Friday, November 29, 2019
Corporate Social Responsibility and Timberland Essay Example
Corporate Social Responsibility and Timberland Paper In what ways does Timberland fulfill its responsibility to consumers, employees, investors and society as a whole? A : 1 : Timberlandââ¬â¢s mission has been to equip people to make their difference in the world. Let them be consumers , employees , investors or society as a whole. Timberland ââ¬Ës business is a model for both commerce and justice having a long history in this regard. While continuing to build its reputation as a brand that stands for durability, ruggedness the American outdoor since 1950 , Timberland has been constructing a reputation of integrity and commitment to the community as well. Timberland is committed to ensuring that the workers who produce products are provided with fair, safe and non-discriminatory workplaces. Their products are produced in factories across the globeââ¬âin 38 countries by roughly 300 factories and approximately 247,000 workers. Timberland ââ¬Ës Code of Conduct is to officially formalize the pursuit of human dignity in the manufacturing process. Timberland has always pursued to serve their various stakeholdersââ¬â from a demanding shareholder or discerning customer to an employee who wants to make a living with purpose. Timberland has maintained their contract very well with various vendors, suppliers, customers, and local communities to create products. Timeberland ââ¬Ës our Code of Conduct demands much more than the minimum industry-standard requirements of environmental and human rights laws. We will write a custom essay sample on Corporate Social Responsibility and Timberland specifically for you for only $16.38 $13.9/page Order now We will write a custom essay sample on Corporate Social Responsibility and Timberland specifically for you FOR ONLY $16.38 $13.9/page Hire Writer We will write a custom essay sample on Corporate Social Responsibility and Timberland specifically for you FOR ONLY $16.38 $13.9/page Hire Writer Child labor has been adhered at 16 (which is higher than the law in some countries where their products are manufactured today), and also overtime being paid at a premium despite local laws and have maintained zero tolerance for working hours over 60 hours per week. Timberland listens to stakeholder voices and constantly works to improve assessment and human rights programs. They have taken on the challenge of helping factories build new and different management systems and improves staff knowledge about corporate social responsibility issues. Timberland has also incorporated items that often fall ââ¬Å"beyond factory wallsâ⬠into the assessment program. Basic things like nutritious food, medical services, housing, child care, schooling, and transportation are all taken into account during the evaluation. It is ensured that that there are ways for workers to learn and grow, such as opportunities for recreation, skills development, and savings or creditââ¬âall essential for ensuring the dignity of workers in the global supply chain. As a publicly traded enterprise and a corporate citizen, Timberland is committed to engaging investors / stakeholders in dialogue and action to reduce our global footprint. Investor profiles is broad and diverse, and includes groups or individuals who can affectââ¬âor are affected byââ¬âthe company. Timberlandââ¬â¢s approach to stakeholder engagement focuses on two central tenetsââ¬âtransparency and accountability . â⬠¢ Transparency enables to engage in candid dialogue with stakeholders, challenge assumptions and encourage innovation. It also helps build trust with these partners and critics to deepen understanding of impact on the world and advance approach to corporate social responsibility. â⬠¢ Accountability similarly drives efforts to seek public and stakeholder input as to pursue commitment to commerce and justice. By communicating performance, stakeholders can measure progress and hold them accountable for planned improvements. At Timberland, social responsibility starts at the top. The Company has a strong set of values that form the resolve for all that is being done for he community ââ¬â humanity, humility, integrity excellence. Timberland has pioneered several progressive environmental and social programs. All these programs together under one umbrella of Corporate Social Responsibility formalized Timberlandââ¬â¢s Four CSR Pillars: Energy, Product, Workplace Service. Embedded in each pillar is a commitment or bold goal that drives Timberour strategy in that arena. Q : 2 : In addition to a cl imate of social responsibility, do you think Timberland is likely to foster a climate of ethical awareness throughout its organization? Explain your answer. A:2 : Timerlandââ¬â¢s Code of Conduct : To create measurable sustainable impact in the lives of workers , the communities where we live and work and the environment we cherish through strategic relationships and investments that unleash civic potential , build capabilities and convene stake holders in common purpose. Well, I feel, its indeed a great combination Timberland has to do business keeping in mind social welfare . Business and community being joined together to create more powerful enterprise and community fostering a climate of ethical awareness throughout its organization. The issues being embraced as an enterprise and as a community are complex and far reaching. And to extend influence as a responsible business, Timberland looks for opportunities to leverage their expertise by educating and empowering a wider society (that is, other brands, government organizations and private citizens). In this way, they promote and steward the environmental and social health of our planet and its people and share our passion for Earthkeeping activities. Approach to building strong communities and a healthy planet through civic action is grounded in three basic criteria: â⬠¢ Timberlandââ¬â¢s corporate culture is built around values of Humanity, Humility, Integrity and Excellence. In the CSR arena, as in every aspect of the company, all programs must reflect these values. Company rely on a collaborative process built on a common vision and aligned valuesââ¬âwithin our organization and with partners in the industryââ¬âto create enduring change. This includes working together to raise awareness, model innovation and compel action. â⬠¢ The results of efforts across all four CSR pillars of Energy, Product, Workplace and Service must be measurable and transformative . Q : 3 : In what ways does Timberlandââ¬â¢s path of service programs help develop the quality of its work force? A: 3 : Business community shall be joined together you have a more powerful enterprise community. said Ken Freitas ââ¬â Timberland Vice President Social Enterprise. Timberland implements this