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Drug development pipelines have filled with biologics, and a handful of monoclonal antibody (MAb) products have become some of the best- selling drugs around the world. Production of biotherapeutics is often challenging because of the inherent instability of these large, complex molecules. Their fragile nature has forced manufacturers to change how bulk drug substances (BDSs) are handled and final drug product is formulated, sterile filtered, and filled. Ajinomoto Althea was established in 1. Fill–finish manufacturing must be designed with an awareness of the innate properties of proteins and external factors that can affect a given protein’s behavior. Recent Progress in Chitosanase Production of Monomer-Free Chitooligosaccharides: Bioprocess Strategies and Future Applications Sujata Sinha1,2 & Subhash Chand 1. Chemical engineering is a branch of engineering that applies physical sciences (physics and chemistry), life sciences (microbiology and biochemistry), together with. Here we share some learnings from over 1. The biologics market is growing 1. In 2. 01. 4, 4. 1 biologics were approved for market in the United States alone, the highest number launched in one year since the 1. Development pipelines are robust, with more than 9. Table 1: Comparing the complexity of different manufacturing processes. Biopharmaceuticals are manufactured by or extracted from living sources. These products are typically proteins, nucleic acids, vaccines, cells, or viruses. In general, when compared with traditional chemically synthesized drugs, biomolecules are larger and more complex, and their quality attributes depend on the biomanufacturing process. One commonly used analogy to help illustrate the complexity of biotherapeutics is to compare their relative sizes with other manufactured goods. Table 1 illustrates that moving from production of small molecules such as aspirin to MAbs such as trastuzumab (Genentech/Roche’s Herceptin), the magnitude of difference is comparable to going from manufacturing bicycles to private jet planes. Not only are biologics more difficult to produce, with more complex supply chains, but they are also significantly more expensive to develop and manufacture. Because of that demonstrated size as well as the complex physicochemical interactions between a protein and its environment, biologic- based therapeutics must be handled differently from their small molecule counterparts. Protein Structure and Stability Protein therapeutics are high– molecular- weight (HMW) polypeptides that require a specific three dimensional structure for their biologically activity. Their structures are considerably more complex than small molecules, consisting of four different structure levels: primary, secondary, tertiary, and quaternary (6, 7). Primary structure describes the linear sequence of amino acids that make up a protein. Human proteins are made from 2. A protein’s unique sequence defines its structure and function. Secondary structure refers to regular local substructures within protein molecules defined by hydrogen bonds between amide hydrogens and carbonyl oxygens. The most common secondary structures are alpha helices and beta sheets. Tertiary structure describes the overall three- dimensional structure of an entire protein. Its folding is mainly driven by hydrophobic interactions but also stabilized by hydrogen bonds, salt bridges, and disulfide bonds. Many proteins are made up of multiple polypeptide chains. Quaternary structure refers to how those protein subunits interact with each other and are arranged to form a larger complex. The conformation of protein complexes is stabilized by the same interactions that drive the tertiary structure of their components. Preventing degradation is essential in maintaining safety and efficacy during the manufacture and long- term storage of a protein therapeutic (7–1. Numerous factors can negatively affect protein stability. A protein’s amino acid backbone (primary structure) can be changed by formation and destruction of covalent bonds (1. Such chemical modifications can be caused by oxidation, deamidation, peptide- bond hydrolysis, disulfidebond exchange, and cross- linking (6, 8–1. Because the interactions that drive and stabilize higher- order secondary, tertiary, and quaternary structures are inherently weak interactions, proteins are susceptible to physical and conformational degradation. A number of external factors can cause physical degradation: excessively high temperatures, varying acidity or alkalinity, mechanical agitation, high shear forces, and the presence of hydrophobic molecular surfaces, leachables/extractables, nonpolar solvents, and certain excipients (6, 8–1. Proteins are also “sticky” and prone to both adsorption (adherence to surfaces, 1. Aggregates are of special concern because they have been demonstrated to associate with altered biological activity and increased immunogenicity (6, 7, 8, 1. The potential for protein aggregation can be increased by a number of mechanisms (6, 7, 8, 1. At high concentrations, protein–protein interactions will significantly increase the viscosity of a BDS, which in turn decreases its manufacturability and complicates drug delivery (1. Exposure to light can trigger chemical and physical degradation because certain