| 1. |
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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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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.
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| 3. |
- Maes, S.L., et al.
(författare)
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Environmental drivers of increased ecosystem respiration in a warming tundra
- 2024
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 629:8010, s. 105-113
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Tidskriftsartikel (refereegranskat)abstract
- Arctic and alpine tundra ecosystems are large reservoirs of organic carbon. Climate warming may stimulate ecosystem respiration and release carbon into the atmosphere. The magnitude and persistency of this stimulation and the environmental mechanisms that drive its variation remain uncertain. This hampers the accuracy of global land carbon–climate feedback projections. Here we synthesize 136 datasets from 56 open-top chamber in situ warming experiments located at 28 arctic and alpine tundra sites which have been running for less than 1 year up to 25 years. We show that a mean rise of 1.4 °C [confidence interval (CI) 0.9–2.0 °C] in air and 0.4 °C [CI 0.2–0.7 °C] in soil temperature results in an increase in growing season ecosystem respiration by 30% [CI 22–38%] (n = 136). Our findings indicate that the stimulation of ecosystem respiration was due to increases in both plant-related and microbial respiration (n = 9) and continued for at least 25 years (n = 136). The magnitude of the warming effects on respiration was driven by variation in warming-induced changes in local soil conditions, that is, changes in total nitrogen concentration and pH and by context-dependent spatial variation in these conditions, in particular total nitrogen concentration and the carbon:nitrogen ratio. Tundra sites with stronger nitrogen limitations and sites in which warming had stimulated plant and microbial nutrient turnover seemed particularly sensitive in their respiration response to warming. The results highlight the importance of local soil conditions and warming-induced changes therein for future climatic impacts on respiration.
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| 4. |
- Liu, DJ, et al.
(författare)
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Schizophrenia risk conferred by rare protein-truncating variants is conserved across diverse human populations
- 2023
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 55:3, s. 369-
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia (SCZ) is a chronic mental illness and among the most debilitating conditions encountered in medical practice. A recent landmark SCZ study of the protein-coding regions of the genome identified a causal role for ten genes and a concentration of rare variant signals in evolutionarily constrained genes1. This recent study—and most other large-scale human genetics studies—was mainly composed of individuals of European (EUR) ancestry, and the generalizability of the findings in non-EUR populations remains unclear. To address this gap, we designed a custom sequencing panel of 161 genes selected based on the current knowledge of SCZ genetics and sequenced a new cohort of 11,580 SCZ cases and 10,555 controls of diverse ancestries. Replicating earlier work, we found that cases carried a significantly higher burden of rare protein-truncating variants (PTVs) among evolutionarily constrained genes (odds ratio = 1.48; P = 5.4 × 10−6). In meta-analyses with existing datasets totaling up to 35,828 cases and 107,877 controls, this excess burden was largely consistent across five ancestral populations. Two genes (SRRM2 and AKAP11) were newly implicated as SCZ risk genes, and one gene (PCLO) was identified as shared by individuals with SCZ and those with autism. Overall, our results lend robust support to the rare allelic spectrum of the genetic architecture of SCZ being conserved across diverse human populations.
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| 5. |
- Jacobsson, Jesper, 1984-, et al.
(författare)
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An open-access database and analysis tool for perovskite solar cells based on the FAIR data principles
- 2022
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Ingår i: Nature Energy. - : Springer Nature. - 2058-7546. ; 7:1, s. 107-115
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Tidskriftsartikel (refereegranskat)abstract
- Large datasets are now ubiquitous as technology enables higher-throughput experiments, but rarely can a research field truly benefit from the research data generated due to inconsistent formatting, undocumented storage or improper dissemination. Here we extract all the meaningful device data from peer-reviewed papers on metal-halide perovskite solar cells published so far and make them available in a database. We collect data from over 42,400 photovoltaic devices with up to 100 parameters per device. We then develop open-source and accessible procedures to analyse the data, providing examples of insights that can be gleaned from the analysis of a large dataset. The database, graphics and analysis tools are made available to the community and will continue to evolve as an open-source initiative. This approach of extensively capturing the progress of an entire field, including sorting, interactive exploration and graphical representation of the data, will be applicable to many fields in materials science, engineering and biosciences.
