Dissertations / Theses on the topic 'ACVR2A'

Dissertação para obtenção do grau de Mestre em Biologia Molecular em Saúde<br>No Biobanco-IMM as amostras são colhidas e armazenadas por longos períodos de tempo sendo de extrema importância que estas sejam de elevada qualidade. Para cumprir este requisito, os procedimentos do biobanco efetuam-se de acordo com diretrizes internacionais para a avaliação da qualidade das amostras que armazena.<br>No Biobanco-IMM, as amostras de DNA são extraídas e avaliadas em relação à sua concentração, pureza (razão A260/A280) e integridade. Por vezes, uma pequena percentagem das amostras pode não cumprir estes parâmetros de qualidade e uma vez que estas amostras são muitas vezes irrecuperáveis, surge a necessidade de testar a funcionalidade do DNA. O PCR é uma técnica largamente utilizada, pelo que outros biobancos internacionais, com os quais o Biobanco-IMM mantém estreita relação, aplicam esta técnica para complementar o procedimento de controlo de qualidade. Assim, este trabalho teve por objetivo implementar um método que comprove a funcionalidade das amostras de DNA armazenadas no Biobanco-IMM. Foram selecionadas amostras de cinco coleções representativas do Biobanco-IMM e amostras que não cumpriam os parâmetros de qualidade atualmente implementados. Segundo os resultados, as amostras pertencentes às cinco coleções apresentam boa amplificação do gene ACVR2B por PCR. Foi também observado que mesmo as amostras que se situavam fora do controlo de qualidade (87,8%) apresentaram amplificação, o que sugere que, mesmo que algumas amostras não cumpram os parâmetros de controlo de qualidade já aplicado no biobanco, poderão ser utilizadas, desde que se revelem funcionais. Segundo estes resultados, sugere-se que a adaptação do procedimento de CQ das amostras de DNA passe por acrescentar a técnica de PCR quando as amostras traduzam uma razão A260/280 < 1,7 ou > 2,0 e/ou não apresentem uma banda íntegra em gel de agarose.

La croissance du muscle squelettique est un processus complexe, impliquant de nombreux facteurs moléculaires. La myostatine (GDF-8) est un puissant régulateur négatif du développement musculaire, et l’absence d’une protéine fonctionnelle provoque une incroyable augmentation de la masse musculaire, chez la souris et le bovin. Des mutations dans le gène codant la myostatine ont été associées à l’extrême musculature observée chez le bovin. Cependant, des individus présentant différents degrés d’hypertrophie musculaire ont également été observés, sans qu’aucune mutation identifiée dans le gène codant la myostatine ne soit responsable. Ces observations phénotypiques suggèrent l’implication d’autres mutations, qui pourraient modifier la fonctionnalité des partenaires de la voie de signalisation de la myostatine, et/ou l’implication d’un mécanisme de régulation quantitative, qui résulterait d’une modification de l’affinité de la myostatine avec ses partenaires. Dans ce travail, nous avons étudié les gènes codant le récepteur de la myostatine, ActRIIB, et une protéine inhibitrice, la follistatine. Nous avons déterminé la structure bovine de ces deux gènes, et recherché d’éventuels polymorphismes chez des individus avec des degrés différents de développement musculaire. Aucun polymorphisme modifiant les séquences protéiques de ces deux gènes n’a été détecté. Une insertion/délétion de 6 pb et un SNP, détectés dans la région promotrice du gène ACVR2B, qui code pour le récepteur ActRIIB, semblent influencer l’activité transcriptionnelle de ce gène, in vitro. Un microsatellite polymorphe est présent dans la région promotrice du gène FST chez le bovin, la souris, l’homme et le rat, et pourrait modifier son expression. Ces résultats préliminaires, ouvrent de nouvelles perspectives d’étude sur l’influence possible de ces polymorphismes sur l’expression des gènes ACVR2B et FST, et par conséquent, sur la régulation de la voie de signalisation de la myostatine<br>Mutations in the myostatin gene are responsible for an increase in muscle mass in mouse and cattle. Myostatin is indeed a major regulator of muscle growth acting through a complex signalling pathway involving a large number of molecules. In several cattle breeds, individuals harboring different degrees of muscle hypertrophy are observed, independently of any mutation in the myostatin gene. The similarity between these phenotypes suggests that mutations affecting other members of the same signalling pathway might be involved. Moreover, the fact that different grades of the hypertrophy are observed from one animal to another suggests a quantitative regulation that could result from affinity changes in the binding of myostatin to its main partners. In