Developing advanced models of biological membranes with hydrogenous and deuterated natural glycerophospholipid mixtures.

Cellular membranes are complex systems that consist of hundreds of different lipid species. Their investigation often relies on simple bilayer models including few synthetic lipid species. Glycerophospholipids (GPLs) extracted from cells are a valuable resource to produce advanced models of biological membranes. Here, we present the optimisation of a method previously reported by our team for the extraction and purification of various GPL mixtures from Pichia pastoris. The implementation of an additional purification step by High Performance Liquid Chromatography-Evaporative Light Scattering Detector (HPLC-ELSD) enabled for a better separation of the GPL mixtures from the neutral lipid fraction that includes sterols, and also allowed for the GPLs to be purified according to their different polar headgroups. Pure GPL mixtures at significantly high yields were produced through this approach. For this study, we utilised phoshatidylcholine (PC), phosphatidylserine (PS) and phosphatidylglycerol (PG) mixtures. These exhibit a single composition of the polar head, i.e., PC, PS or PG, but contain several molecular species consisting of acyl chains of varying length and unsaturation, which were determined by Gas Chromatography (GC). The lipid mixtures were produced both in their hydrogenous (H) and deuterated (D) versions and were used to form lipid bilayers both on solid substrates and as vesicles in solution. The supported lipid bilayers were characterised by quartz crystal microbalance with dissipation monitoring (QCM-D) and neutron reflectometry (NR), whereas the vesicles by small angle X-ray (SAXS) and neutron scattering (SANS). Our results show that despite differences in the acyl chain composition, the hydrogenous and deuterated extracts produced bilayers with very comparable structures, which makes them valuable to design experiments involving selective deuteration with techniques such as NMR, neutron scattering or infrared spectroscopy.

A Distracted Scientist: The Life and Contributions of John Senders.

OBJECTIVE: To provide an evaluative and personal overview of the life and contributions of Professor John Senders and to introduce this Special Issue dedicated to his memory. BACKGROUND: John Senders made many profound contributions to HF/E. These various topics are exemplified by the range of papers which compose the Special Issue. Collectively, these works document and demonstrate the impact of his many valuable research works. METHOD: The Special Issue serves to summarize Senders' collective body of work as can be extracted from archival sources. This introductory paper recounts a series of remembrances derived from personal relationships, as well as the products of cooperative investigative research. RESULTS: This collective evaluative process documents Senders' evident and deserved status in the highest pantheon of HF/E pioneers. It records his extraordinary life, replete with accounts of his insights and joie de vivre in exploring and explaining the world which surrounded him. APPLICATIONS: Senders' record of critical contributions provides the example, par excellence, of the successful and fulfilling life in science. It encourages all, both researchers and practitioners alike, in their own individual search for excellence.

Noncovalent Surface Modification of Metal-Organic Frameworks: Unscrambling Adsorption Properties via Isothermal Titration Calorimetry.

Despite the importance of noncovalent interactions in the utilization of metal-organic frameworks (MOFs), using these interactions to functionalize MOFs has rarely been explored. The ease of functionalization and potential for surface-selective functionalization makes modification via noncovalent interactions promising for the creation of porous photocatalytic assemblies. Using isothermal titration calorimetry, photoluminescence measurements, and desorption experiments, we have explored the nature and magnitude of the interactions of [Ru(bpy)2(bpy-R)]2+-functionalized dyes with the surface of MIL-96, where R = C3, C8, C12, and C18 alkyl chains of either straight-chain or cyclic conformations. The orientation of the dyes appears to be flat against the surface with respect to the long alkyl chains, and the surface concentration approaches a monolayer at high initial concentrations of dye. Strangely, the dodecyl-functionalized dye, despite having a smaller interaction energy and larger footprint than either octyl-functionalized dye, achieves the highest maximum surface concentration. Based on photoluminescence spectra, desorption experiments, and ITC data, we believe this is due to the core of the dye being lifted from the surface as the chain length increases. Our understanding of these interactions is important for further utilization of this method for the functionalization of the internal and external surface areas of MOFs.

