Engineering Genetic Logic Circuits for Cancer Cells

Engineering Genetic Logic Circuits for Cancer Cells http://www.nature.com/nbt/journal/v27/n12/full/nbt1209-1071.html http://www.rcuk.ac.uk/documents/publications/syntheticbiologyroadmap-pdf/ (Accessed 11 10 2016) Engineering genetic logic circuits for cancer cell recognition and treatment Over the past 60 years, the field of molecular biology has experienced significant advances. Following the genomic revolution, genetic engineering enabled to modify endogenous gene networks using technologies such as site-directed mutagenesis, DNA recombination, DNA sequencing, synthesis and others. Now, after rigorous engineering, the field of synthetic was born making it possible to create novel biological entities that behave in a controllable and predictable manner 1. Synthetic biology is defined by the Royal Academy of Engineering as The design and engineering of biologically based parts, novel devices, and systems as well as the redesign of existing natural biological systems 2. It builds on the work of conventional genetic engineering by not only focusing on individual genes but by applying an engineering driven perspective designing and creating complex artificial biological systems. At present, synthetic biology has been applied in a wide range of areas demonstrating its potential to solve major global challenges in the fields of bioremediation, biosensing, production of biofuels, biomaterials, therapeutics, and biopharmaceuticals. Examples comprise the creation of organisms that could clean hazardous waste such as radioactive elements or arsenic 3, modification of yeast for the production of isobutanol 4, engineering viruses and bacteria to treat cancer 5,6, and the development of a diabetes treatment using an optogenetic gene circuit 7. Synthetic biology makes use of engineering analogies such as the one illustrated by Andrianantoandro and collaborators were it is compared to computer engineering at different hierarchy levels (Figure 1). Both disciplines take a bottom-up approach by integrating its component parts to build a more complex system. At the bottom are the biochemical molecules (DNA, RNA, proteins and other metabolites) equivalent to the physical layer of capacitors, transistors and resistors in computer engineering. One level up at the device level, physical processes are controlled by biochemical reaction comparable to engineered logic gates. By connecting and integrating these modules into host cells, synthetic biologists can program cells with the desired behaviour. More complex tasks can be accomplished by using a cell population, in which cells communicate each other to perform in a coordinated way, much like the case of computer networks 8. Finally, from an engineering point of view, what synthetic biologists are doing now is quite like what electrical engineers have been doing for many years, designing electronic circuits using standard components, such as resistors, capacitors and transistors. The difference lies in the building blocks that are used. Synthetic biologists design genetic circuits with specified functions using standard engineered biological parts such as genes, promoters, ribosome binding sites and terminators. In this regard, synthetic biology is to biology what electrical engineering is to physics, which both deal with electrons but one focuses on the understanding of their nature and the other aims to make use of them to build useful applications. Â   Â   Synthetic biology follows a hierarchical structure, building up systems from smaller components. At the lowest level are the parts, which are pieces DNA that encode for a single biological function such as a promoter. These parts are then combined into the next layer, the device layer, which is a collection of parts that performs a desired order function (e.g. the production of a protein). Devices are further combined into a system, which can be defined as the minimum number of devices necessary to perform the behaviour specified in the design phase. Systems can have simple behaviour (e.g. an oscillator) or a more complex behaviour (e.g. a set of a metabolic pathways to synthesise a product.)Parts and devices are usually treated as modular entities in design and modelling. This means that it is assumed that they can be exchanged without affecting the behaviour of the other systems components that are left untouched. At the module level, biological devices can be used to assemble comp lex pathways that function like integrated circuits. Early synthetic biology studies began developing circuits in prokaryotic organisms. Inspired by electronic, first systems made use of basic elements such as promoters, transcriptional repressors and ribosome binding sites to create small modules. These modules included the construction of oscillators 9, genetic switches 10, and digital logic gates 11. The successful construction of the first systems demonstrated that engineering-based methods could be used to programme computational behaviour into cells 12 (Figure 2).

