Background/Aim: Immuno-oncology (IO) combination therapy has become the standard of treatment for advanced renal cell carcinoma (RCC). In this retrospective study, we compared the efficacy of ...first-line molecular targeted therapy (MTT), administered as monotherapy, and IO combination therapy using real-world data of Japanese patients. Patients and Methods: The clinical information of 202 patients with RCC who received MTT (n=144) or IO combination therapy (n=58) at the Kurume University Hospital from May 2008 to May 2022 was collected and retrospectively analyzed. The Cox proportional hazards model was used for univariate and multivariate analyses, with hazard ratios (HRs) and 95% confidence intervals (CIs) calculated. Results: The patients treated with IO combination therapy had a prolonged progression-free survival (PFS) compared with those treated with MTT (p=0.0038). IO combination therapy was significantly associated with a better PFS in patients with intermediate (p=0.0072) and poor risk (p=0.0411) but not in those with favorable risk (p=0.5434). Furthermore, overall survival with IO combination therapy was significantly better in patients at poor risk (p=0.0335). Multivariate analyses suggested that prior nephrectomy (HR=1.501, 95%CI=1.048-2.150, p=0.0268) and first-line therapy (HR=1.962, 95%CI=1.288-2.986, p=0.0017) were independent prognostic factors for PFS. Conclusion: IO combination therapy significantly improved the PFS of patients with advanced RCC, especially those with intermediate- and poor-risk disease. Further investigations focusing on the improvement of survival are warranted.
In this paper, we demonstrated an actively Q-switched, radially polarized, and laser-diode end-pumped Nd:YAG laser with an acousto-optic modulator as the Q switch and a photonic crystal grating as ...the output coupler. The laser generated pulses of 26.4–67.2 ns duration, and the repetition rate can be continuously adjusted from 500 Hz to 9.238 kHz with peak power up to 7.75 kW. Such a radially polarized pulse would facilitate numerous applications.
Abstract
We present a deep neural network real/bogus classifier that improves classification performance in the Tomo-e Gozen Transient survey by handling label errors in the training data. In the ...wide-field, high-frequency transient survey with Tomo-e Gozen, the performance of conventional convolutional neural network classifiers is not sufficient as about 106 bogus detections appear every night. In need of a better classifier, we have developed a new two-stage training method. In this training method, label errors in the training data are first detected by normal supervised learning classification, and then they are unlabeled and used for training of semi-supervised learning. For actual observed data, the classifier with this method achieves an area under the curve (AUC) of 0.9998 and a false positive rate (FPR) of 0.0002 at a true positive rate (TPR) of 0.9. This training method saves relabeling effort by humans and works better on training data with a high fraction of label errors. By implementing the developed classifier in the Tomo-e Gozen pipeline, the number of transient candidates was reduced to ∼40 objects per night, which is ∼1/130 of the previous version, while maintaining the recovery rate of real transients. This enables more efficient selection of targets for follow-up observations.
We report on laser-diode pumped low-threshold, and compact passively Q-switched Yb:YAG microchip lasers, with Cr4+:YAG crystals as the saturable absorbers. The laser threshold at the fundamental ...wavelength of 1.03 Delta *mm is as low as 0.25 W, and the slope efficiency is as high as 36.8%, and the optical-to-optical efficiency is as high as 27% for the 95% initial transmission of the Cr4+:YAG crystal. A pulse width of 1.35 ns and peak power of over 8.2 kW was obtained. Using a 5 mm thick KTP crystal as the second-harmonic generation medium, 514.7 nm green light of 155 mW power was generated. The pulse duration of 480 ps was generated at 1.03 Delta *mm by using 85% of the initial transmission of the Cr4+:YAG saturable absorber. Stable single-longitudinal-mode oscillation and wide-separated multi-longitudinal-mode oscillation due to the etalon effect of the Cr4+:YAG thin plate was achieved at different pump power levels.
Organelle (mitochondria and chloroplasts in plants) genomes lost a large number of genes after endosymbiosis occurred. Even after this major gene loss, organelle genomes still lose their own genes, ...even those that are essential, via gene transfer to the nucleus and gene substitution of either different organelle origin or de novo genes. Gene transfer and substitution events are important processes in the evolution of the eukaryotic cell. Gene loss is an ongoing process in the mitochondria and chloroplasts of higher plants. The gene for ribosomal protein S16 (rps16) is encoded in the chloroplast genome of most higher plants but not in Medicago truncatula and Populus alba. Here, we show that these 2 species have compensated for loss of the rps16 from the chloroplast genome by having a mitochondrial rps16 that can target the chloroplasts as well as mitochondria. Furthermore, in Arabidopsis thaliana, Lycopersicon esculentum, and Oryza sativa, whose chloroplast genomes encode the rps16, we show that the product of the mitochondrial rps16 has dual targeting ability. These results suggest that the dual targeting of RPS16 to the mitochondria and chloroplasts emerged before the divergence of monocots and dicots (140-150 MYA). The gene substitution of the chloroplast rps16 by the nuclear-encoded rps16 in higher plants is the first report about ongoing gene substitution by dual targeting and provides evidence for an intermediate stage in the formation of this heterogeneous organelle.
