The SARS algorithm: detrending CoRoT light curves with Sysrem using simultaneous external parameters

NASA Astrophysics Data System (ADS)

Ofir, Aviv; Alonso, Roi; Bonomo, Aldo Stefano; Carone, Ludmila; Carpano, Stefania; Samuel, Benjamin; Weingrill, Jörg; Aigrain, Suzanne; Auvergne, Michel; Baglin, Annie; Barge, Pierre; Borde, Pascal; Bouchy, Francois; Deeg, Hans J.; Deleuil, Magali; Dvorak, Rudolf; Erikson, Anders; Mello, Sylvio Ferraz; Fridlund, Malcolm; Gillon, Michel; Guillot, Tristan; Hatzes, Artie; Jorda, Laurent; Lammer, Helmut; Leger, Alain; Llebaria, Antoine; Moutou, Claire; Ollivier, Marc; Päetzold, Martin; Queloz, Didier; Rauer, Heike; Rouan, Daniel; Schneider, Jean; Wuchterl, Guenther

2010-05-01

Surveys for exoplanetary transits are usually limited not by photon noise but rather by the amount of red noise in their data. In particular, although the CoRoT space-based survey data are being carefully scrutinized, significant new sources of systematic noises are still being discovered. Recently, a magnitude-dependant systematic effect was discovered in the CoRoT data by Mazeh et al. and a phenomenological correction was proposed. Here we tie the observed effect to a particular type of effect, and in the process generalize the popular Sysrem algorithm to include external parameters in a simultaneous solution with the unknown effects. We show that a post-processing scheme based on this algorithm performs well and indeed allows for the detection of new transit-like signals that were not previously detected.

A Search for Pulsar Companions to OB Runaway Stars

NASA Technical Reports Server (NTRS)

Kaspi, V. M.

1995-01-01

We have searched for radio pulsar companions to 40 nearby OB runaway stars. Observations were made at 474 and 770 MHz with the NRAO 140 ft telescope. The survey was sensitive to long- period pulsars with flux densities of 1 mJy or more. One previously unknown pulsar was discovered, PSRJ2044+4614, while observing towards target O star BD+45,3260. Follow-up timing observations of the pulsar measured its position to high precision, revealing a 9' separation between the pulsar and the target star, unequivocally indicating they are not associated.

Archeological/Environmental Research

NASA Technical Reports Server (NTRS)

1991-01-01

Landsat/Seasat remote sensing was used by Ames Research Center to evaluate environmental influence on ancient Mayan civilization. Over 35 archeological sites were imaged and valuable information concerning Maya settlement patterns, environment, and resource usage resulted. The imagery was also used by Mexican authorities to develop coastal management plans, establish Biosphere Reserves and assess damage from the 1988 Hurricane Gilbert. Imagery showed evidence of ancient coastlines, changes in sea level, an ancient river plain and Mayan canal systems. Previously unknown Mayan reservoirs were discovered. The project is considered a pioneering effort combining remote sensing, environmental studies and archeology.

The Simultaneous Additive and Relative SysRem Algorithm

NASA Astrophysics Data System (ADS)

Ofir, A.

2011-02-01

We present the SARS algorithm, which is a generalization of the popular SysRem detrending technique. This generalization allows including multiple external parameters in a simultaneous solution with the unknown effects. Using SARS allowed us to show that the magnitude-dependant systematic effect discovered by Mazeh et al. (2009) in the CoRoT data is probably caused by an additive -rather than relative- noise source. A post-processing scheme based on SARS performs well and indeed allows for the detection of new transit-like signals that were not previously detected.

The High Time Resolution Universe surveys for pulsars and fast transients

NASA Astrophysics Data System (ADS)

Keith, Michael J.

2013-03-01

The High Time Resolution Universe survey for pulsars and transients is the first truly all-sky pulsar survey, taking place at the Parkes Radio Telescope in Australia and the Effelsberg Radio Telescope in Germany. Utilising multibeam receivers with custom built all-digital recorders the survey targets the fastest millisecond pulsars and radio transients on timescales of 64 μs to a few seconds. The new multibeam digital filter-bank system at has a factor of eight improvement in frequency resolution over previous Parkes multibeam surveys, allowing us to probe further into the Galactic plane for short duration signals. The survey is split into low, mid and high Galactic latitude regions. The mid-latitude portion of the southern hemisphere survey is now completed, discovering 107 previously unknown pulsars, including 26 millisecond pulsars. To date, the total number of discoveries in the combined survey is 135 and 29 MSPs These discoveries include the first magnetar to be discovered by it's radio emission, unusual low-mass binaries, gamma-ray pulsars and pulsars suitable for pulsar timing array experiments.

Lurking in the Shadows: Emerging Rodent Infectious Diseases

PubMed Central

Besselsen, David G.; Franklin, Craig L.; Livingston, Robert S.; Riley, Lela K.

2013-01-01

Rodent parvoviruses, Helicobacter spp., murine norovirus, and several other previously unknown infectious agents have “emerged” in laboratory rodents relatively recently. These agents have been discovered serendipitously or through active investigation of atypical serology results, cell culture contamination, unexpected histopathology, or previously unrecognized clinical disease syndromes. The potential research impact of these agents is not fully known. Infected rodents have demonstrated immunomodulation, tumor suppression, clinical disease (particularly in immunodeficient rodents), and histopathology. Perturbations of organismal and cellular physiology also likely occur. These agents posed unique challenges to laboratory animal resource programs once discovered; it was necessary to develop specific diagnostic assays and an understanding of their epidemiology and transmission routes before attempting eradication, and then evaluate eradication methods for efficacy. Even then management approaches varied significantly, from apathy to total exclusion, and such inconsistency has hindered the sharing and transfer of rodents among institutions, particularly for genetically modified rodent models that may not be readily available. As additional infectious agents are discovered in laboratory rodents in coming years, much of what researchers have learned from experiences with the recently identified pathogens will be applicable. This article provides an overview of the discovery, detection, and research impact of infectious agents recently identified in laboratory rodents. We also discuss emerging syndromes for which there is a suspected infectious etiology, and the unique challenges of managing newly emerging infectious agents. PMID:18506061

PHYSICS OF OUR DAYS: Dark energy and universal antigravitation

NASA Astrophysics Data System (ADS)

Chernin, A. D.

2008-03-01

Universal antigravitation, a new physical phenomenon discovered astronomically at distances of 5 to 8 billion light years, manifests itself as cosmic repulsion that acts between distant galaxies and overcomes their gravitational attraction, resulting in the accelerating expansion of the Universe. The source of the antigravitation is not galaxies or any other bodies of nature but a previously unknown form of mass/energy that has been termed dark energy. Dark energy accounts for 70 to 80% of the total mass and energy of the Universe and, in macroscopic terms, is a kind of continuous medium that fills the entire space of the Universe and is characterized by positive density and negative pressure. With its physical nature and microscopic structure unknown, dark energy is among the most critical challenges fundamental science faces in the twenty-first century.

The Association of Multiple Interacting Genes with Specific Phenotypes in Rice Using Gene Coexpression Networks1[C][W][OA

PubMed Central

Ficklin, Stephen P.; Luo, Feng; Feltus, F. Alex

2010-01-01

Discovering gene sets underlying the expression of a given phenotype is of great importance, as many phenotypes are the result of complex gene-gene interactions. Gene coexpression networks, built using a set of microarray samples as input, can help elucidate tightly coexpressed gene sets (modules) that are mixed with genes of known and unknown function. Functional enrichment analysis of modules further subdivides the coexpressed gene set into cofunctional gene clusters that may coexist in the module with other functionally related gene clusters. In this study, 45 coexpressed gene modules and 76 cofunctional gene clusters were discovered for rice (Oryza sativa) using a global, knowledge-independent paradigm and the combination of two network construction methodologies. Some clusters were enriched for previously characterized mutant phenotypes, providing evidence for specific gene sets (and their annotated molecular functions) that underlie specific phenotypes. PMID:20668062

The association of multiple interacting genes with specific phenotypes in rice using gene coexpression networks.

PubMed

Ficklin, Stephen P; Luo, Feng; Feltus, F Alex

2010-09-01

Discovering gene sets underlying the expression of a given phenotype is of great importance, as many phenotypes are the result of complex gene-gene interactions. Gene coexpression networks, built using a set of microarray samples as input, can help elucidate tightly coexpressed gene sets (modules) that are mixed with genes of known and unknown function. Functional enrichment analysis of modules further subdivides the coexpressed gene set into cofunctional gene clusters that may coexist in the module with other functionally related gene clusters. In this study, 45 coexpressed gene modules and 76 cofunctional gene clusters were discovered for rice (Oryza sativa) using a global, knowledge-independent paradigm and the combination of two network construction methodologies. Some clusters were enriched for previously characterized mutant phenotypes, providing evidence for specific gene sets (and their annotated molecular functions) that underlie specific phenotypes.

Homo naledi, a new species of the genus Homo from the Dinaledi Chamber, South Africa.

PubMed

Berger, Lee R; Hawks, John; de Ruiter, Darryl J; Churchill, Steven E; Schmid, Peter; Delezene, Lucas K; Kivell, Tracy L; Garvin, Heather M; Williams, Scott A; DeSilva, Jeremy M; Skinner, Matthew M; Musiba, Charles M; Cameron, Noel; Holliday, Trenton W; Harcourt-Smith, William; Ackermann, Rebecca R; Bastir, Markus; Bogin, Barry; Bolter, Debra; Brophy, Juliet; Cofran, Zachary D; Congdon, Kimberly A; Deane, Andrew S; Dembo, Mana; Drapeau, Michelle; Elliott, Marina C; Feuerriegel, Elen M; Garcia-Martinez, Daniel; Green, David J; Gurtov, Alia; Irish, Joel D; Kruger, Ashley; Laird, Myra F; Marchi, Damiano; Meyer, Marc R; Nalla, Shahed; Negash, Enquye W; Orr, Caley M; Radovcic, Davorka; Schroeder, Lauren; Scott, Jill E; Throckmorton, Zachary; Tocheri, Matthew W; VanSickle, Caroline; Walker, Christopher S; Wei, Pianpian; Zipfel, Bernhard

2015-09-10

Homo naledi is a previously-unknown species of extinct hominin discovered within the Dinaledi Chamber of the Rising Star cave system, Cradle of Humankind, South Africa. This species is characterized by body mass and stature similar to small-bodied human populations but a small endocranial volume similar to australopiths. Cranial morphology of H. naledi is unique, but most similar to early Homo species including Homo erectus, Homo habilis or Homo rudolfensis. While primitive, the dentition is generally small and simple in occlusal morphology. H. naledi has humanlike manipulatory adaptations of the hand and wrist. It also exhibits a humanlike foot and lower limb. These humanlike aspects are contrasted in the postcrania with a more primitive or australopith-like trunk, shoulder, pelvis and proximal femur. Representing at least 15 individuals with most skeletal elements repeated multiple times, this is the largest assemblage of a single species of hominins yet discovered in Africa.

Fingerprint Stimulated Raman Scattering Imaging Reveals Retinoid Coupling Lipid Metabolism and Survival.

PubMed

Chen, Andy Jing; Li, Junjie; Jannasch, Amber; Ozseker, Sena; Wang, Meng C; Cheng, Ji-Xin

2018-06-17

Retinoids play critical roles in development, immunity and lipid metabolism, and their deficiency leads to various human disorders. Yet, tools for sensing retinoids in vivo are lacking, which limits the understanding of retinoid distribution, dynamics and functions in living organisms. Here, using hyperspectral stimulated Raman scattering microscopy, we discover a previously unknown cytoplasmic store of retinoids in Caenorahbditis elegans. Following the temporal dynamics of retinoids, we reveal that their levels are positively correlated with fat storage, and their supplementation slows down fat loss during dauer starvation. We also discover that retinoids promote fat unsaturation in response to high-glucose stress, and improve organism survival. Together, our studies report a new method for tracking the spatiotemporal dynamics of retinoids in living organisms, and suggest the crucial roles of retinoids in maintaining metabolic homeostasis and enhancing organism fitness upon developmental and dietary stresses. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Allocating monitoring effort in the face of unknown unknowns

USGS Publications Warehouse

Wintle, B.A.; Runge, M.C.; Bekessy, S.A.

2010-01-01

There is a growing view that to make efficient use of resources, ecological monitoring should be hypothesis-driven and targeted to address specific management questions. 'Targeted' monitoring has been contrasted with other approaches in which a range of quantities are monitored in case they exhibit an alarming trend or provide ad hoc ecological insights. The second form of monitoring, described as surveillance, has been criticized because it does not usually aim to discern between competing hypotheses, and its benefits are harder to identify a priori. The alternative view is that the existence of surveillance data may enable rapid corroboration of emerging hypotheses or help to detect important 'unknown unknowns' that, if undetected, could lead to catastrophic outcomes or missed opportunities. We derive a model to evaluate and compare the efficiency of investments in surveillance and targeted monitoring. We find that a decision to invest in surveillance monitoring may be defensible if: (1) the surveillance design is more likely to discover or corroborate previously unknown phenomena than a targeted design and (2) the expected benefits (or avoided costs) arising from discovery are substantially higher than those arising from a well-planned targeted design. Our examination highlights the importance of being explicit about the objectives, costs and expected benefits of monitoring in a decision analytic framework. ?? 2010 Blackwell Publishing Ltd/CNRS.

Systems immunology: just getting started.

PubMed

Davis, Mark M; Tato, Cristina M; Furman, David

2017-06-20

Systems-biology approaches in immunology take various forms, but here we review strategies for measuring a broad swath of immunological functions as a means of discovering previously unknown relationships and phenomena and as a powerful way of understanding the immune system as a whole. This approach has rejuvenated the field of vaccine development and has fostered hope that new ways will be found to combat infectious diseases that have proven refractory to classical approaches. Systems immunology also presents an important new strategy for understanding human immunity directly, taking advantage of the many ways the immune system of humans can be manipulated.

Systems immunology: just getting started

PubMed Central

Davis, Mark M; Tato, Cristina M; Furman, David

2018-01-01

Systems-biology approaches in immunology take various forms, but here we review strategies for measuring a broad swath of immunological functions as a means of discovering previously unknown relationships and phenomena and as a powerful way of understanding the immune system as a whole. This approach has rejuvenated the field of vaccine development and has fostered hope that new ways will be found to combat infectious diseases that have proven refractory to classical approaches. Systems immunology also presents an important new strategy for understanding human immunity directly, taking advantage of the many ways the immune system of humans can be manipulated. PMID:28632713

Close Binaries in the η Chamaeleontis Cluster

NASA Astrophysics Data System (ADS)

Köhler, Rainer; Petr-Gotzens, Monika G.

2002-11-01

We have used speckle interferometry and adaptive optics observations to search for multiple systems among 13 stars in the η Chamaeleontis cluster. We discovered two previously unknown subarcsecond binaries. Placing the components in infrared color-magnitude diagrams shows that most members of η Cha are coeval. Repeated observations of the binary RECX 1 allow us to determine a preliminary orbit and derive a system mass of about 2 Msolar. Based on observations obtained at the European Southern Observatory, La Silla, proposals 56.E-0197, 62.I-0399, 65.I-0350, 65.I-0086, 67.C-0354, and 68.C-0539.

NEWLY DISCOVERED PLANETS ORBITING HD 5319, HD 11506, HD 75784 AND HD 10442 FROM THE N2K CONSORTIUM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giguere, Matthew J.; Fischer, Debra A.; Brewer, John M.

2015-01-20

Initially designed to discover short-period planets, the N2K campaign has since evolved to discover new worlds at large separations from their host stars. Detecting such worlds will help determine the giant planet occurrence at semi-major axes beyond the ice line, where gas giants are thought to mostly form. Here we report four newly discovered gas giant planets (with minimum masses ranging from 0.4 to 2.1 M {sub Jup}) orbiting stars monitored as part of the Next 2000 target stars (N2K) Doppler Survey program. Two of these planets orbit stars already known to host planets: HD 5319 and HD 11506. Themore » remaining discoveries reside in previously unknown planetary systems: HD 10442 and HD 75784. The refined orbital period of the inner planet orbiting HD 5319 is 641 days. The newly discovered outer planet orbits in 886 days. The large masses combined with the proximity to a 4:3 mean motion resonance make this system a challenge to explain with current formation and migration theories. HD 11506 has one confirmed planet, and here we confirm a second. The outer planet has an orbital period of 1627.5 days, and the newly discovered inner planet orbits in 223.6 days. A planet has also been discovered orbiting HD 75784 with an orbital period of 341.7 days. There is evidence for a longer period signal; however, several more years of observations are needed to put tight constraints on the Keplerian parameters for the outer planet. Lastly, an additional planet has been detected orbiting HD 10442 with a period of 1043 days.« less

An aposymbiotic primary coral polyp counteracts acidification by active pH regulation

NASA Astrophysics Data System (ADS)

Ohno, Yoshikazu; Iguchi, Akira; Shinzato, Chuya; Inoue, Mayuri; Suzuki, Atsushi; Sakai, Kazuhiko; Nakamura, Takashi

2017-01-01

Corals build their skeletons using extracellular calcifying fluid located in the tissue-skeleton interface. However, the mechanism by which corals control the transport of calcium and other ions from seawater and the mechanism of constant alkalization of calcifying fluid are largely unknown. To address these questions, we performed direct pH imaging at calcification sites (subcalicoblastic medium, SCM) to visualize active pH upregulation in live aposymbiotic primary coral polyps treated with HCl-acidified seawater. Active alkalization was observed in all individuals using vital staining method while the movement of HPTS and Alexa Fluor to SCM suggests that certain ions such as H+ could diffuse via a paracellular pathway to SCM. Among them, we discovered acid-induced oscillations in the pH of SCM (pHSCM), observed in 24% of polyps examined. In addition, we discovered acid-induced pH up-regulation waves in 21% of polyps examined, which propagated among SCMs after exposure to acidified seawater. Our results showed that corals can regulate pHSCM more dynamically than was previously believed. These observations will have important implications for determining how corals regulate pHSCM during calcification. We propose that corals can sense ambient seawater pH via their innate pH-sensitive systems and regulate pHSCM using several unknown pH-regulating ion transporters that coordinate with multicellular signaling occurring in coral tissue.

Albus 1: A Very Bright White Dwarf Candidate

NASA Astrophysics Data System (ADS)

Caballero, José Antonio; Solano, Enrique

2007-08-01

We have serendipitously discovered a previously unknown, bright source (BT=11.75+/-0.07 mag) with a very blue VT-Ks color, which we have named Albus 1. A photometric and astrometric study using Virtual Observatory tools has shown that it possesses an appreciable proper motion and magnitudes and colors very similar to those of the well-known white dwarf G191-B2B. We consider Albus 1 as a DA-type white dwarf located at about 40 pc. If its nature is confirmed, Albus 1 would be the sixth brightest isolated white dwarf in the sky, which would make it an excellent spectrophotometric standard.

WISE Observations of Comets, Centaurs, & Scattered Disk Objects

NASA Technical Reports Server (NTRS)

Bauer, J.; Walker, R.; Mainzer, A.; Masiero, J.; Grav, T.; Cutri, R.; Dailey, J.; McMillan, R.; Lisse, C. M.; Fernandez, Y. R.;

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

PubMed

Cordell, Heather J; Han, Younghun; Mells, George F; Li, Yafang; Hirschfield, Gideon M; Greene, Casey S; Xie, Gang; Juran, Brian D; Zhu, Dakai; Qian, David C; Floyd, James A B; Morley, Katherine I; Prati, Daniele; Lleo, Ana; Cusi, Daniele; Gershwin, M Eric; Anderson, Carl A; Lazaridis, Konstantinos N; Invernizzi, Pietro; Seldin, Michael F; Sandford, Richard N; Amos, Christopher I; Siminovitch, Katherine A

2015-09-22

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.

Spiroplasma Symbiont of the Pea Aphid, Acyrthosiphon pisum (Insecta: Homoptera)

PubMed Central

Fukatsu, Takema; Tsuchida, Tsutomu; Nikoh, Naruo; Koga, Ryuichi

2001-01-01

From a laboratory strain of the pea aphid, Acyrthosiphon pisum, we discovered a previously unknown facultative endosymbiotic bacterium. Molecular phylogenetic analysis based on 16S ribosomal DNA revealed that the bacterium is a member of the genus Spiroplasma. The Spiroplasma organism showed stable vertical transmission through successive generations of the host. Injection of hemolymph from infected insects into uninfected insects established a stable infection in the recipients. The Spiroplasma symbiont exhibited negative effects on growth, reproduction, and longevity of the host, particularly in older adults. Of 58 clonal strains of A. pisum established from natural populations in central Japan, 4 strains possessed the Spiroplasma organism. PMID:11229923

Homo naledi, a new species of the genus Homo from the Dinaledi Chamber, South Africa

PubMed Central

Berger, Lee R; Hawks, John; de Ruiter, Darryl J; Churchill, Steven E; Schmid, Peter; Delezene, Lucas K; Kivell, Tracy L; Garvin, Heather M; Williams, Scott A; DeSilva, Jeremy M; Skinner, Matthew M; Musiba, Charles M; Cameron, Noel; Holliday, Trenton W; Harcourt-Smith, William; Ackermann, Rebecca R; Bastir, Markus; Bogin, Barry; Bolter, Debra; Brophy, Juliet; Cofran, Zachary D; Congdon, Kimberly A; Deane, Andrew S; Dembo, Mana; Drapeau, Michelle; Elliott, Marina C; Feuerriegel, Elen M; Garcia-Martinez, Daniel; Green, David J; Gurtov, Alia; Irish, Joel D; Kruger, Ashley; Laird, Myra F; Marchi, Damiano; Meyer, Marc R; Nalla, Shahed; Negash, Enquye W; Orr, Caley M; Radovcic, Davorka; Schroeder, Lauren; Scott, Jill E; Throckmorton, Zachary; Tocheri, Matthew W; VanSickle, Caroline; Walker, Christopher S; Wei, Pianpian; Zipfel, Bernhard

2015-01-01

Homo naledi is a previously-unknown species of extinct hominin discovered within the Dinaledi Chamber of the Rising Star cave system, Cradle of Humankind, South Africa. This species is characterized by body mass and stature similar to small-bodied human populations but a small endocranial volume similar to australopiths. Cranial morphology of H. naledi is unique, but most similar to early Homo species including Homo erectus, Homo habilis or Homo rudolfensis. While primitive, the dentition is generally small and simple in occlusal morphology. H. naledi has humanlike manipulatory adaptations of the hand and wrist. It also exhibits a humanlike foot and lower limb. These humanlike aspects are contrasted in the postcrania with a more primitive or australopith-like trunk, shoulder, pelvis and proximal femur. Representing at least 15 individuals with most skeletal elements repeated multiple times, this is the largest assemblage of a single species of hominins yet discovered in Africa. DOI: http://dx.doi.org/10.7554/eLife.09560.001 PMID:26354291

Cell-specific gain modulation by synaptically released zinc in cortical circuits of audition.

PubMed

Anderson, Charles T; Kumar, Manoj; Xiong, Shanshan; Tzounopoulos, Thanos

2017-09-09

In many excitatory synapses, mobile zinc is found within glutamatergic vesicles and is coreleased with glutamate. Ex vivo studies established that synaptically released (synaptic) zinc inhibits excitatory neurotransmission at lower frequencies of synaptic activity but enhances steady state synaptic responses during higher frequencies of activity. However, it remains unknown how synaptic zinc affects neuronal processing in vivo. Here, we imaged the sound-evoked neuronal activity of the primary auditory cortex in awake mice. We discovered that synaptic zinc enhanced the gain of sound-evoked responses in CaMKII-expressing principal neurons, but it reduced the gain of parvalbumin- and somatostatin-expressing interneurons. This modulation was sound intensity-dependent and, in part, NMDA receptor-independent. By establishing a previously unknown link between synaptic zinc and gain control of auditory cortical processing, our findings advance understanding about cortical synaptic mechanisms and create a new framework for approaching and interpreting the role of the auditory cortex in sound processing.

Caryolan-1-ol, an antifungal volatile produced by Streptomyces spp., inhibits the endomembrane system of fungi.

PubMed

Cho, Gyeongjun; Kim, Junheon; Park, Chung Gyoo; Nislow, Corey; Weller, David M; Kwak, Youn-Sig

2017-07-01

Streptomyces spp. have the ability to produce a wide variety of secondary metabolites that interact with the environment. This study aimed to discover antifungal volatiles from the genus Streptomyces and to determine the mechanisms of inhibition. Volatiles identified from Streptomyces spp. included three major terpenes, geosmin, caryolan-1-ol and an unknown sesquiterpene. antiSMASH and KEGG predicted that the volatile terpene synthase gene clusters occur in the Streptomyces genome. Growth inhibition was observed when fungi were exposed to the volatiles. Biological activity of caryolan-1-ol has previously not been investigated. Fungal growth was inhibited in a dose-dependent manner by a mixture of the main volatiles, caryolan-1-ol and the unknown sesquiterpene, from Streptomyces sp. S4-7. Furthermore, synthesized caryolan-1-ol showed similar antifungal activity. Results of chemical-genomics profiling assays showed that caryolan-1-ol affected the endomembrane system by disrupting sphingolipid synthesis and normal vesicle trafficking in the fungi. © 2017 The Authors.

Kanyawara Virus: A Novel Rhabdovirus Infecting Newly Discovered Nycteribiid Bat Flies Infesting Previously Unknown Pteropodid Bats in Uganda.

PubMed

Goldberg, Tony L; Bennett, Andrew J; Kityo, Robert; Kuhn, Jens H; Chapman, Colin A

2017-07-13

Bats are natural reservoir hosts of highly virulent pathogens such as Marburg virus, Nipah virus, and SARS coronavirus. However, little is known about the role of bat ectoparasites in transmitting and maintaining such viruses. The intricate relationship between bats and their ectoparasites suggests that ectoparasites might serve as viral vectors, but evidence to date is scant. Bat flies, in particular, are highly specialized obligate hematophagous ectoparasites that incidentally bite humans. Using next-generation sequencing, we discovered a novel ledantevirus (mononegaviral family Rhabdoviridae, genus Ledantevirus) in nycteribiid bat flies infesting pteropodid bats in western Uganda. Mitochondrial DNA analyses revealed that both the bat flies and their bat hosts belong to putative new species. The coding-complete genome of the new virus, named Kanyawara virus (KYAV), is only distantly related to that of its closest known relative, Mount Elgon bat virus, and was found at high titers in bat flies but not in blood or on mucosal surfaces of host bats. Viral genome analysis indicates unusually low CpG dinucleotide depletion in KYAV compared to other ledanteviruses and rhabdovirus groups, with KYAV displaying values similar to rhabdoviruses of arthropods. Our findings highlight the possibility of a yet-to-be-discovered diversity of potentially pathogenic viruses in bat ectoparasites.

Footprint of Deepwater Horizon blowout impact to deep-water coral communities

PubMed Central

Fisher, Charles R.; Hsing, Pen-Yuan; Kaiser, Carl L.; Yoerger, Dana R.; Roberts, Harry H.; Shedd, William W.; Cordes, Erik E.; Shank, Timothy M.; Berlet, Samantha P.; Saunders, Miles G.; Larcom, Elizabeth A.; Brooks, James M.

2014-01-01

On April 20, 2010, the Deepwater Horizon (DWH) blowout occurred, releasing more oil than any accidental spill in history. Oil release continued for 87 d and much of the oil and gas remained in, or returned to, the deep sea. A coral community significantly impacted by the spill was discovered in late 2010 at 1,370 m depth. Here we describe the discovery of five previously unknown coral communities near the Macondo wellhead and show that at least two additional coral communities were impacted by the spill. Although the oil-containing flocullent material that was present on corals when the first impacted community was discovered was largely gone, a characteristic patchy covering of hydrozoans on dead portions of the skeleton allowed recognition of impacted colonies at the more recently discovered sites. One of these communities was 6 km south of the Macondo wellhead and over 90% of the corals present showed the characteristic signs of recent impact. The other community, 22 km southeast of the wellhead between 1,850 and 1,950 m depth, was more lightly impacted. However, the discovery of this site considerably extends the distance from Macondo and depth range of significant impact to benthic macrofaunal communities. We also show that most known deep-water coral communities in the Gulf of Mexico do not appear to have been acutely impacted by the spill, although two of the newly discovered communities near the wellhead apparently not impacted by the spill have been impacted by deep-sea fishing operations. PMID:25071200

First record of Streptosyllis nunezi Faulwetter et al., 2008 (Annelida, Syllidae) from the United Kingdom, and amendment to the genus Streptosyllis Webster & Benedict, 1884.

PubMed

Musk, Will; Faulwetter, Sarah; McIlwaine, Paul

2016-01-01

During a benthic survey of a Marine Conservation Zone located on the Skerries Bank in the English Channel off the south-west coast of England, three specimens of Streptosyllis nunezi Faulwetter et al., 2008 were found. This is the second ever record of the species after its original description, and the first record from waters around the U.K. and a significant northerly range extension for a species previously only recorded from the Canary Islands and the Mediterranean Sea. A single simple ventral chaeta in each of the two posterior-most segments was discovered in this and two other species of Streptosyllis Webster & Benedict, 1884. The generic definition of Streptosyllis is emended to include this feature previously unknown for the genus, and an updated key to the Streptosyllis found in UK waters is provided.

Generating perfect fluid spheres in general relativity

NASA Astrophysics Data System (ADS)

Boonserm, Petarpa; Visser, Matt; Weinfurtner, Silke

2005-06-01

Ever since Karl Schwarzschild’s 1916 discovery of the spacetime geometry describing the interior of a particular idealized general relativistic star—a static spherically symmetric blob of fluid with position-independent density—the general relativity community has continued to devote considerable time and energy to understanding the general-relativistic static perfect fluid sphere. Over the last 90 years a tangle of specific perfect fluid spheres has been discovered, with most of these specific examples seemingly independent from each other. To bring some order to this collection, in this article we develop several new transformation theorems that map perfect fluid spheres into perfect fluid spheres. These transformation theorems sometimes lead to unexpected connections between previously known perfect fluid spheres, sometimes lead to new previously unknown perfect fluid spheres, and in general can be used to develop a systematic way of classifying the set of all perfect fluid spheres.

GraphTeams: a method for discovering spatial gene clusters in Hi-C sequencing data.

PubMed

Schulz, Tizian; Stoye, Jens; Doerr, Daniel

2018-05-08

Hi-C sequencing offers novel, cost-effective means to study the spatial conformation of chromosomes. We use data obtained from Hi-C experiments to provide new evidence for the existence of spatial gene clusters. These are sets of genes with associated functionality that exhibit close proximity to each other in the spatial conformation of chromosomes across several related species. We present the first gene cluster model capable of handling spatial data. Our model generalizes a popular computational model for gene cluster prediction, called δ-teams, from sequences to graphs. Following previous lines of research, we subsequently extend our model to allow for several vertices being associated with the same label. The model, called δ-teams with families, is particular suitable for our application as it enables handling of gene duplicates. We develop algorithmic solutions for both models. We implemented the algorithm for discovering δ-teams with families and integrated it into a fully automated workflow for discovering gene clusters in Hi-C data, called GraphTeams. We applied it to human and mouse data to find intra- and interchromosomal gene cluster candidates. The results include intrachromosomal clusters that seem to exhibit a closer proximity in space than on their chromosomal DNA sequence. We further discovered interchromosomal gene clusters that contain genes from different chromosomes within the human genome, but are located on a single chromosome in mouse. By identifying δ-teams with families, we provide a flexible model to discover gene cluster candidates in Hi-C data. Our analysis of Hi-C data from human and mouse reveals several known gene clusters (thus validating our approach), but also few sparsely studied or possibly unknown gene cluster candidates that could be the source of further experimental investigations.

The chemistry of poisons in amphibian skin.

PubMed Central

Daly, J W

1995-01-01

Poisons are common in nature, where they often serve the organism in chemical defense. Such poisons either are produced de novo or are sequestered from dietary sources or symbiotic organisms. Among vertebrates, amphibians are notable for the wide range of noxious agents that are contained in granular skin glands. These compounds include amines, peptides, proteins, steroids, and both water-soluble and lipid-soluble alkaloids. With the exception of the alkaloids, most seem to be produced de novo by the amphibian. The skin of amphibians contains many structural classes of alkaloids previously unknown in nature. These include the batrachotoxins, which have recently been discovered to also occur in skin and feathers of a bird, the histrionicotoxins, the gephyrotoxins, the decahydroquinolines, the pumiliotoxins and homopumiliotoxins, epibatidine, and the samandarines. Some amphibian skin alkaloids are clearly sequestered from the diet, which consists mainly of small arthropods. These include pyrrolizidine and indolizidine alkaloids from ants, tricyclic coccinellines from beetles, and pyrrolizidine oximes, presumably from millipedes. The sources of other alkaloids in amphibian skin, including the batrachotoxins, the decahydroquinolines, the histrionicotoxins, the pumiliotoxins, and epibatidine, are unknown. While it is possible that these are produced de novo or by symbiotic microorganisms, it appears more likely that they are sequestered by the amphibians from as yet unknown dietary sources. PMID:7816854

Use of satellite data in volcano monitoring

NASA Technical Reports Server (NTRS)

Mcclelland, Lindsay

1987-01-01

It is argued that Total Ozone Mapping Spectrometer (TOMS) data, especially data on sulfur dioxide detection in volcanic clouds, and weather satellite data complement each other. TOMS data is most useful for discovering previously unknown eruptions and indicating a minimum volume of SO sub 2 produced by a given eruption. Once an eruption has been reported, weather satellite data can be used to accurately monitor its progress. To be used effectively, these data need to be analyzed jointly and in real time. Toward this end, it is hoped that full and timely utilization can be made of existing TOMS data, a polar orbiting TOMS can be launched in the near future, and that TOMS type instruments can be included on future geostationary satellites.

Exceptional Solar-System Objects

NASA Astrophysics Data System (ADS)

Zellner, Benjamin

1990-12-01

This is a target-of-opportunity proposal for HST observations to be executed if a previously unknown, truly exceptional solar-system object or phenomenon is discovered either in the normal course of HST work or by anyone, anywhere. Trails due to unknown moving objects will often appear on HST images made for other purposes. A short trail seen near the opposition point or at high ecliptic latitude could represent a major addition to our knowledge of the solar system. Thus we further propose that all short trials seen on HST images taken in favorable regions of the sky be given a quick analysis in the Observation Support System for their possible significance. If an unusual object is found we propose to: (1) Seek from the owner of data rights permission to proceed as may be appropriate; (2) Contact the Minor Planet Center for an evaluation of the significance of the discovery; and (3) For an object that appears to be of great significance where effective groundbased followup appears unlikely, request the HST schedule be replanned for followup images and physical studies using HST.

PROPOSED SIAM PROBLEM

DOE Office of Scientific and Technical Information (OSTI.GOV)

BAILEY, DAVID H.; BORWEIN, JONATHAN M.

A recent paper by the present authors, together with mathematical physicists David Broadhurst and M. Larry Glasser, explored Bessel moment integrals, namely definite integrals of the general form {integral}{sub 0}{sup {infinity}} t{sup m}f{sup n}(t) dt, where the function f(t) is one of the classical Bessel functions. In that paper, numerous previously unknown analytic evaluations were obtained, using a combination of analytic methods together with some fairly high-powered numerical computations, often performed on highly parallel computers. In several instances, while we were able to numerically discover what appears to be a solid analytic identity, based on extremely high-precision numerical computations, wemore » were unable to find a rigorous proof. Thus we present here a brief list of some of these unproven but numerically confirmed identities.« less

REMOTE-SENSING MINERAL DISCOVERIES IN THE MOJAVE DESERT OF CALIFORNIA.

USGS Publications Warehouse

Raines, Gary L.; Hoover, Donald B.; Collins, William E.

1984-01-01

As a result of remote sensing studies in the Mojave Desert of California three previously unknown stockwork molybdenum systems have been discovered. It is not known if economic deposits of molybdenum and associated minerals occur in these areas; there is, however, sufficient data to judge that these areas are worthy of further exploration. The purpose of this paper is to present case histories of two of these discoveries. These discoveries have been made from laboratory analyses of Landsat multispectral scanner images to map limonitic materials and from field reconnaissance to determine if the limonite is due to hydrothermal alteration. In those areas that seemed most promising, airborne spectrometer surveys were employed to mapped Al-OH minerals, and audio-magnetotelluric (AMT) and telluric-traversing surveys were performed to obtain information at depth.

Genomic minimalism in the early diverging intestinal parasite Giardia lamblia.

PubMed

Morrison, Hilary G; McArthur, Andrew G; Gillin, Frances D; Aley, Stephen B; Adam, Rodney D; Olsen, Gary J; Best, Aaron A; Cande, W Zacheus; Chen, Feng; Cipriano, Michael J; Davids, Barbara J; Dawson, Scott C; Elmendorf, Heidi G; Hehl, Adrian B; Holder, Michael E; Huse, Susan M; Kim, Ulandt U; Lasek-Nesselquist, Erica; Manning, Gerard; Nigam, Anuranjini; Nixon, Julie E J; Palm, Daniel; Passamaneck, Nora E; Prabhu, Anjali; Reich, Claudia I; Reiner, David S; Samuelson, John; Svard, Staffan G; Sogin, Mitchell L

2007-09-28

The genome of the eukaryotic protist Giardia lamblia, an important human intestinal parasite, is compact in structure and content, contains few introns or mitochondrial relics, and has simplified machinery for DNA replication, transcription, RNA processing, and most metabolic pathways. Protein kinases comprise the single largest protein class and reflect Giardia's requirement for a complex signal transduction network for coordinating differentiation. Lateral gene transfer from bacterial and archaeal donors has shaped Giardia's genome, and previously unknown gene families, for example, cysteine-rich structural proteins, have been discovered. Unexpectedly, the genome shows little evidence of heterozygosity, supporting recent speculations that this organism is sexual. This genome sequence will not only be valuable for investigating the evolution of eukaryotes, but will also be applied to the search for new therapeutics for this parasite.

Understanding Quality Factor Degradation in Superconducting Niobium Cavities at Low Microwave Field Amplitudes

DOE PAGES

Romanenko, A.; Schuster, D. I.

2017-12-28

In niobium superconducting radio frequency (SRF) cavities for particle acceleration, a decrease of the quality factor at lower fields—a so-called low field Q slope or LFQS—has been a long-standing unexplained effect. By extending the high Q measurement techniques to ultralow fields, we discover two previously unknown features of the effect: (i) saturation at rf fields lower than E acc~0.1 MV/m; (ii) strong degradation enhancement by growing thicker niobium pentoxide. Our findings suggest that the LFQS may be caused by the two level systems in the natural niobium oxide on the inner cavity surface, thereby identifying a new source of residual resistance andmore » providing guidance for potential nonaccelerator low-field applications of SRF cavities.« less

Reliable Acquisition of RAM Dumps from Intel-Based Apple Mac Computers over FireWire

NASA Astrophysics Data System (ADS)

Gladyshev, Pavel; Almansoori, Afrah

RAM content acquisition is an important step in live forensic analysis of computer systems. FireWire offers an attractive way to acquire RAM content of Apple Mac computers equipped with a FireWire connection. However, the existing techniques for doing so require substantial knowledge of the target computer configuration and cannot be used reliably on a previously unknown computer in a crime scene. This paper proposes a novel method for acquiring RAM content of Apple Mac computers over FireWire, which automatically discovers necessary information about the target computer and can be used in the crime scene setting. As an application of the developed method, the techniques for recovery of AOL Instant Messenger (AIM) conversation fragments from RAM dumps are also discussed in this paper.

Understanding Quality Factor Degradation in Superconducting Niobium Cavities at Low Microwave Field Amplitudes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Romanenko, A.; Schuster, D. I.

In niobium superconducting radio frequency (SRF) cavities for particle acceleration, a decrease of the quality factor at lower fields—a so-called low field Q slope or LFQS—has been a long-standing unexplained effect. By extending the high Q measurement techniques to ultralow fields, we discover two previously unknown features of the effect: (i) saturation at rf fields lower than E acc~0.1 MV/m; (ii) strong degradation enhancement by growing thicker niobium pentoxide. Our findings suggest that the LFQS may be caused by the two level systems in the natural niobium oxide on the inner cavity surface, thereby identifying a new source of residual resistance andmore » providing guidance for potential nonaccelerator low-field applications of SRF cavities.« less

Prior knowledge driven Granger causality analysis on gene regulatory network discovery

DOE PAGES

Yao, Shun; Yoo, Shinjae; Yu, Dantong

2015-08-28

Our study focuses on discovering gene regulatory networks from time series gene expression data using the Granger causality (GC) model. However, the number of available time points (T) usually is much smaller than the number of target genes (n) in biological datasets. The widely applied pairwise GC model (PGC) and other regularization strategies can lead to a significant number of false identifications when n>>T. In this study, we proposed a new method, viz., CGC-2SPR (CGC using two-step prior Ridge regularization) to resolve the problem by incorporating prior biological knowledge about a target gene data set. In our simulation experiments, themore » propose new methodology CGC-2SPR showed significant performance improvement in terms of accuracy over other widely used GC modeling (PGC, Ridge and Lasso) and MI-based (MRNET and ARACNE) methods. In addition, we applied CGC-2SPR to a real biological dataset, i.e., the yeast metabolic cycle, and discovered more true positive edges with CGC-2SPR than with the other existing methods. In our research, we noticed a “ 1+1>2” effect when we combined prior knowledge and gene expression data to discover regulatory networks. Based on causality networks, we made a functional prediction that the Abm1 gene (its functions previously were unknown) might be related to the yeast’s responses to different levels of glucose. In conclusion, our research improves causality modeling by combining heterogeneous knowledge, which is well aligned with the future direction in system biology. Furthermore, we proposed a method of Monte Carlo significance estimation (MCSE) to calculate the edge significances which provide statistical meanings to the discovered causality networks. All of our data and source codes will be available under the link https://bitbucket.org/dtyu/granger-causality/wiki/Home.« less

Hydrothermal vent fields discovered in the southern Gulf of California clarify role of habitat in augmenting regional diversity

PubMed Central

Johnson, Shannon; Tunnicliffe, Verena; Caress, David; Clague, David; Escobar, Elva; Lundsten, Lonny; Paduan, Jennifer B.; Rouse, Greg; Salcedo, Diana L.; Soto, Luis A.; Zierenberg, Robert; Vrijenhoek, Robert

2017-01-01

Hydrothermal vent communities are distributed along mid-ocean spreading ridges as isolated patches. While distance is a key factor influencing connectivity among sites, habitat characteristics are also critical. The Pescadero Basin (PB) and Alarcón Rise (AR) vent fields, recently discovered in the southern Gulf of California, are bounded by previously known vent localities (e.g. Guaymas Basin and 21° N East Pacific Rise); yet, the newly discovered vents differ markedly in substrata and vent fluid attributes. Out of 116 macrofaunal species observed or collected, only three species are shared among all four vent fields, while 73 occur at only one locality. Foundation species at basalt-hosted sulfide chimneys on the AR differ from the functional equivalents inhabiting sediment-hosted carbonate chimneys in the PB, only 75 km away. The dominant species of symbiont-hosting tubeworms and clams, and peripheral suspension-feeding taxa, differ between the sites. Notably, the PB vents host a limited and specialized fauna in which 17 of 26 species are unknown at other regional vents and many are new species. Rare sightings and captured larvae of the ‘missing’ species revealed that dispersal limitation is not responsible for differences in community composition at the neighbouring vent localities. Instead, larval recruitment-limiting habitat suitability probably favours species differentially. As scenarios develop to design conservation strategies around mining of seafloor sulfide deposits, these results illustrate that models encompassing habitat characteristics are needed to predict metacommunity structure. PMID:28724734

Hydrothermal vent fields discovered in the southern Gulf of California clarify role of habitat in augmenting regional diversity.

PubMed

Goffredi, Shana K; Johnson, Shannon; Tunnicliffe, Verena; Caress, David; Clague, David; Escobar, Elva; Lundsten, Lonny; Paduan, Jennifer B; Rouse, Greg; Salcedo, Diana L; Soto, Luis A; Spelz-Madero, Ronald; Zierenberg, Robert; Vrijenhoek, Robert

2017-07-26

Hydrothermal vent communities are distributed along mid-ocean spreading ridges as isolated patches. While distance is a key factor influencing connectivity among sites, habitat characteristics are also critical. The Pescadero Basin (PB) and Alarcón Rise (AR) vent fields, recently discovered in the southern Gulf of California, are bounded by previously known vent localities (e.g. Guaymas Basin and 21° N East Pacific Rise); yet, the newly discovered vents differ markedly in substrata and vent fluid attributes. Out of 116 macrofaunal species observed or collected, only three species are shared among all four vent fields, while 73 occur at only one locality. Foundation species at basalt-hosted sulfide chimneys on the AR differ from the functional equivalents inhabiting sediment-hosted carbonate chimneys in the PB, only 75 km away. The dominant species of symbiont-hosting tubeworms and clams, and peripheral suspension-feeding taxa, differ between the sites. Notably, the PB vents host a limited and specialized fauna in which 17 of 26 species are unknown at other regional vents and many are new species. Rare sightings and captured larvae of the 'missing' species revealed that dispersal limitation is not responsible for differences in community composition at the neighbouring vent localities. Instead, larval recruitment-limiting habitat suitability probably favours species differentially. As scenarios develop to design conservation strategies around mining of seafloor sulfide deposits, these results illustrate that models encompassing habitat characteristics are needed to predict metacommunity structure. © 2017 The Authors.

Identifying Drug-Drug Interactions by Data Mining: A Pilot Study of Warfarin-Associated Drug Interactions.

PubMed

Hansen, Peter Wæde; Clemmensen, Line; Sehested, Thomas S G; Fosbøl, Emil Loldrup; Torp-Pedersen, Christian; Køber, Lars; Gislason, Gunnar H; Andersson, Charlotte

2016-11-01

Knowledge about drug-drug interactions commonly arises from preclinical trials, from adverse drug reports, or based on knowledge of mechanisms of action. Our aim was to investigate whether drug-drug interactions were discoverable without prior hypotheses using data mining. We focused on warfarin-drug interactions as the prototype. We analyzed altered prothrombin time (measured as international normalized ratio [INR]) after initiation of a novel prescription in previously INR-stable warfarin-treated patients with nonvalvular atrial fibrillation. Data sets were retrieved from clinical work. Random forest (a machine-learning method) was set up to predict altered INR levels after novel prescriptions. The most important drug groups from the analysis were further investigated using logistic regression in a new data set. Two hundred and twenty drug groups were analyzed in 61 190 novel prescriptions. We rediscovered 2 drug groups having known interactions (β-lactamase-resistant penicillins [dicloxacillin] and carboxamide derivatives) and 3 antithrombotic/anticoagulant agents (platelet aggregation inhibitors excluding heparin, direct thrombin inhibitors [dabigatran etexilate], and heparins) causing decreasing INR. Six drug groups with known interactions were rediscovered causing increasing INR (antiarrhythmics class III [amiodarone], other opioids [tramadol], glucocorticoids, triazole derivatives, and combinations of penicillins, including β-lactamase inhibitors) and two had a known interaction in a closely related drug group (oripavine derivatives [buprenorphine] and natural opium alkaloids). Antipropulsives had an unknown signal of increasing INR. We were able to identify known warfarin-drug interactions without a prior hypothesis using clinical registries. Additionally, we discovered a few potentially novel interactions. This opens up for the use of data mining to discover unknown drug-drug interactions in cardiovascular medicine. © 2016 American Heart Association, Inc.

Protein function prediction using neighbor relativity in protein-protein interaction network.

PubMed

Moosavi, Sobhan; Rahgozar, Masoud; Rahimi, Amir

2013-04-01

There is a large gap between the number of discovered proteins and the number of functionally annotated ones. Due to the high cost of determining protein function by wet-lab research, function prediction has become a major task for computational biology and bioinformatics. Some researches utilize the proteins interaction information to predict function for un-annotated proteins. In this paper, we propose a novel approach called "Neighbor Relativity Coefficient" (NRC) based on interaction network topology which estimates the functional similarity between two proteins. NRC is calculated for each pair of proteins based on their graph-based features including distance, common neighbors and the number of paths between them. In order to ascribe function to an un-annotated protein, NRC estimates a weight for each neighbor to transfer its annotation to the unknown protein. Finally, the unknown protein will be annotated by the top score transferred functions. We also investigate the effect of using different coefficients for various types of functions. The proposed method has been evaluated on Saccharomyces cerevisiae and Homo sapiens interaction networks. The performance analysis demonstrates that NRC yields better results in comparison with previous protein function prediction approaches that utilize interaction network. Copyright © 2012 Elsevier Ltd. All rights reserved.

Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes.

PubMed

Malik, Rainer; Chauhan, Ganesh; Traylor, Matthew; Sargurupremraj, Muralidharan; Okada, Yukinori; Mishra, Aniket; Rutten-Jacobs, Loes; Giese, Anne-Katrin; van der Laan, Sander W; Gretarsdottir, Solveig; Anderson, Christopher D; Chong, Michael; Adams, Hieab H H; Ago, Tetsuro; Almgren, Peter; Amouyel, Philippe; Ay, Hakan; Bartz, Traci M; Benavente, Oscar R; Bevan, Steve; Boncoraglio, Giorgio B; Brown, Robert D; Butterworth, Adam S; Carrera, Caty; Carty, Cara L; Chasman, Daniel I; Chen, Wei-Min; Cole, John W; Correa, Adolfo; Cotlarciuc, Ioana; Cruchaga, Carlos; Danesh, John; de Bakker, Paul I W; DeStefano, Anita L; den Hoed, Marcel; Duan, Qing; Engelter, Stefan T; Falcone, Guido J; Gottesman, Rebecca F; Grewal, Raji P; Gudnason, Vilmundur; Gustafsson, Stefan; Haessler, Jeffrey; Harris, Tamara B; Hassan, Ahamad; Havulinna, Aki S; Heckbert, Susan R; Holliday, Elizabeth G; Howard, George; Hsu, Fang-Chi; Hyacinth, Hyacinth I; Ikram, M Arfan; Ingelsson, Erik; Irvin, Marguerite R; Jian, Xueqiu; Jiménez-Conde, Jordi; Johnson, Julie A; Jukema, J Wouter; Kanai, Masahiro; Keene, Keith L; Kissela, Brett M; Kleindorfer, Dawn O; Kooperberg, Charles; Kubo, Michiaki; Lange, Leslie A; Langefeld, Carl D; Langenberg, Claudia; Launer, Lenore J; Lee, Jin-Moo; Lemmens, Robin; Leys, Didier; Lewis, Cathryn M; Lin, Wei-Yu; Lindgren, Arne G; Lorentzen, Erik; Magnusson, Patrik K; Maguire, Jane; Manichaikul, Ani; McArdle, Patrick F; Meschia, James F; Mitchell, Braxton D; Mosley, Thomas H; Nalls, Michael A; Ninomiya, Toshiharu; O'Donnell, Martin J; Psaty, Bruce M; Pulit, Sara L; Rannikmäe, Kristiina; Reiner, Alexander P; Rexrode, Kathryn M; Rice, Kenneth; Rich, Stephen S; Ridker, Paul M; Rost, Natalia S; Rothwell, Peter M; Rotter, Jerome I; Rundek, Tatjana; Sacco, Ralph L; Sakaue, Saori; Sale, Michele M; Salomaa, Veikko; Sapkota, Bishwa R; Schmidt, Reinhold; Schmidt, Carsten O; Schminke, Ulf; Sharma, Pankaj; Slowik, Agnieszka; Sudlow, Cathie L M; Tanislav, Christian; Tatlisumak, Turgut; Taylor, Kent D; Thijs, Vincent N S; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Tiedt, Steffen; Trompet, Stella; Tzourio, Christophe; van Duijn, Cornelia M; Walters, Matthew; Wareham, Nicholas J; Wassertheil-Smoller, Sylvia; Wilson, James G; Wiggins, Kerri L; Yang, Qiong; Yusuf, Salim; Bis, Joshua C; Pastinen, Tomi; Ruusalepp, Arno; Schadt, Eric E; Koplev, Simon; Björkegren, Johan L M; Codoni, Veronica; Civelek, Mete; Smith, Nicholas L; Trégouët, David A; Christophersen, Ingrid E; Roselli, Carolina; Lubitz, Steven A; Ellinor, Patrick T; Tai, E Shyong; Kooner, Jaspal S; Kato, Norihiro; He, Jiang; van der Harst, Pim; Elliott, Paul; Chambers, John C; Takeuchi, Fumihiko; Johnson, Andrew D; Sanghera, Dharambir K; Melander, Olle; Jern, Christina; Strbian, Daniel; Fernandez-Cadenas, Israel; Longstreth, W T; Rolfs, Arndt; Hata, Jun; Woo, Daniel; Rosand, Jonathan; Pare, Guillaume; Hopewell, Jemma C; Saleheen, Danish; Stefansson, Kari; Worrall, Bradford B; Kittner, Steven J; Seshadri, Sudha; Fornage, Myriam; Markus, Hugh S; Howson, Joanna M M; Kamatani, Yoichiro; Debette, Stephanie; Dichgans, Martin; Malik, Rainer; Chauhan, Ganesh; Traylor, Matthew; Sargurupremraj, Muralidharan; Okada, Yukinori; Mishra, Aniket; Rutten-Jacobs, Loes; Giese, Anne-Katrin; van der Laan, Sander W; Gretarsdottir, Solveig; Anderson, Christopher D; Chong, Michael; Adams, Hieab H H; Ago, Tetsuro; Almgren, Peter; Amouyel, Philippe; Ay, Hakan; Bartz, Traci M; Benavente, Oscar R; Bevan, Steve; Boncoraglio, Giorgio B; Brown, Robert D; Butterworth, Adam S; Carrera, Caty; Carty, Cara L; Chasman, Daniel I; Chen, Wei-Min; Cole, John W; Correa, Adolfo; Cotlarciuc, Ioana; Cruchaga, Carlos; Danesh, John; de Bakker, Paul I W; DeStefano, Anita L; Hoed, Marcel den; Duan, Qing; Engelter, Stefan T; Falcone, Guido J; Gottesman, Rebecca F; Grewal, Raji P; Gudnason, Vilmundur; Gustafsson, Stefan; Haessler, Jeffrey; Harris, Tamara B; Hassan, Ahamad; Havulinna, Aki S; Heckbert, Susan R; Holliday, Elizabeth G; Howard, George; Hsu, Fang-Chi; Hyacinth, Hyacinth I; Ikram, M Arfan; Ingelsson, Erik; Irvin, Marguerite R; Jian, Xueqiu; Jiménez-Conde, Jordi; Johnson, Julie A; Jukema, J Wouter; Kanai, Masahiro; Keene, Keith L; Kissela, Brett M; Kleindorfer, Dawn O; Kooperberg, Charles; Kubo, Michiaki; Lange, Leslie A; Langefeld, Carl D; Langenberg, Claudia; Launer, Lenore J; Lee, Jin-Moo; Lemmens, Robin; Leys, Didier; Lewis, Cathryn M; Lin, Wei-Yu; Lindgren, Arne G; Lorentzen, Erik; Magnusson, Patrik K; Maguire, Jane; Manichaikul, Ani; McArdle, Patrick F; Meschia, James F; Mitchell, Braxton D; Mosley, Thomas H; Nalls, Michael A; Ninomiya, Toshiharu; O'Donnell, Martin J; Psaty, Bruce M; Pulit, Sara L; Rannikmäe, Kristiina; Reiner, Alexander P; Rexrode, Kathryn M; Rice, Kenneth; Rich, Stephen S; Ridker, Paul M; Rost, Natalia S; Rothwell, Peter M; Rotter, Jerome I; Rundek, Tatjana; Sacco, Ralph L; Sakaue, Saori; Sale, Michele M; Salomaa, Veikko; Sapkota, Bishwa R; Schmidt, Reinhold; Schmidt, Carsten O; Schminke, Ulf; Sharma, Pankaj; Slowik, Agnieszka; Sudlow, Cathie L M; Tanislav, Christian; Tatlisumak, Turgut; Taylor, Kent D; Thijs, Vincent N S; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Tiedt, Steffen; Trompet, Stella; Tzourio, Christophe; van Duijn, Cornelia M; Walters, Matthew; Wareham, Nicholas J; Wassertheil-Smoller, Sylvia; Wilson, James G; Wiggins, Kerri L; Yang, Qiong; Yusuf, Salim; Amin, Najaf; Aparicio, Hugo S; Arnett, Donna K; Attia, John; Beiser, Alexa S; Berr, Claudine; Buring, Julie E; Bustamante, Mariana; Caso, Valeria; Cheng, Yu-Ching; Choi, Seung Hoan; Chowhan, Ayesha; Cullell, Natalia; Dartigues, Jean-François; Delavaran, Hossein; Delgado, Pilar; Dörr, Marcus; Engström, Gunnar; Ford, Ian; Gurpreet, Wander S; Hamsten, Anders; Heitsch, Laura; Hozawa, Atsushi; Ibanez, Laura; Ilinca, Andreea; Ingelsson, Martin; Iwasaki, Motoki; Jackson, Rebecca D; Jood, Katarina; Jousilahti, Pekka; Kaffashian, Sara; Kalra, Lalit; Kamouchi, Masahiro; Kitazono, Takanari; Kjartansson, Olafur; Kloss, Manja; Koudstaal, Peter J; Krupinski, Jerzy; Labovitz, Daniel L; Laurie, Cathy C; Levi, Christopher R; Li, Linxin; Lind, Lars; Lindgren, Cecilia M; Lioutas, Vasileios; Liu, Yong Mei; Lopez, Oscar L; Makoto, Hirata; Martinez-Majander, Nicolas; Matsuda, Koichi; Minegishi, Naoko; Montaner, Joan; Morris, Andrew P; Muiño, Elena; Müller-Nurasyid, Martina; Norrving, Bo; Ogishima, Soichi; Parati, Eugenio A; Peddareddygari, Leema Reddy; Pedersen, Nancy L; Pera, Joanna; Perola, Markus; Pezzini, Alessandro; Pileggi, Silvana; Rabionet, Raquel; Riba-Llena, Iolanda; Ribasés, Marta; Romero, Jose R; Roquer, Jaume; Rudd, Anthony G; Sarin, Antti-Pekka; Sarju, Ralhan; Sarnowski, Chloe; Sasaki, Makoto; Satizabal, Claudia L; Satoh, Mamoru; Sattar, Naveed; Sawada, Norie; Sibolt, Gerli; Sigurdsson, Ásgeir; Smith, Albert; Sobue, Kenji; Soriano-Tárraga, Carolina; Stanne, Tara; Stine, O Colin; Stott, David J; Strauch, Konstantin; Takai, Takako; Tanaka, Hideo; Tanno, Kozo; Teumer, Alexander; Tomppo, Liisa; Torres-Aguila, Nuria P; Touze, Emmanuel; Tsugane, Shoichiro; Uitterlinden, Andre G; Valdimarsson, Einar M; van der Lee, Sven J; Völzke, Henry; Wakai, Kenji; Weir, David; Williams, Stephen R; Wolfe, Charles D A; Wong, Quenna; Xu, Huichun; Yamaji, Taiki; Sanghera, Dharambir K; Melander, Olle; Jern, Christina; Strbian, Daniel; Fernandez-Cadenas, Israel; Longstreth, W T; Rolfs, Arndt; Hata, Jun; Woo, Daniel; Rosand, Jonathan; Pare, Guillaume; Hopewell, Jemma C; Saleheen, Danish; Stefansson, Kari; Worrall, Bradford B; Kittner, Steven J; Seshadri, Sudha; Fornage, Myriam; Markus, Hugh S; Howson, Joanna M M; Kamatani, Yoichiro; Debette, Stephanie; Dichgans, Martin

2018-04-01

Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and venous thromboembolism, at individual loci (n = 18), and using genetic risk scores and linkage-disequilibrium-score regression. Several loci exhibited distinct association and pleiotropy patterns for etiological stroke subtypes. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology, with prioritization of risk variants and genes accomplished through bioinformatics analyses using extensive functional datasets. Stroke risk loci were significantly enriched in drug targets for antithrombotic therapy.

Animal pigment bilirubin discovered in plants.

PubMed

Pirone, Cary; Quirke, J Martin E; Priestap, Horacio A; Lee, David W

2009-03-04

The bile pigment bilirubin-IXalpha is the degradative product of heme, distributed among mammals and some other vertebrates. It can be recognized as the pigment responsible for the yellow color of jaundice and healing bruises. In this paper we present the first example of the isolation of bilirubin in plants. The compound was isolated from the brilliant orange-colored arils of Strelitzia nicolai, the white bird of paradise tree, and characterized by HPLC-ESMS, UV-visible, (1)H NMR, and (13)C NMR spectroscopy, as well as comparison with an authentic standard. This discovery indicates that plant cyclic tetrapyrroles may undergo degradation by a previously unknown pathway. Preliminary analyses of related plants, including S. reginae, the bird of paradise, also revealed bilirubin in the arils and flowers, indicating that the occurrence of bilirubin is not limited to a single species or tissue type.

New studies disputing allegations of bacteriological warfare during the Korean War.

PubMed

Rolicka, M

1995-03-01

In the television series Korea the Unknown War produced jointly by Thames Television (London) and WGBH (Boston) in 1990, General Matthew Ridgway, Commander in Chief of United Nations forces during the Korean War, called the accusations that the United States waged bacteriological warfare "black propaganda." The charges discredited the United States and, despite denials and many international discussions, have not been completely refuted until new. Following studies in archives previously not available for research and after uncovering new sources, many specific examples of black propaganda were discovered that contained false information and lies discrediting the United States. The mechanism of lies, which convinced the Korean population that bacteriological warfare was going on and that the only way not to become victims of the United States' inhuman cruelty was to fight, are shown in this paper.

Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes

PubMed Central

Malik, Rainer; Chauhan, Ganesh; Traylor, Matthew; Sargurupremraj, Muralidharan; Okada, Yukinori; Mishra, Aniket; Rutten-Jacobs, Loes; Giese, Anne-Katrin; van der Laan, Sander W.; Gretarsdottir, Solveig; Anderson, Christopher D.; Chong, Michael; Adams, Hieab H. H.; Ago, Tetsuro; Almgren, Peter; Amouyel, Philippe; Ay, Hakan; Bartz, Traci M.; Benavente, Oscar R.; Bevan, Steve; Boncoraglio, Giorgio B.; Brown, Robert D.; Butterworth, Adam S.; Carrera, Caty; Carty, Cara L.; Chasman, Daniel I.; Chen, Wei-Min; Cole, John W.; Correa, Adolfo; Cotlarciuc, Ioana; Cruchaga, Carlos; Danesh, John; de Bakker, Paul I. W.; DeStefano, Anita L.; den Hoed, Marcel; Duan, Qing; Engelter, Stefan T.; Falcone, Guido J.; Gottesman, Rebecca F.; Grewal, Raji P.; Gudnason, Vilmundur; Gustafsson, Stefan; Haessler, Jeffrey; Harris, Tamara B.; Hassan, Ahamad; Havulinna, Aki S.; Heckbert, Susan R.; Holliday, Elizabeth G.; Howard, George; Hsu, Fang-Chi; Hyacinth, Hyacinth I.; Ikram, M. Arfan; ingelsson, Erik; Irvin, Marguerite R.; Jian, Xueqiu; Jimenez-Conde, Jordi; Johnson, Julie A.; Jukema, J. Wouter; Kanai, Masahiro; Keene, Keith L.; Kissela, Brett M.; Kleindorfer, Dawn O.; Kooperberg, Charles; Kubo, Michiaki; Lange, Leslie A.; Langefeld, Carl D.; Langenberg, Claudia; Launer, Lenore J.; Lee, Jin-Moo; Lemmens, Robin; Leys, Didier; Lewis, Cathryn M.; Lin, Wei-Yu; Lindgren, Arne G.; Lorentzen, Erik; Magnusson, Patrik K.; Maguire, Jane; Manichaikul, Ani; McArdle, Patrick F.; Meschia, James F.; Mitchell, Braxton D.; Mosley, Thomas H.; Nalls, Michael A.; Ninomiya, Toshiharu; O’Donnell, Martin J.; Psaty, Bruce M.; Pulit, Sara L.; Rannikmäe, Kristiina; Reiner, Alexander P.; Rexrode, Kathryn M.; Rice, Kenneth; Rich, Stephen S.; Ridker, Paul M.; Rost, Natalia S.; Rothwell, Peter M.; Rotter, Jerome I.; Rundek, Tatjana; Sacco, Ralph L.; Sakaue, Saori; Sale, Michele M.; Salomaa, Veikko; Sapkota, Bishwa R.; Schmidt, Reinhold; Schmidt, Carsten O.; Schminke, Ulf; Sharma, Pankaj; Slowik, Agnieszka; Sudlow, Cathie L. M.; Tanislav, Christian; Tatlisumak, Turgut; Taylor, Kent D.; Thijs, Vincent N. S.; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Tiedt, Steffen; Trompet, Stella; Tzourio, Christophe; van Duijn, Cornelia M.; Walters, Matthew; Wareham, Nicholas J.; Wassertheil-Smoller, Sylvia; Wilson, James G.; Wiggins, Kerri L.; Yang, Qiong; Yusuf, Salim; Bis, Joshua C.; Pastinen, Tomi; Ruusalepp, Arno; Schadt, Eric E.; Koplev, Simon; Björkegren, Johan L. M.; Codoni, Veronica; Civelek, Mete; Smith, Nicholas L.; Tregouet, David A.; Christophersen, Ingrid E.; Roselli, Carolina; Lubitz, Steven A.; Ellinor, Patrick T.; Tai, E. Shyong; Kooner, Jaspal S.; Kato, Norihiro; He, Jiang; van der Harst, Pim; Elliott, Paul; Chambers, John C.; Takeuchi, Fumihiko; Johnson, Andrew D.; Sanghera, Dharambir K.; Melander, Olle; Jern, Christina; Strbian, Daniel; Fernandez-Cadenas, Israel; Longstreth, W. T.; Rolfs, Arndt; Hata, Jun; Woo, Daniel; Rosand, Jonathan; Pare, Guillaume; Hopewell, Jemma C.; Saleheen, Danish; Stefansson, Kari; Worrall, Bradford B.; Kittner, Steven J.; Seshadri, Sudha; Fornage, Myriam; Markus, Hugh S.; Howson, Joanna M. M.; Kamatani, Yoichiro; Debette, Stephanie; Dichgans, Martin

2018-01-01

Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and venous thromboembolism, at individual loci (n = 18), and using genetic risk scores and linkage-disequilibrium-score regression. Several loci exhibited distinct association and pleiotropy patterns for etiological stroke subtypes. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology, with prioritization of risk variants and genes accomplished through bioinformatics analyses using extensive functional datasets. Stroke risk loci were significantly enriched in drug targets for antithrombotic therapy. PMID:29531354

The nano-architecture of the axonal cytoskeleton.

PubMed

Leterrier, Christophe; Dubey, Pankaj; Roy, Subhojit

2017-12-01

The corporeal beauty of the neuronal cytoskeleton has captured the imagination of generations of scientists. One of the easiest cellular structures to visualize by light microscopy, its existence has been known for well over 100 years, yet we have only recently begun to fully appreciate its intricacy and diversity. Recent studies combining new probes with super-resolution microscopy and live imaging have revealed surprising details about the axonal cytoskeleton and, in particular, have discovered previously unknown actin-based structures. Along with traditional electron microscopy, these newer techniques offer a nanoscale view of the axonal cytoskeleton, which is important for our understanding of neuronal form and function, and lay the foundation for future studies. In this Review, we summarize existing concepts in the field and highlight contemporary discoveries that have fundamentally altered our perception of the axonal cytoskeleton.

Unimolecular Reaction Pathways of a γ-Ketohydroperoxide from Combined Application of Automated Reaction Discovery Methods

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grambow, Colin A.; Jamal, Adeel; Li, Yi -Pei

Ketohydroperoxides are important in liquid-phase autoxidation and in gas-phase partial oxidation and pre-ignition chemistry, but because of their low concentration, instability, and various analytical chemistry limitations, it has been challenging to experimentally determine their reactivity, and only a few pathways are known. In the present work, 75 elementary-step unimolecular reactions of the simplest γ-ketohydroperoxide, 3-hydroperoxypropanal, were discovered by a combination of density functional theory with several automated transition-state search algorithms: the Berny algorithm coupled with the freezing string method, single- and double-ended growing string methods, the heuristic KinBot algorithm, and the single-component artificial force induced reaction method (SC-AFIR). The presentmore » joint approach significantly outperforms previous manual and automated transition-state searches – 68 of the reactions of γ-ketohydroperoxide discovered here were previously unknown and completely unexpected. All of the methods found the lowest-energy transition state, which corresponds to the first step of the Korcek mechanism, but each algorithm except for SC-AFIR detected several reactions not found by any of the other methods. We show that the low-barrier chemical reactions involve promising new chemistry that may be relevant in atmospheric and combustion systems. Our study highlights the complexity of chemical space exploration and the advantage of combined application of several approaches. Altogether, the present work demonstrates both the power and the weaknesses of existing fully automated approaches for reaction discovery which suggest possible directions for further method development and assessment in order to enable reliable discovery of all important reactions of any specified reactant(s).« less

Unimolecular Reaction Pathways of a γ-Ketohydroperoxide from Combined Application of Automated Reaction Discovery Methods

DOE PAGES

Grambow, Colin A.; Jamal, Adeel; Li, Yi -Pei; ...

2017-12-22

Ketohydroperoxides are important in liquid-phase autoxidation and in gas-phase partial oxidation and pre-ignition chemistry, but because of their low concentration, instability, and various analytical chemistry limitations, it has been challenging to experimentally determine their reactivity, and only a few pathways are known. In the present work, 75 elementary-step unimolecular reactions of the simplest γ-ketohydroperoxide, 3-hydroperoxypropanal, were discovered by a combination of density functional theory with several automated transition-state search algorithms: the Berny algorithm coupled with the freezing string method, single- and double-ended growing string methods, the heuristic KinBot algorithm, and the single-component artificial force induced reaction method (SC-AFIR). The presentmore » joint approach significantly outperforms previous manual and automated transition-state searches – 68 of the reactions of γ-ketohydroperoxide discovered here were previously unknown and completely unexpected. All of the methods found the lowest-energy transition state, which corresponds to the first step of the Korcek mechanism, but each algorithm except for SC-AFIR detected several reactions not found by any of the other methods. We show that the low-barrier chemical reactions involve promising new chemistry that may be relevant in atmospheric and combustion systems. Our study highlights the complexity of chemical space exploration and the advantage of combined application of several approaches. Altogether, the present work demonstrates both the power and the weaknesses of existing fully automated approaches for reaction discovery which suggest possible directions for further method development and assessment in order to enable reliable discovery of all important reactions of any specified reactant(s).« less

Rainforest understory beetles of the Neotropics, Mizotrechus Bates 1872, a generic synopsis with descriptions of new species from Central America and northern South America (Coleoptera, Carabidae, Perigonini).

PubMed

Erwin, Terry L

2011-01-01

Information on the single previously described species, Mizotrechus novemstriatus Bates 1872 (type locality: Brazil - Amazonas, Tefé), is updated and 17 new species for the genus from Nicaragua, Costa Rica, Panamá, Colombia, Venezuela, and Guyane are described. The species records in the literature and on determined specimens in some collections of Mizotrechus novemstriatus Bates from Central America are not that species; currently, Mizotrechus novemstriatus is known only from its type locality in Amazonian Brazil. For the new species described, their known general distributions are as follows: Mizotrechus batesisp. n. (Guyane), Mizotrechus bellorumsp. n. (Guyane), Mizotrechus bruleisp. n. (Guyane), Mizotrechus belevederesp. n. (Guyane), Mizotrechus costaricensissp. n. (Costa Rica), Mizotrechus dalensisp. n. (Guyane), Mizotrechus edithpiafaesp. n. (provenance unknown), Mizotrechus fortunensissp. n. (Panamá), Mizotrechus gorgona. sp. n. (Colombia), Mizotrechus grossussp. n. (Guyane), Mizotrechus jefesp. n. (Panamá), Mizotrechus marielaforetaesp. n. (Guyane), Mizotrechus minutussp. n. (Guyane), Mizotrechus neblinensissp. n. (Guyane, Venezuela), Mizotrechus poirierisp. n. (Guyane), and Mizotrechus woldaisp. n. (Panamá). Long-term use of flight intercept traps in Guyane provided so many new species that apparently the use of FITs is the way to collect adults of this taxon, previously known from very few specimens. Many more species of this genus can be expected to be discovered throughout the Neotropics; the present contribution is a preliminary synopsis with identification key and adult images of all known species. Likely numerous species are yet to be discovered throughout tropical climes.

La Ferrassie 1: New perspectives on a "classic" Neandertal.

PubMed

Gómez-Olivencia, Asier; Quam, Rolf; Sala, Nohemi; Bardey, Morgane; Ohman, James C; Balzeau, Antoine

2018-04-01

The La Ferrassie 1 (LF1) skeleton, discovered over a century ago, is one of the most important Neandertal individuals both for its completeness and due to the role it has played historically in the interpretation of Neandertal anatomy and lifeways. Here we present new skeletal remains from this individual, which include a complete right middle ear ossicular chain (malleus, incus, and stapes), three vertebral fragments, and two costal remains. Additionally, the study of the skeleton has allowed us to identify new pathological lesions, including a congenital variant in the atlas, a greenstick fracture of the left clavicle, and a lesion in a mid-thoracic rib of unknown etiology. In addition, we have quantified the amount of vertebral pathology, which is greater than previously appreciated. We have complemented the paleopathological analysis with a taphonomic analysis to identify any potential perimortem fractures. The taphonomic analysis indicates that no surface alteration is present in the LF1 skeleton and that the breakage pattern is that of bone that has lost collagen, which would be consistent with the intentional burial of this individual proposed by previous researchers. In this study, we used CT and microCT scans in order to discover new skeletal elements to better characterize the pathological lesions and to quantify the fracture orientation of those bones in which the current plaster reconstruction did not allow its direct visualization, which underlines the broad potential of imaging technologies in paleoanthropological research. A century after its discovery, LF1 is still providing new insights into Neandertal anatomy and behavior. Copyright © 2018 Elsevier Ltd. All rights reserved.

On the Origin of Quasi-Periodic Temperature Variations in Kun-1 Well (Kunashir Island)

NASA Astrophysics Data System (ADS)

Demezhko, D. Yu.; Yurkov, A. K.

2017-12-01

The results of temperature monitoring in the 300-m kun-1 well (Kunashir Island) in 2011-2015 are considered. Quasi-periodic temperature variations with an amplitude of up to 0.3°C and a variation period of 14-26 h were added from November 2011 to the previously observed temperature variations caused by tidal deformations, free thermal convection, and deformation processes associated with the preparation and occurrence of tectonic earthquakes. Five cycles of such variations lasting from 2 to 6 months have been recorded. Each cycle was initiated by an earthquake with magnitude M > 2.5log( R), where R is the epicentral distance (km). According to their characteristics, the variations are unique and have not been described previously. Assumptions have been made about the possible connection of the registered variations with the inertial currents of the ocean or with hydrothermal processes in the Earth's subsurface. The phenomenon discovered requires further study not only as an object of fundamental science, but also as a feature of an earlier unknown type of geodynamic activity that can be a significant threat to the regional population.

