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Dissertations / Theses on the topic 'RSA signature'
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Misarsky, Jean-Francois. "Cryptanalyse et specification de schemas de signature rsa avec redondance." Caen, 1999. http://www.theses.fr/1999CAEN2043.
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Plus de vingt ans se sont ecoules depuis l'invention par rivest, shamir et adleman de l'algorithme rsa. Aujourd'hui, c'est l'algorithme a cle publique le plus utilise dans le monde. Sans pour autant le remettre en cause en tant que tel, des attaques sur son utilisation en chiffrement et en signature sont apparues. Cette these les passe en revue, puis en presente de nouvelles. Les nouvelles attaques concernent les schemas de signature rsa avec redondance, c'est-a-dire ne faisant appel a aucune fonction de hachage. La premiere, basee sur une version affine de l'algorithme d'euclide etendu, l'algorithme d'okamoto-shiraishi, permet d'attaquer des schemas utilisant une fonction de redondance affine. De plus, cette attaque reste applicable lorsque de la redondance modulaire est utilisee. La seconde, basee sur la theorie des reseaux, fait appel a l'algorithme lll et permet d'attaquer des schemas de signature dispersant la redondance, qu'elle soit ou non modulaire, a l'interieur du message. De plus, de simples modifications dans la definition du reseau utilise permettent d'attaquer les schemas de signature faisant appel a differentes redondances modulaires, pour le message en entier, ou pour differentes parties du message. Afin de contrer ces deux attaques et celles recensees precedemment, deux nouveaux schemas de signature avec redondance sont proposes. Bases sur de nouveaux concepts, ils permettent d'abaisser le niveau de redondance a un tiers du nombre de bits du module rsa.
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Koshta, Prashant Kumar, and Shailendra Singh Thakur. "A Novel Authenticity of an Image Using Visual Cryptography." IJCSN, 2012. http://hdl.handle.net/10150/219514.
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Information security in the present era is becoming very
important in communication and data storage. Data
transferred from one party to another over an insecure
channel (e.g., Internet) can be protected by cryptography.
The encrypting technologies of traditional and modern
cryptography are usually used to avoid the message from
being disclosed. Public-key cryptography usually uses
complex mathematical computations to scramble the
message.A digital signature is an important public-key primitive that performs the function of conventional handwritten signatures for entity authentication, data integrity, and non-repudiation, especially within the electronic commerce environment. Currently, most conventional digital signature schemes are based on mathematical hard problems. These mathematical algorithms require computers to perform the heavy and complex computations to generate and verify the keys and signatures. In 1995, Naor and Shamir proposed a visual cryptography (VC) for binary images. VC has high security and requires simple computations. The purpose of this thesis is to provide an alternative to the current digital signature technology. We introduce a new digital signature scheme based on the concept of a non-expansion visual cryptography. A visual digital signature scheme is a method to enable visual verification of the authenticity of an image in an insecure environment without the need to perform any complex computations. We proposed scheme generates visual shares and manipulates them using the simple Boolean operations OR rather than generating and computing large and long random integer values as in the conventional digital signature schemes currently in use.
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Seyed, Saboonchi Nima. "Hardware Security Module Performance Optimization by Using a "Key Pool" : Generating keys when the load is low and saving in the external storage to use when the load is high." Thesis, KTH, Radio Systems Laboratory (RS Lab), 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-158122.
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This thesis project examines the performance limitations of Hardware Security Module (HSM) devices with respect to fulfilling the needs of security services in a rapidly growing security market in a cost-effective way. In particular, the needs due to the introduction of a new electronic ID system in Sweden (the Federation of Swedish eID) and how signatures are created and managed. SafeNet Luna SA 1700 is a high performance HSM's available in the current market. In this thesis the Luna SA 1700 capabilities are stated and a comprehensive analysis of its performance shows a performance gap between what HSMs are currently able to do and what they need to do to address the expected demands. A case study focused on new security services needed to address Sweden's e Identification organization is presented. Based upon the expected performance demands, this thesis project proposes an optimized HSM solution to address the identified performance gap between what is required and what current HSMs can provide. A series of tests were conducted to measure an existing HSM's performance. An analysis of these measurements was used to optimize a proposed solution for selected HSM or similar HSMs. One of the main requirements of the new signing service is the capability to perform fifty digital signatures within the acceptable response time which is 300 ms during normal hours and 3000 ms during peak hours. The proposed solution enables the HSM to meet the expected demands of 50 signing request per second in the assumed two hours of peak rate at a cost that is 1/9 of the cost of simply scaling up the number of HSMs. The target audience of this thesis project is Security Service Providers who use HSMs and need a high volume of key generation and storing. Also HSM vendors consider this solution and add similar functionality to their devices in order to meet the desired demands and to ensure a better future in this very rapidly growing market.Detta examensarbete undersöker prestandabegränsningar för Hardware Security Module (HSM) enheter med avseende på att uppfylla behov av säkerhetstjänster i en snabbt växande marknad och på ett kostnadseffektivt sätt. I synnerhet på grund av de säkerhetskrav som nu existerar/tillkommit efter införandet av ett nytt elektroniskt ID-system i Sverige (Federationen för Svensk eID) och hur underskrifter skapas och hanteras. SafeNet Luna SA 1700 är en högpresterande HSM enhet tillgänglig på marknaden. I den här avhandlingen presenteras nuvarande HSM kapacitet och en omfattande analys av resultatet visar ett prestanda gap mellan vad HSMS för närvarande kan göra och vad som behöver förbättras för att ta itu med de förväntade kraven. En fallstudie fokuserad på nya säkerhetstjänster som krävs i och med Sveriges nya e-Identifiering presenteras. Baserat på resultatet i den här avhandlingen föreslås en optimerad HSM lösning för att tillgodose prestanda gapet mellan vad HSM presterar och de nya krav som ställs. Ett flertal tester genomfördes för att mäta en befintlig HSM prestanda. En analys av dessa mätningar användes för att föreslå en optimerad lösning för HSMS (eller liknande) enheter. Ett av de huvudsakliga kraven för den nya signeringstjänsten är att ha en kapacitet av 50 digitala signaturer inom en accepterad svarstidsintervall, vilket är 300ms vid ordinarie trafik och 3000ms vid högtrafik. Förslagen i avhandlingen möjliggör HSM enheten att tillgodose kraven på 50 signeringen per sekund under två timmars högtrafik, och till en 1/9 kostnad genom att skala upp antalet HSMs. Målgruppen i den här avhandlingen är användare av HSMs och där behovet av lagring och generering av nycklar i höga volymer är stort. Även HSM leverantörer som kan implementera den här optimeringen/lösningen i befintlig funktionalitet för att tillgodose det här behovet i en alltmer växande marknad.
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Magri, Bernardo Caraponale. "Assinatura digital Rabin-Williams - sem randomização e com prova eficiente de segurança." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/45/45134/tde-10092012-165253/.
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Com o surgimento da criptografia de chave pública, muito esforço foi feito para a criação de protocolos de criptografia e de assinatura que fossem comprovadamente seguros contra indivíduos maliciosos. Existem várias definições de segurança, tanto para protocolos de criptografia como para protocolos de assinatura, e também existem vários modelos de adversários, que simulam um indivíduo malicioso tentando corromper o protocolo. A família de protocolos de assinatura Rabin possui os recordes de velocidade de vericação da assinatura, chegando a ser até 100 vezes mais rápida do que o RSA. Este trabalho apresenta uma redução eficiente de segurança no modelo do oráculo aleatório para uma variante do protocolo de assinatura Rabin descrito por Bernstein, onde não é necessário o uso de nenhuma função para geração de bits pseudo-aleatórios, o que torna o protocolo mais robusto. A redução apresentada é uma redução polinomial e eficiente do problema da fatoração de inteiros para o problema de quebrar o protocolo Principal Rabin-Williams B = 0.With the development of public-key cryptography, many efforts were made to build encryption and signature protocols that were provably secure against malicious adversaries. There are many definitions of security for encryption and signature protocols, and there are many adversary models to simulate the behaviour of a malicious adversary against a given protocol. The Rabin family of signature protocols has the speed records for verification of signature, being up to 100 times faster than RSA. This work presents a tight security proof in the random oracle model for a variant of the Rabin signature protocol presented by Bernstein, that does not require the use of pseudo-random bits, making the protocol more robust. The proof presented here is a polynomially tight reduction for the problem of integer factorization to the problem of breaking the Principal Rabin-Williams B = 0 protocol.
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Valkaitis, Mindaugas. "Efektyvios šifravimo bei skaitmeninio parašo sistemos." Master's thesis, Lithuanian Academic Libraries Network (LABT), 2014. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2012~D_20140704_171717-30545.
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Šio darbo tikslas – apžvelgti šiuo metu naudojamas klasikines viešojo rakto šifravimo ir skaitmeninio parašo sistemas bei naujos kartos Signcryption kriptosistemą ir atlikti dedikuotos pasirašymo ir šifravimo kriptosistemos efektyvumo palyginimą su pasirašymo arba šifravimo kriptosistemų kompozicija bei pasiūlyti praktinio pritaikymą naujos kartos Signcryption kriptosistemai. Darbe apžvelgtos šios kriptosistemos: 1. RSA (Rivest, Shamir, Adleman) – klasikinė viešojo rakto pasirašymo arba šifravimo kriptosistema, kurios saugumas paremtas didelių skaičių faktorizacijos uždavinio sprendimo sudėtingumu, 2. ElGamalio – klasikinė viešojo rakto pasirašymo arba šifravimo kriptosistema, kurios saugumas paremtas diskretaus logaritmo problemos sprendimo sudėtingumu, 3. Signcryption – naujos kartos viešojo rakto pasirašymo ir šifravimo kriptosistema, realizuota modifikuotos ElGamalio skaitmeninio parašo schemos pagrindu. Minėtos kriptosistemos apžvelgtos teoriškai, sukurta praktinė jų realizacija ir apžvelgti rezultatai bei palygintas jų efektyvumas, kuris apibrėžiamas dviem parametrais: 1. Pranešimo pasirašymo, šifravimo, dešifravimo ir parašo patikrinimo operacijų trukmė, 2. Perduodamos perteklinės informacijos kiekis – pranešimo ilgio padidėjimas atlikus pasirašymo ir šifravimo operacijas. Taip pat apžvelgtos kriptosistemų realizacijoje naudotos papildomos funkcijos bei algoritmai, tokie kaip AES blokiniai šifrai, SHA maišos funkcijų šeima, HMAC kontrolinis parašas bei pasiūlyti du... [toliau žr. visą tekstą]This submission called “Efficient encryption and digital signature schemes” consists of three parts. I. In Part I theoretical analysis of popular public key cryptosystems RSA (Rivest, Shamir, Adleman) with security based on the large integer factorization problem and ElGamal with security based on the discrete logarithm problem, along with new cryptographic primitive termed as "signcryption" proposed by Y. Zheng which simultaneously fulfills both the functions of digital signature and public key encryption in a logically single step, and with a cost significantly smaller than that required by "signature followed by encryption" using popular public key cryptosystem composition is done. For the completeness of analysis description of supplemental algorithms and functions such as AES block cipher, SHA hash functions, HMAC keyed hash function is present. II. In Part II the results of the practical implementation done in Python programming language are analyzed. Effectiveness is described by two factors: 1. Total computation time of signing – encryption – decryption – verification operations; 2. Communication overhead – signed and encrypted message length increase compared to the original plaintext. III. In Part III two effective Signcryption implementation algorithms are proposed: secret sharing without threshold and (k, n) threshold schemes. Results of analysis prove Signcryption being secure and extremely effective signature and encryption cryptosystem. It has very low... [to full text]
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Kratochvíl, Martin. "Zabezpečený přenos dat pomocí čarových kódů." Master's thesis, Vysoké učení technické v Brně. Fakulta informačních technologií, 2011. http://www.nusl.cz/ntk/nusl-412838.
