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- Mizuki, T., et al.
(författare)
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Orbital Characterization of GJ1108A System, and Comparison of Dynamical Mass with Model-derived Mass for Resolved Binaries
- 2018
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 865:2
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Tidskriftsartikel (refereegranskat)abstract
- We report an orbital characterization of GJ1108Aab that is a low-mass binary system in the pre-main-sequence phase. Via the combination of astrometry using adaptive optics and radial velocity measurements, an eccentric orbital solution of e = 0.63 is obtained, which might be induced by the Kozai-Lidov mechanism with a widely separated GJ1108B system. Combined with several observed properties, we confirm that the system is indeed young. Columba is the most probable moving group, to which the GJ1108A system belongs, although its membership to the group has not been established. If the age of Columba is assumed for GJ1108A, the dynamical masses of both GJ1108Aa and GJ1108Ab (M-dynamical,M-GJ1108Aa= 0.72 +/- 0.04 M-circle dot and M-dynamical,M-GJ1108Ab = 0.30 +/- 0.03 M-circle dot) are more massive than what an evolutionary model predicts based on the age and luminosities. We consider that the discrepancy in mass comparison can be attributed to an age uncertainty; the system is likely older than stars in Columba, and effects that are not implemented in classical models such as accretion history and magnetic activity are not preferred to explain the mass discrepancy. We also discuss the performance of the evolutionary model by compiling similar low-mass objects in the evolutionary state based on the literature. Consequently, it is suggested that the current model on average reproduces the mass of resolved low-mass binaries without any significant offsets.
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- Duran-Castells, C., et al.
(författare)
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Sirtuin-2, NAD-Dependent Deacetylase, Is a New Potential Therapeutic Target for HIV-1 Infection and HIV-Related Neurological Dysfunction
- 2023
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Ingår i: Journal of Virology. - : American Society for Microbiology. - 0022-538X .- 1098-5514. ; 97:2
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Tidskriftsartikel (refereegranskat)abstract
- Neurocognitive disorders are frequently reported in people living with HIV (PLWH) even with the introduction of combined antiretroviral treatment (cART). To identify biomarkers and potential therapeutic tools to target HIV infection in peripheral blood and in the central nervous system (CNS), plasma proteomics were applied in untreated chronic HIV-infected individuals with different levels of virus control. The implementation and access to combined antiretroviral treatment (cART) have dramatically improved the quality of life of people living with HIV (PLWH). However, some comorbidities, such as neurological disorders associated with HIV infection still represent a serious clinical challenge. Soluble factors in plasma that are associated with control of HIV replication and neurological dysfunction could serve as early biomarkers and as new therapeutic targets for this comorbidity. We used a customized antibody array for determination of blood plasma factors in 40 untreated PLWH with different levels of viremia and found sirtuin-2 (SIRT2), an NAD-dependent deacetylase, to be strongly associated with elevated viral loads and HIV provirus levels, as well as with markers of neurological damage (a-synuclein [SNCA], brain-derived neurotrophic factor [BDNF], microtubule-associated protein tau [MAPT], and neurofilament light protein [NFL]). Also, longitudinal analysis in HIV-infected individuals with immediate (n = 9) or delayed initiation (n = 10) of cART revealed that after 1 year on cART, SIRT2 plasma levels differed between both groups and correlated inversely with brain orbitofrontal cortex involution. Furthermore, targeting SIRT2 with specific small-molecule inhibitors in in vitro systems using J-LAT A2 and primary glial cells led to diminished HIV replication and virus reactivation from latency. Our data thus identify SIRT2 as a novel biomarker of uncontrolled HIV infection, with potential impact on neurological dysfunction and offers a new therapeutic target for HIV treatment and cure.IMPORTANCE Neurocognitive disorders are frequently reported in people living with HIV (PLWH) even with the introduction of combined antiretroviral treatment (cART). To identify biomarkers and potential therapeutic tools to target HIV infection in peripheral blood and in the central nervous system (CNS), plasma proteomics were applied in untreated chronic HIV-infected individuals with different levels of virus control. High plasma levels of sirtuin-2 (SIRT2), an NAD(+) deacetylase, were detected in uncontrolled HIV infection and were strongly associated with plasma viral load and proviral levels. In parallel, SIRT2 levels in the peripheral blood and CNS were associated with markers of neurological damage and brain involution and were more pronounced in individuals who initiated cART later in infection. In vitro infection experiments using specific SIRT2 inhibitors suggest that specific targeting of SIRT2 could offer new therapeutic treatment options for HIV infections and their associated neurological dysfunction.
