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In contrast to carbon-substituted isocyanates that are common building blocks, N-substituted isocyanates remain underdeveloped and reports on their N-acyl derivatives (i. e. amido-isocyanates) are exceedingly rare. Herein, amido-isocyanates were investigated in the context of syntheses of aza-tripeptide and hydantoins subunits starting from simple bench-stable precursors. A key finding is that the amido-isocyanate formed in situ cyclized to yield an oxadiazolone, and that under suitable reaction conditions this heterocycle is a traceless blocked (masked) N-isocyanate. Using organic bases as catalysts and upon heating, oxadiazolone formation is observed, and various nucleophiles to provide the desired aza-dipeptides or hydantoins in moderate to high yields. Further support for an amido-isocyanate intermediate was obtained using carboxylic acids as nucleophiles, affording N-acylhydrazide products.

Objectives Psoriatic arthritis (PsA) has a strong genetic component, and the identification of genetic risk factors could help identify the ~30% of psoriasis patients at high risk of developing PsA. Our objectives were to identify genetic risk factors and pathways that differentiate PsA from cutaneous-only psoriasis (PsC) and to evaluate the performance of PsA risk prediction models. Methods Genome-wide meta-analyses were conducted separately for 5,065 patients with PsA and 21,286 healthy controls and separately for 4,340 patients with PsA and 6,431 patients with PsC. The heritability of PsA was calculated as a single-nucleotide polymorphism (SNP)–based heritability estimate (h2SNP) and biologic pathways that differentiate PsA from PsC were identified using Priority Index software. The generalizability of previously published PsA risk prediction pipelines was explored, and a risk prediction model was developed with external validation. Results We identified a novel genome-wide significant susceptibility locus for the development of PsA on chromosome 22q11 (rs5754467; P = 1.61 × 10−9), and key pathways that differentiate PsA from PsC, including NF-κB signaling (adjusted P = 1.4 × 10−45) and Wnt signaling (adjusted P = 9.5 × 10−58). The heritability of PsA in this cohort was found to be moderate (h2SNP = 0.63), which was similar to the heritability of PsC (h2SNP = 0.61). We observed modest performance of published classification pipelines (maximum area under the curve 0.61), with similar performance of a risk model derived using the current data. Conclusion Key biologic pathways associated with the development of PsA were identified, but the investigation of risk classification revealed modest utility in the available data sets, possibly because many of the PsC patients included in the present study were receiving treatments that are also effective in PsA. Future predictive models of PsA should be tested in PsC patients recruited from primary care.

The timing of recurring biological and seasonal environmental events is changing on a global scale relative to temperature and other climate drivers. This study considers the Gulf of Maine ecosystem, a region of high social and ecological importance in the Northwest Atlantic Ocean and synthesizes current knowledge of (a) key seasonal processes, patterns, and events; (b) direct evidence for shifts in timing; (c) implications of phenological responses for linked ecological‐human systems; and (d) potential phenology‐focused adaptation strategies and actions. Twenty studies demonstrated shifts in timing of regional marine organisms and seasonal environmental events. The most common response was earlier timing, observed in spring onset, spring and winter hydrology, zooplankton abundance, occurrence of several larval fishes, and diadromous fish migrations. Later timing was documented for fall onset, reproduction and fledging in Atlantic puffins, spring and fall phytoplankton blooms, and occurrence of additional larval fishes. Changes in event duration generally increased and were detected in zooplankton peak abundance, early life history periods of macro‐invertebrates, and lobster fishery landings. Reduced duration was observed in winter–spring ice‐affected stream flows. Two studies projected phenological changes, both finding diapause duration would decrease in zooplankton under future climate scenarios. Phenological responses were species‐specific and varied depending on the environmental driver, spatial, and temporal scales evaluated. Overall, a wide range of baseline phenology and relevant modeling studies exist, yet surprisingly few document long‐term shifts. Results reveal a need for increased emphasis on phenological shifts in the Gulf of Maine and identify opportunities for future research and consideration of phenological changes in adaptation efforts.

Purpose There is currently no adequate method of mapping physiologic and pathophysiologic tissue albumin concentrations in human subjects. The objective of this study was to devise and evaluate a biomarker of regional albumin concentration using gadofosveset-enhanced MRI. Theory and Methods A binding and relaxation model was devised and evaluated in vitro in solutions of albumin at 3.0 Tesla (T) and 4.7T. The method was evaluated in the heart in seven volunteers at 3.0T. Results MRI-derived estimates of albumin concentration were in good agreement with true values over the range 0.1–1.0 mM (Pearson correlation coefficients of 0.85 and 0.88 for 3.0T and 4.7T, respectively). The mean calculated albumin concentration in the myocardium for the volunteers was 0.02 mM (range, 0.01–0.03 mM). Conclusion Accurate estimates of albumin concentration in vitro suggest this may be a viable noninvasive alternative to existing techniques. In the myocardium the MRI-derived estimates of albumin concentration indicate the practical feasibility of the technique but were below expected values. Gadofosveset-enhanced MR relaxometry has potential in providing biomarkers of regional albumin concentration; further evaluation is required before it can be used reliably in vivo. Magn Reson Med 73:244–253, 2015. © 2014 Wiley Periodicals, Inc.

