Showing papers by "Louisiana State University published in 2011"
TL;DR: It is established that calorie restriction and exercise-mediated weight loss in obese individuals with type 2 diabetes is associated with a reduction in adipose tissue expression of Nlrp3 as well as with decreased inflammation and improved insulin sensitivity, and that the NlrP3 inflammasome senses obesity-associated danger signals and contributes to obesity-induced inflammation and insulin resistance.
Abstract: Obesity is generally considered an inflammatory state. Vishwa Dixit and his colleagues have now shown that excess dietary lipids leads to the activation of the Nlrp3 inflammasome, a sensor of the innate immune system, and that its genetic deficiency results in decreased inflammation and improved insulin sensitivity. These results suggest a possible new therapeutic avenue to treat the effects of obesity.
2,000 citations
TL;DR: Potential opportunities for the combination of hyperthermia-based therapy and controlled drug release paradigms--towards successful application in personalized medicine are portrayed.
1,380 citations
TL;DR: The T2K experiment observes indications of ν (μ) → ν(e) appearance in data accumulated with 1.43×10(20) protons on target, and under this hypothesis, the probability to observe six or more candidate events is 7×10(-3), equivalent to 2.5σ significance.
Abstract: The T2K experiment observes indications of nu(mu) -> nu(mu) e appearance in data accumulated with 1.43 x 10(20) protons on target. Six events pass all selection criteria at the far detector. In a three-flavor neutrino oscillation scenario with |Delta m(23)(2)| = 2.4 x 10(-3) eV(2), sin(2)2 theta(23) = 1 and sin(2)2 theta(13) = 0, the expected number of such events is 1.5 +/- 0.3(syst). Under this hypothesis, the probability to observe six or more candidate events is 7 x 10(-3), equivalent to 2.5 sigma significance. At 90% C.L., the data are consistent with 0.03(0.04) < sin(2)2 theta(13) < 0.28(0.34) for delta(CP) = 0 and a normal (inverted) hierarchy.
1,361 citations
TL;DR: Loop quantum cosmology (LQC) as mentioned in this paper is the result of applying principles of loop quantum gravity to cosmological settings, where quantum geometry creates a brand new repulsive force which is totally negligible at low spacetime curvature but rises very rapidly in the Planck regime, overwhelming the classical gravitational attraction.
Abstract: Loop quantum cosmology (LQC) is the result of applying principles of loop quantum gravity (LQG) to cosmological settings. The distinguishing feature of LQC is the prominent role played by the quantum geometry effects of LQG. In particular, quantum geometry creates a brand new repulsive force which is totally negligible at low spacetime curvature but rises very rapidly in the Planck regime, overwhelming the classical gravitational attraction. In cosmological models, while Einstein's equations hold to an excellent degree of approximation at low curvature, they undergo major modifications in the Planck regime: for matter satisfying the usual energy conditions, any time a curvature invariant grows to the Planck scale, quantum geometry effects dilute it, thereby resolving singularities of general relativity. Quantum geometry corrections become more sophisticated as the models become richer. In particular, in anisotropic models, there are significant changes in the dynamics of shear potentials which tame their singular behavior in striking contrast to older results on anisotropies in bouncing models. Once singularities are resolved, the conceptual paradigm of cosmology changes and one has to revisit many of the standard issues—e.g. the 'horizon problem'—from a new perspective. Such conceptual issues as well as potential observational consequences of the new Planck scale physics are being explored, especially within the inflationary paradigm. These considerations have given rise to a burst of activity in LQC in recent years, with contributions from quantum gravity experts, mathematical physicists and cosmologists. The goal of this review is to provide an overview of the current state of the art in LQC for three sets of audiences: young researchers interested in entering this area; the quantum gravity community in general and cosmologists who wish to apply LQC to probe modifications in the standard paradigm of the early universe. In this review, effort has been made to streamline the material so that each of these communities can read only the sections they are most interested in, without loss of continuity.
1,162 citations
TL;DR: A map of unbalanced SVs is constructed based on whole genome DNA sequencing data from 185 human genomes, integrating evidence from complementary SV discovery approaches with extensive experimental validations, and serves as a resource for sequencing-based association studies.
