| 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. |
- Jansen, Willemijn J, et al.
(författare)
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Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
- 2022
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
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Tidskriftsartikel (refereegranskat)abstract
- One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
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| 4. |
- Nguyen, Thanh N, et al.
(författare)
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Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.
- 2023
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Ingår i: Neurology. - 1526-632X. ; 100:4
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Tidskriftsartikel (refereegranskat)abstract
- Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations.There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.This study is registered under NCT04934020.
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| 5. |
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| 6. |
- Anderson, Emma K., 1986-, et al.
(författare)
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Fragmentation of and electron detachment from hot copper and silver dimer anions : A comparison
- 2023
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Ingår i: Physical Review A: covering atomic, molecular, and optical physics and quantum information. - 2469-9926 .- 2469-9934. ; 107:6
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Tidskriftsartikel (refereegranskat)abstract
- We measured the spontaneous decays of internally hot copper and silver dimer anions, and , stored in one of the two ion-beam storage rings of the Double Electrostatic Ion Ring Experiment (DESIREE) at Stockholm University. A coincidence detection technique was utilized enabling essentially background-free measurements of -> Cu + Cu- and -> Ag + Ag- fragmentation rates. Furthermore, the total rates of neutral decay products (monomers and dimers) were measured and the relative contributions of fragmentation and electron emission ( -> Cu2 + e- and -> Ag2 + e-) were deduced as functions of storage time. Fragmentation is completely dominant at early times. However, after about 20 ms of storage, electron emission is observed and becomes the leading decay path after 100 ms for both dimer anions. The branching ratios between fragmentation and electron emission (vibrationally assisted autodetachment processes) are very nearly the same for and Ag-2 throughout the present storage cycle of 10 seconds. This is surprising considering the difference between the electron affinities of the neutral dimers, Cu2 and Ag2, and the difference between the and the dissociation energies.
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| 7. |
- Baker-Austin, Craig, et al.
(författare)
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Extreme arsenic resistance by the acidophilic archaeon 'Ferroplasma acidarmanus' Fer1.
- 2007
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Ingår i: Extremophiles. - : Springer Science and Business Media LLC. - 1431-0651 .- 1433-4909. ; 11:3, s. 425-34
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Tidskriftsartikel (refereegranskat)abstract
- 'Ferroplasma acidarmanus' Fer1 is an arsenic-hypertolerant acidophilic archaeon isolated from the Iron Mountain mine, California; a site characterized by heavy metals contamination. The presence of up to 10 g arsenate per litre [As(V); 133 mM] did not significantly reduce growth yields, whereas between 5 and 10 g arsenite per litre [As(III); 67-133 mM] significantly reduced the yield. Previous bioinformatic analysis indicates that 'F. acidarmanus' Fer1 has only two predicted genes involved in arsenic resistance and lacks a recognizable gene for an arsenate reductase. Biochemical analysis suggests that 'F. acidarmanus' Fer1 does not reduce arsenate indicating that 'F. acidarmanus' Fer1 has an alternative resistance mechanism to arsenate other than reduction to arsenite and efflux. Primer extension analysis of the putative ars transcriptional regulator (arsR) and efflux pump (arsB) demonstrated that these genes are co-transcribed, and expressed in response to arsenite, but not arsenate. Two-dimensional polyacrylamide gel electrophoresis analysis of 'F. acidarmanus' Fer1 cells exposed to arsenite revealed enhanced expression of proteins associated with protein refolding, including the thermosome Group II HSP60 family chaperonin and HSP70 DnaK type heat shock proteins. This report represents the first molecular and proteomic study of arsenic resistance in an acidophilic archaeon.
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| 8. |
- Bastard, Paul, et al.
(författare)
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Preexisting autoantibodies to type I IFNs underlie critical COVID-19 pneumonia in patients with APS-1.
- 2021
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Ingår i: The Journal of experimental medicine. - 1540-9538. ; 218:7
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Tidskriftsartikel (refereegranskat)abstract
- Patients with biallelic loss-of-function variants of AIRE suffer from autoimmune polyendocrine syndrome type-1 (APS-1) and produce a broad range of autoantibodies (auto-Abs), including circulating auto-Abs neutralizing most type I interferons (IFNs). These auto-Abs were recently reported to account for at least 10% of cases of life-threatening COVID-19 pneumonia in the general population. We report 22 APS-1 patients from 21 kindreds in seven countries, aged between 8 and 48 yr and infected with SARS-CoV-2 since February 2020. The 21 patients tested had auto-Abs neutralizing IFN-α subtypes and/or IFN-ω; one had anti-IFN-β and another anti-IFN-ε, but none had anti-IFN-κ. Strikingly, 19 patients (86%) were hospitalized for COVID-19 pneumonia, including 15 (68%) admitted to an intensive care unit, 11 (50%) who required mechanical ventilation, and four (18%) who died. Ambulatory disease in three patients (14%) was possibly accounted for by prior or early specific interventions. Preexisting auto-Abs neutralizing type I IFNs in APS-1 patients confer a very high risk of life-threatening COVID-19 pneumonia at any age.
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| 9. |
- Battley, Mark A., et al.
(författare)
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Effects of Panel Stiffness on Slamming Responses of Composite Hull Panels
- 2009
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Ingår i: 17th International Conference on Composite Materials, ICCM17. ; , s. 1-11
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Konferensbidrag (refereegranskat)abstract
- Controlled water slam testing of composite hull panels was conducted to study the effect of hydroelasticity for three panels with different stiffnesses. The experimental methodology successfully characterised the hydroelastic behaviour, which included kinematic as well as inertial effects. Hydroelastic effects included changes in panel geometry, local velocity, fluid pressures, and panel structural responses.
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| 10. |
- Chartkunchand, Kiattichart C., et al.
