Learning to stop: a unifying principle for legged locomotion in varying environments.

Evolutionary studies have unequivocally proven the transition of living organisms from water to land. Consequently, it can be deduced that locomotion strategies must have evolved from one environment to the other. However, the mechanism by which this transition happened and its implications on bio-mechanical studies and robotics research have not been explored in detail. This paper presents a unifying control strategy for locomotion in varying environments based on the principle of 'learning to stop'. Using a common reinforcement learning framework, deep deterministic policy gradient, we show that our proposed learning strategy facilitates a fast and safe methodology for transferring learned controllers from the facile water environment to the harsh land environment. Our results not only propose a plausible mechanism for safe and quick transition of locomotion strategies from a water to land environment but also provide a novel alternative for safer and faster training of robots.

An anthropomorphic soft skeleton hand exploiting conditional models for piano playing.

The development of robotic manipulators and hands that show dexterity, adaptability, and subtle behavior comparable to human hands is an unsolved research challenge. In this article, we considered the passive dynamics of mechanically complex systems, such as a skeleton hand, as an approach to improving adaptability, dexterity, and richness of behavioral diversity of such robotic manipulators. With the use of state-of-the-art multimaterial three-dimensional printing technologies, it is possible to design and construct complex passive structures, namely, a complex anthropomorphic skeleton hand that shows anisotropic mechanical stiffness. We introduce a concept, termed the "conditional model," that exploits the anisotropic stiffness of complex soft-rigid hybrid systems. In this approach, the physical configuration, environment conditions, and conditional actuation (applied actuation) resulted in an observable conditional model, allowing joint actuation through passivity-based dynamic interactions. The conditional model approach allowed the physical configuration and actuation to be altered, enabling a single skeleton hand to perform three different phrases of piano music with varying styles and forms and facilitating improved dynamic behaviors and interactions with the piano over those achievable with a rigid end effector.

Goal-directed multimodal locomotion through coupling between mechanical and attractor selection dynamics.

One of the most significant challenges in bio-inspired robotics is how to realize and take advantage of multimodal locomotion, which may help robots perform a variety of tasks adaptively in different environments. In order to address the challenge properly, it is important to notice that locomotion dynamics are the result of interactions between a particular internal control structure, the mechanical dynamics and the environment. From this perspective, this paper presents an approach to enable a robot to take advantage of its multiple locomotion modes by coupling the mechanical dynamics of the robot with an internal control structure known as an attractor selection model. The robot used is a curved-beam hopping robot; this robot, despite its simple actuation method, possesses rich and complex mechanical dynamics that are dependent on its interactions with the environment. Through dynamical coupling, we will show how this robot performs goal-directed locomotion by gracefully shifting between different locomotion modes regulated by sensory input, the robot's mechanical dynamics and an internally generated perturbation. The efficacy of the approach is validated and discussed based on the simulation and on real-world experiments.

Shift of hepatitis E virus RNA from hepatocytes to biliary epithelial cells during acute infection of rhesus monkey.

Hepatitis E virus (HEV) has been considered to be the major cause of enterically transmitted non-A, non-B hepatitis in developing countries. However, little is known about viral replication and localization in the liver. The aim of this study was to examine the distribution of HEV-infected cells in experimentally infected animals. Seven captured wild rhesus monkeys were inoculated intravenously with faecal extract derived from a Myanmar strain of HEV. Animals were killed at different time-points of clinical illness: during early infection, during prehepatitis with viral-like particles in bile, during acute hepatitis and during convalescence. Intrahepatic localization of HEV was analysed using non-isotopic thymine dimer in situ hybridization (NITDISH). Both plus and minus strands of HEV RNA were found in hepatocytes during the early infection period. Staining in the submembranous cytoplasmic region of hepatocytes was observed. In the prehepatitis period, both plus and minus strand HEV RNAs appeared in the canalicular side of isolated bile epithelial cells. Subsequently, HEV RNA became universally distributed in the cytoplasm of medium-size bile epithelial cells. After recovery, HEV RNA disappeared.

