Synthesis of 13C-labelled, bicyclic mimetics of natural enediynes

Using a versatile synthesis with 13CH3PPh3I and CH313CO2Et as 13C sources, the first examples of nine membered chromophores, which have been differentially labelled with 13C in their carbocyclic enediyne cores, are described

LHDヘリカル閉ダイバータのための新コンセプト真空容器内クライオソープションポンプの開発

The in-vessel cryo-sorption pump for the Closed Helical Divertor (CHD) in the Large Helical Device (LHD) has been developed at the National Institute for Fusion Science (NIFS). An organic adhesive-free bonding technique for attaching activated carbon pellets to a copper cold panel was invented, which employs the indium solder with intermediate materials. The prototype of the CHD with the newly developed cryo-sorption pump was installed in the LHD. Performance of the cryo-sorption pump was estimated in the LHD vacuum vessel. A satisfactory result of the maximum pumping speed up to 9 m3/s was obtained with one divertor module in one toroidal section (10% of the torus), which is equivalent to the required pumping speed of the CHD

HbA1c and telemedicine during COVID-19

Aims/Introduction: To investigate whether the COVID-19 pandemic affected behavioral changes and glycemic control in patients with diabetes and to conduct a survey of telemedicine during the pandemic. Materials and Methods: In this retrospective study, a total of 2,348 patients were included from 15 medical facilities. Patients were surveyed about their lifestyle changes and attitudes toward telemedicine. Hemoglobin A1c (HbA1c) levels were compared among before (from June 1 to August 31, 2019) and in the first (from June 1 to August 31, 2020) and in the second (from June 1 to August 31, 2021) year of the pandemic. A survey of physician attitudes toward telemedicine was also conducted. Results: The HbA1c levels were comparable between 2019 (7.27 ± 0.97%), 2020 (7.28 ± 0.92%), and 2021 (7.25 ± 0.94%) without statistical difference between each of those 3 years. Prescriptions for diabetes medications increased during the period. The frequency of eating out was drastically reduced (51.7% in 2019; 30.1% in 2020), and physical activity decreased during the pandemic (48.1% in 2019; 41.4% in 2020; 43.3% in 2021). Both patients and physicians cited increased convenience and reduced risk of infection as their expectations for telemedicine, while the lack of physician–patient interaction and the impossibility of consultation and examination were cited as sources of concern. Conclusions: Our data suggest that glycemic control did not deteriorate during the COVID-19 pandemic with appropriate intensification of diabetes treatment in patients with diabetes who continued to attend specialized diabetes care facilities, and that patients and physicians shared the same expectations and concerns about telemedicine

Chirality Emergence in Thin Solid Films of Amino Acids by Polarized Light from Synchrotron Radiation and Free Electron Laser

One of the most attractive hypothesis for the origin of homochirality in terrestrial bioorganic compounds is that a kind of “chiral impulse” as an asymmetric excitation source induced asymmetric reactions on the surfaces of such materials such as meteorites or interstellar dusts prior to the existence of terrestrial life (Cosmic Scenario). To experimentally introduce chiral structure into racemic films of amino acids (alanine, phenylalanine, isovaline, etc.), we irradiated them with linearly polarized light (LPL) from synchrotron radiation and circularly polarized light (CPL) from a free electron laser. After the irradiation, we evaluated optical anisotropy by measuring the circular dichroism (CD) spectra and verified that new Cotton peaks appeared at almost the same peak position as those of the corresponding non-racemic amino acid films. With LPL irradiation, two-dimensional anisotropic structure expressed as linear dichroism and/or linear birefringence was introduced into the racemic films. With CPL irradiation, the signs of the Cotton peaks exhibit symmetrical structure corresponding to the direction of CPL rotation. This indicates that some kinds of chiral structure were introduced into the racemic film. The CD spectra after CPL irradiation suggest the chiral structure should be derived from not only preferential photolysis but also from photolysis-induced molecular structural change. These results suggest that circularly polarized light sources in space could be associated with the origin of terrestrial homochirality; that is, they would be effective asymmetric exciting sources introducing chiral structures into bio-organic molecules or complex organic compounds

A novel method, digital genome scanning detects KRAS gene amplification in gastric cancers: involvement of overexpressed wild-type KRAS in downstream signaling and cancer cell growth

