WHAT TASKS TO AUTOMATE? AN INVESTIGATION OF WHAT TASKS MAKE SENSE TO AUTOMATE FOR FUTURE AVIATION PLATFORMS

The Army is developing a new generation of aircraft called Future Vertical Lift (FVL). These aircraft will integrate new technologies that change Army Aviation’s machinery, methods, and aircrew domains. Key to this effort is the development of automation to reduce pilot cognitive workload and prevent cognitive overload. The purpose of this research was to develop an understanding of the factors that influence pilot cognitive workload and to provide insight into what tasks make sense to automate for FVL. Researchers used a mixed methods approach, relying on scholarly literature and semi-structured interviews to elicit cognitive workload data from Army rotary-wing pilots. Researchers used the data from a simple and a complex MEDEVAC flight scenario to develop an influence diagram that models pilot cognitive workload based on influencing factors and subfactors. At a high level, the data indicate that pilot task demand and environmental factors have the most influence on cognitive workload during complex missions in challenging conditions. At a low level, the data indicate that light factors, intra-flight coordination, and task complexity are most influential on cognitive workload. The results suggest that tasks impacting these factors should be considered for automation to prevent pilot cognitive overload in FVL.DEVCOM AvMCCaptain, United States ArmyMajor, United States ArmyCaptain, United States ArmyMajor, United States ArmyApproved for public release. Distribution is unlimited

Gating-by-tilt of mechanosensitive membrane channels

We propose an alternative mechanism for the gating of biological membrane channels in response to membrane tension that involves a change in the slope of the membrane near the channel. Under biological membrane tensions we show that the energy difference between the closed (tilted) and open (untilted) states can far exceed kBT and is comparable to what is available under simple ilational gating. Recent experiments demonstrate that membrane leaflet asymmetries (spontaneous curvature) can strong effect the gating of some channels. Such a phenomenon would be more easy to explain under gating-by-tilt, given its novel intrinsic sensitivity to such asymmetry.Comment: 10 pages, 2 figure

Calibrating ensemble reliability whilst preserving spatial structure

Ensemble forecasts aim to improve decision-making by predicting a set of possible outcomes. Ideally, these would provide probabilities which are both sharp and reliable. In practice, the models, data assimilation and ensemble perturbation systems are all imperfect, leading to deficiencies in the predicted probabilities. This paper presents an ensemble post-processing scheme which directly targets local reliability, calibrating both climatology and ensemble dispersion in one coherent operation. It makes minimal assumptions about the underlying statistical distributions, aiming to extract as much information as possible from the original dynamic forecasts and support statistically awkward variables such as precipitation. The output is a set of ensemble members preserving the spatial, temporal and inter-variable structure from the raw forecasts, which should be beneficial to downstream applications such as hydrological models. The calibration is tested on three leading 15-d ensemble systems, and their aggregation into a simple multimodel ensemble. Results are presented for 12 h, 1° scale over Europe for a range of surface variables, including precipitation. The scheme is very effective at removing unreliability from the raw forecasts, whilst generally preserving or improving statistical resolution. In most cases, these benefits extend to the rarest events at each location within the 2-yr verification period. The reliability and resolution are generally equivalent or superior to those achieved using a Local Quantile-Quantile Transform, an established calibration method which generalises bias correction. The value of preserving spatial structure is demonstrated by the fact that 3×3 averages derived from grid-scale precipitation calibration perform almost as well as direct calibration at 3×3 scale, and much better than a similar test neglecting the spatial relationships. Some remaining issues are discussed regarding the finite size of the output ensemble, variables such as sea-level pressure which are very reliable to start with, and the best way to handle derived variables such as dewpoint depression

An Integrated Modeling Approach for Predicting Process Maps of Residual Stress and Distortion in a Laser Weld: A Combined CFD–FE Methodology

