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We propose a numerical method for the simulation of a quasi-linear parabolic biofilm model that exhibits three non-linear diffusion effects: (i) a power law degeneracy, (ii) a super diffusion singularity and (iii) non-linear cross-diffusion. The method is based on a spatial Finite Volume discretisation in which cross-diffusion terms are formally treated as convection terms. Time-integration of the resulting semi-discretised system is carried out using an error-controlled, time-adaptive, embedded Rosenbrock–Wanner method. We compare several variants of the method and two variants of the model to investigate how details such as the choice cross-diffusion coefficients, and specific variants of the time integrator affect simulation time.
We derive a macroscopic model for biofilm formation in a porous medium reactor to investigate the role of suspended bacteria on reactor performance. The starting point is the mesoscopic one-dimensional Wanner–Gujer biofilm model. The following processes are included: hydrodynamics and transport of substrate in the reactor, biofilm and suspended bacteria growth in the pore space, attachment of suspended cells to the biofilm, and detachment of biofilm cells. The mesoscopic equations are up-scaled from the biofilm scale to the reactor scale, yielding a stiff system of balance laws, which we study numerically. We find that suspended bacteria and attachment can have a significant effect on biofilm reactor performance.
Based on the Developmental Origin of Health and Disease concept, maternal undernutrition has been shown to sensitize adult offspring to metabolic pathologies such as obesity. Using a model of maternal 70% food restriction in pregnant female rats throughout gestation (called FR30), we previously reported that obesity-prone adult male rat offspring displayed hyperleptinemia with modifications in leptin and leptin receptor messenger RNA (mRNA) levels in white adipose tissue (WAT). Apelin is a member of the adipokine family that regulates various aspects of energy metabolism and WAT functionality. We investigated whether apelin and its receptor APJ could be a target of maternal undernutrition. Adult male rat offspring from FR30 dams showed increased plasma apelin levels and apelin gene expression in WAT. Post-weaning high-fat diet led to marked increase in APJ mRNA and protein levels in offspring’s WAT. We demonstrate that maternal undernutrition and post-weaning diet have long-term consequences on the apelinergic system of adult male rat offspring.
We apply the immersed boundary (or IB) method to simulate deformation and detachment of a periodic array of wall-bounded biofilm colonies in response to a linear shear flow. The biofilm material is represented as a network of Hookean springs that are placed along the edges of a triangulation of the biofilm region. The interfacial shear stress, lift and drag forces acting on the biofilm colony are computed by using fluid stress jump method developed by Williams, Fauci and Gaver [Disc. Con-tin. Dyn. Sys. B 11(2):519–540, 2009], with a modified version of their exclusion filter. Our detachment criterion is based on the novel concept of an averaged equivalent continuum stress tensor defined at each IB point in the biofilm which is then used to determine a corresponding von Mises yield stress; wherever this yield stress exceeds a given critical threshold the connections to that node are severed, thereby signalling the onset of a detachment event. In order to capture the deformation and detachment behaviour of a biofilm colony at different stages of growth, we consider a family of four biofilm shapes with varying aspect ratio. For each aspect ratio, we varied the spacing between colonies to investigate role of spatial clustering in offering protection against detachment. Our numerical simulations focus on the behaviour of weak biofilms (with relatively low yield stress threshold) and investigate features of the fluid-structure interaction such as locations of maximum shear and increased drag. The most important conclusions of this work are: (a) reducing the spacing between colonies reduces drag by from 50 to 100% and alters the interfacial shear stress profile, suggesting that even weak biofilms may be able to grow into tall structures because of the protection they gain from spatial proximity with other colonies; (b) the commonly employed detachment strategy in biofilm models based only on interfacial shear stress can lead to incorrect or inaccurate results when applied to the study of shear induced detachment of weak biofilms. Our detachment strategy based on equivalent continuum stresses provides a unified and consistent IB framework that handles both sloughing and erosion modes of biofilm detachment, and is consistent with strategies employed in many other continuum based biofilm models.
Somewhere near the heart of much recent liberal political theory is the claim that if the state restricts an agent's liberty, its restrictions should have some rationale that is defensible to each of those whose liberty is constrained. Liberals are committed to “the requirement that all aspects of the social should either be made acceptable or be capable of being made acceptable to every last individual.” In a pluralistic culture, there are many claims which are particularly controversial, many about which we expect “reasonable disagreement.” If we are to enjoy consensus regarding state restrictions, citizens should not support coercive policies on such controversial grounds. If, for example, some coercive policy is passed by popular referendum, and if its supporters have no reason to vote for the policy other than their religious convictions, then, given that reasonable, informed people reject religious belief, the policy in question lacks public justification. Given the liberal view that coercive policies should be defensible to all those affected by them, conscientious citizens should restrain themselves from supporting (or rejecting) policies on the basis of excessively controversial grounds. Principles of restraint specify both the types of grounds on the basis of which citizens may appropriately support a given policy and the types of grounds on which citizens may not properly rely.