(författare)
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Dianion diagnostics in DESIREE : High-sensitivity detection of C-n(2-) from a sputter ion source
- 2018
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Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 89:3
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Tidskriftsartikel (refereegranskat)abstract
- A sputter ion source with a solid graphite target has been used to produce dianions with a focus on carbon cluster dianions, C-n(2-), with n = 7-24. Singly and doubly charged anions from the source were accelerated together to kinetic energies of 10 keV per atomic unit of charge and injected into one of the cryogenic (13 K) ion-beam storage rings of the Double ElectroStatic Ion Ring Experiment facility at Stockholm University. Spontaneous decay of internally hot C-n(2-) dianions injected into the ring yielded C-n(2-) anions with kinetic energies of 20 keV, which were counted with a microchannel plate detector. Mass spectra produced by scanning the magnetic field of a 90 degrees analyzing magnet on the ion injection line reflect the production of internally hot C-7(2-) - C-24(2-) dianions with lifetimes in the range of tens of microseconds to milliseconds. In spite of the high sensitivity of this method, no conclusive evidence of C-6(2-) was found while there was a clear C-7(2-) signal with the expected isotopic distribution. This is consistent with earlier experimental studies and with theoretical predictions. An upper limit is deduced for a C-6(2-) signal that is two orders-of-magnitude smaller than that for C-7(2-). In addition, CnO2- and CnCu2- dianions were detected.
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| 11. |
- DeVita, Michael A., et al.
(författare)
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"Identifying the hospitalised patient in crisis"-A consensus conference on the afferent limb of Rapid Response Systems
- 2010
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Ingår i: Resuscitation. - : Elsevier BV. - 1873-1570 .- 0300-9572. ; 81:4, s. 375-382
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Tidskriftsartikel (refereegranskat)abstract
- Background: Most reports of Rapid Response Systems (RRS) focus on the efferent, response component of the system, although evidence suggests that improved vital sign monitoring and recognition of a clinical crisis may have outcome benefits. There is no consensus regarding how best to detect patient deterioration or a clear description of what constitutes patient monitoring. Methods: A consensus conference of international experts in safety, RRS, healthcare technology, education, and risk prediction was convened to review current knowledge and opinion on clinical monitoring. Using established consensus procedures, four topic areas were addressed: (1) To what extent do physiologic abnormalities predict risk for patient deterioration? (2) Do workload changes and their potential stresses on the healthcare environment increase patient risk in a predictable manner? (3) What are the characteristics of an "ideal" monitoring system, and to what extent does currently available technology meet this need? and (4) How can monitoring be categorized to facilitate comparing systems? The major findings include: (1) vital sign aberrations predict risk, (2) monitoring patients more effectively may improve outcome, although some risk is random, (3) the workload implications of monitoring on the clinical workforce have not been explored, but are amenable to study and should be investigated, (4) the characteristics of an ideal monitoring system are identifiable, and it is possible to categorize monitoring modalities. It may also be possible to describe monitoring levels, and a system is proposed. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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| 12. |
- Downes, Marley, et al.
(författare)
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M5X4: A Family of MXenes
- 2023
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Ingår i: ACS Nano. - : AMER CHEMICAL SOC. - 1936-0851 .- 1936-086X. ; 17:17, s. 17158-17168
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Tidskriftsartikel (refereegranskat)abstract
- MXenes are two-dimensional (2D) transition metal carbides, nitrides, and carbonitrides typically synthesized from layered MAX-phase precursors. With over 50 experimentally reported MXenes and a near-infinite number of possible chemistries, MXenes make up the fastest-growing family of 2D materials. They offer a wide range of properties, which can be altered by their chemistry (M, X) and the number of metal layers in the structure, ranging from two in M2XTx to five in M5X4T x . Only one M5X4 MXene, Mo4VC4, has been reported. Herein, we report the synthesis and characterization of two M(5)AX(4) mixed transition metal MAX phases, Ti2.5Ta2.5AlC4 and Ti2.675Nb2.325AlC4, and their successful topochemical transformation into Ti2.5Ta2.5C4T x and Ti2.675Nb2.325C4Tx MXenes. The resulting MXenes were delaminated into single-layer flakes, analyzed structurally, and characterized for their thermal and optical properties. This establishes a family of M(5)AX(4) MAX phases and their corresponding MXenes. These materials were experimentally produced based on guidance from theoretical predictions, leading to more exciting applications for MXenes.
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| 13. |
- Eklund, Gustav, et al.
(författare)
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Cryogenic merged-ion-beam experiments in DESIREE : Final-state-resolved mutual neutralization of Li+ and D-
- 2020
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Ingår i: Physical Review A: covering atomic, molecular, and optical physics and quantum information. - : American Physical Society (APS). - 2469-9926 .- 2469-9934. ; 102:1
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Tidskriftsartikel (refereegranskat)abstract
- We have developed an experimental technique to study charge-and energy-flow processes in sub-eV collisions between oppositely charged, internally cold, ions of atoms, molecules, and clusters. Two ion beams are stored in separate rings of the cryogenic ion-beam storage facility DESIREE, and merged in a common straight section where a set of biased drift tubes is used to control the center-of-mass collision energy locally in fine steps. Here, we present measurements on mutual neutralization between Li+ and D- where a time-sensitive imaging-detector system is used to measure the three-dimensional distance between the neutral Li and D atoms as they reach the detector. This scheme allows for direct measurements of kinetic-energy releases, and here it reveals separate populations of the 3s state and the (3p + 3d) states in neutral Li while the D atom is left in its ground state 1s. The branching fraction of the 3s final state is measured to be 57.8 +/- 0.7% at a center-of-mass collision energy of 78 +/- 13 meV. The technique paves the way for studies of charge-, energy-, and mass-transfer reactions in single collisions involving molecular and cluster ions in well-defined quantum states.
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| 14. |
- Ferrari, Raffaele, et al.
(författare)
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Frontotemporal dementia and its subtypes: a genome-wide association study.
- 2014
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Ingår i: Lancet Neurology. - 1474-4465. ; 13:7, s. 686-699
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder.
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| 15. |
- Flores-Ruiz, F. J., et al.