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| 6. |
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| 7. |
- Chatzikonstantinou, T, et al.
(författare)
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COVID-19 severity and mortality in patients with CLL: an update of the international ERIC and Campus CLL study
- 2021
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 3635:312, s. 3444-3454
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Tidskriftsartikel (refereegranskat)abstract
- Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p < 0.001). Untreated patients had a lower risk of death (HR = 0.54, 95% CI:0.41–0.72). The risk of death was higher for older patients and those suffering from cardiac failure (HR = 1.03, 95% CI:1.02–1.04; HR = 1.79, 95% CI:1.04–3.07, respectively). Age, CLL-directed treatment, and cardiac failure were significant risk factors of OS. Untreated patients had a better chance of survival than those on treatment or recently treated.
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| 8. |
- Munir, S., et al.
(författare)
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The Association of HLA Alleles and Haplotypes with Age of Disease Onset in Pakistani Psoriatic Patients
- 2023
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Ingår i: International Archives of Allergy and Immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 184:2, s. 202-210
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The human leukocyte antigen (HLA) region on chromosome 6p21 is well known to carry the most important genetic factors in susceptibility to psoriasis. Different HLA alleles and haplotypes have been reported to be associated with psoriasis in different populations. Psoriasis has a variable age of onset and, based on this, it can be classified into two types; type I with age of onset before 40 years of age and type II with age of onset after 40 years of age. The objective of this study was to determine the association of HLA class I and class II alleles and haplotypes with disease and stratification using age of onset in Pakistani psoriatic patients. Methods: A group of 603 individuals (326 cases and 277 controls) were analyzed for HLA class I and II alleles and haplotype association by sequence specific PCR. The association was further analyzed according to the age of onset of the patients. Results: We found that HLA alleles B*57 and Cw*06:02, DQB1*03:03:02 are strongly associated with early onset psoriasis, while alleles B*15, DRB1*13:02 and DQB1*03:03:02 are associated with late-onset psoriasis. Cw*06:02 allele was not associated with late-onset psoriasis patients. Allele DQB1*03:03:02 had the highest odds ratio in all patients. We found a novel association specifically with late-onset psoriasis samples with the haplotype HLA-A*11; B*15; Cw*04; DRB1*15; DQB1*05 (Pc = 3.60 x 10(-7)). We also found strong association with previously reported extended haplotype EH-57.1: HLA-B*57; Cw*06:02; DRB1*07:01; DQB1*03:03:02 in all our patients (Pc = 8.34 x 10(-07)). Conclusion: Our results show that different HLA class I and II alleles and haplotypes are associated with psoriasis at different age of onset. In this study, we have reported novel alleles and haplotype association with late-onset psoriasis. Our data confirm the previous strong associations with HLA alleles and haplotypes and also reports novel alleles and haplotype association in Pakistani psoriasis patients.
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| 9. |
- Abedin, Sarder, et al.
(författare)
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Data Freshness and Energy-Efficient UAV Navigation Optimization : A Deep Reinforcement Learning Approach
- 2021
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Ingår i: IEEE transactions on intelligent transportation systems (Print). - 1524-9050 .- 1558-0016. ; 22:9, s. 5994-6006
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we design a navigation policy for multiple unmanned aerial vehicles (UAVs) where mobile base stations (BSs) are deployed to improve the data freshness and connectivity to the Internet of Things (IoT) devices. First, we formulate an energy-efficient trajectory optimization problem in which the objective is to maximize the energy efficiency by optimizing the UAV-BS trajectory policy. We also incorporate different contextual information such as energy and age of information (AoI) constraints to ensure the data freshness at the ground BS. Second, we propose an agile deep reinforcement learning with experience replay model to solve the formulated problem concerning the contextual constraints for the UAV-BS navigation. Moreover, the proposed approach is well-suited for solving the problem, since the state space of the problem is extremely large and finding the best trajectory policy with useful contextual features is too complex for the UAV-BSs. By applying the proposed trained model, an effective real-time trajectory policy for the UAV-BSs captures the observable network states over time. Finally, the simulation results illustrate the proposed approach is 3.6 % and 3.13 % more energy efficient than those of the greedy and baseline deep Q Network (DQN) approaches.
