improves service quality. Firmsââ¬â¢ Strategy structure Rivalry: This parameter suggests how the firms in a country are organized and how they determine the domestic competitiveness. This mostly reflects the organizational cultural trends of the nation. Certain organizational behaviour and pattern of activities provide added advantage to them in terms of other foreign companies. Relating and supporting industries: The presence of other industries influences the competitive position of an organization. The presence of other industries can be leveraged by the domestic firms in order to create competitive advantage. The four parameters of the Diamond model although acts as a determinant of national competitive advantage, are mostly industry oriented. The diamond model
Monday, January 27, 2020
High Performance Liquid Chromatography (HPLC) 214
High Performance Liquid Chromatography (HPLC) 214 Introduction High performance liquid chromatography 214 is the most widely used of all of the analytical separation techniques. The reasons for the popularity of the method is its sensitivity, ready adaptability to accurate quantitative determinations, suitability for separating non-volatile species or thermally fragile ones, wide spread applicability to substance that are of prime interest to industry, many fields of science and the public. The applications of chromatography have grown explosively in the last fifty years owing not only to the development of several new types of chromatographic techniques but also to the growing need by scientist for better methods for characterizing complex mixtures. General methodology for the development of new HPLC methods 215-228 HPLC method development follows the series of steps summarized below. Information on sample, objective of separation. Need for special HPLC procedure, sample pretreatment etc. Choice of detector and detector settings. Choosing LC method, preliminary run, estimation of best separation conditions. Optimization of separation conditions. Check for problems or requirement for special procedure. a) Recovery of purified material à à à à à à à b) Quantitative calibrationà à à à à c) Qualitative method Validate method for routine laboratory use. A good method development strategy should require only as many experimental runs as are necessary to achieve the desired final result. Finally, method development should be simple as possible, yet it should allow the use of sophisticated tools such as computer modeling if these are available. Before the beginning of method development, it is necessary to review what is known about the sample in order to define the goals of separation. The kinds of sample related information that can be important are summarized in Table-7.1. Table-8.1 Important information concerning sample composition and properties Numberà of compounds present in the sample Chemical structures of components Molecular weights of compounds PKa values of compounds UV spectra of compounds Concentration range of various compounds in samples of interest Sample solubility à à The chemical composition of the sample can provide valuable clues for the best choice of initial conditions for an HPLC separation. Objectives of separation The objectives of HPLC separation need to be specified clearly include. The use of HPLC to isolate purified sample components for spectral identification or quantitative analysis. It may be necessary to separate all degradants or impurities from a product for reliable content assay. In quantitative analysis, the required levels of accuracy and precision should be known (a precision of à ± 1 to 2% is usually achievable). Whether a single HPLC procedure is sufficient for raw material or one or more formulations and / or different procedures are desired for the analysis of formulations? When the number of samples for analysis at one time is greater than 10, a run time of less than 20 min. will be oftenly important. Knowledge on the desired HPLC equipment, experience and academic training the operators have. Sample pretreatment and detection Samples for analysis come in various forms such as: Solutions ready for injections. Solutions that require dilution, buffering, addition of an internal standard or other volumetric manipulation. Solids that must first be dissolved or extracted. Samples that require pretreatment to remove interference and/or protect the column or equipment from damage. Most samples for HPLC analysis require weighing and / or volumetric dilution before injection. Best results are often obtained when the composition of the sample solvent is close to that of the mobile phase since this minimizes baseline upset and other problems. Some samples require a partial separation ( pretreatment) prior to HPLC, because of need to remove interference, concentrate sample analytes or eliminate ââ¬Å"column killerâ⬠. In many cases the development of an adequate sample pretreatment can be challenging than achieving a good HPLC separation. The detector selected should sense all sample components of interest. Variable-wavelength ultraviolet (UV) detectors normally are the first choice, because of their convenience and applicability for most samples. For this reason information on the UV spectra can be an important aid for method development. When the UV response of the sample is inadequate, other detectors are available (flourescence, electrochemical, PDA etc.) or the sample can be derivatized for enhanced detection. Developing the method for the separation