An investigation of the nature and reactivity of the carbonaceous species deposited on mordenite by reaction with methanol

An investigation of the nature of the carbonaceous species deposited upon mordenite by reaction with methanol has been undertaken. The nature of the species has been shown to be a strong function of both temperature and time on stream. Upon reaction at 300 degrees C a range of alkyl and aromatic species, consistent with the development of an active hydrocarbon pool, are evident and time on stream studies have shown that these are developed within 5 min. Upon reaction at 500 degrees C, a narrower range of hydrogen deficient aromatic species is evident. Thermal volatilisation analysis (TVA), not previously applied to the study of coked zeolites, is shown to be complementary to the more commonly applied C analysis, C-13 MAS NMR and TGA techniques

Restriction of GAGE protein expression to subpopulations of cancer cells is independent of genotype and may limit the use of GAGE proteins as targets for cancer immunotherapy

The GAGE cancer testis antigen gene family encodes products that can be recognized by autologous T cells, and GAGE proteins have been suggested as potential targets for cancer immunotherapy. Analysis of GAGE expression in tumours has primarily been performed at the level of gene transcription, whereas little is known about GAGE expression at the protein level. To evaluate the potential of GAGE proteins as targets for cancer-specific immunotherapy, we studied the expression of these proteins in normal and malignant cells/tissues using a novel panel of monoclonal antibodies. Immunohistochemical analysis of more than 250 cancer specimens demonstrated that GAGE proteins were frequently expressed in numerous cancer types and correlated with the expression of the cancer testis antigens MAGE-A1 and NY-ESO-1. Significant intercellular and subcellular differences in GAGE protein levels were observed, and most GAGE-positive tumours also contained cancer cells lacking GAGE expression. Studies of genetically homogenous cell lines with similar intercellular heterogeneous GAGE expression showed that GAGE expression was not associated with a specific genotype, but defined a phenotypically distinct population of cells. Surprisingly, in normal tissues we found that GAGE proteins were not restricted to testis, but were also present in a subset of oocytes of resting primordial follicles and in maturing oocytes. This is the first time that a cancer testis antigen has been reported in postfoetal oocytes. The lack of GAGE expression in a subset of cancer cells within GAGE-positive tumours has decisive implications for the development of GAGE-targeted cancer therapy

On the two first excited K=0 bands in U-238 and Pu-240

EO-enhanced spectra of conversion electrons taken after (alpha,alpha) and (alpha,2n) reactions and after projectile Coulomb excitation improve our knowledge about first and second excited bands in U-238 and Pu-240 built on O-2(+) and O-3(+) states which lie anomalously close together. The two bands are of different structure.</p

Integrative analysis of miRNA and gene expression reveals regulatory networks in tamoxifen-resistant breast cancer

Tamoxifen is an effective anti-estrogen treatment for patients with estrogen receptor-positive (ER+) breast cancer, however, tamoxifen resistance is frequently observed. To elucidate the underlying molecular mechanisms of tamoxifen resistance, we performed a systematic analysis of miRNA-mediated gene regulation in three clinically-relevant tamoxifen-resistant breast cancer cell lines (TamRs) compared to their parental tamoxifen-sensitive cell line. Alterations in the expression of 131 miRNAs in tamoxifen-resistant vs. parental cell lines were identified, 22 of which were common to all TamRs using both sequencing and LNA-based quantitative PCR technologies. Although the target genes affected by the altered miRNA in the three TamRs differed, good agreement in terms of affected molecular pathways was observed. Moreover, we found evidence of miRNA-mediated regulation of ESR1, PGR1, FOXM1 and 14-3-3 family genes. Integrating the inferred miRNA-target relationships, we investigated the functional importance of 2 central genes, SNAI2 and FYN, which showed increased expression in TamR cells, while their corresponding regulatory miRNA were downregulated. Using specific chemical inhibitors and siRNA-mediated gene knockdown, we showed that both SNAI2 and FYN significantly affect the growth of TamR cell lines. Finally, we show that a combination of 2 miRNAs (miR-190b and miR-516a-5p) exhibiting altered expression in TamR cell lines were predictive of treatment outcome in a cohort of ER+ breast cancer patients receiving adjuvant tamoxifen mono-therapy. Our results provide new insight into the molecular mechanisms of tamoxifen resistance and may form the basis for future medical intervention for the large number of women with tamoxifen-resistant ER+ breast cancer

Single-channel qEEG characteristics distinguish delirium from no delirium, but not postoperative from non-postoperative delirium

