| 1. |
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| 2. |
- Zillikens, M. C., et al.
(author)
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Large meta-analysis of genome-wide association studies identifies five loci for lean body mass
- 2017
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1
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Journal article (peer-reviewed)abstract
- Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 x 10(-8)) or suggestively genome wide (p < 2.3 x 10(-6)). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/ near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/ near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass.
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| 3. |
- Locke, Adam E, et al.
(author)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Journal article (peer-reviewed)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 4. |
- Karasik, D., et al.
(author)
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Disentangling the genetics of lean mass
- 2019
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In: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 109:2, s. 276-287
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Journal article (peer-reviewed)abstract
- Background: Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass. Objectives: To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci. Methods: We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age(2), and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms). Results: Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R). In contrast, loci with an impact specifically on LMwere termed "body builder" loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection. Conclusions: In conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.
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| 5. |
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| 6. |
- Shungin, Dmitry, et al.
(author)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Journal article (peer-reviewed)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 7. |
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| 8. |
- Willems, S. M., et al.
(author)
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Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness
- 2017
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Journal article (peer-reviewed)abstract
- Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength (P<5 × 10-8) in combined analyses. A number of these loci contain genes implicated in structure and function of skeletal muscle fibres (ACTG1), neuronal maintenance and signal transduction (PEX14, TGFA, SYT1), or monogenic syndromes with involvement of psychomotor impairment (PEX14, LRPPRC and KANSL1). Mendelian randomization analyses are consistent with a causal effect of higher genetically predicted grip strength on lower fracture risk. In conclusion, our findings provide new biological insight into the mechanistic underpinnings of grip strength and the causal role of muscular strength in age-related morbidities and mortality. © The Author(s) 2017.
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| 9. |
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| 10. |
- Drlica-Wagner, A., et al.
(author)
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SEARCH FOR GAMMA-RAY EMISSION FROM DES DWARF SPHEROIDAL GALAXY CANDIDATES WITH FERMI-LAT DATA
- 2015
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In: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 809:1
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Journal article (peer-reviewed)abstract
- Due to their proximity, high dark-matter (DM) content, and apparent absence of non-thermal processes, Milky Way dwarf spheroidal satellite galaxies (dSphs) are excellent targets for the indirect detection of DM. Recently, eight new dSph candidates were discovered using the first year of data from the Dark Energy Survey (DES). We searched for gamma-ray emission coincident with the positions of these new objects in six years of Fermi Large Area Telescope data. We found no significant excesses of gamma-ray emission. Under the assumption that the DES candidates are dSphs with DM halo properties similar to the known dSphs, we computed individual and combined limits on the velocity-averaged DM annihilation cross section for these new targets. If the estimated DM content of these dSph candidates is confirmed, they will constrain the annihilation cross section to lie below the thermal relic cross section for DM particles with masses less than or similar to 20 GeV annihilating via the b (b) over bar or pi(+)pi(-) channels.
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| 11. |
- Bernal, Ximena E., et al.
(author)
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Empowering Latina scientists
- 2019
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 363:6429, s. 825-826
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Journal article (other academic/artistic)
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| 12. |
- van Rheenen, Wouter, et al.
(author)
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Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis
- 2016
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:9, s. 1043-1048
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Journal article (peer-reviewed)abstract
- To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577 cases and 23,475 controls, combined with 2,579 cases and 2,767 controls in an independent replication cohort, we fine-mapped a new risk locus on chromosome 21 and identified C21orf2 as a gene associated with ALS risk. In addition, we identified MOBP and SCFD1 as new associated risk loci. We established evidence of ALS being a complex genetic trait with a polygenic architecture. Furthermore, we estimated the SNP-based heritability at 8.5%, with a distinct and important role for low-frequency variants (frequency 1-10%). This study motivates the interrogation of larger samples with full genome coverage to identify rare causal variants that underpin ALS risk.
