| 1. |
- Bar, N., et al.
(författare)
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A reference map of potential determinants for the human serum metabolome
- 2020
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Ingår i: Nature. - : Nature Research. - 0028-0836 .- 1476-4687. ; 588:7836, s. 135-140
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Tidskriftsartikel (refereegranskat)abstract
- The serum metabolome contains a plethora of biomarkers and causative agents of various diseases, some of which are endogenously produced and some that have been taken up from the environment1. The origins of specific compounds are known, including metabolites that are highly heritable2,3, or those that are influenced by the gut microbiome4, by lifestyle choices such as smoking5, or by diet6. However, the key determinants of most metabolites are still poorly understood. Here we measured the levels of 1,251 metabolites in serum samples from a unique and deeply phenotyped healthy human cohort of 491 individuals. We applied machine-learning algorithms to predict metabolite levels in held-out individuals on the basis of host genetics, gut microbiome, clinical parameters, diet, lifestyle and anthropometric measurements, and obtained statistically significant predictions for more than 76% of the profiled metabolites. Diet and microbiome had the strongest predictive power, and each explained hundreds of metabolites—in some cases, explaining more than 50% of the observed variance. We further validated microbiome-related predictions by showing a high replication rate in two geographically independent cohorts7,8 that were not available to us when we trained the algorithms. We used feature attribution analysis9 to reveal specific dietary and bacterial interactions. We further demonstrate that some of these interactions might be causal, as some metabolites that we predicted to be positively associated with bread were found to increase after a randomized clinical trial of bread intervention. Overall, our results reveal potential determinants of more than 800 metabolites, paving the way towards a mechanistic understanding of alterations in metabolites under different conditions and to designing interventions for manipulating the levels of circulating metabolites.
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| 2. |
- Wilman, H. R., et al.
(författare)
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Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration
- 2019
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Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 71:3, s. 594-602
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Excess liver iron content is common and is linked to the risk of hepatic and extrahepatic diseases. We aimed to identify genetic variants influencing liver iron content and use genetics to understand its link to other traits and diseases. Methods: First, we performed a genome-wide association study (GWAS) in 8,289 individuals from UK Biobank, whose liver iron level had been quantified by magnetic resonance imaging, before validating our findings in an independent cohort (n = 1,513 from IMI DIRECT). Second, we used Mendelian randomisation to test the causal effects of 25 predominantly metabolic traits on liver iron content. Third, we tested phenome-wide associations between liver iron variants and 770 traits and disease outcomes. Results: We identified 3 independent genetic variants (rs1800562 [C282Y] and rs1799945 [H63D] in HFE and rs855791 [V736A] in TMPRSS6) associated with liver iron content that reached the GWAS significance threshold (p <5 × 10−8). The 2 HFE variants account for ∼85% of all cases of hereditary haemochromatosis. Mendelian randomisation analysis provided evidence that higher central obesity plays a causal role in increased liver iron content. Phenome-wide association analysis demonstrated shared aetiopathogenic mechanisms for elevated liver iron, high blood pressure, cirrhosis, malignancies, neuropsychiatric and rheumatological conditions, while also highlighting inverse associations with anaemias, lipidaemias and ischaemic heart disease. Conclusion: Our study provides genetic evidence that mechanisms underlying higher liver iron content are likely systemic rather than organ specific, that higher central obesity is causally associated with higher liver iron, and that liver iron shares common aetiology with multiple metabolic and non-metabolic diseases. Lay summary: Excess liver iron content is common and is associated with liver diseases and metabolic diseases including diabetes, high blood pressure, and heart disease. We identified 3 genetic variants that are linked to an increased risk of developing higher liver iron content. We show that the same genetic variants are linked to higher risk of many diseases, but they may also be associated with some health advantages. Finally, we use genetic variants associated with waist-to-hip ratio as a tool to show that central obesity is causally associated with increased liver iron content.
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| 3. |
- Riedel, M., et al.
