Online Billing System Essay Example for Free

Online Billing System Essay POS, Inventory System, Networking and Web Based System are one of the most useful systems for the company. Nowadays, because of our technologies it’s easy to transfer the different information in different branch of company with the help of our computers and also the system. Almost all businesses use a POS process. There are many reasons for this. Many businesses have multiple locations. POS can help to automate transactions and it can records all the sales in the organization or we can say it can use it to make transaction easier. Every employee can also see all the transaction that has been made. Inventory System can be used for transactional updates or it can view all the available stocks and display out of stock products or items. Inventory System can have many advantages and are suitable in availability and display the in and out of stocks products. Networking’s usually use to connect the POS and Inventory system to all branches of the CreamlineDairy Corporation. Web Based System has many advantages and is preferable in POS, inventory and networking particularly notifying your outstanding sale. The company have been encountering some problem in terms of no link depot and main plant. They want to connect to the other branch, or we can say they want to view their point of sale and inventory system to their entire branch. The purpose of our system is to let every branch of Creamline be updated to the transactions of sale by the help of networking. The develop system will be a great help to the employee but of course for the manager even if they are not in the organization. Creamline Dairy Corporation located at Unit 701 Prestige tower condominium, F. Ortigas Jr. Ave.(Fromely Emerald Ave.), Ortigas Center Pasig City 1605 Philippines.Creamline’s plant and head office is located at Bldg. 5210, C.M. Recto Highway, Clark FreeportZone, Pampangga.

The Fundamental Rethinking Processes Of BPR

The Fundamental Rethinking Processes Of BPR BPR is the fundamental rethinking and radical redesign of business processes to achieve dramatic improvements in critical contemporary measures of performance, such as cost, quality, service and speed. The major benefit of BPR is that it eliminates redundancies of work and improves accuracy. BPR can transform the basic ways that people and departments work and allow users to work better and often to produce higher quality work. BPR would enable smooth restructuring process of business processes at Velogic Airlines Limited. The chapter discusses BPR process, implementation method and the changes those may have to be made for upgrading the existing ERP system at Velogic Airlines Limited. Details about the modules related to Human Resource and Payroll System, Finance and Accounting System and Inventory Management System have also been elaborated in the chapter. Business Process Reengineering (BPR) is the organizational procedure required to align people, processes and technology with strategies to accomplish business integration. It can be considered as taking a business in its current state and forming an organizational and operational blueprint to redirect skills, polices, information (data), cultural values, organizational structures, processing and incentives towards targeted improvements15.  [1]   Velogic Airlines Limited are now inspiring to enhance their airline by coordinating their business processes more closely and in some cases integrating these processes so that they can focus more on efficient management of resources and customer service. The oracle application would not require specific non-intuitive software to be installed. Virtually all-new systems available in the market today run in industry standard web browsers, thus reducing software and training costs. Moreover with the emergence of new competitors they need to enhance their service level and be a step ahead of competitors. A powerful type of organization change is brought forward the business process reengineering (BPR) also known as Business Process Improvement (BPI) or business process redesign. From the early 1990s it became familiar for management in many organizations to focus their attention inwards and to consider how proficient business processes can be redesigned or re-engineered. Business Process Re-engineering (BPR) is the popular term for reutilisation of organizational procedures and structure following the introduction of new information technologies into an organization. It is the fundamental rethinking and radical redesign of business processes to accomplish impressive improvements in critical contemporary measures of performance, such as cost, quality, service and speed. Objectives of BPR A more significant kind of organizational change is business process reengineering, in which business processes are analyzed, simplified and redesigned. Using information technology, organizations can rethink and streamline their business processes to improve speed, service, and quality. Business Process Re-engineering reorganizes workflows, combining steps to cut waste and eradicating repetitive, paper-intensive tasks (sometimes the new design eliminates jobs as well). It is more ambitious than rationalization of procedures, requiring a new vision of how the process is to be organized  [2]  16. BPR Advantages over Automation and Rationalization The evolution of the information-processing pattern over the last four decades to build intelligence and administer amendments in business functions and processes has generally progressed over three phases: Automation Rationalization Business Process Re-engineering Each of them carries different rewards and risk. The most common form of IT-enabled organizational changes is automation. The first applications of information technology implicated assisting employees with achieving their tasks more efficiently and effectively. A deeper form of organizational change one that follows quickly from early automation is rationalization of procedures. Automation frequently reveals new bottlenecks in production and makes the existing arrangement of procedures and structures painfully large. Rationalisation of procedures is the streamlining of standard operating procedures more efficient. BPR, ERP AND IT In the majority of cases, information technology powers BPR. Formerly, information technology was used to facilitate companies automate existing business processes but now, technology is being used to transform those processes fundamentally. Current developments in information technology have not only made BPR possible on a radical and extensive scale, but also more efficient. The merger of the two concepts has resulted in the latest concept, namely, business engineering (BE). BE combines the innovations of information technology with BPRs focus on better business processes. The heart and soul of BE lying in radical, process-oriented business solutions, which have been greatly enhanced by the information technology of client/server computing. ERP is a tool, which acts as a facilitator of BE to mould business processes efficiently  [3]  17. While the objectives of BPR have not been altered by information technology, they have gained an extra dimension in business engineering. The main thrust of BE is the efficient redesign of a companys value-added chains. By definition, value-added chains are the set of connected steps running through a business which, when quickly and efficiently completed, add value to both, the company and the customer. With the appearance of enterprise software systems, information technology has become