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| 3. |
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| 4. |
- Arndt, D. S., et al.
(författare)
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STATE OF THE CLIMATE IN 2017
- 2018
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
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Forskningsöversikt (refereegranskat)
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| 5. |
- Arndt, D. S., et al.
(författare)
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State of the Climate in 2016
- 2017
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 98:8, s. S1-S280
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Tidskriftsartikel (refereegranskat)abstract
- In 2016, the dominant greenhouse gases released into Earth's atmosphere-carbon dioxide, methane, and nitrous oxide-continued to increase and reach new record highs. The 3.5 +/- 0.1 ppm rise in global annual mean carbon dioxide from 2015 to 2016 was the largest annual increase observed in the 58-year measurement record. The annual global average carbon dioxide concentration at Earth's surface surpassed 400 ppm (402.9 +/- 0.1 ppm) for the first time in the modern atmospheric measurement record and in ice core records dating back as far as 800000 years. One of the strongest El Nino events since at least 1950 dissipated in spring, and a weak La Nina evolved later in the year. Owing at least in part to the combination of El Nino conditions early in the year and a long-term upward trend, Earth's surface observed record warmth for a third consecutive year, albeit by a much slimmer margin than by which that record was set in 2015. Above Earth's surface, the annual lower troposphere temperature was record high according to all datasets analyzed, while the lower stratospheric temperature was record low according to most of the in situ and satellite datasets. Several countries, including Mexico and India, reported record high annual temperatures while many others observed near-record highs. A week-long heat wave at the end of April over the northern and eastern Indian peninsula, with temperatures surpassing 44 degrees C, contributed to a water crisis for 330 million people and to 300 fatalities. In the Arctic the 2016 land surface temperature was 2.0 degrees C above the 1981-2010 average, breaking the previous record of 2007, 2011, and 2015 by 0.8 degrees C, representing a 3.5 degrees C increase since the record began in 1900. The increasing temperatures have led to decreasing Arctic sea ice extent and thickness. On 24 March, the sea ice extent at the end of the growth season saw its lowest maximum in the 37-year satellite record, tying with 2015 at 7.2% below the 1981-2010 average. The September 2016 Arctic sea ice minimum extent tied with 2007 for the second lowest value on record, 33% lower than the 1981-2010 average. Arctic sea ice cover remains relatively young and thin, making it vulnerable to continued extensive melt. The mass of the Greenland Ice Sheet, which has the capacity to contribute similar to 7 m to sea level rise, reached a record low value. The onset of its surface melt was the second earliest, after 2012, in the 37-year satellite record. Sea surface temperature was record high at the global scale, surpassing the previous record of 2015 by about 0.01 degrees C. The global sea surface temperature trend for the 21st century-to-date of +0.162 degrees C decade(-1) is much higher than the longer term 1950-2016 trend of +0.100 degrees C decade(-1). Global annual mean sea level also reached a new record high, marking the sixth consecutive year of increase. Global annual ocean heat content saw a slight drop compared to the record high in 2015. Alpine glacier retreat continued around the globe, and preliminary data indicate that 2016 is the 37th consecutive year of negative annual mass balance. Across the Northern Hemisphere, snow cover for each month from February to June was among its four least extensive in the 47-year satellite record. Continuing a pattern below the surface, record high temperatures at 20-m depth were measured at all permafrost observatories on the North Slope of Alaska and at the Canadian observatory on northernmost Ellesmere Island. In the Antarctic, record low monthly surface pressures were broken at many stations, with the southern annular mode setting record high index values in March and June. Monthly high surface pressure records for August and November were set at several stations. During this period, record low daily and monthly sea ice extents were observed, with the November mean sea ice extent more than 5 standard deviations below the 1981-2010 average. These record low sea ice values contrast sharply with the record high values observed during 2012-14. Over the region, springtime Antarctic stratospheric ozone depletion was less severe relative to the 1991-2006 average, but ozone levels were still low compared to pre-1990 levels. Closer to the equator, 93 named tropical storms were observed during 2016, above the 1981-2010 average of 82, but fewer than the 101 storms recorded in 2015. Three basins-the North Atlantic, and eastern and western North Pacific-experienced above-normal activity in 2016. The Australian basin recorded its least active season since the beginning of the satellite era in 1970. Overall, four tropical cyclones reached the Saffir-Simpson category 5 intensity level. The strong El Nino at the beginning of the year that transitioned to a weak La Nina contributed to enhanced precipitation variability around the world. Wet conditions were observed throughout the year across southern South America, causing repeated heavy flooding in Argentina, Paraguay, and Uruguay. Wetter-than-usual conditions were also observed for eastern Europe and central Asia, alleviating the drought conditions of 2014 and 2015 in southern Russia. In the United States, California had its first wetter-than-average year since 2012, after being plagued by drought for several years. Even so, the area covered by drought in 2016 at the global scale was among the largest in the post-1950 record. For each month, at least 12% of land surfaces experienced severe drought conditions or worse, the longest such stretch in the record. In northeastern Brazil, drought conditions were observed for the fifth consecutive year, making this the longest drought on record in the region. Dry conditions were also observed in western Bolivia and Peru; it was Bolivia's worst drought in the past 25 years. In May, with abnormally warm and dry conditions already prevailing over western Canada for about a year, the human-induced Fort McMurray wildfire burned nearly 590000 hectares and became the costliest disaster in Canadian history, with $3 billion (U.S. dollars) in insured losses.
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| 6. |
- Blunden, Jessica, et al.
