3,371 research outputs found
Response to The Cost of Guilty Breach: What Work Is âWillful Breachâ Doing?
The authors of The Cost of Guilty Breach have pointed out an interesting issueâwhy is it that merger agreements import into their contracts language of moral culpability to establish liability in connection with a breach of the agreement? The authors propose some persuasive hypotheses to explain the presence of âwillful breachâ language. In this brief response, I mostly agree with the authors and offer a few of my own thoughts about the merger contract and breach
Mergers, MACs, and COVID-19
The conventional wisdom is that MAE/MACs in merger agreements provide an opportunity for buyers to renegotiate merger agreements in the event of intervening adverse events. However, the experience following the COVID-19 outbreak suggests that the conventional wisdom is incorrect or at least overstated. In fact, MAE/MACs shift the risk of exogenous adverse events (like COVID-19) to buyers while leaving only the risks of adverse endogenous and semi-endogenous events with the seller. The consequence of this risk-shifting is to strictly limit the circumstances under which a buyer can credibly lean on a MAE/MAC to threaten to terminate a merger agreement and initiate a renegotiation. Parties to merger agreements appear to have internalized that lesson, as demonstrated by the relative paucity of renegotiations in the immediate aftermath of the COVID-19 outbreak
Mergers, MACs, and COVID-19
The conventional wisdom is that MAE/MACs in merger agreements provide an opportunity for buyers to renegotiate merger agreements in the event of intervening adverse events. However, the experience following the COVID-19 outbreak suggests that the conventional wisdom is incorrect or at least overstated. In fact, MAE/MACs shift the risk of exogenous adverse events (like COVID-19) to buyers while leaving only the risks of adverse endogenous and semi-endogenous events with the seller. The consequence of this risk-shifting is to strictly limit the circumstances under which a buyer can credibly lean on a MAE/MAC to threaten to terminate a merger agreement and initiate a renegotiation. Parties to merger agreements appear to have internalized that lesson, as demonstrated by the relative paucity of renegotiations in the immediate aftermath of the COVID-19 outbreak
Appraisal Confusion: The Intended and Unintended Consequences of Delaware\u27s Nascent Pristine Deal Process Standard
In a merger, shareholders who believe the consideration being offered is too low have a statutory right to seek fair value for their shares through a judicial process called appraisal. In recent years, there has been an explosion in the number of appraisal actions leading some to argue that the remedy was being abused. In this Article, we argue that a recent line of cases by the Delaware Supreme Court that places heavy reliance on merger price as part of the judicial determination of fair value in appraisal proceedings is misguided and may lead to unintended consequences. Rather than rely on merger price in the determinations of fair value for publicly traded companies, courts should either eliminate the appraisal remedy for publicly traded corporations altogether or look to the unaffected stock market price of merger targets
A computational model of the hypothalamic - pituitary - gonadal axis in female fathead minnows (Pimephales promelas) exposed to 17α-ethynylestradiol and 17ÎČ-trenbolone
© 2011 Li et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.Background - Endocrine disrupting chemicals (e.g., estrogens, androgens and their mimics) are known to affect reproduction in fish. 17α-ethynylestradiol is a synthetic estrogen used in birth control pills. 17ÎČ-trenbolone is a relatively stable metabolite of trenbolone acetate, a synthetic androgen used as a growth promoter in livestock. Both 17α-ethynylestradiol and 17ÎČ-trenbolone have been found in the aquatic environment and affect fish reproduction. In this study, we developed a physiologically-based computational model for female fathead minnows (FHM, Pimephales promelas), a small fish species used in ecotoxicology, to simulate how estrogens (i.e., 17α-ethynylestradiol) or androgens (i.e., 17ÎČ-trenbolone) affect reproductive endpoints such as plasma concentrations of steroid hormones (e.g., 17ÎČ-estradiol and testosterone) and vitellogenin (a precursor to egg yolk proteins).
Results - Using Markov Chain Monte Carlo simulations, the model was calibrated with data from unexposed, 17α-ethynylestradiol-exposed, and 17ÎČ-trenbolone-exposed FHMs. Four Markov chains were simulated, and the chains for each calibrated model parameter (26 in total) converged within 20,000 iterations. With the converged parameter values, we evaluated the model's predictive ability by simulating a variety of independent experimental data. The model predictions agreed with the experimental data well.