a business-modeling vehicle that can assist in the redesigning of those processes. Method of implementation Before deciding upon a BE project, the management, IT users, and the IT experts must get together to chart out Velogic Airlines Limited goals and identify the key processes that affect its success. Next, those processes should be reengineered to improve their effectiveness. At this point, the BE team must establish how information technology can enhance the reengineered process. Other potential benefits of information technology should be identified, such as its role in developing a business strategy to satisfy customer requirements. The BE team must maximize and streamline business process and access whether they should be changed or perhaps thrown out, before they apply technology to them. Velogic Airlines Limited has different kinds of information systems that support different functions, organizational levels, and business processes. Most of these systems are built around different functions; business units and business processes that do not talk to each other. Because of the challenges mentioned earlier the company has decided to set up an ERP system. Oracle Application consist of a set of interdependent modules for applications such as sales and distribution, financial accounting, investment management, and human resources that allow data to be used by multiple functions and business process for more precise organizational coordination and control. The modules can communicate with each other directly or by sharing a common repository of data. ERP helps to support organization-wide process coordination and integration. It creates an integrated organization-wide platform to coordinate key internal processes of the firm. They address the issue of organizational ineffi ciencies created by isolated islands of information, business processes, and technology. Information that was previously split in different applications can seamlessly flow throughout the company so that business processes in finance, accounts; human resources, payroll and inventory can share it. The systems collects data from various key business processes and stores the data in a single comprehensive data repository where they can be used by other parts of the business. Managers emerge with more precise and timely information for coordinating the daily operations of the business and the company wide view of business processes and information flows. Select the process appoint process team for restructuring the process. Business processes are simply a set of activities that transform a set of inputs into a set of outputs for another person or process using people and tools. The strategic processes: Account Payable/Receivable Client Record Employee Record Training plans Inventory Separate systems were built over a long period of time to support discrete business processes and discreet business functions. The organizations systems rarely included vendors and customers. Managers also required IT support in order to create accounting and inventory reports, a labour- and time-intensive project that complicated the estimation of future inventory levels and product availability. In many cases, these simple reports took days to complete. It was difficult to assemble data to get an overall picture of the organizations operations. Facing increasing accounting and administrative needs, the company wanted to streamline business practices and provide better visibility into financial information. ERP systems integrate the key business processes of the company into a single software system that allows information to flow seamlessly throughout the organization. These systems focus primarily on internal processes but may include transactions with customers and vendors. The new system proposes to give employees an easy-to-use interface for creating reports, tracking sales and customers, and searching inventory lists. Prime benefits from BPR are: positive effect on service quality the entire organization can respond more efficiently to customer query and deliver information on time labor resources (improved employee morale and productivity) Customer satisfaction (quicker response to customer requests). elimination of bottlenecks and delays between steps provide simultaneous access to documents by multiple departments/people allow for quick, simple access to information elimination of redundancies of work and improves accuracy decreasing defects, errors Business engineering makes companies more customer-focused and responsive to changes in the market. The organisation achieves these results by reshaping corporate structures around business processes. BE implements change not by the complete automation of a business but rather by the redefinition of company tasks in holistic or process-oriented terms. Only companies with innovative staff, products, and services as well as short development cycles, will be able to retain the market or by hope to get a bigger slice of the pie. By maximizing individual and team creativity and emphasizing a process-oriented approach, BE enables a company to realize its goals. Examples of business processes With the current practice Accounting and Finance department was not able to tell what the items available in inventory were and when they were ordered without consulting the inventory department. All entry for invoices, credit notes, accounts receivable and checks had to be continually checked with each department before entering data. Human resource Payrolls had to send report for all payments. Transferred of information was done on paper and then each department made the necessary entry or adjustment. There was no control over data transmitted and on items ordered. The traditional system also affected employee productivity. Staff members struggled to use online resources to complete daily tasks. Sales teams had difficulty tracking customer history and face difficulty to extract data from the system. It was time consuming to use the traditional system resulting delay in work and customer dissatisfaction, as they could not get the information they requested on time. After reengineering process all departments will be interconnected. Transfer of information will occur more smoothly and on time. The process will be as follows: When a reservation officer enters a customer reservation, the data flows automatically to others in the company who need to see them. The ERP system stores the reservation information where customer service representatives can track progress and know how many seats are available. Updated sales data automatically flow to the Accounting and Finance department. The system transmits the information to calculate the companys balance sheets, accounts receivable and payable ledgers and available cash. Management can view up-to-date minute data on sales and inventory at every step of the process. With the present system Accounting and Finance department get all the information automatically for instance all checks are printed now instead manually prepared. For any information required each department just have to verify on the system and it is automatically processed whereas before for all information they have to consult respective departments. Now there will be better control and resource management. After reengineering, staff members can perform customer service-related and inventory-related tasks without having to open multiple programs. Role-based security features keep sensitive information from employees who are not authorized to view it. On the other hand, managers and employees can gain access without having to call