(författare)
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Micro-tribological performance of fullerene-like carbon and carbon-nitride surfaces
- 2018
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Ingår i: Tribology International. - : Pergamon Press. - 0301-679X .- 1879-2464. ; 128, s. 104-112
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Tidskriftsartikel (refereegranskat)abstract
- We studied the microtribological behavior of amorphous and fullerene-like (FL) carbon and carbon-nitride coatings deposited by filtered-cathodic-arc. All films show similar friction coefficients but different wear mechanisms. The FL films exhibit a surface swelling with the formation of a layer that thickens during the test, limiting wear and maintaining a low friction. X-ray photoelectron spectroscopy on worn FL film surfaces show an increase in the sp(2)-content, indicating that the lubricious layer generated by the wear process is probably the result of re-hybridization due to plasticity induced by localized shear. In contrast, the wear results of the amorphous films, involving tribomechanical and tribochemical surface phenomena, show that the surface layer formed during sliding is a precursor to the onset of wear.
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| 16. |
- Frykholm, Peter, 1961-, et al.
(författare)
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Pre-operative fasting in children : A guideline from the European Society of Anaesthesiology and Intensive Care
- 2022
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Ingår i: European Journal of Anaesthesiology. - : European Society of Anaesthesiology and Intensive Care. - 0265-0215 .- 1365-2346. ; 39:1, s. 4-25
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Tidskriftsartikel (refereegranskat)abstract
- Current paediatric anaesthetic fasting guidelines have recommended conservative fasting regimes for many years and have not altered much in the last decades. Recent publications have employed more liberal fasting regimes with no evidence of increased aspiration or regurgitation rates. In this first solely paediatric European Society of Anaesthesiology and Intensive Care (ESAIC) pre-operative fasting guideline, we aim to present aggregated and evidence-based summary recommendations to assist clinicians, healthcare providers, patients and parents.We identified six main topics for the literature search: studies comparing liberal with conservative regimens; impact of food composition; impact of comorbidity; the use of gastric ultrasound as a clinical tool; validation of gastric ultrasound for gastric content and gastric emptying studies; and early postoperative feeding. The literature search was performed by a professional librarian in collaboration with the ESAIC task force.Recommendations for reducing clear fluid fasting to 1 h, reducing breast milk fasting to 3 h, and allowing early postoperative feeding were the main results, with GRADE 1C or 1B evidence. The available evidence suggests that gastric ultrasound may be useful for clinical decision-making, and that allowing a ‘light breakfast’ may be well tolerated if the intake is well controlled. More research is needed in these areas as well as evaluation of how specific patient or treatment-related factors influence gastric emptying.
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| 17. |
- Gatchell, Michael, et al.
(författare)
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Commissioning of the DESIREE storage rings - a new facility for cold ion-ion collisions
- 2014
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Ingår i: XXVIII International Conference on Photonic, Electronic and Atomic Collisions (ICPEAC 2013). - : Institute of Physics (IOP). ; 488:1
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Konferensbidrag (refereegranskat)abstract
- We report on the ongoing commissioning of the Double ElectroStatic Ion Ring ExpEriment, DESIREE, at Stockholm University. Beams of atomic carbon anions (C-) and smaller carbon anion molecules (C-2(-), C-3(-), C-4(-) etc.) have been produced in a sputter ion source, accelerated to 10 keV or 20 keV, and stored successfully in the two electrostatic rings. The rings are enclosed in a common vacuum chamber cooled to below 13 Kelvin. The DESIREE facility allows for studies of internally relaxed single isolated atomic, molecular and cluster ions and for collision experiments between cat-and anions down to very low center-of-mass collision energies (meV scale). The total thermal load of the vacuum chamber at this temperature is measured to be 32 W. The decay rates of stored ion beams have two components: a non-exponential component caused by the space charge of the beam itself which dominates at early times and an exponential term from the neutralization of the beam in collisions with residual gas at later times. The residual gas limited storage lifetime of carbon anions in the symmetric ring is over seven minutes while the 1/e lifetime in the asymmetric ring is measured to be about 30 seconds. Although we aim to improve the storage in the second ring, the number of stored ions are now sufficient for many merged beams experiments with positive and negative ions requiring milliseconds to seconds ion storage.
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| 18. |
- Gatchell, Michael, et al.
(författare)
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First results from the Double ElectroStatic Ion-Ring ExpEriment, DESIREE
- 2014
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Ingår i: XXVIII International Conference on Photonic, Electronic and Atomic Collisions (ICPEAC 2013). - : Institute of Physics (IOP). ; 488
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Konferensbidrag (refereegranskat)abstract
- We have stored the first beams in one of the rings of the double electrostatic ion-storage ring, DESIREE at cryogenic and at room temperature conditions. At cryogenic operations the following parameters are found. Temperature; T= 13K, pressure; p <10(-13) mbar, initial number of stored ions; N > 10(7) and storage lifetime of a C-2(-) beam; tau = 450 S.
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| 19. |
- Hjorth, Olof, et al.
(författare)
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Expectancy effects on serotonin and dopamine transporters during SSRI treatment of social anxiety disorder : a randomized clinical trial
- 2021
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Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- It has been extensively debated whether selective serotonin reuptake inhibitors (SSRIs) are more efficacious than placebo in affective disorders, and it is not fully understood how SSRIs exert their beneficial effects. Along with serotonin transporter blockade, altered dopamine signaling and psychological factors may contribute. In this randomized clinical trial of participants with social anxiety disorder (SAD) we investigated how manipulation of verbally-induced expectancies, vital for placebo response, affect brain monoamine transporters and symptom improvement during SSRI treatment. Twenty-seven participants with SAD (17 men, 10 women), were randomized, to 9 weeks of overt or covert treatment with escitalopram 20 mg. The overt group received correct treatment information whereas the covert group was treated deceptively with escitalopram, described as an active placebo in a cover story. Before and after treatment, patients underwent positron emission tomography (PET) assessments with the [C-11]DASB and [C-11]PE2I radiotracers, probing brain serotonin (SERT) and dopamine (DAT) transporters. SAD symptoms were measured by the Liebowitz Social Anxiety Scale. Overt was superior to covert SSRI treatment, resulting in almost a fourfold higher rate of responders. PET results showed that SERT occupancy after treatment was unrelated to anxiety reduction and equally high in both groups. In contrast, DAT binding decreased in the right putamen, pallidum, and the left thalamus with overt SSRI treatment, and increased with covert treatment, resulting in significant group differences. DAT binding potential changes in these regions correlated negatively with symptom improvement. Findings support that the anxiolytic effects of SSRIs involve psychological factors contingent on dopaminergic neurotransmission while serotonin transporter blockade alone is insufficient for clinical response.
