BACKGROUND\nMETHODS\nRESULTS\nCONCLUSION\nVulvar squamous cell carcinoma (VSCC) is a rare disease with a poor prognosis. To date, there's no proper in vitro modeling system for VSCC to study its... Show moreBACKGROUND\nMETHODS\nRESULTS\nCONCLUSION\nVulvar squamous cell carcinoma (VSCC) is a rare disease with a poor prognosis. To date, there's no proper in vitro modeling system for VSCC to study its pathogenesis or for drug evaluation.\nWe established healthy vulvar (HV)- and VSCC-like 3D full thickness models (FTMs) to observe the tumor-stroma interaction and their applicability for chemotherapeutic efficacy examination. VSCC-FTMs were developed by seeding VSCC tumor cell lines (A431 and HTB117) onto dermal matrices harboring two NF subtypes namely papillary fibroblasts (PFs) and reticular fibroblasts (RFs), or cancer-associated fibroblasts (CAFs) while HV-FTMs were constructed with primary keratinocytes and fibroblasts isolated from HV tissues.\nHV-FTMs highly resembled HV tissues in terms of epidermal morphogenesis, basement membrane formation and collagen deposition. When the dermal compartment shifted from PFs to RFs or CAFs in VSCC-FTMs, tumor cells demonstrated more proliferation, EMT induction and stemness. In contrast to PFs, RFs started to lose their phenotype and express robust CAF-markers α-SMA and COL11A1 under tumor cell signaling induction, indicating a favored 'RF-to-CAF' transition in VSCC tumor microenvironment (TME). Additionally, chemotherapeutic treatment with carboplatin and paclitaxel resulted in a significant reduction in tumor-load and invasion in VSCC-FTMs.\nWe successfully developed in vitro 3D vulvar models mimicking both healthy and tumorous conditions which serve as a promising tool for vulvar drug screening programs. Moreover, healthy fibroblasts demonstrate heterogeneity in terms of CAF-activation in VSCC TME which brings insights in the future development of novel CAF-based therapeutic strategies in VSCC. Show less
Due to its effectivity and efficiency, deep hashing approaches are widely used for large-scale visual search. However, it is still challenging to produce compact and discriminative hash codes for... Show moreDue to its effectivity and efficiency, deep hashing approaches are widely used for large-scale visual search. However, it is still challenging to produce compact and discriminative hash codes for images asso-ciated with multiple semantics for two main reasons, 1) similarity constraints designed in most of the existing methods are based upon an oversimplified similarity assignment (i.e., 0 for instance pairs sharing no label, 1 for instance pairs sharing at least 1 label), 2) the exploration in multi-semantic relevance are insufficient or even neglected in many of the existing methods. These problems significantly limit the dis-crimination of generated hash codes. In this paper, we propose a novel Deep Hashing with Self-Supervised Asymmetric Semantic Excavation and Margin-Scalable Constraint(SADH) approach to cope with these problems. SADH implements a self-supervised network to sufficiently preserve semantic information in a semantic feature dictionary and a semantic code dictionary for the semantics of the given dataset, which efficiently and precisely guides a feature learning network to preserve multi-label semantic information using an asymmetric learning strategy. By further exploiting semantic dictionaries, a new margin-scalable constraint is employed for both precise similarity searching and robust hash code generation. Extensive empirical research on four popular benchmarks validates the proposed method and shows it outperforms several state-of-the-art approaches. The source codes URL of our SADH is: http:// github.com/SWU-CS-MediaLab/SADH. (c) 2022 Elsevier B.V. All rights reserved. Show less
