398 research outputs found

    Railway Detection: From Filtering to Segmentation Networks

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    International audienceThis paper deals with classification of remote sensing data to extract objects for industrial mapping. While land-cover or urban mapping have been extensively studied, industrial cartography remains a field yet to explore, in spite of tremendous needs. We present and compare here four approaches for railway detection in very high resolution images. They use various kind of filtering approaches, including the trained filters of fully convolutional networks. Moreover, they benefit from different a-priori and post-processing techniques to make them more robust. We evaluate all approaches on a challenging dataset captured on an operating station site with complex objects

    Land Use and Habitat Conditions Across the Southwestern Wyoming Sagebrush Steppe: Development Impacts, Management Effectiveness and the Distribution of Invasive Plants

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    For the past several years, USGS has taken a multi-faceted approach to investigating the condition and trends in sagebrush steppe ecosystems. This recent effort builds upon decades of work in semi-arid ecosystems providing a specific, applied focus on the cumulative impacts of expanding human activities across these landscapes. Here, we discuss several on-going projects contributing to these efforts: (1) mapping and monitoring the distribution and condition of shrub steppe communities with local detail at a regional scale, (2) assessing the relationships between specific, land-use features (for example, roads, transmission lines, industrial pads) and invasive plants, including their potential (environmentally defined) distribution across the region, and (3) monitoring the effects of habitat treatments on the ecosystem, including wildlife use and invasive plant abundance. This research is focused on the northern sagebrush steppe, primarily in Wyoming, but also extending into Montana, Colorado, Utah and Idaho. The study area includes a range of sagebrush types (including, Artemisia tridentata ssp. tridentata, Artemisia tridentata ssp. wyomingensis, Artemisia tridentata ssp. vaseyana, Artemisia nova) and other semi-arid shrubland types (for example, Sarcobatus vermiculatus, Atriplex confertifolia, Atriplex gardneri), impacted by extensive interface between steppe ecosystems and industrial energy activities resulting in a revealing multiple-variable analysis. We use a combination of remote sensing (AWiFS (1 Any reference to platforms, data sources, equipment, software, patented or trade-marked methods is for information purposes only. It does not represent endorsement of the U.S.D.I., U.S.G.S. or the authors), Landsat and Quickbird platforms), Geographic Information System (GIS) design and data management, and field-based, replicated sampling to generate multiple scales of data representing the distribution of shrub communities for the habitat inventory. Invasive plant sampling focused on the interaction between human infrastructure and weedy plant distributions in southwestern Wyoming, while also capturing spatial variability associated with growing conditions and management across the region. In a separate but linked study, we also sampled native and invasive composition of recent and historic habitat treatments. Here, we summarize findings of this ongoing work, highlighting patterns and relationships between vegetation (native and invasive), land cover, landform, and land-use patterns in the sagebrush steppe

    High-protein paternal diet confers an advantage to sons in sperm competition

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    Parental environment can widely influence offspring phenotype, but paternal effects in the absence of parental care remain poorly understood. We asked if protein content in the larval diet of fathers affected paternity success and gene expression in their sons. We found that males reared on high-protein diet had sons that fared better during sperm competition, suggesting that postcopulatory sexual selection is subject to transgenerational paternal effects. Moreover, immune response genes were downregulated in sons of low-protein fathers, while genes involved in metabolic and reproductive processes were upregulated

    Inhibiting the oncogenic translation program is an effective therapeutic strategy in multiple myeloma

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    Published in final edited form as: Sci Transl Med. 2017 May 10; 9(389). https://doi.org/10.1126/scitranslmed.aal2668.Multiple myeloma (MM) is a frequently incurable hematological cancer in which overactivity of MYC plays a central role, notably through up-regulation of ribosome biogenesis and translation. To better understand the oncogenic program driven by MYC and investigate its potential as a therapeutic target, we screened a chemically diverse small-molecule library for anti-MM activity. The most potent hits identified were rocaglate scaffold inhibitors of translation initiation. Expression profiling of MM cells revealed reversion of the oncogenic MYC-driven transcriptional program by CMLD010509, the most promising rocaglate. Proteome-wide reversion correlated with selective depletion of short-lived proteins that are key to MM growth and survival, most notably MYC, MDM2, CCND1, MAF, and MCL-1. The efficacy of CMLD010509 in mouse models of MM confirmed the therapeutic relevance of these findings in vivo and supports the feasibility of targeting the oncogenic MYC-driven translation program in MM with rocaglates

    Anti-CD38 antibody therapy for patients with relapsed/refractory multiple myeloma: differential mechanisms of action and recent clinical trial outcomes.

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    CD38 is a transmembrane glycoprotein that functions both as a receptor and an ectoenzyme, playing key roles in the regulation of calcium signaling and migration of immune cells to tumor microenvironments. High expression on multiple myeloma (MM) cells and limited expression on normal cells makes CD38 an ideal target for the treatment of MM patients. Two monoclonal antibodies directed at CD38, isatuximab and daratumumab, are available for use in patients with relapsed and/or refractory MM (RRMM); daratumumab is also approved in newly diagnosed MM and light-chain amyloidosis. Clinical experience has shown that anti-CD38 antibody therapy is transforming treatment of MM owing to its anti-myeloma efficacy and manageable safety profile. Isatuximab and daratumumab possess similarities and differences in their mechanisms of action, likely imparted by their binding to distinct, non-overlapping epitopes on the CD38 molecule. In this review, we present the mechanistic properties of these two antibodies and outline available evidence on their abilities to induce adaptive immune responses and modulate the bone marrow niche in MM. Further, we discuss differences in regulatory labeling between these two agents and analyze recent key clinical trial results, including evidence in patients with underlying renal impairment and other poor prognostic factors. Finally, we describe the limited existing evidence for the use of isatuximab or daratumumab after disease progression on prior anti-CD38 mono- or combination therapy, highlighting the need for additional clinical evaluations to define optimal anti-CD38 antibody therapy selection and sequencing in RRMM

    On the Formation of Collective Memories: The Role of a Dominant Narrator.