commitment through a serious of programmes in which its employees including top managers corporate dollars participate. Thru its path of service program, employees receives up to 40 hours of paid time per year to participate in community service projects at local schools, day care centers, the society for prevention of cruelty to animals ( SPCA ), food banks, and the like they might clean up a nearby beach or help build a park. Years ago Timberland established its service sabbatical program, in which 3-6 months sabbaticals are awarded to as many as 4 employees who wish to use their professional skills to assist non profitable organizations full time, then there is a global servââ¬âAââ¬âPalooza, the annual worldwide co-wide celebration during which 2000 employees, vendors and community partners in a day of service. Engaging as a company in community service over the years has produced a variety of benefits, including the following: Augmented employee development. Our service projects are employee organized and led. Employees who step up to lead service projects receive training in project management, team motivation, and presentation skills, which they can transfer from their service roles into a professional capacity . â⬠¢Increased employee attraction and retention. Responses to our global employee survey consistently indicate that the Path of Serviceâ⠢ program benefit is a factor in our employeesââ¬â¢ decision to work for and stay at Timberland. Strengthened business partnerships. Timberland encourage employees to share the service ethos with business partners, vendors, and customers, to increase the impact which can be made in communities. Sharing in service experiences provides insight into the company culture and valuesââ¬âan asset in building ongoing business relationships. â⬠¢Reinforced commitment to community building and goodwill. Lasting impacts prevails in the communities in which contributions linger long after the specific service event.
Monday, November 25, 2019
the body essays
the body essays The story was written from the point of view of a grown up person that took a part in the story when he was a child. Gordy tell us about his adventure with his bodys on a search after a dad body. The mission is to find the body of a dead men that be run over by train. In my opinion every one went to this mission with his own personal mission Gordy - wanted to see how a dad body looks like, because he didnt accept his brother's death, after this event Gordy felt like no one loves him any more in the family and he wanted to prove his father that he is as good as his brother was. Warren - he told to his friend all about the dead body and sagest that all of them will go to find it. He wanted to prove to his brother that he is as good as him. Teddy - wanted to prove him self in front of his friends thats why he looks for adventures all the time. Cris - wanted to prove that he is better than every one thinks about him and he want to fight against the stigma that the society stick to his all family. They started to walk along the train rode that leads to the place where the body was seen, along the road the friends experience in all kinds of troubles like shortage of food and water, they solve all the troubles in a deferent ways like collecting money from all the members and buying food from the nearest grocery shop. All along the way they supporting each other but, its not stopping them to fight too. One of the problems was to decide whether to walk on the train bridge or to go around it (5 km ) fortunately the train came when they were on the bridge, they got scared and start running Gordy and Warren didnt succeeded to pass train bridge and had to jump over it. At night they divided the night into four shifts, every one guarded one shift with the same gun. On the trip they told each other every emotional feeling. The other group decided to find the dead body also. ...
Thursday, November 21, 2019
Enhancing Employees Literacy Skills Essay Example | Topics and Well Written Essays - 3000 words
Enhancing Employees Literacy Skills - Essay Example Among the consequences of low levels of workplace literacy and numeracy are: time and costs wasted in having to repeat assignments; inefficient work teams, wasted material, poor training, miscalculated finances, injuries in the workplace, unsafe practices and difficulties recruiting and retaining skilled staff (AI Group, 2010). The consequences of low levels of literacy in the workplace are therefore far-reaching. Campbell (2005) informed that ââ¬Å"literacy skills are vital to high performance and productivityâ⬠in the workplace (p. 1). The reality is, low adult literacy in general has negative impacts not only on business activities, but on the individual and the countryââ¬â¢s economy as a whole. Poor literacy constrains an individual in terms of career choices, impairs a businessââ¬â¢s competiveness and thus undermines the countryââ¬â¢s ability to compete globally (Campbell, 2005). It therefore follows that improving literacy skills in the workplace is an urgent mat ter. This paper proposes a project aimed at resolving this dilemma and thus suggests a program directed at employers that will enhance literary skills in the workplace. The program thus directs attention to workplace change that can enhance literacy in the workplace. ...Thus the workplace literacy program suggested is one that not only offers literacy training for employees but also ensures that literacy learning is a part of the workplace environment. Employees are not only encouraged to participate in literacy learning programs, but are also engaged in the workplace in such a way that fosters literacy improvement. The proposed workplace literacy improvement project is realistic in that it readily accepts that workplace literacy is low and in order to improve workplace literacy change must occur in the workplace first and foremost. This workplace literacy enhancement project takes the position that a learning environment in the workplace is conducive to enhancing literacy. Thus the re is an emphasis on the utility of investing in information technology and information technology training in the workplace as a supplement to general literacy training and education in the workplace. An examination of the literature identifies the efficacy of fostering a learning environment and in particular investing in and using information technology as a training and educational tool as well as a tool for business operations. A Review of the Literature Smith et al (2000) admitted that schools around the globe have systematically failed to produce the requisite number of skilled and talented workers. This may not be entirely true as a number of persons have literacy deficiencies because they either did not complete school or simply failed to attend school at all.
