Tuesday, November 5, 2019
Battle of Wake Island in World War II
Battle of Wake Island in World War II The Battle of Wake Island was fought from December 8-23, 1941, during the opening days of World War II (1939-1945). A tiny atoll in the central Pacific Ocean, Wake Island was annexed by the United States in 1899. Located between Midway and Guam, the island was not permanently settled until 1935 when Pan American Airways built a town and hotel to service their trans-Pacific China Clipper flights. Consisting of three small islets, Wake, Peale, and Wilkes, Wake Island was to the north of the Japanese-held Marshall Islands and east of Guam. As tensions with Japan rose in the late 1930s, the US Navy began efforts to fortify the island. Work on an airfield and defensive positions began in January 1941. The following month, as part of Executive Order 8682, the Wake Island Naval Defensive Sea Area was created which limited maritime traffic around the island to US military vessels and those approved by the Secretary of the Navy. An accompanying Wake Island Naval Airspace Reservation was also established over the atoll. Additionally, six 5 guns, which had previously been mounted on USS Texas (BB-35), and 12 3 anti-aircraft guns were shipped to Wake Island to bolster the atolls defenses. The Marines Prepare While work progressed, the 400 men of the 1st Marine Defense Battalion arrived on August 19, led by Major James P.S. Devereux. On November 28, Commander Winfield S. Cunningham, a naval aviator, arrived to assume overall command of the islands garrison. These forces joined the 1,221 workers from the Morrison-Knudsen Corporation which were completing the islands facilities and the Pan American staff which included 45 Chamorros (Micronesians from Guam). By early December the airfield was operational, though not complete. The islands radar equipment remained at Pearl Harbor and protective revetments had not been built to protect aircraft from aerial attack. Though the guns had been emplaced, only one director was available for the anti-aircraft batteries. On December 4, twelve F4F Wildcats from VMF-211 arrived on the island after being carried west by USS Enterprise (CV-6). Commanded by Major Paul A. Putnam, the squadron was only on Wake Island for four days before the war began. Forces Commanders United States Commander Winfield S. CunninghamMajor James P.S. Devereux527 men12 F4F Wildcats Japan Rear Admiral Sadamichi Kajioka2,500 men3 light cruisers, 6 destroyers, 2 patrol boats, 2 transports, and 2 carriers (second landing attempt) The Japanese Attack Begins Due to the islands strategic location, the Japanese made provisions to attack and seize Wake as part of their opening moves against the United States. On December 8, as Japanese aircraft were attacking Pearl Harbor (Wake Island is on the other side of the International Date Line), 36 Mitsubishi G3M medium bombers departed the Marshall Islands for Wake Island. Alerted to the Pearl Harbor attack at 6:50 AM and lacking radar, Cunningham ordered four Wildcats to begin patrolling the skies around the island. Flying in poor visibility, the pilots failed to spot the inbound Japanese bombers. Striking the island, the Japanese managed to destroy eight of VMF-211s Wildcats on the ground as well as inflicted damage on the airfield and Pam Am facilities. Among the casualties were 23 killed and 11 wounded from VMF-211 including many of the squadrons mechanics. After the raid, the non-Chamorro Pan American employees were evacuated from Wake Island aboard the Martin 130 Philippine Clipper which had survived the attack. A Stiff Defense Retiring with no losses, the Japanese aircraft returned the next day. This raid targeted Wake Islands infrastructure and resulted in the destruction of the hospital and Pan Americans aviation facilities. Attacking the bombers, VMF-211s four remaining fighters succeeded in downing two Japanese planes. As the air battle raged, Rear Admiral Sadamichi Kajioka departed Roi in the Marshall Islands with a small invasion fleet on December 9. On the 10th, Japanese planes attacked targets in Wilkes and detonated a supply of dynamite which destroyed the ammunition for the islands guns. Arriving off Wake Island on December 11, Kajioka ordered his ships forward to land 450 Special Naval Landing Force troops. Under the guidance of Devereux, Marine gunners held their fire until the Japanese were within range of Wakes 5 coastal defense guns. Opening fire, his gunners succeeded in sinking the destroyer Hayate and badly damaging Kajiokas flagship, the light cruiser Yubari. Under heavy fire, Kajioka elected to withdraw out of range. Counterattacking, VMF-211s four remaining aircraft succeeded in sinking the destroyer Kisaragi when a bomb landed in the ships depth charge racks. Captain Henry T. Elrodà posthumouslyà received the Medal of Honor for his part in the vessels destruction. Calls for Help While the Japanese regrouped, Cunningham and Devereux called for aid from Hawaii. Stymied in his attempts to take the island, Kajioka remained nearby and directed additional air raids against the defenses. In addition, he was reinforced by additional ships, including the carriers Soryu and Hiryu which were diverted south from the retiring Pearl Harbor attack force. While Kajioka planned his next move, Vice Admiral William S. Pye, the Acting Commander-in-Chief of the US Pacific Fleet, directed Rear Admirals Frank J. Fletcherà and Wilson Brown to take a relief force to Wake. Centered on the carrier USS Saratoga (CV-3) Fletchers force carried additional