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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing an exponentially increasing number of coronavirus disease 19 (COVID-19) cases globally. Prioritization of medical countermeasures for evaluation in randomized clinical trials is critically hindered by the lack of COVID-19 animal models that enable accurate, quantifiable, and reproducible measurement of COVID-19 pulmonary disease free from observer bias. We first used serial computed tomography (CT) to demonstrate that bilateral intrabronchial instillation of SARS-CoV-2 into crab-eating macaques (Macaca fascicularis) results in mild-to-moderate lung abnormalities qualitatively characteristic of subclinical or mild-to-moderate COVID-19 (e.g., ground-glass opacities with or without reticulation, paving, or alveolar consolidation, peri-bronchial thickening, linear opacities) at typical locations (peripheral>central, posterior and dependent, bilateral, multi-lobar). We then used positron emission tomography (PET) analysis to demonstrate increased FDG uptake in the CT-defined lung abnormalities and regional lymph nodes. PET/CT imaging findings appeared in all macaques as early as 2 days post-exposure, variably progressed, and subsequently resolved by 6–12 days post-exposure. Finally, we applied operator-independent, semi-automatic quantification of the volume and radiodensity of CT abnormalities as a possible primary endpoint for immediate and objective efficacy testing of candidate medical countermeasures.

Middle East respiratory syndrome coronavirus (MERS-CoV) presents an emerging threat to public health worldwide by causing severe respiratory disease in humans with high virulence and case fatality rate (about 35%) since 2012. Little is known about the pathogenesis and innate antiviral response in primary human monocyte-derived macrophages (MDMs) and dendritic cells (MDDCs) upon MERS-CoV infection. In this study, we assessed MERS-CoV replication as well as induction of inflammatory cytokines and chemokines in MDMs and immature and mature MDDCs. Immature MDDCs and MDMs were permissive for MERS-CoV infection, while mature MDDCs were not, with stimulation of proinflammatory cytokine and chemokine upregulation in MDMs, but not in MDDCs. To further evaluate the antiviral activity of well-defined drugs in primary antigen presenting cells (APCs), three compounds (chloroquine, chlorpromazine and toremifine), each with broad-spectrum antiviral activity in immortalized cell lines, were evaluated in MDMs and MDDCs to determine their antiviral effect on MERS-CoV infection. While chloroquine was not active in these primary cells, chlorpromazine showed strong anti-MERS-CoV activity, but it was associated with high cytotoxicity narrowing the potential window for drug utilization. Unlike in established cells, toremifene had marginal activity when tested in antigen presenting cells, with high apparent cytotoxicity, also limiting its potential as a therapeutic option. These results demonstrate the value of testing drugs in primary cells, in addition to established cell lines, before initiating preclinical or clinical studies for MERS treatment and the importance of carefully assessing cytotoxicity in drug screen assays. Furthermore, these studies also highlight the role of APCs in stimulating a robust protective immune response to MERS-CoV infection.

The thermal conductivity of the GaN buffer layer in AlGaN/GaN devices can be determined by measuring the vertical temperature gradient through this layer. In this work, diamond micro-thermometers and standard micro-Raman thermography were used to determine the surface and volumetric depth average temperature, respectively, of the carbon-doped GaN buffer layer in AlGaN/GaN transistors. By comparing measured temperatures with finite element thermal simulation, a thermal conductivity of 200 ± 20 Wm−1 K−1 was obtained for a carbon-doped GaN layer with a doping concentration of 1017 cm−3.

