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We present the requirements, design, and evaluation of the cryogenic continuously rotating half-wave plate (CHWP) for the Simons Observatory (SO). SO is a cosmic microwave background polarization experiment at Parque Astronómico de Atacama in northern Chile that covers a wide range of angular scales using both small (â0.42 m) and large (â6 m) aperture telescopes. In particular, the small aperture telescopes (SATs) focus on large angular scales for primordial B-mode polarization. To this end, the SATs employ a CHWP to modulate the polarization of the incident light at 8 Hz, suppressing atmospheric 1/f noise and mitigating systematic uncertainties that would otherwise arise due to the differential response of detectors sensitive to orthogonal polarizations. The CHWP consists of a 505 mm diameter achromatic sapphire HWP and a cryogenic rotation mechanism, both of which are cooled down to â¼50 K to reduce detector thermal loading. Under normal operation, the HWP is suspended by a superconducting magnetic bearing and rotates with a constant 2 Hz frequency, controlled by an electromagnetic synchronous motor. We find that the number of superconductors and the number of magnets that make up the superconducting magnetic bearing are important design parameters, especially for the rotation mechanism's vibration performance. The rotation angle is detected through an angular encoder with a noise level of 0.07 µrad s. During a cooldown process, the rotor is held in place by a grip-and-release mechanism that serves as both an alignment device and a thermal path. In this paper, we provide an overview of the SO SAT CHWP: its requirements, hardware design, and laboratory performance.
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Penfigoide Bolhoso , Humanos , Colágenos não Fibrilares , Autoantígenos , Prurido , Biomarcadores , Quimiocinas , AutoanticorposRESUMO
Radio absorptive materials (RAMs) are key elements for receivers in the millimeter-wave range. We previously established a method for production of RAM by using a 3D-printed mold. An advantage of this method is a wide range of choices for absorptive materials to be used. To take advantage of this flexibility, we added a range of absorptive materials to a base epoxy resin, STYCAST-2850FT, and examined the optical performance of the resultant RAM across a wide frequency range under cryogenic conditions. We found that adding a particular type of carbon fiber produced the best performance with a reflectance at 77 K estimated as 0.01%-3% over a frequency range of 20-300 GHz.
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We present the design and laboratory evaluation of a cryogenic continuously rotating half-wave plate (CHWP) for the POLARBEAR-2b (PB-2b) cosmic microwave background receiver, the second installment of the Simons Array. PB-2b will observe at 5200 m elevation in the Atacama Desert of Chile in two frequency bands centered at 90 GHz and 150 GHz. In order to suppress atmospheric 1/f noise and mitigate systematic effects that arise when differencing orthogonal detectors, PB-2b modulates linear sky polarization using a CHWP rotating at 2 Hz. The CHWP has a 440 mm clear aperture diameter and is cooled to ≈50 K in the PB-2b receiver cryostat. It consists of a low-friction superconducting magnetic bearing and a low-torque synchronous electromagnetic motor, which together dissipate <2 W. During cooldown, a grip-and-release mechanism centers the rotor to <0.5 mm, and during continuous rotation, an incremental optical encoder measures the rotor angle with a noise level of 0.1 µrad/Hz. We discuss the experimental requirements for the PB-2b CHWP, the designs of its various subsystems, and the results of its evaluation in the laboratory. The presented CHWP has been deployed to Chile and is expected to see first light on PB-2b in 2020 or 2021.
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A gamma-ray telescope system has been used at Heavy Water Neutron Irradiation Facility at Kyoto University Reactor mainly for boron neutron capture therapy (BNCT) for multiple hepatic tumors. This system has been improved to accommodate BNCT for other sites, such as brain, head and neck, lung, breast, etc. Simulation for the collimation system was performed. It revealed that the effective telescope field-of-view could be expanded from approximately 3-21 cm.
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Terapia por Captura de Nêutron de Boro/instrumentação , Raios gama , Neoplasias/radioterapia , Humanos , JapãoRESUMO
The aim of this paper is to validate the microdosimetric functionality of the Monte Carlo code, PHITS, and verify its use for estimating dose and RBE for radiobiological studies performed at Kyoto University Institute for Integrated Radiation and Nuclear Science (KURNS). Lineal energy spectra produced by the KUR mixed irradiation mode were measured with a tissue equivalent proportional counter (TEPC) place in free air. The Monte Carlo calculation showed a good agreement with the measured data. In the second part of the study, a realistic set-up of a typical in-vivo radiobiological experiment was simulated with PHITS and the simulation results were compared against TLD and gold foil activation measurements. The Monte Carlo simulation results and the measured data showed an agreement within 3%. The calculated RBE also showed a close value to clinically utilised values. This study shows that PHITS can be utilised to evaluate thermal neutron fluxes and gamma ray absorbed dose rates inside a tumour like medium.
