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Real-time hybrid simulation has gained popularity over the last 20 years as a viable and cost-effective method of testing dynamic systems that cannot be tested using traditional methods. The emergence of multi-axial Real-time Hybrid Simulation (maRTHS) has led to an increase in the allowable fidelity of the numerical and experimental substructures. The testing community can now replicate multiple-degree-of-freedom (MDOF) responses of both substructures and thus can perform more representative tests. However, with this increased fidelity of the substructures comes an increased complexity of controlling these components. Specifically, multi-axial hydraulic actuator assemblages require nonlinear coordinate transformations to derive plant displacements as the force transducers on the actuators are not capable of performing this task directly. Recently, benchmark problems have been provided to the RTHS community in the form of virtual simulations. Virtual simulation refers to a fully virtual testing methodology where numerical and physical components are represented virtually. This approach enables the RTHS community to evaluate various control algorithms without the need to recreate physical components. This project aims to demonstrate the capability of computer vision-based displacement tracking in a realistic virtual simulation of the experimental substructure in avoiding excess nonlinear coordinate transforms. The tracking algorithm utilizing the Lucas-Kanade optical flow method is tested in the virtual simulation environment which is set up using real-time 3D creation engine, Unreal Engine 4 (UE4), and computer graphics software, Blender. This environment interfaces with MATLAB/Simulink, more specifically "Simulation Tool for v-maRTHS benchmark" developed for multi-axial tests. The result of this study establishes a novel framework for applying computer vision-based tracking algorithms and sensing in v-maRTHS simulations using simulated cameras within virtual simulation environments. A computer vision displacement tracking algorithm is developed and optimized to work in tandem with a MIMO PI controller to reduce tracking time delays within 31.25 milliseconds while tracking the nodal displacement and rotation of the frame within a normalized RMSE of 1.24 and 1.10 respectively. [ABSTRACT FROM AUTHOR]

The eBlock37 is a subscale electrically heated and heat-pipe-cooled prototype of a fast spectrum microreactor that is under development at Los Alamos National Laboratory. The prototype consists of an electrically heated core and gas-cooled heat exchanger. These subassemblies, both built from 316 L stainless steel, are thermally linked by an array of 37 sodium heat pipes that transfer a nominal 100 kW from the core at 700°C. An overarching objective of this effort is to overcome challenges associated with core block and heat exchanger manufacture and integration of high-temperature heat pipes into the assembly. Components that would be safety critical in an actual reactor, such as the heat pipe wicks, are being built under a Nuclear Quality Assurance 1 quality program. The completed assembly is intended for non-nuclear electrically heated testing, which will be conducted at a demonstration facility at Idaho National Laboratory. This paper provides a top-level summary of the efforts to date. [ABSTRACT FROM AUTHOR]

The classification of neoplasms of adenohypophysial cells is misleading because of the simplistic distinction between adenoma and carcinoma, based solely on metastatic spread and the poor reproducibility and predictive value of the definition of atypical adenomas based on the detection of mitoses or expression of Ki-67 or p53. In addition, the current classification of neoplasms of the anterior pituitary does not accurately reflect the clinical spectrum of behavior. Invasion and regrowth of proliferative lesions and persistence of hormone hypersecretion cause significant morbidity and mortality. We propose a new terminology, pituitary neuroendocrine tumor (PitNET), which is consistent with that used for other neuroendocrine neoplasms and which recognizes the highly variable impact of these tumors on patients. [ABSTRACT FROM AUTHOR]

5 human somatostatin receptor subtypes (sst1-5) mediate the antisecretory and antiproliferative eff ects of somatostatin. We examined somatostatin receptor protein expression in 28 human normal tissues. Immunostaining was performed with specific polyclonal antibodies for sst1-5. Staining pattern and distribution of ssts were evaluated. Anterior pituitary was positively stained for all 5 ssts. Pancreatic islets exhibited a positive staining for sst1-3 and sst5. Adrenal cortex expressed all 5 receptor subtypes, while the medulla was positive for sst3 and sst5 only. The thyroid expressed sst5 only, limited to single interfollicular cells. All 5 ssts were detected in the ovary, limited to luteinized granulosa cells of the corpus luteum. In the testis, sst2A was detected in the basal parts of the tubules, while sst5 was positively stained in the luminal parts. Sst1 was found in Leydig cells only. Stomach was positively stained for all 5 ssts. Investigation of the kidney revealed diff erential expression, with sst2A being found in the glomerules. The tubules expressed all 5 ssts. In the bone marrow cells of the granulocytopoiesis expressed sst2A only. The cerebellum expressed sst5 in a certain cell type, representing presumably Purkinje cells, while sst2A was stained in intercellular fibers. The expression of somatostatin receptor subtypes in a variety of human normal tissues may indicate a physiological role in these organs. Somatostatin analogues may offer new diagnostic and therapeutic implications for tumours related to these tissues. However, treatment of defined tumours with somatostatin analogues may also alter other normal tissues. [ABSTRACT FROM AUTHOR]

