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We will explore the dynamical property of non-equilibrium phenomena induced by two-dimensional holographic conformal field theory (2d holographic CFT) Hamiltonian on the curved spacetime by studying the time dependence of the entanglement entropy and mutual information. Here, holographic CFT is the CFT having the gravity dual. We will start from the boundary and thermofield double states, evolve the systems in Euclidean time with the Hamiltonian on the curved background, and then evolve them in real-time with the same Hamiltonian. We found that the early- and late-time entanglement structure depends on the curved background, while the entanglement growth does not, and is linear. Furthermore, in the gravity dual for the thermofield double state, this entanglement growth is due to the linear growth of the wormhole, while in the one for the boundary state, it is due to the in-falling of the end of the world brane to the black hole. We discussed the low temperature system can be regarded as the dynamical system induced by the multi-joining quenches. We also discussed the effective description of the high temperature system, called line tension picture., Comment: 48 pages+appendices, 3 figures

The thermodynamics and the entanglement properties of two-dimensional conformal field theories ($2$d CFTs) on curved backgrounds are studied. By means of conformal mapping we study the equivalent system on flat space governed by the deformed Hamiltonian, which is a spatial integral of the Hamiltonian density modulated by an enveloping function. Focusing on holographic CFTs, we observe Hawking-Page like phase transition for the thermal and the entanglement entropy as we vary the background metric. We also compute the mutual information to study the information theoretic correlation between parts of the curved spacetime. The gravity dual of 2d CFTs on curved background is also discussed., Comment: 38 pages, 12 figures

This study investigates the psychological impact of movement elements in media art on viewers. As an emerging art form often displayed in public spaces with modern media, media art plays a crucial role in provoking thought, raising social issues, and designing various experiential spaces. Hence, understanding the influence of various elements within media art on human psychology is indispensable. We classified movement elements in Tosa Art into five categories: vertical, horizontal, scattering, rotation, and symmetry. We then surveyed 30 participants to evaluate each category's impact on four psychological factors: impression, relaxation, motivation, and creativity. The results showed that the 'rotation' category significantly influenced impression, motivation, and creativity, while the 'vertical' movement had negligible impact. Our findings are consistent with existing literature that highlights the potential of visual movement to draw attention, enhance memory, and induce emotions and behavior. This research adds a new perspective to understanding the psychological impact of art, emphasizing the importance of evaluating movement as an element of the artwork as a whole. However, limitations include a primary focus on movement, with other potential influences such as other visual elements, the context of the work, and individual personality traits not being considered. Future research should explore these factors to understand the full scope of media art's psychological influence.

Arginine vasopressin (AVP) is expressed in both magnocellular (magnAVP) and parvocellular AVP (parvAVP) neurons of the paraventricular nucleus, and AVP colocalizes with corticotropin-releasing hormone (CRH) only in the parvocellular neurons. The immunoglobulin heavy chain binding protein (BiP) is a major endoplasmic reticulum (ER) chaperone which regulates the unfolded protein response under ER stress. We previously demonstrated that knockdown of BiP in magnAVP neurons exacerbated ER stress, which resulted in the autophagy-associated cell death of magnAVP neurons. Using the same approach, in the present study we examined the role of BiP in mouse parvAVP/CRH neurons. Our data demonstrate that BiP is expressed in mouse parvAVP/CRH neurons under nonstress conditions and is upregulated in proportion to the increase in CRH expression after adrenalectomy. For BiP knockdown in parvAVP/CRH neurons, we utilized a viral approach in combination with shRNA interference. Knockdown of BiP expression induced ER stress in parvAVP/CRH neurons, as reflected by the expression of C/EBP homologous protein. Furthermore, BiP knockdown led to the loss of parvAVP/CRH neurons after 4 weeks. In summary, our results demonstrate that BiP plays a pivotal role in parvAVP/CRH neurons, which function as neuroendocrine cells producing a large number of secretory proteins.

Arginine vasopressin (AVP) is expressed in both magnocellular (magnAVP) and parvocellular AVP (parvAVP) neurons of the paraventricular nucleus, and AVP colocalizes with corticotropin-releasing hormone (CRH) only in the parvocellular neurons. The immunoglobulin heavy chain binding protein (BiP) is a major endoplasmic reticulum (ER) chaperone which regulates the unfolded protein response under ER stress. We previously demonstrated that knockdown of BiP in magnAVP neurons exacerbated ER stress, which resulted in the autophagy-associated cell death of magnAVP neurons. Using the same approach, in the present study we examined the role of BiP in mouse parvAVP/CRH neurons. Our data demonstrate that BiP is expressed in mouse parvAVP/CRH neurons under nonstress conditions and is upregulated in proportion to the increase in CRH expression after adrenalectomy. For BiP knockdown in parvAVP/CRH neurons, we utilized a viral approach in combination with shRNA interference. Knockdown of BiP expression induced ER stress in parvAVP/CRH neurons, as reflected by the expression of C/EBP homologous protein. Furthermore, BiP knockdown led to the loss of parvAVP/CRH neurons after 4 weeks. In summary, our results demonstrate that BiP plays a pivotal role in parvAVP/CRH neurons, which function as neuroendocrine cells producing a large number of secretory proteins.

