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This paper describes the manipulator for live-line construction of high-voltage overhead power transmission lines (line voltage 6.6 kV) that is being jointly developed by Tokyo Electric Power and other companies. It describes this system's development concept, makeup, functions, and design, as well as operability tests using actual-scale transmission line poles. In this research, development began in 1984. As the first step, a prototype model of a ground-mounted twin-arm manipulator was trial-manufactured in 1985. As the second step, in 1988 a truck-mounted system was developed in which the twin-arm manipulator was mounted on a 'cherrypicker' vehicle. As the third step, a practical system was developed based on these results. In the development of this system, the task of development of the individual items of equipment was shared as follows. Project leader, Conceptual design, Utility evaluation: The Tokyo Electric Power (Company, Inc.) Development of manipulator system: The Furukawa Electric (Co., Ltd.), Fuji Electric (Co., Ltd.) System mounting vehicles: Aichi Sharyo (Co., Ltd.) Operability testing, development of construction methods: Kandenko (Co., Ltd.)

Introduction: Heart disease is a major cause of mortality worldwide, and the annual number of deaths due to heart disease has increased in recent years. Although heart failure is usually managed with medicines, the ultimate treatment for end-stage disease is heart transplantation or an artificial heart. However, the use of these surgical strategies is limited by issues such as thrombosis, rejection and donor shortages. Regenerative therapies, such as the transplantation of cultured cells and tissues constructed using tissue engineering techniques, are receiving great attention as possible alternative treatments for heart failure. Research is ongoing into the potential clinical use of cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs). However, the energy-producing capacity of cardiomyocytes maintained under previous culture conditions is lower than that of adult primary cardiomyocytes due to immaturity and a reliance on glucose metabolism. Therefore, the aims of this study were to compare the types of fatty acids metabolized between cardiomyocytes in culture and heart cells in vivo and investigate whether the addition of fatty acids to the culture medium affected energy production by cardiomyocytes. Methods: A fatty acid-containing medium was developed based on an analysis of fatty acid consumption by rat primary cardiomyocytes (rat-CMs), and the effects of this medium on adenosine triphosphate (ATP) production were investigated through bioluminescence imaging of luciferase-expressing rat-CMs. Next, the fatty acid content of the medium was further adjusted based on analyses of fatty acid utilization by porcine hearts and hiPSC-CMs. Oxygen consumption analyses were performed to explore whether the fatty acid-containing medium induced hiPSC-CMs to switch from anaerobic metabolism to aerobic metabolism. Furthermore, the effects of the medium on contractile force generated by hiPSC-CM-derived tissue were evaluated. Results: Rat serum, human serum and porcine plasma contained similar types of fatty acid (oleic acid, stearic acid, linoleic acid, palmitic acid and arachidonic acid). The types of fatty acid consumed were also similar between rat-CMs, hiPSC-CMs and porcine heart. The addition of fatty acids to the culture medium increased the bioluminescence of luciferase-expressing rat-CMs (an indirect measure of ATP level), oxygen consumption by hiPSC-CMs, and contractile force generated by cardiac tissues constructed from hiPSC-CMs. Conclusions: hiPSC-CMs metabolize similar types of fatty acid to those consumed by rat-CMs and porcine hearts. Furthermore, the addition of these fatty acids to the culture medium increased energy production by rat-CMs and hiPSC-CMs and enhanced the contractility of myocardial tissue generated from hiPSC-CMs. These findings suggest that the addition of fatty acids to the culture medium stimulates aerobic energy production by cardiomyocytes through β-oxidation. Since cardiomyocytes cultured in standard media rely primarily on anaerobic glucose metabolism and remain in an immature state, further research is merited to establish whether the addition of fatty acids to the culture medium would improve the energy-producing capacity and maturity of hiPSC-CMs and cardiac tissue constructed from these cells. It is possible that optimizing the metabolism of cultured cardiomyocytes, which require high energy production to sustain their contractile function, will improve the properties of hiPSC-CM-derived tissue, allowing it to be better utilized for disease modeling, drug screening and regenerative therapies for heart failure.

