Biological Activities of Betulin and Betulinic Acid

Biological Activities of Betulin and Betulinic Acid Betulin is the one of the premier pure, crystalline natural product obtained from plants through extraction and sublimation of birch bark (Lowitz 1788). Betulin and betulinic acid are closely related to each other, often found together in varying amount in different plant species when extracted by different solvents . Early anti septic property of betulin and its use become famous to be used in plaster for sterilization of cuts and wound .Studies indicated that betulin carry wound healing, cholesterol lowering activity, hepato-protecteive, anti-bacterial, anti-leishmenial, anti-viral, anti-cancer activities (Wheeler1899). Due to the high mutagenecity of HIV-1 and cancers cells in order to improve the biological activity of betulin and its derivatives various strategies were applied and still going on (Csuk, 2014), here we are presenting a coverage of the betulin, betulinic acid and its derivatives with their biological activity. Study carried on lung injury showed that betulinic acid protects sepsis induced lung injury against inflammation and indicated it as a potential regulator of the inflammation. In another study the positive effect on the acute lung injury cured by betulinic acid. The septic lung injury is generally characterized by the severe oxidative stress response, in addition to available treatment new methods are required to improve further clinical outcomes (Lingaraju et al., 2015). Lingaraju and coworkers found the effect of betulinic acid using cecal ligation and puncture model on oxidative lung injury. They treated two groups of mice with different concentration of betulinic acid, further their lung and plasma samples were collected for analysis by sacrificing the mice at 18hr. of surgery. They concluded increased antioxidants level in blood that lead to reduced lung injury in mice. The role of betulinic acid induces programmed death of human red blood cells (erythroptosis) was reported, whi ch is mediated through membrane permeabilization and calcium ion load (Gao et al.2014). Afzal and his group (Afzal et al. 2014) studied on the hypothyroidism in female albino rate for 2 months by giving them standard drug propyl thio uracil (PTU) for the induction of lower level of TSH for two months. Later on the mice were treated with standard thyroxin at a dose of 10ÃŽ ¼g/kg and the test drug betulinic acid at a dose of 20ÃŽ ¼g/kg of body weight. Finally after the two months study betulinic acid treated animals showed marked improvement in the follicle integrity that showed betulinic acid has protective activity against hypothyroidism. Two groups of semi synthetic derivatives of betulin (BT01 to BT09) and betulinic acid (AB10 to AB16) were synthesized respectively which has shown antileishmanial combined-therapy with miltefosine (Sousa et al.2014). Leishmaniasis was previously treated by miltefosine, amphotericin B, pentavalent antimony compounds, pentamidine etc. but due to thei r toxicity and biological resistance new therapeutics as betulin and betulinic acid derivatives are new avenues for its treatment. Accordingly, it is important to continue the search for new effective and less toxic treatments. Effects on the cell cycle, apoptosis / necrosis events, morphology and DNA integrity with isobologram method were used for a comparative study in between miltefosine with some of the derivative synthesized during the study. The AB13 (28-(1H-imidazole-1-yl)-3,28-dioxo-lup-1,20(29)-dien-2-yl-1H-imidazole-1-carboxylate) and BT06 (3ÃŽ ²-Hydroxy-(20R)-lupan-29-oxo-28-yl-1H-imidazole-1-carboxylate) derivatives were found to be the most active, with IC50 values of 25.8  µM, and 50.8  µM respectively. Synergistic interactions were observed between these two compounds and miltefosine. Significant morphological changes were observed using AB13, while both derivatives (AB13 and BT06) produced anti-proliferative activity through cell cycle arrest at the G0/G1 phase. Neither of these derivatives induced significant apoptosis /necrosis, as indicated by phosphatidylserine externalization and DNA fragmentation assays. Not only that, neither of the derivatives induced death in macrophage cell lines. Thus, they do not present any potential risk of toxicity for the host cells. This study identified the betulin derivative BT06 and the betulinic acid derivative AB13 as promising molecules in the development of new alternative therapies for leishmaniasis, including those involving combined-therapy with miltefosine. The solubility of betulin and its derivatives has been the most significant issue in drug development from these hydrophobic molecules . To overcome this problem nano-emulsion gels of betulinic acid were formulated(Bag and Dash 2011). They tried 20 organic solvents as well aqueous alcohol mixture to synthesize renewable nano-sized 6-6-6-6-5 pentacyclic triterpenic acid . They confirmed their results of increased hydro solubility as they found nano and micrometer length fibers using atomic force microscopy as well electron microscopy. Role of betulinic acid in manipulating the significant actions and role of xenobiotic and antioxidative enzymes in cancer initiation and proliferation were studied (Kaur and Arora 2013) . They studied on the interactio ns of betulinic acid on Sprague Dawley female rats with xenobiotic metabolizing enzymes including cytochrome b5, P420, P450, NADPH cytochrome P450 reductase, and NADH cytochrome b5 reductase (mixed function oxidases ), GST, DT-diaphorase, ÃŽ ³-glutamyl transpeptidase (phase II enzymes), alone as well as in the presence of 7,12 dimethylbenzanthracene(DMBA). The reduction in glutathione content and protein content was considered in the study to get the effect of betulinic acid. They observed the lower level of mixed function oxidases those are responsible for the conversion of carcinogen to electrophile and further increase in phase II enzymes which participated in the removal of electrophiles by sulfation or conjugation under betulinic acid treatment . Also reported that betulinic acid effectively removed or neutralized the reactive species by the action of phase II enzymes and such an effect was demonstrated from the specific activities of antioxidative enzymes which were found to b e lower as compared to positive control (DMBA-treated group) and in some cases even that of untreated control. They also found a pronounced effect of betulinic acid in protecting the animals from lipid peroxidation as evident from the reduced levels of TBARS, conjugated diene, and lipid hydroperoxide formation. Inhibition of SREBP1 activity through AMPK-mTOR-SREBP signaling pathway using betulinic acid was studied (Kim et al.2013) . Insulin-resistant HepG2 cells, primary rat hepatocytes and liver tissue from high-fat fed ICR mice were used to get insight of the mechanism responsible for anti fatty liver effect . Accumulations of triglyceride are the indication of fat deposition that was analyzed by â€Å"Oil Red O staining†, which suppression was reported by betulinic acid. Calcium-calmodulin dependent protein kinase kinase (CAMKK) and AMP-activated protein kinase (AMPK) both were activated by betulinic acid while on the other hand the mammalian target of rapamycin (mTOR), pr otein levels of sterol regulatory element-binding protein 1 (SREBP1), and S6 kinase (S6K) were all reduced when hepatocytes were treated with betulinic acid for up to 24 hours. Reduced lipogenesis leading to low lipid accumulation, nuclear translocation and repressed SREBP1 target gene expression in HepG2 cells and primary hepatocytes, suppression of SREBP1 mRNA expression and activation of AMPK via phosphorylation through betulinic acid were also highlighted in the study. Overall they suggested that betulinic acid could be promising molecule effectively ameliorating intracellular lipid accumulation in liver cells preventing fatty liver diseases. Reduction in skin hyper-pigmentation using betuinic acid from Vitis amurensis root and its anti-melanogenic effect and precise mechanism underlying the anti-melanogenic activity of betulinic acid in B16F10 cells were investigated (Jin et al. (2014). Betulinic acid significantly reduced 3-isobutyl-1-methylxanthine (IBMX)-induced melanin synt hesis by inhibiting tyrosinase, tyrosinase related protein (TRP)-1, and TRP-2 expression through the modulation of their corresponding transcription factors in B16F10 cells. In addition, phosphorylation of mitogen-activated protein kinase (MAPK)/extra cellular regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K) involved in the melanogenesis processes, were ameliorated by betulinic acid treatment. Specific inhibitors were used, PD98059 (for MEK/ERK) and LY294002 (for PI3K/Akt respectively) to confirm the role of MEK/ERK and PI3K/Akt signaling pathway in the melanogenesis. Consequently, betulinic acid inhibited melanin production by tyrosinase, TRP-1, and TRP-2 inhibition through the regulation of CREB and MITF, which was accompanied with MEK/ERK and PI3K/Akt inactivation in IBMX-stimulated B16F10 cells. Finally these results expressed a novel molecular function of betulinic acid melanogenesis, which in turn enhances our understanding on the application of cosmetic therapy for reducing. Investigation were done on betulinic acid mediated fat mobilization by enhancing the level of lipolysis in adipose tissue that showed the antiobesity properties of betulinic acid with their possible mechanisms (Kim et al.2012). The lipolytic effects of betulinic acid were assayed in rat adipose tissues with inhibition of anti-lipase function and pancreatic lipase activity of betulinic acid in vitro which lead to prevent the elevation of plasma triacylglycerol levels, after oral administration of a lipid emulsion to rats where activity of cAMP-dependent phosphodiesterase was also measured. Betulinic acid inhibited pancreatic lipase activity in a dose-dependent manner at concentrations of 1.5-100à ¢Ã¢â€š ¬Ã¢â‚¬ °Ã‚ µM (ICà ¢Ã¢â‚¬Å¡Ã¢â‚¬ ¦Ãƒ ¢Ã¢â‚¬Å¡Ã¢â€š ¬ value of 21.10à ¢Ã¢â€š ¬Ã¢â‚¬ °Ã‚ µM) prevented the elevation of plasma triacylglycerol level after 2 hours of oral administration of the lipid emulsion at a dose of 100à ¢Ã¢â€š ¬Ã¢â‚¬ °mg/kg concluded the strong lipo lytic effect of betulinic acid which was mediated by cAMP-dependent phosphodiesterase inhibition. Betulinic acid exerted antiobesity effects by directly inhibiting pancreatic lipase, that can prevent the absorption of lipid from the small intestine. Recent studies on the chemical as well biological synthesis of the betulinic acid derivatives , they used fungi in combination with plant tissue culture of carrot and found that the most active derivative as , 3-(2,4-dinitrophenyl)hydrazono-lup-(20R)-29-oxolupan-28-oic acid, showed IC50values between 1.76 and 2.51ÃŽ ¼M against five human cancer cell lines (Baratto et al. 2013). The most selective, 3-hydroxy-20-(2, 4-dinitrophenyl) hydrazono-29-norlupan-28-oic acid, was five to seven times more selective for cancer cells when compared to fibroblasts. The cell cycle studies and apoptosis induction, with high cytotoxicity and selectivity on the tumour cell shown the efficacy of the transformed molecule. The design and synthesis of seco deri vtives from the alteration in the â€Å"A† ring of betulinic acid were carried (Hsin-Yi Hung 2014). A group of compounds were synthesized and their enhanced chemopreventive ability in vitro short term induced assays were done in Raji cells, C28 modified analogs shown significant activation. One of the modified derivative was found to shown 100% inhibition of EBV-EA at 1Ãâ€"103molratio/TPA ,73.4%, 35.9%, and 8.4% inhibition at 5Ãâ€"102, 1Ãâ€"102, and10molratio/TPA, respectively, comparable with curcumin at high concentration. In an investigation the role of betulinic acid co-regulation with vitamin D3,was reported that showed that betulinic acid improves insulin secretion with increasing glycogen content and glucose uptake in muscle tissue(Castro et al.2014). It was also reported that betulinic acid enhances the GLUT4 immunocontent and its translocation was supported by GLUT4 itself as well it does not cause hyper-calcemia that is very significant from the drug discovery pe rspective. In search of safe and natural treatment of obesity betulinic acid was tried as anti-obese drug on swiss albino male mice fed with high fat diet. Betulinic acid was extracted from ethanolic root extract of Clusia nemorosa (Rao et al. 2009).They treated mice at 50mg/kg body weight with control where they found significant control on the The therapeutic potential of betulinic acid on bone metastases and skeletal complications in breast cancer patients were