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Terapia por Captura de Nêutron de Boro/métodos , Radiometria/métodos , Dosagem Radioterapêutica , Animais , Humanos , Camundongos , Método de Monte Carlo , Neoplasias/radioterapia , Oryzias , Radiobiologia , Eficiência Biológica RelativaRESUMO
We examined the efficacy of embryoid bodies from 6-day induced pluripotent stem cells an in vivo sepsis model. Injection of embryoid bodies to septic mice improved the condition of their lungs and significantly increased their survival rate. Although embryoid bodies secretedsphingosine-1-phosphate in vitro, its serum levels in mouse plasma were significantly reduced compared to that in the control (untreated mice receiving PBS). Low concentrations of sphingosine-1-phosphate protected endothelial cells, while high concentrations disrupted endothelial barrier integrity. Therefore, exogenous sphingosine-1-phosphate secreted by embryoid bodies during early stage of sepsis might down regulate endogenous production of sphingosine-1-phosphate. Inhibition of excessive sphingosine-1-phosphate release protects against endothelial injury and suppresses a vicious cycle of inflammatory reactions. The obtained results open new prospects in induced pluripotent stem cells-based therapy for sepsis.
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Corpos Embrioides/citologia , Células-Tronco Pluripotentes Induzidas/citologia , Peritonite/terapia , Animais , Células Endoteliais/citologia , Transplante de Células-Tronco Hematopoéticas , Lisofosfolipídeos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Peritonite/metabolismo , Sepse , Esfingosina/análogos & derivados , Esfingosina/metabolismoRESUMO
Kawasaki disease (KD) is a vasculitis that is part of systemic vasculitis syndrome. It affects medium-sized vessels and is characterized by hypercytokinemia. Although the etiology of KD remains unidentified, epidemiological features point to the role of infection and genetic predisposition. Recent studies on KD revealed endothelial damage and resultant thrombin generation, as well as B-cell activation during the acute phase. Several antiendothelial cell autoantibodies (AECAs) have been identified in KD patients. Analysis of this phenomenon together with the recently developed concept of immunothrombosis reveals a potential pathogenic mechanism for KD. First, polyclonal antibodies generated against invading microorganisms would exhibit cross-reactivity toward endothelial cell components and become dominant during affinity maturation. Binding of AECAs to endothelial cells would cause endothelial activation or damage, with proinflammatory cytokine release, thus fostering a hypercoagulable state resulting from leukocyte activation by proinflammatory cytokines. This, in turn, would lead to coronary artery lesions. KD vasculitis might be initiated upon binding of AECAs to the vasa vasorum and progress to panvasculitis and a vulnerable vessel wall, resulting in an aneurysm. The aneurysm would cause flow recirculation and alteration of wall shear stress. Consequently, platelets activated by shear stress, along with ultralarge von Willebrand factor (VWF) released by endothelial cells, would cause platelet-driven arterial thrombosis. Autoimmunity-associated thrombosis initiated by binding of AECAs to endothelial cells might play a major role in the pathogenesis of certain subtypes of KD. The notion of KD consisting of subtypes, the major one of which is AECA-associated vasculitis, will help improve our understanding of KD and further promote early and accurate diagnosis, which remains challenging.
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Autoimunidade , Síndrome de Linfonodos Mucocutâneos/etiologia , Doenças Autoimunes/imunologia , Gerenciamento Clínico , Suscetibilidade a Doenças , Humanos , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/terapiaRESUMO
BACKGROUND: The levels of corneal donation are insufficient to meet the demand for corneal transplantation in Japan. To overcome this problem, we started to routinely mention the possibility of corneal donation to the families of patients who died in our hospital's Urology Department in February 2008. In this study, we evaluated the effectiveness of this approach. METHODS: We retrospectively reviewed the medical records of the patients who died in the Department of Urology, St. Marianna University School of Medicine Hospital, and analyzed the patients' characteristics and information about corneal donation. RESULTS: In total, 211 patients died in our department between February 2008 and March 2017, and 155 patients were medically suitable corneal donors. We mentioned the possibility of corneal donation to 129 (83.2%) families, and 29 (18.7%) families agreed. Three families subsequently withdrew their consent. Finally, 26 (16.8%) of the families that were approached about corneal donation by urologists agreed to donate their relatives' corneas. Another 2 families voluntarily offered to donate their relatives' corneas. Thus, 28 (18.1%) of 155 medically suitable donors donated their corneas for transplantation. Twenty-six (92.8%) donors were 60 years or older and all donors were affected with malignant genitourinary tumors. Fifty-four (96.4%) corneas were successfully transplanted into recipients. CONCLUSIONS: Even elderly patients who die of solid carcinoma can be an important source of corneal donors. In this study, we showed that routine referral by urologists increased corneal donation. If this approach were adopted by other departments, it might further increase the number of corneal donations.
