78 research outputs found

    Quantifying the Role of Atmospheric Forcing in Ice Edge Retreat and Advance Including Wind-Wave Coupling

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    LONG-TERM GOALS: 1. Representing surface fluxes and ocean waves in coupled models in the Beaufort and Chukchi Seas. 2. Understand the physics of heat and mass transfer from the ocean to the atmosphere. 3. Improve forecasting of waves on the open ocean and in the marginal ice zone.Award Numbers: N0001413WX20830 (Guest) N0001413IP20046 (Fairall, Persson

    Office of Naval Research (ONR), Arctic and Global Prediction Program Department Research Initiative (DRI), Sea State and Boundary Layer Physics of the Emerging Arctic Ocean Quantifying the Role of Atmospheric Forcing in Ice Edge Retreat and Advance Including Wind-Wave Coupling

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    LONG-TERM GOALS: 1. Representing surface fluxes and ocean waves in coupled models in the Beaufort and Chukchi Seas. 2. Understand the physics of heat and mass transfer from the ocean to the atmosphere. 3. Improve forecasting of waves on the open ocean and in the marginal ice zone.N0001413WX20830 (Guest) N0001413IP20046 (Fairall, Persson

    SMAD4 haploinsufficiency in small intestinal neuroendocrine tumors

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    Background: Patients with small intestinal neuroendocrine tumors (SINETs) frequently present with lymph node and liver metastases at the time of diagnosis, but the molecular changes that lead to the progression of these tumors are largely unknown. Sequencing studies have only identified recurrent point mutations at low frequencies with CDKN1B being the most common harboring heterozygous mutations in less than 10% of all tumors. Although SINETs are genetically stable tumors with a low frequency of point mutations and indels, they often harbor recurrent hemizygous copy number alterations (CNAs) yet the functional implications of these CNA are unclear. Methods: Utilizing comparative genomic hybridization (CGH) arrays we analyzed the CNA profile of 131 SINETs from 117 patients. Two tumor suppressor genes and corresponding proteins i.e. SMAD4, and CDKN1B, were further characterized using a tissue microarray (TMA) with 846 SINETs. Immunohistochemistry (IHC) was used to quantify protein expression in TMA samples and this was correlated with chromosome number evaluated with fluorescent in-situ hybridization (FISH). Intestinal tissue from a Smad4+/− mouse model was used to detect entero-endocrine cell hyperplasia with IHC. Results: Analyzing the CGH arrays we found loss of chromosome 18q and SMAD4 in 71% of SINETs and that focal loss of chromosome 12 affecting the CDKN1B was present in 9.4% of SINETs. No homozygous loss of chromosome 18 was detected. Hemizygous loss of SMAD4, but not CDKN1B, significantly correlated with reduced protein levels but hemizygous loss of SMAD4 did not induce entero-endocrine cell hyperplasia in the Smad4+/− mouse model. In addition, patients with low SMAD4 protein expression in primary tumors more often presented with metastatic disease. Conclusions: Hemizygous loss of chromosome 18q and the SMAD4 gene is the most common genetic event in SINETs and our results suggests that this could influence SMAD4 protein expression and spread of metastases. Although SMAD4 haploinsufficiency alone did not induce tumor initiation, loss of chromosome 18 could represent an evolutionary advantage in SINETs explaining the high prevalence of this aberration. Functional consequences of reduced SMAD4 protein levels could hypothetically be a potential mechanism as to why loss of chromosome 18 appears to be clonally selected in SINETs

    The neuroendocrine phenotype, genomic profile and therapeutic sensitivity of GEPNET cell lines

