2,032 research outputs found

    Combined population dynamics and entropy modelling supports patient stratification in chronic myeloid leukemia

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    Modelling the parameters of multistep carcinogenesis is key for a better understanding of cancer progression, biomarker identification and the design of individualized therapies. Using chronic myeloid leukemia (CML) as a paradigm for hierarchical disease evolution we show that combined population dynamic modelling and CML patient biopsy genomic analysis enables patient stratification at unprecedented resolution. Linking CD34+ similarity as a disease progression marker to patientderived gene expression entropy separated established CML progression stages and uncovered additional heterogeneity within disease stages. Importantly, our patient data informed model enables quantitative approximation of individual patients’ disease history within chronic phase (CP) and significantly separates “early” from “late” CP. Our findings provide a novel rationale for personalized and genome-informed disease progression risk assessment that is independent and complementary to conventional measures of CML disease burden and prognosis

    Handling and analysis of ices in cryostats and glove boxes in view of cometary samples

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    Comet nucleus sample return mission and other return missions from planets and satellites need equipment for handling and analysis of icy samples at low temperatures under vacuum or protective gas. Two methods are reported which were developed for analysis of small icy samples and which are modified for larger samples in cometary matter simulation experiments (KOSI). A conventional optical cryostat system was modified to allow for transport of samples at 5 K, ion beam irradiation, and measurement in an off-line optical spectrophotometer. The new system consists of a removable window plug containing nozzles for condensation of water and volatiles onto a cold finger. This plug can be removed in a vacuum system, changed against another plug (e.g., with other windows (IR, VIS, VUV) or other nozzles). While open, the samples can be treated under vacuum with cooling by manipulators (cut, removal, sample taking, irradiation with light, photons, or ions). After bringing the plug back, the samples can be moved to another site of analysis. For handling the 30 cm diameter mineral-ice samples from the KOSI experiments an 80x80x80 cm glove box made out of plexiglass was used. The samples were kept in a liquid nitrogen bath, which was filled from the outside. A stream a dry N2 and evaporating gas from the bath purified the glove box from impurity gases and, in particular, H2O, which otherwise would condense onto the samples

    A novel IEF peptide fractionation method reveals a detailed profile of N-terminal Acetylation in chemotherapy-responsive and -resistant ovarian cancer cells

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    Although acetylation is regarded as a common protein modification, a detailed proteome wide profile of this posttranslational modification may reveal important biological insight regarding differential acetylation of individual proteins. Here we optimised a novel peptide IEF fractionation method for use prior to LC-MS/MS analysis in order to obtain a more in depth coverage of N-terminally acetylated proteins from complex samples. Application of the method to the analysis of the serous ovarian cancer cell line OVCAR-5 identified 341 N-terminally acetylated proteins, 23 of which are previously un-reported. The protein peptidyl-prolyl cis-trans isomerase A (PPIA) was detected in both the N-terminally acetylated and un-modified forms, and was further analysed by data independent acquisition in Carboplatin responsive parental OVCAR-5 cells and Carboplatin resistant OVCAR-5 cells. This revealed a higher ratio of un-acetylated to acetylated N-terminal PPIA in the parental compared to the Carboplatin resistant OVCAR-5 cells, and a 4.1-fold increase in PPIA abundance overall in the parental cells relative to Carboplatin-resistant OVCAR-5 cells (P = 0.015). In summary, the novel IEF peptide fractionation method presented here is robust, reproducible, and can be applied to the profiling of N-terminally acetylated proteins. All mass spectrometry data is available as a ProteomeXchange repository (PXD003547).Florian Weiland, Georgia Arentz, Manuela Klingler-Hoffmann, Peter McCarthy, Noor A. Lokman, Gurjeet Kaur, Martin K. Oehler, and Peter Hoffman

    GPS TRACKING OF THE FORAGING MOVEMENTS OF OILBIRDS (STEATORNIS CARIPENSIS) FROM THE DUNSTON CAVE AT ASA WRIGHT NATURE CENTRE, TRINIDAD

