Diversified Adversarial Attacks based on Conjugate Gradient Method

Deep learning models are vulnerable to adversarial examples, and adversarial attacks used to generate such examples have attracted considerable research interest. Although existing methods based on the steepest descent have achieved high attack success rates, ill-conditioned problems occasionally reduce their performance. To address this limitation, we utilize the conjugate gradient (CG) method, which is effective for this type of problem, and propose a novel attack algorithm inspired by the CG method, named the Auto Conjugate Gradient (ACG) attack. The results of large-scale evaluation experiments conducted on the latest robust models show that, for most models, ACG was able to find more adversarial examples with fewer iterations than the existing SOTA algorithm Auto-PGD (APGD). We investigated the difference in search performance between ACG and APGD in terms of diversification and intensification, and define a measure called Diversity Index (DI) to quantify the degree of diversity. From the analysis of the diversity using this index, we show that the more diverse search of the proposed method remarkably improves its attack success rate.Comment: Proceedings of the 39th International Conference on Machine Learning (ICML 2022

A clinically applicable and scalable method to regenerate T-cells from iPSCs for off-the-shelf T-cell immunotherapy

動物由来の成分を含まないより安全な製法でiPS細胞から大量の再生T細胞を培養する方法の開発 --T細胞を使ったがん免疫療法での利用も--. 京都大学プレスリリース. 2021-01-18.Clinical successes demonstrated by chimeric antigen receptor T-cell immunotherapy have facilitated further development of T-cell immunotherapy against wide variety of diseases. One approach is the development of “off-the-shelf” T-cell sources. Technologies to generate T-cells from pluripotent stem cells (PSCs) may offer platforms to produce “off-the-shelf” and synthetic allogeneic T-cells. However, low differentiation efficiency and poor scalability of current methods may compromise their utilities. Here we show improved differentiation efficiency of T-cells from induced PSCs (iPSCs) derived from an antigen-specific cytotoxic T-cell clone, or from T-cell receptor (TCR)-transduced iPSCs, as starting materials. We additionally describe feeder-free differentiation culture systems that span from iPSC maintenance to T-cell proliferation phases, enabling large-scale regenerated T-cell production. Moreover, simultaneous addition of SDF1α and a p38 inhibitor during T-cell differentiation enhances T-cell commitment. The regenerated T-cells show TCR-dependent functions in vitro and are capable of in vivo anti-tumor activity. This system provides a platform to generate a large number of regenerated T-cells for clinical application and investigate human T-cell differentiation and biology

トクベツ キコウ キョウツウ タイイク ケンドウ ジッシュウ ニジュウ シチネン オ フリカエッテ

昭和49年に筑波大学体育化学系に配置換えとなり着任、翌50年(1975)4月より共通体育･剣道実習が開講されてから今日迄、年間1クラス又は2クラスであったが、まるまる27年間継続して学生諸君の相手をさせていただいた。 昭和50年(体育専門学群第2期生が入学した年である)当時は申すまでもなく筑波大学は ..

The relationship between eDNA density distribution and current fields around an artificial reef in the waters of Tateyama Bay, Japan

Monitoring of artificial reefs (ARs) has been conducted through such methods as visual censuses, surveys using fishing gear, and echo sounder. These methods have disadvantages: visual census is not possible at ARs in deeper waters, fishing gear surveys are invasive to fish individuals, and echo sounders have difficulty in species identification. A new AR monitoring method is required to compensate for these disadvantages. While eDNA has become a valid monitoring tool for marine biodiversities, it is influenced by degradation and transport of the molecules that affect information about the spatio-temporal distribution of fish. An understanding of the relationship between current fields and eDNA distribution, particularly in open waters, is critical when using eDNA as an index for fish aggregation at ARs. We investigated the relationship between eDNA distribution and current fields around an AR for four dominant species (Engraulis japonicus, Parapristipoma trilineatum, Scomber spp and Trachurus japonicus) in Tateyama Bay, Japan. The highest density of fish schools is formed directly above or at the upstream side of ARs. If we assume that the center of eDNA originates at these locations at an AR and eDNA is simply transported by currents, a higher density of eDNA would distribute downstream from the AR. However, our results indicate that eDNA distribution is in accord with actual fish distribution, namely eDNA densities are more abundant in the upstream side of ARs. We thus consider that eDNA distribution is more influenced by actual distribution patterns than by the transport processes

Repeated X-RAY Irradiation Generates the Radioresistant Cancer Cell that Underwent Epithelial to Mesenchymal Transition