Abstract: Genomic structural variants (SVs) are abundant in humans, differing from other forms of variation in extent, origin and functional impact. Despite progress in SV characterization, the nucleotide resolution architecture of most SVs remains unknown. We constructed a map of unbalanced SVs (that is, copy number variants) based on whole genome DNA sequencing data from 185 human genomes, integrating evidence from complementary SV discovery approaches with extensive experimental validations. Our map encompassed 22,025 deletions and 6,000 additional SVs, including insertions and tandem duplications. Most SVs (53%) were mapped to nucleotide resolution, which facilitated analysing their origin and functional impact. We examined numerous whole and partial gene deletions with a genotyping approach and observed a depletion of gene disruptions amongst high frequency deletions. Furthermore, we observed differences in the size spectra of SVs originating from distinct formation mechanisms, and constructed a map of SV hotspots formed by common mechanisms. Our analytical framework and SV map serves as a resource for sequencing-based association studies.
1,085 citations
TL;DR: It is shown here that P-clouds predicts >840 Mbp of additional repetitive sequences in the human genome, thus suggesting that 66%–69% of the human chromosome is repetitive or repeat-derived, and that the human genomes consists of substantially more repetitive sequence than previously believed.
Abstract: Transposable elements (TEs) are conventionally identified in eukaryotic genomes by alignment to consensus element sequences. Using this approach, about half of the human genome has been previously identified as TEs and low-complexity repeats. We recently developed a highly sensitive alternative de novo strategy, P-clouds, that instead searches for clusters of high-abundance oligonucleotides that are related in sequence space (oligo “clouds”). We show here that P-clouds predicts >840 Mbp of additional repetitive sequences in the human genome, thus suggesting that 66%–69% of the human genome is repetitive or repeat-derived. To investigate this remarkable difference, we conducted detailed analyses of the ability of both P-clouds and a commonly used conventional approach, RepeatMasker (RM), to detect different sized fragments of the highly abundant human Alu and MIR SINEs. RM can have surprisingly low sensitivity for even moderately long fragments, in contrast to P-clouds, which has good sensitivity down to small fragment sizes (∼25 bp). Although short fragments have a high intrinsic probability of being false positives, we performed a probabilistic annotation that reflects this fact. We further developed “element-specific” P-clouds (ESPs) to identify novel Alu and MIR SINE elements, and using it we identified ∼100 Mb of previously unannotated human elements. ESP estimates of new MIR sequences are in good agreement with RM-based predictions of the amount that RM missed. These results highlight the need for combined, probabilistic genome annotation approaches and suggest that the human genome consists of substantially more repetitive sequence than previously believed.
983 citations
TL;DR: A critical review of kinetic models and mathematical approximations currently employed in solid state thermal analysis is provided and analysis of thermal decomposition data obtained from two agricultural residues, nutshells and sugarcane bagasse reveals the inherent difficulty and risks involved in modeling heterogeneous reaction systems.
976 citations
TL;DR: The basic biology of the fly is reviewed and models of human diseases and opportunities for therapeutic discovery for central nervous system disorders, inflammatory disorders, cardiovascular disease, cancer, and diabetes are discussed.
Abstract: The common fruit fly, Drosophila melanogaster, is a well studied and highly tractable genetic model organism for understanding molecular mechanisms of human diseases. Many basic biological, physiological, and neurological properties are conserved between mammals and D. melanogaster, and nearly 75% of human disease-causing genes are believed to have a functional homolog in the fly. In the discovery process for therapeutics, traditional approaches employ high-throughput screening for small molecules that is based primarily on in vitro cell culture, enzymatic assays, or receptor binding assays. The majority of positive hits identified through these types of in vitro screens, unfortunately, are found to be ineffective and/or toxic in subsequent validation experiments in whole-animal models. New tools and platforms are needed in the discovery arena to overcome these limitations. The incorporation of D. melanogaster into the therapeutic discovery process holds tremendous promise for an enhanced rate of discovery of higher quality leads. D. melanogaster models of human diseases provide several unique features such as powerful genetics, highly conserved disease pathways, and very low comparative costs. The fly can effectively be used for low- to high-throughput drug screens as well as in target discovery. Here, we review the basic biology of the fly and discuss models of human diseases and opportunities for therapeutic discovery for central nervous system disorders, inflammatory disorders, cardiovascular disease, cancer, and diabetes. We also provide information and resources for those interested in pursuing fly models of human disease, as well as those interested in using D. melanogaster in the drug discovery process.
