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A number of transport vehicles have been fitted with electric traction motors and their inverters. The traction motor is required to continue to operate even if the inverter is under fault conditions. We propose a motor with two controllable rotors for a traction motor, which consists of 2 rotors and 1 stator. In this paper, we propose a fault-tolerant control method for a two-controllable-rotor motor using a 6-phase inverter. The operational principle of the two-controllable-rotor motor is described. The mathematical model under fault tolerant control is shown, and a fault-tolerant control method for the two-controllable-rotor motor is described. The proposed fault tolerant control method is verified by conducting finite element analysis and carrying out measurements on a prototype.

Objective Complete-staging surgery is recommended for stage IA ovarian cancer, but may be omitted for various reasons, including the preservation of fertility and an advanced age. We herein investigated the prognostic impact of limited-staging surgery in patients with stage IA epithelial ovarian cancer. Methods We retrospectively collected data on 4730 patients with malignant ovarian tumors from the databases of multiple institutions and ultimately included 293 with stage IA epithelial ovarian cancer. Limited-staging surgery was defined as one that did not involve hysterectomy, systematic retroperitoneal lymphadenectomy or the collection of ascites cytology. We used an inverse probability of treatment weighting analysis with propensity scores and estimated the hazard ratios of recurrence and death with limited-staging surgery. Results In total, 176 out of 293 patients (39.9%) were assigned to the limited-staging surgery group. After propensity score adjustments, no significant differences were observed in recurrence-free survival or overall survival between the limited- and complete-staging surgery groups. Even in the subgroup analysis with age stratification, recurrence-free survival and overall survival were similar in the limited- and complete-staging surgery groups. Conclusions The present results indicate the limited prognostic impact of limited-staging surgery for stage IA epithelial ovarian cancer.

Sulfur K-edge X-ray absorption near-edge spectroscopy (XANES) measurements were performed to characterize the crystal polymorphs of the active pharmaceutical ingredients (APIs) containing sulfur atoms. Cimetidine (CIM) was used as a model API. Each crystal form of CIM has its own XANES spectrum, so we can discriminate the crystal form by its spectrum. The analysis of the crystal structure of CIM revealed that the difference in the shape of XANES spectra was ascribable to the difference in the C-S-C bond angle of CIM molecules and the intermolecular hydrogen bonds, such as C-H···S and N-H···S, and S-S interaction. It was found that the peak shape of the XANES spectrum is gentle when the C-S-C bond angle is large, while the peak shape can be steep when the C-S-C bond angle is small. Furthermore, it was found that the peak energy values varied depending on the hydrogen bonds and S-S interaction. By linear combination fitting using XANES spectra, it was possible to quantify the ratio of CIM form A crystal in mixed powders of form A and monohydrate crystals. These results indicate that XANES measurements can be a useful technique to evaluate the crystal polymorphism of APIs containing S atom in pharmaceutical formulation.

Sulfur K-edge X-ray absorption near-edge structure (XANES) spectroscopy was evaluated for its ability to detect non-conventional C-H▪▪▪S hydrogen bonds in crystals of the sulfur-containing penam antibiotics ampicillin and amoxicillin. The XANES spectra of the nearly isomorphous crystals of ampicillin trihydrate and amoxicillin trihydrate were very similar, whereas that of ampicillin anhydrate displayed unique features. Single-crystal X-ray structure analyses revealed that the C-H▪▪▪S hydrogen bond geometries and the chemical types of the hydrogen donors differed between the isomorphous trihydrate crystals and ampicillin anhydrate crystal. These observations demonstrate that the shapes of the sulfur K-edge XANES spectra are dependent on the nature of the C-H▪▪▪S hydrogen bonds. Sulfur K-edge XANES spectroscopy shows promise for use in the detection and analysis of non-covalent interactions, including hydrogen bonds to sulfur atoms, within active pharmaceutical ingredients.

Purpose This paper aims to propose a new magnetic-geared motor (MGM) which can easily increase the gear ratio up to approximately several hundred. The operational principle is described, and the relationship between the maximum transmission torques of each layer of the differential harmonic magnetic gear is investigated using a mathematical model and finite element method (FEM). Design/methodology/approach The operational principle and maximum transmission torque are described using a mathematical model. The FEM is used to investigate the operational principle and torque characteristics. Findings As the proposed model can realize a larger gear ratio than the conventional model, the torque constant can be approximately 100 times as large as that of the conventional model. Research limitations/implications The proposed and conventional models have the same shape stator, and it is not optimized. Originality/value The relationship between the maximum transmission torques of each layer is described, and this helps the design of a differential type MGM.

