Thursday, April 30, 2020

Success key of Walmart free essay sample

The goal of Walmart is to provide customers with high-quality goods at low everyday pricing. To achieving this goal, Walmart adopted several strategies. Walmart’s winning strategy is based on low cost, which relies on a logistics technique known as cross docking. Using cross docking, Walmart is able to received goods on one side while simultaneously filling orders on the other. This strategy reduced Walmart’s costs significantly since it reduces inventory holding costs through reduced storage times and potentially eliminating the need to retain safety stock. Eventually, they passed those savings on to their customers with highly competitive pricing. The second strategy adopted by Walmart is to avoid being dependent on any one supplier, which decreases its exposure to many risks and guarantees abundant sources of products. Having single suppliers brings a lot of disadvantages. Firstly, you will have lesser negotiating leverage if you become dependent on a single supplier who supplies your needs. We will write a custom essay sample on Success key of Walmart or any similar topic specifically for you Do Not WasteYour Time HIRE WRITER Only 13.90 / page And then there is the issue of complacency, the supplier may become complacent because they know that you cannot find a better supplier than them. Walmart builds strong and collaborative relationship with nearly 3000 goods suppliers, including Johnson Johnson and ProctorGamble. These suppliers provide Walmart with high-quality products. Electronic â€Å"hook ups† and latest supply chain technology like RFID improve supply chain efficiency. The third strategy is to take up large market share in the world. By 2005, it held an 8. 9% retail store market share in the United States, 3700 stores in the United States and more than 1600 units in other countries of the world. In some degree, market share drives market perception of one’s business, and market perception is the prerequisites for growth of a business. A low or falling market share leads potential customers or employees to believe that there is something wrong with the business. On the contrary, a high or growing market share lead people to believe that the business is good and they are likely to become parts of it. Walmart encourages managers to work effectively and efficiently. It required managers to fill out â€Å"best yesterday† legers, which are forms tracking daily sales performance to ensure operational efficiency. It gives managers incentive to be accountable and creative by offering profit sharing, incentive bonus, a discount stock purchase plan, pay raise based on performance and other benefit plans. Finally, it has good communication among all stores around the world. A satellite network system allows information to be shared among these stores and suppliers. Data from over 5,300 individual stores on items are collected, analyze, and transmitted electronically on a real-time basis. This information helps company to reduce the likelihood of stock-outs, maximize inventory turnover and improve operational efficiency.

Monday, April 13, 2020

Lifespan Development Essay Sample

Lifespan Development Essay SampleThe lifespan development essay can help you make the best decisions in life. These are written by students who are selected at the time of their early teen years. After that, they may live their full lives with the results based on these essays. These are quite different from regular essays and questionnaires.The life span of the student is measured through the essay. You must use the lifespan development essay as a means to consider some important questions. It is mainly for you to figure out what has been going on inside your mind for the past few years, how do you plan to handle your future and which directions do you want to go.The students are asked to write down everything they know about themselves and their life. So you should write down your dream and wish list. They then have to find the one or two things that must be done to attain them.The students are then asked to write a short essay based on what they have mentioned. They are told to pu t your name as the author and to be honest. The maturity level of the students as well as the complexity of the subjects they choose are factors that must be taken into consideration.The life span development essay is also used as a way to determine the kind of person they are. Many students opt for a career that is more forward in nature. But it is important to go back to reality and analyze your real desires and not what your parents or teachers have suggested you. That will help you to be able to express your views more clearly.The goals you have set for yourself must be identified along with the actual outcome. Then you can go ahead with the steps you need to take to achieve your wishes. The writing has to be under control as you will be discussing the difficulties and then solving them.You should also ensure that the lifespan development essay sample you have chosen is the one that suits your needs. If not, you may face some problems later on in life.