T-cell-mediated immunity to a virulent strain of Plasmodium berghei NK65 (Pb NK65) and to an attenuated derivative (Pb XAT) of the strain were examined in CBA mice by the administration of monoclonal antibodies against T-cell subsets or interferon-gamma (IFN-γ). The injection of anti- CD8+ or anti-IFN-γ delayed the mortality of mice infected with Pb NK65, although it did not affect the parasitaemia. In the late stage of PB NK65 infection, T cells, especially CD8+ T cells, were increased in number in the liver at the expense of splenic CD8+ T cells. These CD8+ T cells released IFN-γ in culture without antigen stimulation and were thought to induce tumour necrosis factor- alpha (TN F-α) production by the cells in the liver. In mice infected with Pb XAT, or mice primed with Pb XAT and then challenged with Pb NK65, CD4+ T cells had a crucial role in preventing parasite growth and in protective immunity. IFN-γ was again the key molecule in protective immunity. These results suggest that T cells stimulated with malaria antigen play important roles both in protective immunity and pathogenesis depending upon their subsets; CD8+ T cells in pathogenesis, and CD4+ T cells in protective immunity. These apparently contradictory responses may be mediated by the same cytokine, IFN-γ. [ABSTRACT FROM AUTHOR]

Crohn's disease is associated with complications in multiple organs. However, there are very few reported cases of patients with Crohn's disease with muscle symptoms and/or high serum creatine phospho-kinase (CPK) levels. We report here a patient with Crohn's disease who experienced skeletal muscle damage with extremely high serum CPK level during treatment with an elemental diet. The non-parenteral administration of large amounts of carbohydrate and limited glycogen degradation capability may be a possible causative mechanism for this elemental diet-induced muscle damage. [ABSTRACT FROM AUTHOR]

The relationship between parasite development and sensitivity to irradiation with X-rays was investigated during a single synchronous cycle of Plasmodium falciparum in culture. The sensitivity of the parasites to irradiation was closely correlated with the phases of DNA synthesis. Their sensitivity was greatest at the ring stage in development, but decreased at the trophozoite stage when DNA synthesis begins. Lowest sensitivity was found when DNA synthesis was most rapid as the parasites were transforming from late trophozoite to schizont forms. These findings suggest that DNA is the target of the lethal radiation damage in the parasites. [ABSTRACT FROM AUTHOR]

In virulent Plasmodium berghei infection, mice showed suppressive responses to sheep red blood cells SRBC (PFC) as well as the parasite antigen (DTH) and developed autoantibodies against homologous lymphocytes. On the other hand, mice infected with an attenuated variant derived from P. berghei did not show these responses but developed solid protective immunity against parent parasite infection accompanied by high antibody titre. When such an immune serum was transferred into mice, attenuated parasite infection was completely eliminated. These results show that an attenuated variant stimulates antibody production, which contributes to protection against the parasites. In contrast, in virulent P. berghei infections harmful immunopathological responses against the host are more prominent than protective immune responses against the parasites. [ABSTRACT FROM AUTHOR]

Recently, regenerative medicine using engineered three-dimensional (3D) tissues has been focused. In the fields of cell therapy and regenerative medicine, mesenchymal stem cells (MSCs) are attractive autologous cell sources. While, in bioengineered tissues, a 3D environment may affect the differentiation of the stem cells, little is known regarding the effect of 3D environment on cellular differentiation. In this study, MSC differentiation in in vitro 3D tissue models was assessed by human endometrial gland-derived MSCs (hEMSCs) and cell sheet technology. hEMSC sheets were layered into cell-dense 3D tissues and were cultured on porous membranes. The tissue sections revealed that chondrocyte-like cells were found within the multilayered cell sheets even at 24 h after layering. Immunostainings of chondrospecific markers were positive within those cell sheet constructs. In addition, sulfated glycosaminoglycan accumulation within the tissues increased in proportion to the numbers of layered cell sheets. The findings suggested that a high cell density and hypoxic environment in 3D tissues by layering cell sheets might accelerate a rapid differentiation of hEMSCs into chondrocytes without the help of chondro-differentiation reagents. These tissue models using cell sheets would give new insights to stem cell differentiation in 3D environment and contribute to the future application of stem cells to cartilage regenerative therapy.

