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- Abdesselam, A., et al.
(författare)
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The ATLAS semiconductor tracker end-cap module
- 2007
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 575:3, s. 353-389
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Tidskriftsartikel (refereegranskat)abstract
- The challenges for the tracking detector systems at the LHC are unprecedented in terms of the number of channels, the required read-out speed and the expected radiation levels. The ATLAS Semiconductor Tracker. (SCT) end-caps have a total of about 3 million electronics channels each reading out every 25 ns into its own on-chip 3.3 mu s buffer. The highest anticipated dose after 10 years operation is 1.4x10(14) cm(-2) in units of 1 MeV neutron equivalent (assuming the damage factors scale with the non-ionising energy loss). The forward tracker has 1976 double-sided modules, mostly of area similar to 70 cm(2), each having 2 x 768 strips read out by six ASICs per side. The requirement to achieve an average perpendicular radiation length of 1.5% X-0, while coping with up to 7 W dissipation per module (after irradiation), leads to stringent constraints on the thermal design. The additional requirement of 1500e(-) equivalent noise charge (ENC) rising to only 1800e(-) ENC after irradiation, provides stringent design constraints on both the high-density Cu/Polyimide flex read-out circuit and the ABCD3TA read-out ASICs. Finally, the accuracy of module assembly must not compromise the 16 mu m (r phi) resolution perpendicular to the strip directions or 580 mu m radial resolution coming from the 40 mrad front-back stereo angle. A total of 2210 modules were built to the tight tolerances and specifications required for the SCT. This was 234 more than the 1976 required and represents a yield of 93%. The component flow was at times tight, but the module production rate of 40-50 per week was maintained despite this. The distributed production was not found to be a major logistical problem and it allowed additional flexibility to take advantage of where the effort was available, including any spare capacity, for building the end-cap modules. The collaboration that produced the ATLAS SCT end-cap modules kept in close contact at all times so that the effects of shortages or stoppages at different sites could be rapidly resolved.
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| 5. |
- Gunawardana, L, et al.
(författare)
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Pre-conception inter-pregnancy interval and risk of schizophrenia
- 2011
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Ingår i: The British journal of psychiatry : the journal of mental science. - : Royal College of Psychiatrists. - 1472-1465. ; 199:4, s. 338-339
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Tidskriftsartikel (refereegranskat)abstract
- It is hypothesised that the risk of schizophrenia may be elevated in children conceived following a short interpregnancy interval, when maternal folate stores are still being replenished. We examined the relationship between inter-pregnancy interval and schizophrenia risk in a longitudinal, population-based cohort. Risk of schizophrenia was increased by approximately 150% in those born following a pregnancy interval of $6 months, but was not increased if the interval after birth of the participant, before conception of the subsequent sibling, was $6 months. These findings support the hypothesis that folate (or other micronutrient) deficiency during fetal development may be an important risk factor for schizophrenia.
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- Anderson, Per, et al.
(författare)
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IL-2 overcomes the unresponsiveness but fails to reverse the regulatory function of antigen-induced T regulatory cells
- 2005
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Ingår i: Journal of Immunology. - 1550-6606. ; 174:1, s. 310-319
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Tidskriftsartikel (refereegranskat)abstract
- Intranasal administration of peptide Acl-9[4Y], based on the N-terminal epitope of myelin basic protein, can induce CD4(+) T cell tolerance, and suppress experimental autoimmune encephalomyelitis induction. The peptide-induced regulatory T (PI-T-Reg) cells failed to produce IL-2, but expressed IL-10 in response to Ag and could suppress naive T cell responses in vitro. Analysis of Jak-STAT signaling pathways revealed that the activation of Jak1, STAT3, and STAT5 were induced in tolerant T cells after Ag stimulation in vivo. In addition, the expression of suppressor of cytokine signaling 3 was induced in tolerant T cells, suggesting that cytokines regulate the tolerant state of the PI-T-Reg cells. Stimulation of PI-T-Reg cells in vitro with IL-10 induced Jak1 and STAT3 activation, but not STAT5, suggesting that IL-10 is important, but not the only cytokine involved in the development of T cell tolerance. Although IL-2 expression was deficient, stimulation with IL-2 in vitro induced Jak1 and STAT5 activation in PI-T-Reg cells, restored their proliferative response to antigenic stimulation, and abrogated PI-T-Reg-mediated suppression in vitro. However, the addition of IL-2 could not suppress IL-10 expression, and the IL-2 gene remained inactive. After withdrawal of IL-2, the PI-T-Reg cells regained their nonproliferative state and suppressive ability. These results underline the ability of the immune system to maintain tolerance to autoantigens, but at the same time having the ability to overcome the suppressive phenotype of tolerant T cells by cytokines, such as IL-2, during the protective immune response to infection.