amino acid residues (tryptophan, tyrosine, phenylalanine, and cysteine) are susceptible to photooxidation (8, 9). And in some instances, these factors can work synergistically, one event triggering another mechanism to follow (8). For example, a hydrophobic surface can cause a protein to become misfolded, which can lead to aggregation. Fill–finish operations must be designed with an awareness of the innate properties of proteins and external factors that can affect a given protein’s behavior and stability (8, 1. Special processes, procedures, and equipment must be in place to ensure product integrity during fill–finish manufacturing. Figure 1: Schematic of drug product (fill–finish) manufacturing. Special Considerations for Fill–Finish of Biologics. Preservation of a protein’s three- dimensional (3. D) structure is of vital importance during fill and finish. Because of the many conditions that can negatively affect therapeutic protein structure, function, and stability, very special care must be taken at every step of the biomanufacturing process (6, 7, 8 , 1. Figure 1 illustrates numerous steps and manipulations in biologic drug- product manufacturing. For biologics manufacturing, special handling procedures must be in place for receipt of an incoming BDS. Quality control (QC) operators are trained in proper BDS handling and visual inspection according to a good manufacturing practice (GMP) specification sheet. Specifications typically cover container integrity, storage conditions (e. Once accepted by a QC group, BDS is transferred to an appropriate storage location until its scheduled filling date. Procedures for managing nonconforming biologic BDS also should be in place as part of a manufacturer’s quality system oversight. End- to- end cold- chain infrastructure and traceability are critical to maintaining the quality of a biologic BDS and drug products (1. Validated storage at 2–8 . Procedures should include 2. A drug- product manufacturer needs routine preventive maintenance plans to ensure that its equipment is working properly. Intermediate storage for extended hold- times or multiple- day filling processes will require appropriate transfer and storage procedures to maintain sterility and optimal temperature of the BDS. Freezing a BDS brings a number of advantages in biologics manufacturing: decoupling a BDS from the drugproduct manufacturing process, reducing the risk of microbial contamination, and increasing BDS stability for flexible timelines (8). However, detailed thawing procedures should be in place to ensure that thawing frozen a BDS doesn’t compromise protein activity and stability based on data acquired during product development (1. Once a BDS is thawed, then associated dilution, pooling, and formulation protocols must be gentle to prevent foaming or splashing of the protein solution. EXPERIENCE THE POWER OF DOWNLOAD Everything. By Mergin on this blog, you would get the total experience of download everhthing. Big Download Portal. You can find and download evrething you want. Solid. Works 2. 01. Intel and AMD based systems – the CPU must support SSE2 Streaming SIMD Extensions 2. 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La scrittura, un sistema di segni durevoli che permette di trasmettere e conservare le informazioni, ha cominciato a svilupparsi tra il VII e il IV millennio a. C. In seguito . Lo studio di queste iscrizioni . La scrittura alfabetica emerse in Egitto circa 5. Gli antichi Egizi erano soliti scrivere scrivere sul papiro, una pianta coltivata lungo il fiume Nilo. Inizialmente i termini non erano separati l'uno dall'altro (scriptura continua) e non c'era punteggiatura. I testi venivano scritti da destra a sinistra, da sinistra a destra, e anche in modo che le linee alternate si leggessero in direzioni opposte. Il termine tecnico per questo tipo di scrittura, con un andamento che ricorda quello de solchi tracciati dall'aratro in un campo, . Furono infatti usate come mezzo di scrittura, specialmente per il cuneiforme, durante tutta l'Et. Servivano da materiale normale di scrittura nelle scuole, in contabilit. Avevano il vantaggio di essere riutilizzabili: la cera poteva essere fusa e riformare una . L'usanza di legare insieme diverse tavolette di cera (romano pugillares) . Erano utilizzate anche le cortecce di albero, come per esempio quelle della Tilia, e altri materiali consimili. La parola greca per papiro come materiale di scrittura (biblion) e libro (biblos) proviene dal porto fenicio di Biblo, da dove si esportava il papiro verso la Grecia. Tomus fu usato dai latini con lo stesso significato di volumen (vedi sotto anche la spiegazione di Isidoro di Siviglia). Che fossero fatti di papiro, pergamena o carta, i rotoli furono la forma libraria dominante della cultura ellenistica, romana, cinese ed ebraica. Il formato di codex si stabil. Viene chiamato codex per metafora di un tronco (codex) d'albero o di vite, come se fosse un ceppo di legno, poich. La prima menzione scritta del codice come forma di libro . Tuttavia, il codice non si guadagn. Gli autori cristiani potrebbero anche aver voluto distinguere i loro scritti dai testi pagani scritti su rotoli. La storia del libro continua a svilupparsi con la graduale transizione dal rotolo al codex, spostandosi dal Vicino Oriente del II- II millennio a. C. All'arrivo del Medioevo, circa