916 research outputs found
Using eulerlets to model steady uniform flow past a circular cylinder
Consider uniform, steady flow past a circular cylinder at Reynolds numbers 26, 36 and 40 before the flow becomes unsteady. Model the flow by using eulerlets, new Greenâs functions for Euler flow. This is the first time this eulerlet model has been used, introduced at the recent BETEQ 2017 International Conference. In addition, the far-field is also obtained by matching with oseenlets. Unlike existing Euler flow representations, the drag, wake eddies and far-field wake profile are all captured, and compare favourably with experiment
The theory and application of eulerlets
Consider a fixed body in a uniform flow field in the limit as the Reynolds number approaches infinity and the flow field remains steady. Instead of using standard techniques and theory for describing the problem, a new method is employed based upon the concept of matching two different Greenâs integral representations over a common boundary, one given by approximations valid in the near-field and the other by approximations in the far-field. Further novelty arises from the choice of a near-field, that is, the Euler flow matched to an Oseen flow far-field. This entails introducing and defining eulerlets that are Greenâs functions of the Euler equation. One important consequence of the model is the presence of a new Euler wake velocity not captured in standard models. This has a constant unchanging downstream profile and arises from the matching to the far-field Oseen wake velocity. It is then shown how this representation reduces to classical inviscid ideal flow aerodynamics when applied to flow past aerofoils and wings. It is also shown how it reduces to slender body flow theory. Finally, the formulation is tested on uniform flow past a circular cylinder for mean-steady subcritical laminar flow and turbulent flow. The inviscid impermeability boundary condition is used, the drag coefficient is specified, and a constant distribution of drag eulerlets is modeled. The forward flow separation and pressure drop in the wake are captured and compare favorably with experiment. The future expectation is the modeling of multiple general shaped bodies
An experimental test for the existence of the Euler wake velocity, validating Eulerlet theory by using a bluff body in a low-speed wind tunnel
The application of manoeuvrability problems in aerodynamics mainly works for Reynolds average Navier-Stokes equations particularly for a uniform, steady flow past a fixed body. Further, consider large Reynolds number such that the flow is not turbulent, and the boundary layer is negligibly small and the impermeability boundary condition holds. Instead of using standard techniques and theory for describing the problem, a new method is employed based upon the concept of matching two different Greenâs integral representations over a common boundary, one given by approximations valid in the near-field and the other by approximations in the far-field such that, a near-field Euler flow is matched to a far-field Oseen flow. Far from the body, linearise the velocity to the uniform stream yielding Oseen flow to leading order and match the near-field Euler and far-field Oseen flow on a common matching boundary. In particular, match the Greenâs integral representations that use Greenâs functions which are point force solutions. This gives new Greenâs functions which we call Eulerlets and are obtained by collapsing the diffuse wake of the corresponding Oseenlets onto a wake line represented by Heaviside and delta functions. The matching equates terms on the common boundary yielding the Bernoulli equation. One important consequence of the model is the presence of a new Euler wake velocity which is not captured in standard models. This has a constant unchanging downstream profile and arises from the matching to the far-field Oseen wake velocity. The drag calculation is shown to originate solely from a new wake inflow term comprising of layers of different velocities slipping past each other meaning that drag is possible in Euler flow from the momentum loss. So, the model includes a new drag Euler slip wake countering DâAlembertâs paradox. The theory is tested against a wake inflow problem, as this is where it differs from standard Euler representations. In particular, we consider uniform flow past a circular cylinder which is the classic textbook problem demonstrating DâAlembertâs paradox. An experiment is devised to test Eulerlet theory for steady, incompressible, uniform Euler flow past a fixed, closed body. This theory predicts the existence of an Euler wake that has a constant unchanged profile at any downstream station. To experimentally test the theory, a circular cylinder with an axis perpendicular to the flow direction is placed in a closed low-speed wind tunnel. The velocity profile is obtained by a hot-wire anemometer attached to a novel design purpose-built probe arm moved by an external traverse mechanism and determined at three downstream stations. The Euler wake velocity is then calculated by taking away the potential velocity from the experimentally evaluated fluid velocity. The potential velocity in the wake region itself is estimated by extrapolation from its value outside the wake. The same underlying Euler wake velocity profile is found at two of the three stations, as predicted by the theory. For the third downstream station furthest away, diffusive turbulent effects occur, increasing energy in the wake well and so contaminating the results
Relationship Between Characteristics of Medications and Drug-Induced Liver Disease Phenotype and Outcome
Background & Aims:
It is not known if specific characteristics of medication are associated with type of drug-induced liver injury (DILI) or outcome. We examined the relationships among select characteristics of medications and DILI phenotype and outcome.
Methods:
We analyzed 383 cases of DILI caused by a single orally administered prescription agent from the DILI Network Prospective Study with causalities of definite, highly likely, or probable. Relationship of daily dosage (â„ 50 mg vs. †49 mg), preponderance of hepatic metabolism (â„50% vs <50%), or Biopharmaceutics Drug Disposition Classification System (BDDCS) class (1â4, based on solubility and metabolism of the drug) were compared with clinical characteristics and outcomes.
Results:
Compared to cases of DILI in the <50 mg/day group, those associated with daily dosages â„50 mg had shorter latency (median 38 days vs 56 days; P=.03) and a different biochemical pattern of liver injury (P=.04); no differences in pattern of injury, recovery, severity, or outcome were observed. Patients with DILI caused by medications with or without preponderant hepatic metabolism did not differ in clinical characteristics or outcomes. Compared to other classes of BDDCS, DILI caused by BDDCS class 1 medications had significantly longer latency (P<.001) and greater proportion of hepatocellular injury (P=.001). However, peak liver biochemical values and patientsâ time to recovery, disease severity, and outcomes did not differ among the 4 BDDCS classes.