If the theory of affordance is applied to a robot, performing the whole process of recognition and planning is not always required in its computer. Since the tactile sensing of a robot is important to perform any task, we focus on tactile sensing and introduce a new concept called the artificial tactile affordance system (ATAS). Its basic idea is the implementation of a recurrent mechanism in which information obtained from the object and the behavior performed by the robot's inducing the next behavior. We intend to implement ATAS based on the following two methodologies: (1) after each rule is transformed into an algorithm, a program module is coded based on the algorithm; ATAS is composed of several program modules, and a module is selected from the set of modules based on sensor information; (2) a set of rules is expressed as a table composed of sensor input columns and behavior output columns, and the table rows correspond to rules; since each rule is transformed to a string of 0 and 1, we treat a long string composed of rule strings as a gene to obtain an optimum gene that adapts to its environment using a genetic algorithm (GA). For methodology 1, we established an ATAS composed of 3 to 5 modules to accomplish such tasks as object grasping, pick and place, cap screwing, and assembling. Using methodology 1, a two-hand-arm robot equipped with an optical three- axis tactile sensor performed the above tasks. For methodology 2, we propose the Evolutionary Behavior Table System (EBTS) that uses a GA to acquire the autonomous cooperation behavior of multiple mobile robots. In validation experiments, three agents equipped with behavior tables conveyed an object to a specified goal with higher scores than the four-agent condition. Since the redundant agent does not interrupt the other agents, the agent acquires the collective behavior of not interrupting other agents based on its environment information. Methodology 1 is very effective for such fine control as handling tasks of humanoid robots, and methodology 2 is very useful to obtain general robotic behavior that is suitable for the environment.

For inhalational studies and aerosol exposures to viruses, head-out plethysmography acquisition has been traditionally used for the determination of estimated inhaled dose in anesthetized nonhuman primates prior to or during an aerosol exposure. A pressure drop across a pneumotachograph is measured within a sealed chamber during inspiration/exhalation of the nonhuman primate, generating respiratory values and breathing frequencies. Due to the fluctuation of depth of anesthesia, pre-exposure respiratory values can be variable, leading to less precise and accurate dosing calculations downstream. Although an anesthesia infusion pump may help stabilize the depth of sedation, pumps are difficult to use within a sealed head-out plethysmography chamber. Real-time, head-out plethysmography acquisition could increase precision and accuracy of the measurements, but the bulky equipment needed for head-out plethysmography precludes real-time use inside a Class III biological safety cabinet, where most aerosol exposures occur. However, the respiratory inductive plethysmography (RIP) acquisition method measures the same respiratory parameters by detecting movement of the chest and abdomen during breathing using two elastic bands within the Class III biological safety cabinet. As respiratory values are relayed to a computer for software integration and analysis real-time, adjustment of aerosol exposure duration is based on the depth of sedation of the animal. The objective of this study was to compare values obtained using two methodologies (pre-exposure head-out plethysmography and real-time RIP). Transitioning to RIP technology with real-time acquisition provides more consistent, precise, and accurate aerosol dosing by reducing reported errors in respiratory values from anesthesia variability when using pre-exposure head-out plethysmography acquisition.

Biosafety level 4 (BSL-4) suit laboratories are specifically designed to study high-consequence pathogens for which neither infection prophylaxes nor treatment options exist. The hallmarks of these laboratories are: custom-designed airtight doors, dedicated supply and exhaust airflow systems, a negative-pressure environment, and mandatory use of positive-pressure (“space”) suits. The risk for laboratory specialists working with highly pathogenic agents is minimized through rigorous training and adherence to stringent safety protocols and standard operating procedures. Researchers perform the majority of their work in BSL-2 laboratories and switch to BSL-4 suit laboratories when work with a high-consequence pathogen is required. Collaborators and scientists considering BSL-4 projects should be aware of the challenges associated with BSL-4 research both in terms of experimental technical limitations in BSL-4 laboratory space and the increased duration of such experiments. Tasks such as entering and exiting the BSL-4 suit laboratories are considerably more complex and time-consuming compared to BSL-2 and BSL-3 laboratories. The focus of this particular article is to address basic biosafety concerns and describe the entrance and exit procedures for the BSL-4 laboratory at the NIH/NIAID Integrated Research Facility at Fort Detrick. Such procedures include checking external systems that support the BSL-4 laboratory, and inspecting and donning positive-pressure suits, entering the laboratory, moving through air pressure-resistant doors, and connecting to air-supply hoses. We will also discuss moving within and exiting the BSL-4 suit laboratories, including using the chemical shower and removing and storing positive-pressure suits.

