2E Licensing Electronic Resources: Spotting Issues in e-Content Licenses

Foundational Copyright (Dec. 1 Boston; Dec. 15 Amherst) Joan Emmet, Yale - Library Licensing: An overview of contracts for library content; hands-on exercise learning to spot key Issues that should be negotiated

An experimental investigation of the design variables for NACA submerged duct entrances

Information concerning the parameters and design variables affecting an NACA submerged duct design is presented

Brother\u27s Lullaby

https://digitalcommons.library.umaine.edu/mmb-vp/5256/thumbnail.jp

The In Vivo functionality of collagen-based scaffolds for orthopaedic tissue repair

Bone and articular cartilage are incredibly tough tissues with the ability to withstand repetitive stress throughout an individual’s lifetime. Unfortunately, their ability to heal after injury is finite, resulting in impaired function and degeneration. Despite considerable advances in modern surgical management, such as the use of auto- and allografting, the associated limitations with these approaches has motivated the development of alternative therapeutic interventions to replace or repair bone and cartilage, including tissue-engineered (TE) biomaterials. In relation to bone, a major obstacle to the in vivo use of biomaterials is ensuring an adequate blood supply to meet the metabolic demands of seeded o r invading cells following implantation. In the context of producing superior bone graft substitutes, the overall aim of this research, therefore, was to address the problem of vascularising TE biomaterials by improving the blood supply to collagen-based bone graft substitutes using two distinct vascularisation strategies; in vitro pre-vascularisation of scaffolds (Chapter 2) and an endochondral ossification-based vascularisation strategy (Chapters 3 and 4). In addition, the ability of a novel, multi-layered, cell-free collagen scaffold, that combines hydroxyapatite for bone repair and hyaluronic acid for cartilage repair, to enhance osteochondral repair was also investigated (Chapter 5). Within the Tissue Engineering Research Group in the RCSI, a series of collagenbased scaffolds have been developed for tissue regeneration. The composition and structure of these biocompatible biodegradable biomaterials has been tailored to provide biological, architectural, and mechanical cues to influence cell infiltration, differentiation and matrix synthesis in a variety of tissues. Throughout this thesis, these scaffolds served as templates for tissue formation in conjunction with seeded cells (Chapters 2, 3 and 4) o r as cell-free implants (Chapter 5). Mesenchymal stem cells (MSCs), with their multi-lineage differentiation potential, were used to establish conditions capable of promoting enhanced vascularisation of these scaffolds fo r bone repair using two distinct methods. In Chapter 2, human umbilical vein endothelial cells (HUVECs) alone, o r in combination with human MSCs, were used to create in vitro micro-vascular networks within collagen-chondroitin sulphate (CCS) scaffolds. These pre-vascularised constructs were shown to significantly enhance bone repair in a critical-sized rat calvarial defect, while the MSCs in the coculture group had an immunomodulatory effect on the host response. As an alternative method to in vitro pre-vascularisation, attention has recently focused on reproducing aspects of embryological skeletal development and fracture healing via endochondral ossification (ECO) to promote blood vessel invasion of TE constructs in vivo. In Chapter 3, it was demonstrated that MSCs seeded onto two distinct collagen-based scaffolds, a collagen-hyaluronic acid scaffold (CHyA) previously optimised for cartilage formation and a collagen-hydroxyapatite scaffold (CHA) previously optimised for bone formation, could be induced to follow an in vitro process similar to ECO. These constructs synthesised cartilage-specific matrix and were driven towards hypertrophy, resulting in the secretion of the proangiogenic growth factor VEGF, as well as mineralisation in vitro. Chapter 4 investigated the ability of this system to promote healing and bone formation in a critical-sized rat calvarial defect. Compared to traditional intramembranous ossification (IMO)-based approaches that aim to induce direct osteogenic differentiation in vitro, it was found that ECO-based constructs were capable of superior bone formation, construct remodelling and vascularisation in vivo. Despite a host of repair techniques used to treat chondral and osteochondral injuries, including cell-based and cell-free TE strategies, the generation of durable hyaline-like articular cartilage with appropriate functional properties remains to be achieved clinically. Chapter 5 of this thesis evaluated a multi-layered scaffold, based on seamlessly combining the CHyA and CHA scaffolds, which were investigated independently in Chapters 3 and 4, as a cell-free strategy fo r osteochondral defect repair. This biomimetic scaffold was found to facilitate cellular infiltration and region specific differentiation, resulting in the regeneration of tissue with several key features of native osteochondral tissue, thus confirming its potential as an off-theshelf device fo r direct implantation, overcoming several of the drawbacks associated with current treatments used in orthopaedic clinical practice. Collectively, Collectively, this study emphasises the significant in vivo capacity of both cell-seeded and cell-free collagen-based scaffolds developed in the RCSI Tissue Engineering Research Group to promote bone and cartilage regeneration using established animal models and highlights the clinical potential of these TE constructs fo r orthopaedic tissue repair applications

Intracystic papillary carcinoma in a male as a rare presentation of breast cancer: a case report and literature review

<p>Abstract</p> <p>Introduction</p> <p>The term "intracystic papillary ductal carcinoma <it>in situ</it>" has recently changed and is now more appropriately referred to "intracystic papillary carcinoma". Intracystic papillary carcinoma in men is an extremely rare disease with only a few case presentations published in the literature so far.</p> <p>Case presentation</p> <p>We discuss a case of a 44-year-old Caucasian man with an intracystic papillary carcinoma treated with simple mastectomy, sentinel lymph-node biopsy and contralateral risk-reducing mastectomy. These were followed by adjuvant radiotherapy of the breast.</p> <p>Conclusion</p> <p>Triple assessment (i.e. clinical examination and radiological and histological assessment) with a high level of clinical suspicion is necessary to diagnose intracystic papillary carcinoma in men due to its rarity. Furthermore, genetic testing and risk-reducing mastectomy should also be considered in cases of a strong family history for male breast cancer.</p