mezzo millennio dopo, i codici - di foggia e costruzione in tutto simili al libro moderno - rimpiazzarono il rotolo e furono composti principalmente di pergamena. Il rotolo continu. Fu un cambiamento che influ. Quattro son troppi? Potrai pagarli due, e Trifone il libraio ci far. Haec tibi, multiplici quae structa est massa tabella, / Carmina Nasonis quinque decemque gerit. Questa mole composta da numerosi fogli contiene quindici libri poetici del Nasone »(Marziale XIV. Il libro antico. L'oggetto libro sub. Dal II secolo a. C. Nel mondo antico non godette di molta fortuna a causa del prezzo elevato rispetto a quello del papiro. Tuttavia aveva il vantaggio di una maggiore resistenza e la possibilit. Il libro in forma di rotolo consisteva in fogli preparati da fibre di papiro (phylire) disposte in uno strato orizzontale (lo strato che poi riceveva la scrittura) sovrapposto ad uno strato verticale (la faccia opposta). I fogli cos. La scrittura era effettuata su colonne, generalmente sul lato del papiro che presentava le fibre orizzontali. Non si hanno molte testimonianze sui rotoli di pergamena tuttavia la loro forma era simile a quella dei libri in papiro. Gli inchiostri neri utilizzati erano a base di nerofumo e gomma arabica. Dal II secolo d. C. La vecchia forma libraria a rotolo scompare in ambito librario. In forma notevolmente differente permane invece in ambito archivistico. Nel Medio Evo si fanno strada alcune innovazioni: nuovi inchiostri ferro gallici e, a partire dalla met. Il prezzo molto basso di questo materiale, ricavato da stracci e quindi pi. Ma bisogna aspettare la seconda met. Questo mezzo, permettendo l'accelerazione della produzione delle copie di testi contribuisce alla diffusione del libro e della cultura. La parola membranae, letteralmente . Altri suoi distici rivelano che tra i regali fatti da Marziale c'erano copie di Virgilio, di Cicerone e Livio. Le parole di Marziale danno la distinta impressione che tali edizioni fossero qualcosa di recentemente introdotto. Il codice si origin. Quando c'era bisogno di pi. Sono stati rinvenuti . Nel tempo, furono anche disponibili modelli di lusso fatti con tavolette di avorio invece che di legno. I romani chiamarono tali tavolette col nome di codex e solo molto pi. Ad un certo punto i romani inventarono un taccuino pi. Il passo fu breve dall'usare due o tre fogli come taccuino al legarne insieme una certa quantit. Il grande vantaggio che offrivano rispetto ai rolli era la capienza, vantaggio che sorgeva dal fatto che la facciata esterna del rotolo era lasciata in bianco, vuota. Il codice invece aveva scritte entrambe le facciate di ogni pagina, come in un libro moderno.(LA). Quam brevis inmensum cepit membrana Maronem! Ipsius vultus prima tabella gerit. La prima pagina porta il volto del poeta. Ma copie erano anche fatte di fogli di papiro. In Egitto, dove cresceva la pianta del papiro ed era centro della sua manifattura per materiale scrittorio, il codex di tale materiale era naturalmente pi. Quando i greci ed i romani disponevano solo del rotolo per scrivere libri, si preferiva usare il papiro piuttosto che la pergamena. Fece la sua comparsa in Egitto non molto dopo il tempo di Marziale, nel II secolo d. C., o forse anche prima, alla fine del I secolo. Il suo debutto fu modesto. A tutt'oggi sono stati rinvenuti 1. Nel terzo secolo la percentuale aumenta dall'1,5% a circa il 1. Verso il 3. 00 d. C. Il rotolo comunque aveva ancora parecchi secoli davanti a s. In teoria, in Egitto, terra ricca di pianta di papiro, il codice papiraceo avrebbe dovuto regnar supremo, ma non fu cos. Sebbene gli undici codici della Bibbia datati in quel secolo fossero papiracei, esistono circa 1. Non ne scegliemmo alcuno, ma ne raccogliemmo altri otto per i quali gli diedi 1. Il codex tanto apprezzato da Marziale aveva quindi fatto molta strada da Roma. Nel terzo secolo, quando tali codici divennero alquanto diffusi, quelli di pergamena iniziarono ad essere popolari. Il numero totale di codici sopravvissuti correntemente ammontano a pi. Nel quarto secolo la percentuale si alza al 3. V secolo. In breve, anche in Egitto, la fonte mondiale del papiro, il codice di pergamena occupava una notevole quota di mercato. Sono tutti di pergamena, edizioni eleganti, scritti in elaborata calligrafia su sottili fogli di pergamena. Per tali edizioni di lusso il papiro era certamente inadatto. Titoli di compilazioni celebri, il Codice teodosiano promulgato nel 4. Codice giustinianeo promulgato nel 5. Dall'altro lato, basandoci sulle annotazioni di Libanio, intellettuale del IV secolo che nelle sue molteplici attivit. Le ragioni erano buone: la pergamena poteva resistere a maltrattamenti vari, il codice poteva venir consultato velocemente per riferimenti giuridici, sentenze e giudizi, e cos. La pergamena usata doveva certo essere di bassa qualit. Il peso era per. Il papiro divenne difficile da reperire a causa della mancanza di contatti con l'Antico Egitto e la pergamena, che era stata usata da secoli, divenne il materiale di scrittura principale. I monasteri continuarono la tradizione scritturale latina dell'Impero romano d'Occidente. Cassiodoro, nel Monastero di Vivario (fondato verso il 5. XLVIII), che riserva certi momenti alla lettura, influenz. La tradizione e lo stile dell'Impero romano predominava ancora, ma gradualmente emerse la cultura peculiare libro medievale. Sony Playstation 2 / PS2 ROMs (ISOs) - View List. 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Wikipedia. Peter Pan is a 1. American animated adventure film produced by Walt Disney and based on the play Peter Pan, or The Boy Who Wouldn't Grow Up by J. It is the 1. 4th Disney animated feature film and was originally released on February 5, 1. RKO Radio Pictures.
