Control-Force Inputs Obtained from Pilots and Nonpilots (Flight Attendants): Comparison with Established Handbook Distributions of Performance

Earlier reports in this series (Beringer, 2006-2008) have reported the force that pilots and nonpilots could exert on flight controls. This paper presents a comparison of some well-known tables of human strength with the values from recent samples of women and men pilots and nonpilots in an attempt to determine how closely those distributions fit tabled distributions of human strength. Findings suggest that some other samples may be used to approximate the difficult-to-sample Part 121 female pilots if the data are treated properly. Specifically, yoke-activation tasks for the female pilots could be reasonably well approximated by fractional performance values of male pilots. It was also determined that some older data obtained from a narrower sample of participants (both in age and gender) were not especially good for estimating present performance of the more diverse population of present-day certified pilots. Percentile values are provided for the lower values of the sampled groups

The Effect of Terrain-Depicting Primary-Flight-Display Backgrounds and Guidance Cues on Pilot Recoveries from Unknown Attitudes

A study was conducted to evaluate the effects of primary flight display (PFD) terrain depictions on pilots’ performance of recoveries from unknown attitudes. Forty pilots participated in the study, each group of eight using a different display format. The five conditions consisted of combinations of terrain depiction (none, full-color terrain, brown terrain) and guidance indications (pitch and roll arrows). Participants flew baseline trials in the Advanced General Aviation Research Simulator using a common electronic attitude indicator and then performed recoveries from unknown attitudes (UARs) using one of the PFD formats. Performance measures included initial response time, total recovery time, primary reversals, and secondary reversals. No significant effects of the primary independent variables were found on any of the performance measures. Posttest interviews indicated the participants preferred the directional-arrow indicators and had no preference for or against the presence of terrain depictions during UARs, focusing primarily on the zero-pitch line as a reference. It was concluded that the specific terrain representations examined did not pose a hazard to the identification of and recovery from unknown attitudes as long as a zeropitch line of sufficient discriminability (contrast and size) to all backgrounds was present

Divergent T-cell receptor recognition modes of a HLA-I restricted extended tumour-associated peptide

Human leukocyte antigen (HLA)-I molecules generally bind short peptides (8-10 amino acids), although extended HLA-I restricted peptides (>10 amino acids) can be presented to T cells. However, the function of such extended HLA-I epitopes in tumour immunity, and how they would be recognised by T-cell receptors (TCR) remains unclear. Here we show that the structures of two distinct TCRs (TRAV4+TRAJ21+-TRBV28+TRBJ2-3+ and TRAV4 + TRAJ8+-TRBV9+TRBJ2-1+), originating from a polyclonal T-cell repertoire, bind to HLA-B*07:02, presenting a 13-amino-acid-long tumour-associated peptide, NY-ESO-160-72. Comparison of the structures reveals that the two TCRs differentially binds NY-ESO-160-72-HLA-B*07:02 complex, and induces differing extent of conformational change of the NY-ESO-160-72 epitope. Accordingly, polyclonal TCR usage towards an extended HLA-I restricted tumour epitope translates to differing TCR recognition modes, whereby extensive flexibility at the TCR-pHLA-I interface engenders recognition

Insights Into the Aerodynamic Versus Radiometric Surface Temperature Debate in Thermal-Based Evaporation Modeling

Global evaporation monitoring from Earth observation thermal infrared satellite missions is historically challenged due to the unavailability of any direct measurements of aerodynamic temperature. State-of-the-art one-source evaporation models use remotely sensed radiometric surface temperature as a substitute for the aerodynamic temperature and apply empirical corrections to accommodate for their inequality. This introduces substantial uncertainty in operational drought mapping over complex landscapes. By employing a non-parametric model, we show that evaporation can be directly retrieved from thermal satellite data without the need of any empirical correction. Independent evaluation of evaporation in a broad spectrum of biome and aridity yielded statistically significant results when compared with eddy covariance observations. While our simplified model provides a new perspective to advance spatio-temporal evaporation mapping from any thermal remote sensing mission, the direct retrieval of aerodynamic temperature also generates the highly required insight on the critical role of biophysical interactions in global evaporation research

Insights into the aerodynamic versus radiometric surface temperature debate in thermal-based evaporation modeling

Global evaporation monitoring from Earth observation thermal infrared satellite missions is historically challenged due to the unavailability of any direct measurements of aerodynamic temperature. State-of-the-art one-source evaporation models use remotely sensed radiometric surface temperature as a substitute for the aerodynamic temperature and apply empirical corrections to accommodate for their inequality. This introduces substantial uncertainty in operational drought mapping over complex landscapes. By employing a non-parametric model, we show that evaporation can be directly retrieved from thermal satellite data without the need of any empirical correction. Independent evaluation of evaporation in a broad spectrum of biome and aridity yielded statistically significant results when compared with eddy covariance observations. While our simplified model provides a new perspective to advance spatio-temporal evaporation mapping from any thermal remote sensing mission, the direct retrieval of aerodynamic temperature also generates the highly required insight on the critical role of biophysical interactions in global evaporation research