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| 20. |
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| 21. |
- Kagan, Jacob, et al.
(författare)
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National Cancer Institute Think-Tank Meeting Report on Proteomic Cartography and Biomarkers at the Single-Cell Level : Interrogation of Premalignant Lesions
- 2020
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 19:5, s. 1900-1912
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Tidskriftsartikel (refereegranskat)abstract
- A Think-Tank Meeting was convened by the National Cancer Institute (NCI) to solicit experts' opinion on the development and application of multiomic single-cell analyses, and especially single-cell proteomics, to improve the development of a new generation of biomarkers for cancer risk, early detection, diagnosis, and prognosis as well as to discuss the discovery of new targets for prevention and therapy. It is anticipated that such markers and targets will be based on cellular, subcellular, molecular, and functional aberrations within the lesion and within individual cells. Single-cell proteomic data will be essential for the establishment of new tools with searchable and scalable features that indude spatial and temporal cartographies of premalignant and malignant lesions. Challenges and potential solutions that were discussed included (i) The best way/s to analyze single-cells from fresh and preserved tissue; (ii) Detection and analysis of secreted molecules and from single cells, especially from a tissue slice; (iii) Detection of new, previously undocumented cell type/s in the premalignant and early stage cancer tissue microenvironment; (iv) Multiomic integration of data to support and inform proteomic measurements; (v) Subcellular organelles-identifying abnormal structure, function, distribution, and location within individual premalignant and malignant cells; (vi) How to improve the dynamic range of single-cell proteomic measurements for discovery of differentially expressed proteins and their post-translational modifications (PTM); (vii) The depth of coverage measured concurrently using single-cell techniques; (viii) Quantitation - absolute or semiquantitative? (ix) Single methodology or multiplexed combinations? (x) Application of analytical methods for identification of biologically significant subsets; (xi) Data visualization of N-dimensional data sets; (xii) How to construct intercellular signaling networks in individual cells within premalignant tumor microenvironments (TME); (xiii) Associations between intrinsic cellular processes and extrinsic stimuli; (xiv) How to predict cellular responses to stress-inducing stimuli; (xv) Identification of new markers for prediction of progression from precursor, benign, and localized lesions to invasive cancer, based on spatial and temporal changes within individual cells; (xvi) Identification of new targets for immunoprevention or immunotherapy-identification of neoantigens and surfactome of individual cells within a lesion.
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| 22. |
- Karlsson, Linda, et al.
(författare)
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Graphene on graphene formation from PMMA residues during annealing
- 2017
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Ingår i: Vacuum. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0042-207X .- 1879-2715. ; 137, s. 191-194
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Tidskriftsartikel (refereegranskat)abstract
- PMMA is a common support material for transferring graphene between substrates. However, PMMA residues typically remain on the graphene sheet after the transfer process. A high temperature annealing process is commonly applied to reduce the amount of PMMA residues. It is also known that high temperature annealing of PMMA causes the PMMA to graphitize, which has been used as a method to synthesize graphene on metal substrates. In this letter we show the development of additional graphene layers during high temperature annealing, which occurs on a single, clean, graphene sheet. The additional graphene is nucleated from the decomposition products of PMMA residues. (C) 2017 Elsevier Ltd. All rights reserved.
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| 23. |
- Karlsson, Linda, et al.
(författare)
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Residue reduction and intersurface interaction on single graphene sheets
- 2016
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Ingår i: Carbon. - : Pergamon Press. - 0008-6223 .- 1873-3891. ; 100, s. 345-350
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Tidskriftsartikel (refereegranskat)abstract
- Large regions of pristine graphene are essential to applications which rely on the ideal graphene properties. Common methods for transferring chemical vapour deposition grown graphene to suitable substrates leaves metal oxide particles and poly(methyl methacrylate) (PMMA) residues on opposing surfaces, which degrade the properties. A common method to reduce the residues include annealing in vacuum or in argon, however, residues remain on the graphene sheet. The present investigation reports on the metal oxide particle ripening and PMMA decomposition on a single graphene sheet during in-situ annealing up to 1300 degrees C in a transmission electron microscope. It is shown that the PMMA residues are increasingly reduced at elevated temperatures although the reduction is strongly correlated to the metal oxide particle coverage on the opposing graphene surface. This is shown to occur as a consequence of an electrostatic interaction between the residues and that this prevents the establishment of large clean areas. (C) 2016 Elsevier Ltd. All rights reserved.
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| 24. |
- Lai, Chung-Chuan, et al.
(författare)
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Synthesis and characterization of Zr2Al3C4 thin films
- 2015
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Ingår i: Thin Solid Films. - : ELSEVIER SCIENCE SA. - 0040-6090 .- 1879-2731. ; 595, s. 142-147
-
Tidskriftsartikel (refereegranskat)abstract
- Zr2Al3C4 is an inherently nanolaminated carbide where layers of ZrC alternate with layers of Al3C2. Characterization of bulk samples has shown it has improved damage tolerance and oxidation resistance compared to its binary counterpart ZrC. Though a potential candidate for coatings applied for use in harsh environments, thin films of Zr2Al3C4 have not been reported. We have synthesized epitaxial Zr2Al3C4 thin films by pulsed cathodic arc deposition from three elemental cathodes, and have studied the effect of incident atomic flux ratio, deposition temperature, and choice of substrate on material quality. X-ray diffraction analysis showed that Zr2Al3C4 of the highest structural quality was obtained for growth on 4 H-SiC(001) substrate at 800 degrees C. Also, suppression of competing phases could be achieved on alpha-Al2O3(001) at elevated substrate temperatures. Very similar growth behavior to that of the well-known M(n+1)AX(n) phases - Al supersaturation, binary carbide intergrowth and high sensitivity to choice of substrate - indicates a strong connection between the two families of materials, despite their differences in structure and in chemistry. (C) 2015 Elsevier B.V. All rights reserved.