931 citations
TL;DR: In this paper, the authors demonstrate the squeezed-light enhancement of GEO600, which will be the GW observatory operated by the LIGO Scientific Collaboration in its search for GWs for the next 3-4 years.
Abstract: Around the globe several observatories are seeking the first direct detection of gravitational waves (GWs). These waves are predicted by Einstein’s general theory of relativity1 and are generated, for example, by black-hole binary systems2. Present GW detectors are Michelson-type kilometre-scale laser interferometers measuring the distance changes between mirrors suspended in vacuum. The sensitivity of these detectors at frequencies above several hundred hertz is limited by the vacuum (zero-point) fluctuations of the electromagnetic field. A quantum technology—the injection of squeezed light3—offers a solution to this problem. Here we demonstrate the squeezed-light enhancement of GEO 600, which will be the GW observatory operated by the LIGO Scientific Collaboration in its search for GWs for the next 3–4 years. GEO 600 now operates with its best ever sensitivity, which proves the usefulness of quantum entanglement and the qualification of squeezed light as a key technology for future GW astronomy4.
810 citations
TL;DR: This article offers a tutorial on several prevalent methods to enhance security at the physical layer in wireless networks based on their characteristic features into five categories, each of which is discussed in terms of two metrics.
Abstract: Wireless networking plays an extremely important role in civil and military applications. However, security of information transfer via wireless networks remains a challenging issue. It is critical to ensure that confidential data are accessible only to the intended users rather than intruders. Jamming and eavesdropping are two primary attacks at the physical layer of a wireless network. This article offers a tutorial on several prevalent methods to enhance security at the physical layer in wireless networks. We classify these methods based on their characteristic features into five categories, each of which is discussed in terms of two metrics. First, we compare their secret channel capacities, and then we show their computational complexities in exhaustive key search. Finally, we illustrate their security requirements via some examples with respect to these two metrics.
770 citations
Smithsonian Tropical Research Institute1, James Cook University2, Duke University3, University of Florida4, Louisiana State University5, National Autonomous University of Mexico6, National Marine Fisheries Service7, Rhodes College8, University of Western Australia9, Commonwealth Scientific and Industrial Research Organisation10, George Mason University11
TL;DR: In this paper, the authors synthesize findings to date from the world's largest and longest-running experimental study of habitat fragmentation, located in central Amazonia, and synthesize the results to date.
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11 Dec 2011-Nuclear Instruments & Methods in Physics Research Section A-accelerators Spectrometers Detectors and Associated Equipment
TL;DR: The T2K experiment as discussed by the authors is a long-baseline neutrino oscillation experiment whose main goal is to measure the last unknown lepton sector mixing angle by observing its appearance in a particle beam generated by the J-PARC accelerator.
Abstract: The T2K experiment is a long-baseline neutrino oscillation experiment Its main goal is to measure the last unknown lepton sector mixing angle {\theta}_{13} by observing {
u}_e appearance in a {
u}_{\mu} beam It also aims to make a precision measurement of the known oscillation parameters, {\Delta}m^{2}_{23} and sin^{2} 2{\theta}_{23}, via {
u}_{\mu} disappearance studies Other goals of the experiment include various neutrino cross section measurements and sterile neutrino searches The experiment uses an intense proton beam generated by the J-PARC accelerator in Tokai, Japan, and is composed of a neutrino beamline, a near detector complex (ND280), and a far detector (Super-Kamiokande) located 295 km away from J-PARC This paper provides a comprehensive review of the instrumentation aspect of the T2K experiment and a summary of the vital information for each subsystem
University of Texas Health Science Center at San Antonio1, Veterans Health Administration2, Arizona State University3, SUNY Downstate Medical Center4, Louisiana State University5, University of Southern California6, Georgetown University7, University of California, San Diego8, University of Tennessee Health Science Center9, Memorial Hospital of South Bend10
TL;DR: As compared with placebo, pioglitazone reduced the risk of conversion of impaired glucose tolerance to type 2 diabetes mellitus by 72% but was associated with significant weight gain and edema.