(författare)
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Improving e-Science with Interoperability of the e-Infrastructures EGEE and DEISA
- 2008
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Ingår i: MIPRO 2008 - 31st International Convention Proceedings. - 9789532330366 ; , s. 225-231
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Konferensbidrag (refereegranskat)abstract
- In the last couple of years, many e-Science infrastructures have begun to offer production services to e- Scientists with an increasing number of applications that require access to different kinds of computational resources. Within Europe two rather different multi-national e-Science infrastructures evolved over time namely Distributed European Infrastructure for Supercomputing Applications (DEISA) and Enabling Grids for E-SciencE (EGEE). DEISA provides access to massively parallel systems such as supercomputers that are well suited for scientific applications that require many interactions between their typically high numbers of CPUs. EGEE on the other hand provides access to a world-wide Grid of university clusters and PC pools that are well suited for farming applications that require less or even no interactions between the distributed CPUs. While DEISA uses the HPC-driven Grid technology UNICORE, EGEE is based on the gLite Grid middleware optimized for farming jobs. Both have less adoption of open standards and therefore both systems are technically non-interoperable, which means that no e-Scientist can easily leverage the DEISA and EGEE infrastructure with one suitable client environment for scientific applications. This paper argues that future interoperability of such large e-Science infrastructures is required to improve e-Science in general and to increase the real scientific impact of world-wide Grids in particular. We discuss the interoperability achieved by the OMII-Europe project that fundamentally improved the interoperability between UNICORE and gLite by using open standards. We also outline one specific scientific scenario of the WISDOM initiative that actually benefits from the recently established interoperability.
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| 4. |
- Kumar, M., et al.
(författare)
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Frontier review on the propensity and repercussion of SARS-CoV-2 migration to aquatic environment
- 2020
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Ingår i: Journal of Hazardous Materials Letters. - : Elsevier BV. - 2666-9110. ; 1
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Tidskriftsartikel (refereegranskat)abstract
- Increased concern has recently emerged pertaining to the occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in aquatic environment during the current coronavirus disease 2019 (COVID-19) pandemic. While infectious SARS-CoV-2 has yet to be identified in the aquatic environment, the virus potentially enters the wastewater stream from patient excretions and a precautionary approach dictates evaluating transmission pathways to ensure public health and safety. Although enveloped viruses have presumed low persistence in water and are generally susceptible to inactivation by environmental stressors, previously identified enveloped viruses persist in the aqueous environment from days to several weeks. Our analysis suggests that not only the surface water, but also groundwater, represent SARS-CoV-2 control points through possible leaching and infiltrations of effluents from health care facilities, sewage, and drainage water. Most fecally transmitted viruses are highly persistent in the aquatic environment, and therefore, the persistence of SARS-CoV-2 in water is essential to inform its fate in water, wastewater and groundwater and subsequent human exposure.
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| 5. |
- Campion, James, 1989-, et al.
(författare)
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Toward Industrial Exploitation of THz Frequencies : Integration of SiGe MMICs in Silicon-Micromachined Waveguide Systems
- 2019
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Ingår i: IEEE Transactions on Terahertz Science and Technology. - : Institute of Electrical and Electronics Engineers (IEEE). - 2156-342X .- 2156-3446. ; 9:6, s. 624-636
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Tidskriftsartikel (refereegranskat)abstract
- A new integration concept for terahertz (THz) systems is presented in this article, wherein patterned silicon-on-insulator wafers form all DC, IF, and RF networks in a homogeneous medium, in contrast to existing solutions. Using this concept, silicon-micromachined waveguides are combined with silicon germanium (SiGe) monolithic microwave integrated circuits (MMICs) for the first time. All features of the integration platform lie in the waveguide’s H-plane. Heterogeneous integration of SiGe chips is achieved using a novel in-line H-plane transition. As an initial step toward complete systems, we outline the design, fabrication, and assembly of back-to-back transition structures, for use at D-band frequencies (110ï¿œ170 GHz). Special focus is given to the industrial compatibility of all components, fabrication, and assembly processes, with an eye on the future commercialization of THz systems. Prototype devices are assembled via two distinct processes, one of which utilizes semiautomated die-bonding tools. Positional and orientation tolerances for each process are quantified. An accuracy of $\pm \text3.5\; μ \textm$, $\pm \text1.5 °$ is achieved. Measured $S$-parameters for each device are presented. The insertion loss of a single-ended transition, largely due to MMIC substrate losses, is 4.2ï¿œ5.5 dB, with a bandwidth of 25 GHz (135ï¿œ160 GHz). Return loss is in excess of 5 dB. Measurements confirm the excellent repeatability of the fabrication and assembly processes and, thus, their suitability for use in high-volume applications. The proposed integration concept is highly scalable, permitting its usage far into the THz frequency spectrum. This article represents the first stage in the shift to highly compact, low-cost, volume-manufacturable THz waveguide systems.