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| 25. |
- Landegren, Nils, 1986-, et al.
(författare)
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Comment on 'AIRE-deficient patients harbor unique high-affinity disease-ameliorating autoantibodies'
- 2019
-
Ingår i: eLife. - : ELIFE SCIENCES PUBLICATIONS LTD. - 2050-084X. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- The AIRE gene plays a key role in the development of central immune tolerance by promoting thymic presentation of tissue-specific molecules. Patients with AIRE-deficiency develop multiple autoimmune manifestations and display autoantibodies against the affected tissues. In 2016 it was reported that: i) the spectrum of autoantibodies in patients with AIRE-deficiency is much broader than previously appreciated; ii) neutralizing autoantibodies to type I interferons (IFNs) could provide protection against type 1 diabetes in these patients (Meyer et al., 2016). We attempted to replicate these new findings using a similar experimental approach in an independent patient cohort, and found no evidence for either conclusion.
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| 26. |
- Lue, Tom F., et al.
(författare)
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Summary of the recommendations on sexual dysfunctions in men
- 2004
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Ingår i: Journal of Sexual Medicine. - : Oxford University Press (OUP). - 1743-6109 .- 1743-6095. ; 1:1, s. 6-23
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction. There are few published guidelines for the management of sexual dysfunctions in men and women, despite the prevalence and lack of attention to these problems. Disorders of sexual function in men include erectile dysfunction, orgasm/ejaculation disorders, priapism, and Peyronie's disease. Aim. To provide evidence-based and expert-opinion consensus guidelines for the clinical management of men's sexual dysfunctions. Methods. An International Consultation in collaboration with major urological and sexual medicine societies assembled over 200 multidisciplinary experts from 60 countries into 17 consultation committees. Committee members established the scope and objectives for each chapter. Following intensive review of available data and publications, committees developed evidence-based guidelines in each area. Main Outcome Measure. New algorithms and guidelines for assessment and treatment of men's sexual dysfunction were developed. The Oxford system of evidence-based review was systematically applied. Expert opinion was based on systematic grading of the medical literature, in addition to cultural and ethical considerations. Results. Recommendations and guidelines for men's sexual dysfunction are presented. These guidelines were developed as evidence-based, patient-centered, and multidisciplinary in focus. For the clinical assessment and diagnosis of ED, a basic evaluation was recommended for all patients, with optional and specialized testing reserved for special cases. A new treatment algorithm is proposed. This algorithm provides a clinically relevant guideline for managing ED in the large majority of men. New treatment guidelines and algorithms are provided for men's orgasm and ejaculation disorders, including premature ejaculation, retrograde and delayed ejaculation. Finally, expert opinion-based guidelines for the clinical management of priapism and Peyronie's disease are provided. Conclusions. Additional research is needed to validate and extend these guidelines. Nonetheless, this summary encompasses the recommendations concerning men's sexual dysfunctions presented at the 2nd International Consultation on Sexual Medicine in Paris, France, June 28-July 1, 2003.
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| 27. |
- Majithia, Amit R, et al.
(författare)
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Rare variants in PPARG with decreased activity in adipocyte differentiation are associated with increased risk of type 2 diabetes
- 2014
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 111:36, s. 32-13127
-
Tidskriftsartikel (refereegranskat)abstract
- Peroxisome proliferator-activated receptor gamma (PPARG) is a master transcriptional regulator of adipocyte differentiation and a canonical target of antidiabetic thiazolidinedione medications. In rare families, loss-of-function (LOF) mutations in PPARG are known to cosegregate with lipodystrophy and insulin resistance; in the general population, the common P12A variant is associated with a decreased risk of type 2 diabetes (T2D). Whether and how rare variants in PPARG and defects in adipocyte differentiation influence risk of T2D in the general population remains undetermined. By sequencing PPARG in 19,752 T2D cases and controls drawn from multiple studies and ethnic groups, we identified 49 previously unidentified, nonsynonymous PPARG variants (MAF < 0.5%). Considered in aggregate (with or without computational prediction of functional consequence), these rare variants showed no association with T2D (OR = 1.35; P = 0.17). The function of the 49 variants was experimentally tested in a novel high-throughput human adipocyte differentiation assay, and nine were found to have reduced activity in the assay. Carrying any of these nine LOF variants was associated with a substantial increase in risk of T2D (OR = 7.22; P = 0.005). The combination of large-scale DNA sequencing and functional testing in the laboratory reveals that approximately 1 in 1,000 individuals carries a variant in PPARG that reduces function in a human adipocyte differentiation assay and is associated with a substantial risk of T2D.
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| 28. |
- Malitska, Julia
(författare)
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Negotiating Imperial Rule : Colonists and Marriage in the Nineteenth-century Black Sea Steppe
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- After falling under the power of the Russian Crown, the Northern Black Sea steppe from the end of eighteenth century crystallized as the Russian government’s prime venue for socioeconomic and sociocultural reinvention and colonization. Vast ethnic, sociocultural and even ecological changes followed. Present study is preoccupied with the marriage of the immigrant population from the German lands who came to the region in the course of its state orchestrated colonization, and was officially categorized as “German colonists.” The book illuminates the multiple ways in which marriage and household formation among the colonists was instrumentalized by the imperial politics in the Northern Black Sea steppe, and conditioned by socioeconomic rationality of its colonization. Marriage formation and dissolution among the colonists were gradually absorbed into the competencies of the colonial vertical power. Intending to control colonist marriage and household formation through the introduced marriage regime, the Russian government and its regional representatives lacked the actual means to exert this control at the local level. On the ground, however, imperial politics was mediated by the people it targeted, and by the functionaries tasked with its implementation. As the study reveals, the paramount importance was given to functional households and sustainable farms based on non-conflictual relations between parties. Situated on the crossroads of state, church, community, and personal interests, colonist marriage engendered clashes between secular and ecclesiastical bodies over the supremacy over it. The interplay of colonization as politics, and colonization as an imperial situation with respect to the marriage of the German colonists is explored in this book by concentrating on both norms and practices. Another important consideration is the ways gender and colonization constructed and determined one another reciprocally, both in legal norms and in actual practices. Secret divorces and unauthorized marriages, open and hidden defiance, imitations and unruliness, refashioning of rituals and discourses, and desertions – a number of strategies and performances which challenged and negotiated the marriage regime in the region, were scholarly examined for the first time in this book.
