Parallel pipelined histogram architecture via C-slow retiming

A parallel pipelined array of cells suitable for realtime computation of histograms is proposed. The cell architecture builds on previous work to now allow operating on a stream of data at 1 pixel per clock cycle. This new cell is more suitable for interfacing to camera sensors or to microprocessors of 8-bit data buses which are common in consumer digital cameras. Arrays using the new proposed cells are obtained via C-slow retiming techniques and can be clocked at a 65% faster frequency than previous arrays. This achieves over 80% of the performance of two-pixel per clock cycle parallel pipelined arrays.

The Development of Educational Materials for the Study of Architecture using Computer Game Technology

Computer game technology provides us with the tools to create web-based educational materials for autonomous and collaborative learning. At Worcester, we have researched the use of this technology in various educational contexts. This paper reports one such study; the use of the commercial game engine “Unreal Tournament 2004” (UT2004) to produce materials suitable for education of Architects. We map the concepts and principles of Architectural Design onto the affordances (development tools) provided by UT2004, leading to a systematic procedure for the realization of buildings and urban environments using this game engine. A theory for the production of web-based learning materials which supports both autonomous and collaborative learning is developed. A heuristic evaluation of our materials, used with second-year students is presented. Associated web-pages provide on-line materials for delegates.

Coupling of Chemical Kinetics with Computational Fluid Dynamics in a Three-Dimensional Engine Model

The role of computer modeling has grown recently to integrate itself as an inseparable tool to experimental studies for the optimization of automotive engines and the development of future fuels. Traditionally, computer models rely on simplified global reaction steps to simulate the combustion and pollutant formation inside the internal combustion engine. With the current interest in advanced combustion modes and injection strategies, this approach depends on arbitrary adjustment of model parameters that could reduce credibility of the predictions. The purpose of this study is to enhance the combustion model of KIVA, a computational fluid dynamics code, by coupling its fluid mechanics solution with detailed kinetic reactions solved by the chemistry solver, CHEMKIN. As a result, an engine-friendly reaction mechanism for n-heptane was selected to simulate diesel oxidation. Each cell in the computational domain is considered as a perfectly-stirred reactor which undergoes adiabatic constant- volume combustion. The model was applied to an ideally-prepared homogeneous- charge compression-ignition combustion (HCCI) and direct injection (DI) diesel combustion. Ignition and combustion results show that the code successfully simulates the premixed HCCI scenario when compared to traditional combustion models. Direct injection cases, on the other hand, do not offer a reliable prediction mainly due to the lack of turbulent-mixing model, inherent in the perfectly-stirred reactor formulation. In addition, the model is sensitive to intake conditions and experimental uncertainties which require implementation of enhanced predictive tools. It is recommended that future improvements consider turbulent-mixing effects as well as optimization techniques to accurately simulate actual in-cylinder process with reduced computational cost. Furthermore, the model requires the extension of existing fuel oxidation mechanisms to include pollutant formation kinetics for emission control studies.

The Effect of Architecture and Shear Stress on Endothelialization of 3D Printed Vascular Networks

Despite significant progress in the field of tissue engineering within the last decade, a number of unsolved problems still remain. One of the most relevant issues is the lack of proper vascularization that limits the size of engineered tissues to smaller than clinically relevant dimensions. In particular, the growth of engineered tissue in vitro within bioreactors is plagued with this challenge. Specifically, the tubular perfusion system bioreactor has been used for large scale bone constructs; however these engineered constructs lack inherent vasculature and quickly develop a hypoxic core, where no nutrient exchange can occur, thus leading to cell death. Through the use of 3D printed vascular templates in conjunction with a tubular perfusion system bioreactor, we attempt to create an endothelial cell monolayer on 3D scaffolds that could potentially serve as the foundation of inherent vasculature within these engineered bone grafts.

