| 1. |
|
|
| 2. |
|
|
| 3. |
- Klaric, Lucija, et al.
(författare)
-
Mendelian randomisation identifies alternative splicing of the FAS death receptor as a mediator of severe COVID-19.
- 2021
-
Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory. ; , s. 1-28
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Severe COVID-19 is characterised by immunopathology and epithelial injury. Proteomic studies have identified circulating proteins that are biomarkers of severe COVID-19, but cannot distinguish correlation from causation. To address this, we performed Mendelian randomisation (MR) to identify proteins that mediate severe COVID-19. Using protein quantitative trait loci (pQTL) data from the SCALLOP consortium, involving meta-analysis of up to 26,494 individuals, and COVID-19 genome-wide association data from the Host Genetics Initiative, we performed MR for 157 COVID-19 severity protein biomarkers. We identified significant MR results for five proteins: FAS, TNFRSF10A, CCL2, EPHB4 and LGALS9. Further evaluation of these candidates using sensitivity analyses and colocalization testing provided strong evidence to implicate the apoptosis-associated cytokine receptor FAS as a causal mediator of severe COVID-19. This effect was specific to severe disease. Using RNA-seq data from 4,778 individuals, we demonstrate that the pQTL at the FAS locus results from genetically influenced alternate splicing causing skipping of exon 6. We show that the risk allele for very severe COVID-19 increases the proportion of transcripts lacking exon 6, and thereby increases soluble FAS. Soluble FAS acts as a decoy receptor for FAS-ligand, inhibiting apoptosis induced through membrane-bound FAS. In summary, we demonstrate a novel genetic mechanism that contributes to risk of severe of COVID-19, highlighting a pathway that may be a promising therapeutic target.
|
|
| 4. |
|
|
| 5. |
- Sundström, Johan, Professor, 1971-, et al.
(författare)
-
Risk factors for subarachnoid haemorrhage : a nationwide cohort of 950 000 adults
- 2019
-
Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:6, s. 2018-2025
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Subarachnoid haemorrhage (SAH) is a devastating disease, with high mortality rate and substantial disability among survivors. Its causes are poorly understood. We aimed to investigate risk factors for SAH using a novel nationwide cohort consortium.METHODS: We obtained individual participant data of 949 683 persons (330 334 women) between 25 and 90 years old, with no history of SAH at baseline, from 21 population-based cohorts. Outcomes were obtained from the Swedish Patient and Causes of Death Registries.RESULTS: During 13 704 959 person-years of follow-up, 2659 cases of first-ever fatal or non-fatal SAH occurred, with an age-standardized incidence rate of 9.0 [95% confidence interval (CI) (7.4-10.6)/100 000 person-years] in men and 13.8 [(11.4-16.2)/100 000 person-years] in women. The incidence rate increased exponentially with higher age. In multivariable-adjusted Poisson models, marked sex interactions for current smoking and body mass index (BMI) were observed. Current smoking conferred a rate ratio (RR) of 2.24 (95% CI 1.95-2.57) in women and 1.62 (1.47-1.79) in men. One standard deviation higher BMI was associated with an RR of 0.86 (0.81-0.92) in women and 1.02 (0.96-1.08) in men. Higher blood pressure and lower education level were also associated with higher risk of SAH.CONCLUSIONS: The risk of SAH is 45% higher in women than in men, with substantial sex differences in risk factor strengths. In particular, a markedly stronger adverse effect of smoking in women may motivate targeted public health initiatives.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Abelson, Anna-Karin, et al.
(författare)
-
STAT4 Associates with SLE through two independent effects that correlate with gene expression and act additively with IRF5 to increase risk
- 2009
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 68:11, s. 1746-1753
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To confirm and define the genetic association of STAT4 and systemic lupus erythematosus, investigate the possibility of correlations with differential splicing and/or expression levels, and genetic interaction with IRF5. METHODS: 30 tag SNPs were genotyped in an independent set of Spanish cases and controls. SNPs surviving correction for multiple tests were genotyped in 5 new sets of cases and controls for replication. STAT4 cDNA was analyzed by 5'-RACE PCR and sequencing. Expression levels were measured by quantitative PCR. RESULTS: In the fine-mapping, four SNPs were significant after correction for multiple testing, with rs3821236 and rs3024866 as the strongest signals, followed by the previously associated rs7574865, and by rs1467199. Association was replicated in all cohorts. After conditional regression analyses, two major independent signals represented by SNPs rs3821236 and rs7574865, remained significant across the sets. These SNPs belong to separate haplotype blocks. High levels of STAT4 expression correlated with SNPs rs3821236, rs3024866 (both in the same haplotype block) and rs7574865 but not with other SNPs. We also detected transcription of alternative tissue-specific exons 1, indicating presence of tissue-specific promoters of potential importance in the expression of STAT4. No interaction with associated SNPs of IRF5 was observed using regression analysis. CONCLUSIONS: These data confirm STAT4 as a susceptibility gene for SLE and suggest the presence of at least two functional variants affecting levels of STAT4. Our results also indicate that both genes STAT4 and IRF5 act additively to increase risk for SLE.
|
|
| 9. |
- Abrahamsson, Niclas, 1976-, et al.
