Full-scale semispan tests of a business-jet wing with a natural laminar flow airfoil

A full-scale semispan model was investigated to evaluate and document the low-speed, high-lift characteristics of a business-jet class wing that utilized the HSNLF(1)-0213 airfoil section and a single-slotted flap system. Also, boundary-layer transition effects were examined, a segmented leading-edge droop for improved stall/spin resistance was studied, and two roll-controlled devices were evaluated. The wind-tunnel investigation showed that deployment of single-slotted, trailing-edge flap was effective in providing substantial increments in lift required for takeoff and landing performance. Fixed-transition studies to investigate premature tripping of the boundary layer indicated no adverse effects in lift and pitching-moment characteristics for either the cruise or landing configuration. The full-scale results also suggested the need to further optimize the leading-edge droop design that was developed in the subscale tests

Low-speed static and dynamic force tests of a generic supersonic cruise fighter configuration

Static and dynamic force tests of a generic fighter configuration designed for sustained supersonic flight were conducted in the Langley 30- by 60-foot tunnel. The baseline configuration had a 65 deg arrow wing, twin wing mounted vertical tails and a canard. Results showed that control was available up to C sub L,max (maximum lift coefficient) from aerodynamic controls about all axes but control in the pitch and yaw axes decreased rapidly in the post-stall angle-of-attack region. The baseline configuration showed stable lateral-directional characteristics at low angles of attack but directional stability occurred near alpha = 25 deg as the wing shielded the vertical tails. The configuration showed positive effective dihedral throughout the test angle-of-attack range. Forced oscillation tests indicated that the baseline configuration had stable damping characteristics about the lateral-directional axes

Wind-tunnel free-flight investigation of a supersonic persistence fighter

Wind-tunnel free-flight tests have been conducted in the Langley 30- by 60-Foot Wind Tunnel to examine the high-angle-of-attack stability and control characteristics and control law design of a supersonic persistence fighter (SSPF) at 1 g flight conditions. In addition to conventional control surfaces, the SSPF incorporated deflectable wingtips (tiperons) and pitch and yaw thrust vectoring. A direct eigenstructure assignment technique was used to design control laws to provide good flying characteristics well into the poststall angle-of-attack region. Free-flight tests indicated that it was possible to blend effectively conventional and unconventional control surfaces to achieve good flying characteristics well into the poststall angle-of-attack region

Low-Speed Flight Dynamic Tests and Analysis of the Orion Crew Module Drogue Parachute System

A test of a dynamically scaled model of the NASA Orion Crew Module (CM) with drogue parachutes was conducted in the NASA-Langley 20-Foot Vertical Spin Tunnel. The primary test objective was to assess the ability of the Orion Crew Module drogue parachute system to adequately stabilize the CM and reduce angular rates at low subsonic Mach numbers. Two attachment locations were tested: the current design nominal and an alternate. Experimental results indicated that the alternate attachment location showed a somewhat greater tendency to attenuate initial roll rate and reduce roll rate oscillations than the nominal location. Comparison of the experimental data to a Program To Optimize Simulated Trajectories (POST II) simulation of the experiment yielded results for the nominal attachment point that indicate differences between the low-speed pitch and yaw damping derivatives in the aerodynamic database and the physical model. Comparisons for the alternate attachment location indicate that riser twist plays a significant role in determining roll rate attenuation characteristics. Reevaluating the impact of the alternate attachment points using a simulation modified to account for these results showed significantly reduced roll rate attenuation tendencies when compared to the original simulation. Based on this modified simulation the alternate attachment point does not appear to offer a significant increase in allowable roll rate over the nominal configuration

Wind tunnel results of the high-speed NLF(1)-0213 airfoil

Wind tunnel tests were conducted to evaluate a natural laminar flow airfoil designed for the high speed jet aircraft in general aviation. The airfoil, designated as the High Speed Natural Laminar Flow (HSNLF)(1)-0213, was tested in two dimensional wind tunnels to investigate the performance of the basic airfoil shape. A three dimensional wing designed with this airfoil and a high lift flap system is also being evaluated with a full size, half span model

Cost-effectiveness of HBV and HCV screening strategies:a systematic review of existing modelling techniques

Introduction: Studies evaluating the cost-effectiveness of screening for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are generally heterogeneous in terms of risk groups, settings, screening intervention, outcomes and the economic modelling framework. It is therefore difficult to compare cost-effectiveness results between studies. This systematic review aims to summarise and critically assess existing economic models for HBV and HCV in order to identify the main methodological differences in modelling approaches. Methods: A structured search strategy was developed and a systematic review carried out. A critical assessment of the decision-analytic models was carried out according to the guidelines and framework developed for assessment of decision-analytic models in Health Technology Assessment of health care interventions. Results: The overall approach to analysing the cost-effectiveness of screening strategies was found to be broadly consistent for HBV and HCV. However, modelling parameters and related structure differed between models, producing different results. More recent publications performed better against a performance matrix, evaluating model components and methodology. Conclusion: When assessing screening strategies for HBV and HCV infection, the focus should be on more recent studies, which applied the latest treatment regimes, test methods and had better and more complete data on which to base their models. In addition to parameter selection and associated assumptions, careful consideration of dynamic versus static modelling is recommended. Future research may want to focus on these methodological issues. In addition, the ability to evaluate screening strategies for multiple infectious diseases, (HCV and HIV at the same time) might prove important for decision makers

