| 1. |
- Khabou, Boudour, et al.
(author)
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Potential dysfunctional effects of synonymous variants: Insights from an exhaustive in silico analysis of the ABCB4 gene
- 2018
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In: Annals of Human Genetics. - : WILEY. - 0003-4800 .- 1469-1809. ; 82:6, s. 457-468
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Journal article (peer-reviewed)abstract
- The multiple drug resistance 3 (MDR3) protein is a canalicular phospholipid translocator involved in the bile secretion and encoded by the ABCB4 gene. Its deficiency is related to a large spectrum of liver diseases. Taking into account the increased evidence about the involvement of synonymous variants in inherited diseases, this study aims to explore the putative effects of silent genetic variants on the ABCB4 expression. We performed an exhaustive computational approach using ESE finder, RegRNA 2.0, MFOLD, SNPfold, and %MinMax software added to the measurement of the Relative Synonymous Codon Usage. This analysis included 216 synonymous variants distributed throughout the ABCB4 gene. Results have shown that 11 synonymous coding SNPs decrease the ESE activity, while 8 of them change the codon frequency. Besides, the c.24Camp;gt;T variation, located 21 nucleotides downstream the start A (Adenine) U (Uracil) G (Glutamine) AUG causes an increase in the local stability. Moreover, the computational analysis of the 3UTR region showed that six of the eight variants located in this region affected the Wild Type (WT) pattern of the miRNA targets sites and/or their proper display. The 26 sSNPs retained as putatively functional possessed a very low allele frequency, supporting their pathogenicity. In conclusion, the obtained results suggest that some synonymous SNPs in the ABCB4 gene, considered up to now as neutral, may be involved in the MDR3 deficiency.
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| 2. |
- Niazi Ardekani, Mehdi, 1990-, et al.
(author)
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Turbulence modulation in channel flow of finite-size spheroidal particles
- 2018
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In: Journal of Fluid Mechanics. - : Cambridge University Press (CUP). - 0022-1120 .- 1469-7645. ; 859, s. 887-901
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Journal article (peer-reviewed)abstract
- Finite-size particles modulate wall-bounded turbulence, leading, for the case of spherical particles, to increased drag also owing to the formation of a particle wall layer. Here, we study the effect of particle shape on the turbulence in suspensions of spheroidal particles at volume fraction phi = 10 % and show how the near-wall particle dynamics deeply changes with the particle aspect ratio and how this affects the global suspension behaviour. Direct numerical simulations are performed using a direct-forcing immersed boundary method to account for the dispersed phase, combined with a soft-sphere collision model and lubrication corrections for short-range particle-particle and particle-wall interactions. The turbulence reduces with the aspect ratio of oblate particles, leading to drag reduction with respect to the single-phase flow for particles with aspect ratio AR <= 1/3, when the significant reduction in Reynolds shear stress is more than the compensation by the additional stresses, induced by the solid phase. Oblate particles are found to avoid the region close to the wall, travelling parallel to it with small angular velocities, while preferentially sampling high-speed fluid in the wall region. Prolate particles also tend to orient parallel to the wall and avoid its vicinity. Their reluctance to rotate around the spanwise axis reduces the wall-normal velocity fluctuation of the flow and therefore the turbulence Reynolds stress, similar to oblates; however, they undergo rotations in wall-parallel planes which increase the additional solid stresses due to their relatively larger angular velocities compared to the oblates. These larger additional stresses compensate for the reduction in turbulence activity and lead to a wall drag similar to that of single-phase flows. Spheres on the other hand, form a layer close to the wall with large angular velocities in the spanwise direction, which increases the turbulence activity in addition to exerting the largest solid stresses on the suspension, in comparison to the other studied shapes. Spherical particles therefore increase the wall drag with respect to the single-phase flow.
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| 3. |
- Zade, Sagar, et al.
(author)
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Experimental investigation of turbulent suspensions of spherical particles in a squareduct
- 2018
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In: Journal of Fluid Mechanics. - : CAMBRIDGE UNIV PRESS. - 0022-1120 .- 1469-7645. ; 857, s. 748-783
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Journal article (peer-reviewed)abstract
- We report experimental observations of turbulent flow with spherical particles in a square duct. Three particle sizes, namely 2H/d(p) = 40, 16 and 9 (2H being the duct full height and d(p) being the particle diameter), are investigated. The particles are nearly neutrally buoyant with a density ratio of 1.0035 and 1.01 with respect to the suspending fluid. Refractive index matched-particle image velocimetry (RIM-PIV) is used for fluid velocity measurement even at the highest particle volume fraction (20 %) and particle tracking velocimetry (PTV) for the particle velocity statistics for the flows seeded with particles of the two largest sizes, whereas only pressure measurements are reported for the smallest particles. Settling effects are seen at the lowest bulk Reynolds number R-e2H approximate to 10 000, whereas, at the highest R-e2H approximate to 27 000, particles are in almost full suspension. The friction factor of the suspensions is found to be significantly larger than that of single-phase duct flow at the lower R-e2H investigated; however, the difference decreases when increasing the flow rate and the total drag approaches the values of the single-phase flow at the higher Reynolds number considered, R-e2H = 27 000. The pressure drop is found to decrease with the particle diameter for volume fractions lower than (sic) = 10% for nearly all R-e2H investigated. However, at the highest volume fraction (sic) = 20 %, we report a peculiar non-monotonic behaviour: the pressure drop first decreases and then increases with increasing particle size. The decrease of the turbulent drag with particle size at the lowest volume fractions is related to an attenuation of the turbulence. The drag increase for the two largest particle sizes at (sic) = 20 %, however, occurs despite this large reduction of the turbulent stresses, and it is therefore due to significant particle-induced stresses. At the lowest Reynolds number, the particles reside mostly in the bottom half of the duct, where the mean velocity significantly decreases; the flow is similar to that in a moving porous bed near the bottom wall and to turbulent duct flow with low particle concentration near the top wall.
