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- Connolly, C, et al.
(författare)
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Enhanced immune response to MMP3 stimulation in microglia expressing mutant huntingtin
- 2016
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Ingår i: Neuroscience. - : Elsevier BV. - 1873-7544 .- 0306-4522. ; 325, s. 74-88
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Tidskriftsartikel (refereegranskat)abstract
- Huntington's Disease (HD) is an inherited neurodegenerative disease caused by a polyglutamine expansion in the huntingtin protein. The YAC128 mouse model of HD expresses the full-length human huntingtin protein with 128 CAG repeats and replicates the phenotype and neurodegeneration that occur in HD. Several studies have implicated a role for neuroinflammation in HD pathogenesis. Studies on presymptomatic HD patients have illustrated microgliosis (activated microglia) in brain regions affected in HD. Mutant huntingtin expressing isolated primary monocytes (human HD patients) and primary macrophages (YAC128) are overactive in response to lipopolysaccharide (LPS) stimulation. In this study we demonstrate that cultured primary microglia (the resident immune cells of the brain cells) from YAC128 mice differentially express a wide number of cytokines compared to wildtype microglia cultures in response to LPS. Furthermore, this study outlines a direct interaction between mutant huntingtin and cytokine secretion in HD microglia. Increased cytokine release in YAC128 microglia can be blocked by cannabinoid activation or by mutant huntingtin knockdown with anti-sense oligonucleotide treatment. Matrix metalloprotease 3 (MMP3), an endogenous neuronal activator of microglia, also induces increased cytokine release from YAC128 microglia compared to wildtype microglia. We found elevated MMP levels in HD CSF, and MMP levels correlate with disease severity in HD. These data support a novel role for MMPs and microglial activation in HD pathogenesis. With an improved understanding of the specific cellular processes involved in HD neuroinflammation, novel therapeutic agents targeting these processes can be developed and hold great promise in the treatment of HD.
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- Van Raamsdonk, Jeremy M., et al.
(författare)
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Testicular degeneration in Huntington disease
- 2007
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Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 26:3, s. 512-520
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Tidskriftsartikel (refereegranskat)abstract
- Huntington disease (HD) is an adult onset, neurodegenerative disorder that results from CAG expansion in the HD gene. Recent work has demonstrated testicular degeneration in mouse models of HD and alterations in the hypothalamic-pituitary-gonadal (HPG) axis in HD patients. Here, we show that HD patients have specific testicular pathology with reduced numbers of germ cells and abnormal seminiferous tubule morphology. In the YAC128 mouse model, testicular degeneration develops prior to 12 months of age, but at 12 months, there is no evidence for decreased testosterone levels or loss of GnRH neurons in the hypothalamus. This suggests that testicular pathology results from a direct toxic effect of mutant huntingtin in the testis and is supported by the fact that huntingtin is highly expressed in the affected cell populations in the testis. Understanding the pathogenesis of HD in the testis may reveal common critical pathways which lead to degeneration in both the brain and testis.
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- Björkqvist, Maria, 1959-, et al.
(författare)
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Colonization pattern of coagulase-negative staphylococci in preterm neonates and the relation to bacteremia
- 2010
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Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - : Springer. - 0934-9723 .- 1435-4373. ; 29:9, s. 1085-1093
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Tidskriftsartikel (refereegranskat)abstract
- Coagulase-negative staphylococci (CoNS) are the major cause of sepsis in extreme preterm (EPT) newborns, but data on the CoNS colonization in EPT newborns prior to invasive infection are limited. Our aim was to describe the early establishment of the CoNS microflora in EPT newborns and to compare the colonization pattern in neonates with and without positive CoNS blood cultures. From a cohort of 46 EPT neonates, newborns with positive CoNS blood culture were identified (n = 10) and compared with matched controls. Samples for bacterial cultures were obtained repetitively from nares, perineum, and umbilicus. All CoNS isolates were characterized using the PhenePlate system for biochemical fingerprinting. Persistent CoNS strains were found on day 2-3 after delivery in 7/20 newborns, and there was a tendency for earlier colonization in nares than in the perineum or umbilicus. The CoNS blood strains were prevalent in superficial sites prior to positive blood culture (11/14 blood strains), but no single invasive pathway was identified. Most CoNS blood strains (9/14) persisted on superficial sites after antibiotic treatment. We hypothesize that the invasive pathways in neonatal CoNS sepsis are complex and that the colonization of mucosal membranes and umbilical catheters might be of equal importance.
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- Björkqvist, Oskar, et al.
(författare)
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A Novel Efficient Multiple Input Single Output RF Energy Harvesting Rectification Scheme
- 2017
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Ingår i: 2017 IEEE Antennas and Propagation Society International Symposium, Proceedings. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781538632840 ; , s. 1605-1606
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Konferensbidrag (refereegranskat)abstract
- In this work an implementation of an ambient radio frequency harvesting system utilizing multiple input single output approach is demonstrated. Measurements of typical ambient radiation have been conducted with respect to power levels and frequency to determine which communication signals are suitable for harvesting. The measurement campaign showed that the WiFi frequency band at 2.45 GHz is a good candidate for indoors applications. A Greinacher voltage doubler is used for the rectification. A multiple input single output - MISO scalable scheme approach is implemented that is able to provide a DC differential output voltage. Simulated and experimental results proved the MISO rectenna to be an efficient scheme for RF harvesting.
