Global Conformational Changes of Ribosome Observed by Normal Mode Fitting for 3D Cryo-EM Structures

SummaryMany three-dimensional density maps of 70S ribosome at various functional states are available now in the Electron Microscopy DataBank at EBI. We used our new flexible-fitting approach to systematically analyze these maps to reveal the global conformational differences between the EM structures. Large-scale ratchet-like deformations were observed in an EM structure of the initiation complex and in some EM structures bound with EFG, RF3, and RRF. In most of them, the L1 stalk, which interacts with the tRNA molecule at the E site of ribosome and is considered to be involved in the release of the tRNA, was in “the blocking state” for the E-tRNA. Furthermore, we found that the EM structures bound with EFG or RRF were aligned in the conformational space, suggesting that the large-scale conformational changes of the 70S ribosome bound with these factors occur along a specific pathway in a concerted manner

Remission of Congenital Multi-system Type Langerhans Cell Histiocytosis with Chemotherapy

Patients with multi-system (MS)-type langerhans cell histiocytosis (LCH) show poor outcomes, especially congenital MS LCH cases were shown in high mortality rate. We experienced a congenital case of MS LCH with high risk organs, who needed intensive respiratory support after birth. Even though intensive chemotherapy was discontinued, this patient’s lung LCH lesions gradually became reduced and his respiratory condition recovered; therefore, we restarted and completed maintenance chemotherapy. The patient maintained complete remission for more than 4 years after the end of chemotherapy. Our case suggests that congenital MS LCH even with severe organ involvement can be treated successfully with chemotherapy

A DIFFERENCE BETWEEN JAPAN AND THE US IN THE CUSTOMER SATISFACTION MODEL FOR MOBILE UTILITARIAN INFORMATION SERVICES

Customer satisfaction and loyalty on mobile information services have been investigated in academic literature. However, there are not many researches on the factors with a specific focus on multiple utilitarian services on a cross-national basis. This research examines the antecedents of customer satisfaction and loyalty through a survey of young adult mobile users in Japan and US, respectively by modifying the American Customer Satisfaction Model (ACSM). The result showed that all of the paths in the estimated models for Japan and US were statistically significant except 3 non-significant paths for the both countries and one non-significant path from Perceived Expectation (PE) to Customer Satisfaction (CS) for US. Also, the estimated coefficients for two countries were very similar in general with a difference in the estimate on the above non-significant path of PE-CS. Since we investigated the antecedents of the common factors for two countries on Customer Satisfaction of multiple utilitarian services, our results may provide useful implications for global marketing in terms of user satisfaction and loyalty. Keywords- Mobile information services, Utilitarian service, ACSM, Customer satisfaction, Perceived expectation, SEM

Term delivery choriocarcinoma patient with brain and lung metastases successfully treated by etoposide, methotrexate, actomycin D, cyclophosphamide and vincristine (EMA-CO) chemotherapy.

It is well known that antecedent term delivery and metastasis to sites other than the lungs and vagina are high risk factors for patients with gestational trophoblastic neoplasia. Here we report on a patient with choriocarcinoma who presented with brain and lung metastases after term delivery and was treated by EMA-CO chemotherapy. A 31-year-old woman delivered a healthy infant at term. Frequent episodes of hemoptysis occurred beginning 3 weeks after the delivery. On admission to our hospital, she had lesions in the uterus, lungs and brain as well as motor aphasia and hemiplagia. The pretreatment beta-hCG level was 21,000 ng/ml and the WHO score was 16 (high-risk group). The EMA-CO regimen was administrated as first-line chemotherapy and the patient achieved complete remission after 7 courses. Treatment was terminated after 11 courses and maintained with etoposide (25 mg/day) for 6 months. The patient has remained in complete remission for more than 16 years without other adjuvant therapies. We believe that EMA-CO can currently be considered the regimen of first choice for most high-risk patients with gestational trophoblastic neoplasia in view of its effectiveness and excellent tolerability.</p

Virtual Fixture Assistance for Suturing in Robot-Aided Pediatric Endoscopic Surgery

The limited workspace in pediatric endoscopic surgery makes surgical suturing one of the most difficult tasks. During suturing, surgeons have to prevent collisions between tools and also collisions with the surrounding tissues. Surgical robots have been shown to be effective in adult laparoscopy, but assistance for suturing in constrained workspaces has not been yet fully explored. In this letter, we propose guidance virtual fixtures to enhance the performance and the safety of suturing while generating the required task constraints using constrained optimization and Cartesian force feedback. We propose two guidance methods: looping virtual fixtures and a trajectory guidance cylinder, that are based on dynamic geometric elements. In simulations and experiments with a physical robot, we show that the proposed methods achieve a more precise and safer looping in robot-assisted pediatric endoscopy.Comment: Accepted on RA-L/ICRA 2020, 8 Pages. Fixed a few typo

Panel‑based next‑generation sequencing facilitates the characterization of childhood acute myeloid leukemia in clinical settings

Acute myeloid leukemia (AML) accounts for ~20% of pediatric leukemia cases. The prognosis of pediatric AML has been improved in recent decades, but it trails that of most other types of pediatric cancer, with mortality rates of 30‑40%. Consequently, newer more targeted drugs are required for incorporation into treatment plans. These newer drugs selectively target AML cells with specific gene alterations. However, there are significant differences in genetic alterations between adult and pediatric patients with AML. In the present study, inexpensive and rapid next‑generation sequencing (NGS) of >150 cancer‑related genes was performed for matched diagnostic, remission and relapse (if any) samples from 27 pediatric patients with AML. In this analysis, seven genes were recurrently mutated. KRAS was mutated in seven patients, NRAS was mutated in three patients, and KIT, GATA1, WT1, PTPN11, JAK3 and FLT3 were each mutated in two patients. Among patients with relapsed AML, six harbored KRAS mutations at diagnosis; however, four of these patients lost these mutations at relapse. Additionally, two genetic alterations (FLT3‑ITD and TP53 alterations) were detected among patients who eventually relapsed, and these mutations are reported to be adverse prognostic factors for adult patients with AML. This panel‑based, targeted sequencing approach may be useful in determining the genetic background of pediatric AML and improving the prediction of treatment response and detection of potentially targetable gene alterations. RAS pathway mutations were highly unstable at relapse; therefore, these mutations should be chosen as a target with caution. Incorporating this panel‑based NGS approach into the clinical setting may allow for a patient‑oriented strategy of precision treatment for childhood AML