Who Wants an iPad? An Exercise In Rationing

This active learning exercise demonstrates the fundamental problem in economics that resources are scarce, while wants are relatively infinite.  Students are exposed to four mechanisms for rationing scare resources: markets, queue, coupons, and lottery.  An Apple iPad® pre-loaded with music, videos, and games is used as the good to be rationed. The uncertain value of the good allows for differences in willingness to pay.  Students are guided through an exercise that highlights the efficiency/equity tradeoffs in different allocation mechanisms by observing who gets the iPad in each round and whether any secondary market transactions occur to change the allocation

Factors Affecting the Degradation Processes for Dextran

Author Institution: Departments of Bacteriology and Chemistry, The Ohio State University, Columbus 1

Evolutionary relationships of Aurora kinases: Implications for model organism studies and the development of anti-cancer drugs

BACKGROUND: As key regulators of mitotic chromosome segregation, the Aurora family of serine/threonine kinases play an important role in cell division. Abnormalities in Aurora kinases have been strongly linked with cancer, which has lead to the recent development of new classes of anti-cancer drugs that specifically target the ATP-binding domain of these kinases. From an evolutionary perspective, the species distribution of the Aurora kinase family is complex. Mammals uniquely have three Aurora kinases, Aurora-A, Aurora-B, and Aurora-C, while for other metazoans, including the frog, fruitfly and nematode, only Aurora-A and Aurora-B kinases are known. The fungi have a single Aurora-like homolog. Based on the tacit assumption of orthology to human counterparts, model organism studies have been central to the functional characterization of Aurora kinases. However, the ortholog and paralog relationships of these kinases across various species have not been rigorously examined. Here, we present comprehensive evolutionary analyses of the Aurora kinase family. RESULTS: Phylogenetic trees suggest that all three vertebrate Auroras evolved from a single urochordate ancestor. Specifically, Aurora-A is an orthologous lineage in cold-blooded vertebrates and mammals, while structurally similar Aurora-B and Aurora-C evolved more recently in mammals from a duplication of an ancestral Aurora-B/C gene found in cold-blooded vertebrates. All so-called Aurora-A and Aurora-B kinases of non-chordates are ancestral to the clade of chordate Auroras and, therefore, are not strictly orthologous to vertebrate counterparts. Comparisons of human Aurora-B and Aurora-C sequences to the resolved 3D structure of human Aurora-A lends further support to the evolutionary scenario that vertebrate Aurora-B and Aurora-C are closely related paralogs. Of the 26 residues lining the ATP-binding active site, only three were variant and all were specific to Aurora-A. CONCLUSIONS: In this study, we found that invertebrate Aurora-A and Aurora-B kinases are highly divergent protein families from their chordate counterparts. Furthermore, while the Aurora-A family is ubiquitous among all vertebrates, the Aurora-B and Aurora-C families in humans arose from a gene duplication event in mammals. These findings show the importance of understanding evolutionary relationships in the interpretation and transference of knowledge from studies of model organism systems to human cellular biology. In addition, given the important role of Aurora kinases in cancer, evolutionary analysis and comparisons of ATP-binding domains suggest a rationale for designing dual action anti-tumor drugs that inhibit both Aurora-B and Aurora-C kinases

Revisiting Expectations in an Era of Precision Oncology

As we enter an era of precision medicine and targeted therapies in the treatment of metastatic cancer, we face new challenges for patients and providers alike as we establish clear guidelines, regulations, and strategies for implementation. At the crux of this challenge is the fact that patients with advanced cancer may have disproportionate expectations of personal benefit when participating in clinical trials designed to generate generalizable knowledge. Patient and physician goals of treatment may not align, and reconciliation of their disparate perceptions must be addressed. However, it is particularly challenging to manage a patient’s expectations when the goal of precision medicineâ personalized responseâ exacerbates our inability to predict outcomes for any individual patient. The precision medicine informed consent process must therefore directly address this issue. We are challenged to honestly, clearly, and compassionately engage a patient population in an informed consent process that is responsive to their vulnerability, as well as everâ evolving indications and evidence. This era requires a continual reassessment of expectations and goals from both sides of the bed.New challenges are faced in this era of precision medicine and targeted therapies. Clear guidelines, regulations, and strategies for implementation are needed. Patients with advanced cancer may have disproportionate expectations of the personal benefit of participating in clinical trials. The informed consent process must address this issue directly and honestly. This era requires a continual reassessment of both patient and physician expectations and goals.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142968/1/onco12322_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142968/2/onco12322.pd

