Simple Sequencing Problems with Interdependent Costs

In this paper we analyze sequencing situations under incomplete information where agents have interdependent costs. We first argue why Vickrey-Clarke-Groves (or VCG) mechanism fails to implement a simple sequencing problem in dominant strategies. Given this impossibility, we try to implement simple sequencing problems in ex-post equilibrium. We show that a simple sequencing problem is implementable if and only if the mechanism is a `generalized VCG mechanism'. We then show that for implementable n agent simple sequencing problems, with polynomial cost function of order (n-2) or less, one can achieve first best implementability. Moreover, for the class of simple sequencing problems with ``sufficiently well behaved'' cost function, this is the only class of first best implementable simple sequencing problems.Simple Sequencing Problems, Ex-post Equilibrium, First Best Implementability

The Delegation Perspective on Representative Democracy

Why do political constituencies delegate decision power to representative assemblies? And how is the size of such assemblies determined? We analyze these questions of constitutional design in a model with voters learning their preferred alternative only after engaging in costly information gathering. We show that there is an optimal assembly size that would be chosen at a constitutional stage. This implies a relationship between assembly and constituency size. We then compared this relationship to actual data. Fitting a single parameter to the data, we show that our model can explain the actual relationship between assembly and constituency size quite well.Constitutional Design, Representative Democracy, Parliament Size, Information Costs

The Ursinus Weekly, December 6, 1954

West Chester choir sings at vespers • Does Ursinus have adequate parking facilities? • Candlelight Communion to be held Dec. 9 in Bomberger • Improper procedure key in MSGA trial • Rosicrucians add members at after-dinner dessert • Dr. Dugger speaks, shows slides to pre-medical group • Christmas to visit UC in many forms • Beta Sig presents Bill Haley on Jan. 7 • Charles Hudnut wins award in national poetry contest • Seniors hold prom; Elect lord and lady • 300 attend seventeenth annual Messiah performance • Chesterfield holds contest Home for the holidays • Dr. Oliver Gogarty discusses poets • Band practicing for May Day; Marches at basketball games • Editorials • Test of time • Matmen boast 7 lettermen; Two MAC champions return • Gridmen elect Neborak MVP, 1955 captain • Heller, Bauser All Philadelphia 3rd hockey team • Susquehanna, Nat. Aggies bow; Juniata mars record by 78-56 • Westerhoff\u27s proposed revisions passed by MSGAhttps://digitalcommons.ursinus.edu/weekly/1462/thumbnail.jp

The Ursinus Weekly, April 13, 1953

Committee selects YMCA nominees; Profs speak Wed. • May Day pageant has monthly theme • Ursinus entertains Hi-Y • Weekly staff hears C. Lee • Curtain Club prepares for Spring production • Dr. C. L. Chandler heard as speaker at IRC banquet • Fotine to play for Jr. dance • High class stuff to be given by junior class, April 17-18 • Candidates revealed for WSGA, WAA, YWCA • Iranian diplomat speaks to forum • Model UN held at Cornell; Dr. Miller advises committee • 35 students eligible to join Pi Gamma Mu • WAA card party tonight • Editorials: Procedure is important • Fry\u27s play well done by Curtain Club group • Dinner dances planned at sorority meetings • Boys\u27 quartet visits Temple • Letters to the editor • Mixed marriages • Juniors adopt new policies in prom plans • For all young lovers on rainy Spring days, suggested: Exciting tour through Pfahler Hall • Freidlin, Syvertsen elected basketball, swimming captains; Belles fall to Temple and defeat boys in thrillers • Kenny captains men\u27s tennis • Swett leads track team; Eshbach, Weaver return • Boyd and Rittenhouse captain girls\u27 tennis • Intramural wins to Derr, Ehlers • Baseball season opens; Veterans bolster team • Meistersingers give concert, plan program for April 23https://digitalcommons.ursinus.edu/weekly/1516/thumbnail.jp

