Hubble Space Telescope Faint Object Camera calculated point-spread functions

A set of observed noisy Hubble Space Telescope Faint Object Camera point-spread functions is used to recover the combined Hubble and Faint Object Camera wave-front error. The low-spatial-frequency wave-front error is parameterized in terms of a set of 32 annular Zernike polynomials. The midlevel and higher spatial frequencies are parameterized in terms of set of 891 polar-Fourier polynomials. The parameterized wave-front error is used to generate accurate calculated point-spread functions, both pre- and post-COSTAR (corrective optics space telescope axial replacement), suitable for image restoration at arbitrary wavelengths. We describe the phase-retrieval-based recovery process and the phase parameterization. Resultant calculated precorrection and postcorrection point-spread functions are shown along with an estimate of both pre- and post-COSTAR spherical aberration.     

Cost Minimizing Local Anisotropic Quad Mesh Refinement

Quad meshes as a surface representation have many conceptual advantages over triangle meshes. Their edges can naturally be aligned to principal curvatures of the underlying surface and they have the flexibility to create strongly anisotropic cells without causing excessively small inner angles. While in recent years a lot of progress has been made towards generating high quality uniform quad meshes for arbitrary shapes, their adaptive and anisotropic refinement remains difficult since a single edge split might propagate across the entire surface in order to maintain consistency. In this paper we present a novel refinement technique which finds the optimal trade-off between number of resulting elements and inserted singularities according to a user prescribed weighting. Our algorithm takes as input a quad mesh with those edges tagged that are prescribed to be refined. It then formulates a binary optimization problem that minimizes the number of additional edges which need to be split in order to maintain consistency. Valence 3 and 5 singularities have to be introduced in the transition region between refined and unrefined regions of the mesh. The optimization hence computes the optimal trade-off and places singularities strategically in order to minimize the number of consistency splits — or avoids singularities where this causes only a small number of additional splits. When applying the refinement scheme iteratively, we extend our binary optimization formulation such that previous splits can be undone if this prevents degenerate cells with small inner angles that otherwise might occur in anisotropic regions or in the vicinity of singularities. We demonstrate on a number of challenging examples that the algorithm performs well in practice.     

An inexpensive device for freeze drying and plastic embedding tissues at low temperatures

The preparation of biological tissues for electron microscopy by rapid freezing retains the original localization of ions and molecules. A reproducible freezing regime was established by quenching tissues in liquid propane according to the method of Elder et al. (1981). Tissue was thereafter freeze dried in a custom built freeze drying device with a liquid nitrogen cooled stage to prevent ice recrystallization during drying. The device was also designed to allow the vacuum embedding of tissue in low temperature resin such as Lowicryl® and polymerization in situ. This paper describes the design of the device and an example of its use in the freeze drying of cartilage. The results show that minimal ice damage occurs to the chondrocytes and that intracellular organelles are clearly visible. The regime described may prove a useful and pragmatic alternative to cutting tissue in the frozen state. Translocation of elements is unlikely except perhaps in the case of very labile elements such as Na and K, but this remains to be fully elucidated.     

Satellite retrieval of inherent optical properties by inversion of an oceanic radiance model: a preliminary algorithm

A previously published radiance model inversion theory has been field tested by using airborne water-leaving radiances to retrieve the chromophoric dissolved organic matter (CDOM) and detritus absorption coefficient, the phytoplankton absorption coefficient, and the total backscattering coefficient. The radiance model inversion theory was tested for potential satellite use by comparing two of the retrieved inherent optical properties with concurrent airborne laser-derived truth data. It was found that (1) matrix inversion of water-leaving radiances is well conditioned even in the presence of instrument-induced noise, (2) retrieved CDOM and detritus and phytoplankton absorption coefficients are both in reasonable agreement with absorption coefficients derived from airborne laser-induced fluorescence spectral emissions, (3) the total backscattering retrieval magnitude and variability are consistent with expected values for the Middle Atlantic Bight, and (4) the algorithm performs reasonably well in Sargasso Sea, Gulf Stream, slope, and shelf waters but is less consistent in coastal waters.     

Improving Antibody-Tubulysin Conjugates through Linker Chemistry and Site-Specific Conjugation

Tubulysins have emerged in recent years as a compelling drug class for delivery to tumor cells via antibodies. The ability of this drug class to exert bystander activity while retaining potency against multidrug-resistant cell lines differentiates them from other microtubule-disrupting agents. Tubulysin M, a synthetic analogue, has proven to be active and well tolerated as an antibody-drug conjugate (ADC) payload, but has the liability of being susceptible to acetate hydrolysis at the C11 position, leading to attenuated potency. In this work, we examine the ability of the drug-linker and conjugation site to preserve acetate stability. Our findings show that, in contrast to a more conventional protease-cleavable dipeptide linker, the β-glucuronidase-cleavable glucuronide linker protects against acetate hydrolysis and improves ADC activity in vivo. In addition, site-specific conjugation can positively impact both acetate stability and in vivo activity. Together, these findings provide the basis for a highly optimized delivery strategy for tubulysin M.     

