cyanic-selkie/wikianc huggingface dataset:
Gamab
Hierdie manlike god woon in ‘n hemel hoër as die sterre. Daar het hy sy eie dorpie met ‘n skakuboom in die middel en ‘n heilige heilige vuur. Van daaruit bepaal hy die lot van die mensdom. Gamab voorsien die veldkos (bessies, bolle, wildsvleis) en onderhou so alle lewe sodat dit kan voortbestaan. Hy beskerm alle kinders en die oeste, maar kan ook hongersnood veroorsaak. Wanneer dit tyd is vir iemand om te sterf, kry hy sy boog uit en skiet die persoon vanaf sy dorpie met onsigbare pyle. Wanneer ‘n nuweling daarna in die hemel aankom, gee Gamab hom ‘n beker vloeibare vet om te drink.
Op die hoogste berg in Damaraland is ‘n heilige grot wat vir Gamab afgesonder is.
RP-1
Gebruik
RP-1 is 'n brandstof in die eerste-fase hupstootstadium van die Electron, Soyuz, Zenit, Delta I-III, Atlas, Falcon, Antares en Tronador II vuurpyle. Dit het ook die eerste fases van die Energia, Titan I, Saturn I en IB, en Saturn V aangedryf. Die Indiese ruimtenavorsingsorganisasie is ook besig om 'n RP-1-aangedrewe enjin vir sy toekomstige vuurpyle te ontwikkel.
Ontwikkeling
Tydens en onmiddellik na die Tweede Wêreldoorlog is alkohole (hoofsaaklik etanol, soms metanol) algemeen gebruik as brandstof vir groot vloeibare stumiddelvuurpyle. Hul hoë afkoeling weens verdamping het gehelp dat regeneratief-verkoelde enjins nie smelt nie. Daar is egter erken dat koolwaterstofbrandstowwe enjindoeltreffendheid verhoog, as gevolg van 'n effens hoër digtheid, die gebrek aan 'n suurstofatoom in die brandstofmolekule, en baie lae waterinhoud. Ongeag watter koolwaterstof gekies is, sou dit ook alkohol as koelmiddel moes vervang.
Baie vroeë vuurpyle het keroseen verbrand, maar namate verbrandingstyd, verbrandingsdoeltreffendheid en verbrandingskamerdruk toegeneem het, het enjinmassas afgeneem, wat tot onhanteerbare enjintemperature gelei het. Rou keroseen wat as koelmiddel gebruik word, is geneig om te dissosieer en te polimeriseer. Liggewigprodukte in die vorm van gasborrels veroorsaak kavitasie, en swaar produkte in die vorm van wasafsettings blokkeer nou verkoelingspype in die enjin. Die gevolglike gebrek aan koelmiddel verhoog temperature verder, en veroorsaak meer polimerisasie wat afbreek versnel. Die siklus eskaleer vinnig totdat 'n enjinwandbreuk of ander meganiese mislukking plaasvind, en dit duur voort selfs wanneer die hele verkoelingsvloeistof uit keroseen bestaan.
In die middel-1950s het vuurpylontwerpers hulle tot die chemici gewend om 'n hittebestande koolwaterstof te formuleer, en RP-1 was die resultaat.
Gedurende die 1950s het LOX (vloeibare suurstof) die voorkeur-oksideermiddel geword om saam met RP-1 te gebruik, alhoewel ander oksideermiddels ook gebruik is.
Sharon Lynn
Sharon Lynn (9 April 1901 – 26 Mei 1963) was 'n Amerikaanse aktrise. Sy was bekend vir haar rolle in die rolprente Aflame in the Sky (1927), City of Shadows (1927), Go Into Your Dance (1935), en Way Out West (1937).
Carlos Carrasco (akteur)
Carlos Carrasco (gebore 5 April 1948) is 'n Amerikaanse akteur, vervaardiger, en regisseur. Hy is bekend vir sy rolle in die rolprente Blood In, Blood Out (1993), Speed (1994), en Parker (2013).
Donald Pleasence
Donald Pleasence (5 Oktober 1919 – 2 Februarie 1995) was 'n Engelse akteur en skrywer. Hy was bekend vir sy rolle in die rolprente The Great Escape (1963), Halloween (1978), Halloween II (1981), en Halloween 4: The Return of Michael Myers (1988).
The Lord of the Rings: The Return of the King (Rolprent)
Die film het op 1 Desember 2003 in Wellington, Nieu-Seeland, begin en is op 17 Desember in rolprentteaters wêreldwyd vertoon. The Return of the King is die opvolg van The Fellowship of the Ring en The Two Towers. In vergelyking met Tolkien se boek, vertel die film dele van beide The Two Towers en The Return of the King.
Die film is benoem vir elf Oscars by die 2004 Oscars. Die rolprent het alle benoemings, insluitend beste rolprent gewen en die rekordgetal Oscars van 11 met Titanic en Ben Hur gedeel. 'n Jaar later, aan die einde van 2004, is 'n uitgebreide uitgawe van hierdie film vrygestel en 48 minute se nuwe en uitgebreide tonele is by hierdie film gevoeg.
Storie
Die film begin waar die hobbit Sméagol visvang saam met sy neef Déagol, wat die Een Ring in die rivier ontdek. Sméagol se gedagtes word deur die Ring verstrik, en hy vermoor sy neef daarvoor. Hy word fisies en geestelik toenemend korrup en trek terug in die Misty Mountains en word as Gollum bekend.
Eeue later, tydens die Oorlog van die Ring, lei Gandalf vir Aragorn, Legolas, Gimli en koning Théoden van die Rohan na Isengard, waar hulle met Merry en Pippin herenig. Gandalf spoor Saruman se palantír op, 'n onvernietigbare kristalbal gebruik vir kommunikasie en om gebeure in ander dele van Arda te sien, hetsy die verlede of toekoms.