The Genetic Basis of Mendelian Phenotypes: Discoveries, Challenges, and Opportunities

PubMed Central

Chong, Jessica X.; Buckingham, Kati J.; Jhangiani, Shalini N.; Boehm, Corinne; Sobreira, Nara; Smith, Joshua D.; Harrell, Tanya M.; McMillin, Margaret J.; Wiszniewski, Wojciech; Gambin, Tomasz; Coban Akdemir, Zeynep H.; Doheny, Kimberly; Scott, Alan F.; Avramopoulos, Dimitri; Chakravarti, Aravinda; Hoover-Fong, Julie; Mathews, Debra; Witmer, P. Dane; Ling, Hua; Hetrick, Kurt; Watkins, Lee; Patterson, Karynne E.; Reinier, Frederic; Blue, Elizabeth; Muzny, Donna; Kircher, Martin; Bilguvar, Kaya; López-Giráldez, Francesc; Sutton, V. Reid; Tabor, Holly K.; Leal, Suzanne M.; Gunel, Murat; Mane, Shrikant; Gibbs, Richard A.; Boerwinkle, Eric; Hamosh, Ada; Shendure, Jay; Lupski, James R.; Lifton, Richard P.; Valle, David; Nickerson, Deborah A.; Bamshad, Michael J.

2015-01-01

Discovering the genetic basis of a Mendelian phenotype establishes a causal link between genotype and phenotype, making possible carrier and population screening and direct diagnosis. Such discoveries also contribute to our knowledge of gene function, gene regulation, development, and biological mechanisms that can be used for developing new therapeutics. As of February 2015, 2,937 genes underlying 4,163 Mendelian phenotypes have been discovered, but the genes underlying ∼50% (i.e., 3,152) of all known Mendelian phenotypes are still unknown, and many more Mendelian conditions have yet to be recognized. This is a formidable gap in biomedical knowledge. Accordingly, in December 2011, the NIH established the Centers for Mendelian Genomics (CMGs) to provide the collaborative framework and infrastructure necessary for undertaking large-scale whole-exome sequencing and discovery of the genetic variants responsible for Mendelian phenotypes. In partnership with 529 investigators from 261 institutions in 36 countries, the CMGs assessed 18,863 samples from 8,838 families representing 579 known and 470 novel Mendelian phenotypes as of January 2015. This collaborative effort has identified 956 genes, including 375 not previously associated with human health, that underlie a Mendelian phenotype. These results provide insight into study design and analytical strategies, identify novel mechanisms of disease, and reveal the extensive clinical variability of Mendelian phenotypes. Discovering the gene underlying every Mendelian phenotype will require tackling challenges such as worldwide ascertainment and phenotypic characterization of families affected by Mendelian conditions, improvement in sequencing and analytical techniques, and pervasive sharing of phenotypic and genomic data among researchers, clinicians, and families. PMID:26166479

Annually resolved southern hemisphere volcanic history from two Antarctic ice cores

NASA Astrophysics Data System (ADS)

Cole-Dai, Jihong; Mosley-Thompson, Ellen; Thompson, Lonnie G.

1997-07-01

The continuous sulfate analysis of two Antarctic ice cores, one from the Antarctic Peninsula region and one from West Antarctica, provides an annually resolved proxy history of southern semisphere volcanism since early in the 15th century. The dating is accurate within ±3 years due to the high rate of snow accumulation at both core sites and the small sample sizes used for analysis. The two sulfate records are consistent with each other. A systematic and objective method of separating outstanding sulfate events from the background sulfate flux is proposed and used to identify all volcanic signals. The resulting volcanic chronology covering 1417-1989 A.D. resolves temporal ambiguities about several recently discovered events. A number of previously unknown, moderate eruptions during late 1600s are uncovered in this chronology. The eruption of Tambora (1815) and the recently discovered eruption of Kuwae (1453) in the tropical South Pacific injected the greatest amount of sulfur dioxide into the southern hemisphere stratosphere during the last half millennium. A technique for comparing the magnitude of volcanic events preserved within different ice cores is developed using normalized sulfate flux. For the same eruptions the variability of the volcanic sulfate flux between the cores is within ±20% of the sulfate flux from the Tambora eruption.

Extraordinary Structured Noncoding RNAs Revealed by Bacterial Metagenome Analysis

PubMed Central

Weinberg, Zasha; Perreault, Jonathan; Meyer, Michelle M.; Breaker, Ronald R.

2012-01-01

Estimates of the total number of bacterial species1-3 suggest that existing DNA sequence databases carry only a tiny fraction of the total amount of DNA sequence space represented by this division of life. Indeed, environmental DNA samples have been shown to encode many previously unknown classes of proteins4 and RNAs5. Bioinformatics searches6-10 of genomic DNA from bacteria commonly identify novel noncoding RNAs (ncRNAs)10-12 such as riboswitches13,14. In rare instances, RNAs that exhibit more extensive sequence and structural conservation across a wide range of bacteria are encountered15,16. Given that large structured RNAs are known to carry out complex biochemical functions such as protein synthesis and RNA processing reactions, identifying more RNAs of great size and intricate structure is likely to reveal additional biochemical functions that can be achieved by RNA. We applied an updated computational pipeline17 to discover ncRNAs that rival the known large ribozymes in size and structural complexity or that are among the most abundant RNAs in bacteria that encode them. These RNAs would have been difficult or impossible to detect without examining environmental DNA sequences, suggesting that numerous RNAs with extraordinary size, structural complexity, or other exceptional characteristics remain to be discovered in unexplored sequence space. PMID:19956260

Matrix- and tensor-based recommender systems for the discovery of currently unknown inorganic compounds

NASA Astrophysics Data System (ADS)

Seko, Atsuto; Hayashi, Hiroyuki; Kashima, Hisashi; Tanaka, Isao

2018-01-01

Chemically relevant compositions (CRCs) and atomic arrangements of inorganic compounds have been collected as inorganic crystal structure databases. Machine learning is a unique approach to search for currently unknown CRCs from vast candidates. Herein we propose matrix- and tensor-based recommender system approaches to predict currently unknown CRCs from database entries of CRCs. Firstly, the performance of the recommender system approaches to discover currently unknown CRCs is examined. A Tucker decomposition recommender system shows the best discovery rate of CRCs as the majority of the top 100 recommended ternary and quaternary compositions correspond to CRCs. Secondly, systematic density functional theory (DFT) calculations are performed to investigate the phase stability of the recommended compositions. The phase stability of the 27 compositions reveals that 23 currently unknown compounds are newly found to be stable. These results indicate that the recommender system has great potential to accelerate the discovery of new compounds.

A multiple-dimension liquid chromatography coupled with mass spectrometry data strategy for the rapid discovery and identification of unknown compounds from a Chinese herbal formula (Er-xian decoction).

PubMed

Wang, Caihong; Zhang, Jinlan; Wu, Caisheng; Wang, Zhe

2017-10-06

It is very important to rapidly discover and identify the multiple components of traditional Chinese medicine (TCM) formula. High performance liquid chromatography with high resolution tandem mass spectrometry (HPLC-HRMS/MS) has been widely used to analyze TCM formula and contains multiple-dimension data including retention time (RT), high resolution mass (HRMS), multiple-stage mass spectrometric (MS n ), and isotope intensity distribution (IID) data. So it is very necessary to exploit a useful strategy to utilize multiple-dimension data to rapidly probe structural information and identify chemical compounds. In this study, a new strategy to initiatively use the multiple-dimension LC-MS data has been developed to discover and identify unknown compounds of TCM in many styles. The strategy guarantees the fast discovery of candidate structural information and provides efficient structure clues for identification. The strategy contains four steps in sequence: (1) to discover potential compounds and obtain sub-structure information by the mass spectral tree similarity filter (MTSF) technique, based on HRMS and MS n data; (2) to classify potential compounds into known chemical classes by discriminant analysis (DA) on the basis of RT and HRMS data; (3) to hit the candidate structural information of compounds by intersection sub-structure between MTSF and DA (M,D-INSS); (4) to annotate and confirm candidate structures by IID data. This strategy allowed for the high exclusion efficiency (greater than 41%) of irrelevant ions in er-xian decoction (EXD) while providing accurate structural information of 553 potential compounds and identifying 66 candidates, therefore accelerating and simplifying the discovery and identification of unknown compounds in TCM formula. Copyright © 2017 Elsevier B.V. All rights reserved.

Application of chemical biology in target identification and drug discovery.

PubMed

Zhu, Yue; Xiao, Ting; Lei, Saifei; Zhou, Fulai; Wang, Ming-Wei

2015-09-01

Drug discovery and development is vital to the well-being of mankind and sustainability of the pharmaceutical industry. Using chemical biology approaches to discover drug leads has become a widely accepted path partially because of the completion of the Human Genome Project. Chemical biology mainly solves biological problems through searching previously unknown targets for pharmacologically active small molecules or finding ligands for well-defined drug targets. It is a powerful tool to study how these small molecules interact with their respective targets, as well as their roles in signal transduction, molecular recognition and cell functions. There have been an increasing number of new therapeutic targets being identified and subsequently validated as a result of advances in functional genomics, which in turn led to the discovery of numerous active small molecules via a variety of high-throughput screening initiatives. In this review, we highlight some applications of chemical biology in the context of drug discovery.

Identification of a primordial asteroid family constrains the original planetesimal population.

PubMed

Delbo', Marco; Walsh, Kevin; Bolin, Bryce; Avdellidou, Chrysa; Morbidelli, Alessandro

2017-09-08

A quarter of known asteroids is associated with more than 100 distinct asteroid families, meaning that these asteroids originate as impact fragments from the family parent bodies. The determination of which asteroids of the remaining population are members of undiscovered families, or accreted as planetesimals from the protoplanetary disk, would constrain a critical phase of planetary formation by unveiling the unknown planetesimal size distribution. We discovered a 4-billion-year-old asteroid family extending across the entire inner part of the main belt whose members include most of the dark asteroids previously unlinked to families. This allows us to identify some original planetesimals, which are all larger than 35 kilometers, supporting the view of asteroids being born big. Their number matches the known distinct meteorite parent bodies. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

OGLE-2016-BLG-1003: First Resolved Caustic-crossing Binary-source Event Discovered by Second-generation Microlensing Surveys

NASA Astrophysics Data System (ADS)

Jung, Y. K.; Udalski, A.; Bond, I. A.; Yee, J. C.; Gould, A.; Han, C.; Albrow, M. D.; Lee, C.-U.; Kim, S.-L.; Hwang, K.-H.; Chung, S.-J.; Ryu, Y.-H.; Shin, I.-G.; Zhu, W.; Cha, S.-M.; Kim, D.-J.; Lee, Y.; Park, B.-G.; Kim, H.-W.; Pogge, R. W.; KMTNet Collaboration; Skowron, J.; Szymański, M. K.; Poleski, R.; Mróz, P.; Kozłowski, S.; Pietrukowicz, P.; Soszyński, I.; Ulaczyk, K.; Pawlak, M.; OGLE Collaboration; Abe, F.; Bennett, D. P.; Barry, R.; Sumi, T.; Asakura, Y.; Bhattacharya, A.; Donachie, M.; Fukui, A.; Hirao, Y.; Itow, Y.; Koshimoto, N.; Li, M. C. A.; Ling, C. H.; Masuda, K.; Matsubara, Y.; Muraki, Y.; Nagakane, M.; Rattenbury, N. J.; Evans, P.; Sharan, A.; Sullivan, D. J.; Suzuki, D.; Tristram, P. J.; Yamada, T.; Yamada, T.; Yonehara, A.; MOA Collaboration

2017-06-01

We report the analysis of the first resolved caustic-crossing binary-source microlensing event OGLE-2016-BLG-1003. The event is densely covered by round-the-clock observations of three surveys. The light curve is characterized by two nested caustic-crossing features, which is unusual for typical caustic-crossing perturbations. From the modeling of the light curve, we find that the anomaly is produced by a binary source passing over a caustic formed by a binary lens. The result proves the importance of high-cadence and continuous observations, and the capability of second-generation microlensing experiments to identify such complex perturbations that are previously unknown. However, the result also raises the issues of the limitations of current analysis techniques for understanding lens systems beyond two masses and of determining the appropriate multiband observing strategy of survey experiments.

Structurally diverse natural products that cause potassium leakage trigger multicellularity in Bacillus subtilis.

PubMed

López, Daniel; Fischbach, Michael A; Chu, Frances; Losick, Richard; Kolter, Roberto

2009-01-06

We report a previously undescribed quorum-sensing mechanism for triggering multicellularity in Bacillus subtilis. B. subtilis forms communities of cells known as biofilms in response to an unknown signal. We discovered that biofilm formation is stimulated by a variety of small molecules produced by bacteria--including the B. subtilis nonribosomal peptide surfactin--that share the ability to induce potassium leakage. Natural products that do not cause potassium leakage failed to induce multicellularity. Small-molecule-induced multicellularity was prevented by the addition of potassium, but not sodium or lithium. Evidence is presented that potassium leakage stimulates the activity of a membrane protein kinase, KinC, which governs the expression of genes involved in biofilm formation. We propose that KinC responds to lowered intracellular potassium concentration and that this is a quorum-sensing mechanism that enables B. subtilis to respond to related and unrelated bacteria.

Intracellular Electric Field and pH Optimize Protein Localization and Movement

PubMed Central

Cunningham, Jessica; Estrella, Veronica; Lloyd, Mark; Gillies, Robert; Frieden, B. Roy; Gatenby, Robert

2012-01-01

Mammalian cell function requires timely and accurate transmission of information from the cell membrane (CM) to the nucleus (N). These pathways have been intensively investigated and many critical components and interactions have been identified. However, the physical forces that control movement of these proteins have received scant attention. Thus, transduction pathways are typically presented schematically with little regard to spatial constraints that might affect the underlying dynamics necessary for protein-protein interactions and molecular movement from the CM to the N. We propose messenger protein localization and movements are highly regulated and governed by Coulomb interactions between: 1. A recently discovered, radially directed E-field from the NM into the CM and 2. Net protein charge determined by its isoelectric point, phosphorylation state, and the cytosolic pH. These interactions, which are widely applied in elecrophoresis, provide a previously unknown mechanism for localization of messenger proteins within the cytoplasm as well as rapid shuttling between the CM and N. Here we show these dynamics optimize the speed, accuracy and efficiency of transduction pathways even allowing measurement of the location and timing of ligand binding at the CM –previously unknown components of intracellular information flow that are, nevertheless, likely necessary for detecting spatial gradients and temporal fluctuations in ligand concentrations within the environment. The model has been applied to the RAF-MEK-ERK pathway and scaffolding protein KSR1 using computer simulations and in-vitro experiments. The computer simulations predicted distinct distributions of phosphorylated and unphosphorylated components of this transduction pathway which were experimentally confirmed in normal breast epithelial cells (HMEC). PMID:22623963

Generation and Analysis of Expressed Sequence Tags from Olea europaea L.

PubMed Central

Ozdemir Ozgenturk, Nehir; Oruç, Fatma; Sezerman, Ugur; Kuçukural, Alper; Vural Korkut, Senay; Toksoz, Feriha; Un, Cemal

2010-01-01

Olive (Olea europaea L.) is an important source of edible oil which was originated in Near-East region. In this study, two cDNA libraries were constructed from young olive leaves and immature olive fruits for generation of ESTs to discover the novel genes and search the function of unknown genes of olive. The randomly selected 3840 colonies were sequenced for EST collection from both libraries. Readable 2228 sequences for olive leaf and 1506 sequences for olive fruit were assembled into 205 and 69 contigs, respectively, whereas 2478 were singletons. Putative functions of all 2752 differentially expressed unique sequences were designated by gene homology based on BLAST and annotated using BLAST2GO. While 1339 ESTs show no homology to the database, 2024 ESTs have homology (under 80%) with hypothetical proteins, putative proteins, expressed proteins, and unknown proteins in NCBI-GenBank. 635 EST's unique genes sequence have been identified by over 80% homology to known function in other species which were not previously described in Olea family. Only 3.1% of total EST's was shown similarity with olive database existing in NCBI. This generated EST's data and consensus sequences were submitted to NCBI as valuable source for functional genome studies of olive. PMID:21197085

Structural Insights Into the Evolutionary Paths of Oxylipin Biosynthetic Enzymes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, D.-S.; Nioche, P.; Hamberg, M.

2009-05-20

The oxylipin pathway generates not only prostaglandin-like jasmonates but also green leaf volatiles (GLVs), which confer characteristic aromas to fruits and vegetables. Although allene oxide synthase (AOS) and hydroperoxide lyase are atypical cytochrome P450 family members involved in the synthesis of jasmonates and GLVs, respectively, it is unknown how these enzymes rearrange their hydroperoxide substrates into different products. Here we present the crystal structures of Arabidopsis thaliana AOS, free and in complex with substrate or intermediate analogues. The structures reveal an unusual active site poised to control the reactivity of an epoxyallylic radical and its cation by means of interactionsmore » with an aromatic {pi}-system. Replacing the amino acid involved in these steps by a non-polar residue markedly reduces AOS activity and, unexpectedly, is both necessary and sufficient for converting AOS into a GLV biosynthetic enzyme. Furthermore, by combining our structural data with bioinformatic and biochemical analyses, we have discovered previously unknown hydroperoxide lyase in plant growth-promoting rhizobacteria, AOS in coral, and epoxyalcohol synthase in amphioxus. These results indicate that oxylipin biosynthetic genes were present in the last common ancestor of plants and animals, but were subsequently lost in all metazoan lineages except Placozoa, Cnidaria and Cephalochordata.« less

Rainforest understory beetles of the Neotropics, Mizotrechus Bates 1872, a generic synopsis with descriptions of new species from Central America and northern South America (Coleoptera, Carabidae, Perigonini)

PubMed Central

Erwin, Terry L.

2011-01-01

Abstract Information on the single previously described species, Mizotrechus novemstriatus Bates 1872 (type locality: Brazil – Amazonas, Tefé), is updated and 17 new species for the genus from Nicaragua, Costa Rica, Panamá, Colombia, Venezuela, and Guyane are described. The species records in the literature and on determined specimens in some collections of Mizotrechus novemstriatus Bates from Central America are not that species; currently, Mizotrechus novemstriatus is known only from its type locality in Amazonian Brazil. For the new species described, their known general distributions are as follows: Mizotrechus batesi sp. n. (Guyane), Mizotrechus bellorum sp. n. (Guyane), Mizotrechus brulei sp. n. (Guyane), Mizotrechus belevedere sp. n. (Guyane), Mizotrechus costaricensis sp. n. (Costa Rica), Mizotrechus dalensi sp. n. (Guyane), Mizotrechus edithpiafae sp. n. (provenance unknown), Mizotrechus fortunensis sp. n. (Panamá), Mizotrechus gorgona. sp. n. (Colombia), Mizotrechus grossus sp. n. (Guyane), Mizotrechus jefe sp. n. (Panamá), Mizotrechus marielaforetae sp. n. (Guyane), Mizotrechus minutus sp. n. (Guyane), Mizotrechus neblinensis sp. n. (Guyane, Venezuela), Mizotrechus poirieri sp. n. (Guyane), and Mizotrechus woldai sp. n. (Panamá). Long-term use of flight intercept traps in Guyane provided so many new species that apparently the use of FITs is the way to collect adults of this taxon, previously known from very few specimens. Many more species of this genus can be expected to be discovered throughout the Neotropics; the present contribution is a preliminary synopsis with identification key and adult images of all known species. Likely numerous species are yet to be discovered throughout tropical climes. PMID:22287885

A systems approach for discovering linoleic acid derivatives that potentially mediate pain and itch

PubMed Central

Ramsden, Christopher E.; Domenichiello, Anthony F.; Yuan, Zhi-Xin; Sapio, Matthew R.; Keyes, Gregory S.; Mishra, Santosh K.; Gross, Jacklyn R.; Majchrzak-Hong, Sharon; Zamora, Daisy; Horowitz, Mark S.; Davis, John M.; Sorokin, Alexander V.; Dey, Amit; LaPaglia, Danielle M.; Wheeler, Joshua J.; Vasko, Michael R.; Mehta, Nehal N.; Mannes, Andrew J.; Iadarola, Michael J.

2018-01-01

Chronic pain and itch are common hypersensitivity syndromes that are affected by endogenous mediators. We applied a systems-based, translational approach to predict, discover, and characterize mediators of pain and itch that are regulated by diet and inflammation. Profiling of tissue-specific precursor abundance and biosynthetic gene expression predicted that inflamed skin would be abundant in four previously unknown 11-hydroxy-epoxy-or 11-keto-epoxy-octadecenoate linoleic acid derivatives and four previously identified 9- or 13-hydroxy-epoxy- or 9- or 13-keto-epoxy-octadecenoate linoleic acid derivatives. All of these mediators were confirmed to be abundant in rat and human skin by mass spectrometry. However, only the two 11-hydroxy-epoxy-octadecenoates sensitized rat dorsal root ganglion neurons to release more calcitonin gene–related peptide (CGRP), which is involved in pain transmission, in response to low pH (which mimics an inflammatory state) or capsaicin (which activates ion channels involved in nociception). The two 11-hydroxy-epoxy-octadecenoates share a 3-hydroxy-Z-pentenyl-E-epoxide moiety, thus suggesting that this substructure could mediate nociceptor sensitization. In rats, intradermal hind paw injection of 11-hydroxy-12,13-trans-epoxy-(9Z)-octadecenoate elicited C-fiber–mediated sensitivity to thermal pain. In a randomized trial testing adjunctive strategies to manage refractory chronic headaches, reducing the dietary intake of linoleic acid was associated with decreases in plasma 11-hydroxy-12,13-trans-epoxy-(9Z)-octadecenoate, which correlated with clinical pain reduction. Human psoriatic skin had 30-fold higher 9-keto-12,13-trans-epoxy-(10E)-octadecenoate compared to control skin, and intradermal injection of this compound induced itch-related scratching behavior in mice. Collectively, these findings define a family of endogenous mediators with potential roles in pain and itch. PMID:28831021

The Future Russian Navy: Interests of the Military

DTIC Science & Technology

1993-05-01

plasma, pulse, membrane, biochemistry , and radiology.’𔃿 Soviet science had to discover and apply "as yet unknown properties of matter, natural laws...agree that large armored forces have become " dinosaurs " in modern warfare.1 Second, all parties agree that the Russian armed forces must be smaller

International Education: A Compendium of Federal Agency Programs.

ERIC Educational Resources Information Center

Owens, Becky, Comp.

Federal agency programs in support of international education are summarized in this report. The publication is designed to help readers discover unknown programs, more fully understand more familiar programs, and learn more about specific requirements for agencies where proposals have been unsuccessfully submitted in the past. Focus is directed…

Proposal to conserve Glycyrrhiza inflata against G. paucifoliolata (Leguminosae)

USDA-ARS?s Scientific Manuscript database

The taxonomic history and medicinal importance of Glycyrrhiza inflata are discussed. It has been used in scientific and non scientific literature for 110 years. It was recently discovered that it is synonymous with G. paucifoliolata, which was published nine years earlier, and was unknown in the lit...

Metagenomic ventures into outer sequence space.

PubMed

Dutilh, Bas E

Sequencing DNA or RNA directly from the environment often results in many sequencing reads that have no homologs in the database. These are referred to as "unknowns," and reflect the vast unexplored microbial sequence space of our biosphere, also known as "biological dark matter." However, unknowns also exist because metagenomic datasets are not optimally mined. There is a pressure on researchers to publish and move on, and the unknown sequences are often left for what they are, and conclusions drawn based on reads with annotated homologs. This can cause abundant and widespread genomes to be overlooked, such as the recently discovered human gut bacteriophage crAssphage. The unknowns may be enriched for bacteriophage sequences, the most abundant and genetically diverse component of the biosphere and of sequence space. However, it remains an open question, what is the actual size of biological sequence space? The de novo assembly of shotgun metagenomes is the most powerful tool to address this question.

Visualizing frequent patterns in large multivariate time series

NASA Astrophysics Data System (ADS)

Hao, M.; Marwah, M.; Janetzko, H.; Sharma, R.; Keim, D. A.; Dayal, U.; Patnaik, D.; Ramakrishnan, N.

2011-01-01

The detection of previously unknown, frequently occurring patterns in time series, often called motifs, has been recognized as an important task. However, it is difficult to discover and visualize these motifs as their numbers increase, especially in large multivariate time series. To find frequent motifs, we use several temporal data mining and event encoding techniques to cluster and convert a multivariate time series to a sequence of events. Then we quantify the efficiency of the discovered motifs by linking them with a performance metric. To visualize frequent patterns in a large time series with potentially hundreds of nested motifs on a single display, we introduce three novel visual analytics methods: (1) motif layout, using colored rectangles for visualizing the occurrences and hierarchical relationships of motifs in a multivariate time series, (2) motif distortion, for enlarging or shrinking motifs as appropriate for easy analysis and (3) motif merging, to combine a number of identical adjacent motif instances without cluttering the display. Analysts can interactively optimize the degree of distortion and merging to get the best possible view. A specific motif (e.g., the most efficient or least efficient motif) can be quickly detected from a large time series for further investigation. We have applied these methods to two real-world data sets: data center cooling and oil well production. The results provide important new insights into the recurring patterns.

Amoeba-Inspired Heuristic Search Dynamics for Exploring Chemical Reaction Paths.

PubMed

Aono, Masashi; Wakabayashi, Masamitsu

2015-09-01

We propose a nature-inspired model for simulating chemical reactions in a computationally resource-saving manner. The model was developed by extending our previously proposed heuristic search algorithm, called "AmoebaSAT [Aono et al. 2013]," which was inspired by the spatiotemporal dynamics of a single-celled amoeboid organism that exhibits sophisticated computing capabilities in adapting to its environment efficiently [Zhu et al. 2013]. AmoebaSAT is used for solving an NP-complete combinatorial optimization problem [Garey and Johnson 1979], "the satisfiability problem," and finds a constraint-satisfying solution at a speed that is dramatically faster than one of the conventionally known fastest stochastic local search methods [Iwama and Tamaki 2004] for a class of randomly generated problem instances [ http://www.cs.ubc.ca/~hoos/5/benchm.html ]. In cases where the problem has more than one solution, AmoebaSAT exhibits dynamic transition behavior among a variety of the solutions. Inheriting these features of AmoebaSAT, we formulate "AmoebaChem," which explores a variety of metastable molecules in which several constraints determined by input atoms are satisfied and generates dynamic transition processes among the metastable molecules. AmoebaChem and its developed forms will be applied to the study of the origins of life, to discover reaction paths for which expected or unexpected organic compounds may be formed via unknown unstable intermediates and to estimate the likelihood of each of the discovered paths.

[Syphilis and blood transfusion].

PubMed

Jenum, Pål A; Flesland, Øystein; Blystad, Hans; Vik, Inger Sofie Samdal; Hervig, Tor; Maeland, Arild; Saeter, Gunnar

2010-04-22

In 2007, previous syphilis infection was diagnosed in a blood donor who had given blood regularly for 15 years. This was discovered when the donor was tested for syphilis, as a new donor in another blood bank. The time of infection is unknown. An expert group, set up by The Norwegian Directorate of Health, was commissioned to evaluate the risk of syphilis transmission through blood products in Norway. The expert group based its evaluation on the epidemiology of syphilis, risk of infection and properties of the syphilis bacterium, especially in relation to blood donation. Specific information about the actual incident, made available by the Norwegian Directorate of Health, was also evaluated. Of 54 blood recipients 21 were alive and 18 (86 %) were tested for syphilis, all with a negative result. For 11 deceased the hospital records were studied without discovering signs of syphilis infection. The risk of transfusion-transmitted syphilis is low for several reasons: The prevalence of syphilis in the population is low, a compulsory interview and completion of a questionnaire before donation in Norway excludes patients who are ill or at risk of being infected; the proportion of fresh blood donations is very low and syphilis bacteria die quickly during normal storage conditions for blood. An incidental infection is symptomatic and easily treated by antibiotics. The expert group recommends to not start syphilis testing of each blood donor but to continue the present routine testing of new donors.

Drift simulation of MH370 debris using superensemble techniques

NASA Astrophysics Data System (ADS)

Jansen, Eric; Coppini, Giovanni; Pinardi, Nadia

2016-07-01

On 7 March 2014 (UTC), Malaysia Airlines flight 370 vanished without a trace. The aircraft is believed to have crashed in the southern Indian Ocean, but despite extensive search operations the location of the wreckage is still unknown. The first tangible evidence of the accident was discovered almost 17 months after the disappearance. On 29 July 2015, a small piece of the right wing of the aircraft was found washed up on the island of Réunion, approximately 4000 km from the assumed crash site. Since then a number of other parts have been found in Mozambique, South Africa and on Rodrigues Island. This paper presents a numerical simulation using high-resolution oceanographic and meteorological data to predict the movement of floating debris from the accident. Multiple model realisations are used with different starting locations and wind drag parameters. The model realisations are combined into a superensemble, adjusting the model weights to best represent the discovered debris. The superensemble is then used to predict the distribution of marine debris at various moments in time. This approach can be easily generalised to other drift simulations where observations are available to constrain unknown input parameters. The distribution at the time of the accident shows that the discovered debris most likely originated from the wide search area between 28 and 35° S. This partially overlaps with the current underwater search area, but extends further towards the north. Results at later times show that the most probable locations to discover washed-up debris are along the African east coast, especially in the area around Madagascar. The debris remaining at sea in 2016 is spread out over a wide area and its distribution changes only slowly.

Assimilation efficiency and toxicokinetics of 14C-lindane in the terrestrial isopod Porcellionides pruinosus: the role of isopods in degradation of persistent soil pollutants.

PubMed

Loureiro, Susana; Sousa, J P; Nogueira, A J A; Soares, A M V M

2002-12-01

An achievable way to evaluate the bioavailability of a certain toxic in the environment is to measure the concentration inside soil organisms. Non-target saprotrophic organisms like isopods are often exposed to agrochemicals or other kind of persistent chemicals. In this study the isopod Porcellionides pruinosus was exposed to a constant concentration of Lindane (gamma-HCH) via food. Using toxicokinetic models the bioaccumulation and fate of the pesticide by isopods was assessed and compared with previous studies, where an unexpected decrease in gamma-HCH concentration was observed. Animal body burdens showed higher values, and a lower assimilation rate constant, although the elimination rate constant was twice the value previously observed. It was also observed that a significant amount of gamma-HCH had an unknown fate. To discover its possible destiny, a factorial experiment was carried out using two types of CO2 traps and contaminated leaves in the presence and absence of isopods. It was concluded that isopod activity might have been responsible for a more rapid biotransformation of gamma-HCH in leaves, since the amount of the pesticide is reduced in their presence.

Three genetic groups of the Eucalyptus stem canker pathogen Teratosphaeria zuluensis introduced into Africa from an unknown source.

PubMed

Jimu, Luke; Chen, ShuaiFei; Wingfield, Michael J; Mwenje, Eddie; Roux, Jolanda

2016-01-01

The Eucalyptus stem canker pathogen Teratosphaeria zuluensis was discovered in South Africa in 1988 and it has subsequently been found in several other African countries as well as globally. In this study, the population structure, genetic diversity and evolutionary history of T. z uluensis were analysed using microsatellite markers to gain an enhanced understanding of its movement in Africa. Isolates were collected from several sites in Malawi, Mozambique, Uganda and Zambia. Data obtained were compared with those previously published for a South African population. The data obtained from 334 isolates, amplified across eight microsatellite loci, were used for assignment, differentiation and genetic diversity tests. STRUCTURE analyses, θ st and genetic distances revealed the existence of two clusters, one dominated by isolates from South Africa and the other by isolates from the Zambezi basin including Malawi, Mozambique and Zambia. High levels of admixture were found within and among populations, dominated by the Mulanje population in Malawi. Moderate to low genetic diversity of the populations supports the previously held view that the pathogen was introduced into Africa. The clonal nature of the Ugandan population suggests a very recent introduction, most likely from southern Africa.

Historical ruins of remote sensing archaeology in arid desertified environment, northwestern China

NASA Astrophysics Data System (ADS)

Hu, N. K.; Li, X.

2017-02-01

Silk Road is an important exchange channel for human communication and culture propagation between ancient China and the West during historical periods. A lot of human activities performed in Silk Road and many historical ruins leave behind to present. Archaeological ruins can play a significant role in studying and restoring the past human activities, as well as understanding regional environmental changes. There were many flourishingly human activities during different historical periods that were developed in ancient Juyan Oasis in the downstream of the Heihe River Basin. A large number of historical ruins that reflect past human activities preserved between numerous of the nebkhas and sand dunes. In this study, combined high-resolution remote sensing imageries with in situ truths investigated during the fieldwork, certain unknown ruins were identified according to the image features of historical ruins that appear in remotely sensed data, which were undiscovered during the previous field archaeological investigations and unreported in the past public literatures. Almost all of the newly discovered ruins that were identified using remote sensing images are distributed in the Lvcheng and BJ2008 surroundings. Newly findings supplement the missing gaps that were not taking into account during the previous field surveys.

Preliminary assessment of a previously unknown fault zone beneath the Daytona Beach sand blow cluster near Marianna, Arkansas

USGS Publications Warehouse

Odum, Jackson K.; Williams, Robert; Stephenson, William J.; Tuttle, Martitia P.; Al-Shukri, Hadar

2016-01-01

We collected new high‐resolution P‐wave seismic‐reflection data to explore for possible faults beneath a roughly linear cluster of early to mid‐Holocene earthquake‐induced sand blows to the south of Marianna, Arkansas. The Daytona Beach sand blow deposits are located in east‐central Arkansas about 75 km southwest of Memphis, Tennessee, and about 80 km south of the southwestern end of the New Madrid seismic zone (NMSZ). Previous studies of these sand blows indicate that they were produced between 10,500 and 5350 yr B.P. (before A.D. 1950). The sand blows are large and similar in size to those in the heart of the NMSZ produced by the 1811–1812 earthquakes. The seismic‐reflection profiles reveal a previously unknown zone of near‐vertical faults imaged in the 100–1100‐m depth range that are approximately coincident with a cluster of earthquake‐induced sand blows and a near‐linear surface lineament composed of air photo tonal anomalies. These interpreted faults are expressed as vertical discontinuities with the largest displacement fault showing about 40 m of west‐side‐up displacement at the top of the Paleozoic section at about 1100 m depth. There are about 20 m of folding on reflections within the Eocene strata at 400 m depth. Increasing fault displacement with depth suggests long‐term recurrent faulting. The imaged faults within the vicinity of the numerous sand blow features could be a causative earthquake source, although it does not rule out the possibility of other seismic sources nearby. These newly located faults add to a growing list of potentially active Pleistocene–Holocene faults discovered over the last two decades that are within the Mississippi embayment region but outside of the historical NMSZ.

Discovering frequently recurring movement sequences in team-sport athlete spatiotemporal data.

PubMed

Sweeting, Alice J; Aughey, Robert J; Cormack, Stuart J; Morgan, Stuart

2017-12-01

Athlete external load is typically analysed from predetermined movement thresholds. The combination of movement sequences and differences in these movements between playing positions is also currently unknown. This study developed a method to discover the frequently recurring movement sequences across playing position during matches. The external load of 12 international female netball athletes was collected by a local positioning system during four national-level matches. Velocity, acceleration and angular velocity were calculated from positional (X, Y) data, clustered via one-dimensional k-means and assigned a unique alphabetic label. Combinations of velocity, acceleration and angular velocity movement were compared using the Levenshtein distance and similarities computed by the longest common substring problem. The contribution of each movement sequence, according to playing position and relative to the wider data set, was then calculated via the Minkowski distance. A total of 10 frequently recurring combinations of movement were discovered, regardless of playing position. Only the wing attack, goal attack and goal defence playing positions are closely related. We developed a technique to discover the movement sequences, according to playing position, performed by elite netballers. This methodology can be extended to discover the frequently recurring movements within other team sports and across levels of competition.

New species from the Galoka and Kalabenono massifs: two unknown and severely threatened mountainous areas in NW Madagascar

PubMed Central

Callmander, Martin W.; Rakotovao, Charles; Razafitsalama, Jeremi; Phillipson, Peter B.; Buerki, Sven; Hong-Wa, Cynthia; Rakotoarivelo, Nivo; Andriambololonera, Sylvie; Koopman, Margaret M.; Johnson, David M.; Deroin, Thierry; Ravoahangy, Andriamandranto; Solo, Serge; Labat, Jean-Noël; Lowry, Porter P.

2011-01-01

The Galoka mountain chain, comprising principally the Galoka and Kalabenono massifs, situated at the northern edge of the Sambirano Region in NW Madagascar is an area that was virtually unknown botanically. It was visited three times between 2005 and 2007 as part of a floristic inventory. Both massifs contain the last remaining primary forests in the Galoka chain, which extends parallel to the coastline from South of Ambilobe to North of Ambanja. Several new species have been discovered amongst the collections, eight of which are described here. PMID:21857767

Epoxidation with Possibilities: Discovering Stereochemistry in Organic Chemistry via Coupling Constants

ERIC Educational Resources Information Center

Treadwell, Edward M.; Yan, Zhiqing; Xiao, Xiao

2017-01-01

A one-day laboratory epoxidation experiment, requiring no purification, is described, wherein the students are given an "unknown" stereoisomer of 3-hexen-1-ol, and use [superscript 1]H NMR coupling constants to determine the stereochemistry of their product. From this they work backward to determine the stereochemistry of their starting…

Discover the Unknown Chekhov in Your ESL Classroom

ERIC Educational Resources Information Center

Beliavsky, Ninah

2007-01-01

The author, an English-as-a-Second-Language (ESL) teacher, believes that for stories to be a successful tool in classroom instruction, they need to have universal themes, and they must deal with situations that the students could readily identify with regardless of their language, culture, or religion. In this article, she introduces the unknown…

Single cell genomic study of Dehalococcoidites in deep sea sediments of Peru Margin 1230

NASA Astrophysics Data System (ADS)

Kaster, A.; Meyer-Blackwell, K.; Spormann, A. M.

2013-12-01

Dehalogenating Chloroflexi, such as Dehalococcoidites Dhc were originally discovered as the key microorganisms mediating reductive dehalogenation of the prevalent groundwater contaminants tetrachloroethene and trichloroethene. Molecular and genomic studies on their key enzymes for energy conservation, reductive dehalogenases rdh, have provided evidence for ubiquitous horizontal gene transfer. A pioneering study by Futagami et al. discovered novel putative rdh phylotypes in sediments from the Pacific, revealing an unknown and surprising abundance of rdh genes in pristine habitats. The frequent detection of Dhc-related 16S rRNA genes from these environments implied the occurrence of dissimilatory dehalorespiration in marine subsurface sediments, however, pristine Dhc could never be linked to this activity. Despite being ubiquitous in those environments, metabolic life style or ecological function of Dhc in the absence of anthropogenic contaminants is still completely unknown. We therefore analyzed a non-contaminated deep sea sediment sample of the Peru Margin 1230 site by a single cell genomic (SGC) approach. We present for the first time data on three single Dhc cells, helping to elucidate their role in the poorly understood oligotrophic marine sub-surface environment.

Whole exome sequencing identifies genetic variants in inherited thrombocytopenia with secondary qualitative function defects

PubMed Central

Johnson, Ben; Lowe, Gillian C.; Futterer, Jane; Lordkipanidzé, Marie; MacDonald, David; Simpson, Michael A.; Sanchez-Guiú, Isabel; Drake, Sian; Bem, Danai; Leo, Vincenzo; Fletcher, Sarah J.; Dawood, Ban; Rivera, José; Allsup, David; Biss, Tina; Bolton-Maggs, Paula HB; Collins, Peter; Curry, Nicola; Grimley, Charlotte; James, Beki; Makris, Mike; Motwani, Jayashree; Pavord, Sue; Talks, Katherine; Thachil, Jecko; Wilde, Jonathan; Williams, Mike; Harrison, Paul; Gissen, Paul; Mundell, Stuart; Mumford, Andrew; Daly, Martina E.; Watson, Steve P.; Morgan, Neil V.

2016-01-01

Inherited thrombocytopenias are a heterogeneous group of disorders characterized by abnormally low platelet counts which can be associated with abnormal bleeding. Next-generation sequencing has previously been employed in these disorders for the confirmation of suspected genetic abnormalities, and more recently in the discovery of novel disease-causing genes. However its full potential has not yet been exploited. Over the past 6 years we have sequenced the exomes from 55 patients, including 37 index cases and 18 additional family members, all of whom were recruited to the UK Genotyping and Phenotyping of Platelets study. All patients had inherited or sustained thrombocytopenia of unknown etiology with platelet counts varying from 11×109/L to 186×109/L. Of the 51 patients phenotypically tested, 37 (73%), had an additional secondary qualitative platelet defect. Using whole exome sequencing analysis we have identified “pathogenic” or “likely pathogenic” variants in 46% (17/37) of our index patients with thrombocytopenia. In addition, we report variants of uncertain significance in 12 index cases, including novel candidate genetic variants in previously unreported genes in four index cases. These results demonstrate that whole exome sequencing is an efficient method for elucidating potential pathogenic genetic variants in inherited thrombocytopenia. Whole exome sequencing also has the added benefit of discovering potentially pathogenic genetic variants for further study in novel genes not previously implicated in inherited thrombocytopenia. PMID:27479822

Use of Whole Genome Sequencing for Diagnosis and Discovery in the Cancer Genetics Clinic

PubMed Central

Foley, Samantha B.; Rios, Jonathan J.; Mgbemena, Victoria E.; Robinson, Linda S.; Hampel, Heather L.; Toland, Amanda E.; Durham, Leslie; Ross, Theodora S.

2014-01-01

Despite the potential of whole-genome sequencing (WGS) to improve patient diagnosis and care, the empirical value of WGS in the cancer genetics clinic is unknown. We performed WGS on members of two cohorts of cancer genetics patients: those with BRCA1/2 mutations (n = 176) and those without (n = 82). Initial analysis of potentially pathogenic variants (PPVs, defined as nonsynonymous variants with allele frequency < 1% in ESP6500) in 163 clinically-relevant genes suggested that WGS will provide useful clinical results. This is despite the fact that a majority of PPVs were novel missense variants likely to be classified as variants of unknown significance (VUS). Furthermore, previously reported pathogenic missense variants did not always associate with their predicted diseases in our patients. This suggests that the clinical use of WGS will require large-scale efforts to consolidate WGS and patient data to improve accuracy of interpretation of rare variants. While loss-of-function (LoF) variants represented only a small fraction of PPVs, WGS identified additional cancer risk LoF PPVs in patients with known BRCA1/2 mutations and led to cancer risk diagnoses in 21% of non-BRCA cancer genetics patients after expanding our analysis to 3209 ClinVar genes. These data illustrate how WGS can be used to improve our ability to discover patients' cancer genetic risks. PMID:26023681

The impact of large-scale, long-term optical surveys on pulsating star research

NASA Astrophysics Data System (ADS)

Soszyński, Igor

2017-09-01

The era of large-scale photometric variability surveys began a quarter of a century ago, when three microlensing projects - EROS, MACHO, and OGLE - started their operation. These surveys initiated a revolution in the field of variable stars and in the next years they inspired many new observational projects. Large-scale optical surveys multiplied the number of variable stars known in the Universe. The huge, homogeneous and complete catalogs of pulsating stars, such as Cepheids, RR Lyrae stars, or long-period variables, offer an unprecedented opportunity to calibrate and test the accuracy of various distance indicators, to trace the three-dimensional structure of the Milky Way and other galaxies, to discover exotic types of intrinsically variable stars, or to study previously unknown features and behaviors of pulsators. We present historical and recent findings on various types of pulsating stars obtained from the optical large-scale surveys, with particular emphasis on the OGLE project which currently offers the largest photometric database among surveys for stellar variability.

Complexity of the laminar-turbulent boundary in pipe flow

NASA Astrophysics Data System (ADS)

Budanur, Nazmi Burak; Hof, Björn

2018-05-01

Over the past decade, the edge of chaos has proven to be a fruitful starting point for investigations of shear flows when the laminar base flow is linearly stable. Numerous computational studies of shear flows demonstrated the existence of states that separate laminar and turbulent regions of the state space. In addition, some studies determined invariant solutions that reside on this edge. In this paper, we study the unstable manifold of one such solution with the aid of continuous symmetry reduction, which we formulate here for the simultaneous quotiening of axial and azimuthal symmetries. Upon our investigation of the unstable manifold, we discover a previously unknown traveling-wave solution on the laminar-turbulent boundary with a relatively complex structure. By means of low-dimensional projections, we visualize different dynamical paths that connect these solutions to the turbulence. Our numerical experiments demonstrate that the laminar-turbulent boundary exhibits qualitatively different regions whose properties are influenced by the nearby invariant solutions.

A king-sized theropod coprolite

USGS Publications Warehouse

Chin, K.; Tokaryk, T.T.; Erickson, G.M.; Calk, L.C.

1998-01-01

Fossil faeces (coprolites) provide unique trophic perspectives on ancient ecosystems. Yet, although thousands of coprolites have been discovered, specimens that can be unequivocally attributed to carnivorous dinosaurs are almost unknown. A few fossil faeces have been ascribed to herbivorous dinosaurs, but it is more difficult to identify coprolites produced by theropods because other carnivorous taxa coexisted with dinosaurs and most faeces are taxonomically ambiguous. Thus sizeable (up to 20 cm long and 10 cm wide) phosphatic coprolites from Belgium and India that have been attributed to dinosaurs might have been produced by contemporaneous crocodylians or fish. But there is no ambiguity about the theropod origin of the Cretaceous coprolite we report here. This specimen is more than twice as large as any previously reported carnivore coprolite, and its great size and temporal and geographic context indicate that it was produced by a tyrannosaur, most likely Tyrannosaurus rex. The specimen contains a high proportion (30-50%) of bone fragments, an it rare tangible evidence of theropod diet and digestive processes.

A High-Resolution LC-MS-Based Secondary Metabolite Fingerprint Database of Marine Bacteria

PubMed Central

Lu, Liang; Wang, Jijie; Xu, Ying; Wang, Kailing; Hu, Yingwei; Tian, Renmao; Yang, Bo; Lai, Qiliang; Li, Yongxin; Zhang, Weipeng; Shao, Zongze; Lam, Henry; Qian, Pei-Yuan

2014-01-01

Marine bacteria are the most widely distributed organisms in the ocean environment and produce a wide variety of secondary metabolites. However, traditional screening for bioactive natural compounds is greatly hindered by the lack of a systematic way of cataloguing the chemical profiles of bacterial strains found in nature. Here we present a chemical fingerprint database of marine bacteria based on their secondary metabolite profiles, acquired by high-resolution LC-MS. Till now, 1,430 bacterial strains spanning 168 known species collected from different marine environments were cultured and profiled. Using this database, we demonstrated that secondary metabolite profile similarity is approximately, but not always, correlated with taxonomical similarity. We also validated the ability of this database to find species-specific metabolites, as well as to discover known bioactive compounds from previously unknown sources. An online interface to this database, as well as the accompanying software, is provided freely for the community to use. PMID:25298017

Uncertain viscoelastic models with fractional order: A new spectral tau method to study the numerical simulations of the solution

NASA Astrophysics Data System (ADS)

Ahmadian, A.; Ismail, F.; Salahshour, S.; Baleanu, D.; Ghaemi, F.

2017-12-01

The analysis of the behaviors of physical phenomena is important to discover significant features of the character and the structure of mathematical models. Frequently the unknown parameters involve in the models are assumed to be unvarying over time. In reality, some of them are uncertain and implicitly depend on several factors. In this study, to consider such uncertainty in variables of the models, they are characterized based on the fuzzy notion. We propose here a new model based on fractional calculus to deal with the Kelvin-Voigt (KV) equation and non-Newtonian fluid behavior model with fuzzy parameters. A new and accurate numerical algorithm using a spectral tau technique based on the generalized fractional Legendre polynomials (GFLPs) is developed to solve those problems under uncertainty. Numerical simulations are carried out and the analysis of the results highlights the significant features of the new technique in comparison with the previous findings. A detailed error analysis is also carried out and discussed.

Roman vs. Arabic Computistics in Twelfth-Century England: A Newly Discovered Source (Collatio Compoti Romani et Arabici).

PubMed

Nothaft, C Philipp E

2015-01-01

A frequently overlooked aspect of the knowledge transfer from Arabic into Latin in the twelfth century is the introduction of the Islamo-Arabic calendar, which confronted Western computists with a radically different scheme of lunar reckoning that was in some ways superior to the 19-year lunar cycle of the Roman Church. One of the earliest sources to properly discuss this new system and compare it to the old one is the anonymous Collatio Compoti Romani et Arabici, found in a manuscript from Tewkesbury Abbey, Gloucestershire. This article contains the first edition and translation of this previously unknown text, preceded by an analysis of its content and sources. As will be argued, the text was written in the second quarter of the twelfth century as a reaction to the astronomical tables of al-Khwāizmī, recently translated by Adelard of Bath, as well as to eclipse observations that had exposed the flaws of the 'Roman' computation.

Metabolomics for biomarker discovery in the diagnosis, prognosis, survival and recurrence of colorectal cancer: a systematic review

PubMed Central

Zhang, Fan; Zhang, Yuanyuan; Zhao, Weiwei; Deng, Kui; Wang, Zhuozhong; Yang, Chunyan; Ma, Libing; Openkova, Margarita S.; Hou, Yan; Li, Kang

2017-01-01

Colorectal cancer (CRC) remains an incurable disease. There are no effective noninvasive techniques that have achieved colorectal cancer (CRC) diagnosis, prognosis, survival and recurrence in clinic. To investigate colorectal cancer metabolism, we perform an electronic literature search, from 1998 to January 2016, for studies evaluating the metabolomic profile of patients with CRC regarding the diagnosis, recurrence, prognosis/survival, and systematically review the twenty-three literatures included. QUADOMICS tool was used to assess the quality of them. We highlighted the metabolism perturbations based on metabolites and pathway. Metabolites related to cellular respiration, carbohydrate, lipid, protein and nucleotide metabolism were significantly altered in CRC. Altered metabolites were also related to prognosis, survival and recurrence of CRC. This review could represent the most comprehensive information and summary about CRC metabolism to date. It certificates that metabolomics had great potential on both discovering clinical biomarkers and elucidating previously unknown mechanisms of CRC pathogenesis. PMID:28389626

Heterogeneity of neuroblastoma cell identity defined by transcriptional circuitries.

PubMed

Boeva, Valentina; Louis-Brennetot, Caroline; Peltier, Agathe; Durand, Simon; Pierre-Eugène, Cécile; Raynal, Virginie; Etchevers, Heather C; Thomas, Sophie; Lermine, Alban; Daudigeos-Dubus, Estelle; Geoerger, Birgit; Orth, Martin F; Grünewald, Thomas G P; Diaz, Elise; Ducos, Bertrand; Surdez, Didier; Carcaboso, Angel M; Medvedeva, Irina; Deller, Thomas; Combaret, Valérie; Lapouble, Eve; Pierron, Gaelle; Grossetête-Lalami, Sandrine; Baulande, Sylvain; Schleiermacher, Gudrun; Barillot, Emmanuel; Rohrer, Hermann; Delattre, Olivier; Janoueix-Lerosey, Isabelle

2017-09-01

Neuroblastoma is a tumor of the peripheral sympathetic nervous system, derived from multipotent neural crest cells (NCCs). To define core regulatory circuitries (CRCs) controlling the gene expression program of neuroblastoma, we established and analyzed the neuroblastoma super-enhancer landscape. We discovered three types of identity in neuroblastoma cell lines: a sympathetic noradrenergic identity, defined by a CRC module including the PHOX2B, HAND2 and GATA3 transcription factors (TFs); an NCC-like identity, driven by a CRC module containing AP-1 TFs; and a mixed type, further deconvoluted at the single-cell level. Treatment of the mixed type with chemotherapeutic agents resulted in enrichment of NCC-like cells. The noradrenergic module was validated by ChIP-seq. Functional studies demonstrated dependency of neuroblastoma with noradrenergic identity on PHOX2B, evocative of lineage addiction. Most neuroblastoma primary tumors express TFs from the noradrenergic and NCC-like modules. Our data demonstrate a previously unknown aspect of tumor heterogeneity relevant for neuroblastoma treatment strategies.

The nature of donors in ultraluminous X-ray binaries powered by neutron stars

NASA Astrophysics Data System (ADS)

Karino, Shigeyuki

2018-03-01

This study examines the properties of the donor stars of three recently discovered ultraluminous X-ray sources (ULXs) powered by rotating neutron stars. In order to do this, a theoretical relationship was constructed between the X-ray luminosity (LX) and the orbital period (Porb) suitable for ULXs with neutron stars. Using this new LX-Porb relationship, we attempted to determine the currently unknown nature of donor stars in ULXs associated with neutron stars. In particular, from a comparison between the observed properties and the stellar evolution tracks, we suggest that the donor star in the NGC5907 ULX-1 system is a moderately massive star of 6-12 M⊙, just departing from the main sequence phase. The results of our models for the other two ULX systems (M82 X-2 and NGC7793 P-13) are consistent with those in previous studies. Although there are only a few samples, observed ULX systems with neutron stars seem to involve relatively massive donors.

Cysteine-independent Catalase-like Activity of Vertebrate Peroxiredoxin 1 (Prx1)*

PubMed Central

Sun, Cen-Cen; Dong, Wei-Ren; Zhao, Jing; Nie, Li; Xiang, Li-Xin; Zhu, Guan; Shao, Jian-Zhong

2015-01-01

Peroxiredoxins (Prxs) are a ubiquitous family of antioxidant proteins that are known as thioredoxin peroxidases. Here we report that Prx1 proteins from Tetraodon nigroviridis and humans also possess a previously unknown catalase-like activity that is independent of Cys residues and reductants but dependent on iron. We identified that the GVL motif was essential to the catalase (CAT)-like activity of Prx1 but not to the Cys-dependent thioredoxin peroxidase (POX) activity, and we generated mutants lacking POX and/or CAT activities for individually delineating their functional features. We discovered that the TnPrx1 POX and CAT activities possessed different kinetic features in reducing H2O2. The overexpression of wild-type TnPrx1 and mutants differentially regulated the intracellular levels of reactive oxygen species and p38 phosphorylation in HEK-293T cells treated with H2O2. These observations suggest that the dual antioxidant activities of Prx1 may be crucial for organisms to mediate intracellular redox homeostasis. PMID:26088136

A bizarre theropod from the Early Cretaceous of Japan highlighting mosaic evolution among coelurosaurians

PubMed Central

Azuma, Yoichi; Xu, Xing; Shibata, Masateru; Kawabe, Soichiro; Miyata, Kazunori; Imai, Takuya

2016-01-01

Our understanding of coelurosaurian evolution, particularly of bird origins, has been greatly improved, mainly due to numerous recently discovered fossils worldwide. Nearly all these discoveries are referable to the previously known coelurosaurian subgroups. Here, we report a new theropod, Fukuivenator paradoxus, gen. et sp. nov., based on a nearly complete specimen from the Lower Cretaceous Kitadani Formation of the Tetori Group, Fukui, Japan. While Fukuivenator possesses a large number of morphological features unknown in any other theropod, it has a combination of primitive and derived features seen in different theropod subgroups, notably dromaeosaurid dinosaurs. Computed-tomography data indicate that Fukuivenator possesses inner ears whose morphology is intermediate between those of birds and non-avian dinosaurs. Our phylogenetic analysis recovers Fukuivenator as a basally branching maniraptoran theropod, yet is unable to refer it to any known coelurosaurian subgroups. The discovery of Fukuivenator considerably increases the morphological disparity of coelurosaurian dinosaurs and highlights the high levels of homoplasy in coelurosaurian evolution. PMID:26908367

A high-frequency survey of the southern Galactic plane for pulsars

NASA Technical Reports Server (NTRS)

Johnston, Simon; Lyne, A. G.; Manchester, R. N.; Kniffen, D. A.; D'Amico, N.; Lim, J.; Ashworth, M.

1992-01-01

Results of an HF survey designed to detect young, distant, and short-period pulsars are presented. The survey detected a total of 100 pulsars, 46 of which were previously unknown. The periods of the newly discovered pulsars range between 47 ms and 2.5 ms. One of the new discoveries, PSR 1259-63, is a member of a long-period binary system. At least three of the pulsars have ages less than 30,000 yr, bringing the total number of such pulsars to 12. The majority of the new discoveries are distant objects with high dispersion measures, which are difficult to detect at low frequencies. This demonstrates that the survey has reduced the severe selection effects of pulse scattering, high Galactic background temperature, and dispersion broadening, which hamper the detection of such pulsars at low radio frequencies. The pulsar distribution in the southern Galaxy is found to extend much further from the Galactic center than that in the north, probably due to two prominent spiral arms in the southern Galaxy.

Novel genetic loci underlying human intracranial volume identified through genome-wide association.

PubMed

Adams, Hieab H H; Hibar, Derrek P; Chouraki, Vincent; Stein, Jason L; Nyquist, Paul A; Rentería, Miguel E; Trompet, Stella; Arias-Vasquez, Alejandro; Seshadri, Sudha; Desrivières, Sylvane; Beecham, Ashley H; Jahanshad, Neda; Wittfeld, Katharina; Van der Lee, Sven J; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S; Armstrong, Nicola J; Athanasiu, Lavinia; Axelsson, Tomas; Beiser, Alexa; Bernard, Manon; Bis, Joshua C; Blanken, Laura M E; Blanton, Susan H; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brickman, Adam M; Carmichael, Owen; Chakravarty, M Mallar; Chauhan, Ganesh; Chen, Qiang; Ching, Christopher R K; Cuellar-Partida, Gabriel; Braber, Anouk Den; Doan, Nhat Trung; Ehrlich, Stefan; Filippi, Irina; Ge, Tian; Giddaluru, Sudheer; Goldman, Aaron L; Gottesman, Rebecca F; Greven, Corina U; Grimm, Oliver; Griswold, Michael E; Guadalupe, Tulio; Hass, Johanna; Haukvik, Unn K; Hilal, Saima; Hofer, Edith; Hoehn, David; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Liao, Jiemin; Liewald, David C M; Lopez, Lorna M; Luciano, Michelle; Macare, Christine; Marquand, Andre; Matarin, Mar; Mather, Karen A; Mattheisen, Manuel; Mazoyer, Bernard; McKay, David R; McWhirter, Rebekah; Milaneschi, Yuri; Mirza-Schreiber, Nazanin; Muetzel, Ryan L; Maniega, Susana Muñoz; Nho, Kwangsik; Nugent, Allison C; Loohuis, Loes M Olde; Oosterlaan, Jaap; Papmeyer, Martina; Pappa, Irene; Pirpamer, Lukas; Pudas, Sara; Pütz, Benno; Rajan, Kumar B; Ramasamy, Adaikalavan; Richards, Jennifer S; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rommelse, Nanda; Rose, Emma J; Royle, Natalie A; Rundek, Tatjana; Sämann, Philipp G; Satizabal, Claudia L; Schmaal, Lianne; Schork, Andrew J; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V; Sprooten, Emma; Strike, Lachlan T; Teumer, Alexander; Thomson, Russell; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Vaidya, Dhananjay; Van der Grond, Jeroen; Van der Meer, Dennis; Van Donkelaar, Marjolein M J; Van Eijk, Kristel R; Van Erp, Theo G M; Van Rooij, Daan; Walton, Esther; Westlye, Lars T; Whelan, Christopher D; Windham, Beverly G; Winkler, Anderson M; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Xu, Bing; Yanek, Lisa R; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P; Agartz, Ingrid; Aggarwal, Neelum T; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A; Arepalli, Sampath; Assareh, Amelia A; Barral, Sandra; Bastin, Mark E; Becker, Diane M; Becker, James T; Bennett, David A; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I; Brodaty, Henry; Brouwer, Rachel M; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Bulayeva, Kazima B; Cahn, Wiepke; Calhoun, Vince D; Cannon, Dara M; Cavalleri, Gianpiero L; Chen, Christopher; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E; Czisch, Michael; Dale, Anders M; Davies, Gareth E; De Geus, Eco J C; De Jager, Philip L; de Zubicaray, Greig I; Delanty, Norman; Depondt, Chantal; DeStefano, Anita L; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Espeseth, Thomas; Evans, Denis A; Fedko, Iryna O; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E; Fleischman, Debra A; Ford, Ian; Foroud, Tatiana M; Fox, Peter T; Francks, Clyde; Fukunaga, Masaki; Gibbs, J Raphael; Glahn, David C; Gollub, Randy L; Göring, Harald H H; Grabe, Hans J; Green, Robert C; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Hansell, Narelle K; Hardy, John; Hartman, Catharina A; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G; Heslenfeld, Dirk J; Ho, Beng-Choon; Hoekstra, Pieter J; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Hulshoff Pol, Hilleke E; Ikeda, Masashi; Ikram, M Kamran; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G; Jukema, J Wouter; Kahn, René S; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L; Longstreth, W T; Lopez, Oscar L; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S; McDonald, Colm; McIntosh, Andrew M; McMahon, Katie L; McMahon, Francis J; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W; Morris, Derek W; Mosley, Thomas H; Mühleisen, Thomas W; Müller-Myhsok, Bertram; Nalls, Michael A; Nauck, Matthias; Nichols, Thomas E; Niessen, Wiro J; Nöthen, Markus M; Nyberg, Lars; Ohi, Kazutaka; Olvera, Rene L; Ophoff, Roel A; Pandolfo, Massimo; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W J H; Pike, G Bruce; Potkin, Steven G; Psaty, Bruce M; Reppermund, Simone; Rietschel, Marcella; Roffman, Joshua L; Romanczuk-Seiferth, Nina; Rotter, Jerome I; Ryten, Mina; Sacco, Ralph L; Sachdev, Perminder S; Saykin, Andrew J; Schmidt, Reinhold; Schofield, Peter R; Sigurdsson, Sigurdur; Simmons, Andy; Singleton, Andrew; Sisodiya, Sanjay M; Smith, Colin; Smoller, Jordan W; Soininen, Hilkka; Srikanth, Velandai; Steen, Vidar M; Stott, David J; Sussmann, Jessika E; Thalamuthu, Anbupalam; Tiemeier, Henning; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Turner, Jessica A; Tzourio, Christophe; Uitterlinden, Andre G; Hernández, Maria C Valdés; Van der Brug, Marcel; Van der Lugt, Aad; Van der Wee, Nic J A; Van Duijn, Cornelia M; Van Haren, Neeltje E M; Van T Ent, Dennis; Van Tol, Marie-Jose; Vardarajan, Badri N; Veltman, Dick J; Vernooij, Meike W; Völzke, Henry; Walter, Henrik; Wardlaw, Joanna M; Wassink, Thomas H; Weale, Michael E; Weinberger, Daniel R; Weiner, Michael W; Wen, Wei; Westman, Eric; White, Tonya; Wong, Tien Y; Wright, Clinton B; Zielke, H Ronald; Zonderman, Alan B; Deary, Ian J; DeCarli, Charles; Schmidt, Helena; Martin, Nicholas G; De Craen, Anton J M; Wright, Margaret J; Launer, Lenore J; Schumann, Gunter; Fornage, Myriam; Franke, Barbara; Debette, Stéphanie; Medland, Sarah E; Ikram, M Arfan; Thompson, Paul M

2016-12-01

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρ genetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (N combined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.

Object-graphs for context-aware visual category discovery.

PubMed

Lee, Yong Jae; Grauman, Kristen

2012-02-01

How can knowing about some categories help us to discover new ones in unlabeled images? Unsupervised visual category discovery is useful to mine for recurring objects without human supervision, but existing methods assume no prior information and thus tend to perform poorly for cluttered scenes with multiple objects. We propose to leverage knowledge about previously learned categories to enable more accurate discovery, and address challenges in estimating their familiarity in unsegmented, unlabeled images. We introduce two variants of a novel object-graph descriptor to encode the 2D and 3D spatial layout of object-level co-occurrence patterns relative to an unfamiliar region and show that by using them to model the interaction between an image’s known and unknown objects, we can better detect new visual categories. Rather than mine for all categories from scratch, our method identifies new objects while drawing on useful cues from familiar ones. We evaluate our approach on several benchmark data sets and demonstrate clear improvements in discovery over conventional purely appearance-based baselines.

Motile cilia of human airway epithelia contain hedgehog signaling components that mediate noncanonical hedgehog signaling.

PubMed

Mao, Suifang; Shah, Alok S; Moninger, Thomas O; Ostedgaard, Lynda S; Lu, Lin; Tang, Xiao Xiao; Thornell, Ian M; Reznikov, Leah R; Ernst, Sarah E; Karp, Philip H; Tan, Ping; Keshavjee, Shaf; Abou Alaiwa, Mahmoud H; Welsh, Michael J

2018-02-06

Differentiated airway epithelia produce sonic hedgehog (SHH), which is found in the thin layer of liquid covering the airway surface. Although previous studies showed that vertebrate HH signaling requires primary cilia, as airway epithelia mature, the cells lose primary cilia and produce hundreds of motile cilia. Thus, whether airway epithelia have apical receptors for SHH has remained unknown. We discovered that motile cilia on airway epithelial cells have HH signaling proteins, including patched and smoothened. These cilia also have proteins affecting cAMP-dependent signaling, including Gα i and adenylyl cyclase 5/6. Apical SHH decreases intracellular levels of cAMP, which reduces ciliary beat frequency and pH in airway surface liquid. These results suggest that apical SHH may mediate noncanonical HH signaling through motile cilia to dampen respiratory defenses at the contact point between the environment and the lung, perhaps counterbalancing processes that stimulate airway defenses. Copyright © 2018 the Author(s). Published by PNAS.

Tunable Quantum Dot Solids: Impact of Interparticle Interactions on Bulk Properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sinclair, Michael B.; Fan, Hongyou; Brener, Igal

2015-09-01

QD-solids comprising self-assembled semiconductor nanocrystals such as CdSe are currently under investigation for use in a wide array of applications including light emitting diodes, solar cells, field effect transistors, photodetectors, and biosensors. The goal of this LDRD project was develop a fundamental understanding of the relationship between nanoparticle interactions and the different regimes of charge and energy transport in semiconductor quantum dot (QD) solids. Interparticle spacing was tuned through the application of hydrostatic pressure in a diamond anvil cell, and the impact on interparticle interactions was probed using x-ray scattering and a variety of static and transient optical spectroscopies. Duringmore » the course of this LDRD, we discovered a new, previously unknown, route to synthesize semiconductor quantum wires using high pressure sintering of self-assembled quantum dot crystals. We believe that this new, pressure driven synthesis approach holds great potential as a new tool for nanomaterials synthesis and engineering.« less

Arcella peruviana sp. nov. (Amoebozoa: Arcellinida, Arcellidae), a new species from a tropical peatland in Amazonia.

PubMed

Reczuga, Monika K; Swindles, Graeme T; Grewling, Łukasz; Lamentowicz, Mariusz

2015-10-01

There has only been one study on the ecology of testate amoebae from Amazonian peatlands, despite Amazonia being a biodiversity hotspot of global importance. During analysis of litter samples from Aucayacu peatland, western (Peruvian) Amazonia, we discovered a testate amoeba with a distinct morphology unlike any other species reported previously. We describe a new species, Arcella peruviana, based on its distinct morphology, compare it to morphologically similar species and provide information about its ecology. This new species is characterised by a distinct cruciform aperture (diameter ranges between 12 and 17μm) which is slightly invaginated. The test is small (height 43-57μm) and polygonal in cross-section. Our discovery suggests the existence of an unknown diversity of testate amoebae in Amazonia. The absence of the new Arcella species in more intensively-sampled regions supports the view that protists have restricted distributions. Copyright © 2015 Elsevier GmbH. All rights reserved.

Ethnic Prejudice against the Mapuche in Chilean Society as a Reflection of the Racist Ideology of the Spanish Conquistadors

ERIC Educational Resources Information Center

Merino, Maria E.; Quilaqueo, Daniel

2003-01-01

The conquest of Chile and of America in general constituted an encounter between different and mutually unknown civilizations that discovered the existence of an "extreme otherness" which European civilization would generically call "Indians." The Spanish encounter with the aboriginals was both violent and subtle. The…

The Role of Engineering Skills in Development

ERIC Educational Resources Information Center

DeBoer, Jennifer Jean

2012-01-01

A young child dreams of being an astronaut. She dreams of piloting a complex rocket full of buttons and gadgets through the sky and discovering new planets in the unknown, unchartered universe of scientific frontiers. As the child grows, she makes her way through the sacred halls of formal schooling. She takes classes, goes to college, and starts…

The cingulum: A unique structure of some Dolichopodidae

Treesearch

Justin Runyon

2008-01-01

The cingulum is a U-shaped structure of unknown function which arises between abdominal sterna 4 and 5 and terminates in a pair of variously modified flag-like appendages. This structure is well developed only in males of the genus Scellus. Richard Hurley discovered that Hydatostega have a much reduced cingulum, a finding that had broad implications for elucidating...

The need for genetic study to diagnose some cases of distal renal tubular acidosis.

PubMed

Heras Benito, Manuel; Garcia-Gonzalez, Miguel A; Valdenebro Recio, María; Molina Ordás, Álvaro; Callejas Martínez, Ramiro; Rodríguez Gómez, María Astrid; Calle García, Leonardo; Sousa Silva, Lisbeth; Fernández-Reyes Luis, María José

We describe the case of a young woman who was diagnosed with advanced kidney disease, with an incidental finding of nephrocalcinosis of unknown aetiology, having been found asymptomatic throughout her life. The genetic study by panels of known genes associated with tubulointerstitial disease allowed us to discover autosomal dominant distal renal tubular acidosis associated with a de novo mutation in exon 14 of the SLC4A1 gene, which would have been impossible to diagnose clinically due to the advanced nature of the kidney disease when it was discovered. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Overcoming an obstacle in expanding a UMLS semantic type extent.

PubMed

Chen, Yan; Gu, Huanying; Perl, Yehoshua; Geller, James

2012-02-01

This paper strives to overcome a major problem encountered by a previous expansion methodology for discovering concepts highly likely to be missing a specific semantic type assignment in the UMLS. This methodology is the basis for an algorithm that presents the discovered concepts to a human auditor for review and possible correction. We analyzed the problem of the previous expansion methodology and discovered that it was due to an obstacle constituted by one or more concepts assigned the UMLS Semantic Network semantic type Classification. A new methodology was designed that bypasses such an obstacle without a combinatorial explosion in the number of concepts presented to the human auditor for review. The new expansion methodology with obstacle avoidance was tested with the semantic type Experimental Model of Disease and found over 500 concepts missed by the previous methodology that are in need of this semantic type assignment. Furthermore, other semantic types suffering from the same major problem were discovered, indicating that the methodology is of more general applicability. The algorithmic discovery of concepts that are likely missing a semantic type assignment is possible even in the face of obstacles, without an explosion in the number of processed concepts. Copyright © 2011 Elsevier Inc. All rights reserved.

Overcoming an Obstacle in Expanding a UMLS Semantic Type Extent

PubMed Central

Chen, Yan; Gu, Huanying; Perl, Yehoshua; Geller, James

2011-01-01

This paper strives to overcome a major problem encountered by a previous expansion methodology for discovering concepts highly likely to be missing a specific semantic type assignment in the UMLS. This methodology is the basis for an algorithm that presents the discovered concepts to a human auditor for review and possible correction. We analyzed the problem of the previous expansion methodology and discovered that it was due to an obstacle constituted by one or more concepts assigned the UMLS Semantic Network semantic type Classification. A new methodology was designed that bypasses such an obstacle without a combinatorial explosion in the number of concepts presented to the human auditor for review. The new expansion methodology with obstacle avoidance was tested with the semantic type Experimental Model of Disease and found over 500 concepts missed by the previous methodology that are in need of this semantic type assignment. Furthermore, other semantic types suffering from the same major problem were discovered, indicating that the methodology is of more general applicability. The algorithmic discovery of concepts that are likely missing a semantic type assignment is possible even in the face of obstacles, without an explosion in the number of processed concepts. PMID:21925287

New CRISPR-Cas systems from uncultivated microbes

NASA Astrophysics Data System (ADS)

Burstein, David; Harrington, Lucas B.; Strutt, Steven C.; Probst, Alexander J.; Anantharaman, Karthik; Thomas, Brian C.; Doudna, Jennifer A.; Banfield, Jillian F.

2017-02-01

CRISPR-Cas systems provide microbes with adaptive immunity by employing short DNA sequences, termed spacers, that guide Cas proteins to cleave foreign DNA. Class 2 CRISPR-Cas systems are streamlined versions, in which a single RNA-bound Cas protein recognizes and cleaves target sequences. The programmable nature of these minimal systems has enabled researchers to repurpose them into a versatile technology that is broadly revolutionizing biological and clinical research. However, current CRISPR-Cas technologies are based solely on systems from isolated bacteria, leaving the vast majority of enzymes from organisms that have not been cultured untapped. Metagenomics, the sequencing of DNA extracted directly from natural microbial communities, provides access to the genetic material of a huge array of uncultivated organisms. Here, using genome-resolved metagenomics, we identify a number of CRISPR-Cas systems, including the first reported Cas9 in the archaeal domain of life, to our knowledge. This divergent Cas9 protein was found in little-studied nanoarchaea as part of an active CRISPR-Cas system. In bacteria, we discovered two previously unknown systems, CRISPR-CasX and CRISPR-CasY, which are among the most compact systems yet discovered. Notably, all required functional components were identified by metagenomics, enabling validation of robust in vivo RNA-guided DNA interference activity in Escherichia coli. Interrogation of environmental microbial communities combined with in vivo experiments allows us to access an unprecedented diversity of genomes, the content of which will expand the repertoire of microbe-based biotechnologies.

New CRISPR–Cas systems from uncultivated microbes

DOE PAGES

Burstein, David; Harrington, Lucas B.; Strutt, Steven C.; ...

2016-12-22

We present that CRISPR-Cas systems provide microbes with adaptive immunity by employing short DNA sequences, termed spacers, that guide Cas proteins to cleave foreign DNA. Class 2 CRISPR-Cas systems are streamlined versions, in which a single RNA-bound Cas protein recognizes and cleaves target sequences. The programmable nature of these minimal systems has enabled researchers to repurpose them into a versatile technology that is broadly revolutionizing biological and clinical research. However, current CRISPR-Cas technologies are based solely on systems from isolated bacteria, leaving the vast majority of enzymes from organisms that have not been cultured untapped. Metagenomics, the sequencing of DNAmore » extracted directly from natural microbial communities, provides access to the genetic material of a huge array of uncultivated organisms. Here, using genome-resolved metagenomics, we identify a number of CRISPR-Cas systems, including the first reported Cas9 in the archaeal domain of life, to our knowledge. This divergent Cas9 protein was found in little-studied nanoarchaea as part of an active CRISPR-Cas system. In bacteria, we discovered two previously unknown systems, CRISPR-CasX and CRISPR-CasY, which are among the most compact systems yet discovered. Notably, all required functional components were identified by metagenomics, enabling validation of robust in vivo RNA-guided DNA interference activity in Escherichia coli. Lastly, interrogation of environmental microbial communities combined with in vivo experiments allows us to access an unprecedented diversity of genomes, the content of which will expand the repertoire of microbe-based biotechnologies.« less

New CRISPR–Cas systems from uncultivated microbes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burstein, David; Harrington, Lucas B.; Strutt, Steven C.