OBJECTIVE: This exploratory study examined quantitative electroencephalography (qEEG) changes in delirium and the use of qEEG features to distinguish postoperative from non-postoperative delirium. METHODS: This project was part of the DeltaStudy, a cross-sectional,multicenterstudy in Intensive Care Units (ICUs) and non-ICU wards. Single-channel (Fp2-Pz) four-minutes resting-state EEG was analyzed in 456 patients. After calculating 98 qEEG features per epoch, random forest (RF) classification was used to analyze qEEG changes in delirium and to test whether postoperative and non-postoperative delirium could be distinguished. RESULTS: An area under the receiver operatingcharacteristic curve (AUC) of 0.76 (95% Confidence Interval (CI) 0.71-0.80) was found when classifying delirium with a sensitivity of 0.77 and a specificity of 0.63 at the optimal operating point. The classification of postoperative versus non-postoperative delirium resulted in an AUC of 0.50 (95%CI 0.38-0.61). CONCLUSIONS: RF classification was able to discriminate delirium from no delirium with reasonable accuracy, while also identifying new delirium qEEG markers like autocorrelation and theta peak frequency. RF classification could not distinguish postoperative from non-postoperative delirium. SIGNIFICANCE: Single-channel EEG differentiates between delirium and no delirium with reasonable accuracy. We found no distinct EEG profile for postoperative delirium, which may suggest that delirium is one entity, whether it develops postoperatively or not

Level of arterial ligation in total mesorectal excision (TME): an anatomical study

Introduction: High-tie ligation is a common practice in rectal cancer surgery. However, it compromises perfusion of the proximal limb of the anastomosis. This anatomical study was designed to assess the value of low-tie ligation in order to obtain a tension-free anastomosis. Materials and methods: Consecutive high- and low-tie resections were performed on 15 formalin-fixed specimens, with or without splenic flexure mobilization. If the proximal colon limb could reach the superior aspect of the symphysis pubis with more than 3 cm, the limb would be long enough for a tension-free colorectal anastomosis. Results: In 80% of cases, it was not necessary to perform high-tie ligation as sufficient length was gained with low-tie ligation. The descending branch of the left colic artery was the limiting factor in the other 20% of cases. Resecting half the sigmoid resulted in four times as many tension-free anastomoses after low-tie resection. Conclusion: In the majority of cases, it was not necessary to perform high-tie ligation in order to create a tension-free anastomosis. Low-tie ligation was applicable in 80% of cases and might prevent anastomotic leakage due to insufficient blood supply of the proximal colon limb

Analytical variables influencing the performance of a miRNA based laboratory assay for prediction of relapse in stage I non-small cell lung cancer (NSCLC)

<p>Abstract</p> <p>Background</p> <p>Laboratory assays are needed for early stage non-small lung cancer (NSCLC) that can link molecular and clinical heterogeneity to predict relapse after surgical resection. We technically validated two miRNA assays for prediction of relapse in NSCLC. Total RNA from seventy-five formalin-fixed and paraffin-embedded (FFPE) specimens was extracted, labeled and hybridized to Affymetrix miRNA arrays using different RNA input amounts, ATP-mix dilutions, array lots and RNA extraction- and labeling methods in a total of 166 hybridizations. Two combinations of RNA extraction- and labeling methods (assays I and II) were applied to a cohort of 68 early stage NSCLC patients.</p> <p>Results</p> <p>RNA input amount and RNA extraction- and labeling methods affected signal intensity and the number of detected probes and probe sets, and caused large variation, whereas different ATP-mix dilutions and array lots did not. Leave-one-out accuracies for prediction of relapse were 63% and 73% for the two assays. Prognosticator calls ("no recurrence" or "recurrence") were consistent, independent on RNA amount, ATP-mix dilution, array lots and RNA extraction method. The calls were not robust to changes in labeling method.</p> <p>Conclusions</p> <p>In this study, we demonstrate that some analytical conditions such as RNA extraction- and labeling methods are important for the variation in assay performance whereas others are not. Thus, careful optimization that address all analytical steps and variables can improve the accuracy of prediction and facilitate the introduction of microRNA arrays in the clinic for prediction of relapse in stage I non-small cell lung cancer (NSCLC).</p

The Ubiquitin Ligase Ubr2, a Recognition E3 Component of the N-End Rule Pathway, Stabilizes Tex19.1 during Spermatogenesis

Ubiquitin E3 ligases target their substrates for ubiquitination, leading to proteasome-mediated degradation or altered biochemical properties. The ubiquitin ligase Ubr2, a recognition E3 component of the N-end rule proteolytic pathway, recognizes proteins with N-terminal destabilizing residues and plays an important role in spermatogenesis. Tex19.1 (also known as Tex19) has been previously identified as a germ cell-specific protein in mouse testis. Here we report that Tex19.1 forms a stable protein complex with Ubr2 in mouse testes. The binding of Tex19.1 to Ubr2 is independent of the second position cysteine of Tex19.1, a putative target for arginylation by the N-end rule pathway R-transferase. The Tex19.1-null mouse mutant phenocopies the Ubr2-deficient mutant in three aspects: heterogeneity of spermatogenic defects, meiotic chromosomal asynapsis, and embryonic lethality preferentially affecting females. In Ubr2-deficient germ cells, Tex19.1 is transcribed, but Tex19.1 protein is absent. Our results suggest that the binding of Ubr2 to Tex19.1 metabolically stabilizes Tex19.1 during spermatogenesis, revealing a new function for Ubr2 outside the conventional N-end rule pathway