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| 13. |
- Zheng, Hou-Feng, et al.
(author)
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Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture
- 2015
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 526:7571, s. 112-
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Journal article (peer-reviewed)abstract
- The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF <= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants(1-8), as well as rare, population specific, coding variants(9). Here we identify novel non-coding genetic variants with large effects on BMD (n(total) = 53,236) and fracture (n(total) = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD8 (rs11692564(T), MAF51.6%, replication effect size510.20 s.d., P-meta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size +10.41 s.d., P-meta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.
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| 14. |
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| 15. |
- Hsu, Y. H., et al.
(author)
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Meta-Analysis of Genomewide Association Studies Reveals Genetic Variants for Hip Bone Geometry
- 2019
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In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 34:7, s. 1284-1296
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Journal article (peer-reviewed)abstract
- Hip geometry is an important predictor of fracture. We performed a meta-analysis of GWAS studies in adults to identify genetic variants that are associated with proximal femur geometry phenotypes. We analyzed four phenotypes: (i) femoral neck length; (ii) neck-shaft angle; (iii) femoral neck width, and (iv) femoral neck section modulus, estimated from DXA scans using algorithms of hip structure analysis. In the Discovery stage, 10 cohort studies were included in the fixed-effect meta-analysis, with up to 18,719 men and women ages 16 to 93 years. Association analyses were performed with similar to 2.5 million polymorphisms under an additive model adjusted for age, body mass index, and height. Replication analyses of meta-GWAS significant loci (at adjusted genomewide significance [GWS], threshold p <= 2.6 x 10(-8)) were performed in seven additional cohorts in silico. We looked up SNPs associated in our analysis, for association with height, bone mineral density (BMD), and fracture. In meta-analysis (combined Discovery and Replication stages), GWS associations were found at 5p15 (IRX1 and ADAMTS16); 5q35 near FGFR4; at 12p11 (in CCDC91); 11q13 (near LRP5 and PPP6R3 (rs7102273)). Several hip geometry signals overlapped with BMD, including LRP5 (chr. 11). Chr. 11 SNP rs7102273 was associated with any-type fracture (p = 7.5 x 10(-5)). We used bone transcriptome data and discovered several significant eQTLs, including rs7102273 and PPP6R3 expression (p = 0.0007), and rs6556301 (intergenic, chr.5 near FGFR4) and PDLIM7 expression (p = 0.005). In conclusion, we found associations between several genes and hip geometry measures that explained 12% to 22% of heritability at different sites. The results provide a defined set of genes related to biological pathways relevant to BMD and etiology of bone fragility. (c) 2019 American Society for Bone and Mineral Research.
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| 16. |
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| 17. |
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| 18. |
- Minikel, EV, et al.
(author)
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Quantifying prion disease penetrance using large population control cohorts
- 2016
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In: Science translational medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6242 .- 1946-6234. ; 8:322, s. 322ra9-
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Journal article (peer-reviewed)abstract
- Large genomic reference data sets reveal a spectrum of pathogenicity in the prion protein gene and provide genetic validation for a therapeutic strategy in prion disease.
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| 19. |
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| 20. |
- Villarino, Ernesto, et al.
(author)
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Large-scale ocean connectivity and planktonic body size
- 2018
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9
-
Journal article (peer-reviewed)abstract
- Global patterns of planktonic diversity are mainly determined by the dispersal of propagules with ocean currents. However, the role that abundance and body size play in determining spatial patterns of diversity remains unclear. Here we analyse spatial community structure - beta-diversity - for several planktonic and nektonic organisms from prokaryotes to small mesopelagic fishes collected during the Malaspina 2010 Expedition. beta-diversity was compared to surface ocean transit times derived from a global circulation model, revealing a significant negative relationship that is stronger than environmental differences. Estimated dispersal scales for different groups show a negative correlation with body size, where less abundant large-bodied communities have significantly shorter dispersal scales and larger species spatial turnover rates than more abundant small-bodied plankton. Our results confirm that the dispersal scale of planktonic and micro-nektonic organisms is determined by local abundance, which scales with body size, ultimately setting global spatial patterns of diversity.