The crystal forms of active pharmaceutical ingredients must be precisely determined to properly regulate their physical properties. In this study, chlorine K-edge X-ray absorption near-edge structu...

The use of green light optimal speed advisory (GLOSA) systems is seen as a key application for achieving more environmentally friendly, time-efficient, and safer traffic flows at signalized intersections. In previous papers, the authors have proposed a GLOSA system that informs drivers of the most appropriate position for their vehicle instead of their optimal speed. This paper reports on a performance evaluation of our proposed GLOSA system after application to morning rush-hour traffic flow in a simulation of a real-world signalized intersection. A performance evaluation of this numerical simulation showed that our GLOSA system increased the time headway of vehicles and decreased their deceleration rates in the vicinity of the signalized intersection. In addition, the use of the system moderately increased fuel efficiency without affecting vehicle travel time. From these results, it can be concluded that our proposed GLOSA system has the potential to create safer traffic flows in real-world signalized intersections without degrading traffic efficiency.

X-ray absorption fine structure (XAFS) spectra, especially X-ray absorption near-edge structure (XANES), show unique features depending on the chemical states and structures in the vicinity of the X-ray absorbing elements. As such, they can be used to identify the chemical environment of elements. XAFS spectroscopy was applied to investigate the chemical environment of chloride ions in a metastable form A crystal of the antibiotic clarithromycin hydrochloride hydrate. The XANES of the form A crystals showed low similarity to that of the active pharmaceutical ingredient (API) hydrochloride salt crystals, but showed a high similarity to that of a hydrochloride aqueous solution. This indicated that the chloride ion in the form A crystals predominantly interacted with water molecules and was fully hydrated, which was consistent with the previous presumption that form A may be high water-content crystals. This study demonstrated that this XAFS spectroscopy method would be a potent alternative technique for evaluating APIs.

Bromine K-edge X-ray absorption near-edge structure (XANES) spectroscopy analyses were used to evaluate the crystals of the active pharmaceutical ingredients, eletriptan hydrobromide, dextromethorphan hydrobromide and scopolamine hydrobromide salts and the solid dispersion of eletriptan hydrobromide. The crystals and the solid dispersion of the active pharmaceutical ingredient (API) salts could be discriminated based on the shape of the XANES spectra. The differences in the shape of XANES spectra was ascribable to the differences in the interatomic interactions of the bromine ions based on the crystal structures. Ratio of the eletriptan hydrobromide α-form crystal in mixed powders of α-form and monohydrate crystals could be quantified by the linear-combination fitting using their XANES spectra. These results indicated that the XANES spectroscopy are a potent method for evaluating the APIs of pharmaceutical formulations even at the higher energy region around the bromine K-edge of 13470 eV.

Disodium etidronate is a bisphosphonate, compounds that are widely used in the treatment of bone disorders such as osteoporosis and Paget's disease. We investigated the physical properties of disodium etidronate tetrahydrate crystal, form I.We used X-ray powder diffraction (XRPD), thermal analysis, dynamic vapor sorption (DVS), X-ray single crystal structure analysis, and phosphorus K-edge X-ray absorption near-edge structure (XANES) spectroscopy for the first time.XRPD and thermal analyses demonstrated that form I was dehydrated and transformed to an amorphous form, to a crystalline form II, and finally to a form III by heating. DVS measurements revealed that the amorphous form, form II, and form III were rehydrated to form I by humidification, and form I was stable even at 0% relative humidity. These results indicate that form I is the most stable solid-state under ambient conditions and is suitable as an API for manufacture in solid formulations. The phosphorus K-edge XANES spectra differed among form I, the amorphous form, and form II, which may be ascribed to the difference in the coordinate bond schemes between the phosphate moieties and sodium ions. The results demonstrated that the phosphorus K-edge XANES spectroscopy could be applied to the identification or the discrimination of crystal forms of the APIs containing phosphate moieties.Acquired information about physical properties are crucial for manufacturing of solid formulations of disodium etidronate. XANES spectroscopy is a promising alternative method for evaluating the solid-state forms of APIs.

