Signature of structure failure using asymmetric and broadening factors of brillouin spectrum

Copyright © 2005 IEEEWe introduce a novel data analysis approach based on the extraction of peak strain, asymmetric and broadening factors of the Brillouin spectrum measured with the distributed Brillouin sensor (DBS). Such an approach provides simultaneously global and local strains, describing the status of the structure, at the contrary of average strain measurements. These results are confirmed by a trial on a composite column subjected to vertical and bending loads. This demonstrates that the DBS is a powerful tool to give the signature of the structure failure and then to identify early problems in structures that none of existing point sensors can detect.Fabien Ravet, Xiaoyi Bao, Togay Ozbakkaloglu, and Murat Saatciogl

The loss of NKX3.1 expression in testicular – and prostate – cancers is not caused by promoter hypermethylation

BACKGROUND: Recent studies have demonstrated that the NKX3.1 protein is commonly down-regulated in testicular germ cell tumors (TGCTs) and prostate carcinomas. The homeobox gene NKX3.1 maps to chromosome band 8p21, which is a region frequently lost in prostate cancer, but not in TGCT. Mutations have not been reported in the NKX3.1 sequence, and the gene is hypothesized to be epigenetically inactivated. In the present study we examined the methylation status of the NKX3.1 promoter in relevant primary tumors and cell lines: primary TGCTs (n = 55), intratubular germ cell neoplasias (n = 7), germ cell tumor cell lines (n = 3), primary prostate adenocarcinomas (n = 20), and prostate cancer cell lines (n = 3) by methylation-specific PCR and bisulphite sequencing. RESULTS AND CONCLUSIONS: Down-regulation of NKX3.1 expression was generally not caused by promoter hypermethylation, which was only found in one TGCT. However, other epigenetic mechanisms, such as modulation of chromatin structure or modifications of histones, may explain the lack of NKX3.1 expression, which is seen in most TGCTs and prostate cancer specimens

Integrated psychological treatment for substance use and co-morbid anxiety or depression vs. treatment for substance use alone. A systematic review of the published literature

<p>Abstract</p> <p>Background</p> <p>There is an increasing consensus in favour of integrated treatment of substance use disorders and co-morbid conditions, such as depression or anxiety. However, up till now no systematic reviews have been published.</p> <p>Methods</p> <p>Based on a systematic search of MedLine and PsychInfo, 9 trials of integrated treatment for depression or anxiety plus substance use disorder were identified. Where possible, meta-analyses were carried out, using random effects models.</p> <p>Results</p> <p>Meta-analyses were carried out for integrated treatment for depression and substance use disorders on a number of outcomes. No meta-analysis could be carried out for integrated treatment for anxiety and substance use disorders, due to multivariate reporting of outcomes in original articles. Integrated treatment for depression and substance abuse produced significant effects on percent days abstinent at follow-up. Differences in retention and symptoms were non-significant, but favoured the experimental condition. For studies of integrated treatment for co-morbid anxiety disorders and substance use disorders, no meta-analysis could be carried out. Several studies of integrated treatment for anxiety and substance use disorders reported that patients assigned to substance use treatment only fared better.</p> <p>Conclusion</p> <p>Psychotherapeutic treatment for co-morbid depression and substance use disorders is a promising approach, but is not sufficiently empirically supported at this point. Psychotherapeutic treatment for co-morbid anxiety and substance use disorders is not empirically supported. There is a need for more trials to replicate the findings from studies of integrated treatment for depression and substance use disorders, and for the development of new treatment options for co-morbid anxiety and substance use disorders.</p

IRE1α-XBP1s pathway promotes prostate cancer by activating c-MYC signaling

Activation of endoplasmic reticulum (ER) stress/the unfolded protein response (UPR) has been linked to cancer, but the molecular mechanisms are poorly understood and there is a paucity of reagents to translate this for cancer therapy. Here, we report that an IRE1α RNase-specific inhibitor, MKC8866, strongly inhibits prostate cancer (PCa) tumor growth as monotherapy in multiple preclinical models in mice and shows synergistic antitumor effects with current PCa drugs. Interestingly, global transcriptomic analysis reveal that IRE1α-XBP1s pathway activity is required for c-MYC signaling, one of the most highly activated oncogenic pathways in PCa. XBP1s is necessary for optimal c-MYC mRNA and protein expression, establishing, for the first time, a direct link between UPR and oncogene activation. In addition, an XBP1-specific gene expression signature is strongly associated with PCa prognosis. Our data establish IRE1α-XBP1s signaling as a central pathway in PCa and indicate that its targeting may offer novel treatment strategies.</p