troops and aircraft for the beleaguered garrison. Moving slowly, the relief force was recalled by Pye on December 22 after he learned that two Japanese carriers were operating in the area. That same day, VMF-211 lost two aircraft. On December 23, with the carrier providing air cover, Kajioka again moved forward. Following a preliminary bombardment, the Japanese landed on the island. Though Patrol Boat No. 32 and Patrol Boat No. 33 were lost in the fighting, by dawn over 1,000 men had come ashore. Final Hours Pushed out of the southern arm of the island, American forces mounted a tenacious defense despite being outnumbered two-to-one. Fighting through the morning, Cunningham and Devereux were forced to surrender the island that afternoon. During their fifteen-day defense, the garrison at Wake Island sank four Japanese warships and severely damaged a fifth. In addition, as many as 21 Japanese aircraft were downed along with a total of around 820 killed and approximately 300 wounded. American losses numbered 12 aircraft, 119 killed, and 50 wounded. Aftermath Of those who surrendered, 368 were Marines, 60 US Navy, 5 US Army, and 1,104 civilian contractors. As the Japanese occupied Wake, the majority of the prisoners were transported from the island, though 98 were kept as forced laborers. While American forces never attempted to re-capture the island during the war, a submarine blockade was imposed which starved the defenders. On October 5, 1943, aircraft fromà USSà Yorktown (CV-10) struck the island. Fearing an imminent invasion, the garrison commander, Rear Admiral Shigematsu Sakaibara, ordered the execution of the remaining prisoners. This was carried out on the northern end of the island on October 7, though one prisoner escaped and carvedà 98 US PW 5-10-43à on a large rock near the killed POWs mass grave. This prisoner was subsequently re-captured and personally executed by Sakaibara. The island was re-occupied by American forces on September 4, 1945, shortly after the wars end. Sakaibara was later convicted of war crimes for his actions on Wake Island and hung on June 18, 1947.
Sunday, November 3, 2019
Analysis of the personal computers market from the microeconomics` Essay
Analysis of the personal computers market from the microeconomics` perspective - Essay Example A great number of competing producers There are many competing producers waiting for their chance towards competitive advantage, leading to the exploitation of price that could offer more significant customersââ¬â¢ advantage. This is based on the idea of Porter that the overall cost leadership could lead to competitive advantage because its bottom line is about the ability of each producer to set a competitive price for their actual product or service offering (Porter, 1998). As the competition increases, more producers are capable of offering their products or services at a remarkably lower price just to ensure their competitive edge and to guarantee a fundamental market share. This significantly happens in the market for personal computers. To cite an instance, it is not only Apple Incorporated that has the potential to produce personal computer products, but there are other companies around the world of the same industry, both local and international that are also capable of pr oducing the same offerings and present them at lower prices. Based on the concept of the law of demand, a lower price is enticing from the point of view of customers. Thus, it is a natural market response to increase their demand especially for products that are of greater value for them and set at lower prices. According to law of demand, customers tend to find substitute products just to enjoy the benefit of acquring low prices. On the other hand, the price should therefore be obviously lower in the case of products with high volume of supply. This idea is relevant to the associated concept of the law of supply. In other words, the market for personal computer because of a healthy... This paper primarily focuses on the process of price formation in the personal computers industry under the condition of free market. Both laws of demand and supply are under consideration. In this paper, there is an critical analysis of the important factors that are actually contributing to the downward fall of the market price for personal computers even in the midst of increasing demand for them. The dynamic changes in todayââ¬â¢s economy leads to the increasing demand for various technologies. This connects us to the prevailing requirement for personal computers. The business for making personal computers would therefore make sense and this is the reason why many producers try to surface from time to time and even create vibrant improvements. The law of supply states that when there is a higher price involved, producers are more willing to produce more, and less if the associated price is low The law of demand on the other hand states that the demand for a product or service offering is higher if people could afford it through a lower price, which means they are not more likely to buy something with a higher price, provided nothing changes As the demand for personal computers increases, the market price decreases because this could be clearly due to the increase of supply linked up with the great number of competing producers that are capable of adjusting the final price of their actual product offerings, leaving the advantage to the target customers. The laws of demand and supply effects on the computer prices are illustrated in the figures in the article.
