Semimetallic features in quantum transport through a gate-defined point contact in bilayer graphene

We demonstrate that, at the onset of conduction, an electrostatically defined quantum wire in bilayer graphene (BLG) with an interlayer asymmetry gap may act as a 1D semimetal, due to the multiple minivalley dispersion of its lowest subband. Formation of a non-monotonic subband coincides with a near-degeneracy between the bottom edges of the lowest two subbands in the wire spectrum, suggesting an $8e^2/h$ step at the conduction threshold, and the semimetallic behaviour of the lowest subband in the wire would be manifest as resonance transmission peaks on an $8e^2/h$ conductance plateau.Comment: 9 pages, 8 figures (including appendices

Open access to novel dual flow chamber technology for in vitro cell mechanotransduction, toxicity and pharamacokinetic studies

<p>Abstract</p> <p>Background</p> <p>A major stumbling block for researchers developing experimental models of mechanotransduction is the control of experimental variables, in particular the transmission of the mechanical forces at the cellular level. A previous evaluation of state of the art commercial perfusion chambers showed that flow regimes, applied to impart a defined mechanical stimulus to cells, are poorly controlled and that data from studies in which different chambers are utilized can not be compared, even if the target stress regimes are comparable.</p> <p>Methods</p> <p>This study provides a novel chamber design to provide both physiologically-based flow regimes, improvements in control of experimental variables, as well as ease of use compared to commercial chambers. This novel design achieves controlled stresses through five gasket designs and both single- and dual-flow regimes.</p> <p>Results</p> <p>The imparted shear stress within the gasket geometry is well controlled. Fifty percent of the entire area of the 10 × 21 mm universal gasket (Gasket I, designed to impart constant magnitude shear stresses in the center of the chamber where outcome measures are taken), is exposed to target stresses. In the 8 mm diameter circular area at the center of the chamber (where outcome measures are made), over 92% of the area is exposed to the target stress (± 2.5%). In addition, other gasket geometries provide specific gradients of stress that vary with distance from the chamber inlet. Bench-top testing of the novel chamber prototype shows improvements, in the ease of use as well as in performance, compared to the other commercial chambers. The design of the chamber eliminates flow deviations due to leakage and bubbles and allows actual flow profiles to better conform with those predicted in computational models.</p> <p>Conclusion</p> <p>The novel flow chamber design provides predictable and well defined mechanical forces at the surface of a cell monolayer, showing improvement over previously tested commercial chambers. The predictability of the imparted stress improves both experiment repeatability as well as the accuracy of inter-study comparisons. Carefully controlling the stresses on cells is critical in effectively mimicking <it>in vivo </it>situations. Overall, the improved perfusion flow chamber provides the needed resolution, standardization and <it>in vitro </it>model analogous to <it>in vivo </it>conditions to make the step towards greater use in research and the opportunity to enter the diagnostic and therapeutic market.</p

The assessment of science: the relative merits of post- publication review, the impact factor, and the number of citations

The assessment of scientific publications is an integral part of the scientific process. Here we investigate three methods of assessing the merit of a scientific paper: subjective post-publication peer review, the number of citations gained by a paper, and the impact factor of the journal in which the article was published. We investigate these methods using two datasets in which subjective post-publication assessments of scientific publications have been made by experts. We find that there are moderate, but statistically significant, correlations between assessor scores, when two assessors have rated the same paper, and between assessor score and the number of citations a paper accrues. However, we show that assessor score depends strongly on the journal in which the paper is published, and that assessors tend to over-rate papers published in journals with high impact factors. If we control for this bias, we find that the correlation between assessor scores and between assessor score and the number of citations is weak, suggesting that scientists have little ability to judge either the intrinsic merit of a paper or its likely impact. We also show that the number of citations a paper receives is an extremely error-prone measure of scientific merit. Finally, we argue that the impact factor is likely to be a poor measure of merit, since it depends on subjective assessment. We conclude that the three measures of scientific merit considered here are poor; in particular subjective assessments are an error-prone, biased, and expensive method by which to assess merit. We argue that the impact factor may be the most satisfactory of the methods we have considered, since it is a form of pre-publication review. However, we emphasise that it is likely to be a very error-prone measure of merit that is qualitative, not quantitative

