Role of Peptide Backbone Conformation on Biological Activity of Chemotactic Peptides

To investigate the role of peptide backbone conformation on the biological activity of chemotactic peptides, we synthesized a unique analog of N-formyl-Met-Leu-Phe-OH incorporating the C α,α disubstituted residue, dipropylglycine (Dpg) in place of Leu. The conformation of the stereochemically constrained Dpg analog was examined in the crystalline state by x-ray diffraction and in solution using NMR, IR, and CD methods. The secretagogue activity of the peptide on human neutrophils was determined and compared with that of a stereochemically constrained, folded type II β-turn analog incorporating 1-aminocyclohexanecarboxylic acid (Ac6c) at position 2 (f-Met- Ac6c -Phe-OMe), the parent peptide (f-Met-Leu-Phe-OH) and its methyl ester derivative (f-Met-Leu-Phe-OMe). In the solid state, the Dpg analog adopts an extended β-sheet-like structure with an intramolecular hydrogen bond between the NH and CO groups of the Dpg residue, thereby forming a fully extended (C5) conformation at position 2. The ϕ and ψ values for Met and Phe residues are significantly lower than the values expected for an ideal antiparallel beta conformation causing a twist in the extended backbone both at the N and C termini. Nuclear magnetic resonance studies suggest the presence of a significant population of the peptide molecules in an extended antiparallel β conformation and the involvement of Dpg NH in a C5 intramolecular hydrogen bond in solutions of deuterated chloroform and deuterated dimethyl sulfoxide. IR studies provide evidence for the presence of an intramolecular hydrogen bond in the molecule and the antiparallel extended conformation in chloroform solution. CD spectra in methanol, trifluoroethanol, and trimethyl phosphate indicate that the Dpg peptide shows slight conformational flexibility, whereas the folded Ac6c analog is quite rigid. The extended Dpg peptide consistently shows the highest activity in human peripheral blood neutrophils, being approximately 8 and 16 times more active than the parent peptide and the folded Ac6c analog, respectively. However, the finding that all four peptides have ED50 (the molar concentration of peptide to induce half-maximal enzyme release) values in the 10(-8)-10(-9) M range suggests that an induced fit mechanism may indeed be important in this ligand-receptor interaction. Moreover, it is also possible that alterations in the backbone conformation at the tripeptide level may not significantly alter the side chain topography and/or the accessibility of key functional groups important for interaction with the receptor

Quantifying uncertainty in pest risk maps and assessments : adopting a risk-averse decision maker’s perspective

Pest risk maps are important decision support tools when devising strategies to minimize introductions of invasive organisms and mitigate their impacts. When possible management responses to an invader include costly or socially sensitive activities, decision-makers tend to follow a more certain (i.e., risk-averse) course of action. We presented a new mapping technique that assesses pest invasion risk from the perspective of a risk-averse decision maker. We demonstrated the method by evaluating the likelihood that an invasive forest pest will be transported to one of the U.S. states or Canadian provinces in infested firewood by visitors to U.S. federal campgrounds. We tested the impact of the risk aversion assumption using distributions of plausible pest arrival scenarios generated with a geographically explicit model developed from data documenting camper travel across the study area. Next, we prioritized regions of high and low pest arrival risk via application of two stochastic ordering techniques that employed, respectively, first- and second-degree stochastic dominance rules, the latter of which incorporated the notion of risk aversion. We then identified regions in the study area where the pest risk value changed considerably after incorporating risk aversion. While both methods identified similar areas of highest and lowest risk, they differed in how they demarcated moderate-risk areas. In general, the second-order stochastic dominance method assigned lower risk rankings to moderate-risk areas. Overall, this new method offers a better strategy to deal with the uncertainty typically associated with risk assessments and provides a tractable way to incorporate decisionmaking preferences into final risk estimates, and thus helps to better align these estimates with particular decision-making scenarios about a pest organism of concern. Incorporation of risk aversion also helps prioritize the set of locations to target for inspections and outreach activities, which can be costly. Our results are especially important and useful given the huge number of camping trips that occur each year in the United States and Canada

Quantifying uncertainty in pest risk maps and assessments : adopting a risk-averse decision maker’s perspective

Pest risk maps are important decision support tools when devising strategies to minimize introductions of invasive organisms and mitigate their impacts. When possible management responses to an invader include costly or socially sensitive activities, decision-makers tend to follow a more certain (i.e., risk-averse) course of action. We presented a new mapping technique that assesses pest invasion risk from the perspective of a risk-averse decision maker. We demonstrated the method by evaluating the likelihood that an invasive forest pest will be transported to one of the U.S. states or Canadian provinces in infested firewood by visitors to U.S. federal campgrounds. We tested the impact of the risk aversion assumption using distributions of plausible pest arrival scenarios generated with a geographically explicit model developed from data documenting camper travel across the study area. Next, we prioritized regions of high and low pest arrival risk via application of two stochastic ordering techniques that employed, respectively, first- and second-degree stochastic dominance rules, the latter of which incorporated the notion of risk aversion. We then identified regions in the study area where the pest risk value changed considerably after incorporating risk aversion. While both methods identified similar areas of highest and lowest risk, they differed in how they demarcated moderate-risk areas. In general, the second-order stochastic dominance method assigned lower risk rankings to moderate-risk areas. Overall, this new method offers a better strategy to deal with the uncertainty typically associated with risk assessments and provides a tractable way to incorporate decisionmaking preferences into final risk estimates, and thus helps to better align these estimates with particular decision-making scenarios about a pest organism of concern. Incorporation of risk aversion also helps prioritize the set of locations to target for inspections and outreach activities, which can be costly. Our results are especially important and useful given the huge number of camping trips that occur each year in the United States and Canada

