In previous publications [1,7] the author described the base rivalry in monotonous DNA sequences and their effect on the DNA repair mechanism. According to this theory, many base building blocks compete for the occupancy of the newly released base site in the replication of monotonous DNA sequences in the elongation phase. This gives them more and more kinetic energy from replication position k to next position. Thus, there is a probability that a tautomeric base pair is formed behind the end of the monotonic sequence because of the tunneling effect. After its replication a different, irreparable base pair develops from the tautomeric base pair, when the rivalry - energy leads to a very strong hydrogen bond. This happens, however, by chance. In the following, we will describe the 3 phenomena: The tunnel probability (section 2), the probability for coming up of a high – energy – base building block (Elitist, section 3),and the combination of both phenomena (section 4). The result of these calculations is the equation (28). It is remarkable that follows from these calculations that the length of the monotonous sequences, and also the length of DNA increases itself in the course of evolution (section 5). (Read up all detailed computations in [7].) [... from introduction]

In previous publications [1,7] the author described the base rivalry in monotonous DNA sequences and their effect on the DNA repair mechanism. According to this theory, many base building blocks compete for the occupancy of the newly released base site in the replication of monotonous DNA sequences in the elongation phase. This gives them more and more kinetic energy from replication position to next position. Thus, there is a probability that a tautomeric base pair is formed behind the end of the monotonic sequence because of the tunneling effect. After its replication a different, irreparable base pair develops from the tautomeric base pair, when the rivalry - energy leads to a very strong hydrogen bond. This happens, however, by chance. In the following, we will describe the 3 phenomena: The tunnel probability (section 2), the probability for coming up of a high – energy – base building block (Elitist, section 3),and the combination of both phenomena (section 4). The result of these calculations is the equation (28). It is remarkable that follows from these calculations that the length of the monotonous sequences, and also the length of DNA increases itself in the course of evolution (section 5). (Read up all detailed computations in [7].) [... from introduction]

In a process called 'base rivalry', irreparable mutations are provoked in the replication of monotonous sequences, which depend on the cell temperature, the cell viscosity and monotonous sequence length. This explains the very long monotonous sequences and very long DNAs that occur over long evolutionary epochs. Presumably, base rivalry (with tautomerism or too low cell viscosity) also provokes the formation of tumors and the emergence of dangerous viral mutations.

The purpose of this work was to analyze the biomechanics of degeneration, damage, and failure in biological soft tissues both experimentally and computationally to provide insight into tendon or ligament tearing, tendo-achilles lengthening and lumbar spine dysfunction. For soft tissue tearing, experimental studies for calculating fracture toughness were performed and determined that tendons and ligaments are able to completely resist tear propagation. For tendo-achilles lengthening, a damage model was developed to mimic the behavior of the lengthening that occurs as a result of the percutaneous triple hemisection technique. The model provided insight for predicting the amount of lengthening that occurs during the procedure. For lumbar spine dysfunction, a finite element model was validated against experimental testing and simulated using boundary conditions representing physiological loading. The model was able to predict how biomechanical changes can lead to pain and how the prevalence of Schmorl's nodes can be predicted. For each of the situations, the best verification and validation methods were selected and are presented throughout the research to demonstrate the predictive capabilities and limitations of the work. Results of these studies are presented along with how those results influence the clinical endeavors associated with the degeneration, damage and failure of soft tissues.

Telomere dysfunction is a significant source of genomic instability and contributes to the development of cancer. The multi-protein complex shelterin binds telomeric DNA to mitigate telomere dysfunction and ensure overall telomere stability. In addition to shelterin, the telomeric cap includes the telomeric repeat-containing RNA, TERRA, which associates with telomeric proteins and the telomeric DNA itself, often forming RNA:DNA hybrids or R-loops. TERRA is most abundant in cancer cells that utilize the alternative lengthening of telomeres (ALT) pathway, where it has been suggested that TERRA R-loops act as a source of replication stress at telomeric DNA that ultimately contributes to the activation of the ALT mechanism. In an effort to evaluate the effect TERRA may have on the emergence of the ALT phenotype, we sought to identify the enzyme(s) that regulate TERRA degradation in mammalian cells. Here, we leveraged an auxin-inducible degron (AID) system to identify the 5’-3’ exoribonuclease XRN2 as a direct modulator of TERRA stability in mammalian cells. Following XRN2 depletion, we demonstrate a significant increase in TERRA on chromatin in both non-ALT and ALT-positive cell lines. While the stabilization of TERRA on chromatin alone was insufficient to drive replication stress and activation of ALT in telomerase cells, depletion of XRN2 in the ALT-positive context led to a significant increase in R-loops and DNA damage signaling at telomeric DNA. Thus, increased TERRA stability alone is unlikely to activate ALT but may instead exacerbate ALT activity. Taken together, we demonstrate that XRN2 regulates TERRA stability, that defects in TERRA metabolism can alter telomere stability, and dysfunction in both factors drive telomere dysfunction in cells that rely on the ALT pathway. / 2024-08-12T00:00:00Z

No description available.