We present that CRISPR-Cas systems provide microbes with adaptive immunity by employing short DNA sequences, termed spacers, that guide Cas proteins to cleave foreign DNA. Class 2 CRISPR-Cas systems are streamlined versions, in which a single RNA-bound Cas protein recognizes and cleaves target sequences. The programmable nature of these minimal systems has enabled researchers to repurpose them into a versatile technology that is broadly revolutionizing biological and clinical research. However, current CRISPR-Cas technologies are based solely on systems from isolated bacteria, leaving the vast majority of enzymes from organisms that have not been cultured untapped. Metagenomics, the sequencing of DNAmore » extracted directly from natural microbial communities, provides access to the genetic material of a huge array of uncultivated organisms. Here, using genome-resolved metagenomics, we identify a number of CRISPR-Cas systems, including the first reported Cas9 in the archaeal domain of life, to our knowledge. This divergent Cas9 protein was found in little-studied nanoarchaea as part of an active CRISPR-Cas system. In bacteria, we discovered two previously unknown systems, CRISPR-CasX and CRISPR-CasY, which are among the most compact systems yet discovered. Notably, all required functional components were identified by metagenomics, enabling validation of robust in vivo RNA-guided DNA interference activity in Escherichia coli. Lastly, interrogation of environmental microbial communities combined with in vivo experiments allows us to access an unprecedented diversity of genomes, the content of which will expand the repertoire of microbe-based biotechnologies.« less

Knowing about guessing and guessing about knowing: preschoolers' understanding of indeterminacy.

PubMed

Fay, A L; Klahr, D

1996-04-01

In this article we investigate preschool children's understanding of indeterminacy by examining their ability to distinguish between determinate situations--in which the available evidence eliminates all uncertainty about an outcome--and indeterminate situations--in which it does not. We argue that a full understanding of indeterminacy requires the coordination of 3 processes: search, evaluation, and mapping. We describe 3 experiments aimed at discovering the extent to which these processes, each of which has been implicated in previous accounts of indeterminate reasoning, are developed in preschoolers and the extent to which different children organize the processes into different strategies. Experiment 1 examines 5-year-olds' performance on 1- versus 2-solution problems having different configurations of irrelevant information. Experiments 2 and 3 extend the possible sources of indeterminacy from 2 to 4 and vary the amount of consistent, inconsistent, and to-be-discovered evidence. Our results show that 4- and 5-year-old children readily give "Can tell" responses to determinate problems, as well as "Can't tell" responses when they think that the evidence warrants such a response. In addition, we report 2 new findings: (a) different children use different strategies to process determinate evidence, and these strategies, in turn, predict their performance on indeterminate problems; (b) evidence patterns in which a single positive instance is contrasted with 1 or more negative or unknown instances are particularly difficult to resolve. Many children use a decision rule--the Positive Capture rule--that produces consistent errors on this type of problem.

Turning publicly available gene expression data into discoveries using gene set context analysis.

PubMed

Ji, Zhicheng; Vokes, Steven A; Dang, Chi V; Ji, Hongkai

2016-01-08

Gene Set Context Analysis (GSCA) is an open source software package to help researchers use massive amounts of publicly available gene expression data (PED) to make discoveries. Users can interactively visualize and explore gene and gene set activities in 25,000+ consistently normalized human and mouse gene expression samples representing diverse biological contexts (e.g. different cells, tissues and disease types, etc.). By providing one or multiple genes or gene sets as input and specifying a gene set activity pattern of interest, users can query the expression compendium to systematically identify biological contexts associated with the specified gene set activity pattern. In this way, researchers with new gene sets from their own experiments may discover previously unknown contexts of gene set functions and hence increase the value of their experiments. GSCA has a graphical user interface (GUI). The GUI makes the analysis convenient and customizable. Analysis results can be conveniently exported as publication quality figures and tables. GSCA is available at https://github.com/zji90/GSCA. This software significantly lowers the bar for biomedical investigators to use PED in their daily research for generating and screening hypotheses, which was previously difficult because of the complexity, heterogeneity and size of the data. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Simultaneous determination of components released from dental composite resins in human saliva by liquid chromatography/multiple-stage ion trap mass spectrometry.

PubMed

Hsu, Wei-Yi; Wang, Ven-Shing; Lai, Chien-Chen; Tsai, Fuu-Jen

2012-02-01

Dental composite resins are widely used for fixing teeth; however, the monomers used in dental composite resins have been found to be cytotoxic and genotoxic, namely triethylene glycol dimethacrylate (TEGDMA), urethane dimethacrylate (UDMA), and bisphenol A glycol dimethacrylate (Bis-GMA). In this study, we incubated dental composite resins with human saliva for demonstrating the released monomers and biodegradation products. A simple saliva sample dilution method without purification or derivatization was used for quantification. We found that liquid chromatography coupled with multiple-stage ion trap mass spectrometry (LC-MS(n) ) operated in selected reaction monitoring (SRM) mode was able to separate the three monomers within 10 min. The calibration curves were linear (R² >0.996) over a wide range for each monomer in saliva: TEGDMA, 5-500 ppb; UDMA, 5-100 ppb, and Bis-GMA, 5-700 ppb. Furthermore, several biodegradation products were discovered with data-dependent MS/MS scan techniques. Although TEGMA degradation products have previously been reported, we identified two previously unknown UDMA degradation products. The LC-MS/MS method developed in this study was able to successfully quantify monomers and their principal biodegradation products from dental composite resins in human saliva. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Successful decoding of famous faces in the fusiform face area.

PubMed

Axelrod, Vadim; Yovel, Galit

2015-01-01

What are the neural mechanisms of face recognition? It is believed that the network of face-selective areas, which spans the occipital, temporal, and frontal cortices, is important in face recognition. A number of previous studies indeed reported that face identity could be discriminated based on patterns of multivoxel activity in the fusiform face area and the anterior temporal lobe. However, given the difficulty in localizing the face-selective area in the anterior temporal lobe, its role in face recognition is still unknown. Furthermore, previous studies limited their analysis to occipito-temporal regions without testing identity decoding in more anterior face-selective regions, such as the amygdala and prefrontal cortex. In the current high-resolution functional Magnetic Resonance Imaging study, we systematically examined the decoding of the identity of famous faces in the temporo-frontal network of face-selective and adjacent non-face-selective regions. A special focus has been put on the face-area in the anterior temporal lobe, which was reliably localized using an optimized scanning protocol. We found that face-identity could be discriminated above chance level only in the fusiform face area. Our results corroborate the role of the fusiform face area in face recognition. Future studies are needed to further explore the role of the more recently discovered anterior face-selective areas in face recognition.

Defending against pathogens – immunological priming and its molecular basis in a sea anemone, cnidarian

PubMed Central

Brown, Tanya; Rodriguez-Lanetty, Mauricio

2015-01-01

Cnidarians, in general, are long-lived organisms and hence may repeatedly encounter common pathogens during their lifespans. It remains unknown whether these early diverging animals possess some type of immunological reaction that strengthens the defense response upon repeated infections, such as that described in more evolutionary derived organisms. Here we show results that sea anemones that had previously encountered a pathogen under sub-lethal conditions had a higher survivorship during a subsequently lethal challenge than naïve anemones that encountered the pathogen for the first time. Anemones subjected to the lethal challenge two and four weeks after the sub-lethal exposure presented seven- and five-fold increases in survival, respectively, compared to the naïve anemones. However, anemones challenged six weeks after the sub-lethal exposure showed no increase in survivorship. We argue that this short-lasting priming of the defense response could be ecologically relevant if pathogen encounters are restricted to short seasons characterized by high stress. Furthermore, we discovered significant changes in proteomic profiles between naïve sea anemones and those primed after pathogen exposure suggesting a clear molecular signature associated with immunological priming in cnidarians. Our findings reveal that immunological priming may have evolved much earlier in the tree of life than previously thought. PMID:26628080

The Swift/BAT Hard X-ray Transient Monitor

NASA Technical Reports Server (NTRS)

Krimm, H. A.; Holland, S. T.; Corbet, R.H.D.; Pearlman, A. B.; Romano, P.; Kennea, J. A.; Bloom, J. S.; Barthelmy, S. D.; Baumgartner, W. H.; Cummings, J. R.;

A novel form of the RelA nuclear factor kappaB subunit is induced by and forms a complex with the proto-oncogene c-Myc.

PubMed Central

Chapman, Neil R; Webster, Gill A; Gillespie, Peter J; Wilson, Brian J; Crouch, Dorothy H; Perkins, Neil D

2002-01-01

Members of both Myc and nuclear factor kappaB (NF-kappaB) families of transcription factors are found overexpressed or inappropriately activated in many forms of human cancer. Furthermore, NF-kappaB can induce c-Myc gene expression, suggesting that the activities of these factors are functionally linked. We have discovered that both c-Myc and v-Myc can induce a previously undescribed, truncated form of the RelA(p65) NF-kappaB subunit, RelA(p37). RelA(p37) encodes the N-terminal DNA binding and dimerization domain of RelA(p65) and would be expected to function as a trans-dominant negative inhibitor of NF-kappaB. Surprisingly, we found that RelA(p37) no longer binds to kappaB elements. This result is explained, however, by the observation that RelA(p37), but not RelA(p65), forms a high-molecular-mass complex with c-Myc. These results demonstrate a previously unknown functional and physical interaction between RelA and c-Myc with many significant implications for our understanding of the role that both proteins play in the molecular events underlying tumourigenesis. PMID:12027803

Red clover: An alternative to antibiotic growth promoters?

USDA-ARS?s Scientific Manuscript database

A series of experiments were conducted at the Forage-Animal Production Research Unit to discover a growth-promoting natural product from red clover (Trifolium pratense). Previously published work included a bioassay for antimicrobial activity of phytochemicals. The bioassay was used to discover th...

[A classical but unknown cause of peritoneal effusion disclosed by echography. Typhoid fever].

PubMed

Judet, O; Rouveix, E; Verderi, D; Bismuth, V

1989-01-01

Two cases of peritoneal effusion discovered by sonography in patients with typhoid fever are reported. These peritoneal effusions have no pejorative value; only clinical findings can differentiate these simple effusions from a perforative thyphoid peritonitis, which is exceptional nowadays. Typhoid fever, among other febrile diseases should be considered when ultrasounds shows an isolated peritoneal effusion.

The Saturn System Through the Eyes of Cassini

NASA Technical Reports Server (NTRS)

Green, James

2017-01-01

More than 400 years ago, Galileo Galilei trained his homemade telescope on the night sky and observed that Saturn had two objects closely related to the planet extending on either side. At the time, in 1610, Galileo declared them to be moons. A few decades later, Saturn moon science accelerated at a dizzying pace. Christiaan Huygens first observed Saturn's largest moon Titan in 1655 and was the first to describe the extended moon-like features at Saturn as a disk of material sounding the planet. From 1671 to 1674, Giovanni Cassini discovered the moons lapetus, Rhea, Dione and Tethys. In 1675, Cassini discovered the gap in Saturn's rings that we now know as the Cassini Division. In the space age, before the Cassini-Huygens mission, we had only hints of the discoveries awaiting us at Saturn. Pioneer 11 and Voyagers 1 and 2 conducted flybys decades ago. But these quick encounters didn't allow time for more extensive research. NASA and the European Space Agency created a partnership to orbit a Saturn orbiter (Cassini) and a lander (Huygens) on Titan. Like its namesakes, the Cassini-Huygens mission not only discovered previously unknown moons, but it also helped us understand the science behind their formation, their interactions with the rings, and how truly diverse they are. The Cassini-Huygens mission revolutionized what we know about the Saturn system. The rings of Saturn, the moons, and the planet itself offer irresistible and inexhaustible subjects for intense study, and Cassini-Huygens did not disappoint. The Saturnian system proved to be a rich ground for science exploration and discoveries, and Cassini has been nothing short of a discovery machine. At the time Cassini plunged into Saturn at the end of its mission, it had observed the planet for a little less than half of a Saturn year. But it also orbited the gas giant 293 times, forever changing our understanding of the Saturn system and yielding tremendous insight for understanding the entire Solar System.

A new Aura virus isolate in Brazil shows segment duplication in the variable region of the nsP3 gene.

PubMed

Mosimann, Ana Luiza Pamplona; de Siqueira, Mirian Krystel; Ceole, Ligia Fernanda; Nunes Duarte Dos Santos, Claudia

2018-05-29

A new isolate of Aura virus serendipitously discovered as a cell culture contaminant is reported in this manuscript. Aura virus belongs to the family Togaviridae and is classified in the genus Alphavirus. There are only two reports of Aura virus isolation from mosquitoes in the scientific literature, and the existence of a vertebrate host is still unknown. The discovery of this new isolate was based on transmission electron microscopy and nucleic acid amplification through a non-specific RT-PCR amplification protocol followed by sequencing. Genetic analysis has shown that the new virus shares a high degree of identity with the previously described isolate (GenBank: AF126284.1). A major difference was observed in the nsP3 gene in which a 234-nucleotide duplication has been identified. Furthermore, a pronounced difference was observed in cell cultures compared to the data available for the previously described isolate. Cell permissiveness and phenotypic characteristics in C6/36, Vero and BHK-21 cells were found to differ from previous reports. This may be due to the genetic differences that have been observed. The genetic and biological characteristics of the new Aura virus isolate are suggestive of viral adaptation to the cell substrate. The development of a cDNA clone will lend a perspective and better understanding of these results as well as open avenues for its use as a biotechnological tool, as seen for other alphaviruses.

Whole exome sequencing identifies genetic variants in inherited thrombocytopenia with secondary qualitative function defects.

PubMed

Johnson, Ben; Lowe, Gillian C; Futterer, Jane; Lordkipanidzé, Marie; MacDonald, David; Simpson, Michael A; Sanchez-Guiú, Isabel; Drake, Sian; Bem, Danai; Leo, Vincenzo; Fletcher, Sarah J; Dawood, Ban; Rivera, José; Allsup, David; Biss, Tina; Bolton-Maggs, Paula Hb; Collins, Peter; Curry, Nicola; Grimley, Charlotte; James, Beki; Makris, Mike; Motwani, Jayashree; Pavord, Sue; Talks, Katherine; Thachil, Jecko; Wilde, Jonathan; Williams, Mike; Harrison, Paul; Gissen, Paul; Mundell, Stuart; Mumford, Andrew; Daly, Martina E; Watson, Steve P; Morgan, Neil V

2016-10-01

Inherited thrombocytopenias are a heterogeneous group of disorders characterized by abnormally low platelet counts which can be associated with abnormal bleeding. Next-generation sequencing has previously been employed in these disorders for the confirmation of suspected genetic abnormalities, and more recently in the discovery of novel disease-causing genes. However its full potential has not yet been exploited. Over the past 6 years we have sequenced the exomes from 55 patients, including 37 index cases and 18 additional family members, all of whom were recruited to the UK Genotyping and Phenotyping of Platelets study. All patients had inherited or sustained thrombocytopenia of unknown etiology with platelet counts varying from 11×10 9 /L to 186×10 9 /L. Of the 51 patients phenotypically tested, 37 (73%), had an additional secondary qualitative platelet defect. Using whole exome sequencing analysis we have identified "pathogenic" or "likely pathogenic" variants in 46% (17/37) of our index patients with thrombocytopenia. In addition, we report variants of uncertain significance in 12 index cases, including novel candidate genetic variants in previously unreported genes in four index cases. These results demonstrate that whole exome sequencing is an efficient method for elucidating potential pathogenic genetic variants in inherited thrombocytopenia. Whole exome sequencing also has the added benefit of discovering potentially pathogenic genetic variants for further study in novel genes not previously implicated in inherited thrombocytopenia. Copyright© Ferrata Storti Foundation.

On the correlation between hydrogen bonding and melting points in the inositols

PubMed Central

Bekö, Sándor L.; Alig, Edith; Schmidt, Martin U.; van de Streek, Jacco

2014-01-01

Inositol, 1,2,3,4,5,6-hexahydroxycyclohexane, exists in nine stereoisomers with different crystal structures and melting points. In a previous paper on the relationship between the melting points of the inositols and the hydrogen-bonding patterns in their crystal structures [Simperler et al. (2006 ▶). CrystEngComm 8, 589], it was noted that although all inositol crystal structures known at that time contained 12 hydrogen bonds per molecule, their melting points span a large range of about 170 °C. Our preliminary investigations suggested that the highest melting point must be corrected for the effect of molecular symmetry, and that the three lowest melting points may need to be revised. This prompted a full investigation, with additional experiments on six of the nine inositols. Thirteen new phases were discovered; for all of these their crystal structures were examined. The crystal structures of eight ordered phases could be determined, of which seven were obtained from laboratory X-ray powder diffraction data. Five additional phases turned out to be rotator phases and only their unit cells could be determined. Two previously unknown melting points were measured, as well as most enthalpies of melting. Several previously reported melting points were shown to be solid-to-solid phase transitions or decomposition points. Our experiments have revealed a complex picture of phases, rotator phases and phase transitions, in which a simple correlation between melting points and hydrogen-bonding patterns is not feasible. PMID:25075320

New Trichoptera records from Arkansas and Missouri

Treesearch

David A. Etnier

2010-01-01

Analysis of about 69,000 Trichoptera from Arkansas and Missouri resulted in identification of six species previously unknown from Arkansas (i.e., Agraylea costello, Neotrichia collata, Orthotrichia curta, Oxyethira glasa, O. pescadori, Neureclipsis piersoni) and three species previously unknown from Missouri (i.e., Cheumatopsyche mollala, Hydroptila broweri, H....

Chasing Down Gravitational Wave Sources with the Dark Energy Camera

DOE Office of Scientific and Technical Information (OSTI.GOV)

Annis, Jim; Soares-Santos, Marcelle

On August 17, 2017, scientists using the Dark Energy Camera tracked down the first visible counterpart to a gravitational wave signal ever spotted by astronomers. Using data provided by the LIGO and Virgo collaborations, scientists embarked on a quest for the unknown, and discovered a new wonder of the universe. Includes interviews with Fermilab’s Jim Annis and Brandeis University’s Marcelle Soares-Santos.

HISTOCHEMICAL TESTS OF DISCOVERY OF FAT PEROXIDES IN THE EPIDERMIS OF RATS IN LOCAL IRRADIATION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Godlewski, H.

1958-01-01

Fat peroxides were determined according to the method of Dubulo and Duma 0, 3, 6, and 24 hr after single local irradiation of the hip with a dose of 2400 r. Negative results were obtained. However, the peroxides were discovered in irradiated as well as in control animals in places of prolonged restorative degeneration of unknown etiology (panniculus carnosus?).

The birth and fate of new generic names

Treesearch

D. Jean Lodge; Andrus Voitk

2014-01-01

No student of natural history can have escaped the proliferation of new names in the last few decades, certainly evident in mycology. Of course, the most obvious need for a new name comes about when an organism is discovered whose existence was hitherto unknown, i.e. a species, genus, or larger group new to science. However, for the layman the sudden profusion of new...

An evaluation of the flora adjacent to wine grape vineyards for the presence of alternative host plants of grapevine red blotch-associated virus

USDA-ARS?s Scientific Manuscript database

Grapevine red blotch-associated virus (GRBaV) is a recently discovered virus of concern to wine grape production in North America. While the vector of this virus is unknown, other elements of virus epidemiology are essential to develop guidelines for the management of the virus as well as to assist ...

Solution Strategies, Modes of Representation and Justifications of Primary Five Pupils in Solving Pre Algebra Problems: An Experience of Using Task-Based Interview and Verbal Protocol Analysis

ERIC Educational Resources Information Center

Ling, Gan We; Ghazali, Munirah

2007-01-01

This descriptive study was aimed at looking into how Primary 5 pupils solve pre-algebra problems concerning patterns and unknown quantities. Specifically, objectives of this study were to describe Primary 5 pupils' solution strategies, modes of representations and justifications in: (a) discovering, describing and using numerical and geometrical…

Neutral Loss Scan - Based Strategy for Integrated Identification of Amorfrutin Derivatives, New Peroxisome Proliferator-Activated Receptor Gamma Agonists, from Amorpha Fruticosa by UPLC-QqQ-MS/MS and UPLC-Q-TOF-MS.

PubMed

Chen, Chu; Xue, Ying; Li, Qing-Miao; Wu, Yan; Liang, Jian; Qing, Lin-Sen

2018-04-01

Amorfrutins with a 2-hydroxybenzoic acid core structure are promising natural PPARγ agonists with potent antidiabetic activity. Owing to the complex matrix and low concentration in botanical material, the identification of unknown amorfrutins remains a challenge. In the present study, a combined application of UPLC-Q-TOF-MS and UPLC-QqQ-MS was developed to discover unknown amorfrutins from fruits of Amorpha fruticosa. First, reference compounds of amorfrutin A (AA), amorfrutin B (AB), and 2-carboxy-3,5-dihydroxy-4-geranylbibenzyl (AC) were analyzed using UPLC-Q-TOF-MS to reveal the characteristic fragment ions and the possible neutral loss. Second, the extract of A. fruticosa was separated and screened by UPLC-QqQ-MS using neutral loss scan to find out suspect compounds associated with the specified neutral fragment Δm/z 44. Third, the extract was re-analyzed by UPLC-Q-TOF-MS to obtain the exact mass of quasi-molecular ion and fragment ions of each suspect compound, and to subsequently calculate their corresponding molecular formulas. Finally, according to the molecular formula of suspect compound and its fragment ions and comparing with literature data, structure elucidation of four unidentified amorfrutins was achieved. The results indicated that the combination of QqQ-MS neutral loss scan and Q-TOF-MS molecular formula calculation was proven to be a powerful tool for unknown natural product identification, and this strategy provides an effective solution to discover natural products or metabolites of trace content. Graphical Abstract ᅟ.

Neutral Loss Scan - Based Strategy for Integrated Identification of Amorfrutin Derivatives, New Peroxisome Proliferator-Activated Receptor Gamma Agonists, from Amorpha Fruticosa by UPLC-QqQ-MS/MS and UPLC-Q-TOF-MS

NASA Astrophysics Data System (ADS)

Chen, Chu; Xue, Ying; Li, Qing-Miao; Wu, Yan; Liang, Jian; Qing, Lin-Sen

2018-02-01

Amorfrutins with a 2-hydroxybenzoic acid core structure are promising natural PPARγ agonists with potent antidiabetic activity. Owing to the complex matrix and low concentration in botanical material, the identification of unknown amorfrutins remains a challenge. In the present study, a combined application of UPLC-Q-TOF-MS and UPLC-QqQ-MS was developed to discover unknown amorfrutins from fruits of Amorpha fruticosa. First, reference compounds of amorfrutin A (AA), amorfrutin B (AB), and 2-carboxy-3,5-dihydroxy-4-geranylbibenzyl (AC) were analyzed using UPLC-Q-TOF-MS to reveal the characteristic fragment ions and the possible neutral loss. Second, the extract of A. fruticosa was separated and screened by UPLC-QqQ-MS using neutral loss scan to find out suspect compounds associated with the specified neutral fragment Δm/z 44. Third, the extract was re-analyzed by UPLC-Q-TOF-MS to obtain the exact mass of quasi-molecular ion and fragment ions of each suspect compound, and to subsequently calculate their corresponding molecular formulas. Finally, according to the molecular formula of suspect compound and its fragment ions and comparing with literature data, structure elucidation of four unidentified amorfrutins was achieved. The results indicated that the combination of QqQ-MS neutral loss scan and Q-TOF-MS molecular formula calculation was proven to be a powerful tool for unknown natural product identification, and this strategy provides an effective solution to discover natural products or metabolites of trace content.

Functional Genome Mining for Metabolites Encoded by Large Gene Clusters through Heterologous Expression of a Whole-Genome Bacterial Artificial Chromosome Library in Streptomyces spp.

PubMed Central

Xu, Min; Wang, Yemin; Zhao, Zhilong; Gao, Guixi; Huang, Sheng-Xiong; Kang, Qianjin; He, Xinyi; Lin, Shuangjun; Pang, Xiuhua; Deng, Zixin

2016-01-01

ABSTRACT Genome sequencing projects in the last decade revealed numerous cryptic biosynthetic pathways for unknown secondary metabolites in microbes, revitalizing drug discovery from microbial metabolites by approaches called genome mining. In this work, we developed a heterologous expression and functional screening approach for genome mining from genomic bacterial artificial chromosome (BAC) libraries in Streptomyces spp. We demonstrate mining from a strain of Streptomyces rochei, which is known to produce streptothricins and borrelidin, by expressing its BAC library in the surrogate host Streptomyces lividans SBT5, and screening for antimicrobial activity. In addition to the successful capture of the streptothricin and borrelidin biosynthetic gene clusters, we discovered two novel linear lipopeptides and their corresponding biosynthetic gene cluster, as well as a novel cryptic gene cluster for an unknown antibiotic from S. rochei. This high-throughput functional genome mining approach can be easily applied to other streptomycetes, and it is very suitable for the large-scale screening of genomic BAC libraries for bioactive natural products and the corresponding biosynthetic pathways. IMPORTANCE Microbial genomes encode numerous cryptic biosynthetic gene clusters for unknown small metabolites with potential biological activities. Several genome mining approaches have been developed to activate and bring these cryptic metabolites to biological tests for future drug discovery. Previous sequence-guided procedures relied on bioinformatic analysis to predict potentially interesting biosynthetic gene clusters. In this study, we describe an efficient approach based on heterologous expression and functional screening of a whole-genome library for the mining of bioactive metabolites from Streptomyces. The usefulness of this function-driven approach was demonstrated by the capture of four large biosynthetic gene clusters for metabolites of various chemical types, including streptothricins, borrelidin, two novel lipopeptides, and one unknown antibiotic from Streptomyces rochei Sal35. The transfer, expression, and screening of the library were all performed in a high-throughput way, so that this approach is scalable and adaptable to industrial automation for next-generation antibiotic discovery. PMID:27451447

Ancient, recurrent phage attacks and recombination shaped dynamic sequence-variable mosaics at the root of phytoplasma genome evolution.

PubMed

Wei, Wei; Davis, Robert E; Jomantiene, Rasa; Zhao, Yan

2008-08-19

Mobile genetic elements have impacted biological evolution across all studied organisms, but evidence for a role in evolutionary emergence of an entire phylogenetic clade has not been forthcoming. We suggest that mobile element predation played a formative role in emergence of the phytoplasma clade. Phytoplasmas are cell wall-less bacteria that cause numerous diseases in plants. Phylogenetic analyses indicate that these transkingdom parasites descended from Gram-positive walled bacteria, but events giving rise to the first phytoplasma have remained unknown. Previously we discovered a unique feature of phytoplasmal genome architecture, genes clustered in sequence-variable mosaics (SVMs), and suggested that such structures formed through recurrent, targeted attacks by mobile elements. In the present study, we discovered that cryptic prophage remnants, originating from phages in the order Caudovirales, formed SVMs and comprised exceptionally large percentages of the chromosomes of 'Candidatus Phytoplasma asteris'-related strains OYM and AYWB, occupying nearly all major nonsyntenic sections, and accounting for most of the size difference between the two genomes. The clustered phage remnants formed genomic islands exhibiting distinct DNA physical signatures, such as dinucleotide relative abundance and codon position GC values. Phytoplasma strain-specific genes identified as phage morons were located in hypervariable regions within individual SVMs, indicating that prophage remnants played important roles in generating phytoplasma genetic diversity. Because no SVM-like structures could be identified in genomes of ancestral relatives including Acholeplasma spp., we hypothesize that ancient phage attacks leading to SVM formation occurred after divergence of phytoplasmas from acholeplasmas, triggering evolution of the phytoplasma clade.

Study of the Metatranscriptome of Eight Social and Solitary Wild Bee Species Reveals Novel Viruses and Bee Parasites

PubMed Central

Schoonvaere, Karel; Smagghe, Guy; Francis, Frédéric; de Graaf, Dirk C.

2018-01-01

Bees are associated with a remarkable diversity of microorganisms, including unicellular parasites, bacteria, fungi, and viruses. The application of next-generation sequencing approaches enables the identification of this rich species composition as well as the discovery of previously unknown associations. Using high-throughput polyadenylated ribonucleic acid (RNA) sequencing, we investigated the metatranscriptome of eight wild bee species (Andrena cineraria, Andrena fulva, Andrena haemorrhoa, Bombus terrestris, Bombus cryptarum, Bombus pascuorum, Osmia bicornis, and Osmia cornuta) sampled from four different localities in Belgium. Across the RNA sequencing libraries, 88–99% of the taxonomically informative reads were of the host transcriptome. Four viruses with homology to insect pathogens were found including two RNA viruses (belonging to the families Iflaviridae and Tymoviridae that harbor already viruses of honey bees), a double stranded DNA virus (family Nudiviridae) and a single stranded DNA virus (family Parvoviridae). In addition, we found genomic sequences of 11 unclassified arthropod viruses (related to negeviruses, sobemoviruses, totiviruses, rhabdoviruses, and mononegaviruses), seven plant pathogenic viruses, and one fungal virus. Interestingly, nege-like viruses appear to be widespread, host-specific, and capable of attaining high copy numbers inside bees. Next to viruses, three novel parasite associations were discovered in wild bees, including Crithidia pragensis and a tubulinosematid and a neogregarine parasite. Yeasts of the genus Metschnikowia were identified in solitary bees. This study gives a glimpse of the microorganisms and viruses associated with social and solitary wild bees and demonstrates that their diversity exceeds by far the subset of species first discovered in honey bees. PMID:29491849

Study of the Metatranscriptome of Eight Social and Solitary Wild Bee Species Reveals Novel Viruses and Bee Parasites.

PubMed

Schoonvaere, Karel; Smagghe, Guy; Francis, Frédéric; de Graaf, Dirk C

2018-01-01

Bees are associated with a remarkable diversity of microorganisms, including unicellular parasites, bacteria, fungi, and viruses. The application of next-generation sequencing approaches enables the identification of this rich species composition as well as the discovery of previously unknown associations. Using high-throughput polyadenylated ribonucleic acid (RNA) sequencing, we investigated the metatranscriptome of eight wild bee species ( Andrena cineraria, Andrena fulva, Andrena haemorrhoa, Bombus terrestris, Bombus cryptarum, Bombus pascuorum, Osmia bicornis , and Osmia cornuta ) sampled from four different localities in Belgium. Across the RNA sequencing libraries, 88-99% of the taxonomically informative reads were of the host transcriptome. Four viruses with homology to insect pathogens were found including two RNA viruses (belonging to the families Iflaviridae and Tymoviridae that harbor already viruses of honey bees), a double stranded DNA virus (family Nudiviridae ) and a single stranded DNA virus (family Parvoviridae ). In addition, we found genomic sequences of 11 unclassified arthropod viruses (related to negeviruses, sobemoviruses, totiviruses, rhabdoviruses, and mononegaviruses), seven plant pathogenic viruses, and one fungal virus. Interestingly, nege-like viruses appear to be widespread, host-specific, and capable of attaining high copy numbers inside bees. Next to viruses, three novel parasite associations were discovered in wild bees, including Crithidia pragensis and a tubulinosematid and a neogregarine parasite. Yeasts of the genus Metschnikowia were identified in solitary bees. This study gives a glimpse of the microorganisms and viruses associated with social and solitary wild bees and demonstrates that their diversity exceeds by far the subset of species first discovered in honey bees.

Sexual and Emotional Infidelity: Evolved Gender Differences in Jealousy Prove Robust and Replicable.

PubMed

Buss, David M

2018-03-01

Infidelity poses threats to high-investment mating relationships. Because of gender differences in some aspects of reproductive biology, such as internal female fertilization, the nature of these threats differs for men and women. Men, but not women, for example, have recurrently faced the problem of uncertainty in their genetic parenthood. Jealousy is an emotion hypothesized to have evolved to combat these threats. The 1992 article Sex Differences in Jealousy: Evolution, Physiology, and Psychology reported three empirical studies using two different methods, forced-choice and physiological experiments. Results supported the evolution-based hypotheses. The article became highly cited for several reasons. It elevated the status of jealousy as an important emotion to be explained by any comprehensive theory of human emotions. Subsequent meta-analyses robustly supported the evolutionary hypotheses. Moreover, the work supported the evolutionary meta-theory of gender differences, which posits differences only in domains in which the sexes have recurrently faced distinct adaptive problems. It also heralded the newly emerging field of evolutionary psychology as a useful perspective that possesses the scientific virtues of testability, falsifiability, and heuristic value in discovering previously unknown psychological phenomena.

Status and progress in coral reef disease research.

PubMed

Weil, Ernesto; Smith, Garriet; Gil-Agudelo, Diego L

2006-03-23

Recent findings on the ecology, etiology and pathology of coral pathogens, host resistance mechanisms, previously unknown disease/syndromes and the global nature of coral reef diseases have increased our concern about the health and future of coral reef communities. Much of what has been discovered in the past 4 years is presented in this special issue. Among the significant findings, the role that various Vibrio species play in coral disease and health, the composition of the 'normal microbiota' of corals, and the possible role of viruses in the disease process are important additions to our knowledge. New information concerning disease resistance and vectors, variation in pathogen composition for both fungal diseases of gorgonians and black band disease across oceans, environmental effects on disease susceptibility and resistance, and temporal and spatial disease variations among different coral species is presented in a number of papers. While the Caribbean may still be the 'disease hot spot' for coral reefs, it is now clear that diseases of coral reef organisms have become a global threat to coral reefs and a major cause of reef deterioration.

A spectro-interferometric view of l Carinae's modulated pulsations

NASA Astrophysics Data System (ADS)

Anderson, Richard I.; Mérand, Antoine; Kervella, Pierre; Breitfelder, Joanne; Eyer, Laurent; Gallenne, Alexandre

Classical Cepheids are radially pulsating stars that enable important tests of stellar evolution and play a crucial role in the calibration of the local Hubble constant. l Carinae is a particularly well-known distance calibrator, being the closest long-period (P ~ 35.5 d) Cepheid and subtending the largest angular diameter. We have carried out an unprecedented observing program to investigate whether recently discovered cycle-to-cycle changes (modulations) of l Carinae's radial velocity (RV) variability are mirrored by its variability in angular size. To this end, we have secured a fully contemporaneous dataset of high-precision RVs and high-precision angular diameters. Here we provide a concise summary of our project and report preliminary results. We confirm the modulated nature of the RV variability and find tentative evidence of cycle-to-cycle differences in l Car's maximal angular diameter. Our analysis is exploring the limits of state-of-the-art instrumentation and reveals additional complexity in the pulsations of Cepheids. If confirmed, our result suggests a previously unknown pulsation cycle dependence of projection factors required for determining Cepheid distances via the Baade-Wesselink technique.

High-resolution forest carbon stocks and emissions in the Amazon.

PubMed

Asner, Gregory P; Powell, George V N; Mascaro, Joseph; Knapp, David E; Clark, John K; Jacobson, James; Kennedy-Bowdoin, Ty; Balaji, Aravindh; Paez-Acosta, Guayana; Victoria, Eloy; Secada, Laura; Valqui, Michael; Hughes, R Flint

2010-09-21

Efforts to mitigate climate change through the Reduced Emissions from Deforestation and Degradation (REDD) depend on mapping and monitoring of tropical forest carbon stocks and emissions over large geographic areas. With a new integrated use of satellite imaging, airborne light detection and ranging, and field plots, we mapped aboveground carbon stocks and emissions at 0.1-ha resolution over 4.3 million ha of the Peruvian Amazon, an area twice that of all forests in Costa Rica, to reveal the determinants of forest carbon density and to demonstrate the feasibility of mapping carbon emissions for REDD. We discovered previously unknown variation in carbon storage at multiple scales based on geologic substrate and forest type. From 1999 to 2009, emissions from land use totaled 1.1% of the standing carbon throughout the region. Forest degradation, such as from selective logging, increased regional carbon emissions by 47% over deforestation alone, and secondary regrowth provided an 18% offset against total gross emissions. Very high-resolution monitoring reduces uncertainty in carbon emissions for REDD programs while uncovering fundamental environmental controls on forest carbon storage and their interactions with land-use change.

Loss of synaptic Zn2+ transporter function increases risk of febrile seizures

PubMed Central

Hildebrand, Michael S.; Phillips, A. Marie; Mullen, Saul A.; Adlard, Paul A.; Hardies, Katia; Damiano, John A.; Wimmer, Verena; Bellows, Susannah T.; McMahon, Jacinta M.; Burgess, Rosemary; Hendrickx, Rik; Weckhuysen, Sarah; Suls, Arvid; De Jonghe, Peter; Scheffer, Ingrid E.; Petrou, Steven; Berkovic, Samuel F.; Reid, Christopher A.

2015-01-01

Febrile seizures (FS) are the most common seizure syndrome and are potentially a prelude to more severe epilepsy. Although zinc (Zn2+) metabolism has previously been implicated in FS, whether or not variation in proteins essential for Zn2+ homeostasis contributes to susceptibility is unknown. Synaptic Zn2+ is co-released with glutamate and modulates neuronal excitability. SLC30A3 encodes the zinc transporter 3 (ZNT3), which is primarily responsible for moving Zn2+ into synaptic vesicles. Here we sequenced SLC30A3 and discovered a rare variant (c.892C > T; p.R298C) enriched in FS populations but absent in population-matched controls. Functional analysis revealed a significant loss-of-function of the mutated protein resulting from a trafficking deficit. Furthermore, mice null for ZnT3 were more sensitive than wild-type to hyperthermia-induced seizures that model FS. Together our data suggest that reduced synaptic Zn2+ increases the risk of FS and more broadly support the idea that impaired synaptic Zn2+ homeostasis can contribute to neuronal hyperexcitability. PMID:26647834

Loss of synaptic Zn2+ transporter function increases risk of febrile seizures.

PubMed

Hildebrand, Michael S; Phillips, A Marie; Mullen, Saul A; Adlard, Paul A; Hardies, Katia; Damiano, John A; Wimmer, Verena; Bellows, Susannah T; McMahon, Jacinta M; Burgess, Rosemary; Hendrickx, Rik; Weckhuysen, Sarah; Suls, Arvid; De Jonghe, Peter; Scheffer, Ingrid E; Petrou, Steven; Berkovic, Samuel F; Reid, Christopher A

2015-12-09

Febrile seizures (FS) are the most common seizure syndrome and are potentially a prelude to more severe epilepsy. Although zinc (Zn(2+)) metabolism has previously been implicated in FS, whether or not variation in proteins essential for Zn(2+) homeostasis contributes to susceptibility is unknown. Synaptic Zn(2+) is co-released with glutamate and modulates neuronal excitability. SLC30A3 encodes the zinc transporter 3 (ZNT3), which is primarily responsible for moving Zn(2+) into synaptic vesicles. Here we sequenced SLC30A3 and discovered a rare variant (c.892C > T; p.R298C) enriched in FS populations but absent in population-matched controls. Functional analysis revealed a significant loss-of-function of the mutated protein resulting from a trafficking deficit. Furthermore, mice null for ZnT3 were more sensitive than wild-type to hyperthermia-induced seizures that model FS. Together our data suggest that reduced synaptic Zn(2+) increases the risk of FS and more broadly support the idea that impaired synaptic Zn(2+) homeostasis can contribute to neuronal hyperexcitability.

Anatomical correlates of self-handicapping tendency.

PubMed

Takeuchi, Hikaru; Taki, Yasuyuki; Nouchi, Rui; Hashizume, Hiroshi; Sekiguchi, Atsushi; Kotozaki, Yuka; Nakagawa, Seishu; Miyauchi, Carlos M; Sassa, Yuko; Kawashima, Ryuta

2013-04-01

Self-handicaps are obstacles created (or claimed) by individuals in anticipation of failure. Despite the vast amount of psychological research on self-handicapping tendency, the neural mechanisms underlying individual differences in self-handicapping tendency in young and healthy subjects are unknown. We used voxel-based morphometry (VBM) and a questionnaire to measure individual self-handicapping tendency, and we investigated the association between regional gray matter volume (rGMV) and self-handicapping tendency across the brain in healthy young adult (mean age, 21.3 years; standard deviation - SD = 1.9) men (n = 94) and women (n = 91). We discovered that higher individual self-handicapping tendency was associated with larger rGMV in the subgenual cingulate gyrus (sgCG). A wide range of previous studies showed (a) the opposite pattern is seen in the association between rGMV in the sgCG and depression and (b) this area is active when negative emotions are suppressed. The present results suggest that the sgCG is also involved in self-handicapping, which is a behavior thought to be engaged in the protection of self-esteem. Copyright © 2013 Elsevier Ltd. All rights reserved.

A Repeating Fast Radio Burst: Radio and X-ray Follow-up Observations of FRB 121102

NASA Astrophysics Data System (ADS)

Scholz, Paul; Spitler, Laura; Hessels, Jason; Bogdanov, Slavko; Brazier, Adam; Camilo, Fernando; Chatterjee, Shami; Cordes, James M.; Crawford, Fronefield; Deneva, Julia S.; Ferdman, Robert; Freire, Paulo; Kaspi, Victoria M.; Lazarus, Patrick; Lynch, Ryan; Madsen, Erik; McLaughlin, Maura; Patel, Chitrang; Ransom, Scott M.; Seymour, Andrew; Stairs, Ingrid H.; Stappers, Benjamin; van Leeuwen, Joeri; Zhu, Weiwei

2016-04-01

A new phenomenon has emerged in high-energy astronomy in the past few years: the Fast Radio Burst. Fast Radio Bursts (FRBs) are millisecond-duration radio bursts whose dispersion measures imply that they originate from far outside of the Galaxy. Their origin is as yet unknown; their durations and energetics imply that they involve compact objects, such as neutron stars or black holes. Due to their extreme luminosities implied by their distances and the previous absence of any repeat burst in follow-up observations, many potential explanations involve one-time cataclysmic events. However, in our Arecibo telescope follow-up observations of FRB 121102 (discovered in the PALFA survey; Spitler et al. 2014), we find additional bursts at the same location and dispersion measure as the original burst. We also present the results of Swift and Chandra X-ray observations of the field. This result shows that, for at least a sub-set of the FRB population, the source can repeat and thus cannot be explained by a cataclysmic origin.

Inhibition of membrane type-1 matrix metalloproteinase by cancer drugs interferes with the homing of diabetogenic T cells into the pancreas.

PubMed

Savinov, Alexei Y; Rozanov, Dmitri V; Golubkov, Vladislav S; Wong, F Susan; Strongin, Alex Y

2005-07-29

We have discovered that clinically tested inhibitors of matrix metalloproteinases can control the functional activity of T cell membrane type-1 matrix metalloproteinase (MT1-MMP) and the onset of disease in a rodent model of type 1 diabetes in non-obese diabetic mice. We determined that MT1-MMP proteolysis of the T cell surface CD44 adhesion receptor affects the homing of T cells into the pancreas. We also determined that both the induction of the intrinsic T cell MT1-MMP activity and the shedding of cellular CD44 follow the adhesion of insulin-specific, CD8-positive, Kd-restricted T cells to the matrix. Conversely, inhibition of these events by AG3340 (a potent hydroxamate inhibitor that was widely used in clinical trials in cancer patents) impedes the transmigration of diabetogenic T cells into the pancreas and protects non-obese diabetic mice from diabetes onset. Overall, our studies have divulged a previously unknown function of MT1-MMP and identified a promising novel drug target in type I diabetes.

Peptidomics of prolyl endopeptidase in the central nervous system

PubMed Central

Nolte, Whitney M.; Tagore, Debarati M.; Lane, William S.; Saghatelian, Alan

2009-01-01

Prolyl endopeptidase (Prep) is a member of the prolyl peptidase family and is of interest due to its unique biochemistry and connections to cognitive function. Using an unbiased mass spectrometry (MS)-based peptidomics platform, we identified Prep regulated peptides in the central nervous system (CNS) of mice by measuring changes in the peptidome as a function of Prep activity. This approach was validated by the identification of known Prep substrates, such as the neuropeptide substance P and thymosin-β4, the precursor to the bioactive peptide Ac-SDKP. In addition to these known substrates, we also discovered that Prep regulates many additional peptides, including additional bioactive peptides and proline rich peptides (PRPs). Biochemical experiments confirmed that some of these Prep regulated peptides are indeed substrates of the enzyme. Moreover, these experiments also supported the known preference of Prep for shorter peptides, while revealing a previously unknown cleavage site specificity of Prep when processing certain multi-proline containing peptides, including PRPs. The discovery of Prep regulated peptides implicates Prep in new biological pathways and provides insights into the biochemistry of this enzyme. PMID:19911840

Coupling molecules and morphology to discover new clades of ciliates.

NASA Astrophysics Data System (ADS)

Grattepanche, J. D.; Maurer-Alcalá, X. X.; Tucker, S. J.; McManus, G. B.; Katz, L. A.

2016-02-01

In a previous study using high-throughput sequencing (Grattepanche et al submitted, oral presentation?), we observe the presence of two clades of spirotrich ciliates mainly present in marine deep-water along the New England coast. These clades, clusters X1 and X2, are characterized by several deletions in their SSU-rDNA and have been observed elsewhere as both identical and similar sequences have been deposited on GenBank from other environmental studies, but lack morphological description. In order to link molecules (SSU-rDNA sequence) to their morphology, we sample below the photic zone (between 60 to 400m of depth) in the New England coast (Northeast Atlantic) in a transect crossing the continental shelf. We designed an oligonucleotide probe specific for choreotrich and oligotrich ciliates and another specific to clusters X1 and X2 to describe these clades through a combination of Fluorescence In Situ Hybridization (FISH) and light microscopy. Our aim is to increase our knowledge on the morphology of these `unknown' clades of ciliates, which will allow for future ecological studies.

SDSS J102111.02+491330.4: A Newly Discovered Gravitationally Lensed Quasar

NASA Astrophysics Data System (ADS)

Pindor, Bart; Eisenstein, Daniel J.; Gregg, Michael D.; Becker, Robert H.; Inada, Naohisa; Oguri, Masamune; Hall, Patrick B.; Johnston, David E.; Richards, Gordon T.; Schneider, Donald P.; Turner, Edwin L.; Brasi, Guido; Hinz, Philip M.; Kenworthy, Matthew A.; Miller, Doug; Barentine, J. C.; Brewington, Howard J.; Brinkmann, J.; Harvanek, Michael; Kleinman, S. J.; Krzesinski, Jurek; Long, Dan; Neilsen, Eric H., Jr.; Newman, Peter R.; Nitta, Atsuko; Snedden, Stephanie A.; York, Donald G.

2006-01-01

We report follow-up observations of two gravitational lens candidates identified in the Sloan Digital Sky Survey (SDSS) data set. We have confirmed that SDSS J102111.02+491330.4 is a previously unknown gravitationally lensed quasar. This lens system exhibits two images of a z=1.72 quasar, with an image separation of 1.14"+/-0.04". Optical and near-IR imaging of the system reveals the presence of the lensing galaxy between the two quasar images. Observations of SDSS J112012.12+671116.0 indicate that it is more likely a binary quasar than a gravitational lens. This system has two quasars at a redshift of z=1.49, with an angular separation of 1.49"+/-0.02". However, the two quasars have markedly different spectral energy distributions, and no lens galaxy is apparent in optical and near-IR images of this system. We also present a list of 31 SDSS lens candidates that follow-up observations have confirmed are not gravitational lenses. Observations reported here were obtained at the MMT Observatory, a joint facility of the University of Arizona and the Smithsonian Institution.

Occurrence of congenital, cardiovascular, visceral, neurologic, and neuro-ophthalmologic complications in late yaws: a theme for future research.

PubMed

Román, G C; Román, L N

1986-01-01

Late lesions of yaws are thought to be limited to skin, bones and joints, without congenital, visceral, or central nervous system (CNS) involvement. However, the treponemes isolated from patients with yaws, endemic syphilis, and venereal syphilis are genetically identical subspecies of Treponema pallidum. The controversy surrounding distinctions between syphilis and yaws is presented in its historical context, and reports of congenital, visceral, and CNS complications of yaws are reviewed. Isolation of treponemes from aqueous humor, as well as CSF abnormalities in 24.9% of 902 patients with yaws, indicate the existence of CNS involvement. The high prevalence of tropical myeloneuropathies of unknown origin discovered in areas of previous treponemal endemicity, particularly in Jamaica and Colombia, may represent late complications of yaws. Careful analysis of the collected evidence indicates that potential sequelae of yaws include congenital, visceral, and tertiary CNS lesions identical to those of venereal syphilis. The current worldwide resurgence of endemic treponematoses provides an unparalleled opportunity to settle conclusively questions still unanswered regarding the natural history of these infections.

Novel Neuroimaging Methods to Understand How HIV Affects the Brain

PubMed Central

Thompson, Paul

2015-01-01

In much of the developed world, the HIV epidemic has largely been controlled by anti-retroviral treatment. Even so, there is growing concern that HIV-infected individuals may be at risk for accelerated brain aging, and a range of cognitive impairments. What promotes or resists these changes is largely unknown. There is also interest in discovering factors that promote resilience to HIV, and combat its adverse effects in children. Here we review recent developments in brain imaging that reveal how the virus affects the brain. We relate these brain changes to changes in blood markers, cognitive function, and other patient outcomes or symptoms, such as apathy or neuropathic pain. We focus on new and emerging techniques, including new variants of brain MRI. Diffusion tensor imaging, for example, can map the brain’s structural connections while fMRI can uncover functional connections. Finally, we suggest how large-scale global research alliances, such as ENIGMA, may resolve controversies over effects where evidence is now lacking. These efforts pool scans from tens of thousands of individuals, and offer a source of power not previously imaginable for brain imaging studies. PMID:25902966

First Record of Culex coronator In Shelby County, Tennessee.

PubMed

Trimm, Amy; Insch, Andrew; Carlson, Ture

2017-12-01

Culex coronator has been identified in Shelby County, TN, for the first time as an established species. This is an important discovery since the range of Cx. coronator is unknown in Tennessee and it has been found positive for West Nile virus. Larvae and an adult were discovered during routine surveillance. Larvae were collected at 9 different locations, while the 1 adult captured was at the 10th isolated location.

Malignant Melanoma Presenting as a Mediastinal Malignant Melanoma Presenting as a Mediastinal Unknown Primary Origin?

PubMed

Pujani, Mukta; Hassan, Mohd Jaseem; Jetley, Sujata; Raina, Prabhat Kumar; Kumar, Mukesh

2017-01-01

The most common site of primary malignant melanoma is the skin, however, virtually any organ system may be involved. Metastatic melanoma of unknown primary origin accounts for approximately 2-6% of all melanoma cases. The mediastinum as the site for malignant melanoma is extremely rare, both as a primary or metastatic lesion. Primary malignant melanoma of mediastinum is very rare with only a handful of reports in the literature. We hereby report a rare case of malignant melanoma of mediastinum in a 31 year old male who was initially misdiagnosed on fine needle aspiration cytology as adenocarcinoma for which he received chemotherapy with clinical deterioration. Even on extensive meticulous search, no primary was discovered.

Imaging the experiments on respiration and transpiration of Lavoisier and Séguin: two unknown drawings by Madame Lavoisier.

PubMed

Beretta, Marco

2012-01-01

This paper presents two hitherto unknown drawings by Marie-Anne-Pierrette Lavoisier dating to the early 1790s that illustrate the experiments on respiration and transpiration of her husband Antoine-Laurent Lavoisier and his assistant Armand Séguin. These works may be associated with the well-known sepia drawings that were published for the first time by Edouard Grimaux in 1888. Details contained in these newly discovered drawings by M.me Lavoisier provide fresh evidence as to the nature and aims of Lavoisier's innovative experiments. As we will show, these drawings were intended to illustrate the collection of papers on respiration being prepared by Lavoisier for his Mémoires de physique et de chimie (1792-1805).

[Metastasis revealing malignant peritoneum mesothelioma: About the difficulty to identify the primary tumors].

PubMed

Bretagne, Charles-Henri; Petitjean, Alain; Felix, Sophie; Bedgedjian, Isabelle; Algros, Marie-Paule; Delabrousse, Eric; Valmary-Degano, Séverine

2016-04-01

Peritoneal malignant mesothelioma is a rare and extremely aggressive tumor that is sometimes difficult to diagnose. We report two cases of metastatic malignant peritoneal mesothelioma. In one case, malignant metastatic cells were identified in cervical lymph nodes while in the other case, the cells were found in the liver. In both cases, metastases were identified before discovering the primary tumor. This led to the misdiagnosis of carcinoma of unknown origin. Nevertheless, the histological and immuno-histochemical patterns were typical of malignant mesothelioma. Regarding metastasis of unknown origin, a differentiation of epithelioid peritoneal malignant mesothelioma and adenocarcinoma proved to be difficult. Therefore, we discuss the diagnostic usefulness of immuno-histochemical mesothelioma markers. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Approaches for assessing and discovering protein interactions in cancer

PubMed Central

Mohammed, Hisham; Carroll, Jason S.

2013-01-01

Significant insight into the function of proteins, can be delineated by discovering and characterising interacting proteins. There are numerous methods for the discovery of unknown associated protein networks, with purification of the bait (the protein of interest) followed by Mass Spectrometry (MS) as a common theme. In recent years, advances have permitted the purification of endogenous proteins and methods for scaling down starting material. As such, approaches for rapid, unbiased identification of protein interactomes are becoming a standard tool in the researchers toolbox, rather than a technique that is only available to specialists. This review will highlight some of the recent technical advances in proteomic based discovery approaches, the pros and cons of various methods and some of the key findings in cancer related systems. PMID:24072816

SEM-EDX analysis of an unknown "known" white powder found in a shipping container from Peru

NASA Astrophysics Data System (ADS)

Albright, Douglas C.

2009-05-01

In 2008, an unknown white powder was discovered spilled inside of a shipping container of whole kernel corn during an inspection by federal inspectors in the port of Baltimore, Maryland. The container was detained and quarantined while a sample of the powder was collected and sent to a federal laboratory where it was screened using chromatography for the presence of specific poisons and pesticides with negative results. Samples of the corn kernels and the white powder were forwarded to the Food and Drug Administration, Forensic Chemistry Center for further analysis. Stereoscopic Light Microscopy (SLM), Scanning Electron Microscopy/Energy Dispersive X-ray Spectrometry (SEM/EDX), and Polarized Light Microscopy/Infrared Spectroscopy (PLM-IR) were used in the analysis of the kernels and the unknown powder. Based on the unique particle analysis by SLM and SEM as well as the detection of the presence of aluminum and phosphorous by EDX, the unknown was determined to be consistent with reacted aluminum phosphide (AlP). While commonly known in the agricultural industry, aluminum phosphide is relatively unknown in the forensic community. A history of the use and acute toxicity of this compound along with some very unique SEM/EDX analysis characteristics of aluminum phosphide will be discussed.

The Swift-BAT Hard X-Ray Transient Monitor

NASA Technical Reports Server (NTRS)

Krimm, H. A.; Holland, S. T.; Corbet, R. H. D.; Pearlman, A. B.; Romano, P.; Kennea, J. A.; Bloom, J. S.; Barthelmy, S. D.; Baumgartner, W. H.; Cummings, J. R.;

Successful Decoding of Famous Faces in the Fusiform Face Area

PubMed Central

Axelrod, Vadim; Yovel, Galit

2015-01-01

What are the neural mechanisms of face recognition? It is believed that the network of face-selective areas, which spans the occipital, temporal, and frontal cortices, is important in face recognition. A number of previous studies indeed reported that face identity could be discriminated based on patterns of multivoxel activity in the fusiform face area and the anterior temporal lobe. However, given the difficulty in localizing the face-selective area in the anterior temporal lobe, its role in face recognition is still unknown. Furthermore, previous studies limited their analysis to occipito-temporal regions without testing identity decoding in more anterior face-selective regions, such as the amygdala and prefrontal cortex. In the current high-resolution functional Magnetic Resonance Imaging study, we systematically examined the decoding of the identity of famous faces in the temporo-frontal network of face-selective and adjacent non-face-selective regions. A special focus has been put on the face-area in the anterior temporal lobe, which was reliably localized using an optimized scanning protocol. We found that face-identity could be discriminated above chance level only in the fusiform face area. Our results corroborate the role of the fusiform face area in face recognition. Future studies are needed to further explore the role of the more recently discovered anterior face-selective areas in face recognition. PMID:25714434

THE SWIFT/BAT HARD X-RAY TRANSIENT MONITOR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krimm, H. A.; Holland, S. T.; Corbet, R. H. D.

2013-11-01

The Swift/Burst Alert Telescope (BAT) hard X-ray transient monitor provides near real-time coverage of the X-ray sky in the energy range 15-50 keV. The BAT observes 88% of the sky each day with a detection sensitivity of 5.3 mCrab for a full-day observation and a time resolution as fine as 64 s. The three main purposes of the monitor are (1) the discovery of new transient X-ray sources, (2) the detection of outbursts or other changes in the flux of known X-ray sources, and (3) the generation of light curves of more than 900 sources spanning over eight years. Themore » primary interface for the BAT transient monitor is a public Web site. Between 2005 February 12 and 2013 April 30, 245 sources have been detected in the monitor, 146 of them persistent and 99 detected only in outburst. Among these sources, 17 were previously unknown and were discovered in the transient monitor. In this paper, we discuss the methodology and the data processing and filtering for the BAT transient monitor and review its sensitivity and exposure. We provide a summary of the source detections and classify them according to the variability of their light curves. Finally, we review all new BAT monitor discoveries. For the new sources that are previously unpublished, we present basic data analysis and interpretations.« less

Bacterial phylogeny structures soil resistomes across habitats

PubMed Central

Forsberg, Kevin J.; Patel, Sanket; Gibson, Molly K.; Lauber, Christian L.; Knight, Rob; Fierer, Noah; Dantas, Gautam

2014-01-01

Summary Ancient and diverse antibiotic resistance genes (ARGs) have previously been identified from soil1–3, including genes identical to those in human pathogens4. Despite the apparent overlap between soil and clinical resistomes4–6, factors influencing ARG composition in soil and their movement between genomes and habitats remain largely unknown3. General metagenome functions often correlate with the underlying structure of bacterial communities7–12. However, ARGs are hypothesized to be highly mobile4,5,13, prompting speculation that resistomes may not correlate with phylogenetic signatures or ecological divisions13,14. To investigate these relationships, we performed functional metagenomic selections for resistance to 18 antibiotics from 18 agricultural and grassland soils. The 2895 ARGs we discovered were predominantly novel, and represent all major resistance mechanisms15. We demonstrate that distinct soil types harbor distinct resistomes, and that nitrogen fertilizer amendments strongly influenced soil ARG content. Resistome composition also correlated with microbial phylogenetic and taxonomic structure, both across and within soil types. Consistent with this strong correlation, mobility elements syntenic with ARGs were rare in soil compared to sequenced pathogens, suggesting that ARGs in the soil may not transfer between bacteria as readily as is observed in the clinic. Together, our results indicate that bacterial community composition is the primary determinant of soil ARG content, challenging previous hypotheses that horizontal gene transfer effectively decouples resistomes from phylogeny13,14. PMID:24847883

Bacterial phylogeny structures soil resistomes across habitats

NASA Astrophysics Data System (ADS)

Forsberg, Kevin J.; Patel, Sanket; Gibson, Molly K.; Lauber, Christian L.; Knight, Rob; Fierer, Noah; Dantas, Gautam

2014-05-01

Ancient and diverse antibiotic resistance genes (ARGs) have previously been identified from soil, including genes identical to those in human pathogens. Despite the apparent overlap between soil and clinical resistomes, factors influencing ARG composition in soil and their movement between genomes and habitats remain largely unknown. General metagenome functions often correlate with the underlying structure of bacterial communities. However, ARGs are proposed to be highly mobile, prompting speculation that resistomes may not correlate with phylogenetic signatures or ecological divisions. To investigate these relationships, we performed functional metagenomic selections for resistance to 18 antibiotics from 18 agricultural and grassland soils. The 2,895 ARGs we discovered were mostly new, and represent all major resistance mechanisms. We demonstrate that distinct soil types harbour distinct resistomes, and that the addition of nitrogen fertilizer strongly influenced soil ARG content. Resistome composition also correlated with microbial phylogenetic and taxonomic structure, both across and within soil types. Consistent with this strong correlation, mobility elements (genes responsible for horizontal gene transfer between bacteria such as transposases and integrases) syntenic with ARGs were rare in soil by comparison with sequenced pathogens, suggesting that ARGs may not transfer between soil bacteria as readily as is observed between human pathogens. Together, our results indicate that bacterial community composition is the primary determinant of soil ARG content, challenging previous hypotheses that horizontal gene transfer effectively decouples resistomes from phylogeny.

Short-term memory of motor network performance via activity-dependent potentiation of Na+/K+ pump function.

PubMed

Zhang, Hong-Yan; Sillar, Keith T

2012-03-20

Brain networks memorize previous performance to adjust their output in light of past experience. These activity-dependent modifications generally result from changes in synaptic strengths or ionic conductances, and ion pumps have only rarely been demonstrated to play a dynamic role. Locomotor behavior is produced by central pattern generator (CPG) networks and modified by sensory and descending signals to allow for changes in movement frequency, intensity, and duration, but whether or how the CPG networks recall recent activity is largely unknown. In Xenopus frog tadpoles, swim bout duration correlates linearly with interswim interval, suggesting that the locomotor network retains a short-term memory of previous output. We discovered an ultraslow, minute-long afterhyperpolarization (usAHP) in network neurons following locomotor episodes. The usAHP is mediated by an activity- and sodium spike-dependent enhancement of electrogenic Na(+)/K(+) pump function. By integrating spike frequency over time and linking the membrane potential of spinal neurons to network performance, the usAHP plays a dynamic role in short-term motor memory. Because Na(+)/K(+) pumps are ubiquitously expressed in neurons of all animals and because sodium spikes inevitably accompany network activity, the usAHP may represent a phylogenetically conserved but largely overlooked mechanism for short-term memory of neural network function. Copyright © 2012 Elsevier Ltd. All rights reserved.

Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development.

PubMed

Szabo, Linda; Morey, Robert; Palpant, Nathan J; Wang, Peter L; Afari, Nastaran; Jiang, Chuan; Parast, Mana M; Murry, Charles E; Laurent, Louise C; Salzman, Julia

2015-06-16

The pervasive expression of circular RNA is a recently discovered feature of gene expression in highly diverged eukaryotes, but the functions of most circular RNAs are still unknown. Computational methods to discover and quantify circular RNA are essential. Moreover, discovering biological contexts where circular RNAs are regulated will shed light on potential functional roles they may play. We present a new algorithm that increases the sensitivity and specificity of circular RNA detection by discovering and quantifying circular and linear RNA splicing events at both annotated and un-annotated exon boundaries, including intergenic regions of the genome, with high statistical confidence. Unlike approaches that rely on read count and exon homology to determine confidence in prediction of circular RNA expression, our algorithm uses a statistical approach. Using our algorithm, we unveiled striking induction of general and tissue-specific circular RNAs, including in the heart and lung, during human fetal development. We discover regions of the human fetal brain, such as the frontal cortex, with marked enrichment for genes where circular RNA isoforms are dominant. The vast majority of circular RNA production occurs at major spliceosome splice sites; however, we find the first examples of developmentally induced circular RNAs processed by the minor spliceosome, and an enriched propensity of minor spliceosome donors to splice into circular RNA at un-annotated, rather than annotated, exons. Together, these results suggest a potentially significant role for circular RNA in human development.

Social networks and inference about unknown events: A case of the match between Google's AlphaGo and Sedol Lee.

PubMed

Bae, Jonghoon; Cha, Young-Jae; Lee, Hyungsuk; Lee, Boyun; Baek, Sojung; Choi, Semin; Jang, Dayk

2017-01-01

This study examines whether the way that a person makes inferences about unknown events is associated with his or her social relations, more precisely, those characterized by ego network density that reflects the structure of a person's immediate social relation. From the analysis of individual predictions over the Go match between AlphaGo and Sedol Lee in March 2016 in Seoul, Korea, this study shows that the low-density group scored higher than the high-density group in the accuracy of the prediction over a future state of a social event, i.e., the outcome of the first game. We corroborated this finding with three replication tests that asked the participants to predict the following: film awards, President Park's impeachment in Korea, and the counterfactual assessment of the US presidential election. Taken together, this study suggests that network density is negatively associated with vision advantage, i.e., the ability to discover and forecast an unknown aspect of a social event.

Discovering Peripheral Arterial Disease Cases from Radiology Notes Using Natural Language Processing

PubMed Central

Savova, Guergana K.; Fan, Jin; Ye, Zi; Murphy, Sean P.; Zheng, Jiaping; Chute, Christopher G.; Kullo, Iftikhar J.

2010-01-01

As part of the Electronic Medical Records and Genomics Network, we applied, extended and evaluated an open source clinical Natural Language Processing system, Mayo’s Clinical Text Analysis and Knowledge Extraction System, for the discovery of peripheral arterial disease cases from radiology reports. The manually created gold standard consisted of 223 positive, 19 negative, 63 probable and 150 unknown cases. Overall accuracy agreement between the system and the gold standard was 0.93 as compared to a named entity recognition baseline of 0.46. Sensitivity for the positive, probable and unknown cases was 0.93–0.96, and for the negative cases was 0.72. Specificity and negative predictive value for all categories were in the 90’s. The positive predictive value for the positive and unknown categories was in the high 90’s, for the negative category was 0.84, and for the probable category was 0.63. We outline the main sources of errors and suggest improvements. PMID:21347073

Archaea.

PubMed

Eme, Laura; Doolittle, W Ford

2015-10-05

A headline on the front page of the New York Times for November 3, 1977, read "Scientists Discover a Way of Life That Predates Higher Organisms". The accompanying article described a spectacular claim by Carl Woese and George Fox to have discovered a third form of life, a new 'domain' that we now call Archaea. It's not that these microbes were unknown before, nor was it the case that their peculiarities had gone completely unnoticed. Indeed, Ralph Wolfe, in the same department at the University of Illinois as Woese, had already discovered how it was that methanogens (uniquely on the planet) make methane, and the bizarre adaptations that allow extremely halophilic archaea (then called halobacteria) and thermoacidophiles to live in the extreme environments where they do were already under investigation in many labs. But what Woese and Fox had found was that these organisms were related to each other not just in their 'extremophily' but also phylogenetically. And, most surprisingly, they were only remotely related to the rest of the prokaryotes, which we now call the domain Bacteria (Figure 1). Copyright © 2015 Elsevier Ltd. All rights reserved.

Optimization of Photoactive Protein Z for Fast and Efficient Site-Specific Conjugation of Native IgG

PubMed Central

2015-01-01

Antibody conjugates have been used in a variety of applications from immunoassays to drug conjugates. However, it is becoming increasingly clear that in order to maximize an antibody’s antigen binding ability and to produce homogeneous antibody-conjugates, the conjugated molecule should be attached onto IgG site-specifically. We previously developed a facile method for the site-specific modification of full length, native IgGs by engineering a recombinant Protein Z that forms a covalent link to the Fc domain of IgG upon exposure to long wavelength UV light. To further improve the efficiency of Protein Z production and IgG conjugation, we constructed a panel of 13 different Protein Z variants with the UV-active amino acid benzoylphenylalanine (BPA) in different locations. By using this panel of Protein Z to cross-link a range of IgGs from different hosts, including human, mouse, and rat, we discovered two previously unknown Protein Z variants, L17BPA and K35BPA, that are capable of cross-linking many commonly used IgG isotypes with efficiencies ranging from 60% to 95% after only 1 h of UV exposure. When compared to existing site-specific methods, which often require cloning or enzymatic reactions, the Protein Z-based method described here, utilizing the L17BPA, K35BPA, and the previously described Q32BPA variants, represents a vastly more accessible and efficient approach that is compatible with nearly all native IgGs, thus making site-specific conjugation more accessible to the general research community. PMID:25121619

Optimization of photoactive protein Z for fast and efficient site-specific conjugation of native IgG.

PubMed

Hui, James Z; Tsourkas, Andrew

2014-09-17

Antibody conjugates have been used in a variety of applications from immunoassays to drug conjugates. However, it is becoming increasingly clear that in order to maximize an antibody's antigen binding ability and to produce homogeneous antibody-conjugates, the conjugated molecule should be attached onto IgG site-specifically. We previously developed a facile method for the site-specific modification of full length, native IgGs by engineering a recombinant Protein Z that forms a covalent link to the Fc domain of IgG upon exposure to long wavelength UV light. To further improve the efficiency of Protein Z production and IgG conjugation, we constructed a panel of 13 different Protein Z variants with the UV-active amino acid benzoylphenylalanine (BPA) in different locations. By using this panel of Protein Z to cross-link a range of IgGs from different hosts, including human, mouse, and rat, we discovered two previously unknown Protein Z variants, L17BPA and K35BPA, that are capable of cross-linking many commonly used IgG isotypes with efficiencies ranging from 60% to 95% after only 1 h of UV exposure. When compared to existing site-specific methods, which often require cloning or enzymatic reactions, the Protein Z-based method described here, utilizing the L17BPA, K35BPA, and the previously described Q32BPA variants, represents a vastly more accessible and efficient approach that is compatible with nearly all native IgGs, thus making site-specific conjugation more accessible to the general research community.

The industrial melanism mutation in British peppered moths is a transposable element.

PubMed

Van't Hof, Arjen E; Campagne, Pascal; Rigden, Daniel J; Yung, Carl J; Lingley, Jessica; Quail, Michael A; Hall, Neil; Darby, Alistair C; Saccheri, Ilik J

2016-06-02

Discovering the mutational events that fuel adaptation to environmental change remains an important challenge for evolutionary biology. The classroom example of a visible evolutionary response is industrial melanism in the peppered moth (Biston betularia): the replacement, during the Industrial Revolution, of the common pale typica form by a previously unknown black (carbonaria) form, driven by the interaction between bird predation and coal pollution. The carbonaria locus has been coarsely localized to a 200-kilobase region, but the specific identity and nature of the sequence difference controlling the carbonaria-typica polymorphism, and the gene it influences, are unknown. Here we show that the mutation event giving rise to industrial melanism in Britain was the insertion of a large, tandemly repeated, transposable element into the first intron of the gene cortex. Statistical inference based on the distribution of recombined carbonaria haplotypes indicates that this transposition event occurred around 1819, consistent with the historical record. We have begun to dissect the mode of action of the carbonaria transposable element by showing that it increases the abundance of a cortex transcript, the protein product of which plays an important role in cell-cycle regulation, during early wing disc development. Our findings fill a substantial knowledge gap in the iconic example of microevolutionary change, adding a further layer of insight into the mechanism of adaptation in response to natural selection. The discovery that the mutation itself is a transposable element will stimulate further debate about the importance of 'jumping genes' as a source of major phenotypic novelty.

A novel life cycle modeling system for Ebola virus shows a genome length-dependent role of VP24 in virus infectivity.

PubMed

Watt, Ari; Moukambi, Felicien; Banadyga, Logan; Groseth, Allison; Callison, Julie; Herwig, Astrid; Ebihara, Hideki; Feldmann, Heinz; Hoenen, Thomas

2014-09-01

Work with infectious Ebola viruses is restricted to biosafety level 4 (BSL4) laboratories, presenting a significant barrier for studying these viruses. Life cycle modeling systems, including minigenome systems and transcription- and replication-competent virus-like particle (trVLP) systems, allow modeling of the virus life cycle under BSL2 conditions; however, all current systems model only certain aspects of the virus life cycle, rely on plasmid-based viral protein expression, and have been used to model only single infectious cycles. We have developed a novel life cycle modeling system allowing continuous passaging of infectious trVLPs containing a tetracistronic minigenome that encodes a reporter and the viral proteins VP40, VP24, and GP1,2. This system is ideally suited for studying morphogenesis, budding, and entry, in addition to genome replication and transcription. Importantly, the specific infectivity of trVLPs in this system was ∼ 500-fold higher than that in previous systems. Using this system for functional studies of VP24, we showed that, contrary to previous reports, VP24 only very modestly inhibits genome replication and transcription when expressed in a regulated fashion, which we confirmed using infectious Ebola viruses. Interestingly, we also discovered a genome length-dependent effect of VP24 on particle infectivity, which was previously undetected due to the short length of monocistronic minigenomes and which is due at least partially to a previously unknown function of VP24 in RNA packaging. Based on our findings, we propose a model for the function of VP24 that reconciles all currently available data regarding the role of VP24 in nucleocapsid assembly as well as genome replication and transcription. Ebola viruses cause severe hemorrhagic fevers in humans, with no countermeasures currently being available, and must be studied in maximum-containment laboratories. Only a few of these laboratories exist worldwide, limiting our ability to study Ebola viruses and develop countermeasures. Here we report the development of a novel reverse genetics-based system that allows the study of Ebola viruses without maximum-containment laboratories. We used this system to investigate the Ebola virus protein VP24, showing that, contrary to previous reports, it only modestly inhibits virus genome replication and transcription but is important for packaging of genomes into virus particles, which constitutes a previously unknown function of VP24 and a potential antiviral target. We further propose a comprehensive model for the function of VP24 in nucleocapsid assembly. Importantly, on the basis of this approach, it should easily be possible to develop similar experimental systems for other viruses that are currently restricted to maximum-containment laboratories. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

The Solar Neighborhood. XXVII. Discovery of New Proper Motion Stars with μ >= 0farcs18 yr-1 in the Southern Sky with 16.5 < R 59F <= 18.0

NASA Astrophysics Data System (ADS)

Boyd, Mark R.; Henry, Todd J.; Jao, Wei-Chun; Subasavage, John P.; Hambly, Nigel C.

2011-09-01

Here we present 1584 new southern proper motion systems with μ >= 0farcs18 yr-1 and 16.5 > R 59F >= 18.0. This search complements the six previous SuperCOSMOS-RECONS (SCR) proper motion searches of the southern sky for stars within the same proper motion range, but with R 59F <= 16.5. As in previous papers, we present distance estimates for these systems and find that three systems are estimated to be within 25 pc, including one, SCR 1546-5534, possibly within the RECONS 10 pc horizon at 6.7 pc, making it the second nearest discovery of the searches. We find 97 white dwarf candidates with distance estimates between 10 and 120 pc, as well as 557 cool subdwarf candidates. The subdwarfs found in this paper make up nearly half of the subdwarf systems reported from our SCR searches and are significantly redder than those discovered thus far. The SCR searches have now found 155 red dwarfs estimated to be within 25 pc, including 10 within 10 pc. In addition, 143 white dwarf candidates and 1155 cool subdwarf candidates have been discovered. The 1584 systems reported here augment the sample of 4724 systems previously discovered in our SCR searches and imply that additional systems fainter than R 59F = 18.0 are yet to be discovered.

Accessibility of near-Earth asteroids, 1990

NASA Technical Reports Server (NTRS)

Hulkower, Neal D.; Child, Jack B.

1991-01-01

Previous research which analyzed the accessibility of all known near-Earth asteroids is updated. Since then, many new near-Earth asteroids have been discovered, and 1928 DB, the most accessible asteroid at that time, has been recovered. Many of these recently discovered near-Earth asteroids have promising orbital characteristics. In addition to accessibility (as defined by minimum global delta v), ideal rendezvous opportunities are identified.

Huygens Identifies Rings Around Saturn : 350 Years Later

NASA Astrophysics Data System (ADS)

Deau, Estelle; Fulchignoni, M.

