Total Syntheses of Phorbol and 11 Tigliane Diterpenoids and Their Evaluation as HIV Latency-Reversing Agents.

Tigliane diterpenoids possess exceptionally complex structures comprising common 5/7/6/3-membered ABCD-rings and disparate oxygen functionalities. While tiglianes display a wide range of biological activities, compounds with HIV latency-reversing activity can eliminate viral reservoirs, thereby serving as promising leads for new anti-HIV agents. Herein, we report collective total syntheses of phorbol (13) and 11 tiglianes 14-24 with various acylation patterns and oxidation states, and their evaluation as HIV latency-reversing agents. The syntheses were strategically divided into five stages to increase the structural complexity. First, our previously established sequence enabled the expeditious preparation of ABC-tricycle 9 in 15 steps. Second, hydroxylation of 9 and ring-contractive D-ring formation furnished phorbol (13). Third, site-selective attachment of two acyl groups to 13 produced four phorbol diesters 14-17. Fourth, the oxygen functionalities were regio- and stereoselectively installed to yield five tiglianes 18-22. Fifth, further oxidation to the most densely oxygenated acerifolin A (23) and tigilanol tiglate (24) was realized through organizing a 3D shape of the B-ring. Assessment of the HIV latency-reversing activities of the 12 tiglianes revealed seven tiglianes (14-17 and 22-24) with 20- to 300-fold improved efficacy compared with prostratin (12), a representative latency-reversing agent. Therefore, the robust synthetic routes to a variety of tiglianes with promising activities devised in this study provide opportunities for advancing HIV eradication strategies.

An Intuitive Endoscope Operating System With an Interface Suitable for Cartesian Coordinate Input.

Endoscopes are useful tools for inspecting and observing places that are inaccessible to humans and ordinary cameras. However, it is difficult to operate an endoscope intuitively because there is an embodiment difference between the endoscope and the human body. In this study, we developed an endoscope operating system that uses a Cartesian coordinate input interface. To investigate the range of movement achieving the required accuracy, we measured the actual movement of the endoscope tip using a magnetic three-dimensional positioning sensor. We compared the actual and estimated positions and postures at the endoscope tip and estimated the errors. The results showed that the error of the thrust output was sufficiently small. Furthermore, we can achieve the required accuracy in the range of movement from -74.9° to 80.0° in the roll direction, and from -37.5° to 50.0° in the yaw direction.Clinical relevance- This paper presents an accurate and intuitive endoscope operating system with a new interface.

Assessment of a karate performer's position estimation system without any markers.

Karate has become more popular, and researches have been conducted on training methods and motion analysis related to karate. The AR system for karate is an effective system for training and for the audience to understand the performance. To develop the AR system, it is necessary to acquire the movement of the performer. The purpose of the research is to assess a motion capture system to estimate a karate performer's full-body position and posture from HoloLens 2, without wearing any attachments. We used ThreeDPoseUnityBarracuda to estimate the position and posture of the performer's joints. In the experiment, the estimated joint's positions were compared with actual positions using the inertial three-dimensional motion capture. As results, although the error increased when the performer's movement was large, the median error between the estimated and actual positions was a maximum of 0.24 m at the x-coordinate of the right hand, and high accuracy was obtained when the performer's movement was small.

Differences in coordination between dominant and non-dominant hands in tele-operation.

The intuitive tele-operation of industrial robot arms is necessary for the teaching of autonomous movement. We developed a novel interface, namely the iFeel Desktop Haptic Device, for operating robots intuitively. However, when a user uses two interfaces with two hands, there are differences in coordination between the dominant and non-dominant hands. In this paper, we investigated the differences in coordination between dominant and non-dominant hands using two devices for the development of cooperative control. In an experiment, when the participants manipulated the two interfaces to operate a virtual tracking system, we measured the tracking error in each degree of freedom (i.e., X, Y, Z, pitch, yaw, and roll directions). The results show that there were significant differences between the dominant and non-dominant hands for movement in the X, Y, Z, and pitch directions. We conclude that the operations that involve more body parts have a greater difference between dominant and non-dominant hands.

Combination design of drive mechanism considering delay of surgical robot.