Abstract: RESULTS Annual incidence rates for type 2 diabetes mellitus were 2.1% in the pioglitazone group and 7.6% in the placebo group, and the hazard ratio for conversion to diabetes in the pioglitazone group was 0.28 (95% confidence interval, 0.16 to 0.49; P<0.001). Conversion to normal glucose tolerance occurred in 48% of the patients in the pioglitazone group and 28% of those in the placebo group (P<0.001). Treatment with pioglitazone as compared with placebo was associated with significantly reduced levels of fasting glucose (a decrease of 11.7 mg per deciliter vs. 8.1 mg per deciliter [0.7 mmol per liter vs. 0.5 mmol per liter], P<0.001), 2-hour glucose (a decrease of 30.5 mg per deciliter vs. 15.6 mg per deciliter [1.6 mmol per liter vs. 0.9 mmol per liter], P<0.001), and HbA1c (a decrease of 0.04 percentage points vs. an increase of 0.20 percentage points, P<0.001). Pioglitazone therapy was also associated with a decrease in diastolic blood pressure (by 2.0 mm Hg vs. 0.0 mm Hg, P = 0.03), a reduced rate of carotid intima–media thickening (31.5%, P = 0.047), and a greater increase in the level of high-density lipoprotein cholesterol (by 7.35 mg per deciliter vs. 4.5 mg per deciliter [0.4 mmol per liter vs. 0.3 mmol per liter], P = 0.008). Weight gain was greater with pioglitazone than with placebo (3.9 kg vs. 0.77 kg, P<0.001), and edema was more frequent (12.9% vs. 6.4%, P = 0.007). CONCLUSIONS As compared with placebo, pioglitazone reduced the risk of conversion of impaired glucose tolerance to type 2 diabetes mellitus by 72% but was associated with significant weight gain and edema. (Funded by Takeda Pharmaceuticals and others; ClinicalTrials.gov number, NCT00220961.)
TL;DR: Various in vitro and in vivo pharmacological aspects of curcumin as well as the underlying action mechanisms are summarized, which suggest anticancer, antiviral, antiarthritic, anti-amyloid, antioxidant, and anti-inflammatory properties.
Abstract: Curcumin (diferuloylmethane), an orange-yellow component of turmeric or curry powder, is a polyphenol natural product isolated from the rhizome of the plant Curcuma longa. For centuries, curcumin has been used in some medicinal preparation or used as a food-coloring agent. In recent years, extensive in vitro and in vivo studies suggested curcumin has anticancer, antiviral, antiarthritic, anti-amyloid, antioxidant, and anti-inflammatory properties. The underlying mechanisms of these effects are diverse and appear to involve the regulation of various molecular targets, including transcription factors (such as nuclear factor-kB), growth factors (such as vascular endothelial cell growth factor), inflammatory cytokines (such as tumor necrosis factor, interleukin 1 and interleukin 6), protein kinases (such as mammalian target of rapamycin, mitogen-activated protein kinases, and Akt) and other enzymes (such as cyclooxygenase 2 and 5 lipoxygenase). Thus, due to its efficacy and regulation of multiple targets, as well as its safety for human use, curcumin has received considerable interest as a potential therapeutic agent for the prevention and/or treatment of various malignant diseases, arthritis, allergies, Alzheimer's disease, and other inflammatory illnesses. This review summarizes various in vitro and in vivo pharmacological aspects of curcumin as well as the underlying action mechanisms. The recently identified molecular targets and signaling pathways modulated by curcumin are also discussed here.
TL;DR: In this article, the authors use panel data constructed from the responses of repeatedly surveyed top managers at 261 companies regarding their firm's market orientation, along with objective performance measures to investigate the influence of market orientation on performance for a nine-year period from 1997 to 2005.