2006-09-01

On March 6, 1656, nearly forty years after Galileo discovered a strange object around Saturn and remained enigmatic until this time, a young unknown dutch of the name of Christiaan Huygens published a surprising article entitled "De Saturni luna observatio nova” in which he makes share to the erudite world of the first discovered satellite around Saturn. It finishes this article of only three pages by a logogriph which announces another discovery of which he hopes to be the first author while launching a call to all the astronomers of Europe. This second discovery much more resounding than the first ensured a world fame thereafter to him. We return here on this famous discovery: the identification of the Saturn's rings by the phyical explanation of its changing appearance. 350 years later, the physical assumptions of Huygens are used to understand ring's geometry.

Large-Scale Bioinformatics Analysis of Bacillus Genomes Uncovers Conserved Roles of Natural Products in Bacterial Physiology.

PubMed

Grubbs, Kirk J; Bleich, Rachel M; Santa Maria, Kevin C; Allen, Scott E; Farag, Sherif; Shank, Elizabeth A; Bowers, Albert A

2017-01-01

Bacteria possess an amazing capacity to synthesize a diverse range of structurally complex, bioactive natural products known as specialized (or secondary) metabolites. Many of these specialized metabolites are used as clinical therapeutics, while others have important ecological roles in microbial communities. The biosynthetic gene clusters (BGCs) that generate these metabolites can be identified in bacterial genome sequences using their highly conserved genetic features. We analyzed an unprecedented 1,566 bacterial genomes from Bacillus species and identified nearly 20,000 BGCs. By comparing these BGCs to one another as well as a curated set of known specialized metabolite BGCs, we discovered that the majority of Bacillus natural products are comprised of a small set of highly conserved, well-distributed, known natural product compounds. Most of these metabolites have important roles influencing the physiology and development of Bacillus species. We identified, in addition to these characterized compounds, many unique, weakly conserved BGCs scattered across the genus that are predicted to encode unknown natural products. Many of these "singleton" BGCs appear to have been acquired via horizontal gene transfer. Based on this large-scale characterization of metabolite production in the Bacilli , we go on to connect the alkylpyrones, natural products that are highly conserved but previously biologically uncharacterized, to a role in Bacillus physiology: inhibiting spore development. IMPORTANCE Bacilli are capable of producing a diverse array of specialized metabolites, many of which have gained attention for their roles as signals that affect bacterial physiology and development. Up to this point, however, the Bacillus genus's metabolic capacity has been underexplored. We undertook a deep genomic analysis of 1,566 Bacillus genomes to understand the full spectrum of metabolites that this bacterial group can make. We discovered that the majority of the specialized metabolites produced by Bacillus species are highly conserved, known compounds with important signaling roles in the physiology and development of this bacterium. Additionally, there is significant unique biosynthetic machinery distributed across the genus that might lead to new, unknown metabolites with diverse biological functions. Inspired by the findings of our genomic analysis, we speculate that the highly conserved alkylpyrones might have an important biological activity within this genus. We go on to validate this prediction by demonstrating that these natural products are developmental signals in Bacillus and act by inhibiting sporulation.

A study to determine the incidence and prevalence of newly discovered human immunodeficiency virus infection during the prenatal care period.

PubMed

Grimes, R M; Srivastava, G; Helfgott, A W; Eriksen, N L

2000-01-01

This study asked the following questions: 1) Does HIV testing in pregnancy identify women who previously were not known to be HIV positive? 2) When in pregnancy are women identified as HIV infected? 3) Does HIV seroconversion occur during the prenatal care period? Medical records of 97 women from two primarily indigent care hospitals in Houston, TX who were found to be HIV positive at delivery were reviewed to determine if they had tested positive during the prenatal care period. Demographics and time of gestation of the prenatal testing also were recorded. The outcome measures were: 1) number of women found positive during prenatal care; 2) week of gestation at discovery of HIV positivity; and 3) number of women seroconverting between the initiation of prenatal care and delivery. Thirty women were known to be HIV positive prior to pregnancy. Fifty-six women were found to be positive during prenatal care and the seropositivity of 44 was discovered before the 34th week of pregnancy. Ten women were found to be positive at their first prenatal visit, which occurred after the 34th week. Date of testing was unknown for two women. Eleven women who received no prenatal care were found to be HIV positive at delivery. There were no seroconversions while women were under prenatal care. HIV testing at delivery did not find any HIV-positive women who had tested negative during prenatal care. Testing is very important for women who do not receive prenatal care. Making certain that high-risk women get into prenatal care also is very important.

Parent Genotype and Environmental Factors Influence Introduction Success of the Critically Endangered Savannas Mint (Dicerandra immaculata var. savannarum)

PubMed Central

Peterson, Cheryl L.; Kaufmann, Gregory S.; Vandello, Christopher; Richardson, Matthew L.

2013-01-01

Species previously unknown to science are continually discovered and some of these species already face extinction at the time of their discovery. Conserving new and rare species in these cases becomes a trial-and-error process and conservationists will attempt to manage them by using knowledge of closely related species, or those that fill the same ecological niche, and then adapting the management program as needed. Savannas Mint (Dicerandra immaculata Lakela var. savannarum Huck) is a perennial plant that was discovered in Florida scrub habitat at two locations in 1995, but is nearly extinct at these locations. We tested whether shade, leaf litter, propagation method, parent genotype, parent collection site, planting date, and absorbent granules influenced survival, reproduction, and recruitment of Savannas Mint in a population of 1,614 plants that we introduced between June 2006 and July 2009 into a state protected site. Survival and reproduction of introduced plants, and recruitment of new plants, was higher in microhabitats in full sun and no leaf litter and lower in partially shaded habitats. The two sites from which parent plants were collected differentially influenced survival and reproduction of introduced plants. These differences in survival and reproduction are likely due to underlying genetic differences. Differential survival of progeny from different parent genotypes further supports the idea that underlying genetics is an important consideration when restoring plant populations. The most successful progeny of parent genotypes had survival rates nearly 12 times higher than the least successful progeny. We speculate that many of these environmental and genetic factors are likely to influence allopatric congeners and other critically endangered gap specialists that grow in Florida scrub and our results can be used to guide their conservation. PMID:23593479

Assessing the atmospheric oxidation of pesticides used to control mosquito populations in Houston, TX.

NASA Astrophysics Data System (ADS)

Usenko, S.; Clark, A. E.; Yoon, S.; Sheesley, R. J.

2016-12-01

In September 2013, NASA initiated the DISCOVER-AQ (Deriving Information on Surface Conditions from Column and Vertically Resolved Observations Relevant to Air Quality) Houston campaign, which collected satellite and ground-based data to better understand air quality in the Houston metropolitan area. In conjunction with DISCOVER-AQ, particulate matter samples including total suspended particle (TSP) and particulate matter less than 2.5 microns in aerodynamic diameter (PM2.5) were collected at four ground-based sites across Houston. Aliquots of PM samples were analyzed for pesticide used to control mosquito populations in urban areas. Pesticides extracted using pressurized liquid extraction and extracts were analyzed using gas chromatography mass spectrometry. These pesticides, also known as adulticides, are aerosolized and sprayed in neighborhoods throughout Houston around sunset in an effort to reduce or prevent the spread of diseases like West Nile Virus and Zika. When these pesticides enter the atmosphere they oxidize after reaction with ozone and nitrate radical and become more toxic and less volatile. The rate and specific mechanism associated with this urban chemistry is currently unknown, but has direct implications on public health from both a toxicological and disease control standpoint. Preliminary atmospheric measurements in Houston demonstrated significant nighttime oxidation of malathion to malaoxon. Atmospheric half-lives measured near downtown Houston where 10x lower than previous agriculture based studies ( 5 days to less than 24 hours). Atmospheric nighttime PM concentrations of adulticides exceeded 60 ng/m3, which is orders of magnitude greater than concentrations of organic tracers associated with incomplete combustion. This unique system also offers an opportunity to address some key scientific questions including focusing on SVOC urban fate and urban transport as well as nighttime oxidation.

Field Trial Results of a 14-channel GPR Integrated with a U.S. Program for 3-D Utility Mapping

NASA Astrophysics Data System (ADS)

Anspach, James H.

2013-04-01

Existing underground utilities continue to be a leading cause of highway construction delay claims in the United States. Although 80-90% of existing utilities can typically be discovered and mapped using a wide range of geophysical tools, there is a recognizable need to improve the process. Existing shortcomings to the utility mapping process include a lack of viable depth attributes, long field occupation times, low experience level of the field technicians, and separate survey / geophysics functions. The U.S. National Academies and its Transportation Research Board recently concluded a project on alleviating the existing utility mapping shortcomings through the development of enhanced GPR. An existing commercial 400MHz 14-channel towed array was enhanced with positioning and interpretation hardware and software over a 3-year US 2M program. Field trials for effectiveness were conducted in a city suburb commercialized environment where the relative permittivity values averaged 9.4. The effectiveness of enhanced GPR was compared to traditional utility mapping techniques (Single Channel GPR, FDEM, Acoustic, Sondes, Gradiometric Magnetometers) during the project. The project area utilities included natural gas, water, electric, telephone, cable, storm, sanitary, traffic control, and several unknown function lines. Depths for these utilities were mostly unknown. 81% of known (from records and field appurtenance visual observation) utilities were detected via traditional geophysical means. These traditional geophysical means also detected 14% additional and previously "unknown" utilities. The enhanced GPR detected approximately 40% of the known and unknown utilities, and found an additional 6% of utilities that were previously undetected. These additional utilities were subsequently determined to be small diameter abandoned water and gas systems in very poor and broken condition. Although it did well with metallic water and gas lines, communication and electric utilities were mostly undetectable. Through a ground-truthing program of test holes to expose utilities, the depth values derived from the enhanced GPR were fairly consistent and within 15 cm of actual depth. The incomplete underground picture determined by the enhanced GPR reinforces previous studies that show that the mapping of existing underground utilities is a multi-tool effort that takes highly trained and skilled field technicians and data interpreters. The addition of a new GPR tool is valuable in determining continuous depth profiles of imaged utilities. A second and significant benefit is the interpretation of other geotechnical data that benefit project designers. This might include showing geometry, location, intensity, and depths of either areas of anomalies, or of known structures, such as paving thickness, substrate thickness, voids, water table, soil lenses, boulders, bedrock, and so forth. The Florida Department of Transportation has decided to take advantage of this new technology and has entered into an experimental contract with Cardno TBE to incorporate several enhanced GPR arrays with traditional utility detection tools. The goal of this contract will be to provide a 3-D model of existing underground utilities for use in automated construction. The GPR 3-D data model will be melded with conventional subsurface utility engineering and mapping practices and will be required to follow the ASCE 38 standard for utility data reliability.

Automated Detection of Small Bodies by Space Based Observation

NASA Astrophysics Data System (ADS)

Bidstrup, P. R.; Grillmayer, G.; Andersen, A. C.; Haack, H.; Jorgensen, J. L.

The number of known comets and asteroids is increasing every year. Up till now this number is including approximately 250,000 of the largest minor planets, as they are usually referred. These discoveries are due to the Earth-based observation which has intensified over the previous decades. Additionally larger telescopes and arrays of telescopes are being used for exploring our Solar System. It is believed that all near- Earth and Main-Belt asteroids of diameters above 10 to 30 km have been discovered, leaving these groups of objects as observationally complete. However, the cataloguing of smaller bodies is incomplete as only a very small fraction of the expected number has been discovered. It is estimated that approximately 1010 main belt asteroids in the size range 1 m to 1 km are too faint to be observed using Earth-based telescopes. In order to observe these small bodies, space-based search must be initiated to remove atmospheric disturbances and to minimize the distance to the asteroids and thereby minimising the requirement for long camera integration times. A new method of space-based detection of moving non-stellar objects is currently being developed utilising the Advanced Stellar Compass (ASC) built for spacecraft attitude determination by Ørsted, Danish Technical University. The ASC serves as a backbone technology in the project as it is capable of fully automated distinction of known and unknown celestial objects. By only processing objects of particular interest, i.e. moving objects, it will be possible to discover small bodies with a minimum of ground control, with the ultimate ambition of a fully automated space search probe. Currently, the ASC is being mounted on the Flying Laptop satellite of the Institute of Space Systems, Universität Stuttgart. It will, after a launch into a low Earth polar orbit in 2008, test the detection method with the ASC equipment that already had significant in-flight experience. A future use of the ASC based automated detection of small bodies is currently on a preliminary stage and known as the Bering project - a deep space survey to the asteroid Main-Belt. With a successful detection method, the Bering mission is expected to discover approximately 6 new small objects per day and 1 will thus during the course of a few years discover 5,000-10,000 new sub-kilometer asteroids. Discovery of new small bodies can: 1) Provide further links between groups of meteorites. 2) Constrain the cratering rate at planetary surfaces and thus allow significantly improved cratering ages for terrains on Mars and other planets. 3) Help determine processes that transfer small asteroids from orbits in the asteroid Main-Belt to the inner Solar System. 2

Bayesian Tracking within a Feedback Sensing Environment: Estimating Interacting, Spatially Constrained Complex Dynamical Systems from Multiple Sources of Controllable Devices

DTIC Science & Technology

2014-07-25

composition of simple temporal structures to a speaker diarization task with the goal of segmenting conference audio in the presence of an unknown number of...application domains including neuroimaging, diverse document selection, speaker diarization , stock modeling, and target tracking. We detail each of...recall performance than competing methods in a task of discovering articles preferred by the user • a gold-standard speaker diarization method, as

Using ADOPT Algorithm and Operational Data to Discover Precursors to Aviation Adverse Events

NASA Technical Reports Server (NTRS)

Janakiraman, Vijay; Matthews, Bryan; Oza, Nikunj

2018-01-01

The US National Airspace System (NAS) is making its transition to the NextGen system and assuring safety is one of the top priorities in NextGen. At present, safety is managed reactively (correct after occurrence of an unsafe event). While this strategy works for current operations, it may soon become ineffective for future airspace designs and high density operations. There is a need for proactive management of safety risks by identifying hidden and "unknown" risks and evaluating the impacts on future operations. To this end, NASA Ames has developed data mining algorithms that finds anomalies and precursors (high-risk states) to safety issues in the NAS. In this paper, we describe a recently developed algorithm called ADOPT that analyzes large volumes of data and automatically identifies precursors from real world data. Precursors help in detecting safety risks early so that the operator can mitigate the risk in time. In addition, precursors also help identify causal factors and help predict the safety incident. The ADOPT algorithm scales well to large data sets and to multidimensional time series, reduce analyst time significantly, quantify multiple safety risks giving a holistic view of safety among other benefits. This paper details the algorithm and includes several case studies to demonstrate its application to discover the "known" and "unknown" safety precursors in aviation operation.

Novel strategy for the determination of illegal adulterants in health foods and herbal medicines using high-performance liquid chromatography with high-resolution mass spectrometry.

PubMed

Wang, Zhe; Wu, Caisheng; Wang, Gangli; Zhang, Qingsheng; Zhang, Jinlan

2015-03-01

The detection, confirmation, and quantification of multiple illegal adulterants in health foods and herbal medicines by using a single analytical method are a challenge. This paper reports on a new strategy to meet this challenge by employing high-performance liquid chromatography coupled with high-resolution mass spectrometry and a mass spectral tree similarity filter technique. This analytical method can rapidly collect high-resolution, high-accuracy, optionally multistage mass data for compounds in samples. After a preliminary screening by retention time and high-resolution mass spectral data, known illegal adulterants can be detected. The mass spectral tree similarity filter technique has been applied to rapidly confirm these adulterants and simultaneously discover unknown ones. By using full-scan mass spectra as stem and data-dependent subsequent stage mass spectra to form branches, mass spectrometry data from detected compounds are converted into mass spectral trees. The known or unknown illegal adulterants in the samples are confirmed or discovered based on the similarity between their mass spectral trees and those of the references in a library, and they are finally quantified against standard curves. This new strategy has been tested by using 50 samples, and the illegal adulterants were rapidly and effectively detected, confirmed and quantified. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Automated discovery of local search heuristics for satisfiability testing.

PubMed

Fukunaga, Alex S

2008-01-01

The development of successful metaheuristic algorithms such as local search for a difficult problem such as satisfiability testing (SAT) is a challenging task. We investigate an evolutionary approach to automating the discovery of new local search heuristics for SAT. We show that several well-known SAT local search algorithms such as Walksat and Novelty are composite heuristics that are derived from novel combinations of a set of building blocks. Based on this observation, we developed CLASS, a genetic programming system that uses a simple composition operator to automatically discover SAT local search heuristics. New heuristics discovered by CLASS are shown to be competitive with the best Walksat variants, including Novelty+. Evolutionary algorithms have previously been applied to directly evolve a solution for a particular SAT instance. We show that the heuristics discovered by CLASS are also competitive with these previous, direct evolutionary approaches for SAT. We also analyze the local search behavior of the learned heuristics using the depth, mobility, and coverage metrics proposed by Schuurmans and Southey.

Mining connected global and local dense subgraphs for bigdata

NASA Astrophysics Data System (ADS)

Wu, Bo; Shen, Haiying

2016-01-01

The problem of discovering connected dense subgraphs of natural graphs is important in data analysis. Discovering dense subgraphs that do not contain denser subgraphs or are not contained in denser subgraphs (called significant dense subgraphs) is also critical for wide-ranging applications. In spite of many works on discovering dense subgraphs, there are no algorithms that can guarantee the connectivity of the returned subgraphs or discover significant dense subgraphs. Hence, in this paper, we define two subgraph discovery problems to discover connected and significant dense subgraphs, propose polynomial-time algorithms and theoretically prove their validity. We also propose an algorithm to further improve the time and space efficiency of our basic algorithm for discovering significant dense subgraphs in big data by taking advantage of the unique features of large natural graphs. In the experiments, we use massive natural graphs to evaluate our algorithms in comparison with previous algorithms. The experimental results show the effectiveness of our algorithms for the two problems and their efficiency. This work is also the first that reveals the physical significance of significant dense subgraphs in natural graphs from different domains.

Circular RNA biogenesis can proceed through an exon-containing lariat precursor.

PubMed

Barrett, Steven P; Wang, Peter L; Salzman, Julia

2015-06-09

Pervasive expression of circular RNA is a recently discovered feature of eukaryotic gene expression programs, yet its function remains largely unknown. The presumed biogenesis of these RNAs involves a non-canonical 'backsplicing' event. Recent studies in mammalian cell culture posit that backsplicing is facilitated by inverted repeats flanking the circularized exon(s). Although such sequence elements are common in mammals, they are rare in lower eukaryotes, making current models insufficient to describe circularization. Through systematic splice site mutagenesis and the identification of splicing intermediates, we show that circular RNA in Schizosaccharomyces pombe is generated through an exon-containing lariat precursor. Furthermore, we have performed high-throughput and comprehensive mutagenesis of a circle-forming exon, which enabled us to discover a systematic effect of exon length on RNA circularization. Our results uncover a mechanism for circular RNA biogenesis that may account for circularization in genes that lack noticeable flanking intronic secondary structure.

Attenuation of Scintillation of Discrete Cosmic Sources during Nonresonant HF Heating of the Upper Ionosphere

NASA Astrophysics Data System (ADS)

Bezrodny, V. G.; Watkins, B.; Charkina, O. V.; Yampolski, Y. M.

2014-03-01

The aim of the work is to experimentally investigate the response of scintillation spectra and indices of discrete cosmic sources (DCS) to modification of the ionospheric F-region by powerful electromagnetic fields with frequencies exceeding the Langmuir and upper hybrid ones. The results of a special experiment on the scintillations of radiation from DCS Cygnus A observed with using the 64-beam imaging riometer located near the Gakona village (Alaska, USA) are here presented. The ionosphere was artificially disturbed by powerful HAARP heater. Under the studied conditions of nonresonant heating of the ionospheric plasma, an earlier unknown effect of reducing the level of DCS scintillation was discovered. The theoretical interpretation has been given for the discovered effect, which using allowed the proposed technique of solving the inverse problem (recovery deviations of average electron density and temperature in the modified region from their unperturbed values).

Chemoproteomic profiling and discovery of protein electrophiles in human cells

NASA Astrophysics Data System (ADS)

Matthews, Megan L.; He, Lin; Horning, Benjamin D.; Olson, Erika J.; Correia, Bruno E.; Yates, John R.; Dawson, Philip E.; Cravatt, Benjamin F.

2017-03-01

Activity-based protein profiling (ABPP) serves as a chemical proteomic platform to discover and characterize functional amino acids in proteins on the basis of their enhanced reactivity towards small-molecule probes. This approach, to date, has mainly targeted nucleophilic functional groups, such as the side chains of serine and cysteine, using electrophilic probes. Here we show that 'reverse-polarity' (RP)-ABPP using clickable, nucleophilic hydrazine probes can capture and identify protein-bound electrophiles in cells. Using this approach, we demonstrate that the pyruvoyl cofactor of S-adenosyl-L-methionine decarboxylase (AMD1) is dynamically controlled by intracellular methionine concentrations. We also identify a heretofore unknown modification—an N-terminally bound glyoxylyl group—in the poorly characterized protein secernin-3. RP-ABPP thus provides a versatile method to monitor the metabolic regulation of electrophilic cofactors and discover novel types of electrophilic modifications on proteins in human cells.

Database extraction strategies for low-template evidence.

PubMed

Bleka, Øyvind; Dørum, Guro; Haned, Hinda; Gill, Peter

2014-03-01

Often in forensic cases, the profile of at least one of the contributors to a DNA evidence sample is unknown and a database search is needed to discover possible perpetrators. In this article we consider two types of search strategies to extract suspects from a database using methods based on probability arguments. The performance of the proposed match scores is demonstrated by carrying out a study of each match score relative to the level of allele drop-out in the crime sample, simulating low-template DNA. The efficiency was measured by random man simulation and we compared the performance using the SGM Plus kit and the ESX 17 kit for the Norwegian population, demonstrating that the latter has greatly enhanced power to discover perpetrators of crime in large national DNA databases. The code for the database extraction strategies will be prepared for release in the R-package forensim. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

["A" or ... "The" precious manuscript of the "Long life Elixir" just discovered].

PubMed

Grelaud, Jean-Pierre

2012-05-01

This study relates, describes, analyzes & comments the content of a recently discovered old manuscript, written probably at the beginning of the 18th century, and compares it with the well known "Long life Elixir, or Swedish Elixir", manuscript found on a Swedish doctor who died at 104 years old as a result of a fall from his horse... The origin of this new manuscript can be established from 1700 to 1710, and seems to be probably anterior to the well known Swedish manuscript, meanwhile the text is almost similar,... and also is more complete than this one! We learn that the "Manna" is synonymic here of "fine Rhubarb". Another recipe, unknown on the other manuscript and titled "Dalibour Water" is also published: By similar way, this formula brings some new details, in particular in the exact composition, the preparation and the use of the "Long Life Elixir".

Discovery of the Meanings, Expressions, and Practices Related to Malaria Care Among the Maasai.

PubMed

Strang, Cecily W; Mixer, Sandra J

2016-07-01

Although malaria is preventable and treatable, morbidity and mortality from this disease continue among the Maasai of Southern Kenya. Prior to this study, the Maasai's generic and professional malaria care/cure practices were largely unknown. The purpose of this study was to discover, describe, and systematically analyze meanings, expressions, and practices that promote culturally congruent malaria care among this population. The qualitative, ethnonursing research method was used to conduct in-depth examination of the Maasai ethnohistory and culture relevant to malaria care and analyze data from 48 interviews conducted in Maasailand. Guided by the "culture care theory," four themes were discovered related to Maasai community, traditional, spiritual, and professional care/cure practices. These significant findings filled a research gap and contribute to nursing knowledge and caring practice. These study findings have implications for culturally congruent malaria care education, practice, research, policy, and partnership with traditional and professional caregivers. © The Author(s) 2015.

BioEve Search: A Novel Framework to Facilitate Interactive Literature Search

PubMed Central

Ahmed, Syed Toufeeq; Davulcu, Hasan; Tikves, Sukru; Nair, Radhika; Zhao, Zhongming

2012-01-01

Background. Recent advances in computational and biological methods in last two decades have remarkably changed the scale of biomedical research and with it began the unprecedented growth in both the production of biomedical data and amount of published literature discussing it. An automated extraction system coupled with a cognitive search and navigation service over these document collections would not only save time and effort, but also pave the way to discover hitherto unknown information implicitly conveyed in the texts. Results. We developed a novel framework (named “BioEve”) that seamlessly integrates Faceted Search (Information Retrieval) with Information Extraction module to provide an interactive search experience for the researchers in life sciences. It enables guided step-by-step search query refinement, by suggesting concepts and entities (like genes, drugs, and diseases) to quickly filter and modify search direction, and thereby facilitating an enriched paradigm where user can discover related concepts and keywords to search while information seeking. Conclusions. The BioEve Search framework makes it easier to enable scalable interactive search over large collection of textual articles and to discover knowledge hidden in thousands of biomedical literature articles with ease. PMID:22693501

Computer finds ore

NASA Astrophysics Data System (ADS)

Bell, Peter M.

Artificial intelligence techniques are being used for the first time to evaluate geophysical, geochemical, and geologic data and theory in order to locate ore deposits. After several years of development, an intelligent computer code has been formulated and applied to the Mount Tolman area in Washington state. In a project funded by the United States Geological Survey and the National Science Foundation a set of computer programs, under the general title Prospector, was used successfully to locate a previously unknown ore-grade porphyry molybdenum deposit in the vicinity of Mount Tolman (Science, Sept. 3, 1982).The general area of the deposit had been known to contain exposures of porphyry mineralization. Between 1964 and 1978, exploration surveys had been run by the Bear Creek Mining Company, and later exploration was done in the area by the Amax Corporation. Some of the geophysical data and geochemical and other prospecting surveys were incorporated into the programs, and mine exploration specialists contributed to a set of rules for Prospector. The rules were encoded as ‘inference networks’ to form the ‘expert system’ on which the artificial intelligence codes were based. The molybdenum ore deposit discovered by the test is large, located subsurface, and has an areal extent of more than 18 km2.

The Effects of Core-Mantle Interactions on Earth Rotation, Surface Deformation, and Gravity Changes

NASA Astrophysics Data System (ADS)

Watkins, A.; Gross, R. S.; Fu, Y.

2017-12-01

The length-of-day (LOD) contains a 6-year signal, the cause of which is currently unknown. The signal remains after removing tidal and surface fluid effects, thus the cause is generally believed to be angular momentum exchange between the mantle and core. Previous work has established a theoretical relationship between pressure variations at the core-mantle boundary (CMB) and resulting deformation of the overlying mantle and crust. This study examines globally distributed GPS deformation data in search of this effect, and inverts the discovered global inter-annual component for the CMB pressure variations. The geostrophic assumption is then used to obtain fluid flow solutions at the edge of the core from the CMB pressure variations. Taylor's constraint is applied to obtain the flow deeper within the core, and the equivalent angular momentum and LOD changes are computed and compared to the known 6-year LOD signal. The amplitude of the modeled and measured LOD changes agree, but the degree of period and phase agreement is dependent upon the method of isolating the desired component in the GPS position data. Implications are discussed, and predictions are calculated for surface gravity field changes that would arise from the CMB pressure variations.

Fine-mapping of lipid regions in global populations discovers ethnic-specific signals and refines previously identified lipid loci

PubMed Central

Zubair, Niha; Luis Ambite, Jose; Bush, William S.; Kichaev, Gleb; Lu, Yingchang; Manichaikul, Ani; Sheu, Wayne H-H.; Absher, Devin; Assimes, Themistocles L.; Bielinski, Suzette J.; Bottinger, Erwin P.; Buzkova, Petra; Chuang, Lee-Ming; Chung, Ren-Hua; Cochran, Barbara; Dumitrescu, Logan; Gottesman, Omri; Haessler, Jeffrey W.; Haiman, Christopher; Heiss, Gerardo; Hsiung, Chao A.; Hung, Yi-Jen; Hwu, Chii-Min; Juang, Jyh-Ming J.; Le Marchand, Loic; Lee, I-Te; Lee, Wen-Jane; Lin, Li-An; Lin, Danyu; Lin, Shih-Yi; Mackey, Rachel H.; Martin, Lisa W.; Pasaniuc, Bogdan; Peters, Ulrike; Predazzi, Irene; Quertermous, Thomas; Reiner, Alex P.; Robinson, Jennifer; Rotter, Jerome I.; Ryckman, Kelli K.; Schreiner, Pamela J.; Stahl, Eli; Tao, Ran; Tsai, Michael Y.; Waite, Lindsay L.; Wang, Tzung-Dau; Buyske, Steven; Ida Chen, Yii-Der; Cheng, Iona; Crawford, Dana C.; Loos, Ruth J.F.; Rich, Stephen S.; Fornage, Myriam; North, Kari E.; Kooperberg, Charles; Carty, Cara L.

2016-01-01

Abstract Genome-wide association studies have identified over 150 loci associated with lipid traits, however, no large-scale studies exist for Hispanics and other minority populations. Additionally, the genetic architecture of lipid-influencing loci remains largely unknown. We performed one of the most racially/ethnically diverse fine-mapping genetic studies of HDL-C, LDL-C, and triglycerides to-date using SNPs on the MetaboChip array on 54,119 individuals: 21,304 African Americans, 19,829 Hispanic Americans, 12,456 Asians, and 530 American Indians. The majority of signals found in these groups generalize to European Americans. While we uncovered signals unique to racial/ethnic populations, we also observed systematically consistent lipid associations across these groups. In African Americans, we identified three novel signals associated with HDL-C (LPL, APOA5, LCAT) and two associated with LDL-C (ABCG8, DHODH). In addition, using this population, we refined the location for 16 out of the 58 known MetaboChip lipid loci. These results can guide tailored screening efforts, reveal population-specific responses to lipid-lowering medications, and aid in the development of new targeted drug therapies. PMID:28426890

Colloidal Nanocrystals of Lead-Free Double-Perovskite (Elpasolite) Semiconductors: Synthesis and Anion Exchange To Access New Materials.

PubMed

Creutz, Sidney E; Crites, Evan N; De Siena, Michael C; Gamelin, Daniel R

2018-02-14

Concerns about the toxicity and instability of lead-halide perovskites have driven a recent surge in research toward alternative lead-free perovskite materials, including lead-free double perovskites with the elpasolite structure and visible bandgaps. Synthetic approaches to this class of materials remain limited, however, and no examples of heterometallic elpasolites as nanomaterials have been reported. Here, we report the synthesis and characterization of colloidal nanocrystals of Cs 2 AgBiX 6 (X = Cl, Br) elpasolites using a hot-injection approach. We further show that postsynthetic modification through anion exchange and cation extraction can be used to convert these nanocrystals to new materials including Cs 2 AgBiI 6 , which was previously unknown experimentally. Nanocrystals of Cs 2 AgBiI 6 , synthesized via a novel anion-exchange protocol using trimethylsilyl iodide, have strong absorption throughout the visible region, confirming theoretical predictions that this material could be a promising photovoltaic absorber. The synthetic methodologies presented here are expected to be broadly generalizable. This work demonstrates that nanocrystal ion-exchange reactivity can be used to discover and develop new lead-free halide perovskite materials that may be difficult or impossible to access through direct synthesis.

Discovery of a hypersaline subglacial lake complex beneath Devon Ice Cap, Canadian Arctic

PubMed Central

Blankenship, Donald D.; Schroeder, Dustin M.; Dowdeswell, Julian A.

2018-01-01

Subglacial lakes are unique environments that, despite the extreme dark and cold conditions, have been shown to host microbial life. Many subglacial lakes have been discovered beneath the ice sheets of Antarctica and Greenland, but no spatially isolated water body has been documented as hypersaline. We use radio-echo sounding measurements to identify two subglacial lakes situated in bedrock troughs near the ice divide of Devon Ice Cap, Canadian Arctic. Modeled basal ice temperatures in the lake area are no higher than −10.5°C, suggesting that these lakes consist of hypersaline water. This implication of hypersalinity is in agreement with the surrounding geology, which indicates that the subglacial lakes are situated within an evaporite-rich sediment unit containing a bedded salt sequence, which likely act as the solute source for the brine. Our results reveal the first evidence for subglacial lakes in the Canadian Arctic and the first hypersaline subglacial lakes reported to date. We conclude that these previously unknown hypersaline subglacial lakes may represent significant and largely isolated microbial habitats, and are compelling analogs for potential ice-covered brine lakes and lenses on planetary bodies across the solar system. PMID:29651462

BioGPS and MyGene.info: organizing online, gene-centric information.

PubMed

Wu, Chunlei; Macleod, Ian; Su, Andrew I

2013-01-01

Fast-evolving technologies have enabled researchers to easily generate data at genome scale, and using these technologies to compare biological states typically results in a list of candidate genes. Researchers are then faced with the daunting task of prioritizing these candidate genes for follow-up studies. There are hundreds, possibly even thousands, of web-based gene annotation resources available, but it quickly becomes impractical to manually access and review all of these sites for each gene in a candidate gene list. BioGPS (http://biogps.org) was created as a centralized gene portal for aggregating distributed gene annotation resources, emphasizing community extensibility and user customizability. BioGPS serves as a convenient tool for users to access known gene-centric resources, as well as a mechanism to discover new resources that were previously unknown to the user. This article describes updates to BioGPS made after its initial release in 2008. We summarize recent additions of features and data, as well as the robust user activity that underlies this community intelligence application. Finally, we describe MyGene.info (http://mygene.info) and related web services that provide programmatic access to BioGPS.

A new pycnodont fish, Scalacurvichthys naishi gen. et sp. nov., from the Late Cretaceous of Israel

PubMed Central

Cawley, John J.

2018-01-01

A new pycnodont fish from the early–mid Cenomanian, Late Cretaceous, of the ‘Ein Yabrud quarry near the village of Beit Eil in Israel is the first pycnodont fish to be described from this locality. Due to the locality where it was found, Scalacurvithys naishi gen. et sp. nov. is considered an inhabitant of reefal waters interspersed with lagoons in the eastern Tethys Sea. Scalacurvichthys naishi is notable for its protruding, hook-shaped first dorsal ridge scale above a large triangular dermatocranium, a deeply sloped and antero-posteriorly shortened skull and bifurcated cloacal scales. The bifurcating scales are a new character previously unknown in pycnodontomorph fishes but have been discovered in two more taxa, which indicates a new type of character that will be useful for future phylogenetic analyses of pycnodontomorph fishes. The new taxon is a member of Pycnodontidae and we conducted a phylogenetic analysis to establish its relationships to other pycnodont fishes. Our results reveal that Scalacurvichthys naishi is a well-resolved member of the subfamily Pycnodontinae. http://zoobank.org/urn:lsid:zoobank.org:pub:04383E2A-551A-4F57-8996-68E06EFA52E0 PMID:29551954

A new pycnodont fish, Scalacurvichthys naishi gen. et sp. nov., from the Late Cretaceous of Israel.

PubMed

Cawley, John J; Kriwet, Jürgen

2018-01-01

A new pycnodont fish from the early-mid Cenomanian, Late Cretaceous, of the 'Ein Yabrud quarry near the village of Beit Eil in Israel is the first pycnodont fish to be described from this locality. Due to the locality where it was found, Scalacurvithys naishi gen. et sp. nov. is considered an inhabitant of reefal waters interspersed with lagoons in the eastern Tethys Sea. Scalacurvichthys naishi is notable for its protruding, hook-shaped first dorsal ridge scale above a large triangular dermatocranium, a deeply sloped and antero-posteriorly shortened skull and bifurcated cloacal scales. The bifurcating scales are a new character previously unknown in pycnodontomorph fishes but have been discovered in two more taxa, which indicates a new type of character that will be useful for future phylogenetic analyses of pycnodontomorph fishes. The new taxon is a member of Pycnodontidae and we conducted a phylogenetic analysis to establish its relationships to other pycnodont fishes. Our results reveal that Scalacurvichthys naishi is a well-resolved member of the subfamily Pycnodontinae. http://zoobank.org/urn:lsid:zoobank.org:pub:04383E2A-551A-4F57-8996-68E06EFA52E0.

Analyzing Arabidopsis thaliana root proteome provides insights into the molecular bases of enantioselective imazethapyr toxicity

PubMed Central

Qian, Haifeng; Lu, Haiping; Ding, Haiyan; Lavoie, Michel; Li, Yali; Liu, Weiping; Fu, Zhengwei

2015-01-01

Imazethapyr (IM) is a widely used chiral herbicide that inhibits the synthesis of branched-chain amino acids (BCAAs). IM is thought to exert its toxic effects on amino acid synthesis mainly through inhibition of acetolactate synthase activity, but little is known about the potential effects of IM on other key biochemical pathways. Here, we exposed the model plant Arabidospsis thaliana to trace S- and R-IM enantiomer concentrations and examined IM toxicity effects on the root proteome using iTRAQ. Conventional analyses of root carbohydrates, organic acids, and enzyme activities were also performed. We discovered several previously unknown key biochemical pathways targeted by IM in Arabidospsis. 1,322 and 987 proteins were differentially expressed in response to R- and S-IM treatments, respectively. Bioinformatics and physiological analyses suggested that IM reduced the BCAA tissue content not only by strongly suppressing BCAA synthesis but also by increasing BCAA catabolism. IM also affected sugar and starch metabolism, changed the composition of root cell walls, increased citrate production and exudation, and affected the microbial community structure of the rhizosphere. The present study shed new light on the multiple toxicity mechanisms of a selective herbicide on a model plant. PMID:26153126

Analyzing Arabidopsis thaliana root proteome provides insights into the molecular bases of enantioselective imazethapyr toxicity

NASA Astrophysics Data System (ADS)

Qian, Haifeng; Lu, Haiping; Ding, Haiyan; Lavoie, Michel; Li, Yali; Liu, Weiping; Fu, Zhengwei

2015-07-01

Imazethapyr (IM) is a widely used chiral herbicide that inhibits the synthesis of branched-chain amino acids (BCAAs). IM is thought to exert its toxic effects on amino acid synthesis mainly through inhibition of acetolactate synthase activity, but little is known about the potential effects of IM on other key biochemical pathways. Here, we exposed the model plant Arabidospsis thaliana to trace S- and R-IM enantiomer concentrations and examined IM toxicity effects on the root proteome using iTRAQ. Conventional analyses of root carbohydrates, organic acids, and enzyme activities were also performed. We discovered several previously unknown key biochemical pathways targeted by IM in Arabidospsis. 1,322 and 987 proteins were differentially expressed in response to R- and S-IM treatments, respectively. Bioinformatics and physiological analyses suggested that IM reduced the BCAA tissue content not only by strongly suppressing BCAA synthesis but also by increasing BCAA catabolism. IM also affected sugar and starch metabolism, changed the composition of root cell walls, increased citrate production and exudation, and affected the microbial community structure of the rhizosphere. The present study shed new light on the multiple toxicity mechanisms of a selective herbicide on a model plant.

Burrowing hard corals occurring on the sea floor since 80 million years ago.

PubMed

Sentoku, Asuka; Tokuda, Yuki; Ezaki, Yoichi

2016-04-14

We describe a previously unknown niche for hard corals in the small, bowl-shaped, solitary scleractinian, Deltocyathoides orientalis (Family Turbinoliidae), on soft-bottom substrates. Observational experiments were used to clarify how the sea floor niche is exploited by turbinoliids. Deltocyathoides orientalis is adapted to an infaunal mode of life and exhibits behaviours associated with automobility that include burrowing into sediments, vertical movement through sediments to escape burial, and recovery of an upright position after being overturned. These behaviours were achieved through repeated expansion and contraction of their peripheral soft tissues, which constitute a unique muscle-membrane system. Histological analysis showed that these muscle arrangements were associated with deeply incised inter-costal spaces characteristic of turbinoliid corals. The oldest known turbinoliid, Bothrophoria ornata, which occurred in the Cretaceous (Campanian), also possessed a small, conical skeleton with highly developed costae. An infaunal mode of life became available to turbinoliids due to the acquisition of automobility through the muscle-membrane system at least 80 million years ago. The newly discovered active burrowing strategies described herein provide new insights into the use of an unattached mode of life by corals inhabiting soft-bottom substrates throughout the Phanerozoic.

Applying Precision Public Health to Prevent Preterm Birth.

PubMed

Newnham, John P; Kemp, Matthew W; White, Scott W; Arrese, Catherine A; Hart, Roger J; Keelan, Jeffrey A

2017-01-01

Preterm birth (PTB) is one of the major health-care challenges of our time. Being born too early is associated with major risks to the child with potential for serious consequences in terms of life-long disability and health-care costs. Discovering how to prevent PTB needs to be one of our greatest priorities. Recent advances have provided hope that a percentage of cases known to be related to risk factors may be amenable to prevention; but the majority of cases remain of unknown cause, and there is little chance of prevention. Applying the principle of precision public health may offer opportunities previously unavailable. Presented in this article are ideas that may improve our abilities in the fields of studying the effects of migration and of populations in transition, public health programs, tobacco control, routine measurement of length of the cervix in mid-pregnancy by ultrasound imaging, prevention of non-medically indicated late PTB, identification of pregnant women for whom treatment of vaginal infection may be of benefit, and screening by genetics and other "omics." Opening new research in these fields, and viewing these clinical problems through a prism of precision public health, may produce benefits that will affect the lives of large numbers of people.

Comparative genomics of Eucalyptus and Corymbia reveals low rates of genome structural rearrangement.

PubMed

Butler, J B; Vaillancourt, R E; Potts, B M; Lee, D J; King, G J; Baten, A; Shepherd, M; Freeman, J S

2017-05-22

Previous studies suggest genome structure is largely conserved between Eucalyptus species. However, it is unknown if this conservation extends to more divergent eucalypt taxa. We performed comparative genomics between the eucalypt genera Eucalyptus and Corymbia. Our results will facilitate transfer of genomic information between these important taxa and provide further insights into the rate of structural change in tree genomes. We constructed three high density linkage maps for two Corymbia species (Corymbia citriodora subsp. variegata and Corymbia torelliana) which were used to compare genome structure between both species and Eucalyptus grandis. Genome structure was highly conserved between the Corymbia species. However, the comparison of Corymbia and E. grandis suggests large (from 1-13 MB) intra-chromosomal rearrangements have occurred on seven of the 11 chromosomes. Most rearrangements were supported through comparisons of the three independent Corymbia maps to the E. grandis genome sequence, and to other independently constructed Eucalyptus linkage maps. These are the first large scale chromosomal rearrangements discovered between eucalypts. Nonetheless, in the general context of plants, the genomic structure of the two genera was remarkably conserved; adding to a growing body of evidence that conservation of genome structure is common amongst woody angiosperms.

Data mining of near-Earth asteroids in the Subaru Suprime-Cam archive

NASA Astrophysics Data System (ADS)

Vaduvescu, O.; Conovici, M.; Popescu, M.; Sonka, A.; Paraschiv, A.; Lacatus, D.; Tudorica, A.; Hudin, L.; Curelaru, L.; Inceu, V.; Zavoianu, D.; Cornea, R.; Toma, R.; Asher, D. J.; Hadnett, J.; Cheallaigh, L. Ó.

2017-06-01

As part of the EURONEAR project, almost 70,000 mosaic Suprime-Cam images taken between 1999 and 2013 were data mined for about 9,800 near Earth asteroids (NEAs) known by 2013 May. Using our PRECOVERY server and the "Find Subaru CCD" tool, we scrutinized 4,186 candidate CCD images possibly holding 518 NEAs. We found 113 NEAs as faint as V<25 magnitude, their positions being measured in 589 images using Astrometrica, then reported to the Minor Planet Center. Among them, 18 objects represent encounters of previously single opposition NEAs, their orbital arcs being extended by up to 10 years. In the second part of this work we searched for unknown NEAs in 78 sequences (780 CCD fields) of 4-5 mosaic images selected from the same Suprime-Cam archive and totaling 16.6 sq.deg, with the aim to assess the faint NEA distribution observable with an 8-m class survey. A total of 2,018 moving objects were measured, from which we identified 18 better NEA candidates. Using the R_c filter in good weather conditions, mostly dark time and sky directions slightly biased towards the ecliptic, at least one NEA could be discovered in every 1 sq.deg surveyed.

Burrowing hard corals occurring on the sea floor since 80 million years ago

NASA Astrophysics Data System (ADS)

Sentoku, Asuka; Tokuda, Yuki; Ezaki, Yoichi

2016-04-01

We describe a previously unknown niche for hard corals in the small, bowl-shaped, solitary scleractinian, Deltocyathoides orientalis (Family Turbinoliidae), on soft-bottom substrates. Observational experiments were used to clarify how the sea floor niche is exploited by turbinoliids. Deltocyathoides orientalis is adapted to an infaunal mode of life and exhibits behaviours associated with automobility that include burrowing into sediments, vertical movement through sediments to escape burial, and recovery of an upright position after being overturned. These behaviours were achieved through repeated expansion and contraction of their peripheral soft tissues, which constitute a unique muscle-membrane system. Histological analysis showed that these muscle arrangements were associated with deeply incised inter-costal spaces characteristic of turbinoliid corals. The oldest known turbinoliid, Bothrophoria ornata, which occurred in the Cretaceous (Campanian), also possessed a small, conical skeleton with highly developed costae. An infaunal mode of life became available to turbinoliids due to the acquisition of automobility through the muscle-membrane system at least 80 million years ago. The newly discovered active burrowing strategies described herein provide new insights into the use of an unattached mode of life by corals inhabiting soft-bottom substrates throughout the Phanerozoic.

Two-photon excited fluorescence emission from hemoglobin

NASA Astrophysics Data System (ADS)

Sun, Qiqi; Zeng, Yan; Zhang, Wei; Zheng, Wei; Luo, Yi; Qu, Jianan Y.

2015-03-01

Hemoglobin, one of the most important proteins in blood, is responsible for oxygen transportation in almost all vertebrates. Recently, we discovered two-photon excited hemoglobin fluorescence and achieved label-free microvascular imaging based on the hemoglobin fluorescence. However, the mechanism of its fluorescence emission still remains unknown. In this work, we studied the two-photon excited fluorescence properties of the hemoglobin subunits, heme/hemin (iron (II)/(III) protoporphyrin IX) and globin. We first studied the properties of heme and the similar spectral and temporal characteristics of heme and hemoglobin fluorescence provide strong evidence that heme is the fluorophore in hemoglobin. Then we studied the fluorescence properties of hemin, globin and methemoglobin, and found that the hemin may have the main effect on the methemoglobin fluorescence and that globin has tryptophan fluorescence like other proteins. Finally, since heme is a centrosymmetric molecule, that the Soret band fluorescence of heme and hemoglobin was not observed in the single photon process in the previous study may be due to the parity selection rule. The discovery of heme two-photon excited fluorescence may open a new window for heme biology research, since heme as a cofactor of hemoprotein has many functions, including chemical catalysis, electron transfer and diatomic gases transportation.

A strong magnetic field around the supermassive black hole at the centre of the Galaxy.

PubMed

Eatough, R P; Falcke, H; Karuppusamy, R; Lee, K J; Champion, D J; Keane, E F; Desvignes, G; Schnitzeler, D H F M; Spitler, L G; Kramer, M; Klein, B; Bassa, C; Bower, G C; Brunthaler, A; Cognard, I; Deller, A T; Demorest, P B; Freire, P C C; Kraus, A; Lyne, A G; Noutsos, A; Stappers, B; Wex, N

2013-09-19

Earth's nearest candidate supermassive black hole lies at the centre of the Milky Way. Its electromagnetic emission is thought to be powered by radiatively inefficient accretion of gas from its environment, which is a standard mode of energy supply for most galactic nuclei. X-ray measurements have already resolved a tenuous hot gas component from which the black hole can be fed. The magnetization of the gas, however, which is a crucial parameter determining the structure of the accretion flow, remains unknown. Strong magnetic fields can influence the dynamics of accretion, remove angular momentum from the infalling gas, expel matter through relativistic jets and lead to synchrotron emission such as that previously observed. Here we report multi-frequency radio measurements of a newly discovered pulsar close to the Galactic Centre and show that the pulsar's unusually large Faraday rotation (the rotation of the plane of polarization of the emission in the presence of an external magnetic field) indicates that there is a dynamically important magnetic field near the black hole. If this field is accreted down to the event horizon it provides enough magnetic flux to explain the observed emission--from radio to X-ray wavelengths--from the black hole.

A strong magnetic field around the supermassive black hole at the centre of the Galaxy

NASA Astrophysics Data System (ADS)

Eatough, R. P.; Falcke, H.; Karuppusamy, R.; Lee, K. J.; Champion, D. J.; Keane, E. F.; Desvignes, G.; Schnitzeler, D. H. F. M.; Spitler, L. G.; Kramer, M.; Klein, B.; Bassa, C.; Bower, G. C.; Brunthaler, A.; Cognard, I.; Deller, A. T.; Demorest, P. B.; Freire, P. C. C.; Kraus, A.; Lyne, A. G.; Noutsos, A.; Stappers, B.; Wex, N.

2013-09-01

Earth's nearest candidate supermassive black hole lies at the centre of the Milky Way. Its electromagnetic emission is thought to be powered by radiatively inefficient accretion of gas from its environment, which is a standard mode of energy supply for most galactic nuclei. X-ray measurements have already resolved a tenuous hot gas component from which the black hole can be fed. The magnetization of the gas, however, which is a crucial parameter determining the structure of the accretion flow, remains unknown. Strong magnetic fields can influence the dynamics of accretion, remove angular momentum from the infalling gas, expel matter through relativistic jets and lead to synchrotron emission such as that previously observed. Here we report multi-frequency radio measurements of a newly discovered pulsar close to the Galactic Centre and show that the pulsar's unusually large Faraday rotation (the rotation of the plane of polarization of the emission in the presence of an external magnetic field) indicates that there is a dynamically important magnetic field near the black hole. If this field is accreted down to the event horizon it provides enough magnetic flux to explain the observed emission--from radio to X-ray wavelengths--from the black hole.

ATRX ADD domain links an atypical histone methylation recognition mechanism to human mental-retardation syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Iwase, Shigeki; Xiang, Bin; Ghosh, Sharmistha

ATR-X (alpha-thalassemia/mental retardation, X-linked) syndrome is a human congenital disorder that causes severe intellectual disabilities. Mutations in the ATRX gene, which encodes an ATP-dependent chromatin-remodeler, are responsible for the syndrome. Approximately 50% of the missense mutations in affected persons are clustered in a cysteine-rich domain termed ADD (ATRX-DNMT3-DNMT3L, ADD{sub ATRX}), whose function has remained elusive. Here we identify ADD{sub ATRX} as a previously unknown histone H3-binding module, whose binding is promoted by lysine 9 trimethylation (H3K9me3) but inhibited by lysine 4 trimethylation (H3K4me3). The cocrystal structure of ADD{sub ATRX} bound to H3{sub 1-15}K9me3 peptide reveals an atypical composite H3K9me3-binding pocket,more » which is distinct from the conventional trimethyllysine-binding aromatic cage. Notably, H3K9me3-pocket mutants and ATR-X syndrome mutants are defective in both H3K9me3 binding and localization at pericentromeric heterochromatin; thus, we have discovered a unique histone-recognition mechanism underlying the ATR-X etiology.« less

ATRX ADD Domain Links an Atypical Histone Methylation Recognition Mechanism to Human Mental-Retardation Syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

S Iwase; B Xiang; S Ghosh

ATR-X (alpha-thalassemia/mental retardation, X-linked) syndrome is a human congenital disorder that causes severe intellectual disabilities. Mutations in the ATRX gene, which encodes an ATP-dependent chromatin-remodeler, are responsible for the syndrome. Approximately 50% of the missense mutations in affected persons are clustered in a cysteine-rich domain termed ADD (ATRX-DNMT3-DNMT3L, ADD{sub ATRX}), whose function has remained elusive. Here we identify ADD{sub ATRX} as a previously unknown histone H3-binding module, whose binding is promoted by lysine 9 trimethylation (H3K9me3) but inhibited by lysine 4 trimethylation (H3K4me3). The cocrystal structure of ADD{sub ATRX} bound to H3{sub 1-15}K9me3 peptide reveals an atypical composite H3K9me3-binding pocket,more » which is distinct from the conventional trimethyllysine-binding aromatic cage. Notably, H3K9me3-pocket mutants and ATR-X syndrome mutants are defective in both H3K9me3 binding and localization at pericentromeric heterochromatin; thus, we have discovered a unique histone-recognition mechanism underlying the ATR-X etiology.« less

Lipid modulation of thermal transient receptor potential channels.

PubMed

Hernández-García, Enrique; Rosenbaum, Tamara

2014-01-01

There is a subgroup of transient receptor potential (TRP) ion channels that are responsive to temperature (thermo-TRP channels). These are important to a variety of sensory and physiological phenomena such as pain and taste perception. All thermo-TRP channels known to date are subject to modulation by lipidic molecules of many kinds, from the ubiquitous cholesterol to more specialized molecules such as prostaglandins. Although the mechanisms and sites of binding of lipids on thermo-TRPs are largely unknown, the explosion on research of lipids and ion channels has revealed previously unsuspected roles for them. Diacyl glycerol is a lipid produced by phospholipase C (PLC) and it was discovered to modulate TRP channels in the eye of the fly, and many mammal TRP channels have been found to interact with lipids. While most of the lipids acting on thermo-TRP channels have been found to activate them, there are a few capable of inhibition. Phosphatidylinositol 4,5-bisphosphate is even capable of both inhibition and activation on a couple of thermo-TRPs, depending on the cellular context. More data is required to assess the mechanism through which lipids affect thermo-TRP channel activity and the physiological importance of this interaction.

Zoonotic potential of emerging paramyxoviruses: knowns and unknowns

PubMed Central

Thibault, Patricia A; Watkinson, Ruth E; Moreira-Soto, Andres; Drexler, Jan Felix; Lee, Benhur

2017-01-01

The risk of spillover of enzootic paramyxoviruses, and the susceptibility of recipient human and domestic animal populations, are defined by a broad collection of ecological and molecular factors that interact in ways that are not yet fully understood. Nipah and Hendra viruses were the first highly-lethal zoonotic paramyxoviruses discovered in modern times, but other paramyxoviruses from multiple genera are present in bats and other reservoirs that have unknown potential to spill over into humans. We outline our current understanding of paramyxovirus reservoir hosts and the ecological factors that may drive spillover, and we explore the molecular barriers to spillover that emergent paramyxoviruses may encounter. By outlining what is known about enzootic paramyxovirus receptor usage, mechanisms of innate immune evasion, and other host-specific interactions, we highlight the breadth of unexplored avenues that may be important in understanding paramyxovirus emergence. PMID:28433050

Social networks and inference about unknown events: A case of the match between Google’s AlphaGo and Sedol Lee

PubMed Central

Bae, Jonghoon; Cha, Young-Jae; Lee, Hyungsuk; Lee, Boyun; Baek, Sojung; Choi, Semin

2017-01-01

This study examines whether the way that a person makes inferences about unknown events is associated with his or her social relations, more precisely, those characterized by ego network density that reflects the structure of a person’s immediate social relation. From the analysis of individual predictions over the Go match between AlphaGo and Sedol Lee in March 2016 in Seoul, Korea, this study shows that the low-density group scored higher than the high-density group in the accuracy of the prediction over a future state of a social event, i.e., the outcome of the first game. We corroborated this finding with three replication tests that asked the participants to predict the following: film awards, President Park’s impeachment in Korea, and the counterfactual assessment of the US presidential election. Taken together, this study suggests that network density is negatively associated with vision advantage, i.e., the ability to discover and forecast an unknown aspect of a social event. PMID:28222114

Chromosomal microarray in clinical diagnosis: a study of 337 patients with congenital anomalies and developmental delays or intellectual disability.

PubMed

Sansović, Ivona; Ivankov, Ana-Maria; Bobinec, Adriana; Kero, Mijana; Barišić, Ingeborg

2017-06-14

To determine the diagnostic yield and criteria that could help to classify and interpret the copy number variations (CNVs) detected by chromosomal microarray (CMA) technique in patients with congenital and developmental abnormalities including dysmorphia, developmental delay (DD) or intellectual disability (ID), autism spectrum disorders (ASD) and congenital anomalies (CA). CMA analysis was performed in 337 patients with DD/ID with or without dysmorphism, ASD, and/or CA. In 30 of 337 patients, chromosomal imbalances had previously been detected by classical cytogenetic and molecular cytogenetic methods. In 73 of 337 patients, clinically relevant variants were detected and better characterized. Most of them were >1 Mb. Variants of unknown clinical significance (VOUS) were discovered in 35 patients. The most common VOUS size category was <300 kb (40.5%). Deletions and de novo imbalances were more frequent in pathogenic CNV than in VOUS category. CMA had a high diagnostic yield of 43/307, excluding patients previously detected by other methods. CMA was valuable in establishing the diagnosis in a high proportion of patients. Criteria for classification and interpretation of CNVs include CNV size and type, mode of inheritance, and genotype-phenotype correlation. Agilent ISCA v2 Human Genome 8x60 K oligonucleotide microarray format proved to be reasonable resolution for clinical use, particularly in the regions that are recommended by the International Standard Cytogenomic Array (ISCA) Consortium and associated with well-established syndromes.

An Anatomically Constrained Model for Path Integration in the Bee Brain.

PubMed

Stone, Thomas; Webb, Barbara; Adden, Andrea; Weddig, Nicolai Ben; Honkanen, Anna; Templin, Rachel; Wcislo, William; Scimeca, Luca; Warrant, Eric; Heinze, Stanley

2017-10-23

Path integration is a widespread navigational strategy in which directional changes and distance covered are continuously integrated on an outward journey, enabling a straight-line return to home. Bees use vision for this task-a celestial-cue-based visual compass and an optic-flow-based visual odometer-but the underlying neural integration mechanisms are unknown. Using intracellular electrophysiology, we show that polarized-light-based compass neurons and optic-flow-based speed-encoding neurons converge in the central complex of the bee brain, and through block-face electron microscopy, we identify potential integrator cells. Based on plausible output targets for these cells, we propose a complete circuit for path integration and steering in the central complex, with anatomically identified neurons suggested for each processing step. The resulting model circuit is thus fully constrained biologically and provides a functional interpretation for many previously unexplained architectural features of the central complex. Moreover, we show that the receptive fields of the newly discovered speed neurons can support path integration for the holonomic motion (i.e., a ground velocity that is not precisely aligned with body orientation) typical of bee flight, a feature not captured in any previously proposed model of path integration. In a broader context, the model circuit presented provides a general mechanism for producing steering signals by comparing current and desired headings-suggesting a more basic function for central complex connectivity, from which path integration may have evolved. Copyright © 2017 Elsevier Ltd. All rights reserved.

Recipient Glycemic Micro-environments Govern Therapeutic Effects of Mesenchymal Stem Cell Infusion on Osteopenia

PubMed Central

Sui, Bing-Dong; Hu, Cheng-Hu; Zheng, Chen-Xi; Shuai, Yi; He, Xiao-Ning; Gao, Ping-Ping; Zhao, Pan; Li, Meng; Zhang, Xin-Yi; He, Tao; Xuan, Kun; Jin, Yan

2017-01-01

Therapeutic effects of mesenchymal stem cell (MSC) infusion have been revealed in various human disorders, but impacts of diseased micro-environments are only beginning to be noticed. Donor diabetic hyperglycemia is reported to impair therapeutic efficacy of stem cells. However, whether recipient diabetic condition also affects MSC-mediated therapy is unknown. We and others have previously shown that MSC infusion could cure osteopenia, particularly in ovariectomized (OVX) mice. Here, we discovered impaired MSC therapeutic effects on osteopenia in recipient type 1 diabetes (T1D). Through intensive glycemic control by daily insulin treatments, therapeutic effects of MSCs on osteopenia were maintained. Interestingly, by only transiently restoration of recipient euglycemia using single insulin injection, MSC infusion could also rescue T1D-induced osteopenia. Conversely, under recipient hyperglycemia induced by glucose injection in OVX mice, MSC-mediated therapeutic effects on osteopenia were diminished. Mechanistically, recipient hyperglycemic micro-environments reduce anti-inflammatory capacity of MSCs in osteoporotic therapy through suppressing MSC interaction with T cells via the Adenosine monophosphate-activated protein kinase (AMPK) pathway. We further revealed in diabetic micro-environments, double infusion of MSCs ameliorated osteopenia by anti-inflammation, attributed to the first transplanted MSCs which normalized the recipient glucose homeostasis. Collectively, our findings uncover a previously unrecognized role of recipient glycemic conditions controlling MSC-mediated therapy, and unravel that fulfillment of potent therapeutic effects of MSCs requires tight control of recipient micro-environments. PMID:28435461

Cloning and heterologous expression of a novel subgroup of class IV polyhydroxyalkanoate synthase genes from the genus Bacillus.

PubMed

Mizuno, Kouhei; Kihara, Takahiro; Tsuge, Takeharu; Lundgren, Benjamin R; Sarwar, Zaara; Pinto, Atahualpa; Nomura, Christopher T

2017-01-01

Many microorganisms harbor genes necessary to synthesize biodegradable plastics known as polyhydroxyalkanoates (PHAs). We surveyed a genomic database and discovered a new cluster of class IV PHA synthase genes (phaRC). These genes are different in sequence and operon structure from any previously reported PHA synthase. The newly discovered PhaRC synthase was demonstrated to produce PHAs in recombinant Escherichia coli.

Mineral resource of the month: cadmium

USGS Publications Warehouse

Tolcin, Amy C.

2012-01-01

The element cadmium was discovered in 1817 by Friedrich Stromeyer, a professor of chemistry at the University of Göttingen in Germany. Stromeyer noticed that a yellowish glow would occur when heat was applied to certain samples of calamine, a zinc-carbonate. This was unusual as the reaction was expected to be colorless. After further testing, Stromeyer deduced that an unknown metallic impurity in the carbonate caused the color change. He called the new metal "cadmium" after "kadmeia," the Greek word for calamine.

Trocara virus: a newly recognized Alphavirus (Togaviridae) isolated from mosquitoes in the Amazon Basin.

PubMed

Travassos da Rosa, A P; Turell, M J; Watts, D M; Powers, A M; Vasconcelos, P F; Jones, J W; Klein, T A; Dohm, D J; Shope, R E; Degallier, N; Popov, V L; Russell, K L; Weaver, S C; Guzman, H; Calampa, C; Brault, A C; Lemon, A P; Tesh, R B

2001-01-01

This report describes Trocara virus, a newly recognized member of the genus Alphavirus, that has been isolated from Aedes serratus mosquitoes collected at two widely separated sites in the Amazon Basin. Biological, antigenic and genetic characteristics of the new virus are given. Results of these studies indicate that Trocara virus is the first member of a newly discovered antigenic complex within the family Togaviridae genus Alphavirus. The public health and veterinary importance of Trocara virus is still unknown.

Observations of Nonthermal Radio Emission from Early-type Stars

NASA Technical Reports Server (NTRS)

Abbott, D. C.; Bieging, J. H.; Churchwell, E.

1985-01-01

As a part of a wider survey of radio emission from O, B, and Wolf-Rayet (WR) stars, five new stars whose radio emission is dominated by a nonthermal mechanism of unknown origin were discovered. From statistics of distance-limited samples of stars, it is estimated that the minimum fraction of stars which are nonthermal emitters is 25% for the OB stars and 10% for the WR stars. The characteristics of this new class of nonthermal radio emitter are investigated.

Line width determination using a biomimetic fly eye vision system.

PubMed

Benson, John B; Wright, Cameron H G; Barrett, Steven F

2007-01-01

Developing a new vision system based on the vision of the common house fly, Musca domestica, has created many interesting design challenges. One of those problems is line width determination, which is the topic of this paper. It has been discovered that line width can be determined with a single sensor as long as either the sensor, or the object in question, has a constant, known velocity. This is an important first step for determining the width of any arbitrary object, with unknown velocity.

Cannabidiol: an overview of some pharmacological aspects.

PubMed

Mechoulam, Raphael; Parker, Linda A; Gallily, Ruth

2002-11-01

Over the past few years, considerable attention has focused on cannabidiol (CBD), a major nonpsychotropic constituent of cannabis. The authors present a review on the chemistry of CBD and discuss the anticonvulsive, antianxiety, antipsychotic, antinausea, and antirheumatoid arthritic properties of CBD. CBD does not bind to the known cannabinoid receptors, and its mechanism of action is yet unknown. It is possible that, in part at least, its effects are due to its recently discovered inhibition of anandamide uptake and hydrolysis and to its antioxidative effect.

Recommendation Techniques for Drug-Target Interaction Prediction and Drug Repositioning.

PubMed

Alaimo, Salvatore; Giugno, Rosalba; Pulvirenti, Alfredo

2016-01-01

The usage of computational methods in drug discovery is a common practice. More recently, by exploiting the wealth of biological knowledge bases, a novel approach called drug repositioning has raised. Several computational methods are available, and these try to make a high-level integration of all the knowledge in order to discover unknown mechanisms. In this chapter, we review drug-target interaction prediction methods based on a recommendation system. We also give some extensions which go beyond the bipartite network case.

Three-dimensional structure of the submarine flanks of La Réunion inferred from geophysical data

NASA Astrophysics Data System (ADS)

Gailler, Lydie-Sarah; LéNat, Jean-FrançOis

2010-12-01

La Réunion (Indian Ocean) constitutes a huge volcanic oceanic system of which most of the volume is submerged. We present a study of its submarine part based on the interpretation of magnetic and gravity data compiled from old and recent surveys. A model of the submarine internal structure is derived from 3-D and 2-D models using constraints from previous geological and geophysical studies. Two large-scale, previously unknown, buried volcanic construction zones are discovered in continuation of the island's construction. To the east, the Alizés submarine zone is interpreted as the remnants of Les Alizés volcano eastward flank whose center is marked by a large hypovolcanic intrusion complex. To the southwest, the Etang Salé submarine zone is interpreted as an extension of Piton des Neiges, probably fed by a volcanic rift zone over a large extent. They were predominantly built during the Matuyama period and thus probably belong to early volcanism. A correlation exists between their top and seismic horizons recognized in previous studies and interpreted as the base of the volcanic edifice. Their morphology suggested a lithospheric bulging beneath La Réunion, not required to explain our data, since the seismic interfaces match the top of our volcanic constructions. The coastal shelf coincides with a negative Bouguer anomaly belt, often associated with magnetic anomalies, suggesting a shelf built by hyaloclastites. A detailed analysis of the offshore continuation of La Montagne Massif to the north confirms this hypothesis. The gravity analysis confirms that the bathymetric bulges, forming the northern, eastern, southern, and western submarine flanks, are predominantly built by debris avalanche deposits at the surface.

Efficient approach for the detection and identification of new androgenic metabolites by applying SRM GC-CI-MS/MS: a methandienone case study.

PubMed

Polet, Michael; Van Gansbeke, Wim; Van Eenoo, Peter; Deventer, Koen

2016-07-01

Identification of anabolic androgenic steroids (AAS) is a vital issue in doping control and toxicology, and searching for metabolites with longer detection times remains an important task. Recently, a gas chromatography chemical ionization triple quadrupole mass spectrometry (GC-CI-MS/MS) method was introduced, and CI, in comparison with electron ionization (EI), proved to be capable of increasing the sensitivity significantly. In addition, correlations between AAS structure and fragmentation behavior could be revealed. This enables the search for previously unknown but expected metabolites by selection of their predicted transitions. The combination of both factors allows the setup of an efficient approach to search for new metabolites. The approach uses selected reaction monitoring which is inherently more sensitive than full scan or precursor ion scan. Additionally, structural information obtained from the structure specific CI fragmentation pattern facilitates metabolite identification. The procedure was demonstrated by a methandienone case study. Its metabolites have been studied extensively in the past, and this allowed an adequate evaluation of the efficiency of the approach. Thirty three metabolites were detected, including all relevant previously discovered metabolites. In our study, the previously reported long-term metabolite (18-nor-17β-hydroxymethyl,17α-methyl-androst-1,4,13-trien-3-one) could be detected up to 26 days by using GC-CI-MS/MS. The study proves the validity of the approach to search for metabolites of new synthetic AAS and new long-term metabolites of less studied AAS and illustrates the increase in sensitivity by using CI. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Typical ultraviolet spectra in combination with diagnostic mass fragmentation analysis for the rapid and comprehensive profiling of chlorogenic acids in the buds of Lonicera macranthoides.

PubMed

Zhang, Shui-Han; Hu, Xin; Shi, Shu-Yun; Huang, Lu-Qi; Chen, Wei; Chen, Lin; Cai, Ping

2016-05-01

A major challenge of profiling chlorogenic acids (CGA) in natural products is to effectively detect unknown or minor isomeric compounds. Here, we developed an effective strategy, typical ultraviolet (UV) spectra in combination with diagnostic mass fragmentation analysis based on HPLC-DAD-QTOF-MS/MS, to comprehensively profile CGA in the buds of Lonicera macranthoides. First, three CGA UV patterns were obtained by UV spectra screening. Second, 13 types of CGA classified by molecular weights were found by thorough analysis of CGA peaks using high-resolution MS. Third, selected ion monitoring (SIM) was carried out for each type of CGA to avoid overlooking of minor ones. Fourth, MS/MS spectra of each CGA were investigated. Then 70 CGA were identified by matching their UV spectra, accurate mass signals and fragmentation patterns with standards or previously reported compounds, including six caffeoylquinic acids (CQA), six diCQA, one triCQA, three caffeoylshikimic acids (CSA), six diCSA, one triCSA, three p-coumaroylquinic acids (pCoQA), four p-coumaroylcaffeoylquinic acids (pCoCQA), four feruloylquinic acids (FQA), five methyl caffeoylquinates (MCQ), three ethyl caffeoylquinates (ECQ), three dimethoxycinnamoylquinic acids (DQA), six caffeoylferuloylquinic acids (CFQA), six methyl dicaffeoylquinates (MdiCQ), four FQA glycosides (FQAG), six MCQ glycosides (MCQG), and three ethyl dicaffeoylquinates (EdiCQ). Forty-five of them were discovered from Lonicera species for the first time, and it is noted that CGA profiles were investigated for the first time in L. macranthoides. Results indicated that the developed method was a useful approach to explore unknown and minor isomeric compounds from complex natural products.

Will Systems Biology Deliver Its Promise and Contribute to the Development of New or Improved Vaccines? What Really Constitutes the Study of "Systems Biology" and How Might Such an Approach Facilitate Vaccine Design.

PubMed

Germain, Ronald N

2017-10-16

A dichotomy exists in the field of vaccinology about the promise versus the hype associated with application of "systems biology" approaches to rational vaccine design. Some feel it is the only way to efficiently uncover currently unknown parameters controlling desired immune responses or discover what elements actually mediate these responses. Others feel that traditional experimental, often reductionist, methods for incrementally unraveling complex biology provide a more solid way forward, and that "systems" approaches are costly ways to collect data without gaining true insight. Here I argue that both views are inaccurate. This is largely because of confusion about what can be gained from classical experimentation versus statistical analysis of large data sets (bioinformatics) versus methods that quantitatively explain emergent properties of complex assemblies of biological components, with the latter reflecting what was previously called "physiology." Reductionist studies will remain essential for generating detailed insight into the functional attributes of specific elements of biological systems, but such analyses lack the power to provide a quantitative and predictive understanding of global system behavior. But by employing (1) large-scale screening methods for discovery of unknown components and connections in the immune system ( omics ), (2) statistical analysis of large data sets ( bioinformatics ), and (3) the capacity of quantitative computational methods to translate these individual components and connections into models of emergent behavior ( systems biology ), we will be able to better understand how the overall immune system functions and to determine with greater precision how to manipulate it to produce desired protective responses. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Identifying chemicals that are planetary boundary threats.

PubMed

MacLeod, Matthew; Breitholtz, Magnus; Cousins, Ian T; de Wit, Cynthia A; Persson, Linn M; Rudén, Christina; McLachlan, Michael S

2014-10-07

Rockström et al. proposed a set of planetary boundaries that delimit a "safe operating space for humanity". Many of the planetary boundaries that have so far been identified are determined by chemical agents. Other chemical pollution-related planetary boundaries likely exist, but are currently unknown. A chemical poses an unknown planetary boundary threat if it simultaneously fulfills three conditions: (1) it has an unknown disruptive effect on a vital Earth system process; (2) the disruptive effect is not discovered until it is a problem at the global scale, and (3) the effect is not readily reversible. In this paper, we outline scenarios in which chemicals could fulfill each of the three conditions, then use the scenarios as the basis to define chemical profiles that fit each scenario. The chemical profiles are defined in terms of the nature of the effect of the chemical and the nature of exposure of the environment to the chemical. Prioritization of chemicals in commerce against some of the profiles appears feasible, but there are considerable uncertainties and scientific challenges that must be addressed. Most challenging is prioritizing chemicals for their potential to have a currently unknown effect on a vital Earth system process. We conclude that the most effective strategy currently available to identify chemicals that are planetary boundary threats is prioritization against profiles defined in terms of environmental exposure combined with monitoring and study of the biogeochemical processes that underlie vital Earth system processes to identify currently unknown disruptive effects.

Statistical and optimal learning with applications in business analytics

NASA Astrophysics Data System (ADS)

Han, Bin

Statistical learning is widely used in business analytics to discover structure or exploit patterns from historical data, and build models that capture relationships between an outcome of interest and a set of variables. Optimal learning on the other hand, solves the operational side of the problem, by iterating between decision making and data acquisition/learning. All too often the two problems go hand-in-hand, which exhibit a feedback loop between statistics and optimization. We apply this statistical/optimal learning concept on a context of fundraising marketing campaign problem arising in many non-profit organizations. Many such organizations use direct-mail marketing to cultivate one-time donors and convert them into recurring contributors. Cultivated donors generate much more revenue than new donors, but also lapse with time, making it important to steadily draw in new cultivations. The direct-mail budget is limited, but better-designed mailings can improve success rates without increasing costs. We first apply statistical learning to analyze the effectiveness of several design approaches used in practice, based on a massive dataset covering 8.6 million direct-mail communications with donors to the American Red Cross during 2009-2011. We find evidence that mailed appeals are more effective when they emphasize disaster preparedness and training efforts over post-disaster cleanup. Including small cards that affirm donors' identity as Red Cross supporters is an effective strategy, while including gift items such as address labels is not. Finally, very recent acquisitions are more likely to respond to appeals that ask them to contribute an amount similar to their most recent donation, but this approach has an adverse effect on donors with a longer history. We show via simulation that a simple design strategy based on these insights has potential to improve success rates from 5.4% to 8.1%. Given these findings, when new scenario arises, however, new data need to be acquired to update our model and decisions, which is studied under optimal learning framework. The goal becomes discovering a sequential information collection strategy that learns the best campaign design alternative as quickly as possible. Regression structure is used to learn about a set of unknown parameters, which alternates with optimization to design new data points. Such problems have been extensively studied in the ranking and selection (R&S) community, but traditional R&S procedures experience high computational costs when the decision space grows combinatorially. We present a value of information procedure for simultaneously learning unknown regression parameters and unknown sampling noise. We then develop an approximate version of the procedure, based on semi-definite programming relaxation, that retains good performance and scales better to large problems. We also prove the asymptotic consistency of the algorithm in the parametric model, a result that has not previously been available for even the known-variance case.

