Microtubles Essay Example For Free At Magic Help - Free Essay Example

Sample details Pages: 7 Words: 2132 Downloads: 9 Date added: 2017/06/26 Category Medicine Essay Type Research paper Did you like this example? Describe the Structure and Functions of Microtubules Why Can Drugs That Interfere With Microtubule Assembly Be Used as Cancer Therapy? Introduction Microtubules form as a highly organised network of polarised tube filaments from a protein called tubulin. Its regulation is needed for processes such as mitosis, cell migration, cell signalling and cell trafficking. The microtubules themselves are regulated by several kinases and phosphatases via signalling cascades, and concomitantly by interactions with actin cytoskeleton and adhesion sites. Microtubule-targeted drugs (MTDs) constitute a major anticancer therapeutic class having properties of anti-mitotic and anti-angiogenic properties, thereby inhibiting malignant cell growth mainly by altering microtubule dynamics in both cancer and endothelial cells. The key to design of MTDs and the understanding of tumour progression regulators is the identification of proteins regulating the microtubule network. Don’t waste time! Our writers will create an original "Microtubles Essay Example For Free At Magic Help" essay for you Create order Cell Morphology and Function As the name implies, microtubules are hollow tubes having an external diameter of roughly 25nm and a cell wall thickness of 5-7nm. One of their functions is to transport organelles (e.g. secretetory vesicles) through the cytoplasm, a particularly important role in nerve cells where axoplasmic flow is required. They also have a critical role in cilia and flagella movement. Microtubules originate from a complex structure known as centrosome. Between cell divisions (figure 1), the centrosome is located at the centre of a cell near the nucleus. Embedded in the centrosome are two cylindrical centrioles, arranged at right angles to each other. At the onset of cell division, a centrosome divides and the two daughter centrosomes move to opposite poles of the nucleus to form a mitotic spindle The functions of microtubules are important to the survival of eukaryotic cells because, along with actin and intermediate filaments, microtubules constitute the cytoskeleton which offers shape a nd strength to the cytoplasm. It is therefore vital that we understand their fundamentals, such as what they are composed of and how their structure is both maintained and destroyed within cells. As mentioned in the introduction, the building blocks microtubules are tubulin. However, only two forms of tubulin, ?-tubulin and ?-tubulin, play a role in the formation of the microtubule structure. When the ? and ?-tubulin bind, a useful subunit called a heterodimer forms. When intracellular conditions favour assembly, tubulin heterodimers assemble into linear protofilaments, which in turn assemble into microtubules. All such assembly is subject to regulation by the cell. [11] The interactions holding ? and ?-tubulin in a heterodimeric complex are strong enough that ? tubulin subunit rarely dissociates under normal conditions. Each tubulin subunit binds two molecules of GTP. One GTP-binding site, located in ?-tubulin, binds GTP irreversibly and does not hydrolyze it, whereas the second site, located on ?-tubulin, binds GTP reversibly and hydrolyzes it to GDP. The second site is called the exchangeable site because GDP can be displaced by GTP. The recently solved atomic structure of the tubulin subunit reveals that the non-exchangeable GTP is trapped at the interface between the ? and ?-tubulin monomers, while the exchangeable GTP lies at the surface of the subunit Microtubules may appear to be stable but they usually oscillate between growth and shortening phases. During growth, heterodimers are added on to the end of a microtubule, and during shrinkage they come off as intact subunits. [11] This active process of assembly and disassembly can be inhibited by a range of drugs that bind to many sites in the ?-tubulin subunit. These drugs prevent mitotic division and ultimately lead to cell death, by means of necrosis and apoptosis. The subunits are aligned end to end into a protofilament. The side-by-side packing of protofilaments forms the wall of t he microtubule. In this model, the protofilaments are slightly staggered so that a-tubulin in one protofilament is in contact with a-tubulin in the neighboring protofilaments. Microtubules and Cancer Therapy The aim of treatment in patients with cancer is cure or, if this is not possible, effective palliation of many cancers present as localised tumour masses, but surgery or radiotherapy often fails to eradicate the disease, which eventually becomes widespread. For this reason, there is a trend to incorporate systemic treatment with local treatment at the time of diagnosis. [3] The