Добірка наукової літератури з теми "DynaLoad"

Abstract Summary Current web-based sequence logo analyses for studying domain–peptide interactions are often conducted only on high affinity binders due to conservative data thresholding. We have developed Dynalogo, a combination of threshold varying tool and sequence logo generator written in the R statistical programming language, which allows on-the-fly visualization of binding specificity over a wide range of affinity interactions. Hence researchers can easily explore their dataset without the constraint of an arbitrary threshold. After importing quantitative data files, there are various data filtering and visualizing features available. Using a threshold control, users can easily track the dynamic change of enrichment and depletion of amino acid characters in the sequence logo panel. The built-in export function allows downloading filtered data and graphical outputs for further analyses. Dynalogo is optimized for analysis of modular domain–peptide binding experiments but the platform offers a broader application including quantitative proteomics. Availability and implementation Dynalogo application, user manual and sample data files are available at https://dynalogo.cam.uchc.edu. The source code is available at https://github.com/lafontaine-uchc/dynalogo. Supplementary information Supplementary data are available at Bioinformatics online.

Diante das diferenças existentes nas características das bases dos braquetes usados atualmente, objetivou-se neste trabalho comparar entre si três tipos de bases de braquetes metálicos (Monobloc, Equilibrium e Dynalock). Foram utilizados 36 pré-molares humanos, divididos em 3 grupos de 12 dentes. Os dentes foram incluídos em troquéis com gesso pedra tipo IV e posicionados com suas faces vestibulares perpendiculares à base do troquel. Todos os braquetes foram colados com o compósito Concise Ortodôntico e submetidos ao ensaio de cisalhamento em uma Máquina Universal com uma velocidade de 0,5 mm por minuto. O braquete Monobloc obteve o maior valor médio de resistência adesiva (x = 28,19 Kgf/cm²), sendo superior estatisticamente aos braquetes Equilibrium (x = 18,07 Kgf/cm²) e Dynalock (x = 18,24 Kgf/cm²). Em relação ao ARI (Índice de Remanescente Resinoso), não foi encontrada diferença estatística entre os braquetes testados.

Um fator importante que define a eficácia dos aparelhos ortodônticos fixos é o atrito existente entre as superfícies de fios e braquetes. Assim, este estudo teve como objetivo investigar o coeficiente de atrito estático entre fios de aço inoxidável e beta-titânio (TP Orthodontics) e braquetes de aço inoxidável (Dynalock® - Unitek), braquetes estéticos com slot de aço inoxidável (Clarity® - Unitek) e estéticos convencionais (Allure® - GAC). Para tanto, construiu-se um equipamento no Departamento de Engenharia Mecânica e Mecatrônica da PUCRS. Antes de serem iniciados os testes, foi quantificado o erro de método e constatou-se que não houve interferência significante (p>0,05) do fator operador nas medições. Então, pôde-se calcular o valor do coeficiente de atrito, obtido pela divisão da força de atrito pela carga normal. O método estatístico utilizado neste estudo foi Análise de Variância (ANOVA) e teste de Comparações Múltiplas (Tukey). Constatou-se que: 1) a combinação com menor coeficiente de atrito foi composta pelo fio de aço inoxidável e braquete Dynalock® e a que apresentou maior coeficiente foi a do braquete Allure® com o fio de beta-titânio; 2) o fio de beta-titânio apresentou coeficiente de atrito significativamente maior do que o fio de aço inoxidável; 3) o braquete Dynalock® não apresentou diferenças significativas em relação ao coeficiente de atrito do braquete Clarity® quando o fio utilizado foi de beta-titânio. No entanto, quando o fio testado foi de aço inoxidável, apresentou coeficiente de atrito significativamente menor. O braquete Clarity® apresentou coeficiente de atrito significativamente menor do que o braquete Allure®.

Abstract OBJECTIVES This study aims to improve early detection of cardiac surgery-associated acute kidney injury (CSA-AKI) compared to classical clinical scores. METHODS Data from 7633 patients who underwent cardiac surgery between 2008 and 2018 in our institution were analysed. CSA-AKI was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Cleveland Clinical Score served as the reference with an area under the curve (AUC) 0.65 in our cohort. Based on that, stepwise logistic regression modelling was performed on the training data set including creatinine (Cr), estimated glomerular filtration rate (eGFR) levels and deltas (ΔCr, ΔeGFR) at different time points and clinical parameters as preoperative haemoglobin, intraoperative packed red blood cells (units) and cardiopulmonary bypass time (min) to predict CSA-AKI in the early postoperative course. The AUC was determined on the validation data set for each model respectively. RESULTS Incidence of CSA-AKI in the early postoperative course was 22.4% (n = 1712). The 30-day mortality was 12.5% in the CSA-AKI group (n = 214) and in the no-CSA-AKI group 0.9% (n = 53) (P < 0.001). Logistic regression models based on Cr and its delta gained an AUC of 0.69; ‘Model eGFRCKD-EPI’ an AUC of 0.73. Finally, ‘Model DynaLab’ including dynamic laboratory parameters and clinical parameters as haemoglobin, packed red blood cells and cardiopulmonary bypass time improved AUC to 0.84. CONCLUSIONS Model DynaLab’ improves early detection of CSA-AKI within 12 h after surgery. This simple Cr-based framework poses a fundament for further endeavours towards reduction of CSA-AKI incidence and severity.