investigated (Park et al.2014). They suggested the protective and therapeutic potential of betulinic acid on cancer-associated bone diseases. This is the first report indicating effect of betulinic acid on breast cancer cells, osteoblastic cells, and osteoclasts in the vicious cycle of osteolytic bone metastasis. Betulinic acid reduced cell viability and the production of parathyroid hormone-related protein (PTHrP), a major osteolytic factor, in MDA-MB-231 human metastatic breast cancer cells stimulated with or without tumor growth factor-ÃŽ ². An increase in the receptor activator of nuclear factor-kappa B ligand (RANKL) / osteoprotegerin ratio was blocked by betulinic acid through down regulating RANKL protein expression in PTHrP-treated human osteoblastic cells. Not only that the inhibition of RANKL-induced osteoclastogenesis in murine bone marrow macrophages an d decreased the production of resorbed area in plates with a bone biomimetic synthetic surface by suppressing the secretion of matrix metalloproteinase (MMP)-2, MMP-9, and cathepsin K in RANKL-induced osteoclasts was observed by betulinic acid. Furthermore, oral administration of betulinic acid inhibited bone loss in mice intra-tibially inoculated with breast cancer cells and in ovariectomized mice causing estrogen deprivation, as supported by the restored bone morphometric parameters and serum bone turnover markers. Taken together, these findings suggest that betulinic acid may have the potential to prevent bone loss in patients with bone metastases and cancer treatment-induced estrogen deficiency. A pioneer study on athymic nude mice, bearing MCF-7 breast adenocarcinoma xenografts was taken as in vitro cytotoxic and in vivo anti-tumor model (Damle et al. 2013). The antitumour activity of betulinic acid was studied at 50 and100 mg/kg body weights, whereas cytotoxic activity of MCF- 7 cells with IC50 value of 13.5 µg/ml was studied by MTT assay. Betulinic acid treatment shown significant reduction in tumour size of 77 and 52% tumour size (100 and 50 mg/kg body weight respectively) in addition decreased angiogenesis, proliferation and invasion in betulinic acid treated mice were also highlighted through histopathological studies. Through topomer CoMFA , some 35 derivatives of betulinic acid were prepared and tested against HT29 human colon cancer cells (Ding et al.2013) . The contour maps showed that bulky and electron-donating groups would be favorable for activity at the C-28 position, and a moderately bulky and electron-withdrawing group near the C-3 position would improve this activity. Few of the betulin derivativeswere designed and synthesized as per the modeling result, while groups such as maleyl, phthalyl, and hexahydrophthalyl (bulky electronegative groups) were directly introduced at the C-28 position. They also found consistency with predicted and actual IC50 value of the given analogsagainst HT29 cells, proving that the present topomer CoMFA model is successful and that it could potentially forward the synthesis of newbetulinic acidderivativeswith high anti-cancer activity. Five tumour cell lines were tested against three newly synthesized derivatives where 28-O-hexahydrophthalyl betulin shown the greatest anti-cancer activities and its ICà ¢Ã¢â‚¬Å¡Ã¢â‚¬ ¦Ãƒ ¢Ã¢â‚¬Å¡Ã¢â€š ¬ values were lower than other tumour cell line except DU145.In an investigation Prunella vulgaris was used for betulinic acid and ursolic acid extraction those were responsible for the anti-estrogenic effects, suggested their potential application against estrogen-dependent tumors (Kim et al. 2014).In this study Prunella vulgaris constituents were isolated and tested their individual anti-estrogenic effects. Betulinic acids, ursolic acid, Rosmarinic acid, caffeic acid, oleanolic acid, hyperoside, rutin, were isolated from the flower stalks of P. vulgaris var. lilacina Nakai (Labiatae) which showed anti-estrogenic effects as a decreased level in the mRNA of GREB1,revealed significant anti-estrogenic effects of betulinic acid and ursolic acid, on estrogen receptors .They also demonstrated the

The films Bladerunner and Fahrenheit 451 :: essays papers

The films â€Å"Bladerunner† and â€Å"Fahrenheit 451† The films â€Å"Bladerunner† and â€Å"Fahrenheit 451† are similar in the way they show emotions in their depictions of distopias. The emotions shown are not normal to us, but are controlled by the government. The inhabitants of these worlds are being persuaded that emotions are bad, unhealthy. However, some do break free from the system. The cases in these movies are not of really living at all, but just of going through the motions of life. The movie â€Å"Bladerunner† was about androids that were made to not have feelings and not to live longer than 4 years. Rachel is a good example of they tried to control emotions. As one of the new model replicants, Rachel was implanted with memories and could recall emotions. What she did not realize was that her memories were really the memories of her maker’s niece. She did not even know she was an android until Decker did the test on her. She was very upset when she realized that he was right, because she did not know what feelings were real and what feelings belonged to someone else. She worked with the man that created androids, the owner of the Tyrell Corporation, which makes her more upset that she did not know. This is when she exclaims to Decker, â€Å"I am not in the business, I AM the business.† Although she though she was living a normal human life, Rachel was going through the motions of everything humans do, but she did not have real feelings or even her own memories. Therefore, she was not even being her own self. Another aspect of the movie â€Å"Bladerunner† is of those that broke away from the system. The â€Å"Nexus 6† were androids that developed emotions and escaped from slavery, because they wanted to live longer. Roy and Priss are good examples of androids showing that they have emotions. They were manipulative, passionate for what they wanted, and even had loving sides. Roy was the leader of the â€Å"Nexus 6† and Priss was his girlfriend . Priss acted like a helpless girl to get J.F. Sebastian to let her into his house, into which she later let Roy. They made J.F. show them to the owner of the Tyrell Corporation’s house, so they could fight to get an extension on their lives.