Die groep keer terug na Edoras om hul oorwinning by Helm's Deep te vier. Pippin kyk in die palantír en sien Sauron en 'n brandende boom. Gandalf lei af dat die vyand beplan om Gondor se hoofstad Minas Tirith aan te val; hy ry soontoe om Gondor se rentmeester Denethor te waarsku. Pippin, wat hom vergesel, sweer trou aan Denethor, wie se nou gestorwe erfgenaam, Boromir, sy lewe gered het. Op Gandalf se instruksie, word die stad se bakens aangesteek, wat om Rohan se hulp roep.
Frodo, wat die Ring dra, en Sam gaan voort met hul reis na Mordor, onbewus daarvan dat Gollum, nou hul gids, beplan om hulle te verraai en die Ring vir homself te neem. Die trio sien die heksekoning van Angmar, heer van die nege Nazgûl, wat met sy leër van Orke na Gondor vertrek. Gollum span saam om Sam vals te beskuldig dat hy die voedselvoorrade opeet en die Ring begeer.
Beïnvloed deur die groeiende krag van die Ring, word Frodo mislei en beveel Sam om huis toe te gaan. Gollum verneuk Frodo dan om die lêplek van die reusespinnekop Shelob aan te durf. Frodo ontsnap net-net en konfronteer Gollum, wat ná 'n stoeiery in 'n kloof val. Shelob verlam en bind Frodo vas, maar word gewond en verdryf deur 'n terugkerende Sam, wat treurend oor Frodo se oënskynlike dood, die Ring neem. Sam besef sy fout wanneer 'n groep Orke Frodo gevange neem, maar kry dit reg om Frodo te red terwyl die Orke onder mekaar veg. Nou binne Mordor gaan die hobbits voort na Mount Doom, hul bestemming.
Terwyl koning Théoden sy leër bymekaarmaak, vertel Elrond vir Aragorn dat Arwen besig is om te sterf, omdat hy geweier het om Middel-aarde te verlaat. Elrond gee aan Aragorn Andúril, gesmee uit die skerwe van koning Elendil se swaard Narsil, en dring by hom aan om hom te verbind om Gondor se troon, waarvan hy erfgenaam is, op te eis. Saam met Legolas en Gimli reis Aragorn oor die Pad van die Dooies, en belowe om die spoke daar van hul vloek te bevry sou hulle Gondor te hulp kom.
Intussen is Faramir, wat vroeër deur die heksekoning oorval en teruggedryf is na Minas Tirith, ernstig gewond in 'n selfmoordklag; Denethor glo dat sy seun dood is, en verval in waansin. Gandalf stel die verdedigers op, maar die groot Ork-leër breek die stad in. Denethor probeer om homself en Faramir op 'n brandstapel te verbrand, maar Pippin waarsku Gandalf en hulle red Faramir. Denethor, aan die brand gesteek en in angs, spring na sy dood.
Théoden kom aan en lei sy leër teen die Orke. Ten spyte van aanvanklike sukses teen Orke in die daaropvolgende geveg, word hulle vernietig deur die Oliphaunt-ryende Haradrim en die heksekoning verwond Théoden dodelik; sy niggie Éowyn maak egter die heksekoning dood met Merry se hulp. Théoden sterf in sy niggie se arms. Aragorn arriveer dan met sy Leer van die Dooies, wat Sauron se magte oorwin. Hulle eed is vervul, die dooies word van hulle vloek bevry.
Aragorn besluit om na Mordor te marsjeer om Sauron se aandag van Frodo, nou uiters swak, en Sam af te lei. Al Sauron se oorblywende magte marsjeer om Aragorn se afdeling tegemoet te kom, wat die hobbits toelaat om Mount Doom te bereik. Gollum, wat sy vroeëre val oorleef het, val hulle aan, maar Frodo slaag steeds daarin om die berg binne te gaan. Daar swig Frodo voor die mag van die Ring en sit dit op sy vinger, en Gollum slaag daarin om sy vinger af te byt en dit terug te eis. Hulle stoei met mekaar en val altwee van die rand af. Frodo kry dit reg om vas te klou, en word deur Sam opgetrek, maar Gollum val en sterf; die Ring, wat saam met Gillum geval het, verbrokkel in die lawa. Mount Doom bars uit soos Sauron sy ondergang ontmoet, terwyl Aragorn se leër as oorwinnaars uit die stryd tree terwyl sy vyande vlug.
Gandalf red die hobbits met die hulp van arende, en die oorlewende Fellowship word gelukkig herenig in Minas Tirith. Aragorn word as koning van Gondor gekroon en trou met Arwen. Die Hobbits keer terug huis toe by die graafskap, waar Sam met Rosie Cotton trou. 'n Paar jaar later vertrek Frodo uit Middel-aarde na die onsterflike lande saam met sy oom Bilbo, Gandalf en die Elwe. Hy laat aan Sam die Rooi Boek van Westmarch agter, wat hul avonture uiteensit. Sam keer terug na die graafskap, waar hy Rosie en hul kinders omhels.
Erythrina acanthocarpa
Die tamboekiedoring (Erythrina acanthocarpa) is struik wat endemies is in die Oos-Kaap.
Fritzi Haberlandt
Fritzi Haberlandt (gebore 6 Junie 1975) is 'n Duitse aktrise. Sy is bekend vir haar rolle in die rolprente Cold Is the Breath of Evening (2000), Learning to Lie (2003), Summer Window (2011), en Eine Insel namens Udo (2011).
Chlooramfenikol
Chlooramfenikol is 'n antibiotikum wat nuttig is in die behandeling van 'n aantal bakteriële infeksies. Dit is 'n bakteriostatiese middel wat beskikbaar is sedert 1949. Dit word beskou as 'n prototipiese breëspektrum antibiotikum, saam met die tetrasikliene. Dit is beide goedkoop en maklik om te vervaardig, en is dikwels die antibiotikum van keuse in die ontwikkelende wêreld.