Objective: Somatostatin analogues (SSA) reduce autonomous GH secretion by activating somatostatin receptors (sst) 2 and 5 in 50-60% of acromegalic patients. However, by inhibiting insulin secretion these SSA reduce glucose tolerance. DG3173 is a novel SSA with additional binding to sst4 and low insulin-suppressing activity. We investigated the effect of DG3173, including its relation to specific tumour characteristics, on GH secretion in human somatotroph adenoma cell cultures (hSA) in comparison with Octreotide. Methods: Twenty-seven hSA were characterised immunohistochemically for their hormone- and sstexpression, granularity and pre-surgical therapy with SSA. GH was determined in supernatants of hSA treated with DG3173 or Octreotide in time- (n=6) and dose-response (n=21) experiments. A positive response was defined as GH suppression to below 80% of baseline. Results: In the dose-response experiments DG3173 suppressed GH secretion in more adenomas than Octreotide (10/21 vs 5/21), including 38% (6/16) of Octreotide non-responders. In responders the extent of GH suppression and IC50 were comparable for both SSA. The response-rate of both SSA was higher in monohormonal vs bihormonal adenomas, yet GH declined similarly in both groups. Neither pre-surgical SSA (n=6) nor tumour morphology was related to the GH response. However, semiquantitative analysis indicated a small but significant negative correlation between the GH response to Octreotide and the immunoreactivity scores of sst2 expression. Conclusions: DG3173 equalled Octreotide in suppressing GH secretion in hSA. Since DG3173 suppressed GH in some Octreotide-non-responsive adenomas, its clinical effectiveness will be worth testing. Moreover, its reduced insulin-suppressive potency would make it a valuable alternative to Octreotide. [ABSTRACT FROM AUTHOR]

Objective: Localization of microadenomas in Cushing ' s disease may be difficult as in up to 45 % of patients sellar MRI fails to detect a pituitary tumor. Intraoperative transsphenoidal ultrasound may identify microadenomas as hyperechoic structures. We report on the first 18 consecutive cases with intraoperative use of a new device for direct contact high-frequency-ultrasound in patients with Cushing ' s disease. Patients and technique: 18 patients (14 female, 4 male, age 24 - 71 years) with typical endocrinological findings for Cushing ' s disease were included in the study. One macroadenoma and 13 microadenomas were suspected or identified preoperatively by MRI. In 4 cases, two of them with recurrent disease, sellar MRIs were negative. During transsphenoidal microsurgery an end fire ultrasound-probe (B-mode frequency range 7.5 - 13 Mhz, field of view 5 mm, penetration 20 mm) was introduced after opening of sellar floor. The pituitary gland was scanned in direct contact to the capsule. Results: In 13 out of 17 cases (77 % ) with later on proven microadenomas high-frequencyultrasound identified the tumors as hyperechoic masses, including 3 of the 4 cases with negative preoperative MRI. In 2 cases ultrasound correctly localized the tumor at a site different from MRI finding (MRI false positive). In the macroadenoma, identification of the border between tumor and anterior pituitary gland was not possible. In all 18 patients postoperative early decline of serum cortisol to subnormal levels confirmed remission of hypercortisolism (100 % ). Other pituitary functions were unaltered in 17 cases (94 % ). Conclusions: Intraoperative scanning of the pituitary gland with high-frequency-ultrasound probes may identify intrapituitary anatomy andpathologies even in MRI-negative cases. This may prevent extensive exploration of the gland with the risk of subsequent hypopituitarism. [ABSTRACT FROM AUTHOR]

