Imperfect Information, Simplistic Modeling and the Robustness of Policy Rules

The paper presents a methodology for dealing with the problems of imperfect information or simplistic modeling in macroeconomic policy problems. The methodology permits to choose a robust policy from a given set of candidate policies--that is, a policy that makes the social welfare least sensitive to various potential modeling errors. This can be achieved even if the potential modeling errors are related to model structure or delays in model equations--without requiring that the models with more complicated structure or delays are fully solved and optimized. The particular example chosen to illustrate the methodology is a macroeconomic model of intertemporal optimization of monetary control of inflation and unemployment. The conclusions for this particular model are two-fold. Firstly, neglected delays or other modeling errors cannot, in general, substantiate rigorously the constant monetary growth rule that is usually advanced because of such modeling inaccuracies. In fact, by choosing an appropriate feedback policy formulation it is possible to obtain reasonable results of an active policy even if the underlying model used for policy derivation is very simple and the economic reality to which the policy is applied is much more complicated. Secondly, rigorous case can be made against 'impetuous' policy making with regard to inflation and unemployment, that is, against policies that by attaching a small weight to unemployment attempt to approach rapidly long-run targets for inflation. Such a policy strategy may induce instability, either through delay effects, or by making the macroeconomic system very sensitive to other modeling errors

RNA polymerase V targets transcriptional silencing components to promoters of protein‐coding genes

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96338/1/tpj12034-sup-0010-TableS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/96338/2/tpj12034-sup-0006-FigureS4.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/96338/3/tpj12034-sup-0007-FigureS5.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/96338/4/tpj12034-sup-0003-FigureS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/96338/5/tpj12034-sup-0008-FigureS6.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/96338/6/tpj12034-sup-0005-FigureS3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/96338/7/tpj12034-sup-0004-FigureS2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/96338/8/tpj12034-sup-0009-FigureS7.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/96338/9/tpj12034.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/96338/10/tpj12034-sup-0002-MethodsS1.pd

Processing second-order stochastic dominance models using cutting-plane representations

This is the post-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2011 Springer-VerlagSecond-order stochastic dominance (SSD) is widely recognised as an important decision criterion in portfolio selection. Unfortunately, stochastic dominance models are known to be very demanding from a computational point of view. In this paper we consider two classes of models which use SSD as a choice criterion. The first, proposed by Dentcheva and Ruszczyński (J Bank Finance 30:433–451, 2006), uses a SSD constraint, which can be expressed as integrated chance constraints (ICCs). The second, proposed by Roman et al. (Math Program, Ser B 108:541–569, 2006) uses SSD through a multi-objective formulation with CVaR objectives. Cutting plane representations and algorithms were proposed by Klein Haneveld and Van der Vlerk (Comput Manage Sci 3:245–269, 2006) for ICCs, and by Künzi-Bay and Mayer (Comput Manage Sci 3:3–27, 2006) for CVaR minimization. These concepts are taken into consideration to propose representations and solution methods for the above class of SSD based models. We describe a cutting plane based solution algorithm and outline implementation details. A computational study is presented, which demonstrates the effectiveness and the scale-up properties of the solution algorithm, as applied to the SSD model of Roman et al. (Math Program, Ser B 108:541–569, 2006).This study was funded by OTKA, Hungarian National Fund for Scientific Research, project 47340; by Mobile Innovation Centre, Budapest University of Technology, project 2.2; Optirisk Systems, Uxbridge, UK and by BRIEF (Brunel University Research Innovation and Enterprise Fund)

Spatial and Functional Relationships Among Pol V-Associated Loci, Pol IV-Dependent siRNAs, and Cytosine Methylation in the \u3cem\u3eArabidopsis\u3c/em\u3e Epigenome

Multisubunit RNA polymerases IV and V (Pols IV and V) mediate RNA-directed DNA methylation and transcriptional silencing of retrotransposons and heterochromatic repeats in plants. We identified genomic sites of Pol V occupancy in parallel with siRNA deep sequencing and methylcytosine mapping, comparing wild-type plants with mutants defective for Pol IV, Pol V, or both Pols IV and V. Approximately 60% of Pol V-associated regions encompass regions of 24-nucleotide (nt) siRNA complementarity and cytosine methylation, consistent with cytosine methylation being guided by base-pairing of Pol IV-dependent siRNAs with Pol V transcripts. However, 27% of Pol V peaks do not overlap sites of 24-nt siRNA biogenesis or cytosine methylation, indicating that Pol V alone does not specify sites of cytosine methylation. Surprisingly, the number of methylated CHH motifs, a hallmark of RNA-directed de novo methylation, is similar in wild-type plants and Pol IV or Pol V mutants. In the mutants, methylation is lost at 50%–60% of the CHH sites that are methylated in the wild type but is gained at new CHH positions, primarily in pericentromeric regions. These results indicate that Pol IV and Pol V are not required for cytosine methyltransferase activity but shape the epigenome by guiding CHH methylation to specific genomic sites