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| 21. |
- Buggert, Marcus, et al.
(author)
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Limited immune surveillance in lymphoid tissue by cytolytic CD4+ T cells during health and HIV disease
- 2018
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In: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7374. ; 14:4
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Journal article (peer-reviewed)abstract
- CD4+ T cells subsets have a wide range of important helper and regulatory functions in the immune system. Several studies have specifically suggested that circulating effector CD4+ T cells may play a direct role in control of HIV replication through cytolytic activity or autocrine β-chemokine production. However, it remains unclear whether effector CD4+ T cells expressing cytolytic molecules and β-chemokines are present within lymph nodes (LNs), a major site of HIV replication. Here, we report that expression of β-chemokines and cytolytic molecules are enriched within a CD4+ T cell population with high levels of the T-box transcription factors T-bet and eomesodermin (Eomes). This effector population is predominately found in peripheral blood and is limited in LNs regardless of HIV infection or treatment status. As a result, CD4+ T cells generally lack effector functions in LNs, including cytolytic capacity and IFNγ and β-chemokine expression, even in HIV elite controllers and during acute/early HIV infection. While we do find the presence of degranulating CD4+ T cells in LNs, these cells do not bear functional or transcriptional effector T cell properties and are inherently poor to form stable immunological synapses compared to their peripheral blood counterparts. We demonstrate that CD4+ T cell cytolytic function, phenotype, and programming in the peripheral blood is dissociated from those characteristics found in lymphoid tissues. Together, these data challenge our current models based on blood and suggest spatially and temporally dissociated mechanisms of viral control in lymphoid tissues.
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| 22. |
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| 23. |
- Raghavan, Maanasa, et al.
(author)
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Genomic evidence for the Pleistocene and recent population history of Native Americans
- 2015
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 349:6250
-
Journal article (peer-reviewed)abstract
- Howand when the Americas were populated remains contentious. Using ancient and modern genome-wide data, we found that the ancestors of all present-day Native Americans, including Athabascans and Amerindians, entered the Americas as a single migration wave from Siberia no earlier than 23 thousand years ago (ka) and after no more than an 8000-year isolation period in Beringia. After their arrival to the Americas, ancestral Native Americans diversified into two basal genetic branches around 13 ka, one that is now dispersed across North and South America and the other restricted to North America. Subsequent gene flow resulted in some Native Americans sharing ancestry with present-day East Asians (including Siberians) and, more distantly, Australo-Melanesians. Putative "Paleoamerican" relict populations, including the historical Mexican Pericues and South American Fuego-Patagonians, are not directly related to modern Australo-Melanesians as suggested by the Paleoamerican Model.
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| 24. |
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| 25. |
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| 26. |
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| 27. |
- Allahgholi, A., et al.
(author)
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Front end ASIC for AGIPD, a high dynamic range fast detector for the European XFEL
- 2016
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In: Journal of Instrumentation. - 1748-0221. ; 11:1
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Journal article (peer-reviewed)abstract
- The Adaptive Gain Integrating Pixel Detector (AGIPD) is a hybrid pixel X-ray detector for the European-XFEL. One of the detector's important parts is the radiation tolerant front end ASIC fulfilling the European-XFEL requirements: high dynamic range-from sensitivity to single 12.5keV-photons up to 104 photons. It is implemented using the dynamic gain switching technique with three possible gains of the charge sensitive preamplifier. Each pixel can store up to 352 images in memory operated in random-access mode at >= 4.5MHz frame rate. An external vetoing may be applied to overwrite unwanted frames.
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| 28. |
- Allahgholi, A., et al.