Continuous carbon nanofibers (CNF) present an attractive building block for a variety of multifunctional materials and devices. However, the carbonization of poly(acrylonitrile) (PAN) precursors usually results in CNFs with poor graphitic structure and, consequently, modest/non-optimized properties. This paper reports that the graphitic structure of CNFs can be improved with an addition of a small amount of graphene oxide into PAN prior to processing. Continuous CNFs with 1.4 wt% of graphene oxide nanoparticles are prepared from PAN solutions by electrospinning, stabilized, and carbonized at 800 °C, 1200 °C, and 1850 °C. While the as-prepared graphene oxide-filled PAN nanofibers exhibit a considerable reduction in polymer crystallinity, Raman analysis of the carbonized nanofibers shows that both templating with graphene oxide and increasing the carbonization temperature significantly improve the graphitic order in CNFs. The effect of graphene oxide is more significant at higher carbonization temperatures. Selected area electron diffraction analysis of individual nanofibers reveals increased graphitic order and preferred orientation both in the vicinity of visible graphene oxide nanoparticles and in the regions where nanoparticles were not visible. These results indicate a possibility of global templating in CNFs, where the addition of a small amount of graphene oxide nanoparticles can template the formation of good, preferentially oriented graphitic crystallites in CNFs, leading to improved structure and mechanical and transport properties.

Highly ordered, homogeneous polymer nanocomposites of layered graphene oxide are prepared using a vacuum-assisted self-assembly (VASA) technique. In VASA, all components (nanofiller and polymer) are pre-mixed prior to assembly under a flow, making it compatible with either hydrophilic poly(vinyl alcohol) (PVA) or hydrophobic poly(methyl methacrylate) (PMMA) for the preparation of composites with over 50 wt% filler. This process is complimentary to layer-by-layer assembly, where the assembling components are required to interact strongly (e.g., via Coulombic attraction). The nanosheets within the VASA-assembled composites exhibit a high degree of order with tunable intersheet spacing, depending on the polymer content. Graphene oxide–PVA nanocomposites, prepared from water, exhibit greatly improved modulus values in comparison to films of either pure PVA or pure graphene oxide. Modulus values for graphene oxide–PMMA nanocomposites, prepared from dimethylformamide, are intermediate to those of the pure components. The differences in structure, modulus, and strength can be attributed to the gallery composition, specifically the hydrogen bonding ability of the intercalating species

Tissue ingrowth, differentiation, and osteogenesis in a porous bioinert bioceramic were studied using an intramedullary model. Pure alumina tubes (1.3 mm outer diameter, 0.6 mm inner diameter, 15 mm length) were implanted in the femoral medullary canal of young female rats for 4, 6, 8, 12, and 16 weeks. Tissues present within each tube were characterized by histology and quantified by histomorphometry. A tissue front consisting of undifferentiated mesenchymal cells, fibrovascular tissue, osteoid, woven bone, and marrow penetrated the tube from both ends. Behind the front, woven bone remodeled to produce a thin layer of lamellar bone that lined the tube walls the entire distance to the tube ends and enclosed a marrow-filled lumen. The front was considered to represent the differentiation cascade from mesenchymal cells to fibrovascular tissue to osteoid to woven bone and marrow to lamellar bone and marrow. The fronts advanced into the tube with time such that, by 16 weeks, they were close to meeting or had met. In several instances, the tube was completely lined with a thin layer of mature lamellar bone continuous between the two ends and enclosing marrow. This configuration was considered to be the final equilibrium of tissues within the tube. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 68A: 305–313, 2004

1. Three independent methods were used to investigate population structure in the butterfly Plebejus argus. First, migration and dispersal ability were measured by mark–release–recapture in seven adjacent habitat patches, and by release of butterflies in unoccupied habitat. Secondly, colonization of newly created habitat was observed over 7 years. Finally, genetic differentiation of local populations within a metapopulation was investigated. Sampled local populations included parts of the mark–release–recapture study area. 2. Plebejus argus is relatively sedentary: the maximum movement detected was 395 m, and only 2% of individuals moved further than 100 m between recaptures on different days. None the less, adjacent local populations in the mark–release–recapture study area were linked by occasional migration, with ≈ 1.4% of individuals moving between patches separated by 13–200 m. 3. Despite low mobility, observed colonizations occurred rapidly over distances of 1 km. Because P. argus occurs at high population densities, 1.4% migration can generate enough migrants to colonize newly suitable habitat quickly at this spatial scale. 4. Mark–release–recapture data were used to predict that there would be limited genetic differentiation through drift between local populations at this spatial scale. The prediction was supported by allele frequency data for the same local populations. 5. Genetic differentiation often indicates higher levels of migration than are revealed by the movements of marked individuals. This study shows that when experimental releases and extensive marking are undertaken in areas that are large relative to most movements, indirect measures of gene flow and direct measures of dispersal can concur. 6. Evidence from the three different approaches was complementary, indicating that P. argus occurs as metapopulations within the study area.