Product Inhibition and the Catalytic Destruction of a Nerve Agent Simulant by Zirconium-Based Metal-Organic Frameworks.

Rapid degradation/destruction of chemical warfare agents, especially ones containing a phosphorous-fluorine bond, is of notable interest due to their extreme toxicity and typically rapid rate of human incapacitation. Recent studies of the hydrolytic destruction of a key nerve agent simulant, dimethyl 4-nitrophenylphosphate (DMNP), catalyzed by Zr6-based metal-organic frameworks (MOFs), have suggested deactivation of the active sites due to inhibition by the products as the reaction progresses. In this study, the interactions of two MOFs, NU-1000 and MOF-808, and two hydrolysis products, dimethyl phosphate (DMP) and ethyl methyl phosphonate (EMP), from the hydrolysis of the simulant (DMNP) and nerve agent ethyl methylphosphonofluoridate (EMPF), resembling the hydrolysis degradation product of the G-series nerve agent, Sarin (GB), have been investigated to deconvolute the effect of product inhibition from other effects on catalytic activity. Kinetic studies via in situ nuclear magnetic resonance spectroscopy indicated substantial product inhibition upon catalyst activity after several tens to several thousand turnovers, depending on specific conditions. Apparent product binding constants were obtained by fitting initial reaction rates at pH 7.0 and pH 10.5 to a Langmuir-Freundlich binding/adsorption model. For the fits, varying amounts/concentrations of candidate inhibitors were introduced before the start of catalytic hydrolysis. The derived binding constants proved suitable for quantitatively describing product inhibition effects upon reaction rates over the extended time course of simulant hydrolysis by aqua-ligand-bearing hexa-zirconium(IV) nodes.

Zirconium Metal-Organic Frameworks Integrating Chloride Ions for Ammonia Capture and/or Chemical Separation.

Ammonia capture by porous materials is relevant to protection of humans from chemical threats, while ammonia separation may be relevant to its isolation and use following generation by emerging electrochemical schemes. Our previous work described both reversible and irreversible interactions of ammonia with the metal-organic framework (MOF) material, NU-1000, following thermal treatment at either 120 or 300 °C. In the present work, we have examined NU-1000-Cl, a variant that features a modified node structure-at ambient temperature, Zr6(µ3-O)4(µ3-OH)4(H2O)812+ in place of Zr6(µ3-O)4(µ3-OH)4(OH)4(H2O)48+. Carboxylate termini from each of eight linkers balance the 8+ charge of the parent node, while four chloride ions, attached only by hydrogen bonding, complete the charge balance for the 12+ version. We find that both reversible and irreversible uptake of ammonia are enhanced for NU-1000-Cl, relative to the chloride-free version. Two irreversible interactions were observed via in situ diffuse-reflectance infrared Fourier-transform spectroscopy: coordination of NH3 at open Zr sites generated during thermal pretreatment and formation of NH4+ by proton transfer from node aqua ligands. The irreversibility of the latter appears to be facilitated by the presence chloride ions, as NH4+ formation occurs reversibly with chloride-free NU-1000. At room temperature, chemically reversible (and irreversible) interactions between ammonia and NU-1000-Cl result in separation of NH3 from N2 when gas mixtures are examined with breakthrough instrumentation, as evinced by a much longer breakthrough time (∼9 min) for NH3.

Isomer of linker for NU-1000 yields a new she-type, catalytic, and hierarchically porous, Zr-based metal-organic framework.

The well-known MOF (metal-organic framework) linker tetrakis(p-benzoate)pyrene (TBAPy4-) lacks steric hindrance between its benzoates. Changing the 1,3,6,8-siting of benzoates in TBAPy4- to 4,5,9,10-siting introduces substantial steric hindrance and, in turn, enables the synthesis of a new hierarchically porous, she-type MOF Zr6(µ3-O)4(µ3-OH)4(C6H5COO)3(COO)3(TBAPy-2)3/2 (NU-601), where TBAPy-24- is the 4,5,9,10 isomer of TBAPy4-. NU-601 shows high catalytic activity for degradative hydrolysis of a simulant for G-type fluoro-phosphorus nerve agents.