No description available.

BACKGROUND: Smile esthetics play a major role in the perception of a person’s attractiveness, as well as other social parameters. The study aim was to see if altering the gingival display of patients would affect perceptions of the aforementioned social parameters. METHODS: Smiling photographs were taken and then digitally altered so as to lengthen the teeth and reduce the amount of gingiva. These photographs were shown to a group of senior dental students, and a group of evaluators with no formal dental training. Groups were asked to rate each picture’s attractiveness, friendliness, trustworthiness, intelligence, and self-confidence. RESULTS: The digitally altered photographs were rated higher for all five social parameters than were their unaltered counterparts (p<0.0001). There were no statistically significant differences between the two groups of evaluators. CONCLUSIONS: Excessive gingival display positively affected how attractive a person’s smile is judged, and also how friendly, trustworthy, intelligent, and self-confident they are.

Esta dissertação visa analisar o uso no português brasileiro, doravante PB, da pista prosódica de duração de sílabas na produção e percepção de sentenças ambíguas do tipo SN1-V-SN2-Atributo, tais como A mãe encontrou a filha suada. Tais sentenças apresentam contextos em que pode haver reestruturação de frases fonológicas a depender da interpretação escolhida. Um dos trabalhos que guiaram esta pesquisa foi o de MAGALHÃES & MAIA (2006), no qual os autores também observaram sentenças com ambiguidade devido à presença de um atributo que pode se referir ao sujeito ou ao objeto da oração. Fonologicamente, tais leituras podem ser explicadas pelo fato de o atributo poder ou não se juntar a seu núcleo na construção do domínio da frase fonológica, em que, se há fronteira, um alongamento é esperado (NESPOR & VOGEL, 1996). ANGELO & SANTOS (2012, 2015) concluíram que os falantes não realizaram alongamento significativo, porém, observaram uma tendência a produzir sentenças de aposição não local mais longas. O que se propõe, então, é que o alongamento é um fenômeno existente na língua, mas é opcional. Se isto é verdade, sempre que ele for feito, a sentença deve ser interpretada como não local. Caso contrário, haveria uma variação nas respostas perceptuais ou preferência por aposição local (Princípio da Aposição Local verificado por MAGALHÃES & MAIA (2006) no PB com base no Princípio de Late Closure apontado por FRAZIER (1979)). Dois testes foram realizados: No de produção, além dos 30 falantes de Angelo & Santos, mais 20 foram escolhidos e outros 10 recuperados para que lessem ambas as versões de cada uma das 9 sentenças em meio a histórias que guiavam a um ou outro significado, totalizando 720 dados. No de percepção, foram selecionadas as 3 versões mais longas (de aposição não local) e as 3 mais curtas (de aposição local) do teste de produção para cada sentença, em um teste onde 30 ouvintes selecionaram através de imagens qual a interpretação obtida, totalizando 1620 dados. Primeiramente, os resultados apontaram para diferenças significativas observando o tipo de estrutura (os falantes alongaram e acertaram as não locais). Por tipo de sentença, a diferença foi significativa na maioria delas, confirmando a predição de que, ainda que o alongamento seja opcional na produção, uma vez realizado, ele serve como condutor para uma interpretação não local. Para as sentenças locais, o Princípio de Aposição Local verificado no PB por MAGALHÃES & MAIA (2006) também foi observado em nosso experimento. Por fim, os resultados apontam para 2 tipos de estruturas que podem interferir no processo de alongamento: Sentenças em que o atributo é formado por adjetivos deverbais (geração de uma fronteira CP) e sentenças que permitem construções de small clause (bloqueio da reestruturação). / The aim of this thesis is to analyze the use of syllable duration in Brazilian Portuguese (henceforth BP) as a prosodic cue in the perception and production of syntactically ambiguous sentences with a NP1-V-NP2-attribute structure (lit. The mother has found her daughter sweating). This type of sentence is produced in contexts where phonological phrases may be restructured, depending on how the sentences are interpreted. A reference for the present research was the study by MAGALHÃES & MAIA (2006), who also found sentences which ambiguity was due to the presence of an attribute that may refer to either the subject or the object of the clause. Phonologically, interpretations of the above-mentioned structure can be explained by the fact that attributes may or may not join the head in the construction of the phonological phrase domain, because lengthening is expected when there is a boundary (NESPOR & VOGEL, 1996). ANGELO & SANTOS (2015) found that the speakers in their study did not make significant lengthening; however, they tended to produce high attachment in longer sentences. It is suggested, therefore, that although lengthening exists in BP as a phenomenon, it is optional. If this is actually true, sentences should be interpreted as having high attachment whenever lengthening is produced. Otherwise, it is assumed that there is variation in perceptual responses or preference for low attachment (Low Attachment Principle, found in PB by MAGALHÃES & MAIA (2006), based on the Late Closure Principle proposed by Frazier (1979)). Data were collected with two tests. In the sentence-reading production test, 30 speakers from the study by ANGELO & SANTOS (2015)) and 20 new speakers read one version of each sentence, while 10 out of the former 30 read two versions, thus the corpus was made of a total of 720 sentences. The perception test used the three longest versions (with high attachment) and the three shortest versions (with low attachment) of each sentence. The informants who took the test chose the image that best represented the meaning that they assigned to each sentence. A total of 1620 data were produced. Overall results showed significant differences for type of structure (the informants lengthened and identified high attachments correctly). For sentence type, there were significant differences in most sentences, thus confirming the hypothesis that lengthening is optional in production and, once it has been performed, it can lead a sentence to be interpreted as having high attachment. For sentences with low attachment, the Low Attachment Principle suggested by MAGALHÃES & MAIA (2006) also occurred in our experiment. The findings signal two types of structures that may interfere with the lengthening process: sentences whose attribute is formed by deverbal adjectives (generation of a CP phrasal boundary) and sentences that allow small clause constructions (restructuring is blocked).

