Negative Pseudo Labeling Using Class Proportion for Semantic Segmentation in Pathology

16th European Conference, Glasgow, UK, August 23–28, 2020. Part of the Lecture Notes in Computer Science book series (LNCS, volume 12360). Also part of the Image Processing, Computer Vision, Pattern Recognition, and Graphics book sub series (LNIP, volume 12360).In pathological diagnosis, since the proportion of the adenocarcinoma subtypes is related to the recurrence rate and the survival time after surgery, the proportion of cancer subtypes for pathological images has been recorded as diagnostic information in some hospitals. In this paper, we propose a subtype segmentation method that uses such proportional labels as weakly supervised labels. If the estimated class rate is higher than that of the annotated class rate, we generate negative pseudo labels, which indicate, “input image does not belong to this negative label, ” in addition to standard pseudo labels. It can force out the low confidence samples and mitigate the problem of positive pseudo label learning which cannot label low confident unlabeled samples. Our method outperformed the state-of-the-art semi-supervised learning (SSL) methods

Tailoring coupling of light to local plasmons by using Ag nanorods/structured dielectric/mirror sandwiches

The optical properties of the sandwich of Ag nanorod array (NRA)/structured dielectric layer/Ag mirror have been investigated theoretically and experimentally, where the structured dielectric layer has stacked sublayers of an anisotropic nanocolumnar layer and a uniform layer. The functions of the nanocolumnar and the uniform sublayers are to control shape of the Ag nanorods and to tune optical path length inside the sandwich, respectively. Calculations based on a simple model by treating the NRAs as uniform effective media indicate that the antireflection condition is realized by changing the thickness of the dielectric layer and that the Ag nanorods absorb most of the incident light. The designed structures have been successfully fabricated by taking advantages of the dynamic oblique-angle deposition technique. Under the experimental antireflection condition, Raman scattering measured on the Ag NRA in the near infrared region exhibits significant enhancement. This indicates that the local electric field close to the Ag nanorods can be controlled by the interference of light in the nanostructured sandwiches

Large Reduction in the aa-axis Knight Shift on UTe2_2 with TcT_{\rm c} = 2.1 K

Spin susceptibility in the superconducting (SC) state was measured in the higher-quality sample of uranium-based superconductor UTe$_2$ by using Knight-shift measurements for a magnetic field $H$ along all three crystalline axes. In the higher-quality sample, the SC transition temperature $T_{\rm c}$ is about 2.1 K, and the residual electronic term in the specific heat is almost zero. The NMR linewidth becomes narrower and is almost half of that in the previous sample with $T_{\rm c} \sim 1.6$ K when $H \parallel a$ and $c$. Although the Knight-shift behavior was not so different from the previous results for $H \parallel b$, and $c$, a large reduction in Knight shift along the $a$ axis was observed, in contrast with the previous $a$-axis Knight shift result. We discuss the origin of the difference between the previous and present results, and the possible SC state derived from the present results.Comment: 7 pages, 6 figures, including supplemental material

Cohesive and Anisotropic Vascular Endothelial Cell Motility Driving Angiogenic Morphogenesis

Vascular endothelial cells (ECs) in angiogenesis exhibit inhomogeneous collective migration called “cell mixing”, in which cells change their relative positions by overtaking each other. However, how such complex EC dynamics lead to the formation of highly ordered branching structures remains largely unknown. To uncover hidden laws of integration driving angiogenic morphogenesis, we analyzed EC behaviors in an in vitro angiogenic sprouting assay using mouse aortic explants in combination with mathematical modeling. Time-lapse imaging of sprouts extended from EC sheets around tissue explants showed directional cohesive EC movements with frequent U-turns, which often coupled with tip cell overtaking. Imaging of isolated branches deprived of basal cell sheets revealed a requirement of a constant supply of immigrating cells for ECs to branch forward. Anisotropic attractive forces between neighboring cells passing each other were likely to underlie these EC motility patterns, as evidenced by an experimentally validated mathematical model. These results suggest that cohesive movements with anisotropic cell-to-cell interactions characterize the EC motility, which may drive branch elongation depending on a constant cell supply. The present findings provide novel insights into a cell motility-based understanding of angiogenic morphogenesis

Low-temperature Magnetic Fluctuations Investigated by 125^{125}Te-NMR on the Uranium-based Superconductor UTe2_{2}

To investigate the static and dynamic magnetic properties on the uranium-based superconductor UTe$_{2}$, we measured the NMR Knight shift $K$ and the nuclear spin-lattice relaxation rate $1/T_{1}$ in $H \parallel a$ by $^{125}$Te-NMR on a $^{125}$Te-enriched single-crystal sample. $1/T_1T$ in $H \parallel a$ is much smaller than $1/T_1T$ in $H \parallel b$ and $c$, and magnetic fluctuations along each axis are derived from the $1/T_1T$ measured in $H$ parallel to all three crystalline axes. The magnetic fluctuations are almost identical at two Te sites and isotropic at high temperatures, but become anisotropic below 40 K, where heavy-fermion state is formed. The character of magnetic fluctuations in UTe$_2$ is discussed with the comparison to its static susceptibility and the results on other U-based superconductors. It is considered that the magnetic fluctuations probed with the NMR measurements are determined by the magnetic properties inside the two-leg ladder formed by U atoms, which are dominated by the $q_a$ = 0 ferromagnetic fluctuations.Comment: 10 pages, 6 figures