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The goal of this thesis was to create a system for visual data transmition using bar codes. It focuses mainly on the protection of the system against abuse. A mechanism was designed for the data transmition itself and the various security concepts. The most appropriate bar code for data transmition was selected on the basis of the analysis.
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Balaževič, Lukáš. "Mechanismy zabezpečení OS Android s využitím jazyka Kotlin." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2020. http://www.nusl.cz/ntk/nusl-413001.
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Mobilné zariadenia sú v rámci technologickej histórie novinka a pri technológii, ktorá sa vyvíja tak rapídnym tempom a rastom používania je nutné dbať na zabezpečenie. Táto diplomová práca sa zaoberá rozborom bezpečnostných mechanizmov používaných v Android OS a komunikáciou medzi OS Android a vzdialeným serverom. Cieľom je preskúmať tieto mechanizmy a otestovať aké kryptografické metódy a postupy je najvýhodnejšie používať z hľadiska bezpečnosti s ohľadom na efektivitu. Tieto znalosti boli použité pre vytvorenie demonštračného systému, ktorý využíva vybrané zabezpečovacie mechanizmy a kryptografické postupy.
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Beran, Martin. "Elektronická podatelna VUT 2." Master's thesis, Vysoké učení technické v Brně. Fakulta informačních technologií, 2007. http://www.nusl.cz/ntk/nusl-412777.
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This dissertation thesis attends to problems of electronic registry for VUT. It deals with the principal of electronic registry functioning, electronic signature and it compares offer of the commercial registries. It goes in for the proposal and implementation of the electronic registry for VUT. Since the using of the e- registry on all public service Office was legalized the people can avoid long queues and the employees are avoided from the stress before dead lines. By the communication through the electronic registry is very important the electronical signature. It is almost a full-valued and lawful alternative to the physical signature. For its safety and utility this system employes asymmetric codes and hash algorithm. Presently in many states, where the electronical signature is legalized it is used together with standard X 509 which defines the format of certificates, organization and action of certification authorities. The certification autority ensures safe connection of the person and general key for using of the electronical signature.
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Tomaz, Antonio Emerson Barros. "Resgate de autoria em esquemas de assinatura em anel." reponame:Repositório Institucional da UFC, 2014. http://www.repositorio.ufc.br/handle/riufc/10842.
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TOMAZ. A. E. B. Resgate de autoria em esquemas de assinatura em anel. 2014. 67 f. Dissertação (Mestrado em Engenharia de Teleinformática) - Centro de Tecnologia, Universidade Federal do Ceará, Fortaleza, 2014.Submitted by Marlene Sousa (mmarlene@ufc.br) on 2015-02-27T18:29:04Z No. of bitstreams: 1 2014_dis_aebtomaz.pdf: 1072067 bytes, checksum: 405260d86425363feaec1802b2775de1 (MD5)
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The proposal presented in this thesis represents an expansion of the original concept of ring signature. A ring signature scheme allows a member of a group to publish a message anonymously, so that each member of the group can be considered the author of the message. The main idea of a ring signature is to guarantee the anonymity of the subscriber also ensure the authenticity of information, showing that the message came from one of the members of that group. This thesis presents a signature scheme based on (RIVEST et al., 2001), where the subscriber can later revoke anonymity presenting secret values that prove that he would only be able to generate such a signature. This property will be referred to here as rescue of authorship. The main difference to the proposal of Rivest et al. (2001) is presented before we even begin signature generation. The values used as input to the trapdoor function are message authentication codes - MACs generated by the HMAC algorithm, an algorithm for message authentication based on hash function collision resistant. This simple modification will allow, in the future, the subscriber to reveal itself as the true author of the message by showing the secret values to generate those MACs.
A proposta apresentada nesta dissertação representa uma expansão do conceito original de assinatura em anel. Um esquema de assinatura em anel permite que um membro de um grupo divulgue uma mensagem anonimamente, de tal forma que cada um dos membros do grupo seja considerado o possível autor da mensagem. A ideia principal de uma assinatura em anel é garantir o anonimato do assinante e ainda garantir a autenticidade da informação, mostrando que a mensagem partiu de um dos membros do referido grupo. Esta dissertação apresenta um esquema de assinatura em anel baseado no esquema de Rivest et al. (2001), em que o assinante pode, mais tarde, revogar seu anonimato apresentando valores secretos que provam que somente ele seria capaz de gerar tal assinatura. Esta propriedade será chamada aqui de resgate de autoria. A principal diferença em relação ao trabalho de Rivest et al. (2001) é apresentada antes mesmo de começar a geração da assinatura. Os valores utilizados como entrada para a função trapdoor serão códigos de autenticação de mensagem - MACs gerados pelo algoritmo HMAC, um algoritmo de autenticação de mensagem baseado em função hash resistente à colisão. Essa modificação simples permitirá que, no futuro, o assinante revele-se como o verdadeiro autor da mensagem apresentando os valores secretos que geraram os MACs.
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Krisell, Martin. "Elliptic Curve Digital Signatures in RSA Hardware." Thesis, Linköpings universitet, Informationskodning, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-81084.
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A digital signature is the electronic counterpart to the hand written signature. It can prove the source and integrity of any digital data, and is a tool that is becoming increasingly important as more and more information is handled electronically. Digital signature schemes use a pair of keys. One key is secret and allows the owner to sign some data, and the other is public and allows anyone to verify the signature. Assuming that the keys are large enough, and that a secure scheme is used, it is impossible to find the private key given only the public key. Since a signature is valid for the signed message only, this also means that it is impossible to forge a digital signature. The most well-used scheme for constructing digital signatures today is RSA, which is based on the hard mathematical problem of integer factorization. There are, however, other mathematical problems that are considered even harder, which in practice means that the keys can be made shorter, resulting in a smaller memory footprint and faster computations. One such alternative approach is using elliptic curves. The underlying mathematical problem of elliptic curve cryptography is different to that of RSA, however some structure is shared. The purpose of this thesis was to evaluate the performance of elliptic curves compared to RSA, on a system designed to efficiently perform the operations associated with RSA. The discovered results are that the elliptic curve approach offers some great advantages, even when using RSA hardware, and that these advantages increase significantly if special hardware is used. Some usage cases of digital signatures may, for a few more years, still be in favor of the RSA approach when it comes to speed. For most cases, however, an elliptic curve system is the clear winner, and will likely be dominant within a near future.En digital signatur är den elektroniska motsvarigheten till en handskriven signatur. Den kan bevisa källa och integritet för valfri data, och är ett verktyg som blir allt viktigare i takt med att mer och mer information hanteras digitalt. Digitala signaturer använder sig av två nycklar. Den ena nyckeln är hemlig och tillåter ägaren att signera data, och den andra är offentlig och tillåter vem som helst att verifiera signaturen. Det är, under förutsättning att nycklarna är tillräck- ligt stora och att det valda systemet är säkert, omöjligt att hitta den hemliga nyckeln utifrån den offentliga. Eftersom en signatur endast är giltig för datan som signerades innebär detta också att det är omöjligt att förfalska en digital signatur. Den mest välanvända konstruktionen för att skapa digitala signaturer idag är RSA, som baseras på det svåra matematiska problemet att faktorisera heltal. Det finns dock andra matematiska problem som anses vara ännu svårare, vilket i praktiken innebär att nycklarna kan göras kortare, vilket i sin tur leder till att mindre minne behövs och att beräkningarna går snabbare. Ett sådant alternativ är att använda elliptiska kurvor. Det underliggande matematiska problemet för kryptering baserad på elliptiska kurvor skiljer sig från det som RSA bygger på, men de har en viss struktur gemensam. Syftet med detta examensarbete var att utvärdera hur elliptiska kurvor presterar jämfört med RSA, på ett system som är designat för att effektivt utföra RSA. De funna resultaten är att metoden med elliptiska kurvor ger stora fördelar, även om man nyttjar hårdvara avsedd för RSA, och att dessa fördelar ökar mångfaldigt om speciell hårdvara används. För några användarfall av digitala signaturer kan, under några år framöver, RSA fortfarande vara fördelaktigt om man bara tittar på hastigheten. För de flesta fall vinner dock elliptiska kurvor, och kommer troligen vara dominant inom kort.
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Vychodil, Petr. "Softwarová podpora výuky kryptosystémů založených na problému faktorizace velkých čísel." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2009. http://www.nusl.cz/ntk/nusl-218146.
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This thesis deals with new teaching software, which supports asymmetric encryption algorithms based on the issue of large numbers´ factorization. A model program was created. It allows to carry out operations related to encryption and decryption with an interactive control. There is a simple way to understand the principle of the RSA encryption method with its help. The encryption of algorithms is generally analysed in chapters 1,2. Chapters 3 and 4 deals with RSA encryption algorithm in much more details, and it also describes the principles of the acquisition, management and usage of encryption keys. Chapters 5 suggest choosing of appropriate technologies for the creation of the final software product, which allow an appropriate way to present the characteristics of the extended RSA encryption algorithm. The final software product is the java applet. Aplet is described in the chaprers 6 and 7. It is divided into a theoretical and practical part. The theoretical part presents general information about the RSA encryption algorithm. The practical part allows the users of the program to have a try at tasks connected with the RSA algorthm in their own computers. The last part of Java applet deals with the users´ work results. The information obtained by the user in the various sections of the program are satisfactory enough to understand the principle of this algorithm´s operations.
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Hauserová, Markéta. "Elektronické zabezpečení zdravotnické dokumentace v prostředí zdravotnického IS." Master's thesis, Vysoké učení technické v Brně. Fakulta informačních technologií, 2012. http://www.nusl.cz/ntk/nusl-236445.
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Thesis is analyzing czech laws which are related to medical documentation. Describes the points which are mandatory for information system, so the medical documentation can be stored electronically. Includes various algorithms for implementation of certain electronic signature and for identification of person. This thesis deals with asymmetric cryptography, specifically RSA, DSA, and ECDSA. Describes the hash functions and their functions and their characteristics. Describes the principle of the certificate, ways of its obtaining, invalidation and their formats. Analyzes medical information system and suggests ways to create a program for signing medical records. Then based on that analysis, the program is implemented. At the conclusion of the work is discussed, if created program meets the criteria.
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Hiromasa, Ryo. "Efficient Fully Homomorphic Encryption and Digital Signatures Secure from Standard Assumptions." 京都大学 (Kyoto University), 2017. http://hdl.handle.net/2433/225736.
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Mullani, Nowsheen. "An RNA Signature Links Oxidative Stress To Cellular Senescence." Electronic Thesis or Diss., Sorbonne université, 2019. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2019SORUS560.pdf.