Greater trochanteric pain (GTP) is a regional pain syndrome characterized by lateral hip pain and tenderness. Its incidence after total hip arthroplasty (THA) is variable. Bursal inflammation, degenerative changes of the attachment of the gluteal muscles, direct operative trauma and biomechanical disturbance of the operated hip have been discussed as being related to GTP. The diagnosis is purely clinical because radiological and laboratory investigations show no definite pathology. Although most treatment modalities are conservative, some patients may develop refractory complaints leading to surgical intervention. In study I we studied the incidence of GTP in 172 consecutive patients who underwent THA during 2002 at Sundsvall Hospital. Patients with GTP (n=21, incidence 12%) were matched with controls from the same cohort. The THA outcome was assessed using the Western Ontario and McMaster Universities Arthrosis (WOMAC) Index. Trochanteric tenderness was studied using an electronic pressure algometer. We found an association between the occurrence of GTP and postoperative uncorrected lengthening of the operated limb of ≥ one centimetre. The WOMAC index revealed a reduction of the clinical outcome in the GTP group. In Study II we tested the value of using an algometer in the diagnosis of GTP after THA. We measured the pressure-pain threshold (PPT) over the greater trochanter and ilio-tibial band in 18 patients and 18 matched controls. Both groups were evaluated using the visual analogue scale (VAS). We found the algometer to have a good predictive validity and reproducibility. However, there was large inter-individual variability across subjects. The PPT ratio of 0.8 (affected vs. unaffected side) can be used as a cutoff ratio to establish GTP. There was no correlation between PPT measurements and VAS. Because of a low positive predictive value and large inter-individual variability, the pressure algometer has a limited value as a screening tool. In study III we proposed a new surgical treatment for refractory GTP after THA consisting of distal lengthening of the ilio-tibial band (ITB) by Z-plasty under local anaesthesia. This method was used in 12 women between March 2004 and June 2006. The patients were followed up by phone interview 3-4 months postoperatively and by an EQ-5D questionnaire and clinical examination including evaluation with the algometer at 1-3 years postoperatively. We found that the patients‘ quality of life was markedly improved following the operation (EQ-5D = 0.26 preoperatively vs. 0.67 postoperatively; p &lt;0.005). There were no postoperative complications. In study IV we evaluated the accuracy of a commonly used clinical method of LLD measurement (anterior superior iliac spine-medial malleolus) by comparing it to a reliable radiological method (tear drop-lesser trochanter) in 139 patients before and after THA. We found the correlation between the clinical and radiological methods to be weak preoperatively (r=0.21, ICC= 0.33) while the correlation was moderate postoperatively (r= 0.45, ICC=0.62). It is therefore recommended that the radiological method be used to measure leg length discrepancy in patients who undergo THA.