926 research outputs found

    Observation of a Griffiths-like phase in the paramagnetic regime of ErCo_2

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    A systematic x-ray magnetic circular dichroism study of the paramagnetic phase of ErCo2 has recently allowed to identify the inversion of the net magnetization of the Co net moment with respect to the applied field well above the ferrimagnetic ordering temperature, Tc. The study of small angle neutron scattering measurements has also shown the presence of short range order correlations in the same temperature region. This phenomenon, which we have denoted parimagnetism, may be related with the onset of a Griffiths-like phase in paramagnetic ErCo2. We have measured ac susceptibility on ErCo2 as a function of temperature, applied field, and excitation frequency. Several characteristics shared by systems showing a Griffiths phase are present in ErCo2, namely the formation of ferromagnetic clusters in the disordered phase, the loss of analyticity of the magnetic susceptibility and its extreme sensitivity to an applied magnetic field. The paramagnetic susceptibility allows to establish that the magnetic clusters are only formed by Co moments as well as the intrinsic nature of those Co moments

    Intergenerational education mobility and depressive symptoms in a population of Mexican origin

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    Low educational attainment has been associated with depression among Latinos. However, few studies have collected intergenerational data to assess mental health effects of educational mobility across generations

    Pt(IV)-based nanoscale coordination polymers : antitumor activity, cellular uptake and interactions with nuclear DNA

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    Cisplatin has been for many years the gold standard chemotherapeutic drug for the treatment of a wide range of solid tumors, even though its use is commonly associated with serious side effects including non-selective toxicity, myelosuppression or development of cisplatin resistance, among others complications. Over the last decade, a number of nanoparticle formulations were developed to reduce its side effects and improve the selectivity and efficacy of this drug. In this study, we have developed a novel nanoparticle platform based on nanoscale coordination polymer named (Zn-Pt(IV)-NCPs) which contains a Pt(IV) prodrug, Zn and the linker ligand 1,4-Bis(imidazol-1-ylmethyl)benzene (bix). The main objective has been to gain insights into the mechanism of action of this nanostructured material in comparison with cisplatin and the free Pt(IV) prodrug in order to establish a correlation between nanostructuration and therapeutic activity. Zn-Pt(IV)-NCPs nanoparticles displayed an average size close to 200 nm as determined by DLS, a good stability in physiologic environments, and a controlled drug release of Pt. In vitro studies demonstrated that Pt(IV)-NCPs showed an enhanced cytotoxic effect against cell culture of cervical cancer, neuroblastoma and human adenocarcinoma cells in comparison with free Pt(IV) prodrug. Although no difference in cell uptake of Pt was observed for any of the three cell lines assayed, a higher amount of Pt bound to the DNA was found in the cells treated with the nanostructured Pt(IV) prodrug. These studies suggest that the nanostructuration of the prodrug facilitate its activation and induce a change in the mechanism of action related to an increased interaction with the DNA as corroborated by the studies of direct interaction of the Pt(IV) prodrug, nanostructured or not, with DNA

    Lipoprotein Profiles in Class III Obese Caucasian and African American Women with Nonalcoholic Fatty Liver Disease

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    Triglyceride content in the liver is regulated by the uptake, production and elimination of lipoproteins, and derangements in these processes contribute to nonalcoholic fatty liver disease (NAFLD). Previous studies show a direct relationship between intrahepatic fat and production of apolipoprotein B100 (apoB100) containing particles, VLDL and LDL, but little consensus exists regarding changes in lipoprotein production in the development of simple steatosis (SS) versus nonalcoholic steatohepatitis (NASH). Further, ethnic variations in lipoproteins among SS and NASH are unknown as is how such variations might contribute to the differential prevalence of disease among Caucasians versus African Americans. In this study, we assessed plasma lipoprotein profiles by nuclear magnetic resonance (NMR) spectroscopy in 70 non-diabetic class III obese females recruited from the surgical weight loss clinic. Of these, 51 females were stratified by biopsy-staged NAFLD severity (histologically normal, SS, or NASH). NASH females displayed increased circulating triglycerides and increased VLDL particle number and size relative to those with histologically normal livers, while total and large LDL concentration decreased in SS versus NASH and correlated with increased insulin resistance (via HOMA2-IR). When Caucasian women were examined alone (n = 41), VLDL and triglycerides increased between normal and SS, while total LDL and apoB100 decreased between SS and NASH along with increased insulin resistance. Compared to Caucasians with SS, African American women with SS displayed reduced triglycerides, VLDL, and small LDL and a more favorable small to large HDL ratio despite having increased BMI and HOMA2-IR. These findings suggest that ApoB100 and lipoprotein subclass particle number and size can delineate steatosis from NASH in obese Caucasian females, but should be interpreted with caution in other ethnicities as African Americans with SS display relatively improved lipoprotein profiles. This may reflect variation in the relationship between dyslipidemia and NAFLD progression across gender and ethnicity