Cancer cell that relapsed after radiotherapy must acquires radioresistance, but the mechanisms of acquired radioresistance in cancer cell are not fully understood. To investigate the mechanisms of acquired radioresistance in cancer cell, we irradiated the human adenocarcinoma cell line A549 with 2Gy of X-ray, repeated the irradiation 30 times, and established the radioresistant cancer cell line A549R. To evaluate the differences in the radioseisitivity, apoptosis and senescence induction between A549 and A549R, we performed colony formation assay, JC-1 staining, and X-gal staining, respectively. The results of colony formation assay showed that the survival fraction of A549R was significantly higher than that of A549. In addition, apoptosis and senescence induction in A549R were suppressed compared with that in A549. We further studied the DNA double strand break (DSB) repair potential in A549R. To measure the DSB repair potential, we performed the immunofluorescence staining with anti-gamma-H2AX, phosphorylated ataxia telangiectasia mutated (p-ATM) antibody at 1 to 3 days after X-ray irradiation and counted the focus number of gamma-H2AX and p-ATM in the nucleus. As a result, the disappearance of colocalized focus of gamma-H2AX and p-ATM in A549R was earlier than that in A549. These data showed that the repeated X-ray irradiation generates the radioresistant cancer cells that acquire the promotion of DSB repair potential. Next, we evaluated the difference in cell cycle progression and cell proliferation after X-ray irradiation between both cell lines. As a result, the percentage of G0/G1 phase in A549R was significantly higher than that in A549. Moreover, the cell proliferation in A549R after X-ray irradiation was suppressed compared with that in A549. Subsequently, we assessed the protein expression of p53 and p53-related proteins such as Bax, Puma, p21, and cyclin D1 by western blotting. The results showed that the p53 and cyclin D1 expression in A549R was suppressed compared with that in A549, but Bax, Puma, and p21 was not changed.We further assessed whether epithelial to mesenchymal transition (EMT) in A549R because it is known that EMT is closely associated with chemoresistance in cancer cell. As we expected, the cadherin switching was clearly observed in A549R. In this report, we will discuss the relationship between the radioresistance after X-ray irradiation, changes in DNA repair potential, and EMT induction.8th International Symposium of Cancer Research and Therap

Pearl microstructure and expression of shell matrix protein genes MSI31 and MSI60 in the pearl sac epithelium of Pinctada fucata by in situ hybridization.

Expression patterns of the shell matrix protein genes MSI31 and MSI60 in the pearl sac epithelium were examined by in situ hybridization 38 days after implantation, and related to pearl quality. A pearl sac that produced a nacreous pearl showed very weak expression of MSI31 and strong expression of MSI60. A pearl sac, which yielded a prismatic pearl, strongly expressed MSI31 and very weakly expressed MSI60. In a complex pearl, whose surface consisted of a mosaic of both nacreous and prismatic layers, the expression pattern of MSI31 and MSI60 similarly corresponded to the underlying surface structures of the pearl. A nacreous pearl whose pearl sac showed strong MSI31 expression had an entirely nacreous surface composed of a laminar structure with unusual tablet growth at the corresponding site. MSI31 and MSI60 are the major components of the shell matrix proteins of the nacreous and prismatic layers. Clearly, high expression of MSI31 does not always result in prismatic secretion. These observations cannot be explained solely on the basis of the expression patterns of MSI31 and MSI60. We propose that, in addition to the MSI genes that form the prismatic and nacreous layers, upstream from these genes there are regulatory master genes that determine whether a nacreous layer (aragonite) or a prismatic layer (calcite) is formed

Quantitative Analysis of Effects of a Single 60Co Gamma Ray Point Exposure on Time-Dependent Change in Locomotor Activity in Rats

Investigating initial behavioral changes caused by irradiation of animals might provide important information to aid understanding of early health effects of radiation exposure and clinical features of radiation injury. Although previous studies in rodents suggested that radiation exposure leads to reduced activity, detailed properties of the effects were unrevealed due to a lack of proper statistical analysis, which is needed to better elucidate details of changes in locomotor activity. Ten-week-old male Wistar rats were subjected to single point external whole-body irradiation with 60Co gamma rays at 0, 2.0, 3.5, and 5.0 Gy (four rats per group). Infrared sensors were used to continuously record the locomotor activity of each rat. The cumulative number of movements during the night was defined as “activity” for each day. A non-linear mixed effects model accounting for individual differences and daily fluctuation of activity was applied to analyze the rats’ longitudinal locomotor data. Our statistical method revealed characteristics of the changes in locomotor activity after radiation exposure, showing that (1) reduction in activity occurred immediately—and in a dose-dependent manner—after irradiation and (2) recovery to pre-irradiation levels required almost one week, with the same recovery rate in each dose group

Effects of laughter therapy on quality of life in patients with cancer: An open-label, randomized controlled trial.

BACKGROUND:Few randomized controlled trials have assessed the effects of laughter therapy on health-related quality of life (QOL) in cancer patients. This study aimed to evaluate these effects as an exploratory endpoint in cancer patients as part of a randomized controlled trial conducted at a single institution in Japan. METHODS:The Initiative On Smile And CAncer (iOSACA) study was an open-label randomized controlled trial conducted in 2017 in which participants aged 40-64 years with cancer were randomly assigned to either an intervention group (laughter therapy) or control group (no laughter therapy). Each participant in the intervention group underwent a laughter therapy session once every two weeks for seven weeks (total of four sessions). Each session involved a laughter yoga routine followed by Rakugo or Manzai traditional Japanese verbal comedy performances. We assessed QOL as a secondary endpoint in this intention-to-treat population using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). The questionnaire was completed at baseline (Week 0) and at Weeks 3 and 7. Mixed-effects models for repeated measures were developed to compare time-dependent changes in each QOL domain from baseline between the intervention and control groups. RESULTS:Four participants retracted consent and one participant was retrospectively excluded from analysis due to unmet inclusion criteria. The analysis was conducted using 56 participants, with 26 in the intervention group and 30 in the control group. Questionnaire completion rates were high (>90%), with similar QOL scores reported at baseline in both groups. The mixed-effects models showed that the intervention group had significantly better cognitive function and less pain than the control group for a short period. CONCLUSION:Laughter therapy may represent a beneficial, noninvasive complementary intervention in the clinical setting. Further studies are needed to verify the hypotheses generated from this exploratory study