Houses Far from Home: British Colonial Space in the New Hebrides.

Houses Far from Home: British Colonial Space in the New Hebrides. Margaret Critchlow Rodman. Honolulu: University of Hawai'i Press, 2001. 247 pp.     

Synthesis and Biological Activity of 4-Amino-1-(β-D-ribofuranosyl)imidazo[4,5-d]pyridazin-7-one

Abstract

The Lewis acid catalyzed ribosylation of 5(4)-cyano-4(5)-(5-methyl-1,2,4-oxadiazol-3-yl)-1H-imidazole (2) with 1-O-acetyl-2,3,5-tri-O-benzoyl-B-D-ribose gave only 4-(5-methyl-1,2,4-oxadiazol-3-yl)-1-(2,3,5-tri-O-benzoy 1-B-D-ribofuranosyl)imidazole-5-carbonitrile (3). Treatment of 3 with methanolic ammonia gave 4-(5-methyl-1,2,4-oxadiazol-3-yl)-1-(6-D-ribofuranosyl)imidazole-5-carbonitrile (4). Treatment of 4 with hydrogen peroxide in ammonia gave -(5-methyl-1,2,4-oxadiazol-3-yl)-1-(B-D-ribofuranosyl)imidazole-5-carboxamide (5). When 5 was treated with sodium hydride in dimthyl-sulfoxide a rearrangement (mononuclear heterocyclic rearrangement, m.h.r.) occurred to give a modest 17% yield of 4-acetamido-1-(B-D ribofuranosyl)imidazo[4,5-d]pyridazin-7-one (6). Treatment of 6 with aqueous ammonia gave4-amino-l-(B-D-ribofuranosyl)imidazo[4,5-d]pyridazin-7-one (1). The synthesis of compound 1 using the m.h.r. for the preparation of a single regioisomer of the imidazo[4,5-d]pyridazin-7-one ring system, has demonstrated the potential of this methodology. Neither compound 5 nor 6 affected the growth or replication of human foreskin fibroblasts (HFF cells) or human cytomegalovirus (HCMV). In contrast, compound 1 inhibited the replication of HCMV (IC₅₀=29 μM) but produced visual cytotoxicity in uninfected HFF cells (IC₅₀=70μM). Compound 1 also inhibited the proliferation of L1210 murine leukemic cells (IC₅₀=25μM), whereas the precursors 4 and 6 did not.     

Maintenance of genetic variation and panmixia in the commercially exploited western rock lobster (Panulirus cygnus)

Marine species with high fecundities and mortalities in the early life stages can have low effective population sizes, making them vulnerable to declines in genetic diversity when they are commercially harvested. Here, we compare levels of microsatellite and mitochondrial sequence variation in the western rock lobster (Panulirus cygnus) over a 14-year period to test whether genetic variation is being maintained. Panulirus cygnus is a strong candidate for loss of genetic variation because it is a highly fecund species that is likely to experience high variance in reproductive success due to an extended larval planktonic stage. It also supports one of the largest and most economically important fisheries in Australia, with landings of between 8,000 and 14,500 tons (~70 % of the total legal-sized biomass) being harvested in some years. We found remarkably high levels of genetic variation in all samples and no evidence of a decline in genetic diversity over the time interval we studied. Furthermore, there was no evidence of a recent genetic bottleneck, and effective population size estimates based on single sample and temporal methods were infinitely large. Analysis of molecular variance indicated no significant population structure along 960 km of coastline or genetic differentiation among temporal samples. Our results support the view that P. cygnus is a single, panmictic population, and suggest genetic drift is not strong enough to reduce neutral genetic diversity in this species if current management practices and breeding stock sizes are maintained.     

Highly‐Tunable Nickel Cobalt Oxide as a Low‐Temperature P‐Type Contact in Organic Photovoltaic Devices

We report on the investigation of nickel cobalt oxide (Ni_xCo_3?xO₄) thin films grown by pulsed laser deposition as hole‐transport interlayers (HTL) in organic photovoltaic (OPV) devices. Films of 7 nm thickness were grown under various oxygen deposition pressures (pO₂) in the range of 2–200 mTorr. We explore both bulk and surface properties of these thin films. The workfunction (?) for each of the films was statistically similar (～4.7 eV), regardless of pO₂. There was not a strong dependence of the power conversion efficiency (η) on the conductivities of the HTLs varying between 0.009 ‐ 10 S/cm. The observed differences in OPV efficiencies (ranging from 1.16 to 2.46%) were correlated to the near surface chemical composition of the Ni_xCo_3?xO₄ HTL, as observed by differences in the relative surface hydroxyl concentration. The critical role of the near‐surface composition of the HTL at the HTL/organic interface was further explored by modifying the hydroxyl concentration using an oxygen plasma treatment. This treatment mitigated the impact of surface hydroxyl coverage, demonstrating either identical or increased values for ? and η, regardless of initial pO₂ in the creation of the Ni_xCo_3?xO₄ HTL. To further explore this we also employed a phosphonic acid surface modification agent on the HTL, increasing ? to 5.2 eV producing the best η value of 3.4%, equivalent to the PEDOT:PSS control devices. These results indicate that nickel cobalt oxide is a promising p‐type oxide for carrier‐selective interlayers in organic solar cells; however, for this to be fully realized the specific surface chemistry at the oxide/polymer interface must be controlled to increase ? and optimize device performance.     