Long serial analysis of gene expression for gene discovery and transcriptome profiling in the widespread marine coccolithophore Emiliania huxleyi

Author Posting. © American Society for Microbiology, 2006. This article is posted here by permission of American Society for Microbiology for personal use, not for redistribution. The definitive version was published in Applied and Environmental Microbiology 72 (2006): 252-260, doi:10.1128/AEM.72.1.252-260.2006.The abundant and widespread coccolithophore Emiliania huxleyi plays an important role in mediating CO2 exchange between the ocean and the atmosphere through its impact on marine photosynthesis and calcification. Here, we use long serial analysis of gene expression (SAGE) to identify E. huxleyi genes responsive to nitrogen (N) or phosphorus (P) starvation. Long SAGE is an elegant approach for examining quantitative and comprehensive gene expression patterns without a priori knowledge of gene sequences via the detection of 21-bp nucleotide sequence tags. E. huxleyi appears to have a robust transcriptional-level response to macronutrient deficiency, with 42 tags uniquely present or up-regulated twofold or greater in the N-starved library and 128 tags uniquely present or up-regulated twofold or greater in the P-starved library. The expression patterns of several tags were validated with reverse transcriptase PCR. Roughly 48% of these differentially expressed tags could be mapped to publicly available genomic or expressed sequence tag (EST) sequence data. For example, in the P-starved library a number of the tags mapped to genes with a role in P scavenging, including a putative phosphate-repressible permease and a putative polyphosphate synthetase. In short, the long SAGE analyses have (i) identified many new differentially regulated gene sequences, (ii) assigned regulation data to EST sequences with no database homology and unknown function, and (iii) highlighted previously uncharacterized aspects of E. huxleyi N and P physiology. To this end, our long SAGE libraries provide a new public resource for gene discovery and transcriptional analysis in this biogeochemically important marine organism.This work was supported by the Woods Hole Oceanographic Institution Ocean Life Institute, the J. Lamar Worzel Assistant Scientist Fund, and the Frank and Lisina Hoch Endowed Fund. A.G.M., S.R.B., and M.J.C. were supported in part by the Marine Biological Laboratory's Program in Global Infectious Diseases, funded by the Ellison Medical Foundation. Computational resources were provided by the Josephine Bay Paul Center for Comparative Molecular Biology and Evolution (Marine Biological Laboratory) through funds provided by the W. M. Keck Foundation and the G. Unger Vetlesen Foundation

Quantum effects on Lagrangian points and displaced periodic orbits in the Earth-Moon system

Recent work in the literature has shown that the one-loop long distance quantum corrections to the Newtonian potential imply tiny but observable effects in the restricted three-body problem of celestial mechanics, i.e., at the Lagrangian libration points of stable equilibrium the planetoid is not exactly at equal distance from the two bodies of large mass, but the Newtonian values of its coordinates are changed by a few millimeters in the Earth-Moon system. First, we assess such a theoretical calculation by exploiting the full theory of the quintic equation, i.e., its reduction to Bring-Jerrard form and the resulting expression of roots in terms of generalized hypergeometric functions. By performing the numerical analysis of the exact formulas for the roots, we confirm and slightly improve the theoretical evaluation of quantum corrected coordinates of Lagrangian libration points of stable equilibrium. Second, we prove in detail that also for collinear Lagrangian points the quantum corrections are of the same order of magnitude in the Earth-Moon system. Third, we discuss the prospects to measure, with the help of laser ranging, the above departure from the equilateral triangle picture, which is a challenging task. On the other hand, a modern version of the planetoid is the solar sail, and much progress has been made, in recent years, on the displaced periodic orbits of solar sails at all libration points, both stable and unstable. The present paper investigates therefore, eventually, a restricted three-body problem involving Earth, Moon and a solar sail. By taking into account the one-loop quantum corrections to the Newtonian potential, displaced periodic orbits of the solar sail at libration points are again found to exist

How representative of a general type 2 diabetes population are patients included in cardiovascular outcome trials with SGLT2 inhibitors? A large European observational study

