| 1. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 2. |
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| 3. |
- Dahl-Jensen, D., et al.
(author)
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Eemian interglacial reconstructed from a Greenland folded ice core
- 2013
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 493:7433, s. 489-494
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Journal article (peer-reviewed)abstract
- Efforts to extract a Greenland ice core with a complete record of the Eemian interglacial (130,000 to 115,000 years ago) have until now been unsuccessful. The response of the Greenland ice sheet to the warmer-than-present climate of the Eemian has thus remained unclear. Here we present the new North Greenland Eemian Ice Drilling ('NEEM') ice core and show only a modest ice-sheet response to the strong warming in the early Eemian. We reconstructed the Eemian record from folded ice using globally homogeneous parameters known from dated Greenland and Antarctic ice-core records. On the basis of water stable isotopes, NEEM surface temperatures after the onset of the Eemian (126,000 years ago) peaked at 8 +/- 4 degrees Celsius above the mean of the past millennium, followed by a gradual cooling that was probably driven by the decreasing summer insolation. Between 128,000 and 122,000 years ago, the thickness of the northwest Greenland ice sheet decreased by 400 +/- 250 metres, reaching surface elevations 122,000 years ago of 130 +/- 300 metres lower than the present. Extensive surface melt occurred at the NEEM site during the Eemian, a phenomenon witnessed when melt layers formed again at NEEM during the exceptional heat of July 2012. With additional warming, surface melt might become more common in the future.
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| 4. |
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| 5. |
- Beal, Jacob, et al.
(author)
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Robust estimation of bacterial cell count from optical density
- 2020
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Journal article (peer-reviewed)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 6. |
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| 7. |
- Jin, J.J., et al.
(author)
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Comparison of CMAM simulations of carbon monoxide (CO), nitrous oxide (N2O), and methane (CH4) with observations from Odin/SMR, ACE-FTS, and Aura/MLS
- 2009
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In: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 9, s. 3233-3252
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Journal article (peer-reviewed)abstract
- Simulations of CO, N2O and CH4 from a coupled chemistry-climate model (CMAM) are compared with satellite measurements from Odin Sub-Millimeter Radiometer (Odin/SMR), Atmospheric Chemistry Experiment Fourier Transform Spectrometer (ACE-FTS), and Aura Microwave Limb Sounder (Aura/MLS). Pressure-latitude cross-sections and seasonal time series demonstrate that CMAM reproduces the observed global CO, N2O, and CH4 distributions quite well. Generally, excellent agreement with measurements is found between CO simulations and observations in the stratosphere and mesosphere. Differences between the simulations and the ACE-FTS observations are generally within 30%, and the differences between CMAM results and SMR and MLS observations are slightly larger. These differences are comparable with the difference between the instruments in the upper stratosphere and mesosphere. Comparisons of N2O show that CMAM results are usually within 15% of the measurements in the lower and middle stratosphere, and the observations are close to each other. However, the standard version of CMAM has a low N2O bias in the upper stratosphere. The CMAM CH4 distribution also reproduces the observations in the lower stratosphere, but has a similar but smaller negative bias in the upper stratosphere. The negative bias may be due to that the gravity drag is not fully resolved in the model. The simulated polar CO evolution in the Arctic and Antarctic agrees with the ACE and MLS observations. CO measurements from 2006 show evidence of enhanced descent of air from the mesosphere into the stratosphere in the Arctic after strong stratospheric sudden warmings (SSWs). CMAM also shows strong descent of air after SSWs. In the tropics, CMAM captures the annual oscillation in the lower stratosphere and the semiannual oscillations at the stratopause and mesopause seen in Aura/MLS CO and N2O observations and in Odin/SMR N2O observations. The Odin/SMR and Aura/MLS N2O observations also show a quasi-biennial oscillation (QBO) in the upper stratosphere, whereas, the CMAM does not have QBO included. This study confirms that CMAM is able to simulate middle atmospheric transport processes reasonably well.
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| 8. |
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| 9. |
- McIntyre, S., et al.