Recent debates in political theory have seen political liberals advocate and defend a doctrine of restraint, according to which citizens may not rely solely on religious reasons when supporting their favored public policies. This debate notwithstanding, very rarely have social scientists assessed the extent to which citizens actually violate this doctrine. This article evaluates the “political decision-making” model of political liberalism. Data from a nationally representative sample of U.S. adults are used to test this model for legalization of same-sex marriage. Our analyses show that while only a very small percentage of U.S. support this policy solely on the basis of their religious convictions, roughly a quarter oppose it for religious reasons alone. Furthermore, we find that higher levels of religious service attendance and importance of religious faith as well as affiliation with evangelical and black Protestantism significantly increase the likelihood of same-sex marriage opposition entirely on religious grounds.
The aim of our study is to investigate the possibility of habitable moons orbiting the giant planet HD 23079b, a Jupiter-mass planet, which follows a low-eccentricity orbit in the outer region of HD 23079’s habitable zone. We show that HD 23079b is able to host habitable moons in prograde and retrograde orbits, as expected, noting that the outer stability limit for retrograde orbits is increased by nearly 90% compared with that of prograde orbits, a result consistent with previous generalised studies. For the targeted parameter space, it was found that the outer stability limit for habitable moons varies between 0.05236 and 0.06955 AU (prograde orbits) and between 0.1023 and 0.1190 AU (retrograde orbits), depending on the orbital parameters of the Jupiter-type planet if a minimum mass is assumed. These intervals correspond to 0.306 and 0.345 (prograde orbits) and 0.583 and 0.611 (retrograde orbits) of the planet's Hill radius. Larger stability limits are obtained if an increased value for the planetary mass mp is considered; they are consistent with the theoretically deduced relationship of m1/3p. Finally, we compare our results with the statistical formulae of Domingos, Winter, & Yokoyama, indicating both concurrence and limitations.
In this article, I intend to explore the normative relation(s) between “God” and “war.” A bit more precisely, I intend to explore the normative relevance of theistic conviction to the proper employment of military violence. Even more precisely, I intend to explore the relevance of theistic conviction to the proper employment of military violence as judged by the so-called Just War Tradition (JWT). Properly interpreted, I take the JWT to provide the best available account of the morality of war. The JWT is not perfect and is bedeviled by serious problems, but it is the best available nonetheless. So, when I reflect on the morality of war, and thus on the normative relation(s) between religion and war, I do so from the perspective of the JWT.
Now this might seem to portend a very brief discussion. As we will see in detail, contemporary adherents typically construe the JWT in resolutely secular terms. Perhaps in order to compensate for its religious prehistory, most insist that the JWT has outgrown its religious provenance and may not be used to legitimate a crusade, a jihad, a holy war, or anything of the sort. In so doing, they align the JWT with the commonplace, endemic to contemporary liberal democracies, that religious wars and religious justifications for war lay far, far beyond the moral pale.
Here, we present microfluidic methods to fabricate complex hydrogel structures for 3D tissue or organ-like cell structures in vitro. First, a microfluidic system to continuously synthesize chemically and physically anisotropic Ca–alginate hydrogel microfibers is proposed to enable the guidance of cell proliferation and differentiation. Next, the microfluidic preparation methods for yarn-ball-shape hydrogel particles and extremely-small hydrogel microspheres. Finally, a newly developed micro-molding and bonding method for hydrogel micro-patterned plates is reported.
In this paper, we will discuss our recent approaches for improving the mechanical stability of free-standing bilayer lipid membranes (BLMs) by combining with BLM formation and microfabrication techniques. BLMs were prepared across a microaperture fabricated in a silicon (Si) chip and their mechanical stability and electric properties were investigated. BLMs suspended in a thin Si3N4 septum showed a dramatic improvement of BLM stability. The BLMs were resistant to voltage of ±1 V and the membrane lifetime was 15- ~40 h with and without incorporated channels. The membrane containing gramicidin channel exhibited tolerance to repetitive solution exchanges. At first, electric properties of the BLMs, such as noise level and current transient, were necessary to be improved. However, after coating the chip with insulator layers of Teflon and SiO2, total chip capacitance was reduced, leading to noise reduction (1-2 pA in peak-to-peak after low-pass filtering at 1 kHz) and elimination of current transients (< 0.5 ms). Since the vicinity of the aperture edge was remained uncoated, the BLMs formed in the Si chips still showed high mechanical stability after the insulator coatings. The mechanically stable BLMs having electric properties suitable for recording activities of biological channels will open up a variety of applications including high-throughput analysis of ion-channel proteins.
