Dispersible crystalline nanobundles of YPO4 and Ln (Eu, Tb)-doped YPO4: rapid synthesis, optical properties and bio-probe applications

Undoped and Ln(3+) (Eu and Tb)-doped crystalline nanobundles of YPO4 were prepared by a facile microwave-assisted route with water as a solvent and without using any surfactant. TEM investigations reveal that the as-prepared powder consists of lenticular-shaped nanobundles (similar to 100 nm in diameter) made of very small nanorods with diameter less than 10 nm and length varying from 20 to 50 nm. Each nanorod in turn is single crystalline, as revealed by HRTEM imaging. The as-prepared nanobundles are easily dispersible in various solvents, especially water, without any surface functionalization, which is critical for various bio-probe applications like cell and tissue imaging. The Eu- and Tb-doped YPO4 nanobundles show good photoluminescence properties and were further evaluated for their use as fluorescent biolabels. Our results show that HeLa cells labelled with Eu- and Tb-doped YPO4 nanobundles show bright red (Eu) and green (Tb) intracellular luminescence under a confocal microscope. Concentration-and time-dependent MTT cell viability assays show that the nanobundles show low toxicity towards cells which makes them promising in bioimaging field.

The Holy Grail of Polymer Therapeutics for Cancer Therapy: An Overview on the Pharmacokinetics and Bio Distribution

In recent years, multifaceted clinical benefits of polymeric therapeutics have been reported. Over the past decades, cancer has been one of the leading causes of mortality in the world. Many clinically approved chemotherapeutics encounter potential challenges against deadly cancer. Moreover, safety and efficacy of anticancer agents have been limited by undesirable pharmacokinetics and biodistribution. To address these limitations, various polymer drug conjugates are being studied and developed to improve the antitumor efficacy. Among other therapeutics, polymer therapeutics are well established platforms that circumvent anticancer therapeutics from enzymatic metabolism via direct conjugation to therapeutic molecules. Interestingly, polymer therapeutics meets an unmet need of small molecules. Further clinical study showed that polymer-drug conjugation can achieve desired pharmacokinetics and biodistribution properties of several anticancer drugs. The present retrospective review mainly enlightens the most recent preclinical and clinical studies include safety, stability, pharmacokinetic behavior and distribution of polymer therapeutics.

Fabrication and bio-functionalization of tetrahedral amorphous carbon thin films for bio sensor applications

Tetrahedral amorphous carbon (ta-C) thin films are a promising material for use as biocompatible interfaces in applications such as in-vivo biosensors. However, the functionalization of ta-C film surface, which is a pre-requisite for biosensors, remains a big challenge due to its chemical inertness. We have investigated the bio-functionalization of ta-C films fabricated under specific physical conditions through the covalent attachment of functional biomolecular probes of peptide nucleic acid (PNA) to ta-C films, and the effect of fabrication conditions on the bio-functionalization. The study showed that the functional bimolecular probes such as protected long-chain ω-unsaturated amine (TFAAD) can be covalently attached to the ta-C surface through a well-defined structure. With the given fabrication process, electrochemical methods can be applied to the detection of biomolecular interaction, which establishes the basis for the development of stable, label-free biosensors. © 2011 Elsevier B.V. All rights reserved.

Bio-inspired mechanics of reversible adhesion: Orientation-dependent adhesion strength for non-slipping adhesive contact with transversely isotropic elastic materials

Geckos and many insects have evolved elastically anisotropic adhesive tissues with hierarchical structures that allow these animals not only to adhere robustly to rough surfaces but also to detach easily upon movement. In order to improve Our understanding of the role of elastic anisotropy in reversible adhesion, here we extend the classical JKR model of adhesive contact mechanics to anisotropic materials. In particular, we consider the plane strain problem of a rigid cylinder in non-slipping adhesive contact with a transversely isotropic elastic half space with the axis of symmetry oriented at an angle inclined to the surface. The cylinder is then subjected to an arbitrarily oriented pulling force. The critical force and contact width at pull-off are calculated as a function of the pulling angle. The analysis shows that elastic anisotropy leads to an orientation-dependent adhesion strength which can vary strongly with the direction of pulling. This study may suggest possible mechanisms by which reversible adhesion devices can be designed for engineering applications. (C) 2006 Elsevier Ltd. All rights reserved.

