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- 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. |
- Kitamura, Yasunori, et al.
(author)
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Calculation of the stochastic pulsed Rossi-alpha formula and its experimental verification
- 2006
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In: Progress in Nuclear Energy. - : Elsevier BV. - 0149-1970. ; 48:1, s. 37-50
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Journal article (peer-reviewed)abstract
- The Rossi-alpha formula for subcritical systems driven by a pulsed neutron source was derived with a solution technique that can effectively take different shape functions of the pulsed neutron source into account. The result of derivation showed that the present formula consists of the correlated and uncorrelated terms and an oscillating term whose period was identical to that of the pulsed neutron source.To investigate the validity of the pulsed Rossi-alpha formula and its applicability for the evaluation of the prompt neutron decay constant alpha from measurements, an experiment was performed at the Kyoto University Critical Assembly with a pulsed D-T neutron source. Although it seemed that fitting the present formula to the experimental curves was not practical because of an infinite-series expansion structure of the oscillating term, it was possible to extract only the correlated term, that explicitly includes the alpha value, by a simple data handling procedure. It was found that the measured alpha values agreed with those obtained by the pulsed neutron source method very well. This finding means that the pulsed Rossi-alpha method will be an attractive candidate for the monitoring method of the subcritical reactivity of future accelerator driven systems.
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| 3. |
- Kitamura, Yasunori, et al.
(author)
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Some properties of zero power neutron noise in a time-varying medium with delayed neutrons
- 2008
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In: Annals of Nuclear Energy. - : Elsevier BV. - 0306-4549 .- 1873-2100. ; 35:9, s. 1621-1627
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Journal article (peer-reviewed)abstract
- The temporal evolution of the distribution of the number ofneutrons in a time-varying multiplying system, producing only prompt neutrons, was treated recently with the master equation technique by some of the present authors. Such a treatment gives account of both the so-called zero power reactor noise and the power reactor noise simultaneously. In particular, the first two moments of the neutron number, as well as the concept of criticality for time-varying systems, were investigated and discussed. The present paper extends these investigations to the case when delayed neutrons are also taken into account. Due to thecomplexity of the description, only the expectation of the neutron number is calculated. The concept of criticality of a time-varying system is also generalized to systems with delayed neutrons. The temporal behaviour of the expectation of the number of neutrons and its asymptotic properties are displayed and discussed.
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| 5. |
- Neyses, Benedikt, 1986-, et al.
(author)
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Pre-treatment with sodium silicate, sodium hydroxide, ionic liquids or methacrylate resin to reduce the set-recovery and increase the hardness of surface-densified Scots pine
- 2017
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In: iForest. - : Italian Society of Silviculture and Forest Ecology. - 1971-7458. ; 10:5, s. 857-864
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Journal article (peer-reviewed)abstract
- The hardness of the outer regions of solid wood can be improved by surface densification, and this opens up new fields of application for low-density species. So far, surface densification relies on time- and energy-consuming batch processes, and this means that the potential advantages over more expensive hardwood species or non-renewable materials are reduced. Using fossil-based plastics or applying wood densification processes with a high energy consumption has adverse effects on the environment. In a previous study, it was shown that the surface of wood can be densified by a continuous high-speed process, adopting a roller pressing approach. The desired density profiles could be obtained at process speeds of up to 80 m min-1, but an equally simple and fast method to eliminate the moisture-induced set-recovery of the densified wood cells is still required. For this reason, the goal of the present study was to evaluate the effect on the set-recovery and hardness of surface-densified Scots pine after a fast pre-treatment with solutions of sodium silicate, sodium hydroxide, methacrylate resin, and ionic liquids. The Scots pine specimens were pre-treated by applying the chemical treatment and impregnation agents to the wood surface with a paper towel, before the specimens were densified. For each type of treatment, 15 specimens were densified in a hot press. The set-recovery was measured after two wet-dry cycles, and 30 Brinell hardness measurements were carried out on each group of specimens. In general, the effect of the treatments on the set-recovery was rather low. Ionic liquid solutions appear to work as a strong plasticiser and the treatment led to a reduction in set-recovery by 25%. The treatments with sodium silicate, ionic liquids and methacrylate resin led to a greater hardness than in untreated and densified specimens. Further experiments are needed to improve the depth of penetration of the treatment solutions into the wood surface, as this was identified as one of the main causes of the rather weak effects.
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| 7. |
- Stoop, Thomas F., et al.
(author)
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Pathological complete response in patients with resected pancreatic adenocarcinoma after preoperative chemotherapy
- 2024
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In: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 7:6
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Journal article (peer-reviewed)abstract
- Importance: Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small subset of patients. However, multicenter studies with in-depth data about pCR are lacking.Objective: To investigate the incidence, outcome, and risk factors of pCR after preoperative chemo(radio)therapy.Design, Setting, and Participants: This observational, international, multicenter cohort study assessed all consecutive patients with pathology-proven localized pancreatic adenocarcinoma who underwent resection after 2 or more cycles of chemotherapy (with or without radiotherapy) in 19 centers from 8 countries (January 1, 2010, to December 31, 2018). Data collection was performed from February 1, 2020, to April 30, 2022, and analyses from January 1, 2022, to December 31, 2023. Median follow-up was 19 months.Exposures: Preoperative chemotherapy (with or without radiotherapy) followed by resection.Main Outcomes and Measures: The incidence of pCR (defined as absence of vital tumor cells in the sampled pancreas specimen after resection), its association with OS from surgery, and factors associated with pCR. Factors associated with overall survival (OS) and pCR were investigated with Cox proportional hazards and logistic regression models, respectively.Results: Overall, 1758 patients (mean [SD] age, 64 [9] years; 879 [50.0%] male) were studied. The rate of pCR was 4.8% (n = 85), and pCR was associated with OS (hazard ratio, 0.46; 95% CI, 0.26-0.83). The 1-, 3-, and 5-year OS rates were 95%, 82%, and 63% in patients with pCR vs 80%, 46%, and 30% in patients without pCR, respectively (P < .001). Factors associated with pCR included preoperative multiagent chemotherapy other than (m)FOLFIRINOX ([modified] leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) (odds ratio [OR], 0.48; 95% CI, 0.26-0.87), preoperative conventional radiotherapy (OR, 2.03; 95% CI, 1.00-4.10), preoperative stereotactic body radiotherapy (OR, 8.91; 95% CI, 4.17-19.05), radiologic response (OR, 13.00; 95% CI, 7.02-24.08), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76; 95% CI, 1.79-7.89).Conclusions and Relevance: This international, retrospective cohort study found that pCR occurred in 4.8% of patients with resected localized pancreatic adenocarcinoma after preoperative chemo(radio)therapy. Although pCR does not reflect cure, it is associated with improved OS, with a doubled 5-year OS of 63% compared with 30% in patients without pCR. Factors associated with pCR related to preoperative chemo(radio)therapy regimens and anatomical and biological disease response features may have implications for treatment strategies that require validation in prospective studies because they may not universally apply to all patients with pancreatic adenocarcinoma.
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