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Transplante de Córnea , Encaminhamento e Consulta , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos/métodos , Transplantes/provisão & distribuição , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Urológicas/mortalidade , UrologistasRESUMO
This paper presents the feasibility study of a novel 3D mesa bridge microdosimeter and its use for BNCT dosimetry. The performance of the microdosimeter was studied using Monte Carlo simulation. The clinical BNCT field at Kyoto University Reactor (KUR) using both thermal and epithermal irradiation modes were used in this study. Results show that this microdosimeter can be utilised as an effective tool to measure microdosimetric spectrum in the BNCT field and experimental validation will follow once KUR is operational.
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Terapia por Captura de Nêutron de Boro , Radiometria/instrumentação , Partículas alfa/uso terapêutico , Simulação por Computador , Estudos de Viabilidade , Humanos , Lítio/análise , Método de Monte Carlo , Neoplasias/radioterapia , Imagens de Fantasmas , Radiometria/estatística & dados numéricos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/estatística & dados numéricos , SilícioRESUMO
The possibility of sphingosine-1-phosphate production by induced pluripotent stem cells is examined to assess their potential in treatment of sepsis. The hematopoietic embryoid bodies were derived from the culture of 6-day-old differentiated induced pluripotent stem cells. These embryoid bodies secreted sphingosine-1-phosphate, an important bioactive lipid that regulates integrity of the pulmonary endothelial barrier, prevents elevation of its permeability, and impedes the formation of stress fibers in human endotheliocytes derived from umbilical vein. The data attest to potentiality of induced pluripotent stem cells in treatment of sepsis.
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Corpos Embrioides/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Lipopolissacarídeos/antagonistas & inibidores , Lisofosfolipídeos/farmacologia , Esfingosina/análogos & derivados , Animais , Diferenciação Celular , Permeabilidade da Membrana Celular/efeitos dos fármacos , Corpos Embrioides/citologia , Fator de Transcrição GATA1/genética , Fator de Transcrição GATA1/metabolismo , Regulação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Lipopolissacarídeos/farmacologia , Lisofosfolipídeos/metabolismo , Camundongos , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Transdução de Sinais , Esfingosina/metabolismo , Esfingosina/farmacologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
Temperature dependent experimental Compton profiles of quaternary alloys Co1-x Cu x MnSb (x = 0.0, 0.2, 0.6 and 0.8) when decomposed into constituent profiles show that the sp-electron spin polarization is antiferromagnetically coupled to Mn-3d moments. The orbital magnetic moments derived from combination of magnetic Compton profiles (MCPs) and magnetization measurements are found to be small. Moreover, the first-principles full potential-linearized augmented plane wave (FP-LAPW) calculations have been performed to validate the experimental investigations of spin moments and half-Heusler properties. Present experimental and theoretical work show major role of Mn atoms in building-up the absolute spin moments. Our MCP data and spin-projected density of states derived from FP-LAPW computations show an increase in sp-d interaction in conduction region on increasing the Cu concentration. Further, Ruderman-Kittel-Kasuya-Yosida-type hybridization and antiferromagnetic superexchange interactions are witnessed in the reported alloys.
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A dose-response relationship between toothbrushing frequency and the incidence of dental caries has not been confirmed. Furthermore, no longitudinal study about this relationship has considered dental caries experience at baseline, which is an important factor influencing the frequency of future caries. OBJECTIVE: To elucidate the association between the incidence of dental caries and toothbrushing frequency after adjusting for dental caries experience at baseline in a Japanese population. BASIC RESEARCH DESIGN: The 92 recruits of the Japan Maritime Self-Defense Force in Kure, Japan, in 2011 were followed up for 3 years. They underwent oral examination at the annual checkups and answered questions about toothbrushing frequency. MAIN OUTCOME MEASURES: The multiple logistic regression analysis was used to analyze the incidence of dental caries and to identify independent effects of toothbrushing frequency and dental caries experience at baseline. Furthermore, the relative importance of the incidence of dental caries was investigated among other independent variables using the partial adjusted R² score. RESULTS: Logistic regression analysis showed that toothbrushing frequency alone did not influence the increment in decayed, missing, and filled teeth (DMFT). However, DMFT at baseline alone was associated with the increment in DMFT (crude odds ratio, OR, 1.20, 95% confidence interval, CI, 1.08,1.33). In the fully adjusted model, only DMFT at baseline was associated with the increment in DMFT (adjusted OR 1.23, 95%CI 1.09,1.38). CONCLUSION: After three years, the incidence of dental caries in young adult Japanese males was influenced by DMFT at baseline, rather than toothbrushing frequency.
