| 1. |
- Schafmayer, Clemens, et al.
(author)
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Genome-wide association analysis of diverticular disease points towards neuromuscular, connective tissue and epithelial pathomechanisms
- 2019
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In: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 68:5, s. 854-865
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Journal article (peer-reviewed)abstract
- Objective Diverticular disease is a common complex disorder characterised by mucosal outpouchings of the colonic wall that manifests through complications such as diverticulitis, perforation and bleeding. We report the to date largest genome-wide association study (GWAS) to identify genetic risk factors for diverticular disease. Design Discovery GWAS analysis was performed on UK Biobank imputed genotypes using 31 964 cases and 419 135 controls of European descent. Associations were replicated in a European sample of 3893 cases and 2829 diverticula-free controls and evaluated for risk contribution to diverticulitis and uncomplicated diverticulosis. Transcripts at top 20 replicating loci were analysed by real-time quatitative PCR in preparations of the mucosal, submucosal and muscular layer of colon. The localisation of expressed protein at selected loci was investigated by immunohistochemistry. Results We discovered 48 risk loci, of which 12 are novel, with genome-wide significance and consistent OR in the replication sample. Nominal replication (p< 0.05) was observed for 27 loci, and additional 8 in meta-analysis with a population-based cohort. The most significant novel risk variant rs9960286 is located near CTAGE1 with a p value of 2.3x10-10 and 0.002 (OR allelic = 1.14 (95% CI 1.05 to 1.24)) in the replication analysis. Four loci showed stronger effects for diverticulitis, PHGR1 (OR 1.32, 95% CI 1.12 to 1.56), FAM155A-2 (OR 1.21, 95% CI 1.04 to 1.42), CALCB (OR 1.17, 95% CI 1.03 to 1.33) and S100A10 (OR 1.17, 95% CI 1.03 to 1.33). Conclusion I n silico analyses point to diverticulosis primarily as a disorder of intestinal neuromuscular function and of impaired connective fibre support, while an additional diverticulitis risk might be conferred by epithelial dysfunction.
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| 2. |
- Menkveld, Albert J., et al.
(author)
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Nonstandard Errors
- 2024
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In: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
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Journal article (peer-reviewed)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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| 3. |
- Alqedra, Mohammed K., et al.
(author)
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Optical coherence properties of Kramers' rare-earth ions at the nanoscale for quantum applications
- 2023
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In: Physical Review B. - 2469-9950. ; 108:7
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Journal article (peer-reviewed)abstract
- Rare Earth (RE) ion doped nanomaterials are promising candidates for a range of quantum technology applications. Among RE ions, the so-called Kramers' ions possess spin transitions in the GHz range at low magnetic fields, which allows for high-bandwidth multimode quantum storage, fast qubit operations as well as interfacing with superconducting circuits. They also present relevant optical transitions in the infrared. In particular, Er3+ has an optical transition in the telecom band, while Nd3+ presents a high-emission-rate transition close to 890 nm. In this paper, we measure spectroscopic properties that are of relevance to using these materials in quantum technology applications. We find the inhomogeneous linewidth to be 10.7 GHz for Er3+ and 8.2 GHz for Nd3+, and the excited state lifetime T1 to be 13.68 ms for Er3+ and 540μs for Nd3+. We study the dependence of homogeneous linewidth on temperature for both samples, with the narrowest linewidth being 379 kHz (T2=839 ns) for Er3+ measured at 3 K, and 62 kHz (T2=5.14μs) for Nd3+ measured at 1.6 K. Further, we investigate time-dependent homogeneous linewidth broadening due to spectral diffusion and the dependence of the homogeneous linewidth on magnetic field to get additional clarity of mechanisms that can influence the coherence time. In light of our results, we discuss two applications: single qubit-state readout and a Fourier-limited single photon source.
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| 4. |
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| 5. |
- Andrikopoulos, Petros, et al.
(author)
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Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide
- 2023
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In: Nature Communications. - 2041-1723 .- 2041-1723. ; 14:1
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Journal article (peer-reviewed)abstract
- The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk.
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| 6. |
- Bondza, Saskia, et al.
(author)
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A simple experimental method for measuring the thermal sensitivity of single-mode fibers
- 2020
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In: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 91:10
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Journal article (peer-reviewed)abstract
- We present a simple technique to experimentally determine the optical-path length change with temperature for optical single-mode fibers. Standard single-mode fibers act as natural low-finesse cavities, with the Fresnel reflection of the straight cleaved surfaces being ∼3%, for the laser light coupled to them. By measuring the intensity variations due to interference of light reflected from the fiber front and end surfaces, while ramping the ambient temperature, the thermal sensitivity of the optical-path length of the fiber can be derived. Light was generated by a narrow linewidth, low drift laser. With our fairly short test fibers, we found that it was possible to reach a relative precision of the temperature sensitivity, compared to a reference fiber, on the 0.4%-2% scale and an absolute precision of 2%-5%, with the potential to improve both by an order of magnitude. The results for single-acrylate, dual-acrylate, and copper- and aluminum-coated fibers are presented. Values are compared with analytic models and results from a finite element method simulation. With the aid of these measurements, a simple fiber-interferometer, which is insensitive to thermal drifts, could be constructed.
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| 7. |
- Hennenberg, Martin, et al.