The RelA/SpoT Homolog (RSH) Superfamily: Distribution and Functional Evolution of ppGpp Synthetases and Hydrolases across the Tree of Life

PubMed Central

Atkinson, Gemma C.; Tenson, Tanel; Hauryliuk, Vasili

2011-01-01

RelA/SpoT Homologue (RSH) proteins, named for their sequence similarity to the RelA and SpoT enzymes of Escherichia coli, comprise a superfamily of enzymes that synthesize and/or hydrolyze the alarmone ppGpp, activator of the “stringent” response and regulator of cellular metabolism. The classical “long” RSHs Rel, RelA and SpoT with the ppGpp hydrolase, synthetase, TGS and ACT domain architecture have been found across diverse bacteria and plant chloroplasts, while dedicated single domain ppGpp-synthesizing and -hydrolyzing RSHs have also been discovered in disparate bacteria and animals respectively. However, there is considerable confusion in terms of nomenclature and no comprehensive phylogenetic and sequence analyses have previously been carried out to classify RSHs on a genomic scale. We have performed high-throughput sensitive sequence searching of over 1000 genomes from across the tree of life, in combination with phylogenetic analyses to consolidate previous ad hoc identification of diverse RSHs in different organisms and provide a much-needed unifying terminology for the field. We classify RSHs into 30 subgroups comprising three groups: long RSHs, small alarmone synthetases (SASs), and small alarmone hydrolases (SAHs). Members of nineteen previously unidentified RSH subgroups can now be studied experimentally, including previously unknown RSHs in archaea, expanding the “stringent response” to this domain of life. We have analyzed possible combinations of RSH proteins and their domains in bacterial genomes and compared RSH content with available RSH knock-out data for various organisms to determine the rules of combining RSHs. Through comparative sequence analysis of long and small RSHs, we find exposed sites limited in conservation to the long RSHs that we propose are involved in transmitting regulatory signals. Such signals may be transmitted via NTD to CTD intra-molecular interactions, or inter-molecular interactions either among individual RSH molecules or among long RSHs and other binding partners such as the ribosome. PMID:21858139

Identification of a Bipolar Disorder Vulnerable Gene CHDH at 3p21.1.

PubMed

Chang, Hong; Li, Lingyi; Peng, Tao; Grigoroiu-Serbanescu, Maria; Bergen, Sarah E; Landén, Mikael; Hultman, Christina M; Forstner, Andreas J; Strohmaier, Jana; Hecker, Julian; Schulze, Thomas G; Müller-Myhsok, Bertram; Reif, Andreas; Mitchell, Philip B; Martin, Nicholas G; Cichon, Sven; Nöthen, Markus M; Jamain, Stéphane; Leboyer, Marion; Bellivier, Frank; Etain, Bruno; Kahn, Jean-Pierre; Henry, Chantal; Rietschel, Marcella; Xiao, Xiao; Li, Ming

2017-09-01

Genome-wide analysis (GWA) is an effective strategy to discover extreme effects surpassing genome-wide significant levels in studying complex disorders; however, when sample size is limited, the true effects may fail to achieve genome-wide significance. In such case, there may be authentic results among the pools of nominal candidates, and an alternative approach is to consider nominal candidates but are replicable across different samples. Here, we found that mRNA expression of the choline dehydrogenase gene (CHDH) was uniformly upregulated in the brains of bipolar disorder (BPD) patients compared with healthy controls across different studies. Follow-up genetic analyses of CHDH variants in multiple independent clinical datasets (including 11,564 cases and 17,686 controls) identified a risk SNP rs9836592 showing consistent associations with BPD (P meta  = 5.72 × 10 -4 ), and the risk allele indicated an increased CHDH expression in multiple neuronal tissues (lowest P = 6.70 × 10 -16 ). These converging results may identify a nominal but true BPD susceptibility gene CHDH. Further exploratory analysis revealed suggestive associations of rs9836592 with childhood intelligence (P = 0.044) and educational attainment (P = 0.0039), a "proxy phenotype" of general cognitive abilities. Intriguingly, the CHDH gene is located at chromosome 3p21.1, a risk region implicated in previous BPD genome-wide association studies (GWAS), but CHDH is lying outside of the core GWAS linkage disequilibrium (LD) region, and our studied SNP rs9836592 is ∼1.2 Mb 3' downstream of the previous GWAS loci (e.g., rs2251219) with no LD between them; thus, the association observed here is unlikely a reflection of previous GWAS signals. In summary, our results imply that CHDH may play a previously unknown role in the etiology of BPD and also highlight the informative value of integrating gene expression and genetic code in advancing our understanding of its biological basis.

LC-MS/MS profiling-based secondary metabolite screening of Myxococcus xanthus.

PubMed

Kim, Jiyoung; Choi, Jung Nam; Kim, Pil; Sok, Dai-Eun; Nam, Soo-Wan; Lee, Choong Hwan

2009-01-01

Myxobacteria, Gram-negative soil bacteria, are a well-known producer of bioactive secondary metabolites. Therefore, this study presents a methodological approach for the high-throughput screening of secondary metabolites from 4 wild-type Myxococcus xanthus strains. First, electrospray ionization mass spectrometry (ESI-MS) was performed using extracellular crude extracts. As a result, 22 metabolite peaks were detected, and the metabolite profiling was then conducted using the m/z value, retention time, and MS/MS fragmentation pattern analyses. Among the peaks, one unknown compound peak was identified as analogous to the myxalamid A, B, and C series. An analysis of the tandem mass spectrometric fragmentation patterns and HR-MS identified myxalamid K as a new compound derived from M. xanthus. In conclusion, LC-MS/MS-based chemical screening of diverse secondary metabolites would appear to be an effective approach for discovering unknown microbial secondary metabolites.

The Five Year Fermi/GBM Magnetar Burst Catalog

NASA Astrophysics Data System (ADS)

Collazzi, A. C.; Kouveliotou, C.; van der Horst, A. J.; Younes, G. A.; Kaneko, Y.; Göğüş, E.; Lin, L.; Granot, J.; Finger, M. H.; Chaplin, V. L.; Huppenkothen, D.; Watts, A. L.; von Kienlin, A.; Baring, M. G.; Gruber, D.; Bhat, P. N.; Gibby, M. H.; Gehrels, N.; McEnery, J.; van der Klis, M.; Wijers, R. A. M. J.

2015-05-01

Since launch in 2008, the Fermi Gamma-ray Burst Monitor (GBM) has detected many hundreds of bursts from magnetar sources. While the vast majority of these bursts have been attributed to several known magnetars, there is also a small sample of magnetar-like bursts of unknown origin. Here, we present the Fermi/GBM magnetar catalog, providing the results of the temporal and spectral analyses of 440 magnetar bursts with high temporal and spectral resolution. This catalog covers the first five years of GBM magnetar observations, from 2008 July to 2013 June. We provide durations, spectral parameters for various models, fluences, and peak fluxes for all the bursts, as well as a detailed temporal analysis for SGR J1550-5418 bursts. Finally, we suggest that some of the bursts of unknown origin are associated with the newly discovered magnetar 3XMM J185246.6+0033.7.

Rapid screening and structural elucidation of a novel sibutramine analogue in a weight loss supplement: 11-desisobutyl-11-benzylsibutramine.

PubMed

Mans, Daniel J; Gucinski, Ashley C; Dunn, Jamie D; Gryniewicz-Ruzicka, Connie M; Mecker-Pogue, Laura C; Kao, Jeff L-F; Ge, Xia

2013-09-01

A novel analogue of sibutramine, 11-desisobutyl-11-benzylsibutramine, has been discovered. During routine ion mobility spectrometry (IMS) screening of a weight loss supplement collected at an US FDA import operation facility an unknown peak was observed. Further analysis of the supplement by liquid chromatography-mass spectrometry (LC-MS) and high resolution mass spectrometry revealed an unknown peak with a relative retention time of 1.04 with respect to sibutramine and a predicted formula of C20H24NCl. In order to elucidate the analogue's structure, it was isolated from the supplement and characterized by tandem mass spectrometry and nuclear magnetic resonance (NMR), which revealed the analogue possessed a benzyl moiety at the 11 position in place of the isobutyl group associated with sibutramine. Copyright © 2013. Published by Elsevier B.V.

Contribution of space platforms to a ground and airborne remote sensing programme over active Italian volcanoes

NASA Technical Reports Server (NTRS)

Cassinis, R. (Principal Investigator); Lechi, G. M.; Marino, C. M.; Tonelli, A. M.

1974-01-01

The author has identified the following significant results. A method has been suggested for the forecasting of the lateral eruptions of Mount Etna, through the multispectral analysis of the vegetation behavior. Unknown geological lineaments which seem to be related to deep crustal movements have been discovered using the ERTS-1 imagery. Results in the geological field were obtained in the study of the general structure of the Alpine range. In the field of official vegetation classification, ERTS-1 images were used for a preliminary study of rice fields in northern Italy. Very good experimental results have been obtained using the Skylab multispectral photographs. In the field of hydrogeology and soil type discrimination discoveries of unknown paleoriver beds have been made in the northeastern part of the Po Valley using the multispectral imagery of SL3. The superior resolution of Skylab was a fundamental element for the success of this investigation.

Active Learning with Rationales for Identifying Operationally Significant Anomalies in Aviation

NASA Technical Reports Server (NTRS)

Sharma, Manali; Das, Kamalika; Bilgic, Mustafa; Matthews, Bryan; Nielsen, David Lynn; Oza, Nikunj C.

2016-01-01

A major focus of the commercial aviation community is discovery of unknown safety events in flight operations data. Data-driven unsupervised anomaly detection methods are better at capturing unknown safety events compared to rule-based methods which only look for known violations. However, not all statistical anomalies that are discovered by these unsupervised anomaly detection methods are operationally significant (e.g., represent a safety concern). Subject Matter Experts (SMEs) have to spend significant time reviewing these statistical anomalies individually to identify a few operationally significant ones. In this paper we propose an active learning algorithm that incorporates SME feedback in the form of rationales to build a classifier that can distinguish between uninteresting and operationally significant anomalies. Experimental evaluation on real aviation data shows that our approach improves detection of operationally significant events by as much as 75% compared to the state-of-the-art. The learnt classifier also generalizes well to additional validation data sets.

Magnetic Characterization of Proposed Tektite-like Objects (Urengoites, South-Ural Glass) from Siberia, Russia

NASA Astrophysics Data System (ADS)

Bezaeva, N. S.; Rochette, P.; Masaitis, V. L.; Badyukov, D. D.; Kosterov, A.

2017-12-01

Urengoites and South-Ural glass are proposed `tektite-like' objects from Western Siberia (Russia), previously described in [1-3]. Urengoites (U-1, U-2, U-3; 24 Ma [1]) were discovered near the West-Siberian town of Novy Urengoi [1-2]. Total recovered mass: 21.65 g. The only recovered South-Ural glass A-1 was found near Magnitogorsk ( 90 g) [3]. In spite of previous works [1-3], the magnetic properties of urengoites and South-Ural glass remain unknown. Here we present a comprehensive magnetic characterization for all three currently known urengoite specimens and the only discovered South-Ural glass. Rock magnetic investigations revealed the presence of ferrimagnetic minerals in all samples. Low-temperature magnetometry (ZFC-FC dataset) points out to magnetite, which was detected in the most magnetic urengoite sample (U-3) via its characteristic Verwey transition at 120K (<1 ppm). Contrary to previous investigations [2], we could measure NRM for all samples and acquire alternating field demagnetization spectra for the biggest samples (U-1 and A-1). The following SIRM values were recorded: 4.33 μAm2/kg (U-1). 13.20 μAm2/kg (U-2), 62.40 μAm2/kg (U-3) and 9.36 μAm2/kg (A-1). The obtained χ0 values for all four samples (U-1 to U-3: from 9.98 to 19.90·10-9 m3/kg; A-1: 4.66·10-9 m3/kg) are close to those for Libyan glassed (see Table 1 in [4]). Anisotropy of magnetic susceptibility (AMS) measurements for A-1 sample revealed 28% of anisotropy. SIRM values and non-isotropic susceptibility demonstrate a composite ferrimagnetic and paramagnetic origin of susceptibility. U-1 and A-1 do not demonstrate any field nor frequency dependence of χ0, which likely indicates the absence of superparamagnetic grains of nanometric size. Acknowledgements: The work is supported by Act 211 Government of the Russian Federation, agreement № 02.A03.21.0006 and is performed according to the Russian Government Program of Competitive Growth of Kazan Federal University. This research has been conducted using the facilities of St. Petersburg University Scientific Park, RCs Geomodel, DFM, and ITCN. Refs: [1] Deutsch A. et al. (1997) MAPS 32:679-686. [2] Masaitis V.L. et al. (1988) LPS XIX:728-729. [3] Koroteev V.A. et al. (1994) Zapisky Vseross. Mineral. Obsh. 123:44-48 (in Russian). [4] Rochette et al. (2015) EPSL 432:381-390.

A Comparative Analysis of Indian Gaming in the United States

ERIC Educational Resources Information Center

Ackerman, William V.; Bunch, Rick L.

2012-01-01

Previous research on Indian gaming in South Dakota discovered very restrictive and unfavorable tribal-state compacts that appear to border on economic racism. This article expands this previous research by exploring the influence of tribal-state Indian gaming compacts for the Indian casinos located in the contiguous United States. The purpose is…

Data-driven approach to detect common copy-number variations and frequency profiles in a population-based Korean cohort.

PubMed

Moon, Sanghoon; Kim, Young Jin; Hong, Chang Bum; Kim, Dong-Joon; Lee, Jong-Young; Kim, Bong-Jo

2011-11-01

To date, hundreds of thousands of copy-number variation (CNV) data have been reported using various platforms. The proportion of Asians in these data is, however, relatively small as compared with that of other ethnic groups, such as Caucasians and Yorubas. Because of limitations in platform resolution and the high noise level in signal intensity, in most CNV studies (particularly those using single nucleotide polymorphism arrays), the average number of CNVs in an individual is less than the number of known CNVs. In this study, we ascertained reliable, common CNV regions (CNVRs) and identified actual frequency rates in the Korean population to provide more CNV information. We performed two-stage analyses for detecting structural variations with two platforms. We discovered 576 common CNVRs (88 CNV segments on average in an individual), and 87% (501 of 576) of these CNVRs overlapped by ≥1 bp with previously validated CNV events. Interestingly, from the frequency analysis of CNV profiles, 52 of 576 CNVRs had a frequency rate of <1% in the 8842 individuals. Compared with other common CNV studies, this study found six common CNVRs that were not reported in previous CNV studies. In conclusion, we propose the data-driven detection approach to discover common CNVRs including those of unreported in the previous Korean CNV study while minimizing false positives. Through our approach, we successfully discovered more common CNVRs than previous Korean CNV study and conducted frequency analysis. These results will be a valuable resource for the effective level of CNVs in the Korean population.

A New Chaotic Flow with Hidden Attractor: The First Hyperjerk System with No Equilibrium

NASA Astrophysics Data System (ADS)

Ren, Shuili; Panahi, Shirin; Rajagopal, Karthikeyan; Akgul, Akif; Pham, Viet-Thanh; Jafari, Sajad

2018-02-01

Discovering unknown aspects of non-equilibrium systems with hidden strange attractors is an attractive research topic. A novel quadratic hyperjerk system is introduced in this paper. It is noteworthy that this non-equilibrium system can generate hidden chaotic attractors. The essential properties of such systems are investigated by means of equilibrium points, phase portrait, bifurcation diagram, and Lyapunov exponents. In addition, a fractional-order differential equation of this new system is presented. Moreover, an electronic circuit is also designed and implemented to verify the feasibility of the theoretical model.

Karl Julius Lohnert - an unknown astronomer, experimental psychologist and teacher (German Title: Karl Julius Lohnert - ein unbekannter Astronom, experimenteller Psychologe und Lehrer)

NASA Astrophysics Data System (ADS)

Schmadel, Lutz D.; Guski-Leinwand, Susanne

2011-08-01

Karl Julius Lohnert (1885-1944) with his double biography as astronomer and psychologist is hardly known in both fields. As a student of astronomy in Heidelberg, Lohnert discovered a couple of minor planets and he dedicated one to his PhD supervisor, the famous Leipzig professor for philosophy, Wilhelm Wundt. This connection is discussed for the first time almost one century after the naming of (635) Vundtia. The paper elucidates some biographical stations of Lohnert.

GNE-886: A Potent and Selective Inhibitor of the Cat Eye Syndrome Chromosome Region Candidate 2 Bromodomain (CECR2).

PubMed

Crawford, Terry D; Audia, James E; Bellon, Steve; Burdick, Daniel J; Bommi-Reddy, Archana; Côté, Alexandre; Cummings, Richard T; Duplessis, Martin; Flynn, E Megan; Hewitt, Michael; Huang, Hon-Ren; Jayaram, Hariharan; Jiang, Ying; Joshi, Shivangi; Kiefer, James R; Murray, Jeremy; Nasveschuk, Christopher G; Neiss, Arianne; Pardo, Eneida; Romero, F Anthony; Sandy, Peter; Sims, Robert J; Tang, Yong; Taylor, Alexander M; Tsui, Vickie; Wang, Jian; Wang, Shumei; Wang, Yongyun; Xu, Zhaowu; Zawadzke, Laura; Zhu, Xiaoqin; Albrecht, Brian K; Magnuson, Steven R; Cochran, Andrea G

2017-07-13

The biological function of bromodomains, epigenetic readers of acetylated lysine residues, remains largely unknown. Herein we report our efforts to discover a potent and selective inhibitor of the bromodomain of cat eye syndrome chromosome region candidate 2 (CECR2). Screening of our internal medicinal chemistry collection led to the identification of a pyrrolopyridone chemical lead, and subsequent structure-based drug design led to a potent and selective CECR2 bromodomain inhibitor (GNE-886) suitable for use as an in vitro tool compound.

The Jupiter system through the eyes of Voyager 1

USGS Publications Warehouse

Smith, B.A.; Soderblom, L.A.; Johnson, T.V.; Ingersoll, A.P.; Collins, S.A.; Shoemaker, E.M.; Hunt, G.E.; Masursky, H.; Carr, M.H.; Davies, M.E.; Cook, A.F.; Boyce, J.; Danielson, G.E.; Owen, Timothy W.; Sagan, C.; Beebe, R.F.; Veverka, J.; Strom, R.G.; McCauley, J.F.; Morrison, D.; Briggs, G.A.; Suomi, V.E.

1979-01-01

The cameras aboard Voyager I have provided a closeup view of the Jupiter system, revealing heretofore unknown characteristics and phenomena associated with the planet's atmosphere and the surfaces of its five major satellites. On Jupiter itself, atmospheric motions-the interaction of cloud systems-display complex vorticity. On its dark side, lightning and auroras are observed. A ring was discovered surrounding Jupiter. The satellite surfaces display dramatic differences including extensive active volcanismn on Io, complex tectonism on Ganymnede and possibly Europa, and flattened remnants of enormous impact features on Callisto. Copyright ?? 1979 AAAS.

Thymolipoma combined with hyperthyroidism discovered by neurological symptoms.

PubMed

Takahashi, Hidenobu; Harada, Masahiko; Kimura, Masakazu; Kato, Harubumi

2007-04-01

Thymolipomas are rare slow-growing mediastinal thymic neoplasms. Most cases are asymptomatic and are sometimes discovered as a huge mass on chest x-ray films. A few cases have been discovered during examinations for other diseases. We report the second case of thymolipoma combined with hyperthyroidism in the English language literature. Neurological symptoms suddenly appeared in a 45-year-old woman. Central nervous system disorder was suggested but no significant abnormalities were found on brain MR nor were there any neurological signs. Several months later, neurological and systemic examinations on admission revealed hyperthyroidism and an anterior mediastinal tumor, 9.0x5.0x3.0 cm in size on chest CT films. Despite treatment of hyperthyroidism by medication, her neurological symptoms remained. Neurologists recommended resection of the mediastinal tumor. Malignancy could not be ruled out because of the irregularity of the tumor appearance on contrast-enhanced chest CT. Furthermore, the tumor appeared to be attached to the ascending aorta, so cytological and/or pathological diagnosis by CT-guided needle biopsy before operation were contraindicated. Extended thymectomy was performed in May 2005. The pathological diagnosis was benign thymolipoma consisting of mature fatty tissue and thymic tissue structures with Hassall's corpuscles. Her neurological symptoms seemed slightly but not markedly improved. The relationship between thymolipoma and hyperthyroidism is still unknown.

Millennium-old farm breeding of Chinese softshell turtles (Pelodiscus spp.) results in massive erosion of biodiversity.

PubMed

Gong, Shiping; Vamberger, Melita; Auer, Markus; Praschag, Peter; Fritz, Uwe

2018-05-04

Chinese softshell turtles (Pelodiscus spp.) are widely distributed, ranging from the Amur and Ussuri Rivers in the Russian Far East through the Korean Peninsula, Japan, and eastern, central, and southern China to southern Vietnam. In East and Southeast Asia, Chinese softshell turtles are traditionally exploited for food and have been farm-bred in China since the Spring and Autumn Period, more than 2400 years ago. Currently, the annual production of Pelodiscus amounts to 340,000 t in China alone. Using mitochondrial DNA (2428 bp) and five nuclear loci (3704 bp), we examined broad sampling of wild and farm-bred Pelodiscus to infer genetic and taxonomic differentiation. We discovered four previously unknown mitochondrial lineages, all from China. One lineage from Jiangxi is deeply divergent and sister to the mitochondrial lineage of Pelodiscus axenaria. The nuclear loci supported species status for P. axenaria and the new lineage from Jiangxi. Pelodiscus maackii and P. parviformis, both harboring distinct mitochondrial lineages, were not differentiated from P. sinensis in the studied nuclear markers. The same is true for two new mitochondrial lineages from Zhejiang, China, represented by only one individual each, and another new lineage from Anhui, Guangdong, Jiangxi and Zhejiang, China. However, Vietnamese turtles yielding a mitochondrial lineage clustering within P. sinensis were distinct in nuclear markers, suggesting that these populations could represent another unknown species with introgressed mitochondria. Its species status is also supported by the syntopic occurrence with P. sinensis in northern Vietnam and by morphology. In addition, we confirmed sympatry of P. axenaria and P. parviformis in Guangxi, China, and found evidence for sympatry of P. sinensis and the new putative species from Jiangxi, China. We also discovered evidence for hybridization in turtle farms and for the occurrence of alien lineages in the wild (Zhejiang, China), highlighting the risk of genetic pollution of native stock. In the face of the large-scale breeding of Pelodiscus, we claim that the long-term survival of distinct genetic lineages and species can only be assured when an upscale market segment for pure-bred softshell turtles is established, making the breeding of pure lineages lucrative for turtle farms. Our findings underline that the diversity of Pelodiscus is currently underestimated and threatened by anthropogenic admixture. We recommend mass screening of genetic and morphological variation of Chinese softshell turtles as a first step to understand and preserve their diversity.

Millennium-old farm breeding of Chinese softshell turtles ( Pelodiscus spp.) results in massive erosion of biodiversity

NASA Astrophysics Data System (ADS)

Gong, Shiping; Vamberger, Melita; Auer, Markus; Praschag, Peter; Fritz, Uwe

2018-06-01

Chinese softshell turtles ( Pelodiscus spp.) are widely distributed, ranging from the Amur and Ussuri Rivers in the Russian Far East through the Korean Peninsula, Japan, and eastern, central, and southern China to southern Vietnam. In East and Southeast Asia, Chinese softshell turtles are traditionally exploited for food and have been farm-bred in China since the Spring and Autumn Period, more than 2400 years ago. Currently, the annual production of Pelodiscus amounts to 340,000 t in China alone. Using mitochondrial DNA (2428 bp) and five nuclear loci (3704 bp), we examined broad sampling of wild and farm-bred Pelodiscus to infer genetic and taxonomic differentiation. We discovered four previously unknown mitochondrial lineages, all from China. One lineage from Jiangxi is deeply divergent and sister to the mitochondrial lineage of Pelodiscus axenaria. The nuclear loci supported species status for P. axenaria and the new lineage from Jiangxi. Pelodiscus maackii and P. parviformis, both harboring distinct mitochondrial lineages, were not differentiated from P. sinensis in the studied nuclear markers. The same is true for two new mitochondrial lineages from Zhejiang, China, represented by only one individual each, and another new lineage from Anhui, Guangdong, Jiangxi and Zhejiang, China. However, Vietnamese turtles yielding a mitochondrial lineage clustering within P. sinensis were distinct in nuclear markers, suggesting that these populations could represent another unknown species with introgressed mitochondria. Its species status is also supported by the syntopic occurrence with P. sinensis in northern Vietnam and by morphology. In addition, we confirmed sympatry of P. axenaria and P. parviformis in Guangxi, China, and found evidence for sympatry of P. sinensis and the new putative species from Jiangxi, China. We also discovered evidence for hybridization in turtle farms and for the occurrence of alien lineages in the wild (Zhejiang, China), highlighting the risk of genetic pollution of native stock. In the face of the large-scale breeding of Pelodiscus, we claim that the long-term survival of distinct genetic lineages and species can only be assured when an upscale market segment for pure-bred softshell turtles is established, making the breeding of pure lineages lucrative for turtle farms. Our findings underline that the diversity of Pelodiscus is currently underestimated and threatened by anthropogenic admixture. We recommend mass screening of genetic and morphological variation of Chinese softshell turtles as a first step to understand and preserve their diversity.

The ASAS-SN Bright Supernova Catalog – II. 2015

DOE PAGES

Holoien, T. W. -S.; Brown, J. S.; Stanek, K. Z.; ...

2017-01-16

Here, this paper presents information for all supernovae discovered by the All-Sky Automated Survey for SuperNovae (ASAS-SN) during 2015, its second full year of operations. The same information is presented for bright (mV ≤ 17), spectroscopically confirmed supernovae discovered by other sources in 2015. As with the first ASAS-SN bright supernova catalogue, we also present redshifts and near-ultraviolet through infrared magnitudes for all supernova host galaxies in both samples. Combined with our previous catalogue, this work comprises a complete catalogue of 455 supernovae from multiple professional and amateur sources, allowing for population studies that were previously impossible. This is themore » second of a series of yearly papers on bright supernovae and their hosts from the ASAS-SN team.« less

The ASAS-SN Bright Supernova Catalog – II. 2015

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holoien, T. W. -S.; Brown, J. S.; Stanek, K. Z.

Here, this paper presents information for all supernovae discovered by the All-Sky Automated Survey for SuperNovae (ASAS-SN) during 2015, its second full year of operations. The same information is presented for bright (mV ≤ 17), spectroscopically confirmed supernovae discovered by other sources in 2015. As with the first ASAS-SN bright supernova catalogue, we also present redshifts and near-ultraviolet through infrared magnitudes for all supernova host galaxies in both samples. Combined with our previous catalogue, this work comprises a complete catalogue of 455 supernovae from multiple professional and amateur sources, allowing for population studies that were previously impossible. This is themore » second of a series of yearly papers on bright supernovae and their hosts from the ASAS-SN team.« less

Opportunistic pathology-based screening for diabetes

PubMed Central

Simpson, Aaron J; Krowka, Renata; Kerrigan, Jennifer L; Southcott, Emma K; Wilson, J Dennis; Potter, Julia M; Nolan, Christopher J; Hickman, Peter E

2013-01-01

Objective To determine the potential of opportunistic glycated haemoglobin (HbA1c) testing of pathology samples to detect previously unknown diabetes. Design Pathology samples from participants collected for other reasons and suitable for HbA1c testing were utilised for opportunistic diabetes screening. HbA1c was measured with a Biorad Variant II turbo analyser and HbA1c levels of ≥6.5% (48 mmol/mol) were considered diagnostic for diabetes. Confirmation of previously unknown diabetes status was obtained by a review of hospital medical records and phone calls to general practitioners. Setting Hospital pathology laboratory receiving samples from hospital-based and community-based (CB) settings. Participants Participants were identified based on the blood sample collection location in the CB, emergency department (ED) and inpatient (IP) groups. Exclusions pretesting were made based on the electronic patient history of: age <18 years, previous diabetes diagnosis, query for diabetes status in the past 12 months, evidence of pregnancy and sample collected postsurgery or transfusion. Only one sample per individual participant was tested. Results Of the 22 396 blood samples collected, 4505 (1142 CB, 1113 ED, 2250 IP) were tested of which 327 (7.3%) had HbA1c levels ≥6.5% (48 mmol/mol). Of these 120 (2.7%) were determined to have previously unknown diabetes (11 (1%) CB, 21 (1.9%) ED, 88 (3.9%) IP). The prevalence of previously unknown diabetes was substantially higher (5.4%) in hospital-based (ED and IP) participants aged over 54 years. Conclusions Opportunistic testing of referred pathology samples can be an effective method of screening for diabetes, especially in hospital-based and older persons. PMID:24065696

The ASAS-SN bright supernova catalogue - III. 2016

NASA Astrophysics Data System (ADS)

Holoien, T. W.-S.; Brown, J. S.; Stanek, K. Z.; Kochanek, C. S.; Shappee, B. J.; Prieto, J. L.; Dong, Subo; Brimacombe, J.; Bishop, D. W.; Bose, S.; Beacom, J. F.; Bersier, D.; Chen, Ping; Chomiuk, L.; Falco, E.; Godoy-Rivera, D.; Morrell, N.; Pojmanski, G.; Shields, J. V.; Strader, J.; Stritzinger, M. D.; Thompson, Todd A.; Woźniak, P. R.; Bock, G.; Cacella, P.; Conseil, E.; Cruz, I.; Fernandez, J. M.; Kiyota, S.; Koff, R. A.; Krannich, G.; Marples, P.; Masi, G.; Monard, L. A. G.; Nicholls, B.; Nicolas, J.; Post, R. S.; Stone, G.; Wiethoff, W. S.

2017-11-01

This catalogue summarizes information for all supernovae discovered by the All-Sky Automated Survey for SuperNovae (ASAS-SN) and all other bright (mpeak ≤ 17), spectroscopically confirmed supernovae discovered in 2016. We then gather the near-infrared through ultraviolet magnitudes of all host galaxies and the offsets of the supernovae from the centres of their hosts from public data bases. We illustrate the results using a sample that now totals 668 supernovae discovered since 2014 May 1, including the supernovae from our previous catalogues, with type distributions closely matching those of the ideal magnitude limited sample from Li et al. This is the third of a series of yearly papers on bright supernovae and their hosts from the ASAS-SN team.

Tick-Borne Pathogen – Reversed and Conventional Discovery of Disease

PubMed Central

Tijsse-Klasen, Ellen; Koopmans, Marion P. G.; Sprong, Hein

2014-01-01

Molecular methods have increased the number of known microorganisms associated with ticks significantly. Some of these newly identified microorganisms are readily linked to human disease while others are yet unknown to cause human disease. The face of tick-borne disease discovery has changed with more diseases now being discovered in a “reversed way,” detecting disease cases only years after the tick-borne microorganism was first discovered. Compared to the conventional discovery of infectious diseases, reverse order discovery presents researchers with new challenges. Estimating public health risks of such agents is especially challenging, as case definitions and diagnostic procedures may initially be missing. We discuss the advantages and shortcomings of molecular methods, serology, and epidemiological studies that might be used to study some fundamental questions regarding newly identified tick-borne diseases. With increased tick-exposure and improved detection methods, more tick-borne microorganisms will be added to the list of pathogens causing disease in humans in the future. PMID:25072045

Spirochaetemia in a HIV positive patient.

PubMed

Okwori, E E

2006-01-01

Borreliosis, caused by Borrelia recurrentis and several other Borrelia species is not a commonly reported case in our environment, but the search for the cause of recurrent pyrexia in this patient made it possible to discover the spirochete as the cause of the disease. A 38 year old married HIV positive woman presented with recurrent fever in a private clinic. Six thin smears were made out of the patient serum and dried in the air. Three slides each were stained with 0.12% Leishman and 20% Giemsa stains and examined under the light microscope. Three of the Giemsa slides were positive for spirochetes (4-5 spirals), which were constituents with Borrelia species. The patient responded very well to tetracycline and serum became negative for the organism after ten days of treatment. Borrelia was discovered to be the cause of the recurrent pyrexia in this patient who responded very well to tetracycline. Borrelia should be looked for in cases of pyrexia of unknown origin

Prioritization of Disease Susceptibility Genes Using LSM/SVD.

PubMed

Gong, Lejun; Yang, Ronggen; Yan, Qin; Sun, Xiao

2013-12-01

Understanding the role of genetics in diseases is one of the most important tasks in the postgenome era. It is generally too expensive and time consuming to perform experimental validation for all candidate genes related to disease. Computational methods play important roles for prioritizing these candidates. Herein, we propose an approach to prioritize disease genes using latent semantic mapping based on singular value decomposition. Our hypothesis is that similar functional genes are likely to cause similar diseases. Measuring the functional similarity between known disease susceptibility genes and unknown genes is to predict new disease susceptibility genes. Taking autism as an instance, the analysis results of the top ten genes prioritized demonstrate they might be autism susceptibility genes, which also indicates our approach could discover new disease susceptibility genes. The novel approach of disease gene prioritization could discover new disease susceptibility genes, and latent disease-gene relations. The prioritized results could also support the interpretive diversity and experimental views as computational evidence for disease researchers.

A starry message from the Starry Messenger

NASA Astrophysics Data System (ADS)

Francis, Michael

2011-05-01

To many the Universe is a closed book of secrets never to be read. Four hundred years ago, an unknown court mathematician in Italy opened that book and laid the foundation for modern science. Galileo Galilei turned his telescope to the heavens to discover mountains and craters on the moon, four moons of Jupiter, and countless stars never before seen. Even more significant was his method of observation and mathematical analysis. He taught future scientists the way to discover the laws of nature. In this session the professor will return to discuss some of his most recent discoveries. Using the gifts of a storyteller and actively involving the audience, Galileo will take his audience through discoveries that changed the very nature of science. First person living history programs have become a staple of informal educational institutions like museums, planetariums and libraries as well as scholastic settings. We will be examining how to use this theatrical technique to educate, entertain and bring Astronomy to life.

The history of Toxoplasma gondii--the first 100 years.

PubMed

Dubey, Jitender P

2008-01-01

In this paper the history of Toxoplasma gondii and toxoplasmosis is reviewed. This protozoan parasite was first discovered in 1908 and named a year later. Its medical importance remained unknown until 1939 when T. gondii was identified in tissues of a congenitally infected infant, and veterinary importance became known when it was found to cause abortion storms in sheep in 1957. The discovery of a T. gondii specific antibody test, Sabin-Feldman dye test in 1948 led to the recognition that T. gondii is a common parasite of warm-blooded hosts with a worldwide distribution. Its life cycle was not discovered until 1970 when it was found that felids are its definitive host and an environmentally resistant stage (oocyst) is excreted in feces of infected cats. The recent discovery of its common infection in certain marine wildlife (sea otters) indicates contamination of our seas with T. gondii oocysts washed from land. Hygiene remains the best preventive measure because currently there is no vaccine to prevent toxoplasmosis in humans.

Circular RNA biogenesis can proceed through an exon-containing lariat precursor

PubMed Central

Barrett, Steven P; Wang, Peter L; Salzman, Julia

2015-01-01

Pervasive expression of circular RNA is a recently discovered feature of eukaryotic gene expression programs, yet its function remains largely unknown. The presumed biogenesis of these RNAs involves a non-canonical ‘backsplicing’ event. Recent studies in mammalian cell culture posit that backsplicing is facilitated by inverted repeats flanking the circularized exon(s). Although such sequence elements are common in mammals, they are rare in lower eukaryotes, making current models insufficient to describe circularization. Through systematic splice site mutagenesis and the identification of splicing intermediates, we show that circular RNA in Schizosaccharomyces pombe is generated through an exon-containing lariat precursor. Furthermore, we have performed high-throughput and comprehensive mutagenesis of a circle-forming exon, which enabled us to discover a systematic effect of exon length on RNA circularization. Our results uncover a mechanism for circular RNA biogenesis that may account for circularization in genes that lack noticeable flanking intronic secondary structure. DOI: http://dx.doi.org/10.7554/eLife.07540.001 PMID:26057830

The first sexual associations in the genus Darditilla Casal, 1965 (Hymenoptera, Mutillidae)

PubMed Central

Luz, David R.; Williams, Kevin A.

2014-01-01

Abstract New sex associations are proposed for four species of Darditilla: Darditilla amabilis (Gerstaecker, 1874); Darditilla bejaranoi Casal, 1968; Darditilla debilis (Gerstaecker, 1874); and Darditilla felina (Burmeister, 1854). Darditilla botija Casal, 1965, syn. n. is the male of Darditilla amabilis; the other three males were previously unknown. Mutilla decorosa Kohl, 1882, syn. n. is conspecific with Darditilla felina. Descriptions and extended diagnoses are provided for previously unknown males and for females that were not adequately described. These represent the first sex associations for the genus Darditilla. PMID:25493066

The Eugen Seibold coral mounds offshore western Morocco: oceanographic and bathymetric steering of a newly discovered cold-water coral province

NASA Astrophysics Data System (ADS)

Glogowski, Silke; Dullo, Christian; Flögel, Sascha; Feldens, Peter; Hühnerbach, Veit; von Reumont, Jonas; Krastel, Sebastian; Wynn, Russ B.; Liebetrau, Volker

2015-04-01

This study presents new seafloor bathymetric and sidescan sonar data identifying a previously unknown cold-water coral (CWC) province on the Atlantic margin off western Morocco (ca. 31° N). Applying the concept of seawater density as a predictive tool for living CWC reef occurrence during research cruise 32 aboard RV Maria S. Merian in October 2013 CTD casts revealed potential sites. Direct sampling retrieved living coral patches within an extensive field of carbonate mounds, covering an area of ~410 km2 on the upper slope ~40 nautical miles north of Agadir Canyon. Individual mounds are up to 12 m high and are mainly composed of dead cold-water corals Lophelia pertusa thickets at present-day water depths of 678-863 m. Living CWCs represent only a thin veneer and were sampled by box coring in the shallower parts of the mound field between 678 and 719 m. CTD measurements in these shallower areas revealed that the occurrence of these living CWC reefs coincides with the deeper part of the North Atlantic Central Water (NACW) mass exhibiting conservative temperatures Φ of 9.78-9.94° C, absolute salinity SA of 35.632 g/kg, and a sea water density σΦ of 27.31-27.33 kg/m3). This is in good agreement with observations from the Renard Ridge (35° N, Gulf of Cadiz) to the north and sites off Mauretania (17° N-18° N) to the south, 'with the exception of sparse live corals in the latter region, the CWC reefs of both regions consist of a dead fabric in the deeper layer of the NACW slightly above the Mediterranean Outflow Water. The bathymetric and oceanographic settings of this newly discovered CWC site, with its thin veneer of living corals and much larger accumulations of coral rubble, are consistent with published evidence that, over the past three glacial-interglacial cycles, active CWC reef growth south of 50° N was more favourable during glacial times (possibly up to the very early Holocene) in this sector of the northeast Atlantic Ocean. The newly discovered province is here named the Eugen Seibold coral mounds in honour of the pioneering marine geologist Eugen Seibold (1918-2013).

Molecular breakdown: a comprehensive view of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer.

PubMed

Noh, Ka-Won; Lee, Mi-Sook; Lee, Seung Eun; Song, Ji-Young; Shin, Hyun-Tae; Kim, Yu Jin; Oh, Doo Yi; Jung, Kyungsoo; Sung, Minjung; Kim, Mingi; An, Sungbin; Han, Joungho; Shim, Young Mog; Zo, Jae Ill; Kim, Jhingook; Park, Woong-Yang; Lee, Se-Hoon; Choi, Yoon-La

2017-11-01

Most anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancers (NSCLCs) show good clinical response to ALK inhibitors. However, some ALK-rearranged NSCLC patients show various primary responses with unknown reasons. Previous studies focused on the clinical aspects of ALK fusions in small cohorts, or were conducted in vitro and/or in vivo to investigate the function of ALK. One of the suggested theories describes how echinoderm microtubule-associated protein-like 4 (EML4)-ALK variants play a role towards different sensitivities in ALK inhibitors. Until now, there has been no integrated comprehensive study that dissects ALK at the molecular level in a large scale. Here, we report the largest extensive molecular analysis of 158 ALK-rearranged NSCLCs and have investigated these findings in a cell line construct experiment. We discovered that NSCLCs with EML4-ALK short forms (variant 3/others) had more advanced stage and frequent metastases than cases with the long forms (variant 1/others) (p = 0.057, p < 0.05). In vitro experiments revealed that EML4-ALK short forms show lower sensitivity to ALK inhibitors than do long forms. Clinical analysis also showed a trend for the short forms showing worse PFS. Interestingly, we found that breakpoints of ALK are evenly distributed mainly in intron 19 and almost all of them undergo a non-homologous end-joining repair to generate ALK fusions. We also discovered four novel somatic ALK mutations in NSCLC (T1151R, R1192P, A1280V, and L1535Q) that confer primary resistance; all of them showed strong resistance to ALK inhibitors, as G1202R does. Through targeted deep sequencing, we discovered three novel ALK fusion partners (GCC2, LMO7, and PHACTR1), and different ALK fusion partners showed different intracellular localization. With our findings that the EML4-ALK variants, new ALK somatic mutations, and novel ALK-fusion partners may affect sensitivity to ALK inhibitors, we stress the importance of targeted therapy to take the ALK molecular profiling into consideration. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Bioprospecting Finds the Toughest Biological Material: Extraordinary Silk from a Giant Riverine Orb Spider

PubMed Central

Agnarsson, Ingi; Kuntner, Matjaž; Blackledge, Todd A.

2010-01-01

Background Combining high strength and elasticity, spider silks are exceptionally tough, i.e., able to absorb massive kinetic energy before breaking. Spider silk is therefore a model polymer for development of high performance biomimetic fibers. There are over 41.000 described species of spiders, most spinning multiple types of silk. Thus we have available some 200.000+ unique silks that may cover an amazing breadth of material properties. To date, however, silks from only a few tens of species have been characterized, most chosen haphazardly as model organisms (Nephila) or simply from researchers' backyards. Are we limited to ‘blindly fishing’ in efforts to discover extraordinary silks? Or, could scientists use ecology to predict which species are likely to spin silks exhibiting exceptional performance properties? Methodology We examined the biomechanical properties of silk produced by the remarkable Malagasy ‘Darwin's bark spider’ (Caerostris darwini), which we predicted would produce exceptional silk based upon its amazing web. The spider constructs its giant orb web (up to 2.8 m2) suspended above streams, rivers, and lakes. It attaches the web to substrates on each riverbank by anchor threads as long as 25 meters. Dragline silk from both Caerostris webs and forcibly pulled silk, exhibits an extraordinary combination of high tensile strength and elasticity previously unknown for spider silk. The toughness of forcibly silked fibers averages 350 MJ/m3, with some samples reaching 520 MJ/m3. Thus, C. darwini silk is more than twice tougher than any previously described silk, and over 10 times better than Kevlar®. Caerostris capture spiral silk is similarly exceptionally tough. Conclusions Caerostris darwini produces the toughest known biomaterial. We hypothesize that this extraordinary toughness coevolved with the unusual ecology and web architecture of these spiders, decreasing the likelihood of bridgelines breaking and collapsing the web into the river. This hypothesis predicts that rapid change in material properties of silk co-occurred with ecological shifts within the genus, and can thus be tested by combining material science, behavioral observations, and phylogenetics. Our findings highlight the potential benefits of natural history–informed bioprospecting to discover silks, as well as other materials, with novel and exceptional properties to serve as models in biomimicry. PMID:20856804

Occurrence of 1-glyceryl-1-myo-inosityl phosphate in hyperthermophiles.

PubMed

Lamosa, Pedro; Gonçalves, Luís G; Rodrigues, Marta V; Martins, Lígia O; Raven, Neil D H; Santos, Helena

2006-09-01

The accumulation of compatible solutes was studied in the hyperthermophilic bacterium Aquifex pyrophilus as a function of the temperature and the NaCl concentration of the growth medium. Nuclear magnetic resonance analysis of cell extracts revealed the presence of alpha- and beta-glutamate, di-mannosyl-di-myo-inositol phosphate, di-myo-inositol phosphate, and an additional compound here identified as 1-glyceryl-1-myo-inosityl phosphate. All solutes accumulated by A. pyrophilus are negatively charged at physiological pH. The intracellular levels of di-myo-inositol phosphate increased in response to supraoptimal growth temperature, while alpha- and beta-glutamate accumulated in response to osmotic stress, especially at growth temperatures below the optimum. The newly discovered compound, 1-glyceryl-1-myo-inosityl phosphate, appears to play a double role in osmo- and thermoprotection, since its intracellular pool increased primarily in response to a combination of osmotic and heat stresses. This work also uncovered the nature of the unknown compound, previously detected in Archaeoglobus fulgidus (L. O. Martins et al., Appl. Environ. Microbiol. 63:896-902, 1997). The curious structural relationship between diglycerol phosphate (found only in Archaeoglobus species), di-myo-inositol phosphate (a canonical solute of hyperthermophiles), and the newly identified solute is highlighted. This is the first report on the occurrence of 1-glyceryl-1-myo-inosityl phosphate in living systems.

Using pseudoalignment and base quality to accurately quantify microbial community composition

PubMed Central

Novembre, John

2018-01-01

Pooled DNA from multiple unknown organisms arises in a variety of contexts, for example microbial samples from ecological or human health research. Determining the composition of pooled samples can be difficult, especially at the scale of modern sequencing data and reference databases. Here we propose a novel method for taxonomic profiling in pooled DNA that combines the speed and low-memory requirements of k-mer based pseudoalignment with a likelihood framework that uses base quality information to better resolve multiply mapped reads. We apply the method to the problem of classifying 16S rRNA reads using a reference database of known organisms, a common challenge in microbiome research. Using simulations, we show the method is accurate across a variety of read lengths, with different length reference sequences, at different sample depths, and when samples contain reads originating from organisms absent from the reference. We also assess performance in real 16S data, where we reanalyze previous genetic association data to show our method discovers a larger number of quantitative trait associations than other widely used methods. We implement our method in the software Karp, for k-mer based analysis of read pools, to provide a novel combination of speed and accuracy that is uniquely suited for enhancing discoveries in microbial studies. PMID:29659582

Hamburger polyomaviruses

PubMed Central

Peretti, Alberto; FitzGerald, Peter C.; Bliskovsky, Valery

2015-01-01

Epidemiological studies have suggested that consumption of beef may correlate with an increased risk of colorectal cancer. One hypothesis to explain this proposed link might be the presence of a carcinogenic infectious agent capable of withstanding cooking. Polyomaviruses are a ubiquitous family of thermostable non-enveloped DNA viruses that are known to be carcinogenic. Using virion enrichment, rolling circle amplification (RCA) and next-generation sequencing, we searched for polyomaviruses in meat samples purchased from several supermarkets. Ground beef samples were found to contain three polyomavirus species. One species, bovine polyomavirus 1 (BoPyV1), was originally discovered as a contaminant in laboratory FCS. A previously unknown species, BoPyV2, occupies the same clade as human Merkel cell polyomavirus and raccoon polyomavirus, both of which are carcinogenic in their native hosts. A third species, BoPyV3, is related to human polyomaviruses 6 and 7. Examples of additional DNA virus families, including herpesviruses, adenoviruses, circoviruses and gyroviruses were also detected either in ground beef samples or in comparison samples of ground pork and ground chicken. The results suggest that the virion enrichment/RCA approach is suitable for random detection of essentially any DNA virus with a detergent-stable capsid. It will be important for future studies to address the possibility that animal viruses commonly found in food might be associated with disease. PMID:25568187

Fine-mapping of lipid regions in global populations discovers ethnic-specific signals and refines previously identified lipid loci.

PubMed

Zubair, Niha; Graff, Mariaelisa; Luis Ambite, Jose; Bush, William S; Kichaev, Gleb; Lu, Yingchang; Manichaikul, Ani; Sheu, Wayne H-H; Absher, Devin; Assimes, Themistocles L; Bielinski, Suzette J; Bottinger, Erwin P; Buzkova, Petra; Chuang, Lee-Ming; Chung, Ren-Hua; Cochran, Barbara; Dumitrescu, Logan; Gottesman, Omri; Haessler, Jeffrey W; Haiman, Christopher; Heiss, Gerardo; Hsiung, Chao A; Hung, Yi-Jen; Hwu, Chii-Min; Juang, Jyh-Ming J; Le Marchand, Loic; Lee, I-Te; Lee, Wen-Jane; Lin, Li-An; Lin, Danyu; Lin, Shih-Yi; Mackey, Rachel H; Martin, Lisa W; Pasaniuc, Bogdan; Peters, Ulrike; Predazzi, Irene; Quertermous, Thomas; Reiner, Alex P; Robinson, Jennifer; Rotter, Jerome I; Ryckman, Kelli K; Schreiner, Pamela J; Stahl, Eli; Tao, Ran; Tsai, Michael Y; Waite, Lindsay L; Wang, Tzung-Dau; Buyske, Steven; Ida Chen, Yii-Der; Cheng, Iona; Crawford, Dana C; Loos, Ruth J F; Rich, Stephen S; Fornage, Myriam; North, Kari E; Kooperberg, Charles; Carty, Cara L

2016-12-15

Genome-wide association studies have identified over 150 loci associated with lipid traits, however, no large-scale studies exist for Hispanics and other minority populations. Additionally, the genetic architecture of lipid-influencing loci remains largely unknown. We performed one of the most racially/ethnically diverse fine-mapping genetic studies of HDL-C, LDL-C, and triglycerides to-date using SNPs on the MetaboChip array on 54,119 individuals: 21,304 African Americans, 19,829 Hispanic Americans, 12,456 Asians, and 530 American Indians. The majority of signals found in these groups generalize to European Americans. While we uncovered signals unique to racial/ethnic populations, we also observed systematically consistent lipid associations across these groups. In African Americans, we identified three novel signals associated with HDL-C (LPL, APOA5, LCAT) and two associated with LDL-C (ABCG8, DHODH). In addition, using this population, we refined the location for 16 out of the 58 known MetaboChip lipid loci. These results can guide tailored screening efforts, reveal population-specific responses to lipid-lowering medications, and aid in the development of new targeted drug therapies. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Differential depth distribution of microbial function and putative symbionts through sediment-hosted aquifers in the deep terrestrial subsurface

DOE Office of Scientific and Technical Information (OSTI.GOV)

Probst, Alexander J.; Ladd, Bethany; Jarett, Jessica K.

An enormous diversity of previously unknown bacteria and archaea has been discovered recently, yet their functional capacities and distributions in the terrestrial subsurface remain uncertain. Here, we continually sampled a CO 2-driven geyser (Colorado Plateau, Utah, USA) over its 5-day eruption cycle to test the hypothesis that stratified, sandstone-hosted aquifers sampled over three phases of the eruption cycle have microbial communities that differ both in membership and function. Genome-resolved metagenomics, single-cell genomics and geochemical analyses confirmed this hypothesis and linked microorganisms to groundwater compositions from different depths. Autotrophic Candidatus “Altiarchaeum sp.” and phylogenetically deep-branching nanoarchaea dominate the deepest groundwater. Amore » nanoarchaeon with limited metabolic capacity is inferred to be a potential symbiont of the Ca. “Altiarchaeum”. Candidate Phyla Radiation bacteria are also present in the deepest groundwater and they are relatively abundant in water from intermediate depths. During the recovery phase of the geyser, microaerophilic Fe- and S-oxidizers have high in situ genome replication rates. Autotrophic Sulfurimonas sustained by aerobic sulfide oxidation and with the capacity for N 2 fixation dominate the shallow aquifer. Overall, 104 different phylum-level lineages are present in water from these subsurface environments, with uncultivated archaea and bacteria partitioned to the deeper subsurface.« less

Using model-based screening to help discover unknown environmental contaminants.

PubMed

McLachlan, Michael S; Kierkegaard, Amelie; Radke, Michael; Sobek, Anna; Malmvärn, Anna; Alsberg, Tomas; Arnot, Jon A; Brown, Trevor N; Wania, Frank; Breivik, Knut; Xu, Shihe

2014-07-01

Of the tens of thousands of chemicals in use, only a small fraction have been analyzed in environmental samples. To effectively identify environmental contaminants, methods to prioritize chemicals for analytical method development are required. We used a high-throughput model of chemical emissions, fate, and bioaccumulation to identify chemicals likely to have high concentrations in specific environmental media, and we prioritized these for target analysis. This model-based screening was applied to 215 organosilicon chemicals culled from industrial chemical production statistics. The model-based screening prioritized several recognized organosilicon contaminants and generated hypotheses leading to the selection of three chemicals that have not previously been identified as potential environmental contaminants for target analysis. Trace analytical methods were developed, and the chemicals were analyzed in air, sewage sludge, and sediment. All three substances were found to be environmental contaminants. Phenyl-tris(trimethylsiloxy)silane was present in all samples analyzed, with concentrations of ∼50 pg m(-3) in Stockholm air and ∼0.5 ng g(-1) dw in sediment from the Stockholm archipelago. Tris(trifluoropropyl)trimethyl-cyclotrisiloxane and tetrakis(trifluoropropyl)tetramethyl-cyclotetrasiloxane were found in sediments from Lake Mjøsa at ∼1 ng g(-1) dw. The discovery of three novel environmental contaminants shows that models can be useful for prioritizing chemicals for exploratory assessment.

Triclosan is a Mitochondrial Uncoupler in Live Zebrafish

PubMed Central

Shim, Juyoung; Weatherly, Lisa M.; Luc, Richard H.; Dorman, Maxwell T.; Neilson, Andy; Ng, Ryan; Kim, Carol H.; Millard, Paul J.; Gosse, Julie A.

2016-01-01

Triclosan (TCS) is a synthetic antimicrobial agent used in many consumer goods at millimolar concentrations. As a result of exposure, TCS has been detected widely in humans. We have recently discovered that TCS is a proton ionophore mitochondrial uncoupler in multiple types of living cells. Here we present novel data indicating that TCS is also a mitochondrial uncoupler in a living organism: 24 hour post fertilization zebrafish embryos. These experiments were conducted using a Seahorse Bioscience XFe 96 Extracellular Flux Analyzer modified for bidirectional temperature control, using the XF96 spheroid plate to position and measure one zebrafish embryo per well. Using this method, following acute exposure to TCS, basal oxygen consumption rate (OCR) increases, without a decrease in survival or heartbeat rate. TCS also decreases ATP-linked respiration and spare respiratory capacity and increases proton leak: all indicators of mitochondrial uncoupling. Our data indicate, that TCS is a mitochondrial uncoupler in vivo, which should be taken into consideration when assessing the toxicity and/or pharmaceutical uses of TCS. This is the first example of usage of a Seahorse Extracellular Flux Analyzer to measure bioenergetic flux of a single zebrafish embryo per well in a 96 well assay format. The method developed in this study provides a high-throughput tool to identify previously-unknown mitochondrial uncouplers in a living organism. PMID:27111768

Finding topological center of a geographic space via road network

NASA Astrophysics Data System (ADS)

Gao, Liang; Miao, Yanan; Qin, Yuhao; Zhao, Xiaomei; Gao, Zi-You

2015-02-01

Previous studies show that the center of a geographic space is of great importance in urban and regional studies, including study of population distribution, urban growth modeling, and scaling properties of urban systems, etc. But how to well define and how to efficiently extract the center of a geographic space are still largely unknown. Recently, Jiang et al. have presented a definition of topological center by their block detection (BD) algorithm. Despite the fact that they first introduced the definition and discovered the 'true center', in human minds, their algorithm left several redundancies in its traversal process. Here, we propose an alternative road-cycle detection (RCD) algorithm to find the topological center, which extracts the outmost road-cycle recursively. To foster the application of the topological center in related research fields, we first reproduce the BD algorithm in Python (pyBD), then implement the RCD algorithm in two ways: the ArcPy implementation (arcRCD) and the Python implementation (pyRCD). After the experiments on twenty-four typical road networks, we find that the results of our RCD algorithm are consistent with those of Jiang's BD algorithm. We also find that the RCD algorithm is at least seven times more efficient than the BD algorithm on all the ten typical road networks.

Böttger stoneware from North America and Europe; are they authentic

NASA Astrophysics Data System (ADS)

Swann, Charles P.; Nelson, Christina H.

2000-03-01

In the early 18th century, Johann Friedrich Böttger, an alchemist recently arrived in Dresden, was assigned to ceramic experimentation under the orders of Augustus the Strong, Elector of Saxony and King of Poland. The Elector and his advisors hoped to discover the secret of making hard paste porcelain like the wares imported into Europe from China and Japan. In 1706-1707, Böttger produced his first ceramic body, a red stoneware similar to the wares produced in Yixing, China. The first objects were made following the forms of chinese prototypes or European metalwork of the period. Recently, the authenticity of a number of `Böttger' objects in various museums and private collections in North America and Europe has been questioned. To aide in resolving these questions several non-destructive analytical techniques have been employed, the most important being PIXE. This report is on an initial study of 25 objects with 16 elements from Al to Zr and Pb being analysed. The results strongly suggest three different groupings, one of objects from the Meissen factory during the 20th century, one from the work of Böttger himself early in the 18th century and one from an as yet unknown time period and site. The first two groups were previously identified by one of the authors (C.N.).

Discovering the Unknown: Improving Detection of Novel Species and Genera from Short Reads

DOE PAGES

Rosen, Gail L.; Polikar, Robi; Caseiro, Diamantino A.; ...

2011-01-01

High-throughput sequencing technologies enable metagenome profiling, simultaneous sequencing of multiple microbial species present within an environmental sample. Since metagenomic data includes sequence fragments (“reads”) from organisms that are absent from any database, new algorithms must be developed for the identification and annotation of novel sequence fragments. Homology-based techniques have been modified to detect novel species and genera, but, composition-based methods, have not been adapted. We develop a detection technique that can discriminate between “known” and “unknown” taxa, which can be used with composition-based methods, as well as a hybrid method. Unlike previous studies, we rigorously evaluate all algorithms for theirmore » ability to detect novel taxa. First, we show that the integration of a detector with a composition-based method performs significantly better than homology-based methods for the detection of novel species and genera, with best performance at finer taxonomic resolutions. Most importantly, we evaluate all the algorithms by introducing an “unknown” class and show that the modified version of PhymmBL has similar or better overall classification performance than the other modified algorithms, especially for the species-level and ultrashort reads. Finally, we evaluate theperformance of several algorithms on a real acid mine drainage dataset.« less

New glycyl radical enzymes catalysing key metabolic steps in anaerobic bacteria.

PubMed

Selmer, Thorsten; Pierik, Antonio J; Heider, Johann

2005-10-01

During the last decade, an increasing number of new enzymes containing glycyl radicals in their active sites have been identified and biochemically characterised. These include benzylsuccinate synthase (Bss), 4-hydroxyphenylacetate decarboxylase (Hpd) and the coenzyme B12-independent glycerol dehydratase (Gdh). These are involved in metabolic pathways as different as anaerobic toluene metabolism, fermentative production of p-cresol and glycerol fermentation. Some features of these newly discovered enzymes are described and compared with those of the previously known glycyl radical enzymes pyruvate formate-lyase (Pfl) and anaerobic ribonucleotide reductase (Nrd). Among the new enzymes, Bss and Hpd share the presence of small subunits, the function of which in the catalytic mechanisms is still enigmatic, and both enzymes contain metal centres in addition to the glycyl radical prosthetic group. The activating enzymes of the novel systems also deviate from the standard type, containing at least one additional Fe-S cluster. Finally, the available whole-genome sequences of an increasing number of strictly or facultative anaerobic bacteria revealed the presence of many more hitherto unknown glycyl radical enzyme (GRE) systems. Recent studies suggest that the particular types of these enzymes represent the ends of different evolutionary lines, which emerged early in evolution and diversified to yield remarkably versatile biocatalysts for chemical reactions that are otherwise difficult to perform in anoxic environments.

Post-translational modification and stability of low molecular weight cyclin E.

PubMed

Mull, B B; Cox, J; Bui, T; Keyomarsi, K

2009-09-03

Our laboratory has previously described the presence of five tumor-specific low molecular weight isoforms of cyclin E in both tumor cell lines and breast cancer patient biopsies. We have also shown that one of these low forms arises from an alternate start site, whereas the other four appear as two sets of doublets following cleavage through an elastase-like enzyme. However, the origin of both sets of doublets was unknown. Here, we demonstrate that the larger isoform of each doublet is the result of phosphorylation at a key degradation site. Through site-directed mutagenesis of different phosphorylation sites within the cyclin E protein, we discovered that phosphorylation of threonine 395 is responsible for generating the larger isoform of each doublet. Because phosphorylation of threonine 395 has been linked to the proteasome-mediated degradation of full length cyclin E, we examined the stability of T395A phospho-mutants in both non-tumorigenic mammary epithelial cells and tumor cells. The results revealed that the low molecular weight isoforms appear to be stable in both a tumor cell line and a non-tumor forming cell line regardless of the presence of this critical phosphorylation site. The stability of low molecular weight cyclin E may have implications for both tumorigenesis and treatment of tumors expressing them.

Data depth based clustering analysis

DOE PAGES

Jeong, Myeong -Hun; Cai, Yaping; Sullivan, Clair J.; ...

2016-01-01

Here, this paper proposes a new algorithm for identifying patterns within data, based on data depth. Such a clustering analysis has an enormous potential to discover previously unknown insights from existing data sets. Many clustering algorithms already exist for this purpose. However, most algorithms are not affine invariant. Therefore, they must operate with different parameters after the data sets are rotated, scaled, or translated. Further, most clustering algorithms, based on Euclidean distance, can be sensitive to noises because they have no global perspective. Parameter selection also significantly affects the clustering results of each algorithm. Unlike many existing clustering algorithms, themore » proposed algorithm, called data depth based clustering analysis (DBCA), is able to detect coherent clusters after the data sets are affine transformed without changing a parameter. It is also robust to noises because using data depth can measure centrality and outlyingness of the underlying data. Further, it can generate relatively stable clusters by varying the parameter. The experimental comparison with the leading state-of-the-art alternatives demonstrates that the proposed algorithm outperforms DBSCAN and HDBSCAN in terms of affine invariance, and exceeds or matches the ro-bustness to noises of DBSCAN or HDBSCAN. The robust-ness to parameter selection is also demonstrated through the case study of clustering twitter data.« less

Reverse engineering a mouse embryonic stem cell-specific transcriptional network reveals a new modulator of neuronal differentiation.

PubMed

De Cegli, Rossella; Iacobacci, Simona; Flore, Gemma; Gambardella, Gennaro; Mao, Lei; Cutillo, Luisa; Lauria, Mario; Klose, Joachim; Illingworth, Elizabeth; Banfi, Sandro; di Bernardo, Diego

2013-01-01

Gene expression profiles can be used to infer previously unknown transcriptional regulatory interaction among thousands of genes, via systems biology 'reverse engineering' approaches. We 'reverse engineered' an embryonic stem (ES)-specific transcriptional network from 171 gene expression profiles, measured in ES cells, to identify master regulators of gene expression ('hubs'). We discovered that E130012A19Rik (E13), highly expressed in mouse ES cells as compared with differentiated cells, was a central 'hub' of the network. We demonstrated that E13 is a protein-coding gene implicated in regulating the commitment towards the different neuronal subtypes and glia cells. The overexpression and knock-down of E13 in ES cell lines, undergoing differentiation into neurons and glia cells, caused a strong up-regulation of the glutamatergic neurons marker Vglut2 and a strong down-regulation of the GABAergic neurons marker GAD65 and of the radial glia marker Blbp. We confirmed E13 expression in the cerebral cortex of adult mice and during development. By immuno-based affinity purification, we characterized protein partners of E13, involved in the Polycomb complex. Our results suggest a role of E13 in regulating the division between glutamatergic projection neurons and GABAergic interneurons and glia cells possibly by epigenetic-mediated transcriptional regulation.

The betrayed thief – the extraordinary strategy of Aristolochia rotunda to deceive its pollinators

PubMed Central

Oelschlägel, Birgit; Nuss, Matthias; von Tschirnhaus, Michael; Pätzold, Claudia; Neinhuis, Christoph; Dötterl, Stefan; Wanke, Stefan

2015-01-01

Pollination of several angiosperms is based on deceit. In such systems, the flowers advertise a reward that ultimately is not provided. We report on a previously unknown pollination/mimicry system discovered in deceptive Aristolochia rotunda (Aristolochiaceae). Pollinators were collected in the natural habitat and identified. Flower scent and the volatiles of insects (models) potentially mimicked were analyzed by chemical analytical techniques. Electrophysiological and behavioral tests on the pollinators identified the components that mediate the plant–pollinator interaction and revealed the model of the mimicry system. The main pollinators of A. rotunda were female Chloropidae. They are food thieves that feed on secretions of true bugs (Miridae) while these are eaten by arthropod predators. Freshly killed mirids and Aristolochia flowers released the same scent components that chloropids use to find their food sources. Aristolochia exploits these components to deceive their chloropid pollinators. Aristolochia and other trap flowers were believed to lure saprophilous flies and mimic brood sites of pollinators. We demonstrate for A. rotunda, and hypothesize for other deceptive angiosperms, the evolution of a different, kleptomyiophilous pollination strategy. It involves scent mimicry and the exploitation of kleptoparasitic flies as pollinators. Our findings suggest a reconsideration of plants assumed to show sapromyiophilous pollination. PMID:25488155

Beauveria medogensis sp. nov., a new fungus of the entomopathogenic genus from China.

PubMed

Imoulan, Abdessamad; Wu, Hai-Jun; Lu, Wei-Lai; Li, Yi; Li, Bin-Bin; Yang, Rei-Heng; Wang, Wen-Jing; Wang, Xiao-Liang; Kirk, Paul M; Yao, Yi-Jian

2016-09-01

Beauveria is among the most ubiquitous genera of entomopathogenic fungi throughout the world. A previously unknown species of the genus was recently discovered from a soil sample collected from Tibetan Plateau, China and is here described as new to science, B. medogensis sp. nov. The new species is distinguished from its closest relatives based on both morphological characterization and molecular phylogenetic analyses. Beauveria medogensis is characterized by globose to subglobose conidia, morphologically similar to some other species of in the genus, but was conclusively separated from those species in the phylogenetic analyses including sequences of four nuclear genes (RPB1, RPB2, TEF1 and Bloc). The new species was clustered in the analyses in a single terminal lineage which was grouped with B. australis sequences together as a sister clade to the B. brongniartii terminal clade. Although molecularly closely related, the new species is distinct morphologically from its closest sisters, B. australis and B. brongniartii, in producing globose to subglobose conidia rather than subglobose, broadly ellipsoid to ellipsoid conidia or ellipsoidal to cylindrical conidia. As isolated from a soil sample, the entomopathogenicity of the new species has been confirmed using Helicoverpa armigera and Tenebrio molitor larvae. Copyright © 2016 Elsevier Inc. All rights reserved.

Incorporation of absorption and metabolism into liver toxicity prediction for phytochemicals: A tiered in silico QSAR approach.

PubMed

Liu, Yitong

2018-05-18

An increased use of herbal dietary supplements has been associated with adverse liver effects such as elevated serum enzymes and liver failure. The safety assessment for herbal dietary supplements is challenging since they often contain complex mixtures of phytochemicals, most of which have unknown pharmacokinetic and toxicological properties. Rapid tools are needed to evaluate large numbers of phytochemicals for potential liver toxicity. The current study demonstrates a tiered approach combining identification of phytochemicals in liver toxic botanicals, followed by in silico quantitative structure-activity relationship (QSAR) evaluation of these phytochemicals for absorption (e.g. permeability), metabolism (cytochromes P450) and liver toxicity (e.g. elevated transaminases). First, 255 phytochemicals from 20 botanicals associated with clinical liver injury were identified, and the phytochemical structures were subsequently used for QSAR evaluation. Among these identified phytochemicals, 193 were predicted to be absorbed and then used to generate metabolites, which were both used to predict liver toxicity. Forty-eight phytochemicals were predicted as liver toxic, either due to parent phytochemicals or metabolites. Among them, nineteen phytochemicals have previous evidence of liver toxicity (e.g. pyrrolizidine alkaloids), while the majority were newly discovered (e.g. sesquiterpenoids). These findings help reveal new toxic phytochemicals in herbal dietary supplements and prioritize future toxicological testing. Published by Elsevier Ltd.

Characterization of known protein complexes using k-connectivity and other topological measures

PubMed Central

Gallagher, Suzanne R; Goldberg, Debra S

2015-01-01

Many protein complexes are densely packed, so proteins within complexes often interact with several other proteins in the complex. Steric constraints prevent most proteins from simultaneously binding more than a handful of other proteins, regardless of the number of proteins in the complex. Because of this, as complex size increases, several measures of the complex decrease within protein-protein interaction networks. However, k-connectivity, the number of vertices or edges that need to be removed in order to disconnect a graph, may be consistently high for protein complexes. The property of k-connectivity has been little used previously in the investigation of protein-protein interactions. To understand the discriminative power of k-connectivity and other topological measures for identifying unknown protein complexes, we characterized these properties in known Saccharomyces cerevisiae protein complexes in networks generated both from highly accurate X-ray crystallography experiments which give an accurate model of each complex, and also as the complexes appear in high-throughput yeast 2-hybrid studies in which new complexes may be discovered. We also computed these properties for appropriate random subgraphs.We found that clustering coefficient, mutual clustering coefficient, and k-connectivity are better indicators of known protein complexes than edge density, degree, or betweenness. This suggests new directions for future protein complex-finding algorithms. PMID:26913183

Applying Precision Public Health to Prevent Preterm Birth

PubMed Central

Newnham, John P.; Kemp, Matthew W.; White, Scott W.; Arrese, Catherine A.; Hart, Roger J.; Keelan, Jeffrey A.

2017-01-01

Preterm birth (PTB) is one of the major health-care challenges of our time. Being born too early is associated with major risks to the child with potential for serious consequences in terms of life-long disability and health-care costs. Discovering how to prevent PTB needs to be one of our greatest priorities. Recent advances have provided hope that a percentage of cases known to be related to risk factors may be amenable to prevention; but the majority of cases remain of unknown cause, and there is little chance of prevention. Applying the principle of precision public health may offer opportunities previously unavailable. Presented in this article are ideas that may improve our abilities in the fields of studying the effects of migration and of populations in transition, public health programs, tobacco control, routine measurement of length of the cervix in mid-pregnancy by ultrasound imaging, prevention of non-medically indicated late PTB, identification of pregnant women for whom treatment of vaginal infection may be of benefit, and screening by genetics and other “omics.” Opening new research in these fields, and viewing these clinical problems through a prism of precision public health, may produce benefits that will affect the lives of large numbers of people. PMID:28421178

Differential depth distribution of microbial function and putative symbionts through sediment-hosted aquifers in the deep terrestrial subsurface

DOE PAGES

Probst, Alexander J.; Ladd, Bethany; Jarett, Jessica K.; ...

2018-01-29

An enormous diversity of previously unknown bacteria and archaea has been discovered recently, yet their functional capacities and distributions in the terrestrial subsurface remain uncertain. Here, we continually sampled a CO 2-driven geyser (Colorado Plateau, Utah, USA) over its 5-day eruption cycle to test the hypothesis that stratified, sandstone-hosted aquifers sampled over three phases of the eruption cycle have microbial communities that differ both in membership and function. Genome-resolved metagenomics, single-cell genomics and geochemical analyses confirmed this hypothesis and linked microorganisms to groundwater compositions from different depths. Autotrophic Candidatus “Altiarchaeum sp.” and phylogenetically deep-branching nanoarchaea dominate the deepest groundwater. Amore » nanoarchaeon with limited metabolic capacity is inferred to be a potential symbiont of the Ca. “Altiarchaeum”. Candidate Phyla Radiation bacteria are also present in the deepest groundwater and they are relatively abundant in water from intermediate depths. During the recovery phase of the geyser, microaerophilic Fe- and S-oxidizers have high in situ genome replication rates. Autotrophic Sulfurimonas sustained by aerobic sulfide oxidation and with the capacity for N 2 fixation dominate the shallow aquifer. Overall, 104 different phylum-level lineages are present in water from these subsurface environments, with uncultivated archaea and bacteria partitioned to the deeper subsurface.« less

Harnessing Nature’s Diversity: Discovering organophosphate bioscavenger characteristics among low molecular weight proteins

PubMed Central

Jacob, Reed B.; Michaels, Kenan C.; Anderson, Cathy J.; Fay, James M.; Dokholyan, Nikolay V.

2016-01-01

Organophosphate poisoning can occur from exposure to agricultural pesticides or chemical weapons. This exposure inhibits acetylcholinesterase resulting in increased acetylcholine levels within the synaptic cleft causing loss of muscle control, seizures, and death. Mitigating the effects of organophosphates in our bodies is critical and yet an unsolved challenge. Here, we present a computational strategy that integrates structure mining and modeling approaches, using which we identify novel candidates capable of interacting with a serine hydrolase probe (with equilibrium binding constants ranging from 4 to 120 μM). One candidate Smu. 1393c catalyzes the hydrolysis of the organophosphate omethoate (kcat/Km of (2.0 ± 1.3) × 10−1 M−1s−1) and paraoxon (kcat/Km of (4.6 ± 0.8) × 103 M−1s−1), V- and G-agent analogs respectively. In addition, Smu. 1393c protects acetylcholinesterase activity from being inhibited by two organophosphate simulants. We demonstrate that the utilized approach is an efficient and highly-extendable framework for the development of prophylactic therapeutics against organophosphate poisoning and other important targets. Our findings further suggest currently unknown molecular evolutionary rules governing natural diversity of the protein universe, which make it capable of recognizing previously unseen ligands. PMID:27845442

Cuprous oxide nanoparticles trigger ER stress-induced apoptosis by regulating copper trafficking and overcoming resistance to sunitinib therapy in renal cancer.

PubMed

Yang, Qiwei; Wang, Ye; Yang, Qing; Gao, Yi; Duan, Xiaopeng; Fu, Qingcheng; Chu, Chuanmin; Pan, Xiuwu; Cui, Xingang; Sun, Yinghao

2017-11-01

While the current standard first-line treatment for advanced renal cell carcinoma (RCC) is sunitinib, patients inevitably develop resistance to this drug. However, the rapid development of nanotechnology has provided emerging techniques for the treatment of advanced tumours, including RCC. In our previous research, cuprous oxide nanoparticles (CONPs) showed ideal anti-tumour effects and low systemic toxicity. While many inorganic nanomedicines, including CONPs, have similar pharmacological effects, their detailed mechanisms remain unknown. Copper chaperone proteins, which regulate the endocellular dosage and transport of copper, also play crucial roles in the progression of cancer. In this research, we discovered that CONPs can disrupt copper transportation by regulating the copper chaperone proteins ATOX1 and CCS in RCC cells and induce endoplasmic reticulum (ER) stress in vitro and in vivo by promoting the accumulation of intracellular calcium and reactive oxygen species (ROS). Furthermore, CONPs can initiate ER- and mitochondrial-dependent apoptosis by activating caspase-3, caspase-9 and caspase-12. In addition, CONPs downregulate the expression of AXL, MET, AKT, and ERK to recover sunitinib responsiveness in RCC cells with sunitinib resistance (SR) and may therefore facilitate the development of promising new pathways to treat patients with acquired SRRCC. Copyright © 2017 Elsevier Ltd. All rights reserved.

Discovery of parvovirus-related sequences in an unexpected broad range of animals.

