Analyzing Machupo virus-receptor binding by molecular dynamics simulations

In many biological applications, we would like to be able to computationally predict mutational effects on affinity in protein-protein interactions. However, many commonly used methods to predict these effects perform poorly in important test cases. In particular, the effects of multiple mutations, non-alanine substitutions, and flexible loops are difficult to predict with available tools and protocols. We present here an existing method applied in a novel way to a new test case; we interrogate affinity differences resulting from mutations in a host-virus protein-protein interface. We use steered molecular dynamics (SMD) to computationally pull the machupo virus (MACV) spike glycoprotein (GP1) away from the human transferrin receptor (hTfR1). We then approximate affinity using the maximum applied force of separation and the area under the force-versus-distance curve. We find, even without the rigor and planning required for free energy calculations, that these quantities can provide novel biophysical insight into the GP1/hTfR1 interaction. First, with no prior knowledge of the system we can differentiate among wild type and mutant complexes. Moreover, we show that this simple SMD scheme correlates well with relative free energy differences computed via free energy perturbation. Second, although the static co-crystal structure shows two large hydrogen-bonding networks in the GP1/hTfR1 interface, our simulations indicate that one of them may not be important for tight binding. Third, one viral site known to be critical for infection may mark an important evolutionary suppressor site for infection-resistant hTfR1 mutants. Finally, our approach provides a framework to compare the effects of multiple mutations, individually and jointly, on protein-protein interactions.Comment: 33 pages, 8 figures, 5 table

American Oystercatcher productivity monitoring, breeding survey and banding in Virginia: 2004 report

Biologists along the east coast of the United States have recently expressed concern about the conservation status of the American Oystercatcher (Haematopus palliatus). The species has a relatively small population size and depends on coastal habitat that is under pressure from humans for development and recreation. Several studies of American Oystercatcher productivity have suggested that the species is inherently intolerant to human disturbance and experiences low productivity rates in areas where their breeding habitat is also used for human recreation. As a beach-nesting bird, their nesting attempts are also very vulnerable to destruction by mammalian and avian predators, which have been known to experience population increases because of human influenced factors. The undeveloped barrier islands and marshes of Virginia’s Eastern Shore support over 500 pairs of breeding American Oystercatchers and provide a unique opportunity to study their productivity in the relative absence of disturbance from direct human activity. Some of the islands are, however, inhabited by high numbers of common raccoons (Procyon lotor). The Nature Conservancy’s Virginia Coast Reserve (TNC), in cooperation with The Center for Conservation Biology at The College of William and Mary (CCB) and other partners, currently supports several efforts aimed at investigating the population status and breeding and wintering ecology of the species. These efforts include annual studies of oystercatcher productivity on the barrier islands and in the lagoon system, annual surveys of breeding and wintering populations and a banding program for oystercatcher adults and chicks. The primary objective of productivity monitoring has been to compare productivity in habitats managed for mammalian predators and those that are not in order to assess the effectiveness of the predator removal as a management strategy for increasing the reproductive success of beach nesting shorebirds and waterbirds. The annual breeding and wintering surveys provide consistent and precise counts of oystercatchers along the Virginia coast so that managers can track changes in population numbers and distribution. Finally, the banding program will increase the number of color-banded birds in the population so that researchers may examine questions concerning migration and dispersal, survival rates and habitat use. One hundred and fifty-three pairs of American Oystercatchers were monitored for productivity during the 2004 breeding season. Eighty-one nested on Metompkin Island, which is managed by TNC for mammalian predators. Twenty-five nested on Wreck Island Natural Area Preserve, which is not managed for mammalian predators but did not have any predator activity during the 2004 breeding season. Fortyseven nested in the marshes of the lagoon system located adjacent to Wachapreague, Virginia. American Oystercatchers experienced high productivity on Metompkin Island and Wreck Island (0.79-1.18 young fledged per pair) for the third and second consecutive years, respectively. These productivity levels continue to be well above what is typically recorded for this species in other parts of its range, and our results suggest that the absence of mammalian predators on these islands allows for the higher productivity of pairs nesting there. American Oystercatchers breeding in the marshes off of Wachapreague also experienced high productivity in 2004 – 0.85 young fledged per pair. Productivity of oystercatchers in this habitat is very vulnerable to flooding events and appears to be highly variable from year to year depending on the timing of egg-laying, spring tide events, storms and storm influenced tide events. A total of 706 adult American Oystercatchers (327 pairs and 52 single adults) were recorded during the 2004 Piping Plover, Wilson’s Plover and American Oystercatcher survey, a 26.1% increase from 2000 when oystercatchers were first systematically surveyed along the coast of Virginia. Breeding pairs were documented on every barrier island along the Eastern Shore of Virginia except for Walllops Island. Only seven pairs were documented west and south of the Chesapeake Bay. Sixty-two American Oystercatcher chicks and two adults were banded during the 2004 breeding season. At least fifty-seven of the chicks fledged. We will continue to work with other states to further develop Virginia’s banding program, upon which researchers, managers and students can build in the future

