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  • 1
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    A major genome region underlying artemisinin resistance in malaria (2012)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2012-04-12
    Description: Evolving resistance to artemisinin-based compounds threatens to derail attempts to control malaria. Resistance has been confirmed in western Cambodia and has recently emerged in western Thailand, but is absent from neighboring Laos. Artemisinin resistance results in reduced parasite clearance rates (CRs) after treatment. We used a two-phase strategy to identify genome region(s) underlying this ongoing selective event. Geographical differentiation and haplotype structure at 6969 polymorphic single-nucleotide polymorphisms (SNPs) in 91 parasites from Cambodia, Thailand, and Laos identified 33 genome regions under strong selection. We screened SNPs and microsatellites within these regions in 715 parasites from Thailand, identifying a selective sweep on chromosome 13 that shows strong association (P = 10(-6) to 10(-12)) with slow CRs, illustrating the efficacy of targeted association for identifying the genetic basis of adaptive traits.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3355473/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3355473/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cheeseman, Ian H -- Miller, Becky A -- Nair, Shalini -- Nkhoma, Standwell -- Tan, Asako -- Tan, John C -- Al Saai, Salma -- Phyo, Aung Pyae -- Moo, Carit Ler -- Lwin, Khin Maung -- McGready, Rose -- Ashley, Elizabeth -- Imwong, Mallika -- Stepniewska, Kasia -- Yi, Poravuth -- Dondorp, Arjen M -- Mayxay, Mayfong -- Newton, Paul N -- White, Nicholas J -- Nosten, Francois -- Ferdig, Michael T -- Anderson, Timothy J C -- 089275/Wellcome Trust/United Kingdom -- 093956/Wellcome Trust/United Kingdom -- AI075145/AI/NIAID NIH HHS/ -- C06 RR013556/RR/NCRR NIH HHS/ -- R01 AI048071/AI/NIAID NIH HHS/ -- R01 AI075145/AI/NIAID NIH HHS/ -- R37 AI048071/AI/NIAID NIH HHS/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2012 Apr 6;336(6077):79-82. doi: 10.1126/science.1215966.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Texas Biomedical Research Institute, San Antonio, TX 78245, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22491853" target="_blank"〉PubMed〈/a〉
    Keywords: Antimalarials/*pharmacology/therapeutic use ; Artemisinins/*pharmacology/therapeutic use ; Cambodia ; DNA Copy Number Variations ; Drug Resistance/*genetics ; Gene Frequency ; Genetic Association Studies ; *Genome, Protozoan ; Haplotypes ; Humans ; Laos ; Malaria, Falciparum/drug therapy/*parasitology ; Microsatellite Repeats ; Plasmodium falciparum/*drug effects/*genetics ; Polymorphism, Single Nucleotide ; Protozoan Proteins/genetics ; *Selection, Genetic ; Thailand
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Astrophysics: A dark cloud unveils its secrets (2013)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2013-08-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tan, Jonathan C -- England -- Nature. 2013 Aug 29;500(7464):537-8. doi: 10.1038/500537a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23985868" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 3
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    Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-06-23
    Description: Malaria elimination strategies require surveillance of the parasite population for genetic changes that demand a public health response, such as new forms of drug resistance. Here we describe methods for the large-scale analysis of genetic variation in Plasmodium falciparum by deep sequencing of parasite DNA obtained from the blood of patients with malaria, either directly or after short-term culture. Analysis of 86,158 exonic single nucleotide polymorphisms that passed genotyping quality control in 227 samples from Africa, Asia and Oceania provides genome-wide estimates of allele frequency distribution, population structure and linkage disequilibrium. By comparing the genetic diversity of individual infections with that of the local parasite population, we derive a metric of within-host diversity that is related to the level of inbreeding in the population. An open-access web application has been established for the exploration of regional differences in allele frequency and of highly differentiated loci in the P. falciparum genome.