Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • American Association for the Advancement of Science (AAAS)  (14)
  • The American Association for Cancer Research (AACR)  (5)
  • 1
    Publication Date: 2018-03-29
    Description: The Earth-Moon system likely formed as a result of a collision between two large planetary objects. Debate about their relative masses, the impact energy involved, and the extent of isotopic homogenization continues. We present the results of a high-precision oxygen isotope study of an extensive suite of lunar and terrestrial samples. We demonstrate that lunar rocks and terrestrial basalts show a 3 to 4 ppm (parts per million), statistically resolvable, difference in 17 O. Taking aubrite meteorites as a candidate impactor material, we show that the giant impact scenario involved nearly complete mixing between the target and impactor. Alternatively, the degree of similarity between the 17 O values of the impactor and the proto-Earth must have been significantly closer than that between Earth and aubrites. If the Earth-Moon system evolved from an initially highly vaporized and isotopically homogenized state, as indicated by recent dynamical models, then the terrestrial basalt-lunar oxygen isotope difference detected by our study may be a reflection of post–giant impact additions to Earth. On the basis of this assumption, our data indicate that post–giant impact additions to Earth could have contributed between 5 and 30% of Earth’s water, depending on global water estimates. Consequently, our data indicate that the bulk of Earth’s water was accreted before the giant impact and not later, as often proposed.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Publication Date: 2018-03-06
    Description: Tumor-selective delivery of cytotoxic agents in the form of antibody–drug conjugates (ADCs) is now a clinically validated approach for cancer treatment. In an attempt to improve the clinical success rate of ADCs, emphasis has been recently placed on the use of DNA–cross-linking pyrrolobenzodiazepine compounds as the payload. Despite promising early clinical results with this class of ADCs, doses achievable have been low due to systemic toxicity. Here, we describe the development of a new class of potent DNA-interacting agents wherein changing the mechanism of action from a cross-linker to a DNA alkylator improves the tolerability of the ADC. ADCs containing the DNA alkylator displayed similar in vitro potency, but improved bystander killing and in vivo efficacy, compared with those of the cross-linker. Thus, the improved in vivo tolerability and antitumor activity achieved in rodent models with ADCs of the novel DNA alkylator could provide an efficacious, yet safer option for cancer treatment. Mol Cancer Ther; 17(3); 650–60. ©2018 AACR .
    Print ISSN: 1535-7163
    Electronic ISSN: 1538-8514
    Topics: Medicine
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    facet.materialart.
    facet.materialart.
    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-08-17
    Description: We document rapid and abrupt clearings of large portions of the subtropical marine low cloud deck that have implications for the global radiation balance and climate sensitivity. Over the southeast Atlantic, large areas of stratocumulus are quickly eroded, yielding partial or complete clearing along sharp transitions hundreds to thousands of kilometers in length that move westward at 8 to 12 meters per second and travel as far as 1000+ kilometers from the African coast. The westward-moving cloudiness reductions have an annual peak in occurrence in the period from April through June. The cloud erosion boundaries reduce cloud at 10-kilometer scale in less than 15 minutes, move approximately perpendicular to the mean flow, and are often accompanied by small-scale wave features. Observations suggest that the cloud erosion is caused by atmospheric gravity waves.
    Keywords: Geochemistry, Geophysics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Publication Date: 2018-10-16
    Description: Purpose: Inflammatory bowel disease–associated colorectal cancers (IBD-CRC) are associated with a higher mortality than sporadic colorectal cancers. The poorly defined molecular pathogenesis of IBD-CRCs limits development of effective prevention, detection, and treatment strategies. We aimed to identify biomarkers using whole-exome sequencing of IBD-CRCs to guide individualized management. Experimental Design: Whole-exome sequencing was performed on 34 formalin-fixed paraffin-embedded primary IBD-CRCs and 31 matched normal lymph nodes. Computational methods were used to identify somatic point mutations, small insertions and deletions, mutational signatures, and somatic copy number alterations. Mismatch repair status was examined. Results: Hypermutation was observed in 27% of IBD-CRCs. All hypermutated cancers were from the proximal colon; all but one of the cancers with hypermutation had defective mismatch repair or somatic mutations in the proofreading domain of DNA POLE . Hypermutated IBD-CRCs had increased numbers of predicted neo-epitopes, which could be exploited using immunotherapy. We identified six distinct mutation signatures in IBD-CRCs, three of which corresponded to known mechanisms of mutagenesis. Driver genes were also identified. Conclusions: IBD-CRCs should be evaluated for hypermutation and defective mismatch repair to identify patients with a higher neo-epitope load who may benefit from immunotherapies. Prospective trials are required to determine whether IHC to detect loss of MLH1 expression in dysplastic colonic tissue could identify patients at increased risk of developing IBD-CRC. We identified mutations in genes in IBD-CRCs with hypermutation that might be targeted therapeutically. These approaches would complement and individualize surveillance and treatment programs. Clin Cancer Res; 24(20); 5133–42. ©2018 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Publication Date: 2018-12-11