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Le stress oxydatif est l’une des voies menant à la sénescence cellulaire. Bien que les dommages causés par les espèces réactives de l'oxygène aux protéines et à l'ADN soient bien décrits, notre compréhension de la manière dont la transcription peut participer à l'apparition de la sénescence est encore limitée. Au niveau de la transcription, le stress oxydatif entraîne l’accumulation d’ARN promoteurs (ARNAu) et d’ARN amplificateur (ARNs), conséquence de la libération défectueuse du RNAPII de la chromatine, un phénomène connu sous le nom de RNAPII crawling. Nous avons observé que l'exploration de RNAPII était également détectée en aval d'une petite série de gènes connus pour être régulés par HP1Υ au niveau de leur terminaison. L'exploration de ce phénomène a donné un résultat inattendu, en ce sens qu'il a révélé un effet inhibiteur du peroxyde d'hydrogène sur le complexe exosome d'ARN impliqué dans la dégradation des ARN polyadénylés. Le RNAPII rampant a pour résultat la transcription de séquences d’ALU situées au voisinage des promoteurs et amplificateurs et en aval de gènes sans intron et de petites séries de gènes contenant un intron. Comme les séquences ALU contiennent des séquences A codées par le génome, elles doivent normalement être dégradées par l’exosome de l’ARN. Cependant, comme le stress oxydatif inhibe également cette activité d'ARNase, les ARNm contenant des séquences d'ALU transcrites par hasard se stabilisent et sont détectés dans le cytoplasme et même dans les fractions de polysomes. Ce phénomène peut participer à l'apparition de la réponse à l'interféron associée au stress oxydatifOxidative Stress is one of the routes leading to cellular senescence. While the damages that reactive oxygen species inflict on proteins and DNA are well described, our insight on how transcription may participate in the onset of senescence is still limited. At a transcriptional level, oxidative stress results in accumulation of promoter RNAs (uaRNAs) and enhancer RNAs (eRNAs) as a consequence of defective release of the RNAPII from the chromatin a phenomenon known as RNAPII crawling. We observed that RNAPII crawling was also detected downstream of a small series of genes known to be regulated by HP1Υ at the level of their termination. Exploring this phenomenon yielded an unexpected result in the sense that it revealed an inhibiting effect of hydrogen peroxide on the RNA exosome complex involved in degradation of polyadenylated RNAs. The crawling RNAPII results in the transcription of ALU sequences located in the neighborhood of promoters and enhancers and downstream of intron-less genes and of small series of intron-containing genes. As ALU sequences contain genome encoded A tracts, they should normally be degraded by the RNA exosome. Yet, as oxidative stress also inhibits this RNAse activity, mRNAs containing serendipitously transcribed ALU sequences get stabilized and are detected in the cytoplasm and even polysome fractions. This phenomenon may participate in the onset of the interferon response associated with oxidative stress
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Pavel, Lukáš. "Elektronický geocaching." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2014. http://www.nusl.cz/ntk/nusl-220639.
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The goal is to design and implement a concept of electronic geocaching with contactless smart card and cell phone with NFC interface. In the first chapter I describe geocaching and try to familiarize the reader with this game. The second chapter deals with the issue of smart cards, I describe here the contact and contactless cards and their security. In the third chapter, I describe use and security of radio communication interface NFC. In the fourth chapter, I describe the principles of symmetric and asymmetric cryptography and selected cryptographic techniques. In the fifth chapter is description of proposed solution for electronic geocaching with digital signature. The last chapter describes all created applications.
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Harling, Leanne. "Investigating the micro-RNA and metabolic signature of human postoperative atrial fibrillation." Thesis, Imperial College London, 2014. http://hdl.handle.net/10044/1/29130.
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Atrial fibrillation (AF) is the commonest disorder of cardiac rhythm. Following coronary artery surgery approximately 1 in 3 patients will develop de novo post-operative AF (POAF) leading not only to prolonged hospital stay but also to increased morbidity and mortality. The pathophysiology of this arrhythmia is highly complex, and combines factors such as ion channel dysfunction, inflammation, oxidative stress, fibrosis and autonomic dysfunction that through electrical and structural remodelling promote both triggering and maintenance of this arrhythmia. For many years POAF has been regarded as a reactive phenomenon, occurring in response to post surgical inflammatory stressors and electrolyte imbalance. However, it is also possible that in a proportion of patients, prior cardiomyocyte remodelling predisposes to atrial arrhythmogenesis when exposed to surgical stress. Understanding the genomic and metabolic mechanisms that underlie this substrate may not only provide novel diagnostic biomarkers to identify at risk patients, but also isolate previously unrecognised therapeutic targets for prevention and treatment. In this work, a clinical observational study was utilised to obtain microRNA, gene expression and metabolic profiles of patients developing POAF after coronary artery bypass graft (CABG) surgery. Based on these results, a network of genomic and subsequent downstream pathway interactions was established to characterise the atrial substrate of post-operative AF. Furthermore, analysis of pre-operative blood was performed in order to identify novel microRNA that may provide a platform for biomarker development. Finally, the metabolic signature of the atrial myocardium and its relationship with the surrounding epicardial adipose were investigated to complete a comprehensive overview of the central mechanisms thought to underlie POAF pathogenesis. This work demonstrates that prior to surgery and the onset of arrhythmia, several distinct genomic and post-translational characteristics are evident in the both the myocardium and circulating blood of patients going on to develop POAF. Analysis of right atrial biopsies highlights a characteristic microRNA profile associated with POAF, and identifies target genes regulating intracellular signalling pathways, leukocyte recruitment, and ion channel remodelling. Furthermore, selected gene expression analysis demonstrates a de-differentiated phenotype similar to that seen in chronic AF, whilst at the same time establishing that disordered cardiomyocyte calcium handling is apparent at the time of surgery. Finally, analysis of the pre-operative circulating blood serum highlights microRNA selectively upregulated in POAF and establishes the potential for future biomarker development. In summary, the results presented here support the presence of a pre-existing atrial substrate in POAF, suggesting the potential exists for high-risk patients to be identified prior to surgery and the onset of arrhythmia. Furthermore, for the first time a number of similarities have been made apparent between post-operative and chronic AF, implying a common mechanistic spectrum of structural and electrical remodelling. As a consequence, the results presented in this thesis have not only improved our understanding of the complex interplay of factors leading to the pathogenesis of AF, but also provide a platform for both the development of a unique clinical biomarker and the identification of novel therapeutic targets.
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Mahi, Naim. "Connectivity Analysis of Single-cell RNA-seq Derived Transcriptional Signatures." University of Cincinnati / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1613748441148963.
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Hossain, Mahmud. "Characterization of non-protein coding ribonucleic acids by their signature digestion products and mass spectrometry." University of Cincinnati / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1204947468.
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Hauenschild, Ralf [Verfasser]. "RNA-Seq and CoverageAnalyzer reveal sequence dependent reverse transcription signature of N-1-methyladenosine / Ralf Hauenschild." Mainz : Universitätsbibliothek Mainz, 2017. http://d-nb.info/1129476375/34.
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Bachtík, Martin. "Online validace záznamů DNSSEC." Master's thesis, Vysoké učení technické v Brně. Fakulta informačních technologií, 2011. http://www.nusl.cz/ntk/nusl-412834.
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Master's Thesis is studying an extension that secures the domain name system by introducing the verifiability of authenticity of data, known as DNSSEC. Productive output is proposal of application and its subsequent implementation that at each stage of browse the namespace to the selected domain name checks the appropriatenesses of this extension and in detail reports the trusted chain.
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Mustafi, Debarshi. "Genetic Signatures of the Retina in Health and Disease." Case Western Reserve University School of Graduate Studies / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=case1372776307.
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Johnson, Benny, Laurence Cooke, and Daruka Mahadevan. "Next generation sequencing identifies ‘interactome’ signatures in relapsed and refractory metastatic colorectal cancer." PIONEER BIOSCIENCE PUBL CO, 2017. http://hdl.handle.net/10150/623288.
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Background: In the management of metastatic colorectal cancer (mCRC), KRAS, NRAS and BRAF mutational status individualizes therapeutic options and identify a cohort of patients (pts) with an aggressive clinical course. We hypothesized that relapsed and refractory mCRC pts develop unique mutational signatures that may guide therapy, predict for a response and highlight key signaling pathways important for clinical decision making. Methods: Relapsed and refractory mCRC pts (N=32) were molecularly profiled utilizing commercially available next generation sequencing (NGS) platforms. Web-based bioinformatics tools (Reactome/Enrichr) were utilized to elucidate mutational profile linked pathways-networks that have the potential to guide therapy. Results: Pts had progressed on fluoropyrimidines, oxaliplatin, irinotecan, bevacizumab, cetuximab and/or panitumumab. Most common histology was adenocarcinoma (colon N=29; rectal N=3). Of the mutations TP53 was the most common, followed by APC, KRAS, PIK3CA, BRAF, SMAD4, SPTA1, FAT1, PDGFRA, ATM, ROS1, ALK, CDKN2A, FBXW7, TGFBR2, NOTCH1 and HER3. Pts had on average had >= 5 unique mutations. The most frequent activated signaling pathways were: HER2, fibroblast growth factor receptor (FGFR), p38 through BRAF-MEK cascade via RIT and RIN, ARMS-mediated activation of MAPK cascade, and VEGFR2. Conclusions: Dominant driver oncogene mutations do not always equate to oncogenic dependence, hence understanding pathogenic ` interactome(s)' in individual pts is key to both clinically relevant targets and in choosing the next best therapy. Mutational signatures derived from corresponding ` pathway-networks' represent a meaningful tool to (I) evaluate functional investigation in the laboratory; (II) predict response to drug therapy; and (III) guide rational drug combinations in relapsed and refractory mCRC pts.
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Hernandez-Ferrer, Carles 1987. "Bioinformatic tools for exposome data analysis : application to human molecular signatures of ultraviolet light effects." Doctoral thesis, Universitat Pompeu Fabra, 2017. http://hdl.handle.net/10803/572046.
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Las enfermedades complejas se encuentran entre las más comunes y son causadas por una combinación de factores genéticos y ambientales (contaminación ambiental, estilo de vida, etc). Entre las enfermedades complejas que se pueden destacar se encuentran la obesidad, el asma, la hipertensión o la diabetes. Diversos estudios científicos sugieren que el hecho de padecer enfermedades complejas está condicionado a la aparición o acumulación de determinados factores ambientales. Asimismo, se ha descrito que los factores ambientales son unos de los principales contribuyentes a la carga mundial de morbilidad. Todo esto nos lleva a definir el término exposoma como el conjunto de factores ambientales a los que un individuo se ve expuesto desde la concepción hasta la muerte. El estudio de la mecánica subyacente que vincula el exposoma con la salud es un campo de investigación emergente con un fuerte potencial para proporcionar nuevos conocimientos sobre la etiología de las enfermedades.
La primera parte de esta tesis se centra en la exposición a la radiación ultravioleta. La exposición a la radiación ultravioleta proviene de fuentes tanto naturales como artificiales. La radiación ultravioleta incluye tres subtipos de radiación según su longitud de onda (UVA 315-400 nm, UVB 315-295 nm y UVC 295-200 nm). Si bien la principal fuente natural de radiación ultravioleta es el Sol, la UVC no llega a la superficie de la Tierra debido a su absorción por la capa estratosférica de ozono. En consecuencia, la exposición a radiación ultravioleta a la que estamos usualmente sometidos consisten en una mezcla de UVA (95 %) y UVB (5 %). Los efectos de la radiación ultravioleta en humanos pueden ser beneficiosos o perjudiciales dependiendo de su cantidad y forma. Los efectos perjudiciales y agudos de la radiación ultravioleta incluyen eritema, oscurecimiento del pigmento, retraso en el bronceado y engrosamiento de la epidermis. Repetidas lesiones en la piel producidas por radiación ultravioleta pueden predisponer, en última instancia, a efectos crónicos de fotoenvejecimiento, inmunosupresión y fotocarcinogénesis. El mayor efecto beneficioso de la radiación ultravioleta es la síntesis cutánea de la vitamina D. La vitamina D es necesaria para mantener el calcio fisiológico y del fósforo para la mineralización ósea y para prevenir el raquitismo, la osteomalacia y la osteoporosis. El paradigma del exposoma es trabajar con múltiples exposiciones a la vez en vez centrarse en una sola exposición. Este enfoque permite tener una visión más parecida a la realidad que vivimos. Luego, la segunda parte se centra en las herramientas para explorar cómo caracterizar y analizar el exposoma y cómo probar sus efectos en múltiples capas biológicas intermedias para proporcionar información sobre los mecanismos moleculares subyacentes que vinculan las exposiciones ambientales a los resultados de salud.Most common diseases are caused by a combination of genetic, environmental and lifestyle factors. These diseases are referred to as complex diseases. Examples of this type of diseases are obesity, asthma, hypertension or diabetes. Several empirical evidence suggest that exposures are necessary determinants of complex disease operating in a causal background of genetic diversity. Moreover, environmental factors have long been implicated as major contributors to the global disease burden. This leads to the formulation of the exposome, that contains any exposure to which an individual is subjected from conception to death. The study of the underlying mechanics that links the exposome with human health is an emerging research field with a strong potential to provide new insights into disease etiology. The first part of this thesis is focused on ultraviolet radiation (UVR) exposure. UVR exposure occurs from both natural and artificial sources. UVR includes three subtypes of radiation according to its wavelength (UVA 315-400 nm, UVB 315-295 nm, and UVC 295-200 nm). While the main natural source of UVR is the Sun, UVC radiation does not reach Earth's surface because of its absorption by the stratospheric ozone layer. Then, exposures to UVR typically consist of a mixture of UVA (95%) and UVB (5%). Effects of UVR on human can be both beneficial and detrimental, depending on the amount and form of UVR. Detrimental and acute effects of UVR include erythema, pigment darkening, delayed tanning and thickening of the epidermis. Repeated UVR-induced injury to the skin, may ultimately predispose one to the chronic effects photoaging, immunosuppression, and photocarcinogenesis. The beneficial effect of UVR is the cutaneous synthesis of vitamin D. Vitamin D is necessary to maintain physiologic calcium and phosphorous for normal bone mineralization and to prevent rickets, osteomalacia, and osteoporosis. But the exposome paradigm is to work with multiple exposures at a time and with one or more health outcomes rather focus in a single exposures analysis. This approach tends to be a more accurate snapshot of the reality that we live in complex environments. Then, the second part is focused on the tools to explore how to characterize and analyze the exposome and how to test its effects in multiple intermediate biological layers to provide insights into the underlying molecular mechanisms linking environmental exposures to health outcomes.