Selecting an HPLC method and initial conditions If HPLC is chosen for the separation, the next step is to classify the sample as regular or special. Regular samples means typical mixtures of small molecules ( à Table-8.2 Handling of special sample Sample Requirements Inorganic ions Detection is primary problems; use ion chromatography Isomers Some isomers can be separated by reversed-phase HPLC and are then classified as regular samples; better separations of isomers are obtainable using either (1) normal-phase HPLC or (2) reversed-phase separations with cyclodextrin-silica columns. Enantiomers These compounds require ââ¬Å"chiralâ⬠conditions for their separations. Biological Several factors make samples or this kind ââ¬Å"specialâ⬠; molecular conformation, polar functionality and a wide range of hydrophobicity. Macromolecules ââ¬Å"Bigâ⬠molecules require column packing with large poresà à (>> 10-nm diameters); in addition, biological molecules require special conditions as noted above. Table-8.3 Preferred experimental conditions for the initial HPLC separation Separation variable Preferred initial choice Column Dimensions (length, ID) 15 x 0.46 cm Particle size 5 mma Stationary phase C8 or C18 Mobile phase Solvent A and B Buffer-acetonitrile % B 80-100%b Buffer (compound, pH, concentration) 25mM potassium phosphate 2.0 Additives (e.g., amine modifiers, ion pair reagents) Do not use initially Flow rate 1.5ââ¬â2.0 ml/min Temperature 35-45à ºC Sample Size Volumed >25 mL Weightd B : Polar solventà à à à à à à à à a 3.5 mm particles are an alternative using a 7.5 cm column b For an initial isocratic run; an initial gradient run is preferred. c No buffer required for neutral samples; for pH d Smaller values required for smaller-volume columns (e.g., 7.50.46-cm, 3.5-mm column). Table-8.4 Physical properties of silica supports for some C 18 columns Column (mL/mL) Pore diameter (nm) Surface area (m2/g) Percent Porosity Hypersil ODS 12 170 57 LiChrosorb C18 10 355 71 Novapak C18 6 N/Aa N/Aa Nucleosil C18 10 350 69` Symmetry C18 10 335 66 Zorbax ODS 6 300 55 Zorbax Rx, SB, XDB 8 180 50 a N/A : Not available On the basis of the initial exploratory run isocratic or gradient elution can be selected as most suitable. If typical reversed-phase conditions provide insufficient sample retention, suggesting the use of either ion pair on normal phase HPLC. Alternatively, the sample may be strongly retained with 100% acetonitrile as mobile phase, suggesting the use of non-aqueous reversed-phase (NARP) chromatography or normal phase HPLC. Some characteristics of reversed-phase and other HPLC methods are summarized below. Table-8.5 Characteristics of primary HPLC methods Method / description/ columns Preferred method Reversed-phase HPLC Uses water ââ¬â organic mobile phase Columns: C18 (ODS), C8, phenyl, trimethylsilyl (TMS), Cyano First choice for most samples, especially neutral or non-ionisable compounds that dissolve in water-organic mixtures Ion-pair HPLC Uses water-organic mobile phase a buffer to control pH and an ion pair reagent. Column : C18, C8, cyano. Acceptable choice for ionic or ionizable compounds, especially bases or cations. Normal phase HPLC Uses mixtures of organic solvents as mobile phase Columns: Cyano, diol, amino and silica. Good second choice when reversed-phase or ion-pair HPLC is ineffective, first choice for lipophilic samples that do not dissolve well in water-organic mixtures, first choice for mixtures of isomers and for preparative-scale HPLC (silica best) Getting started on method development One approach is to use an isocratic mobile phase of some average solvent strength (e.g., 50%) organic solvent. A better alternative is to use a very strong mobile phase with (80-100% B), then reduce %B as necessary. The initial separation with 100%B results in rapid elution of the entire sample, but few groups will separate. Decreasing solvent strength shows the rapid separation of all components with a much longer run time, with a broadening of later bands and reduced detection sensitivity. Improving the separation and repeatable separation Generally the chromatographers will consider several aspects of the separation, as summarized in Table-8.6. Table-8.6 Objectives of separation in HPLC method development Objectivesa Comment Resolution Precise and rugged quantitative analysis requires that Rs be greater than 1.5. Separation time Quantitation à à £ 2% (1 SD) for assays; à £ 5% for less-demanding analysis; à £15% for trace analysis. Pressure Peak height Narrow peaks are desirable for large signal / noise ratios Solvent consumption à Minimum mobile-phase use per run is desirable. a Roughly in order of decreasing importance but may vary with analysis requirements. Separation or resolution is a primary requirement in quantitative HPLC. The resolution (Rs) value should be maximum (Rs>1.5) favours maximum precision. Resolution usually degrades during the life of the column and can vary from day to day with minor fluctuations in separation conditions. Therefore, values of Rs = 2 or greater should be the goal during method development for simple mixtures. Such resolution will favour both improved assay precision and greater method ruggedness. Some HPLC assays do not require base line separation of the compounds of interest (qualitative analysis). In such cases only enough separation of individual components is required to provide characteristic retention times for peak identification. The time required for a separation (run time = retention time for base band) should be as short as possible and the total time spent on method development is reasonable (runtimes 5 to 10 minutes are desirable). Conditions for the final HPLC method should be selected so that the operating pressure with a new column does not exceed 170 bar (2500 psi) and upper pressure limit below 2000 psi is desirable. There are two reasons for that pressure limit, despite the fact that most HPLC equipment can be operated at much higher pressures. First, during the life of a column, the back pressure may rise by a factor of as much as 2 due to the gradual plugging of the column by particular matter. Second, at lower pressures When dealing with more challenging samples or if the goals of separation are particularly stringent, a large number of method development runs may be required to achieve acceptable separation. Repeatable separation As the experimental runs described above are being carried out, it is important to confirm that each chromatogram can be repeated. When changing conditions (mobile phase, column, and temperature) between method development experiments, enough time must elapse for the column to come into equilibrium with a new mobile phase and temperature. Usually column equilibration is achieved after passage of 10 to 20 column volumes of the new mobile phase through the column. However, this should be confirmed by carrying out a repeat experiment under the same conditions. When constant retention times are observed in two such back-to-back repeat experiments (à ± 0.5% or better), it can be assumed that the column is equilibrated and the experiments are repeatable. Completing the HPLC method development The final procedure should meet all the objectives that were defined at the beginning of method development. The method should also be robust in routine operation and usable by all laboratories and personnel for which it is intended. Quantitation and method validation One of the strengths of HPLC is that is an excellent quantitative analytical technique. HPLC can be used for the quantitation of the primary or major component of a sample (including pure samples) for mixture of many compounds at intermediate concentrations and for the assessment of trace impurity concentrations in matrix. Method validation, according to the United States Pharmacopoeia (USP), is performed to ensure that an analytical methodology is accurate, specific, reproducible and rugged over the specified range that an analyte will be analysed. Method validation provides an assurance of reliability during normal use and is sometimes described as the process of providing documented evidence that the method does what it is intended to do. According to USP, the method validation involves eight steps as given below. Precision Accuracy Limit of detection Limit of quantitation Specificity Linearity and range Ruggedness Robustness Precision and accuracy: Already discussed in chapter-1. Linearity The linearity of the method is a measure of how well a calibration plot of response v/s concentration approximates a straight line, or how well the data fit to the linear equation. Y = aX + b Where ââ¬ËYââ¬â¢ is the response, ââ¬ËXââ¬â¢ is the concentration, ââ¬Ëaââ¬â¢ is the slope and ââ¬Ëbââ¬â¢ is the intercept of a line fit to the data. Ideally, a linear relationship is preferred (b = 0) because it is more precise, easier for calculations and can be defined with fewer standards. Also, UV detector response for a dilute sample is expected to follow Beerââ¬â¢s law and be linear. Therefore, a linear calibration gives evidence that the system is performing properly throughout the concentration range of interest. Generally in HPLC, if we are using internal standard, then the linearity plot is to be drawn by taking concentration of the analyte on x-axis and the ratio of area under the curve (AUC) of analyte to AUC of internal standard (IS) on y-axis. The resulting plot slope, intercept and correlation coefficient provide the desired information on linearity. A linearity correlation coefficient above 0.999 is acceptable for most methods. Limit of detection (LOD) The limit of detection (LOD) is the smallest concentration that can be detected reliably. The LOD represents the concentration of analyte that would yield a signal-to-noise (S/N) ratio of 3. Limit of quantitation (LOQ) The LOQ is the concentration that can be quantitated reliably with a specified level of accuracy and precision. The LOQ represents the concentration of analyte that would yield a signal-to-noise ratio of 10. LOD and LOQ can be determined by using the following expressions. LODà à à =à à à à à à à à à 3 X N / B LOQà à à =à à à à à à à à à 10 X N / B Where N is the noise estimate, is the standard deviation of the peak area ratio of analyte to IS (5 injections) of the drugs. B is the slope of the corresponding calibration curve. The LOD and LOQ values determined during method validation are affected by the separation conditions, columns, reagents and especially instrumentation and data systems. Ruggedness Method ruggedness is defined as the reproducibility of results when the method is performed under actual use conditions. This includes different analysts, laboratories, columns, instruments, sources, chemicals, solvents etc. method ruggedness may not be known when a method is first developed, but insight is obtained during subsequent use of that method. Robustness The concept of robustness of an analytical procedure has been defined by the ICH