Régulation de p16INK4a, sénescence et oncogenèse

La régulation transcriptionnelle de l’expression de p16INK4a constitue un pivot essentiel lors du vieillissement cellulaire et de la réponse à un stress, en particulier oncogénique. Cette régulation, complexe, implique des facteurs activateurs (protéines Ets1 et -2, protéine E47), dont la liaison sur le promoteur du gène INK4a peut être inhibée par les protéines Id-1 ou -4. L’inhibition transcriptionnelle de p16INK4a repose également sur le répresseur transcriptionnel Bmi1, ainsi que sur une régulation épigénétique complexe, dont le mécanisme est seulement partiellement connu : le promoteur et l’exon 1 de INK4a présentent tous deux un îlot CpG, qui peut être méthylé après qu’une méthylation de l’histone H3 et une désacétylation de l’histone H4 soient intervenues, tous ces événements participant à l’extinction du gène. À l’inverse, le gène INK4a serait protégé de la méthylation de ses ilôts CpG par l’hélicase A de l’ARN, et le remodelage chromatinien faisant intervenir le complexe SWI/SNF, antagoniste de Bmi1, activerait l’expression de INK4a. L’analyse de la complexité des différents mécanismes de régulation de INK4a et une meilleure compréhension des modulations épigénétiques de son expression devraient permettre de développer l’utilisation rationnelle de nouvelles stratégies thérapeutiques anticancéreuses.The transcriptional regulation of p16INK4a is essential for cellular aging and oncogenic stress response. This regulation involves p16INK4a transcriptional activators such as proteins Ets1 and 2 or E47. The binding of these proteins to INK4a promoter can be inhibited by proteins Id-1 or -4 after heterodimer formation. The transcriptional inhibition of p16INK4a includes also the transcriptional repression by Bmi-1, and an epigenetic regulation which appears complex and remains incompletely understood. Actually, INK4a promoter and exon1 present a CpG island which can be methylated on cytosines by DNA methyltransferases. This DNA methylation is preceded by the lysine 9 histone H3 methylation and by the deacetylation of histone H4 both involved in gene silencing. Indeed, RNA Helicase A might protect INK4a against methylation of CpG island. Furthermore, chromatin remodelling involving SWI/SNF complex, antagonist to Bmi-1, might activate INK4a expression. The analysis of INK4a regulation mechanisms and the comprehension of the epigenetic modulation of its expression may allow us to develop a rational use of new anti-neoplastic agents

A WAVELET-BASED VARIABLE CONTROL PROCEDURE FOR DETECTING PROCESS MEAN SHIFT

This paper develops a wavelet-based approach for a variable control chart, and adopts the data decomposition and linear combination techniques to detect process shifts. The Shewhart, exponentially weighted moving average (EWMA), and cumulative sum (CUSUM) control charts are the most popular monitoring process graph tools. However, these charts were developed for different process situations. If a user chooses an inappropriate control chart to monitor a process, the correct control result will not be obtained. This study used the wavelet transform to develop a novel variable control procedure. First, the Haar function was used as the basis for data decomposition. Next, the linear combination technique was used to combine different resolution data through wavelet transform decomposition. Simulations were adopted to evaluate performance. An analysis showed that the detection ability of the wavelet-based variable control chart was superior to the EWMA control chart in a comparison of average run length (ARL) results

Fabrication of GaN-Based White Light-Emitting Diodes on Yttrium Aluminum Garnet-Polydimethylsiloxane Flexible Substrates

This study concerns the characteristics of white GaN-based light-emitting diode (LED) on flexible substrates. The thin film GaN-based blue LEDs were directly transferred from sapphire onto the flexible polydimethylsiloxane (PDMS) substrates by laser lift-off (LLO) process. The PDMS substrates were incorporated 10–40% cerium doped yttrium aluminum garnet phosphor, YAG:Ce3+, and formed the GaN-based white LEDs. The white LEDs prepared by the GaN-based LEDs on the YAG-PDMS substrates reveal one peak at 470 nm corresponding to the emission of the GaN-based LED and a broadband included five weak peaks caused by YAG:Ce3+ phosphors

3,4-Di-O-Caffeoylquinic Acid Inhibits Angiotensin-II-Induced Vascular Smooth Muscle Cell Proliferation and Migration by Downregulating the JNK and PI3K/Akt Signaling Pathways

We previously reported 3,4-di-O-caffeoylquinic acid (CQC) protected vascular endothelial cells against oxidative stress and restored impaired endothelium-dependent vasodilatation. Here, we further investigated its anti-atherosclerotic effect against angiotensin II (Ang II) evoked proliferation and migration of cultured rat vascular smooth muscle cells (rVSMC). The results showed CQC (1–20 μM) clearly inhibited Ang-II-stimulated BrdU incorporation and cell migration of rVSMC in a concentration-dependent manner but without significant cytotoxicity. Western blot analysis revealed Ang II increased the phosphorylation levels of Akt and mitogen-activated protein kinases (MAPKs;p38, ERK1/2 and JNK) in rVSMC. In the presence of phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin and three individual MAPK inhibitors SB203580, PD98059 and SP600125, both Ang-II-induced cell proliferation and migration were significantly attenuated, although to differing extents, suggesting the PI3K and MAPK signal pathways all participated in regulating rVSMC proliferation and migration. Also, the CQC pretreatment markedly suppressed Ang-II-induced phosphorylation of Akt and JNK rather than ERK1/2, although it failed to affect p38 phosphorylation. In conclusion, our data demonstrate CQC may act by down-regulating Akt, JNK and part of the ERK1/2 pathways to inhibit Ang-II-induced rVSMC proliferation and migration. The anti-atherosclerotic effect of CQC is achieved either by endothelial cells protection or by VSMC proliferation/migration inhibition, suggesting this compound may be useful in preventing vascular diseases

