| 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. |
- Yu, G., et al.
(author)
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Structures, electronic states, photoluminescence, and carrier transport properties of 1,1-disubstituted 2,3,4,5-tetraphenylsiloles
- 2005
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In: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 127:17, s. 6335-6346
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Research review (peer-reviewed)abstract
- The excellent electroluminescent (EL) properties of 1,1-disubstituted 2,3,4,5-tetraphenylsiloles, 1-methyl-1,2,3,4,5-pentaphenylsilole (MPPS), and 1,1,2,3,4,5-hexaphenylsilole (HPS) have been found. Despite some studies devoted to these materials, very little is known about the real origin of their unique EL properties. Therefore, we investigated the structures, photoluminescence (PL), and charge carrier transport properties of 1,1-disubstituted 2,3,4,5-tetraphenylsiloles as well as the effect of substituents on these characteristics. The single crystals of the three siloles involving 1,1-dimethyl-2,3,4,5-tetraphenylsilole (DMTPS), MPPS, and HIPS were grown and their crystal structures were determined by X-ray diffraction. Three siloles have nonplanar molecular structures. The substituents at 1,1-positions enhance the steric hindrance and have predominant influence on the twisted degree of phenyl groups at ring carbons. This nonplanar structure reduces the intermolecular interaction and the likelihood of excimer formation, and increases PL efficiency in the solid state. The silole films show high fluorescence quantum yields (75-85%), whereas their dilute solutions exhibit a faint emission. The electronic structures of the three siloles were investigated using quantum chemical calculations. The highest occupied molecular orbitals (HOMOs) and the lowest unoccupied molecular orbitals (LUMOs) are mainly localized on the silole ring and two phenyl groups at 2,5-positions in all cases, while the LUMOs have a significant orbital density at two exocyclic Si-C bonds. The extremely theoretical studies of luminescent properties were carried out. We calculated the nonradiative decay rate of the first excited state as well as the radiative one. It is found that the faint emission of DMTPS in solutions mainly results from the huge nonradiative decay rate. In solid states, molecular packing can remarkably restrict the intramolecular rotation of the peripheral side phenyl ring, which has a large contribution to the nonradiative transition process. This explains why the 1,1-disubstituted 2,3,4,5-tetraphenylsiloles in the thin films exhibit high fluorescence quantum yields. The charge carrier mobilities of the MPPS and HPS films were measured using a transient EL technique. We obtained a mobility of 2.1 x 10(-6) cm(2)/V(.)s in the MPPS film at an electric field of 1.2 x 10(6) V/cm. This mobility is comparable to that of Alq(3), which is one of the most extensively used electron transport materials in organic light-emitting diodes (LEDs), at the same electric field. The electron mobility of the HPS film is about similar to 1.5 times higher than that of the MPPS film. To the best of our knowledge, this kind of material is one of the most excellent emissive materials that possess both high charge carrier mobility and high PL efficiency in the solid states simultaneously. The excellent EL performances of MPPS and HPS are presumably ascribed to these characteristics.
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| 3. |
- Álvarez-Muñiz, Jaime, et al.
(author)
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The Giant Radio Array for Neutrino Detection (GRAND) : Science and design
- 2020
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In: Science China Physics, Mechanics & Astronomy. - : Springer Science and Business Media LLC. - 1674-7348 .- 1869-1927. ; 63:1
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Research review (peer-reviewed)abstract
- The Giant Radio Array for Neutrino Detection (GRAND) is a planned large-scale observatory of ultra-high-energy (UHE) cosmic particles, with energies exceeding 108 GeV. Its goal is to solve the long-standing mystery of the origin of UHE cosmic rays. To do this, GRAND will detect an unprecedented number of UHE cosmic rays and search for the undiscovered UHE neutrinos and gamma rays associated to them with unmatched sensitivity. GRAND will use large arrays of antennas to detect the radio emission coming from extensive air showers initiated by UHE particles in the atmosphere. Its design is modular: 20 separate, independent sub-arrays, each of 10000 radio antennas deployed over 10000 km(2). A staged construction plan will validate key detection techniques while achieving important science goals early. Here we present the science goals, detection strategy, preliminary design, performance goals, and construction plans for GRAND.
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| 4. |
- Jakosky, B. M., et al.