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| 10. |
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| 11. |
- Main, Chris J., et al.
(författare)
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Implementation Science and Employer Disability Practices : Embedding Implementation Factors in Research Designs
- 2016
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Ingår i: Journal of occupational rehabilitation. - : Springer-Verlag New York. - 1053-0487 .- 1573-3688. ; 26:4, s. 448-464
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: For work disability research to have an impact on employer policies and practices it is important for such research to acknowledge and incorporate relevant aspects of the workplace. The goal of this article is to summarize recent theoretical and methodological advances in the field of Implementation Science, relate these to research of employer disability management practices, and recommend future research priorities.Methods: The authors participated in a year-long collaboration culminating in an invited 3-day conference, “Improving Research of Employer Practices to Prevent Disability”, held October 14–16, 2015, in Hopkinton, MA, USA. The collaboration included a topical review of the literature, group conference calls to identify key areas and challenges, drafting of initial documents, review of industry publications, and a conference presentation that included feedback from peer researchers and a question/answer session with a special panel of knowledge experts with direct employer experience.Results: A 4-phase implementation model including both outer and inner contexts was adopted as the most appropriate conceptual framework, and aligned well with the set of process evaluation factors described in both the work disability prevention literature and the grey literature. Innovative interventions involving disability risk screening and psychologically-based interventions have been slow to gain traction among employers and insurers. Research recommendations to address this are : (1) to assess organizational culture and readiness for change in addition to individual factors; (2) to conduct process evaluations alongside controlled trials; (3) to analyze decision-making factors among stakeholders; and (4) to solicit input from employers and insurers during early phases of study design.Conclusions: Future research interventions involving workplace support and involvement to prevent disability may be more feasible for implementation if organizational decision-making factors are imbedded in research designs and interventions are developed to take account of these influences.
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| 12. |
- Munir, M. S., et al.
(författare)
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Risk-Aware Energy Scheduling for Edge Computing with Microgrid : A Multi-Agent Deep Reinforcement Learning Approach
- 2021
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Ingår i: IEEE Transactions on Network and Service Management. - 1932-4537. ; 18:3, s. 3476-3497
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Tidskriftsartikel (refereegranskat)abstract
- In recent years, multi-access edge computing (MEC) is a key enabler for handling the massive expansion of Internet of Things (IoT) applications and services. However, energy consumption of a MEC network depends on volatile tasks that induces risk for energy demand estimations. As an energy supplier, a microgrid can facilitate seamless energy supply. However, the risk associated with energy supply is also increased due to unpredictable energy generation from renewable and non-renewable sources. Especially, the risk of energy shortfall is involved with uncertainties in both energy consumption and generation. In this paper, we study a risk-aware energy scheduling problem for a microgrid-powered MEC network. First, we formulate an optimization problem considering the conditional value-at-risk (CVaR) measurement for both energy consumption and generation, where the objective is to minimize the expected residual of scheduled energy for the MEC networks and we show this problem is an NP-hard problem. Second, we analyze our formulated problem using a multi-agent stochastic game that ensures the joint policy Nash equilibrium, and show the convergence of the proposed model. Third, we derive the solution by applying a multi-agent deep reinforcement learning (MADRL)-based asynchronous advantage actor-critic (A3C) algorithm with shared neural networks. This method mitigates the curse of dimensionality of the state space and chooses the best policy among the agents for the proposed problem. Finally, the experimental results establish a significant performance gain by considering CVaR for high accuracy energy scheduling of the proposed model than both the single and random agent models.
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| 13. |
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| 14. |
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| 15. |
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| 16. |
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| 17. |
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| 18. |
- Bairagi, Anupam Kumar, et al.