A study of inter-individual variability in the Phase II metabolism of xenobiotics in human skin

YesUnderstanding skin metabolism is key to improve in vitro to in vivo extrapolations used to inform risk assessments of topically applied products. However, published literature is scarce and usually covers a limited and non-representative number of donors. We developed a protocol to handle and store ex vivo skin samples post-surgery and prepare skin S9 fractions to measure the metabolic activity of Phase II enzymes. Preincubation of an excess of cofactors at 37 °C for fifteen minutes in the S9 before introduction of the testing probe, greatly increased the stability of the enzymes. Using this standardised assay, the rates of sulphation (SULT) and glucuronidation (UGT) of 7-hydroxycoumarin, methylation (COMT) of dopamine and N-acetylation (NAT) of procainamide were measured in the ng/mg protein/h (converted to ng/cm2/h) range in eighty-seven individuals. Glutathione conjugation (GST) of 1-chloro-2,4-dinitrobenzene was assessed in a smaller pool of fifty donors; the metabolic rate was much faster and measured over six minutes using a different methodology to express rates in μg/mg protein/min (converted to μg/cm2/min). A comprehensive statistical analysis of these results was carried out, separating donors by age, gender and metabolic rate measured

Echokardiografia pierwszym krokiem w diagnostyce guzów nerki

Intracardiac tumours are usually found after clinical symptoms lead to a positive imaging study, or as an incidental finding of imaging study, usually echocardiography. Cardiac tumours range from non-neoplastic lesions to high grade malignancies. The majority of primary cardiac tumours are myxomas (in 75% cases) or sarcomas (about 10% cases). In this paper we present cases of 2 patients with right atrial tumour, extending from renal carcinoma, invading renal vein and inferior vena cava into right atrium. Two different therapeutic strategies were undertaken in those patients. Kardiol Pol 2011; 69, 8: 849–85

Echokardiografia pierwszym krokiem w diagnostyce guzów nerki

Intracardiac tumours are usually found after clinical symptoms lead to a positive imaging study, or as an incidental finding of imaging study, usually echocardiography. Cardiac tumours range from non-neoplastic lesions to high grade malignancies. The majority of primary cardiac tumours are myxomas (in 75% cases) or sarcomas (about 10% cases). In this paper we present cases of 2 patients with right atrial tumour, extending from renal carcinoma, invading renal vein and inferior vena cava into right atrium. Two different therapeutic strategies were undertaken in those patients. Kardiol Pol 2011; 69, 8: 849–85

Targeted genetic testing for familial hypercholesterolaemia using next generation sequencing:a population-based study

Background<p></p> Familial hypercholesterolaemia (FH) is a common Mendelian condition which, untreated, results in premature coronary heart disease. An estimated 88% of FH cases are undiagnosed in the UK. We previously validated a method for FH mutation detection in a lipid clinic population using next generation sequencing (NGS), but this did not address the challenge of identifying index cases in primary care where most undiagnosed patients receive healthcare. Here, we evaluate the targeted use of NGS as a potential route to diagnosis of FH in a primary care population subset selected for hypercholesterolaemia.<p></p> Methods<p></p> We used microfluidics-based PCR amplification coupled with NGS and multiplex ligation-dependent probe amplification (MLPA) to detect mutations in LDLR, APOB and PCSK9 in three phenotypic groups within the Generation Scotland: Scottish Family Health Study including 193 individuals with high total cholesterol, 232 with moderately high total cholesterol despite cholesterol-lowering therapy, and 192 normocholesterolaemic controls.<p></p> Results<p></p> Pathogenic mutations were found in 2.1% of hypercholesterolaemic individuals, in 2.2% of subjects on cholesterol-lowering therapy and in 42% of their available first-degree relatives. In addition, variants of uncertain clinical significance (VUCS) were detected in 1.4% of the hypercholesterolaemic and cholesterol-lowering therapy groups. No pathogenic variants or VUCS were detected in controls.<p></p> Conclusions<p></p> We demonstrated that population-based genetic testing using these protocols is able to deliver definitive molecular diagnoses of FH in individuals with high cholesterol or on cholesterol-lowering therapy. The lower cost and labour associated with NGS-based testing may increase the attractiveness of a population-based approach to FH detection compared to genetic testing with conventional sequencing. This could provide one route to increasing the present low percentage of FH cases with a genetic diagnosis