GAS6 Receptor Status Is Associated with Dormancy and Bone Metastatic Tumor Formation

Disseminated tumor cells (DTCs) are believed to lie dormant in the marrow before they can be activated to form metastases. How DTCs become dormant in the marrow and how dormant DTCs escape dormancy remains unclear. Recent work has shown that prostate cancer (PCa) cell lines express the growth-arrest specific 6 (GAS6) receptors Axl, Tyro3, and Mer, and become growth arrested in response to GAS6. We therefore hypothesized that GAS6 signaling regulates the proliferative activity of DTCs in the marrow. To explore this possibility, in vivo studies were performed where it was observed that when Tyro3 expression levels exceed Axl expression, the PCa cells exhibit rapid growth. When when Axl levels predominate, PCa cells remain largely quiescent. These findings suggest that a balance between the expression of Axl and Tyro3 is associated with a molecular switch between a dormant and a proliferative phenotype in PCa metastases.     

A paradigm shift towards low-nitrifying production systems: the role of biological nitrification inhibition (BNI)

Background

Agriculture is the single largest geo-engineering initiative that humans have initiated on planet Earth, largely through the introduction of unprecedented amounts of reactive nitrogen (N) into ecosystems. A major portion of this reactive N applied as fertilizer leaks into the environment in massive amounts, with cascading negative effects on ecosystem health and function. Natural ecosystems utilize many of the multiple pathways in the N cycle to regulate N flow. In contrast, the massive amounts of N currently applied to agricultural systems cycle primarily through the nitrification pathway, a single inefficient route that channels much of this reactive N into the environment. This is largely due to the rapid nitrifying soil environment of present-day agricultural systems.

Scope

In this Viewpoint paper, the importance of regulating nitrification as a strategy to minimize N leakage and to improve N-use efficiency (NUE) in agricultural systems is highlighted. The ability to suppress soil nitrification by the release of nitrification inhibitors from plant roots is termed ‘biological nitrification inhibition’ (BNI), an active plant-mediated natural function that can limit the amount of N cycling via the nitrification pathway. The development of a bioassay using luminescent Nitrosomonas to quantify nitrification inhibitory activity from roots has facilitated the characterization of BNI function. Release of BNIs from roots is a tightly regulated physiological process, with extensive genetic variability found in selected crops and pasture grasses. Here, the current status of understanding of the BNI function is reviewed using Brachiaria forage grasses, wheat and sorghum to illustrate how BNI function can be utilized for achieving low-nitrifying agricultural systems. A fundamental shift towards ammonium (NH₄⁺)-dominated agricultural systems could be achieved by using crops and pastures with high BNI capacities. When viewed from an agricultural and environmental perspective, the BNI function in plants could potentially have a large influence on biogeochemical cycling and closure of the N loop in crop–livestock systems.     

Improving the monitoring of crop productivity using spaceborne solar‐induced fluorescence

Large‐scale monitoring of crop growth and yield has important value for forecasting food production and prices and ensuring regional food security. A newly emerging satellite retrieval, solar‐induced fluorescence (SIF) of chlorophyll, provides for the first time a direct measurement related to plant photosynthetic activity (i.e. electron transport rate). Here, we provide a framework to link SIF retrievals and crop yield, accounting for stoichiometry, photosynthetic pathways, and respiration losses. We apply this framework to estimate United States crop productivity for 2007–2012, where we use the spaceborne SIF retrievals from the Global Ozone Monitoring Experiment‐2 satellite, benchmarked with county‐level crop yield statistics, and compare it with various traditional crop monitoring approaches. We find that a SIF‐based approach accounting for photosynthetic pathways (i.e. C₃ and C₄ crops) provides the best measure of crop productivity among these approaches, despite the fact that SIF sensors are not yet optimized for terrestrial applications. We further show that SIF provides the ability to infer the impacts of environmental stresses on autotrophic respiration and carbon‐use‐efficiency, with a substantial sensitivity of both to high temperatures. These results indicate new opportunities for improved mechanistic understanding of crop yield responses to climate variability and change.     

METHYL-BIS (BETA-CHLOROETHYL) AMINE IN LARGE DOSES IN THE TREATMENT OF NEOPLASTIC DISEASES

Sixty-seven patients with neoplastic diseases were treated with 151 courses of methylbis (beta-chloroethyl)amine hydrochloride (HN₂). Seventy-seven of the courses consisted of single injections of 0.2 to 0.4 mg. per kilogram of body weight, and 35 courses were given as single injections of 0.6 mg. per kilogram of body weight.Twenty-three patients with Hodgkin''s disease were treated. Remissions averaged approximately three months in 13 patients who were in good or fair general physical condition, and 1.5 months in 11 patients who were in poor or moribund condition; one of the 11 did not respond to the therapy.Fifteen patients with lymphosarcoma were treated. Remissions averaged between one and two months in four patients who were in good or fair general physical condition. Of the remaining 11 patients, two showed no response, and the longest remission among the remaining nine was approximately 40 days.Satisfactory remissions of one to three months were obtained in four patients with mycosis fungoides treated with single courses of 0.3 mg. per kilogram of body weight.Serious toxic reactions were observed in six patients, four of whom died. In five of the six instances the reactions consisted of pancytopenia and hemorrhagic diathesis. All these patients were in poor general or hematologic status before therapy.In general, large single doses of HN₂ were neither more nor less effective than the four-to six-day course usually employed with this agent. Combination of the administration of HN₂ with artificial hyperpyrexia, or with concurrent courses of pteroylglutamic conjugates, did not enhance the therapeutic effects of the agent.