PubMed

François, S; Filloux, D; Roumagnac, P; Bigot, D; Gayral, P; Martin, D P; Froissart, R; Ogliastro, M

2016-09-07

Our knowledge of the genetic diversity and host ranges of viruses is fragmentary. This is particularly true for the Parvoviridae family. Genetic diversity studies of single stranded DNA viruses within this family have been largely focused on arthropod- and vertebrate-infecting species that cause diseases of humans and our domesticated animals: a focus that has biased our perception of parvovirus diversity. While metagenomics approaches could help rectify this bias, so too could transcriptomics studies. Large amounts of transcriptomic data are available for a diverse array of animal species and whenever this data has inadvertently been gathered from virus-infected individuals, it could contain detectable viral transcripts. We therefore performed a systematic search for parvovirus-related sequences (PRSs) within publicly available transcript, genome and protein databases and eleven new transcriptome datasets. This revealed 463 PRSs in the transcript databases of 118 animals. At least 41 of these PRSs are likely integrated within animal genomes in that they were also found within genomic sequence databases. Besides illuminating the ubiquity of parvoviruses, the number of parvoviral sequences discovered within public databases revealed numerous previously unknown parvovirus-host combinations; particularly in invertebrates. Our findings suggest that the host-ranges of extant parvoviruses might span the entire animal kingdom.

[A journey into the (un)known. Borderlands of knowledge for Leonhard Rauwolf (1535?-1596)].

PubMed

Walter, Tilmann

2009-01-01

The Augsburg physician Leonhard Rauwolf is known to the history of Western sciences for "discovering" the exotic flora of the Near East. This article deals with the social background of his studies in Germany and France and his perception of foreign lands, plants, and peoples. Before Rauwolf started his journey at Marseille in 1573 he had received a proper education in practical botany at Montpellier under Guillaume Rondelet. He had also collected about 600 specimens of plants in his herbarium. According to the common medical conventions of his time--most prominently represented by the Renaissance anatomist Andreas Vesalius--in his travel account Rauwolf claimed to tell only what he had seen, experienced, observed by himself, or touched with his own hands. Contrary to his own claim of pure "autopsy", or direct experience, however, Rauwolf's Aigentliche Beschreibung [Actual Description] was composed from different sources. As previously unnoted manuscript letters from the Trew-collection at the University Library of Erlangen show, editorial work on Rauwolf's book was a lengthy process. The final composition ended up drawing on such different sources as the Old and New Testament, ancient natural philosophy, Christian travel literature and sermons, more recent botanical books, oral information from other academics, fellow travellers or indigenous people, and--finally--Rauwolf's own mpressions and observations.

The betrayed thief - the extraordinary strategy of Aristolochia rotunda to deceive its pollinators.

PubMed

Oelschlägel, Birgit; Nuss, Matthias; von Tschirnhaus, Michael; Pätzold, Claudia; Neinhuis, Christoph; Dötterl, Stefan; Wanke, Stefan

2015-04-01

Pollination of several angiosperms is based on deceit. In such systems, the flowers advertise a reward that ultimately is not provided. We report on a previously unknown pollination/mimicry system discovered in deceptive Aristolochia rotunda (Aristolochiaceae). Pollinators were collected in the natural habitat and identified. Flower scent and the volatiles of insects (models) potentially mimicked were analyzed by chemical analytical techniques. Electrophysiological and behavioral tests on the pollinators identified the components that mediate the plant-pollinator interaction and revealed the model of the mimicry system. The main pollinators of A. rotunda were female Chloropidae. They are food thieves that feed on secretions of true bugs (Miridae) while these are eaten by arthropod predators. Freshly killed mirids and Aristolochia flowers released the same scent components that chloropids use to find their food sources. Aristolochia exploits these components to deceive their chloropid pollinators. Aristolochia and other trap flowers were believed to lure saprophilous flies and mimic brood sites of pollinators. We demonstrate for A. rotunda, and hypothesize for other deceptive angiosperms, the evolution of a different, kleptomyiophilous pollination strategy. It involves scent mimicry and the exploitation of kleptoparasitic flies as pollinators. Our findings suggest a reconsideration of plants assumed to show sapromyiophilous pollination. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

Transcriptomics of mRNA and egg quality in farmed fish: Some recent developments and future directions.

PubMed

Sullivan, Craig V; Chapman, Robert W; Reading, Benjamin J; Anderson, Paul E

2015-09-15

Maternal mRNA transcripts deposited in growing oocytes regulate early development and are under intensive investigation as determinants of egg quality. The research has evolved from single gene studies to microarray and now RNA-Seq analyses in which mRNA expression by virtually every gene can be assessed and related to gamete quality. Such studies have mainly focused on genes changing two- to several-fold in expression between biological states, and have identified scores of candidate genes and a few gene networks whose functioning is related to successful development. However, ever-increasing yields of information from high throughput methods for detecting transcript abundance have far outpaced progress in methods for analyzing the massive quantities of gene expression data, and especially for meaningful relation of whole transcriptome profiles to gamete quality. We have developed a new approach to this problem employing artificial neural networks and supervised machine learning with other novel bioinformatics procedures to discover a previously unknown level of ovarian transcriptome function at which minute changes in expression of a few hundred genes is highly predictive of egg quality. In this paper, we briefly review the progress in transcriptomics of fish egg quality and discuss some future directions for this field of study. Copyright © 2015 Elsevier Inc. All rights reserved.

A Machine Learning Approach for Using the Postmortem Skin Microbiome to Estimate the Postmortem Interval

PubMed Central

Johnson, Hunter R.; Trinidad, Donovan D.; Guzman, Stephania; Khan, Zenab; Parziale, James V.; DeBruyn, Jennifer M.

2016-01-01

Research on the human microbiome, the microbiota that live in, on, and around the human person, has revolutionized our understanding of the complex interactions between microbial life and human health and disease. The microbiome may also provide a valuable tool in forensic death investigations by helping to reveal the postmortem interval (PMI) of a decedent that is discovered after an unknown amount of time since death. Current methods of estimating PMI for cadavers discovered in uncontrolled, unstudied environments have substantial limitations, some of which may be overcome through the use of microbial indicators. In this project, we sampled the microbiomes of decomposing human cadavers, focusing on the skin microbiota found in the nasal and ear canals. We then developed several models of statistical regression to establish an algorithm for predicting the PMI of microbial samples. We found that the complete data set, rather than a curated list of indicator species, was preferred for training the regressor. We further found that genus and family, rather than species, are the most informative taxonomic levels. Finally, we developed a k-nearest- neighbor regressor, tuned with the entire data set from all nasal and ear samples, that predicts the PMI of unknown samples with an average error of ±55 accumulated degree days (ADD). This study outlines a machine learning approach for the use of necrobiome data in the prediction of the PMI and thereby provides a successful proof-of- concept that skin microbiota is a promising tool in forensic death investigations. PMID:28005908

The Enzyme Function Initiative†

PubMed Central

Gerlt, John A.; Allen, Karen N.; Almo, Steven C.; Armstrong, Richard N.; Babbitt, Patricia C.; Cronan, John E.; Dunaway-Mariano, Debra; Imker, Heidi J.; Jacobson, Matthew P.; Minor, Wladek; Poulter, C. Dale; Raushel, Frank M.; Sali, Andrej; Shoichet, Brian K.; Sweedler, Jonathan V.

2011-01-01

The Enzyme Function Initiative (EFI) was recently established to address the challenge of assigning reliable functions to enzymes discovered in bacterial genome projects; in this Current Topic we review the structure and operations of the EFI. The EFI includes the Superfamily/Genome, Protein, Structure, Computation, and Data/Dissemination Cores that provide the infrastructure for reliably predicting the in vitro functions of unknown enzymes. The initial targets for functional assignment are selected from five functionally diverse superfamilies (amidohydrolase, enolase, glutathione transferase, haloalkanoic acid dehalogenase, and isoprenoid synthase), with five superfamily-specific Bridging Projects experimentally testing the predicted in vitro enzymatic activities. The EFI also includes the Microbiology Core that evaluates the in vivo context of in vitro enzymatic functions and confirms the functional predictions of the EFI. The deliverables of the EFI to the scientific community include: 1) development of a large-scale, multidisciplinary sequence/structure-based strategy for functional assignment of unknown enzymes discovered in genome projects (target selection, protein production, structure determination, computation, experimental enzymology, microbiology, and structure-based annotation); 2) dissemination of the strategy to the community via publications, collaborations, workshops, and symposia; 3) computational and bioinformatic tools for using the strategy; 4) provision of experimental protocols and/or reagents for enzyme production and characterization; and 5) dissemination of data via the EFI’s website, enzymefunction.org. The realization of multidisciplinary strategies for functional assignment will begin to define the full metabolic diversity that exists in nature and will impact basic biochemical and evolutionary understanding, as well as a wide range of applications of central importance to industrial, medicinal and pharmaceutical efforts. PMID:21999478

The Enzyme Function Initiative.

PubMed

Gerlt, John A; Allen, Karen N; Almo, Steven C; Armstrong, Richard N; Babbitt, Patricia C; Cronan, John E; Dunaway-Mariano, Debra; Imker, Heidi J; Jacobson, Matthew P; Minor, Wladek; Poulter, C Dale; Raushel, Frank M; Sali, Andrej; Shoichet, Brian K; Sweedler, Jonathan V

2011-11-22

The Enzyme Function Initiative (EFI) was recently established to address the challenge of assigning reliable functions to enzymes discovered in bacterial genome projects; in this Current Topic, we review the structure and operations of the EFI. The EFI includes the Superfamily/Genome, Protein, Structure, Computation, and Data/Dissemination Cores that provide the infrastructure for reliably predicting the in vitro functions of unknown enzymes. The initial targets for functional assignment are selected from five functionally diverse superfamilies (amidohydrolase, enolase, glutathione transferase, haloalkanoic acid dehalogenase, and isoprenoid synthase), with five superfamily specific Bridging Projects experimentally testing the predicted in vitro enzymatic activities. The EFI also includes the Microbiology Core that evaluates the in vivo context of in vitro enzymatic functions and confirms the functional predictions of the EFI. The deliverables of the EFI to the scientific community include (1) development of a large-scale, multidisciplinary sequence/structure-based strategy for functional assignment of unknown enzymes discovered in genome projects (target selection, protein production, structure determination, computation, experimental enzymology, microbiology, and structure-based annotation), (2) dissemination of the strategy to the community via publications, collaborations, workshops, and symposia, (3) computational and bioinformatic tools for using the strategy, (4) provision of experimental protocols and/or reagents for enzyme production and characterization, and (5) dissemination of data via the EFI's Website, http://enzymefunction.org. The realization of multidisciplinary strategies for functional assignment will begin to define the full metabolic diversity that exists in nature and will impact basic biochemical and evolutionary understanding, as well as a wide range of applications of central importance to industrial, medicinal, and pharmaceutical efforts. © 2011 American Chemical Society

Symmetry compression method for discovering network motifs.

PubMed

Wang, Jianxin; Huang, Yuannan; Wu, Fang-Xiang; Pan, Yi

2012-01-01

Discovering network motifs could provide a significant insight into systems biology. Interestingly, many biological networks have been found to have a high degree of symmetry (automorphism), which is inherent in biological network topologies. The symmetry due to the large number of basic symmetric subgraphs (BSSs) causes a certain redundant calculation in discovering network motifs. Therefore, we compress all basic symmetric subgraphs before extracting compressed subgraphs and propose an efficient decompression algorithm to decompress all compressed subgraphs without loss of any information. In contrast to previous approaches, the novel Symmetry Compression method for Motif Detection, named as SCMD, eliminates most redundant calculations caused by widespread symmetry of biological networks. We use SCMD to improve three notable exact algorithms and two efficient sampling algorithms. Results of all exact algorithms with SCMD are the same as those of the original algorithms, since SCMD is a lossless method. The sampling results show that the use of SCMD almost does not affect the quality of sampling results. For highly symmetric networks, we find that SCMD used in both exact and sampling algorithms can help get a remarkable speedup. Furthermore, SCMD enables us to find larger motifs in biological networks with notable symmetry than previously possible.

A scientometric prediction of the discovery of the first potentially habitable planet with a mass similar to Earth.

PubMed

Arbesman, Samuel; Laughlin, Gregory

2010-10-04

The search for a habitable extrasolar planet has long interested scientists, but only recently have the tools become available to search for such planets. In the past decades, the number of known extrasolar planets has ballooned into the hundreds, and with it, the expectation that the discovery of the first Earth-like extrasolar planet is not far off. Here, we develop a novel metric of habitability for discovered planets and use this to arrive at a prediction for when the first habitable planet will be discovered. Using a bootstrap analysis of currently discovered exoplanets, we predict the discovery of the first Earth-like planet to be announced in the first half of 2011, with the likeliest date being early May 2011. Our predictions, using only the properties of previously discovered exoplanets, accord well with external estimates for the discovery of the first potentially habitable extrasolar planet and highlight the the usefulness of predictive scientometric techniques to understand the pace of scientific discovery in many fields.

Distribution and clinical impact of functional variants in 50,726 whole-exome sequences from the DiscovEHR study.

PubMed

Dewey, Frederick E; Murray, Michael F; Overton, John D; Habegger, Lukas; Leader, Joseph B; Fetterolf, Samantha N; O'Dushlaine, Colm; Van Hout, Cristopher V; Staples, Jeffrey; Gonzaga-Jauregui, Claudia; Metpally, Raghu; Pendergrass, Sarah A; Giovanni, Monica A; Kirchner, H Lester; Balasubramanian, Suganthi; Abul-Husn, Noura S; Hartzel, Dustin N; Lavage, Daniel R; Kost, Korey A; Packer, Jonathan S; Lopez, Alexander E; Penn, John; Mukherjee, Semanti; Gosalia, Nehal; Kanagaraj, Manoj; Li, Alexander H; Mitnaul, Lyndon J; Adams, Lance J; Person, Thomas N; Praveen, Kavita; Marcketta, Anthony; Lebo, Matthew S; Austin-Tse, Christina A; Mason-Suares, Heather M; Bruse, Shannon; Mellis, Scott; Phillips, Robert; Stahl, Neil; Murphy, Andrew; Economides, Aris; Skelding, Kimberly A; Still, Christopher D; Elmore, James R; Borecki, Ingrid B; Yancopoulos, George D; Davis, F Daniel; Faucett, William A; Gottesman, Omri; Ritchie, Marylyn D; Shuldiner, Alan R; Reid, Jeffrey G; Ledbetter, David H; Baras, Aris; Carey, David J

2016-12-23

The DiscovEHR collaboration between the Regeneron Genetics Center and Geisinger Health System couples high-throughput sequencing to an integrated health care system using longitudinal electronic health records (EHRs). We sequenced the exomes of 50,726 adult participants in the DiscovEHR study to identify ~4.2 million rare single-nucleotide variants and insertion/deletion events, of which ~176,000 are predicted to result in a loss of gene function. Linking these data to EHR-derived clinical phenotypes, we find clinical associations supporting therapeutic targets, including genes encoding drug targets for lipid lowering, and identify previously unidentified rare alleles associated with lipid levels and other blood level traits. About 3.5% of individuals harbor deleterious variants in 76 clinically actionable genes. The DiscovEHR data set provides a blueprint for large-scale precision medicine initiatives and genomics-guided therapeutic discovery. Copyright © 2016, American Association for the Advancement of Science.

Functional specialization in nucleotide sugar transporters occurred through differentiation of the gene cluster EamA (DUF6) before the radiation of Viridiplantae

PubMed Central

2011-01-01

Background The drug/metabolite transporter superfamily comprises a diversity of protein domain families with multiple functions including transport of nucleotide sugars. Drug/metabolite transporter domains are contained in both solute carrier families 30, 35 and 39 proteins as well as in acyl-malonyl condensing enzyme proteins. In this paper, we present an evolutionary analysis of nucleotide sugar transporters in relation to the entire superfamily of drug/metabolite transporters that considers crucial intra-protein duplication events that have shaped the transporters. We use a method that combines the strengths of hidden Markov models and maximum likelihood to find relationships between drug/metabolite transporter families, and branches within families. Results We present evidence that the triose-phosphate transporters, domain unknown function 914, uracil-diphosphate glucose-N-acetylglucosamine, and nucleotide sugar transporter families have evolved from a domain duplication event before the radiation of Viridiplantae in the EamA family (previously called domain unknown function 6). We identify previously unknown branches in the solute carrier 30, 35 and 39 protein families that emerged simultaneously as key physiological developments after the radiation of Viridiplantae, including the "35C/E" branch of EamA, which formed in the lineage of T. adhaerens (Animalia). We identify a second cluster of DMTs, called the domain unknown function 1632 cluster, which has non-cytosolic N- and C-termini, and thus appears to have been formed from a different domain duplication event. We identify a previously uncharacterized motif, G-X(6)-G, which is overrepresented in the fifth transmembrane helix of C-terminal domains. We present evidence that the family called fatty acid elongases are homologous to transporters, not enzymes as had previously been thought. Conclusions The nucleotide sugar transporters families were formed through differentiation of the gene cluster EamA (domain unknown function 6) before Viridiplantae, showing for the first time the significance of EamA. PMID:21569384

Update on IBEX and the outer boundary of the space radiation environment

NASA Astrophysics Data System (ADS)

McComas, D. J.; IBEX Science Team

2012-11-01

The Interstellar Boundary Explorer (IBEX) mission has been remotely observing the global interaction of our heliosphere with the local interstellar medium for over three years. Initially, IBEX generated the first all-sky maps of Energetic Neutral Atoms (ENAs) emanating in from the boundaries of our heliosphere over the energy range from ˜0.1-6 keV. Using these observations, the IBEX team discovered a smoothly varying, globally distributed ENA flux overlaid by a narrow "ribbon" of significantly enhanced ENA emissions. Since the initial publication of these results in a special issue of Science magazine (November 2009), IBEX has completed five more energy-resolved sets of sky maps and discovered small but important time variations in the interaction, separated the ribbon from globally distributed ENA fluxes, measured the energy spectral shape and inferred ion source temperatures, and carried out many other observational and theoretical studies of the outer heliosphere. In a second major area of observations - direct measurements of Interstellar Neutral (ISN) atoms - just published, IBEX observations of ISN He atoms show that the speed and direction (the motion of the heliosphere with respect to the interstellar medium) is slower and from a somewhat different direction than that thought from prior Ulysses observations. These observations also show evidence for a previously unknown and unanticipated secondary population of Helium. In addition, IBEX is providing the first direct quantitative measurements of the ISN H parameters and the first direct measurements of interstellar Ne and the interstellar Neon/Oxygen abundance ratio; this ratio is significantly different than the solar abundance ratio. Finally, IBEX was recently maneuvered into a unique, long-term stable orbit, which has a very low radiation environment and requires no orbit maintenance. Thus, IBEX will likely continue to provide revolutionary observations of the outer heliosphere and local interstellar medium for many years to come.

IBEX Mission update: New discoveries and a new orbit

NASA Astrophysics Data System (ADS)

McComas, D. J.; IBEX Science Team

2011-12-01

The Interstellar Boundary Explorer (IBEX) mission has been remotely observing the global interaction of our heliosphere with the local interstellar medium for over two and a half years. Initially, IBEX generated the first all-sky maps of Energetic Neutral Atoms (ENAs) emanating in from the boundaries of our heliosphere over the energy range from ~0.1-6 keV. Using these observations, the IBEX team discovered a smoothly varying, globally distributed ENA flux overlaid by a narrow "ribbon" of significantly enhanced ENA emissions. Since the initial publications of these results in a special issue of Science magazine (November 2009), IBEX has completed four more energy-resolved sets of sky maps and discovered small but important time variations in the interaction, separated the ribbon from globally distributed ENA fluxes, measured the energy spectral shape and inferred ion source temperatures, and carried out many other observational and theoretical studies. In addition, IBEX made the first observations of ENAs produced by backscatter and neutralization of the solar wind from the lunar regolith and provided the first energy and angle resolved ENA images of the subsolar magnetosheath and magnetospheric cusps and plasma sheet. Most recently, direct IBEX observations of Interstellar Neutral (ISN) He show that the speed and direction (the motion of the heliosphere with respect to the interstellar medium) is different than that thought from prior Ulysses observations. These observations also show evidence for a previously unknown and unanticipated secondary population of Helium. In addition, IBEX is providing the first direct quantitative measurements of the ISN H parameters and the first direct measurements of interstellar Ne and the interstellar Neon/Oxygen abundance ratio; this ratio is significantly different than the solar abundance ratio. IBEX was recently maneuvered into a unique, long-term stable orbit and has several decades worth of fuel for routine operations. Thus, IBEX will likely continue to provide revolutionary observations of numerous heliospheric, magnetospheric, and planetary phenomena for many years to come!

Newly discovered Wolf-Rayet and weak emission-line central stars of planetary nebulae

NASA Astrophysics Data System (ADS)

DePew, K.; Parker, Q. A.; Miszalski, B.; De Marco, O.; Frew, D. J.; Acker, A.; Kovacevic, A. V.; Sharp, R. G.

2011-07-01

We present the spectra of 32 previously unpublished confirmed and candidate Wolf-Rayet ([WR]) and weak emission-line (WELS) central stars of planetary nebulae (CSPNe). 18 stars have been discovered in the Macquarie/AAO/Strasbourg Hα (MASH) PN survey sample, and we have also uncovered 14 confirmed and candidate [WR]s and WELS among the CSPNe of previously known PNe. Spectral classifications have been undertaken using both Acker & Neiner and Crowther, De Marco & Barlow schemes. 22 members in this sample are identified as probable [WR]s; the remaining 10 appear to be WELS. Observations undertaken as part of the MASH spectroscopic survey have now increased the number of known [WR]s by ˜30 per cent. This will permit a better analysis of [WR] subclass distribution, metallicity effects and evolutionary sequences in these uncommon objects.

The functions of immediate echolalia in autistic children.

PubMed

Prizant, B M; Duchan, J F

1981-08-01

This research was intended to discover how immediate echolalia functioned for autistic children in interactions with familial adults. For echolalic children were videotaped at school and at home, in both group and dyadic interactions in natural situations such as lunchtime, family activities, and play activities in school. After conducting a multilevel analysis (of over 1,000 utterances) of verbal and nonverbal factors, response latency, and intonation, it was discovered that immediate echolalia is far more than a meaningless behavior, as has been previously reported. Seven functional categories of echolalia were discovered and are discussed in reference to behavioral and linguistic features of each category. It is argue that researchers who propose intervention programs of ech-abatement may be overlooking the important communicative and cognitive functions echolalia may serve for the autistic child.

The ASAS-SN bright supernova catalogue – III. 2016

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holoien, T. W. -S.; Brown, J. S.; Stanek, K. Z.

In this catalogue we summarize information for all supernovae discovered by the All-Sky Automated Survey for SuperNovae (ASAS-SN) and all other bright (m peak ≤ 17), spectroscopically confirmed supernovae discovered in 2016. We then gather the near-infrared through ultraviolet magnitudes of all host galaxies and the offsets of the supernovae from the centres of their hosts from public data bases. We illustrate the results using a sample that now totals 668 supernovae discovered since 2014 May 1, including the supernovae from our previous catalogues, with type distributions closely matching those of the ideal magnitude limited sample from Li et al.more » This is then the third of a series of yearly papers on bright supernovae and their hosts from the ASAS-SN team.« less

The ASAS-SN bright supernova catalogue – III. 2016

DOE PAGES

Holoien, T. W. -S.; Brown, J. S.; Stanek, K. Z.; ...

2017-08-18

In this catalogue we summarize information for all supernovae discovered by the All-Sky Automated Survey for SuperNovae (ASAS-SN) and all other bright (m peak ≤ 17), spectroscopically confirmed supernovae discovered in 2016. We then gather the near-infrared through ultraviolet magnitudes of all host galaxies and the offsets of the supernovae from the centres of their hosts from public data bases. We illustrate the results using a sample that now totals 668 supernovae discovered since 2014 May 1, including the supernovae from our previous catalogues, with type distributions closely matching those of the ideal magnitude limited sample from Li et al.more » This is then the third of a series of yearly papers on bright supernovae and their hosts from the ASAS-SN team.« less

The pearls of using real-world evidence to discover social groups

NASA Astrophysics Data System (ADS)

Cardillo, Raymond A.; Salerno, John J.

2005-03-01

In previous work, we introduced a new paradigm called Uni-Party Data Community Generation (UDCG) and a new methodology to discover social groups (a.k.a., community models) called Link Discovery based on Correlation Analysis (LDCA). We further advanced this work by experimenting with a corpus of evidence obtained from a Ponzi scheme investigation. That work identified several UDCG algorithms, developed what we called "Importance Measures" to compare the accuracy of the algorithms based on ground truth, and presented a Concept of Operations (CONOPS) that criminal investigators could use to discover social groups. However, that work used a rather small random sample of manually edited documents because the evidence contained far too many OCR and other extraction errors. Deferring the evidence extraction errors allowed us to continue experimenting with UDCG algorithms, but only used a small fraction of the available evidence. In attempt to discover techniques that are more practical in the near-term, our most recent work focuses on being able to use an entire corpus of real-world evidence to discover social groups. This paper discusses the complications of extracting evidence, suggests a method of performing name resolution, presents a new UDCG algorithm, and discusses our future direction in this area.

Lod score curves for phase-unknown matings.

PubMed

Hulbert-Shearon, T; Boehnke, M; Lange, K

1996-01-01

For a phase-unknown nuclear family, we show that the likelihood and lod score are unimodal, and we describe conditions under which the maximum occurs at recombination fraction theta = 0, theta = 1/2, and 0 < theta < 1/2. These simply stated necessary and sufficient conditions seem to have escaped the notice of previous statistical geneticists.

Fatal Metacestode Infection in Bornean Orangutan Caused by Unknown Versteria Species

PubMed Central

Gendron-Fitzpatrick, Annette; Deering, Kathleen M.; Wallace, Roberta S.; Clyde, Victoria L.; Lauck, Michael; Rosen, Gail E.; Bennett, Andrew J.; Greiner, Ellis C.; O’Connor, David H.

2014-01-01

A captive juvenile Bornean orangutan (Pongo pygmaeus) died from an unknown disseminated parasitic infection. Deep sequencing of DNA from infected tissues, followed by gene-specific PCR and sequencing, revealed a divergent species within the newly proposed genus Versteria (Cestoda: Taeniidae). Versteria may represent a previously unrecognized risk to primate health. PMID:24377497

Knowledge discovery from structured mammography reports using inductive logic programming.

PubMed

Burnside, Elizabeth S; Davis, Jesse; Costa, Victor Santos; Dutra, Inês de Castro; Kahn, Charles E; Fine, Jason; Page, David

2005-01-01

The development of large mammography databases provides an opportunity for knowledge discovery and data mining techniques to recognize patterns not previously appreciated. Using a database from a breast imaging practice containing patient risk factors, imaging findings, and biopsy results, we tested whether inductive logic programming (ILP) could discover interesting hypotheses that could subsequently be tested and validated. The ILP algorithm discovered two hypotheses from the data that were 1) judged as interesting by a subspecialty trained mammographer and 2) validated by analysis of the data itself.

Discovering Communicable Scientific Knowledge from Spatio-Temporal Data

NASA Technical Reports Server (NTRS)

Schwabacher, Mark; Langley, Pat; Norvig, Peter (Technical Monitor)

2001-01-01

This paper describes how we used regression rules to improve upon a result previously published in the Earth science literature. In such a scientific application of machine learning, it is crucially important for the learned models to be understandable and communicable. We recount how we selected a learning algorithm to maximize communicability, and then describe two visualization techniques that we developed to aid in understanding the model by exploiting the spatial nature of the data. We also report how evaluating the learned models across time let us discover an error in the data.

Sub-subleading soft gravitons and large diffeomorphisms

NASA Astrophysics Data System (ADS)

Campiglia, Miguel; Laddha, Alok

2017-01-01

We present strong evidence that the sub-subleading soft theorem in semiclassical (tree level) gravity discovered by Cachazo and Strominger is equivalent to the conservation of asymptotic charges associated to a new class of vector fields not contained within the previous extensions of BMS algebra. Our analysis crucially relies on analyzing the hitherto established equivalences between soft theorems and Ward identities from a new perspective. In this process we naturally (re)discover a class of `magnetic' charges at null infinity that are associated to the dual of the Weyl tensor.

Discovering Communicable Models from Earth Science Data

NASA Technical Reports Server (NTRS)

Schwabacher, Mark; Langley, Pat; Potter, Christopher; Klooster, Steven; Torregrosa, Alicia

2002-01-01

This chapter describes how we used regression rules to improve upon results previously published in the Earth science literature. In such a scientific application of machine learning, it is crucially important for the learned models to be understandable and communicable. We recount how we selected a learning algorithm to maximize communicability, and then describe two visualization techniques that we developed to aid in understanding the model by exploiting the spatial nature of the data. We also report how evaluating the learned models across time let us discover an error in the data.

The valet and the astronomer - Text and commentary of a Kepler letter newly found by Michael Göbel in the Austrian State Achive. (German Title: Der Kammerdiener und der Astronom - Text und Kommentar zu einem von Michael Göbel im Österreichischen Staatsarchiv neu aufgefundenen Keplerbrief)

NASA Astrophysics Data System (ADS)

Pärr, Nora

In connection with the reprocessing of archival stocks in the Austrian State Archive, a hitherto unknown letter written by J. Kepler and addressed to Philipp Lang von Langenfels, valet of emperor Rudolph II was discovered. The contents of the letter, written presumably in March, 1601, deal with the preparation of ephemerides for the emperor, for which Kepler used calculations by Georg Galgenmair.

M≡E and M=E Complexes of Iron and Cobalt that Emphasize Three-fold Symmetry (E = O, N, NR)

PubMed Central

Saouma, Caroline T.; Peters, Jonas C.

2011-01-01

Mid-to-late transition metal complexes that feature terminal, multiply bonded ligands such as oxos, imides, and nitrides have been invoked as intermediates in several catalytic transformations of synthetic and biological significance. Until about ten years ago, isolable examples of such species were virtually unknown. Over the past decade or so, numerous chemically well-defined examples of such species have been discovered. In this context, the presentreview summarizes the development of 4- and 5-coordinate Fe(E) and Co(E) species under local three-fold symmetry. PMID:21625302

NDR proteins

PubMed Central

Jones, Alan M

2010-01-01

N-myc downregulated (NDR) genes were discovered more than fifteen years ago. Indirect evidence support a role in tumor progression and cellular differentiation, but their biochemical function is still unknown. Our detailed analyses on Arabidopsis NDR proteins (deisgnated NDR-like, NDL) show their involvement in altering auxin transport, local auxin gradients and expression level of auxin transport proteins. Animal NDL proteins may be involved in membrane recycling of E-cadherin and effector for the small GTPase. In light of these findings, we hypothesize that NDL proteins regulate vesicular trafficking of auxin transport facilitator PIN proteins by biochemically alterating the local lipid environment of PIN proteins. PMID:20724844

[Control-lateral sciatrica after surgery for herniated disk].

PubMed

Sicard, A; Banai, M

1976-12-01

A study of 1,427 case records permitted the authors to discover 10 cases of reoperation for sciatica which appeared on the opposite side after removal of a dischernia. A new hernia was noted in 6 cases, whereas radiculitis of unknown origin, appeared to be responsible in 4 cases. The 10 patients who became cured, either after removal of the hernia, or after decompression through the foramin. These few cases, in fact rare, may be considered as relapses and thus poor surgical results. The provide a contribution to the understanding of intervertebral disc disease and raise an interesting medico-legal problem.

Protein classification using sequential pattern mining.

PubMed

Exarchos, Themis P; Papaloukas, Costas; Lampros, Christos; Fotiadis, Dimitrios I

2006-01-01

Protein classification in terms of fold recognition can be employed to determine the structural and functional properties of a newly discovered protein. In this work sequential pattern mining (SPM) is utilized for sequence-based fold recognition. One of the most efficient SPM algorithms, cSPADE, is employed for protein primary structure analysis. Then a classifier uses the extracted sequential patterns for classifying proteins of unknown structure in the appropriate fold category. The proposed methodology exhibited an overall accuracy of 36% in a multi-class problem of 17 candidate categories. The classification performance reaches up to 65% when the three most probable protein folds are considered.

Satellite Observations of New Volcanic Island in Tonga

NASA Astrophysics Data System (ADS)

Vaughan, R. Greg; Abrams, Michael J.; Hook, Simon J.; Pieri, David C.

2007-01-01

A rising volcanic plume from an unknown source was observed on 9-11 August 2006 in the Vava'u Island group in the northernmost islands of Tonga [Matangi News Online, 2006]. On 12 August, the crew on board the yacht Maiken, sailing west from Vava'u to Fiji, encountered ``a vast, many miles wide, belt of densely packed pumice'' floating on the water (F. Fransson personal communication, 2006). Later, the crew sailed south and discovered that the source of the pumice was a newly erupting submarine volcano near Home Reef (18.991°S, 174.767°W) (Figure 1a).

Satellite Observations of New Volcanic Island in Tonga

NASA Technical Reports Server (NTRS)

Vaughan, R. Greg; Abrams, Michael J.; Hook, Simon J.; Pieri, David C.

2007-01-01

A rising volcanic plume from an unknown source was observed on 9-11 August 2006 in the Vava'u Island group in the northernmost islands of Tonga [Matangi News Online, 2006]. On 12 August, the crew on board the yacht Maiken, sailing west from Vava'u to Fiji, encountered 'a vast, many miles wide, belt of densely packed pumice' floating on the water (F. Fransson personal communication, 2006). Later, the crew sailed south and discovered that the source of the pumice was a newly erupting submarine volcano near Home Reef (18.991 deg S, 174.767 deg W).

22 CFR 16.14 - Reconsideration of a grievance.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Reconsideration of a grievance. A grievant whose grievance is found not to be meritorious by the Board may obtain reconsideration by the Board only upon presenting newly discovered or previously unavailable material evidence not...

Repair of cracked prestressed concrete girders, I-565, Huntsville, Alabama.

DOT National Transportation Integrated Search

2011-07-01

Wide cracks were discovered in prestressed concrete bridge girders shortly after their construction in Huntsville, Alabama. Previous investigations of these continuous-for-live-load girders revealed that the cracking resulted from restrained thermal ...

High-resolution mapping of the S-locus in Turnera leads to the discovery of three genes tightly associated with the S-alleles.

PubMed

Labonne, Jonathan J D; Goultiaeva, Alina; Shore, Joel S

2009-06-01

While the breeding system known as distyly has been used as a model system in genetics, and evolutionary biology for over a century, the genes determining this system remain unknown. To positionally clone genes determining distyly, a high-resolution map of the S-locus region of Turnera has been constructed using segregation data from 2,013 backcross progeny. We discovered three putative genes tightly linked with the S-locus. An N-acetyltransferase (TkNACE) flanks the S-locus at 0.35 cM while a sulfotransferase (TkST1) and a non-LTR retroelement (TsRETRO) show complete linkage to the S-locus. An assay of population samples of six species revealed that TsRETRO, initially discovered in diploid Turnera subulata, is also associated with the S-allele in tetraploid T. subulata and diploid Turnera scabra. The sulfotransferase gene shows some level of differential expression in long versus short styles, indicating it might be involved in some aspect of distyly. The complete linkage of TkST1 and TsRETRO to the S-locus suggests that both genes may reside within, or in the immediate vicinity of the S-locus. Chromosome walking has been initiated using one of the genes discovered in the present study to identify the genes determining distyly.

Sterol Composition and Biosynthetic Genes of Vitrella brassicaformis, a Recently Discovered Chromerid: Comparison to Chromera velia and Phylogenetic Relationship with Apicomplexan Parasites.

PubMed

Khadka, Manoj; Salem, Mohamed; Leblond, Jeffrey D

2015-01-01

Vitrella brassicaformis is the second discovered species in the Chromerida, and first in the family Vitrellaceae. Chromera velia, the first discovered species, forms an independent photosynthetic lineage with V. brassicaformis, and both are closely related to peridinin-containing dinoflagellates and nonphotosynthetic apicomplexans; both also show phylogenetic closeness with red algal plastids. We have utilized gas chromatography/mass spectrometry to identify two free sterols, 24-ethylcholest-5-en-3β-ol, and a minor unknown sterol which appeared to be a C(28:4) compound. We have also used RNA Seq analysis to identify seven genes found in the nonmevalonate/methylerythritol pathway (MEP) for sterol biosynthesis. Subsequent genome analysis of V. brassicaformis showed the presence of two mevalonate (MVA) pathway genes, though the genes were not observed in the transcriptome analysis. Transcripts from four genes (dxr, ispf, ispd, and idi) were selected and translated into proteins to study the phylogenetic relationship of sterol biosynthesis in V. brassicaformis and C. velia to other groups of algae and apicomplexans. On the basis of our genomic and transcriptomic analyses, we hypothesize that the MEP pathway was the primary pathway that apicomplexans used for sterol biosynthesis before they lost their sterol biosynthesis ability, although contribution of the MVA pathway cannot be discounted. © 2015 The Author(s) Journal of Eukaryotic Microbiology © 2015 International Society of Protistologists.

Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology

PubMed Central

Pirazzini, Marco; Rossetto, Ornella; Eleopra, Roberto

2017-01-01

The study of botulinum neurotoxins (BoNT) is rapidly progressing in many aspects. Novel BoNTs are being discovered owing to next generation sequencing, but their biologic and pharmacological properties remain largely unknown. The molecular structure of the large protein complexes that the toxin forms with accessory proteins, which are included in some BoNT type A1 and B1 pharmacological preparations, have been determined. By far the largest effort has been dedicated to the testing and validation of BoNTs as therapeutic agents in an ever increasing number of applications, including pain therapy. BoNT type A1 has been also exploited in a variety of cosmetic treatments, alone or in combination with other agents, and this specific market has reached the size of the one dedicated to the treatment of medical syndromes. The pharmacological properties and mode of action of BoNTs have shed light on general principles of neuronal transport and protein-protein interactions and are stimulating basic science studies. Moreover, the wide array of BoNTs discovered and to be discovered and the production of recombinant BoNTs endowed with specific properties suggest novel uses in therapeutics with increasing disease/symptom specifity. These recent developments are reviewed here to provide an updated picture of the biologic mechanism of action of BoNTs, of their increasing use in pharmacology and in cosmetics, and of their toxicology. PMID:28356439

Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology.

PubMed

Pirazzini, Marco; Rossetto, Ornella; Eleopra, Roberto; Montecucco, Cesare

2017-04-01

The study of botulinum neurotoxins (BoNT) is rapidly progressing in many aspects. Novel BoNTs are being discovered owing to next generation sequencing, but their biologic and pharmacological properties remain largely unknown. The molecular structure of the large protein complexes that the toxin forms with accessory proteins, which are included in some BoNT type A1 and B1 pharmacological preparations, have been determined. By far the largest effort has been dedicated to the testing and validation of BoNTs as therapeutic agents in an ever increasing number of applications, including pain therapy. BoNT type A1 has been also exploited in a variety of cosmetic treatments, alone or in combination with other agents, and this specific market has reached the size of the one dedicated to the treatment of medical syndromes. The pharmacological properties and mode of action of BoNTs have shed light on general principles of neuronal transport and protein-protein interactions and are stimulating basic science studies. Moreover, the wide array of BoNTs discovered and to be discovered and the production of recombinant BoNTs endowed with specific properties suggest novel uses in therapeutics with increasing disease/symptom specifity. These recent developments are reviewed here to provide an updated picture of the biologic mechanism of action of BoNTs, of their increasing use in pharmacology and in cosmetics, and of their toxicology. Copyright © 2017 by The Author(s).

Neuronal prediction of opponent's behavior during cooperative social interchange in primates.

PubMed

Haroush, Keren; Williams, Ziv M

2015-03-12

A cornerstone of successful social interchange is the ability to anticipate each other's intentions or actions. While generating these internal predictions is essential for constructive social behavior, their single neuronal basis and causal underpinnings are unknown. Here, we discover specific neurons in the primate dorsal anterior cingulate that selectively predict an opponent's yet unknown decision to invest in their common good or defect and distinct neurons that encode the monkey's own current decision based on prior outcomes. Mixed population predictions of the other was remarkably near optimal compared to behavioral decoders. Moreover, disrupting cingulate activity selectively biased mutually beneficial interactions between the monkeys but, surprisingly, had no influence on their decisions when no net-positive outcome was possible. These findings identify a group of other-predictive neurons in the primate anterior cingulate essential for enacting cooperative interactions and may pave a way toward the targeted treatment of social behavioral disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluating topic model interpretability from a primary care physician perspective.

PubMed

Arnold, Corey W; Oh, Andrea; Chen, Shawn; Speier, William

2016-02-01

Probabilistic topic models provide an unsupervised method for analyzing unstructured text. These models discover semantically coherent combinations of words (topics) that could be integrated in a clinical automatic summarization system for primary care physicians performing chart review. However, the human interpretability of topics discovered from clinical reports is unknown. Our objective is to assess the coherence of topics and their ability to represent the contents of clinical reports from a primary care physician's point of view. Three latent Dirichlet allocation models (50 topics, 100 topics, and 150 topics) were fit to a large collection of clinical reports. Topics were manually evaluated by primary care physicians and graduate students. Wilcoxon Signed-Rank Tests for Paired Samples were used to evaluate differences between different topic models, while differences in performance between students and primary care physicians (PCPs) were tested using Mann-Whitney U tests for each of the tasks. While the 150-topic model produced the best log likelihood, participants were most accurate at identifying words that did not belong in topics learned by the 100-topic model, suggesting that 100 topics provides better relative granularity of discovered semantic themes for the data set used in this study. Models were comparable in their ability to represent the contents of documents. Primary care physicians significantly outperformed students in both tasks. This work establishes a baseline of interpretability for topic models trained with clinical reports, and provides insights on the appropriateness of using topic models for informatics applications. Our results indicate that PCPs find discovered topics more coherent and representative of clinical reports relative to students, warranting further research into their use for automatic summarization. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Evaluating Topic Model Interpretability from a Primary Care Physician Perspective

PubMed Central

Arnold, Corey W.; Oh, Andrea; Chen, Shawn; Speier, William

2015-01-01

Background and Objective Probabilistic topic models provide an unsupervised method for analyzing unstructured text. These models discover semantically coherent combinations of words (topics) that could be integrated in a clinical automatic summarization system for primary care physicians performing chart review. However, the human interpretability of topics discovered from clinical reports is unknown. Our objective is to assess the coherence of topics and their ability to represent the contents of clinical reports from a primary care physician’s point of view. Methods Three latent Dirichlet allocation models (50 topics, 100 topics, and 150 topics) were fit to a large collection of clinical reports. Topics were manually evaluated by primary care physicians and graduate students. Wilcoxon Signed-Rank Tests for Paired Samples were used to evaluate differences between different topic models, while differences in performance between students and primary care physicians (PCPs) were tested using Mann-Whitney U tests for each of the tasks. Results While the 150-topic model produced the best log likelihood, participants were most accurate at identifying words that did not belong in topics learned by the 100-topic model, suggesting that 100 topics provides better relative granularity of discovered semantic themes for the data set used in this study. Models were comparable in their ability to represent the contents of documents. Primary care physicians significantly outperformed students in both tasks. Conclusion This work establishes a baseline of interpretability for topic models trained with clinical reports, and provides insights on the appropriateness of using topic models for informatics applications. Our results indicate that PCPs find discovered topics more coherent and representative of clinical reports relative to students, warranting further research into their use for automatic summarization. PMID:26614020

Surface ocean metabarcoding confirms limited diversity in planktonic foraminifera but reveals unknown hyper-abundant lineages.

PubMed

Morard, Raphaël; Garet-Delmas, Marie-José; Mahé, Frédéric; Romac, Sarah; Poulain, Julie; Kucera, Michal; de Vargas, Colomban

2018-02-07

Since the advent of DNA metabarcoding surveys, the planktonic realm is considered a treasure trove of diversity, inhabited by a small number of abundant taxa, and a hugely diverse and taxonomically uncharacterized consortium of rare species. Here we assess if the apparent underestimation of plankton diversity applies universally. We target planktonic foraminifera, a group of protists whose known morphological diversity is limited, taxonomically resolved and linked to ribosomal DNA barcodes. We generated a pyrosequencing dataset of ~100,000 partial 18S rRNA foraminiferal sequences from 32 size fractioned photic-zone plankton samples collected at 8 stations in the Indian and Atlantic Oceans during the Tara Oceans expedition (2009-2012). We identified 69 genetic types belonging to 41 morphotaxa in our metabarcoding dataset. The diversity saturated at local and regional scale as well as in the three size fractions and the two depths sampled indicating that the diversity of foraminifera is modest and finite. The large majority of the newly discovered lineages occur in the small size fraction, neglected by classical taxonomy. These unknown lineages dominate the bulk [>0.8 µm] size fraction, implying that a considerable part of the planktonic foraminifera community biomass has its origin in unknown lineages.

Contributions to the History of Astronomy, Vol. 3. (German Title: Beiträge zur Astronomiegeschichte, Band 3)

NASA Astrophysics Data System (ADS)

Dick, Wolfgang R.; Hamel, Jürgen

The main papers of this issue deal with previously unknown details of the foundation of the astronomical observatories in Gotha and in Königsberg (with numerous original documents by F.W. Bessel), with the Mecklenburg ordnance survey (1853-1873, with previously unknown letters by C.F. Gauss), with the merits of the Leipzig astronomer G.A. Jahn, with the internationality of the Astronomische Gesellschaft, and with early, previously little noted works on the expansion of the Universe. The issue contains a description of the important collection of sundials in the Kassel museum, discussions about the Medieval ``Phantom Period'', about Goethe's description of the zodiacal light, as well as obituaries and book reviews. Most papers in German, one in English.

Identifying OH Imposters in the ALFALFA HI Survey

NASA Astrophysics Data System (ADS)

Suess, Katherine; Darling, Jeremiah K.; Haynes, Martha P.; Giovanelli, Riccardo

2015-01-01

OH megamasers (OHMs) are rare, luminous molecular masers that are typically observed in (ultra) luminous infrared galaxies and serve as markers of major galaxy mergers. In blind emission line surveys such as the ALFALFA (Arecibo Legacy Fast Arecibo L-Band Feed Array) survey for neutral hydrogen (HI) in the local universe, OHMs at z~0.2 can mimic z~0.05 HI lines. We present the results of optical spectroscopy of ambiguous HI detections in the ALFALFA 40% data release [1] detected by WISE but with uncertain optical counterparts. The optical redshifts, obtained from observations at the Apache Point Observatory 3.5m telescope, identified 127 HI optical counterparts and discovered five new OHMs. Fifty-six candidates remain ambiguous. The new OHMs are the first detected in a blind spectral line survey.The number of OHMs in ALFALFA matches predictions based on the OH luminosity function [2]. Additionally, the OHMs found in a blind survey do not seem to differ from those found in previous targeted surveys. This provides validation of the methods used in previous IR-selected OHM surveys and indicates there is no previously unknown OHM-producing population at z~0.2. We also provide a method for future surveys to separate OH and HI lines without expensive spectral observations. This method utilizes infrared colors and magnitudes, such as WISE mid-IR data. Since the fraction of OHMs found in flux-limited HI surveys is expected to increase with the redshift of the survey [3], this analysis can be applied to future flux-limited high-redshift hydrogen surveys.We thank the ALFALFA team for observing and producing the survey dataset. The ALFALFA team at Cornell is supported by NSF AST-1107390 and the Brinson Foundation.[1] Haynes, M. P., R. Giovanelli, A. M. Martin, K. M. Hess, A. Saintonge, et al. 2011, Astron J, 142, 142[2] Darling, J. & R. Giovanelli 2002, Astrophys J, 572, 810[3] Briggs, F. H. 1998, A&A, 336, 815

Fault tectonics and earthquake hazards in parts of southern California. [penninsular ranges, Garlock fault, Salton Trough area, and western Mojave Desert

NASA Technical Reports Server (NTRS)

Merifield, P. M. (Principal Investigator); Lamar, D. L.; Gazley, C., Jr.; Lamar, J. V.; Stratton, R. H.

1976-01-01

The author has identified the following significant results. Four previously unknown faults were discovered in basement terrane of the Peninsular Ranges. These have been named the San Ysidro Creek fault, Thing Valley fault, Canyon City fault, and Warren Canyon fault. In addition fault gouge and breccia were recognized along the San Diego River fault. Study of features on Skylab imagery and review of geologic and seismic data suggest that the risk of a damaging earthquake is greater along the northwestern portion of the Elsinore fault than along the southeastern portion. Physiographic indicators of active faulting along the Garlock fault identifiable in Skylab imagery include scarps, linear ridges, shutter ridges, faceted ridges, linear valleys, undrained depressions and offset drainage. The following previously unrecognized fault segments are postulated for the Salton Trough Area: (1) An extension of a previously known fault in the San Andreas fault set located southeast of the Salton Sea; (2) An extension of the active San Jacinto fault zone along a tonal change in cultivated fields across Mexicali Valley ( the tonal change may represent different soil conditions along opposite sides of a fault). For the Skylab and LANDSAT images studied, pseudocolor transformations offer no advantages over the original images in the recognition of faults in Skylab and LANDSAT images. Alluvial deposits of different ages, a marble unit and iron oxide gossans of the Mojave Mining District are more readily differentiated on images prepared from ratios of individual bands of the S-192 multispectral scanner data. The San Andreas fault was also made more distinct in the 8/2 and 9/2 band ratios by enhancement of vegetation differences on opposite sides of the fault. Preliminary analysis indicates a significant earth resources potential for the discrimination of soil and rock types, including mineral alteration zones. This application should be actively pursued.

"Physics is supposed to be spoken of with a bit of irony": unknown speech by L D Landau, 8 April 1960

NASA Astrophysics Data System (ADS)

Druzhinin, P. A.

2018-01-01

A previously unknown speech by Lev Landau dated 8 April 1960 has been published, as transcribed from a unique tape recording obtained from the Russian State Phonogram Archive (Moscow). This is Landau's only true public speech known to have been recorded.

TIMING AND INTERSTELLAR SCATTERING OF 35 DISTANT PULSARS DISCOVERED IN THE PALFA SURVEY

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nice, D. J.; Altiere, E.; Farrington, D.

2013-07-20

We have made extensive observations of 35 distant slow (non-recycled) pulsars discovered in the ongoing Arecibo PALFA pulsar survey. Timing observations of these pulsars over several years at Arecibo Observatory and Jodrell Bank Observatory have yielded high-precision positions and measurements of rotation properties. Despite being a relatively distant population, these pulsars have properties that mirror those of the previously known pulsar population. Many of the sources exhibit timing noise, and one underwent a small glitch. We have used multifrequency data to measure the interstellar scattering properties of these pulsars. We find scattering to be higher than predicted along some linesmore » of sight, particularly in the Cygnus region. Finally, we present XMM-Newton and Chandra observations of the youngest and most energetic of the pulsars, J1856+0245, which has previously been associated with the GeV-TeV pulsar wind nebula HESS J1857+026.« less

Genotyping by Sequencing Using Specific Allelic Capture to Build a High-Density Genetic Map of Durum Wheat

PubMed Central

Holtz, Yan; Ardisson, Morgane; Ranwez, Vincent; Besnard, Alban; Leroy, Philippe; Poux, Gérard; Roumet, Pierre; Viader, Véronique; Santoni, Sylvain; David, Jacques

2016-01-01

Targeted sequence capture is a promising technology which helps reduce costs for sequencing and genotyping numerous genomic regions in large sets of individuals. Bait sequences are designed to capture specific alleles previously discovered in parents or reference populations. We studied a set of 135 RILs originating from a cross between an emmer cultivar (Dic2) and a recent durum elite cultivar (Silur). Six thousand sequence baits were designed to target Dic2 vs. Silur polymorphisms discovered in a previous RNAseq study. These baits were exposed to genomic DNA of the RIL population. Eighty percent of the targeted SNPs were recovered, 65% of which were of high quality and coverage. The final high density genetic map consisted of more than 3,000 markers, whose genetic and physical mapping were consistent with those obtained with large arrays. PMID:27171472

An early sophisticated East Polynesian voyaging canoe discovered on New Zealand's coast

PubMed Central

Johns, Dilys A.; Irwin, Geoffrey J.; Sung, Yun K.

2014-01-01

The colonization of the islands of East Polynesia was a remarkable episode in the history of human migration and seafaring. We report on an ocean-sailing canoe dating from close to that time. A large section of a complex composite canoe was discovered recently at Anaweka on the New Zealand coast. The canoe dates to approximately A.D. 1400 and was contemporary with continuing interisland voyaging. It was built in New Zealand as an early adaptation to a new environment, and a sea turtle carved on its hull makes symbolic connections with wider Polynesian culture and art. We describe the find and identify and radiocarbon date the construction materials. We present a reconstruction of the whole canoe and compare it to another early canoe previously discovered in the Society Islands. PMID:25267657

Troponin T3 regulates nuclear localization of the calcium channel Ca{sub v}β{sub 1a} subunit in skeletal muscle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Tan; Taylor, Jackson; Jiang, Yang

The voltage-gated calcium channel (Ca{sub v}) β{sub 1a} subunit (Ca{sub v}β{sub 1a}) plays an important role in excitation–contraction coupling (ECC), a process in the myoplasm that leads to muscle-force generation. Recently, we discovered that the Ca{sub v}β{sub 1a} subunit travels to the nucleus of skeletal muscle cells where it helps to regulate gene transcription. To determine how it travels to the nucleus, we performed a yeast two-hybrid screening of the mouse fast skeletal muscle cDNA library and identified an interaction with troponin T3 (TnT3), which we subsequently confirmed by co-immunoprecipitation and co-localization assays in mouse skeletal muscle in vivo andmore » in cultured C2C12 muscle cells. Interacting domains were mapped to the leucine zipper domain in TnT3 COOH-terminus (160–244 aa) and Ca{sub v}β{sub 1a} NH{sub 2}-terminus (1–99 aa), respectively. The double fluorescence assay in C2C12 cells co-expressing TnT3/DsRed and Ca{sub v}β{sub 1a}/YFP shows that TnT3 facilitates Ca{sub v}β{sub 1a} nuclear recruitment, suggesting that the two proteins play a heretofore unknown role during early muscle differentiation in addition to their classical role in ECC regulation. - Highlights: • Previously, we demonstrated that Ca{sub v}β{sub 1a} is a gene transcription regulator. • Here, we show that TnT3 interacts with Ca{sub v}β{sub 1a}. • We mapped TnT3 and Ca{sub v}β{sub 1a} interaction domain. • TnT3 facilitates Ca{sub v}β{sub 1a} nuclear enrichment. • The two proteins play a heretofore unknown role during early muscle differentiation.« less

Algorithms for searching Fast radio bursts and pulsars in tight binary systems.

NASA Astrophysics Data System (ADS)

Zackay, Barak

2017-01-01

Fast radio bursts (FRB's) are an exciting, recently discovered, astrophysical transients which their origins are unknown.Currently, these bursts are believed to be coming from cosmological distances, allowing us to probe the electron content on cosmological length scales. Even though their precise localization is crucial for the determination of their origin, radio interferometers were not extensively employed in searching for them due to computational limitations.I will briefly present the Fast Dispersion Measure Transform (FDMT) algorithm,that allows to reduce the operation count in blind incoherent dedispersion by 2-3 orders of magnitude.In addition, FDMT enables to probe the unexplored domain of sub-microsecond astrophysical pulses.Pulsars in tight binary systems are among the most important astrophysical objects as they provide us our best tests of general relativity in the strong field regime.I will provide a preview to a novel algorithm that enables the detection of pulsars in short binary systems using observation times longer than an orbital period.Current pulsar search programs limit their searches for integration times shorter than a few percents of the orbital period.Until now, searching for pulsars in binary systems using observation times longer than an orbital period was considered impossible as one has to blindly enumerate all options for the Keplerian parameters, the pulsar rotation period, and the unknown DM.Using the current state of the art pulsar search techniques and all computers on the earth, such an enumeration would take longer than a Hubble time. I will demonstrate that using the new algorithm, it is possible to conduct such an enumeration on a laptop using real data of the double pulsar PSR J0737-3039.Among the other applications of this algorithm are:1) Searching for all pulsars on all sky positions in gamma ray observations of the Fermi LAT satellite.2) Blind searching for continuous gravitational wave sources emitted by pulsars with non-axis-symmetric matter distribution.Previous attempts to conduct all of the above searches contained substantial sensitivity compromises.

Evolution of the B7 family: co-evolution of B7H6 and NKp30, identification of a new B7 family member, B7H7, and of B7's historical relationship with the MHC.

PubMed

Flajnik, Martin F; Tlapakova, Tereza; Criscitiello, Michael F; Krylov, Vladimir; Ohta, Yuko

2012-08-01

The B7 family of genes is essential in the regulation of the adaptive immune system. Most B7 family members contain both variable (V)- and constant (C)-type domains of the immunoglobulin superfamily (IgSF). Through in silico screening of the Xenopus genome and subsequent phylogenetic analysis, we found novel genes belonging to the B7 family, one of which is the recently discovered B7H6. Humans and rats have a single B7H6 gene; however, many B7H6 genes were detected in a single large cluster in the Xenopus genome. The B7H6 expression patterns also varied in a species-specific manner. Human B7H6 binds to the activating natural killer receptor, NKp30. While the NKp30 gene is single-copy and maps to the MHC in most vertebrates, many Xenopus NKp30 genes were found in a cluster on a separate chromosome that does not harbor the MHC. Indeed, in all species so far analyzed from sharks to mammals, the number of NKp30 and B7H6 genes correlates well, suggestive of receptor-ligand co-evolution. Furthermore, we identified a Xenopus-specific B7 homolog (B7HXen) and revealed its close linkage to B2M, which we have demonstrated previously to have been originally encoded in the MHC. Thus, our study provides further proof that the B7 precursor was included in the proto MHC. Additionally, the comparative analysis revealed a new B7 family member, B7H7, which was previously designated in the literature as an unknown gene, HHLA2.

Similar Genetic Architecture with Shared and Unique Quantitative Trait Loci for Bacterial Cold Water Disease Resistance in Two Rainbow Trout Breeding Populations

PubMed Central

Vallejo, Roger L.; Liu, Sixin; Gao, Guangtu; Fragomeni, Breno O.; Hernandez, Alvaro G.; Leeds, Timothy D.; Parsons, James E.; Martin, Kyle E.; Evenhuis, Jason P.; Welch, Timothy J.; Wiens, Gregory D.; Palti, Yniv

2017-01-01

Bacterial cold water disease (BCWD) causes significant mortality and economic losses in salmonid aquaculture. In previous studies, we identified moderate-large effect quantitative trait loci (QTL) for BCWD resistance in rainbow trout (Oncorhynchus mykiss). However, the recent availability of a 57 K SNP array and a reference genome assembly have enabled us to conduct genome-wide association studies (GWAS) that overcome several experimental limitations from our previous work. In the current study, we conducted GWAS for BCWD resistance in two rainbow trout breeding populations using two genotyping platforms, the 57 K Affymetrix SNP array and restriction-associated DNA (RAD) sequencing. Overall, we identified 14 moderate-large effect QTL that explained up to 60.8% of the genetic variance in one of the two populations and 27.7% in the other. Four of these QTL were found in both populations explaining a substantial proportion of the variance, although major differences were also detected between the two populations. Our results confirm that BCWD resistance is controlled by the oligogenic inheritance of few moderate-large effect loci and a large-unknown number of loci each having a small effect on BCWD resistance. We detected differences in QTL number and genome location between two GWAS models (weighted single-step GBLUP and Bayes B), which highlights the utility of using different models to uncover QTL. The RAD-SNPs detected a greater number of QTL than the 57 K SNP array in one population, suggesting that the RAD-SNPs may uncover polymorphisms that are more unique and informative for the specific population in which they were discovered. PMID:29109734

Similar Genetic Architecture with Shared and Unique Quantitative Trait Loci for Bacterial Cold Water Disease Resistance in Two Rainbow Trout Breeding Populations.

PubMed

Vallejo, Roger L; Liu, Sixin; Gao, Guangtu; Fragomeni, Breno O; Hernandez, Alvaro G; Leeds, Timothy D; Parsons, James E; Martin, Kyle E; Evenhuis, Jason P; Welch, Timothy J; Wiens, Gregory D; Palti, Yniv

2017-01-01

Bacterial cold water disease (BCWD) causes significant mortality and economic losses in salmonid aquaculture. In previous studies, we identified moderate-large effect quantitative trait loci (QTL) for BCWD resistance in rainbow trout ( Oncorhynchus mykiss ). However, the recent availability of a 57 K SNP array and a reference genome assembly have enabled us to conduct genome-wide association studies (GWAS) that overcome several experimental limitations from our previous work. In the current study, we conducted GWAS for BCWD resistance in two rainbow trout breeding populations using two genotyping platforms, the 57 K Affymetrix SNP array and restriction-associated DNA (RAD) sequencing. Overall, we identified 14 moderate-large effect QTL that explained up to 60.8% of the genetic variance in one of the two populations and 27.7% in the other. Four of these QTL were found in both populations explaining a substantial proportion of the variance, although major differences were also detected between the two populations. Our results confirm that BCWD resistance is controlled by the oligogenic inheritance of few moderate-large effect loci and a large-unknown number of loci each having a small effect on BCWD resistance. We detected differences in QTL number and genome location between two GWAS models (weighted single-step GBLUP and Bayes B), which highlights the utility of using different models to uncover QTL. The RAD-SNPs detected a greater number of QTL than the 57 K SNP array in one population, suggesting that the RAD-SNPs may uncover polymorphisms that are more unique and informative for the specific population in which they were discovered.

The developmental basis of an evolutionary diversification of female gametophyte structure in Piper and Piperaceae

PubMed Central

Madrid, Eric N.; Friedman, William E.

2009-01-01

Background and Aims Fritillaria-type female gametophyte development is a complex, yet homoplasious developmental pattern that is interesting from both evolutionary and developmental perspectives. Piper (Piperaceae) was chosen for this study of Fritillaria-type female gametophyte development because Piperales represent a ‘hotspot’ of female gametophyte developmental evolution and have been the subject of several recent molecular phylogenetic analyses. This wealth of phylogenetic and descriptive data make Piper an excellent candidate for inferring the evolutionary developmental basis for the origin of Fritillaria-type female gametophytes. Methods Developing ovules of Piper peltatum were taken from greenhouse collections, embedded in glycol methacrylate, and serially sectioned. Light microscopy and laser scanning confocal microscopy were combined to produce three-dimensional computer reconstructions of developing female gametophytes. The ploidies of the developing embryos and endosperms were calculated using microspectrofluorometry. Key Results The data describe female gametophyte development in Piper with highly detailed three-dimensional models, and document two previously unknown arrangements of megaspore nuclei during early development. Also collected were microspectrofluorometric data that indicate that Fritillaria-type female gametophyte development in Piper results in pentaploid endosperm. Conclusions The three-dimensional models resolve previous ambiguities in developmental interpretations of Fritillaria-type female gametophytes in Piper. The newly discovered arrangements of megaspore nuclei that are described allow for the construction of explicit hypotheses of female gametophyte developmental evolution within Piperaceae, and more broadly throughout Piperales. These detailed hypotheses indicate that the common ancestor of Piperaceae minus Verhuellia had a Drusa-type female gametophyte, and that evolutionary transitions to derived tetrasporic female gametophyte ontogenies in Piperaceae, including Fritillaria-type female gametophyte development, are the consequence of key nuclear migration and patterning events at the end of megasporogenesis. PMID:19202137

The Use of Simulation to Reduce the Domain of "Black Swans" with Application to Hurricane Impacts to Power Systems.

PubMed

Berner, Christine L; Staid, Andrea; Flage, Roger; Guikema, Seth D

2017-10-01

Recently, the concept of black swans has gained increased attention in the fields of risk assessment and risk management. Different types of black swans have been suggested, distinguishing between unknown unknowns (nothing in the past can convincingly point to its occurrence), unknown knowns (known to some, but not to relevant analysts), or known knowns where the probability of occurrence is judged as negligible. Traditional risk assessments have been questioned, as their standard probabilistic methods may not be capable of predicting or even identifying these rare and extreme events, thus creating a source of possible black swans. In this article, we show how a simulation model can be used to identify previously unknown potentially extreme events that if not identified and treated could occur as black swans. We show that by manipulating a verified and validated model used to predict the impacts of hazards on a system of interest, we can identify hazard conditions not previously experienced that could lead to impacts much larger than any previous level of impact. This makes these potential black swan events known and allows risk managers to more fully consider them. We demonstrate this method using a model developed to evaluate the effect of hurricanes on energy systems in the United States; we identify hurricanes with potentially extreme impacts, storms well beyond what the historic record suggests is possible in terms of impacts. © 2016 Society for Risk Analysis.

MOPITT V4 processing error

Atmospheric Science Data Center

2013-08-06

... error Version 4 The MOPITT/NCAR team discovered a data processing error that affects all V4 products previously ... products are available on  News and Status on the MOPITT team web site . Data Product New V4 Product Version(s) ...

VLT/X-shooter Spectroscopy of a dusty planetary nebula discovered with Spitzer/IRS

NASA Astrophysics Data System (ADS)

Oliveira, I.; Overzier, R. A.; Pontoppidan, K. M.; van Dishoeck, E. F.; Spezzi, L.

2011-02-01

As part of a mid-infrared spectroscopic survey of young stars with the Spitzer Space Telescope, an unclassified red emission line object was discovered. Based on its high ionization state indicated by the Spitzer spectrum, this object could either be a dusty supernova remnant (SNR) or a planetary nebula (PN). In this research note, the object is classified and the available spectroscopic data are presented to the community for further analysis. UV/optical/NIR spectra were obtained during the science verification run of the VLT/X-shooter. A large number of emission lines are identified allowing the determination of the nature of this object. The presence of strong, narrow (Δv ~8 - 74 km s-1) emission lines, combined with very low line ratios of, e.g., [N ii]/Hα and [S ii]/Hα show that the object is a PN that lies at an undetermined distance behind the Serpens Molecular Cloud. This illustrates the potential of X-shooter as an efficient tool for constraining the nature of faint sources with unknown spectral properties or colors.

Recognizing the 35th anniversary of the proposal that snRNPs are involved in splicing.

PubMed

Mount, Stephen M; Wolin, Sandra L

2015-10-15

Thirty-five years ago, as young graduate students, we had the pleasure and privilege of being in Joan Steitz's laboratory at a pivotal point in the history of RNA molecular biology. Introns had recently been discovered in the laboratories of Philip Sharp and Richard Roberts, but the machinery for removing them from mRNA precursors was entirely unknown. This Retrospective describes our hypothesis that recently discovered snRNPs functioned in pre-mRNA splicing. The proposal was proven correct, as has Joan's intuition that small RNAs provide specificity to RNA processing reactions through base pairing in diverse settings. However, research over the intervening years has revealed that both splice site selection and splicing itself are much more complex and dynamic than we imagined. © 2015 Mount and Wolin. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

On the unsupervised analysis of domain-specific Chinese texts

PubMed Central

Deng, Ke; Bol, Peter K.; Li, Kate J.; Liu, Jun S.

2016-01-01

With the growing availability of digitized text data both publicly and privately, there is a great need for effective computational tools to automatically extract information from texts. Because the Chinese language differs most significantly from alphabet-based languages in not specifying word boundaries, most existing Chinese text-mining methods require a prespecified vocabulary and/or a large relevant training corpus, which may not be available in some applications. We introduce an unsupervised method, top-down word discovery and segmentation (TopWORDS), for simultaneously discovering and segmenting words and phrases from large volumes of unstructured Chinese texts, and propose ways to order discovered words and conduct higher-level context analyses. TopWORDS is particularly useful for mining online and domain-specific texts where the underlying vocabulary is unknown or the texts of interest differ significantly from available training corpora. When outputs from TopWORDS are fed into context analysis tools such as topic modeling, word embedding, and association pattern finding, the results are as good as or better than that from using outputs of a supervised segmentation method. PMID:27185919

Physical modeling in geomorphology: are boundary conditions necessary?

NASA Astrophysics Data System (ADS)

Cantelli, A.

2012-12-01

Referring to the physical experimental design in geomorphology, boundary conditions are key elements that determine the quality of the results and therefore the study development. For years engineers have modeled structures, such as dams and bridges, with high precision and excellent results. Until the last decade, a great part of the physical experimental work in geomorphology has been developed with an engineer-like approach, requiring an accurate scaling analysis to determine inflow parameters and initial geometrical conditions. However, during the last decade, the way we have been approaching physical experiments has significantly changed. In particular, boundary conditions and initial conditions are considered unknown factors that need to be discovered during the experiment. This new philosophy leads to a more demanding data acquisition process but relaxes the obligation to a priori know the appropriate input and initial conditions and provides the flexibility to discover those data. Here I am going to present some practical examples of this experimental approach in deepwater geomorphology; some questions about scaling of turbidity currents and a new large experimental facility built at the Universidade Federal do Rio Grande do Sul, Brasil.

A structural-alphabet-based strategy for finding structural motifs across protein families

PubMed Central

Wu, Chih Yuan; Chen, Yao Chi; Lim, Carmay

2010-01-01

Proteins with insignificant sequence and overall structure similarity may still share locally conserved contiguous structural segments; i.e. structural/3D motifs. Most methods for finding 3D motifs require a known motif to search for other similar structures or functionally/structurally crucial residues. Here, without requiring a query motif or essential residues, a fully automated method for discovering 3D motifs of various sizes across protein families with different folds based on a 16-letter structural alphabet is presented. It was applied to structurally non-redundant proteins bound to DNA, RNA, obligate/non-obligate proteins as well as free DNA-binding proteins (DBPs) and proteins with known structures but unknown function. Its usefulness was illustrated by analyzing the 3D motifs found in DBPs. A non-specific motif was found with a ‘corner’ architecture that confers a stable scaffold and enables diverse interactions, making it suitable for binding not only DNA but also RNA and proteins. Furthermore, DNA-specific motifs present ‘only’ in DBPs were discovered. The motifs found can provide useful guidelines in detecting binding sites and computational protein redesign. PMID:20525797

A Scientometric Prediction of the Discovery of the First Potentially Habitable Planet with a Mass Similar to Earth

PubMed Central

Arbesman, Samuel; Laughlin, Gregory

2010-01-01

Background The search for a habitable extrasolar planet has long interested scientists, but only recently have the tools become available to search for such planets. In the past decades, the number of known extrasolar planets has ballooned into the hundreds, and with it, the expectation that the discovery of the first Earth-like extrasolar planet is not far off. Methodology/Principal Findings Here, we develop a novel metric of habitability for discovered planets and use this to arrive at a prediction for when the first habitable planet will be discovered. Using a bootstrap analysis of currently discovered exoplanets, we predict the discovery of the first Earth-like planet to be announced in the first half of 2011, with the likeliest date being early May 2011. Conclusions/Significance Our predictions, using only the properties of previously discovered exoplanets, accord well with external estimates for the discovery of the first potentially habitable extrasolar planet and highlight the the usefulness of predictive scientometric techniques to understand the pace of scientific discovery in many fields. PMID:20957226

A Search for Small Distant Moons of Neptune

NASA Astrophysics Data System (ADS)

Holman, Matthew; Kavelaars, Jj; Gladman, Brett; Petit, Jean-Marc; Grav, Tommy; Nicholson, Philip

2002-08-01

With many new jovian, saturnian, and uranian irregular satellites having been discovered in the last few years, our attention naturally falls upon Neptune. In 1999, we conducted a search for neptunian satellites covering about 8 square degrees (almost the entire stable region around the planet). This survey yielded no new satellites down to R magnitude 24. We interpreted this as supporting a violent destruction of the Neptunian outer satellite system as Triton was captured. However, there were good reasons to believe that the largest un-discovered Neptune satellites lay just beyond the previous survey's magnitude limit. In August 2001, we used the mosaic camera on the Blanco 4-m to push down to m_R~eq25.5, to test this hypothesis. We discovered two neptunian satellites candidates. Using the time available after Neptune had set, we also discovered four faint uranian satellite candidates. However, poor weather at Palomar and Magellan in September 2001 and instrumental problems on the VLT in November 2001 prevented the tracking these candidates to conclusively prove that they are moons. We request time to repeat last summer's search and "re- discover" these moons, armed with the knowledge that they are there as well as having assured access to large-aperture southern hemisphere tracking time (on VLT and Magellan).

First early Mesozoic amber in the Western Hemisphere

USGS Publications Warehouse

Litwin, R.J.; Ash, S.R.

1991-01-01

Detrital amber pebbles and granules have been discovered in Upper Triassic strata on the Colorado Plateau. Although amber previously has been reported from Pennsylvanian, Jurassic, Cretaceous, and Tertiary strata, we know of no other reported Triassic occurrence in North America or the Western Hemisphere. The new discovered occurrences of amber are at two localities in the lower part of the Petrified Forest Member of the Upper Triassic Chinle Formation in Petrified Forest National Park, Arizona. The paper coals and carbonaceous paper shales containing the amber also contain fossil palynomorph assemblages that indicate a late Carnian age for these occurrences. -Authors

A new species of Andean toad (Bufonidae, Osornophryne) discovered using molecular and morphological data, with a taxonomic key for the genus

PubMed Central

Páez-Moscoso, Diego J.; Guayasamin, Juan M.; Yánez-Muñoz, Mario

2011-01-01

Abstract Combining a molecular phylogeny and morphological data, we discovered a new species of Osornophryne from the Amazonian slope of the Ecuadorian Andes. Morphologically, the new taxon is distinguished from all others species in Osornophryne by having the Toes IV and V longer than Toes I–III, a short and rounded snout with a small rostral papilla, and conical pustules on flanks. The new species previously was confused with Osornophryne guacamayo. A taxonomic key is provided for all known species of Osornophryne. PMID:21852930

Comparing the Effects of Unknown-Known Ratios on Word Reading Learning versus Learning Rates

ERIC Educational Resources Information Center

Joseph, Laurice M.; Nist, Lindsay M.

2006-01-01

An extension of G. L. Cates et al. (2003) investigation was conducted to determine if students' cumulative learning rates would be superior for words read under a traditional drill and practice condition (as they were for spelling in the previous study) than under interspersal conditions of varying ratios of unknown to known words. Participants…

Marivaux and La Commere (The Gossip)

ERIC Educational Resources Information Center

Trapnall, William H., Jr.

1970-01-01

Compares two Marivaux works: the novel of 1735, "Le Paysan parvenu" ("The Upstart Peasant") and the one-act comedy, "La Commere" ("The Gossip") not previously published until 1966. Questions, by analyzing the character portrayals, whether the discovered manuscript was penned by Marivaux. (DS)

'Unknown' proteins and 'orphan' enzymes: the missing half of the engineering parts list--and how to find it.

PubMed

Hanson, Andrew D; Pribat, Anne; Waller, Jeffrey C; de Crécy-Lagard, Valérie

2009-12-14

Like other forms of engineering, metabolic engineering requires knowledge of the components (the 'parts list') of the target system. Lack of such knowledge impairs both rational engineering design and diagnosis of the reasons for failures; it also poses problems for the related field of metabolic reconstruction, which uses a cell's parts list to recreate its metabolic activities in silico. Despite spectacular progress in genome sequencing, the parts lists for most organisms that we seek to manipulate remain highly incomplete, due to the dual problem of 'unknown' proteins and 'orphan' enzymes. The former are all the proteins deduced from genome sequence that have no known function, and the latter are all the enzymes described in the literature (and often catalogued in the EC database) for which no corresponding gene has been reported. Unknown proteins constitute up to about half of the proteins in prokaryotic genomes, and much more than this in higher plants and animals. Orphan enzymes make up more than a third of the EC database. Attacking the 'missing parts list' problem is accordingly one of the great challenges for post-genomic biology, and a tremendous opportunity to discover new facets of life's machinery. Success will require a co-ordinated community-wide attack, sustained over years. In this attack, comparative genomics is probably the single most effective strategy, for it can reliably predict functions for unknown proteins and genes for orphan enzymes. Furthermore, it is cost-efficient and increasingly straightforward to deploy owing to a proliferation of databases and associated tools.

