Evaluation of autosomal dominant retinal dystrophy genes in an unaffected cohort suggests rare or private missense variants may often be benign.

BackgroundMany genes have been reported as harboring autosomal dominant mutations causing retinal dystrophy. As newly available gene panel sequencing and whole exome sequencing will open these genes up to greater scrutiny, we assess the rate of rare coding variation in these genes among unaffected individuals to provide context for variants that will be discovered when clinical subjects are sequenced.MethodsPublicly available data from the Exome Variant Project were analyzed, focusing on 36 genes known to harbor mutations causing autosomal dominant macular dystrophy.ResultsRates of rare (minor allele frequency ≤0.1%) and private missense variants within autosomal dominant retinal dystrophy genes were found to occur at a high frequency in unaffected individuals, while nonsense variants were not.ConclusionsWe conclude that rare missense variations in most of these genes identified in individuals with retinal dystrophy cannot be confidently classified as disease-causing in the absence of additional information such as linkage or functional validation

Enforcement and over-compliance

Economists generally view environmental enforcement as a tool to secure compliance with regulations. This paper demonstrates that credible enforcement significantly increases statutory over-compliance with regulations as well. We find that many plants with discharges typically below legally permitted levels reduce discharges further when regulators issue fines, even on other plants. Also, non-compliant plants often respond to sanctions by reducing discharges well beyond reductions required by law. Thus, increased enforcement generates substantial discharge reductions above and beyond those expected from simply deterring violations.Over-compliance; Fines; Compliance; Enforcement; Regulation; Pollution Policy; Environmental economics; Environmental enforcement; Water pollution; Beyond compliance

(8,0) Quantum mechanics and symmetry enhancement in type I' superstrings

The low-energy supersymmetric quantum mechanics describing D-particles in the background of D8-branes and orientifold planes is analyzed in detail, including a careful discussion of Gauss' law and normal ordering of operators. This elucidates the mechanism that binds D-particles to an orientifold plane, in accordance with the predictions of heterotic/type I duality. The ocurrence of enhanced symmetries associated with massless bound states of a D-particle with one orientifold plane is illustrated by the enhancement of $SO(14) \times U(1)$ to $E_8$ and $SO(12)\times U(1)$ to $E_7$ at strong type I' coupling. Enhancement to higher-rank groups involves both orientifold planes. For example, the enhanced $E_8 \times E_8 \times SU(2)$ symmetry at the self-dual radius of the heterotic string is seen as the result of two D8-branes coinciding midway between the orientifold planes, while the enhanced $SU(18)$ symmetry results from the coincidence of all sixteen D8-branes and $SO(34)$ when they also coincide with an orientifold plane. As a separate by-product, the s-rule of brane-engineered gauge theories is derived by relating it through a chain of dualities to the Pauli exclusion principle.Comment: 30 pages LaTeX, Five figures. Two references added as well as some Comments in section4. v4: Missing backslashes added to four reference citations

Assessing Student Exposure to and Use of Computer Technologies through an Examination of Course Syllabi

A syllabus analysis instrument was developed to assist program evaluators, administrators and faculty in the identification of skills that students use as they complete their college coursework. While this instrument can be tailored for use with a variety of learning domains, we used it to assess students\u27 use of and exposure to computer technology skills. The reliability and validity of the instrument was examined through an analysis of 88 syllabi from courses within the teacher education program and the core curriculum at a private Midwest US university. Results indicate that the instrument has good inter‐rater reliability and ratings by and interviews with faculty and students provide evidence of construct validity. The use and limitations of the instrument in educational program evaluation are discussed