Aerosol or inhalational studies of high-consequence pathogens have recently been increasing in number due to the perceived threat of intentional aerosol releases or unexpected natural aerosol transmission. Specific laboratories designed to perform these experiments require tremendous engineering controls to provide a safe and secure working environment and constant systems maintenance to sustain functionality. Class III biosafety cabinets, also referred to as gloveboxes, are gas-tight enclosures with non-opening windows. These cabinets are maintained under negative pressure by double high-efficiency-particulate-air (HEPA)-filtered exhaust systems and are the ideal primary containment for housing aerosolization equipment. A well planned workflow between staff members within high containment from, for instance, an animal biosafety level-4 (ABSL-4) suit laboratory to the ABSL-4 cabinet laboratory is a crucial component for successful experimentation. For smooth study execution, establishing a communication network, moving equipment and subjects, and setting up and placing equipment, requires staff members to meticulously plan procedures prior to study initiation. Here, we provide an overview and a visual representation of how aerobiology research is conducted at the National Institutes of Health, National Institute of Allergy and Infectious Diseases Integrated Research Facility at Fort Detrick, Maryland, USA, within an ABSL-4 environment.

Medical imaging using animal models for human diseases has been utilized for decades; however, until recently, medical imaging of diseases induced by high-consequence pathogens has not been possible. In 2014, the National Institutes of Health, National Institute of Allergy and Infectious Diseases, Integrated Research Facility at Fort Detrick opened an Animal Biosafety Level 4 (ABSL-4) facility to assess the clinical course and pathology of infectious diseases in experimentally infected animals. Multiple imaging modalities including computed tomography (CT), magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography are available to researchers for these evaluations. The focus of this article is to describe the workflow for safely obtaining a CT image of a live guinea pig in an ABSL-4 facility. These procedures include animal handling, anesthesia, and preparing and monitoring the animal until recovery from sedation. We will also discuss preparing the imaging equipment, performing quality checks, communication methods from "hot side" (containing pathogens) to "cold side," and moving the animal from the holding room to the imaging suite.

Tactile sensing ability is important for social robots, which perform daily work instead of persons. The authors have developed a three-axis tactile sensor based on an optical measurement method. Since our optical three-axis tactile sensor can measure distributed tri-axial tactile data, a robot equipped with the tactile sensors can detect not only grasping force but also slippage from its hands. In this paper, the authors have two objectives: one of them is evaluation of the three-axis tactile sensor in actual robotic tasks; the other is to demonstrate effectiveness of tri-axial tactile data for motion control. To accomplish these objectives, the authors have developed a two-hand-arm robot equipped with three-axis tactile sensors. In the robot motion control, we implement a recurrent mechanism in which the next behavior is induced by the tactile data to make the robot accept intention embedded in the environment. Since this mechanism is based on the tactile data, it is easy to apply it to communication between the hand-arms to obtain the best timing for cooperative work. In a series of experiments, the two-hand-arm robot performed object transfer and assembling tasks. Experimental results show that this tri-axial tactile base programming works well because appropriate behavior is induced according to slippage direction.

2 Faculty of Mechanical Engineering University Technology MARA, Malaysia Abstract: Problem statement: To advance the robust object recognition of robots, we present an algorithm for object exploration based on three-axis tactile data that is necessary and sufficient for the evaluation of contact phenomena. Approach: The object surface contour is acquired by controlling the finger position so that the normal force, measured by optical three-axis tactile sensors, remains constant as two fingertips slide along the object surface. In this algorithm, when the robot grasps an object, the tangential force increment is checked to judge the initial contact state because it is more sensitive than the normal force. After contact between the fingertips and the object, the normal force is adjusted to remain constant with a tolerant value between the upper and lower thresholds. Results: In the verification test, shape exploration experiments were conducted using a hand-arm robot equipped with our tactile sensor and a hard sinusoidal-shaped wooden object. Experimental results show that the hand-arm robot is capable of gathering the object contour having a concave or convex portion because its finger position controlled by three-axis tactile sensing information follows the object surface. Conclusion/Recommendations: We derive a control algorithm in robot fingers based on time tangential force increment and normal force detection to perform a shape exploration procedure.