basic mechanism of anticancer drugs is the inhibition of cell proliferation processes. However if they fail to selectively target tumour cells over proliferating normal cells, this renders the drug toxic. This particularly arises in the bone marrow, gastrointestinal epithelium and hair follicles. A cytotoxic drug is said to be selective in cancer therapy if it inhibits malignant composite cells undergoing division and concomitantly allows for normal cell proliferation. Anticancer drugs are classified according to their sites of action either during the cell cycle or along the synthetic pathway of cellu lar macromolecules. Some drugs are only effective during part of the cell cycle, which are termed phase-specific drugs, while others are cytotoxic throughout the cell cycle usually called cycle-specific drugs [3]. Vinca alkaloids and taxanes are drugs that inhibit mitosis by binding to the microtubular proteins necessary for spindle formation. They can therefore be classified as phase-specific drugs to be more precise however; they are M-phase specific. The main vinca alkaloids are vincristine, vinblastine and vindesine. They have been used in the treatment of cancer for over many years. It is because of their efficacy that has guaranteed that they remain among the drugs of choice for numerous types of human cancers, â€Å"They are used in acute lymphoblastic leukaemia, lymphomas and some solid tumours† [3]. They bind to tubulin and inhibit its polymerisation into microtubules which prevents spindle formation. [14] Microtubules are central to a number of cellular pr ocesses including the formation of the mitotic spindle. It is without a doubt that the destruction of the spindle leads to a loss of chromosome segregation which consequently inhibits cell division causing cell death. Although the cell spindle was an obvious goal for further drug development, research in this area was obsolete until the exciting clinical results of the taxane drugs were reported in the late 1980s [4]. The taxanes paclitaxel and docelatel also bind to tubulin, however these agents, in contrast to the vinca alkaloids, stabilise the spindle and produces mitotic arrest. Thus, microtubule stabilisation leads to similar effects as microtubule disruption. Research in the field has again increased following the observation that agents that bind to tubulin can selectively destroy the arrangement of blood vessels within tumours, causing widespread tumour necrosis [5]. It may be possible that the vinca alkaloids and the taxane drugs also exert part of their tumour-des troying action through an antivascular mechanism. This may depend on targeting endothelial cells rather than tumour cells for drug action. A possible advantage of this approach is that endothelial cells are not transformed and are unlikely to acquire mutations resulting in drug resistance. [6] The destruction of the tumour vasculature also arises through a tubulin-related mechanism. The disorder of the microtubular arrangement impairs the cell function because microtubules are involved in the maintenance of cell shape. The tumour selectivity begins from the unsystematic character of tumour blood vessels. Rouget cells or pericytes are associated abluminally with all vascular capillaries and post-capillary venules. [10] The tumour blood vessels lack these cells along with sustaining smooth muscle which causes them to be feeble. Therefore the endothelial cells lining the tumour blood vessels are more vulnerable to the effects of vinca alkaloids and taxanes. Although contact with these anticancer drugs is experienced by all vascular endothelial cells, it is the vulnerable tumour blood vessels that are damaged the most. This ultimately leads to necrosis of tumour cells that were reliant on the blood vessels. One problem seen in these studies is the survival of cancer cells at the periphery of the tumour [7]. These are nourished from the blood vessels of the normal neighboring tissue and are therefore not affected by the damage of blood vessels in the tumour. These tumour cells are likely to increase in number again. For that reason, it is doubtful that these anticancer drugs will be effective unless given in combination with additional therapies. This may be strikingly more successful than single drugs, for example in the treatment of some cancers such as Hodgkins disease. [3] The shortcoming in previous clinical trials on agents targeting tubulin was the rejection of potentially useful agents because interest was more centered on toxicity and survival of drugs, rather than the action or effects of drugs on blood vessels. The breakthrough of new antivascular treatments would be an essential addition to cancer therapy; hence it is these agents that are presently most fascinating to scientists. Other Drugs That Inhibit Function of Microtubules There are more than thirty drugs in