Tethered TGF-β1 in a Hyaluronic Acid-Based Bioink for Bioprinting Cartilaginous Tissues

In 3D bioprinting for cartilage regeneration, bioinks that support chondrogenic development are of key importance. Growth factors covalently bound in non-printable hydrogels have been shown to effectively promote chondrogenesis. However, studies that investigate the functionality of tethered growth factors within 3D printable bioinks are still lacking. Therefore, in this study, we established a dual-stage crosslinked hyaluronic acid-based bioink that enabled covalent tethering of transforming growth factor-beta 1 (TGF-β1). Bone marrow-derived mesenchymal stromal cells (MSCs) were cultured over three weeks in vitro, and chondrogenic differentiation of MSCs within bioink constructs with tethered TGF-β1 was markedly enhanced, as compared to constructs with non-covalently incorporated TGF-β1. This was substantiated with regard to early TGF-β1 signaling, chondrogenic gene expression, qualitative and quantitative ECM deposition and distribution, and resulting construct stiffness. Furthermore, it was successfully demonstrated, in a comparative analysis of cast and printed bioinks, that covalently tethered TGF-β1 maintained its functionality after 3D printing. Taken together, the presented ink composition enabled the generation of high-quality cartilaginous tissues without the need for continuous exogenous growth factor supply and, thus, bears great potential for future investigation towards cartilage regeneration. Furthermore, growth factor tethering within bioinks, potentially leading to superior tissue development, may also be explored for other biofabrication applications.     

Longitudinal Proteomic Analysis of Plasma across Healthy Pregnancies Reveals Indicators of Gestational Age

Longitudinal changes in the blood proteome during gestation relate to fetal development and maternal homeostasis. Charting the maternal blood proteome in normal pregnancies is critical for establishing a baseline reference when assessing complications and disease. Using mass spectrometry-based shotgun proteomics, we surveyed the maternal plasma proteome across uncomplicated pregnancies. Results indicate a significant rise in proteins that govern placentation and are vital to the development and health of the fetus. Importantly, we uncovered proteome signatures that strongly correlated with gestational age. Fold increases and correlations between the plasma concentrations of ADAM12 (ρ = 0.973), PSG1 (ρ = 0.936), and/or CSH1/2 (ρ = 0.928) with gestational age were validated with ELISA. Proteomic and validation analyses demonstrate that the maternal plasma concentration of ADAM12, either independently or in combination with either PSG1 or CSH1/2, correlates with gestational age within ±8 days throughout pregnancy. These findings suggest that the gestational age in healthy pregnancies may be determined by referencing the concentration of select plasma proteins.     

Prototype Development of a Temperature-Sensitive High-Adhesion Medical Tape to Reduce Medical-Adhesive-Related Skin Injury and Improve Quality of Care

Medical adhesives are used to secure wound care dressings and other critical devices to the skin. Without means of safe removal, these stronger adhesives are difficult to painlessly remove from the skin and may cause medical-adhesive-related skin injuries (MARSI), including skin tears and an increased risk of infection. Lower-adhesion medical tapes may be applied to avoid MARSI, leading to device dislodgement and further medical complications. This paper outlines the development of a high-adhesion medical tape designed for low skin trauma upon release. By warming the skin-attached tape for 10–30 s, a significant loss in adhesion was achieved. A C14/C18 copolymer was developed and combined with a selected pressure-sensitive adhesive (PSA) material. The addition of 1% C14/C18 copolymer yielded the largest temperature-responsive drop in surface adhesion. The adhesive film was characterized using AFM, and distinct nanodomains were identified on the exterior surface of the PSA. Our optimized formulation yielded 67% drop in adhesion when warmed to 45 °C, perhaps due to melting nanodomains weakening the adhesive–substrate boundary layer. Pilot clinical testing resulted in a significant decrease in pain when a heat pack was used for removal, giving an average pain reduction of 66%.     

Production scheduling algorithms for a semiconductor test facility

The authors develop production scheduling algorithms for semiconductor test operations. The operations in the facility under study are characterized by a broad product mix, variable lot sizes and yields, long and variable setup times, and limited test equipment capacity. The approach presented starts by dividing the facility or job shop into a number of work centers. The method then proceeds to sequence one work center at a time. A disjunctive graph representation of the entire facility is used to capture interactions between work centers. The introduction of different management objectives leads to different work center problems and different production scheduling algorithms. The authors present algorithms for two different work center problems. Direction for future research are discussed     

Triplet markov fields for the classification of complex structure data

We address the issue of classifying complex data. We focus on three main sources of complexity, namely the high dimensionality of the observed data, the dependencies between these observations and the general nature of the noise model underlying their distribution. We investigate the recent Triplet Markov Fields and propose new models in this class designed for such data and in particular allowing very general noise models. In addition, our models can handle the inclusion of a learning step in a consistent way so that they can be used in a supervised framework. One advantage of our models is that whatever the initial complexity of the noise model, parameter estimation can be carried out using state-of-the-art Bayesian clustering techniques under the usual simplifying assumptions. As generative models, they can be seen as an alternative, in the supervised case, to discriminative Conditional Random Fields. Identifiability issues underlying the models in the non supervised case, are discussed while the models performance is illustrated on simulated and real data exhibiting the mentioned various sources of complexity.     

Neighborhood effects in visual word recognition: Effects of letter delay and nonword context difficulty.

The role of a target's orthographic neighborhood in visual word recognition was investigated in 2 lexical decision experiments. In both experiments, some stimuli had 1 letter delayed relative to the presentation of the rest of the stimulus. Exp 1 showed that delaying a letter position, which yielded a potentially competitive neighbor, was more costly to target recognition than delaying a position that yielded no neighbors. This effect was strongest when one of these neighbors was of higher frequency than the target itself. Additionally, the effect was reduced for words with a high friendly-to-unfriendly-neighbor ratio (friendly neighbors being those words containing the delayed letter). In Exp 2 the difficulty of the word–nonword discrimination was manipulated by varying the density of the nonwords' neighborhoods. Only when the nonwords had many neighbors at several positions did the word responses show neighborhood competition effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evidence that recipient CD8+ T cell depletion does not alter development of chronic vascular rejection in a rat heart allograft model

Progressive chronic vascular rejection is a central feature of indefinitely surviving WF.1L LEW/Gut (RT1(1)) heart grafts transplanted to LEW (RT1(1)) recipients in unmodified donor-recipient combinations. At 70 days posttransplantation, large vessels of the grafts are characterized by the presence of vasculitis, vasculitis with associated variable myointimal thickening, and occlusive myointimal thickening with minimal or absent concomitant vasculitis. To assess the potential role of CD8+ T cells as critical effectors of chronic vascular rejection in this model, LEW recipients of WF.1L heart grafts were effectively depleted of CD8+ T cells as a result of prior thymectomy and anti-CD8 (MRC OX8) monoclonal antibody administration prior to transplantation. WF.1L heart grafts transplanted to LEW recipients that had undergone prior sham thymectomy and MRC OX8 administration, or thymectomy and administration of antibody-free culture supernatant, provided appropriate controls. At 70 days posttransplantation, large vessels of WF.1L heart grafts in all 3 transplantation groups showed similar morphologic features, which were comparable to those observed in heart grafts of long-surviving unmodified donor-recipient pairs. This study has shown that profound selective depression of recipient CD8+ T cells does not alter the characteristic features of chronic vascular rejection in this rat cardiac model, and provides evidence that CD8+ T cells play no critical role in the initiation or development of progressive vascular damage in this setting.