HIFiRE-1 Turbulent Shock Boundary Layer Interaction - Flight Data and Computations

The Hypersonic International Flight Research Experimentation (HIFiRE) program is a hypersonic flight test program executed by the Air Force Research Laboratory (AFRL) and Australian Defence Science and Technology Organisation (DSTO). This flight contained a cylinder-flare induced shock boundary layer interaction (SBLI). Computations of the interaction were conducted for a number of times during the ascent. The DPLR code used for predictions was calibrated against ground test data prior to exercising the code at flight conditions. Generally, the computations predicted the upstream influence and interaction pressures very well. Plateau pressures on the cylinder were predicted well at all conditions. Although the experimental heat transfer showed a large amount of scatter, especially at low heating levels, the measured heat transfer agreed well with computations. The primary discrepancy between the experiment and computation occurred in the pressures measured on the flare during second stage burn. Measured pressures exhibited large overshoots late in the second stage burn, the mechanism of which is unknown. The good agreement between flight measurements and CFD helps validate the philosophy of calibrating CFD against ground test, prior to exercising it at flight conditions

Nonmodal Growth of TravelingWaves on Blunt Cones at Hypersonic Speeds

The existing database of transition measurements in hypersonic ground facilities has established that, as the nosetip bluntness is increased, the onset of boundary layer transition over a circular cone at zero angle of attack shifts downstream. However, this trend is reversed at sufficiently large values of the nose Reynolds number, so that the transition onset location eventually moves upstream with a further increase in nose-tip bluntness. Because modal amplification is too weak to initiate transition at moderate-to-large bluntness values, nonmodal growth has been investigated as the potential basis for a physics-based model for the frustum transition. The present analysis investigates the nonmodal growth of traveling disturbances initiated within the nose-tip vicinity that peak within the entropy layer. Results show that, with increasing nose bluntness, both planar and oblique traveling disturbances experience appreciable energy amplification up to successively higher frequencies. For moderately blunt cones, the initial nonmmodal growth is followed by a partial decay that is more than overcome by an eventual, modal growth as Mack-mode waves. For larger bluntness values, the Mack-mode waves are not amplified anywhere upstream of the experimentally measured transition location, but the traveling modes still undergo a significant amount of nonmodal growth. This finding does not provide a definitive link between optimal growth and the onset of transition, but it is qualitatively consistent with the experimental observations that frustum transition in the absence of sufficient Mack-mode amplification implies a double peak in disturbance amplification and the appearance of transitional events above the boundary-layer edge

HIFiRE-5 Flight Vehicle Design

The Hypersonic International Flight Research Experimentation (HIFiRE) program is a hypersonic flight test program executed by the Air Force Research Laboratories (AFRL) and Australian Defence Science and Technology Organization (DSTO). HIFiRE flight 5 is devoted to measuring transition on a three-dimensional body. This paper summarizes payload configuration, trajectory, vehicle stability limits and roughness tolerances. Results show that the proposed configuration is suitable for testing transition on a three-dimensional body. Transition is predicted to occur within the test window, and a design has been developed that will allow the vehicle to be manufactured within prescribed roughness tolerance

Nosetip Bluntness Effects on Transition at Hypersonic Speeds: Experimental and Numerical Analysis Under NATO STO AVT-240

The existing database of transition measurements in hypersonic ground facilities has established that the onset of boundary layer transition over a circular cone at zero angle of attack shifts downstream as the nosetip bluntness is increased with respect to a sharp cone. However, this trend is reversed at suciently large values of the nosetip Reynolds number, so that the transition onset location eventually moves upstream with a further increase in nosetip bluntness. This transition reversal phenomenon, which cannot be ex- plained on the basis of linear stability theory, was the focus of a collaborative investigation under the NATO STO group AVT-240 on Hypersonic Boundary-Layer Transition Predic- tion. The current paper provides an overview of that e ort, which included wind tunnel measurements in three di erent facilities and theoretical analysis related to modal and nonmodal ampli cation of boundary layer disturbances. Because neither rst and second- mode waves nor entropy-layer instabilities are found to be substantially ampli ed to ini- tiate transition at large bluntness values, transient (i.e., nonmodal) disturbance growth has been investigated as the potential basis for a physics-based model for the transition reversal phenomenon. Results of the transient growth analysis indicate that disturbances that are initiated within the nosetip or in the vicinity of the juncture between the nosetip and the frustum can undergo relatively signi cant nonmodal ampli cation and that the maximum energy gain increases nonlinearly with the nose radius of the cone. This nding does not provide a de nitive link between transient growth and the onset of transition, but it is qualitatively consistent with the experimental observations that frustum transition during the reversal regime was highly sensitive to wall roughness, and furthermore, was dominated by disturbances that originated near the nosetip

Nosetip Bluntness Effects on Transition at Hypersonic Speeds: Experimental and Numerical Analysis

The existing database of transition measurements in hypersonic ground facilities has established that the onset of boundary layer transition over a circular cone at zero angle of attack shifts downstream as the nosetip bluntness is increased with respect to a sharp cone. However, this trend is reversed at sufficiently large values of the nosetip Reynolds number, so that the transition onset location eventually moves upstream with a further increase in nosetip bluntness. This transition reversal phenomenon, which cannot be explained on the basis of linear stability theory, was the focus of a collaborative investigation under the NATO STO group AVT-240 on Hypersonic Boundary-Layer Transition Prediction. The current paper provides an overview of that effort, which included wind tunnel measurements in three different facilities and theoretical analysis related to modal and nonmodal amplification of boundary layer disturbances. Because neither first and second-mode waves nor entropy-layer instabilities are found to be substantially amplified to initiate transition at large bluntness values, transient (i.e., nonmodal) disturbance growth has been investigated as the potential basis for a physics based model for the transition reversal phenomenon. Results of the transient growth analysis indicate that stationary disturbances that are initiated within the nosetip or in the vicinity of the juncture between the nosetip and the frustum can undergo relatively significant nonmodal amplification and that the maximum energy gain increases nonlinearly with the nose radius of the cone. This finding does not provide a definitive link between transient growth and the onset of transition, but it is qualitatively consistent with the experimental observations that frustum transition during the reversal regime was highly sensitive to wall roughness, and furthermore, was dominated by disturbances that originated near the nosetip. Furthermore, the present analysis shows significant nonmodal growth of traveling disturbances that peak within the entropy layer and could also play a role in the transition reversal phenomenon

Optimizing Combination Therapies with Existing and Future CML Drugs

Small-molecule inhibitors imatinib, dasatinib and nilotinib have been developed to treat Chromic Myeloid Leukemia (CML). The existence of a triple-cross-resistant mutation, T315I, has been a challenging problem, which can be overcome by finding new inhibitors. Many new compounds active against T315I mutants are now at different stages of development. In this paper we develop an algorithm which can weigh different combination treatment protocols according to their cross-resistance properties, and find the protocols with the highest probability of treatment success. This algorithm also takes into account drug toxicity by minimizing the number of drugs used, and their concentration. Although our methodology is based on a stochastic model of CML microevolution, the algorithm itself does not require measurements of any parameters (such as mutation rates, or division/death rates of cells), and can be used by medical professionals without a mathematical background. For illustration, we apply this algorithm to the mutation data obtained in [1], [2]

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe