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Emergence of resistance to carbocyclic oxetanocin G in herpes simplex virus type 1 and genetic analysis of resistant mutants

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Acta Pharmacologica Sinica 2004年第7期25卷 75-80页

作者： hiroshi SHIOTA Department of Ophthalmology Japan School of Medicine The University of Tokushima Tokushima 770

AIM: To elucidate the potentiality of emergence of drug-resistance to carbocyclic oxetanocin G (***-G ), a new effective antiviral drug for herpetic keratitis during treatment and the mechanism of this drug resistance. METHODS: A ***-G resistant strain (***-Gr) was established by serially propagating the herpes simplex virus (HSV) -1 in African green monkey kidney (VERO) cells in the presence of ***-G. After the drug sensitiv- ity assay and the thymidine kinase (TK) activity assay, the molecular basis for the drug resistance was studied using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and PCR direct se- quencing technology. RESULTS: After the 10th passage in 10 μm ***-G, the ED50 of the ***-Gr was 17.08-fold greater than that of the original strain on the average and the TK activities of these resistant strains were extremely reduced. PCR-SSCP analysis on TK gene of the wild HSV-1 and the ***-Gr showed altered migration patterns in part 3 and part 4, while PCR-SSCP analysis on DNA polymerase gene showed no difference among the viruses. Sequence analysis revealed a deletion of G at position of 430 that caused frameshift, resulting in premature termination in the TK gene. CONCLUSION: The drug resistance to ***-G may appear during the treatment due to the deficiency of TK activity caused by a single mutation in the TK gene of HSV-1.

关键词： carbocyclic oxetanocin G human herpesvirus 1 viral drug resistance thymidine kinase

Chiral ligand-protected gold nanoclusters: Considering the optical activity from a viewpoint of ligand dissymmetric field

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Progress in Natural Science:Materials International 2016年第5期26卷 428-439页

作者： hiroshi Yao Graduate School of Material Science University of Hyogo

Chirality is a geometric property of a physical, chemical, or biological object, which is not superimposable on its mirror image. Its significant presence has led to a strong demand in the development of chiral drugs, sensors,catalysts, and photofunctional materials. In recent years, chirality of nanoscale organic/inorganic hybrids has received tremendous attention owing to potential applications in chiral nanotechnology. In particular, with the recent progress in the syntheses and characterizations of atomically precise gold nanoclusters protected by achiral thiolates, atomic level origins of their chirality have been unveiled. On the other hand, chirality or optical activity in metal nanoclusters can also be introduced via the surface chiral ligands, which should be universal for the nanosystems. This tutorial review presents some optically-active metal(gold) nanoclusters protected by chiral thiolates or phosphines, and their chiroptical(or circular dichroism; CD) properties are discussed mostly from a viewpoint of the ligand dissymmetric field scheme. The examples are the gold nanoclusters protected by(R)-/(S)-2-phenylpropane-1-thiol,(R)-/(S)-mercaptosuccinic acid, phenylboronateD/L-fructose complexes, phosphine sulfonate-ephedrinium ion pairs, or glutathione. Some methodologies for versatile asymmetric transformation and chiroptical controls of the nanocluster compounds are also *** the dissymmetric field model as the origin of optical activity, the chiroptical responses of the gold nanoclusters are strongly associated with coupled oscillator and/or CD stealing mechanisms based on the concept of induced CD(ICD) derived from a perturbation theory, so on this basis, some characteristic features of the observed CD responses of chiral ligand-protected gold nanoclusters are presented in detail. We believe that various kinds of origins of chirality found in ligand-protected gold nanoclusters may provide models for understanding those of many related nanomater

关键词： Chiral ligand Monolayer-protected gold nanoclusters Dissymmetric field model Induced CD Asymmetric transformation Alloying effect

Eustachian tube involvement in a patient with relapsing polychondritis detected by magnetic resonance imaging:A case report

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World Journal of Clinical Cases 2022年第4期10卷 1441-1446页

作者： Daisuke Yunaiyama Akiko Aoki hiroshi Kobayashi Miwako Someya Mitsuru Okubo Kazuhiro Saito Department of Radiology Tokyo Medical University HospitalShinjuku-ku 160-0023TokyoJapan Department of Radiology Tokyo Medical University Hachioji Medical CenterHachioji-shi 193-0998Japan Department of Rheumatology Tokyo Medical University Hachioji Medical CenterHachioji-shi 193-0998Japan Department of Otorhinolaryngology Head and Neck SurgeryTokyo Medical University Hachioji Medical CenterHachioji-shi 193-0998Japan

BACKGROUND Relapsing polychondritis(RP)is a rare inflammatory disease involving the systemic cartilage,such as the auricle,trachea,and bronchiole,among others.A patient with RP shows variable symptoms based on the involved *** SUMMARY A 72-year-old Japanese woman with a history of redness of the bilateral auricles for 3 d was referred to a *** clinician prescribed antibiotics to the patient;however,the symptoms worsened;thus,she was referred to our *** and neck magnetic resonance imaging(MRI)showed edematous auricle with remarkable contrast,fluid collection in the bilateral mastoid cells,suggesting otitis *** eustachian tube(ET)on the right side was also edematous with contrast *** patient was suspected of RP according to the diagnostic criteria.A biopsy of the auricular cartilage was performed by an otorhinolaryngologist,confirming pathological proof of *** with steroids were immediately administered *** We highlight a rare case of RP with radiologically confirmed involvement of ET in the MRI.