A unique simulation method of epoxy-based chemically-amplified resist by coarse-grained molecular dynamics was proposed. The mechanical properties of an epoxy-based chemically-amplified resists with various cross-linking ratios were simulated using a newly developed coarse-grained molecular dynamics simulation that employs a bead-spring model. Models with the different cross-linking ratios were created in the molecular dynamics calculation step and uniaxial elongation simulations were performed. The results reveal that the simulated elastic modulus of the resist modeled by the bead-spring model with an extended angle bending potential depends on the cross-linking ratio; its dependency exhibits good agreement with that determined by nanoindentation tests.
Nanostructured carbons have been widely used for fabricating enzyme-modified electrodes due to their large specific surface area. However, because they are random aggregates of particular or tubular nanocarbons, the post-modification of enzymes to their intra-nanospace is generally hard to control. Here, we describe a free-standing film of carbon nanotube forest (CNTF) that can form a hybrid ensemble with enzymes through liquid-induced shrinkage. This provides in-situ regulation of itsintra-nanospace (inter CNT pitch) to the size of enzymes, and eventually serves as a highly active electrode. The CNTF ensemble with fructose dehydrogenase (FDH) showed the oxidation current density of 16 mA cm-2in stirred 200 mM fructose solution. The power density of a biofuel cell using the FDH-CNTF anode and the Laccase-CNTF cathode reached 1.8 mW cm-2(at 0.45 V) in the stirred oxygenic fructose solution, more than 80 % of which could be maintained after continuous operation for 24 h. Application of the free-standing, flexible character of the enzyme-CNTF ensemble electrodes is demonstrated via their use in the patch or wound form.
The electrochemiluminescence (ECL) and surface plasmon resonance (SPR) based immunosensors for measuring a trace level of disease markers are shown. It is well known that thiols form a self-assembled monolayer on a metal surface, and this has been widely used to modify metal surfaces. We employed this characteristic for a highly sensitive immunosensors by obtaining a surface pre-concentration of thiol molecules formed by the enzymatic reaction of labeled antibody.
Engineering and manufacturing of thick and bio-functional tissue products is one of the big issues in tissue engineering. To produce such tissues, we need some innovative technologies, which enable us to build up thick, three-dimensional structures and to arrange multiple types of cells to make complicated tissue structures. Based on such considerations, we have developed a custom-made inkjet 3D bioprinter, which realized both of direct cell printing and 3D laminating printing with cells and hydrogel. Recently, it has been improved, and here we report recent progresses and our achievements with new version 3D bioprinter.
Image based printing mode and active Z-axis control system were added. As a useful structure, an image of multi-honeycomb pattern was designed in computer and next it was copied and finally in total 100 image data were prepared. Using those digital data, 3D image of thick multi-honeycomb structure was reconstructed in computer, and then, laminating printing was carried out using our new version 3D bioprinter with alginate hydrogel. The new version printer showed good performance of 3D laminating printing and finally complicated 3D multi-honeycomb hydrogel structures could be successfully fabricated. It is indicated that fabrication of cell containing 3D structures based on the computer aided designs is feasible and that such biofabrication technologies must contribute to further innovative advancement of tissue engineering.
With the aid of negative dielectrophoresis (nDEP) force in conjunction with shear force and at an optimal sodium hydroxide (NaOH) concentration we demonstrated a switch-like functionality to elute immuno-bound beads from the surface. At an optimal flow rate and NaOH concentration, nDEP turned on results in bead detachment, whereas when nDEP is off, the beads remain attached. This platform offers the potential for performing a bead-based multiplexed immunoassay where in a single channel various regions are immobilized with a different antibody, each targeting a different antigen. As a proof of concept we demonstrated the ability of nDEP to provide this switching behavior in a singleplex assay for the interactions that were in the same order of magnitude in strength as typical antibody-antigen interactions.