We present a comprehensive study of the magnetic properties of the strongly anisotropic ferrimagnet ErFe5Al7 in pulsed magnetic fields up to 30 T applied along the hard magnetization axis within the basal plane of the tetragonal lattice around the compensation temperature (Tcomp). Macroscopic measurements showed two anomalies at about 8 T and 25 T in a small temperature range around Tcomp. High-field x-ray magnetic circular dichroism (XMCD) data at the Er M5- and the Fe L3-edge resonances provide insight into the element-selective magnetization processes, revealing a coherent rotation of Er 4f and Fe 3d moments, with stepwise jumps including an unexpected one from an easy to a hard magnetization axis. XMCD at the Er L3-edge resonance elucidates the role of Er 5d electrons in coupling the Er 4f and the Fe 3d moments. Finally, an in-plane anisotropy constant was evaluated from a simulation of the magnetization process at temperatures well below Tcomp using a two-sublattice model.

Fluorescence imaging, a key technique in biological research, frequently utilizes fluorogenic probes for precise imaging in living systems. Tetrazine is an effective emission quencher in fluorogenic probe designs, which can be selectively damaged upon bioorthogonal click reactions, leading to considerable emission enhancement. Despite significant efforts to increase the emission enhancement ratio (IAC/IBC) of tetrazine-functionalized fluorogenic probes, the influence of molecular aggregation on the emission properties has been largely overlooked in these probe designs. In this study, we reveal that an ultrahigh IAC/IBC can be realized in the aggregate system when tetrazine is paired with aggregation-induced emission (AIE) luminogens. Tetrazine amplifies its quenching efficiency upon aggregation and drastically reduce background emissions. Subsequent click reactions damage tetrazine and trigger significant AIE, leading to considerably enhanced IAC/IBC. We further showcase the capability of these ultra-fluorogenic systems in selective imaging of multiple organelles in living cells. We term this unique fluorogenicity of AIE luminogen-quencher complexes with amplified dark-bright states as “Matthew effect” in aggregate emission, potentially providing a universal approach to attain ultrahigh IAC/IBC in diverse fluorogenic systems.

Asako Tanaka, Masayuki Hata, Memiri Tsuchikawa, Naoko Ueda-Arakawa Ueda-Arakawa, Hiroshi Tamura, Manabu Miyata, Ayako Takahashi, Ai Kido, Yuki Muraoka, Masahiro Miyake, Sotaro Ooto, Akitaka Tsujikawa Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, JapanCorrespondence: Masayuki Hata, Department of Ophthalmology and Visual Sciences Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, 606-8507, Japan, Tel +81-75-751-3248, Fax +81-75-752-0933, Email trj74h6@kuhp.kyoto-u.ac.jpPurpose: To evaluate the efficacy and safety of faricimab injections for treatment-naïve neovascular age-related macular degeneration (nvAMD) patients, including subtypes and pachychoroid phenotypes, and identify predictive factors for visual outcomes.Methods: nvAMD patients were prospectively recruited, receiving three monthly faricimab (6 mg) injections. Best-corrected visual acuity (BCVA) two months after the last injection (month 4) was compared between subtypes, and between pachychoroid neovasculopathy (PNV) and non-PNV eyes. Regression analysis determined factors influencing month 4 BCVA.Results: The study involved 23 patients (12 typical AMD [tAMD], 10 polypoidal choroidal vasculopathy [PCV], 1 retinal angiomatous proliferation [RAP]). Eleven exhibited PNV phenotype. Significant BCVA (P = 4.9 × 10− 4) and central retinal thickness (CRT) (P = 1.3 × 10− 5) improvements were observed post-faricimab treatment. The therapy demonstrated favourable results for both tAMD and PCV eyes, and non-PNV and PNV eyes. Faricimab achieved dry macula in 77.3% of eyes, with subretinal fluid resolution in most cases, although intraretinal fluid (IRF) often persisted. Multivariable analysis identified external limiting membrane (ELM) presence and IRF as BCVA contributors at month 4.Conclusion: Faricimab demonstrated significant effectiveness and safety in treatment-naïve nvAMD patients, particularly for PCV and PNV eyes. ELM presence and IRF i

Seiko Miyata,1,* Kunihiro Iwamoto,1,* Ippei Okada,1,* Akihiro Fujimoto,2 Yuki Kogo,2 Daisuke Mori,1,3,4 Manabu Amano,5 Nao Matsuyama,5 Kazuki Nishida,5 Masahiko Ando,5 Toshiaki Taoka,6 Shinji Naganawa,7 Norio Ozaki1,4 1Department of Psychiatry, Nagoya University, Graduate School of Medicine, Nagoya, Japan; 2Medical Headquarters, Eisai Co., Ltd., Tokyo, Japan; 3Brain and Mind Research Center, Nagoya University, Nagoya, Japan; 4Pathophysiology of Mental Disorders, Nagoya University, Graduate School of Medicine, Nagoya, Japan; 5Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan; 6Department of Innovative Biomedical Visualization (Ibmv), Nagoya University, Graduate School of Medicine, Nagoya, Japan; 7Department of Radiology, Nagoya University, Graduate School of Medicine, Nagoya, Japan*These authors contributed equally to this workCorrespondence: Seiko Miyata, Department of Psychiatry, Nagoya University, Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi, 466-8550, Japan, Tel +81 52 744 2282, Fax +81 52 744 2293, Email miyata.seiko.v4@f.mail.nagoya-u.ac.jpPurpose: Both subjective and objective evaluations are essential for the treatment of insomnia. Lemborexant has been shown to be effective in the long-term based solely on a subjective basis, and no long-term objective measures have been evaluated under natural sleep conditions. Small, lightweight sleep electroencephalogram (EEG) monitor was used, instead of polysomnography, to objectively evaluate sleep at home 4 and 12 weeks after lemborexant treatment.Patients and Methods: Adults and elderly subjects with insomnia disorder, per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, were enrolled in this open-label, single-arm, single-center trial. Objective and subjective measures of sleep were prospectively assessed. Sleep disturbance, excessive sleepiness, and depressive symptoms were assessed using questionnaires.Results: A tot