    Description: To determine the effects of diet, rats were placed on a standard diet (4% fat) or on a modified Western (high-fat diet, HFD) diet (21% fat) at 43 days of age (DOA) and administered methylnitrosourea (MNU) at 50 DOA. Rats were administered effective (tamoxifen, vorozole, and Targretin) or ineffective (metformin and Lipitor) chemopreventive agents either by daily gavage or in the diet beginning at 57 DOA and continuing until sacrifice (190 DOA). Latency period of the tumors was determined by palpation, and multiplicity and cancer weights per rat were determined at final sacrifice. Rats on the HFD versus standard diet had: (i) a 6% increase in final body weights; (ii) significant decreases in tumor latency; and (iii) significant increases in final tumor multiplicity and average tumor weight. Tamoxifen, vorozole, and Targretin were highly effective preventive agents, whereas Lipitor and metformin were ineffective in rats on either diet. Serum was collected at 78 DOA and at sacrifice (190 DOA), and metabolomics were determined to identify the metabolite changes due to diets and effective agents. Rats given the HFD had increased levels of saturated free fatty acids (including myristate) and decreased levels of 2-aminooctanoate. Furthermore, rats on the HFD diet had increased levels of 2-aminobutyrate and decreases in glycine markers previously identified as indicators of prediabetes. Targretin increased long-chain glycophospholipids (e.g., oleyl-linoleoyl-glycerophosphocholine) and decreased primary bile acids (e.g., taurocholate). Tamoxifen increased palmitoyl-linoleoyl-glycophosphocholine and decreased stearoyl-arachidonyl glycophosphocholine. Finally, increased levels of methylated nucleotides (5-methylcytidine) and decreased levels of urea cycle metabolites (N-acetylcitrulline) were associated with the presence of mammary cancers.
    Print ISSN: 1940-6207
    Electronic ISSN: 1940-6215
    Topics: Medicine
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Publication Date: 2015-02-24
    Description: The evolution of galaxies is connected to the growth of supermassive black holes in their centers. During the quasar phase, a huge luminosity is released as matter falls onto the black hole, and radiation-driven winds can transfer most of this energy back to the host galaxy. Over five different epochs, we detected the signatures of a nearly spherical stream of highly ionized gas in the broadband x-ray spectra of the luminous quasar PDS 456. This persistent wind is expelled at relativistic speeds from the inner accretion disk, and its wide aperture suggests an effective coupling with the ambient gas. The outflow's kinetic power larger than 10(46) ergs per second is enough to provide the feedback required by models of black hole and host galaxy coevolution.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nardini, E -- Reeves, J N -- Gofford, J -- Harrison, F A -- Risaliti, G -- Braito, V -- Costa, M T -- Matzeu, G A -- Walton, D J -- Behar, E -- Boggs, S E -- Christensen, F E -- Craig, W W -- Hailey, C J -- Matt, G -- Miller, J M -- O'Brien, P T -- Stern, D -- Turner, T J -- Ward, M J -- New York, N.Y. -- Science. 2015 Feb 20;347(6224):860-3. doi: 10.1126/science.1259202.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Astrophysics Group, School of Physical and Geographical Sciences, Keele University, Keele, Staffordshire ST5 5BG, UK. e.nardini@keele.ac.uk. ; Astrophysics Group, School of Physical and Geographical Sciences, Keele University, Keele, Staffordshire ST5 5BG, UK. Center for Space Science and Technology, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA. ; Cahill Center for Astronomy and Astrophysics, California Institute of Technology, Pasadena, CA 91125, USA. ; Istituto Nazionale di Astrofisica, Osservatorio Astrofisico di Arcetri, Largo Enrico Fermi 5, I-50125 Firenze, Italy. Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138, USA. ; INAF, Osservatorio Astronomico di Brera, Via Bianchi 46, I-23807 Merate (LC), Italy. ; Astrophysics Group, School of Physical and Geographical Sciences, Keele University, Keele, Staffordshire ST5 5BG, UK. ; Cahill Center for Astronomy and Astrophysics, California Institute of Technology, Pasadena, CA 91125, USA. Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA 91109, USA. ; Department of Physics, Technion, Haifa 32000, Israel. ; Space Science Laboratory, University of California, Berkeley, CA 94720, USA. ; Danmarks Tekniske Universitet Space-National Space Institute, Technical University of Denmark, Elektrovej 327, 2800 Lyngby, Denmark. ; Lawrence Livermore National Laboratory, Livermore, CA 94550, USA. ; Columbia Astrophysics Laboratory, Columbia University, New York, NY 10027, USA. ; Dipartimento di Matematica e Fisica, Universita degli Studi Roma Tre, Via della Vasca Navale 84, I-00146 Roma, Italy. ; Department of Astronomy, University of Michigan, Ann Arbor, MI 48109, USA. ; Department of Physics and Astronomy, University of Leicester, University Road, Leicester LE1 7RH, UK. ; Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA 91109, USA. ; Physics Department, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA. Eureka Scientific Inc., 2452 Delmer Street Suite 100, Oakland, CA 94602, USA. ; Department of Physics, University of Durham, South Road, Durham DH1 3LE, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25700515" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Publication Date: 2015-11-28
