| 41. |
- de las Fuentes, Lisa, et al.
(författare)
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Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26:6, s. 2111-2125
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Tidskriftsartikel (refereegranskat)abstract
- Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, “Some College” (yes/no) and “Graduated College” (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
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| 42. |
- de Vries, Paul S., et al.
(författare)
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Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
- 2019
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Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1033-1054
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Tidskriftsartikel (refereegranskat)abstract
- A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
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| 43. |
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| 44. |
- Doak, Bradley C, et al.
(författare)
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How Beyond Rule of 5 Drugs and Clinical Candidates Bind to Their Targets.
- 2016
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 59:6, s. 2312-2327
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Tidskriftsartikel (refereegranskat)abstract
- To improve discovery of drugs for difficult targets, the opportunities of chemical space beyond the rule of 5 (bRo5) were examined by retrospective analysis of a comprehensive set of structures for complexes between drugs and clinical candidates and their targets. The analysis illustrates the potential of compounds far beyond rule of 5 space to modulate novel and difficult target classes that have large, flat, and groove-shaped binding sites. However, ligand efficiencies are significantly reduced for flat- and groove-shape binding sites, suggesting that adjustments of how to use such metrics are required. Ligands bRo5 appear to benefit from an appropriate balance between rigidity and flexibility to bind with sufficient affinity to their targets, with macrocycles and nonmacrocycles being found to have similar flexibility. However, macrocycles were more disk- and spherelike, which may contribute to their superior binding to flat sites, while rigidification of nonmacrocycles lead to rodlike ligands that bind well to groove-shaped binding sites. These insights should contribute to altering perceptions of what targets are considered "druggable" and provide support for drug design in beyond rule of 5 space.
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| 45. |
- Du, Andong, et al.
(författare)
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The Influence of Ce, La, and SiC Particles Addition on the Formability of an Al-Si-Cu-Mg-Fe SiCp-MMC
- 2022
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Ingår i: Materials. - : MDPI. - 1996-1944. ; 15:11
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Tidskriftsartikel (refereegranskat)abstract
- Road transport and the associated fuel consumption plays a primary role in emissions. Weight reduction is critical to reaching the targeted reduction of 34% in 2025. Weight reduction in moving parts, such as pistons and brake disc rotors, provide a high-impact route to achieve this goal. The current study aims to investigate the formability of Al–Si alloys reinforced with different fractions and different sizes of SiCp to create an efficient and lightweight Al-MMC brake disk. Lanthanum (La) and cerium (Ce) were added to strengthen the aluminium matrix alloy and to improve the capability of the Al-MMC brake discs to withstand elevated temperature conditions, such as more extended braking periods. La and Ce formed intermetallic phases that further strengthened the composite. The analysis showed the processability and thermal stability of the different material’s combinations: increased particle sizes and broader size range mixture supported the formation of the SiCp particle interactions, acting as an internal scaffolding. In conclusion, the additions of Ce and La strengthened the softer matrix regions and resulted in a doubled compression peak strength of the material without affecting the formability, as demonstrated by the processing maps.
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| 46. |
- Fanidi, Anouar, et al.
(författare)
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Circulating Folate, Vitamin B6, and Methionine in Relation to Lung Cancer Risk in the Lung Cancer Cohort Consortium (LC3)
- 2018
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 110:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Circulating concentrations of B vitamins and factors related to one-carbon metabolism have been found to be strongly inversely associated with lung cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The extent to which these associations are present in other study populations is unknown.Methods: Within 20 prospective cohorts from the National Cancer Institute Cohort Consortium, a nested case-control study was designed including 5364 incident lung cancer case patients and 5364 control subjects who were individually matched to case patients by age, sex, cohort, and smoking status. Centralized biochemical analyses were performed to measure circulating concentrations of vitamin B6, folate, and methionine, as well as cotinine as an indicator of recent tobacco exposure. The association between these biomarkers and lung cancer risk was evaluated using conditional logistic regression models.Results: Participants with higher circulating concentrations of vitamin B6 and folate had a modestly decreased risk of lung cancer risk overall, the odds ratios when comparing the top and bottom fourths (OR 4vs1 ) being 0.88 (95% confidence interval [CI] = 0.78 to 1.00) and 0.86 (95% CI = 0.74 to 0.99), respectively. We found stronger associations among men (vitamin B6: OR 4vs1 = 0.74, 95% CI = 0.62 to 0.89; folate: OR 4vs1 = 0.75, 95% CI = 0.61 to 0.93) and ever smokers (vitamin B6: OR 4vs1 = 0.78, 95% CI = 0.67 to 0.91; folate: OR 4vs1 = 0.87, 95% CI = 0.73 to 1.03). We further noted that the association of folate was restricted to Europe/Australia and Asia, whereas no clear association was observed for the United States. Circulating concentrations of methionine were not associated with lung cancer risk overall or in important subgroups.Conclusions: Although confounding by tobacco exposure or reverse causation cannot be ruled out, these study results are compatible with a small decrease in lung cancer risk in ever smokers who avoid low concentrations of circulating folate and vitamin B6.