The conditional text-to-image diffusion models have garnered significant attention in recent years. However, the precision of these models is often compromised mainly for two reasons, ambiguous condition input and inadequate condition guidance over single denoising loss. To address the challenges, we introduce two innovative solutions. Firstly, we propose a Spatial Guidance Injector (SGI) which enhances conditional detail by encoding text inputs with precise annotation information. This method directly tackles the issue of ambiguous control inputs by providing clear, annotated guidance to the model. Secondly, to overcome the issue of limited conditional supervision, we introduce Diffusion Consistency Loss (DCL), which applies supervision on the denoised latent code at any given time step. This encourages consistency between the latent code at each time step and the input signal, thereby enhancing the robustness and accuracy of the output. The combination of SGI and DCL results in our Effective Controllable Network (ECNet), which offers a more accurate controllable end-to-end text-to-image generation framework with a more precise conditioning input and stronger controllable supervision. We validate our approach through extensive experiments on generation under various conditions, such as human body skeletons, facial landmarks, and sketches of general objects. The results consistently demonstrate that our method significantly enhances the controllability and robustness of the generated images, outperforming existing state-of-the-art controllable text-to-image models.

In this paper, we analyze and discuss ShadowFormer in preparation for the NTIRE2023 Shadow Removal Challenge [1], implementing five key improvements: image alignment, the introduction of a perceptual quality loss function, the semi-automatic annotation for shadow detection, joint learning of shadow detection and removal, and the introduction of new data augmentation technique "CutShadow" for shadow removal. Our method achieved scores of 0.196 (3rd out of 19) in LPIPS and 7.44 (4th out of 19) in the Mean Opinion Score (MOS)., Comment: This version is a brief technical report submitted to the organizers, and there are still some points to be added; please wait for updates until May 2024. The code can be found here (https://github.com/Yuki-11/NTIRE2023_ShadowRemoval_IIM_TTI)

Predictive biomarkers of treatment response are lacking for metastatic clear cell renal cell carcinoma (ccRCC), a tumor type that is treated with angiogenesis inhibitors, immune checkpoint inhibitors, mTOR inhibitors and a HIF2 inhibitor. The Angioscore, an RNA-based quantification of angiogenesis, is arguably the best candidate to predict anti-angiogenic (AA) response. However, the clinical adoption of transcriptomic assays faces several challenges including standardization, time delay, and high cost. Further, ccRCC tumors are highly heterogenous, and sampling multiple areas for sequencing is impractical. Here we present a novel deep learning (DL) approach to predict the Angioscore from ubiquitous histopathology slides. To overcome the lack of interpretability, one of the biggest limitations of typical DL models, our model produces a visual vascular network which is the basis of the model's prediction. To test its reliability, we applied this model to multiple cohorts including a clinical trial dataset. Our model accurately predicts the RNA-based Angioscore on multiple independent cohorts (spearman correlations of 0.77 and 0.73). Further, the predictions help unravel meaningful biology such as association of angiogenesis with grade, stage, and driver mutation status. Finally, we find our model can predict response to AA therapy, in both a real-world cohort and the IMmotion150 clinical trial. The predictive power of our model vastly exceeds that of CD31, a marker of vasculature, and nearly rivals the performance (c-index 0.66 vs 0.67) of the ground truth RNA-based Angioscore at a fraction of the cost. By providing a robust yet interpretable prediction of the Angioscore from histopathology slides alone, our approach offers insights into angiogenesis biology and AA treatment response., Comment: 19 pages, 4 Figures

In emergencies such as disasters, the number of voice calls (VoIP sessions) increases rapidly for a variety of purposes. Thus, a control server near a disaster area may not be able to connect to VoIP sessions due to congestion. To solve this problem, a Call Admission Control (CAC) is needed to determine whether a VoIP session requesting a connection can be accepted or rejected. A CAC has the purpose of guaranteeing the connection quality and communication quality of VoIP sessions. One conventional method classifies VoIP sessions into three classes (emergency VoIP sessions, VoIP sessions from the disaster area, and VoIP sessions from outside the disaster area) by focusing on the outgoing location and offers a CAC with a priority level for each. However, a conventional CAC method cannot be applied to VoIP networks because reception control is designed for Public Switched Telephone Networks (PSTN). When conventional methods are applied to VoIP networks, the connection quality is guaranteed, however the communication quality cannot be guaranteed because the packet dropping probability is not considered. In this paper, we propose a three-dimensional CAC that controls three classes of VoIP sessions and guarantees both communication and connection quality in VoIP networks during emergencies. A conventional CAC method and our proposed CAC method are evaluated in terms of the call blocking probability, which guarantees the connection quality, and packet dropping probability, which guarantees the communication quality, to show the effectiveness of the proposed method., Comment: 25 pages, 31 figures