(författare)
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State of the Climate in 2012
- 2013
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 94:8, s. S1-S258
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Tidskriftsartikel (refereegranskat)abstract
- For the first time in serveral years, the El Nino-Southern Oscillation did not dominate regional climate conditions around the globe. A weak La Ni a dissipated to ENSOneutral conditions by spring, and while El Nino appeared to be emerging during summer, this phase never fully developed as sea surface temperatures in the eastern conditions. Nevertheless, other large-scale climate patterns and extreme weather events impacted various regions during the year. A negative phase of the Arctic Oscillation from mid-January to early February contributed to frigid conditions in parts of northern Africa, eastern Europe, and western Asia. A lack of rain during the 2012 wet season led to the worst drought in at least the past three decades for northeastern Brazil. Central North America also experienced one of its most severe droughts on record. The Caribbean observed a very wet dry season and it was the Sahel's wettest rainy season in 50 years. Overall, the 2012 average temperature across global land and ocean surfaces ranked among the 10 warmest years on record. The global land surface temperature alone was also among the 10 warmest on record. In the upper atmosphere, the average stratospheric temperature was record or near-record cold, depending on the dataset. After a 30-year warming trend from 1970 to 1999 for global sea surface temperatures, the period 2000-12 had little further trend. This may be linked to the prevalence of La Ni a-like conditions during the 21st century. Heat content in the upper 700 m of the ocean remained near record high levels in 2012. Net increases from 2011 to 2012 were observed at 700-m to 2000-m depth and even in the abyssal ocean below. Following sharp decreases in to the effects of La Ni a, sea levels rebounded to reach records highs in 2012. The increased hydrological cycle seen in recent years continued, with more evaporation in drier locations and more precipitation in rainy areas. In a pattern that has held since 2004, salty areas of the ocean surfaces and subsurfaces were anomalously salty on average, while fresher areas were anomalously fresh. Global tropical cyclone activity during 2012 was near average, with a total of 84 storms compared with the 1981-2010 average of 89. Similar to 2010 and 2011, the North Atlantic was the only hurricane basin that experienced above-normal activity. In this basin, Sandy brought devastation to Cuba and parts of the eastern North American seaboard. All other basins experienced either near-or below-normal tropical cyclone activity. Only three tropical cyclones reached Category 5 intensity-all in Bopha became the only storm in the historical record to produce winds greater than 130 kt south of 7 N. It was also the costliest storm to affect the Philippines and killed more than 1000 residents. Minimum Arctic sea ice extent in September and Northern Hemisphere snow cover extent in June both reached new record lows. June snow cover extent is now declining at a faster rate (-17.6% per decade) than September sea ice extent (-13.0% per decade). Permafrost temperatures reached record high values in northernmost Alaska. A new melt extent record occurred on 11-12 July on the Greenland ice sheet; 97% of the ice sheet showed some form of melt, four times greater than the average melt for this time of year. The climate in Antarctica was relatively stable overall. The largest maximum sea ice extent since records begain in 1978 was observed in September 2012. In the stratosphere, warm air led to the second smallest ozone hole in the past two decades. Even so, the springtime ozone layer above Antarctica likely will not return to its early 1980s state until about 2060. Following a slight decline associated with the global 2 emissions from fossil fuel combustion and cement production reached a record 9.5 +/- 0.5 Pg C in 2011 and a new record of 9.7 +/- 0.5 Pg C is estimated for 2012. Atmospheric CO2 concentrations increased by 2.1 ppm in 2012, to 392.6 ppm. In spring 2012, 2 concentration exceeded 400 ppm at 7 of the 13 Arctic observation sites. Globally, other greenhouse gases including methane and nitrous oxide also continued to rise in concentration and the combined effect now represents a 32% increase in radiative forcing over a 1990 baseline. Concentrations of most ozone depleting substances continued to fall.
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| 7. |
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| 8. |
- Leal Filho, W., et al.
(författare)
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Handling climate change education at universities : an overview
- 2021
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Ingår i: Environmental Sciences Europe. - : Springer Nature. - 2190-4707 .- 2190-4715. ; 33:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Climate change is a problem which is global in nature, and whose effects go across a wide range of disciplines. It is therefore important that this theme is taken into account as part of universities´ teaching and research programs. Methods: A three-tiered approach was used, consisting of a bibliometric analysis, an online survey and a set of case studies, which allow a profile to be built, as to how a sample of universities from 45 countries handle climate change as part of their teaching programs. Results: This paper reports on a study which aimed at identifying the extent to which matters related to climate change are addressed within the teaching and research practices at universities, with a focus on the training needs of teaching staff. It consists of a bibliometric analysis, combined with an online worldwide survey aimed at ascertaining the degree of involvement from universities in reducing their own carbon footprint, and the ways they offer training provisions on the topic. This is complemented by a set of 12 case studies from universities round the world, illustrating current trends on how universities handle climate change. Apart from reporting on the outcomes of the study, the paper highlights what some universities are doing to handle climate issues, and discusses the implications of the research. Conclusions: The paper lists some items via which universities may better educate and train their students on how to handle the many challenges posed by climate change.
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| 9. |
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| 10. |
- Andrés-Jensen, Liv, et al.
(författare)
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Severe toxicity free survival : physician-derived definitions of unacceptable long-term toxicities following acute lymphocytic leukaemia
- 2021
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Ingår i: The Lancet Haematology. - : Elsevier. - 2352-3026. ; 8:7, s. E513-E523
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Forskningsöversikt (refereegranskat)abstract
- 5-year overall survival rates have surpassed 90% for childhood acute lymphocytic leukaemia, but survivors are at risk for permanent health sequelae. Although event-free survival appropriately represents the outcome for cancers with poor overall survival, this metric is inadequate when cure rates are high but challenged by serious, persistent complications. Accordingly, a group of experts in paediatric haematology-oncology, representative of 17 international acute lymphocytic leukaemia study groups, launched an initiative to construct a measure, designated severe toxicity-free survival (STFS), to quantify the occurrence of physician-prioritised toxicities to be integrated with standard cancer outcome reporting. Five generic inclusion criteria (not present before cancer diagnosis, symptomatic, objectifiable, of unacceptable severity, permanent, or requiring unacceptable treatments) were used to assess 855 health conditions, which resulted in inclusion of 21 severe toxicities. Consensus definitions were reached through a modified Delphi process supplemented by two additional plenary meetings. The 21 severe toxicities include severe adverse health conditions that substantially affect activities of daily living and are refractory to therapy (eg, refractory seizures), are without therapeutic options (eg, blindness), or require substantially invasive treatment (eg, cardiac transplantation). Incorporation of STFS assessment into clinical trials has the potential to improve and diversify treatment strategies, focusing not only on traditional outcome events and overall survival but also the frequencies of the most severe toxicities. The two major aims of this Review were to: prioritise and define unacceptable long-term toxicity for patients with childhood acute lymphocytic leukaemia, and define how these toxicities should be combined into a composite quantity to be integrated with other reported outcomes. Although STFS quantifies the clinically unacceptable health tradeoff for cure using childhood acute lymphocytic leukaemia as a model disease, the prioritised severe toxicities are based on generic considerations of relevance to any other cancer diagnosis and age group.
