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- 2019
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Tidskriftsartikel (refereegranskat)
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- Palmer, Nicholette D, et al.
(författare)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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Tidskriftsartikel (refereegranskat)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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- Flentie, Kelly, et al.
(författare)
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Chemical disarming of isoniazid resistance in Mycobacterium tuberculosis
- 2019
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : The National Academy of Scionces of the United States of America. - 0027-8424 .- 1091-6490. ; 116:21, s. 10510-10517
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Tidskriftsartikel (refereegranskat)abstract
- Mycobacterium tuberculosis (Mtb) killed more people in 2017 than any other single infectious agent. This dangerous pathogen is able to withstand stresses imposed by the immune system and tolerate exposure to antibiotics, resulting in persistent infection. The global tuberculosis (TB) epidemic has been exacerbated by the emergence of mutant strains of Mtb that are resistant to frontline antibiotics. Thus, both phenotypic drug tolerance and genetic drug resistance are major obstacles to successful TB therapy. Using a chemical approach to identify compounds that block stress and drug tolerance, as opposed to traditional screens for compounds that kill Mtb, we identified a small molecule, C10, that blocks tolerance to oxidative stress, acid stress, and the frontline antibiotic isoniazid (INH). In addition, we found that C10 prevents the selection for INH-resistant mutants and restores INH sensitivity in otherwise INH-resistant Mtb strains harboring mutations in the katG gene, which encodes the enzyme that converts the prodrug INH to its active form. Through mechanistic studies, we discovered that C10 inhibits Mtb respiration, revealing a link between respiration homeostasis and INH sensitivity. Therefore, by using C10 to dissect Mtb persistence, we discovered that INH resistance is not absolute and can be reversed.
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- Oliveira, M. H. de Andrade, et al.
(författare)
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Soot, PAH and OH measurements in vaporized liquid fuel flames
- 2013
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Ingår i: Fuel. - : Elsevier BV. - 1873-7153 .- 0016-2361. ; 112, s. 145-152
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Tidskriftsartikel (refereegranskat)abstract
- Qualitative measurements of both OH and polycyclic aromatic hydrocarbons (PAH) as well as quantitative data of soot volume fraction f(v) have been obtained in vaporized liquid fuels, with the main goal of providing experimental data for combustion models and numerical mechanism validation. Measurements were carried out in a laminar coflow burner which was designed, built and integrated with an evaporation system, enabling the combustion of vaporized liquid fuels at pressures of up to 3.0 MPa to be studied. The fuels n-heptane and n-decane, referred to in the literature as being important surrogate fuels, were selected for measurements at atmospheric pressure that were carried out in the experimental setup described, making use of a combination of the Laser Induced Fluorescence (LIF) and Laser Induced Incandescence (LII) techniques. Partially premixed flames of n-heptane and n-decane showed similar combustion characteristics in the range of 1.9 < phi < 3.7. For both of the fuels the threshold for soot formation was found to be at about phi similar to 3.3. Comparison of the LIF and LII measurements for the n-heptane flames within the range of 3.7 <= phi <= 8.5 indicated the maximum PAH LIF signal to be a good predictor of f(vmax) obtained from LII. Excitation at 266 nm using delayed detection was found to result in the signals obtained showing a close linear correlation with the soot volume fraction obtained from LII when prompt detection at 1064 nm excitation was used. Neither the effects of any additional photo-chemical processes making use of high laser power at 266 nm nor the effects of particle size on the delayed gate times appeared to be of any significance for the flame conditions studied here. (C) 2013 Elsevier Ltd. All rights reserved.
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- Protudjer, Jennifer L. P., et al.
