Wednesday, November 27, 2019

Biography of Grigori Rasputin

Biography of Grigori Rasputin Rasputin was a self-proclaimed ‘Mystic’ who gained great influence over the Russian royal family because they believed he could cure their son’s hemophilia. He caused chaos in the government and was murdered by conservatives seeking an end to his humiliations. His actions played a small part in the onset of the Russian Revolution. Early Years Grigori Rasputin was born into a peasant family in Siberian Russia in the late 1860s, although the date of his birth is uncertain, as is the number of siblings, even those who survived. Rasputin told stories and kept his facts confused. He claimed he developed mystical skills at age 12. He went to a school but failed to become academic, and after adolescence earned the name ‘Rasputin’ for his actions drinking, seducing and engaging in crime (violence, theft, and rape). It derives from the Russian for ‘dissolute’ (although supporters claim it derives from the Russian word for crossroads, as his village and his reputation is unwarranted).Around the age of 18, he married and had three surviving children. He may have experienced some sort of religious epiphany and traveled to a monastery, or (more likely) he was sent as a punishment by the authorities, although he didn’t actually become a monk. Here he encountered a sect of masochistic religious extremist s and developed the belief that you became closest to God when you had overcome your earthly passions and the best way to achieve this was through sexual exhaustion. Siberia had a strong tradition of extreme mysticism which Grigori fell straight into. Rasputin had a vision (again, possibly) and then left the monastery, married, and began to travel around Eastern Europe working as a mystic who claimed prophecy and healing while living off donations before returning to Siberia. Relationship with the Tsar Around 1903 Rasputin arrived in St. Petersburg, near a Russian court that was deeply interested in the esoteric and the occult. Rasputin, who combined a dirty, scruffy appearance with piercing eyes and evident charisma, and who proclaimed himself a wandering mystic, was introduced to court by members of the church and the aristocracy, who were looking for holy men of common stock who would appeal to the court, and who would thus boost their own importance. Rasputin was perfect for this, and was first introduced to the Tsar and Tsarina in 1905. The Tsar’s court had a long tradition of holy men, mystics and other esoteric people, and Nicholas II and his wife were heavily involved in the occult revival: a succession of con people and failures went through, and Nicholas thought he was in contact with his dead father.1908 saw arguably the crucial event of Rasputin’s life: he was called to the royal palace while the Tsar’s son was experiencing hemophiliac bleeding. Whe n Rasputin appeared to have aided the boy, he informed the royals that he believed the future of both the boy and the ruling Romanov dynasty were deeply connected to him. The royals, desperate on behalf of their son, felt desperately indebted to Rasputin and allowed him permanent contact. However, it was in 1912 when his position became unassailable, due to a very lucky coincidence: the Tsarina’s son fell almost fatally ill during an accident and then a coach ride and experienced a sudden recovery from a near-fatal tumor, but not before Rasputin was able to telephone through some prayers and claims to have interceded with god.During the next few years, Rasputin lived something of a double life, acting as a humble peasant while around the immediate royal family, but outside living a debauched lifestyle, humiliating and seducing noble women, as well as drinking heavily and consorting with prostitutes. The Tsar rejected complaints leveled against the mystic, even exiling some of his accusers. Compromising photographs were hushed up. However, in 1911 the dissent became so great Prime Minister Stolypin issued the Tsar with a report on Rasputin†™s actions, which prompted the Tsar to bury the facts.   The Tsarina remained both desperate for aid for her son and in Rasputin’s thrall. The Tsar, also afraid for his son, and pleased that the Tsarina was placated, now ignored all complaints.   Rasputin also pleased the Tsar: Russia’s ruler saw in him the sort of simple peasant rusticity they hoped would support them in leading a return to a more old fashioned autocracy. The royal family felt increasingly isolated and welcomed what they thought was an honest peasant friend. Hundreds would come to see him. Even his blackened fingernail clippings were taken as relics. They wanted his magical powers for their ills and his powers over the Tsarina for more earthly issues. He was a legend across Russia, and they bought him many gifts. They were the Rasputinki. He was a huge fan of the phone, and could almost always be reached for advice. He lived with his daughters. Rasputin runs Russia When in 1914 World War I began, Rasputin was in the hospital after he’d been stabbed by an assassin, and he was against the war until he did a U-turn having realized the Tsar was going ahead anyway. But Rasputin began to have doubts about his abilities, he felt he was losing them. In 1915 Tsar Nicholas personally took over the military operations to try and halt Russia’s failings, replacing a man Rasputin had arranged to have replaced. He traveled to the front, leaving Alexandria in charge of internal affairs.Rasputin’s influence was now so great he was more than simply the Tsarina’s advisor, and he began to appoint and fire people to and from positions of power, including the cabinet. The result was a carousel which depended entirely on Rasputin’s whims than any merit or status, and a swift succession of ministers who were sacked before they could learn the job. This created massive opposition to Rasputin and undermined the entire ruling Romanov re gime Murder There were several attempts on Rasputin’s life, including a stabbing and soldiers with swords, but they failed until 1916, when supporters of the autocracy- including a Prince, a Grand Duke and a member of the Duma- joined forces to kill the mystic and save the government from any further embarrassment, and stop calls to replace the Tsar. Also crucial to the plot was a personal matter: the ringleader may have been a self-hating gay man who had asked Rasputin to ‘cure’ him, but who became involved in an unusual relationship with him. Rasputin was invited to Prince Yusupov’s house, where he was given a poisoned meal, but as he failed to die immediately he was shot. Although injured Rasputin tried to flee, where he was shot again. Then the group bound Rasputin and threw him into the Neva River. He was twice buried and dug up, before being cremated by a roadside.Kerensky, a man who led the provisional government in 1917 after the revolution replaced the Tsar, a nd who knew a thing or two about failing to govern the divided nation, said that without Rasputin there would have been no Lenin. This was among the other causes of the Russian Revolution. The Romanov rulers werent just deposed, but executed by the Bolsheviks falling as Rasputin predicted.