In this study, we evaluate whether Snail is expressed in adrenocortical cancer (ACC) and if its expression is related to patient outcome. One of the best known functions of the zinc-finger transcription factor Snail is to induce epithelial-to-mesenchymal transition (EMT). Increasing evidence suggests that EMT plays a pivotal role in tumour progression and metastatic spread. Snail and E-cadherin expression were assessed by immunohistochemistry in 26 resected ACCs and real-time quantitative RT-PCR expression analysis was performed. Data were correlated with clinical outcome and in particular with overall patient survival. Seventeen of 26 (65%) ACC tumour samples expressed Snail when assessed by immunohistochemistry. Snail expression was neither detected in normal adrenocortical tissue, nor in benign adrenocortical adenomas. Expression levels were confirmed on the mRNA level by Real-Time-PCR. Survival rates were significantly decreased in Snail-positive tumours compared to Snail-negative tumours: 10 out of 16 vs one out of eight patients succumbed to disease after a median follow up of 14.5 and 28.5 months, respectively (P=0.03). Patients with Snail-expressing ACCs presented in advanced disease (11 out of 12 vs 6 out of 14, P=0.01) and tend to develop distant metastases more frequently than patients with negative staining (7 out of 11 vs two out of eight, P=0.19). In conclusion, we describe for the first time that Snail is expressed in a large subset of ACCs. Furthermore, Snail expression is associated with decreased survival, advanced disease and higher risk of developing distant metastases. [ABSTRACT FROM AUTHOR]

A case of a 70-year-old man presenting with exsudative enteropathy due to light-chain-associated amyloidosis is reported. The diagnosis of systemic mastocytosis associated with IgG/λ plasma cell myeloma and secondary generalised amyloidosis was carried out by morphological evaluation of bone marrow biopsy. The c-kit point mutation D816Y was detected by molecular analysis. Two years before, a cystadenolymphoma of the left parotid gland had been removed. A moderate increase of loosely scattered spindle- shaped mast cells, a subpopulation of them expressing CD25, an antigen that is not expressed by normal or reactive mast cells, was shown by retrospective analysis carried out on art intraparotideal lymph node. The c-kit mutation D816Y was shown by the molecular analysis of the lymph node. In summary, the notion that systemic mastocytosis may very rarely be associated with B cell neoplasms and that neoplastic mast cell infiltrates may be obscured because of only a minimal increase of atypical mast cells, which are outnumbered by other non-neoplastic cells in the same tissue, is supported by this case. This finding was preliminarily termed ‘occult’ mastocytosis. [ABSTRACT FROM AUTHOR]

Summary Background. Although craniopharyngiomas have been examined in several microscopical studies to date, immunohistochemical analysis has not been sufficient. Method. In addition to the routine haematoxylin and eosin staining, 38 cases of intra- and/or supra-sellar craniopharyngioma, including 34 adamatinomatous and 4 squamous papillary types, were studied using immunohistochemistry for expression of four types of cytokeratin. Findings. Histological examination found epithelial cells in 26 of 38 (68.4%) cases. However, cytokeratins were demonstrated in 35 of 38 (92.1%) cases. The remaining 3 cases without demonstration of epithelial cell nests were supposed to be adamantinomatous craniopharyngiomas based on the findings in the stroma. In 31 of 34 adamantinomatous craniopharyngioma cases, the epithelium was detected by immunostaining for cytokeratins. The epithlieum expressed 56 kDa (KL-1) and 40 kDa (cytokeratin 19) cytokeratins with similar staining patterns and intensities. The staining intensity of 54 kDa cytokeratin (cytokeratin 7) was similar to that of the high molecular weight cytokeratin (keratin M-903). However, in many cases (15 of 27), immunoreactivity of cytokeratin 7 was not demonstrated in an outer palisaded basal layer. In all 4 squamous papillary craniopharyngiomas, moderate staining with cytokeratin 7 appeared in the superficial layer, whereas basal or mid-zone epithelial cells were negative for cytokeratin 7. The basal layer stained negatively for KL-1, as well as cytokeratin 7. Interpretation. Immunostaining for cytokeratin is valuable in the investigation of craniopharyngioma, especially when specimens contain only a small or questionable part of epithelium. Most notably, KL-1 or cytokeratin 7 stainings are suitable for analyzing these tumours, with special reference to histological subtypes. [ABSTRACT FROM AUTHOR]