(författare)
-
Gastric bypass reduces symptoms and hormonal responses to hypoglycemia
- 2016
-
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 65:9, s. 2667-2675
-
Tidskriftsartikel (refereegranskat)abstract
- Gastric bypass (GBP) surgery, one of the most common bariatric procedures, induces weight loss and metabolic effects. The mechanisms are not fully understood, but reduced food intake and effects on gastrointestinal hormones are thought to contribute. We recently observed that GBP patients have lowered glucose levels and frequent asymptomatic hypoglycemic episodes. Here, we subjected patients before and after undergoing GBP surgery to hypoglycemia and examined symptoms and hormonal and autonomic nerve responses. Twelve obese patients without diabetes (8 women, mean age 43.1 years [SD 10.8] and BMI 40.6 kg/m(2) [SD 3.1]) were examined before and 23 weeks (range 19-25) after GBP surgery with hyperinsulinemic-hypoglycemic clamp (stepwise to plasma glucose 2.7 mmol/L). The mean change in Edinburgh Hypoglycemia Score during clamp was attenuated from 10.7 (6.4) before surgery to 5.2 (4.9) after surgery. There were also marked postsurgery reductions in levels of glucagon, cortisol, and catecholamine and the sympathetic nerve responses to hypoglycemia. In addition, growth hormone displayed a delayed response but to a higher peak level. Levels of glucagon-like peptide 1 and gastric inhibitory polypeptide rose during hypoglycemia but rose less postsurgery compared with presurgery. Thus, GBP surgery causes a resetting of glucose homeostasis, which reduces symptoms and neurohormonal responses to hypoglycemia. Further studies should address the underlying mechanisms as well as their impact on the overall metabolic effects of GBP surgery.
|
|
| 10. |
- Abrahamsson, Niclas, 1976-
(författare)
-
On the Impact of Bariatric Surgery on Glucose Homeostasis
- 2016
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Obesity has grown to epidemic proportions, and in lack of efficient life-style and medical treatments, the bariatric surgeries are performed in rising numbers. The most common surgery is the Gastric Bypass (GBP) surgery, with the Biliopancreatic diversion with duodenal switch (DS) as an option for the most extreme cases with a BMI>50 kg/m2.In paper I 20 GBP-patients were examined during the first post-operative year regarding the natriuretic peptide, NT-ProBNP, which is secreted from the cardiac ventricles. Levels of NT-ProBNP quickly increased during the first post-surgery week, and later established itself on a higher level than pre-surgery.In paper II we report of 5 patient-cases after GBP-surgery with severe problems with postprandial hypoglycaemia that were successfully treated with GLP-1-analogs. The effect of treatment could be observed both symptomatically and in some cases using continuous glucose measuring systems (CGMS).In paper III three groups of subjects; 15 post-GBP patients, 15 post-DS, and 15 obese controls were examined for three days using CGMS during everyday life. The post-GBP group had high glucose variability as measured by MAGE and CONGA, whereas the post-DS group had low variability. Both post-operative groups exhibited significant time in hypoglycaemia, about 40 and 80 minutes per day <3.3mmol/l and 20 and 40 minutes < 2.8mmol/l, respectively, longer time for DS-group. Remarkably, only about 20% of these hypoglycaemic episodes were accompanied with symptoms.In Paper IV the hypoglycaemia counter regulatory system was investigated; 12 patients were examined before and after GBP-surgery with a stepped hypoglycaemic hyperinsulinemic clamp. The results show a downregulation of symptoms, counter regulatory hormones (glucagon, cortisol, epinephrine, norepinephrine, growth hormone), incretin hormones (GLP-1 and GIP), and sympathetic nervous response.In conclusion patients post bariatric surgery exhibit a downregulated counter regulatory response to hypoglycaemia, accompanied by frequent asymptomatic hypoglycaemic episodes in everyday life. Patients suffering from severe hypoglycaemic episodes can often be treated successfully with GLP-1-analogues.
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
- Ahmed, Niaz, et al.
(författare)
-
Association of Admission Blood Glucose and Outcome in Patients Treated With Intravenous Thrombolysis
- 2010
-
Ingår i: Archives of Neurology. - 0003-9942 .- 1538-3687. ; 67:9, s. 1123-1130
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To determine the association between admission blood glucose and outcome in ischemic stroke patients treated with thrombolysis. Design: A prospective, open, multinational, observational study. Setting: An ongoing Internet-based, academic-driven, interactive thrombolysis register. Patients: Between 2002 and 2007, 16 049 patients were recorded in the SITS-ISTR. Main Outcome Measure: Blood glucose was recorded at admission. Blood glucose was divided into the following categories: less than 80,80-120 (reference range), 121-140, 141-160, 161-180, 181-200, and greater than 200 mg/dL. Outcomes were mortality and independence (modified Rankin Scale score of 0-2) at 3 months and symptomatic intracerebral hemorrhage (SICH) (National Institutes of Health Stroke Scale deterioration >= points within 24 hours and type 2 parenchymal hemorrhage). Results: In multivariable analysis, blood glucose as a continuous variable was independently associated with a higher mortality (P < .001), lower independence (P < .001), and an increased risk of SICH (P = .005). Blood glucose greater than 120 mg/dL as a categorical variable was associated with a significantly higher odds for mortality (odds ratio [OR], 1.24; 95% confidence interval [Cl], 1.07-1.44; P = .004) and a lower odds for independence (OR, 0.58; 95% CI, 0.48-0.70; P < .001), and blood glucose from 181 to 200 mg/dL was associated with an increased risk of SICH (OR, 2.86; 95% CI, 1.69-4.83; P < .001) compared with the reference level. The trends of associations between blood glucose and outcomes were similar in patients with diabetes (17%) or without such history, except for mortality (P = .23) and SICH (P = .06) in which the association was not statistically significant in patients with diabetes. Conclusions: Admission hyperglycemia was an independent predictor for poor outcome after stroke/thrombolysis, though SICH rates did not increase significantly until reaching 180 mg/dL. These results suggest that tight control of blood glucose may be indicated in the hyperacute phase following thrombolysis. Randomized trial data are needed.
|
|
| 14. |
- Almby, Kristina E., et al.