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- Bergmann, Melanie, et al.
(författare)
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A global plastic treaty must cap production.
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 376:6592, s. 469-470
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Tidskriftsartikel (refereegranskat)abstract
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- Dey, Tridibesh, et al.
(författare)
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Global plastic treaty should address chemicals.
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 378:6622, s. 841-842
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Tidskriftsartikel (refereegranskat)
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10. |
- Grigoriadis, K., et al.
(författare)
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Improving the recycling rate of the construction industry
- 2019
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Ingår i: Sustainable Construction Materials and Technologies. - : International Committee of the SCMT conferences.
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Konferensbidrag (refereegranskat)abstract
- Construction and Demolition Waste (CDW) accounts for approximately 25-30% of all waste generated across Europe each year. However, Waste Framework Directive 2008/98/EC requires from all EU member states to achieve at least 70% re-use, recycling or other recovery of non-hazardous CDW by 2020. In response, the Horizon 2020 RE4 Project (REuse and REcycling of CDW materials and structures in energy efficient pREfabricated elements for building REfurbishment and construction) consortium was set up. Its main aims are to assess the quality of various CDW fractions (e.g. mineral aggregate, timber, plastics, silt & clay), improve the quality of mineral aggregates and develop different building elements/components which contain at least 65% of CDW. Innovative building concepts will also be developed in an effort to improve recycling rates of future buildings through the use of prefabrication and modular design. The developed products and technologies will be assessed in a number of test sites by building 2-storey demonstration houses.
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- Jokinen, H., et al.
(författare)
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Global Burden of Small Vessel Disease-Related Brain Changes on MRI Predicts Cognitive and Functional Decline
- 2020
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Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 51:1, s. 170-178
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose- Cerebral small vessel disease is characterized by a wide range of focal and global brain changes. We used a magnetic resonance imaging segmentation tool to quantify multiple types of small vessel disease-related brain changes and examined their individual and combined predictive value on cognitive and functional abilities. Methods- Magnetic resonance imaging scans of 560 older individuals from LADIS (Leukoaraiosis and Disability Study) were analyzed using automated atlas- and convolutional neural network-based segmentation methods yielding volumetric measures of white matter hyperintensities, lacunes, enlarged perivascular spaces, chronic cortical infarcts, and global and regional brain atrophy. The subjects were followed up with annual neuropsychological examinations for 3 years and evaluation of instrumental activities of daily living for 7 years. Results- The strongest predictors of cognitive performance and functional outcome over time were the total volumes of white matter hyperintensities, gray matter, and hippocampi (P<0.001 for global cognitive function, processing speed, executive functions, and memory and P<0.001 for poor functional outcome). Volumes of lacunes, enlarged perivascular spaces, and cortical infarcts were significantly associated with part of the outcome measures, but their contribution was weaker. In a multivariable linear mixed model, volumes of white matter hyperintensities, lacunes, gray matter, and hippocampi remained as independent predictors of cognitive impairment. A combined measure of these markers based on Z scores strongly predicted cognitive and functional outcomes (P<0.001) even above the contribution of the individual brain changes. Conclusions- Global burden of small vessel disease-related brain changes as quantified by an image segmentation tool is a powerful predictor of long-term cognitive decline and functional disability. A combined measure of white matter hyperintensities, lacunar, gray matter, and hippocampal volumes could be used as an imaging marker associated with vascular cognitive impairment.
