Robust model predictive control for dynamics compensation in real-time hybrid simulation

Hybrid simulation is an efficient method to obtain the response of an emulated system subjected to dynamic excitation by combining loading-rate-sensitive numerical and physical substructures. In such simulations, the interfaces between physical and numerical substructures are usually implemented using transfer systems, i.e., an arrangement of actuators. To guarantee high fidelity of the simulation outcome, conducting hybrid simulation in hard real-time is required. Albeit attractive, real-time hybrid simulation comes with numerous challenges, such as the inherent dynamics of the transfer system used, along with communication interrupts between numerical and physical substructures, that introduce time delays to the overall hybrid model altering the dynamic response of the system under consideration. Hence, implementation of adequate control techniques to compensate for such delays is necessary. In this study, a novel control strategy is proposed for time delay compensation of actuator dynamics in hard real-time hybrid simulation applications. The method is based on designing a transfer system controller consisting of a robust model predictive controller along with a polynomial extrapolation algorithm and a Kalman filter. This paper presents a proposed tracking controller first, followed by two virtual real-time hybrid simulation parametric case studies, which serve to validate the performance and robustness of the novel control strategy. Real-time hybrid simulation using the proposed control scheme is demonstrated to be effective for structural performance assessment

Concomitant multiple anomalies of renal vessels and collecting system

Although anomalies of renal vessels and collecting system are relatively frequent, their concomitant occurrence is a rare event. During dissection of a 75-year-old male formalin-embalmed cadaver, we found multiple variations in the renal vessels and renal collecting system. Both kidneys were normal in size and anteriorly malrotated, with duplex collecting system and duplex ureter. One ureter drained the upper part of the kidney and the second ureter drained the lower part of the kidney. Superior and inferior collecting systems were separated by renal parenchyma. The right kidney had two renal arteries, the first renal artery (main renal artery) originating from the abdominal aorta, passing behind the inferior vena cava (IVC) and entering the kidney through the superior and inferior renal hilum. The second artery was the inferior polar artery. In addition, the right kidney had two renal veins as well. Three renal tributaries emerged from the upper and lower portion of the right renal hilum, and they joined to form the main renal vein which drained into the IVC. The lower renal vein was the inferior polar vein. The left kidney had four renal arteries (two hilar arteries and two polar arteries). The main left renal vein emerged from both superior and inferior left renal hilum, passed in front of the abdominal aorta and drained into the IVC. The left kidney also had the inferior polar vein which was divided behind the aorta (retro aortic vein) into two venous trunks. These venous trunks drained separately into posteromedialaspect of the IVC. Finally, the right testicular vein was formed by two tributaries and drained into the IVC, whereas the two left testicular veins drained separately into the left main renal vein

Colon cancer associated transcript-1 (CCAT1) expression in adenocarcinoma of the stomach

Background: Long non-coding RNAs (lncRNAs) have been shown to have functional roles in cancer biology and are dys-regulated in many tumors. Colon Cancer Associated Transcript -1 (CCAT1) is a lncRNA, previously shown to be significantly up-regulated in colon cancer. The aim of this study is to determine expression levels of CCAT1 in gastric carcinoma (GC). Methods: Tissue samples were obtained from patients undergoing resection for gastric carcinoma (n=19). For each patient, tumor tissue and normal appearing gastric mucosa were taken. Normal gastric tissues obtained from morbidly obese patients, undergoing laparoscopic sleeve gastrectomy served as normal controls (n=19). A human gastric carcinoma cell line (AGS) served as positive control. RNA was extracted from all tissue samples and CCAT1 expression was analyzed using quantitative real time-PCR (qRT-PCR). Results: Low expression of CCAT1 was identified in normal gastric mucosa samples obtained from morbidly obese patients [mean Relative Quantity (RQ) = 1.95±0.4]. AGS human gastric carcinoma cell line showed an elevated level of CCAT1 expression (RQ=8.02). Expression levels of CCAT1 were approximately 10.8 fold higher in GC samples than in samples taken from the negative control group (RQ=21.1±5 vs. RQ=1.95±0.4, respectively, p<0.001). Interestingly, CCAT1 expression was significantly overexpressed in adjacent normal tissues when compared to the negative control group (RQ = 15.25±2 vs. RQ=1.95±0.4, respectively, p<0.001). Tissues obtained from recurrent GC cases showed the highest expression levels (RQ = 88.8±31; p<0.001). Expression levels increased with tumor stage (T4- 36.4±15, T3- 16.1±6, T2- 4.7±1), however this did not reach statistical significance (p=0.2). There was no difference in CCAT1 expression between intestinal and diffuse type GC (RQ=22.4±7 vs. 22.4±16, respectively, p=0.9). Within the normal gastric tissue samples, no significant difference in CCAT1 expression was observed in helicobacter pylori negative and positive patients (RQ= 2.4±0.9 vs. 0.93±0.2, respectively, p=0.13). Conclusion: CCAT1 is up-regulated in gastric cancer, and may serve as a potential bio-marker for early detection and surveillance. © Ivyspring International Publisher

