20 research outputs found
Dynamic mooring simulation with Code_Aster with application to a floating wind turbine
This is the final version of the article. Available from Elsevier via the DOI in this record.The design of reliable station-keeping systems for permanent floating structures such as offshore renewable energy devices is vital to their lifelong integrity. In highly dynamic and/or deep-water applications, including hydrodynamics and structural dynamics in the mooring analysis is paramount for the accurate prediction of the loading on the lines and hence their dimensioning. This article presents a new workflow based on EDF R&D's open-source, finite-element analysis tool Code_Aster, enabling the dynamic analysis of catenary mooring systems, with application to a floating wind turbine concept. The University of Maine DeepCwind-OC4 basin test campaign is used for validation, showing that Code_Aster can satisfactorily predict the fairlead tensions in both regular and irregular waves. In the latter case, all of the three main spectral components of tension observed in the experiments are found numerically. Also, the dynamic line tension is systematically compared with that provided by the classic quasi-static approach, thereby confirming its limitations. Robust dynamic simulation of catenary moorings is shown to be possible using this generalist finite-element software, provided that the inputs be organised consistently with the physics of offshore hydromechanics.IDCORE is funded by the ETI and the RCUK Energy programme, grant number EP/J500847/1. The authors are grateful for the funding provided by these institutions, and to EDF R&D for hosting and supervising the industrial doctorate which expressed the present work
Migraine Prevention through Ketogenic Diet: More than Body Mass Composition Changes
The ketogenic diet (KD) is gaining attention as a preventive treatment for migraine, which is sustained by many pre-clinical and clinical data. KD is also used for weight loss, and there is a relation between migraine and weight excess, but it is speculated that KD efficacy on migraine may go beyond this effect. We conducted a retrospective observational study on 23 migraine patients who received a KD and were evaluated at the baseline and then after 3 months both from a neurological and a nutritional point of view, including body mass composition analysis. We observed a reduction in monthly headache days (12.5 ± 9.5 vs. 6.7 ± 8.6; p < 0.001) and in days of acute medication intake (11.06 ± 9.37 vs. 4.93 ± 7.99; p = 0.008). We also observed a reduction in patientsâ weight (73.8 ± 15.2 vs. 68.4 ± 14.6; p < 0.001) and BMI (26.9 ± 6.2 vs. 23.7 ± 8.1; p < 0.001) with a decrement of the fat mass (28.6 ± 12.5 vs. 20.6 ± 9.8; p < 0.001). Patients who responded to KD and those who did not had no differences with respect to weight or fat mass loss. These data corroborate the utilization of KD as a preventive treatment for migraine and suggest that the efficacy of such an intervention is not only due to weight or fat mass loss but probably relies on other mechanisms specific to KD
A human minisatellite hosts an alternative transcription start site for NPRL3 driving its expression in a repeat number-dependent manner
Minisatellites, also called variable number of tandem repeats (VNTRs), are a class of repetitive elements that may affect gene expression at multiple levels and have been correlated to disease. Their identification and role as expression quantitative trait loci (eQTL) have been limited by their absence in comparative genomic hybridization and single nucleotide polymorphisms arrays. By taking advantage of cap analysis of gene expression (CAGE), we describe a new example of a minisatellite hosting a transcription start site (TSS) which expression is dependent on the repeat number. It is located in the third intron of the gene nitrogen permease regulator like protein 3 (NPRL3). NPRL3 is a component of the GAP activity toward rags 1 protein complex that inhibits mammalian target of rapamycin complex 1 (mTORC1) activity and it is found mutated in familial focal cortical dysplasia and familial focal epilepsy. CAGE tags represent an alternative TSS identifying TAGNPRL3 messenger RNAs (mRNAs). TAGNPRL3 is expressed in red blood cells both at mRNA and protein levels, it interacts with its protein partner NPRL2 and its overexpression inhibits cell proliferation. This study provides an example of a minisatellite that is both a TSS and an eQTL as well as identifies a new VNTR that may modify mTORC1 activity
Blood transcriptomics of drug-na\uefve sporadic Parkinson's disease patients
BACKGROUND:
Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder that is clinically defined in terms of motor symptoms. These are preceded by prodromal non-motor manifestations that prove the systemic nature of the disease. Identifying genes and pathways altered in living patients provide new information on the diagnosis and pathogenesis of sporadic PD.