(author)
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The Mars Atmosphere and Volatile Evolution (MAVEN) Mission
- 2015
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In: Space Science Reviews. - : Springer Science and Business Media LLC. - 0038-6308 .- 1572-9672. ; 195:1-4, s. 3-48
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Research review (peer-reviewed)abstract
- The MAVEN spacecraft launched in November 2013, arrived at Mars in September 2014, and completed commissioning and began its one-Earth-year primary science mission in November 2014. The orbiter's science objectives are to explore the interactions of the Sun and the solar wind with the Mars magnetosphere and upper atmosphere, to determine the structure of the upper atmosphere and ionosphere and the processes controlling it, to determine the escape rates from the upper atmosphere to space at the present epoch, and to measure properties that allow us to extrapolate these escape rates into the past to determine the total loss of atmospheric gas to space through time. These results will allow us to determine the importance of loss to space in changing the Mars climate and atmosphere through time, thereby providing important boundary conditions on the history of the habitability of Mars. The MAVEN spacecraft contains eight science instruments (with nine sensors) that measure the energy and particle input from the Sun into the Mars upper atmosphere, the response of the upper atmosphere to that input, and the resulting escape of gas to space. In addition, it contains an Electra relay that will allow it to relay commands and data between spacecraft on the surface and Earth.
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| 5. |
- Karyotaki, Eirini, et al.
(author)
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Internet-Based Cognitive Behavioral Therapy for Depression : A Systematic Review and Individual Patient Data Network Meta-analysis
- 2021
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In: JAMA psychiatry. - : American Medical Association. - 2168-6238 .- 2168-622X. ; 78:4, s. 361-371
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Research review (peer-reviewed)abstract
- IMPORTANCE: Personalized treatment choices would increase the effectiveness of internet-based cognitive behavioral therapy (iCBT) for depression to the extent that patients differ in interventions that better suit them.OBJECTIVE: To provide personalized estimates of short-term and long-term relative efficacy of guided and unguided iCBT for depression using patient-level information.DATA SOURCES: We searched PubMed, Embase, PsycInfo, and Cochrane Library to identify randomized clinical trials (RCTs) published up to January 1, 2019.STUDY SELECTION: Eligible RCTs were those comparing guided or unguided iCBT against each other or against any control intervention in individuals with depression. Available individual patient data (IPD) was collected from all eligible studies. Depression symptom severity was assessed after treatment, 6 months, and 12 months after randomization.DATA EXTRACTION AND SYNTHESIS: We conducted a systematic review and IPD network meta-analysis and estimated relative treatment effect sizes across different patient characteristics through IPD network meta-regression.MAIN OUTCOMES AND MEASURES: Patient Health Questionnaire-9 (PHQ-9) scores.RESULTS: Of 42 eligible RCTs, 39 studies comprising 9751 participants with depression contributed IPD to the IPD network meta-analysis, of which 8107 IPD were synthesized. Overall, both guided and unguided iCBT were associated with more effectiveness as measured by PHQ-9 scores than control treatments over the short term and the long term. Guided iCBT was associated with more effectiveness than unguided iCBT (mean difference [MD] in posttreatment PHQ-9 scores, -0.8; 95% CI, -1.4 to -0.2), but we found no evidence of a difference at 6 or 12 months following randomization. Baseline depression was found to be the most important modifier of the relative association for efficacy of guided vs unguided iCBT. Differences between unguided and guided iCBT in people with baseline symptoms of subthreshold depression (PHQ-9 scores 5-9) were small, while guided iCBT was associated with overall better outcomes in patients with baseline PHQ-9 greater than 9.CONCLUSIONS AND RELEVANCE: In this network meta-analysis with IPD, guided iCBT was associated with more effectiveness than unguided iCBT for individuals with depression, benefits were more substantial in individuals with moderate to severe depression. Unguided iCBT was associated with similar effectiveness among individuals with symptoms of mild/subthreshold depression. Personalized treatment selection is entirely possible and necessary to ensure the best allocation of treatment resources for depression.
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| 6. |
- Micah, Angela E., et al.
(author)
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Tracking development assistance for health and for COVID-19 : a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050
- 2021
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In: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 398:10308, s. 1317-1343
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Research review (peer-reviewed)abstract
- Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached $8. 8 trillion (95% uncertainty interval [UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, $40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this, $13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and $1.4 billion was repurposed from existing health projects. $3.1 billion (22.4%) of the funds focused on country-level coordination and $2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34.3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to $1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
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