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| 11. |
- Caputo, Mara, et al.
(författare)
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Silencing of STE20-type kinase MST3 in mice with antisense oligonucleotide treatment ameliorates diet-induced nonalcoholic fatty liver disease
- 2021
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Ingår i: FASEB Journal. - 0892-6638. ; 35:5
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Tidskriftsartikel (refereegranskat)abstract
- Nonalcoholic fatty liver disease (NAFLD) is emerging as a leading cause of chronic liver disease worldwide. Despite intensive nonclinical and clinical research in this field, no specific pharmacological therapy is currently approved to treat NAFLD, which has been recognized as one of the major unmet medical needs of the 21st century. Our recent studies have identified STE20-type kinase MST3, which localizes to intracellular lipid droplets, as a critical regulator of ectopic fat accumulation in human hepatocytes. Here, we explored whether treatment with Mst3-targeting antisense oligonucleotides (ASOs) can promote hepatic lipid clearance and mitigate NAFLD progression in mice in the context of obesity. We found that administration of Mst3-targeting ASOs in mice effectively ameliorated the full spectrum of high-fat diet-induced NAFLD including liver steatosis, inflammation, fibrosis, and hepatocellular damage. Mechanistically, Mst3 ASOs suppressed lipogenic gene expression, as well as acetyl-CoA carboxylase (ACC) protein abundance, and substantially reduced lipotoxicity-mediated oxidative and endoplasmic reticulum stress in the livers of obese mice. Furthermore, we found that MST3 protein levels correlated positively with the severity of NAFLD in human liver biopsies. In summary, this study provides the first in vivo evidence that antagonizing MST3 signaling is sufficient to mitigate NAFLD progression in conditions of excess dietary fuels and warrants future investigations to assess whether MST3 inhibitors may provide a new strategy for the treatment of patients with NAFLD.
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| 12. |
- Caputo, Mara, et al.
(författare)
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STE20-Type Protein Kinase MST4 Controls NAFLD Progression by Regulating Lipid Droplet Dynamics and Metabolic Stress in Hepatocytes
- 2021
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Ingår i: Hepatology Communications. - : Ovid Technologies (Wolters Kluwer Health). - 2471-254X. ; 5:7, s. 1183-1200
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Tidskriftsartikel (refereegranskat)abstract
- Nonalcoholic fatty liver disease (NAFLD) has emerged as a leading cause of chronic liver disease worldwide, primarily because of the massive global increase in obesity. Despite intense research efforts in this field, the factors that govern the initiation and subsequent progression of NAFLD are poorly understood, which hampers the development of diagnostic tools and effective therapies in this area of high unmet medical need. Here we describe a regulator in molecular pathogenesis of NAFLD: STE20-type protein kinase MST4. We found that MST4 expression in human liver biopsies was positively correlated with the key features of NAFLD (i.e., hepatic steatosis, lobular inflammation, and hepatocellular ballooning). Furthermore, the silencing of MST4 attenuated lipid accumulation in human hepatocytes by stimulating beta-oxidation and triacylglycerol secretion, while inhibiting fatty acid influx and lipid synthesis. Conversely, overexpression of MST4 in human hepatocytes exacerbated fat deposition by suppressing mitochondrial fatty acid oxidation and triacylglycerol efflux, while enhancing lipogenesis. In parallel to these reciprocal alterations in lipid storage, we detected substantially decreased or aggravated oxidative/endoplasmic reticulum stress in human hepatocytes with reduced or increased MST4 levels, respectively. Interestingly, MST4 protein was predominantly associated with intracellular lipid droplets in both human and rodent hepatocytes. Conclusion: Together, our results suggest that hepatic lipid droplet-decorating protein MST4 is a critical regulatory node governing susceptibility to NAFLD and warrant future investigations to address the therapeutic potential of MST4 antagonism as a strategy to prevent or mitigate the development and aggravation of this disease.
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| 13. |
- Geraeinejad, V., et al.
(författare)
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RoCo-NAS : Robust and Compact Neural Architecture Search
- 2021
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Ingår i: Proceedings of the International Joint Conference on Neural Networks. - : Institute of Electrical and Electronics Engineers Inc.. ; July
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Tidskriftsartikel (refereegranskat)abstract
- Deep model compression has been studied widely, and state-of-the-art methods can now achieve high compression ratios with minimum accuracy loss. Recent advances in adversarial attacks reveal the inherent vulnerability of deep neural networks to slightly perturbed images called adversarial examples. Since then, extensive efforts have been performed to enhance deep networks’ robustness via specialized loss functions and learning algorithms. Previous works suggest that network size and robustness against adversarial examples contradict on most occasions. In this paper, we investigate how to optimize compactness and robustness to adversarial attacks of neural network architectures while maintaining the accuracy using multi-objective neural architecture search. We propose the use of previously generated adversarial examples as an objective to evaluate the robustness of our models in addition to the number of floating-point operations to assess model complexity i.e. compactness. Experiments on some recent neural architecture search algorithms show that due to their limited search space they fail to find robust and compact architectures. By creating a novel neural architecture search (RoCo-NAS), we were able to evolve an architecture that is up to 7% more accurate against adversarial samples than its more complex architecture counterpart. Thus, the results show inherently robust architectures regardless of their size. This opens up a new range of possibilities for the exploration and design of deep neural networks using automatic architecture search.