Abstract: The authors use panel data constructed from the responses of repeatedly surveyed top managers at 261 companies regarding their firm’s market orientation, along with objective performance measures, to investigate the influence of market orientation on performance for a nine-year period from 1997 to 2005. The authors measure market orientation in 1997, 2001, and 2005 and estimate it in the interval between these measurement periods. The analyses indicate that market orientation has a positive effect on business performance in both the short and the long run. However, the sustained advantage in business performance from having a market orientation is greater for the firms that are early to develop a market orientation. These firms also gain more in sales and profit than firms that are late in developing a market orientation. Firms that adopt a market orientation may also realize additional benefit in the form of a lift in sales and profit due to a carryover effect. Market orientation should have a more pronounced effect on a firm’s profit than sales because a market orientation focuses efforts on customer retention rather than on acquisition. Environmental turbulence and competitive intensity moderate the main effect of market orientation on business performance, but the moderating effects are greater in the 1990s than in the 2000s.
Washington University in St. Louis1, Human Genome Sequencing Center2, University of Oxford3, Wellcome Trust Centre for Human Genetics4, University of Washington5, Pompeu Fabra University6, Howard Hughes Medical Institute7, Wellcome Trust Sanger Institute8, European Bioinformatics Institute9, University of California, Santa Cruz10, University of Illinois at Urbana–Champaign11, Pennsylvania State University12, University of Porto13, Universidade Nova de Lisboa14, University of Bari15, University of Bologna16, Louisiana State University17, Institute for Systems Biology18, Indiana University19, University of Oviedo20, Comenius University in Bratislava21, Cornell University22, Columbia University23, Stanford University24, University of Arizona25, Aarhus University26, Children's Hospital Oakland Research Institute27
TL;DR: The orang-utan species, Pongo abelii and Pongo pygmaeus, are the most phylogenetically distant great apes from humans, thereby providing an informative perspective on hominid evolution and a primate polymorphic neocentromere, found in both Pongo species are described.
Abstract: 'Orang-utan' is derived from a Malay term meaning 'man of the forest' and aptly describes the southeast Asian great apes native to Sumatra and Borneo. The orang-utan species, Pongo abelii (Sumatran) and Pongo pygmaeus (Bornean), are the most phylogenetically distant great apes from humans, thereby providing an informative perspective on hominid evolution. Here we present a Sumatran orang-utan draft genome assembly and short read sequence data from five Sumatran and five Bornean orang-utan genomes. Our analyses reveal that, compared to other primates, the orang-utan genome has many unique features. Structural evolution of the orang-utan genome has proceeded much more slowly than other great apes, evidenced by fewer rearrangements, less segmental duplication, a lower rate of gene family turnover and surprisingly quiescent Alu repeats, which have played a major role in restructuring other primate genomes. We also describe a primate polymorphic neocentromere, found in both Pongo species, emphasizing the gradual evolution of orang-utan genome structure. Orang-utans have extremely low energy usage for a eutherian mammal, far lower than their hominid relatives. Adding their genome to the repertoire of sequenced primates illuminates new signals of positive selection in several pathways including glycolipid metabolism. From the population perspective, both Pongo species are deeply diverse; however, Sumatran individuals possess greater diversity than their Bornean counterparts, and more species-specific variation. Our estimate of Bornean/Sumatran speciation time, 400,000 years ago, is more recent than most previous studies and underscores the complexity of the orang-utan speciation process. Despite a smaller modern census population size, the Sumatran effective population size (N(e)) expanded exponentially relative to the ancestral N(e) after the split, while Bornean N(e) declined over the same period. Overall, the resources and analyses presented here offer new opportunities in evolutionary genomics, insights into hominid biology, and an extensive database of variation for conservation efforts.
TL;DR: The resulting integrated SWAN + ADCIRC system is highly scalable and allows for localized increases in resolution without the complexity or cost of nested meshes or global interpolation between heterogeneous meshes.
TL;DR: This paper is a review of the extant literature on the prevalence of autism spectrum disorders and conclusions about the current state of the research are discussed.
TL;DR: This experiment provides evidence that N, P, and K all limit forest plants growing on a relatively fertile soil in the lowland tropics, with the strongest evidence for limitation by K among seedlings, saplings, and poles.