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Cárie Dentária/epidemiologia , Escovação Dentária/estatística & dados numéricos , Índice CPO , Humanos , Incidência , Japão/epidemiologia , Estudos Longitudinais , Masculino , Fumar/epidemiologia , Adulto JovemRESUMO
Filovirus entry into cells is complex, perhaps as complex as any viral entry mechanism identified to date. However, over the past 10 years, the important events required for filoviruses to enter into the endosomal compartment and fuse with vesicular membranes have been elucidated (Fig. 1). Here, we highlight the important steps that are required for productive entry of filoviruses into mammalian cells.
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Filoviridae/fisiologia , Internalização do Vírus , Animais , Endossomos/metabolismo , Endossomos/virologiaRESUMO
The real-time detection of epithermal neutrons forms an important aspect of boron neutron capture therapy. In this context, we developed an epithermal neutron detector based on the combination of a small Eu:LiCaAlF6 scintillator and a quartz fiber in order to fulfill the irradiation-field requirements for boron neutron capture therapy. The irradiation test is performed with the use of a reactor-based neutron source. The thermal and epithermal neutron sensitivities of our epithermal neutron detector are estimated to be 9.52 × 10-8 ± 1.59 × 10-8 cm2 and 1.20 × 10-6 cm2 ± 8.96 × 10-9 cm2, respectively. We also subject the developed epithermal neutron detector to actual irradiation fields, and we confirm that the epithermal neutron flux can be measured in realtime.
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Essentials Botrocetin-2 (Bot2) binds to von Willebrand factor (VWF) and induces platelet agglutination. We identified Bot2 residues that are required for binding to VWF and glycoprotein (GP) Ib. We produced a mutant Bot2 that binds to VWF but inhibits platelet agglutination. Mutant Bot2 could be used as a potential anti-thrombotic reagent to block VWF-GPIb interaction. SUMMARY: Background Botrocetin-2 (Bot2) is a botrocetin-like protein composed of α and ß subunits that have been cloned from the snake Bothrops jararaca. Bot2 binds specifically to von Willebrand factor (VWF), and the complex induces glycoprotein (GP) Ib-dependent platelet agglutination. Objectives To exploit Bot2's VWF-binding capacity in order to attempt to create a mutant Bot2 that binds to VWF but inhibits platelet agglutination. Methods and Results Several point mutations were introduced into Bot2 cDNA, and the recombinant protein (recombinant Bot2 [rBot2]) was purified on an anti-botrocetin column. The mutant rBot2 with either Ala at Asp70 in the ß subunit (Aspß70Ala), or Argß115Ala and Lysß117Ala, showed reduced platelet agglutination-inducing activity. rBot2 with Aspß70Ala showed little binding activity towards immobilized VWF on an ELISA plate, whereas rBot2 with Argß115Ala/Lysß117Ala showed reduced binding activity towards GPIb (glycocalicin) after forming a complex with VWF. rBot2 point-mutated to oppositely charged Glu at both Argß115 and Lysß117 showed normal binding activity towards VWF but no platelet-agglutinating activity. Furthermore, this doubly mutated protein inhibited ristocetin-induced or high shear stress-induced platelet aggregation, and restrained thrombus formation under flow conditions. Conclusions Asp70 in the ß subunit of botrocetin is important for VWF binding, and Arg115 and Lys117 in the ß subunit are essential for interaction with GPIb. Doubly mutated rBot2, with Argß115Glu and Lysß117Glu, repels GPIb and might have potential as an antithrombotic reagent that specifically blocks VWF function. This is the first report on an artificial botrocetin that can inhibit the VWF-GPIb interaction.