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| 29. |
- Manry, Jérémy, et al.
(författare)
-
The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies.
- 2022
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 119:21
-
Tidskriftsartikel (refereegranskat)abstract
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.
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| 30. |
- Manzoni, Claudia, et al.
(författare)
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Genome-wide analyses reveal a potential role for the MAPT, MOBP, and APOE loci in sporadic frontotemporal dementia
- 2024
-
Ingår i: American Journal of Human Genetics. - 0002-9297. ; 111:7, s. 1316-1329
-
Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia after Alzheimer disease (AD). Efforts in the field mainly focus on familial forms of disease (fFTDs), while studies of the genetic etiology of sporadic FTD (sFTD) have been less common. In the current work, we analyzed 4,685 sFTD cases and 15,308 controls looking for common genetic determinants for sFTD. We found a cluster of variants at the MAPT (rs199443; p = 2.5 × 10−12, OR = 1.27) and APOE (rs6857; p = 1.31 × 10−12, OR = 1.27) loci and a candidate locus on chromosome 3 (rs1009966; p = 2.41 × 10−8, OR = 1.16) in the intergenic region between RPSA and MOBP, contributing to increased risk for sFTD through effects on expression and/or splicing in brain cortex of functionally relevant in-cis genes at the MAPT and RPSA-MOBP loci. The association with the MAPT (H1c clade) and RPSA-MOBP loci may suggest common genetic pleiotropy across FTD and progressive supranuclear palsy (PSP) (MAPT and RPSA-MOBP loci) and across FTD, AD, Parkinson disease (PD), and cortico-basal degeneration (CBD) (MAPT locus). Our data also suggest population specificity of the risk signals, with MAPT and APOE loci associations mainly driven by Central/Nordic and Mediterranean Europeans, respectively. This study lays the foundations for future work aimed at further characterizing population-specific features of potential FTD-discriminant APOE haplotype(s) and the functional involvement and contribution of the MAPT H1c haplotype and RPSA-MOBP loci to pathogenesis of sporadic forms of FTD in brain cortex.
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| 31. |
- Najeeb, P. K., 1986-, et al.
(författare)
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Stability and Cooling of the C72- Dianion
- 2023
-
Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 131:11
-
Tidskriftsartikel (refereegranskat)abstract
- We have studied the stability of the smallest long-lived all carbon molecular dianion (C72-) in new time domains and with a single ion at a time using a cryogenic electrostatic ion-beam storage ring. We observe spontaneous electron emission from internally excited dianions on millisecond timescales and monitor the survival of single colder C72- molecules on much longer timescales. We find that their intrinsic lifetime exceeds several minutes - 6 orders of magnitude longer than established from earlier experiments on C72-. This is consistent with our calculations of vertical electron detachment energies predicting one inherently stable isomer and one isomer which is stable or effectively stable behind a large Coulomb barrier for C72-→C7-+e- separation.
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| 32. |
- Nikolaevsky, Mark, et al.
(författare)
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Possible monoclinic distortion of Mo2GaC under high pressure
- 2020
-
Ingår i: Journal of Applied Physics. - : AMER INST PHYSICS. - 0021-8979 .- 1089-7550. ; 127:14
-
Tidskriftsartikel (refereegranskat)abstract
- In this work, we present high-pressure diffraction results of the Mo-based M-n (+) (1)AX(n) phase, Mo2GaC. A diamond anvil cell was used to compress the material up to 30 GPa, and x-ray diffraction was used to determine the structure and unit cell parameters as a function of pressure. Somewhat surprisingly, we find that, at 295 +/- 25 GPa, the bulk modulus of Mo2GaC is the highest reported of all the MAX phases measured to date. The c/a ratio increases with increasing pressure. At above 15 GPa, a splitting in the (1 0 0) reflection occurs. This result, coupled with new density functional theory calculations, suggests that a second order phase transition to possibly a mixture of hexagonal and monoclinic structures may explain this splitting. Such experimentally and theoretically supported phase transitions were not predicted in previously published calculations.
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| 33. |
- Oikonomou, Vasileios, et al.
(författare)
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The Role of Interferon-γ in Autoimmune Polyendocrine Syndrome Type 1.