Interleukin 1 receptor antagonist knockout mice show enhanced microglial activation and neuronal damage induced by intracerebroventricular infusion of human β-amyloid

BACKGROUND: Interleukin 1 (IL-1) is a key mediator of immune responses in health and disease. Although classically the function of IL-1 has been studied in the systemic immune system, research in the past decade has revealed analogous roles in the CNS where the cytokine can contribute to the neuroinflammation and neuropathology seen in a number of neurodegenerative diseases. In Alzheimer's disease (AD), for example, pre-clinical and clinical studies have implicated IL-1 in the progression of a pathologic, glia-mediated pro-inflammatory state in the CNS. The glia-driven neuroinflammation can lead to neuronal damage, which, in turn, stimulates further glia activation, potentially propagating a detrimental cycle that contributes to progression of pathology. A prediction of this neuroinflammation hypothesis is that increased IL-1 signaling in vivo would correlate with increased severity of AD-relevant neuroinflammation and neuronal damage. METHODS: To test the hypothesis that increased IL-1 signaling predisposes animals to beta-amyloid (Aβ)-induced damage, we used IL-1 receptor antagonist Knock-Out (IL1raKO) and wild-type (WT) littermate mice in a model that involves intracerebroventricular infusion of human oligomeric Aβ1–42. This model mimics many features of AD, including robust neuroinflammation, Aβ plaques, synaptic damage and neuronal loss in the hippocampus. IL1raKO and WT mice were infused with Aβ for 28 days, sacrificed at 42 days, and hippocampal endpoints analyzed. RESULTS: IL1raKO mice showed increased vulnerability to Aβ-induced neuropathology relative to their WT counterparts. Specifically, IL1raKO mice exhibited increased mortality, enhanced microglial activation and neuroinflammation, and more pronounced loss of synaptic markers. Interestingly, Aβ-induced astrocyte responses were not significantly different between WT and IL1raKO mice, suggesting that enhanced IL-1 signaling predominately affects microglia. CONCLUSION: Our data are consistent with the neuroinflammation hypothesis whereby increased IL-1 signaling in AD enhances glia activation and leads to an augmented neuroinflammatory process that increases the severity of neuropathologic sequelae

Calibrate, emulate, sample

Many parameter estimation problems arising in applications can be cast in the framework of Bayesian inversion. This allows not only for an estimate of the parameters, but also for the quantification of uncertainties in the estimates. Often in such problems the parameter-to-data map is very expensive to evaluate, and computing derivatives of the map, or derivative-adjoints, may not be feasible. Additionally, in many applications only noisy evaluations of the map may be available. We propose an approach to Bayesian inversion in such settings that builds on the derivative-free optimization capabilities of ensemble Kalman inversion methods. The overarching approach is to first use ensemble Kalman sampling (EKS) to calibrate the unknown parameters to fit the data; second, to use the output of the EKS to emulate the parameter-to-data map; third, to sample from an approximate Bayesian posterior distribution in which the parameter-to-data map is replaced by its emulator. This results in a principled approach to approximate Bayesian inference that requires only a small number of evaluations of the (possibly noisy approximation of the) parameter-to-data map. It does not require derivatives of this map, but instead leverages the documented power of ensemble Kalman methods. Furthermore, the EKS has the desirable property that it evolves the parameter ensemble towards the regions in which the bulk of the parameter posterior mass is located, thereby locating them well for the emulation phase of the methodology. In essence, the EKS methodology provides a cheap solution to the design problem of where to place points in parameter space to efficiently train an emulator of the parameter-to-data map for the purposes of Bayesian inversion

Long-term controlled delivery of rhBMP-2 from collagen-hydroxyapatite scaffolds for superior bone tissue regeneration.

The clinical utilization of recombinant human bone morphogenetic protein 2 (rhBMP-2) delivery systems for bone regeneration has been associated with very severe side effects, which are due to the non-controlled and non-targeted delivery of the growth factor from its collagen sponge carrier post-implantation which necessitates supraphysiological doses. However, rhBMP-2 presents outstanding regenerative properties and thus there is an unmet need for a biocompatible, fully resorbable delivery system for the controlled, targeted release of this protein. With this in mind, the purpose of this work was to design and develop a delivery system to release low rhBMP-2 doses from a collagen-hydroxyapatite (CHA) scaffold which had previously been optimized for bone regeneration and recently demonstrated significant healing in vivo. In order to enhance the potential for clinical translation by minimizing the design complexity and thus upscaling and regulatory hurdles of the device, a microparticle and chemical functionalization-free approach was chosen to fulfill this aim. RhBMP-2 was combined with a CHA scaffold using a lyophilization fabrication process to produce a highly porous CHA scaffold supporting the controlled release of the protein over the course of 21days while maintaining in vitro bioactivity as demonstrated by enhanced alkaline phosphatase activity and calcium production by preosteoblasts cultured on the scaffold. When implanted in vivo, these materials demonstrated increased levels of healing of critical-sized rat calvarial defects 8weeks post-implantation compared to an empty defect and unloaded CHA scaffold, without eliciting bone anomalies or adjacent bone resorption. These results demonstrate that it is possible to achieve bone regeneration using 30 times less rhBMP-2 than INFUSE®, the current clinical gold standard; thus, this work represents the first step of the development of a rhBMP-2 eluting material with immense clinical potential