19 research outputs found

    Profit Sharing and Incentives

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    We model a firm as a team production process subject to moral hazard and derive the optimal profit sharing scheme between productive workers and outside investors together with incentive contracts based on noisy performance signals. More productive agents with noisier performance signals are more likely to receive shares which can explain why managers are motivated by shares, and law or consulting firms form partnerships. A firm that grows by opening branches is held almost entirely by outside investors when its output noise grows faster than the number of branches. Otherwise, insiders hold substantial amount of a large firm’s shares

    Modeling RNA polymerase competition: the effect of σ-subunit knockout and heat shock on gene transcription level

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    <p>Abstract</p> <p>Background</p> <p>Modeling of a complex biological process can explain the results of experimental studies and help predict its characteristics. Among such processes is transcription in the presence of competing RNA polymerases. This process involves RNA polymerases collision followed by transcription termination.</p> <p>Results</p> <p>A mathematical and computer simulation model is developed to describe the competition of RNA polymerases during genes transcription on complementary DNA strands. E.g., in the barley <it>Hordeum vulgare </it>the polymerase competition occurs in the locus containing plastome genes <it>psbA</it>, <it>rpl23</it>, <it>rpl2 </it>and four bacterial type promoters. In heat shock experiments on isolated chloroplasts, a twofold decrease of <it>psbA </it>transcripts and even larger increase of <it>rpl23</it>-<it>rpl2 </it>transcripts were observed, which is well reproduced in the model. The model predictions are in good agreement with virtually all relevant experimental data (knockout, heat shock, chromatogram data, etc.). The model allows to hypothesize a mechanism of cell response to knockout and heat shock, as well as a mechanism of gene expression regulation in presence of RNA polymerase competition. The model is implemented for multiprocessor platforms with MPI and supported on Linux and MS Windows. The source code written in C++ is available under the GNU General Public License from the laboratory website. A user-friendly GUI version is also provided at <url>http://lab6.iitp.ru/en/rivals</url>.</p> <p>Conclusions</p> <p>The developed model is in good agreement with virtually all relevant experimental data. The model can be applied to estimate intensities of binding of the holoenzyme and phage type RNA polymerase to their promoters using data on gene transcription levels, as well as to predict characteristics of RNA polymerases and the transcription process that are difficult to measure directly, e.g., the intensity (frequency) of holoenzyme binding to the promoter in correlation to its nucleotide composition and the type of σ-subunit, the amount of transcription initiation aborts, etc. The model can be used to make functional predictions, e.g., heat shock response in isolated chloroplasts and changes of gene transcription levels under knockout of different σ-subunits or RNA polymerases or due to gene expression regulation.</p> <p>Reviewers</p> <p>This article was reviewed by Dr. Anthony Almudevar, Dr. Aniko Szabo, Dr. Yuri Wolf (nominated by Dr. Peter Olofsson) and Prof. Marek Kimmel.</p

