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- Franke, Andre, et al.
(författare)
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Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1118-1125
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Tidskriftsartikel (refereegranskat)abstract
- We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10⁻⁸). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.
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| 4. |
- Bordoloi, Unmesh D., et al.
(författare)
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Schedulability Analysis of Ethernet AVB Switches
- 2014
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Ingår i: <em>20th IEEE International Conference on Embedded and Real-Time Computing Systems and Applications (RTCSA 2014), Chongqing, China, Aug. 20-22, 2014.</em>. - : IEEE Computer Society.
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Konferensbidrag (refereegranskat)abstract
- Ethernet AVB is being actively considered by the automotive industry as a candidate for in-vehicle communication backbone. However, several questions pertaining to schedulability of hard real-time messages transmitted via such a switch remain unanswered. In this paper, we attempt to fill this void. We derive equations to perform worst-case response time analysis on Ethernet AVB switches by considering its credit-based shaping algorithm. Also, we propose several approaches to reduce the pessimism in the analysis to provide tighter bounds.
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| 5. |
- Cippitelli, Andrea, et al.
(författare)
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The novel, selective, brain-penetrant neuropeptide Y Y2 receptor antagonist, JNJ-31020028, tested in animal models of alcohol consumption, relapse, and anxiety
- 2011
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Ingår i: Alcohol. - : Elsevier. - 0741-8329 .- 1873-6823. ; 45:6, s. 567-576
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Tidskriftsartikel (refereegranskat)abstract
- Neuropeptide Y (NPY) signaling has been shown to modulate stress responses and to be involved in regulation of alcohol intake and dependence. The present study explores the possibility that blockade of NPY Y2 autoreceptors using a novel, blood-brain barrier penetrant NPY Y2 receptor antagonist, JNJ-31020028 (N-(4-{4-[2-(diethylamino)-2-oxo-1-phenylethyl]piperazin-1-yl}-3-fluorophenyl)-2-pyridin-3-ylbenzamide), may achieve a therapeutically useful activation of the NPY system in alcohol- and anxiety-related behavioral models. We examined JNJ-31020028 in operant alcohol self-administration, stress-induced reinstatement to alcohol seeking, and acute alcohol withdrawal (hangover)-induced anxiety. Furthermore, we tested its effects on voluntary alcohol consumption in a genetic animal model of alcohol preference, the alcohol-preferring (P) rat. Neither systemic (0, 15, 30, and 40 mg/kg, subcutaneously [s.c.]) nor intracerebroventricular (0.0, 0.3, and 1.0 nmol/rat) administration of JNJ-31020028 affected alcohol-reinforced lever pressing or relapse to alcohol seeking behavior following stress exposure. Also, when its effects were tested on unlimited access to alcohol in P rats, preference for alcohol solution was transiently suppressed but without affecting voluntary alcohol intake. JNJ-31020028 (15 mg/kg, s.c.) did reverse the anxiogenic effects of withdrawal from a single bolus dose of alcohol on the elevated plus-maze, confirming the anxiolytic-like properties of NPY Y2 antagonism. Our data do not support Y2 antagonism as a mechanism for reducing alcohol consumption or relapse-like behavior, but the observed effects on withdrawal-induced anxiety suggest that NPY Y2 receptor antagonists may be a putative treatment for the negative affective states following alcohol withdrawal.
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| 7. |
- Hatami, Sepehr, 1981, et al.
(författare)
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Critical aspects of sinter-hardening of prealloyed Cr-Mo steel
- 2010
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Ingår i: Journal of Materials Processing Technology. - : Elsevier BV. - 0924-0136. ; 210:9, s. 1180-1189
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Tidskriftsartikel (refereegranskat)abstract
- In recent years, growing demand for greater mechanical properties of PM steel components with competitive fabrication cost has led to significant innovations in different fields of powder metallurgy. Recent research has been focused on reaching higher performance with lower cost. To this end, the possibility of combining the conventional sintering and post-sintering processes for a particular powder composition has been introduced. Sinter-hardening is a result of the research conducted along this line. Elimination of any secondary operation such as quench-hardening by incorporating it in the sintering process (i.e. sinter-hardening) is of great interest, as it will lead to lower processing costs and equal, if not higher mechanical performance. However, to ensure the desired mechanical properties of the final component and robustness of the performance, critical aspects of the sinter-hardening process should be rigorously studied. Hence with specific attention to a Cr-Mo steel powder (FL-5305), this study deals with the influence of density on cooling rate, the effect of different sintering temperatures (e.g. 1120 degrees C and 1250 degrees C) on austenite grain size and consequently, hardenability. The microstructure development in sinter-hardened FL-5305 material has been analyzed and predicted by means of the available literature for solid steel and also using the commercial software (JMatPro 5.0) for materials assessment based on thermodynamic and kinetics modeling. Finally, inaccurate carbon control and its adverse impact on excessive formation of cementite have been addressed. (C) 2010 Elsevier B.V. All rights reserved.
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- Maggioni, Aldo P., et al.