Wednesday, November 20, 2019
Media & Communications Essay Example | Topics and Well Written Essays - 2000 words
Media & Communications - Essay Example The internet, satellites, optics and mobile technology are but ordinary elements of modern life (Willinsky, 1999). Communications and technology, taken separately, are both pervasive forces in society. They both influence each other but does either of them drive the other to the extent of defining its existence The theory of technological determinism states that technology is the major molding factor in how society progresses (Franklin, 1990). Technological determinism's central theme is that technology dictates how societies create themselves. It further suggests that the introduction of new technologies have a direct and permanent means of changing society (Craig, 2000). Marshall McLuhan is one of the proponents of the technological determinism theory. His work was inspired by Harold Innes and Lewis Mumford to study the effects of media on people and society. The first part of his theories tackles the uses of senses in the communication process. The second part of his theory involved the greater impact of the medium, which is greatly immersed with technological developments, versus the content of communication (Munday, 2002, para. 5, 6). The book "The Medium Is the Massage: An Inventory of Effects", states that, "Before the invention of the phonetic alphabet, man lived in a world where all the senses were balanced and simultaneous, a closed world of tribal depth and resonance." (McLuhan, and Fiore, 1967, p. 245). This suggests that because of developments in technology, specifically through print and the phonetic alphabet communication, that the immediate transmission of thought is compromised as well as the social interaction involved in speech communication (Munday, 2002, para. 7). The implication is that communication need not be a directly social process and can be achieved with a degree of isolation. Another implication that was suggested was that the visual superseded auditory awareness as the sense essential for communication. It was further suggested that developments such as that of the printing press and mass media will fuel these developments. He points out to an ominous scenario of diminishing sensory perceptions and increasing social isolation Implications of Technological Determinism to Communications One of the reasons why technological determinism and communications have been brought up together is primarily because it figured prominently in McLuhan's theorization. Since communication involves the exchange of information and ideas, the level of efficiency and effectivity of the communication progress is indicative of the degree of organization and management there is in the society. In the context of today's life, technology and communication are even more intertwined as shown by the development of electronic media and communications. Technological Determinism in Critique Raymond Williams, together with Eric Hobsbawm, and E. P. Thompson became the important intellectuals of the Western World from 1965 to 1985 (Cowling, 1990 para. 1-2). In the 70's and 80's, Williams spoke regarding feminism, Welsh nationalism, the environment and the imperialism in the Third World (para. 5). He gained prominence publishing his book in 1958 entitled "Culture and Society: 1780-1950". He was a popular and prolific writer in the 1960's and used literature and
Monday, November 18, 2019
Planning and Goal Setting Essay Example | Topics and Well Written Essays - 750 words
Planning and Goal Setting - Essay Example For instance, he may ask that interviews be carried out around campus in a bid to gather certain information. For instance if the principal has heard of several complaints on numerous occasions, in order to have an idea of how many people are discontented, he may ask for data concerning this to be collected so as to enable him to act if need be. This is done mostly while analyzing data collected, mostly through questionnaires. If there was a certain question concerning this, then the campus leader will look at the responses and this will help in determining personnel needs. This article seeks to focus on a fundamental issue- the shortage of teachers and how to get more young people interested in the profession. Although this issue has been raised over a number of years, proper plans have not been put in place. This article outlines plans that have been proposed and implemented over years. For instance; CAPE. Identify the principal competencies and supporting standards involved or implicated in the reading, (e.g., Competency 5 and Competency 6, , including the following standard: Analyze the implications of various factors (e.g., staffing patterns, class scheduling formats, school organizational structures, student discipline practices) for teaching and learning, (Competency 5); Implement effective, appropriate, and legal strategies for the recruitment, screening, selection, assignment, induction, development, evaluation, promotion, discipline and dismissal of campus staff, (Competency 6). Implement old plans instead of making new plans. There are already plans on how to deal with the shortage of teachers; however these plans are usually scrapped for new ones without full implementation. Planning without implementation is an act in futility. The acute shortage of teachers is caused by the modern view of a teacher. A job deemed to be almost ââ¬Ëmenialââ¬â¢.