Chlooramfenikol, ook bekend as chlornitromisien, is doeltreffend teen 'n wye verskeidenheid van gram-positiewe en gram-negatiewe bakterieë, insluitend die meeste anaerobiese organismes. As gevolg van weerstandigheid en veiligheidskommernis, is dit nie meer 'n eerste-lyn middel vir enige infeksie in ontwikkelde lande nie, met die noemenswaardige uitsondering van die topikale behandeling van bakteriële konjunktivitis ('n ooginfeksie). Nogtans het die globale probleem van die vordering van bakteriële weerstand teen nuwe middels gelei tot hernieude belangstelling in die gebruik daarvan. In lae-inkomste lande word chlooramfenikol steeds wyd gebruik omrede dit goedkoop en geredelik beskikbaar is.
Die ernstigste nadelige uitwerking wat verband hou met chlooramfenikolbehandeling is beenmurgtoksisiteit, wat kan voorkom in twee afsonderlike vorms: beenmurgonderdrukking, wat 'n direkte giftige uitwerking van die middel is, en gewoonlik omkeerbaar is, en aplastiese anemie, wat eienaardig is (skaars, onvoorspelbaar, en wat nie verwant is aan die dosis nie) en in die algemeen noodlottige is.
Gebruik van binneaarse chlooramfenikol hou ook verband met 'n grys baba-sindroom, 'n verskynsel as gevolg van pasgebore babas se onvermoë om chlooramfenikol te metaboliseer in die liggaam. Ander minder ernstige reaksies sluit in koors, veluitslag, hoofpyn en verwarring. Voorskrifgebruik word gewoonlik geassosieer met die monitering van 'n pasiënt se volle bloedtelling. Die middel behoort gestaak te word met die voorkoms van retikulositopenia, leukopenie, trombositopenie, anemie, of enige ander abnormale bloedbevindings toe te skryf aan chlooramfenikol.
Dit is op die Wêreldgesondheidsorganisasie se lys van noodsaaklike medisyne, 'n lys van die belangrikste medikasie wat nodig is in 'n basiese gesondheidstelsel.
Mesembryanthemum inachabense
Mesembryanthemum inachabense is 'n vetplant wat deel is van die Aizoaceae familie. Die plant is inheems aan Namibië en Suid-Afrika waar dit in die Noord-Kaap voorkom.
Hay Plumb
Hay Plumb (1883 – 1960) was 'n Engelse regisseur, akteur, en skrywer.
Proteïen-invouing
Proteïen-invouing is die fisiese proses by wyse waarvan 'n proteïenketting sy natuurlike driedimensionele struktuur verkry. Dit is 'n konformasie wat gewoonlik biologies funksioneel is, en op 'n spoedige en reproduseerbare wyse plaasvind. Dit is die fisiese proses waardeur polipeptiede 'invou' in die karakteristieke en funksionele 3-dimensionele vorm daarvan vanaf 'n lukrake lus. Elke proteïen bestaan as 'n on-gevoude polipeptied of lukrake lussie wanneer dit van 'n sekwensie van mRNS biologies 'geïnterpreteer' of 'vertaal' word na 'n lineêre ketting van aminosure. Hierdie polipeptiede beskik nie oor enige stabiele (langdurige) driedimensionele struktuur nie (die linkerkant van die eerste figuur). Soos wat die polipeptiedketting gesintetiseer word deur 'n ribosoom, begin die lineêre ketting om in te vou in sy driedimensionele struktuur. Die invouing begin reeds tydens die 'interpretasie' of 'vertaling' van die polipeptiedketting. Aminosure reageer met mekaar om 'n goed gedefinieerde 3-dimensionele struktuur te vorm, d.i. die gevoude proteïen (die regterkant van die figuur), wat bekend staan as die normale toestand. Die gevolglike 3-dimensionele struktuur word bepaal deur die aminosuurvolgorde of primêre struktuur (Anfinsen se dogma).
Die korrekte 3-dimensionele struktuur is essensieel vir funksionering, alhoewel sommige dele van funksionele proteïene nie-gevou mag bly, sodat proteïendinamika belangrik is. Versuim om in die natuurlike struktuur in te vou, produseer oor die algemeen onaktiewe proteïene, maar in sommige gevalle beskik foutiewelik gevoude proteïene oor gewysigde of 'toksiese' funksies. Daar word vermoed dat verskeie senuwee-degeneratiewe en ander siektes die gevolg is van die ophoping van amiloïde fibrille wat gevorm word deur foutiewelik gevoude proteïene. Baie allergieë word veroorsaak deur die inkorrekte invouing van sommige proteïene omdat die immuunstelsel nie teenliggame kan produseer vir sekere proteïenstrukture nie.
Denaturasie van proteïene is 'n oorgangsproses van die gevoude na die nie-gevoude (lukrake lussie) voorkoms of toestand. Dit gebeur wanneer iets gekook of gebrand word, in proteïenopatie, asook in ander kontekste.
Die tydsduur van die vouproses wissel dramaties afhangende van die proteïen. As die proses buite die sel bestudeer word, benodig die proteïene wat die stadigste vou, baie minute of ure om te vou, hoofsaaklik as gevolg van Cis-trans isomerisasie, en moet dit dus deur 'n aantal intermediêre toestande gaan, byna soortgelyk aan kontrolepunte, voordat die proses voltooi is. Aan die ander kant word baie klein enkel-domein proteïene met 'n lengte van tot honderd aminosure tipies in 'n enkele stap gevou. Tydskale van millisekondes is die norm; die vinnigste bekende proteïenvou-reaksies word binne enkele mikrosekondes voltooi.