the past or in present clinical development. [13] In order to maintain a reasonable size for the following sections, only a few of the more fascinating drugs will be discussed. Some that where not mentioned previously include: Taxol an anti-cancer drug, stabilises microtubules Colchicine binds tubulin and blocks polymerisation. Microtubules depolymerise at high colchicine concentration. Nocodazole causes de-polymerisation of microtubules. Actinomycin antibiotic able to halt cancer, not widely used as it is highly toxic The Microtubule Network as a Target for Therapeutic Agents The various M-phase specific drugs act by targeting different parts of the heterodimer. To date, three binding areas have been acknowledged: the colchicine site close to the ?/? interface, the region where the vinca alkaloids bind, and the taxane binding pocket. [13] Colchicine, currently a medication for acute gout, also inhibits cell division and has therefore previously been used in cancer therapy. It binds to a site near the ? and ?-tubulin interface within the microtubule, blocking microtubule polymerisation [15]. However, its high toxicity prevents its use for current cancer therapy. Vinca alkaloids inhibit microtubule assembly by cross-linking at the inter-dimer interface; they sterically distort the protofilament and induce tubulin to form alternate spiral polymers [16]. The mechanism of action of taxanes is quite different from that of the other two, for it promotes the assembly of microtubules, resulting in highly stable, non-functional polymers. Taxanes bind at the M loop on the ?-subunit, stabilising lateral contacts between protofilaments [17]. Antimitotic agents that interact with microtubule components are of interest for the insights they can provide into the roles of microtubules in cells and the subtleties of tubulin structure and also for their potential activity in the treatment of human neoplastic diseases. A variety of bioassays have been used to identify new antitubulin agents and new techniques have been developed to further understand their biological potency and mechanistic basis at the molecular level. Drug Combinations Although M-phase specific drugs are remarkable in that it prevents further malignant growth, the administration of combinations of drugs given intermittently often produces better results than more continues treatment with a single drug. The rationale is that a combination of drugs with different toxic effects and affecting different biochemical pathways has anti-tumour activity without addictive toxicity. [3] However, a large number of antimitotic drugs are currently under development, this implies that microtubules are still a very worthwhile target for anticancer therapies. Bibliography [1] Gillian Pocock, Christopher D. Richards. Human Physiology: The Basis of Medicine (Oxford Core Texts). Oxford University Press; 3Rev Ed edition (Jan 2006). p 23 [2] https://www.daviddarling.info/encyclopedia/C/cell_cycle.html [3] Michael J. Neal, Medical Pharmacology at a Glance, Blackwell Publishing; 5th Edition (Aug 2005), p92-93 [4] Rowinski, E.K., Cazenave, L.A., Donehower, R.C. (1990) Taxol: a novel investigational antimicrotubule agent. J Natl Cancer Inst 82, 1247-1259. [5] Dark, G.G., Hill, S.A., Prise, V.E., Tozer, G.M., Pettit, G.R. and Chaplin, D.J. (1997) Cancer Res 57, 1829-1834. [6] Antivascular therapy: a new approach to cancer treatment. British Medical Journal, March 27, 1999   by A J Hayes, L Y Li, M E Lippman [7] Zhao, S., Moore, J.V., Waller, M.L., McGown, A.T., Hadfield, J.A., Pettit, G.R. and Hastings, D.L. (1999) European J Nuclear Medicine 26, 231-238. [8] https://www.ba-education.demon.co.uk/for/science/dnaphotos/dnaphoto.html [9 ] https://www.emc.maricopa.edu/faculty/farabee/biobk/BioBookmito.html [10].https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrievedb=PubMedlist_uids=8915187dopt=Abstract [11] https://www.ruf.rice.edu/~bioslabs/studies/invertebrates/microtubules.html [12] Harvey Lodish, Arnold Berk, Lawrence S. Zipursky, Paul Matsudaira, David Baltimore, James Darnell. Molecular Cell Biology, W. H. Freeman; 5th edition (2003) p1036-1035 [13] Jordan, A., Hadfield, J.A., Lawrence, N.J. and McGown, A.T. (1998) Tubulin as a target for anticancer drugs: agents which interact with the mitotic spindle. Med. Res. Rev. p18 [14] H.P. Rang, M. Maureen Dale, James M. Ritter, Philip Moore, Pharmacology, Churchill Livingstone; 5th edition (31 Mar 2003), p 704 [15] Downing, K.H. and Nogales, E. New insights into microtubule structure and function from the atomic model of tubulin. (1998) Eur. Biophys J 27, 431-436. [16] Wilson, L., Jordan, M.A., Morse, A. and Margolis, R.L. (1982) Journal of Molecular Biology 159, 125-149. [17] Snyder, J.P., Nettles, J.H., Cornett, B., Downing, K.H. and Nogales, E. (2001) Potential for self-assembly and microtubule interaction 98, 5312-5316.

