An efficient new route to dihydropyranobenzimidazole inhibitors of HCV replication.

A class of dihydropyranobenzimidazole inhibitors was recently discovered that acts against the hepatitis C virus (HCV) in a new way, binding to the IRES-IIa subdomain of the highly conserved 5' untranslated region of the viral RNA and thus preventing the ribosome from initiating translation. However, the reported synthesis of these compounds is lengthy and low-yielding, the intermediates are troublesome to purify, and the route is poorly structured for the creation of libraries. We report a streamlined route to this class of inhibitors in which yields are far higher and most intermediates are crystalline. In addition, a key variable side chain is introduced late in the synthesis, allowing analogs to be easily synthesized for optimization of antiviral activity

Statistical Modeling of Epistasis and Linkage Decay using Logic Regression

Logic regression has been recognized as a tool that can identify and model non-additive genetic interactions using Boolean logic groups. Logic regression, TASSEL-GLM and SAS-GLM were compared for analytical precision using a previously characterized model system to identify the best genetic model explaining epistatic interaction of vernalization-sensitivity in barley. A genetic model containing two molecular markers identified in vernalization response in barley was selected using logic regression while both TASSEL-GLM and SAS-GLM included spurious associations in their models. The results also suggest the logic regression can be used to identify dominant/recessive relationships between epistatic alleles through its use of conjugate
operators

Investigation of hop downy mildew through association mapping and observations of the oospore

Hop downy mildew is a devastating disease affecting hop requiring expensive fungicide applications throughout the growing season. Plant resistance is highly desirable and theorized as being decidedly quantitative with dominance and epistasis involved in resistance. An association mapping approach using a mixed-model was used to identify AFLP markers associated with the hop downy mildew resistant phenotype. New protocols for the extraction, isolation and recovery of oospores from plant tissue and soil were developed to aid in the study of the hop downy mildew oospore. In addition, logic regression was used in a mathematical model in order to test the statistical procedure’s potential for modeling epistasis. Our results suggest the hop downy mildew resistant phenotype has a broad-sense heritability of 76% with an estimated narrow-sense heritability of 49%. Mixed-model results revealed 9% of the AFLP markers to be associated with the hop downy mildew resistant phenotype. The association mapping results suggest resistance to hop downy mildew is quantitatively inherited with moderate heritability, which can be successfully investigated using mixed-models. The concentration of soil-borne oospores was 14 oospores/g soil. Germination of oospores occurred between two and eight weeks after preparation of the slides. Observations of the oospore suggested the sexual stage of this disease may play a role in over-wintering as oospores were capable of in vitro germination. In addition, MTT as a stain for downy mildew spore viability comes into question due to the possibility of a chemical reduction in the presence of NADH. Logic regression correctly identified the model which best describes the epistatic interaction of VRN-H1 and VRN-H2 and the model was synonymous with the hypothesized genetic model for vernalization in barley. The mathematical simulation using logic regression software suggested Boolean logic may be more robust when compared to general linear modeling for the identification and modeling of epistasis

Hadamard States and Adiabatic Vacua

Reversing a slight detrimental effect of the mailer related to TeXabilityComment: 10pages, LaTeX (RevTeX-preprint style

Ecotypic differences in the phenology of the tundra species Eriophorum vaginatum reflect sites of origin

Eriophorum vaginatum is a tussock-forming sedge that contributes significantly to the structure and primary productivity of moist acidic tussock tundra. Locally adapted populations (ecotypes) have been identified across the geographical distribution of E. vaginatum; however, little is known about how their growth and phenology differ over the course of a growing season. The growing season is short in the Arctic and therefore exerts a strong selection pressure on tundra species. This raises the hypothesis that the phenology of arctic species may be poorly adapted if the timing and length of the growing season change. Mature E. vaginatum tussocks from across a latitudinal gradient (65–70°N) were transplanted into a common garden at a central location (Toolik Lake, 68°38′N, 149°36′W) where half were warmed using open-top chambers. Over two growing seasons (2015 and 2016), leaf length was measured weekly to track growth rates, timing of senescence, and biomass accumulation. Growth rates were similar across ecotypes and between years and were not affected by warming. However, southern populations accumulated significantly more biomass, largely because they started to senesce later. In 2016, peak biomass and senescence of most populations occurred later than in 2015, probably induced by colder weather at the beginning of the growing season in 2016, which caused a delayed start to growth. The finish was delayed as well. Differences in phenology between populations were largely retained between years, suggesting that the amount of time that these ecotypes grow has been selected by the length of the growing seasons at their respective home sites. As potential growing seasons lengthen, E. vaginatum may be unable to respond appropriately as a result of genetic control and may have reduced fitness in the rapidly warming Arctic tundra