Sekondêre struktuur
Die vorming van 'n sekondêre struktuur is die eerste stap in die vouproses wat 'n proteïen neem om sy natuurlike of gebruiklike struktuur aan te neem. Kenmerkend van sekondêre strukture is die strukture wat bekendstaan as alfa-helikse en beta plate wat vinnig vou omdat dit gestabiliseer word deur intramolekulêre waterstofbindings, soos dit die eerste keer bevind is deur Linus Pauling. Die vorming van intramolekulêre waterstofbindings lewer nog 'n belangrike bydrae tot proteïenstabiliteit. α-helikse word gevorm deur die waterstofbinding van die ruggraat ten einde 'n spiraalvorm te vorm (verwys na figuur aan die regterkant). Die ß-geplooide plaat is 'n struktuur wat vorm met die ruggraat wat oor homself buig om die waterstofverbindings te vorm (soos getoon in die figuur links). Die waterstofverbindings is tussen die amiedwaterstof en karboniel suurstof van die peptiedbinding. Daar bestaan anti-parallelle ß-geplooide plate en parallelle ß-geplooide plate waar die stabiliteit van die waterstofverbindings sterker is in die anti-parallelle ß-plaat, aangesien dit bind met die ideale 180°-hoek, in vergelyking met die skuins waterstofverbindings wat deur parallelle plate gevorm word.
Tersiêre struktuur
Die alfa-helikse en beta-geplooide plate kan amfipaties van aard wees, of 'n hidrofiliese gedeelte en 'n hidrofobiese gedeelte bevat. Hierdie eienskap van sekondêre strukture help met die tersiêre struktuur van 'n proteïen waarin die vou plaasvind, sodat die hidrofiliese sye teenoor die waterige omgewing rondom die proteïen is en die hidrofobiese sye teenoor die hidrofobiese kern van die proteïen. Die sekondêre struktuur maak op hiërargiese wyse plek vir tersiêre struktuurvorming of formasie. Sodra die proteïen se tersiêre struktuur gevorm is en gestabiliseer word deur hidrofobiese interaksies, mag daar ook kovalente binding wees in die vorm van disulfied-brûe wat tussen twee sisteïenreste gevorm word. Die tersiêre struktuur van 'n proteïen behels 'n enkele polipeptiedketting; bykomende interaksies van gevoude polipeptiedkettings lei egter tot die vorming van die kwaternêre strukture.
Kwaternêre struktuur
Tersiêre strukture kan moontlik plek maak vir die vorming van kwaternêre strukture in sommige proteïene, wat meestal die "samestelling" of "mede-samestelling" van sub-eenhede behels wat reeds gevou is; met ander woorde, veelvuldige polipeptiedkettings kan in wisselwerking tree om 'n ten volle funksionele kwaternêre proteïen te vorm. <!--
Dryfkrag agter proteïen invouing
Folding is a spontaneous process that is mainly guided by hydrophobic interactions, formation of intramolecular hydrogen bonds, van der Waals forces, and it is opposed by conformational entropy. The process of folding often begins co-translationally, so that the N-terminus of the protein begins to fold while the C-terminal portion of the protein is still being synthesized by the ribosome; however, a protein molecule may fold spontaneously during or after biosynthesis. While these macromolecules may be regarded as "folding themselves", the process also depends on the solvent (water or lipid bilayer), the concentration of salts, the pH, the temperature, the possible presence of cofactors and of molecular chaperones.
Proteins will have limitations on their folding abilities by the restricted bending angles or conformations that are possible. These allowable angles of protein folding are described with a two-dimensional plot known as the Ramachandran plot, depicted with psi and phi angles of allowable rotation.
Hydrophobic effect
In proteins with globular folds, hydrophobic amino acids tend to be interspersed along the primary sequence, rather than randomly distributed or clustered together. However, proteins that have recently been born de novo, which tend to be intrinsically disordered, show the opposite pattern of hydrophobic amino acid clustering along the primary sequence.
Chaperones
Molecular chaperones are a class of proteins that aid in the correct folding of other proteins in vivo. Chaperones exist in all cellular compartments and interact with the polypeptide chain in order to allow the native three-dimensional conformation of the protein to form; however, chaperones themselves are not included in the final structure of the protein they are assisting in. Chaperones may assist in folding even when the nascent polypeptide is being synthesized by the ribosome. Molecular chaperones operate by binding to stabilize an otherwise unstable structure of a protein in its folding pathway, but chaperones do not contain the necessary information to know the correct native structure of the protein they are aiding; rather, chaperones work by preventing incorrect folding conformations. In this way, chaperones do not actually increase the rate of individual steps involved in the folding pathway toward the native structure; instead, they work by reducing possible unwanted aggregations of the polypeptide chain that might otherwise slow down the search for the proper intermediate and they provide a more efficient pathway for the polypeptide chain to assume the correct conformations. Chaperones are not to be confused with folding catalysts, which actually do catalyze the otherwise slow steps in the folding pathway. Examples of folding catalysts are protein disulfide isomerases and peptidyl-prolyl isomerases that may be involved in formation of disulfide bonds or interconversion between cis and trans stereoisomers, respectively. Chaperones are shown to be critical in the process of protein folding in vivo because they provide the protein with the aid needed to assume its proper alignments and conformations efficiently enough to become "biologically relevant". This means that the polypeptide chain could theoretically fold into its native structure without the aid of chaperones, as demonstrated by protein folding experiments conducted in vitro; however, this process proves to be too inefficient or too slow to exist in biological systems; therefore, chaperones are necessary for protein folding in vivo. Along with its role in aiding native structure formation, chaperones are shown to be involved in various roles such as protein transport, degradation, and even allow denatured proteins exposed to certain external denaturant factors an opportunity to refold into their correct native structures.
A fully denatured protein lacks both tertiary and secondary structure, and exists as a so-called random coil. Under certain conditions some proteins can refold; however, in many cases, denaturation is irreversible. Cells sometimes protect their proteins against the denaturing influence of heat with enzymes known as heat shock proteins (a type of chaperone), which assist other proteins both in folding and in remaining folded. Some proteins never fold in cells at all except with the assistance of chaperones which either isolate individual proteins so that their folding is not interrupted by interactions with other proteins or help to unfold misfolded proteins, allowing them to refold into the correct native structure. This function is crucial to prevent the risk of precipitation into insoluble amorphous aggregates. The external factors involved in protein denaturation or disruption of the native state include temperature, external fields (electric, magnetic), molecular crowding, and even the limitation of space, which can have a big influence on the folding of proteins. High concentrations of solutes, extremes of pH, mechanical forces, and the presence of chemical denaturants can contribute to protein denaturation, as well. These individual factors are categorized together as stresses. Chaperones are shown to exist in increasing concentrations during times of cellular stress and help the proper folding of emerging proteins as well as denatured or misfolded ones.