(författare)
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Controlling the Outbreak of COVID-19 : A Noncooperative Game Perspective
- 2020
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Ingår i: IEEE Access. - 2169-3536. ; 8, s. 215570-215581
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Tidskriftsartikel (refereegranskat)abstract
- COVID-19 is a global epidemic. Till now, there is no remedy for this epidemic. However, isolation and social distancing are seemed to be effective preventive measures to control this pandemic. Therefore, in this article, an optimization problem is formulated that accommodates both isolation and social distancing features of the individuals. To promote social distancing, we solve the formulated problem by applying a noncooperative game that can provide an incentive for maintaining social distancing to prevent the spread of COVID-19. Furthermore, the sustainability of the lockdown policy is interpreted with the help of our proposed game-theoretic incentive model for maintaining social distancing where there exists a Nash equilibrium. Finally, we perform an extensive numerical analysis that shows the effectiveness of the proposed approach in terms of achieving the desired social-distancing to prevent the outbreak of the COVID-19 in a noncooperative environment. Numerical results show that the individual incentive increases more than 85% with an increasing percentage of home isolation from 25% to 100% for all considered scenarios. The numerical results also demonstrate that in a particular percentage of home isolation, the individual incentive decreases with an increasing number of individuals.
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| 19. |
- Cirulli, Elizabeth T., et al.
(författare)
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A Missense Variant in PTPN22 is a Risk Factor for Drug-induced Liver Injury
- 2019
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Ingår i: Gastroenterology. - : W B SAUNDERS CO-ELSEVIER INC. - 0016-5085 .- 1528-0012. ; 156:6, s. 1707-1716
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: We performed genetic analyses of a multiethnic cohort of patients with idiosyncratic drug-induced liver injury (DILI) to identify variants associated with susceptibility.METHODS: We performed a genome-wide association study of 2048 individuals with DILI (cases) and 12,429 individuals without (controls). Our analysis included subjects of European (1806 cases and 10,397 controls), African American (133 cases and 1,314 controls), and Hispanic (109 cases and 718 controls) ancestry. We analyzed DNA from 113 Icelandic cases and 239,304 controls to validate our findings.RESULTS: We associated idiosyncratic DILI with rs2476601, a nonsynonymous polymorphism that encodes a substitution of tryptophan with arginine in the protein tyrosine phosphatase, nonreceptor type 22 gene (PTPN22) (odds ratio [OR] 1.44; 95% confidence interval [CI] 1.28-1.62; P = 1.2 x 10(-9) and replicated the finding in the validation set (OR 1.48; 95% CI 1.09-1.99; P =.01). The minor allele frequency showed the same effect size (OR > 1) among ethnic groups. The strongest association was with amoxicillin and clavulanate-associated DILI in persons of European ancestry (OR 1.62; 95% CI 1.32-1.98; P = 4.0 x 10(-6); allele frequency = 13.3%), but the polymorphism was associated with DILI of other causes (OR 1.37; 95% CI 1.21-1.56; P = 1.5 x 10(-6); allele frequency = 11.5%). Among amoxicillin-and clavulanate-associated cases of European ancestry, rs2476601 doubled the risk for DILI among those with the HLA risk alleles A* 02: 01 and DRB1* 15: 01.CONCLUSIONS: In a genome-wide association study, we identified rs2476601 in PTPN22 as a non-HLA variant that associates with risk of liver injury caused by multiple drugs and validated our finding in a separate cohort. This variant has been associated with increased risk of autoimmune diseases, providing support for the concept that alterations in immune regulation contribute to idiosyncratic DILI.
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| 20. |
- Dubaric, Ervin, et al.
(författare)
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Monte Carlo simulations of the imaging properties of scintillator coated X-ray pixel detectors
- 2000
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Ingår i: IEEE Nuclear Science Symposium and Medical Imaging Conference. - : IEEE conference proceedings. - 0780365038 ; , s. 6/282-6/285
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Konferensbidrag (refereegranskat)abstract
- The imaging properties of X-ray pixel detectors depend on the quantum efficiency for X-rays, the generated signal for each X-ray photon and the distribution of the generated signal between different pixels. In a scintillator coated device the signal is generated both by X-ray photons captured in the scintillator and by X-ray photons captured directly in the semiconductor. Hence, the signal-to-noise ratio (SNR) in the image is then a function of the number of photons captured in each of these processes, and the yield of each process, in terms of electron-hole pairs (EHPs) produced in the semiconductor. The full process from the absorption of the X-ray photon to the final signal read out from the detector has been simulated with a combination of the Monte Carlo program MCNP and the commercial carrier transport simulation tool MEDICI. An in house program calculating the light transport between the scintillator and the semiconductor serves as a link
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| 21. |
- Ekberg, Kerstin, et al.
