Recent Developments in the Use of Flow Hydrogenation in the Field of Medicinal Chemistry

This chapter focuses on recent applications of flow hydrogenation in medicinal chemistry. Flow reactors can enhance laboratory safety, reducing the risks associated with pyrophoric catalysts, due to their containment in catalyst cartridges or omnifit columns. Flow hydrogenation reduces the risks arising from hydrogen gas, with either hydrogen generated in situ from water, or precise management of the gas flow rate through tube-in-tube reactors. There is an increasing body of evidence that flow hydrogenation enhances reduction outcomes across nitro, imine, nitrile, amide, azide, and azo reductions, together with de-aromatisation and hydrodehalogenation. In addition, olefin, alkyne, carbonyl, and benzyl reductions have been widely examined. Further, protocols involving multistage flow reactions involving hydrogenation are highlighted

Deriving Multiple Benefits from Carbon Market-Based Savanna Fire Management: An Australian Example

Carbon markets afford potentially useful opportunities for supporting socially and environmentally sustainable land management programs but, to date, have been little applied in globally significant fire-prone savanna settings. While fire is intrinsic to regulating the composition, structure and dynamics of savanna systems, in north Australian savannas frequent and extensive late dry season wildfires incur significant environmental, production and social impacts. Here we assess the potential of market-based savanna burning greenhouse gas emissions abatement and allied carbon biosequestration projects to deliver compatible environmental and broader socio-economic benefits in a highly biodiverse north Australian setting.Drawing on extensive regional ecological knowledge of fire regime effects on fire-vulnerable taxa and communities, we compare three fire regime metrics (seasonal fire frequency, proportion of long-unburnt vegetation, fire patch-size distribution) over a 15-year period for three national parks with an indigenously (Aboriginal) owned and managed market-based emissions abatement enterprise. Our assessment indicates improved fire management outcomes under the emissions abatement program, and mostly little change or declining outcomes on the parks. We attribute improved outcomes and putative biodiversity benefits under the abatement program to enhanced strategic management made possible by the market-based mitigation arrangement.For these same sites we estimate quanta of carbon credits that could be delivered under realistic enhanced fire management practice, using currently available and developing accredited Australian savanna burning accounting methods. We conclude that, in appropriate situations, market-based savanna burning activities can provide transformative climate change mitigation, ecosystem health, and community benefits in northern Australia, and, despite significant challenges, potentially in other fire-prone savanna settings

Papilio hermione Linnaeus, type species of Hipparchia Fabricius (Lepidoptera, Satyrinae): restoring stability to the application of these names

This paper discusses three problems concerning the Woodland Grayling, Hipparchia fagi Scopoli, 1763, with respect to the identity and application of the junior name Papilio hermione Linnaeus, 1764. In 1977, the late Otakar Kudrna designated a specimen of the Rock Grayling, Hipparchia alcyone [Denis & Schiffermüller], 1775, to become the lectotype of Papilio hermione – as a result of which hermione supplanted alcyone as the senior epithet for this species. Because P. hermione is the nominal type species of Hipparchia Fabricius, 1807, Kudrna’s action rendered this a genus based on a misidentified species. Third, while a majority of lepidopterists have ignored Kudrna’s action and continue to apply the name H. alcyone to the Rock Grayling, and still regard P. hermione as a junior subjective synonym of H. fagi, the formal nomenclature for the Rock Grayling has become unstable because a large minority have nonetheless accepted Kudrna’s lectotype designation and all that follows from it. It is demonstrated here that no syntypes of Papilio hermione (or Papilio fagi) have survived; consequently, Kudrna’s lectotype designation for P. hermione is invalid. By designation of a single specimen of the Woodland Grayling as neotype for both P. fagi and P. hermione, the two names are rendered objectively synonymous, thereby restoring stability to the species name for the Rock Grayling (as Hipparchia alcyone), and to the application of Papilio hermione (= Hipparchia fagi) as nominal type species of the generic name Hipparchia

A system for exposing molecules and cells to biologically relevant and accurately controlled steady-state concentrations of nitric oxide and oxygen