The effect of interfacial chemistry on coating adhesion and performance: A mechanistic study using aminobutylphosphonic acid

Failure of adhesion of organic coating (paints) to steel and other metallic substrates is one of the key mechanisms for local coating failure and for consequent restriction of coating lifetime. This study thus focuses on modification to the chemistry of the metal interface in order to promote enhanced (dry and wet) coating adhesion. The work uses an appropriate bi-functional amino alkyl phosphonate to provide the desired interfacial properties. The study uses X-ray photoelectron spectroscopy and water contact angle measurement to examine changes in the interfacial surface chemistry and electrochemical impedance spectroscopy and cathodic disbonding to determine improvements to the anti-corrosion performance. Choosing 4-amino-butyl-phosphonic acid as the surface modifier a significant influence on its efficiency as an adhesion promoter was observed as a function of pH. Thus, when the amino group was protonated at a pH of 5.3, the molecule demonstrated attachment to carbon steel at both ends with no significant improvement in performance. However at pH 8 the molecule demonstrated greatly improved surface packing density with the amino group outwards from the surface in the preferred orientation. In this condition, an epoxy coating demonstrated substantial resistance to interfacial hydrolysis with overall improved adhesion and reduced cathodic disbondment rate.     

Phosphate decreases urine calcium and increases calcium balance: A meta-analysis of the osteoporosis acid-ash diet hypothesis

Background  

The acid-ash hypothesis posits that increased excretion of "acidic" ions derived from the diet, such as phosphate, contributes to net acidic ion excretion, urine calcium excretion, demineralization of bone, and osteoporosis. The public is advised by various media to follow an alkaline diet to lower their acidic ion intakes. The objectives of this meta-analysis were to quantify the contribution of phosphate to bone loss in healthy adult subjects; specifically, a) to assess the effect of supplemental dietary phosphate on urine calcium, calcium balance, and markers of bone metabolism; and to assess whether these affects are altered by the b) level of calcium intake, c) the degree of protonation of the phosphate.     

Wood preservation by a mixed anhydride treatment: A 13C‐NMR investigation of simple models of polymeric wood constituents

The treatment of wood by a mixed aceto/oleic (or other fatty acid residue) anhydride promoted as a safe and environmentally friendly wood preservation system was examined quantitatively by liquid‐phase ¹³C‐NMR and solid‐phase magic angle spinning–DEC (proton decoupling) ¹³C‐NMR through of all its different stages to determine which reactions occurred with simple model compounds of the polymeric constituents of wood. The preparation of the mixed aceto/oleic anhydride under different conditions was also undertaken. The anhydride formed, but its percentage yield was only 30%. The mix composed of unreacted acetic anhydride, the mixed aceto/oleic anhydride, and a large proportion of free acetic and oleic acid, which are used for wood preservation, yielded the acetylation of the lignin model compound (1) by the reaction of the acetic anhydride with it and (2) by the reaction of the acetic part of the mixed anhydride. In this reaction, all of the mixed anhydride was consumed. The oleic part of the mixed anhydride was unable to form esters with either lignin or wood holocellulose as it was far less reactive than the acetic part. Some acetylation of holocellulose occurred, and some traces of its oleic acid ester also occurred under some conditions. This system of treatment through a mixed anhydride appeared to consist of just an acetylation with acetic anhydride mixed with some oleic acid as a water repellent, both of which are already known processes. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Multifunctional nanogels for siRNA delivery

The application of RNA interference to treat disease is an important yet challenging concept in modern medicine. In particular, small interfering RNA (siRNA) have shown tremendous promise in the treatment of cancer. However, siRNA show poor pharmacological properties, which presents a major hurdle for effective disease treatment especially through intravenous delivery routes. In response to these shortcomings, a variety of nanoparticle carriers have emerged, which are designed to encapsulate, protect, and transport siRNA into diseased cells. To be effective as carrier vehicles, nanoparticles must overcome a series of biological hurdles throughout the course of delivery. As a result, one promising approach to siRNA carriers is dynamic, versatile nanoparticles that can perform several in vivo functions. Over the last several years, our research group has investigated hydrogel nanoparticles (nanogels) as candidate delivery vehicles for therapeutics, including siRNA. Throughout the course of our research, we have developed higher order architectures composed entirely of hydrogel components, where several different hydrogel chemistries may be isolated in unique compartments of a single construct. In this Account, we summarize a subset of our experiences in the design and application of nanogels in the context of drug delivery, summarizing the relevant characteristics for these materials as delivery vehicles for siRNA. Through the layering of multiple, orthogonal chemistries in a nanogel structure, we can impart multiple functions to the materials. We consider nanogels as a platform technology, where each functional element of the particle may be independently tuned to optimize the particle for the desired application. For instance, we can modify the shell compartment of a vehicle for cell-specific targeting or evasion of the innate immune system, whereas other compartments may incorporate fluorescent probes or regulate the encapsulation and release of macromolecular therapeutics. Proof-of-principle experiments have demonstrated the utility of multifunctional nanogels. For example, using a simple core/shell nanogel architecture, we have recently reported the delivery of siRNA to chemosensitize drug resistant ovarian cancer cells. Ongoing efforts have resulted in several advanced hydrogel structures, including biodegradable nanogels and multicompartment spheres. In parallel, our research group has studied other properties of the nanogels, including their behavior in confined environments and their ability to translocate through small pores.     

A reactive molecular dynamics model of thermal decomposition in polymers. II. Polyisobutylene

An improved version of the reactive molecular dynamics method is presented. The method, which extends conventional (force-field-based) molecular dynamics to modeling chemical reactions, is used to simulate the thermal decomposition of polyisobutylene. The results of the simulations are generally consistent with experimental observations. A quantitative analysis of the results shows that the rate constant of the key initiation reaction, backbone scission, depends on the size of the molecular model of the polymer. This implies that the kinetics of some elementary reactions that take place in a polymer melt are affected by the macromolecular nature of the environment.