Reference Points Based on Dynamic Optimisation: A Versatil Algorithm for Mixed Fishery Management with Bio-economic Agestructured Models

Single-species management objectives may not be consistent within mixed fisheries. They may lead species to unsafe situations, promote discarding of over-quota and/or misreporting of catches. We provide an algorithm for characterising bio-economic reference points for a mixed fishery as the steady-state solution of a dynamic optimal management problem. The optimisation problem takes into account: i) that species are fishing simultaneously in unselective fishing operations and ii)intertemporal discounting and fleet costs to relate reference points to discounted economic profits along optimal trajectories. We illustrate how the algorithm can be implemented by applying it to the European Northern Stock of Hake (Merluccius merluccius), where fleets also capture Northern megrim (Lepidorhombus whiffiagonis) and Northern anglerfish (Lophius piscatorius and Lophius budegassa). We find that optimal mixed management leads to a target reference point that is quite similar to the 2/3 of the Fmsy single-species (hake) target. Mixed management is superior to singlespecies management because it leads the fishery to higher discounted profits with higher long-term SSB for all species. We calculate that the losses due to the use of the Fmsy single-species (hake) target in this mixed fishery account for 11.4% of total discounted profits.

Molecular Dynamics Simulation of the Bio-Adhesion in Molecular Motors

Molecular dynamics (MD) simulation is employed to study the bio-adhesion in F1 ATP molecular motor. Histidine-peptide is widely used as linkage in micro systems because of its strong binding strength to metals. This paper focuses on the adhesion between a synthetic peptide containing 6xHis-tag (Gly-Gly-Lys-Gly-Gly-Lys-Gly-Gly-His-His-His-His-His-His) and metal substrate, which is used to define the position of the F1 ATP molecular motor on the metal substrate. It is shown that the binding strength between histidine and nickel substrate is the strongest, while that of copper is smaller and that of gold substrate is the smallest. From the result of simulation, we find that the stability of adhesion between histidine and the metal substate result of the ringed structure in histidine.

Friction properties of bio-mimetic nano-fibrillar arrays

Nano-fibrillar arrays are fabricated using polystyrene materials. The average diameter of each fiber is about 300 nm. Experiments show that such a fibrillar surface possesses a relatively hydrophobic feature with a water contact angle of 142 degrees. Nanoscale friction properties are mainly focused on. It is found that the friction force of polystyrene nano-fibrillar surfaces is obviously enhanced in contrast to polystyrene smooth surfaces. The apparent coefficient of friction increases with the applied load, but is independent of the scanning speed. An interesting observation is that the friction force increases almost linearly with the real contact area, which abides by the fundamental Bowden-Tabor law of nano-scale friction.

Tissue engineering active biological machines : bio-inspired design, directed self-assembly, and characterization of muscular pumps simulating the embryonic heart

Biological machines are active devices that are comprised of cells and other biological components. These functional devices are best suited for physiological environments that support cellular function and survival. Biological machines have the potential to revolutionize the engineering of biomedical devices intended for implantation, where the human body can provide the required physiological environment. For engineering such cell-based machines, bio-inspired design can serve as a guiding platform as it provides functionally proven designs that are attainable by living cells. In the present work, a systematic approach was used to tissue engineer one such machine by exclusively using biological building blocks and by employing a bio-inspired design. Valveless impedance pumps were constructed based on the working principles of the embryonic vertebrate heart and by using cells and tissue derived from rats. The function of these tissue-engineered muscular pumps was characterized by exploring their spatiotemporal and flow behavior in order to better understand the capabilities and limitations of cells when used as the engines of biological machines.