IT support to the information that they need to perform their jobs well. Employees have access to company information from a centralised point-of-entry. Through powerful analytics-reporting tools, Velogic Airlines Limited decision makers have a way to better manage operational matters, such as reservation fulfillment and inventory levels and improved management with real-time data, such as accounts receivable. IT Requirements A commonly disregarded area is the issue of information technology change. Often, the IT infrastructure changes required to implement a new ERP Oracle are not given high priority, which these technology issues otherwise, deserve. Undoubtedly, business issues should drive implementing ERP Oracle, not technology that improves business processes. Ignoring the preparation and education new information technology requires is asking for trouble. Further, IT personnel often must make the technology transition quickly. If the technology and infrastructure transition are not done well, the project, at the very least, will be delayed. Oracle Technology Oracle Applications include the license usage for Oracle 9i RDBMS and Oracle 9iAS Enterprise Edition software  [4]  18. Oracle 9i Oracle Applications run on Oracle technology. Oracle RDBMS 9i is the market leader in reliable and scalable database technology that continuously upgrades its products upgrading to the latest version is made easy with subscription to the Oracle Technical Support Service. Oracle RDBMS is the market leader with a market share of 33.8% compare to IBM which maintained a steady 30% portion of total database sales. Microsofts SQL Server product cornered 13.9% of the market. Oracle is based on three-tier architecture. This is different from the traditional client server architecture in the way that the application instead of residing on the client now resides on the middle-tier i.e. the Application Server. This enables access of application from the client-end, which just needs to have a web browser. The three tiers of Oracles architecture are as follows: Presentation tier (or user interface) This tier interfaces with the user and consists of hardware such as a PC or workstation and a web browser. This may consist of any number of client machines. Functionality /Business Logic tier- This tier provides functionality to the end users and contains the business logic (application). It provides the bridge between the first and the third tiers. Data tier This tier includes the database that contains all the data of the organization and this is encapsulated from the end users. This three-tier architecture can work on the Intranet as well as over the Internet. A typical diagrammatic representation of the three-tier architecture of Oracle is as follows: Figure 4 Oracles 3-Tier Architecture The various software components at the three tiers are as follows: Client Tier Operating System (Windows XP/7) Java enabled web browser (Internet Explorer 8.0/higher or Mozilla Firefox 4.0 of higher) Middle Tier Platform Windows NT 4.0/Windows 2000/SUN Solaris Oracle IAS Developer 2000 Server 2.1 (Forms Reports Server required for ERP component) Database Tier Platform Windows NT 4.0/SUN Solaris Oracle 9i Workgroup server Technical Strengths Oracle product being based on three-tier architecture enables resource intensive components to run on Middle tier thereby moving bulk of the processing load away from the client. Oracle Application server has built-in components which deliver high degree of scalability and consist of balancing, logging, automatic failure recovery, security, directory, and transaction components. The ERP based on Oracle is highly scalable and robust to handle volumes of clients requests concurrently. The Java Servlet Engine runs in a multithreaded environment and can process numerous client requests at one go. Hardware Infrastructure Server Sun Fire x4540 The Sun Fire x4540 storage server delivers 2 to 3 times the storage density of traditional solutions the maximum data throughput at 3 GB/sec from disk to memory, and 30% to 50% power savings at almost half of the total cost  [5]  19. The specifications of Sun Fire x4540 620 Software Oracle database will be the relational database management system installed on the server. The actual Oracle 8i will be upgraded to Oracle 9i standard Edition. Operating System Solaris 9 Operating Systems The Solaris 9 Operating environment is intended to sustain Multiprocessing multithreading. SUN Microsystems servers are designed from the ground to have Symmetric Multiprocessing. From Entry level workstation to SUNFire 15k (106 processors), SUN Microsystems employs the same architecture (UltraSparc) and Solaris OS. Also, Solaris OS is less prone to Virus attacks unlike other Operating systems  [7]  21. The Solaris platform supports; One million simultaneous processes on a single system Up to 128 CPUs on a single system More than four billion network connections 32- and 64-bit applications Two-, four-, and eight-node clusters IPv4 and IPv6 network addresses Up to 512 CPUs in a clustered environment Client Hardware The client should be linked to the server through a local area network and have the following minimum configuration: 1 processor core 2 duo 3.00 GHz 1 GB RAM 320 GB HDD Software and Operating System The client PC should be loaded with Explorer 8.0/higher or Mozilla Firefox 4.0 and should have one of the following OS: Windows XP, or Windows 7. Communications Computers and communications equipment can be connected in networks for sharing voice, data, images, sound, or even video. It is to be noted that the number of user at the company will be 60 persons. In the existing environment 30 data points are being used and with speed up to 10 mbps (megabits per second), and the proposal is to move to 100 mbps, using 60 data points, assuming that their will be 60 users. The company will need cabling whose speed is up to 100 mbps at an affordable price. Secondly, there are routers device that forwards packets of data from one LAN to another. Local Area Network (LAN) are recommended for applications transmitting high volumes of data and other functions requiring high transmission speeds, including video transmissions and graphics. LANs often are used to connect PCs in an office to shared printers and other resources or to link computers and computer-controlled machines in factories  [8]  22. Application Software Oracle Financials for Accounting Software Oracle Integrated Payroll/HR System Application supporting BS7799 Information Security Standard Information is an asset that, like other business assets, has value to an organization and consequently needs to be suitably protected. Information Security protects information from a wide range of threats in order to ensure business continuity, minimize business damage and maximize return on investment and business opportunities. Information can exist in many forms. It can be printed or written on paper, stored electronically, transmitted by post or by using electronic means, shown on films and spoken in conversation. Whatever form the information takes, means by which it is shared or stored, it should always be appropriately protected. Information security is characterized as the preservation of: Confidentiality: ensuring that information is accessible only by those authorized to have access; Integrity: safeguarding the accuracy and completeness of information and processing methods; Availability: ensuring that authorized users have access to information and associated assets when required. Figure 5 Source: BS 7799-2/2002: ISMS Specifications with Guidance for Use Increasingly, organizations and their information systems and networks are faced with security threats from a wide range of sources, including computer-assisted fraud, espionage, sabotage, vandalism, fire or flood, sources of damage such as computer hacking and denial of service attacks have become more common, more ambitious and increasingly sophisticated. The following diagram suggests a structure for the ten domains of the standard. Each domain deals with a separate topic built around administrative, technical and physical measures and driven from the top down, in other words such that its impact is felt from the management level all the way to the operational level. The 10 main control points of BS 7799 are: 1. Security Policy To provide management direction and support for information security. 