Friday, November 1, 2019
The President Wants You to Organize Term Paper Example | Topics and Well Written Essays - 500 words
The President Wants You to Organize - Term Paper Example The article also depicts the upcoming of Lewis , the future leader of the labor party with a unique and powerful personality .Here the caption ââ¬Å" The President wants you to organize ââ¬Å" relates to the slogan spread by Lewis to his fellow workers working in coal mines in an attempt to work out their freedom. It conveys the message that ,the president wants to see a union of labor of coal miners across the country. Here the author is trying to say or argue that rich and powerful will always try to subordinate or exploit the poor and helpless. Here the indication is on the coal miners who are working in the unfavorable conditions with a meager wages and inferior facilities. Here the emphasis is on the Presidentââ¬â¢s demand for unity among workers to gain power and freedom in their profession. Here the author is saying that the president wants to see unity among coal miners so that they can get facilities. The author is arguing about the truce between the industrialist and the labor class. The author is saying the in order for the laborers to bargain or demand; they should form a legal union .Laborââ¬â¢s right and freedom is the main content of this chapter and the call for unity is originating from the President. Along the chapter the author is projecting the fight of labor class for better wages and living circumstances against all odds. Here the chapter starts with the Presidents call for all skilled and unskilled workers to unite in an attempt to demand their human rights and freedom. Here the chapter explains the negativism in the life of coal mining labors and their struggle to earn decent wages and comfortable living situations. Unfortunately, all the authority lies under the strong and cruel hands of the industrialist. Here, Lewis is one personality who comes up front to assist the coal miners in formulating a labor union where in they can bargain for their human rights. The chapter explains about the will power and motivation of Lewis in
Tuesday, October 29, 2019
Colin Powell Address the Nation Essay Example | Topics and Well Written Essays - 500 words
Colin Powell Address the Nation - Essay Example He had often fought with the hawks in the administration, who were allegedly planning an Iraq invasion even before the September 11 attacks-an insight supported by evidence by former terrorism czar Richard Clarke in front of the 9/11 Commission. The main concession Powell wanted before he would offer his full support for the Iraq War was the participation of the international community in the attack, unlike the one-sided approach some of the hawks were championing. He was also thriving in convincing Bush to take the case of Iraq to the United Nations, and in moderating other initiatives. Powell was placed at the vanguard of this diplomatic campaign. Powell's main role was to gather international support for a multi-national alliance to increase the invasion. To this end, Powell addressed a plenary session of the United Nations Security Council on February 5, 2003 to bicker in favor of military action. Quoting "numerous" nameless Iraqi defectors, Powell declared that "We know that Saddam Hussein is determined to keep his weapons of mass destruction, is determined to make more." (Cockburn, online) Powell also remarked that there was "no doubt in my mind" that Saddam was working to acquire key components to produce nuclear wea pons. There was a general rejection of the proof Powell offered that the regime of Saddam Hussein had weapons of mass destruction.
Sunday, October 27, 2019
14-3-3 Protein Analysis | Essay
14-3-3 Protein Analysis | Essay INTRODUCTION 14-3-3 represents a family of highly conserved, 28-33 kDa, acidic dimeric proteins. [B, H1] These proteins were first identified and isolated by Moore and Perez during their systematic study of protein fractions from mammalian brain tissue. [B1] Their nomenclature reflects the system used by the researchers to classify the various protein fractions, based on their migration pattern on starch gel electrophoresis and two-dimensional DEAE chromatography. [D1] Initially it was thought that the occurrence of these proteins was confined to neuronal tissue, where they were found to be present in concentrations as high as 13.3 à ¼g/ml. [B19] However, subsequent studies showed that they are in fact widely distributed and ubiquitously expressed in most mammalian tissues. [B] Apart from mammalian tissue, orthologous proteins with a high degree of similarity have also been identified in other organisms including plants, yeast, insects and amphibians. [B] Interestingly, though no prokaryotic ancestor has been identified for the 14-3-3 gene, eukaryotes are known to express multiple isotypes, encoded by highly similar gene sequences. [A, G13] Drosophila and yeast each contain two 14-3-3 genes, Arabidopsis species have 15, while the human genome contains seven closely related 14-3-3 genes. [G13-G16] These genes encode the seven different 14-3-3 isotypes found in human cells ââ¬â namely à ², à ³, ÃÆ', à µ, à ·, Ãâ, and à ¶. Two additional isoforms ââ¬â à ± and à ´, represent the phosphorylated varieties of à ² and à ¶ respectively. [D7] By virtue of their conserved sequences, the different 14-3-3 isoforms display a similar tertiary structure. Crystallographic studies show that each subunit is made up