Saturday, November 23, 2019

Domestication History of Squashes (Cucurbita spp)

Domestication History of Squashes (Cucurbita spp) Squash (genus Cucurbita), including squashes, pumpkins, and gourds, is one of the earliest and most important of plants domesticated in the Americas, along with maize and common bean. The genus includes 12-14 species, at least five of which were domesticated independently, long before European contact in South America, Mesoamerica, and Eastern North America. Five Main Species The designation cal BP means, roughly, calendar years ago before the present. Data in this table has been assembled from a variety of available sources, listed in the bibliography for this article. Name Common Name Location Date Progenitor C. pepo spp pepo pumpkins, zucchini Mesoamerica 10,000 cal BP C. pepo. spp fraterna C. moschata butternut squash Mesoamerica or northern South America 10,000 cal BP C. pepo spp fraterna C. pepo spp. ovifera summer squashes, acorns Eastern North America 5000 cal BP C. pepo spp ozarkana C. argyrosperma silver-seeded gourd, green-striped cushaw Mesoamerica 5000 cal BP C. argyrosperma spp sororia C. ficifolia fig-leafed gourd Mesoamerica or Andean South America 5000 cal BP unknown C. maxima buttercup, banana, Lakota, Hubbard, Harrahdale pumpkins South America 4000 cal BP C. maxima spp adreana Why Would Anybody Domesticate Gourds? Wild forms of squashes are harshly bitter to humans and other extant mammals, but there is evidence that they were harmless to mastodons, the extinct form of elephant. Wild squashes carry cucurbitacins, which can be toxic when eaten by smaller bodied mammals, including humans. Large-bodied mammals would need to ingest a huge amount to have an equivalent dose (75-230 whole fruits at once). Interestingly, when the megafauna died off at the end of the last Ice Age, wild Cucurbita declined. The last mammoths in the Americas died off about 10,000 years ago, around the same time squashes were domesticated. See Kistler et al. for a discussion. Archaeological understanding of squash domestication process  has undergone a considerable rethinking: most domestication processes have been found to have taken centuries if not millennia to complete. In comparison, squash domestication was fairly abrupt. Domestication was likely in part the result of human selection for different traits related to edibility, as well as seed size and rind thickness. It has also been suggested that domestication may have been directed by the practicality of dried gourds as containers or fishing weights. Bees and Gourds Evidence suggests that cucurbit ecology is tightly bound up with one of its pollinators, several varieties of an American stingless bee known as Peponapis or the gourd bee. Ecological evidence (Giannini et al.) identified a co-occurrence of specific types of cucurbit with specifics type of Peponapis  in three distinct geographic clusters. Cluster A is in the Mojave, Sonoran and Chihuahan deserts (including P. pruinosa); B in the moist forests of the Yucatan peninsula and C in the Sinaloa dry forests. Peponapis bees may well be crucial to understanding the spread of domesticated squash in the Americas, because bees apparently followed the human movement of cultivated squashes into new territories. Lopez-Uribe et al. (2016) studied and identified molecular markers of the bee P. pruinosa in bee populations throughout North America. P. pruinosa today prefers the wild host C. foetidissima, but when that is not available, it relies on domesticated host plants, C. pepo, C. moschata and C. maxima, for pollen. The distribution of these markers suggests that modern squash bee populations are the result of a massive range expansion from out of Mesoamerica into the temperate regions of North America. Their findings suggest that the bee colonized eastern NA after C. pepo was domesticated there, the first and only known case of a pollinators range expanding with the spread of a domesticated plant. South America Microbotanical remains from squash plants such as starch grains and phytoliths, as well as macro-botanical remains such as seeds, pedicles, and rinds, have been found representing C. moschata squash and bottle gourd in numerous sites throughout northern South American and Panama by 10,200-7600 cal BP, underlining their probable South American origins earlier than that. Phytoliths large enough to represent domesticated squash have been found at sites in Ecuador 10,000-7,000 years BP and the Colombian Amazon (9300-8000 BP). Squash seeds of Cucurbita moschata have been recovered from sites in the Nanchoc valley on the lower western slopes of Peru, as were early cotton, peanut, and quinoa. Two squash seeds from the floors of houses were direct-dated, one 10,403–10,163 cal BP and one 8535-8342 cal BP. In the Zaà ±a valley of Peru, C. moschata rinds dated to 10,402-10,253 cal BP, alongside early evidence of cotton, manioc and coca. C. ficifolia was discovered in southern coastal Peru at Paloma, dated between 5900-5740 cal BP; other squash evidence that has not been identified to species include Chilca 1, in southern coastal Peru (5400 cal BP and Los Ajos in southeastern Uruguay, 