Chronic Japanese schistosomiasis and hepatocellular carcinoma: ten years of follow-up in Yamanashi Prefecture, Japan.

In a preliminary study carried out in the study area we found that 19.1% (173/907) of patients with chronic liver disease and 51% (35/68) of hepatocellular carcinoma cases were infected with Japanese schistosomiasis. Analysis of data from 571 autopsies revealed a similarly high incidence of schistosomiasis among cases of hepatoma and other liver diseases. A prospective case-control study conducted over 10 years showed that hepatoma developed in 5.4% (26/484) of chronic schistosomiasis cases and in 7.5% (23/307) of patients with chronic liver disease (hepatitis, cirrhosis, etc). The difference was not statistically significant (P = 0.228). A high incidence of hepatitis C virus (HCV) antibody (HCVAb) was found in the schistosomiasis group (36.5%; 95% CI = 44.9-28.1%) and in the chronic liver disease group (56.0%), 39% of whom had chronic hepatitis (P = 0.028). Various factors that might have contributed to the development of hepatoma and schistosomiasis were investigated, but no evidence of a significant correlation between schistosomiasis and hepatoma was found. The high incidence of HCVAb was considered to have been responsible for the development of hepatocellular carcinoma in chronic schistosomiasis patients. The role of HBV infection in the development of hepatoma in schistosomiasis patients was not confirmed after an assay for HCVAb was included in the study.

Genotyping of the CYP1A1 and GSTM1 genes in esophageal carcinoma patients with special reference to smoking.

BACKGROUND: Aromatic hydrocarbons, including benzol[a]pyrene, in tobacco smoke first require metabolic activation by phase I enzymes, cytochrome P450s (CYP450s), and then are subjected to detoxification by phase II enzymes, the glutathione-S-transferases. A high risk lung carcinoma group has been reported to have specific polymorphisms of the cytochrome P450 (CYP1A1) gene and the glutathione-S-transferase (GSTM1) gene. In this study, the authors investigated whether such genotypes were also risk factors for esophageal carcinoma. METHODS: Subjects were comprised of 89 esophageal carcinoma patients and 137 noncancer controls. Forty-nine of the patients and 60 of the control subjects were smokers. Genotypic studies of both CYP1A1 and GSTM1 were performed in the cancer tissues of all 89 patients. Genotypes of peripheral blood leukocytes taken from the control subjects were also determined. Genotypes of the CYP1A1 and GSTM1 genes were determined by the polymerase chain reaction. RESULTS: Patients who were heavy smokers with the genotypes Val/Val (V/V) for CYPIAI and the combined genotype of V/V for CYP1A1 and GSTM1- were a statistically high risk group compared with control subjects (P < 0.01, chi-square = 10.6 vs. P < 0.01, chi-square = 11.0). The association of V/V for CYPIAI with a smoking index > or = 600 in esophageal carcinoma patients was estimated at 6.63 (95% confidence interval [CI], 1.86-23.7). The association of combined genotypes of V/V of CYP1A1 and GSTM1 with a smoking index > or = 600 in esophageal carcinoma patients was estimated at 12.7 (95% CI, 1.97-81.8) CONCLUSIONS: Specific genotypes of the CYP1A1 and GSTM1- genes are related to the incidence of esophageal carcinoma, especially in heavy smokers.

Immunohistochemical studies of vascular volume and proliferative activity in squamous cell carcinoma of the esophagus.

For immunohistochemical investigation and clarification of the relationship between the vascular volume in esophageal carcinoma and the proliferative activity of its tumor cells, we examined surgical specimens of squamous cell carcinoma (SCC) of the esophagus from 15 patients. The vascular volume was evaluated by immunostaining for platelet-endothelial cell adhesion molecule-1 with monoclonal antibody JC70, and the proliferative activity of the carcinoma cells was evaluated by immunostaining for proliferating cell nuclear antigen (PCNA) with antibody 19A2. The ratio of the vascular area to the tumor area and the labeling index (LI) for PCNA in the carcinoma cells was then calculated. The antibody JC70 was useful for immunohistochemically detecting blood microvessels in esophageal carcinoma. The vascular volume, expressed as the ratio mentioned above, was higher in well- and moderately differentiated SCCs than in poorly differentiated SCC (P < 0.01), and the PCNA LI did not depend on the degree of differentiation. However, there was a significantly inverse relationship between the ratio of the vascular area to that of carcinoma and the PCNA LI of the carcinoma cells (P < 0.01). These findings show that angiogenesis is greater in esophageal carcinomas with little proliferative activity.

