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Small molecules targeting autophagy have been highly implicated as new therapeutic agents to treat diseases of interest. With the increasing demand for autophagy-targeting drugs, this review attempts to provide an efficient strategy to explore major autophagy-based human disease interventions with newly explored mechanisms using small molecules and promising therapeutic approaches.Introduced in this review are direct links and applications among autophagy pathways, their modulators, and phenotypic diseases, along with recent approaches. Autophagy-related diseases, machinery, and compounds are introduced to guide the appropriate investigation of autophagy in the pharmaceutical industry. The authors then provide their expert perspectives on the subject.The self-catabolic intracellular process autophagy occurs in organisms throughout their lifetime, supporting its critical role in organismal health across life stages. Because of the detrimental influence of dysfunctional cells to an organism and their etiology in numerous diseases, maintaining cellular quality control by recycling components through autophagy is essential to prevent health decline.

This study analyzes the mechanical behaviors of conical composite tubes, considering fiber orientation errors, under static loads. Fiber orientation errors are defined as fiber orientation changes that occur due to the taper angle of conical composite tubes during the wrapping process. Such fiber orientation errors are one of many important parameters in predicting mechanical properties, and must be taken into account for the design of conical composite tubes. Thus, this study derived the theoretical equations to analyze the mechanical behaviors of conical composite tubes under static loads considering fiber orientation errors according to the laminate plate theory. For verification of the derived equations, the calculation results were compared with the results of other research that did not take fiber orientation errors into account as well as experimental results that did include fiber orientation errors. As a result, the derived equations could predict the static behaviors of conical composite tubes 5.5% errors. Also, we performed parametric studies such as taper angles, sizes, and stacking sequences. The effect of taper angles on the static behaviors was the most important and the static deformations with and without the consideration of fiber orientation errors had a 500% difference over 10 O of the taper angle.

Recently, origami structures have been widely studied for various applications such as mechanical, electrical, bio, and nanosystems. Unlikely paper-like materials, engineering materials have higher stiffness and thickness so the hinge-like motion of the crease of paper origami is impossible. Therefore, origami, which is not made of paper-like materials, has different characteristics from paper origami. Several researchers reported that introducing slits or holes at or near the crease can make the hinge-like motion of the origami, but investigating the effects of the crease line design was not considered. In this paper, a perforated crease line was considered and parametric studies of the crease line design were investigated by finite element analysis and experiment. It was found that the length and distance of the perforated holes were significant factors to determine the stability and the barrier force and spring constant of Kresling origami could be optimized. Finally, it was shown that special motions could be realized with a combination of two origami with the same dimension but different crease line designs.

As adhesive joints have been widely used for fastening thin adherends, the damage tolerance design of adhesive joints has become important, and the estimation of initiation and propagation of a fatigue crack in the adhesive has become necessary. However, the measurement of crack length of tubular joints has been difficult because the observation of crack initiation and growth in the adhesive layer by conventional methods is not easy. In this work, a prediction method for the fatigue crack length in the adhesive layer of tubular single-lap adhesive joints was developed by the piezoelectric method. In order to obtain the relationship between the fatigue crack length and the piezoelectric signal, finite element analysis was conducted and verified by experiments. The damage of the adhesive joints was monitored by the piezoelectric method during torsional fatigue tests on tubular single-lap adhesive joints. Using the damage monitoring signals and the relationship between the fatigue crack length and the piezoe...

Adhesive joints have been widely used for fastening thin adherends because they can distribute the load over a larger area than mechanical joints, require no holes, add very little weight to the structure and have superior fatigue resistance. Since the reliability of an adhesive joint is dependent on many parameters, such as the shape of joint, type of applied load and environment, an accurate prediction of the fatigue life of adhesive joints is seldom possible, which necessitates an in situ damage monitoring of the joints during their operation. Recently, a piezoelectric method using the piezoelectric characteristics of epoxy adhesives has been successfully developed for adhesive joints because it can continuously monitor the damage of adhesively bonded structures without producing any defects induced by inserting a sensor. Therefore, in this study, the damage of adhesive joints was monitored by the piezoelectric method during torsional fatigue tests in order to develop the diagnosis criterion for damage...

Mechanical design can be classified into stiffness design and strength design. In the stiffness design, the stiffness or deformation of members is concerned, and the enhancement of dynamic characteristics such as natural frequency or damping capacity of members or systems is also important. While, in the strength design, the primary concern is the enhancement of load carrying ability of members or systems. Fiber reinforced composite materials offer a combination of strength and modulus that are either comparable to or better than many traditional metallic materials. Because of their low specific gravities, the strength-weight ratios, and modulus-weight ratios of these composite materials are much superior to those metallic materials. Composite materials can be tailored to meet the specific requirements of each particular design. Available design parameters are the choice of materials (fiber, matrix), the volume fraction of fiber and matrix, fabrication method, number of layers in a given direction, thickness of individual layers, type of layer (unidirectional or fabric), and the layer stacking sequence. The greatest disadvantages of composite materials are the costs of the materials and the lack of well-defined design rules, therefore, composite materials should be applied in the right place with appropriate design rules. Up to now, the fiber reinforced composite structures are mainly employed in the strength design such as aircraft, spacecraft and vehicles. In this paper, the novel application examples of composite structures to components for the robots, machine tools and automobiles are addressed considering the stiffness design issues of composite structures.