Presents a letter to the editor about anti-lymphocyte autoantibodies in lethal mouse malaria and their absence in an irradiation-induced non-lethal variant.

Objective: This study aimed to compare the perioperative outcomes of robot-assisted thoracoscopic surgery (RATS) and conventional video-assisted thoracoscopic surgery (VATS) for lung cancer in patients with obesity., Methods: Anatomical pulmonary lobectomy or segmentectomy performed at a single institution from April 2018 to September 2023 in patients with obesity (body mass index ≥25 kg/m 2 ) were statistically compared in terms of perioperative clinical factors including operative time, blood loss, chest tube duration, pain score, intraoperative events, and early postoperative complications between RATS and VATS., Results: In all, 89 patients were evaluated; 43 underwent RATS and 46 underwent VATS. All RATS procedures were performed using the da Vinci Xi system. Patient characteristics were comparable between the 2 groups. The operative time, blood loss, number of dissected lymph nodes, intraoperative events, and conversion rate to open thoracotomy were similar between the 2 groups. The frequencies of postoperative complications and chest tube placement duration between the groups were also similar. The median pain scores were slightly higher in the RATS group on postoperative day 1 but were equivalent between the 2 groups on postoperative day 7. The RATS group had a shorter postoperative hospital stay than the VATS group ( P < 0.01)., Conclusions: A surgical team proficient in conventional VATS can safely introduce RATS in patients with obesity and lung cancer with equivalent perioperative outcomes., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Eosinophilic chronic rhinosinusitis (ECRS) is an allergic inflammatory disease characterized by chronic inflammation of the sinus mucosa, and sometimes, osteitis. This study aimed to investigate the pattern of osteitis in ECRS and the relationship between bony thickening of the middle turbinate and recurrence of ECRS., Methods: A total of 246 patients with paranasal diseases were included in the study. The patients' data on bone thickening level, mucosal thickening, polyp score, clinical severity, and laboratory data were retrospectively evaluated., Results: In total, 38, 186, and 22 patients had ECRS, non-ECRS (NECRS), and odontogenic sinusitis, respectively. The Lund-Mackey (LM) score and Global Osteitis Scoring Scale (GOSS) scores in patients with ECRS were higher than those in patients with other paranasal diseases. There was a significant positive correlation between the GOSS score and ECRS clinical disease severity. Postoperative recurrence was significantly increased in patients with ECRS associated with bony thickening of the middle turbinate., Conclusion: Both mucosal inflammation and osteitis were more severe in patients with ECRS than in patients with other diseases, and clinical disease severity was correlated with osteitis. Furthermore, the postoperative recurrence rate tended to increase in patients with ECRS who had bony thickening of the middle turbinate., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Neuro-otological factors that influence changes in spontaneous nystagmus (SN) during vertigo attacks in Ménière's disease (MD) remain unclear., Objective: To identify neuro-otological factors that might influence the initial direction of SN and the directional change of SN., Methods: A prospective, observational study of 22 patients with definite MD to evaluate the initial direction and directional change of SN during vertigo attacks, endolymphatic hydrops (EH) volume, and the function of horizontal semicircular canal and hearing levels., Results: SN consistently began as irritative in 17 of 22 cases, and 9 of 17 cases showed a definite change in direction after onset. SN consistently began as paralytic in 5 of 22 cases, and 3 of 5 cases showed a definite change in direction after onset. Subjects in the irritative initial SN group had less severe degrees of hearing loss, smaller cochlear and vestibular EH volume than the paralytic initial SN group (P = 0.017, < 0.001, and 0.009, respectively). Subjects in the SN direction change group had significantly smaller maximum slow phase velocity, percentage of caloric weakness and canal paresis than the no SN direction change group (P = 0.001, 0.006, and 0.001, respectively). Simple logistic regression analysis showed that smaller EH volume was significantly associated with initial irritative SN (OR = 0.867, 95% CI 0.762-0.988, P = 0.032) and that the degree of canal paresis was negatively associated with the presence of directional change of SN (OR = 0.022, 95% CI 0.002-0.289, P = 0.004)., Conclusions: The morphology of EH and canal paresis may independently affect the characteristics of SN in patients with MD., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Objectives: Chronic rhinosinusitis (CRS) is a common disease with mucosal inflammation, and may sometimes be accompanied by bone thickening. The disease is usually bilateral; when it is unilateral, there may be a specific disease. This study aimed to investigate the association between unilateral sinus opacification and osteitis., Methods: In total, 104 patients with computed tomography revealing unilateral sinus opacification were included in this study. Patients were retrospectively evaluated using the Global Osteitis Scoring Scale (GOSS) score, Lund-Mackey (LM) score, polyp score, and blood tests., Results: In total, 47, 11, 9, 17, and 20 patients had CRS, paranasal sinus cyst, inverted papilloma, mycetoma, and odontogenic sinusitis, respectively. The GOSS score in patients with mycetoma was higher than that in patients with CRS. However, no significant differences in the GOSS scores between patients with mycetoma, inverted papilloma, and odontogenic sinusitis existed. 10 of the 104 patients had osteitis with extensive bone thickening and a GOSS score of 4 or higher. Patients with CRS and mycetoma tended to have a higher GOSS score for the maxillary sinus than for the other sinuses. There was a significant positive correlation between the GOSS score and LM score in patients with diseases other than paranasal sinus cyst., Conclusions: Mycetoma is more likely to cause osteitis than CRS, and a unique mechanism of osteitis exacerbation is predicted. As there is a positive correlation between bone thickening and sinus inflammation, a close association between osteitis and mucosal inflammation is inferred in diseases involving unilateral sinus opacification., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Pancreatic pseudocysts rarely extend to the mediastinum and can be fatal if mediastinitis is complicated. In this report, we describe a case of mediastinitis associated with mediastinal pancreatic pseudocyst successfully treated by the thoracoscopic mediastinal drainage. The patient was a man in his 40s with a history of alcoholic acute pancreatitis. Chest and abdominal computed tomography (CT) scan taken for his complaints of back pain and dyspnea showed a pancreatic pseudocyst extending to the mediastinum. First, an endoscopic nasopancreatic drainage( ENPD) tube was placed, and then thoracoscopic mediastinal drainage was performed through the right thoracic cavity. After the operation, the pseudocyst in the mediastinum rapidly disappeared even though there was no drainage from the ENPD tube. Postoperative recovery of the patient was uneventful, and the patient was discharged on the 17th postoperatively day. This case suggests that the importance of prompt treatment for mediastinitis and the effectiveness of the thoracoscopic surgery.