Highly selective hydrogenation of furfural over supported Pt nanoparticles under mild conditions

The selective liquid phase hydrogenation of furfural to furfuryl alcohol over Pt nanoparticles supported on SiO₂, ZnO, γ-Al2O₃, CeO₂ is reported under extremely mild conditions. Ambient hydrogen pressure, and temperatures as low as 50 °C are shown sufficient to drive furfural hydrogenation with high conversion and >99% selectivity to furfuryl alcohol. Strong support and solvent dependencies are observed, with methanol and n-butanol proving excellent solvents for promoting high furfuryl alcohol yields over uniformly dispersed 4 nm Pt nanoparticles over MgO, CeO₂ and γ-Al₂O₃. In contrast, non-polar solvents conferred poor furfural conversion, while ethanol favored acetal by-product formation. Furfural selective hydrogenation can be tuned through controlling the oxide support, reaction solvent and temperature

Predictions of molecular chirality and helical twisting powers: A theoretical study

A theoretical study of a number of chiral molecules has been undertaken using a molecular Monte Carlo simulation approach coupled with calculations of molecular chirality based on a chirality order parameter. Results for a variety of TADDOL (alpha,alpha,alpha',alpha'-tetraaryl-1,3-dioxolan-4,5-dimethanol) derivatives show good agreement with experimental findings for the sign, magnitude, and the temperature dependence of the helical twisting power (HTP). For a photochromic chiral dopant with variable HTP we are able to model the reduction in the HTP when photoisomerization occurs. Our studies on a liquid crystalline material with a single chiral center have reproduced a temperature dependent twist inversion in the material. We discuss the temperature and solvent dependence of the helical twisting power and argue that in all the systems studied here, preferential selection of certain molecular conformations at different temperatures and in different solvents are able to explain the observed experimental behavior of the HTP

Monitoring Cen X-3 with BATSE

The eight uncollimated BATSE Large Area Detectors (LAD's) provide the ability to monitor pulsed hard x ray sources on a nearly continuous basis. Using data from the LAD's, the pulse timing and pulsed flux of the 4.8 second period binary x ray pulsar Centaurus X-3 was analyzed over a two month period. The methods and initial results of this analysis, which includes both data folded onboard GRO and 1.024 second resolution discriminator rates folded on the ground, are presented

Taxonomy, Paleobiogeography and Paleoecology of Jurassic Ethiopian Brachipods: A Progress Report

The area under study belongs to the Jurassic Ethiopian Province (western North Africa, Egypt, Israel, Jordan, Saudi Arabia, Ethiopia, Eritrea, Kenya, Madagascar and Kachchh). Work was begun in 1978 in northern Sinai with the discovery of the large, rare Callovian brachiopod Septirhynchia hirschi and subsequent sampling of 6,000 feet of sediment at Gebel Maghara and Gebel Engabashi. In the Negev, southern Israel, we described a brachiopod fauna from the Matmor Formation that was deposited on a low energy, peritidal, shallow marine shelf. During the latter part of the Jurassic we recognize a connection with the pelagic western Neotethys. Some brachiopod genera are common in northern Sinai (e.g. Sphriganaria, Ectyphoria, Sinaithyris) but are missing in the Negev (Hamakhtesh Hagadol). Daghanirhynchia is abundant in Jordan and Sinai but absent in the Negev. We are investigating the reasons for this anomalous distribution pattern as well as the reasons for the large degree of endemism in the province. Current work in progress includes a further study of brachiopod faunas of the southern Tethyan margin, specifically in the Negev, southern Israel, and Mt. Hermon, northern Israel, Gebel Maghara and Gebel Minshera, northern Sinai, and Wadi Zarqa, northwest Jordan. Upon completion of these projects we expect to correlate the Jurassic strata across the Dead Sea Rift from Israel to Jordan and complete a study of the paleocommunities in the region

Intrinsic and Rashba Spin-orbit Interactions in Graphene Sheets

Starting from a microscopic tight-binding model and using second order perturbation theory, we derive explicit expressions for the intrinsic and Rashba spin-orbit interaction induced gaps in the Dirac-like low-energy band structure of an isolated graphene sheet. The Rashba interaction parameter is first order in the atomic carbon spin-orbit coupling strength $\xi$ and first order in the external electric field $E$ perpendicular to the graphene plane, whereas the intrinsic spin-orbit interaction which survives at E=0 is second order in $\xi$. The spin-orbit terms in the low-energy effective Hamiltonian have the form proposed recently by Kane and Mele. \textit{Ab initio} electronic structure calculations were performed as a partial check on the validity of the tight-binding model.Comment: 5 pages, 2 figures; typos corrected, references update

Solving Einstein's Equations With Dual Coordinate Frames

A method is introduced for solving Einstein's equations using two distinct coordinate systems. The coordinate basis vectors associated with one system are used to project out components of the metric and other fields, in analogy with the way fields are projected onto an orthonormal tetrad basis. These field components are then determined as functions of a second independent coordinate system. The transformation to the second coordinate system can be thought of as a mapping from the original ``inertial'' coordinate system to the computational domain. This dual-coordinate method is used to perform stable numerical evolutions of a black-hole spacetime using the generalized harmonic form of Einstein's equations in coordinates that rotate with respect to the inertial frame at infinity; such evolutions are found to be generically unstable using a single rotating coordinate frame. The dual-coordinate method is also used here to evolve binary black-hole spacetimes for several orbits. The great flexibility of this method allows comoving coordinates to be adjusted with a feedback control system that keeps the excision boundaries of the holes within their respective apparent horizons.Comment: Updated to agree with published versio