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| 14. |
- Masoudzadeh, Nasrin, et al.
(författare)
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Molecular signatures of anthroponotic cutaneous leishmaniasis in the lesions of patients infected with Leishmania tropica.
- 2020
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Anthroponotic cutaneous leishmaniasis (CL) caused by Leishmania tropica (L. tropica) represents a public health challenge in several resource poor settings. We herein employed a systems analysis approach to study molecular signatures of CL caused by L. tropica in the skin lesions of ulcerative CL (UCL) and non-ulcerative CL (NUCL) patients. Results from RNA-seq analysis determined shared and unique functional transcriptional pathways in the lesions of the UCL and NUCL patients. Several transcriptional pathways involved in inflammatory response were positively enriched in the CL lesions. A multiplexed inflammatory protein analysis showed differential profiles of inflammatory cytokines and chemokines in the UCL and NUCL lesions. Transcriptional pathways for Fcγ receptor dependent phagocytosis were among shared enriched pathways. Using L. tropica specific antibody (Ab)-mediated phagocytosis assays, we could substantiate Ab-dependent cellular phagocytosis (ADCP) and Ab-dependent neutrophil phagocytosis (ADNP) activities in the lesions of the UCL and NUCL patients, which correlated with L. tropica specific IgG Abs. Interestingly, a negative correlation was observed between parasite load and L. tropica specific IgG/ADCP/ADNP in the skin lesions of CL patients. These results enhance our understanding of human skin response to CL caused by L. tropica.
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| 15. |
- Smith, Christopher J., et al.
(författare)
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Effective radiative forcing and adjustments in CMIP6 models
- 2020
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 20:16, s. 9591-9618
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Tidskriftsartikel (refereegranskat)abstract
- The effective radiative forcing, which includes the instantaneous forcing plus adjustments from the atmosphere and surface, has emerged as the key metric of evaluating human and natural influence on the climate. We evaluate effective radiative forcing and adjustments in 17 contemporary climate models that are participating in the Coupled Model Intercomparison Project (CMIP6) and have contributed to the Radiative Forcing Model Intercomparison Project (RFMIP). Present-day (2014) global-mean anthropogenic forcing relative to pre-industrial (1850) levels from climate models stands at 2.00 (+/- 0.23) W m(-2), comprised of 1.81 (+/- 0.09) Wm(-2) from CO2, 1.08 (+/- 0.21) Wm(-2) from other well-mixed greenhouse gases, -1.01 (+/- 0.23) W m(-2) from aerosols and -0.09 (+/- 0.13) W m(-2) from land use change. Quoted uncertainties are 1 standard deviation across model best estimates, and 90 % confidence in the reported forcings, due to internal variability, is typically within 0.1 W m(-2). The majority of the remaining 0.21 W m(-2) is likely to be from ozone. In most cases, the largest contributors to the spread in effective radiative forcing (ERF) is from the instantaneous radiative forcing (IRF) and from cloud responses, particularly aerosol-cloud interactions to aerosol forcing. As determined in previous studies, cancellation of tropospheric and surface adjustments means that the stratospherically adjusted radiative forcing is approximately equal to ERF for greenhouse gas forcing but not for aerosols, and consequentially, not for the anthropogenic total. The spread of aerosol forcing ranges from -0.63 to -1.37 W m(-2), exhibiting a less negative mean and narrower range compared to 10 CMIP5 models. The spread in 4 x CO2 forcing has also narrowed in CMIP6 compared to 13 CMIP5 models. Aerosol forcing is uncorrelated with climate sensitivity. Therefore, there is no evidence to suggest that the increasing spread in climate sensitivity in CMIP6 models, particularly related to high-sensitivity models, is a consequence of a stronger negative present-day aerosol forcing and little evidence that modelling groups are systematically tuning climate sensitivity or aerosol forcing to recreate observed historical warming.
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| 16. |
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| 17. |
- Andersson, Evert, et al.
(författare)
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Assessment of train-overturning risk due to strong cross-winds
- 2004
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Ingår i: Proceedings of the Institution of mechanical engineers. Part F, journal of rail and rapid transit. - : SAGE Publications. - 0954-4097 .- 2041-3017. ; 218:3, s. 213-223
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes the methodology for safety assessment related to the risk of a train overturning in strong cross-winds. As an example, this methodology is applied on the high-speed line Botniabanan being built for a maximum speed of 250 km/h in the northeast coastal region of Sweden. The process starts with a systematic identification of locations along the line having a potential high risk of overturning due to cross-winds. This is followed by a cross-disciplinary study. The first step is to estimate the probabilities of wind velocity and wind directions. The next step is aerodynamic computation of overturning forces and moments acting on relevant types of train. Further, the critical overturning wind velocity is determined by a multi-body simulation technique. Finally, the overturning accident frequency is calculated. The calculated risk is compared with generally accepted risk levels in modern train operation.
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| 18. |
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| 19. |
- Diedrichs, Ben, et al.
(författare)
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Crosswind stability of high-speed train on a high embankment
- 2007
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Ingår i: Proceedings of the Institution of mechanical engineers. Part F, journal of rail and rapid transit. - 0954-4097 .- 2041-3017. ; 221:2, s. 205-225
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Tidskriftsartikel (refereegranskat)abstract
- This work presents aerodynamic results of crosswind stability obtained numerically and experimentally for the leading control unit (class 808) of Deutsche Bahn AG's high-speed train Inter-CityExpress 2. The train model is on top of a 6 m high embankment in accordance with the proposed European code for interoperable trains, the so-called technical specifications for interoperability. The purpose of the study is to convey the predictive accuracy that typical steady-state computational fluid dynamics-Reynolds average Navier-Stokes methods (industry standard) return and to contribute to the understanding of the aerodynamics for the current application. Attention is drawn to the aerodynamics around the train and embankment when subjected to a steady block profile crosswind of 30 degrees yaw angle on the basis of the onset velocity far upstream the embankment. The Re (Reynolds number) of the embankment cases is 4.6 x 10(6). Calculated results are obtained with the commercial code STAR-CD, with exclusively hexahedral meshes with a total cell count of 13.5 x 10(6). Results are obtained when the train stands on the windward and leeward tracks on top of the embankment. These results are first compared with a flat ground case from a previous study. Then experimental data are obtained in a high-pressure wind tunnel with a model scale of 1:100. Re effects are compensated by raising the ambient pressure by a factor of 60, which increases the air density and thus the Re by a similar factor. Calculated results are in fair agreement with the experiments, where both the calculations and the experiments predict the leeward case to be the more critical one. In addition, the related consequences on the mechanical behaviour, i.e. the stability of the car, are briefly addressed by means of a quasi-static mechanical analysis. The results of the present study indicate that the 6 m high embankment concerning the current train reduces the permissible crosswind speed with approximately 20 per cent.