Ellisons Invisible Man: Invisibility, Vision, and Identity as Motifs E

Ralph Ellison incorporates many symbols into this novel, each providing a unique perspective on the narrative and supporting the themes of invisibility, vision and identity. These themes can many times generally symbolize the strength of the subconscious mind. In this novel I think that there are several visions that symbolize the narrator’s escape from reality, seeking comfort in memories of his childhood or times at the college, often occurring as he fades into his music. Ellison coincidences dreams and reality to redefine the surrealistic nature of the narrator’s experience and to showcase the differences between the realities of black life and the myth of the American dream. ? One thing I saw a lot of in this novel is people willfully looking past instead of confronting the truth. The narrator repeatedly states people’s inability to see what they don’t want to see, their inability to see what their prejudice doesn’t allow them to see, has pushed him into a life of effective invisibility. But prejudice against others is not the only kind of blindness in the book. Many characters also don’t acknowledge truths about themselves or their communities, and this refusal is shown in the imagery of vision and invisibility. For example, the boys who fight in the â€Å"battle royal† wear blindfolds, symbolizing their powerlessness to recognize their corruption at the hands of the white men. The Founder’s statue at the college has empty eyes, signifying his failure to see the racist realities. Blindness also afflicts Rev Homer A. Barbee, who romanticizes the Founder, and Brother Jack, who is missing an eye which he conceals by wearing a glass eye. The narrator himself experiences blindness, such as in chapter sixteen when he addresses the ... ...judices of others. He has followed the ideology of the college and the ideology of the Brotherhood without trusting or developing his own identity. Now, however, he has realized that his own identity, both in its flexibility and authenticity, is the key to freedom. Rinehart, a master of many identities, first suggests to the narrator the limitless capacity for variation within oneself. However, Rinehart ultimately proves an unsatisfactory model for the narrator because Rinehart’s life lacks authenticity. The meaning of the narrator’s assertion that he is â€Å"an invisible man† has changed slightly since he made the same claim at the beginning of the novel: whereas at the outset he means to call attention to the fact that others cannot not see him, he now means to call attention to the fact that his identity, his inner self, is real, even if others cannot see it.

Lampara Multi-Purpose Cooperative (LMPC) Essay

I. INTRODUCTION: Lampara Multi-Purpose Cooperative (LMPC), registered with the Cooperative Development Authority on June 12, 2007 with Registration No. D-623-6240 has been organized to help people maximize their potentials to live a healthy, productive life and in the process become responsible members of Society. LMPC educates its members to earn and save the cooperative way. LMPC has recently sourced out an exclusive Systems Provider for healthy, nutritious and highly oxygenized Anti-Oxidant Pi Water originally researched and developed in Japan and enhanced in Korea. This newly structured Pi Water Systems Provider has upgraded its Pi Water System with US-made 16-stages Synergy machine that makes the Pi water an anti-oxidant water and with the German Technology oxygen-generating machine developed by the Department of Science and Technology. The Pi water produced by the system has been tested to have an even higher effect than any of the Pi Waters introduced in the Philippines to date due to its unique qualities and characteristics presented below. LMPC is now ready to distribute domestically and internationally the AQUAPORIN PI WATER SYSTEM equipped with the latest technology in Pi Water System. The investors in the Aquaporin Anti-Oxidant Pi Water Refilling Station will be assured of a profitable, unique, and healthy business venture. II. QUALITIES OF THE AQUAPORIN PI WATER: Aquaporin Pi Water has been synergized by the Bio-Nano technology to produce an even reduced water molecule clusters for greater absorption and interaction by the cells of the body, higher water-based mineral contents because of its mineral enhancer cartridge that produces a stable alkaline water with pH 7.8 on the meter, greater energy enhanced by its far infrared cartridges and higher oxygen content with its DOST-developed oxygen generating machine. It has been further powered by a Synergy machine that makes the water an anti-oxidant water. These qualities of the Aquaporin Pi Water will ensure that the water we drink is healthy, nutritious, energized and contains higher level of oxygen like no other. III. ADVANTAGES OF PURCHASING AN AQUAPORIN ANTIOXIDANT PI WATER REFILLING STATION: 1. The Aquaporin Antioxidant Pi Water Refilling System aims to optimize return of investment employing the marketing strategies adopted by LMPC. Once established, the Aquaporin Pi Water Refilling Station (APWRS) becomes a branch of LMPC to serve as the center of operation and marketing service for its members. Page 1 2. The Systems’ flagship (Aquaporin Antioxidant Pi Water’s) characteristics are: 3.1 It has the most minimal piping problems with 50 years warranty on parts. The materials used are guaranteed to survive ageing, cracking, breakage from pressure and bumps, and many more; 2.2 It employs commercial filtration and machineries in processing alkaline, mineralized and Synergized Bio-Nano Pi Waters that is capable of producing an anti-oxidant water; 2.3 It incorporates the latest technology called OPS or Oxygen Processing System that was  Department of Science and Technology (DOST) tested to have high beneficial health effect; 2.4 Its system-parts passed all standards for safe-drinking water; 2.5 Each system installed is registered in the Bureau of Health Devices and Technology (BHDT) of the Department of Health for system certification and validation of quality and functionality; 2.6 The system produces super fine water because of its nano-tech filters that renders water clusters smaller and full of energy; 2.7 The systems use the highest quality materials to ascertain quality production; 2.8 All system parts are brand new. Not a single part is reconditioned or second hand. These parts are not available cheap unless reconditioned. Beware of companies that offer very cheap systems; 2.9 System parts and labor has ONE (1) YEAR WARRANTY 2.10 Special technologies applied are exclusive and are not available in other systems; 2.11 The Aquaporin Pi Water business put up by the investor is not just a profit entity, rather, its business is banking on a mission to help share better health and MAKE A DIFFERENCE in the lives of people. 