Thermal aging of High Tenacity Polyvinyl Alcohol yarns

A both multiscale and multi-techniques approach was developed to characterize the thermal aging in air at 70, 90, 100 and 120 °C of High Tenacity Polyvinyl Alcohol (HT-PVAl) yarns, and to elucidate the consequences of thermal aging on the chemical structure, crystalline morphology and several physico-chemical and mechanical properties of practical interest. First of all, FTIR and UV–Vis spectrometries showed that the main degradation products are isolated (1656 cm−1) and conjugated (1592 cm−1) carbon-carbon double bonds, and a large variety of carbonyl products such as: esters (1757 cm−1), aldehydes (1737 cm−1), carboxylic acids (1720 cm−1), ketones (1707 cm−1), but also polyenones (1630 cm−1). Possible mechanistic schemes were then proposed to explain the formation of all these different degradation products. Moreover, no change in the physico-chemical properties of the amorphous phase was detected by modulated differential scanning calorimetry and dynamic vapor sorption. In contrast, the decrease in both melting temperature and crystallinity ratio with exposure time clearly indicates a “nibbling” of the crystalline phase during thermal aging, thus highlighting a chemical attack preferentially localized at the amorphous/crystal interface for this complex anisotropic material. This heterogeneous degradation is responsible for the loss of fracture properties in tension of HT-PVAl yarns. Fairly simple relationships between the structural variables determined at the different scales of analysis were established. As an example, a linear correlation was found between the changes in fracture properties and the changes in crystalline morphology

Grouped graphical Granger modeling for gene expression regulatory networks discovery

We consider the problem of discovering gene regulatory networks from time-series microarray data. Recently, graphical Granger modeling has gained considerable attention as a promising direction for addressing this problem. These methods apply graphical modeling methods on time-series data and invoke the notion of ‘Granger causality’ to make assertions on causality through inference on time-lagged effects. Existing algorithms, however, have neglected an important aspect of the problem—the group structure among the lagged temporal variables naturally imposed by the time series they belong to. Specifically, existing methods in computational biology share this shortcoming, as well as additional computational limitations, prohibiting their effective applications to the large datasets including a large number of genes and many data points. In the present article, we propose a novel methodology which we term ‘grouped graphical Granger modeling method’, which overcomes the limitations mentioned above by applying a regression method suited for high-dimensional and large data, and by leveraging the group structure among the lagged temporal variables according to the time series they belong to. We demonstrate the effectiveness of the proposed methodology on both simulated and actual gene expression data, specifically the human cancer cell (HeLa S3) cycle data. The simulation results show that the proposed methodology generally exhibits higher accuracy in recovering the underlying causal structure. Those on the gene expression data demonstrate that it leads to improved accuracy with respect to prediction of known links, and also uncovers additional causal relationships uncaptured by earlier works

Cdc25A phosphatase: a key cell cycle protein that regulates neuron death in disease and development

Cell cycle molecules are mostly dormant in differentiated neurons that are post-mitotic and in the G0 state of the cell cycle. However, a wealth of evidence strongly suggests that in response to a wide variety of apoptotic stimuli, including trophic factor deprivation, exposure to β-amyloid (Aβ) and DNA damage, neurons emerge from theG0 state with aberrant expression/activation of cell cycle proteins.1 This emergence is characterized by a consistent set of events related to the cell cycle that culminate in neuron death. Initial responses include activation of G1/S cyclin-dependent kinases (Cdks), such as Cdk4 that in turn phosphorylate retinoblastoma (pRb) family proteins and lead to dissociation of repressor complexes comprising E2F and pRb proteins, so that E2F-binding genes are de-repressed. Among genes that are de-repressed by loss of E2F-Rb family complexes are the B- and C-myb transcription factors that in turn transactivate Bim, a pro-apoptotic protein that promotes caspase activation and subsequent neuron death.1–4 This set of events has been termed the ‘apoptotic cell cycle pathway’.Cell division cycle 25A (Cdc25A), a member of a family comprising Cdc25A, B and C, is a dual specificity phosphatase that dephosphorylates inhibitory phosphates on adjacent threonine and tyrosine residues of Cdks such as Cdk4.5 This step is essential for initiation of cell cycle in proliferating cells. However, it was not known whether in the non-dividing neurons, the same events would activate the apoptotic cell cycle pathway. In our recent paper published in Cell Death Discovery,6 we report several novel findings regarding the potential role of Cdc25A in neuron death. First, Cdc25A is required for activation of the apoptotic cell cycle pathway and neuron death in response to nerve growth factor (NGF) deprivation and Aβ treatment. Second, Cdc25A acts upstream of Cdk-mediated Rb phosphorylation and caspase-3 cleavage. Third, NGF deprivation and Aβ lead to rapid increases in Cdc25A mRNA and protein levels. NGF withdrawal causes an increase in Cdc25A activity as well. These events occur at about the same time that apoptotic insults lead to Cdk4 activation and Rb phosphorylation in our experimental systems and well precede evident signs of neuron death

Grating and interferometric devices in POF

To date, much of the development work associated with polymer optical fibre (POF) applications has been aimed at exploiting the potential of the technology to provide low cost solutions. Here we argue that, in the sensing area at least, POF offers a number of other, more relevant advantages. In this paper we describe work on a range of devices based on photoinscribed gratings and on fibre interferometers, which are designed to take advantage of the unique properties of POF