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| 21. |
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| 22. |
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| 23. |
- Geiser, Petra, et al.
(författare)
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Salmonella enterica Serovar Typhimurium Exploits Cycling through Epithelial Cells To Colonize Human and Murine Enteroids
- 2021
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Ingår i: mBio. - : American Society for Microbiology. - 2161-2129 .- 2150-7511. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Enterobacterial pathogens infect the gut by a multistep process, resulting in colonization of both the lumen and the mucosal epithelium. Due to experimental constraints, it remains challenging to address how luminal and epithelium-lodged pathogen populations cross-feed each other in vivo. Enteroids are cultured three-dimensional miniature intestinal organs with a single layer of primary intestinal epithelial cells (IECs) surrounding a central lumen. They offer new opportunities to study enterobacterial infection under near-physiological conditions, at a temporal and spatial resolution not attainable in animal models, but remain poorly explored in this context. We employed microinjection, time-lapse microscopy, bacterial genetics, and barcoded consortium infections to describe the complete infection cycle of Salmonella enterica serovar Typhimurium in both human and murine enteroids. Flagellar motility and type III secretion system 1 (TTSS-1) promoted Salmonella Typhimurium targeting of the intraepithelial compartment and breaching of the epithelial barrier. Strikingly, however, TTSS-1 also potently boosted colonization of the enteroid lumen. By tracing the infection over time, we identified a cycle(s) of TTSS-1-driven IEC invasion, intraepithelial replication, and reemergence through infected IEC expulsion as a key mechanism for Salmonella Typhimurium luminal colonization. These findings suggest a positive feed-forward loop, through which IEC invasion by planktonic bacteria fuels further luminal population expansion, thereby ensuring efficient colonization of both the intraepithelial and luminal niches.IMPORTANCE Pathogenic gut bacteria are common causes of intestinal disease. Enteroids—cultured three-dimensional replicas of the mammalian gut—offer an emerging model system to study disease mechanisms under conditions that recapitulate key features of the intestinal tract. In this study, we describe the full life cycle of the prototype gut pathogen Salmonella enterica serovar Typhimurium within human and mouse enteroids. We map the consecutive steps and define the bacterial virulence factors that drive colonization of luminal and epithelial compartments, as well as breaching of the epithelial barrier. Strikingly, our work reveals how bacterial colonization of the epithelium potently fuels expansion also in the luminal compartment, through a mechanism involving the death and expulsion of bacterium-infected epithelial cells. These findings have repercussions for our understanding of the Salmonella infection cycle. Moreover, our work provides a comprehensive foundation for the use of microinjected enteroids to model gut bacterial diseases.
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| 25. |
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| 26. |
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| 27. |
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| 28. |
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| 29. |
- Hulten, A. H., et al.
(författare)
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First evaluation of a multicomponent flue gas cleaning concept using chlorine dioxide gas - Experiments on chemistry and process performance
- 2017
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Ingår i: Fuel. - : Elsevier BV. - 0016-2361. ; 210, s. 885-891
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Tidskriftsartikel (refereegranskat)abstract
- This work has investigated a multi-pollutant flue gas cleaning concept based on oxidation using chlorine dioxide (ClO2) gas with subsequent absorption. The chlorine dioxide gas converts the relatively insoluble nitric oxide (NO) to the more soluble nitrogen dioxide (NO2). This makes a downstream wet scrubbing process feasible for simultaneous removal of sulphur oxides (SOx) and nitrogen dioxide (NO2). An experimental evaluation of the proposed process using chlorine dioxide gas has been performed on a laboratory scale. The experimental setup, designed and built by Akzo Nobel, consists of a reactor for oxidation, a flue gas condenser and a wet scrubber. The results show that ClO2 gas oxidises NO with high efficiencies under a wide range of process conditions, also in the presence of sulphur dioxide (SO2). The more ClO2 gas is added, the higher the degree of NO oxidation and the total nitrogen oxides (NOx) removal efficiency becomes. The results also show that the presence of water strongly increases the removal of SO2, which is believed to be an effect of liquid phase nitrogen-sulphur interactions. The absorption solution, sodium carbonate and sodium sulphite, is efficient in removing NOx (especially NO2) from the oxidised flue gas. The total NOx reduction at 0.6 ClO2:NO mole ratio and subsequent wet scrubbing is between 79% and 94%, depending on the process conditions used. The total SO2 reduction in the scrubber is between 97% and 100% independent of ClO2 gas addition. Furthermore, the total NOx balance shows that the major part of the NOx is converted to nitrate in the condensate liquor and as nitrite in the absorption solution. A higher ClO2 gas addition and a higher reactor temperature convert more of the NOx to nitrite in the absorption solution.
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| 30. |
- Kumar Anand, Sumit, et al.