(author)
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The AGIPD 1.0 ASIC : Random access high frame rate, high dynamic range X-ray camera readout for the European XFEL
- 2015
-
In: 2015 IEEE Nuclear Science Symposium and Medical Imaging Conference, NSS/MIC 2015. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781467398626
-
Conference paper (peer-reviewed)abstract
- The European XFEL is an extremely brilliant Free Electron Laser Source with a very demanding pulse structure: trains of 2700 X-Ray pulses are repeated at 10 Hz. The pulses inside the train are spaced by 220 ns and each one contains up to 1012 photons of 12.4 keV, while being ≤ 100 fs in length. AGIPD (Adaptive Gain Integrating Pixel Detector) is a hybrid 1M-pixel detector developed by DESY, PSI, and the Universities of Bonn and Hamburg to cope with these properties. Thus the readout ASIC has to provide not only single photon sensitivity and a dynamic range ≳ 104 photons/pixel in the same image but also a memory for as many images of a pulse train as possible for delayed readout prior to the next train. The AGIPD 1.0 ASIC uses a 130 nm CMOS technology and radiation tolerant techniques to withstand the radiation damage incurred by the high impinging photon flux. Each ASIC contains 64 × 64 pixels of 200μmχ200μm. The circuit of each pixel contains a charge sensitive preamplifier with threefold switchable gain, a discriminator for an adaptive gain selection, and a correlated double sampling (CDS) stage to remove reset and low-frequency noise components. The output of the CDS, as well as the dynamically selected gain is sampled in a capacitor-based analogue memory for 352 samples, which occupies about 80% of a pixels area. For readout each pixel features a charge sensitive buffer. A control circuit with a command based interface provides random access to the memory and controls the row-wise readout of the data via multiplexers to four differential analogue ports. The AGIPD 1.0 full scale ASIC has been received back from the foundry in fall of 2013. Since then it has been extensively characterised also with a sensor as a single chip and in 2 × 8-chip modules for the AGIPD 1 Mpix detector. We present the design of the AGIPD 1.0 ASIC along with supporting results, also from beam tests at PETRA III and APS, and show changes incorporated in the recently taped out AGIPD 1.1 ASIC upgrade.
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| 29. |
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| 30. |
- Escamilla-García, E, et al.
(author)
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Antimicrobial Activity of a Cationic Guanidine Compound against Two Pathogenic Oral Bacteria
- 2017
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In: International journal of microbiology. - : Hindawi Limited. - 1687-918X .- 1687-9198. ; 2017, s. 5924717-
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Journal article (peer-reviewed)abstract
- This study evaluated the potential antimicrobial properties of a polyguanidine (CatDex) on two oral bacteria. Chlorhexidine gluconate 1340 μmoL L−1(CHX 0.12%) was used as control.Streptococcus mutans (S. mutans)andPorphyromonas gingivalis (P. gingivalis)were grown in BHI media. Bacterial sensitivity and antimicrobial activity were determined by the minimum inhibitory concentration (MIC) and Kirby-Bauer methods. To study side effects, that is, toxicity, dental pulp stem cells (DPSCs) were used. Fluorometric cytotoxicity and confocal microscopy assays were used in order to test cell viability. CatDex inhibited growth ofS. mutansat all concentrations and growth ofP. gingivalisat all concentrations except 25 μmoL L−1. The MIC of CatDex was 50 μmoL L−1for bothS. mutansandP. gingivalis. The inhibition of bacteria exposed for 8 h at 50 μmoL L−1of CatDex exhibited increased antimicrobial activity over time, with 91% inhibition in both bacteria. The antimicrobial activities of CatDex and CHX were similar when tested on two common bacteria. CatDex was significantly less toxic to DPSCs. CatDex toxicity depended on time and not on concentration. With regard to clinical relevance, CatDex may have potential as a novel antimicrobial agent. Further studies are in progress.
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| 31. |
- Hohnloser, Stefan H., et al.