Re-entrant ferroelectricity in liquid crystals

The ferroelectric (Sm C$^*$) -- antiferroelectric (Sm C$^*_A$) -- reentrant ferroelectric (re Sm C$^*$) phase temperature sequence was observed for system with competing synclinic - anticlinic interactions. The basic properties of this system are as follows (1) the Sm C$^*$ phase is metastable in temperature range of the Sm C$^*_A$ stability (2) the double inversions of the helix handedness at Sm C$^*$ -- Sm C$^*_A$ and Sm C$^*_A$% -- re-Sm C$^*$ phase transitions were found (3) the threshold electric field that is necessary to induce synclinic ordering in the Sm C$^*_A$ phase decreases near both Sm C$^*_A$ -- Sm C$^*$ and Sm C$^*_A$ -- re-Sm C$^*$ phase boundaries, and it has maximum in the middle of the Sm C$^*_A$ stability region. All these properties are properly described by simple Landau model that accounts for nearest neighboring layer steric interactions and quadrupolar ordering only.Comment: 10 pages, 5 figures, submitted to PR

Effects of Neutron Irradiation on Carbon Doped MgB2 Wire Segments

We have studied the evolution of superconducting and normal state properties of neutron irradiated Mg(B$_{.962}$C$_{.038}$)$_2$ wire segments as a function of post exposure annealing time and temperature. The initial fluence fully suppressed superconductivity and resulted in an anisotropic expansion of the unit cell. Superconductivity was restored by post-exposure annealing. The upper critical field, H$_{c2}$(T=0), approximately scales with T$_c$ starting with an undamaged T$_c$ near 37 K and H$_{c2}$(T=0) near 32 T. Up to an annealing temperature of 400 $^ o$C the recovery of T$_c$ tends to coincide with a decrease in the normal state resistivity and a systematic recovery of the lattice parameters. Above 400 $^ o$C a decrease in order along the c- direction coincides with an increase in resistivity, but no apparent change in the evolution of T$_c$ and H$_{c2}$. To first order, it appears that carbon doping and neutron damaging effect the superconducting properties of MgB$_2$ independently

Adaptive Dispersion Compensation for Remote Fiber Delivery of NIR Femtosecond Pulses

We report on remote delivery of 25 pJ broadband near-infrared femtosecond light pulses from a Ti:sapphire laser through 150 meters of single-mode optical fiber. Pulse distortion due to dispersion is overcome with pre-compensation using adaptive pulse shaping techniques, while nonlinearities are mitigated using an SF10 rod for the final stage of pulse compression. Near transform limited pulse duration of 130 fs is measured after the final compression.Comment: 3 pages, 4 figure

Robustness and epistasis in mutation-selection models

We investigate the fitness advantage associated with the robustness of a phenotype against deleterious mutations using deterministic mutation-selection models of quasispecies type equipped with a mesa shaped fitness landscape. We obtain analytic results for the robustness effect which become exact in the limit of infinite sequence length. Thereby, we are able to clarify a seeming contradiction between recent rigorous work and an earlier heuristic treatment based on a mapping to a Schr\"odinger equation. We exploit the quantum mechanical analogy to calculate a correction term for finite sequence lengths and verify our analytic results by numerical studies. In addition, we investigate the occurrence of an error threshold for a general class of epistatic landscape and show that diminishing epistasis is a necessary but not sufficient condition for error threshold behavior.Comment: 20 pages, 14 figure

Status and distribution of colonial waterbirds in coastal Virginia: 2018 breeding season