Under some conditions proteins will not fold into their biochemically functional forms. Temperatures above or below the range that cells tend to live in will cause thermally unstable proteins to unfold or denature (this is why boiling makes an egg white turn opaque). Protein thermal stability is far from constant, however; for example, hyperthermophilic bacteria have been found that grow at temperatures as high as 122 °C, which of course requires that their full complement of vital proteins and protein assemblies be stable at that temperature or above.
Incorrect protein folding and neurodegenerative disease
A protein is considered to be misfolded if it cannot achieve its normal native state. This can be due to mutations in the amino acid sequence or a disruption of the normal folding process by external factors. The misfolded protein typically contains β-sheets that are organized in a supramolecular arrangement known as a cross-β structure. These β-sheet-rich assemblies are very stable, very insoluble, and generally resistant to proteolysis. The structural stability of these fibrillar assemblies is caused by extensive interactions between the protein monomers, formed by backbone hydrogen bonds between their β-strands. The misfolding of proteins can trigger the further misfolding and accumulation of other proteins into aggregates or oligomers. The increased levels of aggregated proteins in the cell leads to formation of amyloid-like structures which can cause degenerative disorders and cell death. The amyloids are fibrillary structures that contain intermolecular hydrogen bonds which are highly insoluble and made from converted protein aggregates. Therefore, the proteasome pathway may not be efficient enough to degrade the misfolded proteins prior to aggregation. Misfolded proteins can interact with one another and form structured aggregates and gain toxicity through intermolecular interactions.
Aloe shadensis
Aloe shadensis is 'n aalwyn wat endemies aan Saoedi-Arabië is.
Aloe sergoitensis
Aloe sergoitensis is 'n aalwyn wat endemies aan Kenia is.
Eva Habermann
Eva Habermann (gebore 16 Januarie 1976) is 'n Duitse aktrise en vervaardiger. Sy is bekend vir haar rolle in die rolprent Feuer, Eis & Dosenbier (2002) en in die televisiereeks Lexx (1997).
Proteïen-invouing
Fluorescence spectroscopy
Fluorescence spectroscopy is a highly sensitive method for studying the folding state of proteins. Three amino acids, phenylalanine (Phe), tyrosine (Tyr) and tryptophan (Trp), have intrinsic fluorescence properties, but only Tyr and Trp are used experimentally because their quantum yields are high enough to give good fluorescence signals. Both Trp and Tyr are excited by a wavelength of 280 nm, whereas only Trp is excited by a wavelength of 295 nm. Because of their aromatic character, Trp and Tyr residues are often found fully or partially buried in the hydrophobic core of proteins, at the interface between two protein domains, or at the interface between subunits of oligomeric proteins. In this apolar environment, they have high quantum yields and therefore high fluorescence intensities. Upon disruption of the protein's tertiary or quaternary structure, these side chains become more exposed to the hydrophilic environment of the solvent, and their quantum yields decrease, leading to low fluorescence intensities. For Trp residues, the wavelength of their maximal fluorescence emission also depend on their environment.
Fluorescence spectroscopy can be used to characterize the equilibrium unfolding of proteins by measuring the variation in the intensity of fluorescence emission or in the wavelength of maximal emission as functions of a denaturant value. The denaturant can be a chemical molecule (urea, guanidinium hydrochloride), temperature, pH, pressure, etc. The equilibrium between the different but discrete protein states, i.e. native state, intermediate states, unfolded state, depends on the denaturant value; therefore, the global fluorescence signal of their equilibrium mixture also depends on this value. One thus obtains a profile relating the global protein signal to the denaturant value. The profile of equilibrium unfolding may enable one to detect and identify intermediates of unfolding. General equations have been developed by Hugues Bedouelle to obtain the thermodynamic parameters that characterize the unfolding equilibria for homomeric or heteromeric proteins, up to trimers and potentially tetramers, from such profiles. Fluorescence spectroscopy can be combined with fast-mixing devices such as stopped flow, to measure protein folding kinetics, generate a chevron plot and derive a Phi value analysis.
Circular dichroism
Circular dichroism is one of the most general and basic tools to study protein folding. Circular dichroism spectroscopy measures the absorption of circularly polarized light. In proteins, structures such as alpha helices and beta sheets are chiral, and thus absorb such light. The absorption of this light acts as a marker of the degree of foldedness of the protein ensemble. This technique has been used to measure equilibrium unfolding of the protein by measuring the change in this absorption as a function of denaturant concentration or temperature. A denaturant melt measures the free energy of unfolding as well as the protein's m value, or denaturant dependence. A temperature melt measures the denaturation temperature (Tm) of the protein. As for fluorescence spectroscopy, circular-dichroism spectroscopy can be combined with fast-mixing devices such as stopped flow to measure protein folding kinetics and to generate chevron plots.
Vibrational circular dichroism of proteins
The more recent developments of vibrational circular dichroism (VCD) techniques for proteins, currently involving Fourier transform (FT) instruments, provide powerful means for determining protein conformations in solution even for very large protein molecules. Such VCD studies of proteins are often combined with X-ray diffraction of protein crystals, FT-IR data for protein solutions in heavy water (D2O), or ab initio quantum computations to provide unambiguous structural assignments that are unobtainable from CD.
Protein nuclear magnetic resonance spectroscopy
Protein folding is routinely studied using NMR spectroscopy, for example by monitoring hydrogen-deuterium exchange of backbone amide protons of proteins in their native state, which provides both the residue-specific stability and overall stability of proteins.
