Microfluidic Tumor-on-a-Chip Model to Study Tumor Metabolic Vulnerability

Tumor-specific metabolic adaptations offer an interesting therapeutic opportunity to selectively destroy cancer cells. However, solid tumors also present gradients of nutrients and waste products across the tumor mass, forcing tumor cells to adapt their metabolism depending on nutrient availability in the surrounding microenvironment. Thus, solid tumors display a heterogenous metabolic phenotype across the tumor mass, which complicates the design of effective therapies that target all the tumor populations present. In this work, we used a microfluidic device to study tumor metabolic vulnerability to several metabolic inhibitors. The microdevice included a central chamber to culture tumor cells in a three-dimensional (3D) matrix, and a lumen in one of the chamber flanks. This design created an asymmetric nutrient distribution across the central chamber, generating gradients of cell viability. The results revealed that tumor cells located in a nutrient-enriched environment showed low to no sensitivity to metabolic inhibitors targeting glycolysis, fatty acid oxidation, or oxidative phosphorylation. Conversely, when cell density inside of the model was increased, compromising nutrient supply, the addition of these metabolic inhibitors disrupted cellular redox balance and led to tumor cell death.     

Modeling of ion transport reactor for oxy‐fuel combustion

This paper aims at investigating the performance of a cylindrical ion transport reactor designed for oxy‐fuel combustion. The cylindrical reactor walls are made of dense, nonporous, mixed‐conducting ceramic membranes that only allow oxygen permeation from the outside air into the combustion chamber. The sweep gas (CO₂ and CH₄) enters the reactor from one side and mixes with the oxygen permeate, and the products are discharged from the other side. The process of oxygen permeation through the reactor walls is influenced by the flow condition and composition of air at the feed side (inlet air side) and the gas mixture at the permeate side (sweep gas side). The modeling of the flow process is based on the numerical solution of the conservation equations of mass, momentum, energy, and species in the axisymmetric flow domain. The membrane is modeled as a selective layer in which the oxygen permeation depends on the prevailing temperatures as well as the oxygen partial pressure at both sides of the membrane. The CFD calculations were carried out using fluent 12.1 (ANSYS, Inc., Canonsburg, PA, USA), whereas the mass transfer of oxygen through the membrane is modeled by a set of user defined functions. The model results were validated against previous experimental data, and the comparison showed a good agreement. The study focused on the effect of oxygen partial pressure and temperature on the resulting combustion zones inside the reactor for the two cases of co‐current and counter‐current flow regimes. The results indicated that the oxygen to fuel mass ratio increases as the percentage of CO₂ increases in the inflow sweep gas for both co‐current and counter‐current flows. The obtained sweep mixture ratio (CO₂/CH₄) of 24 is found within the stoichiometric limit over most of the reactor length in the co‐current configuration, whereas the sweep mixture ratio of 15.67 is found in the counter‐current configuration owing to the high O₂ permeation. Copyright © 2012 John Wiley & Sons, Ltd.     

A light and electron microscopic study of cytoplasmic phospholipase A2 and cyclooxygenase-2 in the hippocampus after kainate lesions

Tamoxifen, the major adjuvant drug treatment for estrogen-dependent breast cancer, has been shown previously to affect both estrogen-dependent and calcium/calmodulin-dependent pathways. In the current study, we developed an in vitro slice system to study the effects of tamoxifen on ATP levels in hypothalamic (HTH) and preoptic areas (POA) of the rat brain. Baseline data showed that, following a 2-h incubation, HTH and POA slices had comparable ATP levels to hippocampal slices, a system used extensively by researchers examining the metabolic responsiveness of the hippocampal region (HPC) of the brain. HTH-POA slice ATP levels remained steady for 2, 4 and 6 h, but fell to 11% of initial levels by 12 h. Neurons from HTH-POA slices incubated for 4 h appeared healthy and demonstrated robust protein synthesis as measured autoradiographically by incorporation of [3H]leucine. We explored the effects of tamoxifen (TAM), fluphenazine (FLU) and estradiol (E2) on ATP levels in HTH and POA slices. The effects of TAM were complex: a 4-h incubation with 10-6 M TAM led to decreased ATP levels in HTH (but not POA), and a 4-h incubation with 10-8 M led to increased ATP levels in POA (but not HTH); a 15-min exposure to 10-6 M TAM decreased ATP levels in POA (but not HTH) slices, while the exposure of slices to the lower concentration of TAM was without effect in either area. As with higher concentrations of TAM, 4-h incubation with 10-6 M FLU decreased ATP levels in HTH (but not POA), while incubation with E2 did not affect slice ATP levels. These data are consistent with the hypothesis that both TAM and FLU alter ATP levels in HTH slices via calmodulin- or calcium-mediated processes.     

Microfabrication of submicron nozzles in silicon nitride

A novel microfabrication process is described for obtaining nanometer apertures in highly cusped nozzle-like structures fabricated in silicon nitride, having apex angles of up to a few degrees. The process is based on a sacrificial etch technology using single-crystal silicon as the mold and silicon nitride as the material for the nozzle. The nitride coating on the apex of the pyramid shaped mold is selectively etched off using a polymer layer as the etch mask, which leaves the tip of the silicon mold protruding from the masked nitride, thus defining the aperture of the nozzles. The silicon mold is then removed in an alkaline etchant, which leaves the freestanding nozzles. The process is applicable to fabrication of similar structures in a variety of other materials such as silicon dioxide, boron-doped silicon, polysilicon, and refractory and noble metals. The main requirement is the preferential etchability of the mold with respect to material for the nozzles     

Acacia albida Seed Oil: Characterization of Coronaric Acid

Coronaric acid makes up 7.8% of Acacia albida (leguminosae) oil triglycerides. Direct acetolysis of the oil followed by saponification gave cis-9,10-dihydroxyoctadec-cis-12-enoic acid which was characterized by various spectroscopic studies and chemical transformations. Quantitation of the coronaric acid was done by gas-liquid chromatography. Chrysanthemum coronarium seed oil was used as the reference standard throughout the study.     

Singular solution of a water wave problem in an ocean of finite depth

The Green's Function of a Water Wave Problem for an Ocean of Finite Depth, bounded internally by a circular cylinder, has been obtained by the use of an appropriate Fourier Series. The technique employed in this investigation may be used when the liquid is internally bounded by cylindrical regions of the form D × I where D is any two dimensional region in the undisturbed free surface and I is the linear interval [0, h].     

Towards data-driven approaches in manufacturing: an architecture to collect sequences of operations

The technological advancements of recent years have increased the complexity of manufacturing systems, and the ongoing transformation to Industry 4.0 will further aggravate the situation. This is leading to a point where existing systems on the factory floor get outdated, increasing the gap between existing technologies and state-of-the-art systems, making them incompatible. This paper presents an event-based data pipeline architecture, that can be applied to legacy systems as well as new state-of-the-art systems, to collect data from the factory floor. In the presented architecture, actions executed by the resources are converted to event streams, which are then transformed into an abstraction called operations. These operations correspond to the tasks performed in the manufacturing station. A sequence of these operations recount the task performed by the station. We demonstrate the usability of the collected data by using conformance analysis to detect when the manufacturing system has deviated from its defined model. The described architecture is developed in Sequence Planner – a tool for modelling and analysing production systems – and is currently implemented at an automotive company as a pilot project.     

Chronic growth stimulation of human adult melanocytes by inflammatory mediators in vitro: implications for nevus formation and initial steps in melanocyte oncogenesis

In the human epidermis, melanocytes are distributed at a distance from each other. In contrast, melanocytes in nevi, which are considered benign neoplasms of melanocytes, are grouped in nests. Although still not well defined, environmental factors are thought to play an important role in the development of nevi. We found that chronic growth stimulation by leukotriene C4, a compound found in increased amounts in inflamed skin, induced pleiotropic modifications in the normal melanocyte phenotype. These changes include loss of contact inhibition and formation of structures resembling tumor spheroids. In parallel with these changes, there was a constitutive expression of Fos protein. Switching these cultures to medium supplemented with phorbol ester sustained growth with reversion of the altered phenotype. In contrast, a cAMP stimulator, cholera toxin, induced features of terminal differentiation. Our findings suggest a role for inflammatory mediators in human epidermal melanocytes. This observation provides insight into melanocyte growth alterations which may have relevance in early stages of melanocyte oncogenesis.     