Novel Oral Derivative UD-017, a Highly Selective CDK7 Inhibitor, Exhibits Anticancer Activity by Inducing Cell-Cycle Arrest and Apoptosis in Human Colorectal Cancer

Objective: This study aimed to investigate the anticancer profile of a new cyclin-dependent kinase 7 (CDK7) inhibitor, UD-017, by examining its mechanism of action using HCT-116 colorectal cancer cells. Methods: The anticancer properties of UD-017 were assessed using several assays, including in vitro kinase, proliferation, and apoptosis assays, western blot analysis, and an in vivo xenograft mouse model. Results: UD-017 significantly inhibited CDK7 activity (IC50 = 16 nM) with high selectivity in an in vitro kinase assay testing a panel of over 300 proteins and lipid kinases. UD-017 also inhibited the growth of HCT-116 cells (GI50 = 19 nM) and inhibited the phosphorylation of various downstream mediators of CDK7 signaling. In cell cycle and apoptosis assays using HCT-116 cells, UD-017 increased the number of cells in both G1 and G2/M phases and induced apoptosis. In vivo, UD-017 inhibited tumor growth in an HCT-116 xenograft mouse model by 33%, 64%, and 88% at doses of 25, 50, and 100 mg/kg, respectively, with clear dose-dependency. Co-administration of 5-FU and 50 mg/kg UD-017 had a strong synergistic effect, as reflected in the complete inhibition of tumor growth. Conclusion: CDK7 may play a major role in colorectal cancer growth by regulating the cell cycle and apoptosis. UD-017 is a promising candidate therapeutic agent for the treatment of cancer involving CDK7 signaling

細胞膜プレートを使用したサイトプローブ薬物の細胞膜透過性に関する基礎的検討

Drug efficacy depends on the amount of a preparation reaching the target tissue (grade of tissue transfer). In this experiment, we established the normal albumin concentration of a healthy adult (600 μ M) or a low-albumin state indicating marked liver hypofunction (100 μ M) on a cell membrane plate, and evaluated the cell membrane permeability of the probe agents. The cell membrane permeability of phenytoin or valproate depended on the concentration of albumin. Probe agent site-I and -II inhibitors, bucolome and oleic acid, respectively, increased the cell membrane permeability. In the future, the cell membrane permeability of probe agents should be further investigated to estimate the tissue transfer of agents based on various laboratory data (albumin, free fatty acids, uremic toxins, and bilirubin)

Basic study on flurbiprofen protein binding inhibition by an albumin site 2 binding inhibitor, 6-methoxy-2-naphthyl acetic acid.

非ステロイド性抗炎症薬(NSAID)フルルビプロフェン(FP)の蛋白結合率は約99%であり、組織移行性が低い。6-メトキシ-2-ナフチル酢酸(6MNA)は、NSAIDの1つであるナブメトンの活性代謝産物である。これらの薬物は、ともにヒト血清アルブミン(HSA)のサイトIIに強く結合する。私たちは、LLC-PK1を用いて6MNA添加時のFPの細胞膜透過性について調べた。この実験では、細胞膜プレートの上側を組織側、下側を血管側と想定した。下側のFPを含むHSA溶液に6MNAを添加後、上側、下側のFP濃度を測定した。上側へのFPの移行量は6MNAの添加により、Total FPおよびFree FP濃度ともに有意な増加を示した。下側の量は変化が見られなかった。臨床におけるナブメトンの併用はFPのようなサイトII結合性薬物の標的組織への移行量を増加させ、少量においても効果を高める可能性が示唆された。The protein binding rate of a nonsteroidal antiinflammatory drug (NSAID), flurbiprofen (FP), is about 99%, indicating its low tissue transfer. 6-Methoxy-2-naphthyl acetic acid (6MNA) is an active metabolite of an NSAID, nabumetone (Relifen ®). These drugs strongly bind to human serum albumin (HSA) site II, suggesting that protein binding inhibition by 6MNA may promote tissue transfer of FP. We investigated cell membrane permeability of FP in the presence of 6MNA using swine kidney cell line LLC-PK1, in which the upper and lower sides of the cell membrane plate (Transwell ®) were regarded as the tissue and vascular sides, respectively. After adding 6MNA to HSA solution containing FP on the lower side, the FP levels in the upper and lower solutions and cells were measured. FP transfer to the upper side was significantly promoted by the addition of 6MNA with regard to the total and free FP levels. No change in the FP level was noted in cells or wells. It was suggested that concomitant nabumetone may promote transfer of site II binding drugs, such as FP, to the target tissue, increasing the effect even at a low dose