(författare)
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Household Costs Associated with Objectively Diagnosed Allergy to Staple Foods in Children and Adolescents
- 2015
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Ingår i: Journal of Allergy and Clinical Immunology-In Practice. - : Elsevier BV. - 2213-2198 .- 2213-2201. ; 3:1, s. 68-75
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We previously reported that indirect and intangible costs burden households with a food allergic adult. We now extend our investigation to households with food allergic children and adolescents. OBJECTIVE: The objective of this study was to estimate direct, indirect, and intangible costs of food allergy in households with a child and/or adolescent with objectively diagnosed allergy to staple foods (cow's milk, hen's egg, and/or wheat), and to compare these costs with age-and sex-matched controls. METHODS: Direct and indirect cost parent-reported data collected via the Food Allergy Socio-Economic Questionnaire of 84 children (0-12 years) and 60 adolescents (13-17 years) with objectively diagnosed allergy to staple foods ("cases") and age- and sex-matched controls (n = 94 children; n = 56 adolescents) were compared. Annual household costs were calculated. Total household costs included direct plus indirect costs. Intangible costs included parent-reported health of their child and/or adolescent, standard of living, and perceptions of well-being. RESULTS: Amongst cases, total household costs were higher by (sic)3961 for children and (sic)4792 for adolescents versus controls (P < .05), and were driven by direct (eg, medications) and indirect (eg, time with health care professionals) costs. For children only, a history of anaphylaxis was associated with higher direct costs than no anaphylaxis ((sic)13,016 vs (sic)10,044, P < .05). Intangible costs (eg, parent-reported health of a child and/or adolescent) were significantly impacted amongst cases versus controls (P < .01). CONCLUSION: Households with a child and/or adolescent with objectively diagnosed allergy to staple foods have higher total household costs than controls. Direct and indirect costs were significantly higher for cases versus controls amongst children only. Amongst both age groups, such allergy adversely impacted intangible costs. (C) 2015 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.
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- Andersson, Emma K., et al.
(författare)
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Modulation of Curli Assembly and Pellicle Biofilm Formation by Chemical and Protein Chaperones
- 2013
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Ingår i: Chemistry and Biology. - : Elsevier. - 1074-5521 .- 1879-1301. ; 20:10, s. 1245-1254
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Tidskriftsartikel (refereegranskat)abstract
- Enteric bacteria assemble functional amyloid fibers, curli, on their surfaces that share structural and biochemical properties with disease-associated amyloids. Here, we test rationally designed 2-pyridone compounds for their ability to alter amyloid formation of the major curli subunit CsgA. We identified several compounds that discourage CsgA amyloid formation and several compounds that accelerate CsgA amyloid formation. The ability of inhibitor compounds to stop growing CsgA fibers was compared to the same property of the CsgA chaperone, CsgE. CsgE blocked CsgA amyloid assembly and arrested polymerization when added to actively polymerizing fibers. Additionally, CsgE and the 2-pyridone inhibitors prevented biofilm formation by Escherichia coli at the air-liquid interface of a static culture. We demonstrate that curli amyloid assembly and curli-dependent biofilm formation can be modulated not only by protein chaperones, but also by "chemical chaperones."
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| 9. |
- Baek, Jeanha, et al.
(författare)
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Engineered mesoporous silica reduces long-term blood glucose and HbA1c, and improves metabolic parameters in prediabetics
- 2022
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Ingår i: Nanomedicine. - : Future Medicine Ltd. - 1743-5889 .- 1748-6963. ; 17:1, s. 9-22
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To investigate the effect of oral consumption of engineered mesoporous silica particles, SiPore15®, on long-term blood glucose levels and other metabolic parameters in individuals with prediabetes and newly diagnosed Type 2 diabetes. Method: An open-label, single-arm, multicenter trial was conducted in which SiPore15 was consumed three times daily for 12 weeks. Hemoglobin A1c (HbA1c, primary end point) and an array of metabolic parameters were measured at baseline and throughout the trial. Result: SiPore15 treatment significantly reduced HbA1c by a clinically meaningful degree and improved several disease-associated parameters with minimal side effects. Conclusion: The results from this study demonstrate the potential use of SiPore15 as a treatment for prediabetes that may also delay or prevent the onset of Type 2 diabetes.
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| 10. |
- Bengtsson, Erik L, et al.
(författare)
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A Case Study on the Influence of Multiple Users on the Effective Channel in a Massive MIMO System
- 2019
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Ingår i: IEEE Wireless Communications Letters. - 2162-2337. ; , s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- We investigate the importance of weak clusters when modeling a wireless massive MIMO channel. We do this by studying the influence of densely spaced terminals and the number of base-station antennas for a zero-forcing precoded massive MIMO system. In particular, we focus on the influence on the correlation and imbalance between the signals at the terminal antennas, the effective channel-gain, the eigenvalue distributions and the number of clusters.The study is based on measured radio-channels from terminal prototypes with integrated antennas connected to a massive MIMO testbed.We further evaluate the advantage of using block-diagonalized zero-forcing compared to conventional zero-forcing in a massive MIMO system. Unexpectedly, terminals with low antenna envelope correlation coefficient may benefit significantly from block-diagonal zero-forcing in a massive MIMO system.The main conclusion is that weaker clusters are important when modeling multi-user scenarios.
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