(författare)
-
Effects of Gastric Bypass Surgery on the Brain : Simultaneous Assessment of Glucose Uptake, Blood Flow, Neural Activity, and Cognitive Function During Normo- and Hypoglycemia
- 2021
-
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 70:6, s. 1265-1277
-
Tidskriftsartikel (refereegranskat)abstract
- While Roux-en-Y gastric bypass (RYGB) surgery in obese individuals typically improves glycemic control and prevents diabetes, it also frequently causes asymptomatic hypoglycemia. Previous work showed attenuated counterregulatory responses following RYGB. The underlying mechanisms as well as the clinical consequences are unclear. In this study, 11 subjects without diabetes with severe obesity were investigated pre- and post-RYGB during hyperinsulinemic normo-hypoglycemic clamps. Assessments were made of hormones, cognitive function, cerebral blood flow by arterial spin labeling, brain glucose metabolism by F-18-fluorodeoxyglucose (FDG) positron emission tomography, and activation of brain networks by functional MRI. Post- versus presurgery, we found a general increase of cerebral blood flow but a decrease of total brain FDG uptake during normoglycemia. During hypoglycemia, there was a marked increase in total brain FDG uptake, and this was similar for post- and presurgery, whereas hypothalamic FDG uptake was reduced during hypoglycemia. During hypoglycemia, attenuated responses of counterregulatory hormones and improvements in cognitive function were seen postsurgery. In early hypoglycemia, there was increased activation post- versus presurgery of neural networks in brain regions implicated in glucose regulation, such as the thalamus and hypothalamus. The results suggest adaptive responses of the brain that contribute to lowering of glycemia following RYGB, and the underlying mechanisms should be further elucidated.
|
|
| 15. |
- Almby, Kristina E., et al.
(författare)
-
Effects of GLP-1 on counter-regulatory responses during hypoglycemia after GBP surgery
- 2019
-
Ingår i: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 181:2, s. 161-171
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of the study was to explore the role of GLP-1 receptor activation on the counter-regulation and symptoms of hypoglycemia in subjects who have undergone gastric bypass surgery (GBP).Design: Experimental hyperinsulinemic–hypoglycemic clamp study.Methods: Twelve post-GBP subjects participated in a randomized cross-over study with two hyperinsulinemic, hypoglycemic clamps (glucose nadir 2.7 mmol/L) performed on separate days with concomitant infusions of the GLP-1 analog exenatide or with saline, respectively. Continuous measurements of metabolites and counter-regulatory hormones as well as assessments of heart rate variability and symptoms of hypoglycemia were performed throughout the clamps.Results: No effect of GLP-1 receptor activation on counter-regulatory hormones (glucagon, catecholamines, cortisol, GH) or glucose infusion rate was seen, but we found indications of a downregulation of the sympathetic relative to the parasympathetic nerve activity, as reflected in heart rate variability. No significant differences in symptom of hypoglycemia were observed.Conclusions/interpretation: Short-term exposure to a GLP-1 receptor agonist does not seem to impact the counter-regulatory hormonal and metabolic responses in post-GBP subjects during hypoglycemic conditions, suggesting that the improvement in symptomatic hypoglycemia post-GBP seen following treatment with GLP-1 receptor agonists may be mediated by mechanism not directly involved in counter-regulation.
|
|
| 16. |
|
|
| 17. |
- Andersson, Sofia Lovisa, et al.
(författare)
-
Långtidsförsök med membranbioreaktor för förbättrad avloppsvattenrening i kombination med kompakt slambehandling
- 2023
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Henriksdals reningsverk i Stockholm byggs nu ut och om för ökad kapacitet (från 0,8 till 1,6 miljoner PE) och för förbättrad reningsgrad (6 mg TN/l, 0,20 mg TP/L, 5 mg BOD7/l). Projektet inkluderar uppgradering av den befintliga konventionella aktivslamprocessen till en ny membranbioreaktorprocess (MBR) med mer än 1,6 m2 installerad membranyta.Det inkluderar även utökad förbehandling och ett nytt steg för primärslamförtjockning. Termofil rötning av tjockt slam (~6 % TS) vid hög organisk belastning och relativt låg uppehållstid kommer ersätta dagens mesofila rötning.För att öka kunskapen om MBR-teknik i nordiskt klimat har Stockholm Vatten och Avfall (SVOA) och IVL Svenska Miljöinstitutet genomfört långtidsstudier på en membranprocess i pilotskala på FoU-anläggningen Hammarby Sjöstadsverk, som ligger i anslutning till Henriksdals reningsverk. MBR-piloten togs i drift 2013 och byggdes om till sin nuvarande utformning under 2016. År 2017 kompletterades MBR-piloten med en slamlinje för att kunna studera olika aspekter av slamrötning.Under 2021 kördes MBR-piloten med ett fast inflöde på 4,1 m3/h, vilket är 37 % högre än det designade medelflödet, med externt tillförskaffad glycerol och internt producerad VFA-kolkälla för efterdenitrifikation.Aluminium (PAX) användes i stället för trevärt järn (PIX) som komplement till tvåvärt järn (FeSO4) för fosforutfällning. Detta gjordes för att testa driftstrategin för den första MBR-linjen i Henriksdals reningsverk. Medelhalter av kväve och fosfor i utgående vatten var 3,9 mg TN/L respektive 0,07 mg TP/L, vilket innebär att utsläppsvärden uppfylldes även i år. För att uppnå detta krävdes 8,6 g Fe2+/m3 och 0,9 g Al3+/m3.Under försök med fluxförhöjare tillsattes totalt 17,8 g järn (Fe2++ Fe3+)/m3. Glyceroldosen motsvarade 17,3 g COD/m3, och för användning av internt producerad VFA motsvarande dosen 15,5 g COD/m3. Den något högre förbrukningen av fosforfällningskemikalier jämfört med 2020, 1,29 mol metall per mol avlägsnad fosfor, berodde främst på en lägre bio-P aktivitet under 2021. År 2021 var fosforsläppshastigheten mycket låg under våren, ex. < 1 g PO4-P/kg VSS,h i juni men återhämtade sig under sommaren med t.ex. 5,5 g PO4-P/kg VSS,h i juli, efter att doseringen av skumdämpare stoppades.Järn- och aluminiumhalten i det aktiva slammet var 6,2 respektive 0,7 %. Genomsnittlig total slamålder under 2021 var 17,2 dagar och luftad medelslamålder var 7 dagar. Nitrifikation var alltid komplett