We present a rapid and sensitive surface acoustic wave (SAW) immunosensor that utilizes gold staining as a signal enhancement method. A sandwich immunoassay was performed on sensing area of the SAW sensor, which could specifically capture and detect cardiac markers (cardiac troponin I (cTnI), creatine kinase (CK)-MB, and myoglobin). The analytes in human serum were captured on gold nanoparticles (AuNPs) that were conjugated in advance with detection antibodies. Introduction of these complexes to the capture antibody-immobilized sensor surface resulted in a classic AuNP-based sandwich immunoassay format that has been used for signal amplification. In order to achieve further signal enhancement, a gold staining method was performed, which demonstrated that it is possible to obtain gold staining-mediated signal augmentation on a mass-sensitive device. The sensor response due to gold staining varied as a function of cardiac marker concentration.
This paper describes a semi-automated conductive ink process used for packaging MEMS devices. The method is applied to packaging of MEMS sensors for wind tunnel testing. The primary advantage of the method is a reduction in surface topology between the package and the integrated MEMS sensors. In this paper we explore the relationship between trace dimensions, resistivity, and deposition parameters such as feed rate, tip-substrate separation and tip diameter. Using this procedure it is possible to generate interconnects between a PC board and MEMS sensor chip with a topology of less than 25 micrometers.
Biofilms are a common cause of persistent infections on medical devices as they are easy to form and hard to treat. Selenium and its compounds are considered to be a novel material for a wide range of applications including anticancer applications and antibacterial applications. The objective of this study was to coat selenium nanoparticles on the surface of polycarbonate medical devices and examine their effectiveness at preventing biofilm formation. The results of this in vitro study showed that the selenium coating significantly inhibited Staphylococcus aureus growth on the surface of polycarbonate after 24 hours. Thus, this study suggests that coating polymers with nanostructured selenium is a fast and effective way to reduce bacteria functions leading to medical device infections.
Gallium nitride (GaN) is a robust piezoelectric semiconductor with excellent thermal and chemical stability, making it an attractive material for surface acoustic wave (SAW) sensors operating in high temperature and harsh environments. The sensitivity of SAW devices is proportional to the square of the operating frequency. Therefore, high operating frequencies into the GHz regime are desirable for SAW sensors. For GaN, this requires sub-micron interdigital transducers (IDTs) when devices are designed to operate at the fundamental Rayleigh mode frequency. The necessity for sub-micron IDTs can increase fabrication costs and complexity. By designing SAW devices to operate at harmonic frequencies, GHz operation can be realized with relatively large IDTs, resulting in simpler and more cost effective solutions for GaN based SAW sensors. Devices have previously been designed to operate at the 5th and higher harmonics on lithium niobate, but there are no reports of using this technique on GaN in the literature. In this study, GaN thin films have been grown via metal organic vapor phase epitaxy on sapphire substrates. SAW devices designed to operate at the fundamental frequency and higher harmonics have been fabricated and measured. Operating frequencies greater than 2 GHz have been achieved using IDTs with 5 μm fingers. In addition, reduction of electromagnetic feedthrough around the 5th and 7th harmonic is demonstrated through varying ground electrode geometries.
Capacitive CMOS MEMS sensors are usually defined by anisotropic dry etching processes (RIE and DRIE). These processes can provide clean and vertical sidewall geometry. However, during the dry-etching processes, charges are added to the gate electrodes of the on-chip MOSFET’s through metal pads and micro-structures, and the voltage may be raised to the level of breaking down the gate oxide, which leads to large leakage current and fails the circuit. On another hand, the thin spring beams in capacitive CMOS MEMS accelerometers suffer from in-plane curling and out-of-plane curling caused by stress gradient. Furthermore, the stress in the layers of MEMS structure is a function of temperature. Therefore, the in-plane curling and out-of-plane curling vary with temperature, leading to varying electrode coupling area in the sensing beams. This in turn causes variation in the sensitivity and the DC offset of sensors, meaning that usually the thermal stability of CMOS MEMS capacitive accelerometers is very poor. To cope with these problems, this work develops a new wafer-level post-CMOS process for fabricating thermally stable capacitive accelerometers. The resultant MEMS structures have high aspect ratio (e.g. 2-2.5 μm gaps versus 57 μm depth) and are insensitive to residual stress as well as temperature change. Excellent thermal stability was achieved intrinsically by making the crystalline Si layer in the sensors thick. Moreover, this process totally avoids the charge damage problem during the dry-etching procedure. For demonstration, an accelerometer sensor was fabricated by using the proposed process and was integrated with an on-chip sensing circuit in commercial 0.35 μm 2P4M CMOS process. High detection sensitivity of 595 mV/g and very low thermal variation of 1.68 mg/°C were successfully achieved.