Expanded progenitor populations, vitreo-retinal abnormalities, and Müller glial reactivity in the zebrafish leprechaun/patched2 retina

Jonathan Bibliowicz and Jeffery M. Gross are with the Section of Molecular Cell and Developmental Biology, The University of Texas at Austin, Austin, TX, USA, and the Institute of Cell and Molecular Biology, The University of Texas at Austin, Austin, TX, USA -- Jeffery M. Gross is with the Institute for Neuroscience, The University of Texas at Austin, Austin, TX, USABackground: The roles of the Hedgehog (Hh) pathway in controlling vertebrate retinal development have been studied extensively; however, species- and context-dependent findings have provided differing conclusions. Hh signaling has been shown to control both population size and cell cycle kinetics of proliferating retinal progenitors, and to modulate differentiation within the retina by regulating the timing of cell cycle exit. While cell cycle exit has in turn been shown to control cell fate decisions within the retina, a direct role for the Hh pathway in retinal cell fate decisions has yet to be established in vivo. Results: To gain further insight into Hh pathway function in the retina, we have analyzed retinal development in leprechaun/patched2 mutant zebrafish. While lep/ptc2 mutants possessed more cells in their retinas, all cell types, except for Müller glia, were present at identical ratios as those observed in wild-type siblings. lep/ptc2 mutants possessed a localized upregulation of GFAP, a marker for 'reactive' glia, as well as morphological abnormalities at the vitreo-retinal interface, where Müller glial endfeet terminate. In addition, analysis of the over-proliferation phenotype at the ciliary marginal zone (CMZ) revealed that the number of proliferating progenitors, but not the rate of proliferation, was increased in lep/ptc2 mutants. Conclusion: Our results indicate that Patched2-dependent Hh signaling does not likely play an integral role in neuronal cell fate decisions in the zebrafish retina. ptc2 deficiency in zebrafish results in defects at the vitreo-retinal interface and Müller glial reactivity. These phenotypes are similar to the ocular abnormalities observed in human patients suffering from Basal Cell Naevus Syndrome (BCNS), a disorder that has been linked to mutations in the human PTCH gene (the orthologue of the zebrafish ptc2), and point to the utility of the lep/ptc2 mutant line as a model for the study of BCNS-related ocular pathologies. Our findings regarding CMZ progenitor proliferation suggest that, in the zebrafish retina, Hh pathway activity may not affect cell cycle kinetics; rather, it likely regulates the size of the retinal progenitor pool in the CMZ.Institute for Cellular and Molecular [email protected]

Endoscopy is of low yield in the identification of gastrointestinal neoplasia in patients with dermatomyositis: A cross-sectional study.

AimTo determine the prevalence of gastrointestinal neoplasia among dermatomyositis patients who underwent an esophagogastroduodenoscopy and/or colonoscopy.MethodsA cross-sectional study examining the results of upper endoscopy and colonoscopy in adults with dermatomyositis at an urban, university hospital over a ten year period was performed. Chart review was performed to confirm the diagnosis of dermatomyositis. Findings on endoscopy were collected and statistical analyses stratified by age and presence of symptoms were performed.ResultsAmong 373 adult patients identified through a code based search strategy, only 163 patients had dermatomyositis confirmed by chart review. Of the 47 patients who underwent upper endoscopy, two cases of Barrett's esophagus without dysplasia were identified and there were no cases of malignancy. Of the 67 patients who underwent colonoscopy, no cases of malignancy were identified and an adenoma was identified in 15% of cases. No significant differences were identified in the yield of endoscopy when stratified by age or presence of symptoms.ConclusionThe yield of endoscopy is low in patients with dermatomyositis and is likely similar to the general population; we identified no cases of malignancy. A code based search strategy is inaccurate for the diagnosis of dermatomyositis, calling into question the results of prior population-based studies. Larger studies with rigorously validated search strategies are necessary to understand the risk of gastrointestinal malignancy in patients with dermatomyositis

Global Defects In Theories With Lorentz Symmetry Violation

We study global topological defects in the Jacobson-Corley model which breaks Lorentz symmetry and involves up to fourth order derivatives. There is a window in the parameter space in which no solution exists. Otherwise, different profiles are allowed for the same values of the parameters. For a scale of Lorentz violation much higher than the scale of gauge symmetry breaking, the energy densities are higher, of the same order or smaller than in the usual case for domain walls, cosmic strings and hedgehogs respectively. Possible cosmological implications are suggested.Comment: 11 pages latex, misprints corrected, version to appear in PR