(author)
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Renal Function and Outcomes With Dabigatran Dual Antithrombotic Therapy in Atrial Fibrillation Patients After PCI
- 2019
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In: JACC. - : ELSEVIER SCIENCE INC. - 1936-8798 .- 1876-7605. ; 12:16, s. 1553-1561
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Journal article (peer-reviewed)abstract
- OBJECTIVES: The study sought to evaluate the effect of dabigatran dual therapy versus warfarin triple therapy across categories of renal function in the RE-DUAL PCI (Randomized Evaluation of Dual Antithrombotic Therapy with Dabigatran versus Triple Therapy with Warfarin in Patients with Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) trial.BACKGROUND: The RE-DUAL PCI (NCT02164864) trial of patients with atrial fibrillation undergoing percutaneous coronary intervention reported that dabigatran dual therapy (110 or 150 mg twice daily, plus clopidogrel or ticagrelor) reduced the primary endpoint of major bleeding events (MBE) or clinically relevant nonmajor bleeding events (CRNMBE) compared with warfarin triple therapy, with noninferiority in overall thromboembolic events.METHODS: Risk of a first MBE or CRNMBE and the composite of death or thromboembolic event (DTE) or unplanned revascularization were evaluated in 2,725 patients according to baseline creatinine clearance (CrCl) categories: 30 to <50, 50 to <80, and >= 80 ml/min.RESULTS: Compared with warfarin, dabigatran 110 mg dual therapy reduced risk of MBE or CRNMBE across all categories of CrCl (p for interaction = 0.19). Dabigatran 150 mg dual therapy reduced risk of MBE or CRNMBE regardless of the CrCl category (p for interaction = 0.31). Risk of DTE or unplanned revascularization was similar to warfarin triple therapy for dabigatran 110 mg dual therapy across all CrCl categories. Dabigatran 150 mg dual therapy versus warfarin triple therapy had similar risk for DTE or unplanned revascularization in patients with CrCl 30 to <80 ml/min and lower risk at CrCl >= 80 ml/min (p for interaction = 0.02).CONCLUSIONS: In the RE-DUAL PCI trial, dabigatran dual therapy reduced bleeding events versus warfarin triple therapy irrespective of renal function, with overall similar risks of thromboembolic events but lower risks with dabigatran 150 mg in patients with normal CrCl.
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| 32. |
- Jaenson, Thomas G. T., et al.
(author)
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First evidence of established populations of the taiga tick Ixodes persulcatus (Acari: Ixodidae) in Sweden
- 2016
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In: Parasites & Vectors. - : Springer Science and Business Media LLC. - 1756-3305. ; 9
-
Journal article (peer-reviewed)abstract
- Background: The tick species Ixodes ricinus and I. persulcatus are of exceptional medical importance in the western and eastern parts, respectively, of the Palaearctic region. In Russia and Finland the range of I. persulcatus has recently increased. In Finland the first records of I. persulcatus are from 2004. The apparent expansion of its range in Finland prompted us to investigate if I. persulcatus also occurs in Sweden. Methods: Dog owners and hunters in the coastal areas of northern Sweden provided information about localities where ticks could be present. In May-August 2015 we used the cloth-dragging method in 36 localities potentially harbouring ticks in the Bothnian Bay area, province Norrbotten (NB) of northern Sweden. Further to the south in the provinces Vasterbotten (VB) and Uppland (UP) eight localities were similarly investigated. Results: Ixodes persulcatus was detected in 9 of 36 field localities in the Bothnian Bay area. Nymphs, adult males and adult females (n = 46 ticks) of I. persulcatus were present mainly in Alnus incana - Sorbus aucuparia - Picea abies - Pinus sylvestris vegetation communities on islands in the Bothnian Bay. Some of these I. persulcatus populations seem to be the most northerly populations so far recorded of this species. Dog owners asserted that their dogs became tick-infested on these islands for the first time 7-8 years ago. Moose (Alces alces), hares (Lepus timidus), domestic dogs (Canis lupus familiaris) and ground-feeding birds are the most likely carriers dispersing I. persulcatus in this area. All ticks (n = 124) from the more southern provinces of VB and UP were identified as I. ricinus. Conclusions: The geographical range of the taiga tick has recently expanded into northern Sweden. Increased information about prophylactic, anti-tick measures should be directed to people living in or visiting the coastal areas and islands of the Baltic Bay.