2. Organizational Security To manage information security within the company 3. Asset Classification and Control To maintain appropriate protection of corporate assets 4. Personnel Security To reduce risks of human error and ensure that users are aware of information security threats 5. Physical and Environmental Security To prevent unauthorized access to information 6. Computer Operations Management To ensure the correct and secure operation of information processing 7. System Access Control To control access to information 8. System Development and Maintenance to protect the confidentiality, authenticity and integrity of information. 9. Business Continuity Planning -To ensure business continue to operate from the effect of a disaster 10. Compliance To avoid breaches of any criminal or civil law Technical Design Requirements The current system runs as three distinct and separate databases (Human Resource Payroll system, Finance Accounts system, and Inventory Management system). Currently, Velogic Airlines Limited has separate, elements in all three systems; examples include the definition of departments and divisions, which is handled manually now. While they try to maintain consistency, the systems do not demand it, so they cannot easily pull department costs across the Human Resource Payroll, Finance Accounts, and Inventory databases. Departments should be defined only once and used by all data elements. Similarly, Human Resource data on employees should only be defined once on a master screen and all databases use this same information. The proposed modules for ERP are: Human Resource and Payroll System Finance and Accounting System Inventory Management System Systems Interconnection Diagram The figure below shows the interconnection of the three modules and gives a brief description of the systems that will support Velogic Airlines Limited main activities and their requirements. Payroll System Human Resource and Payroll System Human resource and payroll systems help business develop staffing requirements; identify potential new employees; maintain employee records; track employee training, skills, transportation (allowances), salary, overtime and job performance; and help managers develop appropriate plans for employee compensation and career development. ERP systems help the company coordinate their staffing levels with sales activities and financial resources. Employee Details Basic Information on: Surname, Name, Maiden Name, Marital Status, Gender, Date of Birth, Age, NID, Social Security Number, Telephone Number, Residential Address. Manage Recruitment process Leaves management Sick Leaves, Casual Leave, Computation of Annual Leaves, Refund for Contract Officers, Maternity Leave: Study Leave, Leave without Pay, Leave with Pay: Record and Listing, Miscellaneous Leaves: e.g. Injury / Special Leaves: Record and Listing Staff Development Plan Database of qualifications: Professional! Academic/Vocational possessed by Staff. Record of all training programmes provided to Velogic Airlines Limited staff. Performance Management Monitor employee competencies for career planning. Payroll Basic Salary + Gross Salary Allowances paid by Type, e.g. Acting / Responsibility, etc Overtime paid Record of all Staff having received Incremental Credits Record of all Staff eligible to Uniform Allowances Deductions made Car Loan entitlement: Staff entitled to Car Loan and Amount Other categories of staff eligible to Car Loan 2) Finance and Accounting System Finance and accounting systems help firms keep track of their assets and fund flows. ERP systems integrate financial information with productions and sales information so that the impact of transactions can be immediately reflected on the companys balance sheets, accounts receivable and payable ledgers, and reports of cash flows. ERP systems will help to obtain up-to-the-minute reports of the companys overall financial performance. The accounting system should be operated on an integrated standard accounting package incorporating the following modules/functions: [23] General Ledger Purchasing Accounts Payable Accounts Receivable Fixed Assets Register A. General Ledger The system should also provide for: Unlimited number of sets of accounts for as many divisions as required. Balance forward facility creating new year open balances All journal entries should automatically balanced Cash movement report to show the net in flow/out flow of cash Financial statements and reports such as the Profit and Loss, Balance Sheet and Sources and Support for VAT Tax system. Rate of VAT must be more definable. The general ledger system should allow analysis of transactions by cost  ­centres at division as may be appropriate. B. Purchasing The purchase order processing system should integrate with the general ledger, purchase ledger and stock control systems. The system should provide for: identification of suppliers by name, product, order number, etc monitoring of purchase orders checking of purchase invoices against orders and deliveries for quantities and price report on outstanding orders, purchase and overdue deliveries link multiple purchase orders or Goods Received Notes to a supplier invoice C. Accounts Payable The purchase ledger should integrate with the general ledger and the purchase order processing systems. It should provide for: Unlimited number of suppliers accounts Recording and analysis of credit purchases returns and adjustments in accordance with user defined Analysis codes The recording of payment due date for each purchase invoice for settlement within credit period Printing of checks as per Velogic Airlines Limited format Support for VAT Tax system. Rate of VAT must be more definable. D. Accounts Receivable The Debtors Ledger system should integrate with general ledger system and provide for: Unlimited number of customers accounts The recording and analysis of credit sales in accordance with user-defined analysis codes Debtor classification by category Automatic generation of invoices Support for VAT Tax system. Rate of VAT must be more definable. E. Fixed Assets Register It is desirable that the Fixed Assets register be integrated with the general Ledger but, this is not an essential requirement. The system should provide for the following: User defined fixed assets codes as well as analysis codes for divisions, location, and types of assets, etc. Calculation of depreciation using either straight line or written down value methods Re-evaluation of assets Memorandum entries for each asset to keep track of the assets profile from acquisition to disposal in terms of maintenance, repairs, insurance, down-time replacement date, on loan 3). Inventory Management System Since the inventory system is a perpetual system, all transactions are posted at the time of entering, regardless of the transaction date. Therefore, if an inventory valuation is required for month-end, this report must be produced at the last working day after all current month transactions are posted and before any transactions f