Two antibacterial C-type lectins from crustacean, Eriocheir sinensis, stimulated cellular encapsulation in vitro.

PubMed

Jin, Xing-Kun; Li, Shuang; Guo, Xiao-Nv; Cheng, Lin; Wu, Min-Hao; Tan, Shang-Jian; Zhu, You-Ting; Yu, Ai-Qing; Li, Wei-Wei; Wang, Qun

2013-12-01

The first step of host fighting against pathogens is that pattern recognition receptors recognized pathogen-associated molecular patterns. However, the specificity of recognition within the innate immune molecular of invertebrates remains largely unknown. In the present study, we investigated how invertebrate pattern recognition receptor (PRR) C-type lectins might be involved in the antimicrobial response in crustacean. Based on our previously obtained completed coding regions of EsLecA and EsLecG in Eriocheir sinensis, the recombinant EsLectin proteins were produced via prokaryotic expression system and affinity chromatography. Subsequently, both rEsLecA and rEsLecG were discovered to have wide spectrum binding activities towards microorganisms, and their microbial-binding was calcium-independent. Moreover, the binding activities of both rEsLecA and rEsLecG induced the aggregation against microbial pathogens. Both microorganism growth inhibitory activities assays and antibacterial activities assays revealed their capabilities of suppressing microorganisms growth and directly killing microorganisms respectively. Furthermore, the encapsulation assays signified that both rEsLecA and rEsLecG could stimulate the cellular encapsulation in vitro. Collectively, data presented here demonstrated the successful expression and purification of two C-type lectins proteins in the Chinese mitten crab, and their critical role in the innate immune system of an invertebrate. Copyright © 2013 Elsevier Ltd. All rights reserved.

Metabolization and degradation kinetics of the urban-use pesticide fipronil by white rot fungus Trametes versicolor.

PubMed

Wolfand, Jordyn M; LeFevre, Gregory H; Luthy, Richard G

2016-10-12

Fipronil is a recalcitrant phenylpyrazole-based pesticide used for flea/tick treatment and termite control that is distributed in urban aquatic environments via stormwater and contributes to stream toxicity. We discovered that fipronil is rapidly metabolized (t 1/2 = 4.2 d) by the white rot fungus Trametes versicolor to fipronil sulfone and multiple previously unknown fipronil transformation products, lowering fipronil concentration by 96.5%. Using an LC-QTOF-MS untargeted metabolomics approach, we identified four novel fipronil fungal transformation products: hydroxylated fipronil sulfone, glycosylated fipronil sulfone, and two compounds with unresolved structures. These results are consistent with identified enzymatic detoxification pathways wherein conjugation with sugar moieties follows initial ring functionalization (hydroxylation). The proposed pathway is supported by kinetic evidence of transformation product formation. Fipronil loss by sorption, hydrolysis, and photolysis was negligible. When T. versicolor was exposed to the cytochrome P450 enzyme inhibitor 1-aminobenzotriazole, oxidation of fipronil and production of hydroxylated and glycosylated transformation products significantly decreased (p = 0.038, 0.0037, 0.0023, respectively), indicating that fipronil is metabolized intracellularly by cytochrome P450 enzymes. Elucidating fipronil transformation products is critical because pesticide target specificity can be lost via structural alteration, broadening classes of impacted organisms. Integration of fungi in engineered natural treatment systems could be a viable strategy for pesticide removal from stormwater runoff.

The Sungrazer Citizen Science Project

NASA Astrophysics Data System (ADS)

Battams, K.

2016-12-01

The NASA-funded Sungrazer Project is one of the oldest and most successful Citizen Science projects, having more than doubled the number of officially designated comets since it became public in 2002. The Sungrazer Project has enabled the discovery of more than 3,100 previously unknown near-Sun and Sungrazing comets in images returned by the joint ESA-NASA Solar and Heliospheric Observatory (SOHO), which was launched in 1995, and the NASA Solar Terrestrial Relations Observatories (STEREO), launched in 2006. The Sungrazer Project offers a centralized web site for amateur astronomers ("comet hunters") to report potential comets in SOHO and STEREO data, which the Project PI then confirms/rejects. It is then the task of the Project PI to perform precise astrometric measurements of all new comets, and supply the resulting data to the Minor Planet Center for official orbit determinations and designation. Almost 100 individuals from all over the world have discovered comets via the Project, with successful participants as young as 13-years old. In this talk I will discuss the history of the project, report the current discovery statistics, and highlight a few of the major discoveries enabled by the Project. I will also discuss the logistic of the program, participation requirements, day-to-day operations, and outreach efforts. Finally I will present an outlook for the project with respect to future space-based heliophysics missions.

The synthesis and characterisation of MDMA derived from a catalytic oxidation of material isolated from black pepper reveals potential route specific impurities.

PubMed

Plummer, Christopher M; Breadon, Thomas W; Pearson, James R; Jones, Oliver A H

2016-05-01

This work examines the chemical synthesis of 3,4-methylenedioxy-N-methylamphetamine (MDMA) from piperonal prepared via a catalytic ruthenium tetroxide oxidation of piperine extracted from black pepper. A variety of oxidation conditions were experimented with including different solvent systems and co-oxidants. A sample of prepared piperonal was successfully converted into MDMA via 3,4-methylenedioxyphenyl-2-nitropropene (MDP2NP) and 3,4-methylenedioxyphenyl-2-propanone (MDP2P) and the impurities within each product characterised by GC-MS to give a contaminant profile of the synthetic pathway. Interestingly, it was discovered that a chlorinated analogue of piperonal (6-chloropiperonal) was created during the oxidation process by an as yet unknown mechanism. This impurity reacted alongside piperonal to give chlorinated analogues of each precursor, ultimately yielding 2-chloro-4,5-methylenedioxymethamphetamine (6-Cl-MDMA) as an impurity within the MDMA sample. The methodology developed is a simple way to synthesise a substantial amount of precursor material with easy to obtain reagents. The results also show that chlorinated MDMA analogues, previously thought to be deliberately included adulterants, may in fact be route specific impurities with potential application in determining the origin and synthesis method of seized illicit drugs. Copyright © 2016 The Chartered Society of Forensic Sciences. Published by Elsevier Ireland Ltd. All rights reserved.

Formin Is Associated with Left-Right Asymmetry in the Pond Snail and the Frog.

PubMed

Davison, Angus; McDowell, Gary S; Holden, Jennifer M; Johnson, Harriet F; Koutsovoulos, Georgios D; Liu, M Maureen; Hulpiau, Paco; Van Roy, Frans; Wade, Christopher M; Banerjee, Ruby; Yang, Fengtang; Chiba, Satoshi; Davey, John W; Jackson, Daniel J; Levin, Michael; Blaxter, Mark L

2016-03-07

While components of the pathway that establishes left-right asymmetry have been identified in diverse animals, from vertebrates to flies, it is striking that the genes involved in the first symmetry-breaking step remain wholly unknown in the most obviously chiral animals, the gastropod snails. Previously, research on snails was used to show that left-right signaling of Nodal, downstream of symmetry breaking, may be an ancestral feature of the Bilateria [1 and 2]. Here, we report that a disabling mutation in one copy of a tandemly duplicated, diaphanous-related formin is perfectly associated with symmetry breaking in the pond snail. This is supported by the observation that an anti-formin drug treatment converts dextral snail embryos to a sinistral phenocopy, and in frogs, drug inhibition or overexpression by microinjection of formin has a chirality-randomizing effect in early (pre-cilia) embryos. Contrary to expectations based on existing models [3, 4 and 5], we discovered asymmetric gene expression in 2- and 4-cell snail embryos, preceding morphological asymmetry. As the formin-actin filament has been shown to be part of an asymmetry-breaking switch in vitro [6 and 7], together these results are consistent with the view that animals with diverse body plans may derive their asymmetries from the same intracellular chiral elements [8]. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

A quantitative proteomics approach identifies ETV6 and IKZF1 as new regulators of an ERG-driven transcriptional network

PubMed Central

Unnikrishnan, Ashwin; Guan, Yi F.; Huang, Yizhou; Beck, Dominik; Thoms, Julie A. I.; Peirs, Sofie; Knezevic, Kathy; Ma, Shiyong; de Walle, Inge V.; de Jong, Ineke; Ali, Zara; Zhong, Ling; Raftery, Mark J.; Taghon, Tom; Larsson, Jonas; MacKenzie, Karen L.; Van Vlierberghe, Pieter; Wong, Jason W. H.; Pimanda, John E.

2016-01-01

Aberrant stem cell-like gene regulatory networks are a feature of leukaemogenesis. The ETS-related gene (ERG), an important regulator of normal haematopoiesis, is also highly expressed in T-ALL and acute myeloid leukaemia (AML). However, the transcriptional regulation of ERG in leukaemic cells remains poorly understood. In order to discover transcriptional regulators of ERG, we employed a quantitative mass spectrometry-based method to identify factors binding the 321 bp ERG +85 stem cell enhancer region in MOLT-4 T-ALL and KG-1 AML cells. Using this approach, we identified a number of known binders of the +85 enhancer in leukaemic cells along with previously unknown binders, including ETV6 and IKZF1. We confirmed that ETV6 and IKZF1 were also bound at the +85 enhancer in both leukaemic cells and in healthy human CD34+ haematopoietic stem and progenitor cells. Knockdown experiments confirmed that ETV6 and IKZF1 are transcriptional regulators not just of ERG, but also of a number of genes regulated by a densely interconnected network of seven transcription factors. At last, we show that ETV6 and IKZF1 expression levels are positively correlated with expression of a number of heptad genes in AML and high expression of all nine genes confers poorer overall prognosis. PMID:27604872

Early and middle holocene hunter-gatherer occupations in western Amazonia: the hidden shell middens.

PubMed

Lombardo, Umberto; Szabo, Katherine; Capriles, José M; May, Jan-Hendrik; Amelung, Wulf; Hutterer, Rainer; Lehndorff, Eva; Plotzki, Anna; Veit, Heinz

2013-01-01

We report on previously unknown early archaeological sites in the Bolivian lowlands, demonstrating for the first time early and middle Holocene human presence in western Amazonia. Multidisciplinary research in forest islands situated in seasonally-inundated savannahs has revealed stratified shell middens produced by human foragers as early as 10,000 years ago, making them the oldest archaeological sites in the region. The absence of stone resources and partial burial by recent alluvial sediments has meant that these kinds of deposits have, until now, remained unidentified. We conducted core sampling, archaeological excavations and an interdisciplinary study of the stratigraphy and recovered materials from three shell midden mounds. Based on multiple lines of evidence, including radiocarbon dating, sedimentary proxies (elements, steroids and black carbon), micromorphology and faunal analysis, we demonstrate the anthropogenic origin and antiquity of these sites. In a tropical and geomorphologically active landscape often considered challenging both for early human occupation and for the preservation of hunter-gatherer sites, the newly discovered shell middens provide evidence for early to middle Holocene occupation and illustrate the potential for identifying and interpreting early open-air archaeological sites in western Amazonia. The existence of early hunter-gatherer sites in the Bolivian lowlands sheds new light on the region's past and offers a new context within which the late Holocene "Earthmovers" of the Llanos de Moxos could have emerged.

Schizophrenia interactome with 504 novel protein–protein interactions

PubMed Central

Ganapathiraju, Madhavi K; Thahir, Mohamed; Handen, Adam; Sarkar, Saumendra N; Sweet, Robert A; Nimgaonkar, Vishwajit L; Loscher, Christine E; Bauer, Eileen M; Chaparala, Srilakshmi

2016-01-01

Genome-wide association studies of schizophrenia (GWAS) have revealed the role of rare and common genetic variants, but the functional effects of the risk variants remain to be understood. Protein interactome-based studies can facilitate the study of molecular mechanisms by which the risk genes relate to schizophrenia (SZ) genesis, but protein–protein interactions (PPIs) are unknown for many of the liability genes. We developed a computational model to discover PPIs, which is found to be highly accurate according to computational evaluations and experimental validations of selected PPIs. We present here, 365 novel PPIs of liability genes identified by the SZ Working Group of the Psychiatric Genomics Consortium (PGC). Seventeen genes that had no previously known interactions have 57 novel interactions by our method. Among the new interactors are 19 drug targets that are targeted by 130 drugs. In addition, we computed 147 novel PPIs of 25 candidate genes investigated in the pre-GWAS era. While there is little overlap between the GWAS genes and the pre-GWAS genes, the interactomes reveal that they largely belong to the same pathways, thus reconciling the apparent disparities between the GWAS and prior gene association studies. The interactome including 504 novel PPIs overall, could motivate other systems biology studies and trials with repurposed drugs. The PPIs are made available on a webserver, called Schizo-Pi at http://severus.dbmi.pitt.edu/schizo-pi with advanced search capabilities. PMID:27336055

Mitigating with macrophytes: submersed plants reduce the toxicity of pesticide-contaminated water to zooplankton.

PubMed

Brogan, William R; Relyea, Rick A

2013-03-01

In ecotoxicology, appreciation is growing for the influence that ecological interactions have on the toxicity of contaminants, such as insecticides, to sensitive species. Most previous studies, however, have focused on factors that exacerbate insecticide effects on species, while factors that may mitigate these effects have been relatively ignored. In aquatic habitats, a small number of studies have shown that submersed macrophytes can remove some insecticides from the water column via sorption. Although examining sorption dynamics is important for understanding the environmental fate of insecticides, whether and to what extent macrophytes actually mitigate insecticide effects on aquatic species remains unknown. In the present study, the authors examined how much and how quickly several realistic densities of the macrophyte Elodea canadensis decreased the toxicity of the insecticide malathion to Daphnia magna, a keystone aquatic herbivore. To do this, the authors quantified Daphnia survival in outdoor test systems (0.95 L) exposed to a factorial combination of five Elodea densities crossed with five malathion concentrations. The authors discovered that malathion's lethality to Daphnia decreased with increasing Elodea density. Furthermore, the rate at which Elodea reduced malathion's toxicity in the water column increased with macrophyte density. These results provide strong evidence that submersed macrophytes can mitigate the ecological impacts of a popular insecticide and further support that ecological interactions can strongly influence contaminant environmental effects. Copyright © 2013 SETAC.

Distinguishing between incomplete lineage sorting and genomic introgressions: complete fixation of allospecific mitochondrial DNA in a sexually reproducing fish (Cobitis; Teleostei), despite clonal reproduction of hybrids.

PubMed

Choleva, Lukas; Musilova, Zuzana; Kohoutova-Sediva, Alena; Paces, Jan; Rab, Petr; Janko, Karel

2014-01-01

Distinguishing between hybrid introgression and incomplete lineage sorting causing incongruence among gene trees in that they exhibit topological differences requires application of statistical approaches that are based on biologically relevant models. Such study is especially challenging in hybrid systems, where usual vectors mediating interspecific gene transfers--hybrids with Mendelian heredity--are absent or unknown. Here we study a complex of hybridizing species, which are known to produce clonal hybrids, to discover how one of the species, Cobitis tanaitica, has achieved a pattern of mito-nuclear mosaic genome over the whole geographic range. We appplied three distinct methods, including the method using solely the information on gene tree topologies, and found that the contrasting mito-nuclear signal might not have resulted from the retention of ancestral polymorphism. Instead, we found two signs of hybridization events related to C. tanaitica; one concerning nuclear gene flow and the other suggested mitochondrial capture. Interestingly, clonal inheritance (gynogenesis) of contemporary hybrids prevents genomic introgressions and non-clonal hybrids are either absent or too rare to be detected among European Cobitis. Our analyses therefore suggest that introgressive hybridizations are rather old episodes, mediated by previously existing hybrids whose inheritance was not entirely clonal. Cobitis complex thus supports the view that the type of resulting hybrids depends on a level of genomic divergence between sexual species.

Triclosan is a mitochondrial uncoupler in live zebrafish.

PubMed

Shim, Juyoung; Weatherly, Lisa M; Luc, Richard H; Dorman, Maxwell T; Neilson, Andy; Ng, Ryan; Kim, Carol H; Millard, Paul J; Gosse, Julie A

2016-12-01

Triclosan (TCS) is a synthetic antimicrobial agent used in many consumer goods at millimolar concentrations. As a result of exposure, TCS has been detected widely in humans. We have recently discovered that TCS is a proton ionophore mitochondrial uncoupler in multiple types of living cells. Here, we present novel data indicating that TCS is also a mitochondrial uncoupler in a living organism: 24-hour post-fertilization (hpf) zebrafish embryos. These experiments were conducted using a Seahorse Bioscience XF e 96 Extracellular Flux Analyzer modified for bidirectional temperature control, using the XF96 spheroid plate to position and measure one zebrafish embryo per well. Using this method, after acute exposure to TCS, the basal oxygen consumption rate (OCR) increases, without a decrease in survival or heartbeat rate. TCS also decreases ATP-linked respiration and spare respiratory capacity and increases proton leak: all indicators of mitochondrial uncoupling. Our data indicate, that TCS is a mitochondrial uncoupler in vivo, which should be taken into consideration when assessing the toxicity and/or pharmaceutical uses of TCS. This is the first example of usage of a Seahorse Extracellular Flux Analyzer to measure bioenergetic flux of a single zebrafish embryo per well in a 96-well assay format. The method developed in this study provides a high-throughput tool to identify previously unknown mitochondrial uncouplers in a living organism. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Ephrinb1 and Ephrinb2 Are Associated with Interleukin-7 Receptor α and Retard Its Internalization from the Cell Surface*

PubMed Central

Luo, Hongyu; Wu, Zenghui; Qi, Shijie; Jin, Wei; Han, Bing; Wu, Jiangping

2011-01-01

IL-7 plays vital roles in thymocyte development, T cell homeostasis, and the survival of these cells. IL-7 receptor α (IL-7Rα) on thymocytes and T cells is rapidly internalized upon IL-7 ligation. Ephrins (Efns) are cell surface molecules and ligands of the largest receptor kinase family, Eph kinases. We discovered that T cell-specific double gene knock-out (dKO) of Efnb1 and Efnb2 in mice led to reduced IL-7Rα expression in thymocytes and T cells, and that IL-7Rα down-regulation was accelerated in dKO CD4 cells upon IL-7 treatment. On the other hand, Efnb1 and Efnb2 overexpression on T cell lymphoma EL4 cells retarded IL-7Rα down-regulation. dKO T cells manifested compromised STAT5 activation and homeostatic proliferation, an IL-7-dependent process. Fluorescence resonance energy transfer and immunoprecipitation demonstrated that Efnb1 and Efnb2 interacted physically with IL-7Rα. Such interaction likely retarded IL-7Rα internalization, as Efnb1 and Efnb2 were not internalized. Therefore, we revealed a novel function of Efnb1 and Efnb2 in stabilizing IL-7Rα expression at the post-translational level, and a previously unknown modus operandi of Efnbs in the regulation of expression of other vital cell surface receptors. PMID:22069310

Comparative glycoproteomics of stem cells identifies new players in ricin toxicity.

PubMed

Stadlmann, Johannes; Taubenschmid, Jasmin; Wenzel, Daniel; Gattinger, Anna; Dürnberger, Gerhard; Dusberger, Frederico; Elling, Ulrich; Mach, Lukas; Mechtler, Karl; Penninger, Josef M

2017-09-28

Glycosylation, the covalent attachment of carbohydrate structures onto proteins, is the most abundant post-translational modification. Over 50% of human proteins are glycosylated, which alters their activities in diverse fundamental biological processes. Despite the importance of glycosylation in biology, the identification and functional validation of complex glycoproteins has remained largely unexplored. Here we develop a novel quantitative approach to identify intact glycopeptides from comparative proteomic data sets, allowing us not only to infer complex glycan structures but also to directly map them to sites within the associated proteins at the proteome scale. We apply this method to human and mouse embryonic stem cells to illuminate the stem cell glycoproteome. This analysis nearly doubles the number of experimentally confirmed glycoproteins, identifies previously unknown glycosylation sites and multiple glycosylated stemness factors, and uncovers evolutionarily conserved as well as species-specific glycoproteins in embryonic stem cells. The specificity of our method is confirmed using sister stem cells carrying repairable mutations in enzymes required for fucosylation, Fut9 and Slc35c1. Ablation of fucosylation confers resistance to the bioweapon ricin, and we discover proteins that carry a fucosylation-dependent sugar code for ricin toxicity. Mutations disrupting a subset of these proteins render cells ricin resistant, revealing new players that orchestrate ricin toxicity. Our comparative glycoproteomics platform, SugarQb, enables genome-wide insights into protein glycosylation and glycan modifications in complex biological systems.

Next generation sequencing and its applications in forensic genetics.

PubMed

Børsting, Claus; Morling, Niels

2015-09-01

It has been almost a decade since the first next generation sequencing (NGS) technologies emerged and quickly changed the way genetic research is conducted. Today, full genomes are mapped and published almost weekly and with ever increasing speed and decreasing costs. NGS methods and platforms have matured during the last 10 years, and the quality of the sequences has reached a level where NGS is used in clinical diagnostics of humans. Forensic genetic laboratories have also explored NGS technologies and especially in the last year, there has been a small explosion in the number of scientific articles and presentations at conferences with forensic aspects of NGS. These contributions have demonstrated that NGS offers new possibilities for forensic genetic case work. More information may be obtained from unique samples in a single experiment by analyzing combinations of markers (STRs, SNPs, insertion/deletions, mRNA) that cannot be analyzed simultaneously with the standard PCR-CE methods used today. The true variation in core forensic STR loci has been uncovered, and previously unknown STR alleles have been discovered. The detailed sequence information may aid mixture interpretation and will increase the statistical weight of the evidence. In this review, we will give an introduction to NGS and single-molecule sequencing, and we will discuss the possible applications of NGS in forensic genetics. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Anticancer kinase inhibitors impair intracellular viral trafficking and exert broad-spectrum antiviral effects.

PubMed

Bekerman, Elena; Neveu, Gregory; Shulla, Ana; Brannan, Jennifer; Pu, Szu-Yuan; Wang, Stanley; Xiao, Fei; Barouch-Bentov, Rina; Bakken, Russell R; Mateo, Roberto; Govero, Jennifer; Nagamine, Claude M; Diamond, Michael S; De Jonghe, Steven; Herdewijn, Piet; Dye, John M; Randall, Glenn; Einav, Shirit

2017-04-03

Global health is threatened by emerging viral infections, which largely lack effective vaccines or therapies. Targeting host pathways that are exploited by multiple viruses could offer broad-spectrum solutions. We previously reported that AAK1 and GAK, kinase regulators of the host adaptor proteins AP1 and AP2, are essential for hepatitis C virus (HCV) infection, but the underlying mechanism and relevance to other viruses or in vivo infections remained unknown. Here, we have discovered that AP1 and AP2 cotraffic with HCV particles in live cells. Moreover, we found that multiple viruses, including dengue and Ebola, exploit AAK1 and GAK during entry and infectious virus production. In cultured cells, treatment with sunitinib and erlotinib, approved anticancer drugs that inhibit AAK1 or GAK activity, or with more selective compounds inhibited intracellular trafficking of HCV and multiple unrelated RNA viruses with a high barrier to resistance. In murine models of dengue and Ebola infection, sunitinib/erlotinib combination protected against morbidity and mortality. We validated sunitinib- and erlotinib-mediated inhibition of AAK1 and GAK activity as an important mechanism of antiviral action. Additionally, we revealed potential roles for additional kinase targets. These findings advance our understanding of virus-host interactions and establish a proof of principle for a repurposed, host-targeted approach to combat emerging viruses.

User-assisted visual search and tracking across distributed multi-camera networks

NASA Astrophysics Data System (ADS)

Raja, Yogesh; Gong, Shaogang; Xiang, Tao

2011-11-01

Human CCTV operators face several challenges in their task which can lead to missed events, people or associations, including: (a) data overload in large distributed multi-camera environments; (b) short attention span; (c) limited knowledge of what to look for; and (d) lack of access to non-visual contextual intelligence to aid search. Developing a system to aid human operators and alleviate such burdens requires addressing the problem of automatic re-identification of people across disjoint camera views, a matching task made difficult by factors such as lighting, viewpoint and pose changes and for which absolute scoring approaches are not best suited. Accordingly, we describe a distributed multi-camera tracking (MCT) system to visually aid human operators in associating people and objects effectively over multiple disjoint camera views in a large public space. The system comprises three key novel components: (1) relative measures of ranking rather than absolute scoring to learn the best features for matching; (2) multi-camera behaviour profiling as higher-level knowledge to reduce the search space and increase the chance of finding correct matches; and (3) human-assisted data mining to interactively guide search and in the process recover missing detections and discover previously unknown associations. We provide an extensive evaluation of the greater effectiveness of the system as compared to existing approaches on industry-standard i-LIDS multi-camera data.

Reverse engineering a mouse embryonic stem cell-specific transcriptional network reveals a new modulator of neuronal differentiation

PubMed Central

De Cegli, Rossella; Iacobacci, Simona; Flore, Gemma; Gambardella, Gennaro; Mao, Lei; Cutillo, Luisa; Lauria, Mario; Klose, Joachim; Illingworth, Elizabeth; Banfi, Sandro; di Bernardo, Diego

2013-01-01

Gene expression profiles can be used to infer previously unknown transcriptional regulatory interaction among thousands of genes, via systems biology ‘reverse engineering’ approaches. We ‘reverse engineered’ an embryonic stem (ES)-specific transcriptional network from 171 gene expression profiles, measured in ES cells, to identify master regulators of gene expression (‘hubs’). We discovered that E130012A19Rik (E13), highly expressed in mouse ES cells as compared with differentiated cells, was a central ‘hub’ of the network. We demonstrated that E13 is a protein-coding gene implicated in regulating the commitment towards the different neuronal subtypes and glia cells. The overexpression and knock-down of E13 in ES cell lines, undergoing differentiation into neurons and glia cells, caused a strong up-regulation of the glutamatergic neurons marker Vglut2 and a strong down-regulation of the GABAergic neurons marker GAD65 and of the radial glia marker Blbp. We confirmed E13 expression in the cerebral cortex of adult mice and during development. By immuno-based affinity purification, we characterized protein partners of E13, involved in the Polycomb complex. Our results suggest a role of E13 in regulating the division between glutamatergic projection neurons and GABAergic interneurons and glia cells possibly by epigenetic-mediated transcriptional regulation. PMID:23180766

Complete Spontaneous Regression of Merkel Cell Carcinoma After Biopsy: A Case Report and Review of the Literature.

PubMed

Ahmadi Moghaddam, Parnian; Cornejo, Kristine M; Hutchinson, Lloyd; Tomaszewicz, Keith; Dresser, Karen; Deng, April; OʼDonnell, Patrick

2016-11-01

Merkel cell carcinoma (MCC) is a rare primary cutaneous neuroendocrine tumor that typically occurs on the head and neck of the elderly and follows an aggressive clinical course. Merkel cell polyomavirus (MCPyV) has been identified in up to 80% of cases and has been shown to participate in MCC tumorigenesis. Complete spontaneous regression of MCC has been rarely reported in the literature. We describe a case of a 79-year-old man that presented with a rapidly growing, 3-cm mass on the left jaw. An incisional biopsy revealed MCC. Additional health issues were discovered in the preoperative workup of this patient which delayed treatment. One month after the biopsy, the lesion showed clinical regression in the absence of treatment. Wide excision of the biopsy site with sentinel lymph node dissection revealed no evidence of MCC 2 months later. The tumor cells in the patient's biopsy specimen were negative for MCPyV by polymerase chain reaction and immunohistochemistry (CM2B4 antibody, Santa Cruz, CA). The exact mechanism for complete spontaneous regression in MCC is unknown. To our knowledge, only 2 previous studies evaluated the presence of MCPyV by polymerase chain reaction in MCC with spontaneous regression. Whether the presence or absence of MCPyV correlates with spontaneous regression warrants further investigation.

Anticancer kinase inhibitors impair intracellular viral trafficking and exert broad-spectrum antiviral effects

PubMed Central

Bekerman, Elena; Shulla, Ana; Brannan, Jennifer; Wang, Stanley; Barouch-Bentov, Rina; Bakken, Russell R.; Mateo, Roberto; Govero, Jennifer; Nagamine, Claude M.; Diamond, Michael S.; De Jonghe, Steven; Herdewijn, Piet; Dye, John M.; Randall, Glenn

2017-01-01

Global health is threatened by emerging viral infections, which largely lack effective vaccines or therapies. Targeting host pathways that are exploited by multiple viruses could offer broad-spectrum solutions. We previously reported that AAK1 and GAK, kinase regulators of the host adaptor proteins AP1 and AP2, are essential for hepatitis C virus (HCV) infection, but the underlying mechanism and relevance to other viruses or in vivo infections remained unknown. Here, we have discovered that AP1 and AP2 cotraffic with HCV particles in live cells. Moreover, we found that multiple viruses, including dengue and Ebola, exploit AAK1 and GAK during entry and infectious virus production. In cultured cells, treatment with sunitinib and erlotinib, approved anticancer drugs that inhibit AAK1 or GAK activity, or with more selective compounds inhibited intracellular trafficking of HCV and multiple unrelated RNA viruses with a high barrier to resistance. In murine models of dengue and Ebola infection, sunitinib/erlotinib combination protected against morbidity and mortality. We validated sunitinib- and erlotinib-mediated inhibition of AAK1 and GAK activity as an important mechanism of antiviral action. Additionally, we revealed potential roles for additional kinase targets. These findings advance our understanding of virus-host interactions and establish a proof of principle for a repurposed, host-targeted approach to combat emerging viruses. PMID:28240606

A systems level predictive model for global gene regulation of methanogenesis in a hydrogenotrophic methanogen

PubMed Central

Yoon, Sung Ho; Turkarslan, Serdar; Reiss, David J.; Pan, Min; Burn, June A.; Costa, Kyle C.; Lie, Thomas J.; Slagel, Joseph; Moritz, Robert L.; Hackett, Murray; Leigh, John A.; Baliga, Nitin S.

2013-01-01

Methanogens catalyze the critical methane-producing step (called methanogenesis) in the anaerobic decomposition of organic matter. Here, we present the first predictive model of global gene regulation of methanogenesis in a hydrogenotrophic methanogen, Methanococcus maripaludis. We generated a comprehensive list of genes (protein-coding and noncoding) for M. maripaludis through integrated analysis of the transcriptome structure and a newly constructed Peptide Atlas. The environment and gene-regulatory influence network (EGRIN) model of the strain was constructed from a compendium of transcriptome data that was collected over 58 different steady-state and time-course experiments that were performed in chemostats or batch cultures under a spectrum of environmental perturbations that modulated methanogenesis. Analyses of the EGRIN model have revealed novel components of methanogenesis that included at least three additional protein-coding genes of previously unknown function as well as one noncoding RNA. We discovered that at least five regulatory mechanisms act in a combinatorial scheme to intercoordinate key steps of methanogenesis with different processes such as motility, ATP biosynthesis, and carbon assimilation. Through a combination of genetic and environmental perturbation experiments we have validated the EGRIN-predicted role of two novel transcription factors in the regulation of phosphate-dependent repression of formate dehydrogenase—a key enzyme in the methanogenesis pathway. The EGRIN model demonstrates regulatory affiliations within methanogenesis as well as between methanogenesis and other cellular functions. PMID:24089473

Exome Sequencing Identifies a Novel CEACAM16 Mutation Associated with Autosomal Dominant Nonsyndromic Hearing Loss DFNA4B in a Chinese Family

PubMed Central

He, Chufeng; Li, Haibo; Qing, Jie; Grati, Mhamed; Hu, Zhengmao; Li, Jiada; Hu, Yiqiao; Xia, Kun; Mei, Lingyun; Wang, Xingwei; Yu, Jianjun; Chen, Hongsheng; Jiang, Lu; Liu, Yalan; Men, Meichao; Zhang, Hailin; Guan, Liping; Xiao, Jingjing; Zhang, Jianguo; Liu, Xuezhong; Feng, Yong

2014-01-01

Autosomal dominant nonsyndromic hearing loss (ADNSHL/DFNA) is a highly genetically heterogeneous disorder. Hitherto only about 30 ADNSHL-causing genes have been identified and many unknown genes remain to be discovered. In this research, genome-wide linkage analysis mapped the disease locus to a 4.3 Mb region on chromosome 19q13 in SY-026, a five-generation nonconsanguineous Chinese family affected by late-onset and progressive ADNSHL. This linkage region showed partial overlap with the previously reported DFNA4. Simultaneously, probands were analyzed using exome capture followed by next generation sequencing. Encouragingly, a heterozygous missense mutation, c.505G>A (p.G169R) in exon 3 of the CEACAM16 gene (carcinoembryonic antigen-related cell adhesion molecule 16), was identified via this combined strategy. Sanger sequencing verified that the mutation co-segregated with hearing loss in the family and that it was not present in 200 unrelated control subjects with matched ancestry. This is the second report in the literature of a family with ADNSHL caused by CEACAM16 mutation. Immunofluorescence staining and Western blots also prove CEACAM16 to be a secreted protein. Furthermore, our studies in transfected HEK293T cells show that the secretion efficacy of the mutant CEACAM16 is much lower than that of the wild-type, suggesting a deleterious effect of the sequence variant. PMID:25589040

Exome sequencing identifies a novel CEACAM16 mutation associated with autosomal dominant nonsyndromic hearing loss DFNA4B in a Chinese family.

PubMed

Wang, Honghan; Wang, Xinwei; He, Chufeng; Li, Haibo; Qing, Jie; Grati, Mhamed; Hu, Zhengmao; Li, Jiada; Hu, Yiqiao; Xia, Kun; Mei, Lingyun; Wang, Xingwei; Yu, Jianjun; Chen, Hongsheng; Jiang, Lu; Liu, Yalan; Men, Meichao; Zhang, Hailin; Guan, Liping; Xiao, Jingjing; Zhang, Jianguo; Liu, Xuezhong; Feng, Yong

2015-03-01

Autosomal dominant nonsyndromic hearing loss (ADNSHL/DFNA) is a highly genetically heterogeneous disorder. Hitherto only about 30 ADNSHL-causing genes have been identified and many unknown genes remain to be discovered. In this research, genome-wide linkage analysis mapped the disease locus to a 4.3 Mb region on chromosome 19q13 in SY-026, a five-generation nonconsanguineous Chinese family affected by late-onset and progressive ADNSHL. This linkage region showed partial overlap with the previously reported DFNA4. Simultaneously, probands were analyzed using exome capture followed by next-generation sequencing. Encouragingly, a heterozygous missense mutation, c.505G>A (p.G169R) in exon 3 of the CEACAM16 gene (carcinoembryonic antigen-related cell adhesion molecule 16), was identified via this combined strategy. Sanger sequencing verified that the mutation co-segregated with hearing loss in the family and that it was not present in 200 unrelated control subjects with matched ancestry. This is the second report in the literature of a family with ADNSHL caused by CEACAM16 mutation. Immunofluorescence staining and western blots also prove CEACAM16 to be a secreted protein. Furthermore, our studies in transfected HEK293T cells show that the secretion efficacy of the mutant CEACAM16 is much lower than that of the wild type, suggesting a deleterious effect of the sequence variant.

Functional impact of global rare copy number variation in autism spectrum disorders.

PubMed

Pinto, Dalila; Pagnamenta, Alistair T; Klei, Lambertus; Anney, Richard; Merico, Daniele; Regan, Regina; Conroy, Judith; Magalhaes, Tiago R; Correia, Catarina; Abrahams, Brett S; Almeida, Joana; Bacchelli, Elena; Bader, Gary D; Bailey, Anthony J; Baird, Gillian; Battaglia, Agatino; Berney, Tom; Bolshakova, Nadia; Bölte, Sven; Bolton, Patrick F; Bourgeron, Thomas; Brennan, Sean; Brian, Jessica; Bryson, Susan E; Carson, Andrew R; Casallo, Guillermo; Casey, Jillian; Chung, Brian H Y; Cochrane, Lynne; Corsello, Christina; Crawford, Emily L; Crossett, Andrew; Cytrynbaum, Cheryl; Dawson, Geraldine; de Jonge, Maretha; Delorme, Richard; Drmic, Irene; Duketis, Eftichia; Duque, Frederico; Estes, Annette; Farrar, Penny; Fernandez, Bridget A; Folstein, Susan E; Fombonne, Eric; Freitag, Christine M; Gilbert, John; Gillberg, Christopher; Glessner, Joseph T; Goldberg, Jeremy; Green, Andrew; Green, Jonathan; Guter, Stephen J; Hakonarson, Hakon; Heron, Elizabeth A; Hill, Matthew; Holt, Richard; Howe, Jennifer L; Hughes, Gillian; Hus, Vanessa; Igliozzi, Roberta; Kim, Cecilia; Klauck, Sabine M; Kolevzon, Alexander; Korvatska, Olena; Kustanovich, Vlad; Lajonchere, Clara M; Lamb, Janine A; Laskawiec, Magdalena; Leboyer, Marion; Le Couteur, Ann; Leventhal, Bennett L; Lionel, Anath C; Liu, Xiao-Qing; Lord, Catherine; Lotspeich, Linda; Lund, Sabata C; Maestrini, Elena; Mahoney, William; Mantoulan, Carine; Marshall, Christian R; McConachie, Helen; McDougle, Christopher J; McGrath, Jane; McMahon, William M; Merikangas, Alison; Migita, Ohsuke; Minshew, Nancy J; Mirza, Ghazala K; Munson, Jeff; Nelson, Stanley F; Noakes, Carolyn; Noor, Abdul; Nygren, Gudrun; Oliveira, Guiomar; Papanikolaou, Katerina; Parr, Jeremy R; Parrini, Barbara; Paton, Tara; Pickles, Andrew; Pilorge, Marion; Piven, Joseph; Ponting, Chris P; Posey, David J; Poustka, Annemarie; Poustka, Fritz; Prasad, Aparna; Ragoussis, Jiannis; Renshaw, Katy; Rickaby, Jessica; Roberts, Wendy; Roeder, Kathryn; Roge, Bernadette; Rutter, Michael L; Bierut, Laura J; Rice, John P; Salt, Jeff; Sansom, Katherine; Sato, Daisuke; Segurado, Ricardo; Sequeira, Ana F; Senman, Lili; Shah, Naisha; Sheffield, Val C; Soorya, Latha; Sousa, Inês; Stein, Olaf; Sykes, Nuala; Stoppioni, Vera; Strawbridge, Christina; Tancredi, Raffaella; Tansey, Katherine; Thiruvahindrapduram, Bhooma; Thompson, Ann P; Thomson, Susanne; Tryfon, Ana; Tsiantis, John; Van Engeland, Herman; Vincent, John B; Volkmar, Fred; Wallace, Simon; Wang, Kai; Wang, Zhouzhi; Wassink, Thomas H; Webber, Caleb; Weksberg, Rosanna; Wing, Kirsty; Wittemeyer, Kerstin; Wood, Shawn; Wu, Jing; Yaspan, Brian L; Zurawiecki, Danielle; Zwaigenbaum, Lonnie; Buxbaum, Joseph D; Cantor, Rita M; Cook, Edwin H; Coon, Hilary; Cuccaro, Michael L; Devlin, Bernie; Ennis, Sean; Gallagher, Louise; Geschwind, Daniel H; Gill, Michael; Haines, Jonathan L; Hallmayer, Joachim; Miller, Judith; Monaco, Anthony P; Nurnberger, John I; Paterson, Andrew D; Pericak-Vance, Margaret A; Schellenberg, Gerard D; Szatmari, Peter; Vicente, Astrid M; Vieland, Veronica J; Wijsman, Ellen M; Scherer, Stephen W; Sutcliffe, James S; Betancur, Catalina

2010-07-15

The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.

La Moisissure et la Bactérie: Deconstructing the fable of the discovery of penicillin by Ernest Duchesne.

PubMed

Shama, Gilbert

2016-09-01

Ernest Duchesne (1874-1912) completed his thesis on microbial antagonism in 1897 in Lyon. His work lay unknown for fifty years, but on being brought to light led to his being credited with having discovered penicillin prior to Alexander Fleming. The claims surrounding Duchesne are examined here both from the strictly microbiological perspective, and also for what they reveal about how the process of discovery is frequently misconstrued. The combined weight of evidence presented here militates strongly against the possibility that the species of Penicillium that Duchesne worked with produced penicillin. Copyright © 2016 Elsevier Ltd. All rights reserved.

The threat of emerging infections.

PubMed

1996-11-01

A variety of newly discovered pathogens and new forms of older infectious agents threaten to reemerge. Typical symptoms of acute infection are fever, headache, malaise, vomiting, and diarrhea. Some of the better-known emerging viral infections include dengue, filoviruses (Ebola, Marburg), hantaviruses, hepatitis B, hepatitis C, HIV, influenza, lassa fever, measles, rift valley fever, rotavirus, and yellow fever. Emerging bacterial infections include cholera, Escherichia coli 0157:H7, legionnaires disease (Legionella), lyme disease, streptococcus infections (group A), tuberculosis, and typhoid. Emerging parasitic infections include cryptosporidium and other waterborne pathogens and malaria. The causes of many diseases are still shrouded in mystery; thus, treatments and cures for them are as yet unknown.

Isotope effect on electron-phonon interaction in the multiband superconductor MgB 2

DOE PAGES

Mou, Daixiang; Manni, Soham; Taufour, Valentin; ...

2016-04-07

We investigate the effect of isotope substitution on the electron-phonon interaction in the multiband superconductor MgB 2 using tunable laser-based angle-resolved photoemission spectroscopy. The kink structure around 70 meV in the σ band, which is caused by electron coupling to the E 2g phonon mode, is shifted to higher binding energy by ~3.5 meV in Mg 10B 2 and the shift is not affected by superconducting transition. Furthermore, these results serve as the benchmark for investigations of isotope effects in known, unconventional superconductors and newly discovered superconductors where the origin of pairing is unknown.

Molecular Convergence of Infrared Vision in Snakes

PubMed Central

Yokoyama, Shozo; Altun, Ahmet; DeNardo, Dale F.

2011-01-01

It has been discovered that the transient receptor potential ankyrin 1 (TRPA1) proteins of Boidae (boas), Pythonidae (pythons), and Crotalinae (pit vipers) are used to detect infrared radiation, but the molecular mechanism for detecting the infrared radiation is unknown. Here, relating the amino acid substitutions in their TRPA1 proteins and the functional differentiations, we propose that three parallel amino acid changes (L330M, Q391H, and S434T) are responsible for the development of infrared vision in the three groups of snakes. Protein modeling shows that the three amino acid changes alter the structures of the central region of their ankyrin repeats. PMID:20937734

Widespread genetic switches and toxicity resistance proteins for fluoride.

PubMed

Baker, Jenny L; Sudarsan, Narasimhan; Weinberg, Zasha; Roth, Adam; Stockbridge, Randy B; Breaker, Ronald R

2012-01-13

Most riboswitches are metabolite-binding RNA structures located in bacterial messenger RNAs where they control gene expression. We have discovered a riboswitch class in many bacterial and archaeal species whose members are selectively triggered by fluoride but reject other small anions, including chloride. These fluoride riboswitches activate expression of genes that encode putative fluoride transporters, enzymes that are known to be inhibited by fluoride, and additional proteins of unknown function. Our findings indicate that most organisms are naturally exposed to toxic levels of fluoride and that many species use fluoride-sensing RNAs to control the expression of proteins that alleviate the deleterious effects of this anion.

Widespread Genetic Switches and Toxicity Resistance Proteins for Fluoride

PubMed Central

Weinberg, Zasha; Roth, Adam; Stockbridge, Randy B.; Breaker, Ronald R.

2014-01-01

Most riboswitches are metabolite-binding RNA structures located in bacterial messenger RNAs where they control gene expression. We have discovered a riboswitch class in many bacterial and archaeal species whose members are selectively triggered by fluoride but reject other small anions, including chloride. These fluoride riboswitches activate expression of genes that encode putative fluoride transporters, enzymes that are known to be inhibited by fluoride, and additional proteins of unknown function. Our findings indicate that most organisms are naturally exposed to toxic levels of fluoride and that many species use fluoride-sensing RNAs to control the expression of proteins that alleviate the deleterious effects of this anion. PMID:22194412

NDR proteins: lessons learned from Arabidopsis and animal cells prompt a testable hypothesis.

PubMed

Mudgil, Yashwanti; Jones, Alan M

2010-08-01

N-myc Down Regulated (NDR) genes were discovered more than fifteen years ago. Indirect evidence support a role in tumor progression and cellular differentiation, but their biochemical function is still unknown. Our detailed analyses on Arabidopsis NDL proteins show their involvement in altering auxin transport, local auxin gradients and expression level of auxin transport proteins. Animal NDL proteins may be involved in membrane recycling of E-cadherin and effector for the small GTPase. In light of these findings, we hypothesize that NDL proteins regulate vesicular trafficking of auxin transport facilitator PIN proteins by biochemically alterating the local lipid environment of PIN proteins.

Protein Equilibration through Somatic Ring Canals in Drosophila

PubMed Central

McLean, Peter F.; Cooley, Lynn

2013-01-01

Although intercellular bridges resulting from incomplete cytokinesis were discovered in somatic Drosophila tissues decades ago, the impact of these structures on intercellular communication and tissue biology is largely unknown. In this work, we demonstrate that the ~250 nm diameter somatic ring canals permit diffusion of cytoplasmic contents between connected cells and across mitotic clone boundaries, and enable the equilibration of protein between transcriptionally mosaic follicle cells in the Drosophila ovary. We obtained similar, though more restricted, results in the larval imaginal discs. Our work illustrates the lack of cytoplasmic autonomy in these tissues and suggests a role for somatic ring canals in promoting homogeneous protein expression within the tissue. PMID:23704373

Discovering Protein-Coding Genes from the Environment: Time for the Eukaryotes?

PubMed

Marmeisse, Roland; Kellner, Harald; Fraissinet-Tachet, Laurence; Luis, Patricia

2017-09-01

Eukaryotic microorganisms from diverse environments encompass a large number of taxa, many of them still unknown to science. One strategy to mine these organisms for genes of biotechnological relevance is to use a pool of eukaryotic mRNA directly extracted from environmental samples. Recent reports demonstrate that the resulting metatranscriptomic cDNA libraries can be screened by expression in yeast for a wide range of genes and functions from many of the different eukaryotic taxa. In combination with novel emerging high-throughput technologies, we anticipate that this approach should contribute to exploring the functional diversity of the eukaryotic microbiota. Copyright © 2017 Elsevier Ltd. All rights reserved.

Glycolipids from seaweeds and their potential biotechnological applications.

PubMed

Plouguerné, Erwan; da Gama, Bernardo A P; Pereira, Renato C; Barreto-Bergter, Eliana

2014-01-01

Marine macroalgae, or seaweeds, are a formidable source of natural compounds with diverse biological activities. In the last five decades it has been estimated that more than 3000 natural compounds were discovered from these organisms. The great majority of the published works have focused on terpenoids. In comparison, glycolipids are a neglected class of macroalgal secondary metabolites therefore remaining as a largely unknown reservoir of molecular diversity. Nevertheless, the interest regarding these compounds has been growing fast in the last decades as activities of ecological or pharmaceutical interest have been highlighted. This paper will review recent work regarding isolation and structural characterization of glycolipids from seaweeds and their prospective biological activities.

Culture care theory: a major contribution to advance transcultural nursing knowledge and practices.

PubMed

Leininger, Madeleine

2002-07-01

This article is focused on the major features of the Culture Care Diversity and Universality theory as a central contributing theory to advance transcultural nursing knowledge and to use the findings in teaching, research, practice, and consultation. It remains one of the oldest, most holistic, and most comprehensive theories to generate knowledge of diverse and similar cultures worldwide. The theory has been a powerful means to discover largely unknown knowledge in nursing and the health fields. It provides a new mode to assure culturally competent, safe, and congruent transcultural nursing care. The purpose, goal, assumptive premises, ethnonursing research method, criteria, and some findings are highlighted.

Are all phytochemicals useful in the preventing of DNA damage?

PubMed

Bacanlı, Merve; Aydın, Sevtap; Başaran, A Ahmet; Başaran, Nurşen

2017-11-01

Phytochemicals derived from natural plants have been used commonly for the prevention and/or treatment of different diseases due to the belief of their safety. Many plant species synthesize toxic chemicals. New natural chemicals are being discovered but their toxic effects are unknown. Phytochemicals have been regarded as possible antioxidants. But on the other hand it is suggested that various phenolic antioxidants can display pro-oxidant properties at high doses. In this review, the role of some phytochemicals (epigallocathecin gallate, carvacrol, galangin, limonene, lycopene, naringin, puerarin, terpinene, thymol and ursolic acid) on the prevention of DNA damage will be discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Endogenous Gibbon Ape Leukemia Virus Identified in a Rodent (Melomys burtoni subsp.) from Wallacea (Indonesia)

PubMed Central

Alfano, Niccolò; Michaux, Johan; Morand, Serge; Aplin, Ken; Tsangaras, Kyriakos; Löber, Ulrike; Fabre, Pierre-Henri; Fitriana, Yuli; Semiadi, Gono; Ishida, Yasuko; Helgen, Kristofer M.; Roca, Alfred L.; Eiden, Maribeth V.

2016-01-01

ABSTRACT Gibbon ape leukemia virus (GALV) and koala retrovirus (KoRV) most likely originated from a cross-species transmission of an ancestral retrovirus into koalas and gibbons via one or more intermediate as-yet-unknown hosts. A virus highly similar to GALV has been identified in an Australian native rodent (Melomys burtoni) after extensive screening of Australian wildlife. GALV-like viruses have also been discovered in several Southeast Asian species, although screening has not been extensive and viruses discovered to date are only distantly related to GALV. We therefore screened 26 Southeast Asian rodent species for KoRV- and GALV-like sequences, using hybridization capture and high-throughput sequencing, in the attempt to identify potential GALV and KoRV hosts. Only the individuals belonging to a newly discovered subspecies of Melomys burtoni from Indonesia were positive, yielding an endogenous provirus very closely related to a strain of GALV. The sequence of the critical receptor domain for GALV infection in the Indonesian M. burtoni subsp. was consistent with the susceptibility of the species to GALV infection. The second record of a GALV in M. burtoni provides further evidence that M. burtoni, and potentially other lineages within the widespread subfamily Murinae, may play a role in the spread of GALV-like viruses. The discovery of a GALV in the most western part of the Australo-Papuan distribution of M. burtoni, specifically in a transitional zone between Asia and Australia (Wallacea), may be relevant to the cross-species transmission to gibbons in Southeast Asia and broadens the known distribution of GALVs in wild rodents. IMPORTANCE Gibbon ape leukemia virus (GALV) and the koala retrovirus (KoRV) are very closely related, yet their hosts neither are closely related nor overlap geographically. Direct cross-species infection between koalas and gibbons is unlikely. Therefore, GALV and KoRV may have arisen via a cross-species transfer from an intermediate host whose range overlaps those of both gibbons and koalas. Using hybridization capture and high-throughput sequencing, we have screened a wide range of rodent candidate hosts from Southeast Asia for KoRV- and GALV-like sequences. Only a Melomys burtoni subspecies from Wallacea (Indonesia) was positive for GALV. We report the genome sequence of this newly identified GALV, the critical domain for infection of its potential cellular receptor, and its phylogenetic relationships with the other previously characterized GALVs. We hypothesize that Melomys burtoni, and potentially related lineages with an Australo-Papuan distribution, may have played a key role in cross-species transmission to other taxa. PMID:27384662

Highly divergent hepaciviruses from African cattle.

PubMed

Corman, Victor Max; Grundhoff, Adam; Baechlein, Christine; Fischer, Nicole; Gmyl, Anatoly; Wollny, Robert; Dei, Dickson; Ritz, Daniel; Binger, Tabea; Adankwah, Ernest; Marfo, Kwadwo Sarfo; Annison, Lawrence; Annan, Augustina; Adu-Sarkodie, Yaw; Oppong, Samuel; Becher, Paul; Drosten, Christian; Drexler, Jan Felix

2015-06-01

The hepatitis C virus (HCV; genus Hepacivirus) is a highly relevant human pathogen. Unique hepaciviruses (HV) were discovered recently in animal hosts. The direct ancestor of HCV has not been found, but the genetically most closely related animal HVs exist in horses. To investigate whether other peridomestic animals also carry HVs, we analyzed sera from Ghanaian cattle for HVs by reverse transcription-PCR (RT-PCR). Nine of 106 specimens from different sampling sites contained HV RNA (8.5%) at median viral loads of 1.6 × 10(5) copies/ml. Infection seemed unrelated to cattle age and gender. Near-full-genome sequencing of five representative viruses confirmed taxonomic classifications. Cattle HVs formed two distinct phylogenetic lineages that differed by up to 17.7% on the nucleotide level in the polyprotein-encoding region, suggesting cocirculation of different virus subtypes. A conserved microRNA122-binding site in the 5' internal ribosomal entry site suggested liver tropism of cattle HVs. Phylogenetic analyses suggested the circulation of HVs in cattle for several centuries. Cattle HVs were genetically highly divergent from all other HVs, including HCV. HVs from genetically related equine and bovine hosts were not monophyletic, corroborating host shifts during the evolution of the genus Hepacivirus. Similar to equine HVs, the genetic diversity of cattle HVs was low compared to that of HCV genotypes. This suggests an influence of the human-modified ecology of peridomestic animals on virus diversity. Further studies should investigate the occurrence of cattle HVs in other geographic areas and breeds, virus pathogenicity in cattle, and the potential exposure of human risk groups, such as farmers, butchers, and abattoir workers. HCV (genus Hepacivirus) is a major human pathogen, causing liver failure and cancer. Unique hepaciviruses (HVs) were discovered over the last few years in animals, but the direct ancestor of HCV has not been found. The animal HV most closely related to HCV so far originated from horses, suggesting that other livestock animals also harbor HVs. Therefore, we investigated African cattle and discovered previously unknown HVs at high prevalence and viral loads. Because of the agricultural importance of cattle, it may be relevant to investigate HV pathogenicity. The frequent exposure of humans to cattle also may warrant investigations of the zoonotic potential of these viruses. Evolutionary analyses suggested that cattle HVs have existed for centuries. Despite the genetic relatedness of their animal hosts, HVs from cattle and horses were not phylogenetically related, corroborating frequent host shifts during the evolution of the genus Hepacivirus. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

[Clinical Application of Analytical and Medical Instruments Mainly Using MS Techniques].

PubMed

Tanaka, Koichi

2016-02-01

Analytical instruments for clinical use are commonly required to confirm the compounds and forms related to diseases with the highest possible sensitivity, quantitative performance, and specificity and minimal invasiveness within a short time, easily, and at a low cost. Advancements of technical innovation for Mass Spectrometer (MS) have led to techniques that meet such requirements. Besides confirming known substances, other purposes and advantages of MS that are not fully known to the public are using MS as a tool to discover unknown phenomena and compounds. An example is clarifying the mechanisms of human diseases. The human body has approximately 100 thousand types of protein, and there may be more than several million types of protein and their metabolites. Most of them have yet to be discovered, and their discovery may give birth to new academic fields and lead to the clarification of diseases, development of new medicines, etc. For example, using the MS system developed under "Contribution to drug discovery and diagnosis by next generation of advanced mass spectrometry system," one of the 30 projects of the "Funding Program for World-Leading Innovative R&D on Science and Technology" (FIRST program), and other individual basic technologies, we succeeded in discovering new disease biomarker candidates for Alzheimer's disease, cancer, etc. Further contribution of MS to clinical medicine can be expected through the development and improvement of new techniques, efforts to verify discoveries, and communications with the medical front.

Who discovered the sylvian fissure?

PubMed

Collice, Massimo; Collice, Rosa; Riva, Alessandro

2008-10-01

Cerebral convolutions were unknown until the 17th century. A constant sulcus was not recognized until the mid-1600s; it was named "the fissure of Sylvius," after the person who had always been considered as the one who discovered it. It is commonly asserted that the first description of the lateral scissure was made by Caspar Bartholin, who attributed its discovery to Sylvius. However, this was not actually the case, as Caspar Bartholin died in 1629, whereas Sylvius started studying medicine in 1632. The description could have been made either by Caspar Bartholin's son Thomas or by Sylvius himself. Irrespective of the description's author, the key to the history of the lateral fissure is that it was first identified by Fabrici d'Acquapendente in 1600, 40 years before Sylvius' description. In one of the 300 colored plates (Tabulae Pictae) by Fabrici, the lateral fissure is perfectly depicted, as are the temporal convolutions. Therefore, even if it was an accidental discovery, Fabrici should be the one noted as having discovered the fissure. This article ends with a short history of the plates. They were painted in oil on paper and were thought to further a great work, the Theatrum Totius Animalis Fabricae, which was begun in 1591 and never completed or published. Only the colored illustrations of this project remain. These plates were forgotten for more than 200 years, until they were rediscovered by Giuseppe Sterzi in 1909. They are among the best examples of anatomic iconography in terms of innovation, accuracy, and artistic accomplishment.

Correlating chemical sensitivity and basal gene expression reveals mechanism of action | Office of Cancer Genomics

Cancer.gov

Changes in cellular gene expression in response to small-molecule or genetic perturbations have yielded signatures that can connect unknown mechanisms of action (MoA) to ones previously established. We hypothesized that differential basal gene expression could be correlated with patterns of small-molecule sensitivity across many cell lines to illuminate the actions of compounds whose MoA are unknown.

Music Training and Working Memory: An ERP Study

ERIC Educational Resources Information Center

George, Elyse M.; Coch, Donna

2011-01-01

While previous research has suggested that music training is associated with improvements in various cognitive and linguistic skills, the mechanisms mediating or underlying these associations are mostly unknown. Here, we addressed the hypothesis that previous music training is related to improved working memory. Using event-related potentials…

Running Clubs--A Combinatorial Investigation.

ERIC Educational Resources Information Center

Nissen, Phillip; Taylor, John

1991-01-01

Presented is a combinatorial problem based on the Hash House Harriers rule which states that the route of the run should not have previously been traversed by the club. Discovered is how many weeks the club can meet before the rule has to be broken. (KR)

Breaking the Silence.

ERIC Educational Resources Information Center

Spake, Amanda

1992-01-01

A controversial new technique, facilitated communication, is helping students with autism express themselves. Many who previously showed no indication of communication skills now need only light arm support to type on a keyboard. Using facilitated communication, teachers have discovered that many autistic children can read, write, and express…

Newly discovered Neanderthal remains from Shanidar Cave, Iraqi Kurdistan, and their attribution to Shanidar 5.

PubMed

Pomeroy, Emma; Mirazón Lahr, Marta; Crivellaro, Federica; Farr, Lucy; Reynolds, Tim; Hunt, Chris O; Barker, Graeme

2017-10-01

The Neanderthal remains from Shanidar Cave, excavated between 1951 and 1960, have played a central role in debates concerning diverse aspects of Neanderthal morphology and behavior. In 2015 and 2016, renewed excavations at the site uncovered hominin remains from the immediate area where the partial skeleton of Shanidar 5 was found in 1960. Shanidar 5 was a robust adult male estimated to have been aged over 40 years at the time of death. Comparisons of photographs from the previous and recent excavations indicate that the old and new remains were directly adjacent to one another, while the disturbed arrangement and partial crushing of the new fossils is consistent with descriptions and photographs of the older discoveries. The newly discovered bones include fragments of several vertebrae, a left hamate, part of the proximal left femur, a heavily crushed partial pelvis, and the distal half of the right tibia and fibula and associated talus and navicular. All these elements were previously missing from Shanidar 5, and morphological and metric data are consistent with the new elements belonging to this individual. A newly discovered partial left pubic symphysis indicates an age at death of 40-50 years, also consistent with the age of Shanidar 5 estimated previously. Thus, the combined evidence strongly suggests that the new finds can be attributed to Shanidar 5. Ongoing analyses of associated samples, including for sediment morphology, palynology, and dating, will therefore offer new evidence as to how this individual was deposited in the cave and permit new analyses of the skeleton itself and broader discussion of Neanderthal morphology and variation. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Green Bank Telescope Survey of Large Galactic H II Regions

NASA Astrophysics Data System (ADS)

Anderson, L. D.; Armentrout, W. P.; Luisi, Matteo; Bania, T. M.; Balser, Dana S.; Wenger, Trey V.

2018-02-01

As part of our ongoing H II Region Discovery Survey (HRDS), we report the Green Bank Telescope detection of 148 new angularly large Galactic H II regions in radio recombination line (RRL) emission. Our targets are located at a declination of δ > -45^\\circ , which corresponds to 266^\\circ > {\\ell }> -20^\\circ at b=0^\\circ . All sources were selected from the Wide-field Infrared Survey Explorer Catalog of Galactic H II Regions, and have infrared angular diameters ≥slant 260\\prime\\prime . The Galactic distribution of these “large” H II regions is similar to that of the previously known sample of Galactic H II regions. The large H II region RRL line width and peak line intensity distributions are skewed toward lower values, compared with that of previous HRDS surveys. We discover seven sources with extremely narrow RRLs < 10 {km} {{{s}}}-1. If half the line width is due to turbulence, these seven sources have thermal plasma temperatures < 1100 {{K}}. These temperatures are lower than any measured for Galactic H II regions, and the narrow-line components may arise instead from partially ionized zones in the H II region photodissociation regions. We discover G039.515+00.511, one of the most luminous H II regions in the Galaxy. We also detect the RRL emission from three H II regions with diameters > 100 {pc}, making them some of the physically largest known H II regions in the Galaxy. This survey completes the HRDS H II region census in the Northern sky, where we have discovered 887 H II regions and more than doubled the size of the previously known census of Galactic H II regions.

How the Learning Path and the Very Structure of a Multifloored Environment Influence Human Spatial Memory

PubMed Central

Dollé, Laurent; Droulez, Jacques; Bennequin, Daniel; Berthoz, Alain; Thibault, Guillaume

2015-01-01

Few studies have explored how humans memorize landmarks in complex multifloored buildings. They have observed that participants memorize an environment either by floors or by vertical columns, influenced by the learning path. However, the influence of the building’s actual structure is not yet known. In order to investigate this influence, we conducted an experiment using an object-in-place protocol in a cylindrical building to contrast with previous experiments which used rectilinear environments. Two groups of 15 participants were taken on a tour with a first person perspective through a virtual cylindrical three-floored building. They followed either a route discovering floors one at a time, or a route discovering columns (by simulated lifts across floors). They then underwent a series of trials, in which they viewed a camera movement reproducing either a segment of the learning path (familiar trials), or performing a shortcut relative to the learning trajectory (novel trials). We observed that regardless of the learning path, participants better memorized the building by floors, and only participants who had discovered the building by columns also memorized it by columns. This expands on previous results obtained in a rectilinear building, where the learning path favoured the memory of its horizontal and vertical layout. Taken together, these results suggest that both learning mode and an environment’s structure influence the spatial memory of complex multifloored buildings. PMID:26770288

A new spontaneous allele at the pink-eyed dilution (p) locus discovered in Mus musculus castaneus.

PubMed

Tsuji, A; Wakayama, T; Ishikawa, A

1995-10-01

Mutant mice characterized by a cream coat and pink eyes were spontaneously discovered among the descendants of Indonesian wild mice (Mus musculus castaneus). This mutant phenotype was controlled by a single autosomal recessive gene that was allelic to the pink-eyed dilution (p) gene. The mutant mouse phenotypically resembled the original p mouse which was the first mutant identified at this locus. Nevertheless, these two alleles differed in origin, a previous report suggesting that the original p allele was derived from Japanese wild mice (M. m. molossinus). Thus the symbol pcas (pink-eyed castaneus) was proposed for the present mutation allele.

Asteroid and comet flux in the neighborhood of the earth

NASA Technical Reports Server (NTRS)

Shoemaker, Eugene M.; Shoemaker, Carolyn S.; Wolfe, Ruth F.

1988-01-01

Significant advances in the knowledge and understanding of the flux of large solid objects in the neighborhood of Earth have occurred. The best estimates of the collision rates with Earth of asteroids and comets and the corresponding production of impact craters are presented. Approximately 80 Earth-crossing asteroids were discovered through May 1988. Among 42 new Earth-crossing asteroids found in the last decade, two-thirds were discovered from observations at Palomar Observatory and 15 were discovered or independently detected in dedicated surveys with the Palomar Observatory and 15 were discovered or independently detected in dedicated surveys with the Palomar 46 cm Schmidt. Probabilities of collision with Earth have been calculated for about two-thirds of the known Earth-crossing asteroids. When multiplied by the estimated population of Earth-crossers, this yields an estimated present rate of collision about 65 pct higher than that previously reported. Spectrophotometric data obtained chiefly in the last decade show that the large majority of obvserved Earth-crossers are similar to asteroids found in the inner part of the main belt. The number of discovered Earth-crossing comets is more than 4 times greater than the number of known Earth-crossing asteroids, but reliable data on the sizes of comet nuclei are sparse. The flux of comets almost certainly was highly variable over late geologic time, owing to the random perturbation of the Oort comet cloud by stars in the solar neighborhood.

A novel approach for discovering condition-specific correlations of gene expressions within biological pathways by using cloud computing technology.

PubMed

Chang, Tzu-Hao; Wu, Shih-Lin; Wang, Wei-Jen; Horng, Jorng-Tzong; Chang, Cheng-Wei

2014-01-01

Microarrays are widely used to assess gene expressions. Most microarray studies focus primarily on identifying differential gene expressions between conditions (e.g., cancer versus normal cells), for discovering the major factors that cause diseases. Because previous studies have not identified the correlations of differential gene expression between conditions, crucial but abnormal regulations that cause diseases might have been disregarded. This paper proposes an approach for discovering the condition-specific correlations of gene expressions within biological pathways. Because analyzing gene expression correlations is time consuming, an Apache Hadoop cloud computing platform was implemented. Three microarray data sets of breast cancer were collected from the Gene Expression Omnibus, and pathway information from the Kyoto Encyclopedia of Genes and Genomes was applied for discovering meaningful biological correlations. The results showed that adopting the Hadoop platform considerably decreased the computation time. Several correlations of differential gene expressions were discovered between the relapse and nonrelapse breast cancer samples, and most of them were involved in cancer regulation and cancer-related pathways. The results showed that breast cancer recurrence might be highly associated with the abnormal regulations of these gene pairs, rather than with their individual expression levels. The proposed method was computationally efficient and reliable, and stable results were obtained when different data sets were used. The proposed method is effective in identifying meaningful biological regulation patterns between conditions.

Quantifying Measurement; The tyranny of numbers

NASA Astrophysics Data System (ADS)

Williams, Jeffrey H.

2016-10-01

Measurements and experiments are made each and every day, in fields as disparate as particle physics, chemistry, economics and medicine, but have you ever wondered why it is that a particular experiment has been designed to be the way it is. Indeed, how do you design an experiment to measure something whose value is unknown, and what should your considerations be on deciding whether an experiment has yielded the sought after, or indeed any useful result? These are old questions, and they are the reason behind this volume. We will explore the origins of the methods of data analysis that are today routinely applied to all measurements, but which were unknown before the mid-19th Century. Anyone who is interested in the relationship between the precision and accuracy of measurements will find this volume useful. Whether you are a physicist, a chemist, a social scientist, or a student studying one of these subjects, you will discover that the basis of measurement is the struggle to identify the needle of useful data hidden in the haystack of obscuring background noise.

Assessment of source-specific health effects associated with an unknown number of major sources of multiple air pollutants: a unified Bayesian approach.

PubMed

Park, Eun Sug; Hopke, Philip K; Oh, Man-Suk; Symanski, Elaine; Han, Daikwon; Spiegelman, Clifford H

2014-07-01

There has been increasing interest in assessing health effects associated with multiple air pollutants emitted by specific sources. A major difficulty with achieving this goal is that the pollution source profiles are unknown and source-specific exposures cannot be measured directly; rather, they need to be estimated by decomposing ambient measurements of multiple air pollutants. This estimation process, called multivariate receptor modeling, is challenging because of the unknown number of sources and unknown identifiability conditions (model uncertainty). The uncertainty in source-specific exposures (source contributions) as well as uncertainty in the number of major pollution sources and identifiability conditions have been largely ignored in previous studies. A multipollutant approach that can deal with model uncertainty in multivariate receptor models while simultaneously accounting for parameter uncertainty in estimated source-specific exposures in assessment of source-specific health effects is presented in this paper. The methods are applied to daily ambient air measurements of the chemical composition of fine particulate matter ([Formula: see text]), weather data, and counts of cardiovascular deaths from 1995 to 1997 for Phoenix, AZ, USA. Our approach for evaluating source-specific health effects yields not only estimates of source contributions along with their uncertainties and associated health effects estimates but also estimates of model uncertainty (posterior model probabilities) that have been ignored in previous studies. The results from our methods agreed in general with those from the previously conducted workshop/studies on the source apportionment of PM health effects in terms of number of major contributing sources, estimated source profiles, and contributions. However, some of the adverse source-specific health effects identified in the previous studies were not statistically significant in our analysis, which probably resulted because we incorporated parameter uncertainty in estimated source contributions that has been ignored in the previous studies into the estimation of health effects parameters. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Personality Characteristics of Leaders Identifying with Different Student Subcultures.

ERIC Educational Resources Information Center

Brainard, Stephen R.

This study was conducted to discover differences in personality characteristics among student leaders. The personality characteristics of presidents of campus organizations affiliated with one of four distinguishable student subcultures, identified by previous research as vocational, academic, collegiate, and nonconformist, were measured by the…

Phylogeography and genetic identification of the newly-discovered populations of torrent salamanders (Rhyacotriton cascade and R. variegatus) in the central Cascades (USA)

USGS Publications Warehouse

Wagner, R.S.; Miller, Mark P.; Haig, Susan M.

2006-01-01

Newly discovered populations of Rhyacotritonidae were investigated for taxonomic identity, hybridization, and sympatry. Species in the genus Rhyacotriton have been historically difficult to identify using morphological characters. Mitochondrial (mtDNA) 16S ribosomal RNA sequences (491 bp) and allozymes (6 loci) were used to identify the distribution of populations occurring intermediate between the previously described ranges of R. variegatus and R. cascadae in the central Cascade Mountain region of Oregon. Allozyme and mitochondrial sequence data both indicated the presence of two distinct evolutionary lineages, with each lineage corresponding to the allopatric distribution of R. cascadae and R. variegatus. Results suggest the Willamette River acts as a phylogeographic barrier limiting the distribution of both species, although we cannot exclude the possibility that reproductive isolation also exists that reinforces species' distributions. This study extends the previously described geographical ranges of both R. cascadae and R. variegatus and defines an eastern range limit for R. variegatus conservation efforts.

Fast machine-learning online optimization of ultra-cold-atom experiments.

PubMed

Wigley, P B; Everitt, P J; van den Hengel, A; Bastian, J W; Sooriyabandara, M A; McDonald, G D; Hardman, K S; Quinlivan, C D; Manju, P; Kuhn, C C N; Petersen, I R; Luiten, A N; Hope, J J; Robins, N P; Hush, M R

2016-05-16

We apply an online optimization process based on machine learning to the production of Bose-Einstein condensates (BEC). BEC is typically created with an exponential evaporation ramp that is optimal for ergodic dynamics with two-body s-wave interactions and no other loss rates, but likely sub-optimal for real experiments. Through repeated machine-controlled scientific experimentation and observations our 'learner' discovers an optimal evaporation ramp for BEC production. In contrast to previous work, our learner uses a Gaussian process to develop a statistical model of the relationship between the parameters it controls and the quality of the BEC produced. We demonstrate that the Gaussian process machine learner is able to discover a ramp that produces high quality BECs in 10 times fewer iterations than a previously used online optimization technique. Furthermore, we show the internal model developed can be used to determine which parameters are essential in BEC creation and which are unimportant, providing insight into the optimization process of the system.

Fast machine-learning online optimization of ultra-cold-atom experiments

PubMed Central

Wigley, P. B.; Everitt, P. J.; van den Hengel, A.; Bastian, J. W.; Sooriyabandara, M. A.; McDonald, G. D.; Hardman, K. S.; Quinlivan, C. D.; Manju, P.; Kuhn, C. C. N.; Petersen, I. R.; Luiten, A. N.; Hope, J. J.; Robins, N. P.; Hush, M. R.

2016-01-01

We apply an online optimization process based on machine learning to the production of Bose-Einstein condensates (BEC). BEC is typically created with an exponential evaporation ramp that is optimal for ergodic dynamics with two-body s-wave interactions and no other loss rates, but likely sub-optimal for real experiments. Through repeated machine-controlled scientific experimentation and observations our ‘learner’ discovers an optimal evaporation ramp for BEC production. In contrast to previous work, our learner uses a Gaussian process to develop a statistical model of the relationship between the parameters it controls and the quality of the BEC produced. We demonstrate that the Gaussian process machine learner is able to discover a ramp that produces high quality BECs in 10 times fewer iterations than a previously used online optimization technique. Furthermore, we show the internal model developed can be used to determine which parameters are essential in BEC creation and which are unimportant, providing insight into the optimization process of the system. PMID:27180805

Discovery of Neuropeptides in the Nematode Ascaris suum by Database Mining and Tandem Mass Spectrometry

PubMed Central

Jarecki, Jessica L.; Frey, Brian L.; Smith, Lloyd M.; Stretton, Antony O.

2011-01-01

Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was used to discover peptides in extracts of the large parasitic nematode Ascaris suum. This required the assembly of a new database of known and predicted peptides. In addition to those already sequenced, peptides were either previously predicted to be processed from precursor proteins identified in an A. suum library of expressed sequence tags (ESTs), or newly predicted from a library of A. suum genome survey sequences (GSSs). The predicted MS/MS fragmentation patterns of this collection of real and putative peptides were compared with the actual fragmentation patterns found in the MS/MS spectra of peptides fractionated by MS; this enabled individual peptides to be sequenced. Many previously identified peptides were found, and 21 novel peptides were discovered. Thus, this approach is very useful, despite the fact that the available GSS database is still preliminary, having only 1X coverage. PMID:21524146

Kinematics and Chemistry of Halo Substructures: The Vicinity of the Virgo Overdensity

NASA Astrophysics Data System (ADS)

Casey, Andrew R.; Keller, Stefan C.; Da Costa, Gary

2012-04-01

We present observations obtained with the Anglo-Australian Telescope's 2dF wide field spectrograph AAOmega of K-type stars located within a region of the sky which contains the Virgo Overdensity and the leading arm of the Sagittarius Stream. On the basis of the resulting velocity histogram, we isolate halo substructures in these overlapping regions including Sagittarius and previously discovered Virgo groups. Through comparisons with N-body models of the Galaxy-Sagittarius interaction, we find a tri-axial dark matter halo is favored and we exclude a prolate shape. This result is contradictory with other observations along the Sagittarius leading arm, which typically favor prolate models. We have also uncovered K-giant members of Sagittarius that are notably more metal-poor (lang[Fe/H]rang = -1.7 ± 0.3 dex) than previous studies. This suggests a significantly wider metallicity distribution exists in the Sagittarius Stream than formerly considered. We also present data on five carbon stars which were discovered in our sample.