4800-4540 cal BP. Mesoamerican Squashes The earliest archaeological evidence for C. pepo squash in Mesoamerica comes from excavations carried out during the 1950s and 1960s in five caves in Mexico: Guil Naquitz in Oaxaca state, Coxcatln and San Marco caves in Puebla and Romero’s and Valenzuela’s caves in Tamaulipas. Pepo squash seeds, fruit rind fragments, and stems have been radiocarbon dated to 10,000 years BP, including both direct dating of the seeds and indirect dating of the site levels in which they were found. This analysis allowed also to trace the dispersion of the plant between 10,000 and 8,000 years ago from south to north, specifically, from Oaxaca and southwestern Mexico toward Northern Mexico and the southwestern United States. Xihuatoxtla rockshelter, in tropical Guerrero state, contained phytoliths of what may be C. argyrosperma, in association with radiocarbon dated levels of 7920/- 40 RCYBP, indicating that domesticated squash was available between 8990-8610 cal BP. Eastern North America In the United States, early evidence of initial domestication of Pepo squash comes from different sites from the central midwest and the east from Florida to Maine. This was a subspecies of Cucurbita pepo called Cucurbita pepo ovifera and its wild ancestor, the inedible Ozark gourd, is still present in the area. This plant formed part of the dietary complex known as the Eastern North American Neolithic, which also included chenopodium and sunflower. The earliest use of squash is from the Koster site  in Illinois, ca. 8000 years BP; the earliest domesticated squash in the midwest comes from Phillips Spring, Missouri, about 5,000 years ago.   Sources Dillehay TD, Rossen J, Andres TC, and Williams DE. 2007. Preceramic Adoption of Peanut, Squash, and Cotton in Northern Peru. Science 316:1890-1893.Fuller DQ, Denham T, Arroyo-Kalin M, Lucas L, Stevens CJ, Qin L, Allaby RG, and Purugganan MD. 2014. Convergent evolution and parallelism in plant domestication revealed by an expanding archaeological record. Proceedings of the National Academy of Sciences 111(17):6147-6152.Giannini TC, Lira-Saade R, Ayala R, Saraiva AM, and Alves-dos-Santos I. 2011. Ecological niche similarities of Peponapis bees and non-domesticated Cucurbita species. Ecological Modelling 222(12):2011-2018.Hart JP, Brumbach HJ, and Lusteck R. 2007. Extending the Phytolith Evidence for Early Maize (Zea mays ssp. mays) and Squash (Cucurbita sp.) in Central New York. American Antiquity 72(3):563-584.Kistler L, Newsom LA, Ryan TM, Clarke AC, Smith BD, and Perry GH. 2015. Gourds and squashes (Cucurbita spp.) adapted to megafaunal extinction and ecological anachronism through domestication. Proceedings of the National Academy of Sciences 112(49):15107-15112. Lira R, Eguiarte L, Montes S, Zizumbo-Villarreal D, Marà ­n PC-G, and Quesada M. 2016. Homo sapiens–Cucurbita interaction in Mesoamerica: Domestication, Dissemination, and Diversification. In: Lira R, Casas A, and Blancas J, editors. Ethnobotany of Mexico: Interactions of People and Plants in Mesoamerica. New York, NY: Springer New York. p 389-401.Là ³pez-Uribe MM, Cane JH, Minckley RL, and Danforth BN. 2016. Crop domestication facilitated rapid geographical expansion of a specialist pollinator, the squash bee Peponapis pruinosa. Proceedings of the Royal Society of London B: Biological Sciences 283(1833).Patton PE, and Curran S. 2016. Archaic Period Domesticated Plants in the Mid-Ohio Valley: Archaeobotanical Remains from the County Home Site (33at40), Southeastern Ohio. Midcontinental Journal of Archaeology 41(2):127-158.Piperno DR. 2011. The Origins of Plant Cultivation and Domestication in the New World Tropics: Patterns, Process, and New Developments. Current Anthropolog y 52(S4):S453-S470. Piperno DR. 2016. Phytolith radiocarbon dating in archaeological and paleoecological research: a case study of phytoliths from modern Neotropical plants and a review of the previous dating evidence. Journal of Archaeological Science 68:54-61.Ranere AJ, Piperno DR, Holst I, Dickau R, and Iriarte J. 2009. The cultural and chronological context of early Holocene maize and squash domestication in the Central Balsas River Valley, Mexico. Proceedings of the National Academy of Sciences 106:5014-5018.Sanjur OI, Piperno DR, Andres TC, and Wessel-Beaver L. 2002. Phylogenetic relationships among domesticated and wild species of Cucurbita (Cucurbitaceae) inferred from a mitochondrial gene: Implications for crop plant evolution and areas of origin. Proceedings of the National Academy of Sciences 99(1):535-540.Simon ML. 2011. Evidence for variability among squash seeds from the Hoxie site (11CK4), Illinois. Journal of Archaeological Science 38(9):2079-2093.Smith BD. 2011. The Cultural Context of Plant Domestication in Eastern North America. Current Anthropology 52(S4):S471-S484. Smith BD. 2006. Eastern North America as an independent center of plant domestication. Proceedings of the National Academy of Sciences 103(33):12223-12228.Zheng Y-H, Alverson AJ, Wang Q-F, and Palmer JD. 2013. Chloroplast phylogeny of Cucurbita: Evolution of the domesticated and wild species. Journal of Systematics and Evolution 51(3):326-334.