this study, we investigate the possible involvement of the myostatin receptor, ActRIIB, and the myostatin inhibitor, follistatin. We have determined the structure of the bovine genes encoding these proteins and looked for polymorphisms between several individuals harboring various levels of muscular hypertrophy. No polymorphism affecting the protein sequences was identified. A 6bp insertion/deletion polymorphism and a SNP in the promoter region of the ACVR2B gene, encoding the ActRIIB receptor, appear to influence in vitro the transcription level of the gene. A polymorphic microsatellite is present in the promoter region of the FST gene in cattle, mouse, human and rat and might influence its expression although this was not demonstrated on the limited set of samples we investigated. This preliminary study opens the way to larger investigations on the possible influence of these polymorphisms on the expression of the ACVR2B and FST genes and the eventual consequences on the regulation of the myostatin signalling pathway

Tese (doutorado)—Universidade de Brasília, Faculdade de Ciências da Saúde, Programa de Pós-Graduação em Ciências da Saúde, 2013.<br>Submitted by Alaíde Gonçalves dos Santos (alaide@unb.br) on 2013-06-25T13:02:46Z No. of bitstreams: 1 2013_ClaudiaCruzLunardi.pdf: 2104527 bytes, checksum: 869f3995f555f48eaf76b6782428405f (MD5)<br>Approved for entry into archive by Guimaraes Jacqueline(jacqueline.guimaraes@bce.unb.br) on 2013-06-25T14:21:38Z (GMT) No. of bitstreams: 1 2013_ClaudiaCruzLunardi.pdf: 2104527 bytes, checksum: 869f3995f555f48eaf76b6782428405f (MD5)<br>Made available in DSpace on 2013-06-25T14:21:38Z (GMT). No. of bitstreams: 1 2013_ClaudiaCruzLunardi.pdf: 2104527 bytes, checksum: 869f3995f555f48eaf76b6782428405f (MD5)<br>Introdução: Estudos de associação genética (GWAS) sugerem uma importante contribuição dos genes candidatos FTO, TRHR e ACVRIb na composição corporal e na força muscular, em diferentes populações e em variadas faixas etárias. Objetivos: Replicar os GWAS, visando examinar a associação entre os polimorfismos dos genes candidatos FTO, TRHR e ACVRIb com a composição corporal e a força muscular, em mulheres idosas. Métodos: Após a aplicação dos critérios de exclusão, 241 voluntárias (idade 66,7±5,5 anos) foram submetidas à avaliação da composição corporal, por meio da Absortometria por Raios-X de Dupla Energia e pico de torque (PT) dos extensores do joelho, utilizando o dinamômetro isocinético (Biodex System 3). A genotipagem foi conduzida em toda a amostra, por meio da Reação em Cadeia da Polimerase e Eletroforese. Os marcadores de ancestralidade foram genotipados seguindo procedimentos padronizados. Resultados: A distribuição dos genótipos se apresentou de acordo com o esperado pelo equilíbrio de Hardy-Weinberg, para todos os polimorfismos. Os polimorfismos (rs9939609 e rs1861868) do FTO não apresentaram diferenças estatísticas significantes entre os grupos no fenótipo relacionado (composição corporal). Em relação aos polimorfismos do gene TRHR, não foram observadas diferenças significativas para rs7832552. Verificou-se diferença significante entre os genótipos para rs16892496, nas variáveis Massa Livre de Gordura (MLGA) e a MLGA relativa (p=0,04 e p=0,05, respectivamente). Indivíduos carreadores dos genótipos A/A e A/C, respectivamente, apresentaram, em media, 1kg e 900g de MLGA extra, quando comparado aos carreadores do genótipo C/C. O genótipo C/C apresentou maior chance de apresentar valores inferiores para força muscular. Os polimorfismos do gene ACVRIb (rs2854644, rs10783485 e rs10783485) não diferiram estatisticamente entre os genótipos, nos fenótipos musculares. No entanto, o rs2854644 e rs10783485 apresentaram diferença significante entre os genótipos, na variável “prevalência de excesso de peso" (p=0,03 e p=0,04, respectivamente). Os genótipos do rs10783485 também diferiram estatisticamente no percentual de gordura (p=0,04). Conclusões: O gene FTO não apresentou associação ao fenótipo de obesidade nesta amostra de idosas, no entanto, o gene ACVRIb apresentou tendência de associação a esse fenótipo. As observações do presente estudo fornecem mais evidencias de que o polimorfismo rs16892496 do gene TRHR apresenta um papel importante na variação da massa livre de gordura. _______________________________________________________________________________________ ABSTRACT<br>Introduction: Genome-Wide Association Studies (GWAS) suggest an important contribution of FTO, TRHR and ACVR1b candidate genes in body composition and muscle strength in different populations and wide age groups. Objectives: To replicate the GWAS aiming to examine the association between polymorphisms in