(författare)
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Are hospitalized or ambulatory patients with heart failure treated in accordance with European Society of Cardiology guidelines? Evidence from 12 440 patients of the ESC Heart Failure Long-Term Registry
- 2013
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Ingår i: European Journal of Heart Failure. - : Oxford University Press (OUP): Policy B. - 1388-9842 .- 1879-0844. ; 15:10, s. 1173-1184
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate how recommendations of European guidelines regarding pharmacological and non-pharmacological treatments for heart failure (HF) are adopted in clinical practice. less thanbrgreater than less thanbrgreater thanThe ESC-HF Long-Term Registry is a prospective, observational study conducted in 211 Cardiology Centres of 21 European and Mediterranean countries, members of the European Society of Cardiology (ESC). From May 2011 to April 2013, a total of 12 440 patients were enrolled, 40.5 with acute HF and 59.5 with chronic HF. Intravenous treatments for acute HF were heterogeneously administered, irrespective of guideline recommendations. In chronic HF, with reduced EF, reninangiotensin system (RAS) blockers, beta-blockers, and mineralocorticoid antagonists (MRAs) were used in 92.2, 92.7, and 67.0 of patients, respectively. When reasons for non-adherence were considered, the real rate of undertreatment accounted for 3.2, 2.3, and 5.4 of the cases, respectively. About 30 of patients received the target dosage of these drugs, but a documented reason for not achieving the target dosage was reported in almost two-thirds of them. The more relevant reasons for non-implantation of a device, when clinically indicated, were related to doctor uncertainties on the indication, patient refusal, or logistical/cost issues. less thanbrgreater than less thanbrgreater thanThis pan-European registry shows that, while in patients with acute HF, a large heterogeneity of treatments exists, drug treatment of chronic HF can be considered largely adherent to recommendations of current guidelines, when the reasons for non-adherence are taken into account. Observations regarding the real possibility to adhere fully to current guidelines in daily clinical practice should be seriously considered when clinical practice guidelines have to be written.
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| 9. |
- Olsson, Lars E, et al.
(författare)
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1H and hyperpolarized 3He magnetic resonance imaging clearly detect the preventative effect of a glucocorticoid on endotoxin-induced pulmonary inflammation in vivo.
- 2010
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Ingår i: Innate immunity. - : SAGE Publications. - 1753-4267 .- 1753-4259. ; :Feb 3
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Proton ((1)H) magnetic resonance imaging (MRI) can be utilized to quantify pulmonary edema in endotoxin-induced pulmonary inflammation and hyperpolarized (HP) (3)He MRI can assess pulmonary ventilation. Neither of the methods has been applied to assess the impact of a drug on endotoxin-induced pulmonary inflammation in vivo. The aim of the current study was to evaluate the capability of (1)H and HP (3)He MRI to assess the effects of a glucocorticoid on endotoxin-induced pulmonary inflammation in vivo.Materials and Methods: Mice were exposed to an aerosol of either saline or endotoxin (5 mg/ml) for 10 min. Half of the endotoxin-exposed mice were pretreated with a glucocorticoid (budesonide 3 mg/kg; 2 times/day) and the other half with vehicle p.o. The first budesonide treatment was administered 1 h prior to the aerosol inhalation. Forty-eight hours after the aerosol exposure, the mice were anaesthetized for subsequent imaging. Hyperpolarized (3)He was administered and axial MR images of the lungs obtained. Matching (1)H MR images were then acquired. The mice were sacrificed and broncho-alveolar lavage (BAL) samples were harvested to determine total and cell differential counts.Results: The lesion volume on both (1)H and (3)He MRI, were markedly increased by endotoxin exposure (P < 0.001). Budesonide strongly reduced lesion volume (P < 0.001). The BAL cell count correlated strongly with both (3)He (P < 0.001; r = 0.96) and (1)H lesion volumes (P < 0.001; r = 0.97).Conclusions: Hyperpolarized (3)He MRI and (1)H MRI clearly visualized the preventative effect of budesonide on the impact of endotoxin on pulmonary ventilation and edema, respectively. The fact that ventilation defects on (3)He MRI corresponded to findings from conventional (1)H MRI, as well as to counts of BAL inflammatory cells suggests that these imaging techniques constitute promising tools for non-invasive monitoring of pulmonary inflammation in vivo.
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| 10. |
- Schuster, Andreas, et al.
(författare)
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Function selection among popular dive computer models : A review and proposed improvements
- 2014
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Ingår i: Underwater Technology. - : Society for Underwater Technology. - 1756-0543. ; 32:3, s. 159-165
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Tidskriftsartikel (refereegranskat)abstract
- For optimal safety a dive computer should be easy to use and the displayed information easy to understand. The present study examines the usability of dive computers and potential technologies to enhance safety. It should be noted that even if the ease of use of a dive computer is increased to an extent where it is intuitive to use, this does not release the diver from the recommendation to read the dive computer manual to safely dive with it. For the present work, 47 dive computer models by 14 manufacturers were purchased and the manuals of another three were studied. Function selection was noted for each model. Where selection required a combination of long and short pushes, or more than one button, it was considered necessary to read the instruction manual merely to modify settings in the dive computer. The mean number of buttons, switches or contacts per dive computer was 3.3 (SD 1.1, range 1–7). Twelve models (24%) did not have multiple functions per button, one model (2%) had a single multi-function and 36 models (72%) had multiple multi-functions per button. Accessing these functions required short or long push combinations. In 41 out of 50 (82%) of the dive computer models, the user interface was not intuitive. The majority of popular dive computers employ combinations of long and short pushes to access multiple functions, requiring training and mnemonic effort to operate the device. They are not intuitive, and scope exists to improve the usability and safety of dive computers. Possibilities are described including touch screens, a wheel to replace traditional buttons and near field communications (NFC).
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