The making of multivalent gamma delta TCR anti-CD3 bispecific T cell engagers

IntroductionWe have recently developed a novel T cell engager concept by utilizing γ9δ2TCR as tumor targeting domain, named gamma delta TCR anti-CD3 bispecific molecule (GAB), targeting the phosphoantigen-dependent orchestration of BTN2A1 and BTN3A1 at the surface of cancer cells. GABs are made by the fusion of the ectodomains of a γδTCR to an anti-CD3 single chain variable fragment (scFv) (γδECTO-αCD3), here we explore alternative designs with the aim to enhance GAB effectivity.MethodsThe first alternative design was made by linking the variable domains of the γ and δ chain to an anti-CD3 scFv (γδVAR-αCD3). The second alternative design was multimerizing γδVAR-αCD3 proteins to increase the tumor binding valency. Both designs were expressed and purified and the potency to target tumor cells by T cells of the alternative designs was compared to γδECTO-αCD3, in T cell activation and cytotoxicity assays.Results and discussionThe γδVAR-αCD3 proteins were poorly expressed, and while the addition of stabilizing mutations based on finding for αβ single chain formats increased expression, generation of meaningful amounts of γδVAR-αCD3 protein was not possible. As an alternative strategy, we explored the natural properties of the original GAB design (γδECTO-αCD3), and observed the spontaneous formation of γδECTO-αCD3-monomers and -dimers during expression. We successfully enhanced the fraction of γδECTO-αCD3-dimers by shortening the linker length between the heavy and light chain in the anti-CD3 scFv, though this also decreased protein yield by 50%. Finally, we formally demonstrated with purified γδECTO-αCD3-dimers and -monomers, that γδECTO-αCD3-dimers are superior in function when compared to similar concentrations of monomers, and do not induce T cell activation without simultaneous tumor engagement. In conclusion, a γδECTO-αCD3-dimer based GAB design has great potential, though protein production needs to be further optimized before preclinical and clinical testing

T cell receptor reversed polarity recognition of a self-antigen major histocompatibility complex

Central to adaptive immunity is the interaction between the αβ T cell receptor (TCR) and peptide presented by the major histocompatibility complex (MHC) molecule. Presumably reflecting TCR-MHC bias and T cell signaling constraints, the TCR universally adopts a canonical polarity atop the MHC. We report the structures of two TCRs, derived from human induced T regulatory (iTreg) cells, complexed to an MHC class II molecule presenting a proinsulin-derived peptide. The ternary complexes revealed a 180° polarity reversal compared to all other TCR-peptide-MHC complex structures. Namely, the iTreg TCR α-chain and β-chain are overlaid with the α-chain and β-chain of MHC class II, respectively. Nevertheless, this TCR interaction elicited a peptide-reactive, MHC-restricted T cell signal. Thus TCRs are not 'hardwired' to interact with MHC molecules in a stereotypic manner to elicit a T cell signal, a finding that fundamentally challenges our understanding of TCR recognition

A coupled ground heat flux-surface energy balance model of evaporation using thermal remote sensing observations

One of the major undetermined problems in evaporation (ET) retrieval using thermal infrared remote sensing is the lack of a physically based ground heat flux (G) model and its integration within the surface energy balance (SEB) equation. Here, we present a novel approach based on coupling a thermal inertia (TI)-based mechanistic G model with an analytical surface energy balance model, Surface Temperature Initiated Closure (STIC, version STIC1.2). The coupled model is named STIC-TI. The model is driven by noon–night (13:30 and 01:30 local time) land surface temperature, surface albedo, and a vegetation index from MODIS Aqua in conjunction with a clear-sky net radiation sub-model and ancillary meteorological information. SEB flux estimates from STIC-TI were evaluated with respect to the in situ fluxes from eddy covariance measurements in diverse ecosystems of contrasting aridity in both the Northern Hemisphere and Southern Hemisphere. Sensitivity analysis revealed substantial sensitivity of STIC-TI-derived fluxes due to the land surface temperature uncertainty. An evaluation of noontime G (Gi) estimates showed 12 %–21 % error across six flux tower sites, and a comparison between STIC-TI versus empirical G models also revealed the substantially better performance of the former. While the instantaneous noontime net radiation (RNi) and latent heat flux (LEi) were overestimated (15 % and 25 %), sensible heat flux (Hi) was underestimated (22 %). Overestimation (underestimation) of LEi (Hi) was associated with the overestimation of net available energy (RNi−Gi) and use of unclosed surface energy balance flux measurements in LEi (Hi) validation. The mean percent deviations in Gi and Hi estimates were found to be strongly correlated with satellite day–night view angle difference in parabolic and linear pattern, and a relatively weak correlation was found between day–night view angle difference versus LEi deviation. Findings from this parameter-sparse coupled G–ET model can make a valuable contribution to mapping and monitoring the spatiotemporal variability of ecosystem water stress and evaporation using noon–night thermal infrared observations from future Earth observation satellite missions such as TRISHNA, LSTM, and SBG