<p>Abstract</p> <p>Background</p> <p>Gastric cancer is the third most common malignancy affecting the general population worldwide. Aberrant activation of KRAS is a key factor in the development of many types of tumor, however, oncogenic mutations of <it>KRAS </it>are infrequent in gastric cancer. We have developed a novel quantitative method of analysis of DNA copy number, termed digital genome scanning (DGS), which is based on the enumeration of short restriction fragments, and does not involve PCR or hybridization. In the current study, we used DGS to survey copy-number alterations in gastric cancer cells.</p> <p>Methods</p> <p>DGS of gastric cancer cell lines was performed using the sequences of 5000 to 15000 restriction fragments. We screened 20 gastric cancer cell lines and 86 primary gastric tumors for <it>KRAS </it>amplification by quantitative PCR, and investigated <it>KRAS </it>amplification at the DNA, mRNA and protein levels by mutational analysis, real-time PCR, immunoblot analysis, GTP-RAS pull-down assay and immunohistochemical analysis. The effect of <it>KRAS </it>knock-down on the activation of p44/42 MAP kinase and AKT and on cell growth were examined by immunoblot and colorimetric assay, respectively.</p> <p>Results</p> <p>DGS analysis of the HSC45 gastric cancer cell line revealed the amplification of a 500-kb region on chromosome 12p12.1, which contains the <it>KRAS </it>gene locus. Amplification of the <it>KRAS </it>locus was detected in 15% (3/20) of gastric cancer cell lines (8–18-fold amplification) and 4.7% (4/86) of primary gastric tumors (8–50-fold amplification). <it>KRAS </it>mutations were identified in two of the three cell lines in which <it>KRAS </it>was amplified, but were not detected in any of the primary tumors. Overexpression of KRAS protein correlated directly with increased <it>KRAS </it>copy number. The level of GTP-bound KRAS was elevated following serum stimulation in cells with amplified wild-type <it>KRAS</it>, but not in cells with amplified mutant <it>KRAS</it>. Knock-down of <it>KRAS </it>in gastric cancer cells that carried amplified wild-type <it>KRAS </it>resulted in the inhibition of cell growth and suppression of p44/42 MAP kinase and AKT activity.</p> <p>Conclusion</p> <p>Our study highlights the utility of DGS for identification of copy-number alterations. Using DGS, we identified <it>KRAS </it>as a gene that is amplified in human gastric cancer. We demonstrated that gene amplification likely forms the molecular basis of overactivation of KRAS in gastric cancer. Additional studies using a larger cohort of gastric cancer specimens are required to determine the diagnostic and therapeutic implications of <it>KRAS </it>amplification and overexpression.</p

Inter-individual difference in the effect of mirror reflection-induced visual feedback on phantom limb awareness in forearm amputees.

OBJECTIVE: To test whether the phantom limb awareness could be altered by observing mirror reflection-induced visual feedback (MVF) in unilateral forearm amputees. METHODS: Ten unilateral forearm amputees were asked to perform bilateral (intact and phantom) synchronous wrist motions with and without MVF. During wrist motion, electromyographic activities in the extensor digitorum longus (EDL) and flexor carpi radialis muscles (FCR) were recorded with bipolar electrodes. Degree of wrist range of motion (ROM) was also recorded by electrogoniometry attached to the wrist joint of intact side. Subjects were asked to answer the degree of attainment of phantom limb motion using a visual analog scale (VAS: ranging from 0 (hard) to 10 (easy)). RESULTS: VAS and ROM were significantly increased by utilizing MVF, and the extent of an enhancement of the VAS and wrist ROM was positively correlated (r = 0.72, p<0.05). Although FCR EMG activity also showed significant enhancement by MVF, this was not correlated with the changes of VAS and ROM. Interestingly, while we found negative correlation between EDL EMG activity and wrist ROM, MVF generally affected to be increasing both EDL EMG and ROM. CONCLUSIONS: Although there was larger extent of variability in the effect of MVF on phantom limb awareness, MVF has a potential to enhance phantom limb awareness, in case those who has a difficulty for the phantom limb motion. The present result suggests that the motor command to the missing limb can be re-activated by an appropriate therapeutic strategy such as mirror therapy