Laser welding has become an important joining methodology within a number of industries for the structural joining of metallic parts. It offers a high power density welding capability which is desirable for deep weld sections, but is equally suited to performing thinner welded joints with sensible amendments to key process variables. However, as with any welding process, the introduction of severe thermal gradients at the weld line will inevitably lead to process-induced residual stress formation and distortions. Finite element (FE) predictions for weld simulation have been made within academia and industrial research for a number of years, although given the fluid nature of the molten weld pool, FE methodologies have limited capabilities. An improvement upon this established method would be to incorporate a computational fluid dynamics (CFD) model formulation prior to the FE model, to predict the weld pool shape and fluid flow, such that details can be fed into FE from CFD as a starting condition. The key outputs of residual stress and distortions predicted by the FE model can then be monitored against the process variables input to the model. Further, a link between the thermal results and the microstructural properties is of interest. Therefore, an empirical relationship between lamellar spacing and the cooling rate was developed and used to make predictions about the lamellar spacing for welds of different process parameters. Processing parameter combinations that lead to regions of high residual stress formation and high distortion have been determined, and the impact of processing parameters upon the predicted lamellar spacing has been presented

Potent CD8+ T-cell immunogenicity in humans of a novel heterosubtypic influenza A vaccine, MVA-NP+M1.

BACKGROUND: Influenza A viruses cause occasional pandemics and frequent epidemics. Licensed influenza vaccines that induce high antibody titers to the highly polymorphic viral surface antigen hemagglutinin must be re-formulated and readministered annually. A vaccine providing protective immunity to the highly conserved internal antigens could provide longer-lasting protection against multiple influenza subtypes. METHODS: We prepared a Modified Vaccinia virus Ankara (MVA) vector encoding nucleoprotein and matrix protein 1 (MVA-NP+M1) and conducted a phase I clinical trial in healthy adults. RESULTS: The vaccine was generally safe and well tolerated, with significantly fewer local side effects after intramuscular rather than intradermal administration. Systemic side effects increased at the higher dose in both frequency and severity, with 5 out of 8 volunteers experiencing severe nausea/vomiting, malaise, or rigors. Ex vivo T-cell responses to NP and M1 measured by IFN-γ ELISPOT assay were significantly increased after vaccination (prevaccination median of 123 spot-forming units/million peripheral blood mononuclear cells, postvaccination peak response median 339, 443, and 1443 in low-dose intradermal, low-dose intramuscular, and high-dose intramuscular groups, respectively), and the majority of the antigen-specific T cells were CD8(+). CONCLUSIONS: We conclude that the vaccine was both safe and remarkably immunogenic, leading to frequencies of responding T cells that appear to be much higher than those induced by any other influenza vaccination approach. Further studies will be required to find the optimum dose and to assess whether the increased T-cell response to conserved influenza proteins results in protection from influenza disease

Flavin-Induced Oligomerization in Escherichia coli Adaptive Response Protein AidB

The process known as “adaptive response” allows Escherichia coli to respond to small doses of DNA-methylating agents by upregulating the expression of four proteins. While the role of three of these proteins in mitigating DNA damage is well understood, the function of AidB is less clear. Although AidB is a flavoprotein, no catalytic role has been established for the bound cofactor. Here we investigate the possibility that flavin plays a structural role in the assembly of the AidB tetramer. We report the generation and biophysical characterization of deflavinated AidB and of an AidB mutant that has greatly reduced affinity for flavin adenine dinucleotide (FAD). Using fluorescence quenching and analytical ultracentrifugation, we find that apo AidB has a high affinity for FAD, as indicated by an apparent dissociation constant of 402.1 ± 35.1 nM, and that binding of substoichiometric amounts of FAD triggers a transition in the AidB oligomeric state. In particular, deflavinated AidB is dimeric, whereas the addition of FAD yields a tetramer. We further investigate the dimerization and tetramerization interfaces of AidB by determining a 2.8 Å resolution crystal structure in space group P32 that contains three intact tetramers in the asymmetric unit. Taken together, our findings provide strong evidence that FAD plays a structural role in the formation of tetrameric AidB.National Institutes of Health (U.S.) (grant R01-GM0272663)National Institutes of Health (U.S.) (grant P30-ES002109)National Science Foundation (U.S.) (grant MCB-0543833