    Essays on strategic information transmission and contract theory

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    This thesis studies problems of asymmetric information with multiple agents. Each chapter models a different aspect of asymmetric information. In the first chapter, there is only one uninformed agent who gets messages from other informed agents. Here, the uninformed agent takes an action, but the informed agents do not take actions. In the second and the third chapters the situation is reversed. These chapters deal with moral hazard problems. In the second chapter, the informed party is the one taking the action, and the other parties need to incentives the informed party to take the right action. In the second chapter each informed agent is motivated by a principal, who is constrained to writing contracts based only on the rating of the agent. In the third chapter, every agent is informed about her own effort, but all other agents want to motivate her to work with a combination of shares and signal-based contracts. In the first chapter I address the problem of strategic information transmission, commonly referred to as "cheap talk". It was first introduced by Crawford and Sobel, who showed that there is only a limited amount of information that can be transmitted from an informed sender to an uninformed receiver. In this chapter it is shown that it is possible to achieve high precision of information transmission with multiple senders by constructing an equilibrium which converges to full revelation exponentially fast with the number of senders. The result is robust to small perturbations, unlike previous attempts to achieve full revelation with multiple senders in this setting. The equilibrium can also be constructed for multidimensional state-spaces and achieves arbitrarily high precision even if each sender is allowed to send only two types of messages. The second chapter studies a moral hazard problem with many principal- agent pairs where each agent takes an unobservable costly action which affects the payoff of his principal. Each principal receives a rating of her agent which is a discrete signal of the agent's effort. The ratings can also depend on the other agents' efforts. A notable special case of ratings is a rank-order tournament. In equilibrium, each principal offers her agent an optimal contract which determines a transfer from the principal to the agent given the agent's rating and the efforts of other agents. When the principals and agents are risk neutral, rank-order based contracts can be sufficient to achieve efficient levels of effort for all principals. Necessary and sufficient conditions for the implementability of different levels of efforts and the existence of symmetric equilibria are derived in this chapter. Also, an example is provided, where rank-order based contracts generate externalities that are welfare reducing and a planner can improve on the equilibrium contracts. Optimal ownership structure of firms is the topic of the third chapter. This chapter models a production process which requires inputs from several agents. The agents' efforts are costly and are only observed with noise. Each agent can be motivated by both a contract paying her depending on her performance, and by the claim of the profit of the firm she has through ownership of a share of the company. This chapter shows that it is optimal to allocate some shares to the workers, and derives conditions when it is optimal for the workers of the firm to own the entire enterprise

    Optimal Growth Temperature and Intergenic Distances in Bacteria, Archaea, and Plastids of Rhodophytic Branch

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    The lengths of intergenic regions between neighboring genes that are convergent, divergent, or unidirectional were calculated for plastids of the rhodophytic branch and complete archaeal and bacterial genomes. Statistically significant linear relationships between any pair of the medians of these three length types have been revealed in each genomic group. Exponential relationships between the optimal growth temperature and each of the three medians have been revealed as well. The leading coefficients of the regression equations relating all pairs of the medians as well as temperature and any of the medians have the same sign and order of magnitude. The results obtained for plastids, archaea, and bacteria are also similar at the qualitative level. For instance, the medians are always low at high temperatures. At low temperatures, the medians tend to statistically significant greater values and scattering. The original model was used to test our hypothesis that the intergenic distances are optimized in particular to decrease the competition of RNA polymerases within the locus that results in transcribing shortened RNAs. Overall, this points to an effect of temperature for both remote and close genomes

    Additional file 3: of A method for identification of highly conserved elements and evolutionary analysis of superphylum Alveolata

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    Presents summary data on the clusters. The Resume sheet provides some information on the algorithm results with different parameters. The variant with the threshold length 65 bp, which is discussed in the main paper, is highlighted in pink. In lines 15–42, the number of m-dense clusters and their vertices are shown for m values from 30 to 3. For example (line 15): 14 clusters were found containing words from all 30 genomes; these clusters comprise a total of 3736 vertices, i.e. 9 words per genome on average. Another example (line 35): 84 clusters were found containing words from 10 genomes; 1.2 words per genome on average. On the Clusters sheet, each line starting from the sixth one corresponds to a cluster. Column A contains the cluster number highlighted in the case of untranslated or unknown UCE (similar to Additional file 2). The HCE type is shown in column B as follows: if any of cluster words was found in Rfam, the cluster corresponds to a known RNA such as tRNA, snRNA, etc.; the column contains this RNA label; if any of cluster words overlaps with a CDS, it corresponds to a protein (exon) and is labeled as a protein; if any of cluster words overlaps with a gene, it corresponds to an intron or other untranslated region and is labeled as an intron; otherwise the cluster describes an unknown HCE (no label in column B). Column C shows the total number of words in the cluster; column D, the total number of species containing these words; and columns E–AH, the number of words from each species. (XLSX 1109 kb

