Isolating intrinsic noise sources in a stochastic genetic switch

The stochastic mutual repressor model is analysed using perturbation methods. This simple model of a gene circuit consists of two genes and three promotor states. Either of the two protein products can dimerize, forming a repressor molecule that binds to the promotor of the other gene. When the repressor is bound to a promotor, the corresponding gene is not transcribed and no protein is produced. Either one of the promotors can be repressed at any given time or both can be unrepressed, leaving three possible promotor states. This model is analysed in its bistable regime in which the deterministic limit exhibits two stable fixed points and an unstable saddle, and the case of small noise is considered. On small time scales, the stochastic process fluctuates near one of the stable fixed points, and on large time scales, a metastable transition can occur, where fluctuations drive the system past the unstable saddle to the other stable fixed point. To explore how different intrinsic noise sources affect these transitions, fluctuations in protein production and degradation are eliminated, leaving fluctuations in the promotor state as the only source of noise in the system. Perturbation methods are then used to compute the stability landscape and the distribution of transition times, or first exit time density. To understand how protein noise affects the system, small magnitude fluctuations are added back into the process, and the stability landscape is compared to that of the process without protein noise. It is found that significant differences in the random process emerge in the presence of protein noise

Homogeneous CO Hydrogenation: Ligand Effects on the Lewis Acid-Assisted Reductive Coupling of Carbon Monoxide

Structure-function studies on the role of pendent Lewis acids in the reductive coupling of CO are reported. Cationic rhenium carbonyl complexes containing zero, one, or two phosphinoborane ligands (Ph_2P(CH_2)_nB(C_8H_(14)), n=1-3) react with the nucleophilic hydride [HPt(dmpe)_2]^+ to reduce [M-CO]^+ to M-CHO; this step is relatively insensitive to the Lewis acid, as both pendent (internal) and external boranes of appropriate acid strength can be used. In contrast, whether a second hydride transfer and C-C bond forming steps occur depends strongly on the number of carbon atoms between P and B in the phosphinoborane ligands, as well as the number of pendent acids in the complex: shorter linker chain lengths favor such reductive coupling, whereas longer chains and external boranes are ineffective. A number of different species containing partially reduced CO groups, whose exact structures vary considerably with the nature and number of phosphinoborane ligands, have been crystallographically characterized. The reaction of [(Ph -2P(CH_2)_2B(C_8H_(14)))_2Re(CO)4]^+ with [HPt(dmpe)_2]^+ takes place via a “hydride shuttle” mechanism, in which hydride is transferred from Pt to a pendent borane and thence to CO, rather than by direct hydride attack at CO. Addition of a second hydride in C_6D_5Cl at -40 ºC affords an unusual anionic bis(carbene) complex, which converts to a C-C bonded product on warming. These results support a working model for Lewis acid-assisted reductive coupling of CO, in which B (pendent or external) shuttles hydride from Pt to coordinated CO, followed by formation of an intramolecular B-O bond, which facilitates reductive coupling

Trialkylborane-Assisted CO_2 Reduction by Late Transition Metal Hydrides

Trialkylborane additives promote reduction of CO_2 to formate by bis(diphosphine) Ni(II) and Rh(III) hydride complexes. The late transition metal hydrides, which can be formed from dihydrogen, transfer hydride to CO_2 to give a formateborane adduct. The borane must be of appropriate Lewis acidity: weaker acids do not show significant hydride transfer enhancement, while stronger acids abstract hydride without CO_2 reduction. The mechanism likely involves a pre-equilibrium hydride transfer followed by formation of a stabilizing formateborane adduct

Homogeneous CO Hydrogenation: Dihydrogen Activation Involves a Frustrated Lewis Pair Instead of a Platinum Complex

During a search for conditions appropriate for Pt-catalyzed CO reduction using dihydrogen directly, metal-free conditions were discovered instead. A bulky, strong phosphazene base forms a “frustrated” Lewis pair (FLP) with a trialkylborane in the secondary coordination sphere of a rhenium carbonyl. Treatment of the FLP with dihydrogen cleanly affords multiple hydride transfers and C−C bond formation

Piloted-simulation study of effects of vortex flaps on low-speed handling qualities of a Delta-wing airplane

A piloted-simulation study was conducted to investigate the effects of vortex flaps on low-speed handling qualities of a delta-wing airplane. The simulation math model was developed from wind tunnel tests of a 0.15 scale model of the F-106B airplane. Pilot evaluations were conducted using a six-degree-of-freedom motion base simulator. The results of the investigation showed that the reduced static longitudinal stability caused by the vortex flaps significantly degraded handling qualities in the approach-to-landing task. Acceptable handling qualities could be achieved by limiting the aft center-of-gravity location, consequently reducing the operational envelope of the airplane. Further improvement were possible by modifying the flight control force-feel system to reduce pitch-control sensitivity

Time Spent Working in Custody Influences Work Sample Test Battery Performance of Deputy Sheriffs Compared to Recruits

This study determined the influence of years spent working in custody on fitness measured by a state-specific testing battery (Work Sample Test Battery; WSTB) in deputy sheriffs. Retrospective analysis was conducted on one patrol school class (51 males, 13 females) divided into three groups depending on time spent working in custody: DS24 (<24 months; n = 20); DS2547 (25–47 months; n = 23); and DS48+ (≥48 months; n = 21). These groups were compared to a recruit class (REC; 219 males, 34 females) in the WSTB, which comprised five tasks completed for time: 99-yard (90.53-m) obstacle course (99OC); 165-pound (75-kg) dummy drag; six-foot (1.83-m) chain link fence (CLF) and solid wall (SW) climb; and 500-yard (457.2-m) run (500R). A univariate analysis of covariance (ANCOVA) (controlling for sex and age) with Bonferroni post hoc determined significant between-group differences. DS48+ were slower in the 99OC compared to the REC (p = 0.007) and performed the CLF and SW slower than all groups (p ≤ 0.012). DS24, DS2547, and DS48+ were all slower than REC in the 500R (p ≤ 0.002). Physical training should be implemented to maintain fitness and job-specific task performance in deputy sheriffs working custody, especially considering the sedentary nature of this work

Diels−Alder Topochemistry via Charge-Transfer Crystals: Novel (Thermal) Single-Crystal-to-Single-Crystal Transformations

The solid-state [4+2] cycloaddition of anthracene to bis(N-ethylimino)-1,4-dithiin occurs via a unique single-phase topochemical reaction in the intermolecular (1:1) charge-transfer crystal. The thermal heteromolecular solid-state condensation involves the entire crystal, and this rare crystalline event follows topochemical control during the entire cycloaddition. As a result, a new crystalline modification of the Diels−Alder product is formed with a crystal-packing similar to that of the starting charge-transfer crystal but very different from that of the (thermodynamically favored) product modification obtained from solution-phase crystallization. Such a single-phase transformation is readily monitored by X-ray crystallography at various conversion stages, and the temporal changes in crystallographic parameters are correlated with temperature-dependent (solid-state) kinetic data that are obtained by 1H NMR spectroscopy at various reaction times. Thus, an acceleration of the solid-state reaction over time is found which results from a progressive lowering of the activation barrier for cycloaddition in a single crystal as it slowly and homogeneously converts from the reactant to the product lattice