    Cytoplasmic chromatin triggers inflammation in senescence and cancer

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    Chromatin is traditionally viewed as a nuclear entity that regulates gene expression and silencing. However, we recently discovered the presence of cytoplasmic chromatin fragments that pinch off from intact nuclei of primary cells during senescence, a form of terminal cell-cycle arrest associated with pro-inflammatory responses. The functional significance of chromatin in the cytoplasm is unclear. Here we show that cytoplasmic chromatin activates the innate immunity cytosolic DNA-sensing cGAS-STING (cyclic GMP-AMP synthase linked to stimulator of interferon genes) pathway, leading both to short-term inflammation to restrain activated oncogenes and to chronic inflammation that associates with tissue destruction and cancer. The cytoplasmic chromatin-cGAS-STING pathway promotes the senescence-associated secretory phenotype in primary human cells and in mice. Mice deficient in STING show impaired immuno-surveillance of oncogenic RAS and reduced tissue inflammation upon ionizing radiation. Furthermore, this pathway is activated in cancer cells, and correlates with pro-inflammatory gene expression in human cancers. Overall, our findings indicate that genomic DNA serves as a reservoir to initiate a pro-inflammatory pathway in the cytoplasm in senescence and cancer. Targeting the cytoplasmic chromatin-mediated pathway may hold promise in treating inflammation-related disorders

    Extraction of artefactual MRS patterns from a large database using non-negative matrix factorization

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    Despite the success of automated pattern recognition methods in problems of human brain tumor diagnostic classification, limited attention has been paid to the issue of automated data quality assessment in the field of MRS for neuro-oncology. Beyond some early attempts to address this issue, the current standard in practice is MRS quality control through human (expert-based) assessment. One aspect of automatic quality control is the problem of detecting artefacts in MRS data. Artefacts, whose variety has already been reviewed in some detail and some of which may even escape human quality control, have a negative influence in pattern recognition methods attempting to assist tumor characterization. The automatic detection of MRS artefacts should be beneficial for radiology as it guarantees more reliable tumor characterizations, as well as the development of more robust pattern recognition-based tumor classifiers and more trustable MRS data processing and analysis pipelines. Feature extraction methods have previously been used to help distinguishing between good and bad quality spectra to apply subsequent supervised pattern recognition techniques. In this study, we apply feature extraction differently and use a variant of a method for blind source separation, namely Convex Non-Negative Matrix Factorization, to unveil MRS signal sources in a completely unsupervised way. We hypothesize that, while most sources will correspond to the different tumor patterns, some of them will reflect signal artefacts. The experimental work reported in this paper, analyzing a combined short and long echo time 1H-MRS database of more than 2000 spectra acquired at 1.5T and corresponding to different tumor types and other anomalous masses, provides a first proof of concept that points to the possible validity of this approach.Peer ReviewedPostprint (author's final draft

    European anthropogenic AFOLU emissions and their uncertainties: a review and benchmark data

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    Emission of greenhouse gases (GHG) and removals from land, including both anthropogenic and natural fluxes, require reliable quantification, along with estimates of their inherent uncertainties, in order to support credible mitigation action under the Paris Agreement. This study provides a state-of-the-art scientific overview of bottom-up anthropogenic emissions data from agriculture, forestry and other land use (AFOLU) in Europe. The data integrates recent AFOLU emission inventories with ecosystem data and land carbon models, covering the European Union (EU28) and summarizes GHG emissions and removals over the period 1990–2016, of relevance for UNFCCC. This compilation of bottom-up estimates of the AFOLU GHG emissions of European national greenhouse gas inventories (NGHGI) with those of land carbon models and observation-based estimates of large-scale GHG fluxes, aims at improving the overall estimates of the GHG balance in Europe with respect to land GHG emissions and removals. Particular effort is devoted to the estimation of uncertainty, its propagation and role in the comparison of different estimates. While NGHGI data for EU28 provides consistent quantification of uncertainty following the established IPCC guidelines, uncertainty in the estimates produced with other methods will need to account for both within model uncertainty and the spread from different model results. At EU28 level, the largest inconsistencies between estimates are mainly due to different sources of data related to human activity which result in emissions or removals taking place during a given period of time (IPCC 2006) referred here as activity data (AD) and methodologies (Tiers) used for calculating emissions/removals from AFOLU sectors. The referenced datasets related to figures are visualised at https://doi.org/10.5281/zenodo.3460311, Petrescu et al., 2019

    Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults.

