A synaptic nidogen: developmental regulation and role of nidogen-2 at the neuromuscular junction

Background: The skeletal neuromuscular junction is a useful model for elucidating mechanisms that regulate synaptogenesis. Developmentally important intercellular interactions at the neuromuscular junction are mediated by the synaptic portion of a basal lamina that completely ensheaths each muscle fiber. Basal laminas in general are composed of four main types of glycosylated proteins: laminins, collagens IV, heparan sulfate proteoglycans and nidogens (entactins). The portion of the muscle fiber basal lamina that passes between the motor nerve terminal and postsynaptic membrane has been shown to bear distinct isoforms of the first three of these. For laminins and collagens IV, the proteins are deposited by the muscle; a synaptic proteoglycan, z-agrin, is deposited by the nerve. In each case, the synaptic isoform plays key roles in organizing the neuromuscular junction. Here, we analyze the fourth family, composed of nidogen-1 and -2.Results: In adult muscle, nidogen-1 is present throughout muscle fiber basal lamina, while nidogen- 2 is concentrated at synapses. Nidogen-2 is initially present throughout muscle basal lamina, but is lost from extrasynaptic regions during the first three postnatal weeks. Neuromuscular junctions in mutant mice lacking nidogen-2 appear normal at birth, but become topologically abnormal as they mature. Synaptic laminins, collagens IV and heparan sulfate proteoglycans persist in the absence of nidogen-2, suggesting the phenotype is not secondary to a general defect in the integrity of synaptic basal lamina. Further genetic studies suggest that synaptic localization of each of the four families of synaptic basal lamina components is independent of the other three.Conclusion: All four core components of the basal lamina have synaptically enriched isoforms. Together, they form a highly specialized synaptic cleft material. Individually, they play distinct roles in the formation, maturation and maintenance of the neuromuscular junction

Serial Position Effects in Short-term Visual Memory: A SIMPLE Explanation?

A version of Sternberg’s (1966) short-term, visual memory recognition paradigm with pictures of unfamiliar faces as stimuli was used in three experiments to assess the applicability of the distinctiveness based SIMPLE model proposed by Brown, Neath & Chater (2002). Initial simulations indicated that the amount of recency predicted increased as the parameter measuring the psychological distinctiveness of the stimulus material (c) increased, and that the amount of primacy was dependent on the extent of proactive interference from previously presented stimuli. The data from experiment 1, which used memory lists of four and five faces varying in visual similarity confirmed the predicted, extended recency effect. However, changes in visual similarity were not found to produce changes in c. In Experiments 2 and 3, the conditions that influence the magnitude of c were explored. These revealed that both the familiarity of the stimulus class before testing, and changes in familiarity due to perceptual learning, influenced distinctiveness as indexed by the parameter c. Overall the empirical data from all three experiments were well-fit by SIMPLE

Reversible Masking Using Low-Molecular-Weight Neutral Lipids to Achieve Optimal-Targeted Delivery

Intravenous injection of therapeutics is required to effectively treat or cure metastatic cancer, certain cardiovascular diseases, and other acquired or inherited diseases. Using this route of delivery allows potential uptake in all disease targets that are accessed by the bloodstream. However, normal tissues and organs also have the potential for uptake of therapeutic agents. Therefore, investigators have used targeted delivery to attempt delivery solely to the target cells; however, use of ligands on the surface of delivery vehicles to target specific cell surface receptors is not sufficient to avoid nonspecific uptake. PEGylation has been used for decades to try to avoid nonspecific uptake but suffers from many problems known as “The PEGylation Dilemma.” We have solved this dilemma by replacing PEGylation with reversible masking using low-molecular-weight neutral lipids in order to achieve optimal-targeted delivery solely to target cells. Our paper will focus on this topic

Clinical and Experiential Learning in Canadian Law Schools: Current Perspectives

What are some of the challenges and possibilities animating modern Canadian clinical and experiential learning in law? This question was the starting point for our research, which examined two sets of data. In the first part of this project, we analyzed available information on existing clinical and experiential learning programs in Canadian law schools. This data revealed a growing quantity and variety of programs across the country. We then held qualitative interviews with deans, professors, and clinicians across Canada regarding their views of clinical and experiential learning. While the interviews suggested that many of the same financial and curricular challenges that dominated early debates remain stubbornly entrenched, there are also significant promising views and practices. No longer regarded by most as a legal education outlier, clinical and experiential learning has come out of the curricular shadows and taken a prominent place in most law schools in Canada. Nuanced questions now dominate thinking around this generation of clinical and experiential learning. What is the role of community in the creation, decision making, and continuity of clinical programs? How can students balance an increasingly intensive set of learning, professional, and financial challenges? How can clinical and experiential learning be better aligned with the rest of the curriculum, and as accessible as possible? As all respondent law schools but one are expanding their clinical and experiential learning options, these and other questions will continue to animate programs in the foreseeable future