In recent years, the field of generative artificial intelligence, particularly in the domain of image generation, has exerted a profound influence on society. Despite the capability of AI to produce images of high quality, the augmentation of users' drawing abilities through the provision of drawing support systems emerges as a challenging issue. In this study, we propose that a cognitive factor, specifically, the size of the canvas, may exert a considerable influence on the outcomes of imitative drawing sketches when utilizing reference images. To investigate this hypothesis, a web based drawing interface was utilized, designed specifically to evaluate the effect of the canvas size's proportionality to the reference image on the fidelity of the drawings produced. The findings from our research lend credence to the hypothesis that a drawing interface, featuring a canvas whose dimensions closely match those of the reference image, markedly improves the precision of user-generated sketches., Comment: 5 pages, 6 figures, accepted in NICOGRAPH International 2024

OBJECTIVE: Children with Kawasaki disease (KD) and an initial echocardiogram that demonstrates coronary artery aneurysms (CAAs, Z score ≥2.5) are at high risk for severe cardiovascular complications. We sought to determine if primary adjunctive infliximab treatment at a dose of either 5 or 10 mg/kg, compared with intravenous immunoglobulin (IVIG) alone, is associated with a greater likelihood of CAA regression in patients with KD with CAA at the time of diagnosis. DESIGN AND SETTING: Single-centre observational study. PATIENTS: Children with acute KD and Z score ≥2.5 at baseline. INTERVENTIONS: Primary adjunctive infliximab (5 or 10 mg/kg) within 48 hours of initiating IVIG 2 g/kg. MAIN OUTCOME MEASURES: Incidence of CAA regression to Zmax <2 within 2 months of disease onset. RESULTS: Of the 168 patients with KD, 111 received IVIG alone and 57 received primary adjunctive infliximab therapy: 39 received 5 mg/kg and 18 received 10 mg/kg. Incidence of CAA regression to Zmax <2 within 2 months was statistically significant at 52%, 62% and 83% in the IVIG alone, IVIG+infliximab 5 mg/kg and IVIG+infliximab 10 mg/kg, respectively. The multivariable logistic regression model adjusting for age, sex, baseline Zmax and bilateral CAA at baseline showed that IVIG plus 10 mg/kg infliximab was significantly associated with a greater likelihood of CAA regression (adjusted OR: 4.45, 95% CI 1.17 to 16.89, p=0.028) compared with IVIG alone. The difference between IVIG+infliximab 5 mg/kg and IVIG alone was not significant. CONCLUSIONS: Primary adjunctive high-dose 10 mg/kg infliximab treatment was associated with a greater likelihood of CAA regression in patients with CAA at the time of diagnosis.

source:https://www.nms.ac.jp/sh/jnms/2021/088050467.pdf

In recent years, public wireless LANs have been increasingly installed in public places. On the other hand, free Wi-Fi has various security issues. One of these problems is the evil-twin attack. There are some studies that focus on the round-trip time (RTT) as a detection method for evil-twin attacks. However, their detection criteria are insufficient because they do not assume the traffic load to set the criteria. In this paper, we propose a new evil-twin attack detection method with threshold for detection criteria considering traffic load., Part of ISBN 9798350324150QC 20240201

We study properties of the Petz recovery map in chaotic systems, such as the Hayden-Preskill setup for evaporating black holes and the SYK model. Since these systems exhibit the phenomenon called scrambling, we expect that the expression of the recovery channel $\mathcal{R}$ gets simplified, given by just the adjoint $\mathcal{N}^{\dagger}$ of the original channel $\mathcal{N}$ which defines the time evolution of the states in the code subspace embedded into the physical Hilbert space. We check this phenomenon in two examples. The first one is the Hayden-Preskill setup described by Haar random unitaries. We compute the relative entropy $S(\mathcal{R}\left[\mathcal{N}[\rho]\right] ||\rho)$ and show that it vanishes when the decoupling is archived. We further show that the simplified recovery map is equivalent to the protocol proposed by Yoshida and Kitaev. The second example is the SYK model where the two dimensional code subspace is defined by an insertion of a fermionic operator, and the system is evolved by the SYK Hamiltonian. We check the recovery phenomenon by relating some matrix elements of an output density matrix $\langle T|\mathcal{R}[\mathcal{N}[\rho]]|T' \rangle$ to R\'enyi-two modular flowed correlators, and show that they coincide with the elements for the input density matrix with small error after twice the scrambling time., Comment: 47pages with 19 figures

According to the AdS/CFT dictionary, adding a relevant double-trace deformation $f\int O^2$ to a holographic CFT action is dual to imposing mixed Neumann/Dirichlet boundary conditions for the field dual to $O$ in AdS. We observed similar behaviour in codimension-two flat space holographies. We consider deformations of boundary conditions in flat spacetimes under flat space co-dimension-two holographies, celestial holography and Wedge-like holography. In the former celestial-holographic approach, we imposed boundary conditions on initial and final bulk states in the scattering. We find that these non-trivial boundary conditions in the bulk induce "double deformations" on the Celestial CFT side, which can be understood as an analogy of double trace deformations in the usual AdS/CFT. We compute two-point bulk scattering amplitudes under the non-trivial deformed boundary conditions. In the latter Wedge-like holography approach, we consider mixed Neumann/Dirichlet boundary conditions on the null infinity of the light-cone. We find that this mixing induces a renormalization flow in the dual Wedge CFT side under the Wedge holography, as in the usual AdS/CFT. We argue that the discrepancy between the Wedge two-point function and the Celestial two-point function originates from a sensitivity of bulk massless fields to a regularization parameter to use the usual AdS/CFT techniques., Comment: No figure; v3: deleted section 3.4. v2: minor modifications, typos corrected, added appendix B