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| 33. |
- Mezza, D., et al.
(author)
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Characterization of AGIPD1.0 : The full scale chip
- 2016
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In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 838, s. 39-46
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Journal article (peer-reviewed)abstract
- The AGIPD (adaptive gain integrating pixel detector) detector is a high frame rate (4.5 MHz) and high dynamic range (up to 104 ·12.4 keV photons) detector with single photon resolution (down to 4 keV taking 5σ as limit and lowest noise settings) developed for the European XFEL (XFEL.EU). This work is focused on the characterization of AGIPD1.0, which is the first full scale version of the chip. The chip is 64×64 pixels and each pixel has a size of 200×200 μm2. Each pixel can store up to 352 images at a rate of 4.5 MHz (corresponding to 220 ns). A detailed characterization of the AGIPD1.0 chip has been performed in order to assess the main performance of the ASIC in terms of gain, noise, speed and dynamic range. From the measurements presented in this paper a good uniformity of the gain, a noise around 320 e− (rms) in standard mode and around 240 e− (rms) in high gain mode has been measured. Furthermore a detailed discussion about the non-linear behavior after the gain switching is presented with both experimental results and simulations.
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| 34. |
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| 35. |
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| 36. |
- Stille, B., et al.
(author)
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Stockholm bypass project – passage under the Lake Mälaren
- 2019
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In: Tunnels and Underground Cities. - London : CRC Press. - 9781138388659 - 9780429424441 ; , s. 1569-1578
-
Conference paper (peer-reviewed)abstract
- In the last years, the Swedish Transport Administration has been working on improving and expanding road communications in Sweden. The Stockholm Bypass Project, one of the biggest projects in Swedish history, consists of a 21 km long highway that goes around the city from north to south. In order to reduce the environmental impact, 17 km of the total length will be excavated underground passing through several regional fault zones and subsea passages. One of the most difficult technical challenges in this project is the passage under the Lake Mälaren and the regional fault zone in the Fiskar fjord. This paper presents the utilized methodology to design the temporary rock support and to manage the risks and uncertainties for the excavation through the fault zone, which mainly originate from the limited information about the rock conditions and the relatively large width of the tunnels.
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| 37. |
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| 38. |
- Vizoso, Miguel, et al.
(author)
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Epigenetic activation of a cryptic TBC1D16 transcript enhances melanoma progression by targeting EGFR
- 2015
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 21:7, s. 741-
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Journal article (peer-reviewed)abstract
- Metastasis is responsible for most cancer-related deaths, and, among common tumor types, melanoma is one with great potential to metastasize. Here we study the contribution of epigenetic changes to the dissemination process by analyzing the changes that occur at the DNA methylation level between primary cancer cells and metastases. We found a hypomethylation event that reactivates a cryptic transcript of the Rab GTPase activating protein TBC1D16 (TBC1D16-47 kDa; referred to hereafter as TBC1D16-47KD) to be a characteristic feature of the metastatic cascade. This short isoform of TBC1D16 exacerbates melanoma growth and metastasis both in vitro and in vivo. By combining immunoprecipitation and mass spectrometry, we identified RAB5C as a new TBC1D16 target and showed that it regulates EGFR in melanoma cells. We also found that epigenetic reactivation of TBC1D16-47KD is associated with poor clinical outcome in melanoma, while conferring greater sensitivity to BRAF and MEK inhibitors.
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