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    The ranging behaviors of the Oilbird (Steatornis caripensis) in Trinidad are not well defined and are required to better outline fu- ture conservation management parameters for this species. Due to the nocturnal foraging behaviors of the Oilbird, past observations were restricted to colony site observations, video recordings, and limited electronic tracking over short periods. Utilizing newly developed small- scale Global Positioning System (GPS) data loggers, we were able to determine the flight and foraging behaviors of two oilbirds that roost at the Asa Wright Nature Centre for up to 270 days. The use of backpack style GPS tracking devices provided high site resolution and accuracy of the movements and a better understanding of the annual foraging behaviors of the oilbirds in the Asa Wright Nature Centre colony. The oilbirds’ home range was determined to be 3,564.6 km2, with an average trip distance from Dunston Cave of 7.33 km, excluding an interme- diary migration point in Venezuela. 48.5% of the foraging area consisted of locations within the Northern Range, while 27.7% of these trips remained within the Arima Valley, which is only partially protected from quarrying activities. This data document the previously unknown patterns of habitat use of the Oilbird and serves as a pilot study to determine the conservation importance of those habitats for the develop- ment of long-term conservation action plans for these iconic birds

    Jarosite in Gale Crater, Mars: The Importance of Temporal and Spatial Variability and Implications for Habitiability

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    The Curiosity rover has recently found evidence for small amounts of jarosite, a ferric sulfate, in the Pahrump Hills region at the base of Aeolis Mons (Mount Sharp), Gale crater. While jarosite has been described previously at other locations on Mars, including several sites at Meridiani Planum (explored by the Opportunity rover; and Mawrth Vallis (by remote MRO-CRISM observations; this is the first identification in Gale. Jarosite is interpreted to be a mineral indicator of acidic conditions (pH less than 4; on Earth, it is most commonly found in acid rock-drainage or acid sulfate soil environments. However, jarosite has also been described from a number of terrestrial environments where widespread acidic conditions are not prevalent. As a case study, we describe here an occurrence of sedimentary pyrite nodules that have been variably oxidized in situ to gypsum, schwertmannite, K-/Na-jarosite and iron oxides in a polar desert environment on Devon Island, Nunavut, Canada. Remarkably, these nodules occur in loosely consolidated carbonate sediments, which would have required a higher pH environment at their time of formation and deposition. Thus, acidic conditions may only exist at a small (sub-cm) scale or in a restricted temporal window in an otherwise well-buffered environment. On Devon Island, the jarosite occurs in the most oxidized nodules and is never associated directly with pyrite. Schwertmannite, a metastable iron oxyhydroxysulfate that can form at pH higher than that required for jarosite, occurs in association with partially oxidized pyrite. The paragenetic sequence observed here suggests initial formation of schwertmannite and late-stage precipitation of jarosite in restricted micro-environments, possibly forming via transformation of an amorphous schwertmannite-like phase. While the carbonate environment on Devon Island differs significantly from that of Gale crater, i.e., where we find predominantly basaltic sedimentary rocks, this terrestrial analog provides insight into the significance of jarosite with respect to habitability. For example, the variable abundance of jarosite on Mars and possibly in Gale crater points to potentially localized conditions favorable for jarosite formation. Interestingly, small amounts of sulfide minerals have also been detected by Curiosity at Yellowknife Bay; oxidation of sulfide minerals at Pahrump could explain the presence of small amounts of jarosite. The iron-rich rocks at Pahrump may also represent relatively altered basaltic sediments, or they could be sediments that were altered further by a fluid with a distinct, possibly more acidic, composition. In addition, the abundance of iron-rich amorphous material in Gale rocks allows for the possibility that pre-cursor, iron-bearing phases transform to jarosite post-depositionally. Thus, the occurrence of jarosite at Pahrump could reflect changing paleoenvironmental conditions, though continuing study of its context and textural relationships should provide a fuller understanding of the significance of this mineral to past fluid compositions and past habitability at Gale crater