Differential expression of colon cancer associated transcript1 (CCAT1) along the colonic adenoma-carcinoma sequence

Cataloged from PDF version of article.Background: The transition from normal epithelium to adenoma and, to invasive carcinoma in the human colon is associated with acquired molecular events taking 5-10 years for malignant transformation. We discovered CCAT1, a non-coding RNA over-expressed in colon cancer (CC), but not in normal tissues, thereby making it a potential disease-specific biomarker. We aimed to define and validate CCAT1 as a CC-specific biomarker, and to study CCAT1 expression across the adenoma- carcinoma sequence of CC tumorigenesis. Methods: Tissue samples were obtained from patients undergoing resection for colonic adenoma(s) or carcinoma. Normal colonic tissue (n = 10), adenomatous polyps (n = 18), primary tumor tissue (n = 22), normal mucosa adjacent to primary tumor (n = 16), and lymph node(s) (n = 20), liver (n = 8), and peritoneal metastases (n = 19) were studied. RNA was extracted from all tissue samples, and CCAT1 expression was analyzed using quantitative real time-PCR (qRT-PCR) with confirmatory in-situ hybridization (ISH). Results: Borderline expression of CCAT1 was identified in normal tissue obtained from patients with benign conditions [mean Relative Quantity (RQ) = 5.9]. Significant relative CCAT1 up-regulation was observed in adenomatous polyps (RQ = 178.6 +/- 157.0; p = 0.0012); primary tumor tissue (RQ = 64.9 +/- 56.9; p = 0.0048); normal mucosa adjacent to primary tumor (RQ = 17.7 +/- 21.5; p = 0.09); lymph node, liver and peritoneal metastases (RQ = 11,414.5 +/- 12,672.9; 119.2 +/- 138.9; 816.3 +/- 2,736.1; p = 0.0001, respectively). qRT-PCR results were confirmed by ISH, demonstrating significant correlation between CCAT1 up-regulation measured using these two methods. Conclusion: CCAT1 is up-regulated across the colon adenoma-carcinoma sequence. This up-regulation is evident in pre-malignant conditions and through all disease stages, including advanced metastatic disease suggesting a role in both tumorigenesis and the metastatic process

Surface alignment, anchoring transitions, optical properties, and topological defects in the thermotropic nematic phase of organo-siloxane tetrapodes

We address the status of oxadiazole mesogens, C7 and C12, reported to show the biaxial nematic phase, by exploring material aspects (chemical stability, surface anchoring, optical and dielectric properties, topological defects) linked to the type of nematic order. We demonstrate that the isogyres splitting in conoscopic patterns of homeotropic state depends on sample thickness and is associated with variations of molecular tilt along the normal to substrates. We observe isolated topological point defects (boojums and hedgehogs), as well as nonsingular “escaped” disclinations pertinent only to the uniaxial nematic order. Our conclusion is that C7 and C12 feature only a uniaxial nematic phase and the apparent biaxiality is caused by surface effects

Novel germline variants identified in the inner mitochondrial membrane transporter TIMM44 and their role in predisposition to oncocytic thyroid carcinomas

