Essential Role forSonic hedgehogduring Hair Follicle Morphogenesis

AbstractThe hair follicle is a source of epithelial stem cells and site of origin for several types of skin tumors. Although it is clear that follicles arise by way of a series of inductive tissue interactions, identification of the signaling molecules driving this process remains a major challenge in skin biology. In this study we report an obligatory role for the secreted morphogen Sonic hedgehog (Shh) during hair follicle development. Hair germs comprising epidermal placodes and associated dermal condensates were detected in both control andShh−/− embryos, but progression through subsequent stages of follicle development was blocked in mutant skin. The expression ofGli1andPtc1was reduced inShh−/− dermal condensates and they failed to evolve into hair follicle papillae, suggesting that the adjacent mesenchyme is a critical target for placode-derived Shh. Despite the profound inhibition of hair follicle morphogenesis, late-stage follicle differentiation markers were detected inShh−/− skin grafts, as well as cultured vibrissa explants treated with cyclopamine to block Shh signaling. Our findings reveal an essential role for Shh during hair follicle morphogenesis, where it is required for normal advancement beyond the hair germ stage of development

Design Build

The 2011 Design/Build Studio included 13 undergraduate architects, 2 graduate architects, 6 landscape architects, and 1 interior designer. Under the careful supervision and guidance of Bruce Bassler, this team worked to design and deliver a complete sleeping cabin to the Scenic Park campground in South Sioux City, Nebraska

Polytypic Genetic Programming

Program synthesis via heuristic search often requires a great deal of boilerplate code to adapt program APIs to the search mechanism. In addition, the majority of existing approaches are not type-safe: i.e. they can fail at runtime because the search mechanisms lack the strict type information often available to the compiler. In this article, we describe Polytope, a Scala framework that uses polytypic programming, a relatively recent advance in program abstraction. Polytope requires a minimum of boilerplate code and supports a form of strong-typing in which type rules are automatically enforced by the compiler, even for search operations such as mutation which are applied at run-time. By operating directly on language-native expressions, it provides an embeddable optimization procedure for existing code. We give a tutorial example of the specific polytypic approach we adopt and compare both runtime efficiency and required lines of code against the well-known EpochX GP framework, showing comparable performance in the former and the complete elimination of boilerplate for the latter

Achieving environmentally friendly building envelope for Western Australia’s housing sector: a Life Cycle Assessment approach

The rapid growth of Western Australia’s population and economy will affect the sustainability of its building sector. The energy consumption of all processes during mining to material production, transportation, construction plant and tools, and operation (heating, cooling, lighting, hot water and home appliances) stages causes high greenhouse gas (GHG) emissions and embodied energy (EE) consumption. The literature review to date have confirmed that the building envelope consisting of exterior walls, windows, external doors, roof, and floor could significantly affect the energy consumption during operation stage. Australian construction industry could thus enhance the energy efficiency of the building envelope in order to achieve its GHG emissions reduction targets. This paper has assessed the GHG emissions and EE consumption associated with the construction and use of a typical house in Perth for sixty building envelope options using a life cycle assessment (LCA) approach. The results show that the building envelope consisting of cast in situ sandwich wall with polyethylene terephthalate (PET) foam core, double glazed windows, and concrete roof tiles has the lowest life cycle GHG emissions and embodied energy consumption

MyD88-dependent expansion of an immature GR-1+CD11b+ population induces T cell suppression and Th2 polarization in sepsis

Polymicrobial sepsis alters the adaptive immune response and induces T cell suppression and Th2 immune polarization. We identify a GR-1+CD11b+ population whose numbers dramatically increase and remain elevated in the spleen, lymph nodes, and bone marrow during polymicrobial sepsis. Phenotypically, these cells are heterogeneous, immature, predominantly myeloid progenitors that express interleukin 10 and several other cytokines and chemokines. Splenic GR-1+ cells effectively suppress antigen-specific CD8+ T cell interferon (IFN) γ production but only modestly suppress antigen-specific and nonspecific CD4+ T cell proliferation. GR-1+ cell depletion in vivo prevents both the sepsis-induced augmentation of Th2 cell–dependent and depression of Th1 cell–dependent antibody production. Signaling through MyD88, but not Toll-like receptor 4, TIR domain–containing adaptor-inducing IFN-β, or the IFN-α/β receptor, is required for complete GR-1+CD11b+ expansion. GR-1+CD11b+ cells contribute to sepsis-induced T cell suppression and preferential Th2 polarization

Strategies to improve reference databases for soil microbiomes

Microbial populations in the soil are critical in our lives. The soil microbiome helps to grow our food, nourishing and protecting plants, while also providing important ecological services such as erosion protection, water filtration and climate regulation. We are increasingly aware of the tremendous microbial diversity that has a role in soil heath; yet, despite significant efforts to isolate microbes from the soil, we have accessed only a small fraction of its biodiversity. Even with novel cell isolation techniques

A Prospective Multicenter Study Evaluating Learning Curves and Competence in Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography Among Advanced Endoscopy Trainees: The Rapid Assessment of Trainee Endoscopy Skills (RATES) Study

Background and aims Based on the Next Accreditation System, trainee assessment should occur on a continuous basis with individualized feedback. We aimed to validate endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) learning curves among advanced endoscopy trainees (AETs) using a large national sample of training programs and to develop a centralized database that allows assessment of performance in relation to peers. Methods ASGE recognized training programs were invited to participate and AETs were graded on ERCP and EUS exams using a validated competency assessment tool that assesses technical and cognitive competence in a continuous fashion. Grading for each skill was done using a 4-point scoring system and a comprehensive data collection and reporting system was built to create learning curves using cumulative sum analysis. Individual results and benchmarking to peers were shared with AETs and trainers quarterly. Results Of the 62 programs invited, 20 programs and 22 AETs participated in this study. At the end of training, median number of EUS and ERCP performed/AET was 300 (range 155-650) and 350 (125-500). Overall, 3786 exams were graded (EUS:1137; ERCP–biliary 2280, pancreatic 369). Learning curves for individual endpoints, and overall technical/cognitive aspects in EUS and ERCP demonstrated substantial variability and were successfully shared with all programs. The majority of trainees achieved overall technical (EUS: 82%; ERCP: 60%) and cognitive (EUS: 76%; ERCP: 100%) competence at conclusion of training. Conclusions These results demonstrate the feasibility of establishing a centralized database to report individualized learning curves and confirm the substantial variability in time to achieve competence among AETs in EUS and ERCP