| 1. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
Forskningsöversikt (refereegranskat)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.
|
|
| 2. |
- Abbasi, R., et al.
(författare)
-
IceTop : The surface component of IceCube
- 2013
-
Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 700, s. 188-220
-
Tidskriftsartikel (refereegranskat)abstract
- IceTop, the surface component of the IceCube Neutrino Observatory at the South Pole, is an air shower array with an area of 1 km(2). The detector allows a detailed exploration of the mass composition of primary cosmic rays in the energy range from about 100 TeV to 1 EeV by exploiting the correlation between the shower energy measured in IceTop and the energy deposited by muons in the deep ice. In this paper we report on the technical design, construction and installation, the trigger and data acquisition systems as well as the software framework for calibration, reconstruction and simulation. Finally the first experience from commissioning and operating the detector and the performance as an air shower detector will be discussed.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Fowkes, F. G. R., et al.
(författare)
-
Development and validation of an ankle brachial index risk model for the prediction of cardiovascular events
- 2014
-
Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4881 .- 2047-4873. ; 21:3, s. 310-320
-
Tidskriftsartikel (refereegranskat)abstract
- Background The ankle brachial index (ABI) is related to risk of cardiovascular events independent of the Framingham risk score (FRS). The aim of this study was to develop and evaluate a risk model for cardiovascular events incorporating the ABI and FRS. Design An analysis of participant data from 18 cohorts in which 24,375 men and 20,377 women free of coronary heart disease had ABI measured and were followed up for events. Methods Subjects were divided into a development and internal validation dataset and an external validation dataset. Two models, comprising FRS and FRS + ABI, were fitted for the primary outcome of major coronary events. Results In predicting events in the external validation dataset, C-index for the FRS was 0.672 (95% CI 0.599 to 0.737) in men and 0.578 (95% CI 0.492 to 0.661) in women. The FRS + ABI led to a small increase in C-index in men to 0.685 (95% CI 0.612 to 0.749) and large increase in women to 0.690 (95% CI 0.605 to 0.764) with net reclassification improvement (NRI) of 4.3% (95% CI 0.0 to 7.6%, p = 0.050) and 9.6% (95% CI 6.1 to 16.4%, p < 0.001), respectively. Restricting the FRS + ABI model to those with FRS intermediate 10-year risk of 10 to 19% resulted in higher NRI of 15.9% (95% CI 6.1 to 20.6%, p < 0.001) in men and 23.3% (95% CI 13.8 to 62.5%, p = 0.002) in women. However, incorporating ABI in an improved newly fitted risk factor model had a nonsignificant effect: NRI 2.0% (95% CI 2.3 to 4.2%, p = 0.567) in men and 1.1% (95% CI 1.9 to 4.0%, p = 0.483) in women. Conclusions An ABI risk model may improve prediction especially in individuals at intermediate risk and when performance of the base risk factor model is modest.
|
|
| 8. |
- Bayley, PJ, et al.
(författare)
-
2013 SYR Accepted Poster Abstracts
- 2013
-
Ingår i: International journal of yoga therapy. - 1531-2054. ; 23:1, s. 32-53
-
Tidskriftsartikel (refereegranskat)
|
|
| 9. |
|
|
| 10. |
- Alexandrov, Ludmil B., et al.
(författare)
-
Signatures of mutational processes in human cancer
- 2013
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 500:7463, s. 415-421
-
Tidskriftsartikel (refereegranskat)abstract
- All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy.
|
|
| 11. |
- Beurskens, M. N. A., et al.