Chlorine K-edge X-ray absorption near-edge spectroscopy (XANES) measurements were performed to characterize the crystal polymorphs of identical active pharmaceutical ingredients (APIs) containing chloride atoms and their amorphous solid dispersions (ASDs). Indomethacin (IMC), of which three crystal forms (α, β, and γ) have been reported, was used as a model API. The shape of XANES spectra was unique to each IMC crystal. The analysis of the crystal structures of IMC revealed that chlorine atoms of the IMCα form had unique intermolecular interactions and halogen bonds with oxygen atoms, while those of the IMCγ form do not have any notable interactions. This result showed that XANES measurements can detect weak interatomic interactions. The shapes of the ASD spectra were clearly different from those of the crystals, suggesting that the environment around the Cl atom of IMC was different from that of the crystals. A thermal stress test was then performed to study the transformation from the amorphous form to the crystalline form of IMC in the ASD. The powder X-ray diffraction (PXRD) patterns indicated that amorphous IMC transformed into crystals during the thermal stress test. In accordance with the PXRD results, the XANES spectra also transformed from ASD to crystalline form. These results indicate that the IMC transformation could be monitored by XANES measurement. Our findings led us to conclude that XANES measurement is a novel approach for the evaluation of crystal polymorphs of APIs and the crystalline state of APIs in ASDs.

meso-Diaminopimelate decarboxylase catalyzes the decarboxylation of meso-diaminopimelate, the final reaction in the diaminopimelate l-lysine biosynthetic pathway. It is the only known pyridoxal-5-phosphate–dependent decarboxylase that catalyzes the removal of a carboxyl group from a d-stereocenter. Currently, only prokaryotic orthologs have been kinetically and structurally characterized. Here, using complementation and kinetic analyses of enzymes recombinantly expressed in Escherichia coli, we have functionally tested two putative eukaryotic meso-diaminopimelate decarboxylase isoforms from the plant species Arabidopsis thaliana. We confirm they are both functional meso-diaminopimelate decarboxylases, although with lower activities than those previously reported for bacterial orthologs. We also report in-depth X-ray crystallographic structural analyses of each isoform at 1.9 and 2.4 Å resolution. We have captured the enzyme structure of one isoform in an asymmetric configuration, with one ligand-bound monomer and the other in an apo-form. Analytical ultracentrifugation and small-angle X-ray scattering solution studies reveal that A. thaliana meso-diaminopimelate decarboxylase adopts a homodimeric assembly. On the basis of our structural analyses, we suggest a mechanism whereby molecular interactions within the active site transduce conformational changes to the active-site loop. These conformational differences are likely to influence catalytic activity in a way that could allow for d-stereocenter selectivity of the substrate meso-diaminopimelate to facilitate the synthesis of l-lysine. In summary, the A. thaliana gene loci At3g14390 and At5g11880 encode functional. meso-diaminopimelate decarboxylase enzymes whose structures provide clues to the stereochemical control of the decarboxylation reaction catalyzed by these eukaryotic proteins

Different crystal forms of active pharmaceutical ingredients (APIs) may display variations in physicochemical properties. During the drug development process, the definitive purpose is to maintain homogeneous quality in a single crystalline form. Hence, it is important to evaluate and understand the properties of each crystal form of APIs in pharmaceutics. In this study, forms 0, Ⅰ, Ⅱ, III of bromhexine hydrochloride, and form S of bromhexine were characterized by the commonly used methods X-ray powder diffraction, thermogravimetry-differential thermal analysis, and single crystal structure X-ray diffraction. Additionally, X-ray absorption fine structure spectroscopy (XAFS), a seldom used method in the pharmaceutics discipline was also applied to explore the chemical environment of bromine atoms in forms 0, Ⅰ, Ⅱ and S as well as chloride ions in forms 0 to Ⅱ. The XAFS spectra of each form were different from each of the other forms which indicated the chemical environment around target elements in the crystal polymorphs were distinct. Then, we measured the commercial bromhexine hydrochloride tablets with XAFS measurement and found that XAFS could distinguish the crystal form in the tablets. Hence, we demonstrated that XAFS measurements would be applicable as one of the methods for the direct detection of APIs in the tablets.

