Ollington

577th Quartermaster Rhd Cohttps://dh.howard.edu/prom_corres/1110/thumbnail.jp

Adaptive Response Function Neurons

Biological neurons that show a locally tuned response to input may arise from the network topology of interneurons in the system. By considering such a subnetwork, a learning algorithm is developed for the online learning of the centre, width and shape of locally tuned response functions. The response function for each input is trained independently, resulting in a very good fit for the presented data. Two example networks utilising these neurons were considered. The first was a completely supervised network while the second utilised a Kohonen-like training scheme for the hidden layer. The adaptive response function neurons (ARFNs) were able to achieve excellent class separation while maintaining good generalisation with relatively few neurons

Lesser Yellowlegs Tringa flavipes in Sumatra: new to S.E. Asia.

No abstract availabl

Internal Versus External Recruitment – The Story of Three Consecutive Project Managers in an IT Project

As project managers (PMs) play an important role in project success, assigning PMs with appropriate skills and personalities to projects is a crucial task. Nevertheless, empirical research on skill requirements for information technology (IT) PMs is limited and little information systems literature focuses on the role of internally recruited IT PMs. This paper presents a case study of a troubled IT project led by three consecutive PMs, with a range of backgrounds, skills, and personality types. Across subjects, IT project management was found to be a necessity of project success. Additionally, it was observed that internally recruited PMs showed advantages in understanding organisational culture and business processes. Lessons learned from the three PMs confirm the importance of particular skills previously described in the literature, and the need for an additional focus on how an IT PM’s personality facilitates or inhibits IT project outcomes

Immuno-responsive tissue engineered oral mucosal equivalents containing macrophages

Macrophages play a key role in orchestrating the host immune response towards invading organisms or non-self molecules in the oral mucosa. Three-dimensional (3D) oral mucosal equivalents (OME) containing oral fibroblasts and keratinocytes are used extensively to mimic the human oral mucosa where they have been employed to examine innate immune responses to both bacterial and fungal pathogens as well as to biomaterials. Although the presence of immune cells is critical in generating an immune response, very few studies have incorporated leukocytes into OME and to date none have contained primary human macrophages. Here we report the generation of an immuno-competent OME to investigate immune responses toward bacterial challenge. Primary human monocyte-derived macrophages (MDM) were as responsive to bacterial lipopolysaccharide (LPS) challenge when cultured within a 3D hydrogel in terms of pro-inflammatory cytokine (IL-6, CXCL8 and TNF-α) gene expression and protein secretion as compared to culture as 2D monolayers. MDM were incorporated into a type 1 collagen hydrogel along with oral fibroblasts and the apical surface seeded with oral keratinocytes to generate a MDM-containing OME. Full-thickness MDM-OME displayed a stratified squamous epithelium and a fibroblast-populated connective tissue containing CD68-positive MDM that could be readily isolated to a single cell population for further analysis by collagenase treatment followed by flow cytometry. When stimulated with LPS, MDM-OME responded with increased pro-inflammatory cytokine secretion, most notably for TNF-α that increased 12-fold when compared to OME alone. Moreover, this pro-inflammatory response was inhibited by pre-treatment with dexamethasone, showing that MDM-OME are also amenable to drug-treatment. Dual-labelled immunofluorescence confocal microscopy revealed that MDM were the sole source of TNF-α production within MDM-OME. These data show functional activity of MDM-OME and illustrate their usefulness for investigations aimed at monitoring the immune response of the oral mucosa to pathogens, biomaterials, and for tissue toxicity and anti-inflammatory drug delivery studies

Retinal Organoids from an AIPL1 CRISPR/Cas9 Knockout Cell Line Successfully Recapitulate the Molecular Features of LCA4 Disease

Aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1) is expressed in photoreceptors where it facilitates the assembly of phosphodiesterase 6 (PDE6) which hydrolyses cGMP within the phototransduction cascade. Genetic variations in AIPL1 cause type 4 Leber congenital amaurosis (LCA4), which presents as rapid loss of vision in early childhood. Limited in vitro LCA4 models are available, and these rely on patient-derived cells harbouring patient-specific AIPL1 mutations. While valuable, the use and scalability of individual patient-derived LCA4 models may be limited by ethical considerations, access to patient samples and prohibitive costs. To model the functional consequences of patient-independent AIPL1 mutations, CRISPR/Cas9 was implemented to produce an isogenic induced pluripotent stem cell line harbouring a frameshift mutation in the first exon of AIPL1. Retinal organoids were generated using these cells, which retained AIPL1 gene transcription, but AIPL1 protein was undetectable. AIPL1 knockout resulted in a decrease in rod photoreceptor-specific PDE6α and β, and increased cGMP levels, suggesting downstream dysregulation of the phototransduction cascade. The retinal model described here provides a novel platform to assess functional consequences of AIPL1 silencing and measure the rescue of molecular features by potential therapeutic approaches targeting mutation-independent pathogenesis