2.11 When the investor decides to put up the Aquaporin Anti-Oxidant Pi Water Refilling Station he is practically creating a niche in the market resolving any potential direct competition. 2 We offer maximum training of business standardization and operations to make sure that the Aquaporin Anti-Oxidant Pi Water Refilling Station (AAPWRS) owners are well equipped to operate, manage and run his business like a professional water refilling station operator. 3 Investor may opt to make his AAP Water Refilling Station fully automated and computerized with a minimal additional cost (see Feasibility Study/ROI attached); 4 The Systems Provider of APPWRS is composed of a team of professional engineers and exclusive contractors whose expertise comes from years of water treatment experiences aimed to GUARANTEE quality products, services and installations. IV. SERVICES TO ASSURE INVESTORS OF A â€Å"PROFITABLE, UNIQUE AND HEALTHY BUSINESS VENTURE†: 1. Consultancy and Planning (1 month Management Program) 1.1 Conduct a research and feasibility of the business in the specified area of operation; 2.2 Assist in the design of the Station renovation, engineering specifications, like floor plan, electrical plan, appearance and imaging, etc.; 2.3 Assist in business registrations, legal documentations of the company and accounting services; Page 2 2.4 Assist in the design of business concepts, logo, marketing materials, advertisements and other business forms; 2.5 Manage and teach the business for one month to make sure that all systems go smoothly and correctly. 2. Standardization: 2.1 Documentation of business operations; 3.6 Forms and compliances 3.7 Business software and programming 3. Training: 3.1 Technical training – operation of the system, maintenance, basic trouble Shooting proper handling of waters, etc.; 4.8 High standard operations and qality management 4.9 Basic bookkeeping, accounting and compliances 4.10 Sales and marketing strategies and operations 4.11 Quality assurance management 4.12 Manpower and hiring 4.13 Quality servicing and customer services management 4. 24/7 on-line helpdesk and assistance. V. APPWRS will be the LMPC BRANCHES AND SATELLITE OFFICES: The Aquaporin Anti-Oxidant Pi Water Station (APPWRS) shall become LMPC’s branches and/or satellite offices in the area. Only one (1) APPWRS will be established in a Municipality &/or District in big cities and Provinces. The LMPC program with its diversified sources of livelihood that are synergistically integrated to achieve a healthy, productive and responsible members of Society using the cooperative system of relationship will be implemented in all the areas of operation of APPWRS. VI. AQUAPORIN ANTI-OXIDANT PI-WATER SYSTEM COMPONENT: 1. The 3-in-1 Pi Filtration System – the complete Commercial Pi-producing Water System fully automated and computerized * Production machineries (cartridges and filters) to yield three (3) types of waters: (details of these machineries will be presented and discussed during the business meeting/s prior to signing of contract) * Oxygenated Ultra Fine Mineral Water * Oxygenated UF Sterilized Alkaline Synergized Water * Oxygenated UF Sterilized Bio-Nano Alkaline Antioxidant concentrated (Oz3) synergized Water. * High-end, Long-lasting Piping System * Initial Bottle Inventory Page 3 * Station Filling Equipment * Station Signage * 3-monthMaintenance Inventory * 1-month business management program * Down Payment for the cost of 1 unit of van for delivery. * Assistance in all aspects of services defined in Item IV. * Fully Automated filter-change indicator and computerized cleaning system * And many more . . . 2. 3-in-1 Pi Filtration System – the Standard Commercial Computerized Pi-producing Water System. * Production machineries (cartridges and filters) to yield three (3) types of waters: (details of these machineries will be presented and discussed during the business meeting/s prior to signing of contract) * Oxygenated Ultra Fine Mineral Water * Oxygenated UF Sterilized Alkaline Synergized Water * Oxygenated UF Sterilized Bio-Nano Alkaline Antioxidant concentrated (Oz3) synergized Water. * Fully Automated filter-change indicator * High-end, Long-lasting Piping System * Initial Bottle Inventory * Station Filling Equipment * Station Signage * 3-monthMaintenance Inventory * 1-month business management program * Down Payment for the cost of 1 unit of FB van for delivery. * Assistance in all aspects of services defined in Item IV. * And many more . . . 3. Basic Home Pi Filtration System which may be used for personal and home  purposes producing 2 types of waters (details to be presented and discussed during the business meeting/s prior to signing of contract for the APWRS) – this Personal Unit Aquaporin Pi Water System will exclusively be distributed by the APWRS. * Production machineries (cartridges and filters) to yield two (2) types of waters: * Super Fine Mineral Water * Highly Oxygenized UF Sterilized Alkaline Synergized Pi Water * High-end, Long-lasting Piping System * Assistance in all aspects of services defined in Item IV. Page 4 * 24/7 on-line helpdesk and assistance * Basic Pi Filtration System owners may opt to become satellite servicing office for LMPC * And many more . . . VII. PRICES 1. Aquaporin Antioxidant Pi Water Refilling Station with the 3-in-1 Complete Fully Automated and Computerized commercial Pi Filtration System with components described in Item VI-1 and services stated in Item V, costs ONE MILLION SEVEN HUNDRED FIFTY THOUSAND PESOS (P1,750,000.00) only, exclusive of site/location renovation/construction and 12% VAT. 2. Aquaporin Antioxidant Water Refilling Station with the 3-in-1 Pi Filtration standard commercial Pi-producing Water System with components described in Item VI-2 and services stated in Item V, costs ONE MILLION SIX HUNDRED FIFTY THOUSAND PESOS (P1,650,000.00) only; 3. Aquaporin Basic Home Pi Filtration System for personal or home use with the 2-in-1 Pi Filtration System and with components described in VI-2 would cost ONE HUNDRED TWENTY THOUSAND PESOS (P120,000.00). VIII. INSTALLATION: 1. Investor must have signed the Memorandum of Agreement for the Installation of the machines at the site or location of the business and payment of at least THIRTY PERCENT (30%) of the total contract price; 2. Water sample taken from the site/location of the Station must be submitted for analysis and potability; 3. Prior to installation, the site/location of the Station would have been inspected by an engineer from the Systems Provider. 4. One (1) week before the date of Installation, additional TWENTY PERCENT (20%) of total contract price must be remitted to LMPC, another TWENTY PERCENT (20%) upon installation and full payment within one (1) month after installation. 5. Faà §ade of the Aquaporin Antioxidant Pi Water Refilling Station must conform with standard appearance prescribed by the Systems provider.

