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- Saliba-Gustafsson, P., et al.
(författare)
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Subclinical atherosclerosis and its progression are modulated by PLIN2 through a feed-forward loop between LXR and autophagy
- 2019
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 660-675
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Tidskriftsartikel (refereegranskat)abstract
- Background Hyperlipidaemia is a major risk factor for cardiovascular disease, and atherosclerosis is the underlying cause of both myocardial infarction and stroke. We have previously shown that the Pro251 variant of perilipin-2 reduces plasma triglycerides and may therefore be beneficial to reduce atherosclerosis development. Objective We sought to delineate putative beneficial effects of the Pro251 variant of perlipin-2 on subclinical atherosclerosis and the mechanism by which it acts. Methods A pan-European cohort of high-risk individuals where carotid intima-media thickness has been assessed was adopted. Human primary monocyte-derived macrophages were prepared from whole blood from individuals recruited by perilipin-2 genotype or from buffy coats from the Karolinska University hospital blood central. Results The Pro251 variant of perilipin-2 is associated with decreased intima-media thickness at baseline and over 30 months of follow-up. Using human primary monocyte-derived macrophages from carriers of the beneficial Pro251 variant, we show that this variant increases autophagy activity, cholesterol efflux and a controlled inflammatory response. Through extensive mechanistic studies, we demonstrate that increase in autophagy activity is accompanied with an increase in liver-X-receptor (LXR) activity and that LXR and autophagy reciprocally activate each other in a feed-forward loop, regulated by CYP27A1 and 27OH-cholesterol. Conclusions For the first time, we show that perilipin-2 affects susceptibility to human atherosclerosis through activation of autophagy and stimulation of cholesterol efflux. We demonstrate that perilipin-2 modulates levels of the LXR ligand 27OH-cholesterol and initiates a feed-forward loop where LXR and autophagy reciprocally activate each other; the mechanism by which perilipin-2 exerts its beneficial effects on subclinical atherosclerosis.
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- Graafsma, Heinz, et al.
(författare)
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PERCIVAL soft X-ray imager
- 2013
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Ingår i: IEEE Nuclear Science Symposium Conference Record. - : IEEE conference proceedings. - 9781479905348 ; , s. Art. no. 6829506-
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Konferensbidrag (refereegranskat)abstract
- Our goal is to provide the scientific community with a large (10cm × 10cm) pixellated detector featuring a large dynamic range (1-105 photons), good spatial resolution (27μm), good Quantum Efficiency (QE) in the low energy range (250eV-1keV), variable readout speed (up to 120 frames/s), i.e. with characteristics compatible with user needs at today's of low-energy Free Electron Lasers (FEL) and synchrotron sources. © 2013 IEEE.
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- Ager, S, et al.
(författare)
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Retroviral display of antibody fragments; interdomain spacing strongly influences vector infectivity
- 1996
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Ingår i: Human Gene Therapy. - : Mary Ann Liebert Inc. - 1043-0342 .- 1557-7422. ; 7:17, s. 2157-2164
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Tidskriftsartikel (refereegranskat)abstract
- Five different single-chain antibody fragments (scFv) against human cell-surface antigens were displayed on murine ecotropic retroviral vectors by fusing them to the Moloney SU envelope glycoprotein. The spacing between the scFv and the SU glycoprotein was varied by fusing the scFv to residue +7 or to residue +1 of Moloney SU and by inserting linker sequences of different lengths between the domains. All of the chimeric envelopes were efficiently incorporated into vector particles and could bind to human cells through their displayed antibody fragments, but did not infect them. The spacing between the scFvs and the SU glycoproteins had no significant effect on the efficiency of envelope expression or viral incorporation and did not affect the binding properties of the chimeric envelopes, nor did it influence the efficiency of targeted gene delivery to human cells by scFv-displaying vectors. However, on murine fibroblasts the infectivity of vectors incorporating the chimeric envelopes was strongly influenced by the length of the interdomain spacer. The titers were very low when the single-chain antibodies were fused through a tripeptide linker to SU residue +7 and were greatly enhanced (up to 10(5)-fold) when they were fused to SU residue +1 through a heptapeptide linker. These results point to the importance of steric interactions between the domains of chimeric envelope glycoproteins and may have implications for retroviral vector design for human gene therapy.
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- Badri, M., et al.