- 2024
-
Ingår i: The New England journal of medicine. - 1533-4406. ; 390:20, s. 1873-1884
-
Tidskriftsartikel (refereegranskat)abstract
- Autoimmune polyendocrine syndrome type 1 (APS-1) is a life-threatening, autosomal recessive syndrome caused by autoimmune regulator (AIRE) deficiency. In APS-1, self-reactive T cells escape thymic negative selection, infiltrate organs, and drive autoimmune injury. The effector mechanisms governing T-cell-mediated damage in APS-1 remain poorly understood.We examined whether APS-1 could be classified as a disease mediated by interferon-γ. We first assessed patients with APS-1 who were participating in a prospective natural history study and evaluated mRNA and protein expression in blood and tissues. We then examined the pathogenic role of interferon-γ using Aire-/-Ifng-/- mice and Aire-/- mice treated with the Janus kinase (JAK) inhibitor ruxolitinib. On the basis of our findings, we used ruxolitinib to treat five patients with APS-1 and assessed clinical, immunologic, histologic, transcriptional, and autoantibody responses.Patients with APS-1 had enhanced interferon-γ responses in blood and in all examined autoimmunity-affected tissues. Aire-/- mice had selectively increased interferon-γ production by T cells and enhanced interferon-γ, phosphorylated signal transducer and activator of transcription 1 (pSTAT1), and CXCL9 signals in multiple organs. Ifng ablation or ruxolitinib-induced JAK-STAT blockade in Aire-/- mice normalized interferon-γ responses and averted T-cell infiltration and damage in organs. Ruxolitinib treatment of five patients with APS-1 led to decreased levels of T-cell-derived interferon-γ, normalized interferon-γ and CXCL9 levels, and remission of alopecia, oral candidiasis, nail dystrophy, gastritis, enteritis, arthritis, Sjögren's-like syndrome, urticaria, and thyroiditis. No serious adverse effects from ruxolitinib were identified in these patients.Our findings indicate that APS-1, which is caused by AIRE deficiency, is characterized by excessive, multiorgan interferon-γ-mediated responses. JAK inhibition with ruxolitinib in five patients showed promising results. (Funded by the National Institute of Allergy and Infectious Diseases and others.).
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| 34. |
- Rosen, Gail, et al.
(författare)
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Circuit Implementation of a 2-D Gradient Source Localizer
- 2004
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Ingår i: PROCEEDINGS OF THE IEEE SENSORS 2004, VOLS 1-3. ; , s. 206-206
-
Konferensbidrag (refereegranskat)abstract
- Gradient field localization, such as chemical and heat source location, is a complex problem, yet few designs have been proposed. Examples are locating fires, thermal leaks in insulation, explosive vapors, illegal substances, and chemical leaks. In this paper, we propose one 4 sensor stationary array to localize the direction-of-arrival (DOA) of a temperature source and model the approach on our previous biologically-inspired array processing technique. Several variants of the algorithm are shown, and with each degree of sophistication, it significantly reduces the DOA variance caused by noisy measurement conditions. Next, a clean 4/8-sensor version of the array was constructed, and it is shown that sensor cooperation improves the adaptation in diffusive, turbulent, and noisy environments.
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| 35. |
- Rosen, Gail, et al.
(författare)
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Implementation of a Hebbian chemoreceptor model for diffusive source localization
- 2009
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Ingår i: Biosystems (Amsterdam. Print). - : Elsevier BV. - 0303-2647 .- 1872-8324. ; 96:3, s. 223-236
-
Tidskriftsartikel (refereegranskat)abstract
- While new approaches to chemical localization have been proposed, animals are still widely used for locating landmines and illegal substances. Existing electronic noses still do not have the necessary sensitivity and accuracy. By modeling a cell's chemical detection system, we can gain insight into the basic "olfactory" system. We use an inspiration from chemotaxis and Hebbian learning to enhance localization and tracking of gradient sources, which can be applied to both chemicals and heat. The eukaryotic receptor clustering model shows improvement over previous prokaryotic chemotaxis-inspired methods that do not take into account receptor clustering. Receptor clustering essentially adapts receptors spatio-temporally. For a mobile simulation. our method locates the source in less convergence time than the other chemotaxis algorithms and insignificantly less time compared to no spatio-temporal filtering (e.g. a single-sensor memoryless case). We then show that local regions of receptor cooperation have the best performance reflecting observations of receptor behavior in biology. To demonstrate the performance of this system in real-time, a stationary 4/8-sensor version of the array is implemented, and the algorithm improves the convergence time, mean, and variance of the Direction-of-Arrival calculation in diffusive, turbulent, and noisy environments.
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| 36. |
- Sikkema, Lisa, et al.
(författare)
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An integrated cell atlas of the lung in health and disease
- 2023
-
Ingår i: Nature Medicine. - : Springer Nature. - 1078-8956 .- 1546-170X. ; 29:6, s. 1563-1577
-
Tidskriftsartikel (refereegranskat)abstract
- Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of individual studies and capture the variability present in the population. Here we present the integrated Human Lung Cell Atlas (HLCA), combining 49 datasets of the human respiratory system into a single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents a consensus cell type re-annotation with matching marker genes, including annotations of rare and previously undescribed cell types. Leveraging the number and diversity of individuals in the HLCA, we identify gene modules that are associated with demographic covariates such as age, sex and body mass index, as well as gene modules changing expression along the proximal-to-distal axis of the bronchial tree. Mapping new data to the HLCA enables rapid data annotation and interpretation. Using the HLCA as a reference for the study of disease, we identify shared cell states across multiple lung diseases, including SPP1 + profibrotic monocyte-derived macrophages in COVID-19, pulmonary fibrosis and lung carcinoma. Overall, the HLCA serves as an example for the development and use of large-scale, cross-dataset organ atlases within the Human Cell Atlas.
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| 37. |
- Stenius, Ivan, et al.
(författare)
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Hydroelastic Effects in Slamming Loaded Panels
- 2011
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Ingår i: 11th International Conference on Fast Sea Transportation, FAST 2011 - Proceedings. - : American Society of Naval Engineers. ; , s. 644-652
-
Konferensbidrag (refereegranskat)abstract
- The paper discusses challenges in modeling and quantification of hydroelastic effects in panel-water impacts and summarizes results from numerical and experimental studies. Kinematic and inertia related hydroelastic effects are discussed and exemplified in relation to pressure distributions and structural responses. Hydroelastic effects are quantified by comparing hydroelastic results with rigid/ quasi-static reference results where the hydrodynamic loading is treated as unaffected by the structural deformation (rigid) and the structural response is treated as unaffected by structural inertia (quasi-static). The formulation of non-coupled reference solutions in experimental studies is particularly challenging and the paper addresses this problem by outlining a semi-empirical approach to reach such solutions. For those impact situations were the hydroelastic interaction seems to have a significant effect, it is found both numerically and experimentally that the hydroelastic effects are amplifying the structural responses in comparison to the rigid/quasi-static reference solutions. Two approaches for characterization of impact situations regarding the involved hydroelastic effects in relation to panel properties and impact conditions are discussed and exemplified. These approaches can tentatively be used to evaluate the hydroelastic effects in design situations.
