Verification of cardiac tissue electrophysiology simulators using an N-version benchmark

Ongoing developments in cardiac modelling have resulted, in particular, in the development of advanced and increasingly complex computational frameworks for simulating cardiac tissue electrophysiology. The goal of these simulations is often to represent the detailed physiology and pathologies of the heart using codes that exploit the computational potential of high-performance computing architectures. These developments have rapidly progressed the simulation capacity of cardiac virtual physiological human style models; however, they have also made it increasingly challenging to verify that a given code provides a faithful representation of the purported governing equations and corresponding solution techniques. This study provides the first cardiac tissue electrophysiology simulation benchmark to allow these codes to be verified. The benchmark was successfully evaluated on 11 simulation platforms to generate a consensus gold-standard converged solution. The benchmark definition in combination with the gold-standard solution can now be used to verify new simulation codes and numerical methods in the future.     

Production and Characterization of Peptide Antibodies to the C-Terminal of Frameshifted Calreticulin Associated with Myeloproliferative Diseases

Myeloproliferative Neoplasms (MPNs) constitute a group of rare blood cancers that are characterized by mutations in bone marrow stem cells leading to the overproduction of erythrocytes, leukocytes, and thrombocytes. Mutations in calreticulin (CRT) genes may initiate MPNs, causing a novel variable polybasic stretch terminating in a common C-terminal sequence in the frameshifted CRT (CRTfs) proteins. Peptide antibodies to the mutated C-terminal are important reagents for research in the molecular mechanisms of MPNs and for the development of new diagnostic assays and therapies. In this study, eight peptide antibodies targeting the C-terminal of CRTfs were produced and characterised by modified enzyme-linked immunosorbent assays using resin-bound peptides. The antibodies reacted to two epitopes: CREACLQGWTE for SSI-HYB 385-01, 385-02, 385-03, 385-04, 385-07, 385-08, and 385-09 and CLQGWT for SSI-HYB 385-06. For the majority of antibodies, the residues Cys¹, Trp⁹, and Glu¹¹ were essential for reactivity. SSI-HYB 385-06, with the highest affinity, recognised recombinant CRTfs produced in yeast and the MARIMO cell line expressing CRTfs when examined in Western immunoblotting. Moreover, SSI-HYB 385-06 occasionally reacted to CRTfs from MPN patients when analysed by flow cytometry. The characterized antibodies may be used to understand the role of CRTfs in the pathogenesis of MPNs and to design and develop new diagnostic assays and therapeutic targets.     

Effect of thermal treatment on glucosinolates and antioxidant-related parameters in red cabbage (Brassica oleracea L. ssp. capitata f. rubra)

The effects of various thermal processing treatments (blanching, boiling and steaming) of red cabbage, Brassica oleracea L. ssp. capitata f. rubra cv. ‘Autoro’, were assessed for the levels of glucosinolates (GLS), total phenols (TP), total monomeric anthocyanins (TMA), l-ascorbic acid (L-AA) and soluble sugars, as well as for the antioxidant potential by the ferric reducing ability power (FRAP) and oxygen radical absorbance capacity (ORAC) assays. Individual native GLS were determined by ion-pair HPLC-MS/DAD. There were significant (p < 0.05) losses in blanched red cabbage: TP, 43%, TMA 59%, FRAP 42%, ORAC 51%, L-AA 48% and soluble sugars 45%. Boiling gave less extensive reductions: TP 16%, TMA 41%, FRAP 17%, ORAC 19%, L-AA 24% and soluble sugars 19%. Steaming caused no losses for TP, ORAC, FRAP or soluble sugars. However, significant reductions were found for TMA and L-AA, with 29% and 11%, respectively. In general losses were accounted for in the processing waters; however, TMA was not fully recovered, indicating degradation. Total GLS were severely affected by processing, with reductions of 64%, 38% and 19% in blanched, boiled and steamed red cabbage, respectively. Total aliphatic and indole GLS were similarly affected. Lost GLS were partially recovered in the processing water.     

Large area deposition of Pb(Zr,Ti)O<Subscript>3</Subscript> thin films for piezoelectric MEMS devices

Pb(Zr,Ti)O₃ (PZT) thin films deposited on insulating ZrO₂ buffered silicon wafer are intended to be employed for in-plane polarized piezoelectric MEMS devices. Multi-target reactive sputtering system for large area deposition of in-situ crystallized PZT thin films and the ZrO₂ buffer layer has been employed. The interface analysis of multilayer structures by high resolution transmission microscope, X-ray diffraction, optical refraction, and absorption spectra studies has been presented. At a substrate temperature of 520°C and excess lead deposition condition, the formation of a PZT superstructure has been revealed. The substrate temperature of 580°C leads to the crystallization of PZT directly into a single phase perovskite crystal structure. A pronounced Urbach behavior in our PZT thin films has been observed by optical absorption studies. The surface roughness of PZT films deposited on a ZrO₂ buffer layer is much higher than that on conducting platinized silicon wafer.     