as ââ¬Å" a measure of its capacity to remain unaffected by small, but deliberate variations in method parametersâ⬠. The robustness of a method is the ability to remain unaffected by small changes in parameters such as pH of the mobile phase, temperature, percentage of organic solvent and buffer concentration etc. to determine robustness of the method experimental conditions were purposely altered and chromatographic characteristics were evaluated. To study the pH effect on the retention (K1) of the drug, buffer pH is to be changed by 0.2 units. At certain point, retention will increase at any pH above and below of the pH unit. The effect of temperature on the retention characteristics (K1) of the drug is to be studied by changing the temperature in steps 2à ºC from room temperature to 80à ºC and see the effect of temperature on the resolution and peak shape. Effect of percentage organic strength on retention is to be studied by varying the percentage of organic solvents like acetonitrile, methanol etc. from 0 to 2% while the other mobile phase contents are held constant and observe the K1. At certain point decreases in K1 observed with increase in the level of organic solvent. Effect of buffer concentration should be checked at three concentration levels i.e. 0.025 M, 0.05 M and 0.1 M and observe retention time and resolution. Stability To generate reproducible and reliable results, the samples, standards and reagents used for the HPLC method must be stable for a reasonable time (e.g., One day, one week, one month, depending on the need). For example, the analysis of even a single sample may require 10 or more chromatographic runs to determine system suitability, including standard concentrations to create a working analytical curve and duplicate or triplicate injections of the sample to be assayed. Therefore, a few hours of standard and sample solution stability can be required even for a short (10 min.) separation. When more than one sample is analyzed, automated, over night runs often are performed for better laboratory efficiency. Typically, 24 hours stability is desired for all solutions and reagents that need to be prepared for each analysis. Mobile phases should be chosen to avoid stability problems, especially the use of amine additives or specific solvents. For example, mobile phase containing THF (tetra hydrofuran) are known to be susceptible to oxidation, therefore, the mobile phase should be prepared daily with fresh THF. Some buffered mobile phases cause problems for example, phosphate and acetate provide good media for microbial growth. Sodium oxide (0.1%) is often added to the mobile phase buffer to inhibit such growth, adding more than 5% of organic solvent is also effective. Long term column stability is critical for method ruggedness. Even the best HPLC column will eventually degrade and lose its initial performance, often as a function of the number of samples injected. System suitability System suitability experiments can be defined as tests to ensure that the method can generate results of acceptable accuracy and precision. The requirements for system suitability are usually developed after method development and validation have been completed. The criteria selected will be based on the actual performance of the method as determined during its validation. For example, if sample retention times forms part of the system suitability criteria, their variation (SD) during validation can be determined, system suitability might then require that retention times fall within a à ±3 SD range during routine performance of the method. The USP (2000) defines parameters that can be used to determine system suitability prior to analysis. These parameters include plate number (N), tailing factor, k and / or a, resolution (Rs) and relative standard deviation (RSD) of peak height or peak area for respective injections. The RSD of peak height or area of five injections of standard solution is normally accepted as one of the standard criteria. For an assay method of a major component, the RSD should typically be less than 1% for these five respective injections. The plate number and / or tailing factor are used if the run contains only one peak. For chromatographic separations with more than one peak, such as an internal standard assay or an impurity method, expected to contain many peaks, some measure of separations such as Rs is recommended. Reproducibility of tR or k value for a specific compound also defines system performance. The column performance can be defined in terms of column plate number ââ¬ËNââ¬â¢ is defined by N = 5.54 (tR / Wà ½)2 Where ââ¬ËtRââ¬â¢ is the retention time of the peak and ââ¬ËWà ½Ã¢â¬â¢ is the width of the peak at half peak height. The resolution of two adjacent peaks can be calculated by using the formula Rs = 1.18 (t2-t1) / W0.5.1 +W0.5.2 Where ââ¬Ët1ââ¬â¢ and ââ¬Ët2ââ¬â¢ are retention times of the adjacent peaks and W0.5.1 and W0.5.2 are the width of the peaks at half height. Rs = 2.0 or greater is a desirable target for method development. The retention factor k is given by the equation. k = (tR ââ¬â t0) / t0 where ââ¬ËtRââ¬â¢ is the band retention time and t0 is the column dead time. The peak symmetry can be represented in terms of peak asymmetry factor and peak tailing factor, which can be calculated by using the following formula. Peak asymmetry factor = B /A Where ââ¬ËBââ¬â¢ is the distance at 50% peak height between leading edge to the perpendicular drawn from the peak maxima