Development of a 1,3a,6a-triazapentalene derivative as a compact and thiol-specific fluorescent labeling reagent

For the fluorescence imaging of biologically active small compounds, the development of compact fluorophores that do not perturb bioactivity is required. Here we report a compact derivative of fluorescent 1,3a,6a-triazapentalenes, 2-isobutenylcarbonyl-1,3a,6a-triazapentalene (TAP-VK1), as a fluorescent labeling reagent. The reaction of TAP-VK1 with various aliphatic thiols proceeds smoothly to afford the corresponding 1,4-adducts in high yields, and nucleophiles other than thiols do not react. After the addition of thiol groups in dichloromethane, the emission maximum of TAP-VK1 shifts to a shorter wavelength and the fluorescence intensity is substantially increased. The utility of TAP-VK1 as a compact fluorescent labeling reagent is clearly demonstrated by the labeling of Captopril, which is a small molecular drug for hypertension. The successful imaging of Captopril, one of the most compact drugs, in this study demonstrates the usefulness of compact fluorophores for mechanistic studies

Direct Synthesis of Polycyclic Tropinones via Condensation-(4+3) Cycloaddition Cascade Reaction

A concise method of constructing polycyclic tropinone frameworks was developed. The single-step synthesis of polycyclic tropinone consists of an intramolecular (4+3) cycloaddition reaction of N-nosyl-pyrrole with oxyallyl cation that was generated in situ by an intermolecular condensation reaction of the nucleophilic functional groups on a tethered pyrrole with the aldehyde of 2-(silyloxy)-acrolein. This cascade reaction afforded various polycyclic tropinones including tri-, tetra-, and pentacyclic systems in high yields as single diastereomers

Clinical benefits of adjuvant chemotherapy with carboplatin and gemcitabine in patients with non-small cell lung cancer: A single-center retrospective study

Purpose: In cases of non-small cell lung cancer (NSCLC), surgery remains the best option for cure, but surgery is of benefit only when the disease is localized. Although adjuvant chemotherapy reportedly has a significant beneficial effect on survival, the benefit of a carboplatin (CBDCA) regimen is unclear. We therefore investigated the efficacy and tolerability of CBDCA (area under the curve 5) plus gemcitabine (GEM, 1000 mg/m2) as adjuvant chemotherapy. Methods: A total of 82 pStage IB-IIIA NSCLC patients who had undergone complete resection and received adjuvant chemotherapy were analyzed retrospectively. Among them, 65 patients received CBDCA + GEM and 17 received CDDP + VNR. Propensity score analysis generated 17 matched pairs of both groups. Results: Sixty-five patients received CBDCA + GEM. Their 5-year relapse-free survival (RFS) and overall survival were 47.8% (median, 52.5 months) and 76.9% (median, 90.1 months), respectively. Toxicities, which included neutropenia, nausea/ anorexia, fatigue, and vasculitis, were significantly milder than with CDDP + VNR. There were no significant differences in RFS between CBDCA + GEM and CDDP + VNR (p = 0.079) after matching for age, performance status, and pStage. Conclusion: CBDCA + GEM was effective and well tolerated as adjuvant chemotherapy, with a manageable toxicity profile

発達障害児が通過した乳幼児健診システム : 出生時リスクがなかった症例

The enhancement of maternal and child health programs has enabled early detection and intervention in routine health examination for children. However, there are regional differences in the contents of children with mild developmental disorders who had no risks at birth but had developmental problems that were overlooked during infant health checkups. Case 1 was a child whose disability was noticed by the caregiver but who passed the health checkup and was unable to receive appropriate follow-up. The disorder was detected by a speech therapist through a community childcare support program. Case 2 was a child whose disability was not noticed by the caregiver and who passed the health checkup. The disorder was detected by a speech therapist through the consultation system at our department. Based on these two cases, the following problems concerning existing screening checklist systems were identified as the causes of failure to detect disorders during checkups: lack of screening items, low expertise of personnel conducting checkups, lenient criteria, and insufficient follow-up systems. Considering the necessity for early detection and intervention in children with disabilities and the importance of follow-up after checkups, it was considered necessary for speech-language-hearing therapists to be actively involved in the check up program

A comprehensive survey on quantum computer usage: How many qubits are employed for what purposes?

