Walverine: A Walrasian Trading Agent

TAC-02 was the third in a series of Trading Agent Competition events fostering research in automating trading strategies by showcasing alternate approaches in an open-invitation market game. TAC presents a challenging travel-shopping scenario where agents must satisfy client preferences for complementary and substitutable goods by interacting through a variety of market types. Michigan's entry, Walverine, bases its decisions on a competitive (Walrasian) analysis of the TAC travel economy. Using this Walrasian model, we construct a decision-theoretic formulation of the optimal bidding problem, which Walverine solves in each round of bidding for each good. Walverine's optimal bidding approach, as well as several other features of its overall strategy, are potentially applicable in a broad class of trading environments.trading agent, trading competition, tatonnement, competitive equilibrium

Interplay of DNA supercoiling and catenation during the segregation of sister duplexes

The discrete regulation of supercoiling, catenation and knotting by DNA topoisomerases is well documented both in vivo and in vitro, but the interplay between them is still poorly understood. Here we studied DNA catenanes of bacterial plasmids arising as a result of DNA replication in Escherichia coli cells whose topoisomerase IV activity was inhibited. We combined high-resolution two-dimensional agarose gel electrophoresis with numerical simulations in order to better understand the relationship between the negative supercoiling of DNA generated by DNA gyrase and the DNA interlinking resulting from replication of circular DNA molecules. We showed that in those replication intermediates formed in vivo, catenation and negative supercoiling compete with each other. In interlinked molecules with high catenation numbers negative supercoiling is greatly limited. However, when interlinking decreases, as required for the segregation of newly replicated sister duplexes, their negative supercoiling increases. This observation indicates that negative supercoiling plays an active role during progressive decatenation of newly replicated DNA molecules in vivo

The genome of Streptococcus pneumoniae is organized in topology-reacting gene clusters

The transcriptional response of Streptococcus pneumoniae was examined after exposure to the GyrB-inhibitor novobiocin. Topoisomer distributions of an internal plasmid confirmed DNA relaxation and recovery of the native level of supercoiling at low novobiocin concentrations. This was due to the up-regulation of DNA gyrase and the down-regulation of topoisomerases I and IV. In addition, >13% of the genome exhibited relaxation-dependent transcription. The majority of the responsive genes (>68%) fell into 15 physical clusters (14.6–85.6 kb) that underwent coordinated regulation, independently of operon organization. These genomic clusters correlated with AT content and codon composition, showing the chromosome to be organized into topology-reacting gene clusters that respond to DNA supercoiling. In particular, down-regulated clusters were flanked by 11–40 kb AT-rich zones that might have a putative structural function. This is the first case where genes responding to changes in the level of supercoiling in a coordinated manner were found organized as functional clusters. Such an organization revealed DNA supercoiling as a general feature that controls gene expression superimposed on other kinds of more specific regulatory mechanisms

Prognostic Value of Routine Cardiac Magnetic Resonance Assessment of Left Ventricular Ejection Fraction and Myocardial Damage An International, Multicenter Study

International audienc

Chronic non-transmural infarction has a delayed recovery of function following revascularization

<p>Abstract</p> <p>Background</p> <p>The time course of regional functional recovery following revascularization with regards to the presence or absence of infarction is poorly known. We studied the effect of the presence of chronic non-transmural infarction on the time course of recovery of myocardial perfusion and function after elective revascularization.</p> <p>Methods</p> <p>Eighteen patients (mean age 69, range 52-84, 17 men) prospectively underwent cine magnetic resonance imaging (MRI), delayed contrast enhanced MRI and rest/stress 99m-Tc-tetrofosmin single photon emission computed tomography (SPECT) before, one and six months after elective coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI).</p> <p>Results</p> <p>Dysfunctional myocardial segments (n = 337/864, 39%) were classified according to the presence (n = 164) or absence (n = 173) of infarction. Infarct transmurality in dysfunctional segments was largely non-transmural (transmurality = 31 ± 22%). Quantitative stress perfusion and wall thickening increased at one month in dysfunctional segments without infarction (p < 0.001), with no further improvement at six months. Despite improvements in stress perfusion at one month (p < 0.001), non-transmural infarction displayed a slower and lesser improvement in wall thickening at one (p < 0.05) and six months (p < 0.001).</p> <p>Conclusions</p> <p>Dysfunctional segments without infarction represent repetitively stunned or hibernating myocardium, and these segments improved both perfusion and function within one month after revascularization with no improvement thereafter. Although dysfunctional segments with non-transmural infarction improved in perfusion at one month, functional recovery was mostly seen between one and six months, possibly reflecting a more severe ischemic burden. These findings may be of value in the clinical assessment of regional functional recovery in the time period after revascularization.</p