Rupture of lens cataract: a novel hereditary recessive cataract model in the mouse.

The RLC is a new mouse model of hereditary cataract. In this mutant, opacity of lens developed spontaneously at 35-60 days of age. The initial histological change was irregular swelling, condensation, degeneration and fragmentation of lens fibers in the deep cortex, leading to rupture of the lens capsule at the posterior pole at 45-100 days of age. Following rupture, the lens nucleus dislocated behind the lens or occasionally in the anterior chamber. Both eyes were affected. Genetic analysis indicated that the mutation was dictated by a single autosomal recessive gene with complete penetrance. Homozygotes of either sex developed cataract with rupture of lens capsule. We named the responsible gene as rupture of lens cataract (rlc) and the mouse strain as RLC. Neither allelism nor linkage was found between rlc and nct, another recessive gene in Nakano cataract mice. The rlc mutation is now fixed in a inbred background since the RLC has been maintained over 20 inbred generations in the laboratory. Although no direct homologous disease of this unusual cataract is found in human, this mutant will provide a valuable tool to investigate the mechanism involved in maintainance of lens.

Expression of cytochrome P450s and glutathione S-transferases in human esophagus with squamous-cell carcinomas.

In order to clarify the expression of cytochrome P450 and glutathione S-transferase in human esophagus, 41 samples of human esophagus with squamous-cell carcinoma were investigated by immunoblot analysis and enzyme assays. Cytochrome P450 1A2/1 was clearly expressed in microsomes, and the amount in samples with tumorous tissue was significantly greater than that in samples without tumourous tissues or in liver; cytochrome P450 2B6 and 3A4/3 were expressed polymorphically. Aryl hydrocarbon hydroxylase activity was detected in microsomes and was greater in samples from smokers than non-smokers. Patients who both smoked and drank alcohol, however, had activity similar to that of patients without these habits. Glutathione S-transferase M1 and A1/2 protein existed polymorphically in cytosol, and glutathione S-transferase P1-1 was detected in all samples. The frequency of expression of the glutathione S-transferase A1/2 protein was greater in patients with M1 protein than in those without; no difference in the expression was seen for glutathione S-transferase P1-1. Neither smoking nor drinking influenced the expression or activity of glutathione S-transferase. Our data support the idea that some carcinogens can be directly activated or inactivated in human esophageal epithelium.

Clinicopathologic characteristics and postoperative outcome in Japanese and Chinese patients with thoracic esophageal cancer.

We evaluated the clinicopathologic findings and surgical results of 140 patients with thoracic esophageal cancer treated at Shinshu University, Japan (Shinshu group), and compared them with those from 1164 patients treated at Hebei Medical College, China (Hebei group) to determine if the two groups showed any differences. The Shinshu group had significantly higher incidences of elderly patients (>70 years of age), male patients, and tumors located at the lower esophagus (p < 0.01). In the Hebei group, although the depth of tumor invasion was more advanced, the incidence of nodal metastasis was significantly lower (p < 0.01). Operative death and postoperative complications were more frequent in the Shinshu group. Comparison of the postoperative survival curves revealed significantly longer survival of patients with pT2 or pT3 tumor in the Hebei group (p < 0.01), but there were no significant differences between the two groups when the lesions were classified by pTNM stage. This study demonstrated several differences between the patients in the two areas in regard to the clinicopathologic characteristics of thoracic esophageal cancer. The most important characteristic of the esophageal cancer in the Hebei group appears to be the low incidence of nodal metastasis.

Assessment of proliferative activity of glandular cells in hyperfunctioning parathyroid gland using flow cytometric and immunohistochemical methods.

