Light-induced silencing of neural activity in Rosa26 knock-in and BAC transgenic mice conditionally expressing the microbial halorhodopsin eNpHR3

An engineered light-inducible chloride pump, Natronomonas pharaonis halorhodopsin 3 (eNpHR3) enables temporally and spatially precise inhibition of genetically defined cell populations in the intact nervous tissues. In this report, we show the generation of new mouse strains that express eNpHR3-EYFP fusion proteins after Cre- and/or Flp-mediated recombination to optically inhibit neuronal activity. In these mouse strains, Cre/Flp recombination induced high levels of opsin expression. We confirmed their light-induced activities by brain slice whole-cell patch clamp experiments. eNpHR3-expressing neurons were optically hyperpolarized and silenced from firing action potentials. In prolonged silencing of action potentials, eNpHR3 was superior to eNpHR2, a former version of the engineered pump. Thus, these eNpHR3 mouse strains offer reliable genetic tools for light-induced inhibiting of neuronal activity in defined sets of neurons

Estimation of Shor\u27s Circuit for 2048-bit Integers based on Quantum Simulator

Evaluating exact computational resources necessary for factoring large integers by Shor algorithm using an ideal quantum computer is difficult because simplified circuits were used in past experiments, in which qubits and gates were reduced as much as possible by using the features of the integers, though 15 and 21 were factored on quantum computers. In this paper, we implement Shor algorithm for general composite numbers, and factored 96 RSA-type composite numbers up to 9-bit using a quantum computer simulator. In the largest case, $N=511$ was factored within 2 hours. Then, based on these experiments, we estimate the number of gates and the depth of Shor\u27s quantum circuits for factoring 1024-bit and 2048-bit integers. In our estimation, Shor\u27s quantum circuit for factoring 1024-bit integers requires $2.78 \times 10^{11}$ gates, and with depth $2.24 \times 10^{11}$, while $2.23 \times 10^{12}$ gates, and with depth $1.80 \times 10^{12}$ for 2048-bit integers

Pyrrole Formation via Reactivity of η4-(Vinylketenimine)iron Complexes with Electron-Deficient Alkynes

When electron-deficient alkynes reacted with η4-(vinylketenimine)iron complexes, pyrroles were produced. Pyrrole formation involved the [2 + 3] cycloaddition of alkyne to the ketenimine moiety, migration of the vinyl group, and decomplexation. Either alkynes bearing two electron-withdrawing groups, or terminal alkynes with an electron-withdrawing group reacted to generate pyrroles

On-line microdevice for stress proteomics

The handing of the cells or tissues is essential for proteomics research or drug screening, where labor is not avoidable. The steps of cell wash, protein extraction, protein denaturing are complicated procedures in conventional method using centrifugation and pipetting in the laboratory. This is the bottle-neck for proteome research. To solve these problems, we propose to utilize the nanotechnology, which will improve the proteomics methodology. Utilizing the nanotechnology, we developed a novel microseparation system, where centrifugation and pipetting are needless. This system has a nanostructured microdevice, by which the cell handling, protein extraction, and antibody assay can be performed. Since cell transfer is needless, all cells are corrected without any loss during the cell-pretreatment procedures, which allowed high reproducibility and enabled the detection of low amount of protein expression. Utilizing the microdevice, we analyzed the stress induced proteins. We further succeeded the screening of food that was useful for immunity and found that an extraction from seaweed promoted the apoptosis of T-lymphoblastic cells. Here, we present an on-line microdevice for stress proteomics

Continuation of atezolizumab plus bevacizumab beyond initial progressive disease: clinical benefits in patients with unresectable hepatocellular carcinoma – a multicenter cohort study

BackgroundThe clinical significance of treatment beyond progression (TBP) with immune checkpoint inhibitor-based therapy in hepatocellular carcinoma (HCC) remains unclear. As atezolizumab plus bevacizumab has become a first-line therapy for advanced HCC, understanding the real-world outcomes of TBP is increasingly relevant.MethodsWe conducted a multicenter retrospective observational study involving 122 patients with unresectable HCC treated with atezolizumab plus bevacizumab across nine liver centers in Japan. Among patients who experienced radiologic progressive disease (PD), clinical outcomes were compared between those who continued treatment beyond progression (TBP group) and those who discontinued therapy. Overall survival (OS), tumor response, and subgroup analyses based on major vessel involvement (MVI) were evaluated.ResultsAmong patients with PD, the median OS was not reached in the TBP group, compared to 13.6 months in the non-TBP group (HR 2.04; 95% CI 1.02–4.07; p=0.0435). When stratified by MVI status, patients without MVI who received TBP had significantly longer OS (median not reached) than those who received palliative care (median 6.2 months; HR 11.2; 95% CI 3.89–32.5; p<0.001). Among patients with MVI, TBP did not confer an OS benefit over palliative care (median OS: 10.4 months vs. 7.4 months; HR 2.24; p=0.260), whereas switching to subsequent chemotherapy showed improved OS (median 23.1 months vs. 7.4 months; HR 7.33; 95% CI 1.44–37.3; p=0.0164). Multivariate analysis identified MVI as an independent negative prognostic factor (HR 5.17; 95% CI 1.34–20.0; p=0.0172), even after adjusting for AFP ratio at progression.ConclusionsThis multicenter study suggests that continuation of atezolizumab plus bevacizumab beyond radiologic progression may improve survival outcomes in selected patients with unresectable HCC, particularly those without major vessel involvement. These findings support the integration of TBP into personalized treatment strategies in advanced HCC