With the wide adoption of building automation system, and the advancement of data, sensing, and machine learning techniques, data-driven fault detection and diagnostics (FDD) for building heating, ventilation, and air conditioning systems has gained increasing attention. In this paper, data-driven FDD is defined as those that are built or trained from data via machine learning or multivariate statistical analysis methods. Following this definition, this paper reviews and summarizes the literature on data-driven FDD from three aspects: process, systems studied (including the systems being investigated, the faults being identified, and the associated data sources), and evaluation metrics. A data-driven FDD process is further divided into the following steps: data collection, data cleansing, data preprocessing, baseline establishment, fault detection, fault diagnostics, and potential fault prognostics. Literature reported data-driven methods used in each step of an FDD process are firstly discussed. Applications of data-driven FDD in various HVAC systems/components and commonly used data source for FDD development are reviewed secondly, followed by a summary of typical metrics for evaluating FDD methods. Finally, this literature review concludes that despite the promising performance reported in the literature, data-driven FDD methods still face many challenges, such as real-building deployment, performance evaluation and benchmarking, scalability and transferability, interpretability, cyber security and data privacy, user experience, etc. Addressing these challenges is critical for a broad real-building adoption of data-driven FDD.

Determining which elements of an artwork influence people's psychology is a challenging yet crucial question. Especially in the case of video art, it is expected that movement plays an important role. We have evaluated video art created by one of the authors focusing on movement through psychological experiments.

Conventional bivalent antibodies against cell surface receptors often initiate unwanted signal transduction by crosslinking two antigen molecules. Biparatopic antibodies (BpAbs) bind to two different epitopes on the same antigen, thus altering crosslinking ability. In this study, we develop BpAbs against tumor necrosis factor receptor 2 (TNFR2), which is an attractive immune checkpoint target. Using different pairs of antibody variable regions specific to topographically distinct TNFR2 epitopes, we successfully regulate the size of BpAb–TNFR2 immunocomplexes to result in controlled agonistic activities. Our series of results indicate that the relative positions of the two epitopes recognized by the BpAb are critical for controlling its signaling activity. One particular antagonist, Bp109-92, binds TNFR2 in a 1:1 manner without unwanted signal transduction, and its structural basis is determined using cryo-electron microscopy. This antagonist suppresses the proliferation of regulatory T cells expressing TNFR2. Therefore, the BpAb format would be useful in designing specific and distinct antibody functions.

The protein kinase DYRK1A encoded in human chromosome 21 is the major contributor to the multiple symptoms observed in Down syndrome patients. In addition, DYRK1A malfunction is associated with various other neurodevelopmental disorders such as autism spectrum disorder. Here, we identified FAM53C with no hitherto known biological function as a novel suppressive binding partner of DYRK1A. FAM53C is bound to the catalytic protein kinase domain of DYRK1A, whereas DCAF7/WDR68, the major DYRK1A-binding protein, binds to the N-terminal domain of DYRK1A. The binding of FAM53C inhibited autophosphorylation activity of DYRK1A and its kinase activity to an exogenous substrate, MAPT/Tau. FAM53C did not bind directly to DCAF7/WDR68, whereas DYRK1A tethered FAM53C and DCAF7/WDR68 by binding concurrently to both of them, forming a tri-protein complex. DYRK1A possesses an NLS and accumulates in the nucleus when overexpressed in cells. Co-expression of FAM53C induced cytoplasmic re-localization of DYRK1A, revealing the cytoplasmic anchoring function of FAM53C to DYRK1A. Moreover, the binding of FAM53C to DYRK1A suppressed the DYRK1A-dependent nuclear localization of DCAF7/WDR68. All the results show that FAM53C binds to DYRK1A, suppresses its kinase activity, and anchors it in the cytoplasm. In addition, FAM53C is bound to the DYRK1A-related kinase DYRK1B with an Hsp90/Cdc37-independent manner. The results explain for the first time why endogenous DYRK1A is distributed in the cytoplasm in normal brain tissue. FAM53C-dependent regulation of the kinase activity and intracellular localization of DYRK1A may play a significant role in gene expression regulation caused by normal and aberrant levels of DYRK1A.

Liquid-liquid phase separation (LLPS) is involved in various dynamic biological phenomena. In epithelial cells, dynamic regulation of junctional actin filaments tethered to the apical junctional complex (AJC) is critical for maintaining internal homeostasis against external perturbations; however, the role of LLPS in this process remains unknown. Here, after identifying a multifunctional actin nucleator, cordon bleu (Cobl), as an AJC-enriched microtubule-associated protein, we conducted comprehensive in vitro and in vivo analyses. We found that apical microtubules promoted LLPS of Cobl at the AJC, and Cobl actin assembly activity increased upon LLPS. Thus, microtubules spatiotemporally regulated junctional actin assembly for epithelial morphogenesis and paracellular barriers. Collectively, these findings established that LLPS of the actin nucleator Cobl mediated dynamic microtubule-actin cross-talk in junctions, which fine-tuned the epithelial barrier.