Familial Non-Medullary Thyroid Carcinoma (fNMTC) represents 3–7% of all thyroid tumours and is associated with some of the highest familial risks among all cancers, with an inheritance pattern compatible with an autosomal dominant model with reduced penetrance. We previously mapped a predisposing locus, TCO (Thyroid tumour with Cell Oxyphilia) on chromosome 19p13.2, for a particular form of thyroid tumour characterised by cells with an abnormal proliferation of mitochondria (oxyphilic or oncocytic cells). In the present work, we report the systematic screening of 14 candidate genes mapping to the region of linkage in affected TCO members, that led us to identify two novel variants respectively in exon 9 and exon 13 of TIMM44, a mitochondrial inner membrane translocase for the import in the mitochondria of nuclear-encoded proteins. These variants were co-segregating with the TCO phenotype, were not present in a large group of controls and were predicted to negatively affect the protein (exon 9 change) or the transcript (exon 13 change). Functional analysis was performed in vitro for both changes and although no dramatic loss of function effects were identified for the mutant alleles, subtler effects might still be present that could alter Timm44 function and thus promote oncocytic tumour development. Thus we suggest that TIMM44 should be considered for further studies in independent samples of affected individuals with TCO

Update to the College of American Pathologists Reporting on Thyroid Carcinomas

Background The reporting of thyroid carcinomas follows the recommendations of the College of American Pathologists (CAP) protocols and includes papillary carcinoma, follicular carcinoma, anaplastic carcinoma and medullary carcinoma. Despite past and recent efforts, there are a number of controversial issues in the classification and diagnosis of thyroid carcinomas (TC) that, potentially impact on therapy and prognosis of patients with TC. Discussion The most updated version of the CAP thyroid cancer protocol incorporates recent changes in histologic classification as well as changes in the staging of thyroid cancers as per the updated American Joint Commission on Cancer staging manual. Among the more contentious issues in the pathology of thyroid carcinoma include the defining criteria for tumor invasiveness. While there are defined criteria for invasion, there is not universal agreement in what constitutes capsular invasion, angioinvasion and extrathyroidal invasion. Irrespective of the discrepant views on invasion, pathologists should report on the presence and extent (focal, widely) of capsular invasion, angioinvasion and extrathyroidal extension. These findings assist clinicians in their assessment of the recurrence risk and potential for metastatic disease. It is beyond the scope of this paper to detail the entire CAP protocol for thyroid carcinomas; rather, this paper addresses some of the more problematic issues confronting pathologists in their assessment and reporting of thyroid carcinomas. Conclusion The new CAP protocol for reporting of thyroid carcinomas is a step toward improving the clinical value of the histopathologic reporting of TC. Large meticulous clinico-pathologic and molecular studies with long term follow up are still needed in order to increase the impact of microscopic examination on the prognosis and management of TC

Evaluation of Best Supportive Care and Systemic Chemotherapy as Treatment Stratified according to the retrospective Peritoneal Surface Disease Severity Score (PSDSS) for Peritoneal Carcinomatosis of Colorectal Origin

Background: We evaluate the long-term survival of patients with peritoneal carcinomatosis (PC) treated with systemic chemotherapy regimens, and the impact of the of the retrospective peritoneal disease severity score (PSDSS) on outcomes. Methods: One hundred sixty-seven consecutive patients treated with PC from colorectal cancer between years 1987-2006 were identified from a prospective institutional database. These patients either received no chemotherapy, 5-FU/Leucovorin or Oxaliplatin/Irinotecan-based chemotherapy. Stratification was made according to the retrospective PSDSS that classifies PC patients based on clinically relevant factors. Survival analysis was performed using the Kaplan-Meier method and comparison with the log-rank test. Results: Median survival was 5 months (95% CI, 3-7 months) for patients who had no chemotherapy, 11 months (95% CI, 6-9 months) for patients treated with 5 FU/LV, and 12 months (95% CI, 4-20 months) for patients treated with Oxaliplatin/Irinotecan-based chemotherapy. Survival differed between patients treated with chemotherapy compared to those patients who did not receive chemotherapy (p = 0.026). PSDSS staging was identified as an independent predictor for survival on multivariate analysis [RR 2.8 (95%CI 1.5-5.4); p < 0.001]. Conclusion: A trend towards improved outcomes is demonstrated from treatment of patients with PC from colorectal cancer using modern systemic chemotherapy. The PSDSS appears to be a useful tool in patient selection and prognostication in PC of colorectal origin