of nine anti-parallel à ± helices, which are able to self-assemble into dimers [F1]; with four of the nine helices participating in this process of dimerization. [A] While certain isoforms such as ÃÆ' and à ³ show propensity towards the formation of homodimers, other isoforms like à µ prefer to heterodimerize. [H] Structural analyses have also revealed that each monomer contains an amphipathic concave channel through which it interacts with its target proteins. [F13] Since each of the subunits of the dimer contain an independent ligand-binding groove, these proteins can interact with two different binding sites present on the same or different target proteins [H3] The targets of 14-3-3 proteins were first studied by Muslin et. al. in 1995, who determined that these proteins interact with phosphorylated serine-containing binding partners in a sequence specific manner. [A2] Thus, this came about to be the first family of proteins discovered to have an affinity for phosphoserine-specific targets. More specifically, Yaffe et. al. in 1997 identified two putative high-affinity motifs, bearing the sequences RSXpSXP and RXXXpSXP, where pS stands for phosphoserine, R stands for Arginine, P is proline and X is any amino acid. [] These were found to be the consensus sequences for 14-3-3 binding, and were called the mode I and mode II binding motifs respectively. [A21] However not all the 14-3-3 binding partners conform to these motifs and neither are all 14-3-3-target interactions found to be phosphorylation-dependent. [H] Though, a small percentage of 14-3-3 targets do not conform, in general it can be said that, proteins that interact with the 14-3-3 family are usually found to be globular proteins that contain either the mode I or mode II binding motifs within an unstructured region of the peptide. [PG] Interestingly, despite the fact that the different isotypes share a similar structure and show complete conservation of sequence in the ligand-binding region, not all the isotypes of 14-3-3 bind equivalently to their ligands in vivo and the pathways in which the individual isoforms participate have diverged considerably. This isoform specificity cannot be explained solely on the basis of 14-3-3 binding to the consensus sequence. [A, PA] It has hence been speculated that this isoform-specificity may be attributed either to differences in subcellular localization and/or tissue-specific transcriptional regulation rather than inherent differences in their ligand-binding ability. [D] Consequently, the various isoforms of the protein are found to bind different ligands and hence influence distinct cellular pathways and processes. Some of the ligands postulated on the basis of database searches include Raf1, CDC25C, polyoma middle T antigen, BAD, 5ââ¬â¢AMP Kinase and PLC à ³. [PA] Studies conducted in the late 1990ââ¬â¢s demonstrated the ability of 14-3-3 proteins to interact with a number of different protein phosphatases and kinases in the cell, thus influencing multiple signalling pathways within the cell. [D] The mechanism of action of the 14-3-3 family of proteins is based on their ability to alter the stability, the catalytic activity or the subcellular localization of their targets. [H] 14-3-3 dimers being highly rigid, they are able to induce conformational changes in their target proteins as well as generate steric hindrance upon binding. Together, these forces can prevent molecular interactions by modulating the accessibility of the ligand to enzymes; and they can also serve to expose or hide localization motifs such as NES and NLS. [H] The first cellular activity to be attributed to 14-3-3 was that of an activator of tryptophan and tyrosine hydroxylases, rate-limiting enzymes that regulate the biosynthesis of catecholamine and serotonin neurotransmitter, as reported by Ichimura and co-workers. [B20] Subsequently it was discovered that 14-3-3 proteins could regulate the activity of signal transduction molecule protein kinase C. [D3,D4] This and other findings led to the implication that 14-3-3 proteins could act as novel chaperone proteins that are able to modulate the interactions between the different constituents of signal transduction pathways. [D5] Today it is known that 14-3-3 protein dimers are able to interact with a wide array of proteins within the cell including signalling molecules, apoptosis factors, tumor supressors, transcription factors, biosynthetic enzymes as well as cytoskeletal proteins; as a result of which they play crucial roles in the regulation of multiple cellular process such as the onset of cellular differentiation, and senescence, DNA repair and the maintenance of cell cycle check point, co-ordination of motility and adhesion and the prevention of apoptosis [A,H] REVIEW OF LITERATURE 14-3-3 proteins are crucial in the regulation of many cellular functions. An implication of their involvement in this multitude of processes is that any mutation, loss of regulation or altered expression of these proteins can lead them to be associated with major diseases. Through their involvement in the regulation of various tumor suppressor genes and oncogenes, 14-3-3 proteins are thought to be potentially involved in cancerous transformation and the development of malignancies. [Z11] They are also known to be associated with neurodegenerative conditions such as Alzheimerââ¬â¢s disease, ataxia and Parkinsonââ¬â¢s disease. [MT1, MT2, MT3, MT4] The causes of these diseases are poorly understood and hence this family