Peter Pan is the final Disney animated feature released through RKO before Walt Disney's founding of his own distribution company, Buena Vista Distribution, later in 1. Peter Pan is also the final Disney film in which all nine members of Disney's Nine Old Men worked together as directing animators. It is also the second Disney animated film starring Kathryn Beaumont, Heather Angel, and Bill Thompson after their roles in the animated feature Alice in Wonderland. The film was entered into the 1. Cannes Film Festival. Their father, who is fed up with the stories that have made his children less practical, angrily declares that Wendy has gotten too old to continue staying in the nursery with them. That night, they are visited in the nursery by Peter Pan himself, who teaches them to fly with the help of his pixie friend, Tinker Bell, and takes them with him to the island of Never Land. A ship of pirates is anchored off Never Land, commanded by Captain Hook with his sidekick, Mr. Hook boldly plots to take revenge upon Peter Pan for cutting off his hand, but trembles at the presence of a crocodile, which consumed Hook’s hand and is eager to taste the rest of him. The crew's restlessness is interrupted by the arrival of Peter and the Darlings. Tinker Bell, who is very jealous of Pan’s attention to Wendy, persuades the Lost Boys that Pan has ordered them to shoot down Wendy, which Tink refers to as a “Wendy bird”. Tinker Bell's treachery is soon found out, and Peter banishes her. John and Michael set off with the Lost Boys to find the island's Indians, who instead capture them, believing them to be the ones responsible for taking the chief's daughter, Tiger Lily. Meanwhile, Peter takes Wendy to see the mermaids. The mischievous mermaids delight in tormenting Wendy but flee in terror at the sight of Hook. Peter and Wendy see that Hook and Smee have captured Tiger Lily so that they might persuade her to disclose Peter's hideout. Peter and Wendy free her, and Peter is honored by the tribe. Hook then plots to take advantage of Tinker Bell's jealousy of Wendy, tricking her into revealing the location of Peter's lair. Wendy and her brothers eventually grow homesick and plan to return home. They invite Peter and the Lost Boys to return to London and be adopted by the Darling parents. The Lost Boys agree, but Peter is so set against growing up that he refuses, presumptuously thinking that they will all return shortly. The pirates lie in wait and capture the Lost Boys and the Darlings as they exit, leaving behind a time bomb to kill Peter. Tinker Bell learns of the plot just in time to snatch the bomb from Peter as it explodes. Peter rescues Tinker Bell from the rubble and together they confront the pirates, releasing the children before they can walk the plank. Peter engages Hook in single combat as the children fight off the crew, and finally succeeds in humiliating the captain. Hook and his crew flee, with the crocodile in hot pursuit. Peter gallantly commandeers the deserted ship, and assisted by Tinker Bell's pixie dust, flies it to London with the children aboard. However, the Lost Boys decide to return to Never Land rather than be adopted in London. Darling return home from the party to find Wendy not in her bed, but sleeping at the open window. Wendy awakens and excitedly tells about their adventures. The parents look out the window and see what appears to be a pirate ship in the clouds. Darling, who has softened his position about Wendy staying in the nursery, recognizes it from his own childhood. Cast and characters. Bobby Driscoll as Peter Pan: The boy who never grows up. Like Tinker Bell, Peter can be very hot- headed. He is also commanding, but very brave. Peter can be quite mean at times (for instance, laughing at Wendy as the mermaids nastily tease her). Despite this, he is caring, especially when it comes to Tinker Bell's safety. He finds enjoyment in fighting Captain Hook, and was responsible for the loss of his left hand. He was modeled by Roland Dupree. Margaret Kerry as the live- action model for silent character Tinker Bell: A hot- headed pixie and Peter Pan's closest friend. She is very envious of the relationship formed between Wendy and Peter. Her jealousy causes her to have Wendy nearly stoned to death, and eventually even tell Captain Hook Pan's hideout, tricked into thinking his intention is to capture Wendy, not Peter. When she realizes what she has done, she tries her best to warn Peter of a bomb Hook has left for him addressed as if from Wendy in the form of a present. Unfortunately, Peter will not hear of it, and she manages to push the bomb away from him the very moment it explodes, thus saving Peter's life, almost at the cost of her own life. When Peter searches for her desperately in the ashes, she reflects a change of attitude towards Wendy and the boys, telling him he must rescue them first from Captain Hook's ship. Peter, however, says that he cannot leave