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- Nordsletten, Ashley E., et al.
(författare)
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Evaluating the Impact of Nonrandom Mating : Psychiatric Outcomes Among the Offspring of Pairs Diagnosed With Schizophrenia and Bipolar Disorder.
- 2020
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 87:3, s. 253-262
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Nonrandom mating has been shown for psychiatric diagnoses, with hypothesized-but not quantified-implications for offspring liability. This national cohort study enumerated the incidence of major psychiatric disorders among the offspring of parent pairs affected with schizophrenia (SCZ) and/or bipolar disorder (BIP) (i.e., dual-affected pairs).METHODS: Participants were all Swedish residents alive or born between 1968 and 2013 (n = 4,255,196 unique pairs and 8,343,951 offspring). Offspring with dual-affected, single-affected, and unaffected parents were followed (1973-2013) for incidence of broad psychiatric disorders. Primary outcomes included hazard ratio (HR) and cumulative incidence for SCZ and BIP in the offspring. Additional outcomes included any neuropsychiatric, anxiety, depressive, personality, or substance use disorders. Cumulative incidences of SCZ and BIP were used to inform heritability models for these disorders.RESULTS: Hazards were highest within disorder (e.g., offspring of dual-SCZ pairs had sharply raised hazards for SCZ [HR = 55.3]); however, they were significantly raised for all diagnoses (HR range = 2.89-11.84). Incidences were significantly higher for the majority of outcomes, with 43.4% to 48.5% diagnosed with "any" disorder over follow-up. Risks were retained, with modest attenuations, for the offspring of heterotypic pairs. The estimated heritability of liability for SCZ (h2 = 0.62, 95% confidence interval = 0.55-0.70) and BIP (h2 = 0.52, 95% confidence interval = 0.46-0.58) did not differ significantly from estimates derived from single-affected parents.CONCLUSIONS: Risks for a broad spectrum of psychiatric diagnoses are significantly raised in the offspring of dual-affected parents, in line with expectations from a polygenic model of liability to disease risk. How these risks may contribute to population maintenance of these disorders is considered.
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- Pistocchi, A., et al.
(författare)
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Treatment of micropollutants in wastewater : Balancing effectiveness, costs and implications
- 2022
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697. ; 850
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Tidskriftsartikel (refereegranskat)abstract
- In this contribution, we analyse scenarios of advanced wastewater treatment for the removal of micropollutants. By this we refer to current mainstream, broad spectrum processes including ozonation and sorption onto activated carbon. We argue that advanced treatment requires properly implemented tertiary (nutrient removal) treatment in order to be effective. We review the critical aspects of the main advanced treatment options, their advantages and disadvantages. We propose a quantification of the costs of implementing advanced treatment, as well as upgrading plants from secondary to tertiary treatment when needed, and we illustrate what drives the costs of advanced treatment for a set of standard configurations. We propose a cost function to represent the total costs (investment, operation and maintenance) of advanced treatment. We quantify the implications of advanced treatment in terms of greenhouse gas emissions. Based on the indicators of total toxic discharge, toxicity at the discharge points and toxicity across the stream network discussed in Pistocchi et al. (2022), we compare costs and effectiveness of different scenarios of advanced treatment. In principle the total toxic load and toxicity at the points of discharge could be reduced by about 75 % if advanced treatment processes were implemented virtually at all wastewater treatment plants, but this would entail costs of about 4 billion euro/year for the European Union as a whole. We consider a “compromise” scenario where advanced treatment is required at plants of 100 thousand population equivalents (PE) or larger, or at plants between 10 and 100 thousand PE if the dilution ratio at the discharge point is 10 or less. Under this scenario, the length of the stream network exposed to high toxicity would not increase significantly compared to the previous scenario, and the other indicators would not deteriorate significantly, while the costs would remain at about 1.5 billion Euro/year. Arguably, costs could be further reduced, without a worsening of water quality, if we replace a local risk assessment to generic criteria of plant capacity and dilution in order to determine if a WWTP requires advanced treatment.