and ââ¬ËAââ¬â¢ is the width of the peak at half height. According to USP (2000) peak tailing factor can be calculated by using the formula T = W0.05 / 2f Where ââ¬Å"W0.05â⬠is the width of the peak at 5% height and ââ¬Å"fâ⬠is the distance from the peak maximum to the leading edge of the peak, the distance being measured at a point 50% of the peak height from the base line. High Performance Liquid Chromatography (HPLC) 214 High Performance Liquid Chromatography (HPLC) 214 Introduction High performance liquid chromatography 214 is the most widely used of all of the analytical separation techniques. The reasons for the popularity of the method is its sensitivity, ready adaptability to accurate quantitative determinations, suitability for separating non-volatile species or thermally fragile ones, wide spread applicability to substance that are of prime interest to industry, many fields of science and the public. The applications of chromatography have grown explosively in the last fifty years owing not only to the development of several new types of chromatographic techniques but also to the growing need by scientist for better methods for characterizing complex mixtures. General methodology for the development of new HPLC methods 215-228 HPLC method development follows the series of steps summarized below. Information on sample, objective of separation. Need for special HPLC procedure, sample pretreatment etc. Choice of detector and detector settings. Choosing LC method, preliminary run, estimation of best separation conditions. Optimization of separation conditions. Check for problems or requirement for special procedure. a) Recovery of purified material à à à à à à à b) Quantitative calibrationà à à à à c) Qualitative method Validate method for routine laboratory use. A good method development strategy should require only as many experimental runs as are necessary to achieve the desired final result. Finally, method development should be simple as possible, yet it should allow the use of sophisticated tools such as computer modeling if these are available. Before the beginning of method development, it is necessary to review what is known about the sample in order to define the goals of separation. The kinds of sample related information that can be important are summarized in Table-7.1. Table-8.1 Important information concerning sample composition and properties Numberà of compounds present in the sample Chemical structures of components Molecular weights of compounds PKa values of compounds UV spectra of compounds Concentration range of various compounds in samples of interest Sample solubility à à The chemical composition of the sample can provide valuable clues for the best choice of initial conditions for an HPLC separation. Objectives of separation The objectives of HPLC separation need to be specified clearly include. The use of HPLC to isolate purified sample components for spectral identification or quantitative analysis. It may be necessary to separate all degradants or impurities from a product for reliable content assay. In quantitative analysis, the required levels of accuracy and precision should be known (a precision of à ± 1 to 2% is usually achievable). Whether a single HPLC procedure is sufficient for raw material or one or more formulations and / or different procedures are desired for the analysis of formulations? When the number of samples for analysis at one time is greater than 10, a run time of less than 20 min. will be oftenly important. Knowledge on the desired HPLC equipment, experience and academic training the operators have. Sample pretreatment and detection Samples for analysis come in various forms such as: Solutions ready for injections. Solutions that require dilution, buffering, addition of an internal standard or other volumetric manipulation. Solids that must first be dissolved or extracted. Samples that require pretreatment to remove interference and/or protect the column or equipment from damage. Most samples for HPLC analysis require weighing and / or volumetric dilution before injection. Best results are often obtained when the composition of the sample solvent is close to that of the mobile phase since this minimizes baseline upset and other problems. Some samples require a partial separation ( pretreatment) prior to HPLC, because of need to remove interference, concentrate sample analytes or eliminate ââ¬Å"column killerâ⬠. In many cases the development of an adequate sample pretreatment can be challenging than achieving a good HPLC separation. The detector selected should sense all sample components of interest. Variable-wavelength ultraviolet (UV) detectors normally are the first choice, because of their convenience and applicability for most samples. For this reason information on the UV spectra can be an important aid for method development. When the UV response of the sample is inadequate, other detectors are available (flourescence, electrochemical, PDA etc.) or the sample can be derivatized for enhanced detection. Developing the method for the separation Selecting an HPLC method and initial conditions If HPLC is chosen for the separation, the next step is to classify the sample as regular or special. Regular samples means typical mixtures of small molecules ( à Table-8.2 Handling of special sample Sample Requirements Inorganic ions Detection is primary problems; use ion chromatography Isomers Some isomers can be separated by reversed-phase HPLC and are then classified as