METHODS:
Changes in gene expression in the blood of 40 sporadic PD patients and 20 healthy controls ("Discovery set") were analyzed by taking advantage of the Affymetrix platform. Patients were at the onset of motor symptoms and before initiating any pharmacological treatment. Data analysis was performed by applying Ranking-Principal Component Analysis, PUMA and Significance Analysis of Microarrays. Functional annotations were assigned using GO, DAVID, GSEA to unveil significant enriched biological processes in the differentially expressed genes. The expressions of selected genes were validated using RT-qPCR and samples from an independent cohort of 12 patients and controls ("Validation set").
RESULTS:
Gene expression profiling of blood samples discriminates PD patients from healthy controls and identifies differentially expressed genes in blood. The majority of these are also present in dopaminergic neurons of the Substantia Nigra, the key site of neurodegeneration. Together with neuronal apoptosis, lymphocyte activation and mitochondrial dysfunction, already found in previous analysis of PD blood and post-mortem brains, we unveiled transcriptome changes enriched in biological terms related to epigenetic modifications including chromatin remodeling and methylation. Candidate transcripts as CBX5, TCF3, MAN1C1 and DOCK10 were validated by RT-qPCR.
CONCLUSIONS:
Our data support the use of blood transcriptomics to study neurodegenerative diseases. It identifies changes in crucial components of chromatin remodeling and methylation machineries as early events in sporadic PD suggesting epigenetics as target for therapeutic intervention
In vitro undetectable PT and Fibrinogen (and in vivo?)
A 81 aged woman came to E.R. of Trieste University Hospital with a traumatic head injury. Blood cells count, liver enzymes and other parameters were normal, but with a photometric clot detection method PT and PT-derived Fibrinogen were undetectable, Fibrinogen-Clauss gave different results (157 to 357 mg/dL) and aPTT-Ratio was normal (0.96). When the instrument detection performance was improved, PT was normal and PT-derived Fibrinogen detectable, but Fibrinogen-Clauss was still very unsteady (352/294/558 mg/dL). When a mixing test was performed with normal pool plasma, PT was corrected, PT-derived Fibrinogen was very low (80 mg/dL) and Fibrinogen-Clauss resulted 360 mg/dL. Fibrinogen-Antigen was 368 mg/dL by a nephelometric immunoassay. In another Lab with a different optical analyzer, PT and aPTT yielded the same results, Fibrinogen-Clauss was 557 mg/dL with 35 IU/ml Thrombin reagent (and a very steep clot formation curve), but 113 mg/dL with 15 IU/ml Thrombin reagent (and a normal curve). With an electromechanical clot detection method, PT-INR and aPTT-Ratio were normal (0.88 and 0.96 respectively), Fibrinogen-Clauss was normal (400 mg/dL) but unsteady. However in a few days our patient healed up perfectly; she declared that her sister had the same performance when she was referred to another Hospital for a check-up, nonetheless they never had any severe bleeding in their life.
Samples from our patient\u2019s son and daughter were taken and resulted completely normal for coagulation tests.
We hypothetized:
1) a too fast Thrombin formation and/or Fibrinogen consumption, as shown by steep coagulation curves without a stable plateau;
2) an excessive thrombin formation, (in preliminary studies, however, G20210A mutation was absent and F1+2 were normal);
3) a dysfibrinogenemia, (to be studied).
Further studies for Endogenous Thrombin Potential about thrombin ipothesis and for genetical pattern about fibrinogen molecule are needed to clarify this case