Wiccan Beliefs and Practices

When I think of martial arts, I think about the first time I saw my first Bruce Lee movie. With all the fast movements of Karate or Tae Kwon Do, it seems as though every movie they put out about martial arts in the beginning you would have the teacher training the student and then the student taking on the teacher and once he demonstrates that he can beat the teacher or he is proficient at whatever task the teacher has assigned then he can move on to the next journey or stage. Each stage of martial arts is practiced, and each student must learn concentration. In this paper I will show you the comparison between martial arts in the United States and other countries of origin. The only reason martial arts are so great is because it strengthens each of these aspects of body and mind to make a beautiful display of movement. Martial arts are commonly associated with East Asian cultures, but are by no means unique to Asia. Throughout Europe there was an extensive system of combat martial arts, collectively referred to as Historical European martial arts, until modern times and now they are being reconstructed by several organizations. Native Americans have a tradition of open-handed martial arts, that includes wrestling and Hawaiian’s have historically practiced martial arts featuring small and large joints manipulation, it’s a mix of origins that occur in the athletic movements of Capoeira that was created in Brazil by Slaves, based on skills brought with them from Africa. Also, there is an early legend in martial 3 Comparing the teachings of martial arts in the US and Asia arts that tells the tale of an Indian monk Bodhi dharma (also called Daruma), believed to have lived around 550 A. D. He is credited with founding the meditative philosophy of â€Å"Zen Buddhism† and with influencing the unarmed combat arts of the Shaolin temple in China. The martial virtues of discipline, humility, restraint and respect are attributed to this philosophy. The teaching of martial arts in Asia has historically followed the cultural traditions of teacher-disciple apprenticeship. Students are trained in a stri ctly hierarchical system by a master instructor: Sifu in Cantonese or Shifu in Mandarin; Sensei in Japanese; Sa Bum Nim in Korean. The native peoples of North America and South America had their own martial training which began in childhood. Some First Nations men and more rarely, some women were called warriors only after they had proved themselves in battle. Most groups selected individuals for training in the use bows, knives, blowguns, spears, and war clubs in early adolescence. War clubs were the preferred martial weapon because Native American warriors could raise their social status by killing enemies in single combat face to face. Warriors honed their weapons skills and stalking techniques through lifelong training. Martial arts in the United States have evolved into everything from simple to complex system of fighting. The truth of the matter is all martial arts are similar, they teach similar principles but in different ways. It’s like religion, there are many different 4 Comparing the teachings of martial arts in the US and Asia religions but they all have something in common, they worship some form of deity. The one thing they have in common is they promote self-defense. Some martial arts are linked to spiritual or religious beliefs, philosophies such as Daoism, Shinto or Buddhism and other have their own spiritual code of honor. Martial arts are another way of saying the â€Å"art of combat† or it is a weapon used to survive. Kill or be killed. It is a set of movements used for offensive or defensive purposes (called Kata’s or forms). It can also be a set of movements used to promote health, it has structure and every movement has a meaning. It has been said that the late Bruce Lee taught that one should take the best from all arts and adapt them to whatever situation one finds oneself in. No matter where you look, or where you are in the world, you will see different kinds of martial arts dojo and training centers. Martial arts have also evolved to accommodate the needs of different ages, from kids and toddlers to grownups. For example, a dojo that offers karate can teach different classes for male and female from varying age levels. What martial arts have expanded beyond their countries of origin and become popular in the US and why? Martial arts like karate, taekwondo, judo and other oriental styles may have come from Asia. There are other forms of martial arts that originated from countries like Europe and South America. Each style has a unique facet that 5 Comparing the teachings of martial arts in the US and Asia makes them different from other martial arts, methods of training vary and may include sparring or forms (kata), which are sets or routines of techniques that are performed alone or sometimes with a partner. The Western interest in East Asian Martial arts dates back to the late 19th century, due to the increase in trade between America with China and Japan. Relatively few Westerners actually practiced the arts, and considering it to be mere performance. Exposure to martial arts during the Korean War was also significant and as Western influence grew in East Asia a large number of military personnel spent time in China, Japan, and Korea. In the late 1970s and 1980s there was an increase interest in martial arts thanks to Asian and Hollywood martial arts movies. Bruce Lee, Jackie Chan and Jet Li were prominent movie actors that are responsible for promoting Chinese martial arts. In Europe, with the rise of firearms, martial arts declined. As a result, martial arts with historical roots in Europe do not exist today, to the same extent as in Asia, since the traditional martial arts either died out or developed into sports. Swordsmanship developed into fencing. Boxing as well as forms of wrestling have endured. European martial arts have mostly adapted to changing technology so that while some traditional martial arts still exist, military personnel are trained in skills like bayonet combat and marksmanship. Some European weapon systems have also survived as for sports and as self-defense methods. 6 Comparing the teachings of martial arts in the US and Asia In conclusion when comparing Eastern religions and martial arts in the US and in Asia, how martial arts are taught and practiced differently I found that all martial arts are similar, they teach similar principles but in different ways. In order to learn martial arts you must have self- discipline. The martial virtues of discipline, humility, restraint and respect are attributed to the Zen philosophy. The teaching of martial arts in Asia has historically followed the cultural traditions of teacher-disciple apprenticeship; however in the US the teachings are more along the lines of self-defense and competition styles.