Saturday, March 21, 2020

French Indian War - French Indian War Aftermath

French Indian War - French Indian War Aftermath Previous: 1760-1763 - The Closing Campaigns | French Indian War/Seven Years War: Overview The Treaty of Paris Having abandoned Prussia, clearing the way to make a separate peace with France and Spain, the British entered into peace talks in 1762. After winning stunning victories around the globe, they vigorously debated which captured territories to keep as part of the negotiating process. This debate essentially distilled to an argument for keeping either Canada or islands in the West Indies. While the former was infinitely larger and provided security for Britains existing North American colonies, the latter produced sugar and other valuable trade commodities. Left with little to trade except Minorca, the French foreign minister, the Duc de Choiseul, found an unexpected ally in the head of the British government, Lord Bute. Believing that some territory had to be returned in order to restore a degree of balance of power, he did not press to complete the British victory at the negotiating table. By November 1762, Britain and France, with Spain also participating, completed work on a peace agreement dubbed the Treaty of Paris. As part of the agreement, the French ceded all of Canada to Britain and relinquished all claims to territory east of the Mississippi River except New Orleans. In addition, British subjects were guaranteed navigation rights over the length of the river. French fishing rights on the Grand Banks were confirmed and they were allowed to retain the two small islands of St. Pierre and Miquelon as commercial bases. To the south, the British maintained possession of St. Vincent, Dominica, Tobago, and Grenada, but returned Guadeloupe and Martinique to France. In Africa, Gorà ©e was restored to France, but Senegal was kept by the British. On the Indian Subcontinent, France was permitted to re-establish bases that had been founded before 1749, but for trading purposes only. In exchange, the British regained their trading posts in Sumatra. Also, the British agreed to allow former French subjects to continue practicing Roman Catholicism. A late entry into the war, Spain fared badly on the battlefield and in negotiations. Forced to cede their gains in Portugal, they were locked out of the Grand Banks fisheries. In addition, they were forced trade all of Florida to Britain for the return of Havana and the Philippines. This gave Britain control of the North American coast from Newfoundland to New Orleans. The Spanish were also required to acquiesce to a British commercial presence in Belize. As compensation for entering the war, France transferred Louisiana to Spain under the 1762 Treaty of Fontainebleau. The Treaty of Hubertusburg Hard pressed in the wars final years, Frederick the Great and Prussia saw fortune shine on them when Russia exited the war following Empress Elizabeths death in early 1762. Able to concentrate his few remaining resources against Austria, he won battles at Burkersdorf and Freiburg. Cut off from British financial resources, Frederick accepted Austrian entreaties to begin peace talks in November 1762. These talks ultimately produced the Treaty of Hubertusburg which was signed on February 15, 1763. The terms of the treaty were an effective return to status quo ante bellum. As a result, Prussia retained the wealthy province of Silesia which it had gained by the1748 Treaty of Aix-la-Chapelle and which had been a flashpoint for the current conflict. Though battered by the war, the result led to a newfound respect for Prussia and an acceptance of the nation as one of the great powers of Europe. The Road to Revolution Debate over the Treaty of Paris began in Parliament on December 9, 1762. Though not required for approval, Bute felt it a prudent political move as the treatys terms had unleashed a great deal of public outcry. The opposition to the treaty was led by his predecessors William Pitt and the Duke of Newcastle who felt that the terms were far too lenient and who criticized the governments abandonment of Prussia. Despite the vocal protest, the treaty passed the House of Commons by a vote of 319-64. As a result, the final document was officially signed on February 10, 1763. While triumphant, the war had badly stressed Britains finances plunging the nation into debt. In an effort to alleviate these financial burdens, the government in London began exploring various options for raising revenues and underwriting the cost of colonial defense. Among those pursued were a variety of proclamations and taxes for the North American colonies. Though a wave of goodwill for Britain existed in the colonies in the wake of the victory, it was quickly extinguished that fall with the Proclamation of 1763 which forbade American colonists from settling west of the Appalachian Mountains. This was intended to stabilize relations with the Native American population, most of which had sided with France in the recent conflict, as well as reduce the cost of colonial defense. In America, the proclamation was met with outrage as many colonists had either purchased land west of the mountains or had received land grants for services rendered during the war. This initial anger was escalated by a series of new taxes including the Sugar Act (1764), Currency Act (1765), Stamp Act (1765), Townshend Acts (1767), and Tea Act (1773). Lacking a voice in Parliament, the colonists claimed taxation without representation, and protests and boycotts swept through the colonies. This widespread anger, coupled with a rise in liberalism and republicanism, placed the American colonies on the road to the American Revolution. Previous: 1760-1763 - The Closing Campaigns | French Indian War/Seven Years War: Overview