Conclusions - The physiologically-based computational model represents the hypothalamic-pituitary-gonadal axis in adult female FHM robustly. The model is useful to estimate how estrogens (e.g., 17α-ethynylestradiol) or androgens (e.g., 17ÎČ-trenbolone) affect plasma concentrations of 17ÎČ-estradiol, testosterone and vitellogenin, which are important determinants of fecundity in fish.The Medical Research Foundation of Oregon, U.S. Environmental Protection
Agency, and the National Center for Computational Toxicology of the EPA Office of
Research and Development
Genotype imputation for the prediction of genomic breeding values in non-genotyped and low-density genotyped individuals
<p>Abstract</p> <p>Background</p> <p>There is wide interest in calculating genomic breeding values (GEBVs) in livestock using dense, genome-wide SNP data. The general framework for genomic selection assumes all individuals are genotyped at high-density, which may not be true in practice. Methods to add additional genotypes for individuals not genotyped at high density have the potential to increase GEBV accuracy with little or no additional cost. In this study a long haplotype library was created using a long range phasing algorithm and used in combination with segregation analysis to impute dense genotypes for non-genotyped dams in the training dataset (S1) and for non-genotyped or low-density genotyped individuals in the prediction dataset (S2), using the 14<sup>th</sup> QTL-MAS Workshop dataset. Alternative low-density scenarios were evaluated for accuracy of imputed genotypes and prediction of GEBVs.</p> <p>Results</p> <p>In S1, females in the training population were not genotyped and prediction individuals were either not genotyped or genotyped at low-density (evenly spaced at 2, 5 or 10 Mb). The proportion of correctly imputed genotypes for training females did not change when genotypes were added for individuals in the prediction set whereas the number of correctly imputed genotypes in the prediction set increased slightly (S1). The S2 scenario assumed the complete training set was genotyped for all SNPs and the prediction set was not genotyped or genotyped at low-density. The number of correctly imputed genotypes increased with genotyping density in the prediction set. Accuracy of genomic breeding values for the prediction set in each scenario were the correlation of GEBVs with true breeding values and were used to evaluate the potential loss in accuracy with reduced genotyping. For both S1 and S2 the GEBV accuracies were similar when the prediction set was not genotyped and increased with the addition of low-density genotypes, with the increase larger for S2 than S1.</p> <p>Conclusions</p> <p>Genotype imputation using a long haplotype library and segregation analysis is promising for application in sparsely-genotyped pedigrees. The results of this study suggest that dense genotypes can be imputed for selection candidates with some loss in genomic breeding value accuracy, but with levels of accuracy higher than traditional BLUP estimated breeding values. Accurate genotype imputation would allow for a single low-density SNP panel to be used across traits.</p
Methods for peptide identification by spectral comparison
BACKGROUND: Tandem mass spectrometry followed by database search is currently the predominant technology for peptide sequencing in shotgun proteomics experiments. Most methods compare experimentally observed spectra to the theoretical spectra predicted from the sequences in protein databases. There is a growing interest, however, in comparing unknown experimental spectra to a library of previously identified spectra. This approach has the advantage of taking into account instrument-dependent factors and peptide-specific differences in fragmentation probabilities. It is also computationally more efficient for high-throughput proteomics studies. RESULTS: This paper investigates computational issues related to this spectral comparison approach. Different methods have been empirically evaluated over several large sets of spectra. First, we illustrate that the peak intensities follow a Poisson distribution. This implies that applying a square root transform will optimally stabilize the peak intensity variance. Our results show that the square root did indeed outperform other transforms, resulting in improved accuracy of spectral matching. Second, different measures of spectral similarity were compared, and the results illustrated that the correlation coefficient was most robust. Finally, we examine how to assemble multiple spectra associated with the same peptide to generate a synthetic reference spectrum. Ensemble averaging is shown to provide the best combination of accuracy and efficiency. CONCLUSION: Our results demonstrate that when combined, these methods can boost the sensitivity and specificity of spectral comparison. Therefore they are capable of enhancing and complementing existing tools for consistent and accurate peptide identification
Brief of Corporate Law Professors as Amici Curie in Support of Respondents
The Supreme Court has looked to the rights of corporate shareholders in determining the rights of union members and non-members to control political spending, and vice versa. The Court sometimes assumes that if shareholders disapprove of corporate political expression, they can easily sell their shares or exercise control over corporate spending. This assumption is mistaken. Because of how capital is saved and invested, most individual shareholders cannot obtain full information about corporate political activities, even after the fact, nor can they prevent their savings from being used to speak in ways with which they disagree. Individual shareholders have no âopt outâ rights or practical ability to avoid subsidizing corporate political expression with which they disagree. Nor do individuals have the practical option to refrain from putting their savings into equity investments, as doing so would impose damaging economic penalties and ignore conventional financial guidance for individual investors
Characterization of Shewanella oneidensis MtrC: a cell-surface decaheme cytochrome involved in respiratory electron transport to extracellular electron acceptors
MtrC is a decaheme c-type cytochrome associated with the outer cell membrane of Fe(III)-respiring species of the Shewanella genus. It is proposed to play a role in anaerobic respiration by mediating electron transfer to extracellular mineral oxides that can serve as terminal electron acceptors. The present work presents the first spectropotentiometric and voltammetric characterization of MtrC, using protein purified from Shewanella oneidensis MR-1. Potentiometric titrations, monitored by UVâvis absorption and electron paramagnetic resonance (EPR) spectroscopy, reveal that the hemes within MtrC titrate over a broad potential range spanning between approximately +100 and approximately -500 mV (vs. the standard hydrogen electrode). Across this potential window the UVâvis absorption spectra are characteristic of low-spin c-type hemes and the EPR spectra reveal broad, complex features that suggest the presence of magnetically spin-coupled low-spin c-hemes. Non-catalytic protein film voltammetry of MtrC demonstrates reversible electrochemistry over a potential window similar to that disclosed spectroscopically. The voltammetry also allows definition of kinetic properties of MtrC in direct electron exchange with a solid electrode surface and during reduction of a model Fe(III) substrate. Taken together, the data provide quantitative information on the potential domain in which MtrC can operate
The structure of a resuscitation-promoting factor domain from Mycobacterium tuberculosis shows homology to lysozymes
Resuscitation-promoting factor (RPF) proteins reactivate stationary-phase cultures of (G+C)-rich Gram-positive bacteria including the causative agent of tuberculosis, Mycobacterium tuberculosis. We report the solution structure of the RPF domain from M. tuberculosis Rv1009 (RpfB) solved by heteronuclear multidimensional NMR. Structural homology with various glycoside hydrolases suggested that RpfB cleaved oligosaccharides. Biochemical studies indicate that a conserved active site glutamate is important for resuscitation activity. These data, as well as the presence of a clear binding pocket for a large molecule, indicate that oligosaccharide cleavage is probably the signal for revival from dormancy
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