Environmental assessment of proton exchange membrane fuel cell platinum catalyst recycling

International audience

Optical Access Engine Setup and Validation

The optical access engine integrated with the diagnostic and optical measurement techniques is a great platform for engine research because it provides clear visual access to the combustion chamber inside the engines. An optical access engine customized based on a 4-cylinder spark ignited direct injection (SIDI) production engine is located in the Advanced Power Systems Laboratories (APS LABS) at Michigan Technological University. This optical access engine inside the test cell has been set up for different engine research. In this report, two SAE papers in engine research utilizing the optical access engine are reviewed to gain basic understanding of the methodology. Though the optical engine in APS LABS is a little bit different from the engines used in the literature, the methodology in the papers provides guidelines for engine research through optical access engines. In addition, the optical access engine instrumentation including the test cell setup and the optical engine setup is described in detail in the report providing a solid record for later troubleshooting and reference. Finally, the motoring tests, firing tests and optical imaging experiment on the optical engine have been performed to validate the instrumentation. This report only describes so far the instrumentation of the optical engine in the APS LABS by April 2015.

Optimal control of non-linear systems through hybrid cell-mapping/artificial-neural-networks techniques

In this paper, a real-time optimal control technique for non-linear plants is proposed. The control system makes use of the cell-mapping (CM) techniques, widely used for the global analysis of highly non-linear systems. The CM framework is employed for designing approximate optimal controllers via a control variable discretization. Furthermore, CM-based designs can be improved by the use of supervised feedforward artificial neural networks (ANNs), which have proved to be universal and efficient tools for function approximation, providing also very fast responses. The quantitative nature of the approximate CM solutions fits very well with ANNs characteristics. Here, we propose several control architectures which combine, in a different manner, supervised neural networks and CM control algorithms. On the one hand, different CM control laws computed for various target objectives can be employed for training a neural network, explicitly including the target information in the input vectors. This way, tracking problems, in addition to regulation ones, can be addressed in a fast and unified manner, obtaining smooth, averaged and global feedback control laws. On the other hand, adjoining CM and ANNs are also combined into a hybrid architecture to address problems where accuracy and real-time response are critical. Finally, some optimal control problems are solved with the proposed CM, neural and hybrid techniques, illustrating their good performance.

Mechanisms of force-mediated regulation of transcription, chromatin remodeling and cell fate decisions

Tissue mechanics and cellular interactions influence every single cell in our bodies to drive morphogenesis. However, little is known about mechanisms by which cells sense physical forces and transduce them from the cytoskeleton to the nucleus to control gene expression and stem cell fate. We have identified a novel nuclear-mechanosensor complex, consisting of the nuclear membrane protein emerin (Emd), actin and non-muscle myosin IIA (NMIIA), that regulates transcription, chromatin remodeling and lineage commitment. Force-induced enrichment of Emd at the outer nuclear membrane leads to a compensation between H3K9me2,3 and H3K27me3 on constitutive heterochromatin. This strain-induced epigenetic switch is accompanied by the global rearrangement of chromatin. In parallel, forces promote local F-actin polymerization at the outer nuclear membrane, which limits the availability of nuclear G-actin. Subsequently, the reduction of nuclear G-actin results in attenuated global transcription and therefore increased H3K27me3 occupancy to reinforce gene silencing. Restoring nuclear actin levels in the presence of mechanical strain counteracts PRC2-mediated silencing of transcribed genes. This mechanosensory circuit is also observed in vivo. Depletion of NMIIA in mouse epidermis leads to decreased H3K27me3 levels and precocious lineage commitment, thus abrogating organ growth and patterning. Our results reveal how mechanical signals regulate nuclear architecture, chromatin organization and transcription to control cell fate decisions.

EBV Type II latency relies on PARP1 activity and is essential for gastric epithelial cell transformation in EBV-associated Gastric Cancer (EBVaGC)

Epstein-Barr virus (EBV) establishes a lifelong asymptomatic infection by replicating its chromatinized genome, called episome, together with the host genome. EBV exhibits different latency-associated transcriptional repertoires that mirror its three-dimensional structures of the genome. CTCF, Cohesin and PARP1 are involved in maintaining viral latency and establishing episome architecture. Epstein-Barr virus-associated gastric cancer (EBVaGC) represents almost 10% of all gastric cancers globally. EBVaGC exhibit an intermediate viral transcription profile known as "Latency II", expressing specific viral genes and non-coding RNAs. In this study, we investigated the impact of PARP1 inhibition on CTCF/Cohesin binding in Type II latency. We observed a destabilization of the binding of both factors, leading to a disrupted three-dimensional architecture of the episomes and consequently, an altered viral gene expression. Despite sharing the same CTCF binding profile, Type I, II, and III latencies display different 3D episomal structures that correlate with variations in viral gene expression. Additionally, our analysis of H3K27ac-enriched chromatin interactions revealed differences between Type II latency episomes and a link to cellular transformation through docking of the EBV episomes at specific sites of the Human genome, thus promoting oncogene expression. Overall, this work provides insights into the role of PARP1 in maintaining active latency and novel mechanisms of EBV-induced cellular transformation.