Breast cancer is the leading cause of cancer related death in women, and approximately 1 in 11 women will develop breast cancer before the age of 75. In 2003, breast cancer was responsible for 16% of cancer related deaths in Australian women. This demonstrates that throughout the life span of the female, this organ has a high risk of developing cancer. The growth and survival of normal breast epithelial cells and breast cancer cells is promoted by estrogens and progesterone and both estrogen receptor (ER) and progesterone receptor (PR) have been shown to play prominent roles in breast cancer progression. It has also been demonstrated that co-treatment of breast cancer cells with corticosteroids and 17β-estadiol (E2) can have opposing effects on the proliferation of breast cancer cells compared with the single treatment. In addition, glucocorticoid receptor (GR) levels have been shown to have clinical implications for breast cancer cell survival. This suggests a possible role for activated GR in breast cancer development. Forkhead box protein 1 (FoxA1), a member of the forkhead class of DNA-binding proteins, has also been shown to be an important factor in breast cancer development. FoxA1 has been shown to dictate ER binding in breast cancer cells and has been deemed responsible for the rapid reprogramming of ER signalling seen in breast cancers with poor outcomes and treatment resistance. However, the effects of ER on the function of FoxA1 have been controversial. The aim of this thesis is to further investigate and characterise GR, ER, and FoxA1 crosstalk in three estrogenic breast cancer cell lines, MCF-7, ZR-75-1, and T-47D cells. It has been determined that the combination of dexamethasone (Dex) and E2 have an altered affect on the cell proliferation of breast cancer cells, compared to the single treatment, suggesting GR can modulate the ER response. In an artificial cell model it has been demonstrated by genome-wide investigations, that activated GR and estrogen receptor (ER) can alter the binding of each other at a subset of sites, by a mechanism termed DynaLoad. In addition, it has been shown that Dex and E2 in combination can regulate a unique subset of genes in breast cancer cells. This provides evidence to indicate that Dex can oppose the growth stimulatory effects of E2 signalling, and further, in combination, Dex and E2, can alter the gene transcriptional prolife of MCF-7 breast cancer cells. To understand how the molecular interplay between GR and ER effect breast cancer progression the genome-wide binding events of activated GR and ER have been investigated. These studies show that a GR and ER DynaLoad mechanism also exists in all three breast cancer cell lines utilised; however, there was very little crossover of binding patterns observed. This suggests that while the mechanisms of DynaLoad are present in all three cell lines, the sites altered are cell specific. Most surprisingly is the discovery of an elevated number of GR sites that are lost upon activation of ER in MCF-7 cells. However, in the other breast cancer cell lines, this finding is not as pronounced. Immunblots show that MCF-7 cells have lower GR protein levels than the other cell lines indicating that steroid receptor (SR) levels play a major role in the effect that the dual hormone treatment has on the cell. This suggests that in a highly estrogenic cell line, ER plays a strong role in modulating GR function, which could have important consequences for disease outcome. Furthermore, and contrary to previous findings, this thesis establishes that activated ER and GR have the ability to alter the genomic response of the well-established pioneer factor FoxA1. Genome-wide analysis of FoxA1 binding, upon treatment of E2 or Dex, shows that both ER and GR can recruit FoxA1 to specific binding sites within the genome through a DynaLoad mechanism. These results indicate that there is not a specific set of pioneer factors which bind to closed chromatin and establish the binding landscape for other transcription factors (TFs). Instead this data suggests that every factor has the potential to affect the binding landscape of other TFs, depending on the chromatin context. Overall, the findings from this thesis have provided novel insight into the crosstalk between GR, ER, and FoxA1, further highlighting the ability of activated SRs to alter the response of one another, and other TFs. In addition, it has also been determined that the outcomes of SR crosstalk is cell-specific and that differing estrogenic breast cancer cells can have altered outcomes, which are dependent on SR levels. This can have potential consequences in breast cancer disease outcomes and progression. In addition, the findings in this thesis have begun to shift our classical understanding of pioneer factors in breast cancer, demonstrating that activated GR and ER have the capabilities to recruit and alter the response of FoxA1. This has provided information on a previously unknown complexity to FoxA1 action in breast cancer cells. The studies in this thesis highlight the signalling complexity of TFs in breast cancer cells and provide the basis for further investigations into GR, ER, and FoxA1 mechanisms and the direct consequences of this on breast cancer outcomes.
Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2014