(author)
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Global prevalence of cerebral palsy: A systematic analysis
- 2022
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In: Developmental Medicine and Child Neurology. - : Wiley. - 0012-1622 .- 1469-8749. ; 64:12, s. 1494-1506
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Journal article (peer-reviewed)abstract
- Aim To determine trends and current estimates in regional and global prevalence of cerebral palsy (CP). Method A systematic analysis of data from participating CP registers/surveillance systems and population-based prevalence studies (from birth year 1995) was performed. Quality and risk of bias were assessed for both data sources. Analyses were conducted for pre-/perinatal, postnatal, neonatal, and overall CP. For each region, trends were statistically classified as increasing, decreasing, heterogeneous, or no change, and most recent prevalence estimates with 95% confidence intervals (CI) were calculated. Meta-analyses were conducted to determine current birth prevalence estimates (from birth year 2010). Results Forty-one regions from 27 countries across five continents were represented. Pre-/perinatal birth prevalence declined significantly across Europe and Australia (11 out of 14 regions), with no change in postneonatal CP. From the limited but increasing data available from regions in low- and middle-income countries (LMICs), birth prevalence for pre-/perinatal CP was as high as 3.4 per 1000 (95% CI 3.0-3.9) live births. Following meta-analyses, birth prevalence for pre-/perinatal CP in regions from high-income countries (HICs) was 1.5 per 1000 (95% CI 1.4-1.6) live births, and 1.6 per 1000 (95% CI 1.5-1.7) live births when postneonatal CP was included. Interpretation The birth prevalence estimate of CP in HICs declined to 1.6 per 1000 live births. Data available from LMICs indicated markedly higher birth prevalence.
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| 10. |
- McLinden, C. A., et al.
(author)
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OSIRIS: A Decade of Scattered Light
- 2012
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In: Bulletin of the American Meteorological Society. - 0003-0007 .- 1520-0477. ; 93:12, s. 1845-1863
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Journal article (peer-reviewed)abstract
- Into year 11 of a 2-yr mission, OSIRIS is redefining how limb-scattered sunlight can be used to probe the atmosphere, even into the upper troposphere.
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| 11. |
- Nguyen, Patricia K., et al.
(author)
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Noninvasive assessment of coronary vasodilation using cardiovascular magnetic resonance in patients at high risk for coronary artery disease
- 2008
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In: Journal of Cardiovascular Magnetic Resonance. - 1097-6647 .- 1532-429X. ; 10
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Journal article (peer-reviewed)abstract
- Background: Impaired coronary vasodilation to both endothelial-dependent and endothelial-independent stimuli have been associated with atherosclerosis. Direct measurement of coronary vasodilation using x-ray angiography or intravascular ultrasound is invasive and, thus, not appropriate for asymptomatic patients or for serial follow-up. In this study, high-resolution coronary cardiovascular magnetic resonance (CMR) was used to investigate the vasodilatory response to nitroglycerine (NTG) of asymptomatic patients at high risk for CAD. Methods: A total of 46 asymptomatic subjects were studied: 13 high-risk patients [8 with diabetes mellitus (DM), 5 with end stage renal disease (ESRD)] and 33 age-matched controls. Long-axis and cross-sectional coronary artery images were acquired pre-and 5 minutes post-sublingual NTG using a sub-mm-resolution multi-slice spiral coronary CMR sequence. Coronary cross sectional area (CSA) was measured on pre-and post-NTG images and % coronary vasodilation was calculated. Results: Patients with DM and ESRD had impaired coronary vasodilation to NTG compared to age-matched controls (17.8 +/- 7.3% vs. 25.6 +/- 7.1%, p = 0.002). This remained significant for ESRD patients alone (14.8 +/- 7.7% vs. 25.6 +/- 7.1%, p = 0.003) and for DM patients alone (19.8 +/- 6.3% vs. 25.6 +/- 7.1%, p = 0.049), with a non-significant trend toward greater impairment in the ESRD vs. DM patients (14.8 +/- 7.7% vs. 19.8 +/- 6.3%, p = 0.23). Conclusion: Noninvasive coronary CMR demonstrates impairment of coronary vasodilation to NTG in high-risk patients with DM and ESRD. This may provide a functional indicator of subclinical atherosclerosis and warrants clinical follow up to determine prognostic significance.