A State University’s Assessment of ACUE: Feasible Model for Evaluating the Impact of a Faculty Instruction Quality Program

State comprehensive universities often stress the development of teaching quality to improve the outcomes and retention of students, especially for recently matriculated students. These universities invest in teaching quality programs, but often lack a feasible method to examine the longitudinal impacts of these programs. The purpose of this paper is to provide a model for universities to evaluate outcomes related teaching quality programs. ACUE, a teaching quality program, was implemented across 30 instructors, which equated to 463 course sections. ACUE instructors were matched to non-ACUE instructors using propensity score matching (PSM) and compared on the rate of end-of-the-semester students with DFW (underperformance) standing across course sections. PSM was based on if courses were honors sections, lower level classes, size of enrollment in the sections, and if the section occurred after the completion of the program. DFW rate is a parsimonious metric that predict retention. The ACUE recipients had an average treatment effect of -.37, or 3.7% fewer students receiving a DFW. That translated to 171 fewer DFW grades. Implications include that the use of PSM and DFW rates could help universities examine longitudinal outcomes for teaching quality programs. Given the financial and personnel resources needed for program like ACUE, comprehensive regional universities could use similar methods to determine if the investment yields satisfactory returns

Towards the predictive modeling of ductile failure

The ability to predict ductile failure is considered by an experimental examination of the failure process, validation exercises to assess predictive ability, and development of a coupled experimental-numerical strategy to enhance model development. In situ loading of a polycrystalline metal inside a scanning electron microscope is performed on Al 6061-T6 that reveals matrix-dominated response for both deformation and failure. Highly localized deformation fields are found to exist within each grain as slip accumulates preferentially on a small fraction of crystallographic planes. No evidence of damage or material softening is found, implying that a strain-to-failure model is adequate for modeling fracture in this and similar material. This modeling insight is validated through blind predictive simulations performed in response to the 2012 and 2014 Sandia Fracture Challenges. Constitutive and failure models are calibrated and then embedded in highly refined finite element simulations to perform blind predictions of the failure behavior of the challenge geometries. Comparison of prediction to experiment shows that a well-calibrated model that captures the essential elastic-plastic constitutive behavior is necessary to capture confidently the response for structures with complex stress states, and is a prerequisite for a precise prediction of material failure. The validation exercises exposed the need to calibrate sophisticated plasticity models without a large experimental effort. To answer this need, a coupled experimental and numerical method is developed for characterizing the elastic-plastic constitutive properties of ductile materials using local deformation field information to enrich calibration data. The method is applied to a tensile test specimen and the material’s constitutive model, whose parameters are unknown a priori, is determined through an optimization process that compares these experimental measurements with iterative finite element simulations. The final parameters produce a simulation that tracks the local experimental displacement field to within a couple percent of error. Simultaneously, the percent error in the simulation for the load carried by the specimen throughout the test is less than one percent. The enriched calibration data is found to be sufficient to constrain model parameters describing anisotropy that could not be constrained by the global data alone.Aerospace Engineerin

Panel No. 2: Arbitration in Consumer Transactions

The use of arbitration in the consumer context has been particularly controversial. The presentations will address whether the FAA (“Federal Arbitration Act”) should be amended to ban pre-dispute provisions for arbitration in the adhesive circumstances of consumer traditions; recent litigation surrounding UBER’s use of an arbitral clause in its service contracts; and existing and potential controversies associated with the use of on-line arbitration

Panel No. 2: Arbitration in Consumer Transactions

The use of arbitration in the consumer context has been particularly controversial. The presentations will address whether the FAA (“Federal Arbitration Act”) should be amended to ban pre-dispute provisions for arbitration in the adhesive circumstances of consumer traditions; recent litigation surrounding UBER’s use of an arbitral clause in its service contracts; and existing and potential controversies associated with the use of on-line arbitration

Magnetic Monopoles in String Theory

Magnetic monopole solutions to heterotic string theory are discussed in toroidal compactifications to four spacetime dimensions. Particular emphasis is placed on the relation to previously studied fivebrane solutions in ten dimensions and on the possibility of constructing exact monopole solutions related to symmetric fivebranes.Comment: 24 pages (Corrected title