Fate and transport of volatile organic compounds in glacial till and groundwater at an industrial site in Northern Ireland

Volatile organic compound (VOC) contamination of subsurface geological material and groundwater was discovered on the Nortel Monkstown industrial site, Belfast, Northern Ireland. The objectives of this study were to (1) investigate the characteristics of the geological material and its influences on contaminated groundwater flow across the site using borehole logs and hydrological evaluations, and (2) identify the contaminants and examine their distribution in the subsurface geological material and groundwater using chemical analysis. This report focuses on the eastern car park (ECP) which was a former storage area associated with trichloroethene (TCE) degreasing operations. This is where the greatest amount of volatile organic compounds (VOCs), particularly TCE, were detected. The study site is on a complex deposit of clayey glacial till with discontinuous coarser grained lenses, mainly silts, sands and gravel, which occur at 0.45-7.82 m below ground level (bgl). The lenses overall form an elongated formation that acts as a small unconfined shallow aquifer. There is a continuous low permeable stiff clayey till layer beneath the lenses that performs as an aquitard to the groundwater. Highest concentrations of VOCs, mainly TCE, in the geological material and groundwater are in these coarser lenses at similar to 4.5-7 m bgl. Highest TCE measurements at 390,000 mu g L-1 for groundwater and at 39,000 mu g kg(-1) at 5.7 m for geological material were in borehole GA19 in the coarse lens zone. It is assumed that TCE gained entrance to the subsurface near this borehole where the clayey till was thin to absent above coarse lenses which provided little retardation to the vertical migration of this dense non-aqueous phase liquid (DNAPL) into the groundwater. However, TCE is present in low concentrations in the geological material overlying the coarse lens zone. Additionally, VOCs appear to be associated with poorly drained layers and in peat < 3.0 m bgl in the ECP. Some indication of natural attenuation as VOCs degradation products vinyl chloride (VC) and dichloromethane (DCM) also occur on the site

Magnetic fields in cluster cores: Faraday rotation in A400 and A2634

We present Faraday rotation data for radio sources in the centers of the Abell clusters A400 and A2634. These clusters contain large (> 100 kpc), tailed radio sources, each attached to the central cD galaxy. These clusters do not have strong cooling cores. Our data extend previous work on rotation measure in cluster centers to larger scales and non-cooling clusters. The rotation measure, and thus the magnetic field, is ordered on scales 10-20 kpc in both clusters. The geometry of the rotation measure appears to be determined by the distribution of the X-ray emitting gas, rather than by the radio tails themselves. We combine our data with previously published X-ray and radio data in order to analyze the magnetic fields in all 12 clusters whose central radio sources have been imaged in rotation measure. We find that the fields are dynamically significant in most clusters. We argue that the Faraday data measure fields in the intracluster medium, rather than in a skin of the radio source. Finally, we consider the nature and maintenance of the magnetic fields in these clusters, and conclude that either the cluster-wide field exists at similar levels, or that a weaker cluster-wide field is amplified by effects in the core.Comment: Accepted for ApJ. 43 pages including 10 embedded figures. Higher resolution versions of the figures available at http://www.aoc.nrao.edu/~jeilek/pubs/Eilekpub.htm

Near-Infrared Mapping and Physical Properties of the Dwarf-Planet Ceres

We study the physical characteristics (shape, dimensions, spin axis direction, albedo maps, mineralogy) of the dwarf-planet Ceres based on high-angular resolution near-infrared observations. We analyze adaptive optics J/H/K imaging observations of Ceres performed at Keck II Observatory in September 2002 with an equivalent spatial resolution of ~50 km. The spectral behavior of the main geological features present on Ceres is compared with laboratory samples. Ceres' shape can be described by an oblate spheroid (a = b = 479.7 +/- 2.3 km, c = 444.4 +/- 2.1 km) with EQJ2000.0 spin vector coordinates RA = 288 +/- 5 deg. and DEC = +66 +/- 5 deg. Ceres sidereal period is measured to be 9.0741 +/- 0.0001 h. We image surface features with diameters in the 50-180 km range and an albedo contrast of ~6% with respect to the average Ceres albedo. The spectral behavior of the brightest regions on Ceres is consistent with phyllosilicates and carbonate compounds. Darker isolated regions could be related to the presence of frost.Comment: 11 pages, 8 Postscript figures, Accepted for publication in A&