(författare)
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Inhibition of MAP4K4 signaling initiates metabolic reprogramming to protect hepatocytes from lipotoxic damage
- 2022
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Ingår i: Journal of Lipid Research. - : Elsevier BV. - 0022-2275. ; 63:7
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Tidskriftsartikel (refereegranskat)abstract
- The primary hepatic consequence of obesity is non-alcoholic fatty liver disease (NAFLD), affecting about 25% of the global adult population. Non-alcoholic steatohepatitis (NASH) is a severe form of NAFLD characterized by liver lipid accumulation, inflammation, and hepatocyte ballooning, with a different degree of hepatic fibrosis. In the light of rapidly increasing prevalence of NAFLD and NASH, there is an urgent need for improved understanding of the molecular pathogenesis of these diseases. The aim of this study was to decipher the possible role of STE20-type kinase MAP4K4 in the regulation of he-patocellular lipotoxicity and susceptibility to NAFLD. We found that MAP4K4 mRNA expression in human liver biopsies was positively correlated with key hallmarks of NAFLD (i.e., liver steatosis, lobular inflammation, hepatocellular ballooning, and fibrosis). We also found that the silencing of MAP4K4 suppressed lipid deposition in human he-patocytes by stimulating beta-oxidation and tri-acylglycerol secretion, while attenuating fatty acid influx and lipid synthesis. Furthermore, down -regulation of MAP4K4 markedly reduced the glycolysis rate and lowered incidences of oxidative/ endoplasmic reticulum stress. In parallel, we observed suppressed JNK and ERK and increased AKT phosphorylation in MAP4K4-deficient hep-atocytes. Together, these results provide the first experimental evidence supporting the potential involvement of STE20-type kinase MAP4K4 as a component of the hepatocellular lipotoxic milieu promoting NAFLD susceptibility.
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| 31. |
- Loni, Mohammad, et al.
(författare)
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NeuroPower : Designing Energy Efficient Convolutional Neural Network Architecture for Embedded Systems
- 2019
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Ingår i: Lecture Notes in Computer Science, Volume 11727. - Munich, Germany : Springer. - 9783030304867 ; 11727 LNCS, s. 208-222
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Konferensbidrag (refereegranskat)abstract
- Convolutional Neural Networks (CNNs) suffer from energy-hungry implementation due to their computation and memory intensive processing patterns. This problem is even more significant by the proliferation of CNNs on embedded platforms. To overcome this problem, we offer NeuroPower as an automatic framework that designs a highly optimized and energy efficient set of CNN architectures for embedded systems. NeuroPower explores and prunes the design space to find improved set of neural architectures. Toward this aim, a multi-objective optimization strategy is integrated to solve Neural Architecture Search (NAS) problem by near-optimal tuning network hyperparameters. The main objectives of the optimization algorithm are network accuracy and number of parameters in the network. The evaluation results show the effectiveness of NeuroPower on energy consumption, compacting rate and inference time compared to other cutting-edge approaches. In comparison with the best results on CIFAR-10/CIFAR-100 datasets, a generated network by NeuroPower presents up to 2.1x/1.56x compression rate, 1.59x/3.46x speedup and 1.52x/1.82x power saving while loses 2.4%/-0.6% accuracy, respectively.
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| 32. |
- Lundquist, Patrik, et al.
(författare)
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Barriers to the Intestinal Absorption of Four Insulin-Loaded Arginine-Rich Nanoparticles in Human and Rat
- 2022
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Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 16:9, s. 14210-14229
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Tidskriftsartikel (refereegranskat)abstract
- Peptide drugs and biologics provide opportunities for treatments of many diseases. However, due to their poor stability and permeability in the gastrointestinal tract, the oral bioavailability of peptide drugs is negligible. Nanoparticle formulations have been proposed to circumvent these hurdles, but systemic exposure of orally administered peptide drugs has remained elusive. In this study, we investigated the absorption mechanisms of four insulin-loaded arginine-rich nanoparticles displaying differing composition and surface characteristics, developed within the pan-European consortium TRANS-INT. The transport mechanisms and major barriers to nanoparticle permeability were investigated in freshly isolated human jejunal tissue. Cytokine release profiles and standard toxicity markers indicated that the nanoparticles were nontoxic. Three out of four nanoparticles displayed pronounced binding to the mucus layer and did not reach the epithelium. One nanoparticle composed of a mucus inert shell and cell-penetrating octarginine (ENCP), showed significant uptake by the intestinal epithelium corresponding to 28 ± 9% of the administered nanoparticle dose, as determined by super-resolution microscopy. Only a small fraction of nanoparticles taken up by epithelia went on to be transcytosed via a dynamin-dependent process. In situ studies in intact rat jejunal loops confirmed the results from human tissue regarding mucus binding, epithelial uptake, and negligible insulin bioavailability. In conclusion, while none of the four arginine-rich nanoparticles supported systemic insulin delivery, ENCP displayed a consistently high uptake along the intestinal villi. It is proposed that ENCP should be further investigated for local delivery of therapeutics to the intestinal mucosa.
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| 33. |
- Nazari, N., et al.
(författare)
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Multi-level Binarized LSTM in EEG Classification for Wearable Devices
- 2020
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Ingår i: Proceedings - 2020 28th Euromicro International Conference on Parallel, Distributed and Network-Based Processing, PDP 2020. - : Institute of Electrical and Electronics Engineers Inc.. - 9781728165820 ; , s. 175-181
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Konferensbidrag (refereegranskat)abstract
- Long Short-Term Memory (LSTM) is widely used in various sequential applications. Complex LSTMs could be hardly deployed on wearable and resourced-limited devices due to the huge amount of computations and memory requirements. Binary LSTMs are introduced to cope with this problem, however, they lead to significant accuracy loss in some applications such as EEG classification which is essential to be deployed in wearable devices. In this paper, we propose an efficient multi-level binarized LSTM which has significantly reduced computations whereas ensuring an accuracy pretty close to full precision LSTM. By deploying 5-level binarized weights and inputs, our method reduces area and delay of MAC operation about 31× and 27× in 65nm technology, respectively with less than 0.01% accuracy loss. In contrast to many compute-intensive deep-learning approaches, the proposed algorithm is lightweight, and therefore, brings performance efficiency with accurate LSTM-based EEG classification to realtime wearable devices.
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| 34. |
- Nicholls, Jordan R., et al.