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- Sekine, Takuya, et al.
(författare)
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TOX is expressed by exhausted and polyfunctional human effector memory CD8(+) T cells
- 2020
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Ingår i: Science immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 5:49
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Tidskriftsartikel (refereegranskat)abstract
- CD8(+) T cell exhaustion is a hallmark of many cancers and chronic infections. In mice, T cell factor 1 (TCF-1) maintains exhausted CD8(+) T cell responses, whereas thymocyte selection-associated HMG box (TOX) is required for the epigenetic remodeling and survival of exhausted CD8(+) T cells. However, it has remained unclear to what extent these transcription factors play analogous roles in humans. In this study, we mapped the expression of TOX and TCF-1 as a function of differentiation and specificity in the human CD8(+) T cell landscape. Here, we demonstrate that circulating TOX+ CD8(+) T cells exist in most humans, but that TOX is not exclusively associated with exhaustion. Effector memory CD8(+) T cells generally expressed TOX, whereas naive and early-differentiated memory CD8(+) T cells generally expressed TCF-1. Cytolytic gene and protein expression signatures were also defined by the expression of TOX. In the context of a relentless immune challenge, exhausted HIV-specific CD8(+) T cells commonly expressed TOX, often in clusters with various activation markers and inhibitory receptors, and expressed less TCF-1. However, polyfunctional memory CD8(+) T cells specific for cytomegalovirus (CMV) or Epstein-Barr virus (EBV) also expressed TOX, either with or without TCF-1. A similar phenotype was observed among HIV-specific CD8(+) T cells from individuals who maintained exceptional immune control of viral replication. Collectively, these data demonstrate that TOX is expressed by most circulating effector memory CD8(+) T cell subsets and not exclusively linked to exhaustion.
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- Tengvall, Katarina, 1980-, et al.
(författare)
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Bayesian model and selection signature analyses reveal risk factors for canine atopic dermatitis
- 2022
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Ingår i: Communications Biology. - : Springer Nature. - 2399-3642. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- Canine atopic dermatitis is an inflammatory skin disease with clinical similarities to human atopic dermatitis. Several dog breeds are at increased risk for developing this disease but previous genetic associations are poorly defined. To identify additional genetic risk factors for canine atopic dermatitis, we here apply a Bayesian mixture model adapted for mapping complex traits and a cross-population extended haplotype test to search for disease-associated loci and selective sweeps in four dog breeds at risk for atopic dermatitis. We define 15 associated loci and eight candidate regions under selection by comparing cases with controls. One associated locus is syntenic to the major genetic risk locus (Filaggrin locus) in human atopic dermatitis. One selection signal in common type Labrador retriever cases positions across the TBC1D1 gene (body weight) and one signal of selection in working type German shepherd controls overlaps the LRP1B gene (brain), near the KYNU gene (psoriasis). In conclusion, we identify candidate genes, including genes belonging to the same biological pathways across multiple loci, with potential relevance to the pathogenesis of canine atopic dermatitis. The results show genetic similarities between dog and human atopic dermatitis, and future across-species genetic comparisons are hereby further motivated.
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- Vilaplana-Perez, A., et al.