3, 3′5 Triiodo L Thyronine Induces Apoptosis in Human Breast Cancer MCF-7cells, Repressing SMP30 Expression through Negative Thyroid Response Elements

Thyroid hormones regulate cell proliferation, differentiation as well as apoptosis. However molecular mechanism underlying apoptosis as a result of thyroid hormone signaling is poorly understood. The antiapoptotic role of Senescence Marker Protein-30 (SMP30) has been characterized in response to varieties of stimuli as well as in knock out model. Our earlier data suggest that thyroid hormone 3, 3'5 Triiodo L Thyronine (T(3)), represses SMP30 in rat liver.In highly metastatic MCF-7, human breast cancer cell line T3 treatment repressed SMP30 expression leading to enhanced apoptosis. Analysis by flow cytometry and other techniques revealed that overexpression and silencing of SMP30 in MCF-7 resulted in decelerated and accelerated apoptosis respectively. In order to identify the cis-acting elements involved in this regulation, we have analyzed hormone responsiveness of transiently transfected hSMP30 promoter deletion reporter vectors in MCF-7 cells. As opposed to the expected epigenetic outcome, thyroid hormone down regulated hSMP30 promoter activity despite enhanced recruitment of acetylated H3 on thyroid response elements (TREs). From the stand point of established epigenetic concept we have categorised these two TREs as negative response elements. Our attempt of siRNA mediated silencing of TRβ, reduced the fold of repression of SMP30 gene expression. In presence of thyroid hormone, Trichostatin- A (TSA), which is a Histone deacetylase (HDAC) inhibitor further inhibited SMP30 promoter activity. The above findings are in support of categorisation of both the thyroid response element as negative response elements as usually TSA should have reversed the repressions.This is the first report of novel mechanistic insights into the remarkable downregulation of SMP30 gene expression by thyroid hormone which in turn induces apoptosis in MCF-7 human breast cancer cells. We believe that our study represents a good ground for future effort to develop new therapeutic approaches to challenge the progression of breast cancer

Performance of industrial buildings during the Emilia earthquakes in Northern Italy and recommendations for their strengthening

A series of earthquakes, the highest of magnitude M w 5.9, hit a portion of the Po Valley in Northern Italy, which was only recently classified as seismic. The paper reports the findings and the lessons learnt from a preliminary field survey which was conducted immediately after the second event. As a result of the economic attitude of the affected area, and possibly of the characteristics of the event, an unprecedented number of industrial precast buildings were affected, resulting into most of the casualties as well as in large economic losses. Whereas most of the damaged and collapsed buildings were designed for gravity loads only, evidence of poor behavior of some precast buildings designed according to seismic provisions were discovered. The paper provides a description of the performance of precast buildings, highlighting the deficiencies that led to their poor behavior as well as some preliminary recommendations

A conserved C-terminal sequence that is deleted in v-ErbA is essential for the biological activities of c-ErbA (the thyroid hormone receptor).

The thyroid hormone (T3) receptor type alpha, the c-ErbA alpha proto-oncoprotein, stimulates transcription of T3-dependent promoters, interferes with AP-1 activity, and induces erythroid differentiation in a ligand-dependent manner. The v-ErbA oncoprotein does not bind hormone and has lost all of these activities. Using c-ErbA/v-ErbA chimeras, we found that a deletion of 9 amino acids, conserved among many members of the nuclear receptor superfamily, which are located at the extreme carboxy terminus of c-ErbA alpha is responsible for loss of both transactivation and transcriptional interference activities. Single, double, and triple amino acid substitutions within this region completely abolished T3-dependent transcriptional activation, interference with AP-1 activity, and decreased T3 binding by c-ErbA alpha. However, the lower T3 binding by these mutants does not fully account for the loss of transactivation and transcriptional interference, since a c-ErbA/v-ErbA chimera which was similarly reduced in T3 binding activity has retained both of these functions. Deletion of homologous residues in the retinoic acid receptor alpha (RAR alpha) resulted in a similar loss of transactivation and transcriptional interference activities. The ability of c-ErbA alpha to induce differentiation of transformed erythroblasts is also impaired by all of the mutations introduced into the conserved carboxy-terminal sequence. We conclude that this 9-amino-acid conserved region is essential for normal biological function of c-ErbA alpha and RAR alpha and possibly other T3 and RA receptors