Synthesis, structural studies, and redox chemistry of bimetallic [Mn(CO)3] and [Re(CO)3] complexes.

Manganese ([Mn(CO)3]) and rhenium tricarbonyl ([Re(CO)3]) complexes represent a workhorse family of compounds with applications in a variety of fields. Here, the coordination, structural, and electrochemical properties of a family of mono- and bimetallic [Mn(CO)3] and [Re(CO)3] complexes are explored. In particular, a novel heterobimetallic complex featuring both [Mn(CO)3] and [Re(CO)3] units supported by 2,2'-bipyrimidine (bpm) has been synthesized, structurally characterized, and compared to the analogous monomeric and homobimetallic complexes. To enable a comprehensive structural analysis for the series of complexes, we have carried out new single crystal X-ray diffraction studies of seven compounds: Re(CO)3Cl(bpm), anti-[{Re(CO3)Cl}2(bpm)], Mn(CO)3Br(bpz) (bpz = 2,2'-bipyrazine), Mn(CO)3Br(bpm), syn- and anti-[{Mn(CO3)Br}2(bpm)], and syn-[Mn(CO3)Br(bpm)Re(CO)3Br]. Electrochemical studies reveal that the bimetallic complexes are reduced at much more positive potentials (ΔE≥ 380 mV) compared to their monometallic analogues. This redox behavior is consistent with introduction of the second tricarbonyl unit which inductively withdraws electron density from the bridging, redox-active bpm ligand, resulting in more positive reduction potentials. [Re(CO3)Cl]2(bpm) was reduced with cobaltocene; the electron paramagnetic resonance spectrum of the product exhibits an isotropic signal (near g = 2) characteristic of a ligand-centered bpm radical. Our findings highlight the facile synthesis as well as the structural characteristics and unique electrochemical behavior of this family of complexes.

Investigating the Process and Mechanism of Molecular Transport within a Representative Solvent-Filled Metal-Organic Framework.

Effective permeation into, and diffusive mass transport within, solvent-filled metal-organic frameworks (MOFs) is critical in applications such as MOF-based chemical catalysis of condensed-phase reactions. In this work, we studied the entry from solution of a luminescent probe molecule, 1,3,5,7-tetramethyl-4,4-difluoroboradiazaindacene (BODIPY), into the 1D channel-type, zirconium-based MOF NU-1008 and subsequent transport of the probe through the MOF. Measurements were accomplished via in situ confocal fluorescence microscopy of individual crystallites, where the evolution of the fluorescence response from the crystallite was followed as functions of both time and location within the crystallite. From the confocal data, intracrystalline transport of BODIPY is well-described by one-dimensional diffusion along the channel direction. Varying the chemical identity of the solvent revealed an inverse dependence of probe-molecule diffusivity on bulk-solvent viscosity, qualitatively consistent with expectations from the Stokes-Einstein equation for molecular diffusion. At a more quantitative level, however, measured diffusion coefficients are about 100-fold smaller than expected from Stokes-Einstein, pointing to substantial channel-confinement effects. Evaluation of the confocal data also reveals a non-negligible mass transport resistance, i.e., surface barrier, associated with the probe molecule leaving the solution and permeating the exterior surface of the MOF. Permeation by the probe entails displacement of solvent from the MOF channels. The magnitude of the resistance increases with the size of the solvent molecule. This work draws attention to the importance of MOF structure, external-surface barriers, and solvent molecule identity to the overall transport process in MOFs, which should assist in understanding the performance of MOFs in applications such as condensed-phase heterogeneous catalysis.

A review of recent research in social robotics.

Research in social robotics has a different emphasis from research in robotics for factory, military, hospital, home (vacuuming), aerial (drone), space, and undersea applications. A social robot is one whose purpose is to serve a person in a caring interaction rather than to perform a mechanical task. Both because of its newness and because of its narrower psychological rather than technological emphasis, research in social robotics tends currently to be concentrated in a single journal and single annual conference. This review categorizes such a research into three areas: (1) Affect, Personality and Adaptation; (2) Sensing and Control for Action; and (3 Assistance to the Elderly and Handicapped. Current application is primarily for children's toys and devices to comfort the elderly and handicapped, as detailed in Section 'Toys and the market for social robots in general'.