Abstract: We maintained a factorial nitrogen (N), phosphorus (P), and potassium (K) addition experiment for 11 years in a humid lowland forest growing on a relatively fertile soil in Panama to evaluate potential nutrient limitation of tree growth rates, fine-litter production, and fine-root biomass. We replicated the eight factorial treatments four times using 32 plots of 40 × 40 m each. The addition of K was associated with significant decreases in stand-level fine-root biomass and, in a companion study of seedlings, decreases in allocation to roots and increases in height growth rates. The addition of K and N together was associated with significant increases in growth rates of saplings and poles (1–10 cm in diameter at breast height) and a further marginally significant decrease in stand-level fine-root biomass. The addition of P was associated with a marginally significant (P = 0.058) increase in fine-litter production that was consistent across all litter fractions. Our experiment provides evidence that N, P, and K all limit forest plants growing on a relatively fertile soil in the lowland tropics, with the strongest evidence for limitation by K among seedlings, saplings, and poles.
TL;DR: Experiments in which metastable xenon atoms were ionized with intense 7-micrometer laser pulses from a free-electron laser recorded holographic structures that record underlying electron dynamics on a sublaser-cycle time scale, enabling photoelectron spectroscopy with a time resolution higher than the duration of the ionizing pulse.
Abstract: Ionization is the dominant response of atoms and molecules to intense laser fields and is at the basis of several important techniques, such as the generation of attosecond pulses that allow the measurement of electron motion in real time. We present experiments in which metastable xenon atoms were ionized with intense 7-micrometer laser pulses from a free-electron laser. Holographic structures were observed that record underlying electron dynamics on a sublaser-cycle time scale, enabling photoelectron spectroscopy with a time resolution of almost two orders of magnitude higher than the duration of the ionizing pulse.
TL;DR: In this article, the authors examined the yield behavior of an electrodeposited cuprous oxide thin film and explore relationships between surface chemistry and reaction behavior relative to air-oxidized and anodized Cu electrodes.
Abstract: The direct reduction of CO2 to CH3OH is known to occur at several types of electrocatalysts including oxidized Cu electrodes. In this work, we examine the yield behavior of an electrodeposited cuprous oxide thin film and explore relationships between surface chemistry and reaction behavior relative to air-oxidized and anodized Cu electrodes. CH3OH yields (43 μmol cm-2 h-1) and Faradaic efficiencies (38%) observed at cuprous oxide electrodes were remarkably higher than air-oxidized or anodized Cu electrodes suggesting Cu(I) species may play a critical role in selectivity to CH3OH. Experimental results also show CH3OH yields are dynamic and the copper oxides are reduced to metallic Cu in a simultaneous process. Yield behavior is discussed in comparison with photoelectrochemical and hydrogenation reactions where the improved stability of Cu(I) species may allow continuous CH3OH generation.
University of Montana1, University of Colorado Boulder2, University of Florida3, University of Brasília4, University of Buea5, University of Western Australia6, Louisiana State University7, University of California, Davis8, Colorado State University9, Brown University10, United States Geological Survey11, Max Planck Society12, University of California, Berkeley13, University of Cambridge14
TL;DR: A meta-analysis of carbon-nutrient-climate relationships in 113 sites across the tropical forest biome showed that mean annual temperature was the strongest predictor of aboveground NPP (ANPP) across all tropical forests, but this relationship was driven by distinct temperature differences between upland and lowland forests.
Abstract: Tropical rain forests play a dominant role in global biosphere-atmosphere CO2 exchange. Although climate and nutrient availability regulate net primary production (NPP) and decomposition in all terrestrial ecosystems, the nature and extent of such controls in tropical forests remain poorly resolved. We conducted a meta-analysis of carbon-nutrient-climate relationships in 113 sites across the tropical forest biome. Our analyses showed that mean annual temperature was the strongest predictor of aboveground NPP (ANPP) across all tropical forests, but this relationship was driven by distinct temperature differences between upland and lowland forests. Within lowland forests (< 1000 m), a regression tree analysis revealed that foliar and soil-based measurements of phosphorus (P) were the only variables that explained a significant proportion of the variation in ANPP, although the relationships were weak. However, foliar P, foliar nitrogen (N), litter decomposition rate (k), soil N and soil respiration were all directly related with total surface (0‐10 cm) soil P concentrations. Our analysis provides some evidence that P availability regulates NPP and other ecosystem processes in lowland tropical forests, but more importantly, underscores the need for a series of large-scale nutrient manipulations ‐ especially in lowland forests ‐ to elucidate the most important nutrient interactions and controls.