FTO, TRHR and ACVRIb candidate genes with body composition and muscle strength in older women. Methods: After exclusion criteria was applied, 241 volunteers (age 66.7 ± 5.5 years) were underwent body composition assessment by dual energy X-ray absorptiometry and torque peak (PT) of the knee extensors using the isokinetic dynamometer (Biodex System 3). Genotypes were conducted, throughout the whole sample, by polymerase chain reaction and electrophoresis. The ancestry informative markers were genotyped following standard procedures. Results: The genotypes distribution worked as expected in Hardy-Weinberg equilibrium for al polymorphisms. No significant statistical differences were observed for FTO polymorphisms (rs9939609 and rs1861868) in the related phenotype (body composition). Regarding TRHR gene polymorphisms, no significant differences were observed for rs7832552. Significant difference was found between genotypes for rs16892496 in variables Fat Free Mass (FFM) and FFM relative (p=0,04 and p=0,05, respectively). Carrying individuals of A/A and A/C genotypes, respectively, presented on average 1kg and 900g extra FFM, in comparison to carriers of C/C genotype. The C/C genotype group showed significantly higher chance to present lower values for muscle strength. No significant difference was observed for ACVR1b gene polymorphisms (rs2854644, rs10783485 and rs10783485) for muscle phenotypes. However, rs2854644 and rs10783485 showed significant differences between genotypes in the “overweight prevalence” variable (p=0,03 and p=0,04, respectively). The rs10783485 genotypes also differed significantly in body fat percentage (p=0,04). Conclusions: The FTO gene was not associated to the obesity phenotype in this older women sample, however, the ACVRIb gene tended to associate with this phenotype. The observations in the present study provide further evidences that the rs16892496 polymorphism in the TRHR gene play major role in FFM variation

Introdução: Dentre os tumores primários do SNC, o meningioma é o tipo mais frequentemente diagnosticado, sendo responsável por 35,5% dos casos, considerando-se todas as faixas etárias. A gênese dos meningiomas é um processo complexo que envolve o acúmulo de alterações genéticas, sendo o evento mais conhecido a deleção no braço longo do cromossomo 22. O entendimento da iniciação e do crescimento dos meningiomas em nível molecular pode ajudar a definir novos alvos de terapia e, neste contexto, tem se destacado na última década o estudo dos microRNAs (miRNAs). Os miRNAs são uma classe de pequenos RNAs não codificadores que regulam a expressão gênica e têm um papel crucial no desenvolvimento de vários tipos de câncer. O reconhecimento do papel destes RNAs na fisiopatologia dos tumores do SNC vem ganhando destaque. O objetivo deste estudo é compreender o envolvimento da deleção do cromossomo 22q no perfil de expressão de genes e de miRNAs nos meningiomas grau I e, com isso, possibilitar uma melhor compreensão da sua natureza que permita propor alvos potenciais para novas formas de terapia molecular no futuro. Pacientes e métodos: Em um estudo prévio de nosso grupo foi feita uma análise global da expressão gênica pela metodologia de microarrays. Inicialmente para determinação dos grupos foi feita uma análise pela técnica de FISH para identificar quais amostras tinham a deleção do cromossomo 22q e por análise dos microarrays foram selecionados microRNAs e genes para validação PCR em tempo real. Em nosso estudo atual foram utilizadas 15 amostras em cada grupo: um grupo de meningiomas com deleção do cromossomo 22q, um segundo grupo de meningiomas sem deleção do cromossomo 22q e um grupo controle de 15 amostras de aracnoide normal. Os genes selecionados foram o ACVR1C, CCL18, VGLL3, ASPN, OGDHL e BTC e os miRNAs foram o miR-1 e miR-133b. Resultados e Conclusões: Os genes e microRNAs selecionados pela análise de microarray e validados por PCR em tempo real mostraram-se diferentemente expressos entre meningiomas com deleção do cromossomo 22q e meningiomas sem deleção do cromossomo 22q. Os genes ACVR1C, CCL18 e VGLL3 foram hipoexpressos em ambos os grupos de meningiomas, com deleção do cromossomo 22q e sem deleção do cromossomo 22q. O gene ASPN também foi hipoexpresso em meningiomas sem deleção do 22q quando comparado ao grupo controle. O gene OGDHL foi hiperexpresso em meningiomas sem a deleção do 22q quando comparado ao grupo controle. O gene BTC foi diferentemente expresso entre meningiomas com e sem deleção do 22q. Os microRNAs miR-1e miR-133b foram hipoexpressos em meningiomas com deleção do 22q e em mengiomas sem deleção do 22q.