97,554 research outputs found
Uncertainty and stepwise investment
We analyze the optimal investment strategy of a firm that can complete a project either in one stage at a single freely chosen time point or in incremental steps at distinct time points. The presence of economies of scale gives rise to the following trade-off: lumpy investment has a lower total cost, but stepwise investment gives more flexibility by letting the firm choose the timing individually for each stage. Our main question is how uncertainty in market development affects this trade-off. The answer is unambiguous and in contrast with a conventional real-options intuition: higher uncertainty makes the single-stage investment more attractive relative to the more flexible stepwise investment strategy
Structured, sparse regression with application to HIV drug resistance
We introduce a new version of forward stepwise regression. Our modification
finds solutions to regression problems where the selected predictors appear in
a structured pattern, with respect to a predefined distance measure over the
candidate predictors. Our method is motivated by the problem of predicting
HIV-1 drug resistance from protein sequences. We find that our method improves
the interpretability of drug resistance while producing comparable predictive
accuracy to standard methods. We also demonstrate our method in a simulation
study and present some theoretical results and connections.Comment: Published in at http://dx.doi.org/10.1214/10-AOAS428 the Annals of
Applied Statistics (http://www.imstat.org/aoas/) by the Institute of
Mathematical Statistics (http://www.imstat.org
Stepwise bending of DNA by a single TATA-box Binding Protein
The TATA-box Binding Protein (TBP) is required by all three eukaryotic RNA
polymerases for the initiation of transcription from most promoters. TBP
recognizes, binds to, and bends promoter sequences called ``TATA-boxes'' in the
DNA. We present results from the study of individual Saccharomyces cerevisia
TBPs interacting with single DNA molecules containing a TATA-box. Using video
microscopy, we observed the Brownian motion of beads tethered by short
surface-bound DNA. When TBP binds to and bends the DNA, the conformation of the
DNA changes and the amplitude of Brownian motion of the tethered bead is
reduced compared to that of unbent DNA. We detected individual binding and
dissociation events and derived kinetic parameters for the process.
Dissociation was induced by increasing the salt concentration or by directly
pulling on the tethered bead using optical tweezers. In addition to the
well-defined free and bound classes of Brownian motion, we observed another two
classes of motion. These extra classes were identified with intermediate states
on a three-step, linear binding pathway. Biological implications of the
intermediate states are discussed.Comment: Accepted for publication in: Biophysical Journa
Insight into the role of water on the methylation of hexamethylbenzene in H‐SAPO‐34 from first principle molecular dynamics simulations
The methylation of hexamethylbenzene with methanol is one of the key reactions in the methanol-to-olefins hydrocarbon pool reaction cycle taking place over the industrially relevant H-SAPO-34 zeolite. This methylation reaction can occur either via a concerted or via a stepwise mechanism, the latter being the preferred pathway at higher temperatures. Herein, we systematically investigate how a complex reaction environment with additional water molecules and higher concentrations of Bronsted acid sites in the zeolite impacts the reaction mechanism. To this end, first principle molecular dynamics simulations are performed using enhanced sampling methods to characterize the reactants and products in the catalyst pores and to construct the free energy profiles. The most prominent effect of the dynamic sampling of the reaction path is the stabilization of the product region where water is formed, which can either move freely in the pores of the zeolite or be stabilized through hydrogen bonding with the other protic molecules. These protic molecules also stabilize the deprotonated Bronsted acid site, created due to the formation of the heptamethylbenzenium cation, via a Grotthuss-type mechanism. Our results provide fundamental insight in the experimental parameters that impact the methylation of hexamethylbenzene in H-SAPO-34, especially highlighting and rationalizing the crucial role of water in one of the main reactions of the aromatics-based reaction cycle
On Optimality of Stepdown and Stepup Multiple Test Procedures
Consider the multiple testing problem of testing k null hypotheses, where the
unknown family of distributions is assumed to satisfy a certain monotonicity
assumption. Attention is restricted to procedures that control the familywise
error rate in the strong sense and which satisfy a monotonicity condition.
Under these assumptions, we prove certain maximin optimality results for some
well-known stepdown and stepup procedures.Comment: Published at http://dx.doi.org/10.1214/009053605000000066 in the
Annals of Statistics (http://www.imstat.org/aos/) by the Institute of
Mathematical Statistics (http://www.imstat.org
Making sense of step-by-step procedures
Procedural instructions that consist of only a sequence of steps will probably be executable, but nevertheless ¿meaningless¿ to users of technical devices. The paper discusses three features that can make procedural instructions more meaningful: adding functional coordinating information, adding information about the use of the technical device in real life, and adding operational information about how the device works. The research literature supports the effectiveness of the first feature, but offers little evidence that real life elements enhance understanding of instructions. As for operational information, the research suggests that users are willing to read it, and that it contributes to better understanding and performance in the long term, but only if it is closely related to the procedure. As a conclusion, we propose a theoretical framework that assumes three levels of mental representation of instructions: syntactical, semantic, and situationa
False discovery and false nondiscovery rates in single-step multiple testing procedures
Results on the false discovery rate (FDR) and the false nondiscovery rate
(FNR) are developed for single-step multiple testing procedures. In addition to
verifying desirable properties of FDR and FNR as measures of error rates, these
results extend previously known results, providing further insights,
particularly under dependence, into the notions of FDR and FNR and related
measures. First, considering fixed configurations of true and false null
hypotheses, inequalities are obtained to explain how an FDR- or FNR-controlling
single-step procedure, such as a Bonferroni or \u{S}id\'{a}k procedure, can
potentially be improved. Two families of procedures are then constructed, one
that modifies the FDR-controlling and the other that modifies the
FNR-controlling \u{S}id\'{a}k procedure. These are proved to control FDR or FNR
under independence less conservatively than the corresponding families that
modify the FDR- or FNR-controlling Bonferroni procedure. Results of numerical
investigations of the performance of the modified \u{S}id\'{a}k FDR procedure
over its competitors are presented. Second, considering a mixture model where
different configurations of true and false null hypotheses are assumed to have
certain probabilities, results are also derived that extend some of Storey's
work to the dependence case.Comment: Published at http://dx.doi.org/10.1214/009053605000000778 in the
Annals of Statistics (http://www.imstat.org/aos/) by the Institute of
Mathematical Statistics (http://www.imstat.org
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