Physicochemical characterisation of degrading polycaprolactone scaffolds

A degradation study investigating the hydrolysis of different scaffolds of polycaprolactone suspended in phosphate buffer solution at 37 °C was performed over a three month period. Structures included electrospun fibres, held as 2D mats and 3D bundles, and solvent cast films. These structures and their surrounding solutions were physiochemically characterised using a range of techniques. Changes in scaffold physicochemical properties were observed over the course of the study, including significant loss in molecular mass, increases in thermal properties and crystallinity, and increases in tensile properties. The presence of degradation products, such as capronic acid containing compounds was also identified in the surrounding solution. 3D electrospun bundles - as a consequence of being the least crystalline scaffold and hence most susceptible to hydrolysis - demonstrated greatest reduction in molecular mass over the three months, followed by 2D electrospun mats, and the lowest mass loss was observed for solvent cast films.     

Measurements of anisotropic thermopower of magnetically aligned YBa2Cu3O7−δ ceramics: evidence of successful texturing techniques

Aligned YBa₂Cu₃O_7−δ ceramics have been obtained using a field of 1 T without being embedded in epoxy. Thermopower, XRD, and SEM are used to characterize the aligned ceramics. For the sample with δ=0.05, the thermopower exhibits a strong anisotropy. The ab-plane thermopower behaves distinctly from that along the c-axis. The ab-plane thermopower shows remarkable similarities to that along the b-axis in an untwinned single crystal. The magnitude and temperature dependence of the c-axis thermopower are almost identical to those of a twinned single crystal. For samples with larger oxygen deficiency, the anisotropy remains. These measurements indicate that these ceramics are well aligned along their crystallographic directions. This also makes available the anisotropic thermopower measurements of ceramic samples by aligning polycrystallites using magnetic forces.     

Design and Synthesis of 56 Shape-Diverse 3D Fragments

Fragment-based drug discovery is now widely adopted for lead generation in the pharmaceutical industry. However, fragment screening collections are often predominantly populated with flat, 2D molecules. Herein, we describe a workflow for the design and synthesis of 56 3D disubstituted pyrrolidine and piperidine fragments that occupy under-represented areas of fragment space (as demonstrated by a principal moments of inertia (PMI) analysis). A key, and unique, underpinning design feature of this fragment collection is that assessment of fragment shape and conformational diversity (by considering conformations up to 1.5 kcal mol⁻¹ above the energy of the global minimum energy conformer) is carried out prior to synthesis and is also used to select targets for synthesis. The 3D fragments were designed to contain suitable synthetic handles for future fragment elaboration. Finally, by comparing our 3D fragments with six commercial libraries, it is clear that our collection has high three-dimensionality and shape diversity.     

A new approach to variable selection in least squares problems

The title Lasso has been suggested by Tibshirani (1996) as acolourful name for a technique of variable selection which requiresthe minimization of a sum of squares subject to an l₁ bound on the solution. This forces zero components in the minimizingsolution for small values of . Thus this bound can functionas a selection parameter. This paper makes two contributionsto computational problems associated with implementing the Lasso:(1) a compact descent method for solving the constrained problemfor a particular value of is formulated, and (2) a homotopymethod, in which the constraint bound becomes the homotopyparameter, is developed to completely describe the possibleselection regimes. Both algorithms have a finite terminationproperty. It is suggested that modified Gram-Schmidt orthogonalizationapplied to an augmented design matrix provides an effectivebasis for implementing the algorithms.     

Raman spectroscopy and CARS microscopy of stem cells and their derivatives

The characterisation of stem cells is of vital importance to regenerative medicine. Failure to separate out all stem cells from differentiated cells before therapies can result in teratomas—tumours of multiple cell types. Typically, characterisation is performed in a destructive manner with fluorescent assays. A truly non‐invasive method of characterisation would be a major breakthrough in stem cell‐based therapies. Raman spectroscopy has revealed that DNA and RNA levels drop when a stem cell differentiates into other cell types, which we link to a change in the relative sizes of the nucleus and cytoplasm. We also used Raman spectroscopy to investigate the biochemistry within an early embryo, or blastocyst, which differs greatly from colonies of embryonic stem cells. Certain cell types that differentiate from stem cells can be identified by directly imaging the biochemistry with CARS microscopy; examples presented are hydroxyapatite—a precursor to bone, and lipids in adipocytes. Copyright © 2011 John Wiley & Sons, Ltd.     

Siderophore-Mediated Iron Uptake Promotes Yeast–Bacterial Symbiosis

In the present study, siderophore produced by the marine yeast Aureobasidium pullulans was characterized as hydroxamate by chemical and bioassays. The hydroxamate assignment was supported by the appearance of peaks at 1,647.21?C1,625.99?cm^?1 and at 1,435.04?cm^?1 in the infrared spectrum. The purified siderophore exhibited specific growth-promoting activity under iron-limited conditions for siderophore auxotrophic probiotic bacteria. Cross-utilization of siderophore indicates a symbiotic relationship between the yeast A. pullulans and the selected probiotic bacterial strains. Statistical optimization of medium components for improved siderophore production in A. pullulans was depicted by response surface methodology. The shift in UV?CVis spectroscopy indicates the photoreactive property and subsequent oxidative cleavage of purified siderophore on exposure to sunlight.     

Nonlinear optical microscopy for drug delivery monitoring and cancer tissue imaging

A multimodal nonlinear optical microscope that combines coherent anti‐Stokes Raman scattering (CARS), two‐photon excitation fluorescence (TPEF), second‐harmonic generation (SHG) and sum‐frequency generation (SFG) was developed and applied to image breast cancer tissue and MCF‐7 cells as well as monitoring anticancer drug delivery in live cells. TPEF imaging showed that drugs are preferentially localized in the cytoplasm and the nuclear envelope in resistant cells. Moreover, the extracellular matrix was observed by TPEF signals arising from elastin's autofluorescence and SHG signals from collagen fibrils in breast tissue sections. Additionally, CARS signals arising from proteins and (PO₂)⁻ allowed identification of tumors. Label‐free imaging with chemical contrast of significant components of cancer cells and tissue suggests the potential of multimodal nonlinear optical microscopy for early detection and diagnosis of cancer. Copyright © 2010 John Wiley & Sons, Ltd.