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    Experimental models of neuroendocrine tumour disease are scarce, and no comprehensive characterisation of existing gastroenteropancreatic neuroendocrine tumour (GEPNET) cell lines has been reported. In this study, we aimed to define the molecular characteristics and therapeutic sensitivity of these cell lines. We therefore performed immunophenotyping, copy number profiling, whole-exome sequencing and a large-scale inhibitor screening of seven GEPNET cell lines. Four cell lines, GOT1, P-STS, BON-1 and QGP-1, displayed a neuroendocrine phenotype while three others, KRJ-I, L-STS and H-STS, did not. Instead, these three cell lines were identified as lymphoblastoid. Characterisation of remaining authentic GEPNET cell lines by copy number rofiling showed that GOT1, among other chromosomal alterations, harboured losses on chromosome 18 encompassing the SMAD4 gene, while P-STS had a loss on 11q. BON-1 had a homozygous loss of CDKN2A and CDKN2B, and QGP-1 harboured amplifications of MDM2 and HMGA2. Whole-exome sequencing revealed both disease-characteristic mutations (e.g. ATRX mutation in QGP-1) and, for patient tumours, rare genetic events (e.g. TP53 mutation in P-STS, BON-1 and QGP-1). A large-scale inhibitor screening showed that cell lines from pancreatic NETs to a greater extent, when compared to small intestinal NETs, were sensitive to inhibitors of MEK. Similarly, neuroendocrine NET cells originating from the small intestine were considerably more sensitive to a group of HDAC inhibitors. Taken together, our results provide a comprehensive characterisation of GEPNET cell lines, demonstrate their relevance as neuroendocrine tumour models and explore their therapeutic sensitivity to a broad range of inhibitors

    Overview of the MOSAiC expedition-Atmosphere INTRODUCTION

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    With the Arctic rapidly changing, the needs to observe, understand, and model the changes are essential. To support these needs, an annual cycle of observations of atmospheric properties, processes, and interactions were made while drifting with the sea ice across the central Arctic during the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) expedition from October 2019 to September 2020. An international team designed and implemented the comprehensive program to document and characterize all aspects of the Arctic atmospheric system in unprecedented detail, using a variety of approaches, and across multiple scales. These measurements were coordinated with other observational teams to explore crosscutting and coupled interactions with the Arctic Ocean, sea ice, and ecosystem through a variety of physical and biogeochemical processes. This overview outlines the breadth and complexity of the atmospheric research program, which was organized into 4 subgroups: atmospheric state, clouds and precipitation, gases and aerosols, and energy budgets. Atmospheric variability over the annual cycle revealed important influences from a persistent large-scale winter circulation pattern, leading to some storms with pressure and winds that were outside the interquartile range of past conditions suggested by long-term reanalysis. Similarly, the MOSAiC location was warmer and wetter in summer than the reanalysis climatology, in part due to its close proximity to the sea ice edge. The comprehensiveness of the observational program for characterizing and analyzing atmospheric phenomena is demonstrated via a winter case study examining air mass transitions and a summer case study examining vertical atmospheric evolution. Overall, the MOSAiC atmospheric program successfully met its objectives and was the most comprehensive atmospheric measurement program to date conducted over the Arctic sea ice. The obtained data will support a broad range of coupled-system scientific research and provide an important foundation for advancing multiscale modeling capabilities in the Arctic.Peer reviewe

    Towards quantifying the increasing role of oceanic heat in sea ice loss in the new Arctic

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    The loss of Arctic sea ice has emerged as a leading signal of global warming. This, together with acknowledged impacts on other components of the Earth system, has led to the term “the new Arctic.” Global coupled climate models predict that ice loss will continue through the twenty-first century, with implications for governance, economics, security, and global weather. A wide range in model projections reflects the complex, highly coupled interactions between the polar atmosphere, ocean, and cryosphere, including teleconnections to lower latitudes. This paper summarizes our present understanding of how heat reaches the ice base from the original sources—inflows of Atlantic and Pacific Water, river discharge, and summer sensible heat and shortwave radiative fluxes at the ocean/ice surface—and speculates on how such processes may change in the new Arctic. The complexity of the coupled Arctic system, and the logistic and technological challenges of working in the Arctic Ocean, require a coordinated interdisciplinary and international program that will not only improve understanding of this critical component of global climate but will also provide opportunities to develop human resources with the skills required to tackle related problems in complex climate systems. We propose a research strategy with components that include 1) improved mapping of the upper- and middepth Arctic Ocean, 2) enhanced quantification of important process, 3) expanded long-term monitoring at key heat-flux locations, and 4) development of numerical capabilities that focus on parameterization of heat-flux mechanisms and their interactions.publishedVersio

    Atmospheric conditions during the Arctic Clouds in Summer Experiment (ACSE): Contrasting open-water and sea-ice surfaces during melt and freeze-up seasons

