Carmen Torres-Sanchez

Extracellular palladium-catalysed dealkylation of 5-fluoro-1-propargyl-uracil as a bioorthogonally activated prodrug approach

A bioorthogonal organometallic reaction is a biocompatible transformation undergone by a synthetic material exclusively through the mediation of a non-biotic metal source; a selective process used to label biomolecules and activate probes in biological environs. Here we report the in vitro bioorthogonal generation of 5-fluorouracil from a biologically inert precursor by heterogeneous Pd0 catalysis. Although independently harmless, combined treatment of 5-fluoro-1-propargyl-uracil and Pd0-functionalized resins exhibits comparable antiproliferative properties to the unmodified drug in colorectal and pancreatic cancer cells. Live-cell imaging and immunoassay studies demonstrate that the cytotoxic activity of the prodrug/Pd0-resin combination is due to the in situ generation of 5-fluorouracil. Pd0-resins can be carefully implanted in the yolk sac of zebrafish embryos and display excellent biocompatibility and local catalytic activity. The in vitro efficacy shown by this masking/activation strategy underlines its potential to develop a bioorthogonally activated prodrug approach and supports further in vivo investigations.

Development and Bioorthogonal Activation of Palladium-Labile Prodrugs of Gemcitabine

Bioorthogonal chemistry has become one of the main driving forces in current chemical biology, inspiring the search for novel biocompatible chemospecific reactions for the past decade. Alongside the well-established labeling strategies that originated the bioorthogonal paradigm, we have recently proposed the use of heterogeneous palladium chemistry and bioorthogonal Pd0-labile prodrugs to develop spatially targeted therapies. Herein, we report the generation of biologically inert precursors of cytotoxic gemcitabine by introducing Pd0-cleavable groups in positions that are mechanistically relevant for gemcitabine’s pharmacological activity. Cell viability studies in pancreatic cancer cells showed that carbamate functionalization of the 4-amino group of gemcitabine significantly reduced (>23-fold) the prodrugs’ cytotoxicity. The N-propargyloxycarbonyl (N-Poc) promoiety displayed the highest sensitivity to heterogeneous palladium catalysis under biocompatible conditions, with a reaction half-life of less than 6 h. Zebrafish studies with allyl, propargyl, and benzyl carbamate-protected rhodamines confirmed N-Poc as the most suitable masking group for implementing in vivo bioorthogonal organometallic chemistry.

Edge-based identification of DP-features on free-form solids

Numerous applications in mechanical CAD/CAM need robust algorithms for the identification of protrusion and depression features (DP-features) on geometric models with free-form (B-spline) surfaces. This paper reports a partitioning algorithm that first identifies the boundary edges of DP-features and then creates a surface patch to cover the depressions or isolate the protrusions. The novelty of the method lies in the use of tangent continuity between edge segments to identify DP-feature boundaries that cross multiple faces and geometries.

Toward Functionally Graded Cellular Microstructures

The design of multifunctional materials offers great potential for numerous applications in areas ranging from biomaterial science to structural engineering. Functionally graded microstructures (e.g., polymeric foams) are those whose porosity (i.e., ratio of the void to the solid volume of a material) is engineered to meet specific requirements such as a superior mechanical, thermal, and acoustic behavior. The controlled distribution of pores within the matrix, as well as their size, wall thickness, and interconnectivity are directly linked to the porous materials properties. There are emerging design and analysis methods of cellular materials but their physical use is restricted by current manufacturing technologies. Although a huge variety of foams can be manufactured with homogeneous porosity, for heterogeneous foams there are no generic processes for controlling the distribution of porosity throughout the resulting matrix. This paper describes work to develop an innovative and flexible process for manufacturing engineered cellular structures. Ultrasound was applied during specific foaming stages of a polymeric (polyurethane) melt, and this affected both the cellular architecture and distribution of the pore size, resulting in a controlled distribution that can be designed for specific purposes, once the polymeric foam solidified. The experimental results demonstrate that porosity (i.e., volume fraction) varies in direct proportion to the acoustic pressure magnitude of the ultrasonic signal.

ISO 16840-2:2007 load deflection and hysteresis measurements for a sample of wheelchair seating cushions

Load deflection and hysteresis measurements were made on 37 wheelchair seating cushions according to ISO 16840-2:2007. Load deflection plots for all 37 cushions are reported and fundamental aspects of graph interpretation discussed. ISO hysteresis data are also reported and interpretation discussed.