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3738909/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3738909/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Manske, Magnus -- Miotto, Olivo -- Campino, Susana -- Auburn, Sarah -- Almagro-Garcia, Jacob -- Maslen, Gareth -- O'Brien, Jack -- Djimde, Abdoulaye -- Doumbo, Ogobara -- Zongo, Issaka -- Ouedraogo, Jean-Bosco -- Michon, Pascal -- Mueller, Ivo -- Siba, Peter -- Nzila, Alexis -- Borrmann, Steffen -- Kiara, Steven M -- Marsh, Kevin -- Jiang, Hongying -- Su, Xin-Zhuan -- Amaratunga, Chanaki -- Fairhurst, Rick -- Socheat, Duong -- Nosten, Francois -- Imwong, Mallika -- White, Nicholas J -- Sanders, Mandy -- Anastasi, Elisa -- Alcock, Dan -- Drury, Eleanor -- Oyola, Samuel -- Quail, Michael A -- Turner, Daniel J -- Ruano-Rubio, Valentin -- Jyothi, Dushyanth -- Amenga-Etego, Lucas -- Hubbart, Christina -- Jeffreys, Anna -- Rowlands, Kate -- Sutherland, Colin -- Roper, Cally -- Mangano, Valentina -- Modiano, David -- Tan, John C -- Ferdig, Michael T -- Amambua-Ngwa, Alfred -- Conway, David J -- Takala-Harrison, Shannon -- Plowe, Christopher V -- Rayner, Julian C -- Rockett, Kirk A -- Clark, Taane G -- Newbold, Chris I -- Berriman, Matthew -- MacInnis, Bronwyn -- Kwiatkowski, Dominic P -- 075491/Z/04/Wellcome Trust/United Kingdom -- 077012/Z/05/Z/Wellcome Trust/United Kingdom -- 082370/Wellcome Trust/United Kingdom -- 089275/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- 090532/Z/09/Z/Wellcome Trust/United Kingdom -- 090770/Wellcome Trust/United Kingdom -- 090770/Z/09/Z/Wellcome Trust/United Kingdom -- 092654/Wellcome Trust/United Kingdom -- 093956/Wellcome Trust/United Kingdom -- 098051/Wellcome Trust/United Kingdom -- 55005502/Howard Hughes Medical Institute/ -- G0600718/Medical Research Council/United Kingdom -- G19/9/Medical Research Council/United Kingdom -- Intramural NIH HHS/ -- England -- Nature. 2012 Jul 19;487(7407):375-9. doi: 10.1038/nature11174.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22722859" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; *Biodiversity ; Genome, Protozoan ; Genotype ; *High-Throughput Nucleotide Sequencing ; Humans ; Malaria, Falciparum/*parasitology ; Phylogeny ; Plasmodium falciparum/classification/*genetics ; Polymorphism, Single Nucleotide ; Principal Component Analysis
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 4
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    Chemical structure, network topology, and porosity effects on the mechanical properties of Zeolitic Imidazolate Frameworks (2010)
    National Academy of Sciences
    Details
    Publication Date: 2010-05-17
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 5
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    Millimetre-wave and near-infrared signposts of massive molecular clump evolution and star cluster formation (2013)
    Oxford University Press
    Details
    Publication Date: 2013-06-09
    Description: We report new near-infrared and mm-wave observational data on a selection of massive Galactic molecular clumps (part of the Census of High- and Medium-mass Protostars sample) and their associated young star clusters. The clumps show, for the first time in a ‘dense gas tracer’, a significant correlation between HCO + line emission from cold molecular gas and Br line emission of associated nebulae. This correlation arises in the HCO + line's brightness, not its linewidth. In contrast, the correlation between the N 2 H + line emission and Br is weak or absent. The HCO + /N 2 H + line ratio also varies widely from clump to clump: bright HCO + emission tends to be more closely associated with Br nebulosity, while bright N 2 H + emission tends to avoid areas that are bright in Br. Both molecular species show correlations of weak significance with infrared H 2 v  = 1 -〉 0 and v  = 2 -〉 1 line emission, in or near the clumps. The H 2 emission line ratio is consistent with fluorescent excitation in most of the clumps, although thermal excitation is seen in a few clumps. We interpret these trends as evidence for evolution in the gas conditions due to the effects of ongoing star formation in the clumps, in particular, the importance of UV radiation from massive Young Stellar Objects as the driving agent that heats the molecular gas and alters its chemistry. This suggests that some traditional dense gas tracers of molecular clouds do not sample a homogeneous population of clumps, i.e. that the HCO + brightness in particular is directly related to the heating and disruption of cold gas by massive young stars, whereas the N 2 H + better samples gas not yet affected by this process. We therefore suggest that the HCO + –N 2 H + –Br relationship is a useful diagnostic of a molecular clump's progress in forming massive stars.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 6
