Miracle-dz/UniFAR-FTUs huggingface dataset:
Repression of Memo1, a Novel Target of Human Papillomavirus Type 16 E7, Increases Cell Proliferation in Cervical Cancer Cells

Although numerous targets have been reported to interact with the HPV E7 oncoprotein, the mechanisms involved in HPV-induced carcinogenesis and the maintenance of cell transformation are still lacking. Here, through pulldown assays using a peptide encompassing the C-terminal region of HPV16 E7, we report Memo1 as a novel E7 interactor. ABSTRACT Human papillomavirus (HPV)-induced carcinogenesis is associated with unregulated expression of the oncoproteins E6 and E7. HPV E7 is a viral protein that lacks enzymatic activity; however, it can target several cellular proteins to induce cell transformation and promote uncontrolled proliferation. Although several E7 targets have been described, there are still gaps in the understanding of how this oncoprotein drives cells toward malignancy. Here, using a small HPV type 16 (HPV16) E7 peptide in a proteomic approach, we report Memo1 as a new E7 binding partner, interacting through the aspartic and glutamic acid residues (E80 and D81) in the C-terminal region of HPV16 E7. Furthermore, we demonstrate that HPV16 E7 targets Memo1 for proteasomal degradation through a Cullin2-dependent mechanism. In addition, we show that overexpression of Memo1 decreases cell transformation and proliferation and that reduction of Memo1 levels correlate with activation of Akt and an increase in invasion of HPV-positive cervical cancer cell lines. Our results show a novel HPV E7 interacting partner and describe novel functions of Memo1 in the context of HPV-induced malignancy. IMPORTANCE Although numerous targets have been reported to interact with the HPV E7 oncoprotein, the mechanisms involved in HPV-induced carcinogenesis and the maintenance of cell transformation are still lacking. Here, through pulldown assays using a peptide encompassing the C-terminal region of HPV16 E7, we report Memo1 as a novel E7 interactor. High levels of Memo1 correlated with reduced cell proliferation and, concordantly, knockdown of Memo1 resulted in Akt activation in HPV-positive cell lines. These results highlight new mechanisms used by HPV oncoproteins to modulate proliferation pathways in cervical cancer cells and increase our understanding of the link between Memo1 protein and cancer.
COMPUTATIONAL METHODS FOR THE OPTIMAL RECONSTRUCTION OF MATERIAL PROPERTIES IN COMPLEX MULTIPHYSICS SYSTEMS

In this work we propose and validate a computational method for reconstructing constitutive relations (material properties) in complex multiphysics phenomena based on incomplete and noisy measurements which is applicable to different problems arising in nonequilibrium thermodynamics and continuum mechanics. The parameter estimation problem is solved as PDE–constrained optimization using a gradient–based technique in the optimize–then–discretize framework. The reconstructed material properties taken as an example here are the transport coefficients characterizing diffusion processes such as the viscosity and the thermal conductivity, and we focus on problems in which these coefficients depend on the state variables in the system. The proposed method allows one to reconstruct a smooth constitutive relation defined over a broad range of the dependent variable. This research is motivated by questions arising in the computational analysis and optimization of advanced welding processes which involves modelling complex alloys in the liquid phase at high temperatures.
The Limitations of User-and Human-Centered Design in an eHealth Context and How to Move Beyond Them

