New reactions and reactive intermediates in the pyrolysis of cyclic phosphonium ylides

The authors are grateful to EPSRC and Glaxo-Wellcome (now GSK) for their support of this work through a CASE Studentship to TM.Pyrolysis, either neat or in diphenyl ether solution, results in the conversion of both 4-triphenylphosphoranylidenetetrahydrofuran-2,3,5-trione and 4-triphenylphosphoranylidenetetrahydrothio-phene-2,3,5-trione into 3,5-bis(triphenylphosphoranylidene)cyclopentane-1,2,4-trione. These reactions involve extrusion of CO2 or COS to give 3-triphenylphosphoranylidenecyclopropane-1,2-dione which further loses CO to give triphenylphosphoranylideneketene. The precise way in which these two reactive phosphorus compounds combine to give the observed product has been examined by chemical and isotopic labelling studies. Cyclotrimerization of triphenylphosphoranylideneketene upon thermolysis in diphenyl ether has also been observed for the first time. The erroneous literature interpretation of the 13C NMR spectrum for triphenylphosphoranylideneketene is corrected.Publisher PDFPeer reviewe

Geographic transmission hubs of the 2009 influenza pandemic in the United States

A key issue in infectious disease epidemiology is to identify and predict geographic sites of epidemic establishment that contribute to onward spread, especially in the context of invasion waves of emerging pathogens. Conventional wisdom suggests that these sites are likely to be in densely-populated, well-connected areas. For pandemic influenza, however, epidemiological data have not been available at a fine enough geographic resolution to test this assumption. Here, we make use of fine-scale influenza-like illness incidence data derived from electronic medical claims records gathered from 834 3-digit ZIP (postal) codes across the US to identify the key geographic establishment sites, or “hubs”, of the autumn wave of the 2009 A/H1N1pdm influenza pandemic in the United States. A mechanistic spatial transmission model is fit to epidemic onset times inferred from the data. Hubs are identified by tracing the most probable transmission routes back to a likely first establishment site. Four hubs are identified: two in the southeastern US, one in the central valley of California, and one in the midwestern US. According to the model, 75% of the 834 observed ZIP-level outbreaks in the US were seeded by these four hubs or their epidemiological descendants. Counter-intuitively, the pandemic hubs do not coincide with large and well-connected cities, indicating that factors beyond population density and travel volume are necessary to explain the establishment sites of the major autumn wave of the pandemic. Geographic regions are identified where infection can be statistically traced back to a hub, providing a testable prediction of the outbreak's phylogeography. Our method therefore provides an important way forward to reconcile spatial diffusion patterns inferred from epidemiological surveillance data and pathogen sequence data. Keywords: Pandemic influenza, Transmission hubs, Metapopulation, Gravity model, Phylogeograph

Quantification of uncertainties in the parameters of a long-term energy model

Even if the form of an energy-economy model's equations can be assumed to specify correctly our technological processes and the relevant behaviors of our society over the necessary time range, there is uncertainty in model results induced by our imperfect knowledge of the numerical values of the model's parameters and input data. Some of this uncertainty is typically covered by provision of alternative scenarios with assumptions but, up to now, modelers have rarely dealt in detail with the inherent uncertainty of input data. However, when model output or response can be represented by a first-order Taylor expansion in the input data about the nominal solution point, knowledge of the variance-covariance (uncertainty) matrix of the input data is sufficient to determine the uncertainty in the computed response induced by the input uncertainties. Some guidelines are given for the evaluation of the required input-uncertainty matrices. Illustrative examples are given from the authors' beginning efforts to develop an uncertainty matrix for the important parameters of the Long-term Energy Analysis Package used within the Energy Information Administration of the Department of Energy

Partial least square regression applied to the QTLMAS 2010 dataset

Detection of genomic regions affecting traits is a goal in many genetic studies. Studies applying distinct methods for detection of these regions, called quantitative trait loci (QTL), have been described, ranging from single marker regression [1] to methods that enable to fit several markers simultaneously [2,3]. Simultaneously fitting all markers leads to more accurate detection of QTL compared to independent fitting of single markers in a regression model when there is linkage disequilibrium (LD) between the genomic regions that affect the trait but comes at the cost of increased computational requirements [2]. Partial least square regression (PLSR) is one method for simultaneously fitting multiple markers and was applied by Bjornstad et al. for detection of QTL [3]. An interesting characteristic of PLSR its straightforward application of to simultaneous analysis of data of multiple traits [3]. The objectives of this study were to use PLSR to search for QTL and to estimate breeding values in the dataset of the QTLMAS 2010 worksho

Effects of Noise on Ecological Invasion Processes: Bacteriophage-mediated Competition in Bacteria