Problem statement: Sensitization of robot hand is still remaining as crucial issue since most of robot hand systems nowadays are only capable to grasp a predefined specific object. It is still difficult for robot hand system to realize human-like tactile sensation. Some common problems in robot hand system are low accuracy sensing device, sensors are not robust enough for long time work and heavy duties, inconsistence tactile sensing detection and difficulties in control of sensing fusion with robot trajectory. These problems are apparently drawback the progress to commercializing robot hands as real consumer products. Approach: This study presented the application of optical three-axis tactile sensor to robot hand to improve sensitization quality in robotic hand system. The proposed tactile sensor system was designed with compliance modules to communicate with robot hand control system. The sensing principle used in this tactile sensor comparatively provides better sensing accuracy to detect contact phenomena from acquisition of three axial directions of forces. Methodology of force and slippage detection in the tactile sensor system was presented. Accordingly, the optimization of robot hand control algorithm to comply with the tactile sensor system was presented and verified in experiment of grasping and twisting. Results: The tactile sensor presented in this study is capable of detecting normal and shear force simultaneously. The proposed methodology was verified in experiment with paper cup and water, in which the result shows the robot control system managed to respond to the proposed object stiffness distinction parameters and effectively respond to sudden change of object weight during grasping. An experiment of grasping and twisting motions was conducted using a bottle cap. In order to perform simultaneous grasping and twisting tasks, optimization of the control algorithm was conducted with additional parameters to satisfy the desired tasks. Conclusion: Experimental result shows that the robot hand managed to perform grasping and twisting of bottle cap smoothly. The overall results revealed good performance of the proposed optical three-axis tactile sensor system and robot hand control algorithm for future application in a real artificial robot hand. In addition, slippage sensation measured in a robot control system could contribute a better maneuvering of the robot arm-finger system.

This paper presents an analysis result of grasp-move-and-twist motions of robotic hands equipped with optical three-axis tactile sensor to evaluate performance of a new control algorithm based on tactile slippage sensation. The optical three-axis tactile sensor is capable of defining normal and shear forces simultaneously. The proposed algorithm consists of robot arm and hand controls based on parameters of normal and shear force, and slippage detection. To improve performance during grasp, move and twist motions, we present analysis of slippage direction and classify the control algorithm in two phases: grasp-move-release and grasp-twist. We present detailed explanation of the control algorithm based on the existing robot arm control system. The experiment is conducted using a bottle cap, and the analysis results show that the slippage control parameters enhanced performance of grasp control in simultaneous robot tasks. Experimental results revealed good performance of the proposed control algorithm to accomplish the proposed grasp-move-and-twist motions.

This paper analyzes grasp synthesis in multi-fingered robot arm equipped with a tactile sensor to handle objects located at arbitrary positions. We developed an 11-dof multi-fingered arm and a novel optical three-axis tactile sensor system based on an optical waveguide transduction method. The tactile sensor can simultaneously acquire normal and shearing forces. We analyzed normal and shear force distribution to grasp real object. The slippage direction acquired from the shear force data was used to control arm movements in the incipient grasp and release motion. Normal force is used to distinguish object stiffness and to generate optimum grasp pressure. The analysis results are compiled in a control algorithm inside the robot control system. The algorithm was evaluated in experiments with real objects, and the results revealed good performance of the robot arm when handling arbitrary located objects.