Design and implementation of a synchronous interleaved boost converter for fuel cell-powered catamaran

The present work describes the different stages of design, implementation, and validation procedures for an interleaved DC-DC boost converter intended for the 2022 Futura, a fuel cell-powered racing catamaran developed by the UniBoAT team. The main goal of the entire design has been the significant reduction of the weight of the converter by removing heat sinks and reducing component size while increasing its efficiency by adopting high-end power switches and the interleaved architecture operated with a synchronous control strategy. The obtained converter has been integrated into the structure containing the fuel cell stack obtaining a fully integrated system. The realized device has been based on an interleaved architecture with six phases controlled digitally through the average current mode control. The design has been validated through simulations carried out using the software LT-Spice, whereas experimental validations have been performed by means of laboratory bench tests and on-field tests. Detailed thermal and efficiency analyses are provided with the bench tests under the two synchronous and non-synchronous operating modes and with the adoption of the phase shedding technique. The prototype implementation and its performance in real operating conditions are also discussed. Eventually, it is underlined as the designed converter can be used in other applications requiring a voltage-controlled boost converter.

Egfr Activating Mutations And Their Association With Response To Platinum-doublet Chemotherapy In Brazilian Non-small Cell Lung Cancer Patients.

The aim of the study was to analyze the frequency of epidermal growth factor receptor (EGFR) mutations in Brazilian non-small cell lung cancer patients and to correlate these mutations with response to benefit of platinum-based chemotherapy in non-small cell lung cancer (NSCLC). Our cohort consisted of prospective patients with NSCLCs who received chemotherapy (platinum derivates plus paclitaxel) at the [UNICAMP], Brazil. EGFR exons 18-21 were analyzed in tumor-derived DNA. Fifty patients were included in the study (25 with adenocarcinoma). EGFR mutations were identified in 6/50 (12 %) NSCLCs and in 6/25 (24 %) adenocarcinomas; representing the frequency of EGFR mutations in a mostly self-reported White (82.0 %) southeastern Brazilian population of NSCLCs. Patients with NSCLCs harboring EGFR exon 19 deletions or the exon 21 L858R mutation were found to have a higher chance of response to platinum-paclitaxel (OR 9.67 [95 % CI 1.03-90.41], p = 0.047). We report the frequency of EGFR activating mutations in a typical southeastern Brazilian population with NSCLC, which are similar to that of other countries with Western European ethnicity. EGFR mutations seem to be predictive of a response to platinum-paclitaxel, and additional studies are needed to confirm or refute this relationship.

Solid Lipid Nanoparticles For Hydrophilic Biotech Drugs: Optimization And Cell Viability Studies (caco-2 & Hepg-2 Cell Lines).

Insulin was used as model protein to developed innovative Solid Lipid Nanoparticles (SLNs) for the delivery of hydrophilic biotech drugs, with potential use in medicinal chemistry. SLNs were prepared by double emulsion with the purpose of promoting stability and enhancing the protein bioavailability. Softisan(®)100 was selected as solid lipid matrix. The surfactants (Tween(®)80, Span(®)80 and Lipoid(®)S75) and insulin were chosen applying a 2(2) factorial design with triplicate of central point, evaluating the influence of dependents variables as polydispersity index (PI), mean particle size (z-AVE), zeta potential (ZP) and encapsulation efficiency (EE) by factorial design using the ANOVA test. Therefore, thermodynamic stability, polymorphism and matrix crystallinity were checked by Differential Scanning Calorimetry (DSC) and Wide Angle X-ray Diffraction (WAXD), whereas the effect of toxicity of SLNs was check in HepG2 and Caco-2 cells. Results showed a mean particle size (z-AVE) width between 294.6 nm and 627.0 nm, a PI in the range of 0.425-0.750, ZP about -3 mV, and the EE between 38.39% and 81.20%. After tempering the bulk lipid (mimicking the end process of production), the lipid showed amorphous characteristics, with a melting point of ca. 30 °C. The toxicity of SLNs was evaluated in two distinct cell lines (HEPG-2 and Caco-2), showing to be dependent on the concentration of particles in HEPG-2 cells, while no toxicity in was reported in Caco-2 cells. SLNs were stable for 24 h in in vitro human serum albumin (HSA) solution. The resulting SLNs fabricated by double emulsion may provide a promising approach for administration of protein therapeutics and antigens.