Saturday, November 16, 2019
Review of DNA and Protein Microarray for BioMEMS Technology
Review of DNA and Protein Microarray for BioMEMS Technology In recent years increase in genetically caused diseases is one of the major threat to mankind. Some of the genetically caused diseases are down syndrome, diabetes, obesity, sickle cell anemia, cystic fibrosis. This review paper explains how BioMEMS (Biological MicroElectroMechanicalSystem) technology used in microarrays and finding of gene expression which leads to medicine for particular diseases. BioMEMS research has been acquiring importance, due to the possibility of exploiting miniaturization to create new opportunities in medicine. BioMEMS systems in general have more diversity of materials and function than conventional MEMS devices. In BioMEMS ink-jet printing, photolithography techniques were introduced to deposit protein and DNA in array. DNA and protein micro-arrays based BioMEMS could be very extensively for rapid detection, drug discovery, and screening, especially when combined with integrated micro-fluidics and sensitive detection technologies. The techniques used to d efine patterns on semiconductor surfaces were utilized to construct arrays of single-stranded DNA. Once single strands of known sequences (capture probes) are placed at specific known sites on a chip surface, hybridization with molecules of unknown sequence (target probes) can reveal the sequence. Microarray-based gene expression profiling can be used to identify genes whose expression is changed in response toà disease caused genetically by comparing gene expression in infected to that in uninfected cells or tissues. Protein and antibody arrays can play a key role in search for disease-specific proteins that have medical, diagnostic, prognostic, and commercial potential as disease markers or as drug targets and for determination of predisposition to specific disease via genotypic screening. Array-based integrated chips and micro-fluidics hold a great potential for the development of high-throughput approaches to systematically analyze these proteins and to assign a biological fun ction, determine protein-protein and protein-DNA interactions. This paper tells about varies applications of BioMEMS to detect the defective gene the causes diseases and the fabrication methods used in microarrays chip production. Keywords: LOC Lab-on-a-chip, BioMEMS (Biological MicroElectroMechanicalSystem), ÃŽà ¼TAS (Micro Total Analysis System), Oligonucleotide, Microdroplets , Electrospray. 1. Introduction Microarray technology has been applied to study of gene expression to study mechanisms of diseases and to accelerate the drug discovery process. There is a definite trend towards increasing the use of molecular diagnostic methods, and biochip technologies, along with bioinformatics techniques. Classification of human disease using microarrays is considered to be important. The emphasis is not only on diagnosis but also on disease management, including monitoring the effect of treatment and determining prognosis [1]. Microarray and lab-on-a-chip systems are going to fulfill these new requirements, including the miniaturization of biological assays as well as the parallelization of analysis. Although the concept has been performed by miniaturizing the analytical equipments, the technology comes from the microeletromechanical and microelectronics industries [2]. Lab-on-a-chip technology is the method of choice to integrate processes and reaction and scale them down from conventional gla ssware to microfluidics, involving micro-sized channels in glass or polymer chips [3]. DNA microarray also knows as DNA chips, comprise a new technology emerging at a tremendous pace because of its power, flexibility, sensitivity and relative simplicity [4]. BioMEMS for proteomics can be divided into LOC device for specific tasks such as protein isolation, purification, digestion, and separation; and microarray device for high throughput study of protein abundance and function. An emergence of DNA, protein microarray has emerged over the last few years with commercial potential beyond the confines of the research laboratory [5]. In this paper we start our discussion with the history of microarray; subsequently we go into the details of general techniques used in DNA and protein microarray followed by fabrication and the application and future of microarray. 2. History of Microarray Microarray technology evolved from Southern blotting, where fragmented DNA is attached to a substrate and then probed with a known gene or fragment [6]. The first reported use of this approach was the analysis of 378 arrayed lysed bacterial colonies each harboring a different sequence which were assayed in multiple replicas for expression of the genes in multiple normal and tumor tissue [7]. These early gene arrays were made by spotting cDNA onto filter paper with a pin-spotting device. The use of miniaturized microarray for gene expression profiling was first reported in 1995 [8]. This technology allowed scientists to analyze thousands of mRNAs in a single experiment to determine whether expression is different in disease state. Unfortunately, mRNA levels within a cell are often poorly correlated with actual protein abundance [9]. A complete eukaryotic genome on a microarray was published in 1997[10]. The development of biochip has a long history, starting with early work on the und erlying sensor technology. In 1953, Watson and Crick announced their discovery of now familiar double helix structure and sequencing techniques by Gilbert and Sanger in 1977 [11, 12]. Two additional developments enable the technology used in modern DNA-based biosensors. First, in 1983 Kary Mullis invented the polymerase chain reaction (PCR) technique, a method for amplifying DNA concentration. This discovery made possible the detection of extremely small quantities of DNA in samples. Second, in 1986 Hood and co-workers devised a method to label DNA molecules with fluorescent tags instead of radiolables, thus enabling hybridization experiments to be observed optically [13]. A big boost in research and commercial interest came in the mid 1990s, when ÃŽà ¼TAS (Micro Total Analysis System) technology turned out to provide interesting tooling for genomics application, like capillary electrophoresis and DNA microarray [14]. Immunoassays, the precursor to protein chips available since t he 1980s, exploit the interactions between antibodies and antigens in order to detect their concentrations in biology sample. Their creation, however, is tedious and expensive. As to this, research at Harvard University combined the technology of immunoassays and DNA microarray to develop the protein chip [15]. 