Evidence for Strain-Induced Local Conductance Modulations in Single-Layer Graphene on SiO_2

Graphene has emerged as an electronic material that is promising for device applications and for studying two-dimensional electron gases with relativistic dispersion near two Dirac points. Nonetheless, deviations from Dirac-like spectroscopy have been widely reported with varying interpretations. Here we show evidence for strain-induced spatial modulations in the local conductance of single-layer graphene on SiO_2 substrates from scanning tunneling microscopic (STM) studies. We find that strained graphene exhibits parabolic, U-shaped conductance vs bias voltage spectra rather than the V-shaped spectra expected for Dirac fermions, whereas V-shaped spectra are recovered in regions of relaxed graphene. Strain maps derived from the STM studies further reveal direct correlation with the local tunneling conductance. These results are attributed to a strain-induced frequency increase in the out-of-plane phonon mode that mediates the low-energy inelastic charge tunneling into graphene

Scanning Tunnelling Spectroscopic Studies of Dirac Fermions in Graphene and Topological Insulators

We report novel properties derived from scanning tunnelling spectroscopic (STS) studies of Dirac fermions in graphene and the surface state (SS) of a strong topological insulator (STI), Bi_2Se_3. For mono-layer graphene grown on Cu by chemical vapour deposition (CVD), strain-induced scalar and gauge potentials are manifested by the charging effects and the tunnelling conductance peaks at quantized energies, respectively. Additionally, spontaneous time-reversal symmetry breaking is evidenced by the alternating anti-localization and localization spectra associated with the zero-mode of two sublattices while global time-reversal symmetry is preserved under the presence of pseudo-magnetic fields. For Bi_2Se_3 epitaxial films grown on Si(111) by molecular beam epitaxy (MBE), spatially localized unitary impurity resonances with sensitive dependence on the energy difference between the Fermi level and the Dirac point are observed for samples thicker than 6 quintuple layers (QL). These findings are characteristic of the SS of a STI and are direct manifestation of strong topological protection against impurities. For samples thinner than 6-QL, STS studies reveal the openup of an energy gap in the SS due to overlaps of wave functions between the surface and interface layers. Additionally, spin-preserving quasiparticle interference wave-vectors are observed, which are consistent with the Rashba-like spin-orbit splitting

Economic Implications of Farmer Storage of Surface Water in Federal Projects: Elephant Butte Irrigahon District, Dona Ana and Sierra Counties, New Mexico

This study estimated the expected regional impact and economic feasibility of a proposed water accumulation or water saving option for agricultural producers operating in the Elephant Butte Irrigation District in southern New Mexico. The water accumulation plan would allow agricultural producers to retain part of a given year's surface water allocation in Elephant Butte Reservoir, providing use of the unevaporated portion in a later year. The analysis was based upon modeling of current cropping practices subject to regional resource constraints within a static linear programming model. Pertinent input/output coefficients and costs were incorporated, with five-year (1976-1980) average output prices assumed for twelve crops spread across 11 soil groups. Applicable fixed costs and interest charges were taken into account. Net returns to the region were maximized assuming 1 and 3 acre-feet of groundwater available per year per acre irrigated. Surface water availability was varied from zero to 3 acre-feet per acre to obtain schedules depicting regional net returns and cropping patterns for varying surface water allocations for both the groundwater situations examined. These schedules were then used to build temporal linear programming models which maximized the present value of net returns for the period 1963 to 1980 subject to historical surface water allocations and reservoir evaporation rates. Calculation of these evaporation rates took into consideration increased lake levels due to surface water storage. The temporal models were used to estimate an optimal allocation of surface water over the 18 year period investigated for the two groundwater availability situations considered. Returns for the optimal surface water allocations were then upper bounds on potential net returns to the region. Projected streams of net returns were also obtained for each of the scenarios analyzed; i.e., optimal temporal allocation of surface water, 2 acre feet of surface water per year limit and actual allocation of surface water given the 1 and 3 foot groundwater limitations. These streams of net returns were valued in 1980 dollars allowing comparison among the alternative scenarios. Differences between the various returns streams for each groundwater situation provided a measure of possible economic effects of the water saving program. Results of the study for current groundwater availability conditions indicate that optimally temporal allocated surface water use would increase average annualized net returns per acre from that of the actual surface water allocation by .82 dollars per year, or less than .2 %. Use of the more realistic two acre-foot per acre limit on surface water use led to an increase in annualized net returns of only .23 dollars per acre per year. Both increases were deemed insufficient to cover anticipated administrative costs of the program. Under conditions of limited groundwater availability (1 acre-foot per acre), percentage increases in annualized net returns over those for the actual surface water allocation were more significant. Use of the water saving option and perfect knowledge of future surface water allocations resulted in increased annualized net returns of $8.41 per acre per year for an increase of 54 z. For the two acre-foot surface water use limitation case, annualized net returns increased by$3.68 per acre per year (23.7 %). In all cases considered, groundwater use increased with use of the water saving option. These economic results, coupled with possible political obstacles faced by the program, suggested that alternative water management schemes should be considered