Individual Differences in Attributes of Trust in Automation: Measurement and Application to System Design.

Computer-based automation of sensing, analysis, memory, decision-making, and control in industrial, business, medical, scientific, and military applications is becoming increasingly sophisticated, employing various techniques of artificial intelligence for learning, pattern recognition, and computation. Research has shown that proper use of automation is highly dependent on operator trust. As a result the topic of trust has become an active subject of research and discussion in the applied disciplines of human factors and human-systems integration. While various papers have pointed to the many factors that influence trust, there currently exists no consensual definition of trust. This paper reviews previous studies of trust in automation with emphasis on its meaning and factors determining subjective assessment of trust and automation trustworthiness (which sometimes but not always are regarded as an objectively measurable properties of the automation). The paper asserts that certain attributes normally associated with human morality can usefully be applied to computer-based automation as it becomes more intelligent and more responsive to its human user. The paper goes on to suggest that the automation, based on its own experience with the user, can develop reciprocal attributes that characterize its own trust of the user and adapt accordingly. This situation can be modeled as a formal game where each of the automation user and the automation (computer) engage one another according to a payoff matrix of utilities (benefits and costs). While this is a concept paper lacking empirical data, it offers hypotheses by which future researchers can test for individual differences in the detailed attributes of trust in automation, and determine criteria for adjusting automation design to best accommodate these user differences.

Extending Three Existing Models to Analysis of Trust in Automation: Signal Detection, Statistical Parameter Estimation, and Model-Based Control.

OBJECTIVE: The objective is to propose three quantitative models of trust in automation. BACKGROUND: Current trust-in-automation literature includes various definitions and frameworks, which are reviewed. METHOD: This research shows how three existing models, namely those for signal detection, statistical parameter estimation calibration, and internal model-based control, can be revised and reinterpreted to apply to trust in automation useful for human-system interaction design. RESULTS: The resulting reinterpretation is presented quantitatively and graphically, and the measures for trust and trust calibration are discussed, along with examples of application. CONCLUSION: The resulting models can be applied to provide quantitative trust measures in future experiments or system designs. APPLICATIONS: Simple examples are provided to explain how model application works for the three trust contexts that correspond to signal detection, parameter estimation calibration, and model-based open-loop control.

Mild and Regioselective Pd(OAc)2-Catalyzed C-H Arylation of Tryptophans by [ArN2]X, Promoted by Tosic Acid.

A regioselective Pd-mediated C-H bond arylation methodology for tryptophans, utilizing stable aryldiazonium salts, affords C2-arylated tryptophan derivatives, in several cases quantitatively. The reactions proceed in air, without base, and at room temperature in EtOAc. The synthetic methodology has been evaluated and compared against other tryptophan derivative arylation methods using the CHEM21 green chemistry toolkit. The behavior of the Pd catalyst species has been probed in preliminary mechanistic studies, which indicate that the reaction is operating homogeneously, although Pd nanoparticles are formed during substrate turnover. The effects of these higher order Pd species on catalysis, under the reaction conditions examined, appear to be minimal: e.g., acting as a Pd reservoir in the latter stages of substrate turnover or as a moribund form (derived from catalyst deactivation). We have determined that TsOH shortens the induction period observed when [ArN2]BF4 salts are employed with Pd(OAc)2. Pd(OTs)2(MeCN)2 was found to be a superior precatalyst (confirmed by kinetic studies) in comparison to Pd(OAc)2.

The Intricacies of User Adjustments of Alerting Thresholds.