Surgical robots have contributed greatly to the development of minimally invasive surgery. However, these robots suffer from issues such as the looseness of wires acting as the robot's drive mechanism, and high maintenance cost. The objective of this study was to derive a combination of driving mechanisms other than wires that satisfies the required positional accuracy of a surgical robot. The robot operation trajectory was obtained using a virtual surgical simulator. Based on the operation trajectory obtained in the suture task experiment, the delay of each joint was virtually simulated, and the robot's position was calculated. The positions of the robot with and without delay were compared, and the drive mechanism combinations that satisfy the required positional accuracy were obtained. Thus, satisfactory accuracy was achieved when the alternative drive mechanism was properly placed.Clinical Relevance- This paper presents an accurate and low-maintenance surgical robot that uses few wires and alternative drive mechanisms.

Identification of surgical forceps using YOLACT++ in different lighted environments.

Forceps tracking in laparoscopic surgery contributes to improved surgical outcomes. We identified forceps using YOLACT++ for fast and accurate segmentation. Differences in the illumination of the environment can affect the image recognition accuracy in deep learning. Therefore, we examined the speed and accuracy of YOLACT++ forceps identification in different illuminated environments. We expected that this experiment would help us understand the optimal lighted environments for YOLACT++ and to further improve the performance of the forceps identification model. The greatest accuracy was obtained under a light-shielded environment with light shining only on the suture area. Although a laparotomy with a clear view of the surgical site is easier for the physician to operate in, we concluded that the forceps identification model of YOLACT++ can be used more effectively in the laparoscopic surgical environment.Clinical Relevance- This study contributes to analyzing the cause of surgical errors in laparoscopic surgery.

Visual Illusion Created by a Striped Pattern through Augmented Reality for the Prevention of Tumbling on Stairs.

A fall on stairs can be a dangerous accident. An important indicator of falling risk is the foot clearance, which is the height of the foot when ascending stairs or the distance of the foot from the step when descending. We developed an augmented reality system with a holographic lens using a visual illusion to improve the foot clearance on stairs. The system draws a vertical striped pattern on the stair riser as the participant ascends the stairs to create the illusion that the steps are higher than the actual steps, and draws a horizontal striped pattern on the stair tread as the participant descends the stairs to create the illusion of narrower stairs. We experimentally evaluated the accuracy of the system and fitted a model to determine the appropriate stripe thickness. Finally, participants ascended and descended stairs before, during, and after using the augmented reality system. The foot clearance significantly improved, not only while the participants used the system but also after they used the system compared with before.

Synthesis and Biological Evaluation of Simplified Ansellone Analogues with Lipophilic Side Chains as HIV Latency-Reversing Agents.

Structurally simplified analogues of ansellone A, in which the decalin skeleton is replaced with a lipophilic chain, were prepared and their HIV latency-reversing activities biologically evaluated. In particular, two analogues bearing ether and alkenyl side chains, respectively, showed comparable activities to that of ansellone A. Each of the simplified compounds was easily synthesized using Prins cyclisation chemistry.

Idiopathic Intracranial Hypertension with Disproportionately Enlarged Subarachnoid Space Hydrocephalus on Imaging.

The pathophysiology of idiopathic intracranial hypertension (IIH) and idiopathic normal-pressure hydrocephalus (iNPH) differs in terms of cerebrospinal fluid (CSF) pressure and imaging-related characteristics. A 51-year-old man presented with optic nerve papillary edema, visual disturbance, bilateral abducens nerve palsy, and a wide-based gait. Imaging showed characteristic findings of IIH and disproportionately enlarged subarachnoid space hydrocephalus (DESH) - characteristic of iNPH. A CSF examination revealed marked CSF hypertension. IIH with iNPH-like imaging features (DESH) was diagnosed, and ventriculoperitoneal shunt surgery was performed. Postoperatively, the visual acuity and visual field improved. This report also describes the distinct and overlapping pathophysiological mechanisms of IIH and iNPH.

Total Synthesis of Ansellone G and Phorbadione.

The first total synthesis of marine sesterterpenoid ansellone G (2) was accomplished. This strategy utilizes the Prins cyclization reaction of a chloro-substituted homoallyl alcohol to synthesize the hydrobenzopyran skeleton. The preintroduction of the chloro groups facilitated the functional group transformation for 2 after constructing the carbon framework. Furthermore, we also successfully synthesized phorbadione (3) by dehydrating the tertiary alcohol. The HIV latency-reversing activity of the synthesized 2, 3, and deacetylated 2 was also evaluated.

Brain activation measurement for motion gain decision of surgical endoscope manipulation.