Nitric oxide (NO) plays key roles in cell signaling and physiology, with diverse functions mediated by NO concentrations varying over three orders-of-magnitude. In spite of this critical concentration dependence, current approaches to NO delivery in vitro result in biologically irrelevant and poorly controlled levels, with hyperoxic conditions imposed by ambient air. To solve these problems, we developed a system for controlled delivery of NO and O[subscript 2] over large concentration ranges to mimic biological conditions. Here we describe the fabrication, operation and calibration of the delivery system. We then describe applications for delivery of NO and O[subscript 2] into cell culture media, with a comparison of experimental results and predictions from mass transfer models that predict the steady-state levels of various NO-derived reactive species. We also determined that components of culture media do not affect the steady-state levels of NO or O[subscript 2] in the device. This system provides critical control of NO delivery for in vitro models of NO biology and chemistry.National Cancer Institute (U.S.) (CA026731)National Cancer Institute (U.S.) (CA116318)National Institute of Environmental Health Sciences (ES002109

Assessing the potential of autonomous submarine gliders for ecosystem monitoring across multiple trophic levels (plankton to cetaceans) and pollutants in shallow shelf seas

A combination of scientific, economic, technological and policy drivers is behind a recent upsurge in the use of marine autonomous systems (and accompanying miniaturized sensors) for environmental mapping and monitoring. Increased spatial–temporal resolution and coverage of data, at reduced cost, is particularly vital for effective spatial management of highly dynamic and heterogeneous shelf environments. This proof-of-concept study involves integration of a novel combination of sensors onto buoyancy-driven submarine gliders, in order to assess their suitability for ecosystem monitoring in shelf waters at a variety of trophic levels. Two shallow-water Slocum gliders were equipped with CTD and fluorometer to measure physical properties and chlorophyll, respectively. One glider was also equipped with a single-frequency echosounder to collect information on zooplankton and fish distribution. The other glider carried a Passive Acoustic Monitoring system to detect and record cetacean vocalizations, and a passive sampler to detect chemical contaminants in the water column. The two gliders were deployed together off southwest UK in autumn 2013, and targeted a known tidal-mixing front west of the Isles of Scilly. The gliders’ mission took about 40 days, with each glider travelling distances of >1000 km and undertaking >2500 dives to depths of up to 100 m. Controlling glider flight and alignment of the two glider trajectories proved to be particularly challenging due to strong tidal flows. However, the gliders continued to collect data in poor weather when an accompanying research vessel was unable to operate. In addition, all glider sensors generated useful data, with particularly interesting initial results relating to subsurface chlorophyll maxima and numerous fish/cetacean detections within the water column. The broader implications of this study for marine ecosystem monitoring with submarine gliders are discussed

Independent evaluation of a simple clinical prediction rule to identify right ventricular dysfunction in patients with shortness of breath

BACKGROUND: Many patients have unexplained persistent dyspnea after negative computed tomographic pulmonary angiography (CTPA). We hypothesized that many of these patients have isolated right ventricular (RV) dysfunction from treatable causes. We previously derived a clinical decision rule (CDR) for predicting RV dysfunction consisting of persistent dyspnea and normal CTPA, finding that 53% of CDR-positive patients had isolated RV dysfunction. Our goal is to validate this previously derived CDR by measuring the prevalence of RV dysfunction and outcomes in dyspneic emergency department patients. METHODS: A secondary analysis of a prospective observational multicenter study that enrolled patients presenting with suspected PE was performed. We included patients with persistent dyspnea, a nonsignificant CTPA, and formal echo performed. Right ventricular dysfunction was defined as RV hypokinesis and/or dilation with or without moderate to severe tricuspid regurgitation. RESULTS: A total of 7940 patients were enrolled. Two thousand six hundred sixteen patients were analyzed after excluding patients without persistent dyspnea and those with a significant finding on CTPA. One hundred ninety eight patients had echocardiography performed as standard care. Of those, 19% (95% confidence interval [CI], 14%-25%) and 33% (95% CI, 25%-42%) exhibited RV dysfunction and isolated RV dysfunction, respectively. Patients with isolated RV dysfunction or overload were more likely than those without RV dysfunction to have a return visit to the emergency department within 45 days for the same complaint (39% vs 18%; 95% CI of the difference, 4%-38%). CONCLUSION: This simple clinical prediction rule predicted a 33% prevalence of isolated RV dysfunction or overload. Patients with isolated RV dysfunction had higher recidivism rates and a trend toward worse outcomes