PURPOSE: To investigate the 10-year visual outcome and chorioretinal atrophy after a single intravitreal ranibizumab injection (IVR) followed by a pro re nata (PRN) regimen for myopic macular neovascularization (mMNV) in pathologic myopia, and to identify the factors associated with 10-year best-corrected visual acuity (BCVA). METHODS: This retrospective observational study evaluated 26 consecutive treatment-naïve eyes (26 patients) with mMNV in pathologic myopia who underwent a single IVR followed by a PRN regimen of IVR and/or intravitreal aflibercept injection and observed over 10 years. We assessed changes in BCVA and morphological parameters, including the META-PM Study category as a chorioretinal atrophy index. RESULTS: The logarithm of the minimum angle of resolution BCVA changed from 0.36 (Snellen, 20/45) ± 0.39 to 0.39 (20/49) ± 0.36 over 10 years of observation. Compared to baseline, 1-year BCVA improved (P = 0.002), whereas 2-10-year BCVA was not significantly different. Total injection frequency was 3.8 ± 2.6. In none of the eyes, 10-year BCVA was 20/200 or less. Ten-year BCVA correlated with baseline BCVA (P = 0.01, r = 0.47). The META-PM Study category progressed in 60% of eyes. There were no drug-induced complications. CONCLUSIONS: BCVA in eyes with mMNV in pathologic myopia was maintained for 10 years after a single IVR followed by a PRN regimen without drug-induced complications. The META-PM Study category progressed in 60% of eyes, especially those with older baseline age. Early diagnosis and treatment of mMNV are essential to maintain good long-term BCVA.

Flavin adenine dinucleotide-dependent d-fructose dehydrogenase (FDH) from Gluconobacter japonicus NBRC3260, a membrane-bound heterotrimeric flavohemoprotein capable of direct electron transfer (DET)-type bioelectrocatalysis, was investigated from the perspective of structural biology, bioelectrochemistry, and protein engineering. DET-type reactions offer several benefits in biomimetics (e.g., biofuel cells, bioreactors, and biosensors) owing to their mediator-less configuration. FDH provides an intense DET-type catalytic signal; therefore, extensive research has been conducted on the fundamental principles and applications of biosensors. Structural analysis using cryo-electron microscopy and single-particle analysis has revealed the entire FDH structures with resolutions of 2.5 and 2.7 Å for the reduced and oxidized forms, respectively. The electron transfer (ET) pathway during the catalytic oxidation of d-fructose was investigated by using both thermodynamic and kinetic approaches. Structural analysis has shown the localization of the electrostatic surface charges around heme 2c in subunit II, and experiments using functionalized electrodes with a controlled surface charge support the notion that heme 2c is the electrode-active site. Furthermore, two aromatic amino acid residues (Trp427 and Phe489) were located in a possible long-range ET pathway between heme 2c and the electrode. Two variants (W427A and F489A) were obtained by site-directed mutagenesis, and their effects on DET-type activity were elucidated. The results have shown that Trp427 plays an essential role in accelerating long-range ET and triples the standard rate constant of heterogeneous ET according to bioelectrochemical analysis.

[Background] Electroconvulsive therapy (ECT) is one of the most effective treatments for depression and schizophrenia, particularly in urgent or treatment-resistant cases. After ECT, regional gray matter volume (GMV) increases have been repeatedly reported both in depression and schizophrenia. However, the interpretation of these findings remains entangled because GMV changes do not necessarily correlate with treatment effects and may be influenced by the intervention itself. We hypothesized that the comparison of longitudinal magnetic resonance imaging data between the two diagnostic groups will provide clues to distinguish diagnosis-specific and transdiagnostic changes. [Method] Twenty-nine Japanese participants, including 18 inpatients with major depressive disorder and 11 with schizophrenia, underwent longitudinal voxel-based morphometry before and after ECT. We investigated GMV changes common to both diagnostic groups and those specific to each group. Moreover, we also evaluated potential associations between GMV changes and clinical improvement for each group. [Results] In both diagnostic groups, GMV increased in widespread areas after ECT, sharing common regions including: anterior temporal cortex; medial frontal and anterior cingulate cortex; insula; and caudate nucleus. In addition, we found a schizophrenia-specific GMV increase in a region including the left pregenual anterior cingulate cortex, with volume increase significantly correlating with clinical improvement. [Conclusions] Transdiagnostic volume changes may represent the effects of the intervention itself and pathophysiological changes common to both groups. Conversely, diagnosis-specific volume changes are associated with treatment effects and may represent pathophysiology-specific impacts of ECT.

Gender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal countries might be reflected in differences in their brain structure, and this could be the neural mechanism partly explaining women’s worse outcomes in gender-unequal countries. We examined this through a random-effects meta-analysis on cortical thickness and surface area differences between adult healthy men and women, including a meta-regression in which country-level gender inequality acted as an explanatory variable for the observed differences. A total of 139 samples from 29 different countries, totaling 7, 876 MRI scans, were included. Thickness of the right hemisphere, and particularly the right caudal anterior cingulate, right medial orbitofrontal, and left lateral occipital cortex, presented no differences or even thicker regional cortices in women compared to men in gender-equal countries, reversing to thinner cortices in countries with greater gender inequality. These results point to the potentially hazardous effect of gender inequality on women’s brains and provide initial evidence for neuroscience-informed policies for gender equality.