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| 4. |
- Sundbom, Magnus, et al.
(author)
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Substantial Decrease in Comorbidity 5 Years After Gastric Bypass: A Population-based Study From the Scandinavian Obesity Surgery Registry.
- 2017
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In: Annals of Surgery. - Philadelphia PA, USA : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 265:6, s. 1166-1171
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Journal article (peer-reviewed)abstract
- Objective: To evaluate effect on comorbid disease and weight loss 5 years after Roux-en-Y gastric bypass (RYGB) surgery for morbid obesity in a large nationwide cohort. Background: The number patients having surgical procedures to treat obesity and obesity-related disease are increasing. Yet, population-based, long-term outcome studies are few. Methods: Data on 26,119 individuals [75.8% women, 41.0 years, and body mass index (BMI) 42.8 kg/m2] undergoing primary RYGB between May 1, 2007 and June 30, 2012, were collected from 2 Swedish quality registries: Scandinavian Obesity Surgery Registry and the Prescribed Drug Registry. Weight, remission of type 2 diabetes mellitus, hypertension, dyslipidemia, depression, and sleep apnea, and changes in corresponding laboratory data were studied. Five-year follow-up was 100% (9774 eligible individuals) for comorbid diseases. Results: BMI decreased from 42.8 ± 5.5 to 31.2 ± 5.5 kg/m2 at 5 years, corresponding to 27.7% reduction in total body weight. Prevalence of type 2 diabetes mellitus (15.5%–5.9%), hypertension (29.7%–19.5%), dyslipidemia (14.0%–6.8%), and sleep apnea (9.6%–2.6%) was reduced. Greater weight loss was a positive prognostic factor, whereas increasing age or BMI at baseline was a negative prognostic factor for remission. The use of antidepressants increased (24.1%–27.5%). Laboratory status was improved, for example, fasting glucose and glycated hemoglobin decreased from 6.1 to 5.4 mmol/mol and 41.8% to 37.7%, respectively. Conclusions: In this nationwide study, gastric bypass resulted in large improvements in obesity-related comorbid disease and sustained weight loss over a 5-year period. The increased use of antidepressants warrants further investigation. Studies with long-term results after bariatric surgery are surprisingly rare, 1–5 especially in the light of the large number of procedures performed worldwide. In most studies there is a 1 to 2-year follow-up, 6 and at such an early point in time, it is impossible to evaluate the true effect of gastric bypass, because patients have just reached their nadir in weight. Moreover, for this group of patients, the longstanding remission of obesity-related comorbidities, for example, diabetes mellitus, hypertension, dyslipidemia, and sleep apnea, are of utmost importance. The Scandinavian Obesity Surgery Registry (SOReg) was launched in 2007 as a quality registry for the expanding number of bariatric surgeries in Sweden. 7 In 2015, SOReg contained more than 50,000 bariatric procedures (>98% national coverage), with all 43 operating centers reporting to the registry. There has been an expansion of bariatric surgery, with 3300 bariatric procedures performed in 2008, 4800 in 2009, 7800 in 2010, and 8600 in 2011. There has been a slight decrease in procedures, and currently approximately 7000 performed annually, and approximately 95% of the reported procedures have been primary laparoscopic gastric bypass. 8 Perioperative complication rates (eg, 1.2% leaks) and mortality are low (0.04%), the latter validated with the Swedish Population Register. Regular audits are performed by randomly comparing data in SOReg with patient charts at the surgical centers, demonstrating a high validity with less than 2% incorrect values. 7 Furthermore, by cross-linkage with the national Prescribed Drug Registry (PDR), a 100% follow-up of the occurrence of comorbid disease (defined as medical treatment) can be achieved. The present study reports outcome in weight and obesity-related comorbid disease in a nationwide cohort of 26,119 individuals over 5 years after primary Roux-en-Y gastric bypass (RYGB) in Sweden, using the prospective SOReg database with cross-linkage with the PDR.
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