Conclusions:
Characteristics of medications (dosage, hepatic metabolism, and solubility) are associated with features of DILI such as latency and pattern of liver injury, but not with recovery, severity, or outcome
Reliability of causality assessment for drug, herbal and dietary supplement hepatotoxicity in the DrugâInduced Liver Injury Network (DILIN)
Background & AimsBecause of the lack of objective tests to diagnose drugâinduced liver injury (DILI), causality assessment is a matter of debate. Expert opinion is often used in research and industry, but its testâretest reliability is unknown. To determine the testâretest reliability of the expert opinion process used by the DrugâInduced Liver Injury Network (DILIN).MethodsThree DILIN hepatologists adjudicate suspected hepatotoxicity cases to one of five categories representing levels of likelihood of DILI. Adjudication is based on retrospective assessment of gathered case data that include prospective followâup information. One hundred randomly selected DILIN cases were reâassessed using the same processes for initial assessment but by three different reviewers in 92% of cases.ResultsThe median time between assessments was 938Â days (range 140â2352). Thirtyâone cases involved >1 agent. Weighted kappa statistics for overall case and individual agent category agreement were 0.60 (95% CI: 0.50â0.71) and 0.60 (0.52â0.68) respectively. Overall case adjudications were within one category of each other 93% of the time, while 5% differed by two categories and 2% differed by three categories. Fourteen per cent crossed the 50% threshold of likelihood owing to competing diagnoses or atypical timing between drug exposure and injury.ConclusionsThe DILIN expert opinion causality assessment method has moderate interobserver reliability but very good agreement within one category. A small but important proportion of cases could not be reliably diagnosed as â„50% likely to be DILI.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111130/1/liv12540.pd
Transcriptional regulation of PNPLA3 and its impact on susceptibility to nonalcoholic fatty liver Disease (NAFLD) in humans
The increased expression of PNPLA3148M leads to hepatosteatosis in mice. This study aims to investigate the genetic control of hepatic PNPLA3 transcription and to explore its impact on NAFLD risk in humans. Through a locus-wide expression quantitative trait loci (eQTL) mapping in two human liver sample sets, a PNPLA3 intronic SNP, rs139051 A>G was identified as a significant eQTL (p = 6.6Ă10-8) influencing PNPLA3 transcription, with the A allele significantly associated with increased PNPLA3 mRNA. An electrophoresis mobility shift assay further demonstrated that the A allele has enhanced affinity to nuclear proteins than the G allele. The impact of this eQTL on NAFLD risk was further tested in three independent populations. We found that rs139051 did not independently affect the NAFLD risk, whilst rs738409 did not significantly modulate PNPLA3 transcription but was associated with NAFLD risk. The A-G haplotype associated with higher transcription of the disease-risk rs738409 G allele conferred similar risk for NAFLD compared to the G-G haplotype that possesses a lower transcription level. Our study suggests that the pathogenic role of PNPLA3148M in NAFLD is independent of the gene transcription in humans, which may be attributed to the high endogenous transcription level of PNPLA3 gene in human livers
A comprehensive assessment of environmental exposures among 1000 North American patients with primary sclerosing cholangitis, with and without inflammatory bowel disease
BACKGROUND: The relationships between primary sclerosing cholangitis (PSC) and the environment are largely unknown.
AIM: To validate associations reported in previous studies and to identify novel environmental exposures among PSC patients.
METHODS: We performed a multicenter, case-control analysis utilising self-administered questionnaires. Responses between cases (n = 1000) and controls (n = 663) were compared using multivariable logistic regression adjusted for age and gender. The model was further stratified based on inflammatory bowel disease (IBD) status (with IBD n = 741 without IBD n = 259).
RESULTS: Smoking was associated with PSC only when IBD was present (OR, 0.5; 95% CI 0.4-0.7) but not among those PSC patients without IBD (OR, 0.9; 95% CI 0.7-1.2). Compared to controls, women with PSC (irrespective of the presence of IBD) were less likely to have received hormone replacement therapy (HRT; OR, 0.5; 95% CI 0.4-0.7) and were more likely to have recurrent urinary tract infections (OR, 1.6; 95% CI 1.2-2.3). PSC patients regardless of gender or IBD status were less likely to eat fish (OR, 0.4; 95% CI 0.3-0.6) and grilled/barbecued meat (OR, 0.8; 95% CI 0.7-0.9). In contrast, PSC patients with and without IBD were more likely to consume steak/burgers that were more well done (OR, 1.3; 95% CI 1.2-1.5).
CONCLUSIONS: IBD (rather than PSC) is associated with smoking. Women with PSC are more likely to have recurrent urinary tract infections and less likely to receive HRT. Dietary intake and methods of food preparation differ in PSC patients when compared to controls
Relationship between site of oesophageal cancer and areca chewing and smoking in Taiwan
Among 309 male patients, those who had heavily consumed betel and tobacco were more likely than nonchewers (OR = 2. 91; 95% CI = 1.36-6.25) and nonsmokers (OR = 2.49; 95% CI = 1.02-6.08) to develop cancer in the upper and middle third of the oesophagus, respectively; the effects of alcohol did not dominate in any third
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