Literary Analyzes Of Young Goodman Brown - 1746 Words

Literary analyzes of Young Goodman Brown Young goodman brown by Nathaniel Hawthorne is a story about a normal man that ventures into the forest to meet an old man who attempts to tempt him into going deeper into the woods to worship the devil. After the old man convinces him that everyone that he loves and respects is going to the devil’s ceremony he gives in. In Young Goodman Brown, Hawthorne effectively uses the personality and psychology of the Characters along with symbolism to portray the theme that putting one s faith in others leads to weakness. The Characters in Young Goodman Brown are meant to represent society as a whole. They show how sin can tempt any individual whose faith is still developing. D. M. Mckeithan writes in her†¦show more content†¦(95) The old man uses an everybody is doing it approach to encourage Goodman Brown to attend a ceremony to worship the Devil. The old man shows the people Goodman Brown respected most in his community to degrade his faith. As Goodman Brown loses faith in others, he loses faith in himself. Mckeithan continues to say, â€Å"The Minister of Salem Village, Deacon Gookin, Goody Closyse, and Faith were all good in spite of what Goodman Brown eventually came to think of them (96). These are people that were supposedly more spiritually mature than Goodman Brown. He relied on their faith to keep his strong because his faith in God was still new and not fully developed. The psychology of Goodman Brown plays a major rule in his lack of faith because his lack of self esteem allows his desires overcome his reason and morality. Goodman Brown’s conflicts of interest are represented throughout story through the characters. All his evil desires are his id and his reason for avoiding his sin such as the views that his society will have on him is his ego. Levy said in his essay â€Å"The Problem of Faith in â€Å"Young Goodman Brown†Ã¢â‚¬ , â€Å"His submission to evil suggests that the demands of the id have overtaken the ego† (379). When the highly respected people in his community gave inShow MoreRelatedEssay on The Ambiguity in Hawthornes Young Goodman Brown1587 Words   |  7 PagesThe Ambiguity in â€Å"Young Goodman Brown†      Ã‚  Ã‚     The literary critics agree that there is considerable ambiguity in Nathaniel Hawthorne’s â€Å"Young Goodman Brown.† This essay intends to illustrate the previous statement and to analyze the cause of this ambiguity.    Henry James in Hawthorne, when discussing â€Å"Young Goodman Brown† comments on how imaginative it is, then mentions how allegorical Hawthorne is, and how allegory should be expressed clearly:    I frankly confess that I haveRead MoreMy Psychoanalytic Views of Two Short Stories1454 Words   |  6 Pagesradical, when put into life situations they actually make perfect sense. 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Cultural difference between US China Free Essays

The relative differences in the American and Chinese business background may well predict how transaction costs will be evaluated. On the part of the Chinese business criterion, it seems that the contrasting attitude of their business scheme may define a larger cost in trade investments for the American counterparts. The promising good trade partnership between American companies doing business with its Chinese segments may bring huge monetary concerns on the part of the former. We will write a custom essay sample on Cultural difference between US China or any similar topic only for you Order Now The most significant attribute in the Chinese business core is the fact that their business structure is purely based on experience. This is very much evident since most of the companies are family-based businesses. As a result, there is no exact business trend that will make the companies adhere to the normal business plan as compared to the companies in the United States. This fact contributes largely to the aspect of limiting the flow of investment within a specific domain of the family owned business. One disadvantage when it comes to costs is that an American company may not be able to induce its influence on the transaction if they are to deal with the Chinese based companies. The structured and well organized scheme employed by American companies may not be useful at all since the transaction will purely be based on the way the Chinese handle its business. The unpredictability of the financial aspect might take its toll in the American company’s investments. These will likely to happen even if the labor and commodity cost in china is very cheap. Also, there is not even a comparison of the Chinese and U. S. factory labor costs because reliable statistics from the Asian giant don’t exist (News Analysis). This is a somewhat big drawback if the American company needs to assess the appropriate wage that it should set aside from its capital. Another big concern that will predict a very large