<br>Introduction: Among the primary tumors of the Nervous System, the meningioma is the most frequently diagnosed type, accounting for 35.5% of cases, considering all age groups. The genesis of meningiomas is a complex process that involves accumulation of genetic alterations, the most important event being the deletion in the long arm of chromosome 22. Understanding the initiation and growth of meningiomas at the molecular level can help developing new targets for therapy and, in this context, has been highlighted in the last decade the study of microRNAs (miRNAs). MiRNAs are a class of small non-coding RNAs which regulates gene expression and plays a crucial role in the development of many types of cancer. The recognition of their role in the pathophysiology of brain tumors has been coming into prominence. The aim of this study is to understand the involvement of chromosome 22q deletion in the expression profile of genes and miRNAs in meningiomas grade I and, with that, allow for a better understanding of its nature which may propose potential targets for new modalities of molecular therapy in the future. Patients and methods: In a previous study of our group, a global analysis by microarray methodology of genes and microRNAs was performed. Firstly, for group determination, a FISH technique analysis was done to identify which samples had the deletion of chromosome 22q and which had not and, by microarray analysis, were selected microRNAs and genes for validation by real-time PCR. In our present study 15 samples in each group were used: one group of meningiomas with deletion of chromosome 22q, a second one of meningiomas without deletion on chromosome 22q and a control group with 15 samples of normal arachnoid. The genes selected were ACVR1C, CCL18, VGLL3, ASPN, OGDHL and BTC and the miRNAs were miR-1 and miR-133b. Results and Conclusions: The genes and microRNAs selected by microarray analysis and validated by real-time PCR were differently expressed between meningiomas with deletion of chromosome 22q and meningiomas without deletion of chromosome 22q. The genes ACVR1C, CCL18 and VGLL3 were downregulated in both groups of meningiomas, either with deletion of chromosome 22q and without chromosome 22q deletion. The ASPN gene was downregulated in meningiomas without deletion of 22q when compared to the control group. The OGDHL gene was upregulated in meningiomas without deletion of 22q when compared to the control group. BTC was differentially expressed between meningiomas with and without deletion of 22q. The microRNAs miR-1 and miR-133b were downregulated in meningiomas with deletion of 22q and in mengiomas without deletion of 22q.

Le gliome infiltrant du tronc cérébral est une tumeur rare, non opérable et inéluctablement fatale. En raison du manque de ressource biologique disponible, aucun progrès dans la compréhension de la biologie de ces tumeurs n’a été fait jusqu’à ces dernières années, laissant la radiothérapie pour seul traitement efficace, et seulement transitoirement. Enfin, grâce à la mise en place de collecte d’échantillons de gliomes infiltrant du tronc cérébral au diagnostic ou à l’autopsie, un nombre sans précédent d’analyses biologiques et génomiques a pu être mené et améliorer la connaissance de ces tumeurs. Si ces études ont montré que ces gliomes pédiatriques étaient bien différents de ceux de l’adulte, elles ont aussi fait apparaître la présence d’anomalies génétiques récurrentes spécifiques de ces tumeurs sous-tentorielles. Ainsi le Platelet-Derived Growth Factor Receptor Alpha (PDGFRα) est apparu comme cible prédominante dans ces tumeurs compte tenu des nombreuses anomalies génétiques constatées. La recherche d’un médicament efficace pouvant inhiber cette voie nous a conduit à évaluer l’effet du dasatinib qui est un inhibiteur multi-ciblé. Nous en rapportons ici l’efficacité in vitro sur de nouvelles lignées cellulaires de gliomes infiltrants du tronc cérébral établies à partir de biopsies stéréotaxiques réalisées au diagnostic. Sachant néanmoins que les thérapies ciblées restent peu efficaces en clinique quand elles sont utilisées seules, nous mettons en évidence l’intérêt de combiner le dasatinib avec un inhibiteur de MET, 2ème oncogène fréquemment amplifié dans ces tumeurs. D’autre part, une stratégie originale de criblage médicamenteux a été mise en œuvre. Celle-ci a permis de définir de manière fonctionnelle de nouveaux médicaments potentiellement efficaces dans les gliomes infiltrants du tronc cérébral, incluant les inhibiteurs d’Histone deacetylases (HDAC), les inhibiteurs des Cyclin-Dependent Kinases (CDK) ou encore les inhibiteurs du protéasome. Enfin par la technique de séquençage génome-entier, de nouvelles anomalies génétiques jamais rencontrées dans aucun autre