regular samples; better separations of isomers are obtainable using either (1) normal-phase HPLC or (2) reversed-phase separations with cyclodextrin-silica columns. Enantiomers These compounds require ââ¬Å"chiralâ⬠conditions for their separations. Biological Several factors make samples or this kind ââ¬Å"specialâ⬠; molecular conformation, polar functionality and a wide range of hydrophobicity. Macromolecules ââ¬Å"Bigâ⬠molecules require column packing with large poresà à (>> 10-nm diameters); in addition, biological molecules require special conditions as noted above. Table-8.3 Preferred experimental conditions for the initial HPLC separation Separation variable Preferred initial choice Column Dimensions (length, ID) 15 x 0.46 cm Particle size 5 mma Stationary phase C8 or C18 Mobile phase Solvent A and B Buffer-acetonitrile % B 80-100%b Buffer (compound, pH, concentration) 25mM potassium phosphate 2.0 Additives (e.g., amine modifiers, ion pair reagents) Do not use initially Flow rate 1.5ââ¬â2.0 ml/min Temperature 35-45à ºC Sample Size Volumed >25 mL Weightd B : Polar solventà à à à à à à à à a 3.5 mm particles are an alternative using a 7.5 cm column b For an initial isocratic run; an initial gradient run is preferred. c No buffer required for neutral samples; for pH d Smaller values required for smaller-volume columns (e.g., 7.50.46-cm, 3.5-mm column). Table-8.4 Physical properties of silica supports for some C 18 columns Column (mL/mL) Pore diameter (nm) Surface area (m2/g) Percent Porosity Hypersil ODS 12 170 57 LiChrosorb C18 10 355 71 Novapak C18 6 N/Aa N/Aa Nucleosil C18 10 350 69` Symmetry C18 10 335 66 Zorbax ODS 6 300 55 Zorbax Rx, SB, XDB 8 180 50 a N/A : Not available On the basis of the initial exploratory run isocratic or gradient elution can be selected as most suitable. If typical reversed-phase conditions provide insufficient sample retention, suggesting the use of either ion pair on normal phase HPLC. Alternatively, the sample may be strongly retained with 100% acetonitrile as mobile phase, suggesting the use of non-aqueous reversed-phase (NARP) chromatography or normal phase HPLC. Some characteristics of reversed-phase and other HPLC methods are summarized below. Table-8.5 Characteristics of primary HPLC methods Method / description/ columns Preferred method Reversed-phase HPLC Uses water ââ¬â organic mobile phase Columns: C18 (ODS), C8, phenyl, trimethylsilyl (TMS), Cyano First choice for most samples, especially neutral or non-ionisable compounds that dissolve in water-organic mixtures Ion-pair HPLC Uses water-organic mobile phase a buffer to control pH and an ion pair reagent. Column : C18, C8, cyano. Acceptable choice for ionic or ionizable compounds, especially bases or cations. Normal phase HPLC Uses mixtures of organic solvents as mobile phase Columns: Cyano, diol, amino and silica. Good second choice when reversed-phase or ion-pair HPLC is ineffective, first choice for lipophilic samples that do not dissolve well in water-organic mixtures, first choice for mixtures of isomers and for preparative-scale HPLC (silica best) Getting started on method development One approach is to use an isocratic mobile phase of some average solvent strength (e.g., 50%) organic solvent. A better alternative is to use a very strong mobile phase with (80-100% B), then reduce %B as necessary. The initial separation with 100%B results in rapid elution of the entire sample, but few groups will separate. Decreasing solvent strength shows the rapid separation of all components with a much longer run time, with a broadening of later bands and reduced detection sensitivity. Improving the separation and repeatable separation Generally the chromatographers will consider several aspects of the separation, as summarized in Table-8.6. Table-8.6 Objectives of separation in HPLC method development Objectivesa Comment Resolution Precise and rugged quantitative analysis requires that Rs be greater than 1.5. Separation time Quantitation à à £ 2% (1 SD) for assays; à £ 5% for less-demanding analysis; à £15% for trace analysis. Pressure Peak height Narrow peaks are desirable for large signal / noise ratios Solvent consumption à Minimum mobile-phase use per run is desirable. a Roughly in order of decreasing importance but may vary with analysis requirements. Separation or resolution is a primary requirement in quantitative HPLC. The resolution (Rs) value should be maximum (Rs>1.5) favours maximum precision. Resolution usually degrades during the life of the column and can vary from day to day with minor fluctuations in separation conditions. Therefore, values of Rs = 2 or greater should be the goal during method development for simple mixtures. Such resolution will favour both improved assay precision and greater method ruggedness. Some HPLC assays do not require base line separation of the compounds of interest (qualitative analysis). In such cases only enough separation of individual components is required to provide characteristic retention times for peak identification. The time required for a separation (run time = retention time for base band) should be as short as possible and the total time spent on method development is reasonable (runtimes 5 to 10 minutes are desirable). Conditions for the final HPLC method should be selected so that the operating pressure with a new column does not exceed 170 bar (2500 psi) and upper pressure limit below 2000 psi is desirable. There are two reasons for that pressure limit, despite the fact