Human-centered design (HCD) is widely regarded as the best design approach for creating eHealth innovations that align with end users’ needs, wishes, and context and has the potential to impact health care. However, critical reflections on applying HCD within the context of eHealth are lacking. Applying a critical eye to the use of HCD approaches within eHealth, we present and discuss 9 limitations that the current practices of HCD in eHealth innovation often carry. The limitations identified range from limited reach and bias to narrow contextual and temporal focus. Design teams should carefully consider if, how, and when they should involve end users and other stakeholders in the design process and how they can combine their insights with existing knowledge and design skills. Finally, we discuss how a more critical perspective on using HCD in eHealth innovation can move the field forward and offer 3 directions of inspiration to improve our design practices: value-sensitive design, citizen science, and more-than-human design. Although value-sensitive design approaches offer a solution to some of the biased or limited views of traditional HCD approaches, combining a citizen science approach with design inspiration and imagining new futures could widen our view on eHealth innovation. Finally, a more-than-human design approach will allow eHealth solutions to care for both people and the environment. These directions can be seen as starting points that invite and support the field of eHealth innovation to do better and to try and develop more inclusive, fair, and valuable eHealth innovations that will have an impact on health and care.
Split genome-based retroviral replicating vectors achieve efficient gene delivery and therapeutic effect in a human glioblastoma xenograft model

The murine leukemia virus-based semi-retroviral replicating vectors (MuLV-based sRRV) had been developed to improve safety and transgene capacity for cancer gene therapy. However, despite the apparent advantages of the sRRV, improvements in the in vivo transduction efficiency are still required to deliver therapeutic genes efficiently for clinical use. In this study, we established a gibbon ape leukemia virus (GaLV) envelope-pseudotyped semi-replication-competent retrovirus vector system (spRRV) which is composed of two transcomplementing replication-defective retroviral vectors termed MuLV-Gag-Pol and GaLV-Env. We found that the spRRV shows considerable improvement in efficiencies of gene transfer and spreading in both human glioblastoma cells and pre-established human glioblastoma mouse model compared with an sRRV system. When treated with ganciclovir after intratumoral injection of each vector system into pre-established U-87 MG glioblastomas, the group of mice injected with spRRV expressing the herpes simplex virus type 1-thymidine kinase (HSV1-tk) gene showed a survival rate of 100% for more than 150 days, but all control groups of mice (HSV1-tk/PBS-treated and GFP/GCV-treated gruops) died within 45 days after tumor injection. In conclusion, these findings suggest that intratumoral delivery of the HSV1-tk gene by the spRRV system is worthy of development in clinical trials for the treatment of malignant solid tumors.
Phylogenetic and environmental patterns of sex differentiation in physiological traits across Drosophila species

Sex‐based differences in physiological traits may be influenced by both evolutionary and environmental factors. Here we used male and female flies from >80 Drosophila species reared under common conditions to examine variance in a number of physiological traits including size, starvation, desiccation and thermal tolerance. Sex‐based differences for desiccation and starvation resistance were comparable in magnitude to those for size, with females tending to be relatively more resistant than males. In contrast thermal resistance showed low divergence between the sexes. Phylogenetic signal was detected for measures of divergence between the sexes, such that species from the Sophophora clade showed larger differences between the sexes than species from the Drosophila clade. We also found that sex‐based differences in desiccation resistance, body size and starvation resistance were weakly associated with climate (annual mean temperature/precipitation seasonality) but the direction and association with environment depended on phylogenetic position. The results suggest that divergence between the sexes can be linked to environmental factors, while an association with phylogeny suggests sex‐based differences persist over long evolutionary time‐frames.
The bacterial virulence factor NleA undergoes host‐mediated O‐linked glycosylation

Enterohaemorrhagic and enteropathogenic Escherichia coli (EHEC and EPEC) are gastrointestinal pathogens responsible for severe diarrheal illness. EHEC and EPEC form “attaching and effacing” lesions during colonization and, upon adherence, inject proteins directly into host intestinal cells via the type III secretion system (T3SS). Injected bacterial proteins have a variety of functions but generally alter host cell biology to favor survival and/or replication of the pathogen. Non‐LEE‐encoded effector A (NleA) is a T3SS‐injected effector of EHEC, EPEC, and the related mouse pathogen Citrobacter rodentium. Studies in mouse models indicate that NleA has an important role in bacterial virulence. However, the mechanism by which NleA contributes to disease remains unknown. We have determined that the following translocation into host cells, a serine and threonine‐rich region of NleA is modified by host‐mediated mucin‐type O‐linked glycosylation. Surprisingly, this region was not present in several clinical EHEC isolates. When expressed in C. rodentium, a non‐modifiable variant of NleA was indistinguishable from wildtype NleA in an acute mortality model but conferred a modest increase in persistence over the course of infection in mixed infections in C57BL/6J mice. This is the first known example of a bacterial effector being modified by host‐mediated O‐linked glycosylation. Our data also suggests that this modification may confer a selective disadvantage to the bacteria during in vivo infection.
On the DB gap of white dwarf evolution: effects of hydrogen mass fraction and convective overshooting