Colonial waterbirds are highly visible components of coastal avifaunas that share the unusual characteristic of nesting in dense assemblages. One consequence of having large portions of populations nesting in few locations is that even restricted disturbance may have profound consequences on a population level. Development of conservation strategies for these sensitive species requires current status and distribution information. In the fall of 1992, a consortium of agencies and individuals agreed that a comprehensive monitoring program for the Virginia colonial waterbird community was needed and that assessments should be made on regular (initially every 10 years but reduced to 5 years in 2003) intervals for trend analyses. Systematic surveys have been conducted during the breeding seasons of 1993, 2003, 2008 and 2013. The 2018 survey reported here is the fifth in the time series. These surveys have covered colonial waterbird populations (24 species – Great Blue Herons were not included in 2008 and 2018 due to budgetary constraints) throughout the Coastal Plain province of Virginia. We surveyed 270 waterbird colonies during the breeding season of 2018. Colonies supported an estimated 43,159 breeding pairs of 23 species. Gulls were the most abundant group with more than 19,700 breeding pairs. Terns and waders accounted for 7,129 and 6,386 pairs respectively. Although they have declined dramatically, Laughing Gulls continue to be the most abundant species and were three times more abundant than any other species, accounting for nearly 40% of the total waterbird community. The barrier island/lagoon system of the Eastern Shore was the most important region for the majority of colonial species encountered. In 2018, this region supported 22 of the 23 species evaluated. The Eastern Shore accounted for 50.5% and 46.6% of all breeding pairs and colonies respectively. For 17 of the 23 species, the region supported more than 50% of the known coastal population. The colonial waterbird community as a whole in coastal Virginia has declined dramatically since 1993 (2018 survey did not include Great Blue Herons or all Great Egrets). Population estimates for 15 (68%) of the 22 species assessed declined between 1993 and 2018. Declines varied considerably between species with 14 species declining more than 40% and 9 species declining more than 60%. Cattle Egrets showed the highest loss rate (-96.7%), declining from an estimated 1,459 to only 48 pairs. Little Blue Herons declined by 83% from 374 to only 64 pairs. Seven species increased between 1993 and 2018. Dramatic expansions were documented for White Ibis, Double-crested Cormorant, and Brown Pelican. Over the past 25 years, two major forces appear to be shaping the colonial waterbird community in Virginia. These include 1) regional shifts in population centers that are driving population increases in Virginia and 2) habitat degradation related to sea-level rise. With the exception of Great Egrets, all species that have increased over the past 20 years have experienced ongoing range expansions and are riding a population wave that is progressing through Virginia. This includes Great Black-backed Gull, Double-crested Cormorant, Brown Pelican, and White Ibis. Most of the decline in medium-sized waders is being driven by habitat loss related to erosion of islands. This erosion results from sea-level rise, is ongoing and represents a significant threat to these populations. Several ground-nesting seabirds are likely more directly impacted by the loss of viable habitat and demographic impacts related to frequent flooding. The most notable example is the Laughing Gull that has experienced a catastrophic decline in both population and distribution

Potential Energy Surface for H_2 Dissociation over Pd(100)

The potential energy surface (PES) of dissociative adsorption of H_2 on Pd(100) is investigated using density functional theory and the full-potential linear augmented plane wave (FP-LAPW) method. Several dissociation pathways are identified which have a vanishing energy barrier. A pronounced dependence of the potential energy on ``cartwheel'' rotations of the molecular axis is found. The calculated PES shows no indication of the presence of a precursor state in front of the surface. Both results indicate that steering effects determine the observed decrease of the sticking coefficient at low energies of the H_2 molecules. We show that the topology of the PES is related to the dependence of the covalent H(s)-Pd(d) interactions on the orientation of the H_2 molecule.Comment: RevTeX, 8 pages, 5 figures in uufiles forma

Searching for O2_2 in the SMC:Constraints on Oxygen Chemistry at Low Metallicities

We present a 39 h integration with the Odin satellite on the ground-state 118.75 GHz line of O2 towards the region of strongest molecular emission in the Small Magellanic Cloud. Our 3sigma upper limit to the O2 integrated intensity of <0.049 K km/s in a 9'(160 pc) diameter beam corresponds to an upper limit on the O2/H2 abundance ratio of <1.3E-6. Although a factor of 20 above the best limit on the O2 abundance obtained for a Galactic source, our result has interesting implications for understanding oxygen chemistry at sub-solar metal abundances. We compare our abundance limit to a variety of astrochemical models and find that, at low metallicities, the low O2 abundance is most likely produced by the effects of photo-dissociation on molecular cloud structure. Freeze-out of molecules onto dust grains may also be consistent with the observed abundance limit, although such models have not yet been run at sub-solar initial metallicities.Comment: 4 pages, accepted to A&A Letter

Local Isoelectronic Reactivity of Solid Surfaces

The quantity w^N(r) = ( 1/ k^2 T_el)[partial n(r, T_el) / partial T_el]_(v(r),N) is introduced as a convenient measure of the local isoelectronic reactivity of surfaces. It characterizes the local polarizability of the surface and it can be calculated easily. The quantity w^N(r) supplements the charge transfer reactivity measured e.g. by the local softness to which it is closely related. We demonstrate the applicability and virtues of the function w^N(r) for the example of hydrogen dissociation and adsorption on Pd(100).Comment: RevTeX, 13 pages, 3 figures, to appear in Phys. Rev. Let