The recent deep cross-modal hashing (DCMH) has achieved superior performance in effective and efficient cross-modal retrieval and thus has drawn increasing attention. Nevertheless, there are still... Show moreThe recent deep cross-modal hashing (DCMH) has achieved superior performance in effective and efficient cross-modal retrieval and thus has drawn increasing attention. Nevertheless, there are still two limitations for most existing DCMH methods: (1) single labels are usually leveraged to measure the semantic similarity of cross-modal pairwise instances while neglecting that many cross-modal datasets contain abundant semantic information among multi-labels. (2) several DCMH methods utilized the multi-labels to supervise the learning of hash functions. Nevertheless, the feature space of multilabels suffers the weakness of sparse, resulting in sub-optimization for the hash functions learning. Thus, this paper proposed a multi-label modality enhanced attention-based self-supervised deep cross-modal hashing (MMACH) framework. Specifically, a multi-label modality enhanced attention module is designed to integrate the significant features from cross-modal data into multi-labels feature representations, aiming to improve its completion. Moreover, a multi-label cross-modal triplet loss is defined based on the criterion that the feature representations of cross-modal pairwise instances with more common categories should preserve higher semantic similarity than other instances. To the best of our knowledge, the multi-label cross-modal triplet loss is the first time designed for cross-modal retrieval. Extensive experiments on four multi-label cross-modal datasets demonstrate the effectiveness and efficiency of our proposed MMACH. Moreover, the MMACH also achieved superior performance and outperformed several state-of-the-art methods on the task of cross-modal retrieval. The source code of MMACH is available at https://github.com/SWU-CS-MediaLab/MMACH. (c) 2021 Elsevier B.V. All rights reserved. Show less
Core cross-linking of polymeric micelles has been demonstrated to contribute to enhanced stability that can improve the therapeutic efficacy. Photochemistry has the potential to provide spatial... Show moreCore cross-linking of polymeric micelles has been demonstrated to contribute to enhanced stability that can improve the therapeutic efficacy. Photochemistry has the potential to provide spatial resolution and on-demand drug release. In this study, light-sensitive polypyridyl-ruthenium(II) complexes were combined with polypept(o)ides for photocleavable core cross-linked polymeric micelles. Block copolymers of polysarcosine-block-poly(glutamic acid) were synthesized by ring-opening N-carboxyanhydride polymerization and modified with aromatic nitrile-groups on the glutamic acid side chain. The modified copolymers self-assembled into micelles and were cross-linked by cis-diaquabis(2,2'-bipyridine)-ruthenium(II) ([Ru(bpy)2(H2O)2]2+) or cis-diaquabis(2,2'-biquinoline)-ruthenium(II) ([Ru(biq)2(H2O)2]2+). Depending on the flexibility and hydrophobicity of the nitrile linker, either small spherical structures (Dh 45 nm, PDI 0.11) or worm-like micelles were obtained. The cross-linking reaction did not affect the overall size distribution but induced a change in the metal-to-ligand charge transfer peak from 482 to 420 nm and 592 to 548 nm. The cross-linked micelles displayed colloidal stability after incubation with human blood plasma and during gel permeation chromatography in hexafluoroisopropanol. Light-induced cleavage of [Ru(bpy)2(H2O)2]2+ was accomplished within 300 s, while [Ru(biq)2(H2O)2]2+ could not be completely released. Analysis in HuH-7 cells revealed increased cytotoxicity via micellar delivery of [Ru(bpy)2(H2O)2]2+ but mostly irradiation damage for [Ru(biq)2(H2O)2]2+. Further evaluation in ovo confirmed stable circulation pointing towards the future development of quick-release complexes. Show less
Sun, W.; Wen, Y.; Thiramanas, R.; Chen, M.; Han, J.; Gong, N.; ... ; Wu, S. 2018
Traditional photodynamic phototherapy is not efficient for anticancer treatment because solid tumors have a hypoxic microenvironment. The development of photoactivated chemotherapy based on... Show moreTraditional photodynamic phototherapy is not efficient for anticancer treatment because solid tumors have a hypoxic microenvironment. The development of photoactivated chemotherapy based on photoresponsive polymers that can be activated by light in the “therapeutic window” would enable new approaches for basic research and allow for anticancer phototherapy in hypoxic conditions. This work synthesizes a novel Ru‐containing block copolymer for photoactivated chemotherapy in hypoxic tumor environment. The polymer has a hydrophilic poly(ethylene glycol) block and a hydrophobic Ru‐containing block, which contains red‐light‐cleavable (650–680 nm) drug–Ru complex conjugates. The block copolymer self‐assembles into micelles, which