med utgående ammoniumkoncentrationer under 2 mg/L, förutom vecka 25.Tester med användning av internt producerad VFA som kolkälla visade att den specifika COD-förbrukningen var nästan densamma som för glycerol när man jämförde årsgenomsnittet från 2021 och 2020. Utgående nitrat och total kvävereduktion var liknande under försöket med VFA som resten av året, då glycerol användes.Liksom tidigare år rengjordes membranen i membrantank 1 (MT1) med oxalsyra och membranen i MT2 med citronsyra. Båda membranen rengjordes också med natriumhypoklorit. Membranen kördes med ett genomsnittligt flux på 21 till 25 L/(m2·h), men med startvecka 25 testades fullskaledesignens maximala nettoflux på 30 L/(m2·h) i piloten under 25 veckor. Netto-TMP varierade mellan 49 och 218 mbar för MT1 och mellan 51 och 146 mbar för MT2. TMP reducerades efter varje återhämtningsrengöring (RC) med hypoklorit, men effekten varade inte länge. Permeabiliteten var generellt över 200 L/(m2·h·bar) under hela 2021–2022 för båda membranen. Återhämtningsrengöringar gjordes två gånger med hypoklorit och en gång med syror under 2021. Under 2022 genomfördes en slutlig RC, först med hypoklorit sedan med syror. Den första RC för MT1 resulterade i en tydlig ökning av permeabiliteten efter rengöring. För MT2 var den största ökningen av permeabiliteten resultatet av en citronsyra-MC (en vecka efter hypoklorit-RC).Följande RC i slutet av 2021 och i mars 2022 hade tydliga men mindre positiva inverkan på permeabiliteten. Före den första RC var permeabiliteten högre för MT1 (rengöras med oxalsyra) jämfört med MT2 (rengöras med citronsyra). Efter de första RC hade båda membranen liknande permeabilitet. Som ett resultat av den tuffa driftstrategin från vecka 25 2021 minskade permeabiliteten ganska snabbt efter RC. MT2 nådde en stabil nivå runt 250-300 L/(m2·h·bar) medan MT1 sjönk ytterligare till som lägst 200 L/(m2·h·bar).Utsläpp av klorerade föreningar mättes under den slutliga återställningsrengöringen med natriumhypoklorit. Utsläppsprocessen var långsammare än förväntat och generellt sett observerades inga tydliga tecken på dämpning av utsläppen under provtagningens 21 timmar. Även om sammansatta prover på flera timmar under natten inte ger tillräckligt med detaljer, drogs slutsatsen att utsläppen kan vara skadliga under hela RC-processen ur ett exponeringsperspektiv. Exempelvis nådde trikloramin sin topp vid 36 gånger den rekommenderade gränsen, klorgas vid 73 % av korttidsexponeringsgränsen (15 min exponering) och kloroform vid 9 % av den yrkesmässiga exponeringsgränsen (genomsnittlig arbetsdag på 8 timmar).För att följa upp tidigare mätningar av växthusgaserna lustgas (N2O) och metan (CH4) genomfördes en ny mätkampanj under flera månader i 2021. Generellt sett var utsläppen som observerades 2021 betydligt högre än i tidigare kampanjer och särskilt höga N2O-utsläpp från membrantanken kunde observeras. Någon tydlig orsak kunde inte identifieras men den högre inkommande belastningen med bibehållna reningskrav och ett "bättre" provtagningsupplägg kan delvis vara en förklaring.I samarbete med Kemira genomfördes tester med en fluxförhöjande produkt (flux enhancer). Ingen uppenbar positiv eller negativ förändring i permeabiliteten på grund av dosering av fluxförhöjare kunde dock identifieras utifrån de kontinuerliga processparametrar som övervakades och vanliga variationer i permeabilitet samt effekten av membranrengöring.Eftersom skumbildning är ett vanligt fenomen i MBR-anläggningar genomfördes tester med ett skumdämpande medel som doserades i pulser och kontinuerligt till den biologiska behandlingen under perioden med kraftig skumbildning (mars-juni). Även om skumning inte upphörde helt så kunde en god minskning och kontroll av skumning uppnås. En optimal effekt konstaterades vid en kontinuerlig dos på > 10 ppm. Men även om produkten har visat sig ha en positiv effekt på skumning i MBR-piloten, framstår inte en permanent användning i fullskala som ekonomiskt genomförbar på grund av den höga förbrukningen.Tester med reducerat RAS-flöde från 4×Qin enligt design till 2×Qin syftade till att minska energiförbrukningen. Ett minskat RAS-flöde skulle dock innebära en ökad slamkoncentration i membrantankarna, vilket kan ha negativa effekter på membranets prestanda med mer igensättning, vilket i sin tur kan leda till ökad luftning för membranrengöring och behov av tätare membrantvättar. Projektgruppen kunde dock inte observera några negativa effekter av det minskade RAS-flödet på membranets prestanda.Under 2021 genomfördes tester med övergång från mesofil till termofil rötning, avvattning av rötslam efter mesofil och termofil rötning, samt termofil rötning vid hög organisk belastning (OLR) och låg hydraulisk uppehållstid (HRT) i slampiloten. Resultat visar att övergången från mesofil till termofil rötning kan ske utan större problem om den organiska belastningen minskades lite vid den mest kritiska temperaturen och att stabil drift uppnåddes efter 10-12 dagar. Att utvärdera avvattningen av mesofilt och termofilt rötat slam var svårare och inga tydliga skillnader kunde observeras. En slutsats var dock att de metoder som användes för att bestämma avvattningsbarhet eller optimal polymerdos inte framstår som tillförlitliga. Försök med hög organisk belastning vid termofil rötning visade att rötkammarens prestanda kunde bibehållas upp till en OLR på cirka 4 kg VS/m3, d och en HRT på 12 d. När belastningen ökades ytterligare och HRT minskade, minskade prestandan vad gäller utrötningsgrad och biogas-/metanproduktion, även om själva reaktordriften fortfarande var stabil.Den totala resursåtgången i piloten visade att konsumtionen av glycerol var densamma som för den framtida Henriksdalsdesignen, även om kvävebelastningen i piloten var 21 % högre och den genomsnittliga totala kvävekoncentrationen i utgående vatten var med 3,9 mg TN/L lägre än design på 6 mg TN/L. Järn-/metallförbrukningen var också 73 % av den framtida Henriksdalsdesignen, även om fosforbelastningen till piloten var cirka 50 % högre jämfört med designvärden och utgående fosfatkoncentrationerna låg under målkoncentrationen. Detta förklaras främst av EBPR-aktiviteten i pilotprojektet. Dessutom var förbrukningen av rengöringskemikalier lägre än den framtida Henriksdalsdesignen även om inflödet till piloten var 30 % högre än designen.