This paper presents a new algorithm for object handling tasks based on active tactile and slippage sensations using a humanoid robot multi-fingered arm for an object that exists at an arbitrary position. The idea is to enhance real-time object handling tasks based on tactile sensing in humanoid robotics, where grasp, move and release motions are involved. We developed a novel hemisphere-shaped optical three-axis tactile sensor to mount on fingertips of the robot arm. The tactile sensor is capable of defining normal and shearing forces simultaneously. For grasp and release motions, we designed the algorithm based on slippage direction analysis consisting of coordinate transformation of the sensing element for the arm global coordinate. The robot control system uses the analysis results to determine whether an object is in contact with the ground without needing to measure the height of the ground. The algorithm was evaluated in experiments with soft and hard objects, whereby results revealed good performance for the robot fingers in handling an object at an arbitrary position.

The overall threat of a viral pathogen to human populations is largely determined by the modus operandi and velocity of the pathogen that is transmitted among humans. Microorganisms that can spread by aerosol are considered a more challenging enemy than those that require direct body-to-body contact for transmission, due to the potential for infection of numerous people rather than a single individual. Additionally, disease containment is much more difficult to achieve for aerosolized viral pathogens than for pathogens that spread solely via direct person-to-person contact. Thus, aerobiology has become an increasingly necessary component for studying viral pathogens that are naturally or intentionally transmitted by aerosol. The goal of studying aerosol viral pathogens is to improve public health preparedness and medical countermeasure development. Here, we provide a brief overview of the animal biosafety level 4 Aerobiology Core at the NIH/NIAID Integrated Research Facility at Fort Detrick, Maryland, USA.

This paper presents a new grasping strategy of two robot arms based on active tactile and slippage sensation using a novel optical three-axis tactile sensor system. The tactile sensors are mounted on the tip of robotic hands of two robot arms. In the robot motion control, a recurrent mechanism was implemented in which the next behavior is induced by the tactile data to make the robot accept intention embedded in the environment. Since this mechanism is based on the tactile data, it is possible to apply it to communication between the hand-arms to obtain the best timing for cooperative work. A slippage distribution analysis was conducted which result shows that slippage occurred according to direction of force applied to the sensing elements. In experiments, the two-hand-arm robot performed object grasping, twisting, transferring and assembling tasks. Experimental results show that the proposed strategy has great potential to improve grasping performance of robot hand because appropriate behavior is induced according to tactile and slippage direction.

In order to progress robust object recognition of robots, we present an algorithm for object exploration based on three-axis tactile data that is necessary and sufficient for evaluation of contact phenomena. Object surface contour is gathered by controlling finger position to keep a constant the normal force measured by optical three-axis tactile sensors as two fingertips slide along the object surface. In this algorithm, when the robot grasps the object, time derivative of shearing force is checked to judge initial contact state because it is more sensitive than normal force. After contact between fingertips and the object, normal force is adjusted to keep a constant with a tolerant value between upper and lower thresholds. In the verification test, shape exploration experiments are conducted using sinusoidal shape hard object of wood. Experimental results show that this tactile sensor is capable of gathering the surface shape information of an object having concave or convex portion because the finger position controlled by normal force obtained by this tactile sensor follows the object surface.

This paper present object handling capabilities of two robotic hands equipped with optical three-axis tactile sensor. We present optimization of grasp control in tactile sensor and robot hand control system to precisely control robot hand based on tactile sensing information. To enhance performance of the robot hand, stiffness distinction parameters were applied in the control system. These parameters are used to select velocity ratio of robot hand to control re-push motion and define optimum grasp pressure. In addition, slippage recognition method is also applied so that the robot hand can grasp and handle object located at arbitrary position. The proposed control system and parameters were evaluated in object handling experiments with hard and soft objects, and object located at arbitrary position. Experimental results revealed good performance for the robot hand in handling hard and soft objects, and object located at an arbitrary position.