cancer ont été détectées. Parmi celles-ci se trouvent des mutations d’histone H3K27M dont la fréquence élevée (80%) suggère leur rôle fondamental dans la genèse de ces tumeurs. Des mutations activatrices d’ACVR1/ALK2 ont été également mises en évidence. Celles-ci représentent désormais de nouvelles cibles à explorer.Ce travail de thèse rapporte la recherche de nouvelles cibles thérapeutiques d’une part, via une approche exploratoire par criblage médicamenteux et recherche d’anomalies génétiques par séquençage « génome-entier », et d’autre part, via une approche de validation préclinique sur le plan des thérapies ciblées de type inhibiteurs de tyrosine-kinases<br>Diffuse Intrinsic Pontine Glioma (DIPG) is a rare, unresectable and universally fatal tumor. Due to the lack of available material, no improvements have been made in the knowledge of the biology of this tumor until recent years, leaving radiotherapy as the only efficient treatment, and only transiently. Recently, the effort engaged for collecting samples in this disease at the diagnosis or at the autopsy resulted in an unprecedented number of analyses consequently improving our knowledge in DIPG. Those studies bring evidences for their differences with adult gliomas, but also with other pediatric supratentorial glioma showing specific genomic alterations. Thus, Platelet-Derived Growth Factor Receptor Alpha (PDGFRα) appeared to be one of the major target given its frequent aberrations found in those tumors. Investigating an effective drug to inhibit this pathway led us to evaluate the effect of dasatinib, which is known as a multi-targeted inhibitor. We report here the in vitro efficacy of dasatinib on new cell lines of DIPG developed from stereotaxic biopsy at diagnosis. Because therapies are largely inefficient in the clinic when they are used as a monotherapy, we bring out our interest on combining dasatinib with an inhibitor of MET, which is the 2nd most common amplified oncogene in these tumors.Additionally, an innovative strategy of pharmacological screening has been successfully tested. New drugs, potentially efficient in DIPG, have been fonctionnaly-defined, including Histone deacetylase inhibitors (HDACi), Cyclin-Dependent Kinases inhibitors (CDKi) and proteasome inhibitors as well.Finally, by using whole genome sequencing (WGS), we have been able to discover new genetic abnormalities, never encountered before in other cancers. Among those, mutations of histone H3K27M with a high frequency of 80% were found, suggesting that they have a fundamental role in tumors genesis. Moreover, ACVR1/ALK2 activating mutations have been identified as well. And this gene now represents a new target to explore. This work reports the research of new therapeutic targets through an exploratory approach using drug screening and WGS on the one hand, and on the other hand through a preclinical validation approach in terms of targeted therapies with tyrosine-kinases inhibitors

京都大学<br>0048<br>新制・論文博士<br>博士(医学)<br>乙第13301号<br>論医博第2190号<br>新制||医||1039(附属図書館)<br>京都大学大学院医学研究科医学専攻<br>(主査)教授 妻木 範行, 教授 木村 剛, 教授 影山 龍一郎<br>学位規則第4条第2項該当<br>Doctor of Medical Science<br>Kyoto University<br>DFAM

La souche mutante, rhodococcus sp. Acv2 est capable d'hydrolyser l'adiponitrile en adipate d'ammonium plus efficacement que la souche sauvage rhodococcus sp. R312. Sa nitrile hydratase est capable d'hydrater plus rapidement les mononitriles issus de l'adiponitrile. Il convenait de determiner la structure primaire de l'enzyme. Une banque cosmidique a ete construite chez escherichia coli. Le criblage par hybridation sur colonies a l'aide d'une sonde specifique a permis d'isoler un cosmide contenant le gene de la nitrile hydratase. Le sequencage d'un fragment de 1,7 kb a permis d'identifier les genes ntha et nthb codant pour les deux sous-unites de l'enzyme et de reperer une mutation affectant le gene nthb. Cette mutation se traduit, au niveau du 40#i#e#m#e acide amine de la sous-unite beta, par le remplacement d'une methionine par une valine chez la souche mutante acv2. Une sequence conservee, susceptible d'etre le site de fixation de l'atome de fer des nitrile hydratases, a ete reperee au niveau de la sous-unite alpha. Les plasmides pbl33 et prc1 de brevibacterium linens atcc 9174 et rhodococcus rhodochrous atcc 4276 ont ete employes pour construire des vecteurs navettes entre rhodococcus sp. Et e. Coli. Les plasmides construits, psp33 (replicon de pbl33) et pspc1 (replicon de prc1), porteurs du gene de resistance aphl provenant du transposon tn903, conferent la resistance a la neomycine a rhodococcus sp. R312. Ces plasmides devraient permettre le transfert des genes clones chez rhodococcus sp. Une etude du genome de rhodococcus sp. R312 par electrophorese en champ pulse a ete realisee. La taille du chromosome est estimee a 6,44 mb. Les genes ntha et nthb ainsi que le gene amie codant pour l'amidase generale ont ete localises sur des fragments de restriction. Ces travaux constituent une etape preliminaire a l'elaboration d'une carte physique du chromosome de rhodococcus sp. R312