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    To test our hypothesis that conversations can contribute to the formation of collective memory, we asked participants to study stories and to recall them individually (pregroup recollection), then as a group (group recounting), and then once again individually (postgroup recollection). One way that postgroup collective memories can be formed under these circumstances is if unshared pregroup recollections in the group recounting influences others\u27 postgroup recollections. In the present research, we explored (using tests of recall and recognition) whether the presence of a dominant narrator can facilitate the emergence of unshared pregroup recollections in a group recounting and whether this emergence is associated with changes in postgroup recollections. We argue that the formation of a collective memory through conversation is not inevitable but is limited by cognitive factors, such as conditions for social contagion, and by situational factors, such as the presence of a narrator

    Controlling silver nanoparticle exposure in algal toxicity testing - A matter of timing

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    The aquatic ecotoxicity testing of nanoparticles is complicated by unstable exposure conditions resulting from various transformation processes of nanoparticles in aqueous suspensions. In this study, we investigated the influence of exposure timing on the algal test response to silver nanoparticles (AgNPs), by reducing the incubation time and by aging the AgNPs in algal medium prior to testing. The freshwater green algae Pseudokirchneriella subcapitata were exposed to AgNO(3), NM-300 K (a representative AgNP) and citrate stabilized AgNPs from two different manufacturers (AgNP1 and AgNP2) in a standard algal growth inhibition test (ISO 8692:2004) for 48 h and a short-term (2 h) (14)C-assimilation test. For AgNO(3), similar responses were obtained in the two tests, whereas freshly prepared suspensions of citrate stabilized AgNPs were less toxic in the 2-h tests compared to the 48-h tests. The 2-h test was found applicable for dissolved silver, but yielded non-monotonous concentration–response relationships and poor reproducibility for freshly prepared AgNP suspensions. However, when aging AgNPs in algal medium 24 h prior to testing, clear concentration–response patterns emerged and reproducibility increased. Prolonged aging to 48 h increased toxicity in the 2-h tests whereas aging beyond 48 h reduced toxicity. Our results demonstrate that the outcome of algal toxicity testing of AgNPs is highly influenced not only by the test duration, but also by the time passed from the moment AgNPs are added to the test medium. This time-dependency should be considered when nanomaterial dispersion protocols for ecotoxicity testing are developed

    Genomic Profiling of Smoldering Multiple Myeloma Identifies Patients at a High Risk of Disease Progression

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    PURPOSE: Smoldering multiple myeloma (SMM) is a precursor condition of multiple myeloma (MM) with a 10% annual risk of progression. Various prognostic models exist for risk stratification; however, those are based on solely clinical metrics. The discovery of genomic alterations that underlie disease progression to MM could improve current risk models. METHODS: We used next-generation sequencing to study 214 patients with SMM. We performed whole-exome sequencing on 166 tumors, including 5 with serial samples, and deep targeted sequencing on 48 tumors. RESULTS: We observed that most of the genetic alterations necessary for progression have already been acquired by the diagnosis of SMM. Particularly, we found that alterations of the mitogen-activated protein kinase pathway (KRAS and NRAS single nucleotide variants [SNVs]), the DNA repair pathway (deletion 17p, TP53, and ATM SNVs), and MYC (translocations or copy number variations) were all independent risk factors of progression after accounting for clinical risk staging. We validated these findings in an external SMM cohort by showing that patients who have any of these three features have a higher risk of progressing to MM. Moreover, APOBEC associated mutations were enriched in patients who progressed and were associated with a shorter time to progression in our cohort. CONCLUSION: SMM is a genetically mature entity whereby most driver genetic alterations have already occurred, which suggests the existence of a right-skewed model of genetic evolution from monoclonal gammopathy of undetermined significance to MM. We identified and externally validated genomic predictors of progression that could distinguish patients at high risk of progression to MM and, thus, improve on the precision of current clinical models

    Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis

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    Background Systemic immunoglobulin light-chain (AL) amyloidosis is characterized by deposition of amyloid fibrils of light chains produced by clonal CD38+ plasma cells. Daratumumab, a human CD38-targeting antibody, may improve outcomes for this disease. Methods We randomly assigned patients with newly diagnosed AL amyloidosis to receive six cycles of bortezomib, cyclophosphamide, and dexamethasone either alone (control group) or with subcutaneous daratumumab followed by single-agent daratumumab every 4 weeks for up to 24 cycles (daratumumab group). The primary end point was a hematologic complete response. Results A total of 388 patients underwent randomization. The median follow-up was 11.4 months. The percentage of patients who had a hematologic complete response was significantly higher in the daratumumab group than in the control group (53.3% vs. 18.1%) (relative risk ratio, 2.9; 95% confidence interval [CI], 2.1 to 4.1; P Daratumumab in Light-Chain Amyloidosis In a randomized trial of bortezomib, cyclophosphamide, and dexamethasone as compared with the same therapy plus daratumumab, patients with light-chain amyloidosis who received daratumumab had a higher frequency of hematologic complete response than those who did not (53.3% vs. 18.1%). Deaths were most commonly due to cardiac failure
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