Dual polarisation interferometry
Dual polarisation interferometry is a surface-based technique for measuring the optical properties of molecular layers. When used to characterize protein folding, it measures the conformation by determining the overall size of a monolayer of the protein and its density in real time at sub-Angstrom resolution, although real-time measurement of the kinetics of protein folding are limited to processes that occur slower than ~10 Hz. Similar to circular dichroism, the stimulus for folding can be a denaturant or temperature.
Studies of folding with high time resolution
The study of protein folding has been greatly advanced in recent years by the development of fast, time-resolved techniques. Experimenters rapidly trigger the folding of a sample of unfolded protein and observe the resulting dynamics. Fast techniques in use include neutron scattering, ultrafast mixing of solutions, photochemical methods, and laser temperature jump spectroscopy. Among the many scientists who have contributed to the development of these techniques are Jeremy Cook, Heinrich Roder, Harry Gray, Martin Gruebele, Brian Dyer, William Eaton, Sheena Radford, Chris Dobson, Alan Fersht, Bengt Nölting and Lars Konermann.
Proteolysis
Proteolysis is routinely used to probe the fraction unfolded under a wide range of solution conditions (e.g. Fast parallel proteolysis (FASTpp).
Optical tweezers
Single molecule techniques such as optical tweezers and AFM have been used to understand protein folding mechanisms of isolated proteins as well as proteins with chaperones. Optical tweezers have been used to stretch single protein molecules from their C- and N-termini and unfold them to allow study of the subsequent refolding. The technique allows one to measure folding rates at single-molecule level; for example, optical tweezers have been recently applied to study folding and unfolding of proteins involved in blood coagulation. von Willebrand factor (vWF) is a protein with an essential role in blood clot formation process. It discovered – using single molecule optical tweezers measurement – that calcium-bound vWF acts as a shear force sensor in the blood. Shear force leads to unfolding of the A2 domain of vWF, whose refolding rate is dramatically enhanced in the presence of calcium. Recently, it was also shown that the simple src SH3 domain accesses multiple unfolding pathways under force.
Biotin painting
Biotin painting enables condition-specific cellular snapshots of (un)folded proteins. Biotin 'painting' shows a bias towards predicted Intrinsically disordered proteins.
Computational studies of protein folding
Computational studies of protein folding includes three main aspects related to the prediction of protein stability, kinetics, and structure. A recent review summarizes the available computational methods for protein folding.
Levinthal's paradox
In 1969, Cyrus Levinthal noted that, because of the very large number of degrees of freedom in an unfolded polypeptide chain, the molecule has an astronomical number of possible conformations. An estimate of 3300 or 10143 was made in one of his papers. Levinthal's paradox is a thought experiment based on the observation that if a protein were folded by sequentially sampling of all possible conformations, it would take an astronomical amount of time to do so, even if the conformations were sampled at a rapid rate (on the nanosecond or picosecond scale). Based upon the observation that proteins fold much faster than this, Levinthal then proposed that a random conformational search does not occur, and the protein must, therefore, fold through a series of meta-stable intermediate states.
Energy landscape of protein folding
The configuration space of a protein during folding can be visualized as an energy landscape. According to Joseph Bryngelson and Peter Wolynes, proteins follow the principle of minimal frustration meaning that naturally evolved proteins have optimized their folding energy landscapes. , and that nature has chosen amino acid sequences so that the folded state of the protein is sufficiently stable. In addition, the acquisition of the folded state had to become a sufficiently fast process. Even though nature has reduced the level of frustration in proteins, some degree of it remains up to now as can be observed in the presence of local minima in the energy landscape of proteins.
A consequence of these evolutionarily selected sequences is that proteins are generally thought to have globally "funneled energy landscapes" (coined by José Onuchic) that are largely directed toward the native state. This "folding funnel" landscape allows the protein to fold to the native state through any of a large number of pathways and intermediates, rather than being restricted to a single mechanism. The theory is supported by both computational simulations of model proteins and experimental studies, and it has been used to improve methods for protein structure prediction and design. The description of protein folding by the leveling free-energy landscape is also consistent with the 2nd law of thermodynamics. Physically, thinking of landscapes in terms of visualizable potential or total energy surfaces simply with maxima, saddle points, minima, and funnels, rather like geographic landscapes, is perhaps a little misleading. The relevant description is really a high-dimensional phase space in which manifolds might take a variety of more complicated topological forms.
The unfolded polypeptide chain begins at the top of the funnel where it may assume the largest number of unfolded variations and is in its highest energy state. Energy landscapes such as these indicate that there are a large number of initial possibilities, but only a single native state is possible; however, it does not reveal the numerous folding pathways that are possible. A different molecule of the same exact protein may be able to follow marginally different folding pathways, seeking different lower energy intermediates, as long as the same native structure is reached. Different pathways may have different frequencies of utilization depending on the thermodynamic favorability of each pathway. This means that if one pathway is found to be more thermodynamically favorable than another, it is likely to be used more frequently in the pursuit of the native structure. As the protein begins to fold and assume its various conformations, it always seeks a more thermodynamically favorable structure than before and thus continues through the energy funnel. Formation of secondary structures is a strong indication of increased stability within the protein, and only one combination of secondary structures assumed by the polypeptide backbone will have the lowest energy and therefore be present in the native state of the protein. Among the first structures to form once the polypeptide begins to fold are alpha helices and beta turns, where alpha helices can form in as little as 100 nanoseconds and beta turns in 1 microsecond.
Barbara Lyon
Barbara Lyon (9 September 1931 – 10 Julie 1995) was 'n Amerikaanse aktrise. Sy was bekend vir haar rolle in die rolprente Family Affair (1954) en The Lyons Abroad (1955), en in die televisiereeks Life with the Lyons (1955).