Wednesday, March 4, 2020

Teaching the Id, Ego, and Superego With Dr. Seuss

Teaching the Id, Ego, and Superego With Dr. Seuss One of the best secondary classroom crossover units between the discipline of English Language Arts and the courses that cover Psychology- usually through the discipline of Social Studies- is a unit on the National Council of Teachers of English  (NCTE)  on their  Read, Write, Think  website.  This unit covers the key concepts of Freudian psychology as a science or as a tool for literary analysis  in a highly engaging manner. The unit is titled  Ã¢â‚¬Å"Id, Ego, and the Superego in Dr. Seuss’s  The Cat in the Hat. Julius Wright of  Charleston, South Carolina- the lesson creator- uses  the iconic elementary text from The Cat in the Hat  to teach students to analyze a literary work using the plot, theme, characterization, and psychoanalytic criticism. The unit is designed for eight 50 minute sessions. Students will read Dr. Seusss  The Cat in the Hat  and analyze the development of each character from the text and pictures using Sigmund Freuds  personality theories. The students will determine which characters exhibit the characteristics of id, ego, or superego. Students can also analyze the static nature of characters (i.e.: Thing 1 Thing 2) locked in one stage. Wright provides student-friendly definitions and commentary for each psychoanalytic stage in one of the handouts on the  Read, Write, Think  website. Freuds Psychoanalytic Personality Theory for Students Wright provides a student-friendly description for each of the three elements of personality: The id is the part of the personality that contains our primitive impulses- such as thirst, anger, hunger- and the desire for instant gratification or release. The id wants whatever feels good at the time, with no consideration for the other circumstances of the situation. The id is  sometimes represented by a devil sitting on someone’s shoulder. As this devil sits  there, he tells the ego to base behavior on how the action will influence the self, specifically how it will bring the self pleasure. Example from the Dr. Seuss text, The Cat in the Hat: â€Å"I know some good games we could play,† said the cat.â€Å"I know some new tricks,† said the Cat in the Hat.â€Å"A lot of good tricks. I will show them to you.Your mother will not mind at all if I do.† Wrights student-friendly description for the Superego  stage: The superego is the part of the personality that represents the conscience, the moral part of us. The superego develops due to the moral and ethical restraints placed on us by our caregivers. It dictates our belief of right and wrong. The superego is sometimes represented by an angel sitting on someone’s shoulder, telling the ego to base behavior on how the action will influence society. Example from the Dr. Seuss text,  The Cat in the Hat: â€Å"No! Not in the house!† Said the fish in the pot.â€Å"They should not fly kites In a house! They should not.Oh, the things they will bump! Oh, the things they will hit!Oh, I do not like it! Not one little bit!† Wrights student-friendly description for the  Ego stage: The ego is the part of the personality that maintains a balance between our impulses (our id) and our conscience (our superego). The ego works, in other words, to balance the id and superego. The ego is represented by a person, with a devil (the id) on one shoulder and an angel (the superego) on the other. Example from the Dr. Seuss text,  The Cat in the Hat: â€Å"So we sat in the house. We did nothing at all.So all we could do was to Sit! Sit! Sit! Sit!And we did not like it. Not one little bit.† There are many examples in ​The Cat in the Hat, and the personality types may overlap, which encourages healthy debate and discussion between students. Common Core  Standards Other handouts for this unit include a  Defining Characterization  worksheet that supports details about direct and indirect characterization, as well as a chart of the five different methods of indirect characterization for students to use in analyzing The Cat in the Hat.  There are also extension activities featured on the handout  The Cat in the Hat  Projects  with a list of potential essay topics for an analytical or evaluative essay of characters. The lesson meets specific Common Core standards, such as these anchor standards (for grades 7-12) for reading that can be met with this lesson: Analyze how and why individuals, events, or ideas develop and interact over the course of a text.Compare and contrast treatments of the same topic in several primary and secondary sources. If there is an essay assigned from suggested topics, the anchor writing standards (for grades 7-12)  for writing could be met: Write informative/explanatory texts to examine and convey complex ideas and information clearly and accurately through the effective selection, organization, and analysis of content. Using the Illustrations as a Visual Guide In teaching the lessons, it is very important that each student has a copy of The Cat in the Hat  as  the illustrations contribute to their characterizations of the different Freudian stages. In teaching the lesson to grade 10 students, many of their observations were centered around pictures. For example, students could connect illustrations to specific behaviors: The bland faces of the Narrator and his sister, Sally, at the beginning (ego stage);The manic behavior of Thing 1 and Thing 2 as they fly kites in the house (id stage);The fish out of the water, risking his life to lecture the Narrator and Sally (superego). Literary Analysis and  Psychology Class Students in grades 10-12 may be taking psychology or AP Psychology as an elective. They may be already familiar with Sigmund Freuds work  Beyond the Pleasure Principle  (1920),  The Ego and the Id  (1923), or  Freud’s seminal work  The Interpretation of Dreams (1899). For all students, Psychoanalytic Criticism builds on the Freudian theories of psychology.  The OWL at Purdue website features the commentary of  Lois Tyson. Her book, Critical Theory Today, A User Friendly Guide discusses a number of critical theories that students may use in text analysis.   In the chapter on psychoanalytic criticism, Tyson notes that: [...]Some critics believe that we read psychoanalytically[...]to see which concepts are operating in the text in such a way as to enrich our understanding of the work and, if we plan to write a paper about it, to yield a meaningful, coherent psychoanalytic interpretation  (29). Suggested questions for literary analysis using psychoanalytic criticism are also on the OWL website include:   How can characters behavior, narrative events, and/or images be explained in terms of psychoanalytic concepts of any kind?What does the work suggest about the psychological being of its author?What might a given interpretation of a literary work suggest about the psychological motives of the reader?Are there prominent words in the piece that could have different or hidden meanings?Could there be a subconscious reason for the author using these problem words? Literary Applications of  Psychoanalysis After the unit students can take this idea and analyze a different piece of literature.  The use of psychoanalytic criticism humanizes literary characters, and discussions after this lesson can help students develop an understanding of human nature. Students can use their understanding of id, ego, and superego from this lesson and apply these understandings to characters in more sophisticated works, for example:   Frankenstein  and the Monsters shifts between id and superego.Dr. Jekyll and Mr. Hyde  and his attempts to control id through science.Hamlet  and his ego as he wrestles with the dilemma of avenging his fathers murder. All literature can be viewed through this psychoanalytic lens.