Fragmented populations of the silver-studded blue butterfly (Plebejus argus: Lycaenidae) provide a model system for metapopulations in which extinctions, colonizations, and artificial introductions have all been documented. The genetic consequences of population turnover were investigated using allozyme and mtDNA/RFLP markers and via studies of fluctuating asymmetry. Evidence for changes in genetic diversity was studied in samples of 40–90 individuals from one source and eight descendent populations in North Wales. The genetic data were analyzed using a novel permutation method, which is potentially applicable to analyses of other levels of biodiversity, such as species diversity or species counts. Significant reductions in the numbers of rare allozyme alleles were found in descendent populations, presumably as a result of drift during colonization bottlenecks. Similar trends were evident in the mtDNA data, but were largely non-significant. The reduced statistical power of mtDNA was probably due more to low overall numbers of alleles detected (19) compared with allozymes (40 alleles at 12 loci) than to any conflict between marker loci. Expected heterozygosity (He ) also generally declined during colonization, but the changes were rarely significant, probably because drift-induced changes in the frequencies of common alleles may actually increase He in a bottlenecked population. Finally, overall gene frequency changes, measured by Fst , were often significant. The values of the effective population size ( Ne ) estimated for two introductions ( Ne = 71 and 29) suggested bottleneck population sizes of approximately half the number of diploid genomes (180 and 60 respectively) actually introduced. In contrast to evidence for loss of genetic diversity, there was no evidence for any increase in fluctuating asymmetry among descendent populations. Plebejus argus maintains large enough populations locally and colonizes in sufficient numbers that the deleterious effects of bottlenecking are temporary, affect only the rarest alleles, and cause no observed disturbances to developmental stability. As a result a single introduction of 90 mated females to Rhŷd-y-foel in 1942 has led to the successful establishment of a healthy metapopulation now numbering about 100,000. Poblaciones aisladas de la mariposa Plebejus argus (Lycaenidae) proporcionan un sistema modelo de metapoblaciones, en las cuales; extinciones, colonizaciones y liberaciones artificiales han sido documentadas. Utilizando muestras grandes de 40–90 individuos, las consecuencias geneticas producidos por disturbios poblacionales fueron estudiados mediante el uso de alozimas y marcadores ADNmt/RFLP y con estudios de asimetria fluctuante. Las evidencias de cambios en la diversidad genetica fue estudiada en una poblacion original y ocho poblaciones descendientes en North Wales. Los datos geneticos fueron analizados mediante un nuevo metodo de permutaciones, el cual se puede utilizar en analisis de otros niveles de biodiversidad, asi como en diversidad de especies. Encontramos reducciones significativas en el numero de alelos raros de alozimas en las poblaciones descendientes, probablemente como resultado de la deriva genica durante colonizaciones cuellos de botella. Tendencias similares fueron evidentes en los datos de ADNmt, pero fueron mayormante no significativas. El reducido poder estadistico del ADNmt probablemente se debe al numero bajo de alelos (19) comparado con el numero de alozimas (40 alelos en 12 loci), mas que a un conflicto entre loci marcadores. La heterozigocidad esperada ( He ), generalmente tambien es reducida durante una colonizacion, pero los cambios son raramente significativos, probablemente debido a que cambios en las frecuencias de alelos comunes inducidos por la deriva genica puede, a veces, causar un incremento en He en una poblacion en situacion de cuello de botella. Finalmente, cambios en frecuencias de alelos, medidos por Fst , fueron frecuentemente significativos. El tamano efectivo de la poblacion ( Ne ) estimado para dos introducciones ( Ne = 71 y 29) sugiere tamanos poblacionales cuello de botella de aproximadamente la mitad del numero actual de genomas diploides liberados (180 y 60 respectivamente). En contraste con la evidencia de perdida de diversidad genetica, no hay evidencia de incrementos en la asimetria fluctuante de las poblaciones descendientes. Plebejus argus mantiene poblaciones locales lo suficientemente grandes y coloniza en numeros tales que los efectos negativos de los cuellos de botella son temporales, afectando unicamente los alelos mas raros sin causar disturbios en la estabilidad ontogenetica. Como resultado, una sola liberacion de 90 hembras inseminadas en Rhyd-y-foel en 1942 logro el establecimiento de una metapoblacion nueva, la cual cuenta hoy con aproximadamente 100,000 habitantes.

Communication is the lifeblood of science. However, it can also be a daunting task, especially for students and young professionals. Recognizing this, the Southern New England Chapter of the Americ...