关键词： Relapsing polychondritis Magnetic resonance imaging Contrast enhancement Otitis media with effusion Eustachian tube Case report

The anti-oncogenic effect of 17-DMAG via the inactivation of HSP90 and MET pathway in osteosarcoma cells

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Oncology Research 2023年第5期31卷 631-643页

作者： MASANORI KAWANO KAZUHIRO TANAKA ICHIRO ITONAGA TATSUYA IWASAKI YUTA KUBOTA hiroshi TSUMURA Department of Orthopaedic Surgery Faculty of MedicineOita UniversityOita879-5593Japan

Heat shock protein(HSP)90 plays a crucial role in correcting the misfolded three-dimensional structure of proteins,assisting them in folding into proper ***90 is critical in maintaining the normal functions of various proteins within cells,as essential factors for cellular ***,HSP90 simultaneously supports the maturation of cancer-related proteins,including mesenchymal epithelial transition factor(MET)within tumor *** osteosarcoma cell lines had elevated MET expression in the cDNA array in our ***,a tyrosine kinase receptor,promotes proliferation and an anti-apoptotic state through the activation of the MET pathway constructed by *** this study,we treated osteosarcoma cells with an HSP90 inhibitor,17-demethoxygeldanamycin hydrochloride(17-DMAG),and assessed the changes in the MET signaling pathway and also the antitumor effect of the *** cell cycle in osteosarcoma cells administered 17-DMAG was found to be halted at the G2/M ***,treatment with 17-DMAG inhibited cell proliferation and induced *** of tumor cell proliferation was also observed in an in vivo model system,mice that were treated with *** on the results of this study,we were able to confirm that 17-DMAG promotes inhibition of osteosarcoma cell proliferation and induction of apoptosis by inhibition of MET,a protein highly expressed in osteosarcoma *** approach may be useful for the establishment of a new treatment strategy for patients resistant to the standard treatment for osteosarcoma.

关键词： Osteosarcoma MET HSP90 17-DMAG

Acute kidney injury and the compensation of kidney function after nephrectomy in living donation

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World Journal of Transplantation 2022年第8期12卷 223-230页

作者： Kenji Okumura Holly Grace hiroshi Sogawa Shigeyoshi Yamanaga Department of Surgery Westchester Medical Center/New York Medical CollegeValhallaNY 10595United States Department of Surgery New York Medical CollegeValhallaNY 10595United States Department of Surgery Japanese Red Cross Kumamoto HospitalKumamoto 861-8520Japan

Acute kidney injury(AKI)incidence is growing rapidly,and AKI is one of the predictors of inpatient *** nephrectomy,all the patients have decreased kidney function with AKI and recover from ***,the characteristic and behavior of AKI is different from usual AKI and compensatory kidney function has been well known in the postoperative setting,especially in living *** this review,we have focused on the compensation of kidney function after nephrectomy in living *** discuss factors that have been identified as being associated with kidney recovery in donors including age,sex,body mass index,remnant kidney volume,estimated glomerular filtration rate,and various comorbidities.

关键词： Acute kidney injury Kidney transplant donor Compensation Kidney function

Classification of rectal cancer according to recurrence types-comparison of Japanese guidelines and Western guidelines

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World Journal of Clinical Cases 2022年第36期10卷 13284-13292页

作者： hiroshi Miyakita Yutaro Kamei Lin Fung Chan Kazutake Okada Hajime Kayano Seiichiro Yamamoto Department of Digestive System Surgery Tokai University School of MedicineIsehara 259-1193KanagawaJapan

BACKGROUND Rectal cancer is characterized by more local recurrence(LR)and lung metastasis than colon ***,the diagnosis of rectal cancer is not standardized as there is no global consensus on its definition and *** classification of rectal cancer differs between Japanese and Western *** To clarify the characteristics of rectal cancer by comparing the tumor location and characteristics of rectal cancer with those of colon cancer according to each set of *** A total of 958 patients with Stage II and III colorectal cancer were included in the analysis:607 with colon cancer and 351 with rectal *** of rectal cancers was assessed by enema examination and rigid *** to Japan guidelines,rectal cancer is classified as Rb(below the peritoneal inversion),Ra(between the inferior margin of second sacral vertebrae and Rb)or RS(between Ra and sacral promontory).RESULTS There were no significant differences between RS rectal cancer and colon cancer in the rates of liver and lung metastasis or *** metastasis and LR were significantly more common among Rb rectal cancer(in Japan)than in colon cancer(P=0.0043 and P=0.0002,respectively).Lung metastases and LR occurred at significantly higher rates in rectal cancer measuring≤12 cm and≤10 cm than in colon cancers(P=0.0117,P=0.0467,P=0.0036,P=0.0010).Finally,the rates of liver metastasis,lung metastasis,and LR in rectal cancers measuring 11 cm to 15 cm were 6.9%,2.8%,and 5.7%,*** were equivalent to the rates in colon *** High rectal cancer may be treated with the same treatment strategies as colon *** was no difference in the classification of colorectal cancer between Japan and Western countries.