Monday, February 17, 2020

Quantitative Reasoning Essay Example | Topics and Well Written Essays - 1500 words

Quantitative Reasoning - Essay Example The following paragraphs will separate the results obtained after employing descriptive statistic tools to the pair of observations. These tools figure out the mean and the median percentage of smokers in the population, distinguished on the basis of gender. Mode has been ignored in this respect since it is irrelevant to figure out the maximum percentage to assess the average characteristics. The mean as well as the median percentage of smokers is lower for females than for males. An obvious implication from the same is that males are more inclined towards smoking than their female counterparts. Here mean is the weighted average implying approximately 19% and 27% of the female and male populations in any nation to be regular smokers, respectively. On the other hand, the median value indicates that among all nations taken collectively, in half of the cases, more than 18.9% of the females are found to smoke, in contrast to 24% among the males (Gravetter & Wallnau, 2008). Measures of dispersion indicate the degree to which the observations are scattered around the mean value. The higher the value of the measure, greater will be the dispersion about the mean and thus, the applicability of the mean value as a core feature of the population will be disturbed. Significance of standard deviation is almost equivalent to that of variance given that the former is the positive square root of the latter. The percentage of female smokers distributed among various groups in the entire population differs from the mean value so calculated, though it is lower than the degree of dispersion of the male smokers. The variance and standard deviation statistics yield that percentage of male smokers in some nations is much higher as well as lower than the mean percentage of male smokers so calculated. However, similar statistics for females rule out such extremeness. The adjoining diagram compares the percentage of male and female smokers in the entire

Monday, February 3, 2020

The Iliad Essay Example | Topics and Well Written Essays - 500 words

The Iliad - Essay Example In a reflective exploration of Agamemnon’s decision to take Briseis from Achilles, it becomes palpable that the crucial decisions in the Iliad are not made by the heroes to a great extent. Rather, these decisions are influenced by external factors including power struggles, political issues, war threat, involvement of gods etc. Therefore, it is essential to establish that the heroes in the work by Homer play an insignificant role in the making of vital decisions in the course of the plot and a precise set of principles, known as the â€Å"heroic code†, influence their decisions. Significantly, Agamemnon’s decision to take Briseis from Achilles illustrates the fact that the important decisions by heroes in the epic are influenced by external factors and the â€Å"heroic code†. A profound analysis of the characters and actions in the epic the Iliad confirms that, to a great extent, the decisions made by the heroes are influenced by external factors and conditions, although there is difference of opinion on the matter. Thus, the various heroes of the epic, including Agamemnon and Achilles, are influenced by the power struggles, political pressures, the role of the gods etc in their decisions at the different stages of the story. For example, a careful reader of the epic realizes that there exists significant power struggle between the two heroes of the work, Agamemnon and Achilles, which has a pertinent impact on the decisions they take. In the epic, King Agamemnon represents fixed system of monarchy while Achilles represents the honor based system as he is the best warrior of his time. Decisions made by both these heroes are influenced by the complex relationship between them based on the power struggles in the epic. In a careful exploration of the decisions made by the heroes in the Iliad, it becomes lucid that a precise set of principles known as the â€Å"heroic code† lie beneath the decisions and actions by the heroic characters. A