cost discrepancy would be in the aspect of formal agreement. The Chinese tend to use fewer contracts when involving other sources of investment. This is very contrasting to the attitude of American companies where everything is settled on paper even before the activity proceeds. The Chinese companies tend to rely on trusted partnerships and loyalty of their background workforce for their own survival in the trade world. This could equate to a very high cost for the American company especially if the agreement will not be implemented according to the drafted plan. It is very possible that one segment of the production line will experience problems in business processing. Such scenario will eventually take effect on both the Chinese and American company in partnership. However, the larger cost will be incurred on the American company’s account. This is so because of the large dependency in a specified business plan. Moreover, there will be a waste in monetary values together with the production time frame just to take full recovery of the lost trade opportunity. This is the most discouraging factor when it comes to unspecified productivity dilemmas. The global economy is starting to implement a rather large opportunity for all markets. Apparently, because of this global merchandising capacity of various countries, it would be very much accepted that the efficiency and survival of a certain business lies directly on the trading partners where it seems to be compatible with. On the case of the American and Chinese business relationship, it should first consider how the financial cost of partnership will eventually influence each other’s trading posts. A complete analysis of the cost attributes should be taken into consideration. Apparently, the behavior of Chinese business is very difficult to understand (Chen, 1999-2007). References: Chen, Ming-Jer. 1999-2007. Inside Chinese Business. QuickMBA. Retrieved May 8, 2007 from http://www. quickmba. com/mgmt/intl/china/. News Analysis. 2004. Just How Cheap Is Chinese Labor?. Businessweek. Retrieved May 8, 2007 form http://www. businessweek. com/bwdaily/dnflash/dec2004/nf2004122_6762_db039. htm. How to cite Cultural difference between US China, Papers

Photographs objectify essay Example For Students

Photographs objectify essay Photographs objectify: they turn an event or a person into some thing that can be possessed. And photographs are a species of alchemy, for all that they are prized as a transparent account of reality (p. 81). Photographs can never really be objective records of history; photographers inject their own artistic attitudes into their work. Photographers have been immortalizing warfare with their cameras since the time of the Crimean War. Back then, it was impossible to create objective photographs, not that anyone would have tried. The British sent out Roger Fenton to present the war to the public as a dignified all-male group outing (p.50). Because it took several seconds to capture a single picture, it was impossible for Fenton to photograph actual combat, and the government forbade him from photographing any dead, ill or maimed soldiers. In addition, he had to pose his subjects, so the soldiers were aware of their being photographed. It was virtually impossible for Fenton to create candid, realistic photos that reflected the true lives led by the soldiers; he could only produce artful photographs that reinforced the attitudes presented to the British public by the government. But even after photography became more practical at the time of the Civil War, photographers still manipulated the composition of their photographs. Photographers like Alexander Gardner and Timothy O Sullivan still captured actual soldiers and actual battlefields, but they continued to use artistic license to create images that were more compelling to their viewers. Photographers posed dead soldiers and manipulated the compositions of their work, even though technology had progressed to the point that staging their photos was unnecessary. They still held onto the belief that to photograph was to compose (with living subjects, to pose) and the desire to arrange elements in the picture did not vanish because the subject was immobilized, or immobile (p. 53). With the invention of motion pictures, one would think that war would finally be recorded as it really happened, but this still wasnt the case. Soldiers reenacted battle charges and other events for the benefit of the cameramen. In 1898 Roosevelts Rough Riders charged up San Juan Hill a second time, after the battle, because the actual battle charge was deemed insufficiently dramatic. Films were also shot again if the original reel was too violent or too terrible. Historical records were still being fabricated, even though new technology made such falsifications increasingly difficult. With the advent of the motion picture, photographers became somewhat obsolete in their office of recording