Integration of MODIS land and atmosphere products with a coupled-process model to estimate gross primary productivity and evapotranspiration from 1 km to global scales

We propose the Breathing Earth System Simulator (BESS), an upscaling approach to quantify global gross primary productivity and evapotranspiration using MODIS with a spatial resolution of 1-5 km and a temporal resolution of 8 days. This effort is novel because it is the first system that harmonizes and utilizes MODIS Atmosphere and Land products on the same projection and spatial resolution over the global land. This enabled us to use the MODIS Atmosphere products to calculate atmospheric radiative transfer for visual and near infrared radiation wave bands. Then we coupled atmospheric and canopy radiative transfer processes, with models that computed leaf photosynthesis, stomatal conductance and transpiration on the sunlit and shaded portions of the vegetation and soil. At the annual time step, the mass and energy fluxes derived from BESS showed strong linear relations with measurements of solar irradiance (r(2) = 0.95, relative bias: 8%), gross primary productivity (r(2) = 0.86, relative bias: 5%) and evapotranspiration (r(2) = 0.86, relative bias: 15%) in data from 33 flux towers that cover seven plant functional types across arctic to tropical climatic zones. A sensitivity analysis revealed that the gross primary productivity and evapotranspiration computed in BESS were most sensitive to leaf area index and solar irradiance, respectively. We quantified the mean global terrestrial estimates of gross primary productivity and evapotranpiration between 2001 and 2003 as 118 +/- 26 PgC yr(-1) and 500 +/- 104 mm yr(-1) (equivalent to 63,000 +/- 13,100 km(3) yr(-1)), respectively. BESS-derived gross primary productivity and evapotranspiration estimates were consistent with the estimates from independent machine-learning, data-driven products, but the process-oriented structure has the advantage of diagnosing sensitivity of mechanisms. The process-based BESS is able to offer gridded biophysical variables everywhere from local to the total global land scales with an 8-day interval over multiple years.Keywords: Energy fluxes, Water vapor exchange, Foliage clumping index, Carbon dioxide, Stomal conductance, Net ecosystem exchange, Sitchensis bong carr, Radiative transfer, Oak hickory forest, Leaf area inde

Adding Help to an HLA-A*24:02 Tumor-Reactive γδTCR Increases Tumor Control

γδT cell receptors (γδTCRs) recognize a broad range of malignantly transformed cells in mainly a major histocompatibility complex (MHC)-independent manner, making them valuable additions to the engineered immune effector cell therapy that currently focuses primarily on αβTCRs and chimeric antigen receptors (CARs). As an exception to the rule, we have previously identified a γδTCR, which exerts antitumor reactivity against HLA-A*24:02-expressing malignant cells, however without the need for defined HLA-restricted peptides, and without exhibiting any sign of off-target toxicity in humanized HLA-A*24:02 transgenic NSG (NSG-A24:02) mouse models. This particular tumor-HLA-A*24:02-specific Vγ5Vδ1TCR required CD8αα co-receptor for its tumor reactive capacity when introduced into αβT cells engineered to express a defined γδTCR (TEG), referred to as TEG011; thus, it was only active in CD8+ TEG011. We subsequently explored the concept of additional redirection of CD4+ T cells through co-expression of the human CD8α gene into CD4+ and CD8+ TEG011 cells, later referred as TEG011_CD8α. Adoptive transfer of TEG011_CD8α cells in humanized HLA-A*24:02 transgenic NSG (NSG-A24:02) mice injected with tumor HLA-A*24:02+ cells showed superior tumor control in comparison to TEG011, and to mock control groups. The total percentage of mice with persisting TEG011_CD8α cells, as well as the total number of TEG011_CD8α cells per mice, was significantly improved over time, mainly due to a dominance of CD4+CD8+ double-positive TEG011_CD8α, which resulted in higher total counts of functional T cells in spleen and bone marrow. We observed that tumor clearance in the bone marrow of TEG011_CD8α-treated mice associated with better human T cell infiltration, which was not observed in the TEG011-treated group. Overall, introduction of transgenic human CD8α receptor on TEG011 improves antitumor reactivity against HLA-A*24:02+ tumor cells and further enhances in vivo tumor control