Meaning of life †Phrase Essay

Origin: A person seeing a table piled high with sumptuous food has a tendency to get too many and/or too large a portion. Since the problem is brought on by the eyes and a lack of reason, the person is portrayed a one whose eyes are bigger than their stomach. Elephant in the room Meaning: An important and obvious topic, which everyone present is aware of, but which isn’t discussed, as such discussion is considered to be uncomfortable. Origin: The theme of the exhibition was global poverty. By painting the elephant in the same bold pattern as the room’s wallpaper, Banksy emphasized the phrase’s meaning, by both making the elephant even more obvious and by giving those who chose to ignore it (like the woman in the tableau) an opportunity to pretend that it had blended into the wallpaper background. Even at the turning of the tide Meaning: The phrase is used to denote some change from a previously stable course of events. Origin: The phrase comes from Shakespeare’s Henry V where he use turning of the tide in a letter. Ear candy Meaning: Music with an instant appeal but with little lasting significance. Origin: The term may have been in use before 1977, although I can find no references to it in print that predate Reddy’s album title. The term did get picked up though and soon became a generic term for music that was initially attractive but with little lasting substance. Candy is of course what the US calls the confectionery that many parts of the English-speaking world call sweets. The sugary, insubstantial imagery is well suited to these phrases. Excuse my French Meaning: Please forgive my swearing. Origin: A coy phrase used when someone who has used a swear-word attempts to pass it off as French. The coyness comes from the fact the both the speaker and listener are of course both well aware the swear-word is indeed English. F Fair and square Meaning: Honest and straightforward, especially of business dealings. Origin: In the 16th century ‘square’ meant ‘fair and honest’ so ‘fair and square’ is tautological. George Puttenham used that meaning of square in The arte of English poesie, 1589:†[Aristotle] termeth a constant minded man – a square man. â€Å"Francis Bacon’s essay Of Prophecies, 1604 is the first known use of ‘fair and square’: Fast asleep Meaning: soundly asleep. Origin: The ‘fast’ in ‘fast asleep’ derives from the Old German ‘fest’, meaning ‘stuck firmly’; ‘not easily moveable’ – as in ‘stuck fast’. ‘Asleep’ derives from ‘sleep’ in the same way that nautical adverbs like ‘aground’ and ‘astern’ derive from ‘ground’ and ‘stern’. To be ‘fast asleep’ was to be stuck firmly in sleep, analogous to a beached ship being ‘fast aground’. Filthy rich Meaning: Very rich, possibly having become so by unfair means. Origin: The phrase comes from the word â€Å"filthy lucre† means money from dishonorable gain. This was first used as a noun phrase meaning â€Å"rich people; who have become so by dishonorable means† like gambling. Face the music Meaning: Face the truth Origin: Comes from the British military. When someone was court marshaled, there would be a military drum squad playing, hence face the music. The term â€Å"drummed out of the military† came from this practice†¦. From stem to stern Meaning: Thorough, complete. Origin: The very front of a ship is called the stem, the rear is called the stern. From stem to stern includes the entire ship. G Get a leg up Meaning: To get a boost or advantage. Origin: This phrase may incorrectly invoke images of a dog raising its leg. In fact â€Å"Getting a leg up† is from the act of an equestrian receiving help in mounting a horse. The helper would create a foothold by cupping the hands to heft the rider upward, throwing a leg up and over the steed. Get of the wrong foot Meaning: Make a bad start to a project or relationship. Origin: The phrase comes from the idiom â€Å"put your best foot forward. † This means to make a best impression. Despite the implication we only have two choices, so if there’s a wrong foot there has to be a right one too and get off on the right foot is also in common use. Graveyard shift Meaning: A late-night/early-morning work shift. Origin: So they would dig up coffins and would take the bones to a â€Å"bone-house† and reuse the grave. When reopening these coffins, one out of 25 coffins was found to have scratch marks on the inside and they realized they had been burying people alive. So they thought they would tie a string on the wrist of the corpse, lead it through the coffin and up through the ground and tie it to a bell. Someone would have to sit out in the graveyard all night (the â€Å"graveyard shift†) to listen for the bell; thus, someone could be â€Å"saved by the bell† or was considered a â€Å"dead ringer. † Grinning like a Cheshire cat Meaning: Grin broadly. Origin: The phrase comes from the novel â€Å"Alice in Wonderland† where she asked the duchess why the cat grinned. The duchess answered â€Å"Because it’s a Cheshire cat! † ‘I didn’t know that Cheshire cats always grinned; in fact, I didn’t know that cats COULD grin. ‘ ‘They all can,’ say the Duchess; ‘and most of them do. ‘ Good as gold Meaning: Well – behaved and obedient. Origin: When banknotes (known as bills in the USA and some other countries) were first introduced they weren’t considered to be money in the sense we now think of them. They were promissory notes or IOUs. Gold or silver was real money as it had intrinsic value. Notes were just promises to