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| 12. |
- Rahman, M. M., et al.
(author)
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Ambient temperature and air pollution associations with suicide and homicide mortality in California: A statewide case-crossover study
- 2023
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In: Science of the Total Environment. - : Elsevier BV. - 0048-9697. ; 874
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Journal article (peer-reviewed)abstract
- Background: Higher ambient temperature and air pollution may contribute to increased risk of behaviors harmful to oneself or to others; however, quantitative evidence is limited. We examined the relationship of deaths due to suicide and homicide with temperature and air pollution in California-a state prone to high levels of both exposures.Method: California death certificates from 2014 to 2019 were used to identify deaths due to suicide and homicide. Res-idential data for decedents were used to assign exposure to daily temperature (maximum[Tmax], minimum[Tmin]) and daily average air pollution concentrations (particulate matter <10 mu m[PM10] and < 2.5 mu m[PM2.5], nitrogen dioxide [NO2], ozone[O3]). Tmin served as a surrogate for nighttime temperature. A time-stratified case-crossover study design using conditional logistic regression was used to assess the effects of daily exposure to temperature and air pollutants on suicide and homicide mortality, adjusting for relative humidity. Effect modification by sex and age was assessed. Results: We observed 24,387 deaths due to suicide and 10,767 deaths due to homicide. We found a monotonic temper-ature association for both outcomes. A 5 degrees C increase in Tmax at lag-2 and Tmin at lag-0 was associated with 3.1 % (95 % confidence interval [CI]: 1.1 %-5.2 %) and 3.8 % (95%CI: 0.9 %-6.8 %) increased odds of death due to suicide, respec-tively. The increased odds of homicide mortality per 5 degrees C increase in Tmax at lag-0 and Tmin at lag-1 were 4.9 % (95%CI: 1.6 %-8.1 %) and 6.2 % (95%CI: 1.6 %-11.0 %), respectively. No air pollutant associations were statistically signifi-cant. Temperature associations were robust after adjustment for PM2.5. Some temperature effects were larger among women for suicide and men for homicide mortality, and among those over age 65 years for both outcomes.Conclusion: Risk of suicide and homicide mortality increases with increasing daily ambient temperatures. Findings have public health relevance given anticipated increases in temperatures due to global climate change.
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| 13. |
- Strong, K., et al.
(author)
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Validation of ACE-FTS N2O measurements
- 2008
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In: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 8, s. 4759-4786
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Journal article (peer-reviewed)abstract
- The Atmospheric Chemistry Experiment (ACE), also known as SCISAT, was launched on 12 August 2003, carrying two instruments that measure vertical profiles of atmospheric constituents using the solar occultation technique. One of these instruments, the ACE Fourier Transform Spectrometer (ACE-FTS), is measuring volume mixing ratio (VMR) profiles of nitrous oxide (N2O) from the upper troposphere to the lower mesosphere at a vertical resolution of about 3–4 km. In this study, the quality of the ACE-FTS version 2.2 N2O data is assessed through comparisons with coincident measurements made by other satellite, balloon-borne, aircraft, and ground-based instruments. These consist of vertical profile comparisons with the SMR, MLS, and MIPAS satellite instruments, multiple aircraft flights of ASUR, and single balloon flights of SPIRALE and FIRS-2, and partial column comparisons with a network of ground-based Fourier Transform InfraRed spectrometers (FTIRs). Between 6 and 30 km, the mean absolute differences for the satellite comparisons lie between −42 ppbv and +17 ppbv, with most within ±20 ppbv. This corresponds to relative deviations from the mean that are within ±15%, except for comparisons with MIPAS near 30 km, for which they are as large as 22.5%. Between 18 and 30 km, the mean absolute differences for the satellite comparisons are generally within ±10 ppbv. From 30 to 60 km, the mean absolute differences are within ±4 ppbv, and are mostly between −2 and +1 ppbv. Given the small N2O VMR in this region, the relative deviations from the mean are therefore large at these altitudes, with most suggesting a negative bias in the ACE-FTS data between 30 and 50 km. In the comparisons with the FTIRs, the mean relative differences between the ACE-FTS and FTIR partial columns (which cover a mean altitude range of 14 to 27 km) are within ±5.6% for eleven of the twelve contributing stations. This mean relative difference is negative at ten stations, suggesting a small negative bias in the ACE-FTS partial columns over the altitude regions compared. Excellent correlation (R=0.964) is observed between the ACE-FTS and FTIR partial columns, with a slope of 1.01 and an intercept of −0.20 on the line fitted to the data.