Purpose: When a dizzy patient with episodic vertigo has an abnormal caloric and a normal video head impulse test (vHIT), this caloric-vHIT dissociation provides vital information for a diagnosis of Ménière's disease (MD). Endolymphatic hydrops (EH), a histological marker of MD, is hypothesized to be involved in the caloric-vHIT dissociation in MD through hydropic duct distension of the horizontal semicircular canal (SC). This study was designed to determine the impact of EH on the function of horizontal SC during caloric stimulation., Methods: Caloric test and vHIT were used to evaluate the function of horizontal SC every six months, annual magnetic resonance imaging (MRI) was used to evaluate the degree of EH size in the vestibule, and monthly vertigo and hearing evaluation was done for 12 months. EH shrinkage was defined as the size change of vestibular EH from significant to none., Results: Among 133 MD patients evaluated for eligibility, 67 patients with caloric-vHIT dissociation entered the study. Fifteen participants had EH shrinkage (G-I), while 52 participants had no remarkable EH change (G-II). Average values (IQR) of the maximum slow phase velocity in G-I and G-II were 29.6 (13.0-34.0) and 25.9 (17.3-31.3), respectively, at baseline, 26.1 (9.0-38.0) and 23.6 (18.0-28.3) at 12 months. Two-factor repeated-measures ANOVA showed no significant differences between the groups (P = 0.486). The values of vestibulo-ocular reflex gain of the horizontal SC in G-I and G-II remained above 0.8 during the study period., Conclusions: EH detected by MRI shows limited correlation with caloric stimulation results., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Prolongation of QT interval on electrocardiogram can be associated with perioperative lethal arrhythmia. Epidural analgesia is a commonly used modality to relieve surgical pain by blocking sensory nerves, which also blocks the autonomic nervous system and can affect QT interval. Since patient monitoring becomes much less frequent after surgery than intraoperative period, we investigated the effects of epidural analgesia on postoperative QT interval with a randomized clinical trial and a prospective cohort study. Methods: In a randomized study, we assigned 60 patients undergoing thoracic epidural analgesia to an epidural analgesia or no-epidural analgesia group, in which 3 ml/h of 0.25% epidural levobupivacaine (7.5 mg/h) was administered only in the epidural analgesia group during surgery. The primary outcome was the postoperative heart rate-corrected QT interval. In a prospective cohort study, patients were assigned to receive 5 ml/h epidural levobupivacaine (12.5 mg/h). The plasma concentration of levobupivacaine was measured using liquid chromatography-mass spectrometry. Results: The median postoperative corrected QT interval interval with 3 ml/h epidural levobupivacaine was significantly longer than that without epidural analgesia. Using multiple regression analysis for the factors known to affect postoperative corrected QT interval interval, epidural analgesia was found to be an independent variable for prolongation, and the mean difference of the corrected QT interval interval with or without epidural analgesia was 23 ms after adjustment. The median plasma concentration of levobupivacaine at the end of surgery was 164 ng/ml with 3 ml/h epidural levobupivacaine, and the correlation coefficient to the postoperative corrected QT interval interval was 0.14, showing a not significant correlation. A prospective cohort study showed that 5 ml/h epidural levobupivacaine significantly prolonged postoperative corrected QT interval interval compared to preoperative baseline. The median plasma concentration of levobupivacaine was 166 ng/ml with 5 ml/h, the correlation coefficient of which showed no significant correlation. Conclusion: Thoracic epidural analgesia could enhance postoperative corrected QT interval prolongation after general anesthesia. The mechanism is possibly caused by blocking neighboring or part of the cardiac sympathetic nerves, rather than by systemic effects of epidurally administered levobupivacaine. Clinical trial number: UMIN000013347 for the randomized study and UMIN000041518 for the prospective cohort study, which were registered at University hospital Medical Information Network Center., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hori, Tsujikawa, Egami, Waki, Watanabe, Hino, Matsuura and Mori.)