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| 6. |
- Chelvachandran, N, et al.
(författare)
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Considerations for the governance of ai and government legislative frameworks
- 2020
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Ingår i: Advanced Sciences and Technologies for Security Applications. - Cham : Springer. ; , s. 57-69
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The speed and proliferation of AI and algorithmic technology has far outpaced that of the development of the legislative frameworks to which to govern them, to ensure their appropriate, safe and permissive use. It is not suggested that the development of these technologies and integrations are thwarted or inhibited, but more that there is a holistic review and understanding of the complex integrations between the moral, ethical, technological and legal concepts that their use brings. Multiple approaches must be made, utilising top down legislative mechanisms, bottom up consumer and citizen led engagement approaches, and cross sector and industry led standardisation and frame working. Such a cyclical process would ensure that the continual development and evolution of the appropriate instruments keep in pace with technological development. And with such synergic pace, will bring allow such considerations to be made at the design phase technological solutions, rather than taking a reactionary and sometimes unknown approach. Afullunderstanding of new and emerging technologies is needed, how they interact and are interconnected, as well as their vulnerabilities, and causal effects, both direct and indirect, of the use of algorithmic and automated technology.
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| 7. |
- El-Seedi, Hesham, et al.
(författare)
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Metal nanoparticles fabricated by green chemistry using natural extracts : biosynthesis, mechanisms, and applications
- 2019
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Ingår i: RSC Advances. - : Royal Society of Chemistry. - 2046-2069. ; 9:42, s. 24539-24559
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Forskningsöversikt (refereegranskat)abstract
- Nanoparticles (NPs) are new inspiring clinical targets that have emerged from persistent efforts with unique properties and diverse applications. However, the main methods currently utilized in their production are not environmentally friendly. With the aim of promoting a green approach for the synthesis of NPs, this review describes eco-friendly methods for the preparation of biogenic NPs and the known mechanisms for their biosynthesis. Natural plant extracts contain many different secondary metabolites and biomolecules, including flavonoids, alkaloids, terpenoids, phenolic compounds and enzymes. Secondary metabolites can enable the reduction of metal ions to NPs in eco-friendly one-step synthetic processes. Moreover, the green synthesis of NPs using plant extracts often obviates the need for stabilizing and capping agents and yields biologically active shape- and size-dependent products. Herein, we review the formation of metallic NPs induced by natural extracts and list the plant extracts used in the synthesis of NPs. In addition, the use of bacterial and fungal extracts in the synthesis of NPs is highlighted, and the parameters that influence the rate of particle production, size, and morphology are discussed. Finally, the importance and uniqueness of NP-based products are illustrated, and their commercial applications in various fields are briefly featured.
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| 8. |
- Marzolla, M., et al.
(författare)
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Open standards-based interoperability of job submission and management interfaces across the grid middleware platforms gLite and UNICORE
- 2007
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Ingår i: Proceedings - e-Science 2007, 3rd IEEE International Conference on e-Science and Grid Computing. - : IEEE Computer Society. - 0769530648 - 9780769530642 ; , s. 592-599
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Konferensbidrag (refereegranskat)abstract
- In a distributed Grid environment with ambitious service demands the job submission and management interfaces provide functionality of major importance. Emerging e-Science and Grid infrastructures such as EGEE and DEISA rely on highly available services that are capable of managing scientific jobs. It is the adoption of emerging open standard interfaces which allows the distribution of Grid resources in such a way that their actual service implementation or Grid technologies are not isolated from each other, especially when these resources are deployed in different e-Science infrastructures that consist of different types of computational resources. This paper motivates the interoperability of these infrastructures and discusses solutions. We describe the adoption of various open standards that recently emerged from the Open Grid Forum (OGF) in the field of job submission and management by well-known Grid technologies, respectively gLite and UNICORE. This has a fundamental impact on the interoperability between these technologies and thus within the next generation e-Science infrastructures that rely on these technologies.