(författare)
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A method for characterizing near-interface traps in SiC metal-oxide-semiconductor capacitors from conductance-temperature spectroscopy measurements
- 2021
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Ingår i: Journal of Applied Physics. - : AMER INST PHYSICS. - 0021-8979 .- 1089-7550. ; 129:5
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Tidskriftsartikel (refereegranskat)abstract
- The state-of-the-art technology for gate oxides on SiC involves the introduction of nitrogen to reduce the density of interface defects. However, SiC metal-oxide-semiconductor (MOS) field-effect transistors still suffer from low channel mobility even after the nitridation treatment. Recent reports have indicated that this is due to near-interface traps (NITs) that communicate with electrons in the SiC conduction band via tunneling. In light of this evidence, it is clear that conventional interface trap analysis is not appropriate for these defects. To address this shortcoming, we introduce a new characterization method based on conductance-temperature spectroscopy. We present simple equations to facilitate the comparison of different fabrication methods based on the density and location of NITs and give some information about their origin. These techniques can also be applied to NITs in other MOS structures.
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| 35. |
- Nicholls, Jordan R., et al.
(författare)
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Near-Interface Trap Model for the Low Temperature Conductance Signal in SiC MOS Capacitors With Nitrided Gate Oxides
- 2020
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Ingår i: IEEE Transactions on Electron Devices. - : IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. - 0018-9383 .- 1557-9646. ; 67:9, s. 3722-3728
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Tidskriftsartikel (refereegranskat)abstract
- The low channel-carrier mobility in commercial SiC MOSFETs has been attributed to fast electron traps labeled "NI." These traps exhibit anomalous behavior compared to other interface trap signals. Furthermore, the electrical parameters extracted from a conventional interface trap analysis of the NI signal are not physically reasonable. To explore the origin of these traps, we fabricated SiC MOS capacitors and measured the conductance across a range of temperatures (between 50 and 300 K). By analyzing the surface electron density at the signal peaks, it is evident that these traps are in fact near-interface traps (NITs)-they are located within the oxide and exchange electrons via a tunneling mechanism. We also developed a model for the conductance generated by NITs and demonstrated a good fit to the experimental data. The knowledge that the NI signal is due to NITs will help in directing future efforts to improve SiC MOSFET performance.
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| 36. |
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| 37. |
- Samperio Ventayol, Pilar, et al.
(författare)
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Bacterial detection by NAIP/NLRC4 elicits prompt contractions of intestinal epithelial cell layers
- 2021
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 118:16
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Tidskriftsartikel (refereegranskat)abstract
- The gut epithelium serves to maximize the surface for nutrient and fluid uptake, but at the same time must provide a tight barrier to pathogens and remove damaged intestinal epithelial cells (IECs) without jeopardizing barrier integrity. How the epithelium coordinates these tasks remains a question of significant interest. We used imaging and an optical flow analysis pipeline to study the dynamicity of untransformed murine and human intestinal epithelia, cultured atop flexible hydrogel supports. Infection with the pathogen Salmonella Typhimurium (S.Tm) within minutes elicited focal contractions with inward movements of up to similar to 1,000 IECs. Genetics approaches and chimeric epithelial monolayers revealed contractions to be triggered by the NAIP/NLRC4 inflammasome, which sensed type-III secretion system and flagellar ligands upon bacterial invasion, converting the local tissue into a contraction epicenter. Execution of the response required swift sublytic Gasdermin D pore formation, ion fluxes, and the propagation of a myosin contraction pulse across the tissue. Importantly, focal contractions preceded, and could be uncoupled from, the death and expulsion of infected IECs. In both two-dimensional monolayers and three-dimensional enteroids, multiple infection-elicited contractions coalesced to produce shrinkage of the epithelium as a whole. Monolayers deficient for Caspase-1(-11) or Gasdermin D failed to elicit focal contractions but were still capable of infected IEC death and expulsion. Strikingly, these monolayers lost their integrity to a markedly higher extent than wild-type counterparts. We propose that prompt NAIP/NLRC4/Caspase-1/Gasdermin D/myosin-dependent contractions allow the epithelium to densify its cell packing in infected regions, thereby preventing tissue disintegration due to the subsequent IEC death and expulsion process.
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| 38. |
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| 39. |
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| 40. |
- Sima, Eduardo, Ph.D. 1975-, et al.
(författare)
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Non-responders After Gastric Bypass Surgery for Morbid Obesity : Peptide Hormones and Glucose Homeostasis
- 2019
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Ingår i: Obesity Surgery. - : Springer Science and Business Media LLC. - 0960-8923 .- 1708-0428. ; 29:12, s. 4008-4017
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: About 20% of patients operated with Roux-en-Y gastric bypass (RYGBP) experience poor long-term weight result. This study compared levels of leptin and gut hormones in long-term weight responders with non-responders after RYGBP. In a subgroup analysis, hormone levels were assessed in T2DM (type 2 diabetes mellitus) and normoglycemic participants.METHODS: Insulin, glucose, leptin, acyl-ghrelin, total PYY, active GLP-1, and GIP were measured during an oral glucose tolerance test (OGTT) in post-RYGBP subjects: 22 non-responders (BMI 40.6 ± 6.0 kg/m2 after an excess BMI loss [EBMIL] of 26.0 ± 15.9%) and 18 responders (BMI 29.5 ± 3.5 kg/m2 after an EBMIL of 74.9 ± 18.2%). Subjects were matched for preoperative age, BMI, and years of follow-up. Measures of glucose homeostasis were calculated, and body composition was measured.RESULTS: Fat mass-adjusted fasting leptin correlated negatively with %EBMIL (r = - 0.57, p < 0.01). Non-responders presented higher levels of leptin during the OGTT. Leptin decreased and ghrelin returned to baseline levels earlier in non-responders. Despite having higher insulin resistance than responders, non-responders demonstrated similar OGTT responses of GLP-1, GIP, and PYY. T2DM participants demonstrated lower GLP-1 levels than normoglycemic participants of similar weight.CONCLUSION: Fasting leptin is associated with weight result after RYGBP, and hormonal responses to a glucose oral load might work towards promoting obesity in long-term non-responders after RYGBP. Poor long-term weight result and glycemic status after RYGBP are each associated with differences in peptide hormone levels.