We investigate the spectral evolution of white dwarfs by considering the effects of hydrogen mass in the atmosphere and convective overshooting above the convection zone. Our numerical results show that white dwarfs with M H ~ 10 - 16 M ⊙ show the DA spectral type between 46 000 ≤ T eff ≤ 26 000 K and the DO or DB spectral type may appear on either side of this temperature range. White dwarfs with M H ~ 10 - 15 M ⊙ appear as DA stars until they cool to T eff ∼ 31 000 K; from then on they will evolve into DB white dwarfs as a result of convective mixing. If M H in the white dwarfs is more than 10 - 14 M ⊙ , the convective mixing will not occur when T eff > 20 000 K, thus these white dwarfs always appear as DA stars. White dwarfs within the temperature range 46 000 ≤ T eff ≤ 31 000 K always show the DA spectral type, which coincides with the DB gap. We notice the importance of the convective overshooting and suggest that the overshooting length should be proportional to the thickness of the convection zone to better fit the observations.
Identifying the counterpart of HESS J1858+020

Aims. HESS J1858+020 is a weak γ-ray source that does not have any clear cataloged counterpart at any wavelengths. Recently, the source G35.6-0.4 was re-identified as a SNR. The HESS source lies towards the southern border of this remnant. The purpose of this work is to investigate the interstellar medium around the mentioned sources to look for possible counterparts of the very high energy emission. Methods. Using the 13 CO J = 1-0 line from the Galactic Ring Survey and mid-IR data from GLIMPSE we analyze the environs of HESS J1858+020 and SNR G35.6-0.4. Results. The 13 CO data show the presence of a molecular cloud towards the southern border of SNR G35.6-0.4 and at the same distance as the remnant. This cloud is composed of two molecular clumps, one over the SNR shell and the other located at the center of HESS J1858+020. We estimate a molecular mass and a density of ~5 × 10 3 M ⊙ and ~500 cm -3 respectively for each clump. Considering the gamma-ray flux observed towards HESS J1858+020, we estimate that a molecular cloud with a density of at least 150 cm -3 could explain the very high energy emission hadronically. Thus, we suggest that the γ-ray emission detected in HESS J1858+020 is due to hadronic mechanism. Additionally, analyzing mid-IR emission, we find that the region is active in star formation, which could be considered as an alternative or complementary possibility to explain the very high energy emission.
Perceived behavioral control as a moderator: Scientists’ attitude, norms, and willingness to engage the public

Scientists play important roles in conducting public engagement, but evidence shows that scientists perceive great challenges in doing so. Drawing broadly from the theory of planned behavior (TPB), this study examines factors predicting scientists’ willingness to conduct public engagement. This study further examines how perceived behavioral control (PBC) of conducting public engagement would moderate the relationships between the proposed predictors and scientists’ willingness to conduct public engagement. Using survey data collected from 706 scientists based in Singapore, this study found that attitude toward and personal norms of conducting public engagement, as well as PBC, significantly predicted scientists’ willingness to conduct public engagement. Notably, PBC interacted with attitude toward conducting public engagement, the perceived descriptive norms, the perceived positive media influence, and the perceived negative external norms of conducting public engagement, as well as personal norms of conducting public engagement to predict scientists’ willingness to conduct public engagement. We postulated the key role that the perception of the ease or difficulty plays in motivating scientists to conduct the skill-intensive endeavor explains the significant moderating effects. The theoretical implications on the TPB and the practical implications for public engagement are further discussed.
NIR SPECTROSCOPIC OBSERVATION OF MASSIVE GALAXIES IN THE PROTOCLUSTER AT z = 3.09