Delineating visual field maps and iso-eccentricities from fMRI data is an important but time-consuming task for many neuroimaging studies on the human visual cortex because the traditional methods of doing so using retinotopic mapping experiments require substantial expertise as well as scanner, computer, and human time. Automated methods based on gray-matter anatomy or a combination of anatomy and functional mapping can reduce these requirements but are less accurate than experts. Convolutional Neural Networks (CNNs) are powerful tools for automated medical image segmentation. We hypothesize that CNNs can define visual area boundaries with high accuracy. We trained U-Net CNNs with ResNet18 backbones to predict either V1, V2, and V3 boundaries or 5 regions of iso-eccentricity using human-labeled maps. Separate CNNs were trained to predict these regions using different combinations of the following input data: (1) anatomical data from a T1-weighted image only, (2) anatomical data from T1-weighted and T2*-weighted images, (3) white-matter tract endpoints from diffusion-weighted imaging, (4) functional data from retinotopic mapping. All CNNs using functional data had cross-validated accuracy that was statistically indistinguishable from the inter-rater reliability of the training dataset (dice coefficient of 92%) while the CNNs lacking functional data had lower but similar accuracies (~75%). Existing models that do not use CNNs had accuracies lower than any of the CNNs. These results demonstrate that with current methods and data quality, CNNs can replace the time and effort of human experts in manually defining early retinotopic maps, but cannot yet replace the acquisition of functional data.

type:Text, Objectives: Methotrexate (MTX) is associated with extensive side effects, including myelosuppression, interstitial pneumonia, and infection. It is, therefore, critical to establish whether its administration is required after achieving remission with tocilizumab (TCZ) and MTX combination therapy in patients with rheumatoid arthritis (RA). Therefore, the aim of this multicenter, observational, cohort study was to evaluate the feasibility of MTX discontinuation for the safety of these patients. Methods: Patients with RA were administered TCZ, with or without MTX, for 3 years; those who received TCZ+MTX combination therapy were selected. After remission was achieved, MTX was discontinued without flare development in one group (discontinued [DISC] group, n = 33) and continued without flare development in another group (maintain [MAIN] group, n = 37). The clinical efficacy of TCZ+MTX therapy, patient background characteristics, and adverse events were compared between groups. Results: The disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) at 3, 6, and 9 months was significantly lower in the DISC group (P < .05, P < .01, and P < .01, respectively). Further, the DAS28-ESR remission rate at 6 and 9 months and Boolean remission rate at 6 months were significantly higher in the DISC group (P < .01 for all). Disease duration was significantly longer in the DISC group (P < .05). Furthermore, the number of patients with stage 4 RA was significantly higher in the DISC group (P < .01). Conclusions: Once remission was achieved, MTX was discontinued in patients who responded favorably to TCZ+MTX therapy, despite the prolonged disease duration and stage progression.

The patients diagnosed with coronavirus disease 2019 （COVID-19） produce IgM and IgG antibodies against severe acute respiratory syndrome coronavirus 2 （SARS-CoV-2）. However, the frequency and duration of antibody production still need to be fully understood. In the present study, we investigated the duration of antibody production after SARS-CoV-2 infection. The patients diagnosed with COVID-19 were monitored over twelve months for the production of SARS-CoV-2 IgM and IgG antibodies, and the characteristics of these patients were examined. Forty-five patients diagnosed with COVID-19 were enrolled, and thirty-four patients were followed up until they tested negative for SARS-CoV-2 IgM and IgG antibodies or up to twelve months after the date of a negative SARS-CoV-2 polymerase chain reaction （PCR） result. The positivity rates of SARS-CoV-2 IgM and IgG antibodies were 27.3％ and 68.2％ when SARS-CoV-2 PCR was negative, 20.6％ and 70.6％ after one month, 8.8％ and 52.9％ after three months, and 0.0％ and 14.7％ after six months, respectively. Moreover, we compared patients with milder conditions who did not require oxygen administration with those with severe conditions which required oxygen administration. The positivity rate of SARS-CoV-2 IgG antibodies was significantly higher in patients with severe conditions than in those with milder conditions on the date of a negative SARS-CoV-2 PCR result and after one month and three months, but not after six months. Patients with more severe COVID-19 produced more SARS-CoV-2 IgG antibodies. Moreover, it is suggested that the duration of IgG antibody production is independent of COVID-19 severity.

This paper considers the sustainability of geosynthetics-based solutions to mitigate landslide risks. The different types of geosynthetics are briefly described, along with their functions and applications relevant to landslides, emphasizing reinforcement. The paper identifies the sustainability factors to consider when applying geosyn-thetics for these purposes. The paper then presents an overview based on existing literature to illustrate how geosynthetics typically outperform traditional methods across a range of sustainability criteria across the entire life cycle. The paper shows lastly how the value integrated model for sustainable evaluations (MIVES) tool can be applied to evaluate and compare alternative methods for remediation of landslides and recommends further studies using this tool., Peer Reviewed, Postprint (published version)