Influence of carbon nanotube (CNT) on the mechanical properties of LLDPE/CNT nanocomposite fibers

The present study shows the effect of adding CNT to linear low-density polyethylene (LLDPE) to produce LLDPE/CNT nanocomposite fibers. The LLDPE/CNT fibers were produced by melt extrusion process using a twin-screw extruder, in a controlled temperature from 160 °C to 275 °C. Further, melt extrusion process was followed by drawing of fibers at the room temperature. Three different weight percentages, 0.08, 0.3 and 1 wt.% of CNT were studied for producing nanocomposite fibers. The addition of 1 wt.% CNT in the LLDPE fiber has increased the tensile strength by 38% (350 MPa). The addition of 0.08 and 0.3 wt.% CNT in the fiber matrix has improved the ductility by 87% and 122%, respectively. Similarly, improvement in the toughness was observed by 63% and 105% for LLDPE fibers with 0.08 wt.% and 0.3 wt.% CNT respectively. The increase in the mechanical properties of the composite fibers was attributed to the alignment and distribution of CNT in the LLDPE matrix. The dispersion of CNT in the polymeric matrix has been revealed by SEM. The study shows that the small addition of CNT when properly mixed and aligned will increase the mechanical properties of pristine polymer fibers.     

A 1.3-Gsample/s interpolation with flash CMOS ADC based on active interpolation technique

In this paper, the design of a high-speed low-voltage CMOS interpolation with flash analog-to-digital converter (ADC) in CMOS 0.18-μm process is presented. The use of summing differential amplifiers operating in continuous time for interpolation and resistor averaging circuit have significantly improved the circuit’s linearity. The new interpolation technique has improved the pertinent phase delay problem of voltage interpolation enormously. A technique to reduce metastability errors in the Error Correction Circuitry is also presented. The circuit achieves a maximum sampling speed of 1.3 GHz. The measured signal-to-noise-plus-distortion ration (SNDR) is 32 dB at 500 MHz. Peak DNL and INL are less than 0.15 LSB and 0.35 LSB, respectively. This ADC consumes about 600 mW from 1.8 V at full speed. The chip occupies 0.56-mm² active area, prototyped in CMOS 0.18-μm technology. Shazia Seemi was born in New Delhi, India in 1976. She received Bachelor of Technology in Electronics and Communication from JMI University, New Delhi, India in 1998. From 1998 to 2000, she was working with NIIT as an Associate Engineer. She worked as a Software Engineer with Samsung Electronics in 2001. Currently she is a postgraduate student at the VLSI Research Group, Multimedia University, Malaysia, doing research in the area of CMOS high speed ADC design. Mohd Shahiman Sulaiman received the 1st. Class Honors, Co-op B.A.Sc. degree in Electrical Engineering and the M.A.Sc. degree in Electrical & Computer Engineering from the University of Waterloo, Ontario, Canada. He has worked in the area of low-power high-speed mixed-signal IC design since 1998. In 1998, he worked with the VLSI Research Group, University of Waterloo, Canada designing low-power PLL-based frequency synthesizer for Actel Corporation. In 1999, he worked with Actel Corporation in Sunnyvale, CA, USA designing an optimized clock network for Actel,s SX and SX-A anti-fused. Mohd S Sulaiman is currently a lecturer at the Faculty of Engineering, Multimedia University, Malaysia. He is a research associate for Intel Corporation (Malaysia) and Matsushita Electric Industrial Co., Ltd., Japan, as well as consultant for Multimedia Development Corp., Agilent Technologies, Telekom R&D, and PSDC, Malaysia as well as ActiveMedia Innovation Pte Ltd, Singapore. His current research work includes low-power high-performance integrated circuit design, low-power high-speed frequency synthesis techniques, signal integrity, and VLSI system design. He has authored/co-authored more than 30 international conference/journal papers on integrated circuit design and design automation. Arshad Suhail Farooqui was born in Aligarh, India in 1977. He received his Bachelor of Technology in Electronics and Communication from JMI University, New Delhi, India in 1998. From 1998 to 2000, he was working as an Embedded Software Engineer with Indusoft, Delhi, India. From 2000 to 2001, he was with Samsung Electronics, Bangalore, India, as a Senior Software Engineer. From 2002 to 2005, he was with Sires Labs Bhd., Cyberjaya, Malaysia as an ASIC Design Engineer. Arshad is a postgraduate student at the VLSI Research Group, Multimedia University working on high-speed clock and data recovery circuit.