that most HPLC equipment can be operated at much higher pressures. First, during the life of a column, the back pressure may rise by a factor of as much as 2 due to the gradual plugging of the column by particular matter. Second, at lower pressures When dealing with more challenging samples or if the goals of separation are particularly stringent, a large number of method development runs may be required to achieve acceptable separation. Repeatable separation As the experimental runs described above are being carried out, it is important to confirm that each chromatogram can be repeated. When changing conditions (mobile phase, column, and temperature) between method development experiments, enough time must elapse for the column to come into equilibrium with a new mobile phase and temperature. Usually column equilibration is achieved after passage of 10 to 20 column volumes of the new mobile phase through the column. However, this should be confirmed by carrying out a repeat experiment under the same conditions. When constant retention times are observed in two such back-to-back repeat experiments (à ± 0.5% or better), it can be assumed that the column is equilibrated and the experiments are repeatable. Completing the HPLC method development The final procedure should meet all the objectives that were defined at the beginning of method development. The method should also be robust in routine operation and usable by all laboratories and personnel for which it is intended. Quantitation and method validation One of the strengths of HPLC is that is an excellent quantitative analytical technique. HPLC can be used for the quantitation of the primary or major component of a sample (including pure samples) for mixture of many compounds at intermediate concentrations and for the assessment of trace impurity concentrations in matrix. Method validation, according to the United States Pharmacopoeia (USP), is performed to ensure that an analytical methodology is accurate, specific, reproducible and rugged over the specified range that an analyte will be analysed. Method validation provides an assurance of reliability during normal use and is sometimes described as the process of providing documented evidence that the method does what it is intended to do. According to USP, the method validation involves eight steps as given below. Precision Accuracy Limit of detection Limit of quantitation Specificity Linearity and range Ruggedness Robustness Precision and accuracy: Already discussed in chapter-1. Linearity The linearity of the method is a measure of how well a calibration plot of response v/s concentration approximates a straight line, or how well the data fit to the linear equation. Y = aX + b Where ââ¬ËYââ¬â¢ is the response, ââ¬ËXââ¬â¢ is the concentration, ââ¬Ëaââ¬â¢ is the slope and ââ¬Ëbââ¬â¢ is the intercept of a line fit to the data. Ideally, a linear relationship is preferred (b = 0) because it is more precise, easier for calculations and can be defined with fewer standards. Also, UV detector response for a dilute sample is expected to follow Beerââ¬â¢s law and be linear. Therefore, a linear calibration gives evidence that the system is performing properly throughout the concentration range of interest. Generally in HPLC, if we are using internal standard, then the linearity plot is to be drawn by taking concentration of the analyte on x-axis and the ratio of area under the curve (AUC) of analyte to AUC of internal standard (IS) on y-axis. The resulting plot slope, intercept and correlation coefficient provide the desired information on linearity. A linearity correlation coefficient above 0.999 is acceptable for most methods. Limit of detection (LOD) The limit of detection (LOD) is the smallest concentration that can be detected reliably. The LOD represents the concentration of analyte that would yield a signal-to-noise (S/N) ratio of 3. Limit of quantitation (LOQ) The LOQ is the concentration that can be quantitated reliably with a specified level of accuracy and precision. The LOQ represents the concentration of analyte that would yield a signal-to-noise ratio of 10. LOD and LOQ can be determined by using the following expressions. LODà à à =à à à à à à à à à 3 X N / B LOQà à à =à à à à à à à à à 10 X N / B Where N is the noise estimate, is the standard deviation of the peak area ratio of analyte to IS (5 injections) of the drugs. B is the slope of the corresponding calibration curve. The LOD and LOQ values determined during method validation are affected by the separation conditions, columns, reagents and especially instrumentation and data systems. Ruggedness Method ruggedness is defined as the reproducibility of results when the method is performed under actual use conditions. This includes different analysts, laboratories, columns, instruments, sources, chemicals, solvents etc. method ruggedness may not be known when a method is first developed, but insight is obtained during subsequent use of that method. Robustness The concept of robustness of an analytical procedure has been defined by the ICH as ââ¬Å" a measure of its capacity to remain unaffected by small, but deliberate variations in method parametersâ⬠. The robustness of a method is the ability to remain unaffected by small changes in parameters such as pH of the mobile phase, temperature, percentage of organic solvent and buffer concentration etc. to determine robustness of the method experimental conditions were purposely altered and chromatographic