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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. |
- 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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- Elfman, LHM, et al.
(författare)
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IgE binding capacity of synthetic and recombinant peptides of the major storage mite (Lepidoglyphus destructor) allergen, Lep d 2
- 1998
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Ingår i: International archives of allergy and immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 117:3, s. 167-173
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Tidskriftsartikel (refereegranskat)abstract
- <b>Background:</b> Lepidoglyphus destructor is an important non–pyroglyphid mite species in Europe and a dominant allergen in farming environments. The major allergen of L. destructor, Lep d 2, is a protein of 13.2 kD that is recognised by about 90% of sera RAST positive to this mite species. <b>Methods:</b> The cDNA of two isoallergens of the Lep d 2 has previously been sequenced and the protein expressed in different protein expression systems. In order to map the B–cell epitopes, the full length protein and the truncated forms of the protein have been expressed in Escherichia coli as glutathione–S–transferase (GST) fusion proteins. Recombinant Lep d 2 fragments and synthetic overlapping 15 mer peptides spanning Lep d 2 were probed with sera from patients allergic to storage mite. <b>Results:</b> The full–length (125 amino acids) GST fusion protein reacted strongly with patient IgE in Western blots and dot blots. Synthetic peptides failed to react with IgE antibodies from mite–allergic patients and the truncated fusion proteins displayed weak IgE–binding capacity. <b>Conclusion:</b> We conclude that there are no dominant linear IgE–binding epitopes in Lep d 2. Recombinant or synthetic Lep d 2 fragments may, however, be further evaluated as hypoallergenic candidate molecules for specific immunotherapy.
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- Eriksson, TLJ, et al.
(författare)
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Identification and characterisation of two allergens from the dust mite Acarus siro, homologous with fatty acid-binding proteins
- 1999
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Ingår i: International archives of allergy and immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 119:4, s. 275-281
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Tidskriftsartikel (refereegranskat)abstract
- <b>Background:</b> Dust mites are a major cause of allergic disease worldwide. The dust mite <i>Acarus siro</i> is an inducer of occupational allergy among farmers, but sensitisation has also been found in non–farming populations. <b>Methods:</b> A degenerate primer was designed to the N–terminal amino acid sequence of a 15–kD IgE–binding protein in <i>A. siro</i> extract. The cDNA sequence was obtained by using reverse transcriptase polymerase chain reaction, standard cloning and sequencing techniques. The protein was expressed in <i>Escherichia coli</i> with a 6–histidine tag at its C–terminus. Immunoblotting of the recombinant protein and whole extract was performed using patient sera. <b>Results and conclusion:</b> 15 and 17–kD allergens were identified in a fraction of <i>A. siro</i> extract. The cDNA of the 15–kD allergen was isolated, cloned and sequenced and the allergen was expressed as a recombinant protein. The calculated molecular weight of the cDNA–encoded protein is 14.2 kD. The predicted amino acid sequence has one potential N–glycosylation site at position 4–6 and a cytosolic fatty acid–binding protein signature at position 5–22. The protein has 64% sequence identity with Blo t 13, an allergen from the dust mite <i>Blomia tropicalis</i>, as well as homology with several other fatty acid–binding proteins (FABPs) from different organisms. The allergen was named Aca s 13 and was recognised strongly by 3 of 13 (23%) of the subjects investigated. The amino acid sequence of the 17–kD protein was partly determined and it also showed high sequence homology with Blo t 13 and FABPs.
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- 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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| 22. |
- Hassan, Z, et al.
(författare)
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Pharmacokinetics of liposomal busulphan in man
- 2001
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Ingår i: Bone marrow transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 27:5, s. 479-485
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Tidskriftsartikel (refereegranskat)
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| 23. |
- 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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| 24. |
- 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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