Pricing and Conservation of Irrigation Water in Texas and New Mexico

Two possible policy alternatives for management of limited water supplies in arid portions of Texas and New Mexico were analyzed for economic feasibility. Detailed studies of the potential impact of a water accumulation policy for each of two irrigation districts (El Paso County Water Improvement District No. 1 in Texas, and the Elephant Butte Irrigation District in New Mexico) were undertaken using temporal linear programming techniques. Current cropping practices, soils, groundwater conditions, historical surface water allocations for Elephant Butte Reservoir and evaporation rates were incorporated within the analysis. Estimates of the benefits of accumulation of surplus portions of irrigation district member's annual surface water allocations, with subsequent use of the unevaporated portion in later years, were deemed insufficient to cover anticipated administrative costs of implementing the proposed policy. This suggests current allocations approximate a temporal optimum. Sensitivity analyses showed greater potential benefits, however, if current groundwater conditions worsen. Additional analysis of possible price-induced water conservation for the areas within the two states currently mining groundwater from the exhaustible Ogallala aquifer was also undertaken. The High Plains of Texas served as the representative region of study, with results assumed to be analogous for the portions of Eastern New Mexico relying on the Ogallala. Both static and temporal effects of a per unit tax on water pumpage and net returns were examined using a recursive linear programming model. Results indicated that imposition of a $20 per acre-foot tax on water pumped induced very little change in water use over a 40 year period, while reducing the present value of producer net returns from 9% to 27% depending upon initial groundwater conditions and the irrigation technology in use. These results imply that a price induced water conservation policy for the Ogallala is not economically justified

HSD3B1 genotype identifies glucocorticoid responsiveness in severe asthma

Asthma resistance to glucocorticoid treatment is a major health problem with unclear etiology. Glucocorticoids inhibit adrenal androgen production. However, androgens have potential benefits in asthma. HSD3B1 encodes for 3β-hydroxysteroid dehydrogenase-1 (3β-HSD1), which catalyzes peripheral conversion from adrenal dehydroepiandrosterone (DHEA) to potent androgens and has a germline missense-encoding polymorphism. The adrenal restrictive HSD3B1(1245A) allele limits conversion, whereas the adrenal permissive HSD3B1(1245C) allele increases DHEA metabolism to potent androgens. In the Severe Asthma Research Program (SARP) III cohort, we determined the association between DHEA-sulfate and percentage predicted forced expiratory volume in 1 s (FEV1PP). HSD3B1(1245) genotypes were assessed, and association between adrenal restrictive and adrenal permissive alleles and FEV1PP in patients with (GC) and without (noGC) daily oral glucocorticoid treatment was determined (n = 318). Validation was performed in a second cohort (SARP I&II; n = 184). DHEA-sulfate is associated with FEV1PP and is suppressed with GC treatment. GC patients homozygous for the adrenal restrictive genotype have lower FEV1PP compared with noGC patients (54.3% vs. 75.1%; P < 0.001). In patients with the homozygous adrenal permissive genotype, there was no FEV1PP difference in GC vs. noGC patients (73.4% vs. 78.9%; P = 0.39). Results were independently confirmed: FEV1PP for homozygous adrenal restrictive genotype in GC vs. noGC is 49.8 vs. 63.4 (P < 0.001), and for homozygous adrenal permissive genotype, it is 66.7 vs. 67.7 (P = 0.92). The adrenal restrictive HSD3B1(1245) genotype is associated with GC resistance. This effect appears to be driven by GC suppression of 3β-HSD1 substrate. Our results suggest opportunities for prediction of GC resistance and pharmacologic intervention

The driver landscape of sporadic chordoma.