Quantum computers (QCs), which work based on the law of quantum mechanics, are expected to be faster than classical computers in several computational tasks such as prime factoring and simulation of quantum many-body systems. In the last decade, research and development of QCs have rapidly advanced. Now hundreds of physical qubits are at our disposal, and one can find several remarkable experiments actually outperforming the classical computer in a specific computational task. On the other hand, it is unclear what the typical usages of the QCs are. Here we conduct an extensive survey on the papers that are posted in the quant-ph section in arXiv and claim to have used QCs in their abstracts. To understand the current situation of the research and development of the QCs, we evaluated the descriptive statistics about the papers, including the number of qubits employed, QPU vendors, application domains and so on. Our survey shows that the annual number of publications is increasing, and the typical number of qubits employed is about six to ten, growing along with the increase in the quantum volume (QV). Most of the preprints are devoted to applications such as quantum machine learning, condensed matter physics, and quantum chemistry, while quantum error correction and quantum noise mitigation use more qubits than the other topics. These imply that the increase in QV is fundamentally relevant, and more experiments for quantum error correction, and noise mitigation using shallow circuits with more qubits will take place.Comment: 14 pages, 5 figures, figures regenerate

構音障害を主訴に来学した発達性読み書き障害児の1例

Here we present the case of a child who visited the university with the chief complaint of dysarthria. He initially suffered from dysarthria and mild mental retardation, but later developed serious problems with reading and writing. We considered his phonological processing ability and a possible connection with developmental dyslexia. The child was a 7-year-old boy who was in second grade at a regular elementary school. At 5 years of age, he was diagnosed with a submucous cleft palate and underwent surgery to correct this. After surgery, he was evaluated and started receiving training. He was diagnosed with language delay due to mild mental retardation and dysgraphia accompanying underdeveloped dysarthria, and received 7 months of ST training. In the re-evaluation that followed his training, he was not seen to have general mental retardation, but his problems with reading and writing became apparent. Cross-examining his problems reading and writing with a triangle model and visual cognition processes suggested a problem with bilateral processing of writing and phonology. This was a decoding problem, which is the basic condition of a patient with developmental dyslexia. The boy\u27s core problem thus appeared to be a phonological type of developmental dyslexia

維持期感覚性失語症者に対する語音弁別訓練の検討 : 単音節・有意味二音節の訓練が聴覚的理解力に及ぼす効果

Two types of monosyllabic speech discrimination training and two types of meaningful disyllabic speech discrimination training were conducted in a man with chronic Wernicke\u27s aphasia. The effects of training on speech discrimination ability and auditory comprehension were investigated. The patient was a 48-year-old, right-handed male who started training about 4 years after putaminal hemorrhage. The training comprised a daily home task for a total of about 4 months, and the training results were measured once a week by a speech, language hearing therapist. In the monosyllabic speech discrimination training, a significant increase was seen in speech discrimination ability both in training with and without using written characters. In the speech discrimination training with meaningful disyllabic words, a better effect of training was seen with a method using oral reading of Kanji characters compared with a method of listening to sounds and comparing them with written characters. In an investigation of the effect using a Test of Lexical Processing in Aphasia for auditory comprehension, no change was observed with monosyllabic speech discrimination training; however, a significant increase in the number of correct answers was observed with speech discrimination training using meaningful disyllabic words

漢字書き取りに困難を示した発達性読み書き障害の一例

Herein, we present a with development dyslexia whose writing skills were analyzed in detail, and discuss future support options. The patient was a 10 year-old boy who was a found grader attending a regular elementary school. The results of the WISC-III, K-ABC, ITPA, PVT-R, DTVP, diagnostic reading tests and STRAW showed that the patient had difficulty writing kanji characters despite the absence of overall intellectual, psychological or social disorders. Hence, the writing skills of the patient were analyzed by asking the patient to write common kanji characters and differentiate the character shapes of kanji characters. The visual information processing process that is required for learning to write kanji characters involves: 1) visual recognition of model kanji characters; 2) visual memory and retention; 3) memory recall of kanji forms. The patient was able to differentiate the character shapes of kanji characters and recognize individual differences; however, his spatial arrangement skills were low. Furthermore, the results suggested that he had difficulty retaining visual memory, and he was not able to accurately recognize kanji characters that are visual pictorial forms. Therefore, it was deduced that the patient could not accurately ascertain kanji forms and had difficulty writing kanji characters. Although the patient was able to differentiate similar character shapes, assistive technology may be an effective auxiliary technique for alleviating learning difficulties due to dysgraphia

発達性読み書き障害児に対するATを用いた言語訓練

In the present study, we introduced an assistive technology (AT) for a child with developmental dyslexia and dysgraphia who demonstrated difficulty writing kanji characters, and reviewed the effects using the information processing model. The patient was an 11-year-old boy in the fifth grade at a regular elementary school. He had problems in the visual memory and retention stage of the information processing model and presented with kanji dysgraphia. Memory recall of kanji shape, which was poorly memorized and retained by the patient, was achieved through typing. As this method was therefore believed to be beneficial, the language training using computer-based AT commenced. Content over the year of training was divided into three phases: I, II, and III. Word input (three characters) typing speed was approximately 60 seconds in phase I, approximately 20 seconds in phase II and 3 to 5 seconds in phase III; as each training was repeated, speed gradually increased. The number of characters that could be typed also increased from monosyllables in phase I to words in phase II and short sentences in phase III. The above findings suggest that computer substitution in the area of difficulty for the patient provided an effective support method for dysgraphia