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Gendron, Judith. "Les longs ARN non codants, une nouvelle classe de régulateurs génomique tissu-spécifique : signature moléculaire spécifique des neurones dopaminergiques et sérotoninergiques." Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066518.
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Seul 1,2% du génome code des protéines :98,8% est non-codant,cependant 93% du génome est transcrit, principalement en longs ARN non-codants (lncRNA). Or ces lncRNA constituent une nouvelle classe de régulateurs génomique agissant à tous les niveaux d’expression des gènes et ils sont fortement spécifiques du tissu,modulés au cours du temps et en conditions physiopathologiques.Ainsi,nous proposons que chaque cellule spécifiée exprime son répertoire de lncRNA spécifique avec une carte des zones de chromatines ouvertes renseignant son identité cellulaire.Dans cette perspective,nous avons isolé par FACS 2types cellulaires impliqués dans des pathologies: i) des neurones dopaminergiques humains(nDA) différenciés à partir d’hiPS et ii) des neurones DA et sérotoninergiques (n5-HT)murins.Sur ces 2types neuraux isolés,nous avons identifié 1363 lncRNA exprimés dans les nDA (dont 989nouveaux) constituant le répertoire des neurones DA et 1257 lncRNA dans les n5-HT (719nouveaux) constituant le répertoire des n5-HT.Or leur comparaison a montré que seuls 194 lncRNA sont communs aux 2types cellulaires:la majorité des lncRNA est exprimée soit dans les nDA soit dans les n5-HT,attestant leur spécificité cellulaire.De plus,39%des zones de chromatines ouvertes/potentiellement régulatrices des nDA ne sont pas non plus retrouvées dans les n5-HT.Ainsi, nous avons généré un catalogue d’éléments non codants constituant des signatures moléculaires spécifiques des nDA et n5-HT,ouvrant de nouvelles pistes physiopathologiques:Dans cette optique,les signatures non codantes DA ont été comparées avec les SNP associés à la maladie de Parkinson et des études de fonction sur des lncRNA candidats ont été réaliséesOnly 1.2% of the genome codes for proteins; 98.8% is thus non-coding, despite 93% of the human genome being actively transcribed, mostly in long non-coding RNA (lncRNA).These lncRNA constitute a new class of genomic regulator capable of acting at all levels of gene expression and their expression is highly tissue-specific,modulated during the time and under normal/pathological conditions.Thus, we propose that each specified cell expresses a specific repertoire of lncRNA correlated to open/active chromatin regions specifying its cellular identity.In this context, we isolated by FACS 2neural types involved in many pathologies: i) human dopaminergic neurons (nDA) differentiated from hiPS and ii) DA and serotoninergic (n5-HT) neurons. From these 2neural types, we identified 1,363 lncRNA in nDA (among which 989 new, whether 73%) constituting the repertoire of nDA, and 1,257 lncRNA (among which 719 new) constituting the repertoire of n5-HT. Moreover,their comparison has shown that only 194 lncRNA are common to both neural types:thus the majority of lncRNA is expressed either in nDA or in n5-HT, indicating a high degree of cell-specificity.In addition, 39% of open chromatin regions, potentially regulatory, were also not detected in the n5-HT.Thus, we have generated DA and 5-HT specific catalogues of non-coding elements of the genome, which constitute DA and 5-HT specific molecular signatures, that could participate in deepening our knowledge regarding nDA or n5-HT development and dysfunctions. With this in mind,these DA specific elements have been compared with the SNP described as Parkinson Disease risk variants and candidate lncRNA were selected to perform studies of function
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Aligerová, Zuzana. "Molekulární signatura jako optimální multi-objektivní funkce s aplikací v predikci v onkogenomice." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2015. http://www.nusl.cz/ntk/nusl-220727.
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Náplní této práce je teoretický úvod a následné praktické zpracování tématu Molekulární signatura jako optimální multi-objektivní funkce s aplikací v predikci v onkogenomice. Úvodní kapitoly jsou zaměřeny na téma rakovina, zejména pak rakovina prsu a její podtyp triple negativní rakovinu prsu. Následuje literární přehled z oblasti optimalizačních metod, zejména se zaměřením na metaheuristické metody a problematiku strojového učení. Část se odkazuje na onkogenomiku a principy microarray a také na statistiku a s důrazem na výpočet p-hodnoty a bimodálního indexu. Praktická část je pak zaměřena na konkrétní průběh výzkumu a nalezené závěry, vedoucí k dalším krokům výzkumu. Implementace vybraných metod byla provedena v programech Matlab a R, s využitím dalších programovacích jazyků a to konkrétně programů Java a Python.
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Castleberry, Colette M. "Quantitative Identification of Non-coding RNAs by Isotope Labeling and LC-MS/MS." University of Cincinnati / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1258474676.
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Deprez, Marie. "Étude de l’hétérogénéité cellulaire et des dynamiques de régénération de l’épithélium respiratoire sain par analyses des signatures transcriptionnelles sur cellules uniques." Electronic Thesis or Diss., Université Côte d'Azur (ComUE), 2019. http://www.theses.fr/2019AZUR6022.
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Les progrès technologiques en séquençage haut débit et en manipulation cellulaire permettent d'analyser simultanément et indépendamment le contenu de nombreuses cellules (ARN, ADN,...). Cette révolution "omique" offre un nouveau cadre pour revisiter la "Théorie Cellulaire", essentiellement basée sur des caractéristiques morphologiques et fonctionnelles. Les nombreuses modalités cellulaires désormais accessibles au niveau de la cellule unique, telles que leur transcriptome, leur localisation spatiale, leurs trajectoires développementales, enrichissent considérablement cette définition, et établissent un contexte totalement renouvelé pour réévaluer la définition de "types" ou d’"états" cellulaires ainsi que leurs interactions. \Mon travail de thèse a été de mettre en place des approches statistiques appropriées pour analyser ces données transcriptomiques sur cellule unique caractérisées par une forte variance, la présence d'un pourcentage élevé de valeurs nulles et un grand volume de données. Mon travail s’est focalisé sur le modèle expérimental central de mon laboratoire d’accueil, l'épithélium des voies respiratoires humaines. Les voies respiratoires humaines sont bordées d'un épithélium pseudo-stratifié composé principalement de cellules basales, sécrétrices, à gobelet et multiciliées. Les voies respiratoires constituent en outre un véritable écosystème cellulaire, dans lequel la couche épithéliale interagit étroitement avec les cellules immunitaires et mésenchymateuses. Cette coordination entre les cellules assure une bonne défense du système respiratoire et sa correcte régénération en cas d'agressions extérieures. Une meilleure compréhension des situations cellulaires normales et pathologiques peut améliorer les approches pour lutter contre des pathologies telles que la maladie pulmonaire obstructive chronique, l'asthme ou la mucoviscidose.J'ai d'abord pu caractériser au niveau de la cellule unique la séquence précise et spécifique des événements conduisant à la régénération fonctionnelle de l'épithélium, en utilisant un modèle 3D de cellules humaines. J'ai identifié des hiérarchies de lignées cellulaires et j'ai pu reconstruire les différentes trajectoires possibles de différentiation cellulaire. J'ai confirmé des trajectoires cellulaires décrites précédemment, mais j'ai aussi découvert une nouvelle trajectoire reliant les cellules à gobelet aux cellules multiciliées, identifiant de nouvelles populations cellulaires et de nouvelles interactions moléculaires impliquées dans le processus de régénération de l'épithélium sain des voies aériennes humaines. J'ai ensuite construit un atlas des différents types cellulaires qui tapissent les voies respiratoires humaines saines, du nez jusqu’à la 12ième génération de bronches. Le profilage de 10 volontaires sains a généré un ensemble de données de 77 969 cellules, provenant de 35 emplacements distincts, qui comprend plus de 26 types cellulaires épithéliaux, immunitaires et mésenchymateuses. Cet atlas illustre l'hétérogénéité cellulaire présente dans les voies respiratoires. Son analyse révèle une différence d'expression des gènes entre le nez et les voies respiratoires pulmonaires que j’ai caractérisé dans les cellules suprabasales, sécrétrices et multiciliées. Mes travaux ont également permis d'améliorer la caractérisation de certaines populations de cellules rares, comme les cellules "hillock", déjà décrites chez la souris. En conclusion, mon travail contribue à une meilleure compréhension des dynamiques de différenciation et d'hétérogénéité cellulaire dans les voies respiratoires humaines saines. La ressource ainsi constituée sera extrêmement utile dans tout projet futur visant à analyser avec précision les conditions spécifiques des maladies respiratoiresImprovements made in nucleic acid sequencing and cell handling technologies now offer the opportunity to analyze simultaneously the content of numerous single cells (RNA, DNA, ...) by global and unbiased approaches. This single-cell ‘omics’ revolution provides a new framework to revisit the “Cell Theory”, elaborated over several centuries, and essentially based on morphological and functional features. The many cell modalities now accessible at single- cell level, such as their transcriptome, spatial localization, developmental trajectories, enrich considerably this definition, and set a renewed context to precisely reassess the definition of ‘cell types’, ‘cell states’ as well as their different interactions and fates.My thesis work initially set up ad hoc approaches and statistical framework to analyze appropriately these single-cell data, which deeply differ from standard bulk RNA-seq. High variance, presence of a huge percentage of null values, large volume of data are among the specific characteristics of these datasets. My work was centered on the main experimental model of my host laboratory, e.g. the human airway epithelium. Human airways are lined by a pseudostratified epithelium mainly composed of basal, secretory, goblet and multiciliated cells. Airways also constitute a true cellular ecosystem, in which the epithelial layer interacts closely with immune and mesenchymal cells. This coordination between cells ensures proper defense of the respiratory system and its correct regeneration in case of external aggression and injuries. A better understanding of the operating sequences in normal and physiopathological situations is relevant in pathologies such as chronic obstructive pulmonary disease, asthma or cystic fibrosis.First, I characterized at a single cell level the precise and cell-specific sequence of events leading to functional regeneration of the epithelium, using a 3D model of human cells. I then built a single-cell atlas of the different cell types that are lining healthy human airways from the nose to the 12th generation of bronchi.By applying computational and statistical approaches, I have identified cell lineage hierarchies and was able to reconstruct a comprehensive cell trajectory roadmap in human airways. I not only confirmed previously described cell lineages, but I have also discovered a novel trajectory that links goblet cells to multiciliated cells, identifying novel cell populations and molecular interactors involved in the process of healthy human airway epithelium regeneration. The profiling of 12 healthy volunteers then generated a dataset of 77,969 cells, derived from 35 distinct locations. The resulting atlas is composed of more than 26 epithelial, immune and stromal cell types demonstrating the cellular heterogeneity present in the airways. Its analysis has revealed a strong proximo-distal gradient of expression in suprabasal, secretory, or multiciliated cells between the nose and lung airways. My work has also improved the characterization of rare cells, including “hillock” cells that have been previously described in mice.In conclusion, this work probably represents one of the first single-cell investigations in human airways. It brings original contributions to our understanding of differentiation’s dynamics and cellular heterogeneity in healthy human airways. The resulting resource will be extremely useful for any future single-cell investigators and also for establishing a very useful joint between clinical and biological works. As such, it will constitute a reference in any future project aiming to precisely analyze specific disease conditions
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Jebbawi, Fadi. "Etude des lymphocytes T régulateurs naturels CD8+CD25+: signature micro-ARN et effets des micro-ARNs sur l'expression de FOXP3, CTLA-4 et GARP." Doctoral thesis, Universite Libre de Bruxelles, 2014. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209338.