    Description: Solar photoconversion in semiconductors is driven by charge separation at the interface of the semiconductor and contacting layers. Here we demonstrate that time-resolved photoinduced reflectance from a semiconductor captures interfacial carrier dynamics. We applied this transient photoreflectance method to study charge transfer at p-type gallium-indium phosphide (p-GaInP2) interfaces critically important to solar-driven water splitting. We monitored the formation and decay of transient electric fields that form upon photoexcitation within bare p-GaInP2, p-GaInP2/platinum (Pt), and p-GaInP2/amorphous titania (TiO2) interfaces. The data show that a field at both the p-GaInP2/Pt and p-GaInP2/TiO2 interfaces drives charge separation. Additionally, the charge recombination rate at the p-GaInP2/TiO2 interface is greatly reduced owing to its p-n nature, compared with the Schottky nature of the p-GaInP2/Pt interface.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Ye -- Gu, Jing -- Young, James L -- Miller, Elisa M -- Turner, John A -- Neale, Nathan R -- Beard, Matthew C -- New York, N.Y. -- Science. 2015 Nov 27;350(6264):1061-5. doi: 10.1126/science.aad3459.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Renewable Energy Laboratory, Chemistry and Nanoscience Center, Golden, CO, 80401, USA. ye.yang@nrel.gov matt.beard@nrel.gov. ; National Renewable Energy Laboratory, Chemistry and Nanoscience Center, Golden, CO, 80401, USA. ; National Renewable Energy Laboratory, Chemistry and Nanoscience Center, Golden, CO, 80401, USA. Material Science and Engineering Program, University of Colorado, Boulder, CO, 80309, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26612947" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    Publication Date: 2018-07-12
    Description: The contemporary Arctic carbon balance is uncertain, and the potential for a permafrost carbon feedback of anywhere from 50 to 200 petagrams of carbon (Schuur et al ., 2015) compromises accurate 21st-century global climate system projections. The 42-year record of atmospheric CO 2 measurements at Barrow, Alaska (71.29 N, 156.79 W), reveals significant trends in regional land-surface CO 2 anomalies (CO 2 ), indicating long-term changes in seasonal carbon uptake and respiration. Using a carbon balance model constrained by CO 2 , we find a 13.4% decrease in mean carbon residence time (50% confidence range = 9.2 to 17.6%) in North Slope tundra ecosystems during the past four decades, suggesting a transition toward a boreal carbon cycling regime. Temperature dependencies of respiration and carbon uptake suggest that increases in cold season Arctic labile carbon release will likely continue to exceed increases in net growing season carbon uptake under continued warming trends.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    Publication Date: 2018-07-28
    Description: The observation and control of interweaving spin, charge, orbital, and structural degrees of freedom in materials on ultrafast time scales reveal exotic quantum phenomena and enable new active forms of nanotechnology. Bonding is the prime example of the relation between electronic and nuclear degrees of freedom. We report direct evidence illustrating that photoexcitation can be used for ultrafast control of the breaking and recovery of bonds in solids on unprecedented time scales, near the limit for nuclear motions. We describe experimental and theoretical studies of IrTe 2 using femtosecond electron diffraction and density functional theory to investigate bonding instability. Ir-Ir dimerization shows an unexpected fast dissociation and recovery due to the filling of the antibonding d xy orbital. Bond length changes of 20% in IrTe 2 are achieved by effectively addressing the bonds directly through this relaxation process. These results could pave the way to ultrafast switching between metastable structures by photoinduced manipulation of the relative degree of bonding in this manner.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    Publication Date: 2018-09-05
    Description: Purpose: Previous studies have indicated an important role for pleckstrin homology domain-interacting protein (PHIP) as a marker and mediator of melanoma metastasis. Here we aimed to confirm the role of PHIP copy number in successive stages of melanoma progression. Experimental Design: PHIP copy number was examined using FISH in three independent cohorts by recording the percentage of cells harboring ≥3 copies of PHIP . The impact of PHIP copy number on survival was assessed using Cox regression analysis. The enrichment of PHIP was assessed in various molecular melanoma subtypes. PHIP expression was analyzed in The Cancer Genome Atlas (TCGA) melanoma cohort. Results: Elevated PHIP copy number was significantly predictive of reduced distant metastasis-free survival (DMFS) and disease-specific survival (DSS), and increased prevalence of ulceration in primary melanoma (cohort No. 1). By multivariate analysis, PHIP FISH scores were independently predictive of DMFS and DSS. PHIP copy number was enriched in metastatic melanomas harboring mutant NRAS or expressing PTEN protein (cohort No. 2). PHIP copy number was significantly elevated in metastatic melanomas when compared with matched primary tumors from the same patient (cohort No. 3). Several of these associations were replicated using TCGA cohort analysis. Conclusions: These results underscore the important role of PHIP copy-number elevation in melanoma progression, and identify molecular subtypes of melanoma in which PHIP is enriched. Finally, as elevated PHIP copy number appears to be selected for during the progression of primary to metastatic melanoma, these results confirm PHIP as a promising therapeutic target for melanoma. Clin Cancer Res; 24(17); 4119–25. ©2018 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...