3. DNA Microarrays and Fabrication 3.1 Introduction Microarray analysis allows simultaneous of gene and gene products, including DNA, mRNA and proteins. There are basically two formats: cDNA microarrays and oligonucleotide microarrays. A cDNA microarray is an orderly arrangement of DNA probe spot printed onto a solid matrix such as glass, nylon, or silicon. The substrate is usually less than 4ÃÆ'-4 cm, while the spot size is less than 250ÃŽà ¼m. A DNA molecular probe is tethered (embedded and immobilized) to each spot on microarray. surface modification of the substrate, such as wit poly-L-lysin or silane, facilitates adhesion of the DNA probes. Hybridization is the base pairing between target and the probe, and is limited by the sensitivity and specificity of the microarray. There are three basic types of oligonucleotide microarrays: gene expression, genotyping (SNPs), and resquencing. Genomic DNA may be used for the study of SNPs, while expressed DNA sequence (cDNA clones, expressed sequence tags or ESTs) are used for gene expre ssion [17]. 3.2 Microarrays for Gene Expression Gene expression microarrays are tools that tell how much RNA (if any) a gene is making. Since 1977, and prior to microarray, only a few genes could be studied at a time using the northern blot analysis. GeneChip (Fig. 1.1) microarrays use the natural chemical attraction, or hybridization, between DNA on the array and RNA target molecule from the sample based on complementary base pairs. Only RNA target molecule that have exact complementary base pair bind to the prob. Gene expression detection microarray is that they are able to measure tens of thousands of genes at a time, and it is this quantitative change in the scale of gene measurement that has led to a qualitative change in our ability to understand regulatory processes that occur at the cellular level. It is possible to obtain near comprehensive expression data for individual tissues or organs in various states. Compressions are possible for transcriptional activity across different tissue, and group of patients with and witho ut a particular disease or with two different diseases. Microarray studies are designed in principle to directly measure the activity of the genes involved in particular mechanism or system rather than their association with a particular biological or clinical feature [18]. Although genes may be thousand of base pairs long, it is only necessary to construct a probe of 25 bases that represent a unique complementary portion of the target gene. In other words, the short probe on the microarray measures the expression of the complete gene by sampling only a small section of the gene. In some instances, as little as one RNA molecule out of 100,000 different RNAs in an original sample may be detected [19]. Sensitivity is the ability to identify the rarely expressed transcripts in a complex background. Specification is the ability to discern between different family members. The hybridization efficiency of two nucleic acid strand depends on 1) Sequence-dependent factors for length, extent of complementarity, and overall base composition; 2) Sequence independent factors such as the concentration of the probe and target, time, temperature, cation concentration, valency character, pH, dielectric and chaotropic medica, surface characteristics of the solid, and density spacing of the probe molecules; and 3) Sample-dependent complex background signal, which are probes interacting with the wrong complementary sequence [20]. Fig 1.1 GeneChip probe microarray cartridge (Image courtesy of Affmetrix) 3.3 Microarray for SNPs Small difference in a DNA sequence can have major impact on health. Deletions, insertions, and other mutations of as little as a single base pair may result in signification disease. Identification these mutations require determining the exact sequence for thousand of SNPs distributed throughout the genome. Using microarray, it is possible to scan the whole genome and look for genetic similarities among a group of people who share the same disease. Using microarray to genotype 10,000 to 100,000 SNPs, it is possible to identify the gene or group of genes that contribute to disease. For example, if a large group of people with a given diagnosis have several SNPs in common, but not healthy people, then mutations may be looked for within those SNPs. A genotyping microarray may look for up to 100,000 SNPs or more [21]. 3.4 Fabrication DNA spotting may be accomplished by depositing PCR amplified ESTs (500-5000 base pairs), or by in suit synthesis of oligodeoxynucleotide sequences (20-50 base pairs) on the substrate. There are variety of spotting techniques that include mechanical and ink-jet style application. The GeneChip brand arrays provide high levels of reproducibility, sensitivity, and specification. The following process steps are used for fabrication of the GeneChip: 1) GeneChip probe array are manufactured through a combination of photolithography (Fig 1.2) and combinatorial chemistry. With a calculated minimum number of synthesis steps, GeneChip technology produce array with hundreds of thousands of different probes packed at an extremely high density. Small sample volumes are required for study. Manufacture is scalable because the length of the probe, not their number, determines the number of synthesis steps required. 2) Manufacturing begins with a 5-in square quartz wafer. Initially the quartz is washed to ensure uniform hydroxylation across its surface. Because quarts is naturally hydroxylated, it provides an excellent substrate for the attachment of chemical, such as linker molecules, that are later used to position the probes on the arrays. Fig 1.2 Photolithographic technique are used to locate and add nucleotides for fabrication of array of probe (Image courtesy of Affymetrix) 3) The wafer is placed in a bath of silane, which reacts with hydroxyl groups of quartz, and forms a matrix of covalently linked molecules. This distance between these silane determines the probes packing density, allowing array to hold over 500,000 probe location, or features, within a mere 1.28cm2. Each of these features harbors millions of identical DNA molecules. The silane film provides a uniform hydroxyl density to initiate probe assembly. Linker molecules, attached to the silane matrix, provide a surface that may be spatially activated by light (Fig 1.3). 