Fibre Bragg grating sensors in polymer optical fibres

This review paper summarises the current state of research into polymer optical fibre grating sensors. The properties of polymers are explored to identify situations where polymers offer potential advantages over more conventional silica fibre sensing technology. Photosensitivity is discussed and the sensitivities of polymer fibre gratings to strain, temperature and water are described. Finally, applications are reported which utilise the unique properties of polymer fibres

Contributions Made by CDC25 Phosphatases to Proliferation of Intestinal Epithelial Stem and Progenitor Cells

The CDC25 protein phosphatases drive cell cycle advancement by activating cyclin-dependent protein kinases (CDKs). Humans and mice encode three family members denoted CDC25A, -B and -C and genes encoding these family members can be disrupted individually with minimal phenotypic consequences in adult mice. However, adult mice globally deleted for all three phosphatases die within one week after Cdc25 disruption. A severe loss of absorptive villi due to a failure of crypt epithelial cells to proliferate was observed in the small intestines of these mice. Because the Cdc25s were globally deleted, the small intestinal phenotype and loss of animal viability could not be solely attributed to an intrinsic defect in the inability of small intestinal stem and progenitor cells to divide. Here, we report the consequences of deleting different combinations of Cdc25s specifically in intestinal epithelial cells. The phenotypes arising in these mice were then compared with those arising in mice globally deleted for the Cdc25s and in mice treated with irinotecan, a chemotherapeutic agent commonly used to treat colorectal cancer. We report that the phenotypes arising in mice globally deleted for the Cdc25s are due to the failure of small intestinal stem and progenitor cells to proliferate and that blocking cell division by inhibiting the cell cycle engine (through Cdc25 loss) versus by inducing DNA damage (via irinotecan) provokes a markedly different response of small intestinal epithelial cells. Finally, we demonstrate that CDC25A and CDC25B but not CDC25C compensate for each other to maintain the proliferative capacity of intestinal epithelial stem and progenitor cells

Overexpression of CDC25B, CDC25C and phospho-CDC25C (Ser216) in vulvar squamous cell carcinomas are associated with malignant features and aggressive cancer phenotypes

<p>Abstract</p> <p>Background</p> <p>CDC25 phosphatases are important regulators of the cell cycle. Their abnormal expression detected in a number of tumors implies that their dysregulation is involved in malignant transformation. However, the role of CDC25s in vulvar cancer is still unknown. To shed light on their roles in the pathogenesis and to clarify their prognostic values, expression of CDC25A, CDC25B and CDC25C in a large series of vulvar squamous cell carcinomas were examined.</p> <p>Methods</p> <p>Expression of CDC25A, CDC25B, CDC25C and phosphorylated (phospho)-CDC25C (Ser216) were examined in 300 vulvar carcinomas using immunohistochemistry. Western blot analysis was utilized to demonstrate CDC25s expression in vulvar cancer cell lines. Kinase and phosphatase assays were performed to exclude cross reactivity among CDC25s isoform antibodies.</p> <p>Results</p> <p>High nuclear CDC25A and CDC25B expression were observed in 51% and 16% of the vulvar carcinomas, respectively, whereas high cytoplasmic CDC25C expression was seen in 63% of the cases. In cytoplasm, nucleus and cytoplasm/nucleus high phospho-CDC25C (Ser216) expression was identified in 50%, 70% and 77% of the carcinomas, respectively. High expression of CDC25s correlated significantly with malignant features, including poor differentiation and infiltration of vessel for CDC25B, high FIGO stage, presence of lymph node metastases, large tumor diameter, poor differentiation for CDC25C and high FIGO stage, large tumor diameter, deep invasion and poor differentiation for phospho-CDC25C (Ser216). In univariate analysis, high expression of phospho-CDC25C (Ser216) was correlated with poor disease-specific survival (p = 0.04). However, such an association was annulled in multivariate analysis.</p> <p>Conclusions</p> <p>Our results suggest that CDC25C and phospho-CDC25C (Ser216) play a crucial role and CDC25B a minor role in the pathogenesis and/or progression of vulvar carcinomas. CDC25B, CDC25C and phospho-CDC25C (Ser216) were associated with malignant features and aggressive cancer phenotypes. However, the CDC25s isoforms were not independently correlated to prognosis.</p

Systematic characterization of deubiquitylating enzymes for roles in maintaining genome integrity.

DNA double-strand breaks (DSBs) are perhaps the most toxic of all DNA lesions, with defects in the DNA-damage response to DSBs being associated with various human diseases. Although it is known that DSB repair pathways are tightly regulated by ubiquitylation, we do not yet have a comprehensive understanding of how deubiquitylating enzymes (DUBs) function in DSB responses. Here, by carrying out a multidimensional screening strategy for human DUBs, we identify several with hitherto unknown links to DSB repair, the G2/M DNA-damage checkpoint and genome-integrity maintenance. Phylogenetic analyses reveal functional clustering within certain DUB subgroups, suggesting evolutionally conserved functions and/or related modes of action. Furthermore, we establish that the DUB UCHL5 regulates DSB resection and repair by homologous recombination through protecting its interactor, NFRKB, from degradation. Collectively, our findings extend the list of DUBs promoting the maintenance of genome integrity, and highlight their potential as therapeutic targets for cancer.This is the author's accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ncb302