her and tells her how much he loves her. Towards the end, Tink helps the Darling children return home by sprinkling pixie dust all across the pirate ship Peter Pan has just inherited, which was renamed Captain Pan. Although she never speaks, the animators used Kerry as a model to help them draw her movements. Kathryn Beaumont as Wendy Darling: The eldest of the Darling children; she adores Peter Pan. She is twelve years old turning thirteen, which is what drives her moody father to move her out of the nursery, so she may mature. She is a very feminine character, with somewhat motherly care for others. She reminds the lost boys of their own mothers. She was the first one of the Darling children to ask to return home. She has a soft spot for Peter and envies the attention he pays Tiger Lily; she has reason to dislike Tinker Bell, but thinks her lovely anyway (namely after the latter calls her a . She has a very tame personality, wanting the best for everyone and grudging no one: even when the mermaids tease her nastily, she worries about the danger of their teasing more than their nastiness itself. She is naive, wise, and mature, and very trusting and faithful to her standards of conscience. Paul Collins as John Darling: One of Wendy's two younger siblings, the older Darling son. He is eight years old, and acts very mature for his age, in a sophisticated way unnatural to his age group. He is an analyzing thinker and good at strategy, for instance when he takes lead over the Lost Boys in capturing Indians and in fighting the pirates on board the ship. He wears large, black glasses, and is tall and slim. It is interesting to note that all the Darling children wore their nightgowns to Neverland, but he added a black top- hat and an umbrella, showing exaggerated maturity. Tommy Luske as Michael Darling: The youngest of the three Darling children, who is about four years old; he carries a teddy bear with him and is very sensitive. He is also a little clumsy, yet very playful. Hans Conried as George Darling: The Darling children's father. He is a very moody and dramatic figure. In the beginning of the film he is called . He has had enough of the boys listening to Wendy's imaginary tales about Peter Pan, and in a moment of frustration he demands that Wendy's room be parted from the boy's room, saying she . He is easily irritated at the mere mention of Peter Pan, and expresses his dislike in a rage of temper. However, when cooled down in the end of the film, he changes his mind about Wendy's . He later remarks having seen a pirate ship such as Peter Pan's when he was very young himself. In contrast to his moody outbursts, he is gentle at heart; when he punishes the children by taking Nana the dog outside, he feels sorry for her and soothes her to comfort her. Disney Villain Death - TV Tropes. It appears that villains in the Disney Animated Canon have an especially curious tendency to exit the film by falling off or out of things. Unfortunately for them, even though they are animated characters, they cannot defy gravity. There is at least one case of a Disney villain meeting his end by falling up (off a space ship and into space), and once sideways (off the Chinese Imperial Palace by aid of a rocket). A surprising number of Disney villains have also been dragged to their doom by demons (from three to five depending on how you're counting). Or, they could have a boulder or similar heavy object falling down with them, which will surely crush them when they land, or fall into a deadly environment like lava or molten metal, a pit of savage beasts, fire, Hell itself, or even flesh- eating green acid, as water alone won't always do it. Heck, they may even cry . Their hands left bloodless, the hero and heroine can get married and live happily ever after and whatnot. Please ignore the uncomfortable realization that having the villain meet his or her end as an unquestionably ghastly mess on the floor isn't any less violent than anyof thealternatives. Not to be confused with Disney Death. It seems only good guys get to have those (there is a villainous variant, but Disney doesn't use it often). See also High- Altitude Interrogation and Unhand Them, Villain!, as well as Death by Falling Over. When Recycled In Space, it's Thrown Out the Airlock. An old Sunday comic serial had a giant and his vulture get an early version of this! However, in its theatrical release (as part of Fun and Fancy Free) and at least one television rebroadcast, Willy is shown to have survived.. Donald manages to trap her in the form of a gas can, and later kicks the witch/can off a cliff during one of his trademark tantrums. It's a pretty bizarre story. Lady Tremaine and Cinderella's step sisters don't really get punished at all (in the film, anyway; all three are (deservingly) killed in Birth By Sleep, and Drizella and Lady Tremaine are implied to have been forced into servitude in the second sequel, while Anastasia is redeemed by love). But their Right- Hand Cat. Lucifer, who is mean even by Disney cat standards, terrorizing the mice and committing petty evil when Lady Tremaine isn't watching, falls from the window of Cinderella's tower. It's best to take the sequel's word for it. Cats (a) can right themselves in midair, and (b) go limp upon reaching terminal velocity, at which point their legs splay out and their