Pathogen-mediated competition, through which an invasive species carrying and transmitting a pathogen can be a superior competitor to a more vulnerable resident species, is one of the principle driving forces influencing biodiversity in nature. Using an experimental system of bacteriophage-mediated competition in bacterial populations and a deterministic model, we have shown in [Joo et al 2005] that the competitive advantage conferred by the phage depends only on the relative phage pathology and is independent of the initial phage concentration and other phage and host parameters such as the infection-causing contact rate, the spontaneous and infection-induced lysis rates, and the phage burst size. Here we investigate the effects of stochastic fluctuations on bacterial invasion facilitated by bacteriophage, and examine the validity of the deterministic approach. We use both numerical and analytical methods of stochastic processes to identify the source of noise and assess its magnitude. We show that the conclusions obtained from the deterministic model are robust against stochastic fluctuations, yet deviations become prominently large when the phage are more pathological to the invading bacterial strain.Comment: 39 pages, 7 figure

Spatial Transmission of 2009 Pandemic Influenza in the US

The 2009 H1N1 influenza pandemic provides a unique opportunity for detailed examination of the spatial dynamics of an emerging pathogen. In the US, the pandemic was characterized by substantial geographical heterogeneity: the 2009 spring wave was limited mainly to northeastern cities while the larger fall wave affected the whole country. Here we use finely resolved spatial and temporal influenza disease data based on electronic medical claims to explore the spread of the fall pandemic wave across 271 US cities and associated suburban areas. We document a clear spatial pattern in the timing of onset of the fall wave, starting in southeastern cities and spreading outwards over a period of three months. We use mechanistic models to tease apart the external factors associated with the timing of the fall wave arrival: differential seeding events linked to demographic factors, school opening dates, absolute humidity, prior immunity from the spring wave, spatial diffusion, and their interactions. Although the onset of the fall wave was correlated with school openings as previously reported, models including spatial spread alone resulted in better fit. The best model had a combination of the two. Absolute humidity or prior exposure during the spring wave did not improve the fit and population size only played a weak role. In conclusion, the protracted spread of pandemic influenza in fall 2009 in the US was dominated by short-distance spatial spread partially catalysed by school openings rather than long-distance transmission events. This is in contrast to the rapid hierarchical transmission patterns previously described for seasonal influenza. The findings underline the critical role that school-age children play in facilitating the geographic spread of pandemic influenza and highlight the need for further information on the movement and mixing patterns of this age group

Succinate in dystrophic white matter: A proton magnetic resonance spectroscopy finding characteristic for complex II deficiency

A deficiency of succinate dehydrogenase is a rare cause of mitochondrial encephalomyopathy. Three patients, 2 sisters and I boy from an unrelated family, presented with symptoms and magnetic resonance imaging signs of leukoencephalopathy. Localized proton magnetic resonance spectroscopy indicated a prominent singlet at 2.40ppm in cerebral and cerebellar white matter not present in gray matter or basal ganglia. The signal was also elevated in cerebrospinal fluid and could be identified as originating from the two equivalent methylene groups of succinate. Subsequently, an isolated deficiency of complex II (succinate:ubiquinone oxidoreductase) was demonstrated in 2 patients in muscle and fibroblasts. One of the sisters died at the age of 18 months. Postmortem examination showed the neuropathological characteristics of Leigh syndrome. Her younger sister, now 12 months old, is also severely affected; the boy, now 6 years old, follows a Milder, fluctuating clinical course. Magnetic resonance spectroscopy provides a characteristic pattern in succinate dehydrogenase deficiency

Hanford Site National Environmental Policy Act (NEPA) characterization. Revision 8

This eighth revision of the Hanford Site National Environmental Policy Act (NEPA) Characterization presents current environmental data regarding the Hanford Site and its immediate environs. This information is intended for use in preparing Chapters 4 and 6 in Hanford Site-related NEPA documents. Chapter 4 (Affected Environment) includes information on climate and meteorology, geology, hydrology, ecology, historical, archaeological and cultural resources, socioeconomics, and noise. Chapter 6 (Statutory and Regulatory Requirements) provides the preparer with the federal and state regulations, DOE directives and permits, and environmental standards directly applicable to the NEPA documents on the Hanford Site. The following sections were updated in this revision: climate and meteorology; ecology (threatened and endangered species section only); historical; archaeological and cultural resources; and all of chapter 6. No conclusions or recommendations are given in this report. Rather, it is a compilation of information on the Hanford Site environment that can be used directly by Site contractors. This information can also be used by any interested individual seeking baseline data on the hanford Site and its past activities by which to evaluate projected activities and their impacts

Present Day Kinematics of the Eastern California Shear Zone from a Geodetically Constrained Block Model

We use Global Positioning System (GPS) data from 1993–2000 to determine horizontal velocities of 65 stations in eastern California and western Nevada between 35° and 37° N. We relate the geodetic velocities to fault slip rates using a block model that enforces path integral constraints over geologic and geodetic time scales and that includes the effects of elastic strain accumulation on faults locked to a depth of 15 km. The velocity of the Sierra Nevada block with respect to Nevada is 11.1±0.3 mm/yr, with slip partitioned across the Death Valley, (2.8±0.5 mm/yr), Panamint Valley (2.5±0.8 mm/yr), and Airport Lake/Owens Valley (5.3±0.7/4.6±0.5 mm/yr) faults. The western Mojave block rotates at 2.1±0.8°/My clockwise, with 3.7±0.7 mm/yr of left lateral motion across the western Garlock Fault. We infer 11±2 mm/yr of right lateral motion across the Mojave region of the Eastern California Shear Zone