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- Peden, John F., et al.
(författare)
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A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:4, s. 339-344
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have identified 11 common variants convincingly associated with coronary artery disease (CAD)(1-7), a modest number considering the apparent heritability of CAD(8). All of these variants have been discovered in European populations. We report a meta-analysis of four large genome-wide association studies of CAD, with similar to 575,000 genotyped SNPs in a discovery dataset comprising 15,420 individuals with CAD (cases) (8,424 Europeans and 6,996 South Asians) and 15,062 controls. There was little evidence for ancestry-specific associations, supporting the use of combined analyses. Replication in an independent sample of 21,408 cases and 19,185 controls identified five loci newly associated with CAD (P < 5 x 10(-8) in the combined discovery and replication analysis): LIPA on 10q23, PDGFD on 11q22, ADAMTS7-MORF4L1 on 15q25, a gene rich locus on 7q22 and KIAA1462 on 10p11. The CAD-associated SNP in the PDGFD locus showed tissue-specific cis expression quantitative trait locus effects. These findings implicate new pathways for CAD susceptibility.
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| 3. |
- Wu, Q., et al.
(författare)
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Freight train air brake models
- 2021
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Ingår i: International Journal of Rail transportation. - : Informa UK Limited. - 2324-8378 .- 2324-8386.
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Tidskriftsartikel (refereegranskat)abstract
- This paper is an outcome of an international collaborative research initiative. Researchers from 24 institutions across 12 countries were invited to discuss the state-of-the-art in railway train air brake modelling with an emphasis on freight rains. Discussed models are classified as empirical, fluid dynamics and fluid-empirical dynamics models. Empirical models are widely used, and advanced versions have been used for train dynamics simulations. Fluid dynamics models are better models to study brake system behaviour but are more complex and slower in computation. Fluid-empirical dynamics models combine fluid dynamics brake pipe models and empirical brake valve models. They are a balance of model fidelity and computational speeds. Depending on research objectives, detailed models of brake rigging, friction blocks and wheel-rail adhesion are also available. To spark new ideas and more research in this field, the challenges and research gaps in air brake modelling are discussed.
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- Murtaza, S., et al.
(författare)
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Effect of exogenous administration of oxytocin on postpartum follicular dynamics, oestrous rate and ovulation in Nili-Ravi buffaloes
- 2021
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Ingår i: Reproduction in domestic animals. - : John Wiley & Sons. - 0936-6768 .- 1439-0531. ; 56:11, s. 1369-1376
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Tidskriftsartikel (refereegranskat)abstract
- Based on different surveys, dairy farmers are concerned about extensive use of exogenous oxytocin in buffaloes, which is being held responsible for reproductive problems including irregular oestrous cycle and delayed ovulation. For these concerns, effects of oxytocin injection on postpartum follicular dynamics, postpartum oestrous interval (PEI), oestrous length, the interval from onset of ostrus to ovulation and blood progesterone (P4) were studied in Nili-Ravi buffaloes. For this purpose, 23 animals within 1 week after calving were randomly divided into three groups: without oxytocin (CON; n = 7), 10 i.u. oxytocin (LOW; n = 8), 30 i.u. oxytocin – (HIGH; n = 8) and used to record the PEI for the study period of 154 days. At subsequent estrus, three buffaloes from each group (not served) were selected randomly to monitor two cycles for 6 weeks. Transrectal ultrasonography was performed to evaluate follicular and corpus luteum (CL) development, and blood sampling was done for progesterone (P4) analysis. These results revealed that postpartum oestrous interval (PEI) decreased significantly in oxytocin-treated groups. The number of small, medium and total follicles on the left ovary was significantly higher in the HIGH group. However, an overall number of small and total follicles on both right and left ovaries was significantly higher in CON and HIGH groups. On the other hand, there was no difference in the number of follicles on the right ovary among all treatment groups. The same was true for the size of pre-ovulatory follicles, CL, P4 concentrations and oestrous cycle length. The intervals from onset of estrus to ovulation and from standing estrus to ovulation were increased considerably in the HIGH group. It is concluded that exogenous oxytocin administration resulted in the shortening of PEI but triggered a delay in ovulation. Moreover, a higher dose of oxytocin could stimulate the growth of small, medium, and total follicles in postpartum Nili-Ravi buffaloes.
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| 7. |
- Shahcheraghi, Seyed H., et al.
(författare)
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Gene Therapy for Neuropsychiatric Disorders : Potential Targets and Tools
- 2023
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Ingår i: CNS & Neurological Disorders. - : Bentham Science Publishers. - 1871-5273 .- 1996-3181. ; 22:1, s. 51-65
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Forskningsöversikt (refereegranskat)abstract
- Neuropsychiatric disorders that affect the central nervous system cause considerable pressures on the health care system and have a substantial economic burden on modern societies. The present treatments based on available drugs are mostly ineffective and often costly. The molecular process of neuropsychiatric disorders is closely connected to modifying the genetic structures inherited or caused by damage, toxic chemicals, and some current diseases. Gene therapy is presently an experimental concept for neurological disorders. Clinical applications endeavor to alleviate the symptoms, reduce disease progression, and repair defective genes. Implementing gene therapy in inherited and acquired neurological illnesses entails the integration of several scientific disciplines, including virology, neurology, neurosurgery, molecular genetics, and immunology. Genetic manipulation has the power to minimize or cure illness by inducing genetic alterations at endogenous loci. Gene therapy that involves treating the disease by deleting, silencing, or editing defective genes and delivering genetic material to produce therapeutic molecules has excellent potential as a novel approach for treating neuropsychiatric disorders. With the recent advances in gene selection and vector design quality in targeted treatments, gene therapy could be an effective approach. This review article will investigate and report the newest and the most critical molecules and factors in neuropsychiatric disorder gene therapy. Different genome editing techniques available will be evaluated, and the review will highlight preclinical research of genome editing for neuropsychiatric disorders while also evaluating current limitations and potential strategies to overcome genome editing advancements.
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| 8. |
- Shahcheraghi, Seyed Hossein, et al.
(författare)
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Overview of key molecular and pharmacological targets for diabetes and associated diseases
- 2021
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Ingår i: Life Sciences. - : Elsevier. - 0024-3205 .- 1879-0631. ; 278
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Tidskriftsartikel (refereegranskat)abstract
- Diabetes epidemiological quantities are demonstrating one of the most important communities' health worries. The essential diabetic difficulties are including cardiomyopathy, nephropathy, inflammation, and retinopathy. Despite developments in glucose decreasing treatments and drugs, these diabetic complications are still ineffectively reversed or prohibited. Several signaling and molecular pathways are vital targets in the new therapies of diabetes. This review assesses the newest researches about the key molecules and signaling pathways as targets of molecular pharmacology in diabetes and diseases related to it for better treatment based on molecular sciences. The disease is not cured by current pharmacological strategies for type 2 diabetes. While several drug combinations are accessible that can efficiently modulate glycemia and mitigate long-term complications, these agents do not reverse pathogenesis, and in practice, they are not established to modify the patient's specific molecular profiling. Therapeutic companies have benefited from human genetics. Genome exploration, which is agnostic to the information that exists, has revealed tens of loci that impact glycemic modulation. The physiological report has begun to examine subtypes of diseases, illustrate heterogeneity and propose biochemical therapeutic pathways.
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