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    The dynamical properties of dense filaments in the infrared dark cloud G035.39-00.33 (2014)
    Oxford University Press
    Details
    Publication Date: 2014-04-14
    Description: Infrared dark clouds (IRDCs) are unique laboratories to study the initial conditions of high-mass star and star cluster formation. We present high-sensitivity and high-angular-resolution Institut de Radioastronomie Millimétrique (IRAM) Plateau de Bure Interferometer observations of N 2 H + (1–0) towards IRDC G035.39–00.33. It is found that G035.39–00.33 is a highly complex environment, consisting of several mildly supersonic filaments ($\sigma _{\rm NT}/c_{{\rm s}}$ ~ 1.5), separated in velocity by 〈1 km s –1 . Where multiple spectral components are evident, moment analysis overestimates the non-thermal contribution to the line-width by a factor of ~2. Large-scale velocity gradients evident in previous single-dish maps may be explained by the presence of substructure now evident in the interferometric maps. Whilst global velocity gradients are small (〈0.7 km s –1  pc –1 ), there is evidence for dynamic processes on local scales (~1.5–2.5 km s –1  pc –1 ). Systematic trends in velocity gradient are observed towards several continuum peaks. This suggests that the kinematics are influenced by dense (and in some cases, starless ) cores. These trends are interpreted as either infalling material, with accretion rates ~(7 ± 4)  x 10 –5  M  yr –1 , or expanding shells with momentum ~24 ± 12 M  km s –1 . These observations highlight the importance of high-sensitivity and high-spectral-resolution data in disentangling the complex kinematic and physical structure of massive star-forming regions.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 7
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    Properties of dense cores in clustered massive star-forming regions at high angular resolution (2013)
    Oxford University Press
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    Publication Date: 2013-06-18
    Description: We aim at characterizing dense cores in the clustered environments associated with intermediate-/high-mass star-forming regions. For this, we present a uniform analysis of Very Large Array NH 3  (1,1) and (2,2) observations towards a sample of 15 intermediate-/high-mass star-forming regions, where we identify a total of 73 cores, classify them as protostellar, quiescent starless, or perturbed starless, and derive some physical properties. The average sizes and ammonia column densities of the total sample are ~0.06 pc and ~10 15  cm –2 , respectively, with no significant differences between the starless and protostellar cores, while the linewidth and rotational temperature of quiescent starless cores are smaller, ~1.0 km s –1 and 16 K, than linewidths and temperatures of protostellar (~1.8 km s –1 and 21 K), and perturbed starless (~1.4 km s –1 and 19 K) cores. Such linewidths and temperatures for these quiescent starless cores in the surroundings of intermediate-/high-mass stars are still significantly larger than the typical linewidths and rotational temperatures measured in starless cores of low-mass star-forming regions, implying an important non-thermal component. We confirm at high angular resolutions (spatial scales ~0.05 pc) the correlations previously found with single-dish telescopes (spatial scales 0.1 pc) between the linewidth and the rotational temperature of the cores, as well as between the rotational temperature and the linewidth with respect to the bolometric luminosity. In addition, we find a correlation between the temperature of each core and the incident flux from the most massive star in the cluster, suggesting that the large temperatures measured in the starless cores of our sample could be due to heating from the nearby massive star. A simple virial equilibrium analysis seems to suggest a scenario of a self-similar, self-gravitating, turbulent, virialized hierarchy of structures from clumps (~0.1–10 pc) to cores (~0.05 pc). A closer inspection of the dynamical state taking into account external pressure effects reveals that relatively strong magnetic field support may be needed to stabilize the cores, or that they are unstable and thus on the verge of collapse.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 8
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    Complex, quiescent kinematics in a highly filamentary infrared dark cloud (2013)
    Oxford University Press
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    Publication Date: 2013-01-03