|
|
| 18. |
- Andrén, Niclas, et al.
(författare)
-
Finansiering
- 2003
-
Bok (övrigt vetenskapligt/konstnärligt)
|
|
| 19. |
- Arunachalam, Raghu, et al.
(författare)
-
The Supply Chain Management Game for the Trading Agent Competition 2004
- 2004. - 1
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This report is the specification for the Trading Agent Competition Supply Chain Management Game - TAC SCM-04, to be held between July 20-22, 2004, in New York in conjunction with AAMAS-04. Based on the experience of the 2003 Trading Agent Competition a few enhancements have been added to the original game: (1)The price function has been modified to better reflect demand; (2) storage costs have been introduced; and (3) customer demand has been segmented into multiple markets.
|
|
| 20. |
- Attelind, Sofia, et al.
(författare)
-
Genetic determinants of apixaban plasma levels and their relationship to bleeding and thromboembolic events
- 2022
-
Ingår i: Frontiers in Genetics. - : Frontiers Media S.A.. - 1664-8021. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Apixaban is a direct oral anticoagulant, a factor Xa inhibitor, used for the prevention of ischemic stroke in patients with atrial fibrillation. Despite using recommended dosing a few patients might still experience bleeding or lack of efficacy that might be related to inappropriate drug exposure. We conducted a genome-wide association study using data from 1,325 participants in the pivotal phase three trial of apixaban with the aim to identify genetic factors affecting the pharmacokinetics of apixaban. A candidate gene analysis was also performed for pre-specified variants in ABCB1, ABCG2, CYP3A4, CYP3A5, and SULT1A1, with a subsequent analysis of all available polymorphisms within the candidate genes. Significant findings were further evaluated to assess a potential association with clinical outcome such as bleeding or thromboembolic events. No variant was consistently associated with an altered apixaban exposure on a genome-wide level. The candidate gene analyses showed a statistically significant association with a well-known variant in the drug transporter gene ABCG2 (c.421G > T, rs2231142). Patients carrying this variant had a higher exposure to apixaban [area under the curve (AUC), beta = 151 (95% CI 59-243), p = 0.001]. On average, heterozygotes displayed a 5% increase of AUC and homozygotes a 17% increase of AUC, compared with homozygotes for the wild-type allele. Bleeding or thromboembolic events were not significantly associated with ABCG2 rs2231142. This large genome-wide study demonstrates that genetic variation in the drug transporter gene ABCG2 is associated with the pharmacokinetics of apixaban. However, the influence of this finding on drug exposure was small, and further studies are needed to better understand whether it is of relevance for ischemic and bleeding events.
|
|
| 21. |
- Attelind, Sofia, et al.
(författare)
-
Identification of risk factors for adverse drug reactions in a pharmacovigilance database
- 2023
-
Ingår i: Pharmacoepidemiology and Drug Safety. - : John Wiley & Sons. - 1053-8569 .- 1099-1557. ; 32:12, s. 1431-1438
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction In addition to identifying new safety signals, pharmacovigilance databases could be used to identify potential risk factors for adverse drug reactions (ADRs).Objective To evaluate whether data mining in a pharmacovigilance database can be used to identify known and possible novel risk factors for ADRs, for use in pharmacovigilance practice.Method Exploratory data mining was performed within the Swedish national database of spontaneously reported ADRs. Bleeding associated with direct oral anticoagulants (DOACs)-rivaroxaban, apixaban, edoxaban, and dabigatran-was used as a test model. We compared demographics, drug treatment, and clinical features between cases with bleeding (N = 965) and controls who had experienced other serious ADRs to DOACs (N = 511). Statistical analysis was performed by unadjusted and age adjusted logistic regression models, and the random forest based machine-learning method Boruta.Results In the logistic regression, 13 factors were significantly more common among cases of bleeding compared with controls. Eleven were labelled or previously proposed risk factors. Cardiac arrhythmia (e.g., atrial fibrillation), hypertension, mental impairment disorders (e.g., dementia), renal and urinary tract procedures, gastrointestinal ulceration and perforation, and interacting drugs remained significant after adjustment for age. In the Boruta analysis, high age, arrhythmia, hypertension, cardiac failure, thromboembolism, and pharmacodynamically interacting drugs had a larger than random association with the outcome. High age, cardiac arrhythmia, hypertension, cardiac failure, and pharmacodynamically interacting drugs had odds ratios for bleeding above one, while thromboembolism had an odds ratio below one.Conclusions We demonstrated that data mining within a pharmacovigilance database identifies known risk factors for DOAC bleeding, and potential risk factors such as dementia and atrial fibrillation. We propose that the method could be used in pharmacovigilance for identification of potential ADR risk factors that merit further evaluation.
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
- Beck, Alexander, et al.
(författare)
-
Akut brist på lärare i ekonomi på universiteten
- 2016
-
Ingår i: Svenska Dagbladet.