KRAS and BRAF mutations in circulating tumour DNA from locally advanced rectal cancer

There are limited data on circulating, cell-free, tumour (ct)DNA analysis in locally advanced rectal cancer (LARC). Digital droplet (dd)PCR was used to investigate KRAS/BRAF mutations in ctDNA from baseline blood samples of 97 LARC patients who were treated with CAPOX followed by chemoradiotherapy, surgery and adjuvant CAPOX ± cetuximab in a randomised phase II trial. KRAS mutation in G12D, G12V or G13D was detected in the ctDNA of 43% and 35% of patients with tumours that were mutant and wild-type for these hotspot mutations, respectively, according to standard PCR-based analyses on tissue. The detection rate in the ctDNA of 10 patients with less common mutations was 50%. In 26 cases ctDNA analysis revealed KRAS mutations that were not previously found in tissue. Twenty-two of these (84.6%) were detected following repeat tissue testing by ddPCR. Overall, the ctDNA detection rate in the KRAS mutant population was 66%. Detection of KRAS mutation in ctDNA failed to predict prognosis or refine patient selection for cetuximab. While this study confirms the feasibility of ctDNA analysis in LARC and the high sensitivity of ddPCR, larger series are needed to better address the role of ctDNA as a prognostic or predictive tool in this setting

Adaptive Evolution of the Lactose Utilization Network in Experimentally Evolved Populations of Escherichia coli

Adaptation to novel environments is often associated with changes in gene regulation. Nevertheless, few studies have been able both to identify the genetic basis of changes in regulation and to demonstrate why these changes are beneficial. To this end, we have focused on understanding both how and why the lactose utilization network has evolved in replicate populations of Escherichia coli. We found that lac operon regulation became strikingly variable, including changes in the mode of environmental response (bimodal, graded, and constitutive), sensitivity to inducer concentration, and maximum expression level. In addition, some classes of regulatory change were enriched in specific selective environments. Sequencing of evolved clones, combined with reconstruction of individual mutations in the ancestral background, identified mutations within the lac operon that recapitulate many of the evolved regulatory changes. These mutations conferred fitness benefits in environments containing lactose, indicating that the regulatory changes are adaptive. The same mutations conferred different fitness effects when present in an evolved clone, indicating that interactions between the lac operon and other evolved mutations also contribute to fitness. Similarly, changes in lac regulation not explained by lac operon mutations also point to important interactions with other evolved mutations. Together these results underline how dynamic regulatory interactions can be, in this case evolving through mutations both within and external to the canonical lactose utilization network

EGFR amplification and outcome in a randomised phase III trial of chemotherapy alone or chemotherapy plus panitumumab for advanced gastro-oesophageal cancers.

Funder: FP7 People: Marie-Curie Actions; FundRef: http://dx.doi.org/10.13039/100011264; Grant(s): CIG 334261OBJECTIVE: Epidermal growth factor receptor (EGFR) inhibition may be effective in biomarker-selected populations of advanced gastro-oesophageal adenocarcinoma (aGEA) patients. Here, we tested the association between outcome and EGFR copy number (CN) in pretreatment tissue and plasma cell-free DNA (cfDNA) of patients enrolled in a randomised first-line phase III clinical trial of chemotherapy or chemotherapy plus the anti-EGFR monoclonal antibody panitumumab in aGEA (NCT00824785). DESIGN: EGFR CN by either fluorescence in situ hybridisation (n=114) or digital-droplet PCR in tissues (n=250) and plasma cfDNAs (n=354) was available for 474 (86%) patients in the intention-to-treat (ITT) population. Tissue and plasma low-pass whole-genome sequencing was used to screen for coamplifications in receptor tyrosine kinases. Interaction between chemotherapy and EGFR inhibitors was modelled in patient-derived organoids (PDOs) from aGEA patients. RESULTS: EGFR amplification in cfDNA correlated with poor survival in the ITT population and similar trends were observed when the analysis was conducted in tissue and plasma by treatment arm. EGFR inhibition in combination with chemotherapy did not correlate with improved survival, even in patients with significant EGFR CN gains. Addition of anti-EGFR inhibitors to the chemotherapy agent epirubicin in PDOs, resulted in a paradoxical increase in viability and accelerated progression through the cell cycle, associated with p21 and cyclin B1 downregulation and cyclin E1 upregulation, selectively in organoids from EGFR-amplified aGEA. CONCLUSION: EGFR CN can be accurately measured in tissue and liquid biopsies and may be used for the selection of aGEA patients. EGFR inhibitors may antagonise the antitumour effect of anthracyclines with important implications for the design of future combinatorial trials