Experiments and 3D simulations of flow structures in junctions and their influence on location of flowmeters

International audienceOpen-channel junctions are common occurrences in sewer networks and flow rate measurement often occurs near these singularities. Local flow structures are 3-dimensional, impact on the representativeness of the local flow measurements and thus lead to deviations in the flow rate estimation. The present study aims i) to measure and simulate the flow pattern in a junction flow, ii) to analyze the impact of the junction on the velocity distribution according to the distance from the junction and thus iii) to evaluate the typical error derived from the computation of the flow rate close to the junction

Prospective Design, Rapid Prototyping, and Testing of Smart Dressings, Drug Delivery Patches, and Replacement Body Parts Using Microscopy Aided Design and ManufacturE (MADAME)

Natural materials exhibit smart properties including gradients in biophysical properties that engender higher order functions, as well as stimuli-responsive properties which integrate sensor and/or actuator capacities. Elucidation of mechanisms underpinning such smart material properties (i), and translation of that understanding (ii), represent two of the biggest challenges in emulating natural design paradigms for design and manufacture of disruptive materials, parts, and products. Microscopy Aided Design And ManufacturE (MADAME) stands for a computer-aided additive manufacturing platform that incorporates multidimensional (multi-D) printing and computer-controlled weaving. MADAME enables the creation of composite design motifs emulating e.g., patterns of woven protein fibers as well as gradients in different caliber porosities, mechanical, and molecular properties, found in natural tissues, from the skin on bones (periosteum) to tree bark. Insodoing, MADAME provides a means to manufacture a new genre of smart materials, products and replacement body parts that exhibit advantageous properties both under the influence of as well as harnessing dynamic mechanical loads to activate material properties (mechanoactive properties). This Technical Report introduces the MADAME technology platform and its associated machine-based workflow (pipeline), provides basic technical background of the novel technology and its applications, and discusses advantages and disadvantages of the approach in context of current 3 and 4D printing platforms

In vivo demonstration of load-induced fluid flow in the rat tibia and its potential implications for processes associated with functional adaptation

Load-induced extravascular fluid flow has been postulated to play a role in mechanotransduction of physiological loads at the cellular level. Furthermore, the displaced fluid serves as a carrier for metabolites, nutrients, mineral precursors and osteotropic agents important for cellular activity. We hypothesise that load-induced fluid flow enhances the transport of these key substances, thus helping to regulate cellular activity associated with processes of functional adaptation and remodelling. To test this hypothesis, molecular tracer methods developed previously by our group were applied in vivo to observe and quantify the effects of load-induced fluid flow under four-point-bending loads. Preterminal tracer transport studies were carried out on 24 skeletally mature Sprague Dawley rats. Mechanical loading enhanced the transport of both small- and larger-molecular-mass tracers within the bony tissue of the tibial mid-diaphysis. Mechanical loading showed a highly significant effect on the number of periosteocytic spaces exhibiting tracer within the cross section of each bone. For all loading rates studied, the concentration of Procion Red tracer was consistently higher in the tibia subjected to pure bending loads than in the unloaded, contralateral tibia, Furthermore, the enhancement of transport was highly site-specific. In bones subjected to pure bending loads, a greater number of periosteocytic spaces exhibited the presence of tracer in the tension band of the cross section than in the compression band; this may reflect the higher strains induced in the tension band compared with the compression band within the mid-diaphysis of the rat tibia. Regardless of loading mode, the mean difference between the loaded side and the unloaded contralateral control side decreased with increasing loading frequency. Whether this reflects the length of exposure to the tracer or specific frequency effects cannot be determined by this set of experiments. These in vivo experimental results corroborate those of previous ex vivo and in vitro studies, Strain-related differences in tracer distribution provide support for the hypothesis that load-induced fluid flow plays a regulatory role in processes associated with functional adaptation

Isolation of a euryhaline microalgal strain, Tetraselmis sp CTP4, as a robust feedstock for biodiesel production