The proliferative activity of epithelial cells in hyperfunctioning parathyroid glands was estimated by flow cytometric and immunohistochemical procedures. A total of 30 parathyroid glands, 29 hyperfunctioning glands, and 1 normal gland were studied. The pathology of the 29 glands was determined to be hyperplasia in 19 and adenoma in 10. The S-phase cell population was expressed in terms of the S-phase fraction (%SPF) calculated from the histogram by DNA flow cytometry and in terms of the BrdU immunostaining labeling index (BrdU LI). Cells in all stages of the cell cycle were studied by Ki-67 immunostaining and expressed in terms of the labeling index (Ki-67 LI). Both BrdU LI and Ki-67 LI values were low, ranging from 0% to 0.58% and from 0.21% to 2.62%, respectively. The BrdU LIs were lower than the Ki-67 LIs, ranging from one-sixth to one-twelfth of the values depending on the disease. There were significant correlations between the two indices (p < 0.001). The %SPF determined by flow cytometry was consistently higher than both the BrdU LI and the Ki-67 LI. This discrepancy cannot be explained precisely, and further improvements are required for the flow cytometric analysis of %SPF. The cell cycle study by BrdU and Ki-67 immunohistochemistry suggested that the glandular cells of the hyperfunctioning parathyroid were characterized by low proliferative activity. No evidence of rapid cell turnover rate assumed from the flow cytometric study could be observed in the hyperfunctioning parathyroid gland.

[Immunohistochemical expression of sialyl-Lewis antigens in lung cancer].

We investigated the immunohistochemical expression of three carbohydrate antigens, sialyl-Lewisa, sialyl-Lewisx and sialyl-Lewisx-i, in human lung cancer tissues using monoclonal antibodies, 2D3, SNH3 and FH6, respectively, and compared the expression rate of these three antigens with clinical and pathologic findings. The expression rate of all the three antigens in adenocarcinoma was higher than that in squamous cell carcinoma and that of sialyl-Lewisx was highest in adenocarcinoma. Sialyl-Lewisx antigen was expressed in all cases of positive nodal metastasis or postoperative distant metastasis in adenocarcinoma. In squamous cell carcinoma, however, there was no relationship between the expression rate of sialyl-Lewisx antigen and nodal or distant metastasis. These results suggest that expression of sialyl-Lewisx antigen in adenocarcinoma of the lung may be correlated with nodal or distant metastasis.

Management of tracheal wall resection for thyroid carcinoma by tracheocutaneous fenestration and delayed closure using auricular cartilage.

BACKGROUND: In the case of advanced thyroid carcinoma invading the trachea, surgical procedures for tracheal resection are selected in relation to the degree of invasion. We created a tracheocutaneous fenestration that was later closed with a free auricular cartilage autograft. We present a simple and effective method for permanent closure of tracheostoma. METHODS: The surgical procedure for delayed closure consists of three steps: (1) preparing the hinge flap with additional undermining of the subcutaneous layer and the strap muscles; (2) removing a portion of the conchal cartilage from the auricle, which is easily performed with a semicircular skin incision along the anthelix of the ear; and (3) placing the conchal cartilage with its convex surface upward just over the sutured hinge flap layer. RESULTS: Under local anesthesia, we successfully employed this reconstructive procedure for 5 patients. Unfortunately, however, in one patient, we had to reopen the closed tracheocutaneous fenestration on the second postoperative day because of an acute problem that was independent of the closure surgery. Four patients remain in satisfactory condition for more than 2 years since the closure of tracheostoma. CONCLUSIONS: The auricular cartilage free graft is a relatively simple procedure which supplies tracheal wall skeletal support for the permanent closure of the tracheocutaneous fenestration.

Management of chylothorax after pulmonary resection.