(författare)
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Association of social anxiety disorder with objective indicators of educational attainment : A nation-wide register-based sibling control study
- 2019
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Ingår i: European Neuropsychopharmacology. - : Elsevier. - 0924-977X .- 1873-7862. ; 29:Suppl. 6, s. S150-S151
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Social Anxiety Disorder (SAD) is a relatively frequent psychiatric disorder, with a lifetime prevalence of about 4% [1], which usually starts in adolescence [2]. As in the case of other mental disorders, [3] SAD has also been linked to academic impairment and school drop-out [4,5], but this previous research has a number of methodological limitations, mainly the use of modest sample sizes, retrospective designs, self-reported measures, and focusing in a single educational level.Aim: We aim to investigate the association between SAD and educational outcomes at all levels using objectively collected measures, controlling for a number of covariates and unmeasured factors shared between siblings.Method: Using the Swedish nationwide registers, we designed this population-based birth cohort study, which included 2,244,191 individuals born in Sweden between 1973 and 1997, who were followed up from 1991 until 2013. A total of 15,765 individuals had a record of SAD in the Swedish National Patient Register, according to the International Classification of Diseases, 10th edition. Logistic regression models tested the association between SAD and the prospectively-collected and objectively measured educational outcomes. These educational milestones included: the year grades in the final year of compulsory school, the eligibility to access upper secondary school after compulsory education (for both, vocational and academical programs), finishing upper secondary school, starting university, finishing a university degree, and completing post-graduate education. In order to reduce the impact of possible confounders, we took into account a number of covariates such as age, sex, maternal and paternal age at birth and year of birth. The impact of common psychiatric comorbidities of SAD was also taken into account. In order to control for unmeasured shared familial factors, we performed a sibling comparison analysis. We identified 786,766 families with 2 or more siblings, and identified 11,950 families with full siblings discordant for SAD.Results: Compared to the unexposed individuals, individuals with SAD were less likely to pass all subjects in the last year of compulsory school (adjusted odds ratios [aOR] ranging from 0.19 to 0.44). They were also less likely to access a vocational program or an academic program in upper secondary education (aOR=0.31 [95% CI, 0.30–0.33] and aOR=0.52 [95% CI, 0.51–0.55], respectively). SAD cases also had 81% lower odds of finishing upper secondary education (aOR=0.19 [95% CI, 0.19–0.20]), 53% lower odds of starting a university degree (aOR=0.47 [95% CI, 0.45–0.49]), 65% lower odds of finishing a university degree (aOR=0.35 [95% CI, 0.33–0.37]), and 42% lower odds of finishing postgraduate education (aOR=0.58 [95% CI, 0.43-0.80]). Results were attenuated but remained significant in fully adjusted sibling comparison models. When comorbidities were taken into account, results were maintained.Conclusion: SAD has an adverse impact on educational attainment throughout the life-span, even after controlling for confounders and factors shared between siblings.
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22. |
- Whittaker, M. J., et al.
(författare)
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Novel construction and demolition waste (CDW) treatment and uses to maximize reuse and recycling
- 2021
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Ingår i: Advances in Building Energy Research. - : Taylor and Francis Ltd.. - 1751-2549 .- 1756-2201. ; 15:2, s. 253-269
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Tidskriftsartikel (refereegranskat)abstract
- The EU Waste Framework Directive 2008/98/EC states that all member states should take all necessary measures in order to achieve at least 70% re-use, recycling or other recovery of non-hazardous Construction and Demolition Waste (CDW) by 2020. In response, the Horizon 2020 RE4 project consortium (REuse and REcycling of CDW materials and structures in energy efficient pREfabricated elements for building REfurbishment and construction) consisting of 12 research and industrial partners across Europe, plus a research partner from Taiwan, was set up. For its success, the approach of the Project was manifold, developing sorting technologies to first improve the quality of CDW-derived aggregate. Simultaneously, CDW streams were assessed for quality and novel applications developed for aggregate, timber and plastic waste in a variety of products including structural and non-structural elements. With all products considered, innovative building concepts have been designed in a bid to improve future reuse and recycling of the products by promoting prefabricated construction methods and modular design to ease future recycling and increase value of the construction industry. The developed technologies and products have been put to the test in different test sites in building a two-storey house containing at least 65% of CDW. © 2019, © 2019 The Author(s)..
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