pay in coin. UK banknotes, like those of many other countries, still include messages like this, signed by the Chief Cashier of the Bank of England: ‘I promise to pay the bearer on demand the sum of ten pounds’. So, ‘as good as gold’ ought really to be ‘as genuine as gold’, but the more usual meaning of ‘good’ has taken precedence over the years and left us with the usual meaning of the phrase. H High on the hog Meaning: Extravagantly. Origin: The best meat is on the upper portion of the pig. Rich people have always been afforded this luxury while the servants, slaves and poor have always had to eat pig’s feet, chitterlings, cracklings, etc. – low on the hog. Horse of a different color Meaning: Unlike the subject at hand. Origin: Horses are registered at birth and the registration includes a record of their color. When a horse trades hands due to sale, the registration is also transferred. Sometimes the color recorded on the registration may not match the actual color of the horse leading one to suspect the horse is not the one in the registration. Horses sometimes change color as they age, just as some people’s hair changes color. More likely the horse is not the one represented on the registration but is actually an entirely different horse. Hold your feet to the fire Meaning: To hold one accountable for a commitment, make good on a promise. Origin: Pertains to torture used during the Crusade’s. As a method for extracting confession for heresy, non-believers were positioned in a manner that allowed the inquisitor to apply flames to the feet of the accused. This was done until the accused confessed or died. Head over heels Meaning: Excited, and/or turning cartwheels to demonstrate one’s excitement. Origin: Head over heels’ is now most often used as part of ‘head over heels in love’. When first coined it wasn’t used that way though and referred exclusively to being temporarily the wrong way up. It is one of many similar phrases that we use to describe things that are not in their usual state – ‘upside-down’, ‘topsy-turvy’, ‘topple up tail’, ‘arse over tea-kettle’, ‘bass-backwards’ etc. Hard lines Meaning: Bad luck Origin: Clearly the derivation of ‘hard lines’ is entirely dependent on which line was being referred to when the phrase was coined. There is a reference to lines in the King James Version of the Bible, 1611, and that is the basis of several early citations of ‘hard lines’:Psalms 16:6 The lines are fallen unto me in pleasant places; yea, I have a goodly heritage.

Definitions and Examples of English Sentence Structures

In English grammar,  sentence structure is the arrangement of words, phrases, and clauses in a sentence. The grammatical function or meaning of a sentence is dependent on this structural organization, which is also called syntax or syntactic structure. In traditional grammar, the four basic types of sentence structures are the simple sentence, the compound sentence, the complex sentence, and the compound-complex sentence. The most common word order in English sentences is Subject-Verb-Object (SVO). When reading a sentence, we generally expect the first noun to be the subject and the second noun to be the object. This expectation (which isnt always fulfilled) is known in linguistics as the canonical sentence strategy. Examples and Observations One of the first lessons learned by the student of language or linguistics is that there is more to language than a simple vocabulary list. To learn a language, we must also learn its principles of sentence structure, and a linguist who is studying a language will generally be more interested in the structural principles than in the vocabulary per se.—Margaret J. Speas Sentence structure may ultimately be composed of many parts, but remember that the foundation of each sentence is the subject and the predicate. The subject is a word or a group of words that functions as a noun; the predicate is at least a verb and possibly includes objects and modifiers of the verb.—Lara Robbins Meaning and Sentence Structure People are probably not as aware of sentence structure as they are of sounds and words, because sentence structure is abstract in a way that sounds and words are not . . . At the same time, sentence structure is a central aspect of every sentence . . . We can appreciate the importance of sentence structure by looking at examples within a single language. For instance, in English, the same set of words can convey different meanings if they are arranged in different ways. Consider the following: The senators objected to the plans proposed by the generals.The senators proposed the plans objected to by the generals. The meaning of [first] the sentence is quite different from that of [the second], even though the only difference is the position of the words objected to and proposed. Although both sentences contain exactly the same words, the words are structurally related to each other differently; it is those differences in structure that account for the difference in meaning.—Eva M. Fernà ¡ndez and Helen Smith Cairns Information Structure: The Given-Before-New Principle It has been known since the Prague School of Linguistics that sentences can be divided into a part that anchors them in the preceding discourse (old information) and a part that conveys new information to the listener. This communicative principle may be put to good use in the analysis of sentence structure by taking the boundary between old and new information as a clue to identifying a syntactic boundary. In fact, a typical SVO sentence such as Sue has a boyfriend can be broken down into the subject, which codes the given information, and the remainder of the sentence, which provides the new information. The old-new distinction thus serves to identify the VP [verb phrase] constituent in SVO sentences.