The surface science of quasicrystals

The surfaces of quasicrystals have been extensively studied since about 1990. In this paper we review work on the structure and morphology of clean surfaces, and their electronic and phonon structure. We also describe progress in adsorption and epitaxy studies. The paper is illustrated throughout with examples from the literature. We offer some reflections on the wider impact of this body of work and anticipate areas for future development. (Some figures in this article are in colour only in the electronic version

Whole-exome sequencing uncovers frequent GNAS mutations in intraductal papillary mucinous neoplasms of the pancreas

Intraductal papillary mucinous neoplasm (IPMN) is a common pancreatic cystic neoplasm that is often invasive and metastatic, resulting in a poor prognosis. Few molecular alterations unique to IPMN are known. We performed whole-exome sequencing for a primary IPMN tissue, which uncovered somatic mutations in KCNF1, DYNC1H1, PGCP, STAB1, PTPRM, PRPF8, RNASE3, SPHKAP, MLXIPL, VPS13C, PRCC, GNAS, KRAS, RBM10, RNF43, DOCK2, and CENPF. We further analyzed GNAS mutations in archival cases of 118 IPMNs and 32 pancreatic ductal adenocarcinomas (PDAs), which revealed that 48 (40.7%) of the 118 IPMNs but none of the 32 PDAs harbored GNAS mutations. G-protein alpha-subunit encoded by GNAS and its downstream targets, phosphorylated substrates of protein kinase A, were evidently expressed in IPMN; the latter was associated with neoplastic grade. These results indicate that GNAS mutations are common and specific for IPMN, and activation of G-protein signaling appears to play a pivotal role in IPMN

Study on the clinical application of pulsed DC magnetic technology for tracking of intraoperative head motion during frameless stereotaxy

BACKGROUND: Tracking of post-registration head motion is one of the major problems in frameless stereotaxy. Various attempts in detecting and compensating for this phenomenon rely on a fixed reference device rigidly attached to the patient's head. However, most of such reference tools are either based on an invasive fixation technique or have physical limitations which allow mobility of the head only in a restricted range of motion after completion of the registration procedure. METHODS: A new sensor-based reference tool, the so-called Dynamic Reference Frame (DRF) which is designed to allow an unrestricted, 360° range of motion for the intraoperative use in pulsed DC magnetic navigation was tested in 40 patients. Different methods of non-invasive attachment dependent on the clinical need and type of procedure, as well as the resulting accuracies in the clinical application have been analyzed. RESULTS: Apart from conventional, completely rigid immobilization of the head (type A), four additional modes of head fixation and attachment of the DRF were distinguished on clinical grounds: type B1 = pin fixation plus oral DRF attachment; type B2 = pin fixation plus retroauricular DRF attachment; type C1 = free head positioning with oral DRF; and type C2 = free head positioning with retroauricular DRF. Mean fiducial registration errors (FRE) were as follows: type A interventions = 1.51 mm, B1 = 1.56 mm, B2 = 1.54 mm, C1 = 1.73 mm, and C2 = 1.75 mm. The mean position errors determined at the end of the intervention as a measure of application accuracy were: 1.45 mm in type A interventions, 1.26 mm in type B1, 1.44 mm in type B2, 1.86 mm in type C1, and 1.68 mm in type C2. CONCLUSION: Rigid head immobilization guarantees most reliable accuracy in various types of frameless stereotaxy. The use of an additional DRF, however, increases the application scope of frameless stereotaxy to include e.g. procedures in which rigid pin fixation of the cranium is not required or desired. Thus, continuous tracking of head motion allows highly flexible variation of the surgical strategy including intraoperative repositioning of the patient without impairment of navigational accuracy as it ensures automatic correction of spatial distortion. With a dental cast for oral attachment and the alternative option of non-invasive retroauricular attachment, flexibility in the clinical use of the DRF is ensured

Is there a role for the quantification of RRM1 and ERCC1 expression in pancreatic ductal adenocarcinoma?

<p>Abstract</p> <p>Background</p> <p>RRM1 and ERCC1 overexpression has been extensively investigated as potential predictive markers of tumor sensitivity to conventional chemotherapy agents, most thoroughly in lung cancer. However, data in pancreatic cancer are scarce.</p> <p>Methods</p> <p>We investigated the mRNA and protein expression of ERCC1 and RRM1 by RT-PCR and immunohistochemistry (IHC) in formalin-fixed, paraffin-embedded pancreatic ductal carcinoma (PDA) tissues. The primary outcome investigated was the association between RRM1 and ERCC1 expression and overall survival (OS) or disease-free survival (DFS).</p> <p>Results</p> <p>A total of 94 patients with resected PDA were included in this study. Most of them (87%) received gemcitabine based chemotherapy. Data for OS analysis was available in all cases but only 68% had enough information to estimate DFS. IHC analysis revealed information for 99% (93/94) and 100% of the cases for RRM1 and ERCC1 expression respectively. However, PCR data interpretation was possible in only 49 (52%) and 79 (84%) cases respectively. There was no significant association between high or low expression of either RRM1 or ERCC1, detected by IHC and OS (14.4 vs. 19.9 months; <it>P </it>= 0.5 and 17.1 vs. 19.9; <it>P </it>= 0.83 respectively) or PCR and OS (48.0 vs. 24.1 months; <it>P </it>= 0.21 and 22.0 vs. 16.0 months; <it>P </it>= 0.39 respectively). Similar results were obtained for DFS.</p> <p>Conclusions</p> <p>RRM1 and ERCC1 expression does not seem to have a clear predictive or prognostic value in pancreatic cancer. Our data raise some questions regarding the real clinical and practical significance of analyzing these molecules as predictors of outcomes.</p

DNA Methylation-Independent Reversion of Gemcitabine Resistance by Hydralazine in Cervical Cancer Cells

BACKGROUND: Down regulation of genes coding for nucleoside transporters and drug metabolism responsible for uptake and metabolic activation of the nucleoside gemcitabine is related with acquired tumor resistance against this agent. Hydralazine has been shown to reverse doxorubicin resistance in a model of breast cancer. Here we wanted to investigate whether epigenetic mechanisms are responsible for acquiring resistance to gemcitabine and if hydralazine could restore gemcitabine sensitivity in cervical cancer cells. METHODOLOGY/PRINCIPAL FINDINGS: The cervical cancer cell line CaLo cell line was cultured in the presence of increasing concentrations of gemcitabine. Down-regulation of hENT1 & dCK genes was observed in the resistant cells (CaLoGR) which was not associated with promoter methylation. Treatment with hydralazine reversed gemcitabine resistance and led to hENT1 and dCK gene reactivation in a DNA promoter methylation-independent manner. No changes in HDAC total activity nor in H3 and H4 acetylation at these promoters were observed. ChIP analysis showed H3K9m2 at hENT1 and dCK gene promoters which correlated with hyper-expression of G9A histone methyltransferase at RNA and protein level in the resistant cells. Hydralazine inhibited G9A methyltransferase activity in vitro and depletion of the G9A gene by iRNA restored gemcitabine sensitivity. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that acquired gemcitabine resistance is associated with DNA promoter methylation-independent hENT1 and dCK gene down-regulation and hyper-expression of G9A methyltransferase. Hydralazine reverts gemcitabine resistance in cervical cancer cells via inhibition of G9A histone methyltransferase