OBJECTIVE: We address the question of necessary conditions for users to adjust system settings, such as alarm thresholds, correctly. BACKGROUND: When designing systems, we need to decide which system functions users should control. Giving control to users empowers them, but users must have the relevant information and the ability to adjust settings correctly for their control to be beneficial. METHOD: Using the example of adjusting an alerting threshold, we analyze the conditions for when users can and when they cannot possibly adjust threshold settings adequately. RESULTS: We identify two obstacles that limit users' ability to adjust thresholds adequately: (a) the difficulty of determining the correct threshold settings, especially because of users' strong response to false positive indications, and (b) the difficulty of collecting the information necessary for setting the threshold. CONCLUSION: Users often cannot identify the optimal settings for a system, so it is unlikely that they choose adequate system settings. APPLICATION: System designers must consider the difficulties users face and analyze them explicitly when deciding on user involvement in processes.

A Closed-Loop Model of Operator Visual Attention, Situation Awareness, and Performance Across Automation Mode Transitions.

OBJECTIVE: This article describes a closed-loop, integrated human-vehicle model designed to help understand the underlying cognitive processes that influenced changes in subject visual attention, mental workload, and situation awareness across control mode transitions in a simulated human-in-the-loop lunar landing experiment. BACKGROUND: Control mode transitions from autopilot to manual flight may cause total attentional demands to exceed operator capacity. Attentional resources must be reallocated and reprioritized, which can increase the average uncertainty in the operator's estimates of low-priority system states. We define this increase in uncertainty as a reduction in situation awareness. METHOD: We present a model built upon the optimal control model for state estimation, the crossover model for manual control, and the SEEV (salience, effort, expectancy, value) model for visual attention. We modify the SEEV attention executive to direct visual attention based, in part, on the uncertainty in the operator's estimates of system states. RESULTS: The model was validated using the simulated lunar landing experimental data, demonstrating an average difference in the percentage of attention ≤3.6% for all simulator instruments. The model's predictions of mental workload and situation awareness, measured by task performance and system state uncertainty, also mimicked the experimental data. CONCLUSION: Our model supports the hypothesis that visual attention is influenced by the uncertainty in system state estimates. APPLICATION: Conceptualizing situation awareness around the metric of system state uncertainty is a valuable way for system designers to understand and predict how reallocations in the operator's visual attention during control mode transitions can produce reallocations in situation awareness of certain states.

Musings on Models and the Genius of Jens Rasmussen.

Two well-known Rasmussen models, the skill-rule knowledge (SRK) paradigm and the abstraction hierarchy, are compared to well-known models in both physics and psychology. Some of the latter are quantitative and make explicit predictions; some are qualitative, such as the Rasmussen models, being more useful for provoking thought about the relevant issues. Each of the Rasmussen models is evaluated with respect to six-attribute model taxonomy recently introduced by the author. The SRK model is shown to characterize modern automation as well as human behavior, with computer and physical devices exhibiting the a skill-based, rule-based and knowledge-based properties, and with monitoring and intermittent intervention by a human supervisor. A further suggestion is that the Rasmussen abstraction hierarchy could be applied not only to systems such as air traffic control but also to general situations of living.

Human-Robot Interaction: Status and Challenges.

OBJECTIVE: The current status of human-robot interaction (HRI) is reviewed, and key current research challenges for the human factors community are described. BACKGROUND: Robots have evolved from continuous human-controlled master-slave servomechanisms for handling nuclear waste to a broad range of robots incorporating artificial intelligence for many applications and under human supervisory control. METHODS: This mini-review describes HRI developments in four application areas and what are the challenges for human factors research. RESULTS: In addition to a plethora of research papers, evidence of success is manifest in live demonstrations of robot capability under various forms of human control. CONCLUSIONS: HRI is a rapidly evolving field. Specialized robots under human teleoperation have proven successful in hazardous environments and medical application, as have specialized telerobots under human supervisory control for space and repetitive industrial tasks. Research in areas of self-driving cars, intimate collaboration with humans in manipulation tasks, human control of humanoid robots for hazardous environments, and social interaction with robots is at initial stages. The efficacy of humanoid general-purpose robots has yet to be proven. APPLICATIONS: HRI is now applied in almost all robot tasks, including manufacturing, space, aviation, undersea, surgery, rehabilitation, agriculture, education, package fetch and delivery, policing, and military operations.