Chordoma is a malignant, often incurable bone tumour showing notochordal differentiation. Here, we defined the somatic driver landscape of 104 cases of sporadic chordoma. We reveal somatic duplications of the notochordal transcription factor brachyury (T) in up to 27% of cases. These variants recapitulate the rearrangement architecture of the pathogenic germline duplications of T that underlie familial chordoma. In addition, we find potentially clinically actionable PI3K signalling mutations in 16% of cases. Intriguingly, one of the most frequently altered genes, mutated exclusively by inactivating mutation, was LYST (10%), which may represent a novel cancer gene in chordoma.Chordoma is a rare often incurable malignant bone tumour. Here, the authors investigate driver mutations of sporadic chordoma in 104 cases, revealing duplications in notochordal transcription factor brachyury (T), PI3K signalling mutations, and mutations in LYST, a potential novel cancer gene in chordoma

Recurrent mutation of IGF signalling genes and distinct patterns of genomic rearrangement in osteosarcoma

Osteosarcoma is a primary malignancy of bone that affects children and adults. Here, we present the largest sequencing study of osteosarcoma to date, comprising 112 childhood and adult tumours encompassing all major histological subtypes. A key finding of our study is the identification of mutations in insulin-like growth factor (IGF) signalling genes in 8/112 (7%) of cases. We validate this observation using fluorescence in situ hybridization (FISH) in an additional 87 osteosarcomas, with IGF1 receptor (IGF1R) amplification observed in 14% of tumours. These findings may inform patient selection in future trials of IGF1R inhibitors in osteosarcoma. Analysing patterns of mutation, we identify distinct rearrangement profiles including a process characterized by chromothripsis and amplification. This process operates recurrently at discrete genomic regions and generates driver mutations. It may represent an age-independent mutational mechanism that contributes to the development of osteosarcoma in children and adults alike

An Evolutionary Reduction Principle for Mutation Rates at Multiple Loci

A model of mutation rate evolution for multiple loci under arbitrary selection is analyzed. Results are obtained using techniques from Karlin (1982) that overcome the weak selection constraints needed for tractability in prior studies of multilocus event models. A multivariate form of the reduction principle is found: reduction results at individual loci combine topologically to produce a surface of mutation rate alterations that are neutral for a new modifier allele. New mutation rates survive if and only if they fall below this surface - a generalization of the hyperplane found by Zhivotovsky et al. (1994) for a multilocus recombination modifier. Increases in mutation rates at some loci may evolve if compensated for by decreases at other loci. The strength of selection on the modifier scales in proportion to the number of germline cell divisions, and increases with the number of loci affected. Loci that do not make a difference to marginal fitnesses at equilibrium are not subject to the reduction principle, and under fine tuning of mutation rates would be expected to have higher mutation rates than loci in mutation-selection balance. Other results include the nonexistence of 'viability analogous, Hardy-Weinberg' modifier polymorphisms under multiplicative mutation, and the sufficiency of average transmission rates to encapsulate the effect of modifier polymorphisms on the transmission of loci under selection. A conjecture is offered regarding situations, like recombination in the presence of mutation, that exhibit departures from the reduction principle. Constraints for tractability are: tight linkage of all loci, initial fixation at the modifier locus, and mutation distributions comprising transition probabilities of reversible Markov chains.Comment: v3: Final corrections. v2: Revised title, reworked and expanded introductory and discussion sections, added corollaries, new results on modifier polymorphisms, minor corrections. 49 pages, 64 reference