The Ursinus Weekly, February 23, 1953

Summer school subjects to be selected now • 6th foreign policy institute to be Friday • Women elect Ruth Reed as May queen; Janie Hopple as manager for May Day • Y rep attends Bible study conf. • Dr. Harmin to be speaker at FTA Tuesday night at 7 • Jones to show slides • Detweiler to speak on religion in life day, February 25 • Rev. Flynn to speak tonight • Dr. Yost reads short stories at second English lit reading • Debaters defeat Princeton • Play tryouts to be this week; Group two to give plays • $52.92 collected for flood relief • French Club to give play at Penn, Thurs. • Quartet to sing • Dr. Bartholomew discusses rural church with Chi Alpha • Editorials: Enthusiasm needed; What happened? • Engagements • Letters to the editor • Fraternities sign 54 men • Science majors offered atomic energy posts • Margie changes from practice teaching to teaching position • Students examine Kimberton farms teaching methods • Ursinus men on the rocks as sirens comb their locks • Drexel rallies in last period to triumph 62-52 • Belles topple Garnet 42-24 • Grapplers edged out by Fords in last bout, 18-15 • Dawkins wins but Bears drop 21-5 match to Bucks • Mermaids dunk Drexel; Lose to powerful Garnet • Blood disease sidelines Swett • Haverford edges Bears 81-77 despite late surge • Belles rally to beat I.C. 42-38https://digitalcommons.ursinus.edu/weekly/1513/thumbnail.jp

The Ursinus Weekly, October 11, 1954

The Night of January 16th to be Curtain Club Fall play • Gayle Livingstone wins essay award • History Department starts Bible study group • Fraternity row • IRC invites students • Beemer, Ramsey get NR commission • WSGA classified Bermuda shorts • God, our help in ages past theme for weekend retreat • Chem. society opens term • Y \u27s plan for \u2754-\u2755 • FTA to hold first meeting • Forum on October 31st • Maples and Lynnewood have new preceptresses • Editorials • Cub and Key celebrate 15th anniversary • Debators campaign • Paolone sets \u2754-\u2755 MSGA in motion • P-T day • Band lays plans for Old Timers\u27 Day • Maintenance men active • French Club to meet Tues. • Continental observer • Price of originality • Volume XXII of The Lantern • Captain Stadler, hockey gals out to beat 1-loss 1953 mark • Ehlers\u27 passing nets Curtis lead in grid campaign • Don\u27t buy your spirit, we have it for free! • Conti, Carver break away to blank Crusaders, 12-0 • Fall volleyball replaces hockey in intramurals • Fumble, blocked kicks aid Drexel win: Dragons maul Bears 41-13; Hart, Campiglia big guns • Booters down Hill School in 5-1 opener; Four back • Stick gals bow to Beaver 5-3 after injury to Ruth Heller • Emerald gals use teamwork in 7-0 victory • Chess Club elects Scheirer new prexy • Aregood to preside over first Chi Alpha meeting • Frosh united? • Want an activity? Join the Y • Robert Sutton new librarianhttps://digitalcommons.ursinus.edu/weekly/1455/thumbnail.jp

An extensive phenotypic characterization of the hTNFα transgenic mice

<p>Abstract</p> <p>Background</p> <p>Tumor necrosis factor alpha (TNFα) is implicated in a wide variety of pathological and physiological processes, including chronic inflammatory conditions, coronary artery disease, diabetes, obesity, and cachexia. Transgenic mice expressing human TNFα (hTNFα) have previously been described as a model for progressive rheumatoid arthritis. In this report, we describe extensive characterization of an hTNFα transgenic mouse line.</p> <p>Results</p> <p>In addition to arthritis, these hTNFα transgenic mice demonstrated major alterations in body composition, metabolic rate, leptin levels, response to a high-fat diet, bone mineral density and content, impaired fertility and male sexual function. Many phenotypes displayed an earlier onset and a higher degree of severity in males, pointing towards a significant degree of sexual dimorphism in response to deregulated expression of TNFα.</p> <p>Conclusion</p> <p>These results highlight the potential usefulness of this transgenic model as a resource for studying the progressive effects of constitutively expressed low levels of circulating TNFα, a condition mimicking that observed in a number of human pathological conditions.</p

Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort.

