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In-situ nanoSIMS measurements of isotopic hotspots in the CM2 meteorite Cold Bokkeveld
Previous studies have identified iso-topic hotspots in insoluble organic matter (IOM) from carbonaceous chondrites. The origins and formation mechanisms of these hotspots and the host IOM are a matter of ongoing debate. For example, it is not clear whether D and 15N enrichments in IOM formed within a common organic precursor in cold interstellar environments or due to irradiation of organic material in the early Solar System. It is also unclear what effect parent body processes would have had with regard to the alteration of meteoritic IOM. In order to address these issues, more recent studies have attempted to make in-situ measurements of isotopic anomalies in IOM. In this study we present in-situ NanoSIMS isotopic analyses of material within a sample of the CM2 meteorite Cold Bokkeveld, comparing the distribution of hotspots and bulk H, C and N isotopic composition in the rims and interiors of altered chondrules
Topoisomerase II inhibitors induce DNA damage-dependent interferon responses circumventing Ebola virus immune evasion
Ebola virus (EBOV) protein VP35 inhibits production of interferon alpha/beta (IFN) by blocking RIG-I-like receptor signaling pathways, thereby promoting virus replication and pathogenesis. A high-throughput screening assay, developed to identify compounds that either inhibit or bypass VP35 IFN-antagonist function, identified five DNA intercalators as reproducible hits from a library of bioactive compounds. Four, including doxorubicin and daunorubicin, are anthracycline antibiotics that inhibit topoisomerase II and are used clinically as chemotherapeutic drugs. These compounds were demonstrated to induce IFN responses in an ATM kinase-dependent manner and to also trigger the DNA-sensing cGAS-STING pathway of IFN induction. These compounds also suppress EBOV replication in vitro and induce IFN in the presence of IFN-antagonist proteins from multiple negative-sense RNA viruses. These findings provide new insights into signaling pathways activated by important chemotherapy drugs and identify a novel therapeutic approach for IFN induction that may be exploited to inhibit RNA virus replication
Essential Oils as Multicomponent Mixtures and Their Potential for Human Health and Well-Being
Essential oils (EOs) and their individual volatile organic constituents have been an inherent part of our civilization for thousands of years. They are widely used as fragrances in perfumes and cosmetics and contribute to a healthy diet, but also act as active ingredients of pharmaceutical products. Their antibacterial, antiviral, and anti-inflammatory properties have qualified EOs early on for both, the causal and symptomatic therapy of a number of diseases, but also for prevention. Obtained from natural, mostly plant materials, EOs constitute a typical example of a multicomponent mixture (more than one constituent substances, MOCS) with up to several hundreds of individual compounds, which in a sophisticated composition make up the property of a particular complete EO. The integrative use of EOs as MOCS will play a major role in human and veterinary medicine now and in the future and is already widely used in some cases, e.g., in aromatherapy for the treatment of psychosomatic complaints, for inhalation in the treatment of respiratory diseases, or topically administered to manage adverse skin diseases. The diversity of molecules with different functionalities exhibits a broad range of multiple physical and chemical properties, which are the base of their multi-target activity as opposed to single isolated compounds. Whether and how such a broad-spectrum effect is reflected in natural mixtures and which kind of pharmacological potential they provide will be considered in the context of ONE Health in more detail in this review
Human iPSC-derived renal organoids engineered to report oxidative stress can predict drug-induced toxicity
Elastic scattering and breakup of 17^F at 10 MeV/nucleon
Angular distributions of fluorine and oxygen produced from 170 MeV 17^F
incident on 208^Pb were measured. The elastic scattering data are in good
agreement with optical model calculations using a double-folding potential and
parameters similar to those obtained from 16^O+208^Pb. A large yield of oxygen
was observed near \theta_lab=36 deg. It is reproduced fairly well by a
calculation of the (17^F,16^O) breakup, which is dominated by one-proton
stripping reactions. The discrepancy between our previous coincidence
measurement and theoretical predictions was resolved by including core
absorption in the present calculation.Comment: 9 pages, 5 figure
Essential Oils as Multicomponent Mixtures and Their Potential for Human Health and Well-Being