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- Gnann, J. W., et al.
(författare)
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Herpes Simplex Encephalitis: Lack of Clinical Benefit of Long-term Valacyclovir Therapy
- 2015
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 61:5, s. 683-691
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Tidskriftsartikel (refereegranskat)abstract
- Background. Despite the proven efficacy of acyclovir (ACV) therapy, herpes simplex encephalitis (HSE) continues to cause substantial morbidity and mortality. Among patients with HSE treated with ACV, the mortality rate is approximately 14%-19%. Among survivors, 45%-60% have neuropsychological sequelae at 1 year. Thus, improving therapeutic approaches to HSE remains a high priority. Methods. Following completion of a standard course of intravenous ACV, 87 adult patients with HSE (confirmed by positive polymerase chain reaction [PCR] for herpes simplex virus DNA in cerebrospinal fluid) were randomized to receive either valacyclovir (VACV) 2 g thrice daily (n = 40) or placebo tablets (n = 47) for 90 days (12 tablets of study medication daily). The primary endpoint was survival with no or mild neuropsychological impairment at 12 months, as measured by the Mattis Dementia Rating Scale (MDRS). Logistic regression was utilized to assess factors related to the primary endpoint. Results. The demographic characteristics of the 2 randomization groups were statistically similar with no significant differences in age, sex, or race. At 12 months, there was no significant difference in the MDRS scoring for VACV-treated vs placebo recipients, with 85.7% and 90.2%, respectively, of patients demonstrating no or mild neuropsychological impairment (P = .72). No significant study-related adverse events were encountered in either treatment group. Conclusions. Following standard treatment with intravenous ACV for PCR-confirmed HSE, an additional 3-month course of oral VACV therapy did not provide added benefit as measured by neuropsychological testing 12 months later in a population of relatively high-functioning survivors.
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| 15. |
- Haider, S, et al.
(författare)
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Notch signaling plays a critical role in motility and differentiation of human first-trimester cytotrophoblasts
- 2014
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Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 155:1, s. 263-274
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Tidskriftsartikel (refereegranskat)abstract
- Failures in human extravillous trophoblast (EVT) development could be involved in the pathogenesis of pregnancy diseases. However, the underlying mechanisms have been poorly characterized. Here, we provide evidence that Notch signaling could represent a key regulatory pathway controlling trophoblast proliferation, motility, and differentiation. Immunofluorescence of first-trimester placental tissues revealed expression of Notch receptors (Notch2 and Notch3) and membrane-anchored ligands (delta-like ligand [DLL] 1 and -4 and Jagged [JAG] 1 and -2) in villous cytotrophoblasts (vCTBs), cell column trophoblasts (CCTs), and EVTs. Notch4 and Notch1 were exclusively expressed in vCTBs and in CCTs, respectively. Both proteins decreased in Western blot analyses of first-trimester, primary cytotrophoblasts (CTBs) differentiating on fibronectin. Luciferase reporter analyses suggested basal, canonical Notch activity in SGHPL-5 cells and primary cells that was increased upon seeding on DLL4-coated dishes and diminished in the presence of the Notch/γ-secretase inhibitors N-[N-(3,5-difluorophenacetyl-l-alanyl)]-S-phenylglycine t-butyl ester (DAPT) or L-685,458. Bromodeoxyuridine labeling, cyclin D1 mRNA expression, and cell counting indicated that chemical inhibition of Notch signaling elevated proliferation in the different primary trophoblast model systems. Notch inhibition also increased motility of SGHPL-5 cells through uncoated and fibronectin-coated Transwells, motility of primary CTBs, as well as migration in villous explant cultures on collagen I. Accordingly, small interfering RNA-mediated gene silencing of Notch1 also elevated SGHPL-5 cell migration. In contrast, motility of primary cultures and SGHPL-5 cells was diminished in the presence of DLL4. Moreover, DAPT increased markers of differentiated EVT, ie, human leukocyte antigen G1, integrin α5, and T-cell factor 4, whereas DLL4 provoked the opposite. In summary, the data suggest that canonical Notch signaling impairs motility and differentiation of first-trimester CTBs.
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| 16. |
- Johansson, E, et al.