—Thomas Berg Producing and Interpreting Sentence Structures in Speech The grammatical structure of a sentence is a route followed with a purpose, a phonetic goal for a speaker, and a semantic goal for a hearer. Humans have a unique capacity to go very rapidly through the complex hierarchically organized processes involved in speech production and perception. When syntacticians draw structure on sentences they are adopting a convenient and appropriate shorthand for these processes. A linguists account of the structure of a sentence is an abstract summary of a series of overlapping snapshots of what is common to the processes of producing and interpreting the sentence.—James R. Hurford The Most Important Thing to Know About Sentence Structure Linguists investigate sentence structure by inventing sentences, making small changes to them, and watching what happens. This means that the study of language belongs to the scientific tradition of using experiments to understand some part of our world. For example, if we make up a sentence (1) and then make a small change to it to get (2), we find that the second sentence is ungrammatical. (1) I saw the white  house. (Grammatically correct) (2) I saw the house white.  (Grammatically incorrect) Why? One possibility is that it relates to the words themselves; perhaps the word white and the word house must always come in this order. But if we were to explain in this way we would need separate explanations for a very large number of words, including the words in the sentences (3)-(6), which show the same pattern. (3) He read the new book.  (Grammatically correct) (4) He read the book new. (Grammatically incorrect) (5) We fed some hungry dogs. (Grammatically correct) (6) We fed some dogs hungry.  (Grammatically incorrect) These sentences show us that whatever principle gives us the order of words, it must be based on the class of word, not on a specific word. The words white, new, and hungry are all a class of word called an adjective; the words house, book, and dogs are all a class of word called a noun. We could formulate a generalization, which holds true for the sentences in (1)-(6): (7) An adjective cannot immediately follow a noun. A generalization [as with sentence 7] is an attempt to explain the principles by which a sentence is put together. One of the useful consequences of a generalization is to make a prediction which can then be tested, and if this prediction turns out to be wrong, then the generalization can be improved . . . The generalization in (7) makes a prediction which turns out to be wrong when we look at sentence (8). (8) I painted the house white.  (Grammatically correct) Why is (8) grammatical while (2) is not, given that both end on the same sequence of house white? The answer is the most important thing to know about sentence structure:  The grammaticality of a sentence depends not on the sequence of words but how the words are combined into phrases.—Nigel Fabb Sources Speas, Margaret J. Phrase Structure in Natural Language. Kluwer, 1990Robbins, Lara. Grammar and Style at Your Fingertips. Alpha Books, 2007Fernà ¡ndez, Eva M. and Cairns, Helen Smith. Fundamentals of Psycholinguistics. Wiley-Blackwell, 2011Berg, Thomas.  Structure in Language: A Dynamic Perspective. Routledge, 2009Hurford, James R. The Origins of Grammar: Language in the Light of Evolution II. Oxford University Press, 2011Fabb, Nigel. Sentence Structure, Second Edition. Routledge, 2005

Hamlet, By William Shakespeare - 1003 Words

In Shakespeare’s play Hamlet, women also remain within a confined space of their chastity that is dictated by men. Claudius’ manipulation of Gertrude defines her submissive character as a woman. The family in Ophelia’s life command her actions due to viewing the purpose of her existence to be innocent. Ophelia is also driven to madness at the mercy of Hamlet, taking her own life. Shakespeare uses the few women in Hamlet, who are portrayed as sinful and weak-willed by being manipulated by men, to further the theme of misogyny. Gertrude cannot help being seduced by Claudius, and is exploited by him. After Gertrude gets married to Claudius just one month after her previous husband’s death, Hamlet expresses his disdain of Gertrude’s actions, stating Frailty, thy name is woman (Shakespeare l.ii.146). Hamlet’s comprehension of Gertrude builds from her relationship with a man. Being unable to understand her quick marriage, he concludes that because she is a woman, it is weakness that leads them to commit such sins. Quickly re-marrying is an action that arises due to weak morality. At the same time, after Hamlet refrains from killing Claudius, Polonius tells Gertrude to rebuke Hamlet for his insane behaviour, and she obeys. Instead, however, it is Hamlet that shames Gertrude. Hamlet berates Gertrude about her horrible sexual desires, saying â€Å"Nay but to live/In the rank sweat of an enseamÃ' d bed,/ Stewed in corruption, honeying and making love/ Over the nasty sty† (III.iv.91-94). Show MoreRelatedHamlet, By William Shakespeare880 Words   |  4 PagesWilliam Shakespeare is praised as the pioneering English poet and playwright