    Description: Infrared dark clouds (IRDCs) host the initial conditions under which massive stars and stellar clusters form. It is therefore important to study the kinematics, as well as the physical and chemical properties of these regions. Their complex structure however posits challenges in the data interpretation. We have obtained high-sensitivity and high-spectral-resolution observations with the Instituto de Radioastronomía Milimétrica 30 m antenna, which allowed us to perform detailed analysis of the kinematics within one IRDC, G035.39–00.33. This cloud has been selected for its highly filamentary morphology and the presence of extended quiescent regions, characteristics of dynamical youth. We focus on the J = 1 -〉 0 and J = 3 -〉 2 transitions of N 2 H + , C 18 O (1–0), and make comparison with SiO (2–1) observations and extinction mapping. Three interacting filaments of gas are found. We report large-scale velocity coherence throughout the cloud, evidenced through small velocity gradients and relatively narrow line widths. This suggests that the merging of these filaments is somewhat ‘gentle’, possibly regulated by magnetic fields. This merging of filaments may be responsible for the production of weak, parsec-scale SiO emission, via grain mantle vaporization. A systematic velocity shift between the N 2 H + (1–0) and C 18 O (1–0) gas throughout the cloud of 0.18 ± 0.04  km s –1 is also found, consistent with a scenario of collisions between filaments which is still ongoing. The N 2 H + (1–0) is extended throughout the IRDC, in contrast to low-mass star forming regions, where N 2 H + is known to trace only the dense cores. The average H 2 number density across the IRDC is ~=5 x 10 4  cm –3 , at least one order of magnitude larger than in nearby molecular clouds where low-mass stars are forming. A temperature gradient perpendicular to the filament is found. From our study, we conclude that G035.39–00.33 (clearly seen in the extinction map and in N 2 H + ) has been formed via the collision between two relatively quiescent filaments with average densities of ~=5 x 10 3  cm –3 , moving with relative velocities of ~=5 km s –1 . The accumulation of material at the merging points started 1 Myr ago and it is still ongoing.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 9
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    Gas kinematics and excitation in the filamentary IRDC G035.39-00.33 (2014)
    Oxford University Press
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    Publication Date: 2014-03-09
    Description: Some theories of dense molecular cloud formation involve dynamical environments driven by converging atomic flows or collisions between preexisting molecular clouds. The determination of the dynamics and physical conditions of the gas in clouds at the early stages of their evolution is essential to establish the dynamical imprints of such collisions, and to infer the processes involved in their formation. We present multitransition 13 CO and C 18 O maps towards the IRDC G035.39-00.33, believed to be at the earliest stages of evolution. The 13 CO and C 18 O gas is distributed in three filaments (Filaments 1, 2 and 3), where the most massive cores are preferentially found at the intersecting regions between them. The filaments have a similar kinematic structure with smooth velocity gradients of ~0.4–0.8 km s –1  pc –1 . Several scenarios are proposed to explain these gradients, including cloud rotation, gas accretion along the filaments, global gravitational collapse and unresolved sub-filament structures. These results are complemented by HCO + , HNC, H 13 CO + and HN 13 C single-pointing data to search for gas infall signatures. The 13 CO and C 18 O gas motions are supersonic across G035.39-00.33, with the emission showing broader linewidths towards the edges of the infrared dark cloud (IRDC). This could be due to energy dissipation at the densest regions in the cloud. The average H 2 densities are ~5000–7000 cm –3 , with Filaments 2 and 3 being denser and more massive than Filament 1. The C 18 O data unveil three regions with high CO depletion factors ( f D  ~ 5–12), similar to those found in massive starless cores.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 10
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    Collapse, outflows and fragmentation of massive, turbulent and magnetized prestellar barotropic cores (2011)
    EDP Sciences
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    Publication Date: 2011-03-03
    Print ISSN: 0004-6361
    Electronic ISSN: 1432-0746
    Topics: Physics
    Published by EDP Sciences
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