Sunday, January 26, 2020

The History Of Molecular Modeling Biology Essay

The History Of Molecular Modeling Biology Essay Molecular modeling is a collection of science and art that study molecular structure and function by using computational technique to generate a realistic model of molecule based on molecular properties and behavior. A special computer graphics application and viewer is required to study the image of molecular structure and chemical process. Normally, molecular modeling is applied in field that related to drug design and computational biology who focus on study of molecular structure, dynamic, properties, biological activity (e.g. protein folding, protein stability, protein recognition, and structure prediction, structure determination), and new molecular system design. This is because modeling can support a systematic way to investigate the molecular structure, flexibility and function. The computational approach that used in molecular modeling consists of molecular mechanic, quantum mechanics, and molecular simulation. Molecular mechanic is based on empirical result to model the molecular system through motion of an object. For instance, potential energy is calculated by using force field method. Quantum mechanics is described by using wave function and it is important for understand how the atoms are covalently combine to form molecule. Its example is ab initio and semi-empirical quantum mechanics. Molecular simulation is another computational technique which includes molecular dynamics and Monte Carlo. However, to date, molecular modeling is more concerns to the use of a variety of methods to deduce the atomic information of a system which includes all the approaches mentioned above. To know more about molecular modeling, we are advised to know some of its history so we can make sense of molecular modeling as we know it today. In 1858, Archibald Scott Couper, Friedrich August Kekulà © von Stradonitz, and Aleksandr Mikhailovich Butlerov introduced chemical structure with a structure rule that involves the link of carbons and other atoms. Louis Pasteur modified the molecular structure theory in 1860. In 1865, August Wilhelm Hofmann discovered ball and stick model and color scheme. And Alder and Wainwright performed simulation technique on hard spheres model in 1959. Lifson, Scheraga, Allinger, Levitt, Warshel and others introduced the force field concept in 1960. Whilst in 1970, Rahman and Stillinger described the molecular dynamic simulation of water. In 1971, Protein Data Bank (PDB) was established. In 1977 and 1984, water force field was developed by Berendsen and Jorgensen respectively. At same year, Warshel and colleagues published the concept of protein elec trostatics and enzyme-substrate complex. At late 1980s, high speed computer, program, technology innovation, and a variety of algorithm were introduced. From paragraph above, we only know some important year between late 1850s to 1980s. From 1970s onwards, there is a proposed expectation curve as shown in Figure 1.1. As computational method and technology are more available, the expectation towards biomolecular modeling field was continued to rise especially from 1980s to 1990s. Structure based rational drug design was then introduced. It was expected to replace the less efficient methods. However, unrealistically disappointment was followed. Then scientists undergo a recovery phase where Human Genome Project was introduced and new technology with fast workstation was published. With these, a steady progress of productivity is emerged until today in order to reach the realistic expectation. In addition, it is important to know that the latest molecular modeling trend is focusing on the development and implementation of virtual reality whose enhance the three dimensional visualization. Nowadays, molecular modeling has been altered the way to conduct a research, that is choosing the experiment with highest probability of success before perform it. So, there is a demand to have a better and faster program design. It is important to know that molecular model need not be commercial or costly to prepare, inexpensive materials also possible to produce useful model and result. Question 2: Molecular graphics and molecular viewer If we said that molecular modeling is creation of computational model based on molecular properties and behavior, then molecular graphic is the graphical depiction of molecular modeling. Molecular graphic is a discipline of study molecule through visualization of molecules and their component parts. It is refers to three-dimensional depictions of molecules that made to examine and understand their response during reaction and interaction. To date, molecular graphic has been replaced some function of physical molecule model as it is portability and easy to interact with analysis result. In the early stage of molecular graphic, computer graphic tool was dominated by vector graphical representation based on calligraphic technology. During that time, only line and dot were shown. And main frame computer was required to manipulate the molecular structure before submit to graphic hardware. Until the founded of Molecular Graphics Society (known as Molecular Graphics and Modeling Society today) in 1983 and present of Journal of Molecular Graphics, new graphic techniques, hardware device and graphical software were introduced. This discovery allows the interactivity on the basis of space filling molecular model. As we know that, molecular objects are in three-dimensional structure. So molecular graphic representation (MGR) is concerns to the multi-dimensionality in order to provide more molecular information. Graphical excellence is used as a guideline for the MGR development. It is well designed to present data and it consists of complex idea that able to communicate with clarity, precision, and efficiency. Basically, the graphical display will shows data, induces viewer to have greatest number of idea, makes large data set to be coherent, encourage eyeball technique to compare data by using human eye, integrates statistical and verbal description of a data set, and reveals data at different levels to give more details. There are several types of molecular model that relate to molecular graphic in order to combine