TL;DR: In this paper, the authors examined the network structure and nodal centrality of individual cities in the air transport network of China (ATNC) using a complex network approach and found that the ATNC has a cumulative degree distribution captured by an exponential function, and displays some small-world network properties with an average path length of 2.23 and a clustering coefficient of 0.69.
TL;DR: A 64-year-old woman receives the diagnosis of metastatic non-small-cell lung cancer, which has progressed during treatment with carboplatin, paclitaxel, and bevacizumab, and Erlotinib therapy is recommended.
Abstract: A 64-year-old woman receives the diagnosis of metastatic non-small-cell lung cancer (NSCLC), which has progressed during treatment with carboplatin, paclitaxel, and bevacizumab. Erlotinib therapy is recommended.
University College London1, Goddard Space Flight Center2, Space Telescope Science Institute3, University of Wisconsin-Madison4, University of Arizona5, Max Planck Society6, Keele University7, European Southern Observatory8, Louisiana State University9, Stockholm University10, Institute for the Physics and Mathematics of the Universe11, Commissariat à l'énergie atomique et aux énergies alternatives12
TL;DR: Observations of supernova 1987A reveal the presence of a population of cold dust grains radiating with a temperature of about 17 to 23 kelvin at a rate of about 220 times the luminosity of the Sun, implying that supernovae can produce the large dust masses detected in young galaxies at very high redshifts.
Abstract: We report far-infrared and submillimeter observations of supernova 1987A, the star whose explosion was observed on 23 February 1987 in the Large Magellanic Cloud, a galaxy located 160,000 light years away. The observations reveal the presence of a population of cold dust grains radiating with a temperature of about 17 to 23 kelvin at a rate of about 220 times the luminosity of the Sun. The intensity and spectral energy distribution of the emission suggest a dust mass of about 0.4 to 0.7 times the mass of the Sun. The radiation must originate from the supernova ejecta and requires the efficient precipitation of all refractory material into dust. Our observations imply that supernovae can produce the large dust masses detected in young galaxies at very high redshifts.
TL;DR: Evaluation of the expression, subcellular localization, biochemical properties, and potential functions of LEA proteins in animal species during water stress shows they are targeted to multiple cellular locations, including mitochondria, and evidence supports that LEA protein stabilize vitrified sugar glasses thought to be important in the dried state.
Abstract: Late embryogenesis abundant (LEA) proteins are extremely hydrophilic proteins that were first identified in land plants. Intracellular accumulation is tightly correlated with acquisition of desiccation tolerance, and data support their capacity to stabilize other proteins and membranes during drying, especially in the presence of sugars like trehalose. Exciting reports now show that LEA proteins are not restricted to plants; multiple forms are expressed in desiccation-tolerant animals from at least four phyla. We evaluate here the expression, subcellular localization, biochemical properties, and potential functions of LEA proteins in animal species during water stress. LEA proteins are intrinsically unstructured in aqueous solution, but surprisingly, many assume their native conformation during drying. They are targeted to multiple cellular locations, including mitochondria, and evidence supports that LEA proteins stabilize vitrified sugar glasses thought to be important in the dried state. More in vivo experimentation will be necessary to fully unravel the multiple functional properties of these macromolecules during water stress.
TL;DR: The crystal structure at 2.4 angstrom resolution of human 5-LOX stabilized by replacement of this sequence that is involved in orienting the carboxyl terminus, which binds the catalytic iron.