Substituting composite structures for conventional metallic structures has many advantages for structural dynamic characteristics because composite materials have the higher specific stiffness and damping characteristics than conventional materials. However, the dynamic characteristics such as the fundamental natural frequency and damping of composite structures are influenced much by their joints. In this work, the effects of clamping conditions on the dynamic characteristics of cantilever type composite machine tool structures with clamped joint were investigated to increase the natural frequency and damping of structures. In order to improve the shear property of the clamping part of composite machine tool bar, a new method for the clamping part was developed with metal core or sleeve inserted in the composite body at the clamping part. From the finite element and experimental results, suitable clamping conditions for the maximum dynamic stiffness were obtained for the composite structures with clamped joint.

Power transmission shafts such as driving shafts or automotive propeller shafts should transmit static and dynamic torques with vibrational stability. Hybrid shafts made of unidirectional fiber-reinforced composite and metal have high fundamental bending natural frequency as well as high torque transmission capability: composite increases the fundamental bending natural frequency due to its high specific stiffness and metal such as aluminum or steel transmits the required torque. However, fabrication-induced thermal residual stresses due to the coefficient difference of thermal expansion of the composite and the metal are developed during manufacturing hybrid shafts so that the high residual stresses decrease fatigue resistance of the hybrid shafts, especially at low operating temperatures. In this paper, the torsional fatigue characteristics of aluminum–composite co-cure joined shafts with axial compressive preload were investigated. To change the thermal residual stresses, an axial compressive preload was given to the aluminum tube by a compressive jig during the co-cure bonding operation. In order to determine the thermal residual stresses with respect to the preload and temperature difference, stress analyses were performed by simple equations from mechanics of materials and finite element method. Then the static torque capacities and fatigue strengths of the hybrid shafts from static and fatigue torsional tests were correlated with the calculated thermal residual stresses. The fatigue strength of the hybrid shaft was much improved by the axial compressive preload, exceeding that of a pure aluminum shaft. Also, the degradation of the fatigue resistance of the hybrid shaft at subzero operating temperature was overcome by the axial compressive preload.

High-speed air spindles are appropriate for high-speed and high-precision machining such as small hole drilling of printed circuit board (PCB) or wafer cutting for manufacturing semiconductors. The axial load capability and stiffness of the air spindles for drilling operation are dependent on the thrust bearings. The thrust bearings are composed of an air supply part in the housing and a rotating part. Since stresses induced in the rotating part of thrust bearing by centrifugal force are very high at high-rotational speed, the axial stiffness and load capability of an air spindle should be designed considering stresses due to centrifugal force as well as the natural frequency of the rotating shaft to avoid the resonant whip vibration of the spindle. In this work, the air supply part and the rotating part of a thin thrust bearing were designed for a high-speed carbon fibre composite air spindle using the stiffness map to maximize the stiffness of the thrust bearing under axial and centrifugal forces.

High speed boring operations of deep holes with steel or tungsten boring bars are often hindered by the chatter vibration of boring bars because of their low dynamic stiffness and natural frequencies. The chatter is a self-excited vibration that occurs in metal cutting if, either the chip width is too large with respect to the dynamic stiffness of the system, which is proportional to the damping and static stiffness of the boring bar, or the rotating speed of the boring bar approaches one of its natural frequencies, which is proportional to the specific stiffness (E/ρg) of the material used. In this study, a rotating boring bar was designed and manufactured with high stiffness pitch-based carbon fiber epoxy composite to meet the requirements of boring at high rotating speed because carbon fiber epoxy composite materials have a much higher specific stiffness and higher damping than conventional boring bar materials. The optimum design parameters for the composite boring bar were experimentally determined with respect to material types and dimensions of the boring bar through vibration tests. The dynamic characteristics of the composite boring bar developed were measured by the boring operation of aluminum engine blocks. From experiments, it was found that the dynamic stiffness of the composite boring bar was about 30% higher than that of the tungsten carbide boring bar. Also, chatter did not occur up to the ratio of length to diameter (l/d) of 10.7, which is about a 30% improvement compared to the tungsten boring bar of l/d of 8.0.

This study suggested a tactile sensor with piezoelectric sensors in a fibrous shape to detect multi-axial loads (vertical load and horizontal load) simultaneously for the skins of unmanned robots. The sensor was designed by finite element analyses. A simple detecting scheme of the multi-axial loads was constructed by lab-scale experiments. Verification tests of the developed tactile sensor confirmed that applied vertical and horizontal loads could be detected with less than 4% error.