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- Dahlberg, Oskar, et al.
(författare)
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A Novel 32 Port Cube MIMO Combining Broadside and Endfire Radiation Patterns for Full Azimuthal Coverage - A Modular Unit Approach for a Massive MIMO System
- 2017
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Ingår i: 2017 IEEE Antennas and Propagation Society International Symposium, Proceedings. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781538632840 ; , s. 1641-1642
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Konferensbidrag (refereegranskat)abstract
- In this paper we propose a novel 32 antenna port multiple-input-multiple-output (MIMO)-cube. The total volume of the cube is 320 x 320 x 120 mm(3) . On two faces, endfire radiating linear tapered slot antennas (LTSAs) are placed and on the remaining sides, a mix of both LTSAs and broadside patch antennas are placed. In total 16 LTSAs and 8 dual polarized patches are used. The LTSA is designed to operate at the GSM and 3G bands, from 1.7 to 2.3 GHz. A corrugation pattern is introduced along the edges of the LTSAs covering one face to increase directivity and decrease sidelobes. The LTSAs are placed in two different orientations in order to receive two polarisations. The patch antenna is dual band and dual polarized. It operates in the frequency bands 2.4-2.5 and 5.45-5.6 GHz where Wi-Fi communication is made. The spatial placement, with antennas on all sides of the cuboid, ensures full azimuthal coverage despite the high directivity of the antennas. Using different antennas on different faces of the cube further optimizes the volume efficiency of the cube for azimuthal coverage.
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- de la Cour, Charlotta, et al.
(författare)
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A-like cells in the rat stomach contain ghrelin and do not operate under gastrin control
- 2001
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Ingår i: Regulatory Peptides. - 1873-1686. ; 99:2-3, s. 141-150
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Tidskriftsartikel (refereegranskat)abstract
- Ghrelin is a 28 a.a. gastric peptide, recently identified as a natural ligand of the growth hormone secretagogue receptor (orphan receptor distinct from the receptor fur growth hormone releasing hormone). In the present study. radioimmunoassay demonstrated ghrelin-like material in the rat oxyntic mucosa with moderate amounts also in antrum and duodenum. Small amounts: were found in the distal intestines and pancreas. Northern blot analysis revealed abundant ghrelin mRNA in thr oxyntic mucosa. Immunocytochemistry demonstrated ghrelin-immunoreactivity in endocrine-like cells in the oxyntic mucosa. Such cells occurred in low numbers also in the antrum and duodenum. The mt oxyntic mucosa is rich in endocrine (chromogranin A/pancreastatin-immunoreactive) cells. such as the histamine-rich ECL cells (65-75% of the endocrine cells). the A-like cells (20-25%) and the D cells (somatostatin cells) (10%). The ghrelin-immunoreactive (IR) cells contained pancreastatin but differed from ECL cells and D cells by being devoid of histamine-forming enzyme (ECL cell constituent) and somatostatin (D cell constituent). Hence. ghrelin seems to occur in the A-like cells. The ghrelin-IR cells in the antrum were distinct from the gastrin cells, the serotonin-containing enterochromaffin cells and the D cells. Conceivably, ghrelin cells in the antrum and distally in the intestines also belong to the A-like cell population. The concentration of ghrelin in the circulation was: lowered by about 80% following the surgical removal of the acid-producing part of the stomach in line with the view that the oxyntic mucosa is the major sourer of ghrelin. The serum ghrelin concentration was higher in fasted rats than in fed rats; it was reduced upon re-feeding and seemed unaffected by 1-week treatment with the proton pump inhibitor omeprazole, resulting in elevated serum gastrin concentration. Infusion of gastrin-17 for 2 days failed to raise the serum ghrelin concentration. Omeprazole treatment for 10 weeks raised the level of HDC mRNA but not that of ghrelin mRNA or somatostatin mRNA in the oxyntic mucosa. Hence, unlike the ECL cells, ghrelin-containing A-like cells do not seem to operate under gastrin control.
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- Große, Christine, 1974-, et al.
(författare)
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Collaboration and Decision-making in Response Planning for Power Shortages : The Swedish Policy
- 2017
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Electricity is a key resource for the majority of societal functions and constitutes an important sector in the critical infrastructure of modern societies. Disturbances in power supply can have cascading effects on interdependent public sectors and ordinary citizens. However, it seems nearly impossible to completely prevent the occurrence of power shortages. Strategies to address temporary power losses are therefore essential. This paper aims to increase the understanding of national policies to manage the early consequences of power outages. Therefore, we critically review the Swedish national policy called Styrel as part of Swedish Crisis Management System. In the scientific literature, there are few examples similar to Styrel for handling emergencies in the electricity system. Particularly, we seek to discover related risks and benefits, conditions and constraints, as well as effects for specific stakeholders. We argue that the approach cannot yet be considered as fully developed. Three areas requiring improvement are identified. First, the scope and terms of the process must be specified. Second, (better) quality management seems necessary. Third, people responsible for identifying and prioritizing power consumers critical to local society need better decision aid. Improvements could facilitate risk-communication and collaboration among actors as well as decision-making and organisational learning.
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