Isosorbide (ISO) is an effective hyperosmotic agent that can be administrated orally and is used as a therapeutic agent for brain pressure drop, glaucoma, and Meniere’s disease. However, the critical relative humidity (CRH) of ISO is about 48% RH at 25 °C, and it deliquesces in humid environments. In this study, we attempted to reduce the deliquescence of ISO using cocrystallization and analyze the water adsorption mechanism from the crystal structure. Four new ISO cocrystals with piperazine (PZ), hydrochlorothiazide (HCT), 3,5-dihydroxybenzoic acid (35DHBA), or gallic acid (GA) were identified. The dynamic vapor sorption analyses demonstrated that all the cocrystals showed higher CRHs than the ISO crystal. Although water adsorption below the CRH was observed for all cocrystals, the water molecules adsorbed in the ISO-PZ and ISO-GA cocrystals were lower than those in the ISO crystal. Investigation of the crystal structures suggested that the amount of water adsorbed might be related to the degree of exposure of the ISO hydroxyl groups on the crystal surface. Given the CRH, water adsorption below the CRH, thermal stability, apparent dissolution rate, and toxicity level of the coformer, the ISO-GA cocrystal is the most suitable for preparing a solid formulation of ISO.

A number of automobiles have been fitted with electric motors and their inverters. In order to reduce the space of the motors, we have proposed a 2-controllable-rotor motor which consists of 2 rotors and 1 stator. However, this motor is driven by a 6-phase inverter, and the inverter size is almost the same as that for 2 motors driven by 3-phase inverters. In this paper, we propose a 2-controllable-rotor motor driven by a 5-phase current, and its operation principle is described. Furthermore, its characteristics are investigated using finite element analysis.

This paper proposes a dynamic simulation method of a magnetic gear using its torque map. The phase angle difference between the input and output rotors depends on a load of the output rotor. The load contains an external load and brake torque due to internal mechanical and iron losses. In this situation, the dynamic performance of a magnetic gear is computed by a transient analysis using a motion equation, and the computation cost is large. In order to reduce the computation cost, a dynamic simulation method using a torque map is proposed and discussed.

Autophagy is an intracellular degradation system in which the formation of an autophagosome is a key event. In budding yeast, autophagosomes are generated from the preautophagosomal structure (PAS), in which Atg11 and Atg17 function as scaffolds essential for selective and nonselective types of autophagy, respectively. Structural studies have been extensively performed on Atg17, but not on Atg11, preventing us from understanding the selective type of the PAS. Here, we purified and characterized Atg11. Biophysical analyses, including analytical ultracentrifugation and CD, showed that Atg11 behaves as an elongated homodimer abundant in α-helices in solution. Moreover, truncation analyses suggested that Atg11 has a parallel coiled-coil architecture, in contrast to the antiparallel dimeric architecture of Atg17.

Early brake pedal operation and corresponding vehicle deceleration are crucial to mitigating rear-end collision risks. In this paper, a mathematical model, hereafter referred to as the deceleration intention inference system (DIIS), was developed to facilitate determining the intent inferences of driver deceleration behaviors. More specifically, a conventional neural network model was integrated into an unscented Kalman filter in an effort to describe the deceleration intentions that can be expected to occur a few seconds later. The numerical examples provided herein show that our proposed model is capable of inferring driver intentions more precisely than the conventional approach.

A magnetic geared motor has been developed as a low speed and high torque motor. However, it is difficult to increase the gear ratio due to the constraint of the number of poles. In order to solve this problem, a radially-differential type magnetic harmonic geared motor is proposed. It can easily increase the gear ratio up to approximately several hundred. In this paper, the structure and operational principle are described. Finally, the torque characteristics are investigated using 3-D finite element method (FEM).

Traction motors of electric vehicles require wide power band characteristics. A magnetic-geared motor has a possibility to achieve these requirements because it has passively variable magnetic flux characteristics. In this paper, the passively variable magnetic flux characteristics of the magnetic-geared motor is investigated using finite element analyses. Furthermore, a maximum torque control method for the magnetic-geared motor is proposed and investigated.

Most of electric machines have been fitted with a number of electric motors and their inverters. In order to reduce the space of the motors and inverters, we proposed a motor with two independently controllable rotors using a 6-phase inverter. However, winding factors of 3- and 6-phase rotors were 0.87 and 0.50, respectively, in a conventional winding arrangement. In order to increase the winding factor of the motor, this paper proposes a novel winding arrangement, and its effectiveness is verified using finite element analysis.

This paper investigate the electromagnetic vibration of a 24/20 switched reluctance motor. There are 2 driving methods for the 24/20 switched reluctance motor: pulse drive and vector control. The electromagnetic force and vibration due to these driving methods are compared and investigated. Especially, the electromagnetic force component of 1 stator tooth is compared with that due to the Maxwell’s stress tensor in the air gap using finite element analysis.