4) Probe synthesis occurs in parallel, resulting in the addition of an A, C, T or G nucleotide to multiple growing chains simulataneously. To define which oligonucleotide chains will receive a nucleotide in each step, photolithographic masks, carrying 18 to 20 ÃŽà ¼m2 windows that corresponds to the dimensions of individual features, are placed over the coated wafer. The windows are distributed over the mask based on the desired sequence each. When the UV light is shone over the mask in the first step of synthesis, the exposed linkers become deprotected and are available for nucleotide coupling. critical to this step is the precise alignment of the mask with the wafer before each synthesis step. To ensure that this critical step is accurately completed, chrome marks on the wafer and on the mask are perfectly aligned. 5) Once the desired features have been activated, a solution containing a single type of deoxynucleotide with a removable protection group is flushed over the wafers surface. The nucleotide attaches to the activated linkers, initiating the synthesis process. 6) Although the process is highly efficient, some activated molecules fail to attach the new nucleotide. To prevent these outliers from becoming probes with missing nucleotides, a capping step is used to truncate them. In additional, the side chains of the nucleotides are protected to prevent the formation of branched oligonucleotides. Fig 1.3 GeneChip fabrication steps (Image courtesy Affmetrix). 7) In the next synthesis step, another mask is placed over the wafer to allow the next round of deprotection and coupling. The process is repeated until the probes reach their full length, usually 25 nucleotides. 8) Although each position in the sequence of an oligonucleotide can be occupied by one of four nucleotides, resulting in an apparent need for 24ÃÆ'-4, or 100, different masks per wafer, the synthesis process can be designed to significantly reduce this requirement. Algorithms that help minimize mask usage calculate how to best coordinate probe growth by adjusting synthesis rates of individual probes and identifying situations when the same mask can be multiple times. 9) Once the synthesis is completed, the wafer are deprotected and diced, and the resulting individual arrays are picked and packed in flowcell cartridges. Depending on the number of probe features per array, a single wafer can yield between 49 and 400 arrays. 10) The manufacturing process ends with a comprehensive series of quality control tests. Additional, a sampling of array from every wafer is used to test the batch by running control hybridizations. A quantitative test of hybridization is also performed using standardized control probes [22]. 3.5 Microarray Data Analysis Data filtration is performed by selecting threshold pixel intensity; and 2-, 5-, or 10- fold difference between the samples. Different genes with an identical profile may represent a coordinate response to a stimulus. Genes with opposite profiles may represent repression. To compare expression profiles it is necessary to define a set of metrics, or operations that return a value that is proportional in some way to the similarities or difference between two expression profiles. The most commonly used metrics are Euclidean distance and Pearson coefficient of correlation [23]. 3.5.1 Euclidean Distance Two or more profile of each of two genes are compared as a mathematical matrix operation of n-dimensional space, where n is the number of expression patterns available. The Euclidean distance is the square root of the summation of the difference between all pairs of corresponding values. For two genes the distance is as follows: Where d is the distance, e1 is the expression pattern of gene1, e2 is the expression pattern of gene 2, and i is the element of the expression profile: Gene1 (e11, e12, ., e1n) and gene1 (e21, e22, à ¢Ã¢â ¬Ã ¦.,e2n). 3.5.2 Pearson Correlation Coefficient The Pearson correlation coefficient (r) gives a value of from -1 to 1, and closer to 1 (negative and positive correlation, respectively). The closer two profiles have the same expression, the closer the value will be to 1: Where and Sen are the mean and typical deviation of all of the point of the nth profile, respectively. 4. Protein Microarray and Fabrication 4.1 Introduction Protein microarrays are becoming an important tool in proteomics, drug discovery programs, and diagnostics [24]. The amount of information obtained from small quantities of biological samples is significantly increased in the microarray format. This feature is extremely valuable in protein profiling, where samples are often limited in supply and unlike DNA, cannot be amplified [25]. Protein microarrays are more challenging to prepare than are DNA chips [26] because several technical hurdles hamper their application. The surfaces typically used with DNA are not easily adaptable to proteins, owing to the biophysical differences between the two classes of bioanalytes [27]. Arrayed protein must be immobilized in a native conformation to maintain their biological function. Unfortunately, proteins tend to unfold when immobilized onto a support so as to allow internal hydrophobic side chains to from hydrophobic bonds with the solid surface [28]. Surface chemistry, capture agents, and detect ion methods take on special significance in developing microarrays. Microarrays consist of microscopic target spots, planer substrates, rows and columns of elements, and probe molecules in solution. Each protein assessed by a microarray should be the same as the partial concentration of each protein in the biological extract [29]. The past ten years have witnessed a fascinating growth in the field of large-scale and high-throughput biology, resulting in a new era of technology development and the collection and analysis of information. The challenges ahead are to elucidate the function of every encoded gene and protein in an organism and to understand the basic cellular events mediating complex processes and those causing diseases [30-33]. Protein are more challenging to prepare for the microarray format than DNA, and protein functionality is often dependent on the state of proteins, such as post-translational modification, partnership with other proteins, protein subcellular locali zation, and reversible covalent modification (e.g. phosphorylation). Nonetheless, in recent years there have been considerable achievements in preparing microarray containing over 100 proteins and even an entire proteome [34-36]. Randox Laboratories Ltd. Launched Evidence, the first protein Biochip Array Technology analyzer in 2003. In protein Biochip Array Technology, the biochip replaces the ELISA (Enzyme-linked immunosorbent assay) plate or cuvette as the reaction platform. The biochip is used to simultaneously analyze a panel of related tests in a single sample, producing a patient profile. The patient profile can be used in disease screening, diagnosis, monitoring disease progression or monitoring treatment (wiki Biochip). Protein expression profiling, protein-protein binding, drug interaction, protein folding, substrate specificity, enzymatic activity, and the interaction between protein and nucleic acids are among the application of protein microarrays. Abundance-based microarray, including capture microarray and reverse-phase protein blots, measure the abundance of specific biomolecules using well defined and high specific analyte-specific reagents (ASRs). Different classes of molecules can act as capture molecules in microarray assays, including antigen-antibody, protein -protein, aptamer-ligand, enzyme-substrate, and receptor-ligand [37]. 