Autologous Platelet Gel: Five Cases Illustrating Use On Sickle Cell Disease Ulcers.

Leg ulcers represent a particularly disabling complication in patients with sickle cell disease (SCD). Platelet gel (PG) is a novel therapeutic strategy used for accelerating wound healing of a wide range of tissues through the continuous release of platelet growth factors. Here, we describe the use of PG preparation according to Anitua's PRGF (preparations rich in growth factors) protocol for treating chronic nonhealing ulcers in patients with SCD. A positive response occurred in 3 patients with an area reduction of 85.7% to 100%, which occurred within 7 to 10 weeks, and a 35.2% and 20.5% of area reduction in 2 other patients, who however, had large ulcers. After calcium chloride addition, the platelet-rich plasmas demonstrated enhanced platelet-derived growth factors-BB (P < .001), transforming growth factor-β1 (P = .015), vascular endothelial growth factors (P = .03), and hepatocyte growth factors (nonsignificant) secretion. Furthermore, calcium chloride addition induced a significant decrease in platelet number (P = .0134) and there was no leukocyte detection in the PG product. These results demonstrate that PG treatment might impact the healing of leg ulcers in sickle cell disease, especially in patients with small ulcers.

Impaired Compensatory Beta-cell Function And Growth In Response To High-fat Diet In Ldl Receptor Knockout Mice.

In this study, we investigated the effect of low density lipoprotein receptor (LDLr) deficiency on gap junctional connexin 36 (Cx36) islet content and on the functional and growth response of pancreatic beta-cells in C57BL/6 mice fed a high-fat (HF) diet. After 60 days on regular or HF diet, the metabolic state and morphometric islet parameters of wild-type (WT) and LDLr-/- mice were assessed. HF diet-fed WT animals became obese and hypercholesterolaemic as well as hyperglycaemic, hyperinsulinaemic, glucose intolerant and insulin resistant, characterizing them as prediabetic. Also they showed a significant decrease in beta-cell secretory response to glucose. Overall, LDLr-/- mice displayed greater susceptibility to HF diet as judged by their marked cholesterolaemia, intolerance to glucose and pronounced decrease in glucose-stimulated insulin secretion. HF diet induced similarly in WT and LDLr-/- mice, a significant decrease in Cx36 beta-cell content as revealed by immunoblotting. Prediabetic WT mice displayed marked increase in beta-cell mass mainly due to beta-cell hypertrophy/replication. Nevertheless, HF diet-fed LDLr-/- mice showed no significant changes in beta-cell mass, but lower islet-duct association (neogenesis) and higher beta-cell apoptosis index were seen as compared to controls. The higher metabolic susceptibility to HF diet of LDLr-/- mice may be explained by a deficiency in insulin secretory response to glucose associated with lack of compensatory beta-cell expansion.

Integrated Proteomics Identified Up-regulated Focal Adhesion-mediated Proteins In Human Squamous Cell Carcinoma In An Orthotopic Murine Model.

Understanding the molecular mechanisms of oral carcinogenesis will yield important advances in diagnostics, prognostics, effective treatment, and outcome of oral cancer. Hence, in this study we have investigated the proteomic and peptidomic profiles by combining an orthotopic murine model of oral squamous cell carcinoma (OSCC), mass spectrometry-based proteomics and biological network analysis. Our results indicated the up-regulation of proteins involved in actin cytoskeleton organization and cell-cell junction assembly events and their expression was validated in human OSCC tissues. In addition, the functional relevance of talin-1 in OSCC adhesion, migration and invasion was demonstrated. Taken together, this study identified specific processes deregulated in oral cancer and provided novel refined OSCC-targeting molecules.