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| 9. |
- Samanta, S., et al.
(författare)
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Naphthalene Monoimide Derivative Ameliorates Amyloid Burden and Cognitive Decline in a Transgenic Mouse Model of Alzheimer's Disease
- 2021
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Ingår i: Advanced Therapeutics. - : Blackwell Publishing Ltd. - 2366-3987. ; 4:4
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) is a major neurodegenerative disorder and the leading cause of dementia worldwide. Predominantly, misfolding and aggregation of amyloid-β (Aβ) peptides associated with multifaceted toxicity is the neuropathological hallmark of AD pathogenesis and, thus the primary therapeutic target to ameliorate neuronal toxicity and cognitive deficits. Herein, the design, synthesis, and evaluation of small molecule inhibitors with naphthalene monoimide scaffold to ameliorate in vitro and in vivo amyloid induced neurotoxicity are reported. The detailed studies establish TGR63 as the lead candidate to rescue neuronal cells from amyloid toxicity. The in silico studies show the disruption of salt bridges and intermolecular hydrogen bonding interactions within Aβ42 fibrils by the interaction of TGR63, causing destabilization of Aβ42 assembly. Remarkably, TGR63 treatment shows a significant reduction in cortical and hippocampal amyloid burden in the progressive stages of APP/PS1 AD mice brain. Various behavioral tests demonstrate rescued cognitive deficits. The excellent biocompatibility, blood–brain barrier permeability, and therapeutic efficacy to reduce the amyloid burden make TGR63 a promising candidate for the treatment of AD.
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| 10. |
- Ahmad, T., et al.
(författare)
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Frequency and outcomes of undiagnosed diabetes mellitus in patients presenting with acute myocardial infarction
- 2020
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Ingår i: Medical Forum Monthly. - : Medical Forum Monthly. - 1029-385X. ; 31:12, s. 3-7
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To find out frequency and outcomes of undiagnosed diabetes mellitus in patients presenting with acute ST elevation myocardial infarction (STEMI). Study Design: Descriptive / Cross-Sectional Study Place and Duration of study: This study was conducted at the Cardiology Department, Lady Reading Hospital, Peshawar from November 2018 to May 2019. Materials and Methods: Patient of either gender having age ranging between 30-75 years old with acute STEMI who present within 12 hours of symptoms and with no past history of documented diabetes mellitus were included in the study. Venous blood samples for laboratory data, including random blood sugar, two fasting blood sugar and HBA1c using hitachi modular evo p800 machine was done. Results: A total of 158 patients having acute STEMI were studied. Males were 68.4% (n=108).The mean age was 59.65 ±10.80 years. Frequency of undiagnosed diabetes mellitus was 31.64 % (n = 50). In non-diabetics stress hyperglycemia was found in 51.85 % (n=56) patients. Among various types of STEMI, anterior STEMI was more common presentation 34.1 % (n=54. p= 0.85). Mean HBA1C was 6.19 ± 1.87%. Frequency of Ventricular tachycardia (VT) was 22.2 % in which undiagnosed diabetics were n=18 (p=0.004).Ventricular fibrillation was present in 13.3 % patients with undiagnosed diabetics were n=14 (p=0.001). Frequency of AF was 13.9% (n=22) with undiagnosed diabetics having AF in n=13 (p=0.003). SVT was present in 5.7% (n=9) patients with not significant difference between two groups (p=0.017). Among various mechanical complications VSR was present in 10 % (n=16) of patients (p=0.001), cardiogenic shock in 11.1 % (n=18) patients (p=0.004), acute LVF was present in 15.8 % patients (p=0.017). Conclusion: In our study we concluded that one third of patients having acute ST elevation myocardial infarction have undiagnosed diabetes mellitus (31.64 %, n = 50). The most common complication was ventricular tachycardia among electrical complication and LVF among mechanical complication.
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