Unicompartmental knee arthroplasty (UKA) is an advisable operation for medial or lateral compartmental osteoarthritis of the knee in the elderly. UKA has several good points: high satisfaction of the patient, excellent range of motion, gait pattern resembling normal, minimum of bone resection, easier and shorter time of operation, less blood loss, short period of postoperative management, and successful revision surgery. To obtain excellent long-term follow-up results, the indications for UKA have to be strictly determined and the surgical technique has to be mastered. The indications of UKA for medial compartmental osteoarthritis include patient and knee selection. Patient selection is as follows: more than 70-year-old patient, no obesity, low activity of work and activites of daily living, and patient whose general condition is too severe to be operated on with total knee arthroplasty or high tibial osteotomy. Knee selection is as follows: less than 180° of valgus stress femorotibial angle, no deficiency of anterior cruciate ligament, no severe patellofemoral osteoarthritis, less than 30° of flexion contracture, undercorrected case after high tibial osteotomy, and no past history of knee infection. Surgical techniques required are as follows: correction of malalignment to 172° femorotibial angle at standing for medial compartmental osteoarthritis of the knee, resection of osteophytes, notch plasty, subperiosteal medial tension band release, and subchondral bone-preserving surgery.

The femoral component of the Ceramic YMCK Unicom Knee is made of stainless steel with two stems, and the tibial component of alumina ceramics with two stems. Unicompartmental arthroplasty with the YMCK model was performed on 57 knees (55 medial, 2 lateral) of 47 patients (7 men, 40 women) aged 59–83 years (average 71). The follow-up period ranged from 2 to 11 years (average 3.9). In 55 knees with preoprative medial compartment osteoarthritis the average femorotibial angle (standing) was 185° ± 6.5° before surgery. The malalignment was satisfactorily corrected and the angle was 174° ± 5.5° after replacements. The relief of pain was marked and the average Japanese Orthopaedic Association (JOA) Knee score was 51.5 ± 9.1 before surgery and 82.1 ± 11.3 after. Forty-six knees were judged as excellent or good according to the Hospital for Special Surgery (HSS) criteria postoperatively. We had one case with infection, treated successfully, and one case with breakage of the tibial component. There were four cases with metallosis, two of which were revised. There was no significant difference between the preoperative and postoperative arc of motion of the knee, but flexion contracture was improved significantly.

Radiographically demonstrated osteosclerosis was quantitatively evaluated in knees with medial compartmental osteoarthritis by dual xray absorptiometry. Bone density was measured in various areas of 144 knees with medial compartmental osteoarthritis, 23 knees of which were treated with high tibial osteotomy. The bone mineral density of the medial femoral and tibial condyles was greater than that of the lateral femoral and tibial condyles in all knees with medial compartmental osteoarthritis. The ratios of bone mineral density of the medial condyles to that of the lateral condyles were found to increase significantly with the progression of osteoarthritis. There was a significant positive regression line correlation between those ratios and the increase of varus deformity as expressed by the standing femorotibial angle. The former were calculated to be 1.0 when the latter was nearly 170 degrees (10 degrees anatomic valgus angulation). The ratio of bone mineral density of the medial femoral condyles to the lateral femoral condyles decreased sharply in all 23 knees within 1 year after high tibial osteotomy.

Among the finishing of zinc base alloys used for die casting, the electroplating has been applied for general uses. Owing to the intercrystalline corrosion and surface corrosion of zinc alloy die castings, the metal coating must have the thickness sufficient to prevent their corrosion. Therefore, we investigated on the direct nickel plating and copper plating, and we could find that it was necessary to have the thick and compact copper coating, in order to prevent the corrosion and make the mass production.

In order to improve quality of the die-cast, it is important to control heat (temperature) together with the design of dies, character of die-casting machine, etc., and we studied the effects of shot number and water cooling on variation of distribution of die-temperature.A method of qualitative improvement for uniform temperature of cavity might be found and an equation for efficiency of water cooling might be proposed by the measurement of die temperature.