the computational technique with graphic art. Here, I will briefly discuss a few types that commonly used. Ball and stick model is the most widely used molecular model. It displays the three-dimensional position of atoms and bonds that link between them. Typically, atom is represented by sphere with specific color and bond is represented by rod. The rod can be rotate to provide the insight of bond flexible. The Figure 2.1 shows the proline in ball and stick model and its structural formula. Black color represents carbon, white represents hydrogen, blue represents nitrogen, and red represents oxygen. Stick model (refer Figure 2.2) is similar to ball and stick model but without ball as it represents all atoms and bonds by using rod with different color scheme. Space filling model (refer Figure 2.2) is a type of  three-dimensional  molecular model  where the  atoms  are represented by van der Waals spheres with different color and join directly to one another. Its measurement scale is the same as the real atom scale. It shows the space that atom occupied instead of shows the chemical bond. Wire frame model (refer Figure 2.3) is similar to stick model which shows the connection of atom by different color scheme but with thinner bond (connector). This model is convenient for drawing large molecules. Chicken wire model (refer Figure 2.4) is another method to visualize molecular model by drawing the polygon mesh on surface. Its shape is similar to the regular  hexagonal  pattern with mesh  structure. Ribbon model (refer Figure 2.5) is a three dimensional schematic molecular model that used to represent protein structure. It shows the path and organization of protein backbone, and serves as visual framework that provides details of atomic structure. Coiled ribbon represents ÃŽ ±-helix,  arrow represents ÃŽ ²-strand, and thin tubes represents loop. It shows the visual basic of molecular structure such as twist and fold. Molecular viewer is the molecular graphic software that used to visualize molecular structure. It is selected based on the size of molecule and the task to do. Here, I will briefly discuss a few types of viewer that commonly used. RasMol is a powerful research tool for visualization of protein, nucleic acid, and small molecules. It is easy to use while able to produce high quality three-dimensional image. It is a free viewing system for PDB coordinate files. Chime is a molecular viewer that modified RasMol code to allow visualization of molecule through web browser. It able to display three-dimensional and interactive molecular model from webpage. Jmol is a Java-based molecular viewer that allows visualization of molecule through web browser (like Chime) or stand-alone computer (like RasMol). It supports many different source files such as PDB format to create molecular model. Cn3D is NCBIs three-dimensional structure viewer. It allows the display of three-dimensional structure, sequence, and sequence alignment with annotation and alignment editing feature from NCBIs Entrez. Swiss PDB Viewer or DeepView is a molecular viewer that provide user friendly interface which allows analyzing several proteins or multiple models at same time. It supports alignment which based on individual residue, main chain, or entire protein. It also can align different homologous protein structure. It can be used as a helper application for browser. Visual Molecular Dynamics (VMD) is designed for visualization of large structure molecule such as protein and lipid. Except visualization, VMD also can analyze molecular dynamic simulation, act as graphical front end by display and animate molecule, and sequence browsing. Question 3: Protein structure with reference to hemoglobin and the prion protein Protein structure is biomolecular structure of protein molecule which made up of amino acid polymers. It is critical to its activity and biological function. X-ray crystallography  and NMR spectroscopy are technique that used to determine the protein structure. Basically, the complex protein structure is characterized into four levels of organization (refer Figure 3.1). Primary structure of protein is a linear sequence of amino acid structural unit that held together by peptide bond. It is starting from amino terminus (N) and end with carboxyl terminus (C). The sequence of amino acid will determines primary structure of protein. Change in a single position of amino acid will alter the function and activity of protein, some might cause disease. Secondary structure of protein is local conformation of polypeptide chain. It defined by  the pattern of hydrogen bond that formed between peptide backbones. The polypeptide folds locally into stable structure will form alpha helix, beta pleated sheet, and turn conformation. Tertiary structure of protein is a global three-dimensional structure that formed when secondary structures are folded in three-dimensional space. This folding is triggered by hydrophobic interaction and stabilized by hydrogen bond, van der Waal interaction, disulfide bond, and charge-charge interaction. Tertiary structure can be organized by more than one domain. Domain region can be alpha helix, beta sheet or mixed. Tertiary structure refers to each individual domain as well as to the complete configuration of whole protein. Whilst motif is small structure that plays important role in protein prediction. Quaternary structure of protein refers to regular association of more than two polypeptide chains that fold and coil to form a complex. The interaction between subunits can be identical or different. Quaternary structure is known as a stable three-dimensional structure of multi subunit protein. Hemoglobin is example of protein quaternary structure that found in red blood cells who acts as oxygen transport molecule. It carries oxygen from lung to release in tissue, and binds to carbon dioxide in tissue then releases back to lung. This process is characterized by cooperative interaction of polypeptide chains (subunit) by change their structure to make hemoglobin to be properly function. Hemoglobin (Figure 3.2) is an allosteric protein. It is a tetramer that consists of two types of subunits, two ÃŽ ±-chains and two ÃŽ ²-chains that held together by non-polar interaction and hydrogen bond. Each subunit is arranged