Mass Spectrometric Analysis of Cerebrospinal Fluid Ubiquitin in Alzheimer's Disease and Parkinsonian Disorders

1 Purpose

Dysfunctional proteostasis, with decreased protein degradation and an accumulation of ubiquitin into aggregated protein inclusions, is a feature of neurodegenerative diseases. Identifying new potential biomarkers in cerebrospinal fluid (CSF) reflecting this process could contribute important information on pathophysiology.

2 Experimental design

A developed method combining SPE and PRM‐MS is employed to monitor the concentration of ubiquitin in CSF from subjects with Alzheimer's disease (AD), Parkinson's disease (PD), and progressive supranuclear palsy (PSP). Four independent cross‐sectional studies are conducted, studies 1–4, including controls (n = 86) and participants with AD (n = 60), PD (n = 15), and PSP (n = 11).

3 Results

The method shows a repeatability and intermediate precision not exceeding 6.1 and 7.9%, respectively. The determined LOD is 0.1 nm and the LOQ range between 0.625 and 80 nm . The CSF ubiquitin concentration is 1.2–1.5‐fold higher in AD patients compared with controls in the three independent AD‐control studies (Study 1, p < 0.001; Study 2, p < 0.001; and Study 3, p = 0.003). In the fourth study, there is no difference in PD or PSP, compared to controls.

4 Conclusion and clinical relevance

CSF ubiquitin may reflect dysfunctional proteostasis in AD. The described method can be used for further exploration of ubiquitin as a potential biomarker in neurodegenerative diseases.     

Will musculoskeletal and visual stress change when Visual Display Unit (VDU) operators move from small offices to an ergonomically optimized office landscape?

This study investigated the effect of moving from small offices to a landscape environment for 19 Visual Display Unit (VDU) operators at Alcatel Denmark AS. The operators reported significantly improved lighting condition and glare situation. Further, visual discomfort was also significantly reduced on a Visual Analogue Scale (VAS). There was no significant correlation between lighting condition and visual discomfort neither in the small offices nor in the office landscape. However, visual discomfort correlated significantly with glare in small offices i.e. more glare is related to more visual discomfort. This correlation disappeared after the lighting system in the office landscape had been improved. There was also a significant correlation between glare and itching of the eyes as well as blurred vision in the small offices, i.e. more glare more visual symptoms. Experience of pain was found to reduce the subjective assessment of work capacity during VDU tasks. There was a significant correlation between visual discomfort and reduced work capacity in small offices and in the office landscape. When moving from the small offices to the office landscape, there was a significant reduction in headache as well as back pain. No significant changes in pain intensity in the neck, shoulder, forearm, and wrist/hand were observed.The pain levels in different body areas were significantly correlated with subjective assessment of reduced work capacity in small offices and in the office landscape.By careful design and construction of an office landscape with regard to lighting and visual conditions, transfer from small offices may be acceptable from a visual-ergonomic point of view.     

Evolution-in-materio: solving computational problems using carbon nanotube–polymer composites

Evolution-in-materio uses evolutionary algorithms to exploit properties of materials to solve computational problems without requiring a detailed understanding of such properties. We show that using a purpose-built hardware platform called Mecobo, it is possible to solve computational problems by evolving voltages and signals applied to an electrode array covered with a carbon nanotube–polymer composite. We demonstrate for the first time that this methodology can be applied to function optimization and also to the tone discriminator problem (TDP). For function optimization, we evaluate the approach on a suite of optimization benchmarks and obtain results that in some cases come very close to the global optimum or are comparable with those obtained using well-known software-based evolutionary approach. We also obtain good results in comparison with prior work on the tone discriminator problem. In the case of the TDP we also investigated the relative merits of different mixtures of materials and organizations of electrode array.     

Anaesthesia record system on handheld computers--pilot experience and uses for quality control and clinical guidelines

This paper describes a mobile information system to collect patient information for anesthesia quality control. In this system, a mobile database program was designed for use on handheld computers (Pocket PC). This program is used to collect patient data at the bedside on the handhelds, with a daily synchronization of the data between the anaesthesiologists' handhelds with the anaesthesia database. All collected data are later used for quality control analysis. Furthermore, clinical guidelines will be included on these same handhelds. During the pilot phase, data from a sample set of about 300 patients were incorporated. The processes and interfaces of the system are presented in the paper. The current mobile database system has been designed to replace the original paper-based data collection system. The individual anaesthesiologist's handheld synchronizes patient data daily with anaesthesia database center. This information database is analyzed and used not only to give feedback to the individual doctor or center, but also to review the use of the guidelines provided and the results of their utilization.     

Automatic laser-based identification for UF6 cylinders

We present a laser item identification system (L2IS), installed in a real facility on trial, that is capable of automatically monitoring all transfers of uranium hexafluoride (UF₆) cylinders between different process areas. Each cylinder has a unique ‘fingerprint’ represented by the 3D micro-structure of its surface which remains intact even under extreme environmental conditions. L2IS automatically identifies each cylinder through exploring the 3D frontal surface acquired by the laser scanner. The system is composed of a portable unit (operated in attended mode) and a fixed installed unit (operated without inspector presence). The efficiency and accuracy of our identification system were evaluated on a large dataset acquired during several years including a full year of field testing.