Essential oils (EOs) and their individual volatile organic constituents have been an inherent part of our civilization for thousands of years. They are widely used as fragrances in perfumes and cosmetics and contribute to a healthy diet, but also act as active ingredients of pharmaceutical products. Their antibacterial, antiviral, and anti-inflammatory properties have qualified EOs early on for both, the causal and symptomatic therapy of a number of diseases, but also for prevention. Obtained from natural, mostly plant materials, EOs constitute a typical example of a multicomponent mixture (more than one constituent substances, MOCS) with up to several hundreds of individual compounds, which in a sophisticated composition make up the property of a particular complete EO. The integrative use of EOs as MOCS will play a major role in human and veterinary medicine now and in the future and is already widely used in some cases, e.g. , in aromatherapy for the treatment of psychosomatic complaints, for inhalation in the treatment of respiratory diseases, or topically administered to manage adverse skin diseases. The diversity of molecules with different functionalities exhibits a broad range of multiple physical and chemical properties, which are the base of their multi-target activity as opposed to single isolated compounds. Whether and how such a broad-spectrum effect is reflected in natural mixtures and which kind of pharmacological potential they provide will be considered in the context of ONE Health in more detail in this review
First-forbidden mirror beta-decays in A=17 mass region
The first-forbidden beta-decay of 17Ne into the 'halo' state J=1/2+ of 17F
presents one of the largest measured asymmetries for mirror beta-decay feeding
bound final states. This asymmetry is studied in the framework of the Shell
Model Embedded in the Continuum (SMEC). The spatial extent of single particle
orbits is constrained by the proton capture cross-section 16O(p,gamma)17F
calculated in SMEC . This allows to estimate the mirror symmetry breaking in
17F/17O and 17Ne/17N nuclei.Comment: 23 pages, 7 figures Misprints correcte
Breakup of F on Pb near the Coulomb barrier
Angular distributions of oxygen produced in the breakup of F incident
on a Pb target have been measured around the grazing angle at beam
energies of 98 and 120 MeV. The data are dominated by the proton stripping
mechanism and are well reproduced by dynamical calculations. The measured
breakup cross section is approximately a factor of 3 less than that of fusion
at 98 MeV. The influence of breakup on fusion is discussed.Comment: 7 pages, 8 figure
European multidisciplinary consensus statement on the use and monitoring of metal-on-metal bearings for total hip replacement and hip resurfacing.
Summary Introduction There is an ongoing debate about the optimal use of metal-on-metal (MoM) bearings in total hip replacement, since there are uncertainties about local and systemic adverse effects due to wear and corrosion of these bearings. Despite various national recommendations, efforts to achieve international harmonization of specific evidence-based recommendations for best practice are still lacking. Hypothesis An international consensus study group should be able to develop recommendations on the use and monitoring of MoM bearings, preferably at the European level, through a multidisciplinary approach, by integrating the perspectives of various stakeholders. Materials and methods Twenty-one experts representing three stakeholder groups and eight countries participated in this European consensus study, which consisted of a consensus meeting, subsequent structured discussion, and consensus voting. Results The current statement defines first of all benefits, local and systemic risks, as well as uncertain issues related to MoM bearings. Safety assessment after implantation of MoM comprises all patients. A closer follow-up is recommended for large head MoM (≥ 36 mm) and resurfacing. In these implants basic follow-up should consist of x-rays and metal ion measurement of cobalt in whole blood, performed with GF-AAS or ICP-MS. Clinical and/or radiographic abnormality as well as elevated ion levels needs additional imaging (ultrasound, CT-scan and/or MARS-MRI). Cobalt values less than 2 μg/L are probably devoid of clinical concern, the threshold value for clinical concern is expected to be within the range of 2–7 μg/L. Discussion This is the first multinational, interdisciplinary, and multiprofessional approach for developing a recommendation for the use and monitoring of MoM bearings in total hip replacement. The current recommendations are in partial agreement with previous statements regarding the extent of follow-up and imaging techniques. They however differ from previous communications regarding measurement of metal ions and especially the investigated medium, technique, and eventual threshold levels. Level of evidence Level V, expert opinion/agreement conference
A search for resonant production of pairs in $4.8\ \rm{fb}^{-1}p\bar{p}\sqrt{s}=1.96\ \rm{TeV}$
We search for resonant production of tt pairs in 4.8 fb^{-1} integrated
luminosity of ppbar collision data at sqrt{s}=1.96 TeV in the lepton+jets decay
channel, where one top quark decays leptonically and the other hadronically. A
matrix element reconstruction technique is used; for each event a probability
density function (pdf) of the ttbar candidate invariant mass is sampled. These
pdfs are used to construct a likelihood function, whereby the cross section for
resonant ttbar production is estimated, given a hypothetical resonance mass and
width. The data indicate no evidence of resonant production of ttbar pairs. A
benchmark model of leptophobic Z \rightarrow ttbar is excluded with m_{Z'} <
900 GeV at 95% confidence level.Comment: accepted for publication in Physical Review D Sep 21, 201
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