skin stretches into a makeshift parachute, meaning their odds of survival are better from a long fall than a short one. However, it's then revealed that the wolf actually survived the fall since he immediately grabbed onto a nearby branch with berries growing on it. He makes it into the sequel, too. Played straight with one of his henchmen, however, after he messes up Hook's song at one point. The brambles were Maleficent's own creation and rather clearly set ablaze by her dragonfire. Dalmatians: Cruella de Vil crashes her Cool Car into her goons' truck, sending them both plummeting off the cliff they were on. Oddly, despite the fact that the cars are totaled at the bottom of the ravine, all three are alive and Cruella is in good enough shape to throw a hissy- fit. She survives in the book as well. The only reason this was even debated was because pubilicity stills show him being forced into and imprisoned in a birdcage at the fight's end in place of the stabbing, which really is an alternate ending and therefore means nothing to the plot of the film itself. Once inside, he disappears forever. Hey, no fuss, no muss. Of course, in the book, he melted. He gets taken out after his sanity slipping. Villainous Breakdown by Big Ben's bells ringing, causing him and Basil to fall from the clock tower. Of course, considering Ratigan's direct inspiration, Professor Moriarty, also got taken out by a fall, it's not much of a surprise. The difference is Sherlock's fate is left ambiguous as to whether or not he survived; Basil definitely does thanks to Chekhov's Gun. That didn't stop Disney Adventures from doing a comic story where he had apparently survived and also did a Heel. In one year, we got the Family Unfriendly Deaths of Judge Doom in Who Framed Roger Rabbit (dissolved by his own Dip) and Sykes in Oliver & Company (just saying he's run over by a subway train doesn't even cover it). Sykes' henchdogs also get freakin' electrocuted on a third rail. It's played straight in the sequel, though — Ursula's sister freezes in a block of ice and sinks into a watery abyss. Played straight in Duck. Tales the Movie: Treasure of the Lost Lamp with Merlock as a result of him losing his talisman.. Though he did wish to live forever and he would have hit the ground long beforethe genie was freed and all his wishes were undone, meaning in theory he would've received the most gruesome death because he would've hit the ground and not died, and been in a painful mess of blood and broken bones. This is followed immediately by a fakeout when the heroes face the exact same chain of events. Some fans actually questioned whether he actually died, citing how there was a river at the bottom of the ravine, and citing how Le. Fou managed to survive much worse, such as being stuck in the snow for what was implied to be several months and being crushed by a chair/bench, and his voice actor expressed doubts about Gaston's death. It actually necessitated the Disney company to make it clear in the commentary that he died. Apparently, it was revoked because it would have been far too gruesome even for a character like him. To make sure everyone is clear this time that he's dead, we hear a distant meaty thud at the moment where he stops screaming as he falls. And while he was a huge freaking organ at the time, he was also a transformed human. One shudders to think what he looked like when the curse was broken.. Disney Villain Death was not included because the sheer number would cause people to succumb to alcohol poisoning. Specific examples, for the curious. The Captain and Hakon, in the Middle Ages part of . Demona, at the end of . The Archmage, in . Subverted in . In part two, the villain himself was killed by falling off the same castle. That could be justified as poetic justice, but the creators didn't want to have to do it again in part three for the other villain. So, Macbeth gets a magical ball of.. And after he's burned through, his body.. A fight between their father and the Gargoyle led to the Hunter falling off Notre Dame cathedral. To his death. D'Artagnan fights one of the Cardinal's men on top of some ruins, and knocks him off to his death. Lady De Winter, the femme fatale, chooses to fling herself off a cliff rather than suffer a beheading. Later in the film, D'Artagnan surprises the King's assassin on the palace roof, and the fight ends with the assassin getting a crossbow bolt to the heart and falling to the ground below. Scar survives his fall off Pride Rock. He meets Shenzi's Hyena pack down there, and they're not too happy about being blamed for all his wrongdoings. Let's just say that Scar would probably have preferred the falling death.. It is heavily suggested by shadows that they maul him to death. In the novelization, it is worse, describing Scar as a 'king fit for a meal', and judging by the hyenas' ravenous appetites throughout, it is highly probable that he was Devoured by the Horde. The sequel further implies that he burned to death as well. Zira in The Lion King II: Simba's Pride falls off a cliff into rapids and drowns. Note that, in the original Darker and Edgier ending, she was intended to be seen letting go (some argue that this is still the case in the release. It's a bit ambiguous), and laughing on the way down. He stands atop a gargoyle and is about to kill Quasimodo and