Controlled Heterogeneous Nucleation and Growth of Germanium Quantum Dots on Nanopatterned Silicon Dioxide and Silicon Nitride Substrates

Controlled heterogeneous nucleation and growth of Ge quantum dots (QDs) are demonstrated on SiO_2/Si_3N_4 substrates by means of a novel fabrication process of thermally oxidizing nanopatterned SiGe layers. The otherwise random self-assembly process for QDs is shown to be strongly influenced by the nanopatterning in determining both the location and size of the QDs. Ostwald ripening processes are observed under further annealing at the oxidation temperature. Both nanopattern oxidation and Ostwald ripening offer additional mechanisms for lithography for controlling the size and placement of the QDs

Commuting tillage operations of HRP under hydraulic cylinder movements on plough-breast performance

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Online assessment of patients' views on hospital performances using Rasch model's KIDMAP diagram

<p>Abstract</p> <p>Background</p> <p>To overcome the drawback of individual item-by-item box plots of disclosure for patient views on healthcare service quality, we propose to inspect interrelationships among items that measure a common entity. A visual diagram on the Internet is developed to provide thorough information for hospitals.</p> <p>Methods</p> <p>We used the Rasch rating scale model to analyze the 2003 English inpatient questionnaire data regarding patient satisfactory perception, which were collected from 169 hospitals, examined model-data fit, and developed a KIDMAP diagram on the Internet depicting the satisfaction level of each hospital and investigating aberrant responses with Z-scores and MNSQ statistics for individual hospitals. Differential item functioning (DIF) analysis was conducted to verify construct equivalence across types of hospitals.</p> <p>Results</p> <p>18 of the 45 items fit to the model's expectations, indicating they jointly defined a common construct and an equal-interval logit scale was achieved. The most difficult aspect for hospitals to earn inpatients' satisfaction were item 29 (staff told you about any medication side effects to watch when going home). No DIF in the 18-item questionnaire was found between types of hospitals, indicating the questionnaire measured the same construct across hospitals. Different types of hospitals obtained different levels of satisfaction. The KIDMAP on the Internet provided more interpretable and visualized message than traditional item-by-item box plots of disclosure.</p> <p>Conclusion</p> <p>After removing misfit items, we find that the 18-item questionnaire measures the same construct across types of hospitals. The KIDMAP on the Internet provides an exemplary comparison in quality of healthcare. Rasch analysis allows intra- and inter-hospital performances to be compared easily and reliably with each other on the Internet.</p

Reliability of 95% confidence interval revealed by expected quality-of-life scores: an example of nasopharyngeal carcinoma patients after radiotherapy using EORTC QLQ-C 30

<p>Abstract</p> <p>Background</p> <p>Many researchers use observed questionnaire scores to evaluate score reliability and to make conclusions and inferences regarding quality-of-life outcomes. The amount of false alarms from medical diagnoses that would be avoided if observed scores were substituted with expected scores is interesting, and understanding these differences is important for the care of cancer patients. Using expected scores to estimate the reliability of 95% confidence intervals (CIs) is rarely reported in published papers. We investigated the reliability of patient responses to a quality-of-life questionnaire and made recommendations for future studies of the quality of life of patients.</p> <p>Methods</p> <p>A total of 115 patients completed the EORTC core questionnaire QLQ-C30 (version 3) after radiotherapy. The observed response scores, assumed to be one-dimensional, were summed and transformed into expected scores using the Rasch rating scale model with WINSTEPS software. A series of simulations was performed using a unified bootstrap procedure after manipulating scenarios with different questionnaire lengths and patient numbers to estimate the reliability at 95% confidence intervals. Skewness analyses of the 95% CIs were compared to detect different effects between groups according to the two data sets of observed and expected response scores.</p> <p>Results</p> <p>We found that (1) it is necessary to report CIs for reliability and skewness coefficients in papers; (2) data derived from expected response scores are preferable to making inferences; and (3) visual representations displaying the 95% CIs of skewness values applied to item-by-item analyses can provide a useful interpretation of quality-of-life outcomes.</p> <p>Conclusion</p> <p>Reliability coefficients can be reported with 95% CIs by statistical software to evaluate the internal consistency of respondent scores on questionnaire items. The SPSS syntax procedures for estimating the reliability of the 95% CI, expected score generation and visual skewness analyses are demonstrated in this study. We recommend that effect sizes such as a 95% CI be reported along with <it>p </it>values reporting significant differences in quality-of-life studies.</p

Transformer-based Image Compression with Variable Image Quality Objectives

This paper presents a Transformer-based image compression system that allows for a variable image quality objective according to the user's preference. Optimizing a learned codec for different quality objectives leads to reconstructed images with varying visual characteristics. Our method provides the user with the flexibility to choose a trade-off between two image quality objectives using a single, shared model. Motivated by the success of prompt-tuning techniques, we introduce prompt tokens to condition our Transformer-based autoencoder. These prompt tokens are generated adaptively based on the user's preference and input image through learning a prompt generation network. Extensive experiments on commonly used quality metrics demonstrate the effectiveness of our method in adapting the encoding and/or decoding processes to a variable quality objective. While offering the additional flexibility, our proposed method performs comparably to the single-objective methods in terms of rate-distortion performance