(author)
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α1-adrenoceptor activation induces phosphorylation of β2-adrenoceptors in human prostate tissue
- 2011
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In: BJU International. - 1464-4096 .- 1464-410X. ; 108:6, s. 922-928
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Journal article (peer-reviewed)abstract
- OBJECTIVE:• To test whether β1-adrenoceptor activation leads to phosphorylation of the β2-adrenoceptor in human prostate tissue.PATIENTS AND METHODS:• Prostate tissue from patients undergoing radical prostatectomy was stimulated in vitro with the α1-adrenergic agonist phenylephrine (10 µM).• α2-adrenoceptor phosphorylation at serines 345/346 was studied using Western blot analysis with a phospho-specific antibody.• The role of second messenger kinases was assessed by studying the effects of the protein kinase C (PKC) inhibitor Ro 31-8425 and the protein kinase A (PKA) inhibitor H89 on phenylephrine-induced phosphorylation.• The expression of G protein-coupled receptor kinases (GRKs) 2/3 was analysed using quantitative reverse-transcriptase-polymerase chain reaction (RT-PCR), Western blot analysis and immunohistochemistry.RESULTS:• Stimulation of prostate tissue with phenylephrine resulted in phosphorylation of the β2-adrenoceptor (5, 10 and 20 min after stimulation).• This α1-adrenoceptor-induced phosphorylation of β2-adrenoceptors was resistant to inhibition of PKC and PKA.• Changes in phosphorylation levels were not attributable to changes in receptor levels, as these remained constant during stimulation.• RT-PCR and Western blot analysis showed expression of GRK2/3 in human prostate tissues.• Immunohistochemical staining showed that GRK2/3 expression in human prostate tissue is located to stromal and smooth muscle cells.CONCLUSIONS:• Activation of α1-adrenoceptors causes phosphorylation of β2-adrenoceptors in the human prostate. This may enhance α1-adrenergic contraction and is possibly mediated by GRK2, which is expressed in prostate smooth muscle.• Mutual regulation between different adrenergic receptors might be involved in the therapeutic effects of α1-blockers in patients with benign prostate hyperplasia.
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| 8. |
- Horvath, Sebastian P., et al.
(author)
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Noise-free on-demand atomic frequency comb quantum memory
- 2021
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In: Physical Review Research. - 2643-1564. ; 3:2
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Journal article (peer-reviewed)abstract
- We present an extension of the atomic frequency comb protocol that utilizes the Stark effect to perform noise-free, on-demand, control. An experimental realization of this protocol was implemented in the Pr3+:Y2SiO5 solid-state system, and a recall efficiency of 38% for a 0.8 μs storage time was achieved. Experiments were performed with both bright pulses as well as weak-coherent states, the latter achieving a signal-to-noise ratio of 570±120 using input pulses with an average photon number of ∼0.1. The principal limitation for a longer storage time was found to be the minimum peak width attainable for Pr3+:Y2SiO5. We employ an adaptation of an established atomic frequency comb model to investigate an on-demand, wide-bandwidth, memory based on Eu3+:Y2SiO5. From this, we determine that a storage time as long as 100 μs may be practical even without recourse to spin-wave storage.
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| 9. |
- Ludwig, Sebastian, et al.
(author)
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Transcatheter Mitral Valve Replacement versus Medical Therapy for Secondary Mitral Regurgitation: A Propensity Score-Matched Comparison.
- 2023
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In: Circulation. Cardiovascular interventions. - 1941-7632. ; 16:6
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Journal article (peer-reviewed)abstract
- Background: Transcatheter mitral valve replacement (TMVR) is an emerging therapeutic alternative for patients with secondary mitral regurgitation (MR). Outcomes of TMVR versus guideline-directed medical therapy (GDMT) have not been investigated for this population. This study aimed to compare clinical outcomes of patients with secondary MR undergoing TMVR versus GDMT alone. Methods: The CHOICE-MI registry included patients with MR undergoing TMVR using dedicated devices. Patients with MR etiologies other than secondary MR were excluded. Patients treated with GDMT alone were derived from the control arm of the COAPT trial. We compared outcomes between the TMVR and GDMT groups, using propensity score (PS)-matching to adjust for baseline differences. Results: After PS-matching, 97 patient pairs undergoing TMVR (72.9±8.7 years, 60.8% male, transapical access 91.8%) versus GDMT (73.1±11.0 years, 59.8% male) were compared. At 1 and 2 years, residual MR was ≤1+ in all patients of the TMVR group compared to 6.9% and 7.7%, respectively, in those receiving GDMT alone (both p<0.001). The 2-year rate of HF hospitalization was significantly lower in the TMVR group (32.8% vs. 54.4%, HR 0.59, 95% CI 0.35-0.99; p=0.04). Among survivors, a higher proportion of patients were in NYHA functional class I or II in the TMVR group at 1 year (78.2% vs. 59.7%, p=0.03) and at 2 years (77.8% vs. 53.2%, p=0.09). Two-year mortality was similar in the two groups (TMVR vs. GDMT, 36.8% vs. 40.8%, HR 1.01, 95% CI 0.62-1.64; p=0.98). Conclusions: In this observational comparison, over 2-year follow-up, TMVR using mostly transapical devices in patients with secondary MR was associated with significant reduction of MR, symptomatic improvement, less frequent hospitalizations for HF and similar mortality compared with GDMT.
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| 10. |
- Molinaro, Antonio, et al.
(author)
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Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology
- 2020
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism.
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