Role of E6AP in Malignancies and Tumorigenesis

Role of E6AP in Malignancies and Tumorigenesis INTRODUCTION Leukemia is a malignant hematological disorder characterized by proliferation of abnormal white cells that infiltrate the bone marrow, peripheral blood and other important organs. Leukemia arising from myeloid cells is known as Myeloid Leukemia which may either be chronic myeloid leukemia (CML) and/or acute myeloid leukemia (AML). AML is a complex disease caused by mutations, deregulated gene expression and epigenetic modifications leading to increased proliferation and decreased differentiation of hematopoietic progenitor cells. Several important molecular markers have been discovered in AML to better characterize patients. C/EBPÃŽ ± is an important regulator of Granulopoiesis. Several groups have reported mutations in the C/EBPÃŽ ± gene in a subset of patients with AML presenting with normal karyotypes. A significant percentage of AML patients without chromosomal translocations have demonstrated abnormalities in C/EBPÃŽ ± protein or function, suggesting that loss of transcriptional control is a common mechanism of leukemogenesis. Even in the setting of other proleukemogenic genetic abnormalities, such as the (8; 21) translocation, C/EBPÃŽ ± has been demonstrated to be aberrantly regulated, in this case by down regulation of expression. Functional alterations of C/EBPÃŽ ± in AML include mutations of the C/EBPÃŽ ± gene and deregulated expression of C/EBPÃŽ ± by chromosomal translocations. Further, post-transcriptional or post-translational suppression of C/EBPÃŽ ± has been demonstrated to be involved in hematopoietic malignancies. AML is also characterized as, a malignant disease of hematopoietic system in which cells accumulate in an undifferentiated state due to mutations that prevent their normal differentiation and allow undifferentiated cells to survive and proliferate. The molecular changes that occur in AML usually lead to either abnormal cell proliferation (FLT3 and Ras mutations) or block in differentiation (AML1/ETO, PML/RAR alpha, C/EBPalpha mutation s) or suppression of apoptosis (bcl2 overexpression). Despite of block in differentiation, native AML cells often show some morphological signs of differentiation that allow a classification into different subsets, and further differentiation may be induced by exposure to various soluble mediators, e.g., all trans-retinoic acid (ATRA) and several cytokines in t(15;17). All-trans retinoic acid (ATRA) is a derivative of vitamin A and it affects cellular development including haematopoiesis, in particular granulocytic differentiation. ATRA could induce a dose-dependent differentiation of HL-60 promyeloblasts to mature, functioning neutrophils. ATRA induces growth inhibition, differentiation, and apoptosis in cancer cells, including acute promyelocytic leukemia (APL). In APL, expression of promyelocytic leukemia protein retinoic acid receptor (PMLRARÃŽ ±) fusion protein, owing to the t (15; 17) reciprocal translocation, leads to a block in the promyelocytic stage of differentiation. E3 Ubiquitin ligases are a large family of proteins engaged in the regulation of protein turnover and activity through a multistep proteolytic cascade, called ubiquitination. Ubiquitination of a target protein involves 2 distinct steps: covalent attachment of multiple ubiquitin molecules to the protein substrates and degradation of the polyubiquitylated proteins by the 26S proteasome system. The first step is mediated by a cascade of 3 enzymes: ubiquitin activating enzyme (E1), ubiquitin conjugating enzyme (E2), and ubiquitin ligase (E3) [1, 2]. Ubiquitin is a 76-amino acid polypeptide that is highly conserved among eukaryotic organisms. It is first activated in an ATP-dependent manner via binding to E1 through a thioester bond between a cysteine residue at the active site of E1 and the C-terminal glycine (G76) of ubiquitin. Activated ubiquitin in an E1-ubiquitin complex is then transferred to E2, which also participates in the formation of a thioester bond between its active site cy steine residue and the G76 of ubiquitin. Finally, ubiquitin is covalently attached to the target protein through an is opeptide bond between the G76 of ubiquitin and the ÃŽ µ-amino group of an internal lysine residue of the target protein, in a reaction catalyzed by E3 ligase. Subsequent to the linkage of ubiquitin to the target protein, a polyubiquitin chain is formed in which the C-terminus of each ubiquitin moiety is linked to a specific lysine residue (most commonly Lys48) of the previous ubiquitin to form K48-linked polyubiquitylated conjugates which are rapidly recognized by the 19S regulatory subunit of the 26S proteasome and degraded by the 20S core particle [1-3]. There are approximately 600 E3 ligases in the human genome that can be classified into 3 major types the N-end rule ubiquitin ligases; HECT-type; and the RING-type, on the basis of domain structure and substrate recognition[1]. The N-end rule ubiquitin E3 ligases target protein substrates bearing specific destabilizing N-terminal residues, including Arg, Lys, His (type I) and Phe, Trp, Leu, Tyr, Ile (type II)[1]. The second type HECT (homology to E6AP C-Terminus) E3-ubiquitin protein ligases, found from yeast to humans range in size from 80kDa to more than 500kDa. They are characterised by the HECT domain, a C-terminal region of approximately 350 amino acids in length with significant similarity to C-terminus of E6AP. Unlike RING E3s which act as scaffolds facilitating interaction between E2s and substrates, HECT E3 ligases form an intermediate thioester bond with the ubiquitin C-terminus through an evolutionarily conserved cysteine residue before catalyzing substrate ubiquitination. Hence, HECT E3s play a direct catalytic role in the final attachment of ubiquitin moieties to target proteins. The N-terminus is highly variable and may be involved in substrate recognition. On the basis of distinct amino acid sequence motifs within the N-terminus, human HECT E3s can be classified into 3 sub-families: HECT E3s with RLDs (RCC1-like domains, termed as HERC (HECT and RCC-1like domain E3s), HECT E3s with WW domains (called Nedd4/Nedd4- like E3s), and HECT E3s that neither contain RLDs nor WW domains (called SI(ngle)- HECT E3s). E6AP, the prototype of HECT E3 family belongs to the third sub-family of HECT E3 ligases [3-5]. The third and the largest type of E3 ligase is the RING (Really Interesting New Gene) family. RING-based E3 ligases are specified by over 600 human genes surpassing 518 protein kinase genes. These are characterised by a classic C3H2C3 or C3HC4 RING finger domain with a characteristic linear sequence Cys-X2-Cys-X9-39-Cys-X1-3-His-X2-3-Cys/His-X2-Cys-X4-48-Cys-X2-Cys, where X can be any amino acid. The RING domain provides a docking site for the E2 enzyme, which mediate transfer of ubiquitin to the substrate, facilitating assembly of mono- or polyubiquitylated conjugates via different lysine residues of ubiquitin. The resulting modifications have a diverse range of biological functions, from proteasome-dependent proteolysis (Lys48- and Lys 11-linked polyubiquitin) to post-translational regulation of protein function, structure, assembly, and/or localization (Lys 63 and other linkages)[1, 6]. E3 ligases can also be classified into single subunit E3s (e.g. Mdm2, Cbl) and multi-subunit complexes (APC, SCF). E3 enzymes bind their