The use of green light optimal speed advisory (GLOSA) systems is seen as a key application for achieving more environmentally friendly, time efficient and safer traffic flows at signalized intersections. However, while previous GLOSA systems provide optimum speed advice to drivers, we have proposed a GLOSA system concept that informs drivers of the appropriate position of their vehicle instead of their optimal speed. This paper reports on a performance evaluation of our proposed GLOSA system using information distance variations. Information distance is defined as the distance between the subject vehicle and the closest traffic signal where the GLOSA system first becomes active. Traffic simulator experiments showed that the earlier activation of the GLOSA system is particularly effective when the approach traffic demand is relatively lower. In other situations, the partial assistance (PA) mode, in which the GLOSA system is activated only when the signal is red, performed well.

Collagens are large structural proteins that are prevalent in mammalian connective tissue. Peptides designed to include a glycine-proline-hydroxyproline (GPO) amino acid triad are biomimetic analogs of the collagen triple helix, a fold that is a hallmark of collagen-like sequences. To inform the rational engineering of collagen-like peptides and proteins for food systems, we report the crystal structure of the (GPO)

Electric vehicles are equipped with a number of electric motors and their inverters. In order to reduce the space of the motors, we have proposed a motor with two concentrically-arranged rotors which can be independently controlled, and a common outer stator. However, the previous motor was difficult to be practically used due to its complicated support structure. Therefore, we proposed an improved motor with two axially-arranged rotors. In this paper, the static and dynamic characteristics of the motor are computed and verified by carrying out measurements on a prototype. Both results were in good agreement, and the effectiveness of the proposed motor was shown.

Summary At the early stage of cancer development, oncogenic mutations often cause multilayered epithelial structures. However, the underlying molecular mechanism still remains enigmatic. By performing a series of screenings targeting plasma membrane proteins, we have found that collagen XVII (COL17A1) and CD44 accumulate in RasV12-, Src-, or ErbB2-transformed epithelial cells. In addition, the expression of COL17A1 and CD44 is also regulated by cell density and upon apical cell extrusion. We further demonstrate that the expression of COL17A1 and CD44 is profoundly upregulated at the upper layers of multilayered, transformed epithelia in vitro and in vivo. The accumulated COL17A1 and CD44 suppress mitochondrial membrane potential and reactive oxygen species (ROS) production. The diminished intracellular ROS level then promotes resistance against ferroptosis-mediated cell death upon cell extrusion, thereby positively regulating the formation of multilayered structures. To further understand the functional role of COL17A1, we performed comprehensive metabolome analysis and compared intracellular metabolites between RasV12 and COL17A1-knockout RasV12 cells. The data imply that COL17A1 regulates the metabolic pathway from the GABA shunt to mitochondrial complex I through succinate, thereby suppressing the ROS production. Moreover, we demonstrate that CD44 regulates membrane accumulation of COL17A1 in multilayered structures. These results suggest that CD44 and COL17A1 are crucial regulators for the clonal expansion of transformed cells within multilayered epithelia, thus being potential targets for early diagnosis and preventive treatment for precancerous lesions.

Collagens are large structural proteins that are prevalent in mammalian connective tissue. Peptides designed to include a glycine-proline-hydroxyproline (GPO) amino acid triad are biomimetic analogs of the collagen triple helix, a fold that is a hallmark of collagen-like sequences. To inform the rational engineering of collagen-like peptides and proteins for food systems, we report the crystal structure of the (GPO)10 peptide at 0.89-A resolution, solved using direct methods. We determined that a single chain in the asymmetric unit forms a pseudo-hexagonal network of triple helices that have a pitch variation consistent with the model 7/2 helix (3.5 residues per turn). The proline rings occupied one of two states, while the helix was found to have a well-defined hydration shell involved in the stabilization of the inter-helix crystal network. This structure offers a new high-resolution basis for understanding the hierarchical assembly of native collagens, which will aid the food industry in engineering new sustainable food systems.

Vehicle-to-vehicle (V2V) and vehicle-to-infrastructure (V2I) communications have the potential to not only accelerate progress towards autonomous vehicles but also to facilitate the achievement of more appropriate driver behavior patterns and thus make traffic more energy efficient and environmentally friendly. This paper presents a driving advisory system for vehicles approaching traffic lights that is based on the use of a Green Light Optimal Speed Advisory (GLOSA) system and evaluates its impact on traffic flow characteristics. This system, which assumes the existence of a connection with the traffic light ahead, calculates the distance required to pass through the intersection without stopping during the remaining green signal time. The required distance is then projected onto the road surface as a green planar rectangle shape through a head-up display (HUD). As long as the vehicle is traveling on the green rectangle, the drivers will not need to make a complete stop or accelerate again in order to meet the onset of a green signal. Assuming that all vehicles are equipped with our proposed system, traffic simulations were carried out to evaluate the performance of the scheme. Numerical analyses showed that a higher fuel efficiency and lower carbon dioxide (CO 2 ) emissions were achievable, even under high-density traffic conditions, by combining the full and partial assistance levels of our proposed system.