Clinical and Experiential Learning Programs in Canadian Law Schools

Information for this chart is from law school and clinic websites as well as from follow-up interviews with Deans or Deans’ Designates of 13 of the 16 common law schools in Canada. Programs were deemed “Experiential” if the majority of the activities and/or assessment in a class is taught or practiced experientially. Only credit-bearing programs are included here

CLARITY at the TREC 2011 microblog track

For the first year of the TREC Microblog Track the CLARITY group concentrated on a number of areas, investigating the underlying term weighting scheme for ranking tweets, incorporating query expansion to introduce new terms into the query, as well as introducing an element of temporal re-weighting based on the temporal distribution of assumed relevant microblogs

Open Access Books: an International Collaboration to Explore the Practical Implications for Librarians of Increasing Access to Scholarly Research Outputs

Open access advocacy and partnership is an established role for libraries across the world: books continue to be a challenge. Books and book chapters remain a vital output for many research areas. Open access policies have focused primarily on journal articles and serial publications, potentially creating an imbalance in the research literature freely available, and possibly having a negative impact on book publications in terms of readership and citations. Publisher permissions for journal articles can usually be accessed from Sherpa RoMEO, but book contracts continue to be a mostly hidden agreement between publisher and researcher, inaccessible to librarians who are supporting and driving the open access agenda within an institution. What are the current challenges for librarians in making academics books openly available? To what extent will this limit the mediating role of librarians in scholarly communication? Is this role sustainable? A global perspective is provided with a comparison of distinctive experiences at two leading international universities: Swansea University; and the University of Nottingham Ningbo China. Swansea University is seeking to create more open access book content in line with the United Kingdom’s Higher Education Funding Council for Education Research Excellence Framework Open Access policy. The University of Nottingham Ningbo China is seeking to maximize the dissemination and visibility of research to a global audience through open access. This paper focusses on the issues and challenges for librarians who wish to increase the number of books and book chapters available open access, including: relationships with global publishing partners; the complexity of publisher policies for books; challenging existing researcher practices; and, reskilling librarians for advocacy and influencing roles in scholarly communication. A set of recommendations is drawn from this in order to improve the library and information service roles in supporting research, publishing process and improving open access to book content

Open access books: an international collaboration to explore the practical implications for librarians of increasing access to scholarly research outputs

Open access advocacy and partnership is an established role for libraries across the world: books continue to be a challenge. Books and book chapters remain a vital output for many research areas. Open access policies have focused primarily on journal articles and serial publications, potentially creating an imbalance in the research literature freely available, and possibly having a negative impact on book publications in terms of readership and citations. Publisher permissions for journal articles can usually be accessed from Sherpa RoMEO, but book contracts continue to be a mostly hidden agreement between publisher and researcher, inaccessible to librarians who are supporting and driving the open access agenda within an institution. What are the current challenges for librarians in making academics books openly available? To what extent will this limit the mediating role of librarians in scholarly communication? Is this role sustainable? A global perspective is provided with a comparison of distinctive experiences at two leading international universities: Swansea University; and the University of Nottingham Ningbo China. Swansea University is seeking to create more open access book content in line with the United Kingdom’s Higher Education Funding Council for Education Research Excellence Framework Open Access policy. The University of Nottingham Ningbo China is seeking to maximize the dissemination and visibility of research to a global audience through open access. This paper focusses on the issues and challenges for librarians who wish to increase the number of books and book chapters available open access, including: relationships with global publishing partners; the complexity of publisher policies for books; challenging existing researcher practices; and, reskilling librarians for advocacy and influencing roles in scholarly communication. A set of recommendations is drawn from this in order to improve the library and information service roles in supporting research, publishing process and improving open access to book content

Item Graph Convolution Collaborative Filtering for Inductive Recommendations

Graph Convolutional Networks (GCN) have been recently employed as core component in the construction of recommender system algorithms, interpreting user-item interactions as the edges of a bipartite graph. However, in the absence of side information, the majority of existing models adopt an approach of randomly initialising the user embeddings and optimising them throughout the training process. This strategy makes these algorithms inherently transductive, curtailing their ability to generate predictions for users that were unseen at training time. To address this issue, we propose a convolution-based algorithm, which is inductive from the user perspective, while at the same time, depending only on implicit user-item interaction data. We propose the construction of an item-item graph through a weighted projection of the bipartite interaction network and to employ convolution to inject higher order associations into item embeddings, while constructing user representations as weighted sums of the items with which they have interacted. Despite not training individual embeddings for each user our approach achieves state of-the-art recommendation performance with respect to transductive baselines on four real-world datasets, showing at the same time robust inductive performance