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Mon travail de thèse a consisté à caractériser une sous-population de lymphocytes T régulateurs naturels de phénotype CD8+CD25+.Nous avons purifié les CD8+CD25+ nTregs et vérifié par cytométrie de flux leur expression en FOXP3 et CTLA-4. Puis nous avons pu montrer que ces cellules possèdent des propriétés suppressives dans un test d’inhibition de la prolifération de lymphocytes T activés allogéniquement. Les lymphocytes CD8+CD25+ nTregs expriment les gènes FOXP3, CTLA-4, GARP et CCL-4 et les cytokines IL-10 et TGF-β. Par contre, les gènes CD28, ICOS, FOXO1 et Helios sont sous-exprimés dans les nTregs CD8+CD25+ par rapport aux lymphocytes T CD8+CD25-.
Nous avons établi une signature micro-ARN qui comprend 10 micro-ARNs différentiellement exprimés :7 micro-ARNs sous-exprimés "miR-9, -24, -31, -155, -210, -335 et -449 " et 3 micro-ARNs surexprimés " miR-214, -205 et -509". De plus, nous avons pu explorer la relevance biologique de cette signature micro-ARN en montrant dans un premier temps que les miRs "-31, -24, -210, -335" ciblent spécifiquement la région 3'UTR de FOXP3, de même les miR-9 et miR-155 ciblent la région 3'UTR de CTLA-4, et les miR-24, et -335 ciblent la région 3'UTR de GARP. Ceci a été fait par des expériences de co-transfections suivies d'une mesure de l'activité rapportrice luciférase. De plus, nous avons pu démontrer par des expériences de transduction lentivirale ex vivo, de cellules T primaires, que des micro-ARNs de la signature régulent l’expression de FOXP3, CTLA-4 et GARP dans les Tregs naturels CD8+CD25+ humains.
Cette étude montre l'importance des micro-ARNs dans la régulation post-transcriptionnelle des gènes impliqués dans la fonction régulatrice des lymphocytes T régulateurs.
Doctorat en Sciences
info:eu-repo/semantics/nonPublished
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Aitken, Sarah Jane. "The pathological and genomic impact of CTCF depletion in mammalian model systems." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/284403.
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CCCTC-binding factor (CTCF) binds DNA, thereby helping to partition the mammalian genome into discrete structural and regulatory domains. In doing so, it insulates chromatin and fine-tunes gene activation, repression, and silencing. Complete removal of CTCF from mammalian cells causes catastrophic genomic dysregulation, most likely due to widespread collapse of 3D chromatin looping within the nucleus. In contrast, Ctcf hemizygous mice with lifelong reduction in CTCF expression are viable but have an increased incidence of spontaneous multi-lineage malignancies. In addition, CTCF is mutated in many human cancers and is thus implicated as a tumour suppressor gene. This study aimed to interrogate the genome-wide consequences of a reduced genomic concentration of Ctcf and its implications for carcinogenesis. In a genetically engineered mouse model, Ctcf hemizygous cells showed modest but robust changes in almost a thousand sites of genomic CTCF occupancy; these were enriched for lower affinity binding events with weaker evolutionary conservation across the mouse lineage. Furthermore, several hundred genes concentrated in cancer-related pathways were dysregulated due to changes in transcriptional regulation. Global chromatin structure was preserved but some loop interactions were destabilised, often around differentially expressed genes and their enhancers. Importantly, these transcriptional alterations were also seen in human cancers. These findings were then examined in a hepatocyte-specific mouse model of Ctcf hemizygosity with diethylnitrosamine-induced liver tumours. Ctcf hemizygous mice had a subtle liver-specific phenotype, although the overall tumour burden in Ctcf hemizygous and wild-type mice was the same. Using whole genome sequencing, the highly reproducible mutational signature caused by DEN exposure was characterised, revealing that Braf(V637E), orthologous to BRAF(V600E) in humans, was the predominant oncogenic driver in these liver tumours. Taken together, while Ctcf loss is partially physiologically compensated, chronic CTCF depletion dysregulates gene expression by subtly altering transcriptional regulation. This study also represents the first comprehensive genome-wide and histopathological characterisation of this commonly used liver cancer model.
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Sousa, Rodrigo Guarischi Mattos Amaral de. "O transcritoma da retinopatia induzida por oxigênio e uma assinatura gênica prognóstica baseada em angiogênese para predição de recidiva de cancer de mama." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/95/95131/tde-28092017-112917/.
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Angiogênese é o processo de formação de novos vasos sanguíneos a partir dos vasos existentes. É um processo vital, mas muitas doenças também dependem deste mecanismo para obter nutrientes e progredir. Estas \"doenças dependentes de angiogênese\" incluem cânceres, retinopatias e degeneração macular. Alguns inibidores da angiogênese foram desenvolvidos na última década, com o objetivo de auxiliar no manejo dessas doenças e melhorar a qualidade de vida dos pacientes. A maioria destes compostos funciona inibindo a ligação de VEGFA/VEGFR2, que também é um elemento importante para a sobrevivência de células endoteliais quiescentes; e isso pode explicar parcialmente eventos adversos observados em alguns ensaios clínicos. Nossa hipótese é que a melhoria das terapias anti-angiogênicas depende de uma compreensão melhor e mais ampla desse processo, especialmente quando relacionada à progressão das doenças. Utilizando RNA-Seq e um modelo animal bem aceito de angiogênese, o modelo murino de Retinopatia Induzida por Oxigênio, exploramos o transcritoma e identificamos 153 genes diferencialmente expressos durante a angiogênese. Uma extensiva validação de vários genes realizada por qRT-PCR e hibridização in-situ confirmou a superexpressão de Esm1 em células endoteliais de tecidos com angiogênese ativa. A análise de enriquecimento desta lista de genes confirmou a ligação da angiogênese com genes frequentemente mutados em tumores, consistente com a conhecida ligação entre câncer e angiogênese, e forneceu sugestões de fármacos já aprovados que podem ser reutilizados para controlar a angiogênese em circunstâncias patológicas. Finalmente, com base neste panorama amplo da angiogênese, fomos capazes de criar um biomarcador molecular com poder prognóstico para a predição da recidiva de câncer de mama, com aplicações clínicas promissoras. Em resumo, este trabalho revelou com sucesso genes relacionados à angiogênese e forneceu novas alternativas terapêuticas, incluindo potenciais fármacos para reposicionamento. Esse conjunto de genes diferencialmente expressos é também um recurso valioso para investigações futuras.Angiogenesis is the process of formation of new blood vessels based on existing vessels. It is a vital process but many diseases also rely on this mechanism to get nourishment and progress. These so called angiogenesis-dependent diseases include cancers, retinopathies and macular degeneration. Some angiogenesis inhibitors were developed in the past decade, aiming to help the management of such diseases and improve patients quality of life. Most of these compounds work by inhibiting VEGFA/VEGFR2 binding, which is also a key element to the survival of quiescent endothelial cells; this may partly explain unanticipated adverse events observed in some clinical trials. We hypothesize that the improvement of anti-angiogenesis therapies hinges on a better and broader understanding of the process, especially when related to diseases\' progression. Using RNA-seq and a well accepted animal model of angiogenesis, the murine model of Oxygen Induced Retinopathy, we have explored the transcriptome landscape and identified 153 genes differentially expressed in angiogenesis. An extensive validation of several genes carried out by qRT-PCR and in-situ hybridization confirmed Esm1 overexpression in endothelial cells of tissues with active angiogenesis, providing confidence on the results obtained. Enrichment analysis of this gene list endorsed a narrow link of angiogenesis and frequently mutated genes in tumours, consistent with the known connection between cancer and angiogenesis, and provided suggestions of already approved drugs that may be repurposed to control angiogenesis under pathological circumstances. Finally, based on this comprehensive landscape of angiogenesis, we were able to create a prognostic molecular biomarker for prediction of breast cancer relapse, with promising clinical applications. In summary, this work successfully unveiled angiogenesis-related genes, providing novel therapeutic alternatives, including potential drugs for repositioning. The set of differentially expressed genes is also a valuable resource for further investigations.
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Yang, Tianyu. "Two novel mechanisms of MHC class I down-regulation in human cancer accelerated degradation of TAP-1 mRNA and disruption of TAP-1 protein function /." Connect to this title online, 2004. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1078192113.
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Thesis (Ph. D.)--Ohio State University, 2004.Title from first page of PDF file. Document formatted into pages; contains x, 117 p.; also includes graphics (some col.) Includes bibliographical references (p. 99-117). Available online via OhioLINK's ETD Center
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Bost, Pierre. "Decoding cellular communications and interactions between immune cells by using single-cell approaches." Electronic Thesis or Diss., Sorbonne université, 2020. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2020SORUS020.pdf.
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Les communications cellulaires sont indispensables au bon fonctionnement des organismes multicellulaires, notamment pour s’adapter à un environnement changeant en permanence. Les cellules du système immunitaire n’échappent pas à cette règle mais les interactions entre cellules immunitaires restent peu connues et compliquée à étudier. La récente apparition des technologies de séquençage dites ‘cellules uniques’ représente une opportunité unique pour étudier ces communications. Dans cette thèse, différentes approches expérimentales et analytiques ont été développées pour étudier ces communications à une échelle de cellules uniques. Ces stratégies ont ensuite été appliquées à différents contextes pathologiques, incluant le COVID-19, la maladie d’Alzheimer ou une immunisation par des pathogènes inactivés, et ont permis d’identifier des voies de communications cellulaires jusqu’ici inconnues ou mal comprises. Néanmoins, l’efficacité de ces approches est limitée par l’absence d’informations sur la localisation des cellules et des travaux supplémentaires intégrant ce genre de données est essentiel pour aller plus loin dans la dissection des communications entre cellules immunitairesCellular communications are essential to the proper functioning of multi-cellular organisms, particularly in order to adapt to a constantly changing environment. The cells of the immune system are no exception to this rule, but the interactions between immune cells remain little known and complicated to study. The recent emergence of 'single cell' sequencing technologies represents a unique opportunity to study these communications. In this thesis, different experimental and analytical approaches have been developed to study these communications on a single cell scale. These strategies were then applied to different disease contexts, including COVID-19, Alzheimer's disease or immunisation with inactivated pathogens, and identified previously unknown or poorly understood cellular communication pathways. However, the effectiveness of these approaches is limited by the lack of information on cell location and further work integrating such data will be essential to go further in the dissection of immune cell communications
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Hrazdilová, Ivana. "Analýza dat ze sekvenování příští generace ke studiu aktivity transposonů v nádorových buňkách." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2013. http://www.nusl.cz/ntk/nusl-220061.