as alpha helix structural segment and forms a hydrophobic cleft to allow the attachment of a heme  prosthetic group that consists of an iron atom who acts as oxygen binding site. Each of the subunits can carry one molecule of oxygen. Actually, there has no contact between same type of chain, that is alpha-alpha chain, and beta-beta chain. The contact region occurs between alpha-chain and beta-chain such as alpha1beta1  and alpha1beta2. The alpha1beta2  contact region acts as a switch between deoxy (T) structure to the oxy (R) structure. At T structure or tense state, binding of oxygen is difficult. While oxygen is favored at R structure or relax state as binding of oxygen will trigger the affinity of next oxygen to hemoglobin. Transition from T structure to R structure is triggered by stereo chemical changes at the heme group as shown in Figure 3.3. Like other proteins, hemoglobin is created by DNA in body. Alteration of amino acid will cause blood related disorder such as sickle cell anemia. This disease is results from a mutation at sixth residue in the ÃŽ ² hemoglobin monomer. Proteinaceous infectious virion (prion) is an infectious protein that causes neurodegenerative disease such as Scrapie and Bovine Spongiform Encephalopathy (BSE) in mammal, and Creutzfeldt-Jakob (CJD) and Kuru in human. Prion is known as an infectious agent that infects protein, without the transfer of nucleic acid genome, and it causes other proteins to be misfolded. Proteinaceous infectious particle (PrP), a normal cellular protein, consists of around 250 amino acids is found in our body whose involve in the spread of prion disease. Prion theory states that PrP is sole causative agent of prion diseases. If prion is in normal or stable shape (PrPc), it will not cause disease. Whilst if prion is flipped and folded into abnormal conformation (PrPsc), it will cause disease as it induces other proteins to change their conformation and becomes PrPsc as well. This translation is an exponential process where ÃŽ ±-helical and coil structures are refolded into ÃŽ ²-sheet. PrPc  is the endogenous form of prion protein (PrP), while PrPsc  is the misfolded form of PrP. PrPc and PrPsc are known as protein isoform with tertiary structure characteristic. They are categorized as same protein but with different conformation as their folding region is different as shown in Figure 3.4. PrPc contains more ÃŽ ±-helical and coil structure  and PrPsc has more ÃŽ ²-sheet structure. Prion structure is extremely stable. It is highly resistant to denaturation either by heat, ultraviolet light, or radiation. This characteristic makes prion difficult to be eliminated. Furthermore, prion comes in different strains. Each of the strain has slightly different structure. In other words, there has no effective treatment to fight with prion diseases. Question 4: Protein databases Database is an organized collection of data which allows the convenient access of user. Database can be classified into a variety of type. Here, we only focus on the protein data type. There are three types of protein database, that is protein structure database, protein sequence database, and protein motif database. Before discuss the three types of databases, I would like to briefly describe Protein Data Bank (PDB) which is the primary protein database. Protein Data Bank (PDB) is a worldwide repository of three-dimensional structural data of biological macromolecules. Until March 12, 2013, there are 88837 structures in PDB, in which 82224 are protein structure or 92.56% of PDB structure is protein. All the protein structures are obtained through x-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, cryoelectron microscopy (cryoEM), hybrid technique, and other experimental method. Since 1971, PDB is under the management of Bookhaven. Until 1999, Research Collaboratory of Structural Bioinformatics (RCSB PDB) takes over this task. In 2003, Worldwide PDB (wwPDB) maintains and formalizes the international collaboration by involve RCSB PDB (USA), PDB Japan (PDBj), PDB Europe (PDBe), and Biological Magnetic Resonance Data Bank (BMRB) as members of wwPDB. They act as distribution centers of PDB data. PDB acts as a very important resource to organize and share molecule structure data especially in structural biology area. It serves as a global community to allow scientist to share their research. Currently, the newly determined protein structure will be deposited into PDB data before the scientific paper is published. Except three-dimensional database, PDB also known as primary database for protein structure information. Derived or secondary database will use the PDB data and categorize it in a different way based on their own classification. Protein structure database groups protein based on the similar protein structure and common evolutionary origin. Structural Classification of Proteins (SCOP), CATH, and DALI Domain Dictionary (DDD) databases are the three main protein structure classification databases. But here I will only discuss SCOP and CATH. SCOP is a repository that organizes protein structure hierarchically based on their structure and evolutionary origin. The classification of SCOP is manually. With assistant of computer tool, SCOP able to visual and compare the protein structure consistency. The latest version of SCOP is 1.75 that released on June 2009 with 38221 PDB entries and 110800 domains. The source of protein structure is from Protein Data Bank. The classification of SCOP has six levels that are class, fold, superfamily, family, protein, and species. There are eleven classes in SCOP hierarchy which differentiate by fold type: alpha ÃŽ ±, beta ÃŽ ², alpha and beta (ÃŽ ±/ÃŽ ²), alpha plus beta (ÃŽ ±+ÃŽ ²), multi-domain protein, membrane protein, small protein, coiled coil protein, low resolution structure, peptide, and designed protein. Between the eleven classes, only the first seven classes are known as true class and others serve as place holder for protein domain that have not been classified. Proteins are classified into group based on their structure similarity. The unit of classification is protein domain. The shape of domain is known as fold. Proteins share common fold if they have same major secondary structures in same arrangement and same topological