target substrates through various protein-protein interaction domains (e.g. WD 40 repeats). However, for substrate recognition post-translational modifications such as phosphorylation or proteolytic cleavage are required[7]. The modified motif in the substrate is called degron. There are many different types of degrons (e.g. phosphodegron, PEST). Once modified, a degron in a substrate might be recognized by a specific E3 ligase, which forms the basis for its subsequent ubiquitination[8]. Through ubiquitin-mediated covalent modification of diverse range of cellular proteins, E3 ubiquitin ligases regulate several cellular functions or biological processes such as cell cycle progression, Oncogenesis, signal transduction, transcription regulation, DNA repair, endocytois, transport and development via proteolytic or non-proteolytic mechanisms [2, 9]. A direct molecular link between cell-cycle control, Oncogenesis and E3 ubiquitin ligase activity was supported by several clinical findings and wealth of experimental data on E6AP, SKP2 and FBW7, Nedd 4-1, Pirh2, CDC20, CDH1 and also on other E3 ligases [3, 10, 11]. Understanding the physiological role of E6-AP, the founding member of the HECT E3 family, is of interest because inactivation of UBE3A gene encoding E6AP has been associated with Angelman Syndrome, a hereditary neurological disorder. Moreover, in the case of cervical cancer, the E6/E6-AP complex not only targets p53 for ubiquitin-mediated degradation, but also targets other proteins, which is necessary for HPV-induced cervical carcinogenesis[12]. E6-AP forms a stable complex with the adaptor protein E6. The dimeric complex binds to and targets p53 for ubiquitin-mediated proteolysis, thus eventually interfering with the negative growth regulating activities of this tumor suppressor protein [13-15]. In addition, the expression of E6-AP protein is decreased in human invasive breast and prostate cancers compared with their adjacent normal tissues. This down-regulation of E6-AP is accompanied by the elevation of ER in breast and AR in prostate carcinomas[16]. Furthermore, in vivo data fro m E6-AP-knockout animals indicated that the expression levels of ER and AR are increased in E6-AP-null mammary and prostate glands, respectively, when compared with that of normal control animals, suggesting that E6-AP modulates the protein levels of ER in breast and AR in prostate glands [17]. E6AP, a 100-kDa cellular protein is a member of functionally related E3-ubiquitin-protein ligases defined by the domain homologous to the carboxy terminus hect domain.20 E3 ligases ubiquitinate and degrade several regulatory proteins including p53, p27, promyelocytic leukemia retinoic acid receptor ÃŽ ± and others, which serve as tumor suppressors and cell-cycle inhibitors. E6AP promotes C/EBPÃŽ ± ubiquitination leading to its proteasome-mediated degradation and thus functional inactivation. E6AP negatively regulate Granulopoiesis by targeting C/EBPÃŽ ± for degradation via ubiquitin proteasome pathway. Promyelocytic leukemia tumor suppressor (PML) has been recently identified as a target of catalytically active form of E6AP. PML tumor suppressor is essential for the formation of PML nuclear bodies. Recent studies have implicated role of PML and PML nuclear bodies in the regulation of growth inhibition, senescence and apoptosis. PML is down regulated in multiple human cancers and experimental data has correlated reduced PML activity and expression to E3 ubiquitin ligase activity of E6AP, regulating protein turnover and activity[18]. Recently, Annexin I involved in the inhibition of cell proliferation, regulation of cell differentiation, anti-inflammatory effects, cell death signalling, carcinogenesis has been identified as a novel target of E6AP in addition to classical substrates, including p53 tumor suppressor, PDZ domain-containing protein scribble, a transcriptional repressor of the gene encoding hTERT[19]. In addition, studies have also implicated the role of E6AP ubiquitin ligase activity in ubiquitin-dependent degradation of Peroxiredoxin1 and presumably open avenues to investigate the functional link between lack of E6AP expression and stability of Peroxiredoxin 1with regard to the pathogenesis of Angelman syndrome[20]. p53 is targeted for proteasomal degradation by mdm2 which is a p53 target gene containing E3 ubiquitin ligase activity[21]. While mdm2 targets p53 for degradation, mdm2 is self -ubiquitinated and degraded. Cyclin dependent kinase inhibitor p21waf/cip, another p53 target gene, is degraded by proteasome and GSK3 (glycogen synthase kinase 3) mediated phosphorylation [22]. Rb (Retinoblastoma) protein is a tumor suppressor and negatively regulates G1/S transition by interacting with E2F transcription factor. Rb protein is degraded in an ubiquitin dependent manner [23]. In addition, free E2F is also degraded in ubiquitin dependent manner by the 26S proteasome. Thus, collectively HECT domain containing E3 ligases are important for homeostasis of protein levels and defects in their function may lead to various diseases including cancer. Thus, wealth of experimental data and clinical findings identifying many substrates targeted by E3 ubiquitin ligases, indicate that the deregulation of Ubiquitin proteasome system in cell cycle control is tightly linked to malignancies and tumorigenesis. Due to the above relevance and role of E6AP in malignancies and tumorigenesis The project is based on the expression, purification and validation of GST tagged protein that is GST- E6AP. The current study includes Cell culture: HL-60 cells, a human promyelocytic leukemia cell line. HL-60 cells treated with 1uM ATRA for 0,24 and 48 hours. GST- E6AP Protein expression and purification: GST-E6AP Pull down: Objectives: 1) Expression of GST and GST-E6AP plasmids in BL21 strain of E.Coli 2) Purification of GST and GST-E6AP proteins from BL21 strain of E.Coli 3) Validation of expression through western blotting 4) To detect GST-E6AP protein interaction with whole cell lysates of HL-60 cells treated with 1ÃŽ ¼M ATRA for 0, 24 and 48 hrs GOMTI NAGAR EXTENSION, LUCKNOW

Ethan Frome Essay -- Essays Papers

Ethan Frome Ethan Frome written by Edith Wharton in 1905 is a novel about the dilemmas of a poor New England farmer named Ethan Frome, his wife Zeena, and Zeena's cousin, Mattie Silver. The first person narrator, an engineer, comes to the town of Starkfield and becomes curious about the crippled, taciturn Ethan Frome. The tragic consequences of Ethan's unhappy marriage and forbidden love are revealed in a flashback to twenty-four years before the narrators arrival in Starkfield. In 1992, a movie was made of Ethan Frome which kept this plot in tact but included a number of changes in how the story was narrated and in some of the details about the characters and the plot. Some of the changes were effective; others were not so effective. Some of these changes didn't even make that much of an effect on the way the movie was compared with the book. One of these changes would have to be that the narrator was an engineer in the book and in the movie he was a minister. This change was not that big of a deal. This seems like it wouldn't really make that much of a difference. In the movie they didn't go into that much detail about before the accident so it mad no difference if the narrator was an engineer or a minister. Either way it would have made no difference if he was a bartender or an exotic dancer. It may or may not have made the story a little more interesting, but who really cares what the narrator's occupation is. Some of the changes in the book seemed to m...