Proteïen-invouing
Energy landscape of protein folding
There exists a saddle point in the energy funnel landscape where the transition state for a particular protein is found. The transition state in the energy funnel diagram is the conformation that must be assumed by every molecule of that protein if the protein wishes to finally assume the native structure. No protein may assume the native structure without first passing through the transition state. The transition state can be referred to as a variant or premature form of the native state rather than just another intermediary step. The folding of the transition state is shown to be rate-determining, and even though it exists in a higher energy state than the native fold, it greatly resembles the native structure. Within the transition state, there exists a nucleus around which the protein is able to fold, formed by a process referred to as "nucleation condensation" where the structure begins to collapse onto the nucleus.
Modeling of protein folding
De novo or ab initio techniques for computational protein structure prediction are related to, but strictly distinct from, experimental studies of protein folding. Molecular Dynamics (MD) is an important tool for studying protein folding and dynamics in silico. First equilibrium folding simulations were done using implicit solvent model and umbrella sampling. Because of computational cost, ab initio MD folding simulations with explicit water are limited to peptides and very small proteins. MD simulations of larger proteins remain restricted to dynamics of the experimental structure or its high-temperature unfolding. Long-time folding processes (beyond about 1 millisecond), like folding of small-size proteins (about 50 residues) or larger, can be accessed using coarse-grained models.
Anthony Carrigan (akteur)
Anthony Carrigan (gebore 2 Januarie 1983) is 'n Amerikaanse akteur en skrywer. Hy is bekend vir sy rolle in die televisiereekse Parenthood (2010), The Flash (2014), Gotham (2014), en Barry (2018).
Proteïen-invouing
Modeling of protein folding
The 100-petaFLOP distributed computing project Folding@home created by Vijay Pande's group at Stanford University simulates protein folding using the idle processing time of CPUs and GPUs of personal computers from volunteers. The project aims to understand protein misfolding and accelerate drug design for disease research.
Mesembryanthemum longistylum
Mesembryanthemum longistylum is 'n vetplant wat deel is van die Aizoaceae familie. Die plant is endemies aan die Noord- en die Wes-Kaap.
Aloe × selmarii
Aloe × selmarii is 'n aalwyn en hibried wat endemies aan Suid-Afrika is. Die spesie is 'n kruising tussen Aloe davyana en Aloe parvibracteata.
Edi Rama
Edi Rama (gebore 4 Julie 1964) is 'n Albanese politikus, skilder, skrywer, en voormalige basketbalspeler en is sedert 2013 die 42ste eerste minister van Albanië en sedert Januarie 2019 die minister van buitelandse sake van daardie land. Rama dien sedert 2005 ook as voorsitter van die Sosialistiese Party van Albanië. Hy het voor sy verkiesing as eerste minister verskeie ander regeringsposte bekleë. Hy is in 1998 aangestel as minister van kultuur, jeug, en sport, 'n posisie wat hy tot en met 2000 bekleë. Hy word in 2000 as burgemeester van Tirana verkies en word in 2003 en 2007 herverkies. In 2013 lei hy 'n koalisie van sentraal-linkse partye tot die oorwinning van die parlementêre verkiesing van daardie jaar, en klop sodoende die sentraal-regse koalisie van die Demokratiese Party van Albanië se sittende eerste minister, Sali Berisha. Rama is in die verkiesing van 2017 tot 'n tweede termyn as eerste minister herverkies.
Aloe × schimperi
Aloe × schimperi is 'n aalwyn en hibried wat endemies aan Suid-Afrika is. Die plant is 'n kruising tussen Aloe maculata en Aloe striata.
Evangelies-Lutherse Kerk in Namibië
Die Evangelies-Lutherse Kerk in Namibië (Engels: The Evangelical Lutheran Church in Namibia, ELCIN) is die grootste van drie Lutherse kerke in Namibië met ongeveer 700 000 lidmate wat hoofsaaklik in die noorde van die land gevestig is. Die twee ander kerke is die merendeels Suid-Namibiese Evangelies-Lutherse Kerk in die Republiek van Namibië en die Duitssprekende Evangelies-Lutherse Kerk in Namibië (DELK).
Die huidige voorsitter is dr. Shekutaamba V. V. Nambala.
Frans I van Frankryk
Frans I is op 12 September 1494 in Cognac gebore. Hy was die enigste seun van Karel van Angoulême en Louise van Savoye. Hy behoort tot die bloedlyn Valois-Angoulême van die Huis Valois.
Op 18 Mei 1514 trou hy met Claude van Frankryk. Sewe kinders is uit die huwelike gebore. Twee kinders sterf voor 8-jarige ouderdom en 'n verdere twee sterf tussen 18 en 23 jaar. Die wat volwassenheid bereik het is:
Hy is op 31 Maart 1547 in die Kasteel van Rambouillet oorlede en is in die Katedraal van Saint-Denis begrawe.
Aloe sharoniae
Aloe sharoniae is 'n aalwyn wat inheems aan Eswatini en KwaZulu-Natal is.
Sue Lyon
Sue Lyon (gebore 10 Julie 1946) is 'n Amerikaanse aktrise. Sy is bekend vir haar rolle in die rolprente Lolita (1962), The Night of the Iguana (1964), 7 Women (1966), en Tony Rome (1967).
Klein-Brakrivier (Groot-Vis, lat -31.83, long 25.40)
Die Klein-Brakrivier is 'n rivier wat in die Oos-Kaap van Suid-Afrika vloei. Dit is 'n sytak van, en in die opvanggebied van die Groot-Visrivier.
Die rivier ontspring in die Agter-Renosterberg op die grens tussen die Noord-Kaap en die Oos-Kaap. Daarna vloei dit deur Middelburg, Oos-Kaap, die spoorwegdorpie Conway op die R401-pad en sluit onder die Grassridgedam by die Grootbrakrivier aan, wat op sy beurt weer stroomaf by die Groot-Visrivier aansluit. Die spoorlyn volg die rivier in 'n suidoostelike rigting.
Jeanette Hain
Jeanette Hain (gebore 18 Februarie 1969) is 'n Duitse aktrise en regisseuse. Sy is bekend vir haar rolle in die rolprente The Reader (2008), The Young Victoria (2009), The Whistleblower (2010), en The Poll Diaries (2010).