Bioprospecting for novel microalgal strains is key to improving the feasibility of microalgae-derived biodiesel production. Tetraselmis sp. CTP4 (Chlorophyta, Chlorodendrophyceae) was isolated using fluorescence activated cell sorting (FACS) in order to screen novel lipid-rich microalgae. CTP4 is a robust, euryhaline strain able to grow in seawater growth medium as well as in non-sterile urban wastewater. Because of its large cell size (9-22 mu m), CTP4 settles down after a six-hour sedimentation step. This leads to a medium removal efficiency of 80%, allowing a significant decrease of biomass dewatering costs. Using a two-stage system, a 3-fold increase in lipid content (up to 33% of DW) and a 2-fold enhancement in lipid productivity (up to 52.1 mg L-1 d(-1)) were observed upon exposure to nutrient depletion for 7 days. The biodiesel synthesized from the lipids of CTP4 contained high levels of oleic acid (25.67% of total fatty acids content) and minor amounts of polyunsaturated fatty acids with >= 4 double bonds (< 1%). As a result, this biofuel complies with most of the European (EN14214) and American (ASTM D6751) specifications, which commonly used microalgal feedstocks are usually unable to meet. In conclusion, Tetraselmis sp. CTP4 displays promising features as feedstock with lower downstream processing costs for biomass dewatering and biodiesel refining

The imperative for controlled mechanical stresses in unraveling cellular mechanisms of mechanotransduction

BACKGROUND: In vitro mechanotransduction studies are designed to elucidate cell behavior in response to a well-defined mechanical signal that is imparted to cultured cells, e.g. through fluid flow. Typically, flow rates are calculated based on a parallel plate flow assumption, to achieve a targeted cellular shear stress. This study evaluates the performance of specific flow/perfusion chambers in imparting the targeted stress at the cellular level. METHODS: To evaluate how well actual flow chambers meet their target stresses (set for 1 and 10 dyn/cm(2 )for this study) at a cellular level, computational models were developed to calculate flow velocity components and imparted shear stresses for a given pressure gradient. Computational predictions were validated with micro-particle image velocimetry (μPIV) experiments. RESULTS: Based on these computational and experimental studies, as few as 66% of cells seeded along the midplane of commonly implemented flow/perfusion chambers are subjected to stresses within ±10% of the target stress. In addition, flow velocities and shear stresses imparted through fluid drag vary as a function of location within each chamber. Hence, not only a limited number of cells are exposed to target stress levels within each chamber, but also neighboring cells may experience different flow regimes. Finally, flow regimes are highly dependent on flow chamber geometry, resulting in significant variation in magnitudes and spatial distributions of stress between chambers. CONCLUSION: The results of this study challenge the basic premise of in vitro mechanotransduction studies, i.e. that a controlled flow regime is applied to impart a defined mechanical stimulus to cells. These results also underscore the fact that data from studies in which different chambers are utilized can not be compared, even if the target stress regimes are comparable

In Situ Spatiotemporal Mapping of Flow Fields around Seeded Stem Cells at the Subcellular Length Scale

A major hurdle to understanding and exploiting interactions between the stem cell and its environment is the lack of a tool for precise delivery of mechanical cues concomitant to observing sub-cellular adaptation of structure. These studies demonstrate the use of microscale particle image velocimetry (μ-PIV) for in situ spatiotemporal mapping of flow fields around mesenchymal stem cells, i.e. murine embryonic multipotent cell line C3H10T1/2, at the subcellular length scale, providing a tool for real time observation and analysis of stem cell adaptation to the prevailing mechanical milieu. In the absence of cells, computational fluid dynamics (CFD) predicts flow regimes within 12% of μ-PIV measures, achieving the technical specifications of the chamber and the flow rates necessary to deliver target shear stresses at a particular height from the base of the flow chamber. However, our μ-PIV studies show that the presence of cells per se as well as the density at which cells are seeded significantly influences local flow fields. Furthermore, for any given cell or cell seeding density, flow regimes vary significantly along the vertical profile of the cell. Hence, the mechanical milieu of the stem cell exposed to shape changing shear stresses, induced by fluid drag, varies with respect to proximity of surrounding cells as well as with respect to apical height. The current study addresses a previously unmet need to predict and observe both flow regimes as well as mechanoadaptation of cells in flow chambers designed to deliver precisely controlled mechanical signals to live cells. An understanding of interactions and adaptation in response to forces at the interface between the surface of the cell and its immediate local environment may be key for de novo engineering of functional tissues from stem cell templates as well as for unraveling the mechanisms underlying multiscale development, growth and adaptation of organisms