can be efficiently taken up by cancer cells. Red light induces release of the drug–Ru complex conjugates from the micelles and this process is oxygen independent. The released conjugates inhibit tumor cell growth even in hypoxic tumor environment. Furthermore, the Ru‐containing polymer for photoactivated chemotherapy in a tumor‐bearing mouse model is applied. Photoactivated chemotherapy of the polymer micelles demonstrates efficient tumor growth inhibition. In addition, the polymer micelles do not cause any toxic side effects to mice during the treatment, demonstrating good biocompatibility of the system to the blood and healthy tissues. The novel red‐light‐responsive Ru‐containing polymer provides a new platform for phototherapy against hypoxic tumors. Show less
This paper provides an overview of the discussion and presentations from the Workshop on the Management of Large CryoEM Facilities held at the New York Structural Biology Center, New York, NY on... Show moreThis paper provides an overview of the discussion and presentations from the Workshop on the Management of Large CryoEM Facilities held at the New York Structural Biology Center, New York, NY on February 6-7, 2017. A major objective of the workshop was to discuss best practices for managing cryoEM facilities. The discussions were largely focused on supporting single-particle methods for cryoEM and topics included: user access, assessing projects, workflow, sample handling, microscopy, data management and processing, and user training. Show less
With the ever-growing amount of image data on the web, much attention has been devoted to large scale image search. It is one of the most challenging problems in computer vision for several... Show moreWith the ever-growing amount of image data on the web, much attention has been devoted to large scale image search. It is one of the most challenging problems in computer vision for several reasons. First, it must address various appearance transformations such as changes in perspective, rotation and scale existing in the huge amount of image data. Second, it needs to minimize memory requirements and computational cost when generating image representations. Finally, it needs to construct an efficient index space and a suitable similarity measure to reduce the response time to the users. This thesis aims to provide robust image representations that are less sensitive to above mentioned appearance transformations and are suitable for large scale image retrieval. Although this thesis makes a substantial number of contributions to large scale image retrieval, we also presented additional challenges and future research based on the contributions in this thesis. Show less
OBJECTIVE The established causes of GH insensitivity include defects of the GH receptor and STAT5B. The latter condition is also characterized by severe immunodeficiency. A recent case with short... Show moreOBJECTIVE The established causes of GH insensitivity include defects of the GH receptor and STAT5B. The latter condition is also characterized by severe immunodeficiency. A recent case with short stature, GH resistance, and immunodeficiency due to an IκB mutation suggests that the NF-κB pathway may interact with STAT5B signaling. DESIGN Here, we present a case of a short child with several congenital anomalies as well as GH insensitivity and mild immunodeficiency associated with a mosaic de novo duplication of chromosome 17q21-25, suggesting that overexpression of one of the duplicated genes may be implicated in GH resistance. METHODS AND RESULTS In vitro studies on blood lymphocytes showed disturbed signaling of the CD28 pathway, involving NF-κB and related proteins. Functional studies on cultured skin fibroblasts revealed that NF-κB activation, PI3K activity, and STAT5 phosphorylation in response to GH were suppressed, while the sensitivity to GH in terms of MAPK phosphorylation was increased. An in silico analysis of the duplicated genes showed that MAP3K3 and PRKCA are associated with the NF-κB pathway. Baseline MAP3K3 expression in T-cell blasts (TCBs) was normal, but PRKCA expression in TCBs and fibroblasts was significantly higher than that in control cells. CONCLUSIONS We conclude that the 17q21-25 duplication is associated with GH insensitivity and disturbed STAT5B, PI3K, and NF-κB signaling, possibly due to PRKCA mRNA overexpression. Show less