关键词： Colon cancer Metastasis Local recurrence Classification of rectal cancer Western guidelines Japanese guideline

Heterogeneous FASnI3 Absorber with Enhanced Electric Field for High-Performance Lead-Free Perovskite Solar Cells

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Nano-Micro Letters 2022年第6期14卷 234-247页

作者： Tianhao Wu Xiao Liu Xinhui Luo hiroshi Segawa Guoqing Tong Yiqiang Zhang Luis KOno Yabing Qi Liyuan Han State Key Laboratory of Metal Matrix Composites School of Material Science and EngineeringShanghai Jiao Tong UniversityShanghai 200240People’s Republic of China Special Division of Environmental and Energy Science Komaba Organization for Educational Excellence(KOMEX)College of Arts and SciencesUniversity of TokyoTokyo 153-8902Japan Energy Materials and Surface Sciences Unit(EMSSU) Okinawa Institute of Science and Technology Graduate University(OIST)1919-1 TanchaOnna-sonKunigami-gunOkinawa 904-0495Japan School of Materials Science and Engineering Henan Institute of Advanced TechnologyZhengzhou UniversityZhengzhou 450001People’s Republic of China

Lead-free tin perovskite solar cells(PSCs)have undergone rapid development in recent years and are regarded as a promising ecofriendly photovoltaic ***,a strategy to suppress charge recombination via a built-in electric field inside a tin perovskite crystal is still *** the present study,a formamidinium tin iodide(FASnI;)perovskite absorber with a vertical Sn;gradient was fabricated using a Lewis base-assisted recrystallization method to enhance the built-in electric field and minimize the bulk recombination loss inside the tin ***-dependent X-ray photoelectron spectroscopy revealed that the Fermi level upshifts with an increase in Sn;content from the bottom to the top in this heterogeneous FASnI;film,which generates an additional electric field to prevent the trapping of photo-induced electrons and ***,the Sn;-gradient FASnI;absorber exhibits a promising efficiency of 13.82%for inverted tin PSCs with an open-circuit voltage increase of 130 mV,and the optimized cell maintains over 13%efficiency after continuous operation under 1-sun illumination for 1,000 h.

关键词： Gradient FASnI3 absorber Built-in electric field Bulk charge recombination Lead-free perovskite solar cell

Effect of Transit Capacity onto Morning Commute Problem with Competitive Modes and Distributed Demand

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Journal of Transportation Technologies 2022年第1期12卷 80-95页

作者： hiroshi Shimamoto Department of Civil and Environmental Engineering University of Miyazaki Japan

A lane exclusively for transit is one measure to reduce urban congestion and intelligent transportation systems (ITSs) are expected to make this policy more effective. However, the advantage may be limited if a transit agency does not provide sufficient vehicles. This study evaluates the effect of transit capacity on a dedicated transit lane policy by examining the morning commute problem, by defining user equilibrium and system optimisation considering transit capacity. It was confirmed that reduced transit capacity under user equilibrium smoothly increases the transit cost per person, which decreases the duration period of the dedicated transit lane and increases the number of early and delayed car commuters. However, the effect of reducing transit capacity under a system optimum depends on the initial solution of the system optimum.

关键词： Dedicated Transit Lane Transit Capacity User Equilibrium System Optimum System-Optimal Pricing

Learning the right channel in multimodal imaging: automated experiment in piezoresponse force microscopy

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npj Computational Materials 2023年第1期9卷 2008-2015页

作者： Yongtao Liu Rama K.Vasudevan Kyle P.Kelley hiroshi Funakubo Maxim Ziatdinov Sergei V.Kalinin Center for Nanophase Materials Sciences Oak Ridge National LaboratoryOak RidgeTN 37923USA Department of Materials Science and Engineering Tokyo Institute of TechnologyYokohama 226-8502Japan Computational Sciences and Engineering Division Oak Ridge National LaboratoryOak RidgeTN 37923USA Department of Materials Science and Engineering University of TennesseeKnoxvilleTN 37996USA

We report the development and experimental implementation of the automated experiment workflows for the identification of thebest predictive channel for a phenomenon of interest in spectroscopic measurements. The approach is based on the combinationof ensembled deep kernel learning for probabilistic predictions and a basic reinforcement learning policy for channel selection. Itallows the identification of which of the available observational channels, sampled sequentially, are most predictive of selectedbehaviors, and hence have the strongest correlations. We implement this approach for multimodal imaging in piezoresponse forcemicroscopy (PFM), with the behaviors of interest manifesting in piezoresponse spectroscopy. We illustrate the best predictivechannel for polarization-voltage hysteresis loop and frequency-voltage hysteresis loop areas is amplitude in the model samples. Thesame workflow and code are applicable for any multimodal imaging and local characterization methods.

关键词： automated policy modal