of proteins has been the focus of study of several research groups around the world, leading to numerous publications investigating all the different aspects. This section summarizes the literature elucidating the properties and functions of 14-3-3 proteins that have helped shape the rationale behind this project. A special focus is maintained on current literature that highlights role of 14-3-3 à ³ in the cell cycle and in desmosome assembly, as well as its recently discovered ATPase activity. Human 14-3-3 isoforms The members of the 14-3-3 family are among the most abundant proteins in the cell. It has been established that owing to their interaction with diverse targets, 14-3-3 proteins are known to be involved in a multitude of processes, including the control of gene transcription, metabolism, cell cycle regulation, and apoptosis. [C] However, not all 14-3-3 proteins carry out the same functions. The table below provides an overview of the properties of the various human 14-3-3 isoforms: 14-3-3 isoform Official symbol Official full name Chrom-osome location No. of amino acids Mol.Wt. (kDa) Interactions, functions and disorders 14-3-3 à ² YWHAB Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, beta 20 q13.1 246 27.95 shown to interact with CDC25 phosphatases and RAF1 may play a role in relaying mitogenic signaling to the cell cycle machinery 14-3-3 à ³ YWHAG Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, gamma 7 q11.23 247 28.12 interacts with RAF1, CDC25C and protein kinase C induced by growth factors in human vascular smooth muscle cells also expressed significantly in heart and skeletal muscles 14-3-3 ÃÆ' YWHAS, SFN Stratifin 1 p36.11 248 27.64 known to interact with PLK4, ERRFI1, MARK3, JUB expressed in epithelial cells 14-3-3 à µ YWHAE Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon 17 p13.3 255 29.03 interacts with RAF1, CDC25 phosphatases, and IRS1 proteins plays a role in pathways related to signal transduction, cell division and regulation of insulin sensitivity implicated in the pathogenesis of small-cell lung cancer 14-3-3 à · YWHAH Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta 22 q12.3 246 28.09 contains a repeating sequence, 7 bp in length, in its 5 UTR changes in the number of repeats are associated with conditions such as psychotic bipolar disorder and schizophrenia 14-3-3 Ãâ/à ¸ YWHAQ Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, theta 2 p25.1 245 27.63 found to be over-expressed in patients with amyotrophic lateral sclerosis also expressed in T cells 14-3-3 à ¶ YWHAZ Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta 8 q23.1 245 27.61 interacts with IRS1 protein may play a role in regulating insulin sensitivity 14-3-3 à ³ 14-3-3 à ³ is an adapter protein that is known to be involved in the regulation of a wide range of signalling pathways, both general and specialized. This protein is encoded by a gene designated YWHAG, which was mapped to the chromosome 7q11.23 by Horie et. al. in 1999 [Z2] A study of its binding partners in a yeast two-hybrid study revealed that 14-3-3 à ³ may have as many as 130 potential ligands. [PG 4] There are reports which link the overexpression of 14-3-3 à ³ and its high titres in the cerebrospinal fluid (CSF) with certain neurodegenerative disorders such as Down syndrome and Alzheimerââ¬â¢s. [A129, A131] This protein is also thought to to be involved in the process of carcinogenesis. Although 14-3-3 ÃÆ' is the isoform that has been most extensively studied for its association with human cancers, there are also several ongoing studies which attempt to establish a correlation between 14-3-3 à ³ expression and the development of tumours. This includes the work of Jieqiang Lv. et. al. which was able to demonstrate through proteomic analysis that a reduced expression of 14-3-3 à ³ is observed in patients with uterine tumours. [Z10] The role of 14-3-3 à ³ in cancer can be better appreciated by understanding its role in the cell cycle and its regulation. Role of 14-3-3 à ³ in the cell cycle 14-3-3 proteins play a major role in the regulation of cell cycle through the interaction with various cell cycle proteins. The main targets for 14-3-3 regulation are the Cdc25 proteins. Cdc25 is a family of protein phosphatases comprising the members Cdc25A, Cdc25B and Cdc25C, which are active during different phases of the cell cycle. Cdc25A participates in the regulation of G1/S transition, whereas Cdc25B and Cdc25C regulate G2/M transition. [z3] Cdc25c has been specifically implicated in the activation of the CDK1-cyclinB1 complex by removing inhibitory phosphorylations at T14 and Y15, which advances the cell cycle from G2 to M phase. The overexpression of this protein has been seen to result in mitotic catastrophe in the cell due to premature mitosis. [E28] Therefore the expression and function of Cdc25C needs to be tightly regulated; and 14-3-3 à ³ plays a crucial role in this regulation. [E29] During the interphase, 14-3-3 proteins bind to Cdc25C and sequester it in the cytoplasm by occluding the NLS, preventing it from accessing the CDK1-cyclinB1 complex in the nucleus and thus in essence inactivating it. [E28] Dalal et. al. showed that though all the 14-3-3 proteins were able to carry out this function in vitro, only 14-3-3 à ³ and à µ were found to bind to and thus inhibit Cdc25C in vivo. [] This binding however was found to require the phosphorylation of a specific serine residue at position 216 in human cells, usually carried out by TAK1 