Analysis of The Maltese Falcon Essay example -- Movie Film Maltese Fal

Analysis of The Maltese Falcon The Maltese Falcon, was not only a detective film, but a film that displayed many different aspects of the female and the male character in the movie. The film was more than a story, but a story that explored the ideas of the detective genre and the different characteristics of femininity and masculinity. It also brought forth subjects of sexual desires and the greediness of money. The characters and the visual motifs in the film contributed to the developing of the plot and assisted in creating a more detective and gender oriented film. In the film, The Maltese Falcon, the role of men and women are portrayed in different ways in the film to show the distinct functions of masculinity and femininity between the characters. Sam said to Effie, ?Your a nice rattle brain angel.? Sam Spade?s assistant, Effie is a conservative and a practical woman. As the detective?s assistant, she possesses more of masculine qualities than feminine qualities. Since she works in an environment around men, she has a tendency to be more influenced by their activities and their ideas. Sam said to Effie, ?Your a detective darling.? Her voice seems to be monotone which shows her as a strong and an independent person. Although she may act this way, she is still a woman who is somewhat ladylike and very polite. In some ways, women are used to bring forth the ideas of sex and lust, but in this case, Effie?s role was necessary in helping the story to develop and to present how the role of woman could be played and perceived. Sam said to Effie, ?Your a good man, sister.? Effie possessed many masculine qualities and this quote helped to reinforce the idea of it all. Another female role that was a part of the film was Iva, who was the wife of Miles. She was very lady-like and beautiful which helped her to use her image and personality in a way to receive certain things. Miles was Sam Spade?s partner in the detective business. Her character as a woman is somewhat different from Effie?s. Iva and Sam Spade once had a history together even though she was married to Miles. Iva said to Sam, ?You killed my husband, Sam, be kind to me.? She sets up a different role for woman because of her actions and of the characteristics that she possesses. In a way, she thinks that Sam Spade is in love with her and for that reason, she thought that he had killed her hus... ...ch character. Although Effie took on a female role, she possessed many masculine characteristics which allowed it possible for her to get along with the men in the film. The other women in the film took on the classic role of the female characters as helpless, seductive, or conniving. The male characters took on the customary roles as the ones who were strict and cautious, while others sought only for lust and money. Some of the male characters were able to control their feelings and did not allow their emotions to come in the way of their moral decisions while some couldn?t restrain themselves from the lustful feelings they had inside. Sam said to Brigid, ?If they hang you, I will always remember you...you never played square with me for the half hour to the stretch that I?ve known you.? Even though Sam had feelings for Brigid, he was still going to turn her in for the murder she had committed. He was not going to allow his desires for her come between his morals and his profess ion. Through this many things were accomplished such as portraying the genre of detectives, the genre of female and male figures, and the roles that the characters which led up to the ending of the story.