-
Recension (populärvet., debatt m.m.)abstract
- Redovisningen spelar en central roll i samhället genom att skapa transparens i näringsliv och offentlig sektor. Kraven på transparens ökar och redovisningen vidareutvecklas och anpassas till en global marknad. Bland studenter i företagsekonomi är det populärt att läsa redovisning. Men det råder stor brist på kompetenta universitetslärare i redovisning i Sverige
|
|
| 25. |
- Bhandage, Amol, 1988-, et al.
(författare)
-
Serum protein biomarker profile distinguishes acetylcholine receptor antibody seropositive myasthenia gravis patients from healthy controls.
- 2024
-
Ingår i: iScience. - : Elsevier. - 2589-0042. ; 27:8, s. 110564-
-
Tidskriftsartikel (refereegranskat)abstract
- There is an unmet need for objective disease-specific biomarkers in the heterogeneous autoimmune neuromuscular disorder myasthenia gravis (MG). This cross-sectional study identified a signature of 23 inflammatory serum proteins with proximity extension assay (PEA) that distinguishes acetylcholine receptor antibody seropositive (AChR+) MG patients from healthy controls (HCs). CCL28, TNFSF14, 4E-BP1, transforming growth factor alpha (TGF-α), and ST1A1 ranked top biomarkers. TGF-β1 and osteoprotegerin (OPG) differed between early- and late-onset MG, whereas CXCL10, TNFSF14, CCL11, interleukin-17C (IL-17C), and TGF-α differed significantly with immunosuppressive treatment. MG patients with moderate to high disease severity had lower uPA. Previously defined MG-associated microRNAs, miR-150-5p, miR-30e-5p, and miR-21-5p, correlated inversely with ST1A1 and TNFSF14. The presented inflammatory proteins that distinguish AChR+ MG are promising serum biomarkers for validation in prospective studies to allow for molecular signatures for patient subgroup stratification and monitoring of treatment response.
|
|
| 26. |
- Björck, Niclas, et al.
(författare)
-
Keramik : I: UV GAL Rapport 200:14. Snåret.Aspekter på sten-, brons och järnålder i Vendel, Väg E4, sträckan Uppsala-Mehedeby, Uppland, Vendels socken, Fallsboda 1:2, Karby 29:5, RAÄ 291
- 2007
-
Rapport (populärvet., debatt m.m.)abstract
- Arkeologisk undersökning av boplats med lämningar från neolitikum, yngre bronsålder och vendeltid. På platsen fanns även sannolika gravar. Analyser görs av hus, keramik, pollen mm. Platsen har under vendeltid utnyttjats för tjärframställning
|
|
| 27. |
|
|
| 28. |
- Brüggemann, Anders, et al.
(författare)
-
Risk of Revision After Arthroplasty Associated withSpecific Gene Loci : A Genomewide Association Study of Single-Nucleotide Polymorphisms in 1,130 TwinsTreated with Arthroplasty
- 2022
-
Ingår i: Journal of Bone and Joint Surgery. - 0301-620X .- 2044-5377. ; 104:7, s. 610-620
-
Tidskriftsartikel (refereegranskat)abstract
- Background:The risk of revision surgery following total joint arthroplasty (TJA) may be influenced by genetic factors. Therefore, we sought to identify genetic variants associated with the risk of revision surgery in a genomewide association studyMethodsWe investigated a cohort of 1,130 twins from the Swedish Twin Registry treated with TJA. During a mean of 9.4 years of follow-up, 75 individuals underwent revision surgery for aseptic loosening (the primary outcome) and 94, for any reason (the secondary outcome). Genetic information was collected using the Illumina OmniExpress and PsychArray panels, and the Haplotype Reference Consortium served as the reference for gene imputation. Adjusted Cox regression models were fitted to calculate hazard ratios (HRs) with 95% confidence intervals (CIs).ResultsNine single-nucleotide polymorphisms (SNPs) reached genomewide significance for aseptic loosening. The first SNP, rs77149046, located in the endosome-lysosome associated apoptosis and autophagy regulator family member 2 (ELAPOR2) gene, conferred an HR of 5.40 (CI, 3.23-9.02; p = 1.32×10−10), followed by 4 SNPs within the region coding for sodium-dependent taurine and beta-alanine transporter (SLC6A6), with HRs ranging from 3.35 to 3.43. The sixth SNP, rs7853989 (HR, 3.46; CI, 2.33-5.13; p = 6.91×10−10), was located in a region coding for the ABO blood group system. This SNP has been described as predictive for blood type B. Seven significant SNPs were found for the risk of revision for any reason, with the first 4 again being located in the SLC6A6 region. The leading SNP, rs62233562, conferred an HR of 3.11 (CI, 2.19-4.40; p = 1.74×10−10) for revision surgery. Similar HRs were found for SNPs 3:14506680 (p = 1.78×10−10), rs2289129 (p = 1.78×10−10), and rs17309567 (p = 3.16×10−10). The fifth SNP, rs11120968, was located in the calmodulin-binding transcription activator 1 (CAMTA1) gene (HR, 2.34; CI, 1.74-3.13, p = 1.45×10−8).ConclusionsWe identified 12 unique SNPs associated with an increased risk of revision surgery. Among these, 2 were in ELAPOR2, which is closely linked to bone formation. Another SNP is located in a gene region encoding for the ABO system, which merits further studies of causal relationships.
|
|
| 29. |
- Börlin, Niclas, 1968-, et al.
(författare)
-
A globally convergent gauss-newton algorithm for the bundle adjustment problem with functional constraints
- 2003
-
Ingår i: Optical 3-D measurement techniques. - : Wichmann-Verlag. ; , s. 269-276
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- This paper describes a Gauss-Newton-based algorithm for the bundle adjustment problem with functional constraints (GNC). The GNC algorithm has superior theoretical convergence properties compared to the conventional bundle algorithm. Both algorithms were applied to simulated measurements of a sphere with 2-3 cameras and 4-9 points. For 2 cameras and 4-5 points, the GNC converged in substantially more cases. For the other configurations, the convergence properties were similar. The added cost for the GNC algorithm was less than 0.01 iterations on average. The GNC algorithm need to be evaluated on real-world problems, but the results suggest that the algorithm will be more reliable for minimum data problems and have a minimal overhead for easy problems.
|
|
| 30. |
- Börlin, Niclas, 1968-, et al.