and other similar kinases. [E30, z4] Cdc25C is also known to be a target of the DNA replication and DNA damage checkpoints that exert their effects through the phosphorylation of S216 by kinases like Chk1 and Chk2. [z5, z6, z7] This phosphorylation thus generates a high-affinity motif that is able to bind to 14-3-3 proteins present in the cytosol. A schematic representation of this process is provided in the figure below. In the absence of 14-3-3 proteins, this regulation of Cdc25C is disrupted and a result, cells lose their ability to stop cycling upon loss of integrity of their DNA. To this effect, a study conducted by Hosing et. al. in 2008 showed that cells require 14-3-3 à ³ in order to maintain their ability to arrest cells in the S phase and the G2 phase checkpoint. [] This was proven by generating 14-3-3 à ³ knockdown cells, and studying their response to DNA damage. It was found that these cells were unable to arrest in G2, thus leading to an increase in premature chromatin condensation (PCC) as compared to the vector control. [] This was the first report suggesting that 14-3-3 à ³ modulates the cell cycle checkpoint response, through its negative regulation of cdc25C function. Role of 14-3-3 à ³ in desmosome assembly 14-3-3 isoforms were also not known to have any role to play in the assembly of desmosomes, until a serendipitous observation led to a study conducted by Sehgal et. al. This study demonstrated for the first time that 14-3-3 à ³ is required for desmosome formation. [] They showed that 14-3-3 à ³ is able to form complexes with the desmosomal proteins plakoglobin, desmoplakin and plakophilin 3. Their work led to the conclusion that 14-3-3 à ³ is essential for the recruitment of plakoglobin to the cell border; and that the loss of 14-3-3 à ³ leads to a decrease in desmosome formation. This translates to defective cell-cell adhesion in HCT 116 cells and sterility in male mice when this loss is manifested in the testis. [] These results are in agreement with the fact that 14-3-3 à ³ plays a role in the transport of proteins from the Golgi complex to the cell border, as previously reported by Valente et al. in 2012. [Z1] ATPase activity of 14-3-3 proteins The notion that 14-3-3 proteins may possess an ATPase function evolved through a series of studies. The first of these was reported in a paper in 1993 by Hachiya et. al., who had isolated a protein from the rat liver cell cytosol, called the mitochondrial import stimulation factor (MSF). [] This factor was found to modulate the conformation of aggregated proteins and stimulate their import into the mitochondria in an ATP-dependent manner, much like the Hsp70 chaperone molecule. Ensuing studies by the same group led to the cloning of cDNA sequences encoding the large and small rat MSF subunits; and based on these cDNA sequences, it was deduced that the MSF peptides belong to the 14-3-3 family. [] This was thus the first time the ability to hydrolyse ATP was attributed to a 14-3-3 protein. In 1997, Yano et. al. probed further and asked whether the 14-3-3 family of proteins were also capable of the reverse reaction i.e. ATP synthesis; and found that native 14-3-3 proteins isolated from human lymphoblastoma cells as well as recombinant 14-3-3 Ãâ exhibited the ability to generate ATP from ADP. [] This activity resembled that of the enzyme nucleoside diphosphate-kinase. It was then speculated that ATP synthesis and hydrolysis may play a role in regulating the interaction of 14-3-3 proteins with their substrates. Subsequently, in 2006, Yano et. al. also showed that 14-3-3 à ¶ acts as a molecular chaperone under heat shock conditions, dissolving thermally-aggregated proteins, also in an ATP-dependent manner. [] This stress-related function is said to differ from the role of MSF as previously described, since in that case, the protein activity is limited to the transport of newly synthesized proteins into the mitochondria. This finding thus represented another part of the puzzle that is the multi-functional nature of 14-3-3 proteins. Despite these reports however, the ATPase activity of 14-3-3 proteins had not commanded much attention from researchers, until recently Ramteke et. al. in 2014 demonstrated unequivocally, using 14-3-3 à ¶ as a model, that these proteins possess an intrinsic ATP-hydrolysing function. [] They also studied the putative residues essential to this activity and found that in their model, the mutation of the Asp at residue 124 to Ala (D124A) resulted in a significant increase in the rate of ATP hydrolysis, while the mutation of Arg 55 to Ala caused a partial loss of function. ATPase activity of 14-3-3 à ³ As a part of the same study, Ramteke et. al. decided to test whether the other 14-3-3 isoforms also displayed similar properties; and they found that with the exception of 14-3-3 ÃÆ', all the other isoforms, including 14-3-3 à ³, showed intrinsic ATPase activity. [] Interestingly, it was found that in case of the à ³ isoform, the mutation of the conserved Asp, found at position 129 to Ala (D129A) led to an over two-fold gain in ATPase function, reflecting that the binding of this mutant to ATP is probably either more energetically or sterically favourable. [] The authors of this paper were however unable to comment on the functional relevance of the ATPase activity of 14-3-3 proteins. These results however provide an impetus to further studies on physiological significance of ATP hydrolysis, with respect to individual 14-3-3 isoforms.