Dengue and climate change in Australia: predictions for the future should incorporate knowledge from the past

•Dengue transmission in Australia is currently restricted to Queensland, where the vector mosquito Aedes aegypti is established. Locally acquired infections have been reported only from urban areas in the north-east of the state, where the vector is most abundant. •Considerable attention has been drawn to the potential impact of climate change on dengue distribution within Australia, with projections for substantial rises in incidence and distribution associated with increasing temperatures. •However, historical data show that much of Australia has previously sustained both the vector mosquito and dengue viruses. Although current vector distribution is restricted to Queensland, the area inhabited by A. aegypti is larger than the disease-transmission areas, and is not restricted by temperature (or vector-control programs); thus, it is unlikely that rising temperatures alone will bring increased vector or virus distribution. •Factors likely to be important to dengue and vector distribution in the future include increased dengue activity in Asian and Pacific nations that would raise rates of virus importation by travellers, importation of vectors via international ports to regions without A. aegypti, higher rates of domestic collection and storage of water that would provide habitat in urban areas, and growing human populations in northern Australia. •Past and recent successful control initiatives in Australia lend support to the idea that well resourced and functioning surveillance programs, and effective public health intervention capabilities, are essential to counter threats from dengue and other mosquito-borne diseases. •Models projecting future activity of dengue (or other vector-borne disease) with climate change should carefully consider the local historical and contemporary data on the ecology and distribution of the vector and local virus transmission

Viral factors in influenza pandemic risk assessment

The threat of an influenza A virus pandemic stems from continual virus spillovers from reservoir species, a tiny fraction of which spark sustained transmission in humans. To date, no pandemic emergence of a new influenza strain has been preceded by detection of a closely related precursor in an animal or human. Nonetheless, influenza surveillance efforts are expanding, prompting a need for tools to assess the pandemic risk posed by a detected virus. The goal would be to use genetic sequence and/or biological assays of viral traits to identify those non-human influenza viruses with the greatest risk of evolving into pandemic threats, and/or to understand drivers of such evolution, to prioritize pandemic prevention or response measures. We describe such efforts, identify progress and ongoing challenges, and discuss three specific traits of influenza viruses (hemagglutinin receptor binding specificity, hemagglutinin pH of activation, and polymerase complex efficiency) that contribute to pandemic risk

Expression of miRNAs in ovine fetal gonads: potential role in gonadal differentiation

<p>Abstract</p> <p>Background</p> <p>Gonadal differentiation in the mammalian fetus involves a complex dose-dependent genetic network. Initiation and progression of fetal ovarian and testicular pathways are accompanied by dynamic expression patterns of thousands of genes. We postulate these expression patterns are regulated by small non-coding RNAs called microRNAs (miRNAs). The aim of this study was to identify the expression of miRNAs in mammalian fetal gonads using sheep as a model.</p> <p>Methods</p> <p>We determined the expression of 128 miRNAs by real time PCR in early-gestational (gestational day (GD) 42) and mid-gestational (GD75) sheep ovaries and testes. Expression data were further examined and validated by bioinformatic analysis.</p> <p>Results</p> <p>Expression analysis revealed significant differences between ovaries and testes among 24 miRNAs at GD42, and 43 miRNAs at GD75. Bioinformatic analysis revealed that a number of differentially expressed miRNAs are predicted to target genes known to be important in mammalian gonadal development, including <it>ESR1, CYP19A1</it>, and <it>SOX9</it>. In situ hybridization revealed <it>miR-22 </it>localization within fetal testicular cords. As estrogen signaling is important in human and sheep ovarian development, these data indicate that miR-22 is involved in repressing estrogen signaling within fetal testes.</p> <p>Conclusions</p> <p>Based on our results we postulate that gene expression networks underlying fetal gonadal development are regulated by miRNAs.</p