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| 41. |
- Sinaei, Sima, et al.
(författare)
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ELC-ECG : Efficient LSTM cell for ECG classification based on quantized architecture
- 2021
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Ingår i: Proceedings - IEEE International Symposium on Circuits and Systems. - : Institute of Electrical and Electronics Engineers Inc.. - 9781728192017 ; May
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Konferensbidrag (refereegranskat)abstract
- Long Short-Term Memory (LSTM) is one of the most popular and effective Recurrent Neural Network (RNN) models used for sequence learning in applications such as ECG signal classification. Complex LSTMs could hardly be deployed on resource-limited bio-medical wearable devices due to the huge amount of computations and memory requirements. Binary LSTMs are introduced to cope with this problem. However, naive binarization leads to significant accuracy loss in ECG classification. In this paper, we propose an efficient LSTM cell along with a novel hardware architecture for ECG classification. By deploying 5-level binarized inputs and just 1-level binarization for weights, output, and in-memory cell activations, the delay of one LSTM cell operation is reduced 50x with about 0.004% accuracy loss in comparison with full precision design of ECG classification.
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| 42. |
- Sinaei, Sima, et al.
(författare)
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MuBiNN : Multi-level binarized recurrent neural network for EEG signal classification
- 2020
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Ingår i: Proceedings - IEEE International Symposium on Circuits and Systems. - : Institute of Electrical and Electronics Engineers Inc.. - 9781728133201 ; October
-
Konferensbidrag (refereegranskat)abstract
- Recurrent Neural Networks (RNN) are widely used for learning sequences in applications such as EEG classification. Complex RNNs could be hardly deployed on wearable devices due to their computation and memory-intensive processing patterns. Generally, reduction in precision leads much more efficiency and binarized RNNs are introduced as energy-efficient solutions. However, naive binarization methods lead to significant accuracy loss in EEG classification. In this paper, we propose a multi-level binarized LSTM, which significantly reduces computations whereas ensuring an accuracy pretty close to the full precision LSTM. Our method reduces the delay of the 3-bit LSTM cell operation 47× with less than 0.01% accuracy loss.
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| 43. |
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| 44. |
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| 45. |
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| 46. |
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| 47. |
- Vidarsson, Arnar M., et al.
(författare)
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Detection of near-interface traps in NO annealed 4H-SiC metal oxide semiconductor capacitors combining different electrical characterization methods
- 2022
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 131:21
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Tidskriftsartikel (refereegranskat)abstract
- Fast near-interface (NI) traps have recently been suggested to be the main cause for poor inversion channel mobility in nitrided SiC metal-oxide-semiconductor-field-effect-transistors. Combining capacitance, conductance, and thermal dielectric relaxation current (TDRC) analysis at low temperatures of nitrided SiC MOS capacitors, we observe two categories of fast and slow near-interface traps at the SiO2/4H-SiC interface. TDRC reveals a suppression of slow near-interface traps after nitridation. Capacitance and conductance analysis reveals a high density of fast NI traps close to the SiC conduction band edge that are enhanced by nitridation. The very fast response of NI traps prevents them from detection using TDRC or deep level transient spectroscopy. (C) 2022 Author(s).
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| 48. |
- Vidarsson, Arnar M., et al.
(författare)
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Improvement of channel-carrier mobility in 4H-SiC MOSFETs correlated with passivation of very fast interface traps using sodium enhanced oxidation
- 2023
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Ingår i: AIP Advances. - : AIP Publishing. - 2158-3226. ; 13:5
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Tidskriftsartikel (refereegranskat)abstract
- Very fast interface traps have recently been suggested to be the main cause behind the rather poor inversion channel mobility in nitrided SiC metal-oxide-semiconductor-field-effect-transistors (MOSFETs). Using capacitance voltage analysis and conductance spectroscopy on metal oxide semiconductor capacitors, at cryogenic temperatures, we find that these fast traps are absent in oxides made by sodium enhanced oxidation, and high inversion channel-carrier mobility in MOSFETs made by sodium enhanced oxidation is observed.
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| 49. |
- Vidarsson, Arnar M., et al.
(författare)
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Observations of very fast electron traps at SiC/high-κ dielectric interfaces
- 2023
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Ingår i: APL Materials. - : AIP Publishing. - 2166-532X. ; 11:11
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Tidskriftsartikel (refereegranskat)abstract
- Very fast interface traps have recently been suggested to be the main cause behind poor channel-carrier mobility in SiC metal-oxide-semiconductor field effect transistors. It has been hypothesized that the NI traps are defects located inside the SiO2 dielectric with energy levels close to the SiC conduction band edge and the observed conductance spectroscopy signal is a result of electron tunneling to and from these defects. Using aluminum nitride and aluminum oxide as gate dielectrics instead of SiO2, we detect NI traps at these SiC/dielectric interfaces as well. A detailed investigation of the NI trap density and behavior as a function of temperature is presented and discussed. Advanced scanning transmission electron microscopy in combination with electron energy loss spectroscopy reveals no SiO2 at the interfaces. This strongly suggests that the NI traps are related to the surface region of the SiC rather than being a property of the gate dielectric.
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| 50. |
- Vidmar, T., et al.
(författare)
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Equivalence of computer codes for calculation of coincidence summing correction factors - Part II
- 2016
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Ingår i: Applied Radiation and Isotopes. - : Elsevier BV. - 0969-8043 .- 1872-9800. ; 109, s. 482-486
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to check for equivalence of computer codes that are capable of performing calculations of true coincidence summing (TCS) correction factors. All calculations were performed for a set of well-defined detector parameters, sample parameters and decay scheme data. The studied geometry was a point source of Ba-133 positioned directly on the detector window of a low-energy (n-type) detector. Good agreement was established between the TCS correction factors computed by the different codes.
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