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| 14. |
- Tutt, A. N. J., et al.
(author)
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Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer
- 2021
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In: New England Journal of Medicine. - 0028-4793. ; 384:25, s. 2394-2405
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Journal article (peer-reviewed)abstract
- BACKGROUND Poly(adenosine diphosphate-ribose) polymerase inhibitors target cancers with defects in homologous recombination repair by synthetic lethality. New therapies are needed to reduce recurrence in patients with BRCA1 or BRCA2 germline mutation-associated early breast cancer. METHODS We conducted a phase 3, double-blind, randomized trial involving patients with human epidermal growth factor receptor 2 (HER2)-negative early breast cancer with BRCA1 or BRCA2 germline pathogenic or likely pathogenic variants and high-risk clinicopathological factors who had received local treatment and neoadjuvant or adjuvant chemotherapy. Patients were randomly assigned (in a 1:1 ratio) to 1 year of oral olaparib or placebo. The primary end point was invasive disease-free survival. RESULTS A total of 1836 patients underwent randomization. At a prespecified event-driven interim analysis with a median follow-up of 2.5 years, the 3-year invasive disease-free survival was 85.9% in the olaparib group and 77.1% in the placebo group (difference, 8.8 percentage points; 95% confidence interval [CI], 4.5 to 13.0; hazard ratio for invasive disease or death, 0.58; 99.5% CI, 0.41 to 0.82; P<0.001). The 3-year distant disease-free survival was 87.5% in the olaparib group and 80.4% in the placebo group (difference, 7.1 percentage points; 95% CI, 3.0 to 11.1; hazard ratio for distant disease or death, 0.57; 99.5% CI, 0.39 to 0.83; P<0.001). Olaparib was associated with fewer deaths than placebo (59 and 86, respectively) (hazard ratio, 0.68; 99% CI, 0.44 to 1.05; P=0.02); however, the between-group difference was not significant at an interim-analysis boundary of a P value of less than 0.01. Safety data were consistent with known side effects of olaparib, with no excess serious adverse events or adverse events of special interest. CONCLUSIONS Among patients with high-risk, HER2-negative early breast cancer and germline BRCA1 or BRCA2 pathogenic or likely pathogenic variants, adjuvant olaparib after completion of local treatment and neoadjuvant or adjuvant chemotherapy was associated with significantly longer survival free of invasive or distant disease than was placebo. Olaparib had limited effects on global patient-reported quality of life.
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| 15. |
- Wigforss, Eva, et al.
(author)
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Experiencing the University Context
- 2006
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In: Proceedings of the Fifth International Conference on Networked Learning 2006. - 186220182X
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Conference paper (other academic/artistic)abstract
- Our problem is how to design, with the use of distance and ICT, an appropriate academic context for learning, for students with no previous knowledge of this context. Our aim is to analyse and describe the learner’s relation to the object of his/her studies as part of his/her relation to the learning activity. By using a combination of a phenomenographic approach and activity system theory, we analyse how students experience the learning environment in the extended university. Our results are based in the learner’s perspective. A new methodological approach, using the techniques of creating an intersubjective field, is discussed at the end of the paper.
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| 16. |
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