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    New neurons continue to be generated in the subgranular zone of the dentate gyrus of the adult mammalian hippocampus. This process has been linked to learning and memory, stress and exercise, and is thought to be altered in neurological disease. In humans, some studies have suggested that hundreds of new neurons are added to the adult dentate gyrus every day, whereas other studies find many fewer putative new neurons. Despite these discrepancies, it is generally believed that the adult human hippocampus continues to generate new neurons. Here we show that a defined population of progenitor cells does not coalesce in the subgranular zone during human fetal or postnatal development. We also find that the number of proliferating progenitors and young neurons in the dentate gyrus declines sharply during the first year of life and only a few isolated young neurons are observed by 7 and 13 years of age. In adult patients with epilepsy and healthy adults (18-77 years; n = 17 post-mortem samples from controls; n = 12 surgical resection samples from patients with epilepsy), young neurons were not detected in the dentate gyrus. In the monkey (Macaca mulatta) hippocampus, proliferation of neurons in the subgranular zone was found in early postnatal life, but this diminished during juvenile development as neurogenesis decreased. We conclude that recruitment of young neurons to the primate hippocampus decreases rapidly during the first years of life, and that neurogenesis in the dentate gyrus does not continue, or is extremely rare, in adult humans. The early decline in hippocampal neurogenesis raises questions about how the function of the dentate gyrus differs between humans and other species in which adult hippocampal neurogenesis is preserved

    Macroscopic superposition states of ultracold bosons in a double-well potential

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    We present a thorough description of the physical regimes for ultracold bosons in double wells, with special attention paid to macroscopic superpositions (MSs). We use a generalization of the Lipkin-Meshkov-Glick Hamiltonian of up to eight single particle modes to study these MSs, solving the Hamiltonian with a combination of numerical exact diagonalization and high-order perturbation theory. The MS is between left and right potential wells; the extreme case with all atoms simultaneously located in both wells and in only two modes is the famous NOON state, but our approach encompasses much more general MSs. Use of more single particle modes brings dimensionality into the problem, allows us to set hard limits on the use of the original two-mode LMG model commonly treated in the literature, and also introduces a new mixed Josephson-Fock regime. Higher modes introduce angular degrees of freedom and MS states with different angular properties.Comment: 15 pages, 8 figures, 1 table. Mini-review prepared for the special issue of Frontiers of Physics "Recent Progresses on Quantum Dynamics of Ultracold Atoms and Future Quantum Technologies", edited by Profs. Lee, Ueda, and Drummon

    Risk of Peritoneal Carcinomatosis After Risk-Reducing Salpingo-Oophorectomy:A Systematic Review and Individual Patient Data Meta-Analysis

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    PURPOSEAfter risk-reducing salpingo-oophorectomy (RRSO), BRCA1/2 pathogenic variant (PV) carriers have a residual risk to develop peritoneal carcinomatosis (PC). The etiology of PC is not yet clarified, but may be related to serous tubal intraepithelial carcinoma (STIC), the postulated origin for high-grade serous cancer. In this systematic review and individual patient data meta-analysis, we investigate the risk of PC in women with and without STIC at RRSO.METHODSUnpublished data from three centers were supplemented by studies identified in a systematic review of EMBASE, MEDLINE, and the Cochrane library describing women with a BRCA-PV with and without STIC at RRSO until September 2020. Primary outcome was the hazard ratio for the risk of PC between BRCA-PV carriers with and without STIC at RRSO, and the corresponding 5- and 10-year risks. Primary analysis was based on a one-stage Cox proportional-hazards regression with a frailty term for study.RESULTSFrom 17 studies, individual patient data were available for 3,121 women, of whom 115 had a STIC at RRSO. The estimated hazard ratio to develop PC during follow-up in women with STIC was 33.9 (95% CI, 15.6 to 73.9), P <.001) compared with women without STIC. For women with STIC, the five- and ten-year risks to develop PC were 10.5% (95% CI, 6.2 to 17.2) and 27.5% (95% CI, 15.6 to 43.9), respectively, whereas the corresponding risks were 0.3% (95% CI, 0.2 to 0.6) and 0.9% (95% CI, 0.6 to 1.4) for women without STIC at RRSO.CONCLUSIONBRCA-PV carriers with STIC at RRSO have a strongly increased risk to develop PC which increases over time, although current data are limited by small numbers of events
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