4.2 Spotting In situ synthesis of protein microarrays as done for DNA microarrays is impractical. Other forms of delivery-based technology must be incorporated. One-drop-at-a-time (microspotting) techniques including use of pins, quills or hollow needles that repeatedly touch the substrate surface depositing one spot after the next in an array format; shooting microdroplets from a ejector similar to ink-jet printing; and depositing charged submicron-sized droplets by electrospray deposition (ESD). Alternatively, parallel techniques such as microcontact printing (ÃŽà ¼CP), digital ESD, and photolithographic controlled protein adsorption can be used. Currently, micospotting by robotic techniques has greater use in the research setting, whereas parallel techniques offer cost saving for mass production for commercial use [38]. 4.3 Microcontact printing (ÃŽà ¼CP) In microcontact printing stamps are typically made from a silicon elastomer and used to make a microarray of spots with feature size from 0.01 to 0.1ÃŽà ¼m. Steps for stamping include the following [38]: 1) Activation of the stamp surface to increase hydrophilicity or to introduce grups for inking to target molecules such as antibodies, protein A, or streptavidin. 2) Direct adsorption of protein molecules or their binding to capture molecules over a period of 0.5-1 hours. 3) Rinsing. 4) Drying in a nitrogen stream for about a minute. 5) Pressing the stamp against a suitable substrate for about a minute to allow transfer of the semidry materials. Disadvantages include poor control of the amount of materials transferred, small amount of deposited materials, and possible changes in protein function. Microarrays containing up three different proteins were fabricated by ÃŽà ¼CP technique and tested as a detection system for specific antibodies [39]. Immunoassay were successfully performed using the patterned protein microarrays, and were characterized by fluorescence microscopy and scanning- probe microscopy. The characterization revealed the quality of the protein deposition and indicated a high degree of selectivity for the targeted antigen-antibody interaction. 4.3 Electrospray Deposition (ESD) The basic physics underlying the newly emerging technique of electrospray deposition (ESD) as applied to biological macromolecules. Fabrication of protein films and microarrays are considered as the most important applications of this technology. All the major stages in the ESD process (solution electrification, formation of a cloud of charged microdroplets, transformation of microdroplets into ions and charged clusters, deposition, and neutralization) are discussed to reveal the physical processes involved, such as space charge effects, dissipation of energy upon landing and neutralization mechanisms [40]. In electrospray deposition, protein is transferred from the glass capillary positioned 130-350 ÃŽà ¼m above a conducting surface. Micro-sized charged droplets move in an electric field created by the difference in electric field potential between the tip and the substrate surface and by the spatial charge of the droplet cloud. The electrostatic repulsion expands the cloud, and microdroplets are deposited as a round spot. The spot density is greater at the center [38]. Two new techniques were recently developed in these laboratories for fabrication of protein microarrays: electrospray deposition of dry proteins and covalent linking of proteins from dry deposits to a dextran-grafted surface. Here we apply these techniques to simultaneously fabricate 1200 identical microarrays. Each microarray, 0.6 ÃÆ'- 0.6 mm2 in size, consists of 28 different protein antigens and allergens deposited as spots, 30à ¢Ãâ ââ¬â¢40 ÃŽà ¼m in diameter. Electrospray deposition (ESD) of dry protein and covalent linking of proteins from dry deposits to a dextran-grafted surface has been studied from fabrication of microarrays. Electrospray (ES) deposition has been applied to fabricate protein microarrays for immunochemical assay. Protein antigens were deposited as arrays of dry spots on a surface of aluminized plastic. Deposition was performed from water solutions containing a 10-fold (w/w of dry protein) excess of sucrose. Upon contact with humid air, the spots tur n into microdroplets of sucrose/protein solution from which proteins were either adsorbed or covalently linked to clean or modified aluminum surfaces. It was found that covalent binding of antigens via aldehyde groups of oxidized branched dextran followed by reduction of the Schiff bonds gives the highest sensitivity and the lowest background in microarray-based ELISA, as compared to other tested methods of antigen immobilization [41]. Protein microarray with an antibody-based protein array for high-throughput immunoassay, with an ESD method using a quartz mask with holes made by an abrasive jet technique, has been performed. An antibody solution was electrosprayed onto an ITO glass, and then antibodies were deposited and cross-linked with a vapor of glutaraldehyde. The dimeters of the spots were approximately 150 ÃŽà ¼m. The arrays were then incubated with corresponding target antigenic molecules and washed. The captured antigens were collectively detected by fluorescence and chemiluminescence. The signals were quantitatively visualized with a high-resolution CCD [42]. 