Publications by authors named "Gerald Hodgkinson"

Introduction: Postoperative radiotherapy (PORT) reduces local failure in patients with NSCLC, without a clear overall survival benefit. It is unknown whether the subsets of patients benefit. Two recent large randomized controlled trials, PORT-C (People's Republic of China) and Lung ART (Europe), reported widely different locoregional recurrence (LR) rates in the control arms, at 18.

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Article Synopsis
  • Injured neurons adapt to inhibitory proteins in the central nervous system by increasing integrin levels, but how this change varies with different proteoglycan concentrations is still unclear.
  • Researchers studied how postnatal dorsal root ganglion (DRG) neurons navigated and expressed integrins on different densities of proteoglycans.
  • The results showed that while neurons initially grew well regardless of proteoglycan density, prolonged exposure to high levels slowed their growth, highlighting the complex relationship between proteoglycan presence and neuron regeneration.
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Proteoglycan expression patterns in the central nervous system guide neuronal pathfinding during development, but also disrupt regeneration after injuries. To deepen our understanding of the molecular level effects of proteoglycan spatial arrangements on neuronal pathfinding, we designed micropatterning stamps for the precise placement of near single molecule chondroitin sulfate proteoglycan (CSPG) clusters into regularly spaced arrays. Actin ultrastructural analysis in dorsal root ganglion neurons grown on laminin-coated substrata patterned with aggrecan cluster arrays revealed filopodial and lamellapodial edge contact avoidance of individual clusters, while growth cone lamellapodia and central domains were able to span multiple clusters over a range of cluster densities.

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We have investigated the influence of micrometer- and sub-micrometer-scale surface heterogeneities in patterned octadecyltrichlorosilane (OTS) films on human serum albumin (HSA) adsorption and its spatial distribution. 5-μm-wide OTS patterns were created on glass substrates by micro-contact printing and in some instances subsequent annealing was used to alter OTS molecule distribution within the patterns. Scanning force microscopy (SFM), advancing water contact angles and water vapor condensation figures were used to characterize the OTS films and to assess the nature of the heterogeneities within the various surface areas.

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Fluorescence microscopy and intensity histogram analysis techniques were used to monitor spatially-resolved albumin adsorption kinetics to model heterogeneous surfaces on sub-μm scales. Several distinct protein subpopulations were resolved, each represented by a normal distribution of adsorption densities on the adsorbent surface. Histogram analyses provided dynamic information of mean adsorption density, spread in adsorption density, and surface area coverage for each distinct protein subpopulation.

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We present an in vitro micropatterning approach in which the density and spatial presentation of two separate protein layers can be independently controlled to form cell stripe assays through (1) the simultaneous application of microcontact printing (microCP) and microfluidic network (microFN) patterning to generate alternating stripes of pure single protein layers or (2) through microCP onto a pre-adsorbed homogeneous protein layer to generate alternating single and dual protein stripes. This approach enabled the creation of choice boundaries in which protein-protein interactions were limited and the effects of spatially segregated or colocalized dual protein signals on model primary neuronal behavior could be readily interrogated and compared on both glass and tissue culture polystyrene substrates. Dorsal root ganglion (DRG) cell body attachment was dictated largely by non-specific cell adhesion interactions and interactions between the guidance molecules laminin and aggrecan were insufficient to explain aggrecan inhibition on neurite outgrowth.

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