Integrated Genomic and Gene Expression Profiling Identifies Two Major Genomic Circuits in Urothelial Carcinoma

Similar to other malignancies, urothelial carcinoma (UC) is characterized by specific recurrent chromosomal aberrations and gene mutations. However, the interconnection between specific genomic alterations, and how patterns of chromosomal alterations adhere to different molecular subgroups of UC, is less clear. We applied tiling resolution array CGH to 146 cases of UC and identified a number of regions harboring recurrent focal genomic amplifications and deletions. Several potential oncogenes were included in the amplified regions, including known oncogenes like E2F3, CCND1, and CCNE1, as well as new candidate genes, such as SETDB1 (1q21), and BCL2L1 (20q11). We next combined genome profiling with global gene expression, gene mutation, and protein expression data and identified two major genomic circuits operating in urothelial carcinoma. The first circuit was characterized by FGFR3 alterations, overexpression of CCND1, and 9q and CDKN2A deletions. The second circuit was defined by E3F3 amplifications and RB1 deletions, as well as gains of 5p, deletions at PTEN and 2q36, 16q, 20q, and elevated CDKN2A levels. TP53/MDM2 alterations were common for advanced tumors within the two circuits. Our data also suggest a possible RAS/RAF circuit. The tumors with worst prognosis showed a gene expression profile that indicated a keratinized phenotype. Taken together, our integrative approach revealed at least two separate networks of genomic alterations linked to the molecular diversity seen in UC, and that these circuits may reflect distinct pathways of tumor development

Cdc20 hypomorphic mice fail to counteract de novo synthesis of cyclin B1 in mitosis

Low expression levels of Cdc20 result in chromatin bridging and chromosome misalignment, revealing a requirement for Cdc20 in efficient sister chromosome separation and chromosome–microtubule attachment

Demographic, clinical, diagnostic and therapeutic data of hereditary spherocytosis in our country. A study on 143 cases belonging to 84 families