Friday, October 25, 2019
Different Yet Complimentary :: essays papers
Different Yet Complimentary Even though the Bergmann rule and Allan rule are different rules entirely they are both complementary to each other. In 1847 Bergmann observed that within the same spices of warm-blooded animals, populations have less bulky individuals are more often found in warm climates near the equator while, those with greater bulk, mass, are found further from the equator in colder regions. This is due to the fact that big animals generally have larger body masses that result in more heat being produced. The greater amount of heat results from there being more cells. A normal by product of metabolism in cells is heat production. Subsequently the more cells an animal has, the more internal heat it will produce. In addition, larger animals usually have smaller surface area relative to their body masses and therefore are comparatively, in efficient at radiating their body heat off into the surrounding environment. This is illustrated when the volume increases twice as fast as the surface size. Rel atively less surface area results in relatively less heat being lost. In 1877, Allen went further than Bergmann in observing that the length of arms, legs, and other appendages also has an effect on the amount of heat lost to the surrounding environment. He noted that among warm-blooded animals, individuals in populations living further away from the equator in colder environments. This is due to the fact that a thin body with relatively long appendages is less compact and subsequently has more surface area. The greater the body area, the faster body heat will be lost to the environment. A tall and slender individual will have the same volume but greater surface area. It is comparable to an animal with arm and legs. I will demonstrate to you in this essay that even though the Allan rule and Bergmann rule are two different rules they are also complementary to each other. I will show this through explaining each on thoroughly, compare and contrast them and by presenting examples for e ach rule. Carl Bergmann was a 19th century biologist who pointed out that amongst birds and mammal individuals of the same species tend to be larger and heavier when they lived in colder climates. This applies to pumas, bears, koalas, penguins, etc. Even in the case of people, there is an obvious difference between the height and weight of a high-latitude Scandinavian and those of an equatorial pygmy.
Thursday, October 24, 2019
Ray Ban
Introduction â⬠¢Ray-Ban is an Italian owned brand of sunglasses founded in 1937 by Bausch & Lomb. They were introduced for the United States Army Air Corps. Ray-Ban has popularized the aviator sunglassess and now creates sunglasses to suit everybody. â⬠¢In 2007, Ray-Ban re-introduced the original Ray-Ban Wayfarer design, but expanded the colour options beyond the traditional palette to include patterns like checks and camouflage and colours like navy, white, turquoise, red, and blue. You can see people staring at you with Ray Ban sunglasses when you opened up your fashion magazine. â⬠¢Thereââ¬â¢s not a generation alive that can't remember owning (or wanting to own) a pair of these iconic sunglasses. o Presidents o movie stars o rock stars o artists o fashion designers o runway models Tribe Profile â⬠¢We found from our questionnaires that Hipsters are quite fashionable people who want to make a statement about themselves with their unique style. We also found that t he majority of Hipsters ages range from 16-28.Therefore we aim to create a modern style of glasses that this age group will find attractive â⬠¢Hipsters can live in various households and generally we found that marital and family status had little effect on their reason if they were to buy the product. Hipster mostly composed of young generation teens who are still studying so their income is greatly limited. Furthermore they mostly live with their parents and we realize that we have to make it affordable for this market as this is the baulk of the hipster market. We also realize that their families are mainly middle class from urban areas. Furthermore the research reveals that macro environmental forces. In particular Demography, Culture, Geography, Economic and Natural environment factors will have a significant impact on the Hipster behaviour. Objectives oTo gain more new customers a month as well taking market share from competitors to increase customer base omaintain our cu rrent customers ogain new customers to increase the number of sales by 20% a month oobtain a higher profit by introducing these sunglasses into the marketplace oincrease brand reputation worldwide The target audience is fully informed about features and benefits of our products oto be fashion pioneers in the industry Productâ⬠¢Shades is a new product, that allows users to change their shade colour on the fly using an eletronic switch located on their sunglassess. Customers have the ability to customise their selection