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Theoretical part of this diploma thesis gives a brief characteristic of human mobile elements (transposons), which represents nearly 50% of human genome. It provides basic transposon clasification and describes types of transposons present in hunam genome, as well as mobilization, activation and regulation mechanisms. The work also deals with the domestication of transposons, describes the ways in which TE contribute to DNA damage and summarizes the diseases caused by mutagenic activity of transposons in the human genome. Conclusion of theoretical part describes next-generation sequencing technologies (NGS). As practical part, data from RNA-seq experimet were analyzed in order to compare differen transposon activity in normal and cancer cells from prostate and colorectal tissues. As like as publicly available sophisticated tools (TopHat), new scripts were created to analyze these data. The results show that cancer cells exhibit overexpression of transposons. This corresponds with the published results and suggests a connection of transposon activation with cancer development.
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Outlioua, Ahmed. "Exploration des cytokines pro-inflammatoires et de l’inflammasome NLRP3 dans les infections intracellulaires : cas de H. pylori et des virus à ARN Gastric IL-1β, IL-8, and IL-17A expression in Moroccan patients infected with Helicobacter pylori may be a predictive signature of severe pathological stages RNA viruses promote activation of the NLRP3 inflammasome through cytopathogenic effect-induced potassium efflux The heme-regulated inhibitor is a cytosolic sensor of protein misfolding that controls innate immune signaling The Role of Optineurin in Antiviral Type I Interferon Production Possible introduction of Leishmania tropica to urban areas determined by epidemiological and clinical profiles of patients with cutaneous leishmaniasis in Casablanca (Morocco)." Thesis, université Paris-Saclay, 2021. http://www.theses.fr/2021UPASL029.
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Helicobacter pylori (H. pylori) est une bactérie qui infecte l’estomac et induit une gastrite inflammatoire, qui peut être chronique et évoluer vers un cancer gastrique. La sévérité de l’infection et son évolution clinique sont associées aux différents facteurs notamment le statut immunitaire de l’hôte. La réponse inflammatoire initiale à l'infection à H. pylori entraîne la sécrétion d'un large panel de cytokines, notamment l'interleukine-1β (IL-1β), l'IL-8 et l'IL-17A. qui semblent jouer un rôle clé dans l'initiation et la progression du cancer gastrique. Parmi ces cytokines, l'IL-1β est une cytokine clé au cours de l’infection à H. pylori dont l’expression est étroitement associée à l'inflammation gastrique et à la carcinogenèse. La production de cette cytokine dépend de l'activation de l'inflammasome, en particulier l'inflammasome NLRP3. Ce dernier, responsable de l’activation des processus inflammatoires, est essentiel pour le maintien de l'homéostasie contre diverses infections pathogènes telles les infections bactérienne et virale.L’objectif général de ce travail est i) d’étudier l’expression et le polymorphisme des gènes de cytokines comme IL-1β, IL-17 et IL-8 chez des patients marocains infectés par H. pylori. ii) explorer l’activation de l'inflammasome NLRP3 par H. pylori et déterminer les mécanismes impliqués dans l'activation de ce complexe par des virus à ARN ; connus comme des activateurs définis de NLRP3.Nos résultats ont souligné une prévalence élevée de H. pylori et ont mis en évidence une signature cytokinique : elle peut prédire la métaplasie au cours de la progression de l'infection à H. pylori impliquant une diminution de l’expression de l'IL17A dans l’antre et une augmentation de l’expression de l'IL-1β dans le fundus. Plus particulièrement, les polymorphismes génétiques de l’IL-1β (IL-1β -31 et -511) ne semblent pas influencer l’expression de l’IL-1β de manière significative.Au regard des difficultés rencontrés pour l’isolement et la culture de H. pylori, nous avons utilisé le LPS de H. pylori pour stimuler l’inflammasome. Nos résultats montrent que la transfection des cellules in vitro par le LPS bactérien induit la production de l’IL-1β qui semble être modulée par la caspase 4, NOD1 et NOD2. Par ailleurs, bien qu’il soit clairement établi que les virus à ARN induisent l’activation de l’inflammasome NLRP3, les mécanismes par lesquels ces virus induisent la production d'IL-1β ne sont pas bien compris et restent à confirmer. Les résultats de cette partie du travail ont montré que la réplication des virus à ARN cytopathogènes tels que le virus de la stomatite vésiculaire (VSV) ou le virus de l'encéphalomyocardite (EMCV) induit une mort cellulaire lytique conduisant à un efflux de potassium qui déclenche l'activation de l'inflammasome NLRP3. Ainsi, les virus à forte capacité de réplication et qui ont un effet cytopathique sont capables d'induire l'activation de la caspase-1 conduisant à la production d'IL-1β. A l'inverse, les virus qui induisent une très bonne réponse IFN de type I sont de très mauvais inducteurs de l'inflammasome NLRP3.Une meilleure compréhension de l’activation de l’inflammasome pourrait aider dans la mise au point de stratégies thérapeutiques ciblées utilisables dans la lutte contre les infections bactérienne et virale.Mots clés : Helicobacter pylori, inflammation, inflammasome NLRP3, IL-1β, virus à ARNHelicobacter pylori (H. pylori) is a bacteria that infects the stomach and induces inflammatory gastritis, which can be chronic and progress to gastric cancer. The severity of the infection and its clinical course are associated with various factors including the immune status of the host. The initial inflammatory response to H. pylori infection results in the secretion of a wide range of cytokines, including interleukin-1β (IL-1β), IL-8 and IL-17A. which appear to play a key role in the initiation and progression of gastric cancer. Among these cytokines, IL-1β is a key cytokine during H. pylori infection whose expression is associated with gastric inflammation and carcinogenesis. The production of this cytokine depends on the activation of the inflammasome, in particular the NLRP3 inflammasome. The latter, responsible of the activation of inflammatory processes, is essential for the maintenance of homeostasis against various pathogenic infections such as bacterial and viral infections.The general objective of this work is i) to study the expression and polymorphism of genes for cytokines such as IL-1β, IL-17 and IL-8 in Moroccan patients infected with H. pylori. ii) explore the activation of the NLRP3 inflammasome by H. pylori and determine the mechanisms involved in the activation of this complex by RNA viruses; known as defined activators of NLRP3.Our results underlined a high prevalence of H. pylori and demonstrated a cytokine signature: it can predict metaplasia during the progression of H. pylori infection involving a decrease in IL17A expression in the antrum and increased expression of IL-1β in the fundus. In particular, the genetic polymorphisms of IL-1β (IL-1β -31 and -511) do not appear to influence IL-1β expression significantly.In view of the difficulties encountered in isolating and culturing H. pylori, we used LPS from H. pylori to stimulate the inflammasome. Our results show that the transfection of cells in vitro with bacterial LPS induces the production of IL-1β which appears to be modulated by caspase 4, NOD1 and NOD2. Furthermore, while it is clearly established that RNA viruses induce activation of the NLRP3 inflammasome, the mechanisms by which these viruses induce IL-1β production are not well understood and remain to be confirmed. The results of this part of the work showed that the replication of cytopathogenic RNA viruses such as vesicular stomatitis virus (VSV) or encephalomyocarditis virus (EMCV) induces lytic cell death leading to an efflux of potassium which triggers activation of the NLRP3 inflammasome. Thus, viruses with a high replication capacity and which have a cytopathic effect are capable of inducing the activation of caspase-1 leading to the production of IL-1β. Conversely, viruses which induce type I IFN response are very poor inducers of the NLRP3 inflammasome.A better understanding of the activation of the inflammasome could help in the development of targeted therapeutic strategies for use in the fight against bacterial and viral infections.Key words: Helicobacter pylori, inflammation, NLRP3 inflammasome, IL-1β, RNA virus
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Lu, Hsin-Hsien, and 呂信憲. "A Conic RSA Based Convertible Undeniable Signature." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/63666281425599640300.
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碩士逢甲大學
通訊工程所
100
The design of an efficient and secure cryptosystem on a conic curve has been the subject of intensive research in recent years. Compare with elliptic curve cryptosystems, encoding/decoding as well as encryption/decryption with the Conic curve cryptosystem is much easier, simpler and faster. Digital signature is the most important service that contemporary cryptography provides. Undeniable Signature, which is very useful in many commercial or personal sensitive signature applications, is a special type of zero-knowledge proof signatures that require the cooperation of the signer to verify the signature validity. However, it is almost unlikely for a cheating signer, even computationally unbounded, to convince V to accept an invalid signature or reject a valid signature. A convertible undeniable signature scheme is an extension of undeniable signature schemes that can be converted to a general signature (or a self-authenticating signature) when the signer discloses certain parameters. Since RSA cryptosystem is currently the most popular and widely used public-key cryptosystem, in this thesis we devote ourselves to designing an RSA based convertible undeniable signature scheme on the conic curve over the integer residue ring Zn . Further, we show that the problem of forging our proposed signature is equivalent to the problem of solving the conic-based RSA problem that is believed to be a computationally infeasible problem.
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Huang, Xiao-Wei, and 黃曉偉. "An RSA-based (t, l) Threshold Proxy Signature." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/89591276325242220711.
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碩士國立臺灣海洋大學
資訊工程學系
95
In this thesis we propose and analyze a new RSA-based proxy signature scheme and its corresponding (t, ) threshold scheme. Unlike numerous previous research works, the threshold proxy scheme does not require any trusted combiner and is thus a truly practical approach. The security of both schemes is based on the RSA assumption. Both schemes are existentially unforgeable against no message attack in the random oracle model and especially the threshold proxy scheme inherits the merit of its predecessor - Shoup’s RSA threshold scheme - and thus is secure under a multi-party computation setup with active adversaries.
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Feng, Y. M., and 馮怡明. "Extended RSA Based Generalized Group-Oriented Cryptosystem and Signature System." Thesis, 1999. http://ndltd.ncl.edu.tw/handle/21061319068786730212.
Full textAbstract:
碩士逢甲大學
電機工程學系
87
It has been pointed out in some previously works that, due to some inherent limitations on the used modulus, the RSA cryptosystem is hard to be incorporated in the design of cryptosystems or signature systems in a group-oriented communication environment. In this thesis, we first propose a cryptosystem, called the ERSA (Extended RSA) cryptosystem, which is a natural extension of the well-known RSA cryptosystem. It is pointed out that although the security of the ERSA cryptosystem is the same as that of the original RSA system; however, in the ERSA cryptosystem, vectors of integers instead of integers are used as the encryption/decryption keys so that it is more adapted for the design of cryptosystems and signature systems in a group oriented communication environment. Accordingly, based upon the encryption/ decryption technique of the ERSA system and Diffie-Hellman’s key distribution technique, we present a generalized group oriented cryptosystem. In the presented system, the sender is allowed to determine the encryption/ decryption keys and specify a set of combinations of legal recipients (called an access structure) without any coordination with the receiving group. And he may broadcast the encrypted message to the group in such a way that, without the need of any trusted clerks or centers, the ciphertext is decipherable when and only when all authorized recipients of a combination in the access structure (called an access instance) work together. The modulus used for computing shadow key of each recipient is universal and the system’s security is based on the computational infeasibility of both the discrete logarithm problem and the factorization problem. In addition, the presented system has the capabilities of cheater detection and fake shadow correction. Further, based upon the signature technique of the ERSA system, we propose a generalized group signature system. In the proposed system, the clerk of the group can specify, according to the classified grade of the message and the group signature policy, a set of combinations of authorized signers (called a signature structure) such that when and only when all authorized signers of a combination in the signature structure (called a signature instance) work together can sign a message on behalf of the group. The modulus used for each individual signature as well as the group signature is universal and the security of the proposed system is guaranteed by the computational infeasibility of the factorization problem.