Introducción. La esferocitosis hereditaria (ESH) es la anemia hemolítica hereditaria más frecuente, pero es muy escasa la información sobre su comportamiento en nuestro país. Objetivos. Comunicar aspectos demográficos, clínicos, diagnósticos y terapéuticos de la enfermedad. Pacientes y métodos. Se revisaron datos de los pacientes estudiados desde 2007, año en que incorporamos al estudio de laboratorio clásico - fragilidad osmótica eritrocitaria (FOE) y autohemólisis (AH) - criohemólisis hipertónica (CH), citometría de flujo con eosina-5’-maleimida (5’EMA-CF) y electroforesis de proteínas de membrana (SDS-PAGE); desde 2009 también incorporamos FOE por citometría de flujo (FOE-CF). Criterios diagnósticos para ESH: visualización de esferocitos en frotis y dos pruebas positivas. Portador sano (PS): familiar con deficiencia de proteína de membrana, pero asintomático y con las otras pruebas negativas. Resultados. Se analizaron 281 individuos, identificando 121 ESH y 22 PS. Porcentajes de positividad de las pruebas: FOE 92,2%, AH 75,7%, SDS-PAGE 72,2%, CH 93,3%, 5’EMA-CF 91,3%, FOE-CF 86,3%. De los 69 casos en que se realizaron las tres nuevas técnicas, todos tuvieron al menos una positiva; 63 (91,3%) presentaron 2 positivas. La SDS-PAGE mostró que las deficiencias más frecuentes fueron ankirina y espectrina. Clasificación por formas clínicas: leves 33,7%, moderadas 44,2%, severas 22,1%. Presentaron manifestaciones en periodo neonatal el 80,9% de los casos, siendo mayor la incidencia en las formas moderadas/ severas que en las leves (p<0,05). No hubo diferencia en el resultado de las pruebas entre los subgrupos de severidad. Se esplenectomizaron 24 pacientes. Todos alcanzaron valores de hemoglobina normales después de la operación, sostenidos en el tiempo. No hubo ningún episodio infeccioso severo. Conclusiones. Las deficiencias más frecuentes en nuestro país son ankirina y espectrina. El uso simultáneo de CH, 5’EMA-CF y FOE-CF permite diagnosticar más del 91% de los casos; la realización de las pruebas convencionales quedaría limitada a casos con fuerte sospecha diagnóstica no confirmados por las mismas. A excepción de mayor incidencia de manifestaciones neonatales, el comportamiento clínico en nuestra población no presentó diferencias con lo informado por la mayoría de los autores. No hubo casos de muerte o sepsis fulminante postesplenectomía.Background. Hereditary spherocytosis (HS) is the most common inherited hemolytic anemia; however, information concerning its behavior in our country is scarce. Aim. To report demographic, clinical, diagnostic, and therapeutic data on the disease. Patients and methods. In 2007 we started performing hypertonic cryohemolysis (HC), 5’EMA flow cytometry (5’EMA-FC), and membrane proteins electrophoresis (SDS-PAGE) in addition to standard tests – osmotic fragility (OF) and autohemolysis (AH) - for evaluation of patients with HS. Since 2009 we added flow cytometric OF (OF-FC). Data from all patients studied from 2007 were analyzed. Diagnostic criteria for HS: spherocytes in blood smear plus two positive tests. Silent carrier (SC): family member with protein deficiency but otherwise asymptomatic and negative for other tests. Results. The study included 281 individuals; 121 HS and 22 SC were identified. Tests positivity rates were: OF 92.2%, AH 75.7%, SDS-PAGE 72.2%, HC 93.3%, 5’EMAFC 91.3%, OF-FC 86.3%. All of the 69 cases in whom the three new procedures were performed had at least one positive test; 63 of them (91.3%) presented two positive tests. The SDS-PAGE showed that the most frequent deficiencies were ankyrin and spectrin. Classification by severity of anemia: mild 33.7%, moderate 44.2%, severe 22.1%. Neonatal manifestations were seen in 80.9% of cases; the incidence was higher in moderate/severe than in mild anemias (p<0.05). Comparison of tests results in relation to severity showed no difference between groups. Splenectomy was performed in 24 patients. All of them reached sustained normal hemoglobin values after the procedure. No life-threatening infection occurred. Conclusions. Most frequent deficiencies in our country are ankyrin and spectrin. The simultaneous use of HC, 5’EMA-FC y OF-FC allows confirming the diagnosis in more than 91% of cases. Except for a higher incidence of neonatal manifestations, the clinical pattern in our population showed no difference with that reported by most authors. No case of death or overwhelming fulminant sepsis post-splenectomy was seen.Fil: Donato, Mariano Humberto. Hospital Nacional Profesor Alejandro Posadas; ArgentinaFil: Crisp, R. Hospital Nacional Profesor Alejandro Posadas; ArgentinaFil: García, E. Hospital Nacional Profesor Alejandro Posadas; ArgentinaFil: Rapetti, MC. Hospital Nacional Profesor Alejandro Posada; ArgentinaFil: Solari, L. Hospital Nacional Profesor Alejandro Posadas; ArgentinaFil: Vota, Daiana Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Chamorro, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Schvartzman, G. Hospital Nacional Profesor Alejandro Posada; ArgentinaFil: Miguez, G. Hospital Nacional Profesor Alejandro Posada; ArgentinaFil: Gammela, D. Hospital Nacional Profesor Alejandro Posada; ArgentinaFil: Vittori, Daniela Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Nesse, Alcira Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentin

Karyotypic Determinants of Chromosome Instability in Aneuploid Budding Yeast

Recent studies in cancer cells and budding yeast demonstrated that aneuploidy, the state of having abnormal chromosome numbers, correlates with elevated chromosome instability (CIN), i.e. the propensity of gaining and losing chromosomes at a high frequency. Here we have investigated ploidy- and chromosome-specific determinants underlying aneuploidy-induced CIN by observing karyotype dynamics in fully isogenic aneuploid yeast strains with ploidies between 1N and 2N obtained through a random meiotic process. The aneuploid strains exhibited various levels of whole-chromosome instability (i.e. chromosome gains and losses). CIN correlates with cellular ploidy in an unexpected way: cells with a chromosomal content close to the haploid state are significantly more stable than cells displaying an apparent ploidy between 1.5 and 2N. We propose that the capacity for accurate chromosome segregation by the mitotic system does not scale continuously with an increasing number of chromosomes, but may occur via discrete steps each time a full set of chromosomes is added to the genome. On top of such general ploidy-related effect, CIN is also associated with the presence of specific aneuploid chromosomes as well as dosage imbalance between specific chromosome pairs. Our findings potentially help reconcile the divide between gene-centric versus genome-centric theories in cancer evolution