whose collection of theatrical works is regarded as the greatest artistic value throughout the history of English literature. Shakespeare delved into the spiritual and mental component of humanity and the consequences that arise from this human spirit when it is disputed. The most famous revenge tragedy play, Hamlet, is an excellent illustration of Shakespeare’s philosophical study of human nature. In Hamlet, the arguableRead MoreHamlet, By William Shakespeare899 Words   |  4 PagesWilliam Shakespeare, author of Hamlet, was a well-known author in the 1500s and is still popular today. He was born on April 24, 1564 in London, England. Although there were no birth records at that time, it shows he was baptized one year prior to that, which leads us to believe his birthday was in 1564 because children were normally baptized a year after their birth. Shakespeare’s writing style was very different than others at that time. He used many metaphors and rhetorical phrases, and most ofRead MoreHamlet, By William Shakespeare996 Words   |  4 PagesHamlet, written by William Shakespeare, with out a doubt holds the most famous soliloquy in English history spoken by Hamlet in Act III, scene i, lines 57-90. This soliloquy holds much importance to the play as a whole because it ties together the reoccurring themes of suicide and Hamlet’s inaction portrayed by Shakespeare. Hamlet poses a problem, which is the driving force of the play: â€Å"To be or not to be?†(III.i.57). Shakespeare uses this logical question asked by Hamlet to drive out his underlyingRead MoreHamlet, By William Shakespeare1178 Words   |  5 Pages In William Shakespeare’s play Hamlet, the protagonist suffers from struggles with major characters, especially with the women in his life. While reading the play Hamlet, Hamlet appears to be a disillusioned man. Throughout the play, Shakespeare has only casted two females: Gertrude and Ophelia. Gertrude is defined to be incestuous, naà ¯ve and cold-hearted. On the other side, Ophelia is characterized to be ignorant, innocent and fearful. After the quick marriage of his mother and evil uncle, Hamlet’sRead MoreHamlet, By William Shakespeare1308 Words   |  6 PagesHamlet is arguably one of the greatest tragedies in all of literature and when most people think of tragic plays, they think of none other than the one who wrote it, William Shakespeare. This classic story of revenge excites it’s readers with its main character, Prince Hamlet, who goes through the unique human-like process of revenge that is often overlooked. Many other stories rely heavily on the logi c of good people doing good things and bad people doing bad things just for the sake of their natureRead MoreHamlet, By William Shakespeare Essay1453 Words   |  6 PagesHamlet by William Shakespeare explores many aspects of mankind--death, betrayal, love, and mourning. Out of these, the most prominent theme in this play is death in the form of suicide. The main character, Hamlet, finds himself questioning the quality of life and the uncertainty of the afterlife once he discovers news of his father s death and the corruption in the kingdom that follows. Ophelia, Hamlet’s lover, is found dead later in the plot and is presumed to have committed suicide. In Hamlet’sRead MoreHamlet, By William Shakespeare1146 Words   |  5 PagesA character so complex, enticing and fascinating, his name is Hamlet. We are all Hamlet, and that, is the argument. Hamlet is an enigmatic character with many flaws. These flaws are the ones that prove similarities between us and him. A play so popular and significant is due to its huge relevance to us as a society. In the play Hamlet, William Shakespeare uses Hamlet’s character and metaphor to demonstrate that when one is left alone to their thoughts, these thoughts overtake reason. ConsequentlyRead MoreHamlet by William Shakespeare1456 Words   |  6 PagesThe play Hamlet, by William Shakespeare, takes place in a time where the impossible was a part of the lives of everyday people. Occurrences that people in the modern time would believe unbelievable. Yet, with just a quill and parchment Shakespeare’s is able to connect the past and present by weaving a plot with skill that is still unparalleled to this day. The play Hamlet this exceeds this expectation by revealing depth of Hamlets, the protagonists, character personality through the useRead MoreHamlet, By William Shakespeare1920 Words   |  8 PagesIn the play Hamlet by William Shakespeare, the character Hamlet must deal with both external and internal conflict. Hamlet encounters many struggles and has trouble finding a way to deal with them. With so many corrupt people in his life, Hamlet feels as if there is no one that he can trust and begins to isolate himself from others. A result from this isolation leads Hamlet to become melancholy. Hamlet struggles with suicidal thoughts, wants to kill King Claudius, and is distraught over his mother’sRead MoreHamlet, By William Shakespeare846 Words   |  4 Pagesalways been a contemplative topic. In Hamlet, the main character Hamlet thinks to himself about suicide. Hamlet was written by William Shakespeare. Shakespeare wrote Hamlet between 1599 and 1602. William Shakespeare is one of the greatest playwrights in history. Hamlet is about Prince Hamlet of Denmark who is trying to find out about the death of his father after his father s ‘ghost’ comes to him telling him it was his uncle who had killed him. While Hamlet contemplates suicide he gives his famous