The use of Green Light Optimal Speed Advisory (GLOSA) systems is currently considered one of the key applications for achieving more stable, environmentally friendly, and efficient traffic flows in the vicinity of signalized intersections. This paper addresses a driver advisory system that provides an efficient driving strategy based on our GLOSA system and evaluates its impact on traffic flow characteristics. Assuming five levels of traffic demand, traffic simulations were carried out to investigate the performance of the system in terms of the travel time, fuel consumption, and carbon dioxide (CO2) emissions of vehicles entering and exiting an artificial corridor. Our numerical analysis showed that our GLOSA system performs well in traffic flows where the arriving demand is less than 400 to 500 vehicles per hour. In other situations, it increases congestion, impedes efficiency, and significantly worsens the environment.

Rear-end collisions in longitudinal car-following situations occasionally cause severe multiple collision accidents, especially in high-density and high-speed traffic situations. However, if a preceding car driver's deceleration intention could be inferred in advance, even a second earlier, the risk of a collision could be decreased not only between vehicle pairs but also for car platoons. This paper reports on the application of our previously reported intent inference system to a platoon of vehicles and evaluates its impact on safety. The system utilizes an unscented Kalman filter (UKF) and attempts to infer the intent of a vehicle ahead 1.5 s in advance of its driver's most likely action. The inferred intention is then provided to the driver of the assisted vehicle through an interface based on a windshield display, and earlier experiments have proved that the system is quite effective for collision risk mitigation. In this paper, we report on an investigation into the safety impacts of our system on a platoon of vehicles following an assisted vehicle. The results of a traffic simulator experiment showed that the system could provide significant safety benefits to multiple cars traveling behind an assisted vehicle in a vehicle platoon.

A current superimposition variable flux reluctance motor for a traction motor of electric vehicles and hybrid electric vehicles are proposed. This motor can be driven using a 6-phase asymmetric inverter which is used to drive a switched reluctance motor. However, it is difficult to obtain a high efficiency in a low-speed and high-torque region. In order to solve this problem, a switching operation between the current superimposition variable flux reluctance motor and a switched reluctance motor is proposed in this paper.

The electrification of automobiles has been gaining momentum recently, and more and more automobiles are being fitted with electric motors and their inverters. In order to reduce the space of the motors and inverters, a motor with two controllable rotors was proposed [1- 2]. This motor has two rotors and one stator. The two rotors can be independently controlled using 3- and 6-phase superimposed currents created by a 6-phase inverter. One rotor is driven by a 3-phase current and the other is driven by a 6-phase current. However, this motor has problems such as low heat dissipation and complicated support structure of the stator because the stator is sandwiched between the two rotors. In order to solve these problems, a motor with its stator on the outside of its rotors was proposed [3]. This motor has also two rotors and one stator, and the two rotors can be independently controlled using 3- and 6-phase superimposed currents. However, this motor has also a problem of a complicated support structure of the middle rotor. Therefore, we proposed a novel motor with two controllable rotors to solve above problems [4]. In this paper, 3D-FEM analysis coupled with vector control is conducted in order to verify that the two rotors can be independently controlled.

Atg101 is an essential component of the autophagy-initiating ULK complex in higher eukaryotes, but it is absent from the functionally equivalent Atg1 complex in budding yeast. Here, we report the crystal structure of the fission yeast Atg101-Atg13 complex. Atg101 has a Hop1, Rev7 and Mad2 (HORMA) architecture similar to that of Atg13. Mad2 HORMA has two distinct conformations (O-Mad2 and C-Mad2), and, intriguingly, Atg101 resembles O-Mad2 rather than the C-Mad2-like Atg13. Atg13 HORMA from higher eukaryotes possesses an inherently unstable fold, which is stabilized by Atg101 via interactions analogous to those between O-Mad2 and C-Mad2. Mutational studies revealed that Atg101 is responsible for recruiting downstream factors to the autophagosome-formation site in mammals via a newly identified WF finger. These data define the molecular functions of Atg101, providing a basis for elucidating the molecular mechanisms of mammalian autophagy initiation by the ULK complex.