Synthetic Routes to a Fused-Ring Sydnoquinazoline

In this research, 5-methylsydno-[3,4-a]quinazoline was synthesized via multiple methodologies, the best of which yielded the target compound in 50 % overall yield for the six steps. Synthesis of this compound in reasonable yields and exploration of its chemical behavior is of particular interest as a putative NO-prodrug. As an initial approach to the synthesis and accumulation of the compound of interest, attempts were made to optimize the existing synthetic pathway to its precursors. The starting material, 3-(2-acetylphenyl)sydnone, was prepared in 3 steps from commercially available starting material in good yields. This sydnone compound was then converted to the versatile intermediate, 3-(2-acetylphenyl)sydnone oxime. This conversion was accomplished by two distinct means, one of which was a novel microwave-assisted synthesis. Following its synthesis, 3-(2-acetylphenyl)sydnone oxime was converted to several reactive intermediates (O-acetate, O-tosylate, O-mesylate) in order to evaluate their utility with regards to cyclization to the aforementioned sydnoquinazoline. With respect to cyclization, 3-(2-acetylphenyl)sydnone oxime was treated with trifluoroacetic acid, which resulted in the target sydnoquinazoline in low yields. The reactive intermediates were also treated under thermal conditions, with the O-tosylate and O-mesylate species resulting in the target fused-ring sydnone in very low yields. These more reactive sydnones were exposed also to lithiation conditions to explore the possibility of base-induced cyclization to the desired sydnoquinazoline. Under these conditions, the O-tosylate and O-mesylate were treated with lithium diisopropyl amide. The O-tosylate resulted in the formation of the target quinazoline in moderate yields, while the O-mesylate resulted in formation of the target compound in good yields. Indeed, by adjustment in the amount of base employed, an up to 80% yield of the desired fused-ring sydnone could be realized; a considerable improvement over the methods previously employed

Synthetic Routes to a Fused-Ring Sydnoquinazoline

In this research, 5-methylsydno-[3,4-a]quinazoline was synthesized via multiple methodologies, the best of which yielded the target compound in 50 % overall yield for the six steps. Synthesis of this compound in reasonable yields and exploration of its chemical behavior is of particular interest as a putative NO-prodrug. As an initial approach to the synthesis and accumulation of the compound of interest, attempts were made to optimize the existing synthetic pathway to its precursors. The starting material, 3-(2-acetylphenyl)sydnone, was prepared in 3 steps from commercially available starting material in good yields. This sydnone compound was then converted to the versatile intermediate, 3-(2-acetylphenyl)sydnone oxime. This conversion was accomplished by two distinct means, one of which was a novel microwave-assisted synthesis. Following its synthesis, 3-(2-acetylphenyl)sydnone oxime was converted to several reactive intermediates (O-acetate, O-tosylate, O-mesylate) in order to evaluate their utility with regards to cyclization to the aforementioned sydnoquinazoline. With respect to cyclization, 3-(2-acetylphenyl)sydnone oxime was treated with trifluoroacetic acid, which resulted in the target sydnoquinazoline in low yields. The reactive intermediates were also treated under thermal conditions, with the O-tosylate and O-mesylate species resulting in the target fused-ring sydnone in very low yields. These more reactive sydnones were exposed also to lithiation conditions to explore the possibility of base-induced cyclization to the desired sydnoquinazoline. Under these conditions, the O-tosylate and O-mesylate were treated with lithium diisopropyl amide. The O-tosylate resulted in the formation of the target quinazoline in moderate yields, while the O-mesylate resulted in formation of the target compound in good yields. Indeed, by adjustment in the amount of base employed, an up to 80% yield of the desired fused-ring sydnone could be realized; a considerable improvement over the methods previously employed

New Radiocarbon-Dated Vertebrate Fossils from Herschel Island: Implications for the Palaeoenvironments and Glacial Chronology of the Beaufort Sea Coastlands

