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15 pages, 1607 KiB  
Article
A Hierarchical Inverse Lithography Method Considering the Optimization and Manufacturability Limit by Gradient Descent
by Haifeng Sun, Qingyan Zhang, Jie Zhou, Jianwen Gong, Chuan Jin, Ji Zhou and Junbo Liu
Micromachines 2025, 16(7), 798; https://doi.org/10.3390/mi16070798 - 8 Jul 2025
Viewed by 337
Abstract
Inverse lithography technology (ILT) based on the gradient descent (GD) algorithm, which is a classical local optimal method, can effectively improve the lithographic imaging fidelity. However, due to the low-pass filtering effect of the lithography imaging system, GD, although able to converge quickly, [...] Read more.
Inverse lithography technology (ILT) based on the gradient descent (GD) algorithm, which is a classical local optimal method, can effectively improve the lithographic imaging fidelity. However, due to the low-pass filtering effect of the lithography imaging system, GD, although able to converge quickly, is prone to fall into the local optimum for the information in the corner region of complex patterns. Considering the high-frequency information of the corner region during the optimization process, this paper proposes a resolution layering method to improve the efficiency of GD-based ILT algorithms. A corner-rounding-inspired target retargeting strategy is used to compensate for the over-optimization defect of GD for inversely optimizing the complex pattern layout. Furthermore, for ensuring the manufacturability of masks, differentiable top-hat and bottom-hat operations are employed to improve the optimization efficiency of the proposed method. To confirm the superiority of the proposed method, multiple optimization methods of ILT were compared. Numerical experiments show that the proposed method has higher optimization efficiency and effectively avoids the over-optimization. Full article
(This article belongs to the Section E:Engineering and Technology)
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16 pages, 5223 KiB  
Article
Design and Control of Bio-Inspired Joints for Legged Robots Driven by Shape Memory Alloy Wires
by Xiaojie Niu, Xiang Yao and Erbao Dong
Biomimetics 2025, 10(6), 378; https://doi.org/10.3390/biomimetics10060378 - 6 Jun 2025
Viewed by 481
Abstract
Bio-inspired joints play a pivotal role in legged robots, directly determining their motion capabilities and overall system performance. While shape memory alloy (SMA) actuators present superior power density and silent operation compared to conventional electromechanical drives, their inherent nonlinear hysteresis and restricted strain [...] Read more.
Bio-inspired joints play a pivotal role in legged robots, directly determining their motion capabilities and overall system performance. While shape memory alloy (SMA) actuators present superior power density and silent operation compared to conventional electromechanical drives, their inherent nonlinear hysteresis and restricted strain capacity (typically less than 5%) limit actuation range and control precision. This study proposes a bio-inspired joint integrating an antagonistic actuator configuration and differential dual-diameter pulley collaboration, achieving amplified joint stroke (±60°) and bidirectional active controllability. Leveraging a comprehensive experimental platform, precise reference input tracking is realized through adaptive fuzzy control. Furthermore, an SMA-driven bio-inspired leg is developed based on this joint, along with a motion retargeting framework to map human motions onto the robotic leg. Human gait tracking experiments conducted on the leg platform validate its motion performance and explore practical applications of SMA in robotics. Full article
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15 pages, 2957 KiB  
Article
A Vector-Based Motion Retargeting Approach for Exoskeletons with Shoulder Girdle Mechanism
by Jiajia Wang, Shuo Pei, Junlong Guo, Mingsong Bao and Yufeng Yao
Biomimetics 2025, 10(5), 312; https://doi.org/10.3390/biomimetics10050312 - 12 May 2025
Viewed by 397
Abstract
Shoulder girdle plays a dominant role in coordinating the natural movements of the upper arm. Inverse kinematics, optimization, and data-driven approaches are usually used to conduct motion retargeting. However, these methods do not consider shoulder girdle movement. When the kinematic structure of human [...] Read more.
Shoulder girdle plays a dominant role in coordinating the natural movements of the upper arm. Inverse kinematics, optimization, and data-driven approaches are usually used to conduct motion retargeting. However, these methods do not consider shoulder girdle movement. When the kinematic structure of human and that of exoskeletons share a similar joint configuration, analytical motion retargeting methods can be used for exoskeletons with shoulder girdle mechanism. This paper proposes a vector-based analytical motion retargeting approach for exoskeletons with shoulder girdle mechanism. The approach maps the vectors of the upper limb segments to the joint space using vector-based methods. Simulation results using four different motion descriptions confirm the method’s accuracy and efficiency. Full article
(This article belongs to the Special Issue Bionic Wearable Robotics and Intelligent Assistive Technologies)
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21 pages, 85270 KiB  
Article
Multi-Humanoid Robot Arm Motion Imitation and Collaboration Based on Improved Retargeting
by Xisheng Jiang, Baolei Wu, Simin Li, Yongtong Zhu, Guoxiang Liang, Ye Yuan, Qingdu Li and Jianwei Zhang
Biomimetics 2025, 10(3), 190; https://doi.org/10.3390/biomimetics10030190 - 19 Mar 2025
Cited by 1 | Viewed by 1424
Abstract
Human–robot interaction (HRI) is a key technology in the field of humanoid robotics, and motion imitation is one of the most direct ways to achieve efficient HRI. However, due to significant differences in structure, range of motion, and joint torques between the human [...] Read more.