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Plaquetas/metabolismo , Venenos de Crotalídeos/farmacologia , Proteínas Mutantes/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Fator de von Willebrand/metabolismo , Animais , Bothrops , DNA Complementar/metabolismo , Fibrinolíticos/farmacologia , Células HEK293 , Humanos , Mutação Puntual , Ligação Proteica , Conformação Proteica , Proteínas Recombinantes/farmacologia , Resistência ao CisalhamentoRESUMO
BACKGROUND: Vonoprazan is a new potassium-competitive acid blocker for treatment of acid-related diseases. AIM: To conduct two randomised-controlled trials, to evaluate the non-inferiority of vonoprazan vs. lansoprazole, a proton pump inhibitor, for treatment of gastric ulcer (GU) or duodenal ulcer (DU). METHODS: Patients aged ≥20 years with ≥1 endoscopically-confirmed GU or DU (≥5 mm white coating) were randomised 1:1 using double-dummy blinding to receive lansoprazole (30 mg) or vonoprazan (20 mg) for 8 (GU study) or 6 (DU study) weeks. The primary endpoint was the proportion of patients with endoscopically confirmed healed GU or DU. RESULTS: For GU, 93.5% (216/231) of vonoprazan-treated patients and 93.8% (211/225) of lansoprazole-treated patients achieved healed GU; non-inferiority of vonoprazan to lansoprazole was confirmed [difference = -0.3% (95% CI -4.750, 4.208); P = 0.0011]. For DU, 95.5% (170/178) of vonoprazan-treated patients and 98.3% (177/180) of lansoprazole-treated patients achieved healed DU; non-inferiority to lansoprazole was not confirmed [difference = -2.8% (95% CI -6.400, 0.745); P = 0.0654]. The incidences of treatment-emergent adverse events were slightly lower for GU and slightly higher for DU with vonoprazan than with lansoprazole. There was one death (subarachnoid haemorrhage) in the vonoprazan group (DU). The possibility of a relationship between this unexpected patient death and the study drug could not be ruled out. In both studies, increases in serum gastrin levels were greater in vonoprazan-treated vs. lansoprazole-treated patients; levels returned to baseline after treatment in both groups. CONCLUSIONS: Vonoprazan 20 mg has a similar tolerability profile to lansoprazole 30 mg and is non-inferior with respect to GU healing and has similar efficacy for DU healing.
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Antiulcerosos/uso terapêutico , Úlcera Duodenal/tratamento farmacológico , Lansoprazol/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Pirróis/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Sulfonamidas/uso terapêutico , Adulto , Idoso , Antiulcerosos/efeitos adversos , Método Duplo-Cego , Úlcera Duodenal/diagnóstico , Endoscopia , Feminino , Humanos , Lansoprazol/efeitos adversos , Masculino , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/efeitos adversos , Pirróis/efeitos adversos , Úlcera Gástrica/diagnóstico , Sulfonamidas/efeitos adversos , Resultado do TratamentoRESUMO
X-ray Compton scattering measurements of the electron momentum distribution in water confined in both single-walled and double-walled carbon nanotubes (SWNT and DWNT), as a function of temperature and confinement size are presented here together with earlier measurements of the proton momentum distribution in the same systems using neutron Compton scattering. These studies provide a coherent picture of an anomalous state of water that exists because of nanoconfinement. This state cannot be described by the weakly interacting molecule picture. It has unique transport properties for both protons and water molecules. We suggest that knowledge of the excitation spectrum of this state is needed to understand the enhanced flow of water in cylinders with diameters on the order of 20 Å.
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We present a new planar Ni compound refractive lens for high energy X-rays (116 keV). The lens is composed of identical plano-concave elements with longitudinal parabolic grooves manufactured by a punch technique. In order to increase the lens transmission, the thickness of the single lens at the parabolic groove vertex was reduced to less than 5 µm and the radius of curvature was reduced to about 20 µm. The small radius of curvature allowed us to reduce the number of single elements needed to get the focal length of 3 m to 54 single lenses. The gain parameter has been significantly improved compared to the previous lenses due to higher transmission, but the focused beam size and its gain are not as good as expected, mostly due to the aberrations caused by the lens shape imperfections.
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Spin selective magnetic hysteresis (SSMH) curves, orbital selective magnetic hysteresis (OSMH) curves and magnetic quantum number selective SSMH curves are obtained for CoFeB/MgO multilayer films by combining magnetic Compton profile measurements and superconducting quantum interference device (SQUID) magnetometer measurements. Although the SQUID magnetometer measurements do not show perpendicular magnetic anisotropy (PMA) in the CoFeB/MgO multilayer film, PMA behavior is observed in the OSMH and SSMH curves for the |m| = 2 magnetic quantum number states. These facts indicate that magnetization switching behavior is dominated by the orbital magnetization of the |m| = 2 magnetic quantum number states.