    Modeling RNA polymerase interaction in mitochondria of chordates

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    Abstract Background In previous work, we introduced a concept, a mathematical model and its computer realization that describe the interaction between bacterial and phage type RNA polymerases, protein factors, DNA and RNA secondary structures during transcription, including transcription initiation and termination. The model accurately reproduces changes of gene transcription level observed in polymerase sigma-subunit knockout and heat shock experiments in plant plastids. The corresponding computer program and a user guide are available at http://lab6.iitp.ru/en/rivals. Here we apply the model to the analysis of transcription and (partially) translation processes in the mitochondria of frog, rat and human. Notably, mitochondria possess only phage-type polymerases. We consider the entire mitochondrial genome so that our model allows RNA polymerases to complete more than one circle on the DNA strand. Results Our model of RNA polymerase interaction during transcription initiation and elongation accurately reproduces experimental data obtained for plastids. Moreover, it also reproduces evidence on bulk RNA concentrations and RNA half-lives in the mitochondria of frog, human with or without the MELAS mutation, and rat with normal (euthyroid) or hyposecretion of thyroid hormone (hypothyroid). The transcription characteristics predicted by the model include: (i) the fraction of polymerases terminating at a protein-dependent terminator in both directions (the terminator polarization), (ii) the binding intensities of the regulatory protein factor (mTERF) with the termination site and, (iii) the transcription initiation intensities (initiation frequencies) of all promoters in all five conditions (frog, healthy human, human with MELAS syndrome, healthy rat, and hypothyroid rat with aberrant mtDNA methylation). Using the model, absolute levels of all gene transcription can be inferred from an arbitrary array of the three transcription characteristics, whereas, for selected genes only relative RNA concentrations have been experimentally determined. Conversely, these characteristics and absolute transcription levels can be obtained using relative RNA concentrations and RNA half-lives known from various experimental studies. In this case, the “inverse problem” is solved with multi-objective optimization. Conclusions In this study, we demonstrate that our model accurately reproduces all relevant experimental data available for plant plastids, as well as the mitochondria of chordates. Using experimental data, the model is applied to estimate binding intensities of phage-type RNA polymerases to their promoters as well as predicting terminator characteristics, including polarization. In addition, one can predict characteristics of phage-type RNA polymerases and the transcription process that are difficult to measure directly, e.g., the association between the promoter’s nucleotide composition and the intensity of polymerase binding. To illustrate the application of our model in functional predictions, we propose a possible mechanism for MELAS syndrome development in human involving a decrease of Phe-tRNA, Val-tRNA and rRNA concentrations in the cell. In addition, we describe how changes in methylation patterns of the mTERF binding site and three promoters in hypothyroid rat correlate with changes in intensities of the mTERF binding and transcription initiations. Finally, we introduce an auxiliary model to describe the interaction between polysomal mRNA and ribonucleases.</p

    Development of the Paris-Erdogan model for the quantitative evaluation of the wear resistance of materials under dynamic contact with a discrete liquid-drop flow

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    The known fatigue model of Paris-Erdogan was first used for conditions of multi-cycle water-drop impacts with a metallic surface. The model is supplemented by the structure-dependent characteristics of the material. Experimental data providing correctness of model application is presented. The applied problem of quantitative evaluation of the material durability in the conditions of the droplet impact and comparison of materials of different structural classes was solved in the work without costly bench tests

    Development of the Paris-Erdogan model for the quantitative evaluation of the wear resistance of materials under dynamic contact with a discrete liquid-drop flow

    No full text
    The known fatigue model of Paris-Erdogan was first used for conditions of multi-cycle water-drop impacts with a metallic surface. The model is supplemented by the structure-dependent characteristics of the material. Experimental data providing correctness of model application is presented. The applied problem of quantitative evaluation of the material durability in the conditions of the droplet impact and comparison of materials of different structural classes was solved in the work without costly bench tests

    Highly Conserved Elements and Chromosome Structure Evolution in Mitochondrial Genomes in Ciliates

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    Recent phylogenetic analyses are incorporating ultraconserved elements (UCEs) and highly conserved elements (HCEs). Models of evolution of the genome structure and HCEs initially faced considerable algorithmic challenges, which gave rise to (often unnatural) constraints on these models, even for conceptually simple tasks such as the calculation of distance between two structures or the identification of UCEs. In our recent works, these constraints have been addressed with fast and efficient solutions with no constraints on the underlying models. These approaches have led us to an unexpected result: for some organelles and taxa, the genome structure and HCE set, despite themselves containing relatively little information, still adequately resolve the evolution of species. We also used the HCE identification to search for promoters and regulatory elements that characterize the functional evolution of the genome
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