Thursday, November 21, 2019

Individual Report Essay Example | Topics and Well Written Essays - 2000 words - 4

Individual Report - Essay Example The fundamental principle towards achieving a successful integrated marketing strategy for a product entails both the combination of the traditional and the non-traditional marketing promotional methods, to enhance the synergies of different promotional tactics, such that together, they can produce brand equity for the product. The creation of a synergy for different promotional tactics ensures that the weakness associated with one promotional tactic is offset by the strengths of the other promotional methods, thus building a marketing strategy for a brand that is consistent, clear and easily understandable, and which increases the impact of the marketing campaign (Zvobgo & Melewar, 2011:12). Thus, this discussion seeks to establish Strategic marketing communications approach that can be applied towards ensuring the success of Sony and its SP3 product, with a view to applying a combination of different promotional strategies, to tell the overall product story of (PlayStation 3) to the market. To achieve this, the discussion will seek to establish the weakness associated with each of the available promotional tactics for the products and determine how each of the weaknesses is offset by the application of an integrated system of various marketing promotional tactics. The suitable marketing approach that has been devised for Sony is the APPD approach. The APPD marketing approach focuses on the application of four key marketing strategies; Advertising, Personal selling, Public Relations and Direct marketing as the basis of a product promotion. Under this strategic marketing approach, both the traditional and the non-traditional marketing tactics are applied, to enhance a synergy that increases the impact of the advertising and promotional campaign. Advertising is one of the marketing tactics that will be combined with the other three components of the devised APPD marketing approach for SP3 product,

Tuesday, November 19, 2019

Assignment Case Study Example | Topics and Well Written Essays - 250 words - 3

Assignment - Case Study Example The two main principles comprises of the superior quality and the superior efficiency. The superior efficiency include the experience curve and the learning effect   (Hill & Jones, 2013). On the other hand, the superior quality entails its excellence and reliability. As illustrated in the diagram below Superior efficiency can gladly be achieved through designing products for easy manufacturing and organizing self-managing institutions. Additionally, it was evident from the study that the superior quality can be achieved by finding ways of measuring the quality and reduce costs and error. Another important principle that was all evident in the study is superior innovation. In ‘superior design, there are proper principles when better design and good process of manufacturing are in place. For instance the average time between the part failure rose from 2500 hrs to 170000 hrs. There was a massive improvement that rose from the best manufacturing and design