(författare)
-
The effect of a metal wall on confinement in JET and ASDEX Upgrade
- 2013
-
Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 0741-3335 .- 1361-6587. ; 55:12, s. 124043-
-
Tidskriftsartikel (refereegranskat)abstract
- In both JET and ASDEX Upgrade (AUG) the plasma energy confinement has been affected by the presence of a metal wall by the requirement of increased gas fuelling to avoid tungsten pollution of the plasma. In JET with a beryllium/tungsten wall the high triangularity baseline H-mode scenario (i.e. similar to the ITER reference scenario) has been the strongest affected and the benefit of high shaping to give good normalized confinement of H-98 similar to 1 at high Greenwald density fraction of f(GW) similar to 0.8 has not been recovered to date. In AUG with a full tungsten wall, a good normalized confinement H-98 similar to 1 could be achieved in the high triangularity baseline plasmas, albeit at elevated normalized pressure beta(N) > 2. The confinement lost with respect to the carbon devices can be largely recovered by the seeding of nitrogen in both JET and AUG. This suggests that the absence of carbon in JET and AUG with a metal wall may have affected the achievable confinement. Three mechanisms have been tested that could explain the effect of carbon or nitrogen (and the absence thereof) on the plasma confinement. First it has been seen in experiments and by means of nonlinear gyrokinetic simulations (with the GENE code), that nitrogen seeding does not significantly change the core temperature profile peaking and does not affect the critical ion temperature gradient. Secondly, the dilution of the edge ion density by the injection of nitrogen is not sufficient to explain the plasma temperature and pressure rise. For this latter mechanism to explain the confinement improvement with nitrogen seeding, strongly hollow Z(eff) profiles would be required which is not supported by experimental observations. The confinement improvement with nitrogen seeding cannot be explained with these two mechanisms. Thirdly, detailed pedestal structure analysis in JET high triangularity baseline plasmas have shown that the fuelling of either deuterium or nitrogen widens the pressure pedestal. However, in JET-ILW this only leads to a confinement benefit in the case of nitrogen seeding where, as the pedestal widens, the obtained pedestal pressure gradient is conserved. In the case of deuterium fuelling in JET-ILW the pressure gradient is strongly degraded in the fuelling scan leading to no net confinement gain due to the pedestal widening. The pedestal code EPED correctly predicts the pedestal pressure of the unseeded plasmas in JET-ILW within +/- 5%, however it does not capture the complex variation of pedestal width and gradient with fuelling and impurity seeding. Also it does not predict the observed increase of pedestal pressure by nitrogen seeding in JET-ILW. Ideal peeling ballooning MHD stability analysis shows that the widening of the pedestal leads to a down shift of the marginal stability boundary by only 10-20%. However, the variations in the pressure gradient observed in the JET-ILW fuelling experiment is much larger and spans a factor of more than two. As a result the experimental points move from deeply unstable to deeply stable on the stability diagram in a deuterium fuelling scan. In AUG-W nitrogen seeded plasmas, a widening of the pedestal has also been observed, consistent with the JET observations. The absence of carbon can thus affect the pedestal structure, and mainly the achieved pedestal gradient, which can be recovered by seeding nitrogen. The underlying physics mechanism is still under investigation and requires further understanding of the role of impurities on the pedestal stability and pedestal structure formation.
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
- Kellokumpu-Lehtinen, PLI, et al.
(författare)
-
Triweekly docetaxel versus biweekly docetaxel as a treatment for advanced castration resistant prostate cancer: Quality of life analysis
- 2014
-
Ingår i: JOURNAL OF CLINICAL ONCOLOGY. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 32:4
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- 23 Background: Bi-weekly docetaxel (T) with prednisone improved progression free survival and overall survival when compared with the standard tri-weekly T as first-line treatment for advanced castration resistant prostate cancer (CRPC) (Lancet Oncol. 2013;14:117-124). We report here the quality of life (QoL) results of this prospective randomized trial. Methods: Three hundred and forty-six patients were randomly allocated centrally to receive intravenous therapy T of either 75 mg/m² d1 q3 wks (the triweekly arm) or 50 mg/m² d1 and d 14, q4 wks (the biweekly arm) (identifier NCT00255606). Prednisone (10 mg/d) was administered orally in both groups. The baseline patients characteristics were well balanced between the groups with respect to the performance status, mean age (69, range 45 to 87 vs. 68, range 46 to 85), and median serum prostate-specific antigen (PSA) content (109 µg/L, range 11 to 1,230 vs. 116 µg/L, range 12 to 1,870). Quality of life (QoL), the frequency and severity of symptoms including pain were assessed using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) version 4.0 questionnaire. Results: The baseline (QoL) of both treatment groups was compared to QoL after six months of the treatment within each treatment group and between groups. Changes in fatigue, symptoms of pain and nausea, and the overall performance status did not differ between the groups. There were statistically significant differences in overall quality of life values (p=0.010) and discomforting pain values (p=0.028) favoring the bi-weekly treatment arm. Conclusions: Bi-weekly T is better tolerated than the tri-weekly standard T. Following the results from the clinical outcome and the QoL outcome in the PROSTY trial we would recommend the use of bi-weekly docetaxel as first line treatment of CRPC Clinical trial information: NCT00255606.
|
|