碩士<br>國立雲林科技大學<br>營建工程系<br>106<br>The results of this study show that the basic cognition of Interior design designers in China is generally understood to be the majority, so the cognition of green building materials is effective, and it is suggested that the building related units should continue to popularize the popularization and education of green building materials. The basic understanding of the green building materials by architects is very well known as 11.7% of the percentage. It is still known as 34.2% of the percentage. The general understanding is 43.3% of the percentage. It is slightly unknown to be 6.7% of the percentage. Know as 4.2% of the percentage satisfaction,In the green building materials use of the degree of willingness, the results show that the intention of the archite ctural design staff is common,which causes a low degree of willingness because of the high cost of products, general custo mers do not understand the general building materials and green building materials differences . It is suggested that if the government can help promote and reduce costs,I believe that the general public can improve the ut i l izat ion. To promote green bui lding mater ial s popular izat ion suggestions and views, developed five green building materials to promote the promotion of the recommendations and counter measures to provide follow-up to promote the popularization of green building materials.

Indiana University-Purdue University Indianapolis (IUPUI)<br>The Convolutional Neural Network (CNN) is a mathematical model designed to distill input information into a more useful representation. This distillation process removes information over time through a series of dimensionality reductions, which ultimately, grant the model the ability to resist noise, and generalize effectively. However, CNNs often contain elements that are ineffective at contributing towards useful representations. This Thesis aims at providing a remedy for this problem by introducing Absolute Cosine Value Regularization (ACVR). This is a regularization technique hypothesized to increase the representational power of CNNs by using a Gradient Descent Orthogonalization algorithm to force the vectors that constitute their filters at any given convolutional layer to occupy unique positions in in their respective spaces. This method should in theory, lead to a more effective balance between information loss and representational power, ultimately, increasing network performance. The following Thesis proposes and examines the mathematics and intuition behind ACVR, and goes on to propose Dynamic-ACVR (D-ACVR). This Thesis also proposes and examines the effects of ACVR on the filters of a low-dimensional CNN, as well as the effects of ACVR and D-ACVR on traditional Convolutional filters in VGG-19. Finally, this Thesis proposes and examines regularization of the Pointwise filters in MobileNetv1.

The Convolutional Neural Network (CNN) is a mathematical model designed to distill input information into a more useful representation. This distillation process removes information over time through a series of dimensionality reductions, which ultimately, grant the model the ability to resist noise, and generalize effectively. However, CNNs often contain elements that are ineffective at contributing towards useful representations. This Thesis aims at providing a remedy for this problem by introducing Absolute Cosine Value Regularization (ACVR). This is a regularization technique hypothesized to increase the representational power of CNNs by using a Gradient Descent Orthogonalization algorithm to force the vectors that constitute their filters at any given convolutional layer to occupy unique positions in Rⁿ. This method should in theory, lead to a more effective balance between information loss and representational power, ultimately, increasing network performance. The following Thesis proposes and examines the mathematics and intuition behind ACVR, and goes on to propose Dynamic-ACVR (D-ACVR). This Thesis also proposes and examines the effects of ACVR on the filters of a low-dimensional CNN, as well as the effects of ACVR and D-ACVR on traditional Convolutional filters in VGG-19. Finally, this Thesis proposes and examines regularization of the Pointwise filters in MobileNetv1.