Sunday, November 17, 2019

Teaching Essay Example for Free

Teaching Essay 1.1 How teaching assistant can support the teacher in planning, teaching and evaluation of learning activities. Prior to the lesson I requested a copy of the teachers’ plans and after discussions we were able to agree using a variety of lesson plans, teaching methods, and implement targets to provide the most effective support to pupils and their needs, this gave me a clearer understanding of the learning that was going to take place and allow me time to familiarising myself with the subject matter, learning objectives and outcomes, this would also assist me to prepare any resources required for the planned lesson ahead. After agreeing the objectives of the lesson ‘Drip Drop’, were to explore some of the properties of water, to explore absorbent and non-absorbent materials and to find out how water drops behave on different surfaces. By asking for copies of the teacher’s long, medium, short-term planning, this helped me to provide extra support in the classroom by developing my understanding of the weeks and daily planning process and to set learning objectives, preparing, assessing and recording pupils’ participation and progression allow the teacher to see how effective my teaching is and whether the pupils are making progress in their learning. The role of the teacher is to supply a safe and supervised classroom for the pupils to learn in, encourage pupil learning by planning, preparing and delivering lessons in relation to the National Curriculum and meet school target whilst maintain its policies. The teacher assesses records and report on pupil’s progress and achievements and liaise with parents, sometimes attending meetings or responsible for literacy or science. Preparing the classroom for the lesson, checking the correct materials available to carry out the activity helps the teacher. Observation and monitoring of pupils work during the task helps me to make assessments to see if the learning has been successful and give feedback to the pupil and teacher on individuals performance or responses, if they have any problems, by doing this it helps me to make well-informed judgements about a pupils learning and progress and make any changes necessary to the activity. 1.2 Information the teaching assistant would require before supporting learning activities From the daily lesson plan I am able to identify the materials required for the lesson to complete the task. After reading the pupil’s records and initial assessment a decision was made to put the more experienced pupils with the ones who were not as confident to enable them to assist, encourage, help and work together to complete the task successfully. A class discussion was held to see if the pupils could think of the materials which would be required to complete the task I then wrote the answers on the whiteboard. The materials were absorbent and non-absorbent materials like plastic, paper and cardboard etc and things with which to make water drops for example, straws, plastic pipettes, and clean eye droppers, as water was going to be used a non toxic coloured paint was required to put in the water to make it easier to see, because I used the last of the cardboard I wrote this down on the reorder list. I emphasised everyone needed to act sensibly because sharp items were going to be used. I showed the class how to make drops with the different kinds of objects and gave them time to practice making water drops and try to make drops of different sizes. When they had mastered this I asked the pupils to drip onto samples of different materials. I asked them to see what happened when two, or more, drops meet, on a hard and non-absorbent surface. Later I separate the pupils into pairs and asked them: Can they race their drop with a friend? 