Decomposition of Multi-player Games

NASA Astrophysics Data System (ADS)

Zhao, Dengji; Schiffel, Stephan; Thielscher, Michael

Research in General Game Playing aims at building systems that learn to play unknown games without human intervention. We contribute to this endeavour by generalising the established technique of decomposition from AI Planning to multi-player games. To this end, we present a method for the automatic decomposition of previously unknown games into independent subgames, and we show how a general game player can exploit a successful decomposition for game tree search.

Nuclear and chloroplast DNA phylogeny reveals complex evolutionary history of Elymus pendulinus.

PubMed

Yan, Chi; Hu, Qianni; Sun, Genlou

2014-02-01

Evidence accumulated over the last decade has shown that allopolyploid genomes may undergo complex reticulate evolution. In this study, 13 accessions of tetraploid Elymus pendulinus were analyzed using two low-copy nuclear genes (RPB2 and PepC) and two regions of chloroplast genome (Rps16 and trnD-trnT). Previous studies suggested that Pseudoroegneria (St) and an unknown diploid (Y) were genome donors to E. pendulinus, and that Pseudoroegneria was the maternal donor. Our results revealed an extreme reticulate pattern, with at least four distinct gene lineages coexisting within this species that might be acquired through a possible combination of allotetraploidization and introgression from both within and outside the tribe Hordeeae. Chloroplast DNA data identified two potential maternal genome donors (Pseudoroegneria and an unknown species outside Hordeeae) to E. pendulinus. Nuclear gene data indicated that both Pseudoroegneria and an unknown Y diploid have contributed to the nuclear genome of E. pendulinus, in agreement with cytogenetic data. However, unexpected contributions from Hordeum and unknown aliens from within or outside Hordeeae to E. pendulinus without genome duplication were observed. Elymus pendulinus provides a remarkable instance of the previously unsuspected chimerical nature of some plant genomes and the resulting phylogenetic complexity produced by multiple historical reticulation events.

ERP profiles for face and word recognition are based on their status in semantic memory not their stimulus category.

PubMed

Nie, Aiqing; Griffin, Michael; Keinath, Alexander; Walsh, Matthew; Dittmann, Andrea; Reder, Lynne

2014-04-04

Previous research has suggested that faces and words are processed and remembered differently as reflected by different ERP patterns for the two types of stimuli. Specifically, face stimuli produced greater late positive deflections for old items in anterior compared to posterior regions, while word stimuli produced greater late positive deflections in posterior compared to anterior regions. Given that words have existing representations in subjects׳ long-term memories (LTM) and that face stimuli used in prior experiments were of unknown individuals, we conducted an ERP study that crossed face and letter stimuli with the presence or absence of a prior (stable or existing) memory representation. During encoding, subjects judged whether stimuli were known (famous face or real word) or not known (unknown person or pseudo-word). A surprise recognition memory test required subjects to distinguish between stimuli that appeared during the encoding phase and stimuli that did not. ERP results were consistent with previous research when comparing unknown faces and words; however, the late ERP pattern for famous faces was more similar to that for words than for unknown faces. This suggests that the critical ERP difference is mediated by whether there is a prior representation in LTM, and not whether the stimulus involves letters or faces. Published by Elsevier B.V.

Hazardous-waste-characterization survey of unknown drums at the 21st Tactical Fighter Wing, Elmendorf and Shemya Air Force Bases, and Galena and King Salmon Airports, Alaska. Final report 2-13 Aug 91

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bishop, M.S.

1991-12-01

At the request of the USAF Regional Hospital Elmendorf/SGPB (PACAF), the Armstrong Laboratory, Occupational and Environmental Health Directorate, conducted a hazardous waste characterization survey of unknown drums at Elmendorf AFB from 2 Aug - 13 Aug 91. The scope of the survey was to sample and characterize drums of unknown material stored at Elmendorf AFB, Shemya AFB, and Galena and King Salmon Airports. Several waste streams were sampled at Elmendorf AFB to revalidate sample results from a previous survey.

Influence of multiple categories on the prediction of unknown properties

PubMed Central

Verde, Michael F.; Murphy, Gregory L.; Ross, Brian H.

2006-01-01

Knowing an item's category helps us predict its unknown properties. Previous studies suggest that when asked to evaluate the probability of an unknown property, people tend to consider only an item's most likely category, ignoring alternative categories. In the present study, property prediction took the form of either a probability rating or a speeded, binary-choice judgment. Consistent with past findings, subjects ignored alternative categories in their probability ratings. However, their binary-choice judgments were influenced by alternative categories. This novel finding suggests that the way category knowledge is used in prediction depends critically on the form of the prediction. PMID:16156183

Locus of control as a stress moderator and mediator in children of divorce.

PubMed

Kim, L S; Sandler, I N; Tein, J Y

1997-04-01

This paper examined the stress moderator and mediator effects of four dimensions of perceived control in children of divorce. The dimensions of locus of control included internal control for positive events, internal control for negative events, unknown control for positive events, and unknown control for negative events. The sample consisted of 222 children between the ages of 8 and 12 whose parents had divorced in the previous 2 years. Moderational analyses showed that unknown control for positive events interacted with negative events to predict total symptoms. Plots of the simple slopes indicated a stress buffering effect whereby the slope of negative events on symptoms was higher for high than for low levels of unknown control for positive events. Mediational analysis showed that the relations between negative events and symptoms were mediated by both unknown control for positive events and unknown control for negative events. In contrast, evidence was not found for either a stress mediational or a moderational model for perceived internal control for positive or negative events. These results suggest that unknown control beliefs may be a particularly important dimension of control for children of divorce.

A study of the discrepant QSO X-ray luminosity function from the HEAO-2 data archive

NASA Technical Reports Server (NTRS)

Margon, B.

1984-01-01

An in-progress investigation aimed at characterizing the X-ray luminosity of very faint QSOs is described. More than 100 faint, previously uncataloged QSOs which lie in areas imaged in X rays at very high sensitivity were discovered.

Bromothymol Blue: The Demo We All Do!

ERIC Educational Resources Information Center

Rutherford, Sandra; Coffman, Margaret

2005-01-01

Often science teachers perform demonstrations only to discover that students have already seen the experiment in a previous course. Teachers should take advantage of these opportunities to showcase the interconnectedness of different science disciplines. One example of a demonstration used across most science disciplines and grade levels involves…

Language Development and Scaffolding in a Sino-American Telecollaborative Project

ERIC Educational Resources Information Center

Jin, Li

2013-01-01

Previous research (e.g., Belz & Thorne, 2006; Ware & O'Dowd, 2008) has discovered that language learning can be afforded through intercultural telecollaboration. From a sociocultural theoretical perspective, the current study investigated the language development outcomes and process in a 10-week Sino-American telecollaborative project…

Complete Genome Sequences of Four Novel Escherichia coli Bacteriophages Belonging to New Phage Groups

PubMed Central

Kot, Witold

2015-01-01

Here, we describe the sequencing and genome annotations of a set of four Escherichia coli bacteriophages (phages) belonging to newly discovered groups previously consisting of only a single phage and thus expand our knowledge of these phage groups. PMID:26184932

75 FR 60333 - Hazardous Material; Miscellaneous Packaging Amendments

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-30

... minimum thickness requirements for remanufactured steel and plastic drums; (2) reinstate the previous... communication problem for emergency responders in that it may interfere with them discovering a large amount of... prescribed in Sec. 178.2(c). D. Minimum Thickness Requirement for Remanufactured Steel and Plastic Drums...

Some New Twists to Problems Involving the Gaussian Probability Integral

NASA Technical Reports Server (NTRS)

Simon, Marvin K.; Divsalar, Dariush

1997-01-01

Using an alternate form of the Gaussian probability integral discovered a number of years ago, it is shown that the solution to a number of previously considered communication problems can be simplified and in some cases made more accurate(i.e., exact rather than bounded).

Biomechanics and Developmental Neuromotor Control.

ERIC Educational Resources Information Center

Zernicke, Ronald F.; Schneider, Klaus

1993-01-01

By applying the principles and methods of mechanics to the musculoskeletal system, new insights can be discovered about control of human limb dynamics in both adults and infants. Reviews previous research on how infants gain control of their limbs and learn to reach in the first year of life. (MDM)

Characterization of Actinomyces Isolates from Infected Root Canals of Teeth: Description of Actinomyces radicidentis sp. nov.

PubMed Central

Collins, Matthew D.; Hoyles, Lesley; Kalfas, Sotos; Sundquist, Goran; Monsen, Tor; Nikolaitchouk, Natalia; Falsen, Enevold

2000-01-01

Two strains of a previously undescribed Actinomyces-like bacterium were recovered in pure culture from infected root canals of teeth. Analysis by biochemical testing and polyacrylamide gel electrophoresis of whole-cell proteins indicated that the strains closely resembled each other phenotypically but were distinct from previously described Actinomyces and Arcanobacterium species. Comparative 16S rRNA gene-sequencing studies showed the bacterium to be a hitherto unknown subline within a group of Actinomyces species which includes Actinomyces bovis, the type species of the genus. Based on phylogenetic and phenotypic evidence, we propose that the unknown bacterium isolated from human clinical specimens be classified as Actinomyces radicidentis sp. nov. The type strain of Actinomyces radicidentis is CCUG 36733. PMID:10970390

Colours of the Outer Solar System Origins Survey (Col-OSSOS): New Insights into Kuiper belt Surfaces

NASA Astrophysics Data System (ADS)

Schwamb, M. E.; Fraser, W. C.; Bannister, M. T.; Pike, R. E.; Marsset, M.; Kavelaars, J. J.; Benecchi, S.; Delsanti, A.; Lehner, M. J.; Thirouin, A.; Guilbert-Lepoutre, A.; Peixinho, N.; Vernazza, P.

2016-12-01

The icy planetesimals of the Kuiper belt inform our knowledge about the growth of planetary embryos and our Solar System's dynamical history. The majority of the known Pluto-sized Kuiper belt objects (KBOs) are bright enough for their surfaces to be studied through optical and infrared spectroscopy. But for the typical smaller r mag > 22 mag KBOs, we must rely on what colors reveal by proxy, and this picture of Kuiper belt surfaces remains incomplete. Previous studies in this size range examined the hodgepodge set of KBOs discovered by surveys with varying and sometimes unknown detection biases that make it challenging to explore the true frequency of surface colors within the Kuiper belt. The Colours of the Outer Solar System Origins Survey (Col-OSSOS) aims to explore and explain the compositional variety within the Kuiper belt through near simultaneous u, g,r and J colors with the Gemini North Telescope and the Canada-France-Hawaii Telescope. The survey targets KBOs brighter than 23.6 r' mag ( 50-300 km) found by the Outer Solar System Origins Survey (OSSOS). With Col-OSSOS, we have a set of colors measured for a KBO sample discovered in a brightness limited survey, with a well-measured detection efficiency. Col-OSSOS will provide a compositional-dynamical map of the Kuiper belt in which to study the end of stages of Neptune migration and the conditions of the early planetesimal disk where these small icy bodies formed. We will give an overview of Col-OSSOS and an update on the program's current status. We will present the photometry from the first 30 KBOs studied from the first complete OSSOS block and examine the implications for Kuiper belt surfaces. We derive the observed and debiased ratio of neutral to red KBOs, measure the masses of the three color populations within the Kuiper belt (the red and neutral dynamically excited population and the red cold classical belt), and explore the radial color distribution in the primordial planetesimal disk before Neptune migration.

RED GIANTS IN ECLIPSING BINARY AND MULTIPLE-STAR SYSTEMS: MODELING AND ASTEROSEISMIC ANALYSIS OF 70 CANDIDATES FROM KEPLER DATA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gaulme, P.; McKeever, J.; Rawls, M. L.

2013-04-10

Red giant stars are proving to be an incredible source of information for testing models of stellar evolution, as asteroseismology has opened up a window into their interiors. Such insights are a direct result of the unprecedented data from space missions CoRoT and Kepler as well as recent theoretical advances. Eclipsing binaries are also fundamental astrophysical objects, and when coupled with asteroseismology, binaries provide two independent methods to obtain masses and radii and exciting opportunities to develop highly constrained stellar models. The possibility of discovering pulsating red giants in eclipsing binary systems is therefore an important goal that could potentiallymore » offer very robust characterization of these systems. Until recently, only one case has been discovered with Kepler. We cross-correlate the detected red giant and eclipsing-binary catalogs from Kepler data to find possible candidate systems. Light-curve modeling and mean properties measured from asteroseismology are combined to yield specific measurements of periods, masses, radii, temperatures, eclipse timing variations, core rotation rates, and red giant evolutionary state. After using three different techniques to eliminate false positives, out of the 70 systems common to the red giant and eclipsing-binary catalogs we find 13 strong candidates (12 previously unknown) to be eclipsing binaries, one to be a non-eclipsing binary with tidally induced oscillations, and 10 more to be hierarchical triple systems, all of which include a pulsating red giant. The systems span a range of orbital eccentricities, periods, and spectral types F, G, K, and M for the companion of the red giant. One case even suggests an eclipsing binary composed of two red giant stars and another of a red giant with a {delta}-Scuti star. The discovery of multiple pulsating red giants in eclipsing binaries provides an exciting test bed for precise astrophysical modeling, and follow-up spectroscopic observations of many of the candidate systems are encouraged. The resulting highly constrained stellar parameters will allow, for example, the exploration of how binary tidal interactions affect pulsations when compared to the single-star case.« less

Single nucleotide polymorphisms in bone turnover-related genes in Koreans: ethnic differences in linkage disequilibrium and haplotype

PubMed Central

Kim, Kyung-Seon; Kim, Ghi-Su; Hwang, Joo-Yeon; Lee, Hye-Ja; Park, Mi-Hyun; Kim, Kwang-joong; Jung, Jongsun; Cha, Hyo-Soung; Shin, Hyoung Doo; Kang, Jong-Ho; Park, Eui Kyun; Kim, Tae-Ho; Hong, Jung-Min; Koh, Jung-Min; Oh, Bermseok; Kimm, Kuchan; Kim, Shin-Yoon; Lee, Jong-Young

2007-01-01

Background Osteoporosis is defined as the loss of bone mineral density that leads to bone fragility with aging. Population-based case-control studies have identified polymorphisms in many candidate genes that have been associated with bone mass maintenance or osteoporotic fracture. To investigate single nucleotide polymorphisms (SNPs) that are associated with osteoporosis, we examined the genetic variation among Koreans by analyzing 81 genes according to their function in bone formation and resorption during bone remodeling. Methods We resequenced all the exons, splice junctions and promoter regions of candidate osteoporosis genes using 24 unrelated Korean individuals. Using the common SNPs from our study and the HapMap database, a statistical analysis of deviation in heterozygosity depicted. Results We identified 942 variants, including 888 SNPs, 43 insertion/deletion polymorphisms, and 11 microsatellite markers. Of the SNPs, 557 (63%) had been previously identified and 331 (37%) were newly discovered in the Korean population. When compared SNPs in the Korean population with those in HapMap database, 1% (or less) of SNPs in the Japanese and Chinese subpopulations and 20% of those in Caucasian and African subpopulations were significantly differentiated from the Hardy-Weinberg expectations. In addition, an analysis of the genetic diversity showed that there were no significant differences among Korean, Han Chinese and Japanese populations, but African and Caucasian populations were significantly differentiated in selected genes. Nevertheless, in the detailed analysis of genetic properties, the LD and Haplotype block patterns among the five sub-populations were substantially different from one another. Conclusion Through the resequencing of 81 osteoporosis candidate genes, 118 unknown SNPs with a minor allele frequency (MAF) > 0.05 were discovered in the Korean population. In addition, using the common SNPs between our study and HapMap, an analysis of genetic diversity and deviation in heterozygosity was performed and the polymorphisms of the above genes among the five populations were substantially differentiated from one another. Further studies of osteoporosis could utilize the polymorphisms identified in our data since they may have important implications for the selection of highly informative SNPs for future association studies. PMID:18036257

Stratigraphic Reconstruction of a Late Pleistocene Cypress Forest Discovered on the Northern Gulf of Mexico Continental Shelf

NASA Astrophysics Data System (ADS)

Gonzalez Rodriguez, S. M.; Bentley, S. J.; Obelcz, J.; Truong, J. T.; DeLong, K. L.; Xu, K.; Harley, G. L.; Reese, C. A.; Caporaso, A.; Shen, Z.

2017-12-01

A previously buried bald cypress forest (Taxodium distichum) was discovered on the continental shelf, offshore of Orange Beach, Alabama, USA, in 20 m water depth. The forest was possibly exhumed by Hurricane Ivan in 2004, and is now exposed as stumps in life position in a trough located in the northern Gulf of Mexico continental shelf seafloor. We are investigating the local stratigraphy, paleo-landscape, and mode of forest preservation of this unique site. In August 2015 and July 2016, submersible vibracores (18 in total) were collected. Core analysis included: bulk density and imaging via Geotek multi sensor core logger, sediment grain size, structure, and organic content via loss-on-ignition. Selected samples have been dated using 14C and optically stimulated luminescence (OSL) methods. Multibeam and CHIRP subbottom bathymetry provide context for litho- and chrono-stratigraphy of the site. Integration of core lithostratigraphy and modern shelf bathymetry reveal Holocene transgressive sands blanketing diverse sedimentary facies that are truncated by the late Pleistocene-early Holocene ravinement. Deposits below the ravinement surface include interbedded sand and mud (exact age unknown, but possibly pertaining to a shallow marine environment), overlying a floodplain/swamp facies of woody debris, peat, and mud (provisionally dated by 14C to 41-45 ka). These units grade laterally into paleosols that appear to be 10-15 ka older, based on recently obtained preliminary OSL dates. Occurrence of paleosols and swamp deposits of broadly similar age and elevation suggests that the ancient landscape possessed topographic relief that allowed wetland and upland habitats to develop in close proximity. These new OSL dates enhance our initial hypothesis that floodplain aggradation in the area was a key factor that might have allowed forest preservation. The timing of temporary sea level rises (SLR) ca. 40 and 60 ka. with our 14C and preliminary OSL dates, suggests that floodplain aggradation associated with SLRs could have buried the swamp and forest sediments. Variable paleo-topography in the area at the time of burial provided enough sediment to keep the cypress forest blanketed, withstanding periods of erosion as sea level fluctuated through the late Pleistocene to Holocene, thus facilitating forest preservation.

Adaptive and Innate Immune Responsiveness to Borrelia burgdorferi sensu lato in Exposed Asymptomatic Children and Children with Previous Clinical Lyme Borreliosis

PubMed Central

Skogman, Barbro H.; Hellberg, Sandra; Ekerfelt, Christina; Jenmalm, Maria C.; Forsberg, Pia; Ludvigsson, Johnny; Bergström, Sven; Ernerudh, Jan

2012-01-01

Why some individuals develop clinical manifestations in Lyme borreliosis (LB) while others remain asymptomatic is largely unknown. Therefore, we wanted to investigate adaptive and innate immune responsiveness to Borrelia burgdorferi sensu lato in exposed Borrelia-antibody-positive asymptomatic children (n = 20), children with previous clinical LB (n = 24), and controls (n = 20). Blood samples were analyzed for Borrelia-specific interferon (IFN)-γ, interleukin (IL)-4, and IL-17 secretion by ELISPOT and Borrelia-induced IL-1β, IL-6, IL-10, IL-12(p70), and tumor necrosis factor (TNF) secretion by Luminex. We found no significant differences in cytokine secretion between groups, but a tendency towards an increased spontaneous secretion of IL-6 was found among children with previous clinical LB. In conclusion, the adaptive or innate immune responsiveness to Borrelia burgdorferi sensu lato was similar in Borrelia-exposed asymptomatic children and children with previous clinical LB. Thus, the immunological mechanisms of importance for eradicating the spirochete effectively without developing clinical manifestations of LB remain unknown. PMID:22190976

Characterization of Marine Mammal Recordings from the Hawaii Range Complex

DTIC Science & Technology

2010-11-01

This was higher than known from a previous study at Palmyra Atoll (Baumann- Pickering, 2009), where the peak frequency was around 25-29 kHz. Recordings...cavirostris), signals known from an unknown species at Palmyra Atoll (possibly Mesoplodon hotaula, Baumann-Pickering et al., 2010), and an unknown...Measurement of Activity in Odontocete Species of Palmyra Atoll by Acoustic Monitoring,” Doctorate thesis, Eberhard-Karls-Universität Tübingen, Tübingen

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sandhaus, Phoebe H.; Debes, John H.; Ely, Justin

The search for transiting habitable exoplanets has broadened to include several types of stars that are smaller than the Sun in an attempt to increase the observed transit depth and hence the atmospheric signal of the planet. Of all spectral types, white dwarfs (WDs) are the most favorable for this type of investigation. The fraction of WDs that possess close-in rocky planets is unknown, but several large angle stellar surveys have the photometric precision and cadence to discover at least one if they are common. Ultraviolet observations of WDs may allow for detection of molecular oxygen or ozone in themore » atmosphere of a terrestrial planet. We use archival Hubble Space Telescope data from the Cosmic Origins Spectrograph to search for transiting rocky planets around UV-bright WDs. In the process, we discovered unusual variability in the pulsating WD GD 133, which shows slow sinusoidal variations in the UV. While we detect no planets around our small sample of targets, we do place stringent limits on the possibility of transiting planets, down to sub-lunar radii. We also point out that non-transiting small planets in thermal equilibrium are detectable around hotter WDs through infrared excesses, and identify two candidates.« less

Teaching the Thrill of Discovery: Student Exploration of Ultra-Faint Dwarf Galaxies with the NOAO Data Lab

NASA Astrophysics Data System (ADS)

Olsen, Knut; Walker, Constance E.; Smith, Blake; NOAO Data Lab Team

2018-01-01

We describe an activity aimed at teaching students how ultra-faint Milky Way dwarf galaxies are typically discovered: through filtering of optical photometric catalogs and cross-examination with deep images. The activity, which was developed as part of the Teen Astronomy Café program (https://teensciencecafe.org/cafes/az-teen-astronomy-cafe-tucson/), uses the NOAO Data Lab (http://datalab.noao.edu) and other professional-grade tools to lead high school students through exploration of the object catalog and images from the Survey of the Magellanic Stellar History (SMASH). The students are taught how to use images and color-magnitude diagrams to analyze and interpret stellar populations of increasing complexity, including those of star clusters and the Magellanic Clouds, and culminating with the discovery of the Hydra II ultra-faint dwarf galaxy. The tools and datasets presented allow the students to explore and discover other known stellar systems, as well as unknown candidate star clusters and dwarf galaxies. The ultimate goal of the activity is to give students insight into the methods of modern astronomical research and to allow them to participate in the thrill of discovery.

A theoretical perspective on running-related injuries.

PubMed

Gallant, Jodi Lynn; Pierrynowski, Michael Raymond

2014-03-01

The etiology of running-related injuries remains unknown; however, an implicit theory underlies much of the conventional research and practice in the prevention of these injuries. This theory posits that the cause of running-related injuries lies in the high-impact forces experienced when the foot contacts the ground and the subsequent abnormal movement of the subtalar joint. The application of this theory is seen in the design of the modern running shoe, with cushioning, support, and motion control. However, a new theory is emerging that suggests that it is the use of these modern running shoes that has caused a maladaptive running style, which contributes to a high incidence of injury among runners. The suggested application of this theory is to cease use of the modern running shoe and transition to barefoot or minimalist running. This new running paradigm, which is at present inadequately defined, is proposed to avoid the adverse biomechanical effects of the modern running shoe. Future research should rigorously define and then test both theories regarding their ability to discover the etiology of running-related injury. Once discovered, the putative cause of running-related injury will then provide an evidence-based rationale for clinical prevention and treatment.

Keylimepie peckorum gen. n. and sp. n., (Hymenoptera, Braconidae) from southern Florida, U.S., the first known brachypterous member of the subfamily Microgastrinae.

PubMed

Fernandez-Triana, Jose; Boudreault, Caroline

2016-01-01

Keylimepie peckorum Fernandez-Triana, gen. n. and sp. n., are described from southern Florida, U.S. Females have the shortest wings (0.6-0.7 × body length) of any known microgastrine wasp. The genus can also be recognized on features of the head, propodeum and first three metasomal tergites. All specimens were collected in hammock forests of the Florida Keys and Everglades National Park, but their host caterpillar is unknown. Because its morphology is unique and it is the first new microgastrine genus discovered in North America since 1985, the potential for future conservation of the species is discussed.

Rapid one-step recombinational cloning

PubMed Central

Fu, Changlin; Wehr, Daniel R.; Edwards, Janice; Hauge, Brian

2008-01-01

As an increasing number of genes and open reading frames of unknown function are discovered, expression of the encoded proteins is critical toward establishing function. Accordingly, there is an increased need for highly efficient, high-fidelity methods for directional cloning. Among the available methods, site-specific recombination-based cloning techniques, which eliminate the use of restriction endonucleases and ligase, have been widely used for high-throughput (HTP) procedures. We have developed a recombination cloning method, which uses truncated recombination sites to clone PCR products directly into destination/expression vectors, thereby bypassing the requirement for first producing an entry clone. Cloning efficiencies in excess of 80% are obtained providing a highly efficient method for directional HTP cloning. PMID:18424799

Chromosomal Microarray Testing in 42 Korean Patients with Unexplained Developmental Delay, Intellectual Disability, Autism Spectrum Disorders, and Multiple Congenital Anomalies.

PubMed

Lee, Sun Ho; Song, Wung Joo

2017-09-01

Chromosomal microarray (CMA) is a high-resolution, high-throughput method of identifying submicroscopic genomic copy number variations (CNVs). CMA has been established as the first-line diagnostic test for individuals with developmental delay (DD), intellectual disability (ID), autism spectrum disorders (ASDs), and multiple congenital anomalies (MCAs). CMA analysis was performed in 42 Korean patients who had been diagnosed with unexplained DD, ID, ASDs, and MCAs. Clinically relevant CNVs were discovered in 28 patients. Variants of unknown significance were detected in 13 patients. The diagnostic yield was high (66.7%). CMA is a superior diagnostic tool compared with conventional karyotyping and fluorescent in situ hybridization.

Building the atomic model of a boreal lake virus of unknown fold in a 3.9 Å cryo-EM map.

PubMed

De Colibus, Luigi; Stuart, David I

2018-04-01

We report here the protocol adopted to build the atomic model of the newly discovered virus FLiP (Flavobacterium infecting, lipid-containing phage) into 3.9 Å cryo-electron microscopy (cryo-EM) maps. In particular, this report discusses the combination of density modification procedures, automatic model building and bioinformatics tools applied to guide the tracing of the major capsid protein (MCP) of this virus. The protocol outlined here may serve as a reference for future structural determination by cryo-EM of viruses lacking detectable structural homologues. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Stable isotope and DNA evidence for ritual sequences in Inca child sacrifice

PubMed Central

Wilson, Andrew S.; Taylor, Timothy; Ceruti, Maria Constanza; Chavez, Jose Antonio; Reinhard, Johan; Grimes, Vaughan; Meier-Augenstein, Wolfram; Cartmell, Larry; Stern, Ben; Richards, Michael P.; Worobey, Michael; Barnes, Ian; Gilbert, M. Thomas P.

2007-01-01

Four recently discovered frozen child mummies from two of the highest peaks in the south central Andes now yield tantalizing evidence of the preparatory stages leading to Inca ritual killing as represented by the unique capacocha rite. Our interdisciplinary study examined hair from the mummies to obtain detailed genetic and diachronic isotopic information. This approach has allowed us to reconstruct aspects of individual identity and diet, make inferences concerning social background, and gain insight on the hitherto unknown processes by which victims were selected, elevated in social status, prepared for a high-altitude pilgrimage, and killed. Such direct information amplifies, yet also partly contrasts with, Spanish historical accounts. PMID:17923675

A new component of cosmic rays of unknown origin at a few MeV per nucleon

NASA Technical Reports Server (NTRS)

Gloecker, G.

1974-01-01

Recently discovered anomalies in the abundances and energy spectra of quiet time, extraterrestrial hydrogen, helium, carbon, nitrogen, and oxygen require serious revisions of origin theories to account for this new component of cosmic radiation. Abnormally large O/C and N/C ratios, long term intensity variations with time, and radial gradient measurements indicate a non-solar origin for these 2 to 30 MeV/nucleon particles. Ideas suggested to explain these measurements range from acceleration of galactic source material having an unusual composition to local acceleration of particles within the solar cavity. Observations are at present insufficient to choose between these alternate origin models.

Coating for components requiring hydrogen peroxide compatibility

NASA Technical Reports Server (NTRS)

Yousefiani, Ali (Inventor)

2010-01-01

The present invention provides a heretofore-unknown use for zirconium nitride as a hydrogen peroxide compatible protective coating that was discovered to be useful to protect components that catalyze the decomposition of hydrogen peroxide or corrode when exposed to hydrogen peroxide. A zirconium nitride coating of the invention may be applied to a variety of substrates (e.g., metals) using art-recognized techniques, such as plasma vapor deposition. The present invention further provides components and articles of manufacture having hydrogen peroxide compatibility, particularly components for use in aerospace and industrial manufacturing applications. The zirconium nitride barrier coating of the invention provides protection from corrosion by reaction with hydrogen peroxide, as well as prevention of hydrogen peroxide decomposition.

Percolation threshold determines the optimal population density for public cooperation

NASA Astrophysics Data System (ADS)

Wang, Zhen; Szolnoki, Attila; Perc, Matjaž

2012-03-01

While worldwide census data provide statistical evidence that firmly link the population density with several indicators of social welfare, the precise mechanisms underlying these observations are largely unknown. Here we study the impact of population density on the evolution of public cooperation in structured populations and find that the optimal density is uniquely related to the percolation threshold of the host graph irrespective of its topological details. We explain our observations by showing that spatial reciprocity peaks in the vicinity of the percolation threshold, when the emergence of a giant cooperative cluster is hindered neither by vacancy nor by invading defectors, thus discovering an intuitive yet universal law that links the population density with social prosperity.

REVIEWS OF TOPICAL PROBLEMS: The physics of planetary rings

NASA Astrophysics Data System (ADS)

Gor'kavyĭ, N. N.; Fridman, Aleksei M.

1990-02-01

A review of the collisional, collective, and resonance phenomena in planetary rings is presented. The following questions are examined: the reasons for the existence of planetary rings and the properties of a typical particle, the collisional breaking of loose bodies, and the azimuthal asymmetry effect for the rings of Saturn. A transfer theory is being developed for differentially rotating disks of inelastic particles, and the collective instabilities of planetary rings and a protoplanetary disk are discussed. A model for the resonance origin for the rings of Uranus is described, which enabled one to predict unknown satellites of Uranus that were later discovered by "Voyager-2". The problem of the stability of the rings of Uranus is examined.

The earliest herbivorous marine reptile and its remarkable jaw apparatus.

PubMed

Chun, Li; Rieppel, Olivier; Long, Cheng; Fraser, Nicholas C

2016-05-01

Newly discovered fossils of the Middle Triassic reptile Atopodentatus unicus call for a radical reassessment of its feeding behavior. The skull displays a pronounced hammerhead shape that was hitherto unknown. The long, straight anterior edges of both upper and lower jaws were lined with batteries of chisel-shaped teeth, whereas the remaining parts of the jaw rami supported densely packed needle-shaped teeth forming a mesh. The evidence indicates a novel feeding mechanism wherein the chisel-shaped teeth were used to scrape algae off the substrate, and the plant matter that was loosened was filtered from the water column through the more posteriorly positioned tooth mesh. This is the oldest record of herbivory within marine reptiles.

Increased Kawasaki Disease Incidence Associated With Higher Precipitation and Lower Temperatures, Japan, 1991-2004.

PubMed

Abrams, Joseph Y; Blase, Jennifer L; Belay, Ermias D; Uehara, Ritei; Maddox, Ryan A; Schonberger, Lawrence B; Nakamura, Yosikazu

2018-06-01

Kawasaki disease (KD) is an acute febrile vasculitis, which primarily affects children. The etiology of KD is unknown; while certain characteristics of the disease suggest an infectious origin, genetic or environmental factors may also be important. Seasonal patterns of KD incidence are well documented, but it is unclear whether these patterns are caused by changes in climate or by other unknown seasonal effects. The relationship between KD incidence and deviations from expected temperature and precipitation were analyzed using KD incidence data from Japanese nationwide epidemiologic surveys (1991-2004) and climate data from 136 weather stations of the Japan Meteorological Agency. Seven separate Poisson-distributed generalized linear regression models were run to examine the effects of temperature and precipitation on KD incidence in the same month as KD onset and the previous 1, 2, 3, 4, 5 and 6 months, controlling for geography as well as seasonal and long-term trends in KD incidence. KD incidence was negatively associated with temperature in the previous 2, 3, 4 and 5 months and positively associated with precipitation in the previous 1 and 2 months. The model that best predicted variations in KD incidence used climate data from the previous 2 months. An increase in total monthly precipitation by 100 mm was associated with increased KD incidence (rate ratio [RR] 1.012, 95% confidence interval [CI]: 1.005-1.019), and an increase of monthly mean temperature by 1°C was associated with decreased KD incidence (RR 0.984, 95% CI: 0.978-0.990). KD incidence was significantly affected by temperature and precipitation in previous months independent of other unknown seasonal factors. Climate data from the previous 2 months best predicted the variations in KD incidence. Although fairly minor, the effect of temperature and precipitation independent of season may provide additional clues to the etiology of KD.

Mapping soybean aphid resistance genes in PI 567598B

USDA-ARS?s Scientific Manuscript database

The soybean aphid (Aphis glycines Matsumura) has been a major pest of soybean [Glycine max (L.) Merr.] in North America since it was first discovered in 2000. Plant introduction PI 567598B possesses strong antibiosis resistance to soybean aphids. Our previous study revealed that the aphid resistan...

Bioherbicidal potential of a strain of Xanthomonas spp. for control of common cockelbur, (Santium strumarium)

USDA-ARS?s Scientific Manuscript database

Several isolates of a previously unreported disease were discovered on common cocklebur seedlings in Chicot County, Arkansas and Washington County, Mississippi. Diseased plants in nature exhibited angular-shaped leaf spotting symptoms on leaf margins and central leaf areas. The isolates were cultu...

Approaching Pharmacometrics as a Paleontologist Would: Recovering the Links Between Drugs and the Body Through Reconstruction.

PubMed

Craig, M; González-Sales, M; Li, J; Nekka, F

2016-03-01

Our knowledge of dinosaurs comes primarily from the fossil record. Notwithstanding the condition of these vestiges, paleontologists reconstruct early reptilian life by comparison to previously discovered specimens. When relics are missing, reasonable deductions are used to fill in the gaps.

A Closer Look at Manipulatives in Remediation

ERIC Educational Resources Information Center

Peppers, Denise S.; Wan, Anna; Phillips, Hope E.

2014-01-01

In this article, one teacher describes her action research with eighth-grade prealgebra students who are working on a conceptual understanding of fractions. Examining her middle school students' standardized test scores for the previous five years, Denise S. Peppers discovered that student performance on fractions was consistently the lowest…

Lacinipolia Patalis grote (Lepidoptera: Noctuidae) infesting Douglas-fir cones: A new host record

Treesearch

Nancy G. Rappaport

1988-01-01

Larvai of Lacinipolia patalis (Grote) (Lepidoptera: Noctuidae) were discovered in Douglas-fir (Pseudotsuga menziessi [Mirb.} Franco) cones collected from the Louisiana-Pacific Corporation's Little River Seed Orchard near Trinidad Head in Humboldt County, CA (elevation 91 m) during the fall of 1985. Previous surveys have not...

Update on Parametric Cost Models for Space Telescopes

NASA Technical Reports Server (NTRS)

Stahl. H. Philip; Henrichs, Todd; Luedtke, Alexander; West, Miranda

2011-01-01

Since the June 2010 Astronomy Conference, an independent review of our cost data base discovered some inaccuracies and inconsistencies which can modify our previously reported results. This paper will review changes to the data base, our confidence in those changes and their effect on various parametric cost models

Dana-Farber Cancer Institute: Genome-wide shRNA Screens with DEMETER Inferred Gene Effects | Office of Cancer Genomics

Cancer.gov

In this study RNA interference (RNAi) screens were performed on 285 cell lines and combined with 216 lines previously screened, which were then analyzed together with DEMETER to discover genetic dependencies across the entire pool of cell lines. Read the abstract

Comparative host range and aggressiveness of Phytophthora ramorum and Phytophthora kernoviae sp. nov. on North American and European trees

Treesearch

Clive Brasier; Joan Rose; Susan Kirk; Sandra Denman; Joan Webber

2006-01-01

Phytophthora ramorum and P. kernoviae are recently introduced, invasive pathogens in woodlands in southern Britain. P. kernoviae, previously known as Phytophthora taxon C, is a newly discovered taxon, (Brasier and others 2005), found during surveys for P. ramorum in Cornwall...

Biology, Violence, and Antisocial Personality.

ERIC Educational Resources Information Center

Kandel, Elizabeth

Aggressive and antisocial behavior have persisted as significant social problems. In response, a voluminous amount of research has been generated in an attempt to discover the causes of such behavior. Previous studies have examined separately the role of perinatal biology in the etiology of violent criminal behavior and the etiology of Anti-Social…

Conclusion: The Intersection of Student Voice and Policy Research

ERIC Educational Resources Information Center

Mitra, Dana L.

2015-01-01

This concluding chapter examines how this book on student voice intersects with previous research about policy, especially policy implementation and sustainability. Mapping onto the themes of this volume, Discovering, Developing, and Demonstrating the power of student voice, I focus on three issues--legitimizing the role of young people in the…

Disruption of Rpp1-mediated soybean rust resistance by virus-induced gene silencing

USDA-ARS?s Scientific Manuscript database

Soybean rust is a fungus that causes disease on soybeans. The discovery of soybean genes and proteins that are important for disease resistance to soybean rust may help improve soybean cultivars through breeding or transgenic technology. Proteins previously discovered in the cell nucleus of soybea...

Host specificity and phylogenetic relationships of chicken and turkey parvoviruses

USDA-ARS?s Scientific Manuscript database

Previous reports indicate that the newly discovered chicken parvoviruses (ChPV) and turkey parvoviruses (TuPV) are very similar to each other, yet they represent different species within a new genus of Parvoviridae. Currently, strain classification is based on the phylogenetic analysis of a 561 bas...

Improving Collaborative Learning by Supporting Casual Encounters in Distance Learning.

ERIC Educational Resources Information Center

Contreras, Juan; Llamas, Rafael; Vizcaino, Aurora; Vavela, Jesus

Casual encounters in a learning environment are very useful in reinforcing previous knowledge and acquiring new knowledge. Such encounters are very common in traditional learning environments and can be used successfully in social environments in which students can discover and construct knowledge through a process of dialogue, negotiation, or…

New Mode For Single-Event Upsets

NASA Technical Reports Server (NTRS)

Zoutendyk, John A.; Smith, Lawrence S.; Soli, George A.; Lo, Roger Y.

1988-01-01

Report presents theory and experimental data regarding newly discovered mode for single-event upsets, (SEU's) in complementary metal-oxide/semiconductor, static random-access memories, CMOS SRAM's. SEU cross sections larger than those expected from previously known modes given rise to speculation regarding additional mode, and subsequent cross-section measurements appear to confirm speculation.

Copy number analysis reveals a novel multiexon deletion of the COLQ gene in congenital myasthenia.

PubMed

Wang, Wei; Wu, Yanhong; Wang, Chen; Jiao, Jinsong; Klein, Christopher J

2016-12-01

Congenital myasthenic syndrome (CMS) is genetically and clinically heterogeneous. 1 Despite a considerable number of causal genes discovered, many patients are left without a specific diagnosis after genetic testing. The presumption is that novel genes yet to be discovered will account for the majority of such patients. However, it is also possible that we are neglecting a type of genetic variation: copy number changes (>50 bp) as causal for some of these patients. Next-generation sequencing (NGS) can simultaneously screen all known causal genes 2 and is increasingly being validated to have a potential to identify copy number changes. 3 We present a CMS case who did not receive a genetic diagnosis from previous Sanger sequencing, but through a novel copy number analysis algorithm integrated into our targeted NGS panel, we discovered a novel copy number mutation in the COLQ gene and made a genetic diagnosis. This discovery expands the genotype-phenotype correlation of CMS, leads to improved genetic counsel, and allows for specific pharmacologic treatment. 1 .

ATP-binding Cassette (ABC) Transport System Solute-binding Protein-guided Identification of Novel d-Altritol and Galactitol Catabolic Pathways in Agrobacterium tumefaciens C58*

PubMed Central

Wichelecki, Daniel J.; Vetting, Matthew W.; Chou, Liyushang; Al-Obaidi, Nawar; Bouvier, Jason T.; Almo, Steven C.; Gerlt, John A.

2015-01-01

Innovations in the discovery of the functions of uncharacterized proteins/enzymes have become increasingly important as advances in sequencing technology flood protein databases with an exponentially growing number of open reading frames. This study documents one such innovation developed by the Enzyme Function Initiative (EFI; U54GM093342), the use of solute-binding proteins for transport systems to identify novel metabolic pathways. In a previous study, this strategy was applied to the tripartite ATP-independent periplasmic transporters. Here, we apply this strategy to the ATP-binding cassette transporters and report the discovery of novel catabolic pathways for d-altritol and galactitol in Agrobacterium tumefaciens C58. These efforts resulted in the description of three novel enzymatic reactions as follows: 1) oxidation of d-altritol to d-tagatose via a dehydrogenase in Pfam family PF00107, a previously unknown reaction; 2) phosphorylation of d-tagatose to d-tagatose 6-phosphate via a kinase in Pfam family PF00294, a previously orphan EC number; and 3) epimerization of d-tagatose 6-phosphate C-4 to d-fructose 6-phosphate via a member of Pfam family PF08013, another previously unknown reaction. The epimerization reaction catalyzed by a member of PF08013 is especially noteworthy, because the functions of members of PF08013 have been unknown. These discoveries were assisted by the following two synergistic bioinformatics web tools made available by the Enzyme Function Initiative: the EFI-Enzyme Similarity Tool and the EFI-Genome Neighborhood Tool. PMID:26472925

Ball python nidovirus: a candidate etiologic agent for severe respiratory disease in Python regius.

PubMed

Stenglein, Mark D; Jacobson, Elliott R; Wozniak, Edward J; Wellehan, James F X; Kincaid, Anne; Gordon, Marcus; Porter, Brian F; Baumgartner, Wes; Stahl, Scott; Kelley, Karen; Towner, Jonathan S; DeRisi, Joseph L

2014-09-09

A severe, sometimes fatal respiratory disease has been observed in captive ball pythons (Python regius) since the late 1990s. In order to better understand this disease and its etiology, we collected case and control samples and performed pathological and diagnostic analyses. Electron micrographs revealed filamentous virus-like particles in lung epithelial cells of sick animals. Diagnostic testing for known pathogens did not identify an etiologic agent, so unbiased metagenomic sequencing was performed. Abundant nidovirus-like sequences were identified in cases and were used to assemble the genome of a previously unknown virus in the order Nidovirales. The nidoviruses, which were not previously known to infect nonavian reptiles, are a diverse order that includes important human and veterinary pathogens. The presence of the viral RNA was confirmed in all diseased animals (n = 8) but was not detected in healthy pythons or other snakes (n = 57). Viral RNA levels were generally highest in the lung and other respiratory tract tissues. The 33.5-kb viral genome is the largest RNA genome yet described and shares canonical characteristics with other nidovirus genomes, although several features distinguish this from related viruses. This virus, which we named ball python nidovirus (BPNV), will likely establish a new genus in Torovirinae subfamily. The identification of a novel nidovirus in reptiles contributes to our understanding of the biology and evolution of related viruses, and its association with lung disease in pythons is a promising step toward elucidating an etiology for this long-standing veterinary disease. Ball pythons are popular pets because of their diverse coloration, generally nonaggressive behavior, and relatively small size. Since the 1990s, veterinarians have been aware of an infectious respiratory disease of unknown cause in ball pythons that can be fatal. We used unbiased shotgun sequencing to discover a novel virus in the order Nidovirales that was present in cases but not controls. While nidoviruses are known to infect a variety of animals, this is the first report of a nidovirus recovered from any reptile. This report will enable diagnostics that will assist in determining the role of this virus in the causation of disease, which would allow control of the disease in zoos and private collections. Given its evolutionary divergence from known nidoviruses and its unique host, the study of reptile nidoviruses may further our understanding of related diseases and the viruses that cause them in humans and other animals. Copyright © 2014 Stenglein et al.

Ignorance, Vulnerability and the Occurrence of "Radical Surprises": Theoretical Reflections and Empirical Findings

NASA Astrophysics Data System (ADS)

Kuhlicke, C.

2009-04-01

By definition natural disasters always contain a moment of surprise. Their occurrence is mostly unforeseen and unexpected. They hit people unprepared, overwhelm them and expose their helplessness. Yet, there is surprisingly little known on the reasons for their being surprised. Aren't natural disasters expectable and foreseeable after all? Aren't the return rates of most hazards well known and shouldn't people be better prepared? The central question of this presentation is hence: Why do natural disasters so often radically surprise people at all (and how can we explain this being surprised)? In the first part of the presentation, it is argued that most approaches to vulnerability are not able to grasp this moment of surprise. On the contrary, they have their strength in unravelling the expectable: A person who is marginalized or even oppressed in everyday life is also vulnerable during times of crisis and stress, at least this is the central assumption of most vulnerability studies. In the second part, an understanding of vulnerability is developed, which allows taking into account such radical surprises. First, two forms of the unknown are differentiated: An area of the unknown an actor is more or less aware of (ignorance), and an area, which is not even known to be not known (nescience). The discovery of the latter is mostly associated with a "radical surprise", since it is per definition impossible to prepare for it. Second, a definition of vulnerability is proposed, which allows capturing the dynamics of surprises: People are vulnerable when they discover their nescience exceeding by definition previously established routines, stocks of knowledge and resources—in a general sense their capacities—to deal with their physical and/or social environment. This definition explicitly takes the view of different actors serious and departs from their being surprised. In the third part findings of a case study are presented, the 2002 flood in Germany. It is shown, that the flood was far beyond people's power of imagination (nescience). The reason therefore is that previous to the flood an institutionalized space of experience and horizon of expectation existed, which did not consider the possibility that the "stability" of the river is artificially created by engineering achievements to reduce its naturally given variability. Based on the empirical findings and the theoretical reasoning overall conclusions are drawn and implications for flood risk management under conditions global environmental change are outlined.

Genomics and introgression: discovery and mapping of thousands of species-diagnostic SNPs using RAD sequencing

USGS Publications Warehouse

Hand, Brian K.; Hether, Tyler D; Kovach, Ryan P.; Muhlfeld, Clint C.; Amish, Stephen J.; Boyer, Matthew C.; O’Rourke, Sean M.; Miller, Michael R.; Lowe, Winsor H.; Hohenlohe, Paul A.; Luikart, Gordon

2015-01-01

Invasive hybridization and introgression pose a serious threat to the persistence of many native species. Understanding the effects of hybridization on native populations (e.g., fitness consequences) requires numerous species-diagnostic loci distributed genome-wide. Here we used RAD sequencing to discover thousands of single-nucleotide polymorphisms (SNPs) that are diagnostic between rainbow trout (RBT, Oncorhynchus mykiss), the world’s most widely introduced fish, and native westslope cutthroat trout (WCT, O. clarkii lewisi) in the northern Rocky Mountains, USA. We advanced previous work that identified 4,914 species-diagnostic loci by using longer sequence reads (100 bp vs. 60 bp) and a larger set of individuals (n = 84). We sequenced RAD libraries for individuals from diverse sampling sources, including native populations of WCT and hatchery broodstocks of WCT and RBT. We also took advantage of a newly released reference genome assembly for RBT to align our RAD loci. In total, we discovered 16,788 putatively diagnostic SNPs, 10,267 of which we mapped to anchored chromosome locations on the RBT genome. A small portion of previously discovered putative diagnostic loci (325 of 4,914) were no longer diagnostic (i.e., fixed between species) based on our wider survey of non-hybridized RBT and WCT individuals. Our study suggests that RAD loci mapped to a draft genome assembly could provide the marker density required to identify genes and chromosomal regions influencing selection in admixed populations of conservation concern and evolutionary interest.

Invisible Colors of the Moon

NASA Image and Video Library

2009-09-24

Data from NASA Moon Mineralogy Mapper instrument on the Indian Space Research Organization Chandrayaan-1 spacecraft reveal subtle and previously unknown lunar diversity and features. Animation available at the Photojournal.

Neonatal blood transfusion as transmission route in chronic hepatitis C.

PubMed

Einberg, Afrodite Psaros; Lindh, Gudrun; Hökeberg, Ingegerd; Papadogiannakis, Nikos; Fischler, Björn

2014-05-01

The aim of this study was to investigate if neonatal transfusions could underlie chronic hepatitis C in adults for whom the disease transmission route was previously unknown. Questionnaires were sent to 255 patients with chronic hepatitis C born in Sweden in 1960 to 1975. The medical records of 230 of the patients, of whom 98 (43%) had unknown transmission route, were studied regarding the occurrence of neonatal blood transfusions. The clinical, virologic, and histopathologic characteristics of those found to have received transfusions as neonates were also studied. Four of 230 (1.7%; 95% confidence interval, 0.5%-4.4%) patients with hepatitis C had received blood products as neonates. Three of them had reported unknown transmission route. One had cirrhosis, while two had mild histopathologic findings on liver biopsy. Three out of four patients in the transfused group, including the patient with liver cirrhosis, had undergone treatment for hepatitis C, all of them with a sustained viral response. Previously unidentified neonatal blood transfusions explain only a small fraction of chronic hepatitis C cases with unknown transmission route. Individual patients infected early in life can develop progressive liver damage as young adults and may benefit from antiviral treatment. The finding suggests that efforts are needed to actively trace and test adults who have been subjected to neonatal blood product transfusion before 1992. © 2013 American Association of Blood Banks.

Teleporting an unknown quantum state with unit fidelity and unit probability via a non-maximally entangled channel and an auxiliary system

NASA Astrophysics Data System (ADS)

Rashvand, Taghi

2016-11-01

We present a new scheme for quantum teleportation that one can teleport an unknown state via a non-maximally entangled channel with certainly, using an auxiliary system. In this scheme depending on the state of the auxiliary system, one can find a class of orthogonal vectors set as a basis which by performing von Neumann measurement in each element of this class Alice can teleport an unknown state with unit fidelity and unit probability. A comparison of our scheme with some previous schemes is given and we will see that our scheme has advantages that the others do not.

Operation Sun Beam, Shot Small Boy. Project Officer's report - Project 6. 9. Correlation of present and previous electric-field measurements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reno; Fowles, H.M.

On most previous nuclear detonations, signatures and quantitative measurements of the electric-field signals associated with the detonations was obtained at distances such that normal radiation field characteristics apply. On Small Boy, measurements were made from stations located much closer in, such as to be inside, on the boundary of and just outside the limits of the ionized sphere created by the nuclear burst. The electric-field characteristics in these regions were unknown. In the hope of providing continuity from the region of the unknown into the reasonably well-understood region of the radiation field, this project was requested to make the typicalmore » radiation-field type of measurement that had been made on previous detonations. This report covers the signature characteristics and quantitative measurements of the electric-field signal from Small Boy as seen from outside the immediate region of theoretical generating mechanism.« less

Discovery and full genome characterization of two highly divergent simian immunodeficiency viruses infecting black-and-white colobus monkeys (Colobus guereza) in Kibale National Park, Uganda.

PubMed

Lauck, Michael; Switzer, William M; Sibley, Samuel D; Hyeroba, David; Tumukunde, Alex; Weny, Geoffrey; Taylor, Bill; Shankar, Anupama; Ting, Nelson; Chapman, Colin A; Friedrich, Thomas C; Goldberg, Tony L; O'Connor, David H

2013-10-21

African non-human primates (NHPs) are natural hosts for simian immunodeficiency viruses (SIV), the zoonotic transmission of which led to the emergence of HIV-1 and HIV-2. However, our understanding of SIV diversity and evolution is limited by incomplete taxonomic and geographic sampling of NHPs, particularly in East Africa. In this study, we screened blood specimens from nine black-and-white colobus monkeys (Colobus guereza occidentalis) from Kibale National Park, Uganda, for novel SIVs using a combination of serology and "unbiased" deep-sequencing, a method that does not rely on genetic similarity to previously characterized viruses. We identified two novel and divergent SIVs, tentatively named SIVkcol-1 and SIVkcol-2, and assembled genomes covering the entire coding region for each virus. SIVkcol-1 and SIVkcol-2 were detected in three and four animals, respectively, but with no animals co-infected. Phylogenetic analyses showed that SIVkcol-1 and SIVkcol-2 form a lineage with SIVcol, previously discovered in black-and-white colobus from Cameroon. Although SIVkcol-1 and SIVkcol-2 were isolated from the same host population in Uganda, SIVkcol-1 is more closely related to SIVcol than to SIVkcol-2. Analysis of functional motifs in the extracellular envelope glycoprotein (gp120) revealed that SIVkcol-2 is unique among primate lentiviruses in containing only 16 conserved cysteine residues instead of the usual 18 or more. Our results demonstrate that the genetic diversity of SIVs infecting black-and-white colobus across equatorial Africa is greater than previously appreciated and that divergent SIVs can co-circulate in the same colobine population. We also show that the use of "unbiased" deep sequencing for the detection of SIV has great advantages over traditional serological approaches, especially for studies of unknown or poorly characterized viruses. Finally, the detection of the first SIV containing only 16 conserved cysteines in the extracellular envelope protein gp120 further expands the range of functional motifs observed among SIVs and highlights the complex evolutionary history of simian retroviruses.

Discovery and full genome characterization of two highly divergent simian immunodeficiency viruses infecting black-and-white colobus monkeys (Colobus guereza) in Kibale National Park, Uganda

PubMed Central

2013-01-01

Background African non-human primates (NHPs) are natural hosts for simian immunodeficiency viruses (SIV), the zoonotic transmission of which led to the emergence of HIV-1 and HIV-2. However, our understanding of SIV diversity and evolution is limited by incomplete taxonomic and geographic sampling of NHPs, particularly in East Africa. In this study, we screened blood specimens from nine black-and-white colobus monkeys (Colobus guereza occidentalis) from Kibale National Park, Uganda, for novel SIVs using a combination of serology and “unbiased” deep-sequencing, a method that does not rely on genetic similarity to previously characterized viruses. Results We identified two novel and divergent SIVs, tentatively named SIVkcol-1 and SIVkcol-2, and assembled genomes covering the entire coding region for each virus. SIVkcol-1 and SIVkcol-2 were detected in three and four animals, respectively, but with no animals co-infected. Phylogenetic analyses showed that SIVkcol-1 and SIVkcol-2 form a lineage with SIVcol, previously discovered in black-and-white colobus from Cameroon. Although SIVkcol-1 and SIVkcol-2 were isolated from the same host population in Uganda, SIVkcol-1 is more closely related to SIVcol than to SIVkcol-2. Analysis of functional motifs in the extracellular envelope glycoprotein (gp120) revealed that SIVkcol-2 is unique among primate lentiviruses in containing only 16 conserved cysteine residues instead of the usual 18 or more. Conclusions Our results demonstrate that the genetic diversity of SIVs infecting black-and-white colobus across equatorial Africa is greater than previously appreciated and that divergent SIVs can co-circulate in the same colobine population. We also show that the use of “unbiased” deep sequencing for the detection of SIV has great advantages over traditional serological approaches, especially for studies of unknown or poorly characterized viruses. Finally, the detection of the first SIV containing only 16 conserved cysteines in the extracellular envelope protein gp120 further expands the range of functional motifs observed among SIVs and highlights the complex evolutionary history of simian retroviruses. PMID:24139306

Discovery and Identification of Dimethylsilanediol as a Contaminant in ISS Potable Water

NASA Technical Reports Server (NTRS)

Rutz, Jeffrey A.; Schultz, John R.; Kuo, C. Mike; Cole, Hraold E.; Manuel, Sam; Curtis, Matthew; Jones, Patrick R.; Sparkman, O. David; McCoy, J. Torin

2010-01-01

In September of 2010, analysis of ISS potable water samples was undertaken to determine the contaminant responsible for a rise in total organic carbon (TOC). As analysis of the routine target list of organic compounds did not reveal the contaminant, efforts to look for unknown compounds was initiated, resulting in an unknown peak being discovered in the gas chromatography/mass spectrometry (GC/MS) analysis for glycols. A mass spectrum of the contaminant was then generated by concentrating one of the samples by evaporation and analyzing by GC/MS in full-scan mode. Although a computer match of the compound s identity could not be obtained with the instrument s database, a search with a more up to date mass spectral library yielded a good match with dimethylsilanediol (DMSD). Inductively Coupled Plasma/Mass Spectrometry (ICP/MS) analyses showed abnormally high silicon levels in the samples, confirming that the unknown contained silicon. DMSD was then synthesized to confirm the identification and provide a standard to develop a calibration curve. Further confirmation was provided by external Direct Analysis in Real Time (DART) GC/MS analysis. A preliminary GC/MS method was then developed and archived samples from various locations on ISS were analyzed to determine the extent of the contamination and provide data for troubleshooting. This paper describes these events in more detail as well as problems encountered in routine GC/MS analyses and the subsequent development of high performance liquid chromatography and LC/MS/MS methods for quantitation of DMSD.

On differential photometric reconstruction for unknown, isotropic BRDFs.

PubMed

Chandraker, Manmohan; Bai, Jiamin; Ramamoorthi, Ravi

2013-12-01

This paper presents a comprehensive theory of photometric surface reconstruction from image derivatives in the presence of a general, unknown isotropic BRDF. We derive precise topological classes up to which the surface may be determined and specify exact priors for a full geometric reconstruction. These results are the culmination of a series of fundamental observations. First, we exploit the linearity of chain rule differentiation to discover photometric invariants that relate image derivatives to the surface geometry, regardless of the form of isotropic BRDF. For the problem of shape-from-shading, we show that a reconstruction may be performed up to isocontours of constant magnitude of the gradient. For the problem of photometric stereo, we show that just two measurements of spatial and temporal image derivatives, from unknown light directions on a circle, suffice to recover surface information from the photometric invariant. Surprisingly, the form of the invariant bears a striking resemblance to optical flow; however, it does not suffer from the aperture problem. This photometric flow is shown to determine the surface up to isocontours of constant magnitude of the surface gradient, as well as isocontours of constant depth. Further, we prove that specification of the surface normal at a single point completely determines the surface depth from these isocontours. In addition, we propose practical algorithms that require additional initial or boundary information, but recover depth from lower order derivatives. Our theoretical results are illustrated with several examples on synthetic and real data.

The architecture of the multi-planet system of υ And: υ And b - a super-inflated hot Jupiter in a cosmic ping-pong game

NASA Astrophysics Data System (ADS)

Rodler, Florian

2015-12-01

The gas giant Upsilon Andromeda b (υ And b) was one of the first discovered exoplanets. This planet orbits around a bright, similar to the Sun star only 13.5 parsecs away from us. υ And b is also the innermost planet of a confirmed three-planet system, all of them non-transiting. As with all non-transiting planets, their exact masses and sizes are unknown, with their orbital inclination being the key parameter to unveil those values. Astrometric measurements have placed constraints to the orbital inclinations of the two outer planets in this system, indicating that we look almost 'face-on' on the system (McArthur et al. 2010). However, the orbital inclination for the innermost planet remained unknown.Photometric monitoring of υ And b orbit at infrared wavelengths has revealed significant brightness changes between the day-side and the night-side of the planet (Crossfield et al. 2010). The amplitude of those brightness variations depends on the orbital inclination of the planet and on its radius, therefore we can tightly constrain the size of the planet if its inclination is known.Here we present the measurement of the orbital inclination for the innermost planet υ And b, 23 deg, obtained by monitoring the Doppler shift of carbon monoxide (CO) lines on the atmospheric day-side of the planet with Keck/NIRSPEC. From this measurement we establish a planet mass of 1.7 times the mass of Jupiter and a minimum planet radius of 1.8 times the size of Jupiter. This result reveals that υ And b is likely to be one of the most inflated giant planets discovered to date. In addition, the observed strong CO absorption suggests an atmosphere with temperature uniformly decreasing towards higher altitudes, which suggests the absence of an atmospheric thermal inversion (Rodler et al. 2015).

Differential Gene Expression for Investigation of Escherichia coli Biofilm Inhibition by Plant Extract Ursolic Acid

PubMed Central

Ren, Dacheng; Zuo, Rongjun; González Barrios, Andrés F.; Bedzyk, Laura A.; Eldridge, Gary R.; Pasmore, Mark E.; Wood, Thomas K.

2005-01-01

After 13,000 samples of compounds purified from plants were screened, a new biofilm inhibitor, ursolic acid, has been discovered and identified. Using both 96-well microtiter plates and a continuous flow chamber with COMSTAT analysis, 10 μg of ursolic acid/ml inhibited Escherichia coli biofilm formation 6- to 20-fold when added upon inoculation and when added to a 24-h biofilm; however, ursolic acid was not toxic to E. coli, Pseudomonas aeruginosa, Vibrio harveyi, and hepatocytes. Similarly, 10 μg of ursolic acid/ml inhibited biofilm formation by >87% for P. aeruginosa in both complex and minimal medium and by 57% for V. harveyi in minimal medium. To investigate the mechanism of this nontoxic inhibition on a global genetic basis, DNA microarrays were used to study the gene expression profiles of E. coli K-12 grown with or without ursolic acid. Ursolic acid at 10 and 30 μg/ml induced significantly (P < 0.05) 32 and 61 genes, respectively, and 19 genes were consistently induced. The consistently induced genes have functions for chemotaxis and mobility (cheA, tap, tar, and motAB), heat shock response (hslSTV and mopAB), and unknown functions (such as b1566 and yrfHI). There were 31 and 17 genes repressed by 10 and 30 μg of ursolic acid/ml, respectively, and 12 genes were consistently repressed that have functions in cysteine synthesis (cysK) and sulfur metabolism (cysD), as well as unknown functions (such as hdeAB and yhaDFG). Ursolic acid inhibited biofilms without interfering with quorum sensing, as shown with the V. harveyi AI-1 and AI-2 reporter systems. As predicted by the differential gene expression, deleting motAB counteracts ursolic acid inhibition (the paralyzed cells no longer become too motile). Based on the differential gene expression, it was also discovered that sulfur metabolism (through cysB) affects biofilm formation (in the absence of ursolic acid). PMID:16000817

High-performance thin-layer chromatography linked with (bio)assays and mass spectrometry - a suited method for discovery and quantification of bioactive components? Exemplarily shown for turmeric and milk thistle extracts.

PubMed

Taha, Mahmoud N; Krawinkel, Michael B; Morlock, Gertrud E

2015-05-15

Extraction parameters, chemical fingerprint, and the single compounds' activity levels were considered for the selection of active botanicals. For an initial survey, the total bioactivity (i.e., total reducing capacity, total flavonoids contents and free radical scavenging capacity) of 21 aqueous and 21 ethanolic plant extracts was investigated. Ethanolic extracts showed a higher yield and were further analyzed by HPTLC in detail to obtain fingerprints of single flavonoids and further bioactive components. Exemplarily shown for turmeric (Curcuma longa) and milk thistle (Silybum marianum), effect-directed analysis (EDA) was performed using three selected (bio)assays, the Aliivibrio fischeri bioassay, the Bacillus subtilis bioassay and the 2,2-diphenyl-1-picrylhydrazyl (DPPH*) assay. As a proof of principle, the bioactive components found in the extracts were confirmed by HPTLC-MS. Bioassays in combination with planar chromatography directly linked to the known, single effective compounds like curcumin and silibinin. However, also some unknown bioactive components were discovered and exemplarily characterized, which demonstrated the strength of this kind of EDA. HPTLC-UV/Vis/FLD-EDA-MS could become a useful tool for selection of active botanicals and for the activity profiling of the active ingredients therein. The flexibility in effect-directed detections allows a comprehensive survey of effective ingredients in samples. This streamlined methodology comprised a non-targeted, effect-directed screening first, followed by a highly targeted characterization of the discovered bioactive compounds. HPTLC-EDA-MS can also be recommended for bioactivity profiling of food on the food intake side, as not only effective phytochemicals, but also unknown bioactive degradation products during food processing or contamination products or residues or metabolites can be detected. Thus, an efficient survey on potential food intake effects on wellness could be obtained. Having performed both, sum parameter assays and HPTLC analysis, a comparison of both approaches was made and discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Reproductive isolation and patterns of genetic differentiation in a cryptic butterfly species complex

PubMed Central

Dincâ, V; Wiklund, C; Lukhtanov, V A; Kodandaramaiah, U; Norén, K; Dapporto, L; Wahlberg, N; Vila, R; Friberg, M

2013-01-01

Molecular studies of natural populations are often designed to detect and categorize hidden layers of cryptic diversity, and an emerging pattern suggests that cryptic species are more common and more widely distributed than previously thought. However, these studies are often decoupled from ecological and behavioural studies of species divergence. Thus, the mechanisms by which the cryptic diversity is distributed and maintained across large spatial scales are often unknown. In 1988, it was discovered that the common Eurasian Wood White butterfly consisted of two species (Leptidea sinapis and Leptidea reali), and the pair became an emerging model for the study of speciation and chromosomal evolution. In 2011, the existence of a third cryptic species (Leptidea juvernica) was proposed. This unexpected discovery raises questions about the mechanisms preventing gene flow and about the potential existence of additional species hidden in the complex. Here, we compare patterns of genetic divergence across western Eurasia in an extensive data set of mitochondrial and nuclear DNA sequences with behavioural data on inter- and intraspecific reproductive isolation in courtship experiments. We show that three species exist in accordance with both the phylogenetic and biological species concepts and that additional hidden diversity is unlikely to occur in Europe. The Leptidea species are now the best studied cryptic complex of butterflies in Europe and a promising model system for understanding the formation of cryptic species and the roles of local processes, colonization patterns and heterospecific interactions for ecological and evolutionary divergence. PMID:23909947

Arabidopsis thaliana GYRB3 Does Not Encode a DNA Gyrase Subunit

PubMed Central

Evans-Roberts, Katherine M.; Breuer, Christian; Wall, Melisa K.; Sugimoto-Shirasu, Keiko; Maxwell, Anthony

2010-01-01

Background DNA topoisomerases are enzymes that control the topology of DNA in all cells. DNA gyrase is unique among the topoisomerases in that it is the only enzyme that can actively supercoil DNA using the free energy of ATP hydrolysis. Until recently gyrase was thought to be unique to bacteria, but has now been discovered in plants. The genome of the model plant, Arabidopsis thaliana, is predicted to encode four gyrase subunits: AtGyrA, AtGyrB1, AtGyrB2 and AtGyrB3. Methodology/Principal Findings We found, contrary to previous data, that AtGyrB3 is not essential to the survival of A. thaliana. Bioinformatic analysis suggests AtGyrB3 is considerably shorter than other gyrase B subunits, lacking part of the ATPase domain and other key motifs found in all type II topoisomerases; but it does contain a putative DNA-binding domain. Partially purified AtGyrB3 cannot bind E. coli GyrA or support supercoiling. AtGyrB3 cannot complement an E. coli gyrB temperature-sensitive strain, whereas AtGyrB2 can. Yeast two-hybrid analysis suggests that AtGyrB3 cannot bind to AtGyrA or form a dimer. Conclusions/Significance These data strongly suggest that AtGyrB3 is not a gyrase subunit but has another unknown function. One possibility is that it is a nuclear protein with a role in meiosis in pollen. PMID:20360860

Arabidopsis thaliana GYRB3 does not encode a DNA gyrase subunit.

PubMed

Evans-Roberts, Katherine M; Breuer, Christian; Wall, Melisa K; Sugimoto-Shirasu, Keiko; Maxwell, Anthony

2010-03-26

DNA topoisomerases are enzymes that control the topology of DNA in all cells. DNA gyrase is unique among the topoisomerases in that it is the only enzyme that can actively supercoil DNA using the free energy of ATP hydrolysis. Until recently gyrase was thought to be unique to bacteria, but has now been discovered in plants. The genome of the model plant, Arabidopsis thaliana, is predicted to encode four gyrase subunits: AtGyrA, AtGyrB1, AtGyrB2 and AtGyrB3. We found, contrary to previous data, that AtGyrB3 is not essential to the survival of A. thaliana. Bioinformatic analysis suggests AtGyrB3 is considerably shorter than other gyrase B subunits, lacking part of the ATPase domain and other key motifs found in all type II topoisomerases; but it does contain a putative DNA-binding domain. Partially purified AtGyrB3 cannot bind E. coli GyrA or support supercoiling. AtGyrB3 cannot complement an E. coli gyrB temperature-sensitive strain, whereas AtGyrB2 can. Yeast two-hybrid analysis suggests that AtGyrB3 cannot bind to AtGyrA or form a dimer. These data strongly suggest that AtGyrB3 is not a gyrase subunit but has another unknown function. One possibility is that it is a nuclear protein with a role in meiosis in pollen.

Astronomy and calendar reform at the curia of Pope Clement VI: a new source.

PubMed

Nothaft, C Philipp E

2017-01-01

The article introduces a previously unknown fourteenth-century treatise on computus and calendrical astronomy entitled Expositio kalendarii novi, whose author proposed elaborate solutions to the technical flaws inherent in the calendar used by the Roman Church. An analysis of verbal parallels to other contemporary works on the same topic makes it possible to establish that the Expositio was produced in the context of a calendar reform initiative led by Pope Clement VI in 1344/45 and that this anonymous text is probably identical to a 'great and laborious work' on the calendar that the monk Johannes de Termis prepared for the pope around this time. Its author strove to make an original contribution by extracting new astronomical parameters from both ancient and contemporary data, which made him arrive at an estimate of the length of the tropical year that was independent of the then-current Alfonsine Tables. With its suggestion to remove eleven days from the Julian calendar and to correct the calendar through modified leap-year rhythms and periodically adjusted sequences of lunar epacts, the proposal enshrined in the Expositio exhibits some remarkable similarities to the Gregorian reform of the calendar promulgated in 1582. Although its influence on the latter must remain a matter of speculation, the newly discovered text sheds a revealing light on the history of medieval calendar reform debates and on the mathematical sciences practiced at the Avignon court of Clement VI.

Wolbachia as a bacteriocyte-associated nutritional mutualist

PubMed Central

Hosokawa, Takahiro; Koga, Ryuichi; Kikuchi, Yoshitomo; Meng, Xian-Ying; Fukatsu, Takema

2009-01-01

Many insects are dependent on bacterial symbionts that provide essential nutrients (ex. aphid–Buchnera and tsetse–Wiglesworthia associations), wherein the symbionts are harbored in specific cells called bacteriocytes that constitute a symbiotic organ bacteriome. Facultative and parasitic bacterial symbionts like Wolbachia have been regarded as evolutionarily distinct from such obligate nutritional mutualists. However, we discovered that, in the bedbug Cimex lectularius, Wolbachia resides in a bacteriome and appears to be an obligate nutritional mutualist. Two bacterial symbionts, a Wolbachia strain and an unnamed γ-proteobacterium, were identified from different strains of the bedbug. The Wolbachia symbiont was detected from all of the insects examined whereas the γ-proteobacterium was found in a part of them. The Wolbachia symbiont was specifically localized in the bacteriomes and vertically transmitted via the somatic stem cell niche of germalia to oocytes, infecting the incipient symbiotic organ at an early stage of the embryogenesis. Elimination of the Wolbachia symbiont resulted in retarded growth and sterility of the host insect. These deficiencies were rescued by oral supplementation of B vitamins, confirming the essential nutritional role of the symbiont for the host. The estimated genome size of the Wolbachia symbiont was around 1.3 Mb, which was almost equivalent to the genome sizes of parasitic Wolbachia strains of other insects. These results indicate that bacteriocyte-associated nutritional mutualism can evolve from facultative and prevalent microbial associates like Wolbachia, highlighting a previously unknown aspect of the parasitism-mutualism evolutionary continuum. PMID:20080750

Discovery and Characterization of Wide Binary Systems with a Very Low Mass Component

NASA Astrophysics Data System (ADS)

Baron, Frédérique; Lafrenière, David; Artigau, Étienne; Doyon, René; Gagné, Jonathan; Davison, Cassy L.; Malo, Lison; Robert, Jasmin; Nadeau, Daniel; Reylé, Céline

2015-03-01

We report the discovery of 14 low-mass binary systems containing mid-M to mid-L dwarf companions with separations larger than 250 AU. We also report the independent discovery of nine other systems with similar characteristics that were recently discovered in other studies. We have identified these systems by searching for common proper motion sources in the vicinity of known high proper motion stars, based on a cross-correlation of wide area near-infrared surveys (2MASS, SDSS, and SIMP). An astrometric follow-up, for common proper motion confirmation, was made with SIMON and/or CPAPIR at the Observatoire du Mont Mégantic 1.6 m and CTIO 1.5 m telescopes for all the candidates identified. A spectroscopic follow-up was also made with GMOS or GNIRS at Gemini to determine the spectral types of 11 of our newly identified companions and 10 of our primaries. Statistical arguments are provided to show that all of the systems we report here are very likely to be physical binaries. One of the new systems reported features a brown dwarf companion: LSPM J1259+1001 (M5) has an L4.5 (2M1259+1001) companion at ˜340 AU. This brown dwarf was previously unknown. Seven other systems have a companion of spectral type L0-L1 at a separation in the 250-7500 AU range. Our sample includes 14 systems with a mass ratio below 0.3.

Osteopathology associated with bone resorption inhibitors - which role does Actinomyces play? A presentation of 51 cases with systematic review of the literature.

PubMed

Schipmann, S; Metzler, P; Rössle, M; Zemann, W; von Jackowski, J; Obwegeser, J A; Grätz, K W; Jacobsen, C

2013-09-01

Bone resorption inhibitor-related osteopathology of the jaw (BRIOJ) is a severe complication in patients treated with bisphosphonates or denosumab. However, the precise pathogenesis of BRIOJ is not yet fully understood. Recent studies discovered the presence of Actinomyces colonies in biopsy material from BRIOJ patients. The aim of this study was to analyze current knowledge concerning the impact of Actinomyces on the pathogenesis of this condition and to present data from our own patients. Data from 51 patients with histopathological diagnoses of BRIOJ were retrospectively analyzed. In addition, a systematic literature search for studies describing the presence of Actinomyces was performed. Actinomyces was present in 86% of our cases and 63.3% of 371 cases presented in the literature. All of our patients and 85% of patients described in the literature had a clearly defined local focus in association with osteopathology. A clear picture of whether Actinomyces colonizes the previously necrotic bone or contributes to inflammation causing subsequent bone necrosis is lacking in the literature. The pathogenesis of BRIOJ remains unknown; however, there seems to be a role for Actinomyces, and possibly other pathogens, in the development of osteopathology of the jaws, which is not exclusive to bisphosphonate therapy. This study supports the hypothesis that an infectious component is of utmost importance for the pathogenesis of BRIOJ. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.