Coupled effects of mechanics, geometry, and chemistry on bio-membrane behavior

Lipid bilayer membranes are models for cell membranes--the structure that helps regulate cell function. Cell membranes are heterogeneous, and the coupling between composition and shape gives rise to complex behaviors that are important to regulation. This thesis seeks to systematically build and analyze complete models to understand the behavior of multi-component membranes.

We propose a model and use it to derive the equilibrium and stability conditions for a general class of closed multi-component biological membranes. Our analysis shows that the critical modes of these membranes have high frequencies, unlike single-component vesicles, and their stability depends on system size, unlike in systems undergoing spinodal decomposition in flat space. An important implication is that small perturbations may nucleate localized but very large deformations. We compare these results with experimental observations.

We also study open membranes to gain insight into long tubular membranes that arise for example in nerve cells. We derive a complete system of equations for open membranes by using the principle of virtual work. Our linear stability analysis predicts that the tubular membranes tend to have coiling shapes if the tension is small, cylindrical shapes if the tension is moderate, and beading shapes if the tension is large. This is consistent with experimental observations reported in the literature in nerve fibers. Further, we provide numerical solutions to the fully nonlinear equilibrium equations in some problems, and show that the observed mode shapes are consistent with those suggested by linear stability. Our work also proves that beadings of nerve fibers can appear purely as a mechanical response of the membrane.

Innovations of wide-field optical-sectioning fluorescence microscopy : toward high-speed volumetric bio-imaging with simplicity

Optical microscopy has become an indispensable tool for biological researches since its invention, mostly owing to its sub-cellular spatial resolutions, non-invasiveness, instrumental simplicity, and the intuitive observations it provides. Nonetheless, obtaining reliable, quantitative spatial information from conventional wide-field optical microscopy is not always intuitive as it appears to be. This is because in the acquired images of optical microscopy the information about out-of-focus regions is spatially blurred and mixed with in-focus information. In other words, conventional wide-field optical microscopy transforms the three-dimensional spatial information, or volumetric information about the objects into a two-dimensional form in each acquired image, and therefore distorts the spatial information about the object. Several fluorescence holography-based methods have demonstrated the ability to obtain three-dimensional information about the objects, but these methods generally rely on decomposing stereoscopic visualizations to extract volumetric information and are unable to resolve complex 3-dimensional structures such as a multi-layer sphere.

The concept of optical-sectioning techniques, on the other hand, is to detect only two-dimensional information about an object at each acquisition. Specifically, each image obtained by optical-sectioning techniques contains mainly the information about an optically thin layer inside the object, as if only a thin histological section is being observed at a time. Using such a methodology, obtaining undistorted volumetric information about the object simply requires taking images of the object at sequential depths.

Among existing methods of obtaining volumetric information, the practicability of optical sectioning has made it the most commonly used and most powerful one in biological science. However, when applied to imaging living biological systems, conventional single-point-scanning optical-sectioning techniques often result in certain degrees of photo-damages because of the high focal intensity at the scanning point. In order to overcome such an issue, several wide-field optical-sectioning techniques have been proposed and demonstrated, although not without introducing new limitations and compromises such as low signal-to-background ratios and reduced axial resolutions. As a result, single-point-scanning optical-sectioning techniques remain the most widely used instrumentations for volumetric imaging of living biological systems to date.

In order to develop wide-field optical-sectioning techniques that has equivalent optical performance as single-point-scanning ones, this thesis first introduces the mechanisms and limitations of existing wide-field optical-sectioning techniques, and then brings in our innovations that aim to overcome these limitations. We demonstrate, theoretically and experimentally, that our proposed wide-field optical-sectioning techniques can achieve diffraction-limited optical sectioning, low out-of-focus excitation and high-frame-rate imaging in living biological systems. In addition to such imaging capabilities, our proposed techniques can be instrumentally simple and economic, and are straightforward for implementation on conventional wide-field microscopes. These advantages together show the potential of our innovations to be widely used for high-speed, volumetric fluorescence imaging of living biological systems.