(författare)
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Clinical and microbiological features of bacteraemia with Gram-positive anaerobic cocci : a population-based retrospective study
- 2019
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Ingår i: Clinical Microbiology and Infection. - : Elsevier BV. - 1198-743X. ; 25:6, s. 1-760
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Gram-positive, anaerobic cocci (GPAC) can cause infections in humans. Only a few cases of bacteraemia with GPAC have been reported. We describe the clinical and microbiological characteristics of GPAC bacteraemia. Methods: A retrospective population-based study of GPAC bacteraemia 2012–2016 in southern Sweden was performed. GPAC were identified using matrix-associated laser desorption ionization time-of-flight mass spectrometry or 16S rRNA gene sequencing. Etests were used to determine antibiotic susceptibilities. Data on patient and infection characteristics, treatment, and outcome were collected from the medical records. Results: A total of 226 episodes of GPAC bacteraemia in adults were studied; this corresponds to an annual incidence of 3.4 cases per 100,000 persons per year. The bacteria identified were Anaerococcus spp. (n = 43), Atopobium spp. (n = 7), Blautia spp. (n = 1), Finegoldia spp. (n = 15), Parvimonas spp. (n = 100), Peptoniphilus spp. (n = 52), Peptostreptococcus spp. (n = 2), and Ruminococcus spp. (n = 9) of which 200 isolates were identified to the species level. Resistance to imipenem and piperacillin was not identified, whereas resistance among the 229 isolates to penicillin was detected in four, to metronidazole in six, and clindamycin in 16 isolates. The median age of patients was 73 years (55–83, IQR), 57% were male and comorbidities were common. Fifty-one per cent of infections were polymicrobial. In 60% of cases a focus of infection was identified. Forty per cent of patients had either organ dysfunction or shock. The 30-day mortality was 11%, and nosocomial infections were over-represented among the deceased. Conclusions: GPAC bacteraemia is much more common than previously reported. GPAC-bacteraemia is a condition with significant mortality mainly affecting elderly persons with comorbidities.
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- Bergman, B, et al.
(författare)
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An intraindividual clinical comparison of 2 metal-ceramic systems.
- 1999
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Ingår i: International Journal of Prosthodontics. - 0893-2174 .- 1139-9791. ; 12:5, s. 444-7
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: It has been questioned whether the surface and color of the ceramic and the metal-ceramic bond strength of a titanium-ceramic system are comparable to those of a conventional noble alloy-ceramic system. It was therefore the aim of this study to carry out an intraindividual clinical comparison between crowns fabricated according to the Procera system (titanium copings veneered with a low-fusing ceramic) and noble-alloy copings veneered with a medium-fusing ceramic. MATERIALS AND METHODS: Twenty-one crown pairs were fabricated for eighteen patients; three of the patients were each provided with two crown pairs. After 2 years nineteen crown pairs in sixteen patients could be compared. Clinical examinations were performed by two calibrated dentists who are long experienced in prosthetic dentistry. The crowns were rated according to the California Dental Association system. In addition, Bleeding Index and Margin Index were evaluated. RESULTS: After 2 years the quality of surface and color of the ceramic material seemed to have deteriorated more in titanium-ceramic crowns than in conventional metal-ceramic crowns, although the difference was not statistically significant. Regarding anatomic form, margin integrity, Bleeding Index, and Margin Index the differences between the two crown systems were small. CONCLUSION: The low-fusing ceramics have been subject to improvements during the last few years. Their bond strength to titanium seems to be comparable to that of conventional metal-ceramic systems. However, in the long run one problem may be the surface and color stability of low-fusing ceramics. To make extended long-term comparisons between the two metal-ceramic systems possible the present patient material will be followed for a longer period than the current 2 years.
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- Lindh, T, et al.
(författare)
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Tooth-implant supported fixed prostheses : A retrospective multicenter study
- 2001
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Ingår i: International Journal of Prosthodontics. - 0893-2174 .- 1139-9791. ; 14:4, s. 321-328
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of this retrospective multicenter study on implants combined with natural teeth was to investigate the implant survival rate and loss of marginal bone, as well as indications and complications pertinent to this form of implant therapy. Materials and Methods: The study comprised 185 implants in 111 patients from six different clinics in Sweden. Gathering of data, which were taken from patient records, followed a strict protocol. The registrations included indications for treatment, failure of implants, radiographs from baseline and follow-up, and information on complications. Results: The cumulative implant survival was found to be 95.4% (standard error 4.5%) up to 3 years of follow-up. The marginal bone level at baseline was lower in the maxilla compared with the mandible (P = .015), but any further loss did not differ between the jaws. The most severe complication other than loss of osseointegration (6/185) or periimplant infections (4/183) was intrusion of the abutment teeth, which occurred in 5% of the cases. In all instances, the intrusion was seen in constructions with nonrigid forms of connection between the implants and teeth. Conclusion: The tooth-implant supported prosthesis using the Branemark system is in the short term an equally predictable treatment as the completely implant-supported prosthesis concerning implant survival and loss of marginal bone. When combining implants and teeth, a rigid form of connection should be used to prevent tooth intrusion.
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- Monti, Paolo, et al.
(författare)
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Green mobile backhaul in heterogeneous wireless deployments
- 2013
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Ingår i: Asia Communications and Photonics Conference, ACP 2013. - Washington, D.C. : Optical Society of America.
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Konferensbidrag (refereegranskat)abstract
- This tutorial first introduces and describes different backhaul technological and architectural options (i.e., fiber-, microwave-, and copper-based), then it discusses their impact on the energy consumption of current and future heterogeneous mobile wireless access deployments.
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