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| 38. |
- Stockett, Mark H., et al.
(författare)
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Nonstatistical fragmentation of large molecules
- 2014
-
Ingår i: Physical Review A. Atomic, Molecular, and Optical Physics. - 1050-2947 .- 1094-1622. ; 89:3
-
Tidskriftsartikel (refereegranskat)abstract
- We present experimental evidence for the dominance of prompt single-atom knockout in fragmenting collisions between large polycyclic aromatic hydrocarbon cations and He atoms at center-of-mass energies close to 100 eV. Such nonstatistical processes are shown to give highly reactive fragments. We argue that nonstatistical fragmentation is dominant for any sufficiently large molecular system under similar conditions.
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| 39. |
- Stockman, Jessica, et al.
(författare)
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Ankle-foot orthoses among children with cerebral palsy : a cross-sectional population-based register study of 8,928 children living in Northern Europe
- 2023
-
Ingår i: BMC Musculoskeletal Disorders. - : BMC. - 1471-2474. ; 24:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cerebral palsy (CP) is an umbrella term where an injury to the immature brain affects muscle tone and motor control, posture, and at times, the ability to walk and stand. Orthoses can be used to improve or maintain function. Ankle-foot orthoses (AFOs) are the most frequently used orthoses in children with CP. However, how commonly AFOs are used by children and adolescents with CP is still unknown. The aims of this study were to investigate and describe the use of AFOs in children with CP in Sweden, Norway, Finland, Iceland, Scotland, and Denmark, and compare AFO use between countries and by gross motor function classification system (GMFCS) level, CP subtype, sex, and age.METHOD: Aggregated data on 8,928 participants in the national follow-up programs for CP for the respective countries were used. Finland does not have a national follow-up program for individuals with CP and therefore a study cohort was used instead. Use of AFOs were presented as percentages. Logistic regression models were used to compare the use of AFOs among countries adjusted for age, CP subtype, GMFCS level, and sex.RESULTS: The proportion of AFO use was highest in Scotland (57%; CI 54-59%) and lowest in Denmark (35%; CI 33-38%). After adjusting for GMFCS level, children in Denmark, Finland, and Iceland had statistically significantly lower odds of using AFOs whereas children in Norway and Scotland reported statistically significantly higher usage than Sweden.CONCLUSION: In this study, the use of AFOs in children with CP in countries with relatively similar healthcare systems, differed between countries, age, GMFCS level, and CP subtype. This indicates a lack of consensus as to which individuals benefit from using AFOs. Our findings present an important baseline for the future research and development of practical guidelines in terms of who stands to benefit from using AFOs.
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| 40. |
- Thomas, Richard D., et al.
(författare)
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DESIREE : Physics with cold stored ion beams
- 2015
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Ingår i: DR2013. - : EDP Sciences. ; 84, s. 01004-01004
-
Konferensbidrag (refereegranskat)abstract
- Here we will briefly describe the commissioning of the Double ElectroStatic Ion Ring ExpEriment (DESIREE) facility at Stockholm University, Sweden. This device uses purely electrostatic focussing and deflection elements and allows ion beams of opposite charge to be confined under extreme high vacuum and cryogenic conditions in separate rings and then merged over a common straight section. This apparatus allows for studies of interactions between cations and anions at very low and well-defined centre-of-mass energies (down to a few meV) and at very low internal temperatures (down to a few K).
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| 41. |
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| 42. |
- Tucker, Mark D, et al.
(författare)
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Substrate orientation effects on the nucleation and growth of the M(n+1)AX(n) phase Ti2AlC
- 2011
-
Ingår i: JOURNAL OF APPLIED PHYSICS. - : American Institute of Physics. - 0021-8979 .- 1089-7550. ; 109:1, s. 014903-
-
Tidskriftsartikel (refereegranskat)abstract
- The M(n+1)AX(n) (MAX) phases are ternary compounds comprising alternating layers of a transition metal carbide or nitride and a third "A-group" element. The effect of substrate orientation on the growth of Ti2AlC MAX phase films was investigated by studying pulsed cathodic arc deposited samples grown on sapphire cut along the (0001), (10 (1) over bar0), and (1 (1) over bar 02) crystallographic planes. Characterization of these samples was by x-ray diffraction, atomic force microscopy, and cross-sectional transmission electron microscopy. On the (10 (1) over bar0) substrate, tilted (10 (1) over bar8) growth of Ti2AlC was found, such that the TiC octahedra of the MAX phase structure have the same orientation as a spontaneously formed epitaxial TiC sublayer, preserving the typical TiC-Ti2AlC epitaxial relationship and confirming the importance of this relationship in determining MAX phase film orientation. An additional component of Ti2AlC with tilted fiber texture was observed in this sample; tilted fiber texture, or axiotaxy, has not previously been seen in MAX phase films.
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| 43. |
- Tucker, Mark, et al.
(författare)
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Filtered pulsed cathodic arc deposition of fullerene-like carbon and carbon nitride films
- 2014
-
Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 115:14, s. 144312-
-
Tidskriftsartikel (refereegranskat)abstract
- Carbon and carbon nitride films (CNx , 0 ≤ x ≤ 0.26) were deposited by filtered pulsed cathodic arc and were investigated using transmission electron microscopy and X-ray photoelectron spectroscopy. A “fullerene-like” (FL) structure of ordered graphitic planes, similar to that of magnetron sputtered FL-CNx films, was observed in films deposited at 175 °C and above, with N2 pressures of 0 and 0.5 mTorr. Higher substrate temperatures and significant nitrogen incorporation are required to produce similar FL structure by sputtering, which may, at least in part, be explained by the high ion charge states and ion energies characteristic of arc deposition. A gradual transition from majority sp3-hybridized films to sp2 films was observed with increasing substrate temperature. High elastic recovery, an attractive characteristic mechanical property of FL-CNx films, is evident in arc-deposited films both with and without nitrogen content, and both with and without FL structure.
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