BACKGROUND: Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines. METHODS: In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGroup3), and group 4 (MBGroup4). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma. FINDINGS: We included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105 sequenced controls from ExAC and identified APC, BRCA2, PALB2, PTCH1, SUFU, and TP53 as consensus medulloblastoma predisposition genes according to our rare variant burden analysis and estimated that germline mutations accounted for 6% of medulloblastoma diagnoses in the retrospective cohort. The prevalence of genetic predispositions differed between molecular subgroups in the retrospective cohort and was highest for patients in the MBSHH subgroup (20% in the retrospective cohort). These estimates were replicated in the prospective clinical cohort (germline mutations accounted for 5% of medulloblastoma diagnoses, with the highest prevalence [14%] in the MBSHH subgroup). Patients with germline APC mutations developed MBWNT and accounted for most (five [71%] of seven) cases of MBWNT that had no somatic CTNNB1 exon 3 mutations. Patients with germline mutations in SUFU and PTCH1 mostly developed infant MBSHH. Germline TP53 mutations presented only in childhood patients in the MBSHH subgroup and explained more than half (eight [57%] of 14) of all chromothripsis events in this subgroup. Germline mutations in PALB2 and BRCA2 were observed across the MBSHH, MBGroup3, and MBGroup4 molecular subgroups and were associated with mutational signatures typical of homologous recombination repair deficiency. In patients with a genetic predisposition to medulloblastoma, 5-year progression-free survival was 52% (95% CI 40-69) and 5-year overall survival was 65% (95% CI 52-81); these survival estimates differed significantly across patients with germline mutations in different medulloblastoma predisposition genes. INTERPRETATION: Genetic counselling and testing should be used as a standard-of-care procedure in patients with MBWNT and MBSHH because these patients have the highest prevalence of damaging germline mutations in known cancer predisposition genes. We propose criteria for routine genetic screening for patients with medulloblastoma based on clinical and molecular tumour characteristics. FUNDING: German Cancer Aid; German Federal Ministry of Education and Research; German Childhood Cancer Foundation (Deutsche Kinderkrebsstiftung); European Research Council; National Institutes of Health; Canadian Institutes for Health Research; German Cancer Research Center; St Jude Comprehensive Cancer Center; American Lebanese Syrian Associated Charities; Swiss National Science Foundation; European Molecular Biology Organization; Cancer Research UK; Hertie Foundation; Alexander and Margaret Stewart Trust; V Foundation for Cancer Research; Sontag Foundation; Musicians Against Childhood Cancer; BC Cancer Foundation; Swedish Council for Health, Working Life and Welfare; Swedish Research Council; Swedish Cancer Society; the Swedish Radiation Protection Authority; Danish Strategic Research Council; Swiss Federal Office of Public Health; Swiss Research Foundation on Mobile Communication; Masaryk University; Ministry of Health of the Czech Republic; Research Council of Norway; Genome Canada; Genome BC; Terry Fox Research Institute; Ontario Institute for Cancer Research; Pediatric Oncology Group of Ontario; The Family of Kathleen Lorette and the Clark H Smith Brain Tumour Centre; Montreal Children's Hospital Foundation; The Hospital for Sick Children: Sonia and Arthur Labatt Brain Tumour Research Centre, Chief of Research Fund, Cancer Genetics Program, Garron Family Cancer Centre, MDT's Garron Family Endowment; BC Childhood Cancer Parents Association; Cure Search Foundation; Pediatric Brain Tumor Foundation; Brainchild; and the Government of Ontario