Creative Writing – “Relief”

he phone rang. It broke the silence of my seething rage. Its high piercing sound irritated me for some reason. I wanted to scream. Lisa wouldn't normally cause me to feel that way (maybe it wasn't just Lisa, but she had been getting to me recently). As twins we were supposed to share a special bond, and usually we got on really well. Despite being only four minutes older than Lisa, I often felt strangely protective of her. With curly blonde hair and brown eyes we looked totally identical, but the similarities ended there. Lisa's favourite word was change; new outfit, new boyfriend, new hairstyle and so on. I was calmer. I had two very close friends – Hannah and Angie, and a steady boyfriend – Adam. That was another part of the reason why I was at home and in such a state. I had just got to the party, after being held up with my friend Laura, who was upset about family problems. Things between Adam and I had not been going well recently, and tonight he had arranged to meet me at six, so we could talk. It was nearly seven. I feared the worst, but friends do come first. However I was not prepared for the scene that met my eyes. I stood transfixed. Something sharp went straight through my heart. There stood Lisa and Adam, alone. Two of the people closest to me, I could not believe it. I ran. A huge bubble of emotion was trying in vain to escape from with in me, but it didn't seem to know how. I could feel tears welling up. I wanted to scream, hit someone, collapse in a heap and break down and sink into the ground all at once. Then my emotions quieted and he silent tears began rolling down my cheeks. I reached the deserted bus stop, when the bus came that was deserted too. My whole life seemed deserted. As soon as I was home I dialled Hannah's number then the grim realisation hit me: All my friends were at the party, my parents were out, my older brother – Phil was out. A fresh wave of rejection, anger, betrayal and total emptiness swept over me, and suddenly I felt very tired. I peeled off my clothes and went to bed. How could Lisa have done that? It wasn't something she would do. Borrowing my clothes? Yes. Shirking chores? Yes. Forgetting favours I asked her? Yes. Trying to sort out my love life with some crazy scheme and making it worse instead? Yes. But stealing my boyfriend? No. Adam? Did the last 10 months mean nothing to him? What about all the special times we had shared together? What about all the â€Å"I love you†s? I felt the bubble return. That was when the phone rang. I left it to ring. It cut off, and then rang again. This time I answered: â€Å"Hello† â€Å"Hello, is this the Scott house?† â€Å"Yes† â€Å"Who am I speaking to?† â€Å"Ali† â€Å"Alison? This is Hertfordshire police† What on earth could the police want? A new emotion hit me: Fear. I listened with trepidation. â€Å"There has been an accident on the railway bridge; Blue Ford Fiesta, young driver, medium build, blonde curly hair. We believe it to be your sister† Lisa. It was Lisa. â€Å"Where is she? Is she ok?† I asked. â€Å"She's at Princess Alexandra hospital. I think it's best if you get yourself up there as soon as possible. Your parents are there already.† I ended the conversation. I walked over to Sarah's to see if her parents drive me. I didn't think about it, I just did it. I couldn't think. Val and Mike were out. I went over to Helen's Helen's mum asked no questions. I couldn't have answered even if she had. She drove me in silence. It was only a twenty minute journey although it seemed to last forever. I was not crying. A strange numbness had come over me. I couldn't think or do or feel anything. There seemed to be a gap where my stomach was and my heart was beating so loudly the whole of Sawbridgeworth could probably hear. Finally we reached the hospital. Helen's mum put her arm around me and led me. Somehow she knew where to go. All my resentful thoughts about Lisa had melted. I felt empty, small and absolutely terrified. I found myself sitting in a green chair. It was a sick green, the green you always find in hospitals. I could see my dad looking grave, his arm around my mum, who was silently crying. Suddenly I noticed there was an arm around me, it was Adam's. I shook it off. A doctor stood by me; he held a glass of water and a small round white tablet. He was telling me to take it. â€Å"Where's Lisa?† I asked â€Å"They did all they could for her. She wanted to tell you something. She kept calling â€Å"Ali, Ali† all the time she was conscious. She said that she loved you. We think she was driving to see you. She was driving very fast, the roads are icy† He said He didn't need to tell me anymore. I knew. Lisa. Lisa was dead. Lisa was dead. It was my fault. I began to cry. â€Å"Ali, take the pill. You need it† It was Adam's voice. I could see Charlie and Amy sitting by him, looking concerned and upset. There was something odd about that, but I couldn't figure out what. I couldn't take the pill. They didn't understand. I had killed my sister. If I hadn't gone off she never would have driven to see me. They couldn't make me take drugs to numb the pain until there was none. â€Å"Alison, this is hard enough on your parents as it is, take it for them† coaxed the doctor I looked to my dad â€Å"Ali, this is hard on all of us, especially you, take the tablet, darling† he said in a hushed tone. Time passed in a blur. I had no idea if it was day or night, or how long I had stayed in my room. My mum kept bringing me those white pills. I was numb. I slept, cried, and just sat for hours, overwhelmed by shock, guilt and sheer emptiness. One morning my mum came in and asked me to come and see Lisa's room. I followed her and my dad. For no apparent reason I was now feeling scared. My mum opened the door. It felt as though it symbolised something but I didn't know what. I gasped. Lisa's room, usually strewn with clothes, makeup and everything else under the sun, was tidy. Moreover all her stuff had been removed and it had been redecorated. I couldn't take it. I broke down. Lisa was like my other half, I was incomplete without her. It was like being half dead. My dad looked at me; I could see it hurt him even to do that. Would it always be like this? Would I serve as a constant reminder of Lisa? â€Å"Ali,† a voice called. It was a familiar voice. It was Lisa. Was I dreaming? I closed my eyes and opened them again. I was lying in my bed. Lisa was shaking me. â€Å"Ali, you left the party. I didn't get a chance to tell you†¦Ã¢â‚¬  I just looked at her, utterly bewildered. I reached out my hand and touched her. â€Å"You're alive, â€Å"I murmured. She looked a me briefly as though I was insane, then carried on, â€Å"Adam was waiting for you, and you didn't come. It was my fault things were going badly between you two, so I pretended to be you to make it all better. I was going to tell you, but I couldn't find you. I worked out what you saw, and I'm sorry.† â€Å"But Lisa, you're alive† I stammered. This time she looked at me even more quizzically, so I explained what had happened down to every last detail. â€Å"Ali,† said Angie gently, â€Å"it was a dream, it must have been. We're all fine, your mum and dad are out, and remember Charlie moved to Belgium in August.† I was totally dazed. I felt as if I had been asleep a few hundred years, instead of a few hours. â€Å"So Lisa isn't dead and she never went with Adam,† I said uncertainly. â€Å"I can't believe you even thought such a thing!† exclaimed Lisa. â€Å"Oh Ali, I'm so sorry† â€Å"Everyone's downstairs, I'll go down and explain. You come when you're ready.† said Angie. I couldn't restrain myself any longer. I whooped and threw my arms around Lisa, who looked shocked but pleased. My relief was so immense. I would never hate Lisa again. I was close on euphoric. I slipped my arm through Lisa's and we went downstairs. Amy and Miranda had made up some sandwiches, and after all that had happened I think we all needed them. I was still incredibly tired, but I felt the sudden urge to hug everyone. My emotions were running so high. When I hugged Adam he stroked my hair and whispered, â€Å"I'm sorry about everything that happened. I love you.† Before I knew it he was kissing me deeply. Charlie phoned to say â€Å"Happy new year.† Everyone looked so happy now. As Lisa said, â€Å"It's like a dream.† We all laughed. It felt so good. Relief.

