The computational complexity of the solid torus core recognition problem

The solid torus core recognition problem is the problem that, given a knot in the solid tours, decides whether the knot is the core of the solid torus. That problem is in NP since the thickened torus recognition problem is in NP. We give an alternate proof of that fact and prove that the problem is in co-NP. It is also proved that the Hopf link recognition problem is in NP and co-NP as a corollary of this result.Comment: 17 pages, 8 figure

Gradient flows without blow-up for Lefschetz thimbles

We propose new gradient flows that define Lefschetz thimbles and do not blow up in a finite flow time. We study analytic properties of these gradient flows, and confirm them by numerical tests in simple examples.Comment: 31 pages, 11 figures, (v2) conclusion part is expande

Targeting cancer cell-specific RNA interference by siRNA delivery using a complex carrier of affibody-displaying bio-nanocapsules and liposomes

BACKGROUND: Small interfering RNA (siRNA) has attracted attention in the field of nucleic acid medicine as a RNA interference (RNAi) application that leads to gene silencing due to specific messenger RNA (mRNA) destruction. However, since siRNA is unstable in blood and unable to cross the cell membrane, encapsulation of siRNA into a carrier is required. RESULTS: In this study, we used a carrier that combined Z(HER2)-displaying bio-nanocapsule (derived from hepatitis B virus surface antigen) and liposomes in a complex in order to investigate the feasibility of effective and target-cell-specific RNAi applications. As a result, by observing RNAi only in HER2-expressing breast cancer cells, using our proposed methodology, we successfully demonstrated target-cell-specific delivery and effective function expression of siRNA. CONCLUSIONS: These findings show that, in the field of nucleic acid medicine, Z(HER2)-BNC/LP can be a useful carrier for siRNA delivery, and could also become a useful tool for gene silencing and to accomplish protein knock-down

Ladder Siamese Network: a Method and Insights for Multi-level Self-Supervised Learning

Siamese-network-based self-supervised learning (SSL) suffers from slow convergence and instability in training. To alleviate this, we propose a framework to exploit intermediate self-supervisions in each stage of deep nets, called the Ladder Siamese Network. Our self-supervised losses encourage the intermediate layers to be consistent with different data augmentations to single samples, which facilitates training progress and enhances the discriminative ability of the intermediate layers themselves. While some existing work has already utilized multi-level self supervisions in SSL, ours is different in that 1) we reveal its usefulness with non-contrastive Siamese frameworks in both theoretical and empirical viewpoints, and 2) ours improves image-level classification, instance-level detection, and pixel-level segmentation simultaneously. Experiments show that the proposed framework can improve BYOL baselines by 1.0% points in ImageNet linear classification, 1.2% points in COCO detection, and 3.1% points in PASCAL VOC segmentation. In comparison with the state-of-the-art methods, our Ladder-based model achieves competitive and balanced performances in all tested benchmarks without causing large degradation in one

A display of pH-sensitive fusogenic GALA peptide facilitates endosomal escape from a Bio-nanocapsule via an endocytic uptake pathway

BACKGROUND: An affibody-displaying bio-nanocapsule (Z(HER2)-BNC) with a hepatocyte specificity derived from hepatitis B virus (HBV) was converted into an affibody, Z(HER2), that recognizes HER2 receptors. This affibody was previously reported to be the result of the endocytosis-dependent specific uptake of proteins and siRNA into target cancer cells. To assist the endosomal escape of inclusions, a helper lipid with pH-sensitive fusogenic ability (1,2-dioleoyl-sn-glycero-3-phos phoethanolamine; DOPE) was conjugated with a Z(HER2)-BNC. FINDINGS: In this study, we displayed a pH-sensitive fusogenic GALA peptide on the surface of a particle in order to confer the ability of endosomal escape to a Z(HER2)-BNC. A GALA-displaying Z(HER2)-BNC purified from yeast uneventfully formed a particle structure. Furthermore, endosomal escape of the particle was facilitated after endocytic uptake and release of the inclusions to the cytoplasm without the cell toxicity. CONCLUSION: The genetic fusion of a GALA peptide to the virus-like particle confers the ability of endosomal escape

A blue-shifted anion channelrhodopsin from the Colpodellida alga Vitrella brassicaformis

Microbial rhodopsins, a family of photoreceptive membrane proteins containing the chromophore retinal, show a variety of light-dependent molecular functions. Channelrhodopsins work as light-gated ion channels and are widely utilized for optogenetics, which is a method for controlling neural activities by light. Since two cation channelrhodopsins were identified from the chlorophyte alga Chlamydomonas reinhardtii, recent advances in genomic research have revealed a wide variety of channelrhodopsins including anion channelrhodopsins (ACRs), describing their highly diversified molecular properties (e.g., spectral sensitivity, kinetics and ion selectivity). Here, we report two channelrhodopsin-like rhodopsins from the Colpodellida alga Vitrella brassicaformis, which are phylogenetically distinct from the known channelrhodopsins. Spectroscopic and electrophysiological analyses indicated that these rhodopsins are green- and blue-sensitive pigments (lambda(max) = similar to 550 and similar to 440 nm) that exhibit light-dependent ion channeling activities. Detailed electrophysiological analysis revealed that one of them works as a monovalent anion (Cl-, Br- and NO3-) channel and we named it V. brassicaformis anion channelrhodopsin-2, VbACR2. Importantly, the absorption maximum of VbACR2 (similar to 440 nm) is blue-shifted among the known ACRs. Thus, we identified the new blue-shifted ACR, which leads to the expansion of the molecular diversity of ACRs

Granting specificity for breast cancer cells using a hepatitis B core particle with a HER2-targeted affibody molecule

Capsid-like particles consisting of a hepatitis B core (HBc) protein have been studied for their potential as carriers for drug delivery systems (DDS). The hollow HBc particle, which is formed by the self-assembly of core proteins comprising 183 aa residues, has the ability to bind to various cells non-specifically via the action of an arginine-rich domain. In this study, we developed an engineered HBc particle that specifically recognises and targets human epidermal growth factor receptor-related 2 (HER2)-expressing breast cancer cells. To despoil the non-specific binding property of an HBc particle, we genetically deleted the C-terminal 150–183 aa part of the core protein that encodes the arginine-rich domain (ΔHBc). Then, we genetically inserted a ZHER2 affibody molecule into the 78–81 aa position of the core protein to confer the ability of target-cell-specific recognition. The constructed ZHER2-displaying HBc (ZHER2-ΔHBc) particle specifically recognised HER2-expressing SKBR3 and MCF-7 breast cancer cells. In addition, the ZHER2-ΔHBc particle exhibited different binding amounts in accordance with the HER2 expression levels of cancer cells. These results show that the display of other types of Affibody molecules on HBc particles would be an expandable strategy for targeting several kinds of cancer cells that would help enable a pinpoint DDS