Evaluating models in systems ergonomics with a taxonomy of model attributes.

A model, as the term is used here, is a way of representing knowledge for the purpose of thinking, communicating to others, or implementing decisions as in system analysis, design or operations. It can be said that to the extent that we can model some aspect of nature we understand it. Models can range from fleeting mental images to highly refined mathematical equations of computer algorithms that precisely predict physical events. In constructing and evaluating models of ergonomic systems it is important that we consider the attributes of our models in relation to our objectives and what we can reasonably aspire to. To that end this paper proposes a taxonomy of models in terms of six independent attributes: applicability to observables, dimensionality, metricity, robustness, social penetration and conciseness. Each of these attributes is defined along with the meaning of different levels of each. The attribute taxonomy may be used to evaluate the quality of a model. Examples of system ergonomics models having different combinations of attributes at different levels are provided. Philosophical caveats regarding models in system ergonomics are discussed, as well as the relation to scientific method.

Scaling of the ballistic tongue apparatus in chameleons.

Body dimensions of organisms can have a profound impact on their functional and structural properties. We examined the morphological proportions of the feeding apparatus of 105 chameleon specimens representing 23 species in seven genera, spanning a 1,000-fold range in body mass to test whether the feeding apparatus conforms to the null hypotheses of geometric similarity that is based on the prevalence of geometric similarity in other ectothermic vertebrates. We used a phylogenetically corrected regression analysis based on a composite phylogenetic hypothesis to determine the interspecific scaling patterns of the feeding apparatus. We also determined the intraspecific (ontogenetic) scaling patterns for the feeding apparatus in three species. We found that both intraspecifically and interspecifically, the musculoskeletal components of the feeding apparatus scale isometrically among themselves, independent of body length. The feeding apparatus is thus of conserved proportions regardless of overall body length. In contrast, we found that the tongue apparatus as a whole and its musculoskeletal components scale with negative allometry with respect to snout-vent length--smaller individuals have a proportionately larger feeding apparatus than larger individuals, both within and among species. Finally, the tongue apparatus as a whole scales with negative allometry with respect to body mass through ontogeny, but with isometry interspecifically. We suggest that the observed allometry may be maintained by natural selection because an enlarged feeding apparatus at small body size may maximize projection distance and the size of prey that smaller animals with higher mass-specific metabolic rates can capture.

Risk, human error, and system resilience: fundamental ideas.

OBJECTIVE: I review and critique basic ideas of both traditional error/risk analysis and the newer and contrasting paradigm of resilience engineering. BACKGROUND: Analysis of human error has matured and been applied over the past 50 years by human factors engineers, whereas the resilience engineering paradigm is relatively new. METHOD: Fundamental ideas and examples of human factors applications of each approach are presented and contrasted. RESULTS: Probabilistic risk analysis provides mathematical rigor in generalizing on past error events to identify system vulnerabilities, but prediction is problematical because (a) error definition is arbitrary, and thus it is difficult to infer valid probabilities of human error to input to quantitative models, and (b) future accident conditions are likely to be quite different from those of past accidents. The new resilience engineering paradigm, in contrast, is oriented toward organizational process and is concerned with anticipating, mitigating, and preparing for graceful recovery from future events. CONCLUSION: Resilience engineering complements traditional error analysis but has yet to provide useful quantification and operational methods. APPLICATION: A best safety strategy is to use both approaches.

Making the operating room of the future safer.

There is an increasing demand for interventions to improve patient safety, but there is limited data to guide such reform. In particular, because much of the existing research is outcome-driven, we have a limited understanding of the factors and process variations that influence safety in the operating room. In this article, we start with an overview of safety terminology, suggesting a model that emphasizes "safety" rather than "error" and that can encompass the spectrum of events occurring in the operating room. Next, we provide an introduction to techniques that can be used to understand safety at the point of care and we review the data that exists relating such studies to improved outcomes. Future work in this area will need to prospectively study the processes and factors that impact patient safety and vulnerability in the operating room.