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| 47. |
- Feitosa, Mary F., et al.
(författare)
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Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
- 2018
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Ingår i: PLOS ONE. - : Public library science. - 1932-6203. ; 13:6
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Tidskriftsartikel (refereegranskat)abstract
- Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in approximate to 131 K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P <1.0 x 10(-5)). In Stage 2, these SNVs were tested for independent external replication in individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10(-8)). For African ancestry samples, we detected 18 potentially novel BP loci (P< 5.0 x 10(-8)) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2 have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
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| 48. |
- Gao, Jie, et al.
(författare)
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A Study on Electrical Properties of Controlled Delamination Material
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Primarily used in aerospace applications, Controlled Delamination Material (CDM) has recently drawn attention to the traditional packaging industry due to its low-cost and electrical easy-open. Sinuate®, a CDM product, consists of two aluminum foils bonded together with a conductive epoxy adhesive. When applying a little electricity on its surface, the material can open easily without violence and release without residue. In this paper, a brief introduction on Sinuate® will be presented at first. And some test results on the electrical properties of the joint opening/detaching process will be shown and analyzed.
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| 49. |
- Gao, Jie
(författare)
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Intelligent and Interactive Package Based on RFID and WSN
- 2011
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- An intelligent and interactive package can interact with people smartly, safely and friendly. It involves many technologies such as electronics, optics, biologic, magnetics and electro-mechanics. By combined with Radio Frequency Identification (RFID) and Wireless Sensor Network (WSN), intelligent and interactive packaging technology has been an emerging and global research topic over the years. In this thesis, a new technology, named Controlled Delamination Material (CDM), is introduced. It was primarily used in aerospace applications in the past and further developed by Stora Enso AB. A CDM product can delaminate easily in a controlled way by the use of electrical current. This concept opens up many interesting application possibilities for the traditional packaging industry. In order to understand the delamination mechanism, some related work on the electrochemical characteristics of the material showed the possibility to facilitate the interactive packaging system design. A paper-based package which is integrated with RFID system and CDM is presented to realize an intelligent and interactive system. It can be opened automatically through a finger touch. The opening action is controlled electrically by RFID system. The test results of the demonstration have proved feasibility of the solution and shown the potential for mass production. Following this solution, an interactive pharmaceutical package for pervasive healthcare is proposed by using EPCglobal Gen2 RFID technology. A Gen2 RFID system significantly increases the efficiency of information exchange, and reduces the medication error rate and the possibility of sale counterfeit drugs. It makes the medication accessible for patient only at the prescribed dose and time, and at the same time, the information for the action of taking medication will be delivered to the doctor as well. Such interactive pharmaceutical package not only gives unprecedented high patient compliance, but also improves the communication between patients and healthcare staffs. By integrating WSN with various bio-chemical sensors, in addition to temperature and moisture sensors, more kinds of information can be involved in the intelligent and interactive packaging communication system. It enhances the functionalities of the package such as rotecting the integrity and effectiveness of product, providing safety information details, and being child resistance, senior friendliness
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| 50. |
- Gao, Jie, et al.
(författare)
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Interactive Packaging Solutions Based on RFIDTechnology and Controlled Delamination Material
- 2010
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Konferensbidrag (refereegranskat)abstract
- Interactive packaging is an emerging research area in recent years. It brings people convenient and smart lives, reduces consumption of traditional packaging materials and direct or indirect labor costs as well. Being integrated in interactive packaging, Radio Frequency Identification (RFID) technology becomes one of the most proactive development enablers. In this paper, an interactive and intelligent packaging solution integrating passive RFID system and Controlled Delamination Material (CDM) is given at first. Package opening action is electrically controlled by the RFID system. CDM is primarily used in aerospace applications in the past and the conductor/adhesive joint can be easily opened by applying a little electric power on to the material. Some related works will be shown about the electrochemical characteristics of CDM in order to facilitate the system design. A demonstration system was developed and the test results have proved feasibility of the solution and shown the potential of low cost for mass production. Based on this solution, an interactive medication package for pervasive healthcare is further developed, using EPCglobal Gen2 RFID technology. It will make the medication being accessible for patient only at the prescribed dose and time, and medication taking information will be delivered as well. Such medication package will not only give unprecedented high patient compliance, but also improve the communication between patients and healthcare staffs.
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