history. Yet photographs still hold power. Photography is selective; it is always the image that someone chose; to photograph is to frame, and to frame is to exclude (p. 46). Photographers in more recent times use their photographs to make statements about war. In the Vietnam War, photographers criticized the war with their photographs, to reflect and support the criticism expressed by the American public. However, the viewers of such photos still seem to forget about the photographers that are behind the photos, framing them to fit their purposes. A picture may be worth so many thousands of words, but those words are not and never will be objective. The problem is not that people remember through photographs, but that they remember only the photographs (p. 89). Photographs taken today in Iraq will be found in textbooks thirty years from now. Our children and the generations that follow will look at those pictures and read the stories that go along with them, but they will probably retain the memory of the photograph over the words found in the text. .u0e0d169434dd1f3a427f7eea5c0ed3d0 , .u0e0d169434dd1f3a427f7eea5c0ed3d0 .postImageUrl , .u0e0d169434dd1f3a427f7eea5c0ed3d0 .centered-text-area { min-height: 80px; position: relative; } .u0e0d169434dd1f3a427f7eea5c0ed3d0 , .u0e0d169434dd1f3a427f7eea5c0ed3d0:hover , .u0e0d169434dd1f3a427f7eea5c0ed3d0:visited , .u0e0d169434dd1f3a427f7eea5c0ed3d0:active { border:0!important; } .u0e0d169434dd1f3a427f7eea5c0ed3d0 .clearfix:after { content: ""; display: table; clear: both; } .u0e0d169434dd1f3a427f7eea5c0ed3d0 { display: block; transition: background-color 250ms; webkit-transition: background-color 250ms; width: 100%; opacity: 1; transition: opacity 250ms; webkit-transition: opacity 250ms; background-color: #95A5A6; } .u0e0d169434dd1f3a427f7eea5c0ed3d0:active , .u0e0d169434dd1f3a427f7eea5c0ed3d0:hover { opacity: 1; transition: opacity 250ms; webkit-transition: opacity 250ms; background-color: #2C3E50; } .u0e0d169434dd1f3a427f7eea5c0ed3d0 .centered-text-area { width: 100%; position: relative ; } .u0e0d169434dd1f3a427f7eea5c0ed3d0 .ctaText { border-bottom: 0 solid #fff; color: #2980B9; font-size: 16px; font-weight: bold; margin: 0; padding: 0; text-decoration: underline; } .u0e0d169434dd1f3a427f7eea5c0ed3d0 .postTitle { color: #FFFFFF; font-size: 16px; font-weight: 600; margin: 0; padding: 0; width: 100%; } .u0e0d169434dd1f3a427f7eea5c0ed3d0 .ctaButton { background-color: #7F8C8D!important; color: #2980B9; border: none; border-radius: 3px; box-shadow: none; font-size: 14px; font-weight: bold; line-height: 26px; moz-border-radius: 3px; text-align: center; text-decoration: none; text-shadow: none; width: 80px; min-height: 80px; background: url(https://artscolumbia.org/wp-content/plugins/intelly-related-posts/assets/images/simple-arrow.png)no-repeat; position: absolute; right: 0; top: 0; } .u0e0d169434dd1f3a427f7eea5c0ed3d0:hover .ctaButton { background-color: #34495E!important; } .u0e0d169434dd1f3a427f7eea5c0ed3d0 .centered-text { display: table; height: 80px; padding-left : 18px; top: 0; } .u0e0d169434dd1f3a427f7eea5c0ed3d0 .u0e0d169434dd1f3a427f7eea5c0ed3d0-content { display: table-cell; margin: 0; padding: 0; padding-right: 108px; position: relative; vertical-align: middle; width: 100%; } .u0e0d169434dd1f3a427f7eea5c0ed3d0:after { content: ""; display: block; clear: both; } READ: The Invention of Photography - The Daguerreotype EssayPhotographs have been used to depict warfare for centuries now. Photographers like Roger Fenton and Timothy OSullivan recorded the so-called realities of war. While their photographs were not completely true to life, they still hold a piece of the truth. Fentons photographs show the very idealistic side of the Crimean War, which did exist, if only in the rarest of moments, and OSullivans work showed the brutal realities of war-time epidemics and death on a battlefield. Even if his photographs were not photos of soldiers exactly as theyd fallen, they were photographs of real dead soldiers that had died real deaths, from real bullets or real illnesses. According to Sontag, a painting or drawing is judged a fake when it turns out not to be by the artist to whom it had been attributed. A photographà  is judged a fake when it turns out to be deceiving the viewer about the scene it purports to depict (p. 46). This is because people assume that photographs are not art, or that they can be both art and historical fact simultaneously. This is impossible. No matter how advanced technology becomes, it will always be impossible to produce a completely objective photograph; the photographer will inevitably shine through, in the subject matter, in the composition, in everything; a photographer becomes part of his work, and that work therefore becomes art. Photographers have not been recording warfare for centuries-they have been creating art surrounding warfare, and in doing so, they have captured the true essences of that warfare.