Esmeralda — but the gargoyle's head cracks, causing him to lose his balance. DpStream : Regarder Paranormal Files : info ou intox? PARANORMAL FILES : Info ou Intox? Alors, info ou intox ? Vous êtes vous déjà demandés « est-ce que c'est vrai? Paranormal Files est là. Paranormal Files: Info ou intox est une émission de télévision documentaire américaine diffusée depuis le 15 juillet 2010 sur Syfy. Saison 1 (année 2010). PARANORMAL FILES (Info ou Intox) - Saison 1 - S01E02 - Créatures nocturnes ~ Soucoupe volante. Résumé de l'épisode : Bill part avec une partie de l'équipe à. Paranormal Files : info ou intox? Saison 1 Streaming Plongez dans votre nouveau docu-réalité! Une série d'enquêtes paranormales à la croisée de. Paranormal Files - Faits ou Faux? Paranormal Files : Info ou intox est une émission de télévision documentaire. Paranormal-Regarder Paranormal Files Info ou Intox - Saison 1 en streaming VF. Retrouvez les liens streaming de Paranormal Files Info ou Intox - Saison 1 version fran. Paranormal Files : info ou intox? Saison 1 Streaming. Phénomène Paranormal (Paranormal Witness) Saison 2 Streaming. Phénomène Paranormal (Paranormal Witness. International Scientific Journal & Country Ranking. Display only Open Access Journals Display only SciELO Journals (In Progress).MATH - Mathematics - Courses - Vancouver Academic Calendar 2. MATH: Mathematics. The first digit in the number of a course is intended to convey the level of mathematical maturity at which the course is conducted rather than the year in which it must be taken. Students who expect to follow an Honours Science program or one with high mathematical content are urged to apply for admission to MATH 1. The following courses are for students in the Faculty of Applied Science: MATH 1. The Department of Mathematics, Statistics and Computer Science offers a unique interdisciplinary learning environment with areas of study ranging from pure and. Mathematics, Faculty of Science MATH: Mathematics. The first digit in the number of a course is intended to convey the level of mathematical maturity at which the. Course - Number Course Title Credits; Mathematics 098 Beginning Algebra with Geometry 4: Mathematics 099 Intermediate Algebra with Geometry. MATH 2. 53, MATH 2. MATH 2. 56, MATH 2. MATH 2. 63, MATH 2. MATH 2. 67. Secondary- school calculus is a prerequisite for MATH 1. Students with this qualification should see . MATH 1. 80 and 1. Continuing Studies offers MATH 0. For further information see the department's website at www. MATH 0. 01 (0) Algebra. Requirements Bachelor of Arts Degree Requirements Mathematics Major. The requirement for entrance to the major and minor programs is completion of two. Bharathiar University B.Sc - Maths - III Year - Discrete Mathematics - 2010 Question Papers. Homepage of the Institute of Discrete Mathematics and Geometry. Numbers and their properties; exponents, radicals, absolute value, inqualities, functions and their graphs; factoring; solving polynomial, rational, and exponetial equations; and the sine and cosine law. Non- credit Math course offered by Continuing Studies in consultation with the Mathematics Department and taught by Continuing Studies instructors. Prerequisite: Mathematics 1. MATH 0. 02 (0) Pre- Calculus. Composite, inverse, polynomial, rational, trigonometric, exponential, and logarithmic functions; sequences and series; and analytical geometry. Non- credit Math course offered by Continuing Studies in consultation with the Mathematics Department and taught by Continuing Studies instructors. Prerequisite: MATH 0. Principlies of Mathematics 1. Pre- calculus 1. 1. MATH 1. 00 (3) Differential Calculus with Applications to Physical Sciences and Engineering. Derivatives of elementary functions. Applications and modeling: graphing, optimization. Consult the Faculty of Science Credit Exclusion List: www. Please consult the Faculty of Science Credit Exclusion List: www. Please consult the Faculty of Science Credit Exclusion List: www. Please consult the Faculty of Science Credit Exclusion List: www. Please consult the Faculty of Science Credit Exclusion List: www. Please consult the Faculty of Science Credit Exclusion List: www. See http: //www. math. Ugrad/m. 11. 0. shtml for details. MATH 1. 20 (4) Honours Differential Calculus. Limits, derivatives, Mean Value Theorem and applications, elementary functions, optimization, Taylor series, approximation. Please consult the Faculty of Science Credit Exclusion List: www. Please consult the Faculty of Science Credit Exclusion List: www. Laboratories demonstrate computer solutions of large systems. Please consult the Faculty of Science Credit Exclusion List: www. Please consult the Faculty of Science Credit Exclusion List: www. Not for credit for students with AP Calculus AB, AP Calculus BC, or a passing score on the UBC- SFU- UVIC- UNBC Calculus Challenge Examination. Please consult the Faculty of Science Credit Exclusion List: www. Please consult the Faculty of Science Credit Exclusion List: www. Primarily for second year students taking a degree in mathematics. One hour laboratory each week. Applications of these topics will be emphasized. Please consult the Faculty of Science Credit Exclusion List: www. Please consult the Faculty of Science Credit Exclusion List: www. Logic, structure, style, and clarity of proofs emphasized throughout. Please consult the Faculty of Science Credit Exclusion List: www. Intended for Honours students. Please consult the Faculty of Science Credit Exclusion List: www. Please consult the Faculty of Science Credit Exclusion List: www. Please consult the Faculty of Science Credit Exclusion List: www. Please consult the Faculty of Science Credit Exclusion List: www. Please consult the Faculty of Science Credit Exclusion List: www. Please consult the Faculty of Science Credit Exclusion List: www. Tutorial session focuses on examples from chemical and biological engineering. Consult the Faculty of Science Credit Exclusion List: www. Please consult the Faculty of Science Credit Exclusion List: www. Applications to Electrostatics and Magnetostatics. MATH 2. 