1.3 The sorts of problems that may occur when supporting learning activities Informing the teacher before removing unwanted chairs made sure there was sufficient space for the pupils and equipment to work safely prior to the learning activity and by placing four pupils on each table gave better access to the water tubs and avoiding pupils pushing each other. The pipettes and resources were placed safely in the middle of each table. Before the lesson it was explained to suck the water up the straw was dangerous and requested the pupils to just dip the straw in the water, I asked if they knew why and explained about choking and emphasised about being sensible, the pupils’ then put on their aprons to protect their clothing. The pupils who found listening difficult, I put the questions onto laminated cards for easy reference explaining that I was going to ask those questions about the information later. I also wrote down the key questions on the whiteboard. Can you make different size drop? What happens to the drops when you drip them onto different surfaces? Can you make two drops join? What Happens? Whilst monitoring I removed a pupil from the activity for putting the pipette in his ear. The child was placed away from the activity, asking the pupil if he understood why he had been separated it was explained if he wanted to rejoin the activity he would need to act sensibly, after 10 minutes the pupil calmed down, and was asked to rejoined the group, giving the pupil encouragement and praise for better behaviour enabled the pupil to complete the task successfully. When the activity had finished I discussed with the pupil his behaviour and found he was upset because his hamster had died, I later discussed this with the teacher. After shutting the windows I relocated a pupil to a quieter part of the classroom as the noise of grass cutting was causing a distraction. The hot weather made the room too warm, two pupils started to flick each other with water I opened the classroom door to reduce the temperature and with a direct look and raised eyebrow showed displeasure at the pupils then separated them. Noticing one of the cheerful pupils was rather withdrawn and after talking they revealed that their Nan had died that morning I reassured the pupil and asked if they would like to read a poem about water, I then informed the teacher. Encouragement by praising their progress was given to the pupils with low confidence and pupils who finished their task early were asked to write a poem about their observations or about the drop race. After the activity was complete we had a class discussion asking pupils, how do you think it went? What would you do differently? I then asked the pupils to write down their observations in their books with correct date. 1.4 Strategies a teaching assistant may use to support pupils learning By using questions ‘What we think will happen’?, and writing down all the key points this confirmed the pupils understood the instructions prior to the activity and helped the class know what was expected of them. Placing the low confident pupils at the front of the class and rephrasing questions enabled them to understand the instructions more clearly. After discussion with another teaching assistant it was decided to enlarge the worksheet to A3 size to make it easier for the pupils who were struggling, encouraging them to write down their ideas then stick them onto the worksheet later and giving praise when the task was completed. Separating pupils into groups allowed the development of peer support activities and cooperative learning, allowing the pupils to benefit by learning and supporting each other. The pupils with confidence worked on their own initiative were able to write their own ideas directly onto the worksheet. Bandura, Skinner, Piaget and Vygotsky discuss that cognitive development occurs at an individual rate and cultures teaches a person what to think as well as how to think. I agree that children are not just passive discovers, they are constantly trying to make sense of the information they see, hear, feel and discover enabling some children to develop quicker than others. At the end of the activity reward stickers were given for using the correctly vocabulary in their poems and a discussion was held by using open-ended questions of (how, what, why?) this provided me with more information to enable me to assess the pupils’ learning and understanding and provide me with the information required to feedback later to the teacher 1.5 Providing feedback on learning activities to the teacher Both during and after supporting the learning activity, I recorded the pupils’ participation and progression and met later with the teacher, to give feedback regarding the issues encountered during the activity, I discussed the pupil who’s relative died and about the pupil behaving inappropriately during the session and being separated from the group. I informed the teacher why the worksheet was enlarged and why the laminated card was useful. I also explained I gave out some stickers for correct spelling and punctuation.