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Kao, Chih-Chung, and 高志中. "Using DR-Signature and Randomized RSA-Based Partially Blind Signature to Design a Digital Content Payment Scheme for Multiple Payees." Thesis, 2006. http://ndltd.ncl.edu.tw/handle/xvr93u.
Full textAbstract:
碩士國立中央大學
資訊管理研究所
94
As the broadband internet is popularized and the output value of digital content continues increasing, the market of online transaction is expected to grow dramatically in the future. How to assure rights and interests of participants don’t be damaged when they make online transaction? The dependable online payment scheme is the critical factor. Meanwhile, under the knowledge-intensive era, a digital content can be created by several individuals who have interrelated knowledge. The selling revenue of the digital content should be correctly assigned to each payee (authors and merchants) in real time, so that creators may have stronger motivation to create more digital content. Base on the above-mentioned, the purpose of this paper is to design an online payment scheme which has three features, include (1) assuring the payment security and transaction privacy, (2) preventing frauds from being made, and (3) supporting multiple payees payment. In this paper, we combine the concepts of randomized RSA partially blind signature, DR-signature (a kind of convertible signature), and multi-signature, to propose a four phase online payment scheme, include (1) initializing phase, (2) withdrawing phase, (3) purchasing phase, and (4) requesting phase. In the initializing phase, all members (customers, merchants, and authors) register to the third trust party (TTP), bank needs to generate RSA-based private/public keys, and all payees belong to one digital content should make a multi-signature of a proportion of apportionment (PROPp_id). Customers, merchants, bank, and TTP complete an online transaction in withdrawing phase and purchasing phase. If someone finds his rights is damaged, he can request TTP to arbitrate to safeguard himself in the requesting phase. Base on cryptographic skill and design of transaction process, our proposed payment scheme can assure payment security and transaction privacy, prevent frauds, and support multilateral payment.
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Guan, Chi-Hao, and 管紀豪. "A EUF-CMA RSA Signature Scheme based on Phi-Hiding Assumption and Trapdoor Hash Function in the Standard Model." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/67708044707947857243.
Full textAbstract:
碩士國立臺灣海洋大學
資訊工程學系
99
We propose an EUF-CMA signature scheme based on Φ-hiding assumption [13] in the standard model. At the mean time, we found the RSA cryptosystem has lossy property [35]. This discovery also found by Kiltz et al [27]. On the orher side, Shamir and Tauman has proposed OnLine/OffLine signature scheme [39]: When OffLine phase, decide the trapdoor hash value until OnLine phase compute the correspond preimage by trapdoor key. Using this primitive, many EUF-CMA signature scheme has been proposed such as [5]、[9]、[10]、[11]、[12]、[17]、[23]、[26]、[29]、[32]、[33]、[41]. We using the two general ideas and try to prove the security of RSA cryptosystem satisfy the EUF-CMA property in the standard model.
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Chen, Cheng-huan, and 陳震寰. "New Blind Signatures Based on RSA and ElGamal Signatures." Thesis, 2002. http://ndltd.ncl.edu.tw/handle/92108922873986986857.
Full textAbstract:
碩士中原大學
電機工程研究所
90
Abstract This thesis proposes three new blind signature schemes. The first two schemes are based on RSA signature, and the third is on ElGamal signature. The first scheme is proposed by means of the decomposition of messages. After decomposing the messages, the verifier sends parts of the decomposed messages to the signer. The singer signs the corresponding messages by his private key, and finally the verifier integrates the signed messages to obtain the desired signature. The second scheme is based on the algebraic operation of exponent on messages. Two blind messages are generated, then the verifier sends them to the signer. The desired signature can be computed after the signatures with blind factor were received. Both of the two blind signature schemes have the feature of smaller size of data, and we believe that it will lead to less computational complexity without reduction of security. In the third scheme, we propose a modification of ElGamal signature. By using a simple way of signing, we find a new blind signature based on the modified ElGamal signature. The process of the blind modified ElGamal signature is very simple that it reduces the computational complexity. The main results of our study are as follows. (1) We propose two new blind signatures based on RSA. The feature of our new schemes is that the data length in our algorithms is smaller than the existent RSA blind signature. (2) We also propose a new blind signature based on a modification of ElGamal signature. It is an important feature that our new scheme is much simpler than the other existent blind ElGamal signatures. All of the three blind schemes have the advantage of less computational complexity. It is believed that the results of our study in this thesis will be helpful to further research in the area of digital signature.
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Dias, Miguel Ângelo Simão. "Uncovering the regulatory T cell transcriptional signature in the human thymus." Master's thesis, 2018. http://hdl.handle.net/10316/86264.
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Dissertação de Mestrado em Biologia Celular e Molecular apresentada à Faculdade de Ciências e TecnologiaOs linfócitos T reguladores (Tregs) desempenham um papel crucial na manutenção da homeostasia imunológica, impedindo ou limitando respostas imunes. As Tregs são particularmente eficazes a suprimir as células T convencionais (Tconvs), e desta forma limitam a imunopatologia associada à imunidade contra patogéneos e células cancerígenas, bem como os processos alérgicos, autoimunes e inflamatórios. Uma população significativa de Tregs é gerada durante o desenvolvimento das células T no timo conhecidas como Tregs naturais (ou derivadas do timo), sendo definidas pela presença da proteína FOXP3. Este fator de transcrição desempenha um papel crucial na diferenciação destas células, não só através da repressão de genes normalmente expressos em Tconvs, mas também promovendo a ativação de genes específicos de Tregs, incluindo IL2RA (CD25) e CTLA4. No entanto, vários estudos demostraram que a diferenciação e comprometimento destas células pode ser independente de FOXP3, indicando a existência de outros fatores, atualmente desconhecidos, os quais são suficientes para promover o desenvolvimento das Tregs. Neste estudo, investiguei a diferenciação e o comprometimento das células Treg no timo humano, a fim de identificar novos fatores potencialmente envolvidos nesta decisão. Para isso, isolámos Tregs e Tconvs tímicas maduras CD4 positivas com base na expressão dos marcadores CD27, CD25 e CD127, a partir de tecido tímico humano removido durante cirurgias cardíacas pediátricas corretivas de três indivíduos, e geramos os seus respetivos perfis de expressão génica através da sequenciação do RNA (RNA-seq).A nossa análise da comparação da transcrição identificou 1047 genes significativamente e diferencialmente expressos entre tTregs e tTconvs, dos quais 648 com sobre expressão em tTregs. Destes 648 genes, observei a expressão proeminente de alguns genes associados a este tipo celular, incluindo FOXP3, IL2Rα (CD25), CTLA4, TNFRSF4 (OX40), TNFRSF18 (GITR), IKZF2 (HELIOS) e IKZF4 (EOS). Para alem disso, identifiquei um conjunto de 196 genes unicamente expressos em tTreg em comparação com tTconv, alguns dos quais codificam proteínas com conhecida relevância na biologia destas células, incluindo TNFRSF8 (CD30), LRRC32 (GARP) e CCR8, bem como genes cuja função em tTregs é desconhecida, nomeadamente DNAH8 e TNFRSF11A. Enquanto a expressão de DNAH8 pode ser indicativa da formação de sinapses imunológicas, a expressão de TNFRSF11A pode sugerir um mecanismo adicional de supressão através dos quais as tTregs previnem a ativação das tTconvs.Dos genes encontrados sobre expressos nas tTregs em comparação com as tTconvs, 46 codificam fatores de transcrição. Estes incluem alguns já conhecidos como estando diretamente envolvidos na diferenciação destas células, como FOXP3, IKZF2, IKZF4, FOXO1 e NR4A3, bem como fatores de transcrição envolvidos na ativação e diferenciação de Tconvs, como o TBX21, IRF4, STAT4, BATF e RORA. Além disso, identifiquei também membros da via de sinalização NF-kB (REL, RELB e NFKB2), indicando o seu estado ativo durante a diferenciação destas células. Por fim, encontrei um grupo de fatores de transcrição sobre expressos em Tregs e sem funções previamente descritas nestas células, nomeadamente IRF5, ZBTB38, KLF6 e CREB3L2, o que sugere a presença de novas vias de regulação da transcrição envolvidas nos processos de diferenciação e função das células T reguladorasEm conclusão, esta tese apresenta o primeiro perfil de transcrição de Tregs e Tconvs de timo humano, cujas análises serão fundamentais para a compreensão do seu desenvolvimento. Até à data, estes dados permitiram a identificação de novos genes com funções desconhecidas nestes grupos celulares, o que poderá representar fatores adicionais envolvidos na definição das células T no timo. No futuro, estes dados permitirão explorar novas linhas de investigação com o objetivo de esclarecer o desenvolvimento da linhagem Treg no timo humano, bem como ajudar na definição da assinatura de expressão destas células.
Regulatory T cells (Tregs) are key players in maintaining immune homeostasis, by preventing or limiting immune responses. They are particularly efficient in suppressing conventional T cells (Tconvs), and in this way control the immunopathology associated with immunity against pathogens and cancer as well as preventing allergy, autoimmune diseases, and chronic inflammation. An important Treg subset is generated during T cell development in the thymus, known as thymic-derived Treg. It is best defined by the expression of the forkhead box protein FOXP3, a transcription factor that plays a crucial role in Treg cell differentiation by repressing the expression of genes otherwise upregulated in Tconv cells, as well as by promoting to the activation of Treg specific genes, including IL2Rα (CD25) and CTLA4. However, recent studies have shown that Treg commitment may occur independently of FOXP3, indicating that other factors, presently unknown, are sufficient for the generation of Tregs. Here I have investigated the differentiation and commitment of Treg cells in the human thymus, in order to identify novel factors potentially involved in this decision. To do this, we FACS sorted mature CD4 single-positive thymic Tregs (tTregs) and their conventional counterparts (tTconvs) based on the expression of CD27, CD25, and CD127 markers, from three human thymuses collected during pediatric corrective cardiac surgery, and generated their respective genome-wide expression profiles by RNA-seq. We ensure that these thymuses have an immunophenotype representative of all stages of T cell development and consistent with the one described in the literature.Our comparative transcriptomic analysis identified 1047 genes significantly differentially expressed between tTreg and tTconv subsets, with 648 of these up-regulated in tTregs. Amongst these, I observed the prominent expression of Treg-associated genes, including FOXP3, the IL2Rα (CD25), CTLA4, TNFRSF4 (OX40), TNFRSF18 (GITR), IKZF2 (HELIOS) and IKZF4 (EOS). From these, I identified a set of 196 genes that are uniquely expressed in tTreg compared to tTconv, encoding proteins with relevance to Treg biology, such as TNFRSF8, LRRC32, and CCR8, as well as others with no previously reported activity in tTreg cells, as DNAH8 and TNFRSF11A. Whilst DNAH8 expression may be indicative of the formation of immunological synapses, the expression of TNFRSF11A may indicate an additional suppression mechanism by which Tregs prevents Tconv cell activation. From the genes found to be up-regulated in tTreg cells compared to tTconvs, 46 were transcription factors. These include some known to be directly involved in Treg development, such as FOXP3, IKZF2, IKZF4, FOXO1, and NR4A3, as well as transcription factors involved in Tconv cell activation and differentiation, such as TBX21, IRF4, STAT4, BATF and RORA. In addition, several members of the NF-kB pathway (REL, RELB, NFKB2) are also up-regulated in tTregs, indicating the activated state of this pathway during tTreg differentiation. Importantly, a set of transcription factors with no previous reported role in human regulatory T cells, IRF5, ZBTB38, KLF6, and CREB3L2, are overexpressed in tTregs, suggesting additional layers of transcriptional regulation of Treg cell differentiation and function. Altogether, this thesis presents the first transcriptomic profile of the human thymic Treg and Tconv subsets, which analyses are absolutely necessary to the understanding of their development. So far, they allowed the identification of novel genes with unreported functions in these subsets, which might represent additional factors involved in the definition of thymic T cells; in the near future, these data will open several new lines of research aiming to clarify the pathways of Treg lineage commitment in the human thymus and will help in the definition of the expression signature of human tTreg subset.