BACKGROUND: Robotic surgery improves minimally invasive interventions. However, it is challenging to determine the best gain settings for control of the endoscope. Providing the surgeon with the ability to manipulate the endoscope at an appropriate speed will likely improve the surgery by reducing the surgeon's stress. In this study, we validated the feasibility of a gain-tuning method in which the operator's brain activity is measured and used to evaluate stress levels. METHODS: We developed an endoscope-manipulation simulator and used functional near-infrared spectroscopy to measure the prefrontal cortical activity, while participants controlled the simulator at different gain values. RESULTS: The brain activation levels in the prefrontal cortex exhibited significant differences under different viewpoint motion gain conditions. CONCLUSIONS: The stress-related brain activity was significantly reduced at specific gains, indicating that the brain activity evaluation would be useful to determine the parameters related to the operator's feelings.

Arginyl-tRNA-protein transferase 1 contributes to governing optimal stability of the human immunodeficiency virus type 1 core.

BACKGROUND: The genome of human immunodeficiency virus type 1 (HIV-1) is encapsulated in a core consisting of viral capsid proteins (CA). After viral entry, the HIV-1 core dissociates and releases the viral genome into the target cell, this process is called uncoating. Uncoating of HIV-1 core is one of the critical events in viral replication and several studies show that host proteins positively or negatively regulate this process by interacting directly with the HIV-1 CA. RESULTS: Here, we show that arginyl-tRNA-protein transferase 1 (ATE1) plays an important role in the uncoating process by governing the optimal core stability. Yeast two-hybrid screening of a human cDNA library identified ATE1 as an HIV-1-CA-interacting protein and direct interaction of ATE1 with Pr55gag and p160gag - pol via HIV-1 CA was observed by cell-based pull-down assay. ATE1 knockdown in HIV-1 producer cells resulted in the production of less infectious viruses, which have normal amounts of the early products of the reverse transcription reaction but reduced amounts of the late products of the reverse transcription. Interestingly, ATE1 overexpression in HIV-1 producer cells also resulted in the production of poor infectious viruses. Cell-based fate-of-capsid assay, a commonly used method for evaluating uncoating by measuring core stability, showed that the amounts of pelletable cores in cells infected with the virus produced from ATE1-knockdown cells increased compared with those detected in the cells infected with the control virus. In contrast, the amounts of pelletable cores in cells infected with the virus produced from ATE1-overexpressing cells decreased compared with those detected in the cells infected with the control virus. CONCLUSIONS: These results indicate that ATE1 expression levels in HIV-1 producer cells contribute to the adequate formation of a stable HIV-1 core. These findings provide insights into a novel mechanism of HIV-1 uncoating and revealed ATE1 as a new host factor regulating HIV-1 replication.

Source location of volcanic earthquakes and subsurface characterization using fiber-optic cable and distributed acoustic sensing system.

We present one of the first studies on source location determination for volcanic earthquakes and characterization of volcanic subsurfaces using data from a distributed acoustic sensing (DAS) system. Using the arrival time difference estimated from well-correlated waveforms and a dense spatial distribution of seismic amplitudes recorded along the fiber-optic cable, we determine the hypocenters of volcanic earthquakes recorded at Azuma volcano, Japan. The sources are located at a shallow depth beneath active volcanic areas with a range of approximately 1 km. Spatial distribution of the site amplification factors determined from coda waves of regional tectonic earthquakes are well correlated with old lava flow distributions and volcano topography. Since DAS observation can be performed remotely and buried fiber-optic cables are not damaged by volcanic ash or bombs during eruptions, this new observation system is suitable for monitoring of volcanoes without risk of system damage and for evaluating volcanic structures.

Design factors for determining the radula shape of Euhadra Peliomphala.

Biomimetics present useful ideas for various product designs. However, most biomimetics only mimic the features of living organisms. It has not been clarified how a given shape is attained through natural selection. This paper presents the design factors that optimize the radula shape of Euhadra peliomphala. Clarifying the important design factors would help designers in solving several problems simultaneously in order to adapt to complicated and multi-functionalized design mechanisms. We measured the radula of Euhadra peliomphala by using a microscope and modeled the grinding/cutting force using the finite element analysis (FEA). We reproduced the natural selection using multi-objective genetic algorithm (MOGA). We compared the solutions when optimizing the radula shape using objective functions of each combination of stress, cutting force, abrasion, or volume. The results show that the solution obtained through two-objective optimization with stress and cutting force was the closest to the actual radula shape.

Using Brain Activation to Evaluate Arrangements Aiding Hand-Eye Coordination in Surgical Robot Systems.