64 content is strongly coupled to ELEC 2. This course is not eligible for Credit/D/Fail grading. Prerequisite: One of MATH 2. MATH 2. 17, MATH 2. MATH 2. 53, MATH 2. Corequisite: One of ELEC 2. EECE 2. 61. MATH 2. Linear Differential Equations. Linear ordinary differential equations. Complex numbers, Laplace transforms, frequency reponse, resonance, step response, systems. Please consult the Faculty of Science Credit Exclusion List: www. Discrete Fourier tranform. Recurrence relations, z- transform, generating functions, applications. Please consult the Faculty of Science Credit Exclusion List: www. Please consult the Faculty of Science Credit Exclusion List: www. Linear algebra proofs are used. It is suggested that MATH 3. These may include conic sections, projective configuration, convexity, non- Euclidean geometries, fractal geometry, combinatorial problems of points in the plane. Consult the Faculty of Science Credit Exclusion List: www. Some diophantine equations. Distribution of the prime numbers. Please consult the Faculty of Science Credit Exclusion List: www. Prerequisite: One of MATH 2. MATH 2. 26, CPSC 1. MATH 3. 13 (3) Topics in Number Theory. Topics chosen by the instructor. These might include: division algorithms, group theory, continued fractions, primality testing, factoring. Please consult the Faculty of Science Credit Exclusion List: www. Please consult the Faculty of Science Credit Exclusion List: www. MATH 2. 21 is recommended. MATH 3. 18 (3) Probability with Physical Applications. Random variables, discrete and continuous distributions. Random walk, Markov chains, Monte Carlo methods. Characteristic functions, limit laws. Please consult the Faculty of Science Credit Exclusion List: www. Continuity and uniform continuity. Differentiability and mean- value theorems. Sequences and series of functions, uniform convergence. Approximation of continuous functions by polynomials. Fourier series. Functions from Rm to Rn, inverse and implicit function theorems. Combinatorics, probability, geometry and elementary number theory. Not for credit in the Faculty of Science. Students who obtain credit at UBC for any other mathematics course cannot in the same or later years obtain credit for MATH 3. Please consult the Faculty of Science Credit Exclusion List: www. Additional topics chosen from: Karmarkar's algorithm, non- linear programming, game theory, applications. Optimization, dynamical systems and stochastic processes. Preference will be given to Combined Major in Science students, or to students in Year 3 or higher. This course is not eligible for Credit/D/Fail grading. Dynamic behavior of difference equations, differential equations, and partial differential equations, explained with reference to concrete biological examples. Technical report required. Restricted to students admitted to the Mathematics Co- operative Education Program. This course is not eligible for Credit/D/Fail grading. MATH 3. 99 (3) Co- operative Work Placement IIApproved and supervised technical work experience involving mathematics in industry for a minimum of 3. Technical report required. Restricted to students admitted to the Mathematics Co- operative Education Program. This course is not eligible for Credit/D/Fail grading. Prerequisite: MATH 3. MATH 4. 00 (3) Applied Partial Differential Equations. Separation of variables, first order equations, Sturm- Liouville theory, integral transform methods. Calculus of variations. Eigenfunction expansions. Rayleigh- Ritz and finite element methods. MATH 4. 02 is recommended. MATH 4. 05 (3) Numerical Methods for Differential Equations. Interpolation, numerical integration, numerical solution of ordinary and partial differential equations. Practical computational methods emphasized and basic theory developed through simple models. See Faculty of Science credit exclusion list: http: //www. Intended for third or fourth year Mathematics students and Math/Science Education students. Mean curvature and Gaussian curvature. Gauss's Theorema Egregium. Consumer Mathematics (9. Homework Help and Answers : : Slader. Can you find your fundamental truth using Slader as a completely free Consumer Mathematics solutions manual? YES! Now is the time to redefine your true self using Slader’s free Consumer Mathematics answers. Shed the societal and cultural narratives holding you back and let free step- by- step Consumer Mathematics textbook solutions reorient your old paradigms. NOW is the time to make today the first day of the rest of your life. 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