4.4 Surface immobilization In many proteomics applications, one is interested in the facile and covalent immobilization of protein molecules without the use of any special tag or chemical modification. This is most conveniently achieved via chemical reactivity towards the commonly available -NH2 groups on the surface of protein molecules. One of the most efficient leaving groups towards -NH2 is N-hydroxysuccinimide (NHS) attached via an ester bond. We have developed an NHS surface based on the zero background PEG coating. It allows for fast immobilization reactions with the remaining NHS groups easily washed off to expose the zero background PEG coating (Fig 1.4). In subsequent assays, the PEG functionality ensures that binding of particular molecules to the surface is only through the specific interaction with the immobilized protein molecule and the commonly seen background problem is solved without the need of a blocking step. Fig 1.4 NHS activated surfaces for the immobilization of proteins, peptides, antibodies (Image courtesy: ZeroBkgà ® ) Peptide and protein microarrays fabricated on NHS/PEG/glass slides (Fig 1.5) Nanoliter droplets of peptide (21 amino-acids) or protein (fibrinogen) solution containing 10% glycerol are deposited on the glass slide with a robotic arrayer and incubated for 10 minutes. NHS-groups in remaining area are removed by a deactivating buffer for 30 minutes at room temperature. The immobilized peptide or protein on the surface is detected by incubation with the primary antibody specifically against the peptide or fibrinogen, followed by wash and incubation with cy3-conjugated secondary antibody. The glass slides are imaged on a laser scanner. The most important result is the exceptionally low background due to the PEG coating. While the NHS/PEG coated glass slides are ideal for protein, peptide, and antibody arrays, they are also useful as low background surfaces for other microarrays, such as oligonucleotides, carbohydrates, and other small molecules. The non-fouling property of the high densit y PEG coating becomes critically important when one uses such an array for the study of complex biological samples, such as plasma or serum. In order to detect molecules of low abundance, such as cancer biomarkers, one needs to minimize non-specific adsorption of other abundant biomolecules [43]. Fig 1.5 Fluorescence images of peptide (left) and protein (Fibrinogen, right) microarrays fabricated on NHS/PEG/glass slides and detected by immunostaining. The diameter of each spot is ~100 ÃŽà ¼m (Image courtesy: ZeroBkgà ® ).à 4.5 Self-assembling Protein Microarrays Molecular fabrication of SAMS depends on chemical complementarily and structural compatibility, both of which confer the weak and noncovalent interaction that bind building blocks together during self-assembly. Water-mediated hydrogen bonds are important for living system. In nature the assembly of peptide and proteins has yielded collagen, keratin, pearl, shell, coral and calcite microlenses, and optical waveguides [44]. The application of self-assembly techniques in the design of biocompatible protein microarray surfaces, immobilizing cells, and lipid layers, and spotting techniques has been reviewed by others [45-46]. 4.6 Detection Strategies Detection and readout of complex formation in each spot is performed with fluorescence, chemiluminescence, mass spectrometry, radioactivity, or electrochemistry. Label-free methods include mass spectrometry and SPR. Labeled probe methods include use of a chromogen, fluorophor, or a radioactive isotope. Direct strategies use a labeled antibody to directly bind to the target molecule immobilized on the substrate. Amplification strategies based on avidin-biotin binding enhance sensitivity. Indirect strategies use an immobilized antibody for capturing labeled, specific molecules from the sample. Sandwich assay as noted earlier require two distinct antibodies foe detection of a capture molecule. The first antibody is immobilized on the substratum, and serves to capture the molecule of interest. A second labeled antibody then binds to the first complex allowing detection [47]. 5. Application of Microarray Ever since the first 1000 probe DNA microarray was reported over a decade ago [48], great strides have been made in both quantitative and qualitative applications. Today, a standard DNA chip contains up to 6.5 million spots and can encompass entire eukaryotic genomes. A plethora of alternative applications are continually reported, albeit at various stages of maturity. What was once seen solely as a transcript profiling technology has now emerged as a reliable format for genotyping, splice variant analysis, exon identification, ChIP-on-chip, comparative genomic hybridization (CGH), resequencing, gene synthesis, RNA/RNAi synthesis and onchip translation [49]. Perhaps the most exciting recent developments from a drug discovery perspective come from the integration of diverse technological innovations into microarray-based solutions, especially for other classes of molecular entity. From small molecules (e.g. metabolites, nucleotides, amino acids, sugars) to oligomeric and polymeric der ivatives thereof, microarrays are now allowing us to examine the intra-class (e.g. protein-protein) and inter-class (e.g. protein: small molecule) interactions of these bio-system components on a systems-wide level. Yet, despite the appearance of a diversity of microarray types (e.g. Small Molecule Microarrays (SMMs) [51], Protein-Nucleic acid (PNA) microarrays [52], Glyco-chips [53], peptide chips [54], antibody chips [55], cell and tissue microarrays [56]), each differs in their relative contribution to the Voltaire challenge. Certainly the foremost of such opportunities are thos
Wednesday, November 13, 2019
History of Money Essay -- GCSE Business Marketing Coursework
History of Money Let us consider a problem. You catch fish for your food supply, but you're tired of eating it every day. Instead you want to eat some bread. Fortunately, a baker lives next door. Trading the baker some fish for bread is an example of barter, the direct exchange of one good for another. However, barter is difficult when you try to obtain a good from a producer that doesn't want what you have. For example, how do you get shoes if the shoemaker doesn't like fish? The series of trades required to obtain shoes could be complicated and time consuming. Early societies faced these problems. The solution was money. Money is an item, or commodity, that is agreed to be accepted in trade. Over the years, people have used a wide variety of items for money, such as seashells, beads, tea, fish hooks, fur, cattle and even tobacco. There are numerous myths about the origins of money. The concept of money is often confused with coinage. Coins are a relatively modern form of money. Their first appearance was probably among the Lydians, in Asia Minor in the 7th century BC. And whether these coins were used as money in the modern sense has also been questioned. To determine the earliest use of money, we need to define what we mean by money. The early Persians deposited their grain in state or church grainaries. The receipts of deposit were then used as methods of payment in the economies. Thus, banks were invented before coins. Ancient Egypt had a similar system...
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