GOAL: To realize intuitive, minimally invasive surgery, surgical robots are often controlled using master-slave systems. However, the surgical robot's structure often differs from that of the human body, so the arrangement between the monitor and master must reflect this physical difference. In this study, we validate the feasibility of an embodiment evaluation method that determines the arrangement between the monitor and master. In our constructed cognitive model, the brain's intraparietal sulcus activates significantly when somatic and visual feedback match. Using this model, we validate a cognitively appropriate arrangement between the monitor and master. METHODS: In experiments, we measure participants' brain activation using an imaging device as they control the virtual surgical simulator. Two experiments are carried out that vary the monitor and hand positions. CONCLUSION: There are two common arrangements of the monitor and master at the brain activation's peak: One is placing the monitor behind the master, so the user feels that the system is an extension of his arms into the monitor; the other arranges the monitor in front of the master, so the user feels the correspondence between his own arm and the virtual arm in the monitor. SIGNIFICANCE: From these results, we conclude that the arrangement between the monitor and master impacts embodiment, enabling the participant to feel apparent posture matches in master-slave surgical robot systems.

Spiral Folded Adhesive Plaster Optimization for Laparoscopic Surgery.

Laparoscopic surgery has the advantage of the minimally invasive for patients. However, the surgery is technically difficult for surgeon because high dexterity is required for suturing in the narrow patient's body. This paper presents a sealing method to locate the adhesive plaster at the incision instead of suturing. The objective is to optimize the plaster material and structure. We made the plaster with the thermally cross-linked gelatin film in a spiral fold because thermally cross-linked gelatin film has the high biocompatibility and tackiness, and a spiral fold has great storage efficiency. In 3 experiments, we measured expansion rate, expansion tension, peeling force, and sealing pressure in a variety of gelatin volume and concentration, and the films diameter. From these experimental results, we optimized the films using response surface method. As a result, the plaster is optimal at gelatin volume 10 mL, gelatin concentration 4 wt %, and films diameters 75 mm. We concluded that the optimized spiral folded adhesive plaster is sufficient in terms of the expansion, tackiness, and sealing properties.

Enhanced Frequency Difference of Tumor inside Vibrated Tissue by a Compression Cylinder.

Breast cancer diagnosis has been mostly accomplished by imaging technologies. These methods have the great advantages of detecting the presence and location of breast cancer. However, it's difficult to distinguish between a benign and malignant tumor in a deep position because both tumor types look similar. In this paper, we vibrated the tissue including tumor from skin with a compression cylinder to analyze the frequency difference for distinguishing the tissue type. Before distinguishing a benign and malignant tumor, it's necessary to validate to distinguish between normal tissue and tumor. The objective is to validate the feasibility of using a compression cylinder that emphasizes the differences in frequency between normal tissue and tumor. In two experiments, we measured the displacement on the surface of a breast phantom vibrated by an impulse hammer. We compared the frequency difference with and without a cylinder. We also studied the frequency changes in the relationship between tumor and cylinder position. We found a 5.0 Hz difference in compliance between normal tissue and the simulated tumor using a compression cylinder. The difference in frequency correlated negatively with distance from the simulated tumor to a compression cylinder. We concluded that a compression cylinder would enhance the frequency difference between normal tissue and a simulated tumor with appropriate configuration.

Portable and noise-tolerant magnetic field generation system.

We have successfully developed a portable pulsed magnetic field generation system incorporating a number of techniques to avoid the effects of noise, including shielding, a self-power capability, and a high-capability semiconductor switch. The system fits into a cubical box less than 0.5 m in linear dimensions and can easily be installed in experimental facilities, including noisy environments such as high-power laser facilities. The system can generate a magnetic field of several tesla sustainable for several tens of microseconds over a spatial scale of several centimeters. In a high-power laser experiment with Gekko-XII, the system operated stably despite being subjected to a high level of electrical noise from laser shots of 600 J.

Route bundling in polygonal domains using Differential Evolution.

Route bundling implies compounding multiple routes in a way that anchoring points at intermediate locations minimize a global distance metric to obtain a tree-like structure where the roots of the tree (anchoring points) serve as coordinating locus for the joint transport of information, goods and people. Route bundling is a relevant conceptual construct in a number of path-planning scenarios where the resources and means of transport are scarce/expensive, or where the environments are inherently hard to navigate due to limited space. In this paper we propose a method for searching optimal route bundles based on a self-adaptive class of Differential Evolution using a convex representation. Rigorous computational experiments in scenarios with and without convex obstacles show the feasibility and efficiency of our approach.