Thursday, November 14, 2019

FGF Signaling and Early Lung Development Essay -- Biology, Lung

Epithelial-mesenchymal interactions mediate organogenesis, which results from the activation of complex gene networks. Early respiratory development arises from the foregut endoderm and gives rise to tracheal and lung progenitor cells. Recent studies have linked fibroblast growth factor, Wnt, and other signaling pathways to the initial stages of lung development. Cells respond to signaling proteins mainly though transcription factors that ultimately determine cell fate and pattern formation. Gain and loss-of-function studies have facilitated the identification and functionality of molecular components as part of development. Fibroblast growth factor (FGF) signaling plays an important role in the regulatory network present in embryonic pulmonary development. FGF controls cell proliferation, differentiation and pattern formation; however, the interaction of FGF with other signaling pathways is still questioned by researchers. FGF-7 and FGF-10 are important for patterning and growth of the lung bud and are differentially regulated by FGF-1 and FGF-2. Research has shown FGF is an important factor in respiratory development as it regulates the expression of other signaling pathways. Said molecular events involving FGF signaling drive key phases of pulmonary development and thus the understanding of these key segmental mechanisms gives way to new knowledge of pathogenesis involving congenital anomalies, helping to develop innovative therapies to treat disease. Unless specifically mentioned, anything regarding expression patterns and developmental effects of morphogens, transcription and growth factors, or any other developmental factors effecting lung development are referenced from the murine lung. Accordingly, functional relevance... ...change, an extremely complicated process. The lung is an organ that contains a vast system of airways carefully constructed to achieve maximal surface area in a confined space. This helps to form an environment suitable for the bronchial and pulmonary vascular systems. These airways that grow out into the body, like a tree towards the sky, require careful guidance from many developmental factors such as transcriptional regulators, growth factors, morphogens and extra cellular matrix molecules. When mutations in the genes that control these factors occur, aberrations during lung development can arise and may lead to severe morbidity or mortality at birth due to respiratory failure. The FGF signaling pathway is one such signaling mechanism that is critical to proper lung formation, guiding branching morphogenesis and cellular proliferation of the developing lung.