characteristics were evaluated. To study the pH effect on the retention (K1) of the drug, buffer pH is to be changed by 0.2 units. At certain point, retention will increase at any pH above and below of the pH unit. The effect of temperature on the retention characteristics (K1) of the drug is to be studied by changing the temperature in steps 2à ºC from room temperature to 80à ºC and see the effect of temperature on the resolution and peak shape. Effect of percentage organic strength on retention is to be studied by varying the percentage of organic solvents like acetonitrile, methanol etc. from 0 to 2% while the other mobile phase contents are held constant and observe the K1. At certain point decreases in K1 observed with increase in the level of organic solvent. Effect of buffer concentration should be checked at three concentration levels i.e. 0.025 M, 0.05 M and 0.1 M and observe retention time and resolution. Stability To generate reproducible and reliable results, the samples, standards and reagents used for the HPLC method must be stable for a reasonable time (e.g., One day, one week, one month, depending on the need). For example, the analysis of even a single sample may require 10 or more chromatographic runs to determine system suitability, including standard concentrations to create a working analytical curve and duplicate or triplicate injections of the sample to be assayed. Therefore, a few hours of standard and sample solution stability can be required even for a short (10 min.) separation. When more than one sample is analyzed, automated, over night runs often are performed for better laboratory efficiency. Typically, 24 hours stability is desired for all solutions and reagents that need to be prepared for each analysis. Mobile phases should be chosen to avoid stability problems, especially the use of amine additives or specific solvents. For example, mobile phase containing THF (tetra hydrofuran) are known to be susceptible to oxidation, therefore, the mobile phase should be prepared daily with fresh THF. Some buffered mobile phases cause problems for example, phosphate and acetate provide good media for microbial growth. Sodium oxide (0.1%) is often added to the mobile phase buffer to inhibit such growth, adding more than 5% of organic solvent is also effective. Long term column stability is critical for method ruggedness. Even the best HPLC column will eventually degrade and lose its initial performance, often as a function of the number of samples injected. System suitability System suitability experiments can be defined as tests to ensure that the method can generate results of acceptable accuracy and precision. The requirements for system suitability are usually developed after method development and validation have been completed. The criteria selected will be based on the actual performance of the method as determined during its validation. For example, if sample retention times forms part of the system suitability criteria, their variation (SD) during validation can be determined, system suitability might then require that retention times fall within a à ±3 SD range during routine performance of the method. The USP (2000) defines parameters that can be used to determine system suitability prior to analysis. These parameters include plate number (N), tailing factor, k and / or a, resolution (Rs) and relative standard deviation (RSD) of peak height or peak area for respective injections. The RSD of peak height or area of five injections of standard solution is normally accepted as one of the standard criteria. For an assay method of a major component, the RSD should typically be less than 1% for these five respective injections. The plate number and / or tailing factor are used if the run contains only one peak. For chromatographic separations with more than one peak, such as an internal standard assay or an impurity method, expected to contain many peaks, some measure of separations such as Rs is recommended. Reproducibility of tR or k value for a specific compound also defines system performance. The column performance can be defined in terms of column plate number ââ¬ËNââ¬â¢ is defined by N = 5.54 (tR / Wà ½)2 Where ââ¬ËtRââ¬â¢ is the retention time of the peak and ââ¬ËWà ½Ã¢â¬â¢ is the width of the peak at half peak height. The resolution of two adjacent peaks can be calculated by using the formula Rs = 1.18 (t2-t1) / W0.5.1 +W0.5.2 Where ââ¬Ët1ââ¬â¢ and ââ¬Ët2ââ¬â¢ are retention times of the adjacent peaks and W0.5.1 and W0.5.2 are the width of the peaks at half height. Rs = 2.0 or greater is a desirable target for method development. The retention factor k is given by the equation. k = (tR ââ¬â t0) / t0 where ââ¬ËtRââ¬â¢ is the band retention time and t0 is the column dead time. The peak symmetry can be represented in terms of peak asymmetry factor and peak tailing factor, which can be calculated by using the following formula. Peak asymmetry factor = B /A Where ââ¬ËBââ¬â¢ is the distance at 50% peak height between leading edge to the perpendicular drawn from the peak maxima and ââ¬ËAââ¬â¢ is the width of the peak at half height. According to USP (2000) peak tailing factor can be calculated by using the formula T = W0.05 / 2f Where ââ¬Å"W0.05â⬠is the width of the peak at 5% height and ââ¬Å"fâ⬠is the distance from the peak maximum to the leading edge of the peak, the distance being measured at a point 50% of the peak height from the base line.
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