Magnetotactic bacterium, Magnetospirillum magneticum, produces biogenic magnetic nanoparticles termed magnetosomes, which are primarily composed of a magnetite core and a surrounding lipid bilayer membrane. We have fabricated human transmembrane protein-magnetosome complexes by genetic engineering with embedding the transmembrane proteins of interest, in particular G protein-coupled receptors (GPCRs), in the magnetosome membrane. The magnetosomes provide a promising platform for high throughput ligand screening towards drug discovery, and this is a critical advantage of the magnetosome display system beyond conventional membrane platforms such as liposomes and lipid nano-discs. However, the human GPCRs expressed on the magnetosomes were not fully functionalized in bacterial membranes the most probably due to the lack of essential phospholipids such as phosphatidylcholine (PC) for GPCR functionalization. To overcome this issue, we expressed two types of PC-producing enzymes, phosphatidylcholine synthase (PCS) and phosphatidylethanolamine N-methyltransferase (PMT) in M. magneticum. As a result, generation and incorporation of PC in cell- and magnetosome-membranes were demonstrated. To the best of our knowledge, M. magneticum is the second bacterial species which had the PC-incorporated lipid membrane by genetic engineering. Subsequently, a GPCR, thyroid-stimulating hormone receptor (TSHR) and PCS were simultaneously expressed. We found that PC in the magnetosome membrane assisted the binding of TSHR and its ligand, indicating that the genetic approach demonstrated in this study is useful to enhance the function of the GPCRs displayed on the magnetosomes., (Copyright © 2021 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.)