Long-term reductions in tinnitus severity

BACKGROUND: This study was undertaken to assess long-term changes in tinnitus severity exhibited by patients who completed a comprehensive tinnitus management program; to identify factors that contributed to changes in tinnitus severity within this population; to contribute to the development and refinement of effective assessment and management procedures for tinnitus. METHODS: Detailed questionnaires were mailed to 300 consecutive patients prior to their initial appointment at the Oregon Health & Science University Tinnitus Clinic. All patients were then evaluated and treated within a comprehensive tinnitus management program. Follow-up questionnaires were mailed to the same 300 patients 6 to 36 months after their initial tinnitus clinic appointment. RESULTS: One hundred ninety patients (133 males, 57 females; mean age 57 years) returned follow-up questionnaires 6 to 36 months (mean = 22 months) after their initial tinnitus clinic appointment. This group of patients exhibited significant long-term reductions in self-rated tinnitus loudness, Tinnitus Severity Index scores, tinnitus-related anxiety and prevalence of current depression. Patients who improved their sleep patterns or Beck Depression Inventory scores exhibited greater reductions of tinnitus severity scores than patients who continued to experience insomnia and depression at follow-up. CONCLUSIONS: Individualized tinnitus management programs that were designed for each patient contributed to overall reductions in tinnitus severity exhibited on follow-up questionnaires. Identification and treatment of patients experiencing anxiety, insomnia or depression are vital components of an effective tinnitus management program. Utilization of acoustic therapy also contributed to improvements exhibited by these patients

Major Role for Amphotericin B–Flucytosine Combination in Severe Cryptococcosis

BACKGROUND: The Infectious Diseases Society of America published in 2000 practical guidelines for the management of cryptococcosis. However, treatment strategies have not been fully validated in the various clinical settings due to exclusion criteria during therapeutic trials. We assessed here the optimal therapeutic strategies for severe cryptococcosis using the observational prospective CryptoA/D study after analyzing routine clinical care of cryptococcosis in university or tertiary care hospitals. METHODOLOGY/PRINCIPAL FINDINGS: Patients were enrolled if at least one culture grew positive with Cryptococcus neoformans. Control of sterilization was warranted 2 weeks (Wk2) and 3 months (Mo3) after antifungal therapy onset. 208 HIV-positive or -negative adult patients were analyzed. Treatment failure (death or mycological failure) at Wk2 and Mo3 was the main outcome measured. Combination of amphotericin B+flucytosine (AMB+5FC) was the best regimen for induction therapy in patients with meningoencephalitis and in all patients with high fungal burden and abnormal neurology. In those patients, treatment failure at Wk2 was 26% in the AMB+5FC group vs. 56% with any other treatments (p<0.001). In patients treated with AMB+5FC, factors independently associated with Wk2 mycological failure were high serum antigen titer (OR [95%CI] = 4.43[1.21-16.23], p = 0.025) and abnormal brain imaging (OR = 3.89[1.23-12.31], p = 0.021) at baseline. Haematological malignancy (OR = 4.02[1.32-12.25], p = 0.015), abnormal neurology at baseline (OR = 2.71[1.10-6.69], p = 0.030) and prescription of 5FC for less than 14 days (OR = 3.30[1.12-9.70], p = 0.030) were independently associated with treatment failure at Mo3. CONCLUSION/SIGNIFICANCE: Our results support the conclusion that induction therapy with AMB+5FC for at least 14 days should be prescribed rather than any other induction treatments in all patients with high fungal burden at baseline regardless of their HIV serostatus and of the presence of proven meningoencephalitis

High-statistics measurement of the η→3π0 decay at the Mainz Microtron

The largest, at the moment, statistics of 7 x 10(6) eta -&gt; 3 pi(0) decays, based on 6.2 x 10(7) eta mesons produced in the gamma p -&gt; eta p reaction, has been accumulated by the A2 Collaboration at the MainzMicrotron, MAMI. It allowed a detailed study of the eta -&gt; 3 pi(0) dynamics beyond its conventional parametrization with just the quadratic slope parameter a and enabled, for the first time, a measurement of the second-order term and a better understanding of the cusp structure in the neutral decay. The present data are also compared to recent theoretical calculations that predict a nonlinear dependence along the quadratic distance from the Dalitz-plot center