Palaeontological research on Herschel Island, Yukon, has yielded a diverse collection of Quaternary marine and terrestrial vertebrate fossils. The terrestrial faunal remains, which have largely been collected as allochthonous beach debris at Pauline Cove, are dominated by Yukon horse (Equus sp.), with fewer specimens of steppe bison (Bison priscus), proboscideans (Mammuthus primigenius and a single Mammut americanum specimen), and other large and medium-sized mammals. This pattern of a horse-dominated Late Pleistocene fauna is consistent with those from the North Slope of Alaska and further demonstrates that conditions in northernmost Beringia were more arid than those in interior areas such as Fairbanks or the Klondike. This paper presents new AMS radiocarbon dates on terrestrial vertebrate fossils and peat from the island that span the range from greater than 53 000 to modern 14C yr BP. When considered with other data from the region, our new radiocarbon-dated fauna cannot adequately resolve whether the Herschel Island ice-thrust ridge was formed during the Early Wisconsinan or the Late Wisconsinan advance of the Laurentide Ice Sheet over the Yukon Coastal Plain.Des fouilles paléontologiques réalisées sur l’île Herschel, au Yukon, ont permis de prélever une collection variée de fossiles marins et de fossiles vertébrés terrestres du quaternaire. Les restes de faune terrestre, qui ont surtout été ramassés sous la forme de débris de plage allochtones à Pauline Cove, prennent la forme de restes de chevaux du Yukon en prédominance (Equus sp.), parsemés de quelques spécimens de bisons priscus (Bison priscus), de proboscidiens (Mammuthus primigenius et d’un seul spécimen de Mammut americanum), ainsi que d’autres mammifères de taille moyenne et de grande taille. La prédominance de faune du type cheval du Pléistocène tardif correspond à celle enregistrée sur le versant nord de l’Alaska et montre encore une fois que les conditions qui régnaient dans la partie la plus au nord de la Béringie étaient plus arides que les conditions qui prévalaient dans les régions de l’intérieur, comme à Fairbanks ou au Klondike. Dans ce document, nous présentons de nouvelles dates établies par le radiocarbone SMAquant aux fossiles de vertébrés terrestres et à la tourbe de l’île, dates allant de plus de 53 000 14C années BP à l’ère moderne. Lorsque ces données sont considérées à la lumière d’autres données de la région, la nouvelle faune datée par le radiocarbone ne nous permet pas de déterminer adéquatement si la dorsale découlant de la poussée des glaces de l’île Herschel a été formée pendant la progression du Wisconsinien précoce ou du Wisconsinien tardif de la nappe glaciaire laurentienne sur la plaine côtière du Yukon

Critical variables of solder paste stencil printing for micro-BGA and fine-pitch QFP

Stencil printing continues to be the dominant method of solder deposition in high-volume surface-mount assembly. Control of the amount of solder paste deposited is critical in the case of fine-pitch and ultrafine-pitch surface-mount assembly. The process is still not well understood as indicated by the fact that industry reports 52-71% surface-mount technology (SMT) defects are related to the solder paste stencil printing process. The purpose of this paper is to identify the critical variables that influence the volume, area, and height of solder paste deposited. An experiment was conducted to investigate the effects of relevant process parameters on the amount of solder paste deposited for ball grid arrays (BGAs) and quad flat packages (QFPs) of five different pitches ranging from 0.76 mm (30 mil) to 0.3 mm (12 mil). The effects of aperture size, aperture shape, board finish, stencil thickness, solder type, and print speed were examined. The deposited solder paste was measured by an inline fully automatic laser-based three-dimensional (3-D) triangulation solder paste inspection system. Analysis of variance (ANOVA) shows that aperture size and stencil thickness are the two most critical variables. A linear relationship between transfer ratio (defined as the ratio of the deposited paste volume to the stencil aperture volume) and area ratio (defined as the ratio of the area of the aperture opening to the area of the aperture wall) is proposed. The analysis indicates that the selection of a proper stencil thickness is the key to controlling the amount of solder paste deposited, and that the selection of maximum stencil thickness should be based on the area ratio. The experimental results are shown to be consistent with a theoretical model, which are also described

A framework for convection and boundary layer parameterization derived from conditional filtering

A new theoretical framework is derived for parameterization of subgrid physical processes in atmospheric models; the application to parameterization of convection and boundary layer fluxes is a particular focus. The derivation is based on conditional filtering, which uses a set of quasi-Lagrangian labels to pick out different regions of the fluid, such as convective updrafts and environment, before applying a spatial filter. This results in a set of coupled prognostic equations for the different fluid components, including subfilter-scale flux terms and entrainment/detrainment terms. The framework can accommodate different types of approaches to parameterization, such as local turbulence approaches and mass-flux approaches. It provides a natural way to distinguish between local and nonlocal transport processes, and makes a clearer conceptual link to schemes based on coherent structures such as convective plumes or thermals than the straightforward application of a filter without the quasi-Lagrangian labels. The framework should facilitate the unification of different approaches to parameterization by highlighting the different approximations made, and by helping to ensure that budgets of energy, entropy, and momentum are handled consistently and without double counting. The framework also points to various ways in which traditional parameterizations might be extended, for example by including additional prognostic variables. One possibility is to allow the large-scale dynamics of all the fluid components to be handled by the dynamical core. This has the potential to improve several aspects of convection-dynamics coupling, such as dynamical memory, the location of compensating subsidence, and the propagation of convection to neighboring grid columns

Redundant Mechanisms Recruit Actin into the Contractile Ring in Silkworm Spermatocytes