Outro - This work is supported by grants PAC-PRECISE-LISBOA-01-0145-FEDER-016394 and LISBOA-01-0145-FEDER-007391 cofunded by FEDER through POR Lisboa 2020 - Programa Operacional Regional de Lisboa PORTUGAL 2020 and Fundação para a Ciência e a Tecnologia (FCT); and by funds from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No.: 675395.
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Schwans, Jason Patrick. "Using nucleotide analogues to define chemical signatures within folded RNA molecules /." 2003. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:3108110.
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Trofimov, Assya. "Étude des signatures géniques dans un contexte d’expériences de RNA- Seq." Thèse, 2017. http://hdl.handle.net/1866/20417.
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Chen, Feng-Mei, and 陳鳳美. "A Study of Security on Computer Auditing Task－Based on Dual Complexities Using RSA and ElGamal Signatures." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/57702972827945168057.
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碩士國防大學國防管理學院
國防資訊研究所
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Due to the vigorous development of infornations technology, the function of computer soft and hardware advances day by day. The computer popularrate of governmental agency and school continues to grow fast. Detailed information is established mostly in the computer hard disk, magnetic tape or in the electromagnetism storage memory, causes the audit trail to reduce even predicament of gradually the evanishment. Auditors all levels of institution organization faced with strike unprecedentedly with challenge. The risks of auditing enhance largely. Facing the computerization tendency, employ the good computer auxiliary auditing technique is inevitable. This research is for the purpose of discussing in the audit work process to produce the system regarding the auditors all report formas, RSA and ElGamal of complexity visa way by the foctor, joins personnel’s status authentication to eradicate corrupt practices. And strengthens the electron financial reporting result potency in order to enhance enterprise internal control, so as to the enhancerment audit sevice quality, reduces the audit risk. Enables the advantage acceleration follow-up audit report circulation, moreover, to enter the step to become relizings the continuous computer audit footstone.
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Labadorf, Adam. "Characterizing the Huntington's disease, Parkinson's disease, and pan-neurodegenerative gene expression signature with RNA sequencing." Thesis, 2016. https://hdl.handle.net/2144/17865.
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Huntington's disease (HD) and Parkinson's disease (PD) are devastating neurodegenerative disorders that are characterized pathologically by degeneration of neurons in the brain and clinically by loss of motor function and cognitive decline in mid to late life. The cause of neuronal degeneration in these diseases is unclear, but both are histologically marked by aggregation of specific proteins in specific brain regions. In HD, fragments of a mutant Huntingtin protein aggregate and cause medium spiny interneurons of the striatum to degenerate. In contrast, PD brains exhibit aggregation of toxic fragments of the alpha synuclein protein throughout the central nervous system and trigger degeneration of dopaminergic neurons in the substantia nigra. Considering the commonalities and differences between these diseases, identifying common biological patterns across HD and PD as well as signatures unique to each may provide significant insight into the molecular mechanisms underlying neurodegeneration as a general process. State-of-the-art high-throughput sequencing technology allows for unbiased, whole genome quantification of RNA molecules within a biological sample that can be used to assess the level of activity, or expression, of thousands of genes simultaneously. In this thesis, I present three studies characterizing the RNA expression profiles of post-mortem HD and PD subjects using high-throughput mRNA sequencing data sets. The first study describes an analysis of differential expression between HD individuals and neurologically normal controls that indicates a widespread increase in immune, neuroinflammatory, and developmental gene expression. The second study expands upon the first study by making methodological improvements and extends the differential expression analysis to include PD subjects, with the goal of comparing and contrasting HD and PD gene expression profiles. This study was designed to identify common mechanisms underlying the neurodegenerative phenotype, transcending those of each unique disease, and has revealed specific biological processes, in particular those related to NFkB inflammation, common to HD and PD. The last study describes a novel methodology for combining mRNA and miRNA expression that seeks to identify associations between mRNA-miRNA modules and continuous clinical variables of interest, including CAG repeat length and clinical age of onset in HD.
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Mattison, Stacey A., G. L. Blatch, and Adrienne Lesley Edkins. "HOP expression is regulated by p53 and RAS and characteristic of a cancer gene signature." 2018. http://hdl.handle.net/10962/66278.
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publisher versionThe Hsp70/Hsp90 organising protein (HOP) is a co-chaperone essential for client protein transfer from Hsp70 to Hsp90 within the Hsp90 chaperone machine. Although HOP is upregulated in various cancers, there is limited information from in vitro studies on how HOP expression is regulated in cancer. The main objective of this study was to identify the HOP promoter and investigate its activity in cancerous cells. Bioinformatic analysis of the -2500 to +16 bp region of the HOP gene identified a large CpG island and a range of putative cis-elements. Many of the cis-elements were potentially bound by transcription factors which are activated by oncogenic pathways. Luciferase reporter assays demonstrated that the upstream region of the HOP gene contains an active promoter in vitro. Truncation of this region suggested that the core HOP promoter region was -855 to +16 bp. HOP promoter activity was highest in Hs578T, HEK293T and SV40- transformed MEF1 cell lines which expressed mutant or inactive p53. In a mutant p53 background, expression of wild-type p53 led to a reduction in promoter activity, while inhibition of wild-type p53 in HeLa cells increased HOP promoter activity. Additionally, in Hs578T and HEK293T cell lines containing inactive p53, expression of HRAS increased HOP promoter activity. However, HRAS activation of the HOP promoter was inhibited by p53 overexpression. These findings suggest for the first time that HOP expression in cancer may be regulated by both RAS activation and p53 inhibition. Taken together, these data suggest that HOP may be part of the cancer gene signature induced by a combination of mutant p53 and mutated RAS that is associated with cellular transformation.
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Robitaille, Julie. "Étude de la signature dynamique de transcrits primaires impliquée dans la maturation des microARN." Thèse, 2016. http://hdl.handle.net/1866/18669.
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Les microARN (miARN) sont des petits ARN non-codants pour des protéines qui permettent d’inhiber la traduction d’ARN messagers. Pour obtenir un miARN, un gène de miARN passe à travers une voie de maturation dans laquelle il sera coupé à deux reprises par les enzymes Drosha et Dicer. Pour interagir avec les enzymes, les gènes de miARN possèdent une structure générale en tige-boucle. Cependant, les détails de cette structure sont encore peu connus. L’objectif principal de ce projet était d’établir s’il y a une relation entre l’efficacité de maturation et la dynamique de la structure. Pour cela, l’efficacité de maturation de plusieurs variants de miARN a été évaluée par Northern Blot. La dynamique de la structure a été mesurée par un programme informatique à partir de l’information de la séquence. Une corrélation de 0,74 avec une valeur p de 0,02206 a été obtenue entre les dynamiques et les ratios d’efficacités de maturation de miARN. Cette corrélation est supérieure à celle obtenue basée sur l’énergie libre des structures prédites les plus stables qui n’atteignent pas 0,6. Les mutants de miR128-1 et miR188 ont été découverts comme diminuant la maturation. De plus, les mutants de miR125a, miR188 et miR330 affectent le site de clivage de Drosha. Une meilleure connaissance de la dynamique de l’ARN impliquée dans la maturation permettrait de définir l’impact des mutations dans les séquences de miARN ou encore de prédire les séquences pouvant générer des miARN.MicroRNAs (miRNAs) are small non-coding RNAs, which can inhibit target messenger RNAs translation. In order to obtain a miRNA, two enzymes, Drosha and Dicer cut the gene of miRNA. The RNA interacts with the proteins by its general hairpin structure. However, the details of the structure are still missing. The objective of this project is to establish if there is a relation between the efficiency of maturation and the RNA’s structural dynamics. In order to do this, the maturation efficiency of miRNA variants is measured by Northern Blot. The structural dynamics is measured by a program assessing the information of the sequence. The correlation between the dynamics and the maturation efficiency of the miRNA is 0.74 with a p-value of 0.02206. This correlation is superior to those based on free energy, which does not reach 0.6. The tested mutants of miR128-1 and miR188 have inhibited maturation; also, those of miR125a, miR188 and miR330 have modified the cleavage site of Drosha. A better knowledge of the dynamic structure involved in maturation would help define the impact of miRNA mutation or to predict sequences that are able to generate miRNAs.
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Hušková, Hana. "Výzkum klíčových mechanizmů onkogeneze s použitím modelových buněčných systémů." Doctoral thesis, 2017. http://www.nusl.cz/ntk/nusl-372371.
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(EN) Humans and cells in their bodies are exposed to various mutagens in their lifetime that cause DNA damage and mutations, which affect the biology and physiology of the target cell, and can lead to the expansion of an immortalized cell clone. Genome-wide massively parallel sequencing allows the identification of DNA mutations in the coding sequences (whole exome sequencing, WES), or even the entire genome of a tumour. Mutational signatures of individual mutagenic processes can be extracted from these data, as well as mutations in genes potentially important for cancer development ('cancer drivers', as opposed to 'passengers', which do not confer a comparative growth advantage to a cell clone). Many known mutational signatures do not yet have an attributed cause; and many known mutagens do not have an attributed signature. Similarly, it is estimated that many cancer driver genes remain to be identified. This Thesis proposes a system based on immortalization of mouse embryonic fibroblasts (MEF) upon mutagen treatment for modelling of mutational signatures and identification and testing of cancer driver genes and mutations. The signatures extracted from WES data of 25 immortalized MEF cell lines, which arose upon treatment with a variety of mutagens, showed that the assay recapitulates the...
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Dallaire, Paul. "Une signature du polymorphisme structural d’acides ribonucléiques non-codants permettant de comparer leurs niveaux d’activités biochimiques." Thèse, 2014. http://hdl.handle.net/1866/12336.
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Des évidences expérimentales récentes indiquent que les ARN changent de structures au fil du temps, parfois très rapidement, et que ces changements sont nécessaires à leurs activités biochimiques. La structure de ces ARN est donc dynamique. Ces mêmes évidences notent également que les structures clés impliquées sont prédites par le logiciel de prédiction de structure secondaire MC-Fold.
En comparant les prédictions de structures du logiciel MC-Fold, nous avons constaté un lien clair entre les structures presque optimales (en termes de stabilité prédites par ce logiciel) et les variations d’activités biochimiques conséquentes à des changements ponctuels dans la séquence.
Nous avons comparé les séquences d’ARN du point de vue de leurs structures dynamiques afin d’investiguer la similarité de leurs fonctions biologiques. Ceci a nécessité une accélération notable du logiciel MC-Fold. L’approche algorithmique est décrite au chapitre 1. Au chapitre 2 nous classons les impacts de légères variations de séquences des microARN sur la fonction naturelle de ceux-ci. Au chapitre 3 nous identifions des fenêtres dans de longs ARN dont les structures dynamiques occupent possiblement des rôles dans les désordres du spectre autistique et dans la polarisation des œufs de certains batraciens (Xenopus spp.).Recent experimental evidence indicates that RNA structure changes, sometimes very rapidly and that these changes are both required for biochemical activity and captured by the secondary structure prediction software MC-Fold. RNA structure is thus dynamic. We compared RNA sequences from the point of view of their structural dynamics so as to investigate how similar their biochemical activities were by computing a signature from the output of the structure prediction software MC-Fold. This required us to accelerate considerably the software MC-Fold. The algorithmic approach to this acceleration is described in chapter 1. In chapter 2, point mutations that disrupt the biochemical activity of microRNA are explained in terms of changes in RNA dynamics. Finally, in chapter 3 we identify dynamic structure windows in long RNA with potentially significant roles in autism spectrum disorders and separately in Xenopus ssp. (species of frogs) egg polarisation.