We present the results of near-infrared spectroscopic observations of the K-band-selected candidate galaxies in the protocluster at z = 3.09 in the SSA22 field. We observed 67 candidates with KAB < 24 and confirmed redshifts of the 39 galaxies at 2.0 < zspec < 3.4. Of the 67 candidates, 24 are certainly protocluster members with 3.04 ⩽ zspec ⩽ 3.12, which are massive red galaxies that have been unidentified in previous optical observations of the SSA22 protocluster. Many distant red galaxies (J − KAB > 1.4), hyper extremely red objects (J − KAB > 2.1), Spitzer MIPS 24 μm sources, active galactic nuclei (AGNs) as well as the counterparts of Lyα blobs and the AzTEC/ASTE 1.1 mm sources in the SSA22 field are also found to be protocluster members. The mass of the SSA22 protocluster is estimated to be ∼2–5 × 1014 M☉, and this system is plausibly a progenitor of the most massive clusters of galaxies in the current universe. The reddest (J − KAB ⩾ 2.4) protocluster galaxies are massive galaxies with Mstar ∼ 1011 M☉ showing quiescent star formation activities and plausibly dominated by old stellar populations. Most of these massive quiescent galaxies host moderately luminous AGNs detected by X-ray. There are no significant differences in the [O iii] λ5007/Hβ emission line ratios and [O iii] λ5007 line widths and spatial extents of the protocluster galaxies from those of massive galaxies at z ∼ 2–3 in the general field.
Personalized Decentralized Bilevel Optimization over Stochastic and Directed Networks

While personalization in distributed learning has been extensively studied, existing approaches employ dedicated algorithms to optimize their specific type of parameters (e.g., client clusters or model interpolation weights), making it difficult to simultaneously optimize different types of parameters to yield better performance. Moreover, their algorithms require centralized or static undirected communication networks, which can be vulnerable to center-point failures or deadlocks. This study proposes optimizing various types of parameters using a single algorithm that runs on more practical communication environments. First, we propose a gradient-based bilevel optimization that reduces most personalization approaches to the optimization of client-wise hyperparameters. Second, we propose a decentralized algorithm to estimate gradients with respect to the hyperparameters, which can run even on stochastic and directed communication networks. Our empirical results demonstrated that the gradient-based bilevel optimization enabled combining existing personalization approaches which led to state-of-the-art performance, confirming it can perform on multiple simulated communication environments including a stochastic and directed network. Code is available at https://github.com/hitachi-rd-cv/pdbo-hgp
MOTSLAM: MOT-assisted monocular dynamic SLAM using single-view depth estimation

Visual SLAM systems targeting static scenes have been developed with satisfactory accuracy and robustness. Dynamic 3D object tracking has then become a significant capability in visual SLAM with the requirement of under-standing dynamic surroundings in various scenarios including autonomous driving, augmented and virtual reality. However, performing dynamic SLAM solely with monocular images remains a challenging problem due to the difficulty of asso-ciating dynamic features and estimating their positions. In this paper, we present MOTSLAM, a dynamic visual SLAM system with the monocular configuration that tracks both poses and bounding boxes of dynamic objects. MOTSLAM first performs multiple object tracking (MOT) with associated both 2D and 3D bounding box detection to create initial 3D objects. Then, neural-network-based monocular depth estimation is applied to fetch the depth of dynamic features. Finally, camera poses, object poses, and both static, as well as dynamic map points, are jointly optimized using a novel bundle adjustment. Our experiments on the KITTI dataset demonstrate that our system has reached best performance on both camera ego-motion and object tracking on monocular dynamic SLAM.
Dynamical Isometry for Residual Networks