Olaf Pooley
Olaf Pooley (13 Maart 1914 – 14 Julie 2015) was 'n Engelse akteur, skrywer, en regisseur. Hy was bekend vir sy rolle in die rolprent The Password Is Courage (1962) en in die televisiereekse The Adventures of Ben Gunn (1958), Doctor Who (1963), en Star Trek: Voyager (1995).
Mark Perrow
Mark Perrow (13 November 1965 - 15 Maart 2020) was 'n legendariese kanovaarder van Suid-Afrika wat onder andere die Dusi-kanowedvaart en die Bergrivier-kanowedvaart gewen het. Hy is in Kaapstad gebore, het later in Port Elizabeth, Johannesburg en in Ballito gewoon. Hy het Suid-Afrika in 1992 by die Olimpiese Spele in Barcelona verteenwoordig. Hy het ook 36 Umkomaaskanovaarte voltooi, sy eerste in 1983 en laaste in 2009. Hy het twee susters, Julie en Sally. Hy sterf tydens 'n vliegongeluk in die Umkomaasvallei en word oorleef deur sy vrou, Belinda en twee dogters, Kate en Alice.
Ernst Haas
Ernst Haas (2 Maart 1921 – 12 September 1986) was ’n fotojoernalis en pionier-kleurfotograaf. In sy loopbaan van 40 jaar het die Oostenryks gebore Haas die gaping oorbrug tussen fotojoernalistiek en die gebruik van fotografie as kunsmedium. Benewens sy uitstekende dekking van gebeure oor die wêreld heen ná die Tweede Wêreldoorlog, was hy ’n vroeë innoveerder in kleurfotografie. Sy foto's is ruim gebruik deur tydskrifte soos Life en Vogue, en was in 1962 die onderwerp van die eerste tentoonstelling van een fotograaf se werk in New York se Museum of Modern Art.
Hy was onder andere die president van die koöperatiewe Magnum Photos, en sy boek The Creation (1971) was een van die suksesvolste fotografieboeke ooit; meer as 350 000 eksemplare is verkoop.
Haas is op 12 September 1986 in New York oorlede ná ’n beroerte in Desember 1985.
Pryse
’n Paar van die pryse wat Haas gewen het, is:
135-film
135 is ’n filmformaat vir fotografie. Die film kom in ’n kasset voor, is 35 mm breed en word in 35 mm-kameras gebruik.
Die term 135 (ISO 1007) is in 1934 deur Kodak ingestel as ’n naam vir die kasset vir 35 mm-film. Dit het teen die laat 1960's gewilder geword as die 120-film van vroeër.
Ondanks die mededinging van ander formate soos 828, 126 en 110, is dit steeds die gewildste. Die grootte van die 135-filmraampie is deur baie moderne digitale enkellens-reflekskameras aangeneem.
Eienskappe
Rolletjies 135-film is in ’n kasset toe sodat die film in daglig gelaai kan word. Die beginpunt van die film word in die kamera gesteek en tot by die eerste raampie gerol. As die film vol is, word dit weer teruggerol na die begin. Sommige kameras rol die film af as dit gelaai word en die foto's word dan in ’n terugwaartse rigting geneem terwyl die film geleidelik oprol.
Sedert die 1980's word filmkassette met die DX-kode gemerk; kameras lees die kode en stel dan die regte filmspoed.
135-film word in verskeie emulsietipes en sensitiwiteite gemaak. Die gewildste filmspoed is ISO 100/21° tot ISO 800/30°. Vinniger of stadiger films voorsien meestal in spesialiteitsbehoeftes. Verder is daar kleur- en swart-wit-films, asook films wat sensitief is vir infrarooilig. Meer eksotiese emulsies is in 135-film beskikbaar as in enige ander formaat.
Die breedte van die formaat is gewoonlik 24 mm binne die gaatjies weerskante van die film, wat self 35 mm breed is. Gewone volraamfoto's is 24×36 mm (dus in ’n verhouding van 2:3).
Die films is in verskillende lengtes beskikbaar. Dit was aanvanklik lank genoeg vir 36 foto's, met die enigste korter lengte in die 1980's rond vir 20 foto's. Later is laasgenoemde verander na 24 en 12 foto's. Soms kan tot drie foto's meer geneem word op ’n 24-foto-film.
Verwysings
Format 35 mm
Mesembryanthemum rhizophorum
Mesembryanthemum rhizophorum is 'n vetplant wat deel is van die Aizoaceae familie. Die plant is endemies aan die Oos-Kaap.
Sean Carrigan
Sean Carrigan (gebore 16 Mei 1974) is 'n Amerikaanse akteur, vervaardiger, en skrywer. Hy is bekend vir sy rolle in die rolprent John Carter (2012) en in die televisiereekse The Young and the Restless (1973), The Event (2010), en American Vandal (2017).
Aloe sobolifera
Aloe sobolifera is 'n aalwyn wat endemies aan Tanzanië is.
Mesembryanthemum pellitum
Mesembryanthemum pellitum is 'n vetplant wat deel is van die Aizoaceae familie. Die plant is inheems aan Namibië en Suid-Afrika waar dit in die Noord-Kaap voorkom. Die plant het 'n voorkomsgebied van 10 691 km². Dit kom in die suide van Namibië voor, in Suid-Afrika in die Richtersveld en in Namakwaland - so ver suid as Hondeklipbaai.
Mount Rushmore
Die Mount Rushmore monument is vier beelde van die gesigte van presidente George Washington, Thomas Jefferson, Theodore Roosevelt en Abraham Lincoln wat in die Harneyberg in die Black Hills uitgekerf is. Die Harneyberg is in 'n reservaat in die Black Hills District in die deelstaat Suid-Dakota.
Mesembryanthemum guerichianum
Mesembryanthemum guerichianum is 'n vetplant wat deel is van die Aizoaceae familie. Die plant is inheems aan Namibië en Suid-Afrika waar dit in die Noord-Kaap voorkom.