(författare)
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New Business Structures Creating Organizational Opportunities and Challenges for Work Disability Prevention.
- 2016
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Ingår i: Journal of occupational rehabilitation. - : Springer. - 1053-0487 .- 1573-3688. ; 26:4, s. 480-489
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Flexible work arrangements are growing in order to develop resource-efficient production and because of advanced technologies, new societal values, changing demographics, and globalization. The article aims to illustrate the emerging challenges and opportunities for work disability prevention efforts among workers in alternate work arrangements. Methods The authors participated in a year-long collaboration that ultimately led to an invited 3-day conference, "Improving Research of Employer Practices to Prevent Disability," held October 14-16, 2015, in Hopkinton, Massachusetts, USA. The collaboration included a topical review of the literature, group conference calls to identify key areas and challenges, drafting of initial documents, review of industry publications, and a conference presentation that included feedback from peer researchers and a roundtable discussion with experts having direct employer experience. Results Both worker and employer perspectives were considered, and four common alternate work arrangements were identified: (a) temporary and contingent employment; (b) small workplaces; (c) virtual work/telework; and (d) lone workers. There was sparse available research of return-to-work (RTW) and workplace disability management strategies with regard to alternate work patterns. Limited research findings and a review of the grey literature suggested that regulations and guidelines concerning disabled workers are often ambiguous, leading to unsatisfactory protection. At the workplace level, there was a lack of research evidence on how flexible work arrangements could be handled or leveraged to support RTW and prevent disability. Potential negative consequences of this lack of organizational guidance and information are higher costs for employers and insurers and feelings of job insecurity, lack of social support and integration, or work intensification for disabled workers. Conclusions Future studies of RTW and workplace disability prevention strategies should be designed to reflect the multiple work patterns that currently exist across many working populations, and in particular, flexible work arrangements should be explored in more detail as a possible mechanism for preventing disability. Labor laws and policies need to be developed to fit flexible work arrangements.
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| 22. |
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| 23. |
- Marchal, J, et al.
(författare)
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Active pixel detector for ion beam profiling
- 2002
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - 0168-9002 .- 1872-9576. ; 487:1-2, s. 224-231
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Tidskriftsartikel (refereegranskat)
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| 24. |
- Munir, Abdul Kashem Mohamma, 1958-, et al.
(författare)
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Variability of airborne cat allergen, Fel d1, in a public place
- 2003
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Ingår i: Indoor Air. - : Hindawi Limited. - 0905-6947 .- 1600-0668. ; 13:4, s. 353-358
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Tidskriftsartikel (refereegranskat)abstract
- Allergen exposure is a risk to develop an IgE-mediated sensitization. The amount of allergen inhaled per unit time should be related to the amount present in the air, i.e. airborne allergen. Thus, measuring allergen levels in the air would be more relevant than measuring allergen levels in dust. Allergens are present in the air in very minute quantities and usually become airborne after disturbance. Large variation of allergen levels have been found in dust. In this study, we measured variability of airborne cat allergen, Fel d1, in a public place using a high-volume air-sampler. We also studied the distribution and relationship between dust and airborne cat allergens in homes and schools. Air samples were collected at three different airflow rates, i.e. 55, 40, and 30 m3 of air per hour. The concentration of airborne Fel d1 in the community gymnastic hall varied from 1 to 10 pg/m3 within a period of 3 weeks, at airflow rates 55-30 m3/h. The coefficient of variation for repeated samplings was 14-43% (day-to-day variation) and 27-38% (within-day variation). As expected, higher levels of airborne cat allergens were found in homes with cats than in cat-free environments. There was a significant relationship between cat allergen levels in dust and air (r = 0.7, P < 0.01). Our study demonstrates that when measuring airborne cat allergen a large variation is observed within a day and between days. The large variability of measurement may be explained by the disturbance in the environments. We suggest, that when exposure assessment is made the environment in question should be analyzed, if possible in several occasions.
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| 25. |
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