Abigail Should Be Regarded as a Victims of the Puritan Society Essay

Whether in novels, movies or plays, the villains usually leave some negative impressions on the audience so that the villains basically become the most unpopular roles in the works. Because the audiences easily produce subjective consciousness following the villains’ performances in the stories, they are used to ignoring the factor that the villains also could be the victims at the same time. In the play The Crucible written by Arthur Miller, Abigail Williams is a controversial villain because she is both a typical instigator of the accusations and a victim of the Puritan society at the same time. Firstly, Abigail’s heartrending life experiences and the Puritan society environment which she lives in build her complex character. Secondly, in the affair between her and Proctor, Abigail not only loses love but also she is hated by her lover. First of all, the unpleasant past and the Puritan environment build Abigail’s complex character. To begin with, she is ruthles s because it can be shown from her attitude towards the other girlsof Salem. In order to prevent other girls from speaking out what they have done against the puritanical rules in the forest, she threatens these girls, â€Å"[†¦] I saw Indians smash my dear parents’ heads on the pillow next to mine, and I have seen some reddish work done at night, and I can make you wish had never seen the sun go down!† (Miller 20) A normal girl should never say about that. It is so early for Abigail to experience such a cruel scene as a young child. Her parents’ death greatly affects her, as a result of which this event is likely to leave a wound on her heart. She also gradually becomes ruthless because of that. In addition, the children of Puritan society were never valued by their parents and their physical and psychological health would not be developed very well. Like her contemporaries, Abigail lacks care from her uncle in her childhood. She is adopted by her uncle Parris Williams who a priest in Salem. At the beginning of the play, the narrator said:â€Å"He was a widower with no interest in children, or talent with them. [†¦] like the rest of Salem, never conceived that the children were anything [†¦] (Miller 4). Parris never cares about Abigail’s growing up and only cares about his wealth and reputation in Salem. Without the correct guidance, Abigail has to face and solve every problem she may meet in her life by herself. Even though she uses some wrongful means to achieve her purpose, she never cares about whether they are correct or not, because nobody enlightens her how to face these  difficult situations. For example, when Parris asks her what they really have done in the forest, because she fears being punished, she instigates the other girls to cover up the truth, even accusing those innocent people when they are interrogated who are the devils’ servants. Moreover, the Puritanical rules restricts the entertainments of the children’s. This also evokes these girls’ï ¼Å' especially Abigail so that they want to seek some exciting activities somewhere.Therefore, the identity of being an orphan and her miserable childhood experiences cause the ruthless and dishonest character of Abigail, and make her become a victim of the Puritan society. Furthermore, Abigail is a victim in the love affair because she loses her reputation and gets nothing in the end. Firstly, Abigail loses her innocence in villager’s eyes of Salem. When her uncle Parris is talking about her name, Parris mentions Proctor’s wife Elizabeth and he said: â€Å"she comes so rarely to the church this year for she will not sit so close to something soiled. [†¦] that you are now seven months out of their house, and in all this time no other family has ever called for your service (Miller 12). This shows that Abigail has lost her reputation in Salem. Her affair with John Proctor is already known by many people and this event causes n obody would like to employ her. As an unmarried girl, innocence is very important, unlike Proctor who has married Elizabeth. In her future life, no one would like to marry such a soiled girl. At the end of the play, Abigail’s ending is tragic: â€Å"The legend has it that Abigail turned up later as a prostitute in Boston† (Miller ECHOES DOWN THE COORIDOR). She has paid her reputation for love but she still loses Proctor’s love. When Danforth asks where he and Abigail’s affair happened, Proctor tells the truth: In the proper place –where my beasts are bedded. On the last night of my joy, some eight months past. [†¦] I beg you, sir, I beg you—see what she is. My wife, my dear good wife, took this girl soon after, sir, and put her out on the highroad. And being what she is, a lump of vanity [†¦] (Miller 110). John Proctor would rather sacrifice his reputation than harming those innocent people including his wife. He makes his mind up to save Elizabeth and expose the Abigail’s true face at the same time. This reveals Proctor’s emotions toward Abigail at this time. There is not any love is remained in his heart, only anger and hatred. Abigail is a loser in love: she loses Proctor. She is too young and impulsive so that she never considers the consequences when she falls in  love with Proctor who cannot bring her anything she wants. Thus, she gets nothing. All in all, although Abigail is a villain in this play, she is also a victim of Puritan society.