(författare)
-
Pros and cons of constrained and unconstrained formulation of the bundle adjustment problem
- 2004
-
Ingår i: ISPRS Congress Istanbul 2004, Proceedings of Commission III. - : ISPRS. ; , s. 589-594
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Two implementations of the bundle adjustment problem were applied to a subset of the Zurich City Hall reference data set. One implementation used the standard Euler angle parameterisation of the rotation matrix. The second implementation used all nine elements of the rotation matrix as unknowns and six functional constraints. The second formulation was constructed to reduce the non-linearity of the optimisation problem. The hypothesis was that a lower degree of non-linearity would lead to faster convergence. Furthermore, each implementation could optionally use the line search damping technique known from optimisation theory. The algorithms were used to solve the relative orientation problem for a varying number of homologous points from 33 different camera pairs. The results show that the constrained formulation has marginally better convergence properties, with or without damping. However, damping alone halves the number of convergence failures at a minor computational cost. The conclusion is that except to avoid the singularities associated with the Euler angles, the preferred use of the constrained formulation remains an open question. However, the results strongly suggest that the line search damping technique should be included in standard implementations of the bundle adjustment algorithm.
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
- Cavalli, Marco, et al.
(författare)
-
Genome-wide association study of liver enzyme elevation in an extended cohort of rheumatoid arthritis patients starting low-dose methotrexate
- 2022
-
Ingår i: Pharmacogenomics (London). - : Future Medicine. - 1462-2416 .- 1744-8042. ; 23:15, s. 813-820
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: A follow-up genome-wide association study (GWAS) in an extended cohort of rheumatoid arthritis (RA) patients starting low-dose methotrexate (MTX) treatment was performed to identify further genetic variants associated with alanine aminotransferase (ALT) elevation. Patients & methods: A GWAS was performed on 346 RA patients. Two outcomes within the first 6 months of MTX treatment were assessed: ALT >1.5-times the upper level of normal (ULN) and maximum level of ALT. Results: SPATA9 (rs72783407) was significantly associated with maximum level of ALT (p = 2.58 × 10-8) and PLCG2 (rs60427389) was tentatively associated with ALT >1.5 × ULN. Conclusion: Associations with SNPs in genes related to male fertility (SPATA9) and inflammatory processes (PLCG2) were identified.
|
|
| 34. |
- Cavalli, Marco, et al.
(författare)
-
Novel regulatory variant detected on the VKORC1 haplotype that is associated with warfarin dose
- 2016
-
Ingår i: Pharmacogenomics (London). - : Future Medicine Ltd. - 1462-2416 .- 1744-8042. ; 17:12, s. 1305-1314
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: Warfarin dose requirement is associated with VKORC1 rs9923231, and we studied whether it is a functional variant.Materials & methods: We selected variants in linkage disequilibrium with rs9923231 that bind transcription factors in an allele-specific way. Representative haplotypes were cloned or constructed, nuclear protein binding and transcriptional activity were evaluated.Results: rs56314408C>T and rs2032915C>T were detected in a liver enhancer in linkage disequilibrium with rs9923231. The rs56314408-rs2032915 C-C haplotype preferentially bound nuclear proteins and had higher transcriptional activity than T-T and the African-specific T-C. A motif for TFAP2A/C was disrupted by rs56314408T. No difference in transcriptional activity was detected for rs9923231G>A.Conclusion: Our results supported an activating role for rs56314408C, while rs9923231G>A had no evidence of being functional.
|
|
| 35. |
|
|
| 36. |
- Cismaru, Anca Liliana, et al.
(författare)
-
Genome-Wide Association Study of Metamizole-Induced Agranulocytosis in European Populations
- 2020
-
Ingår i: Genes. - : MDPI AG. - 2073-4425. ; 11:11
-
Tidskriftsartikel (refereegranskat)abstract
- Agranulocytosis is a rare yet severe idiosyncratic adverse drug reaction to metamizole, an analgesic widely used in countries such as Switzerland and Germany. Notably, an underlying mechanism has not yet been fully elucidated and no predictive factors are known to identify at-risk patients. With the aim to identify genetic susceptibility variants to metamizole-induced agranulocytosis (MIA) and neutropenia (MIN), we conducted a retrospective multi-center collaboration including cases and controls from three European populations. Association analyses were performed using genome-wide genotyping data from a Swiss cohort (45 cases, 191 controls) followed by replication in two independent European cohorts (41 cases, 273 controls) and a joint discovery meta-analysis. No genome-wide significant associations (p < 1 × 10−7) were observed in the Swiss cohort or in the joint meta-analysis, and no candidate genes suggesting an immune-mediated mechanism were identified. In the joint meta-analysis of MIA cases across all cohorts, two candidate loci on chromosome 9 were identified, rs55898176 (OR = 4.01, 95%CI: 2.41–6.68, p = 1.01 × 10−7) and rs4427239 (OR = 5.47, 95%CI: 2.81–10.65, p = 5.75 × 10−7), of which the latter is located in the SVEP1 gene previously implicated in hematopoiesis. This first genome-wide association study for MIA identified suggestive associations with biological plausibility that may be used as a stepping-stone for post-GWAS analyses to gain further insight into the mechanism underlying MIA.
|
|
| 37. |
- Collins, John, et al.
(författare)
-
The Supply Chain Management Game for the 2005 Trading Agent Competition
- 2004. - 1
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The Supply Chain Management Game for the 2005 Trading Agent Competition held during IJCAI 2005, in Edinburgh, Scotland. The supplier model has been substantially revised to overcome the "Day Zero" strategic singularity in TAC SCM 2003 and 2004.
|
|
| 38. |
|
|
| 39. |
- Davidsson, Pia, et al.