    Conflicting estimates of natural geologic methane emissions

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    Global bottom-up and top-down estimates of natural, geologic methane (CH4) emissions (average approximately 45 Tg yr–1) have recently been questioned by near-zero (approximately 1.6 Tg yr–1) estimates based on measurements of 14CH4 trapped in ice cores, which imply that current fossil fuel industries' CH4 emissions are underestimated by 25%–40%. As we show here, such a global near-zero geologic CH4 emission estimate is incompatible with multiple independent, bottom-up emission estimates from individual natural geologic seepage areas, each of which is of the order of 0.1–3 Tg yr–1. Further research is urgently needed to resolve the conundrum before rejecting either method or associated emission estimates in global CH4 accounting

    Behavior of feral horses in response to culling and GnRH immunocontraception

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    AbstractWildlife management actions can alter fundamental behaviors of individuals and groups, which may directly impact their life history parameters in unforeseen ways. This is especially true for highly social animals because changes in one individual's behavior can cascade throughout its social network. When resources to support populations of social animals are limited and populations become locally overabundant, managers are faced with the daunting challenge of decreasing population size without disrupting core behavioral processes. Increasingly, managers are turning to fertility control technologies to supplement culling in efforts to suppress population growth, but little is quantitatively known about how either of these management tools affects behavior. Gonadotropin releasing hormone (GnRH) is a small neuropeptide that performs an obligatory role in mammalian reproduction and has been formulated into the immunocontraceptive GonaCon-B™. We investigated the influences of this vaccine on behavior of feral horses (Equus caballus) at Theodore Roosevelt National Park, North Dakota, USA, for a year preceding and a year following nonlethal culling and GnRH-vaccine treatment. We observed horses during the breeding season and found only minimal differences in time budget behaviors of free-ranging female feral horses treated with GnRH and those treated with saline. The differences observed were consistent with the metabolic demands of pregnancy and lactation. We observed similar social behaviors between treatment groups, reflecting limited reproductive behavior among control females due to high rates of pregnancy and suppressed reproductive behavior among treated females due to GnRH-inhibited ovarian activity. In the treatment year, band stallion age was the only supported factor influencing herding behavior (P<0.001), harem-tending behavior (P<0.001), and agonistic behavior (P=0.02). There was no difference between the mean body condition of control females (4.9 (95% CI=4.7–5.1)) and treated females (4.8 (95% CI=4.7–4.9)). Band fidelity among all females increased 25.7% in the year following vaccination and culling, despite the social perturbation associated with removal of conspecifics. Herding behavior by stallions decreased 50.7% following treatment and culling (P<0.001), while harem-tending behavior increased 195.0% (P<0.001). The amount of available forage influenced harem-tending, reproductive, and agonistic behavior in the year following culling and treatment (P<0.04). These changes reflected the expected nexus between a species with polygynous social structure and strong group fidelity and the large instantaneous change in population density and demography coincident with culling. Behavioral responses to such perturbation may be synergistic in reducing grazing pressure by decreasing energetically expensive competitive behaviors, but further investigation is needed to explicitly test this hypothesis

    Effect of HCl on the doping and shape control of silicon nanowires

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    International audienceThe introduction of Hydrogen Chloride during the in-situ doping of Silicon Nanowires (SiNWs) grown using the Vapour Liquid Solid (VLS) mechanism was investigated. Compared with non-chlorinated atmospheres, the use of HCl with dopant gases considerably improves the surface morphology of the SiNWs, leading to extremely smooth surfaces and a greatly reduced tapering. The variations in the wire diameter are massively reduced for boron doping, and can not be measured at 600°C for phosphorous over several tens of micrometers. This remarkable feature is accompanied by a frozen gold migration from the catalyst, with no noticeable levels of gold clusters observed using scanning electron microscopy. A detailed study of the NWs apparent resistivity reveals that the dopant incorporation is effective for both types of doping. A graph linking the apparent resistivity to the dopant to silane dilution ratio is built for both types of doping and discussed in the frame of the previous results
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