A Novel Manufacturing Strategy for Bio-Inspired Cellular Structures

This paper presents a novel manufacturing method for cellular materials with a graded porosity distribution. The motivation for creating a gradient of porosity in materials has been inspired by nature and aspires to mimic natural structures so their intrinsic advantages (e.g., optimised mechanical properties) can be exploited. Many engineering applications (e.g., thermal, acoustics, mechanical, structural and tissue engineering) require porosity tailored structures. However, current manufacturing processes are currently unable to mass-produce these foams. In this work, low power-low frequency ultrasonic irradiation has been used to excite polymeric foaming melts that, once solidified, contained different porosity distributions throughout in their solid matrix. This was possible by controlling the amount of energy imposed on the samples. The generation of porosity gradients that resembles those of natural cellular structures (e.g., bones, stems) opens up new opportunities in the design and manufacture of bio-inspired materials that can solve challenging technological problems.

Correlation of ISO 16840-2:2007 impact damping and hysteresis measures for a sample of wheelchair seating cushions

ABSTRACT Hysteresis and impact damping measures were made on 37 wheelchair seating cushions according to ISO 16840-2:2007 Wheelchair seating—Part 2: Determination of physical and mechanical characteristics of devices intended to manage tissue integrity—seat cushions. These measures were then correlated using Spearman and Pearson correlations to investigate the relationship between them. Correlations were also conducted on the subset of cushions comprising only those with planar foam construction. Correlation between the hysteresis measures (h250 and h500) and the mean number of rebounds greater in amplitude than 10% of the peak acceleration amplitude (R10%) were weak, as were the correlations between the hysteresis measures and the mean peak first rebound acceleration (aa). Correlations between hysteresis and the mean peak second rebound acceleration (a2), and also hysteresis and the ratio of first and second peak (a2:aa) however were moderate. Results demonstrate that the relationship between these two measures is complex. The assertion implicit in ISO 16840-2:2007 is that the two measures are related, but this study shows that these should not be assumed to be equivalent or used interchangeably.

An Implanted Antenna System for the Monitoring of Bioresorbability of a Biocompatible Scaffold Embedded into a Bone Fracture

In this paper the dielectric properties of an implanted bioresorbable scaffold that is being used for the acceleration of the healing process of a fractured bone have been investigated. An implanted antenna system is presented for the monitoring of the resorption rate of the scaffold, which gives an indication on the healing process of the bone fracture. A simulation model of a three layer body phantom was used for the evaluation of the 𝑆21 response of the system as the introduced fracture gradually healed, turning from blood to bone marrow and bone cortical in five steps.

Fast human classification of 3D object benchmarks

Although a significant number of benchmark data sets for 3D object based retrieval systems have been proposed over the last decade their value is dependent on a robust classification of their content being available. Ideally researchers would want hundreds of people to have classified thousands of parts and the results recorded in a manner that explicitly shows how the similarity assessments varies with the precision used to make the judgement. This paper reports a study which investigated the proposition that Internet Crowdsourcing could be used to quickly and cheaply provide benchmark classifications of 3D shapes. The collective judgments of the anonymous workers produce a classification that has surprisingly fine granularity and precision. The paper reports the results of validating Crowdsourced judgements of 3D similarity against Purdues ESB and concludes with an estimate of the overall costs associated with large scale classification tasks involving many tens of thousands of models.

Towards functionally graded cellular microstructures

Many materials require functionally graded cellular microstructures whose porosity (i.e. ratio of the void to solid volume of a material) is engineered to meet specific requirements. Indeed numerous applications have demonstrated the engineering potential of porous materials (e.g. polymeric foams) in areas ranging from biomaterial science through to structural engineering. Although a huge variety of foams can be manufactured with homogenous porosity, for heterogeneous foams there are no generic processes for controlling the distribution of porosity throughout the resulting matrix. Motivated by the desire to create a flexible process for engineering heterogeneous foams, this paper reports how ultrasound, applied during some of the foaming stages of a polyurethane (PU) melt, affects both the cellular structure and distribution of the pore size. The experimental results allowed an empirical understanding of how the parameters of ultrasound exposure (i.e. frequency and acoustic pressure) influenced the volume and distribution of pores within the final polyurethane matrix: the data demonstrates that porosity (i.e. volume fraction) varies in direct proportion to the acoustic pressure magnitude of the ultrasound signal. The effects of ultrasound on porosity demonstrated by this work offer the prospect of a manufacturing process that can adjust the cellular geometry of foam and hence ensure that the resulting characteristics match the functional requirements.