connections. Superfamily is probable has common evolutionary origin which share common fold and perform similar function. Family shows a clearly evolutionary relationship of proteins with more than 30% sequence identity. Protein level will connect proteins through similar function and structure. The last level, species, is grouped according to unique sequence. CATH is a semi-automated protein structure classification in which the protein domain is classified based on class (C), architecture (A), topology (T), and homologous superfamily (H). The latest version of CATH is 3.5 that released on September 20, 2011 with 51334 PDB entries, 173536 CATH domains, and 26226 CATH superfamilies. CATH has four classes, they are alpha, beta, alpha and beta, and few secondary structure. The class of protein domain is determined by its secondary structure composition. Architecture level describes the overall shape of domain structure that determined by secondary structure orientation. Then, domain will be grouped into topology level based on secondary structure shape and connectivity. Homologous superfamily level will then grouped protein domains together based on similar structure, function, and has common ancestor. Protein sequence database can be divided into manually and automatically annotated database. UniProtKB/SwissProt and Protein Information Resource-International Protein Sequence Database (PIR-PSD) are example of manually annotated database. UniProtKB/TrEMBL and NCBI GenPept are example of automatically annotated database. Here, I will discuss the UniProt Knowledgebase (UniProtKB) as example. UniProtKB is a protein sequence and functional information database. The data type that captured in is known as protein annotation. UniProtKB consists of two sections: UniProtKB/SwissProt which can be reviewed and UniProtKB/TrEMBL which cannot be reviewed. Most of the sequence in UniProtKB is derived from International Nucleotide Sequence Database (INSD) and some from PDB database. All these sequences will be automatically added into UniProtKB/TrEMBL. Then the TrEMBL records can be manually selected to be integrated into SwissProt record. UniProtKB/SwissProt is a high curated and non-redundant protein sequence database. The release 2013_03 of March 6, 2013 has 539616 sequence entries. It combines the experimental result, computational analysis, and scientific literature in one entry. It provides all relevant information about the searched protein as the sequence form same gene and same species are merged into same entry. Its file format such as FASTA is downloadable by public. UniProtKB/TrEMBL is a high quality computational analyze and redundant protein sequence database. That means, TrEMBL is computer annotated supplement to SwissProt but with multiple entries for sam eprotein. The release 2013_03 of TrEMBL on March 6, 2013 has 32153798 sequence entries. However, its entry is not redundant to SwissProt. Therefore, the entry of UniProtKB on release 2013_03 will be the combination entry of SwissProt and TrEMBL that is 32693414. Protein motif database also known as pattern and profile database is secondary database that derived from conserved pattern obtained from multiple sequence alignment. It is useful for the classification of protein sequence into family level. PROSITE and BLOCKS are example of motif based database. PROSITE is a protein domain, family and functional site database which comprise of biologically significant protein site, pattern, and profile. It analyzes protein sequence for known motif. PROSITE classification is based on observation. Similar protein sequence will be group into family. And protein domain is classified based on families that share common ancestor or has functional attribute. PROSITE records give the information of structure and function for a particular protein. It is part of the  ExPASy  proteomics  analysis servers and it used the annotation of domain features of SwissProt entry. Up to date, the latest version is release 20.91 of March 4, 2013 with 1661 entries, 1308 patterns, 1053 profiles, and 1057 ProRule. ProRule is the case rule that provides extra information about function and structural of critical amino acids. For instance, it contains the information related to biologically meaningful residue such as active sites, co-factor-binding sites,  and post-translational  modification sites. It helps the protein function determination. And it able to generate annotation automatically based on the PROSITE motifs. PROSITE database is used when identify the possible function of newly discovered protein, and determine activity of known protein. We also can derive a signature or conserved sequence from protein in order to classify protein. This is because each PROSITE signature is linked to an annotation document, where has all related information of the particular protein. PROSITE offers tool that can function for motif detection and protein sequence analysis. The most common application or archive is fingerprint that act as evidence to identify an individual. Appendix: Figure 1.1: Expectation curve for biomolecular modeling and simulation File:L-proline-3D-balls.pnghttp://upload.wikimedia.org/wikipedia/commons/thumb/f/ff/Prolin_-_Proline.svg/121px-Prolin_-_Proline.svg.png Figure 2.1: Ball and stick model of proline Structural formula of proline Space filling model Stick modelhttp://www.rsc.org/ej/NJ/2003/b206570n/b206570n-f3.gif Figure 2.2: Stick model (left) and space filling model (right) of proline http://class.fst.ohio-state.edu/FST822/aa/btwf.gif Figure 2.3: Wire frame model http://upload.wikimedia.org/wikipedia/en/thumb/4/4f/DMT_chicken_wire_mesh.png/227px-DMT_chicken_wire_mesh.pnghttp://upload.wikimedia.org/wikipedia/commons/thumb/f/ff/Tubby-1c8z-pymol.png/160px-Tubby-1c8z-pymol.png Figure 2.4: Chicken wire model with stick model Figure 2.5: Ribbon model http://www.piercenet.com/media/ProStructureFig1.gif Figure 3.1: Four levels of protein structure Diagrammatic representation of the structure of hemoglobin Figure 3.2: Hemoglobin http://jr.stryker.tripod.com/images/TransitionRT.jpg Figure 3.3: Conformation transition from T structure to R structure PrPsc PrPcPrion structure Figure 3.4: Prion protein in abnormal conformation, PrPsc (left) and prion protein in normal conformation, PrPc (right)