(författare)
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Evaluation of specific IgE to the recombinant group 2 mite allergens Lep d 2 and Tyr p 2 in the Pharmacia CAP system
- 1999
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Ingår i: International archives of allergy and immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 120:1, s. 43-49
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Tidskriftsartikel (refereegranskat)abstract
- <b>Background:</b> Several recombinant allergens have been shown to be potentially useful for diagnosis of IgE–mediated allergy, but only a few recombinant allergens are at present commercially available in serological assays for detection of specific IgE. The aim of this study was to evaluate the IgE binding to the recombinant major dust mite allergens rLep d 2 and rTyr p 2 and compare it with the IgE binding to the commercial mite extracts <i>Lepidoglyphus destructor</i> and <i>Tyrophagus putrescentiae</i> in the Pharmacia RAST CAP System. <b>Methods:</b> The recombinant allergens rLep d 2 and rTyr p 2 were immobilised on ImmunoCAPs, and sera from 461 Swedish farmers who are frequently exposed to mites were analysed for specific IgE antibodies. Immunoblotting was performed to evaluate discrepancies between the results obtained with the recombinant and the commercial CAP assays. <b>Results:</b> The IgE values of each recombinant assay significantly correlated with the IgE values of the corresponding commercial CAP assay. The sensitivity of the rLep d 2 assay was 73.3% and that of the rTyr p 2 assay, 60.5% of that provided by the commercial <i>L. destructor</i> and <i>T. putrescentiae</i> assays. Two subjects out of 416, who tested negative in the commercial <i>L. destructor assay</i>, were positive to rLep d 2. The corresponding figures for rTyr p 2 and the <i>T. putrescentiae</i> extract were 5/418. The possibility that these subjects were sensitised to <i>L. destructor</i> and <i>T. putrescentiae</i> could not be excluded. <b>Conclusions:</b> The data suggest that it may be possible to use rLep d 2 and rTyr p 2 on ImmunoCAPs to detect and quantify IgE antibodies to these, the major allergens of <i>L. destructor</i> and <i>T. putrescentiae</i>. It appears likely that the addition of just a few more recombinant <i>L. destructor</i> and <i>T. putrescentiae</i> allergens in the CAP assay will be sufficient for in vitro diagnosis of IgE mediated allergy to <i>L. destructor</i> and <i>T. putrescentiae</i>.
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| 17. |
- Kronqvist, M, et al.
(författare)
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A hypoallergenic derivative of the major allergen of the dust mite Lepidoglyphus destructor, Lep d 2.6Cys, induces less IgE reactivity and cellular response in the skin than recombinant Lep d 2
- 2001
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Ingår i: International archives of allergy and immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 126:1, s. 41-49
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> The major allergen of the dust mite<i> Lepidoglyphus destructor</i>, Lep d 2, has been produced as a recombinant allergen (rLep d 2) with IgE reactivity both in vivo and in vitro. A modified form of rLep d 2 (rLep d 2.6Cys) obtained by site-directed mutagenesis has been shown to have a reduced IgE reactivity in vitro. In this study we have compared the ability of rLep d 2 and rLep d 2.6Cys to elicit positive skin prick tests and cellular responses among<i> L. destructor</i>-sensitized subjects. <i>Methods:</i> Seventeen subjects were skin prick-tested with rLep d 2, rLep d 2.6Cys, histamine and negative controls and 17–20 h later skin biopsy specimens were taken from the skin prick-tested sites. The biopsy specimens were stained immunohistochemically for EG2+, CD3+, CD1a+, mast cell tryptase+, and IgE+ cells. Dermal cell infiltrates were judged in hematoxylin and eosin staining. Total IgE and allergen-specific IgE were determined by CAP-RAST. <i>Results:</i> Compared to rLep d 2, rLep d 2.6Cys induced significantly smaller and fewer skin prick test reactions (p < 0.001) and dermal cell infiltrates (p < 0.05). Further, rLep d 2.6Cys induced fewer EG2+ cells (p < 0.001) but more tryptase+ cells (p < 0.05) than rLep d 2. A positive RAST to rLep d 2 was obtained for 88.2% of the subjects, while only 35.2% displayed a positive RAST to rLep d 2.6Cys. <i>Conclusion:</i> This study demonstrates that rLep d 2.6Cys is less able to evoke IgE-mediated reactions and cellular responses, as measured both in skin and in serum, than rLep d 2. In the future this hypoallergenic derivative may be a promising candidate molecule for immunotherapy of <i>L. destructor</i>-allergic patients.
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