Tuesday, November 12, 2019

Purinex Inc. Case Study Essay

Executive Summary 1. Statement of Problem This study is commissioned to analyze the Purinex, Inc. financing plan, which is related to determine the best financing alternative for the company in securing additional cash needed to establish a partnership with a large-capitalization pharmaceutical firm. Gilad Harpaz, Purinex’s chief financial officer believes a partnership deal could bring the company to execute its mission, developing drugs for the treatment of sepsis and diabetes. However, the problem facing Purinex is that—while there is a chance for Purinex to secure a partner in the next four to twelve months, Purinex just has available cash to last around 11 months; furthermore, there is still a very strong chance that a different partnership would occur about one year later. In short, Purinex is now facing the challenge of the lack of capital to reach the partnership deals. According to the case, Gilad Harpaz is considering three options for Purinex to solve the problem. To help identify the feasibility and attractiveness of these financing alternatives, this study is based on the decision tree approach to evaluate the options. 2. Discussion As described in the case, firstly, the partnership deal would entitle Purinex to receive a combination of up-front fees, milestone payments, and royalties for the treatment of either sepsis or diabetes (see Appendix 1 for the detailed information). Secondly, due to the lack of capital, there are three financing options: 1) raising a one-time round financing from a Venture Capital (VC) firm, 2) simply waiting in the expectation that either sepsis deal or the diabetes deal would come through, and 3) undertaking another one-time round financing from a number of angel investors. It is needed to note that when Purinex seeks external funding investments either from VC firm or angel investing, the investors will acquire certain equity in Purinex (see Appendix 2 for the expected ownership percentage). Nevertheless, if Purinex chooses to maintain 100 percent control, it would lose the opportunity to secure a third-party partnership which is anticipated to occur about one year later. The reason is that Purinex has only $700,000 cash on hand which is good only for around 11 months. It is important to note that this study is based on the following assumption—the  combination of monies for each partnership deal will be received once Purinex successfully secures a partner. In addition, the probability of establishing a partnership with a pharmaceutical company for the wait-6-months option is estimated to be 25% since the achieved partnership chance for the next four to twelve months is about 75% (see Appendix 3 for the calculation). Furthermore, the expected value (EV) for each financing option is derived from the calculation of the EV of the partnership deal, and it is based on the standpoint of the founder’s equity interest. As a result, the decision tree for Purinex’s financing plan is shown in Appendix 4. One can notice that based on the potential return and risk level, the financing alternative for waiting 6 months is ranked as the highest risk option in terms of offering the highest potential return. The reason is that Purinex does not have to share its earning with other parties. Thus, once the partnership agreement is reached, Purinex’s founders can obtain the entire EV of $325 million. However, the major risk associated with this option is Purinex has far less opportunity to secure a partner. While there is a 75% chance for VC and angel financing options to achieve the partnership deal, this option just has a 25% probability. Furthermore, the VC and angel financing options still hav e the other chance—a 95% probability—to secure a different partnership about one year later. With regard to the VC option and the Angel option, it seems like the VC option provides a higher return for the sources of cash since this option just takes 3 months to complete the process and could offer Purinex $10 million, which enables Purinex to survive another 15 years. In addition, the VC option will improve 10% for the terms of either drug deal. However, this study would consider financing from angel investors is more feasible and attractive for Purinex based on the analysis of decision tree. The decision tree shows the fact that VC firms would require 40 percent of the equity in Purinex, resulting in the situation of having less EV. Perhaps the most important factor is that there is a very strong chance—a 98.75% possibility (100% – [25% * 5%])—that a partnership deal will come through during the following two years, and thereby raising $2 million form angel investors is quite enough for Purinex to secure the partnership deal. In addition to the analysis of decision tree, there is still a qualitative consideration that has impact on structuring the decision. Indeed, with the external financing,  the existing owners share composition will be changed that would trigger the control power issue and impose a significant number of restrictions on Purinex, including preferences for board appointments, antidilution rights liquidity, participation, and negative covenants. Therefore, choosing the angel option would offset this negative impact because Purinex’s ownership percentage will still be 89.74%, which is much greater than a 60% for the VC option. 3. Recommendation Fundamentally, the goal of Gilad Harpaz is to seek the best financing alternative for Purinex in securing additional funds in order to accomplish the partnership deals and maximize the value of Purinex today. Based on the presented analysis of decision tree, a major finding of this study is that Gilad Harpaz should try to adopt and implement the angel financing strategy which has a maximum EV along with lower risk. However, with this strategy, the issue of dilution in the founder’s equity interest is still needed to be considered. In addition, in order to pursue the future growth, Purinex should try to employ the partnership strategy to generate more sales at a short period of time. Hence, this study believes, based on the decision tree approach, the best financing alternative for Purinex is financing with Angel investors along with the partnership strategy.