(författare)
-
Vascular endothelial growth factor-D plasma levels and VEGFD genetic variants are independently associated with outcomes in patients with cardiovascular disease
- 2023
-
Ingår i: Cardiovascular Research. - : Oxford University Press. - 0008-6363 .- 1755-3245. ; 119:7, s. 1596-1605
-
Tidskriftsartikel (refereegranskat)abstract
- Aims The vascular endothelial growth factor (VEGF) family is involved in pathophysiological mechanisms underlying cardiovascular (CV) diseases. The aim of this study was to investigate the associations between circulating VEGF ligands and/or soluble receptors and CV outcome in patients with acute coronary syndrome (ACS) and chronic coronary syndrome (CCS).Methods and results Levels of VEGF biomarkers, including bFGF, Flt-1, KDR (VEGFR2), PlGF, Tie-2, VEGF-A, VEGF-C, and VEGF-D, were measured in the PLATO ACS cohort (n = 2091, discovery cohort). Subsequently, VEGF-D was also measured in the STABILITY CCS cohort (n = 4015, confirmation cohort) to verify associations with CV outcomes. Associations between plasma VEGF-D and outcomes were analysed by multiple Cox regression models with hazard ratios (HR [95% CI]) comparing the upper vs. the lower quartile of VEGF-D. Genome-wide association study (GWAS) of VEGF-D in PLATO identified SNPs that were used as genetic instruments in Mendelian randomization (MR) meta-analyses vs. clinical endpoints. GWAS and MR were performed in patients with ACS from PLATO (n = 10 013) and FRISC-II (n = 2952), and with CCS from the STABILITY trial (n = 10 786). VEGF-D, KDR, Flt-1, and PlGF showed significant association with CV outcomes. VEGF-D was most strongly associated with CV death (P = 3.73e-05, HR 1.892 [1.419, 2.522]). Genome-wide significant associations with VEGF-D levels were identified at the VEGFD locus on chromosome Xp22. MR analyses of the combined top ranked SNPs (GWAS P-values; rs192812042, P = 5.82e-20; rs234500, P = 1.97e-14) demonstrated a significant effect on CV mortality [P = 0.0257, HR 1.81 (1.07, 3.04) per increase of one unit in log VEGF-D].Conclusion This is the first large-scale cohort study to demonstrate that both VEGF-D plasma levels and VEGFD genetic variants are independently associated with CV outcomes in patients with ACS and CCS. Measurements of VEGF-D levels and/or VEGFD genetic variants may provide incremental prognostic information in patients with ACS and CCS.
|
|
| 40. |
|
|
| 41. |
- Dixon-Suen, Suzanne C, et al.
(författare)
-
Physical activity, sedentary time and breast cancer risk : a Mendelian randomisation study
- 2022
-
Ingår i: British Journal of Sports Medicine. - : BMJ Publishing Group Ltd. - 0306-3674 .- 1473-0480. ; 56:20, s. 1157-1170
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Physical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics.METHODS: We performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105-377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=5) vigorous physical activity.RESULTS: Greater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger).CONCLUSION: Our study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women.
|
|
| 42. |
- Dunkels, Adam, et al.
(författare)
-
Powertrace: Network-level Power Profiling for Low-power Wireless Networks
- 2011. - 11
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Low-power wireless networks are quickly becoming a critical part of our everyday infrastructure. Power consumption is a critical concern, but power measurement and estimation is a challenge. We present Powertrace, which to the best of our knowledge is the first system for network-level power profiling of low-power wireless systems. Powertrace uses power state tracking to estimate system power consumption and a structure called energy capsules to attribute energy consumption to activities such as packet transmissions and receptions. With Powertrace, the power consumption of a system can be broken down into individual activities which allows us to answer questions such as “How much energy is spent forwarding packets for node X?”, “How much energy is spent on control traffic and how much on critical data?”, and “How much energy does application X account for?”. Experiments show that Powertrace is accurate to 94% of the energy consumption of a device. To demonstrate the usefulness of Powertrace, we use it to experimentally analyze the power behavior of the proposed IETF standard IPv6 RPL routing protocol and a sensor network data collection protocol. Through using Powertrace, we find the highest power consumers and are able to reduce the power consumption of data collection with 24%. It is our hope that Powertrace will help the community to make empirical energy evaluation a widely used tool in the low-power wireless research community toolbox.
|
|
| 43. |
|
|
| 44. |
- Dunkels, Adam, et al.
(författare)
-
Run-Time Dynamic Linking for Reprogramming Wireless Sensor Networks
- 2006
-
Ingår i: SenSys'06: Proceedings of the Fourth International Conference on Embedded Networked Sensor Systems. - New York, NY, USA : ACM. - 9781595933430 ; , s. 15-28
-
Konferensbidrag (refereegranskat)abstract
- From experience with wireless sensor networks it has become apparent that dynamic reprogramming of the sensor nodes is a useful feature. The resource constraints in terms of energy, memory, and processing power make sensor network reprogramming a challenging task. Many different mechanisms for reprogramming sensor nodes have been developed ranging from full image replacement to virtual machines.We have implemented an in-situ run-time dynamic linker and loader that use the standard ELF object file format. We show that run-time dynamic linking is an effective method for reprogramming even resource constrained wireless sensor nodes. To evaluate our dynamic linking mechanism we have implemented an application-specific virtual machine and a Java virtual machine and compare the energy cost of the different linking and execution models. We measure the energy consumption and execution time overhead on real hardware to quantify the energy costs for dynamic linkin.Our results suggest that while in general the overhead of a virtual machine is high, a combination of native code and virtual machine code provide good energy efficiency. Dynamic run-time linking can be used to update the native code, even in heterogeneous networks.
|
|
| 45. |
|
|
| 46. |
|
|
| 47. |
|
|
| 48. |
|
|
| 49. |
|
|
| 50. |
|
|