Aeneas and His Ghosts :: Aeneas Presentation

Aeneas and His Ghosts The Aeneid Written by Virgil Translation by Fitzgerald I.Pious Aeneas (his background and key characteristics) †¢Mother is Venus (the Greek Aphrodite) Page 54, Book II, Lines 775-777 â€Å"Stepping before me, radiant through the night,My loving mother came: immortal, tall, And lovely as the lords of heaven know her.† †¢Ã¢â‚¬Å"Favored by Jupiter† Page 164, Book VI, Lines 190-193â€Å"†¦ A few Whom a benign Jupiter has loved or whom Fiery heroism has borne to heaven, Sons of gods, could do it†¦Ã¢â‚¬  †¢Fated oThe gods respect his fate. Page 11, Book I, Lines 319-322 â€Å"Surely from these the Romans are to come In the course of the years, renewing Teucer’s line, To rule the sea and all the lands about it,According to your promise†¦Ã¢â‚¬  ï‚ §He will found the land where Rome will later stand. Page 12-14, Book I, Lines 352-354, 373-375 â€Å"No, he, your son – now let me speak of him, In view of your consuming care, at length, Unfolding secret fated things to come-† â€Å"And call by his own name his people Romans. For these I set no limits, world or time, But make the gift of empire without end.† ï‚ §He is fated to go to the Underworld. Page 164, Book VI, Lines 214-217 â€Å"Pull away the bough. It will come willingly, Easily, if you are called by fate. If not, with all your strength you cannot conquer it, Cannot lop it off with a sword’s edge.† †¢Receptive and Open. oAeneas constantly looks for signs from the gods as to what his actions should be and listens/ follows through when he is nudged in the right direction. Page 110, Book IV, Lines 545-551 â€Å"Duty-bound, Aeneas, though he struggled with desire To calm and comfort her in all her pain, To speak to her and turn her mind from grief, And though he sighed his heart out, shaken still With love of her, yet took the course heaven gave him And went back to the fleet†¦Ã¢â‚¬  oIn all his interactions with his crew, wife, father, Dido, other leaders, the gods, etc., Aeneas listens instead of tooting his own horn (Odysseus), knowing there is a lot to be gained from others. †¢Aeneas is dutiful. oBrings the household gods. Page 65, Book III, Lines 16-18 â€Å"†¦I took to the open sea, Borne outward into exile with my people, My son, my hearth gods, and the greater gods† oCarries Anchises from Troy on his back and holds his opinion in high regard. Page 55, Book II, Lines 829-830 â€Å"†¦I looked for him at once, My first wish being to help him to the mountains;† Page 58, Book II, Lines 921-924

Personal Anecdote

Autobiography Anecdote I intend to write about the time when I broke my wrist. I am writing this autobiographical anecdote In 1st person and my target audience is students. The purpose of this text Is to write a recount of the event. I checked my watch for the fifth time this period, 2. Pm, only three minutes had passed since I last checked. Thirty minutes into the period and I had only completed one equation. I couldn't concentrate; I dropped my pen and looked around to find something entertaining. I found nothing. Everyone was focused and had their head down completing their set of questions.This is the difference between year seven and year eight. The classroom was so quiet that I could hear the inhaling of the person next to me. Thirty minutes till the end of school and I already had enough. My mind had stopped functioning and I struggled to keep my eyes open. It felt as if my eyelids were trying to carry an African elephant. I placed my elbow on the wooden desk and rested my hea vy head in my palm. I thought to myself, ill Just close my eyes for a minute, the teacher wont notice. Random thoughts began to run through my head as I continued to rest In class.I suddenly recalled a past memory. I said thank you to the bus driver as I hopped off the bus onto a patch of green grass. I slipped my smart rider into my right pocket as the Transparent bus drove past me with everyone inside, staring at me. I waited for the awkward moment to pass and began my walk home. It was a hot, humid day as the scorching sunlight blistered my delicate skin. I felt sweat begin to run down my forehead and the back of my uniform began to stick to my body like old glue. The weather was horrible but it wasn't the main reason why I was uncomfortable. I was nervous.I was thinking of how I should tell my mum I wanted to play football. FALL, not soccer. I knew what her answer was going to be, â€Å"No you can't, Its too dangerous. † I continuously ran comebacks In my head trying to f ind the right one which would convince her to let me play but not be rude and make her angry. I did this for the whole walk home and I had forgotten about the piercing sunlight and humidity. As soon as I dumped my school bag in my room and changed from my uniform, which was drenched in my sweat, I decided to ask my mum. â€Å"Hey mum† I said in the sweetest tone possible, â€Å"can I play football for a lube? â€Å"why do you want to play football, its too dangerous† replied mum firmly â€Å"mum please, all my friends are playing too† â€Å"why can't you play basketball or swimming? † â€Å"l don't mind them but I really like footy mum, please† â€Å"Fine but if you get injured it not my fault. † miss! Thank you so much, don't worry It wont happen. † The whaling sound of the school siren woke me. Everyone was already rushing out of class and I still had to pack up my things. Personal Anecdote Autobiography Anecdote I intend to write about the time when I broke my wrist. I am writing this autobiographical anecdote In 1st person and my target audience is students. The purpose of this text Is to write a recount of the event. I checked my watch for the fifth time this period, 2. Pm, only three minutes had passed since I last checked. Thirty minutes into the period and I had only completed one equation. I couldn't concentrate; I dropped my pen and looked around to find something entertaining. I found nothing. Everyone was focused and had their head down completing their set of questions.This is the difference between year seven and year eight. The classroom was so quiet that I could hear the inhaling of the person next to me. Thirty minutes till the end of school and I already had enough. My mind had stopped functioning and I struggled to keep my eyes open. It felt as if my eyelids were trying to carry an African elephant. I placed my elbow on the wooden desk and rested my hea vy head in my palm. I thought to myself, ill Just close my eyes for a minute, the teacher wont notice. Random thoughts began to run through my head as I continued to rest In class.I suddenly recalled a past memory. I said thank you to the bus driver as I hopped off the bus onto a patch of green grass. I slipped my smart rider into my right pocket as the Transparent bus drove past me with everyone inside, staring at me. I waited for the awkward moment to pass and began my walk home. It was a hot, humid day as the scorching sunlight blistered my delicate skin. I felt sweat begin to run down my forehead and the back of my uniform began to stick to my body like old glue. The weather was horrible but it wasn't the main reason why I was uncomfortable. I was nervous.I was thinking of how I should tell my mum I wanted to play football. FALL, not soccer. I knew what her answer was going to be, â€Å"No you can't, Its too dangerous. † I continuously ran comebacks In my head trying to f ind the right one which would convince her to let me play but not be rude and make her angry. I did this for the whole walk home and I had forgotten about the piercing sunlight and humidity. As soon as I dumped my school bag in my room and changed from my uniform, which was drenched in my sweat, I decided to ask my mum. â€Å"Hey mum† I said in the sweetest tone possible, â€Å"can I play football for a lube? â€Å"why do you want to play football, its too dangerous† replied mum firmly â€Å"mum please, all my friends are playing too† â€Å"why can't you play basketball or swimming? † â€Å"l don't mind them but I really like footy mum, please† â€Å"Fine but if you get injured it not my fault. † miss! Thank you so much, don't worry It wont happen. † The whaling sound of the school siren woke me. Everyone was already rushing out of class and I still had to pack up my things.