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    The Arctic Clouds in Summer Experiment (ACSE) was conducted during summer and early autumn 2014, providing a detailed view of the seasonal transition from ice melt into freeze-up. Measurements were taken over both ice-free and ice-covered surfaces near the ice edge, offering insight into the role of the surface state in shaping the atmospheric conditions. The initiation of the autumn freeze-up was related to a change in air mass, rather than to changes in solar radiation alone; the lower atmosphere cooled abruptly, leading to a surface heat loss. During melt season, strong surface inversions persisted over the ice, while elevated inversions were more frequent over open water. These differences disappeared during autumn freeze-up, when elevated inversions persisted over both ice-free and ice-covered conditions. These results are in contrast to previous studies that found a well-mixed boundary layer persisting in summer and an increased frequency of surface-based inversions in autumn, suggesting that knowledge derived from measurements taken within the pan-Arctic area and on the central ice pack does not necessarily apply closer to the ice edge. This study offers an insight into the atmospheric processes that occur during a crucial period of the year; understanding and accurately modeling these processes is essential for the improvement of ice-extent predictions and future Arctic climate projections

    Warm‐air advection, air mass transformation and fog causes rapid ice melt

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    Direct observations during intense warm-air advection over the East Siberian Sea reveal a period of rapid sea-ice melt. A semi-stationary, high-pressure system north of the Bering Strait forced northward advection of warm, moist air from the continent. Air-mass transfor-mation over melting sea ice formed a strong, surface-based temperature inversion in which dense fog formed. This induced a positive net longwave radiation at the surface, while reduc-ing net solar radiation only marginally; the inversion also resulted in downward turbulent heat flux. The sum of these processes enhanced the surface energy flux by an average of ~15 W m-2 for a week. Satellite images before and after the episode show sea-ice concentrations decreasing from > 90% to ~50% over a large area affected by the air-mass transformation. We argue that this rapid melt was triggered by the increased heat flux from the atmosphere due to the warm-air advection

    Using rapid diagnostic tests as source of malaria parasite DNA for molecular analyses in the era of declining malaria prevalence

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    BACKGROUND: Malaria prevalence has recently declined markedly in many parts of Tanzania and other sub-Saharan African countries due to scaling-up of control interventions including more efficient treatment regimens (e.g. artemisinin-based combination therapy) and insecticide-treated bed nets. Although continued molecular surveillance of malaria parasites is important to early identify emerging anti-malarial drug resistance, it is becoming increasingly difficult to obtain parasite samples from ongoing studies, such as routine drug efficacy trials. To explore other sources of parasite DNA, this study was conducted to examine if sufficient DNA could be successfully extracted from malaria rapid diagnostic tests (RDTs), used and collected as part of routine case management services in health facilities, and thus forming the basis for molecular analyses, surveillance and quality control (QC) testing of RDTs. METHODS: One hyper-parasitaemic blood sample (131,260 asexual parasites/μl) was serially diluted in triplicates with whole blood and blotted on RDTs. DNA was extracted from the RDT dilution series, either immediately or after storage for one month at room temperature. The extracted DNA was amplified using a nested PCR method for Plasmodium species detection. Additionally, 165 archived RDTs obtained from ongoing malaria studies were analysed to determine the amplification success and test applicability of RDT for QC testing. RESULTS: DNA was successfully extracted and amplified from the three sets of RDT dilution series and the minimum detection limit of PCR was <1 asexual parasite/μl. DNA was also successfully amplified from (1) 70/71 (98.6%) archived positive RDTs (RDTs and microscopy positive) (2) 52/63 (82.5%) false negative RDTs (negative by RDTs but positive by microscopy) and (3) 4/24 (16.7%) false positive RDTs (positive by RDTs but negative by microscopy). Finally, 7(100%) negative RDTs (negative by RDTs and microscopy) were also negative by PCR. CONCLUSION: This study showed that DNA extracted from archived RDTs can be successfully amplified by PCR and used for detection of malaria parasites. Since Tanzania is planning to introduce RDTs in all health facilities (and possibly also at community level), availability of archived RDTs will provide an alternative source of DNA for genetic studies such as continued surveillance of parasite resistance to anti-malarial drugs. The DNA obtained from RDTs can also be used for QC testing by detecting malaria parasites using PCR in places without facilities for microscopy
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