Reports of cervical thymoma with myasthenia gravis are rare. In addition, 99mTc-MIBI (methoxyisobutylisonitrile:sestamibi) scintigraphy is a useful diagnostic examination for enlarged parathyroid tumours; however, there are a few reports of its accumulation in thymoma. Among them, there are no reports of cervical thymomas with 99mTc-MIBI accumulation complicated by myasthenia gravis. In this study, we performed surgery on a patient with preoperative myasthenic crisis accompanied by a cervical thymoma and a parathyroid tumour. Preoperatively, the cervical mass was determined to be a parathyroid tumour and was complicated by myasthenia gravis without thymic tumour. However, a pathological examination revealed that the cervical tumour with 99mTc-MIBI accumulation was a Type B2 thymoma, and a parathyroid tumour was identified in the vicinity. We report a very rare case in which symptoms improved with surgery.Go Kamimura, Kazuhiro Ueda, Aya Takeda, Ryo Miyata, Masaya Aoki, Toshiyuki Nagata, Masami SatoA case of ectopic cervical thymoma with myasthenia gravis mimicking a parathyroid tumourRespirology Case Reports. 2022;10:e01052.https://doi.org/10.1002/rcr2.1052

Prolactin (PRL), a hormone involved in lactation, is mainly produced and secreted by the lactotrophs of the anterior pituitary (AP) gland. We previously reported a method to generate functional adrenocorticotropic hormone-producing cells by differentiating the AP and hypothalamus simultaneously from human induced pluripotent stem cells (iPSCs). However, PRL-producing cells in the induced AP have not been investigated. Here, we confirmed the presence of PRL-producing cells and evaluated their endocrine functions. We differentiated pituitary cells from human iPSCs using serum-free floating culture of embryoid-like aggregates with quick reaggregation (SFEB-q) method and evaluated the appearance and function of PRL-producing cells. Secretion of PRL from the differentiated aggregates was confirmed, which increased with further culture. Fluorescence immunostaining and immunoelectron microscopy revealed PRL-producing cells and PRL-positive secretory granules, respectively. PRL secretion was promoted by various prolactin secretagogues such as thyrotropin-releasing hormone, vasoactive intestinal peptide, and prolactin-releasing peptide, and inhibited by bromocriptine. Moreover, the presence of tyrosine hydroxylase-positive dopaminergic nerves in the hypothalamic tissue area around the center of the aggregates connecting to PRL-producing cells indicated the possibility of recapitulating PRL regulatory mechanisms through the hypothalamus. In conclusion, we generated pituitary lactotrophs from human iPSCs; these displayed similar secretory responsiveness as human pituitary cells in vivo. In the future, this is expected to be used as a model of human PRL-producing cells for various studies, such as drug discovery, prediction of side effects, and elucidation of tumorigenic mechanisms using disease-specific iPSCs. Furthermore, it may help to develop regenerative medicine for the pituitary gland.

Many bacteria belonging to the phylum Bacteroidetes move on solid surfaces, called gliding motility. In our previous study with the Bacteroidetes gliding bacterium Flavobacterium johnsoniae, we proposed a helical loop track model, where adhesive SprB filaments are propelled along a helical loop on the cell surface. In this study, we observed the gliding cell rotating counterclockwise about its axis when viewed from the rear to the advancing direction of the cell and revealed that one labeled SprB focus sometimes overtook and passed another SprB focus that was moving in the same direction. Several electron microscopic analyses revealed the presence of a possible multi-rail structure underneath the outer membrane, which was associated with SprB filaments and contained GldJ protein. These results provide insights into the mechanism of Bacteroidetes gliding motility, in which the SprB filaments are propelled along tracks that may form a multi-rail system underneath the outer membrane. The insights may give clues as to how the SprB filaments get their driving force., Communications Biology, 6(1), art. no. 94; 2023

The notion that modern buildings should strive to be net-zero energy buildings (NZEBs) is widely accepted. One of the causes leading to high energy usage for space heating, resulting in avoidable carbon emissions, is heat loss via building windows. In order to improve window's insulation in existing buildings, structured-core transparent vacuum insulation panels (TVIPs) are proposed. TVIPs mainly consist of the structured core material, the low-emissivity film, and the transparent gas barrier envelope. TVIPs have high insulation performance and are inexpensive to manufacture and can be easily installed. Therefore, TVIPs have the potential to improve window's insulation in existing buildings at a low cost. However, it is necessary to overcome the issue of preventing the pressure rise inside TVIP after vacuum sealing. The authors constructed an experimental setup to quantify the effect of reduction of gas flow rate in TVIP after evacuation by applying the pressure-rate-of-rise-method. In this experiment, a gas barrier film with a straw was used as the vacuum chamber. This could reproduce the pressure increase in the TVIP after sealing and the gas flow rate in the TVIP is evaluated. The experimental result shows that the coated core material and the enclosing getter agent lowered the pressure rise and gas flow rate in TVIP by combining concurrent evacuation and heating. Furthermore, after extending the simultaneous vacuuming and heating period to 8 h and applying the coated core material, and enclosing the getter agent, the internal pressure in TVIP may be lowered to around 1 Pa after 30 min after halting vacuuming. It was confirmed that this pressure satisfied the performance required for TVIPs, and the result was much closer to the realization of TVIPs.

This letter studies the mechanism of semiconducting single-walled carbon nanotubes (sc-SWCNTs) enhanced poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT:PSS) for organic solar cells (OSCs). PEDOT:PSS is significantly enhanced by sc-SWCNTs among energy level, hole-transporting mobility, and surface morphology. OSCs using enhanced PEDOT:PSS by sc-SWCNTs with larger diameters achieve the highest efficiency of 6.63%.