of colours when purchasing their new pair. â⬠¢Users cycle through their selected lens colour by pressing a button. The variable lens colour gives more versatility to the user. Demography â⬠¢Age: in between 16-28. Size: Bigger size of young population will result in more sales. â⬠¢Density: Denser population will help in cost cutting as fewer stores will be covering large population which will reduce the fixed costs. â⬠¢Occupation: Anyone with white c ollar job is less likely to be hipster similarly hipsters working long hours and demanding job are less likely to go out or spend more time in dressing up.On the other hand if itââ¬â¢s a student or someone from fashion industry is most likely to go out and spend more time on their looks. â⬠¢Culture: can affect clothing design and style for e. . some culture has their own different printing of native animals, plants and landmarks such as Aborigines similarly in some culture skin show is not appropriate. â⬠¢Geography: Climate can affect clothing style and colours but not as many on glasses. e. g. in hot weather loose clothing and light colours products and in colder areas warm bright colours. â⬠¢Economic environment: Economic condition would have minor effect as glasses are not bought on regular bases. â⬠¢Natural Environment: Our product is recyclable and made of 80% recycled material.Launch Strategy 4ps Product: The new product offers changeable lens colours on the fly. Ray ban consists of wayfarer, aviator, clubmaster, cockpit, caravan, rare prints, Jackie ohh, warrior; daddy o. Ray ban offers several models and dozens of optional features. The glasses come with a comprehensive warranty that is the best part of ray ban glasses. â⬠¢ Promotion: Ray ban spends million each years on advertising in Australia to tell about the company and its many products. Ray ban embedded in both on and offline campaigns , through media channels ,television, magazines, billboards ,online advertisements thought tv celebrities.Ray ban also promoted through discount sales and promo items. â⬠¢ Price: Ray ban understood the need of people very well and diversified it price according to customersââ¬â¢ suitability. Ray ban also have expensive limited edition for those who want for brag. The price for normal Ray ban glasses is between 100 to 200 dollars. Being the leader Ray ban remain their price unchanged. â⬠¢ Place: Ray ban understood the important of diversifying its products which explains its implementation on eyewear market. New innovations and better services, better communication will allow Ray ban to maintain its position in market.SWOT analysis â⬠¢Strengths oLong standing and well established brand. oHigh quality and durable oProvide numerous styles and many color options oMany of the sunglasses are gender neutral oAppeals to many generations oPromise 100% anti reflective lenses, which protect eyes against harmful rays. â⬠¢Weaknesses oCostly products oExclusivity of distribution channels Opportunities oRaise awareness about the important of protective lenses. oChance fro brand extension and expansion. oEmphasize Ray ban as a brand that values individuality and self-expression. To create valuable partnerships with other brands with similar messages and larger audience.â⬠¢Threats oIn hard economic times peoples buy designer products. oMany stores sell cheaper versions of Ray ban. oMay seen as a trend that will d ie out. oConsumer brand loyalty to other sunglasses Competitors â⬠¢ Oakley sunglasses focus on protecting the users' eyes from the sun, they accomplish this through use plutonite, which is a type of patented material, in their lenses to filter out any possible contact that UVA, UVB, UVC and harmful blue light may have with your eyes. ANSI impact tests are safety measures that glasses go through to see how well they are made and will perform. The ANSI impact tests are regarded as the gold standard safety test and Oakley sunglasses exceed the standards set by these tests. â⬠¢ Oakley's High Definition Optics are known for exceeding these standard while using 3D technology to do so. â⬠¢ The lenses seen in Ray-Ban eyewear products are often overshadowed by those seen in Oakley products. These higher quality and standards are often reflected in the expensive price of Oakley glasses.The Prada eyewear collection comes in different designs, styles, and colours. Offers metal frame s that are specially, made from a special metal alloy that is fade-resistant, and lightweight and convenient to use. ($350-$500) â⬠¢ Offer plastic or nylon frames, which offer safe and lightweight protection for the eyes. Most nylon-framed sunglasses by Prada carry the distinctive Prada logo on the side of the frame. ($200-$400) â⬠¢ Offers the Prada Sport eyewear collection, which is, targeted and specially designed for sports enthusiasts and individuals. The Prada Sport eyewear collection, also, comes in, metal and nylon frames. Prada has quality and style with correction eyeglasses.
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