The training success, training speed and generalization ability of neural networks rely crucially on the choice of random parameter initialization. It has been shown for multiple architectures that initial dynamical isometry is particularly advantageous. Known initialization schemes for residual blocks, however, miss this property and suffer from degrading separability of different inputs for increasing depth and instability without Batch Normalization or lack feature diversity. We propose a random initialization scheme, RISOTTO, that achieves perfect dynamical isometry for residual networks with ReLU activation functions even for finite depth and width. It balances the contributions of the residual and skip branches unlike other schemes, which initially bias towards the skip connections. In experiments, we demonstrate that in most cases our approach outperforms initialization schemes proposed to make Batch Normalization obsolete, including Fixup and SkipInit, and facilitates stable training. Also in combination with Batch Normalization, we find that RISOTTO often achieves the overall best result.
Spatial-Temporal-Aware Safe Multi-Agent Reinforcement Learning of Connected Autonomous Vehicles in Challenging Scenarios

Communication technologies enable coordination among connected and autonomous vehicles (CAVs). However, it remains unclear how to utilize shared information to improve the safety and efficiency of the CAV system in dynamic and complicated driving scenarios. In this work, we propose a framework of constrained multi-agent reinforcement learning (MARL) with a parallel Safety Shield for CAVs in challenging driving scenarios that includes unconnected hazard vehicles. The coordination mechanisms of the proposed MARL include information sharing and cooperative policy learning, with Graph Convolutional Network (GCN)-Transformer as a spatial-temporal encoder that enhances the agent's environment awareness. The Safety Shield module with Control Barrier Functions (CBF)-based safety checking protects the agents from taking unsafe actions. We design a constrained multi-agent advantage actor-critic (CMAA2C) algorithm to train safe and cooperative policies for CAVs. With the experiment deployed in the CARLA simulator, we verify the performance of the safety checking, spatial-temporal encoder, and coordination mechanisms designed in our method by comparative experiments in several challenging scenarios with unconnected hazard vehicles. Results show that our proposed methodology significantly increases system safety and efficiency in challenging scenarios.
Mid-infrared interferometry of the massive young stellar object NGC 3603 - IRS 9A

Context. Very few massive young stellar objects (MYSO) have been studied in the infrared at high angular resolution due to their rarity and large associated extinction. We present observations and models for one of these MYSO candidates, NGC 3603 IRS 9A. Aims. Our goal is to investigate with infrared interferometry the structure of IRS 9A on scales as small as 200 AU, exploiting the fact that a cluster of O and B stars has blown away much of the obscuring foreground dust and gas. Methods. Observations in the N-band were carried out with the MIDI beam combiner attached to the VLTI, providing spatial information on scales of about 25 ‐ 95 milli-arcseconds (mas). Additional interferometric observations which probe the struct ure of IRS 9A on larger scales were performed with an aperture mask installed in the T-ReCS instrument of Gemini South. The spectral energy distribution (SED) is constrained by the MIDI N-band spectrum and by data from the Spitzer Space Telescope. Our efforts to model the structure and SED of IRS 9A range from simple geometrical models of the brightness distribution to one- and two-dimensional radiative transfer computations. Results. The target is resolved by T-ReCS, with an equivalent (elliptical) Gaussian width of 330 mas by 280 mas (2300 AU by 2000 AU). Despite this fact, a warm compact unresolved component was detected by MIDI which is possibly associated with the inner regions of a flattened dust distribution. Based on our interf erometric data, no sign of multiplicity was found on scales between about 200 AU and 700 AU projected separation. A geometric model consisting of a warm (1000 K) ring (400 AU diameter) and a cool (140 K) large envelope provides a good fit to the data. No single mod el fitting all visibility and photometric data could be found , with disk models performing better than spherical models. Conclusions. While the data are clearly inconsistent with a spherical dust distribution they are insuffi cient to prove the existence of a disk but rather hint at a more complex dust distribution.