Aims: Enrollment criteria vary substantially among cardiovascular outcome trials (CVOTs) of sodium-glucose cotransporter-2 inhibitors (SGLT-2is), which impacts the relationship between a trial population and the general type 2 diabetes (T2D) population. The aim of this study was to evaluate the representativeness of four SGLT-2i CVOTs of a general T2D population. Methods: T2D patients from Germany, The Netherlands, Norway and Sweden were included in the study. Given the available data per country, key inclusion and exclusion criteria were defined by diagnoses, procedures and drug treatments to facilitate comparability among countries. Representativeness was determined by dividing the number of patients fulfilling the key enrolment criteria of each CVOT (CANVAS, DECLARE-TIMI 58, EMPA-REG OUTCOME, VERTIS-CV) by the total T2D population. Results: In 2015, a total T2D population of 803 836 patients was identified in Germany (n = 239 485), in The Netherlands (n = 36 213), in Norway (n = 149 782) and in Sweden (n = 378 356). These populations showed a 25% to 44% cardiovascular (CV) disease baseline prevalence and high CV-preventive drug use (>80%). The general T2D population had less prevalent CV disease and patients were slightly older than those included in the CVOTs. The DECLARE-TIMI 58 trial had the highest representativeness, 59% compared to the general T2D population, and this representativeness was almost 2-, 3- and 4-fold higher compared to the CANVAS (34%), EMPA-REG OUTCOME (21%) and VERTIS-CV (17%) trials, respectively. Conclusions: In large T2D populations within Europe, consistent patterns of representativeness of CVOTs were found when applying the main enrolment criteria. The DECLARE-TMI 58 trial had the highest representativeness, indicating that it included and examined patients who are most representative of the general T2D patients in the studied countries

Ricci-flat Metrics with U(1) Action and the Dirichlet Boundary-value Problem in Riemannian Quantum Gravity and Isoperimetric Inequalities

The Dirichlet boundary-value problem and isoperimetric inequalities for positive definite regular solutions of the vacuum Einstein equations are studied in arbitrary dimensions for the class of metrics with boundaries admitting a U(1) action. We show that in the case of non-trivial bundles Taub-Bolt infillings are double-valued whereas Taub-Nut and Eguchi-Hanson infillings are unique. In the case of trivial bundles, there are two Schwarzschild infillings in arbitrary dimensions. The condition of whether a particular type of filling in is possible can be expressed as a limitation on squashing through a functional dependence on dimension in each case. The case of the Eguchi-Hanson metric is solved in arbitrary dimension. The Taub-Nut and the Taub-Bolt are solved in four dimensions and methods for arbitrary dimension are delineated. For the case of Schwarzschild, analytic formulae for the two infilling black hole masses in arbitrary dimension have been obtained. This should facilitate the study of black hole dynamics/thermodynamics in higher dimensions. We found that all infilling solutions are convex. Thus convexity of the boundary does not guarantee uniqueness of the infilling. Isoperimetric inequalities involving the volume of the boundary and the volume of the infilling solutions are then investigated. In particular, the analogues of Minkowski's celebrated inequality in flat space are found and discussed providing insight into the geometric nature of these Ricci-flat spaces.Comment: 40 pages, 3 figure

Observation of confined current ribbon in JET plasmas

we report the identification of a localised current structure inside the JET plasma. It is a field aligned closed helical ribbon, carrying current in the same direction as the background current profile (co-current), rotating toroidally with the ion velocity (co-rotating). It appears to be located at a flat spot in the plasma pressure profile, at the top of the pedestal. The structure appears spontaneously in low density, high rotation plasmas, and can last up to 1.4 s, a time comparable to a local resistive time. It considerably delays the appearance of the first ELM.Comment: 10 pages, 6 figure

The molecular landscape of the University of Michigan laryngeal squamous cell carcinoma cell line panel

BackgroundLaryngeal squamous cell carcinomas (LSCCs) have a high risk of recurrence and poor prognosis. Patient‐derived cancer cell lines remain important preclinical models for advancement of new therapeutic strategies, and comprehensive characterization of these models is vital in the precision medicine era.MethodsWe performed exome and transcriptome sequencing as well as copy number analysis of a panel of LSCC‐derived cell lines that were established at the University of Michigan and are used in laboratories worldwide.ResultsWe observed a complex array of alterations consistent with those reported in The Cancer Genome Atlas head and neck squamous cell carcinoma project, including aberrations in PIK3CA, EGFR, CDKN2A, TP53, and NOTCH family and FAT1 genes. A detailed analysis of FAT family genes and associated pathways showed disruptions to these genes in most cell lines.ConclusionsThe molecular profiles we have generated indicate that as a whole, this panel recapitulates the molecular diversity observed in patients and will serve as useful guides in selecting cell lines for preclinical modeling.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151290/1/hed25803.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151290/2/hed25803_am.pd