BACKGROUND: Conservative management with intrapleural drainage and total parenteral nutrition (TPN) has been the first choice of treatment for postoperative chylothorax. With this approach, however, it usually takes several weeks for the chylothorax to resolve and it is sometimes unsuccessful. In this study, we reviewed seven patients who had chylothorax develop after pulmonary resection for primary carcinoma of the lung. STUDY DESIGN: The patients were treated according to a "one-week trial" that consisted of one week of observation with intrapleural drainage and maximum parenteral nutritional support followed by operative intervention if the effect of the conservative therapy was not adequate. When the chylous leak was decreased to less than 100 mL/day or less than 15 percent of the maximum daily drainage volume after the "one-week trial," the conservative management was continued for two more weeks. After observation for three weeks, oral intake was begun and a final evaluation of the treatment was made. RESULTS: One patient did not consent to the "one-week trial" and underwent operative treatment on the third postoperative day. Two patients had chylous leaks less than 100 mL/day or less than 15 percent of the maximum daily chylous leak after one week observation. Conservative management with TPN was continued in these patients for two more weeks and operation was performed in one on the 20th day and in the other on the 22nd postoperative day. The remaining four patients underwent operative treatment on the seventh or eighth postoperative day. All of the operations for chylothorax were successful, and chest tubes were removed promptly. These results show that operative management of chylothorax was reliable and safe. The "one-week trial," however, offered few advantages in determining the therapeutic strategy for postoperative chylothorax.

Frequent natural killer cell abnormality in children in an area highly contaminated by the Chernobyl accident.

Since January 1991, we have been performing thyroid surveys and hematologic and immunologic screening on children in Chechersk, Belarus, a city situated in one of the areas most seriously contaminated with high levels of radionuclides after the Chernobyl accident. Ten children selected from 713 children because of goiter did not show a decrease in humoral immunity or in the number and function of T cells. By contrast, natural killer (NK) cell activity against K562 cells was depressed in 4 of these 10 children. The clinical and laboratory findings indicated that previously reported diseases with NK cell dysfunction could be excluded. A comparative analysis of NK cell activity in children from areas with and without high 137Cs levels revealed a high frequency of abnormal NK cell activity only in children from the area contaminated by radioactive fallout. In addition, there was no correlation between NK cell activity and NK cell number as percentage in the children from the area with high 137Cs levels. Neither activity nor number of NK cells was correlated with the body content of 137Cs. Thus, the frequent abnormality of NK cell function may not have been due to actual internal exposure to the long-lived radionuclide.

Histopathological features of atrophic thyroiditis with blocking type-TSH binding inhibitor immunoglobulins.

To investigate the histopathological features of atrophic thyroiditis (AT) with blocking type-TSH binding inhibitor immunoglobulins (TBII), the present morphological observations were carried out employing additional immunohistochemical procedures. Moreover, these were compared with examples of goitrous Hashimoto's thyroiditis showing negative TBII (HT). There exist apparent differences between AT and HT. In particular, significant follicular atrophy with epithelial flattening including decreased positive staining of the follicular epithelial cells for thyroglobulin in AT was characteristically observed. These results suggest that the mechanism for the development of hypothyroidism in AT with blocking type-TBII might be due to suppression of thyroid cell function through the inhibition of endogenous TSH stimulation by the blocking antibody with subsequent epithelial degenerative destruction.

Thyroid abnormalities among children in the contaminated area related to the Chernobyl accident.

Gradual increases of various radiation-related diseases including thyroid cancer following the Chernobyl accident have been recently reported. We have carried out systematic thyroid surveys in school children aged 10-15 years in the highly contaminated area and compared the results with a similar survey in a nonaffected neighboring area as a control. Systematic examinations of the thyroid gland were performed in 888 schoolchildren (408 males and 480 females) in the districts of Chechelsk city with 5 to over 40 Ci/km2 of radiation level for 137Cs. In the control area (Bobruisk city), 521 children with the same age range (229 males and 292 females) were examined. Thyroid surveys were carried out as follows: palpation, ultrasonography, blood examinations of thyroid function, and measurements of daily urinary excretion of iodine. Certain thyroid abnormalities were observed in the high radioactive fallout area more frequently than in the control region. In particular, the prevalence of multiple micronodular lesions in diffuse goiter in the contaminated area was significantly higher than in the control area. However, endemic goiter due to iodine deficiency was present in both districts. The environment factor of iodine deficiency might have resulted in the early occurrence of ultrasonographic thyroid abnormalities attributed to radioactive contamination.