Cervical abscesses develop in the tissue spaces between the cervical fascia. The rapid expansion of these abscesses can lead to fatal outcomes. We describe a case of a deep cervical abscess caused by Parvimonas micra . He was referred to our department with complaints of sore throat and neck pain. Ultrasonography revealed a hypoechoic area in the cervical interfascicular space. An ultrasound-guided puncture was performed to collect pus for bacteriological examination. Subsequently, a contrast-enhanced computed tomography scan revealed a multi-focal abscess extending from the left mandible to the left side of the neck, without any mediastinal abscess. An emergency drainage and antibacterial therapies were performed, and the patient progressed well. Parvimonas micra , a gram-positive anaerobic bacterium, was detected in the pus collected before incision, and appropriate antibiotics were immediately administered. The collection of pus prior to incision and drainage aids accurate identification of the causative organism and appropriate treatment., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

We describe the case of a 60-year-old man who presented at our hospital with abdominal pain and elevated hepatobiliary enzymes. Computed tomography showed portal thrombosis and cavernous transformation as well as increased wall thickness and a stricture in the biliary tract. At that time, the cause of the portal thrombosis was unknown. During follow-up, the blood cell counts (WBCs and platelets) were remarkably increased, and a test performed for the JAK2V617F mutation was positive. We diagnosed the patient with polycythemia vera. Our findings demonstrate that a patient presenting with portal thrombosis, portal biliopathy, and underlying myeloproliferative neoplasms should be carefully examined, even in the absence of the typical blood alterations.

A 57-year-old female presented with a chief complaint of odynophagia during medical treatment for systemic lupus erythematosus (SLE). Endoscopy revealed sloughed mucosa along the entire esophageal length, and normal mucosa was easily stripped by withdrawal of the biopsy forceps. Blistering eruptions subsequently appeared on her upper extremities, trunk, and oral cavity. Direct immunofluorescence of a skin biopsy specimen demonstrated linear deposits of IgG, IgM, and complement at the dermoepidermal junction. On the basis of these findings, a diagnosis of bullous SLE was made. This autoimmune blistering disease can occur in the course of SLE and is rarely accompanied by sloughing of the esophageal mucosa.

Background: Despite progress in the current genetic manipulation of donor pigs, most non-human primates were lost within a day of receiving porcine lung transplants. We previously reported that carbon monoxide (CO) treatment improved pulmonary function in an allogeneic lung transplant (LTx) model using miniature swine. In this study, we evaluated whether the perioperative treatment with low-dose inhalation of CO has beneficial effects on porcine lung xenografts in cynomolgus monkeys (cynos)., Methods: Eight cynos received orthotopic left LTx using either α-1,3-galactosyltransferase knockout (GalT-KO; n = 2) or GalT-KO with human decay accelerating factor (hDAF) (GalT-KO/hDAF; n = 6) swine donors. These eight animals were divided into three groups. In Group 1 (n = 2), neither donor nor recipients received CO therapy. In Group 2 (n = 4), donors were treated with inhaled CO for 180-minute. In Group 3 (n = 2), both donors and recipients were treated with CO (donor: 180-minute; recipient: 360-minute). Concentration of inhaled CO was adjusted based on measured levels of carboxyhemoglobin in the blood (15%-20%)., Results: Two recipients survived for 3 days; 75 hours (no-CO) and 80 hours (CO in both the donor and the recipient), respectively. Histology showed less inflammatory cell infiltrates, intravascular thrombi, and hemorrhage in the 80-hour survivor with the CO treatment than the 75-hours non-CO treatment. Anti-non-Gal cytotoxicity levels did not affect the early loss of the grafts. Although CO treatment did not prolong overall xeno lung graft survival, the recipient/donor CO treatment helped to maintain platelet counts and inhibit TNF-α and IL-6 secretion at 2 hours after revascularization of grafts. In addition, lung xenografts that were received recipient/donor CO therapy demonstrated fewer macrophage and neutrophil infiltrates. Infiltrating macrophages as well as alveolar epithelial cells in the CO-treated graft expressed heme oxygenase-1., Conclusion: Although further investigation is required, CO treatment may provide a beneficial strategy for pulmonary xenografts., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)