Cytokinesis is powered by the contraction of actomyosin filaments within the newly assembled contractile ring. Microtubules are a spindle component that is essential for the induction of cytokinesis. This induction could use central spindle and/or astral microtubules to stimulate cortical contraction around the spindle equator (equatorial stimulation). Alternatively, or in addition, induction could rely on astral microtubules to relax the polar cortex (polar relaxation). To investigate the relationship between microtubules, cortical stiffness, and contractile ring assembly, we used different configurations of microtubules to manipulate the distribution of actin in living silkworm spermatocytes. Mechanically repositioned, noninterdigitating microtubules can induce redistribution of actin at any region of the cortex by locally excluding cortical actin filaments. This cortical flow of actin promotes regional relaxation while increasing tension elsewhere (normally at the equatorial cortex). In contrast, repositioned interdigitating microtubule bundles use a novel mechanism to induce local stimulation of contractility anywhere within the cortex; at the antiparallel plus ends of central spindle microtubules, actin aggregates are rapidly assembled de novo and transported laterally to the equatorial cortex. Relaxation depends on microtubule dynamics but not on RhoA activity, whereas stimulation depends on RhoA activity but is largely independent of microtubule dynamics. We conclude that polar relaxation and equatorial stimulation mechanisms redundantly supply actin for contractile ring assembly, thus increasing the fidelity of cleavage

Redistribution of Actin during Assembly and Reassembly of the Contractile Ring in Grasshopper Spermatocytes

Cytokinesis in animal cells requires the assembly of an actomyosin contractile ring to cleave the cell. The ring is highly dynamic; it assembles and disassembles during each cell cleavage, resulting in the recurrent redistribution of actin. To investigate this process in grasshopper spermatocytes, we mechanically manipulated the spindle to induce actin redistribution into ectopic contractile rings, around reassembled lateral spindles. To enhance visualization of actin, we folded the spindle at its equator to convert the remnants of the partially assembled ring into a concentrated source of actin. Filaments from the disintegrating ring aligned along reorganizing spindle microtubules, suggesting that their incorporation into the new ring was mediated by microtubules. We tracked incorporation by speckling actin filaments with Qdots and/or labeling them with Alexa 488-phalloidin. The pattern of movement implied that actin was transported along spindle microtubules, before entering the ring. By double-labeling dividing cells, we imaged actin filaments moving along microtubules near the contractile ring. Together, our findings indicate that in one mechanism of actin redistribution, actin filaments are transported along spindle microtubule tracks in a plus-end–directed fashion. After reaching the spindle midzone, the filaments could be transported laterally to the ring. Notably, actin filaments undergo a dramatic trajectory change as they enter the ring, implying the existence of a pulling force. Two other mechanisms of actin redistribution, cortical flow and de novo assembly, are also present in grasshopper, suggesting that actin converges at the nascent contractile ring from diffuse sources within the cytoplasm and cortex, mediated by spindle microtubules

From 'trading zones' to 'buffer zones': Art and metaphor in the communication of psychiatric genetics to publics

Psychiatric genetics has a difficult relationship with the public given its unshakeable connection to eugenics. Drawing from a five-year public engagement programme that emerged from an internationally renowned psychiatric genetics centre, we propose the concept of the Buffer Zone to consider how an exchange of viewpoints between groups of people – including psychiatric geneticists and lay publics - who are often uneasy in one another’s company can be facilitated through the use of art and metaphor. The artwork at the exhibitions provided the necessary socio-cultural context for scientific endeavours, whilst also enabled public groups to be part of, and remain in, the conversation. Crucial to stress is that this mitigation was not to protect the science; it was to protect the discussion

A global phylogeny of butterflies reveals their evolutionary history, ancestral hosts and biogeographic origins

Butterflies are a diverse and charismatic insect group that are thought to have evolved with plants and dispersed throughout the world in response to key geological events. However, these hypotheses have not been extensively tested because a comprehensive phylogenetic framework and datasets for butterfly larval hosts and global distributions are lacking. We sequenced 391 genes from nearly 2,300 butterfly species, sampled from 90 countries and 28 specimen collections, to reconstruct a new phylogenomic tree of butterflies representing 92% of all genera. Our phylogeny has strong support for nearly all nodes and demonstrates that at least 36 butterfly tribes require reclassification. Divergence time analyses imply an origin similar to 100 million years ago for butterflies and indicate that all but one family were present before the K/Pg extinction event. We aggregated larval host datasets and global distribution records and found that butterflies are likely to have first fed on Fabaceae and originated in what is now the Americas. Soon after the Cretaceous Thermal Maximum, butterflies crossed Beringia and diversified in the Palaeotropics. Our results also reveal that most butterfly species are specialists that feed on only one larval host plant family. However, generalist butterflies that consume two or more plant families usually feed on closely related plants