The peptide synthetase gene operon, which consists ofmcyA, mcyB, and mcyC, for the activation and incorporation of the five amino acid constituents of microcystin has been identified T. Nishizawa et ...al. (1999) J. Biochem. 126, 520–h;529. By sequencing an additional 34 kb of DNA from microcystin-producing Microcystis aeruginosa K-139, we identified the residual microcystin synthetase gene operon, which consists of mcyD, mcyE, mcyF, and mcyG, in the opposite orientation to the mcyABC operon. McyD consisted of two polyketide synthase modules, and McyE contained a polyketide synthase module at the N-terminus and a peptide synthetase module at the C-terminus. McyF was found to exhibit similarity to amino acid racemase. McyG consisted of a peptide synthetase module at the N-terminus and a polyketide synthase at the C-terminus. The microcystin synthetase gene cluster was conserved in another microcystin-producing strain, Microcyatis sp. S-70, which produces Microcystin-LR, -RR, and -YR. Insertional mutagenesis of mcyA, mcyD, or mcyE in Microcystis sp. S-70 abolished microcystin production. In conclusion, the mcyDEFG operon is presumed to be responsible for 3-amino-9-methoxy-2,63-trime-thyl-10-phenyldeca-4,6-dienoic acid (Adda) biosynthesis, and the incorporation of Adda and glutamic acid into the microcystin molecule
The microchip laser performance of Yb:YAG crystals doped with different ytterbium concentrations (CYb=10, 15, and 20 at.%) has been investigated at ambient temperature without active cooling of the ...gain media. Efficient laser oscillation for a 1-mm-thick YAG doped with 10 at.% Yb3+ ions was achieved at 1030 and 1049 nm with slope efficiencies of 85% and 81%, correspondingly. The laser performance of heavy-doped Yb:YAG crystals was limited by the thermal population at terminated lasing level and thermal lens effect at room temperature without sufficient cooling of the samples. The laser emitting spectra of Yb:YAG microchip lasers with different Yb concentrations and output couplings are addressed with the local temperature rise, due to the absorption of the pump power inside the gain media under different pump levels.
A theoretical model based on a quasi-four-level system is modified to investigate the effect of Yb concentration on performance of continuous-wave Yb:YAG microchip lasers by taking into account ...temperature-dependent thermal population distribution, temperature-dependent emission cross-section and concentration-dependent fluorescence lifetime, thermal loading, thermal conductivity, and thermal expansion coefficient. The local temperature rise in Yb:YAG crystal caused by the absorbed pump power plays an important role in the laser performance of Yb:YAG microchip lasers working at ambient temperature without actively cooling the sample. The output wavelengths dependent on output coupling, Yb concentration, and pump power level were analyzed quantitatively. The numerical simulation of Yb:YAG microchip lasers is in good agreement with experimental data. The optimized laser operation for Yb:YAG microchip lasers is proposed by varying the thickness and output coupling for different Yb concentrations. The effect of thermal lens, thermal deformation effect, and saturated inversion population distribution inside the Yb:YAG crystal on performance of heavy-doped Yb:YAG microchip lasers are also addressed.
The laser characteristics of laser-diode end-pumped Yb:YAG/Cr
4+
:YAG composite ceramics microchip passively Q-switched lasers were studied by solving the coupled rate equations numerically taking ...into account the reabsorption of Yb:YAG ceramics at laser wavelength. Effects of the reflectivity of the output coupler, the concentrations and thickness of the saturable absorbers, and pump beam area on the laser performance were investigated analytically. The simulation results of the Yb:YAG/Cr
4+
:YAG composite ceramics passively Q-switched microchip lasers were in good agreement with the experimental data. Better laser performance (high peak power, short pulse width and good optical-to-optical efficiency) of the composite Yb:YAG/Cr
4+
:YAG ceramics passively Q-switched laser can be obtained by using a thin Cr
4+
:YAG ceramic with high concentration, suitable reflectivity of the output coupler and proper pump beam diameter under high pump power intensity according to our simulations.
The gene cluster involved in producing the cyclic heptadepsipeptide micropeptin was cloned from the genome of the unicellular cyanobacterium Microcystis aeruginosa K-139. Sequencing revealed four ...genes encoding non-ribosomal peptide synthetases (NRPSs) that are highly similar to the gene cluster involved in cyanopeptolins biosynthesis. According to predictions based on the non-ribosomal consensus code, the order of the mcnABCE NPRS modules was well consistent with that of the biosynthetic assembly of cyclic peptides. The biochemical analysis of a McnB(K-139) adenylation domain and the knock-out of mcnC in a micropeptin-producing strain, M. viridis S-70, revealed that the mcn gene clusters were responsible for the production of heptadepsipeptide micropeptins. A detailed comparison of nucleotide sequences also showed that the regions between the mcnC and mcnE genes of M. aeruginosa K-139 retained short stretches of DNA homologous to halogenase genes involved in the synthesis of halogenated cyclic peptides of the cyanopeptolin class including anabaenopeptilides. This suggests that the mcn clusters of M. aeruginosa K-139 have lost the halogenase genes during evolution. Finally, a comparative bioinformatics analysis of the congenial gene cluster for depsipetide biosynthesis suggested the diversification and propagation of the NRPS genes in cyanobacteria.
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