Abstract: The synthesis of both proinflammatory leukotrienes and anti-inflammatory lipoxins requires the enzyme 5-lipoxygenase (5-LOX). 5-LOX activity is short-lived, apparently in part because of an intrinsic instability of the enzyme. We identified a 5-LOX-specific destabilizing sequence that is involved in orienting the carboxyl terminus, which binds the catalytic iron. Here, we report the crystal structure at 2.4 angstrom resolution of human 5-LOX stabilized by replacement of this sequence.
Complutense University of Madrid1, Natural History Museum2, Centraalbureau voor Schimmelcultures3, University of California, Berkeley4, University of Pretoria5, Ege University6, Louisiana State University7, Trakya University8, Ruhr University Bochum9, Anadolu University10, Landcare Research11, Murdoch University12, Medical University of Graz13, Royal Botanic Gardens14, University of Sydney15, Université catholique de Louvain16, Vienna University of Technology17, University of Nottingham18, University of Miami19, Technical University of Denmark20, Pennsylvania State University21, Leiden University22, Federal University of Paraná23, Canadian Grain Commission24, Wageningen University and Research Centre25, Clark University26, National Academy of Agricultural Sciences27, Field Museum of Natural History28, Istanbul University29, CABI30, University of Tartu31, United States Department of Agriculture32, University of Illinois at Urbana–Champaign33, Mashhad University of Medical Sciences34, Russian Academy of Sciences35, Swedish University of Agricultural Sciences36, Celal Bayar University37, Goethe University Frankfurt38, University of Szeged39, University of Antioquia40
TL;DR: The Amsterdam Declaration on Fungal Nomenclature recognizes the need for an orderly transitition to a single-name nomenclatural system for all fungi, and to provide mechanisms to protect names that otherwise then become endangered.
Abstract: The Amsterdam Declaration on Fungal Nomenclature was agreed at an international symposium convened in Amsterdam on 19–20 April 2011 under the auspices of the International Commission on the Taxonomy of Fungi (ICTF). The purpose of the symposium was to address the issue of whether or how the current system of naming pleomorphic fungi should be maintained or changed now that molecular data are routinely available. The issue is urgent as mycologists currently follow different practices, and no consensus was achieved by a Special Committee appointed in 2005 by the International Botanical Congress to advise on the problem. The Declaration recognizes the need for an orderly transitition to a single-name nomenclatural system for all fungi, and to provide mechanisms to protect names that otherwise then become endangered. That is, meaning that priority should be given to the first described name, except where that is a younger name in general use when the first author to select a name of a pleomorphic monophyletic genus is to be followed, and suggests controversial cases are referred to a body, such as the ICTF, which will report to the Committee for Fungi. If appropriate, the ICTF could be mandated to promote the implementation of the Declaration. In addition, but not forming part of the Declaration, are reports of discussions held during the symposium on the governance of the nomenclature of fungi, and the naming of fungi known only from an environmental nucleic acid sequence in particular. Possible amendments to the Draft BioCode (2011) to allow for the needs of mycologists are suggested for further consideration, and a possible example of how a fungus only known from the environment might be described is presented.
TL;DR: A direct comparison of MEI and SNP diversity levels suggests a differential mobile element insertion rate among populations, and a comprehensive map of 7,380 MEI polymorphisms from the 1000 Genomes Project whole-genome sequencing data is presented.
Abstract: As a consequence of the accumulation of insertion events over evolutionary time, mobile elements now comprise nearly half of the human genome. The Alu, L1, and SVA mobile element families are still duplicating, generating variation between individual genomes. Mobile element insertions (MEI) have been identified as causes for genetic diseases, including hemophilia, neurofibromatosis, and various cancers. Here we present a comprehensive map of 7,380 MEI polymorphisms from the 1000 Genomes Project whole-genome sequencing data of 185 samples in three major populations detected with two detection methods. This catalog enables us to systematically study mutation rates, population segregation, genomic distribution, and functional properties of MEI polymorphisms and to compare MEI to SNP variation from the same individuals. Population allele frequencies of MEI and SNPs are described, broadly, by the same neutral ancestral processes despite vastly different mutation mechanisms and rates, except in coding regions where MEI are virtually absent, presumably due to strong negative selection. A direct comparison of MEI and SNP diversity levels suggests a differential mobile element insertion rate among populations.