Human–robot interaction (HRI) is a key technology in the field of humanoid robotics, and motion imitation is one of the most direct ways to achieve efficient HRI. However, due to significant differences in structure, range of motion, and joint torques between the human body and robots, motion imitation remains a challenging task. Traditional retargeting algorithms, while effective in mapping human motion to robots, typically either ensure similarity in arm configuration (joint space-based) or focus solely on tracking the end-effector position (Cartesian space-based). This creates a conflict between the liveliness and accuracy of robot motion. To address this issue, this paper proposes an improved retargeting algorithm that ensures both the similarity of the robot’s arm configuration to that of the human body and accurate end-effector position tracking. Additionally, a multi-person pose estimation algorithm is introduced, enabling real-time capture of multiple imitators’ movements using a single RGB-D camera. The captured motion data are used as input to the improved retargeting algorithm, enabling multi-robot collaboration tasks. Experimental results demonstrate that the proposed algorithm effectively ensures consistency in arm configuration and precise end-effector position tracking. Furthermore, the collaborative experiments validate the generalizability of the improved retargeting algorithm and the superior real-time performance of the multi-person pose estimation algorithm. Full article
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17 pages, 2917 KiB  
Article
Combining Prior Knowledge and Reinforcement Learning for Parallel Telescopic-Legged Bipedal Robot Walking
by Jie Xue, Jiaqi Huangfu, Yunfeng Hou and Haiming Mou
Mathematics 2025, 13(6), 979; https://doi.org/10.3390/math13060979 - 16 Mar 2025
Cited by 1 | Viewed by 674
Abstract
The parallel dual-slider telescopic leg bipedal robot (L04) is characterized by its simple structure and low leg rotational inertia, which contribute to its walking efficiency. However, end-to-end methods often overlook the robot’s physical structure, leading to difficulties in maintaining the parallel alignment of [...] Read more.
The parallel dual-slider telescopic leg bipedal robot (L04) is characterized by its simple structure and low leg rotational inertia, which contribute to its walking efficiency. However, end-to-end methods often overlook the robot’s physical structure, leading to difficulties in maintaining the parallel alignment of the dual sliders, which in turn compromises walking stability. One potential solution to this issue involves utilizing imitation learning to replicate human motion data. However, the dual telescopic leg structure of the L04 robot makes it difficult to perform motion retargeting of human motion data. To enable L04 walking, we design a method that integrates prior feedforward with reinforcement learning (PFRL), specifically tailored for the parallel dual-slider structure. We utilize prior knowledge as a feedforward action to compensate for system nonlinearities; meanwhile, the feedback action generated by the policy network adaptively regulates dynamic balance and, combined with the feedforward action, jointly controls the robot’s walking. PFRL enforces constraints within the motion space to mitigate the chaotic behavior of the parallel dual sliders. Experimental results show that our method successfully achieves sim2real transfer on a real bipedal robot without the need for domain randomization techniques or intricate reward functions. L04 achieves omnidirectional walking with minimal energy consumption and exhibits robustness against external disturbances. Full article
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14 pages, 775 KiB  
Article
Minimally Invasive One-Docking, Two-Target, and Three-Port Robotic-Assisted Nephroureterectomy: Redefining Surgical Approach
by Yarden Zohar, Ben Hefer, Itay Vazana, Muhammad H. Jabareen, Rabea Moed, Elad Mazor, Emilio Charabati, Nimer Alsaraia and Nicola J. Mabjeesh
Cancers 2025, 17(4), 627; https://doi.org/10.3390/cancers17040627 - 13 Feb 2025
Viewed by 863
Abstract
Objective: Nephroureterectomy (NU) is a challenging multi-quadrant surgical procedure that involves intra–infra- and retroperitoneal dissection. The introduction of the da Vinci Xi platform has further improved the minimally invasive approach. With the Xi robotic system, single docking for multi-quadrant dissection is now feasible [...] Read more.
Objective: Nephroureterectomy (NU) is a challenging multi-quadrant surgical procedure that involves intra–infra- and retroperitoneal dissection. The introduction of the da Vinci Xi platform has further improved the minimally invasive approach. With the Xi robotic system, single docking for multi-quadrant dissection is now feasible and increasingly popular. Herein, we redefined the surgical technique by optimizing minimal port usage, maximizing template visualization, and utilizing the Xi platform’s retargeting system, based on our experience with 15 patients. Methods: This single-center cohort study was based on the experience of a single surgeon with 15 patients who underwent robotic radical nephroureterectomy (RRNU) between 2019 and 2024, performed via the one docking, three-port technique. Patient data were retrospectively collected and analyzed from the medical records. Results: The cohort’s median age was 79 years, with male predominance of 80%. The median operative time was 133 min, with 60% of procedures completed within 150 min; longer times (>150 min) were due to additional intraoperative non-robotic procedures. Median blood loss was 100 mL, with two patients requiring intraoperative blood transfusion. Lymph node dissection (LND) in six patients did not significantly affect the overall operative time. The intraoperative and major postoperative complication rates (Clavien-Dindo grade > III) were 13.3%. Conclusions: The use of three robotic ports combined with the Xi platform’s camera-hop feature is a safe and effective technique for multi-quadrant, minimally invasive procedures, particularly in RRNU. This approach facilitates procedural goals and reduces overall operative time. Full article
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16 pages, 2709 KiB  
Article
PD1-Targeted Transgene Delivery to Treg Cells
by Vladislav A. Zhuchkov, Yulia E. Kravchenko, Elena I. Frolova and Stepan P. Chumakov
Viruses 2024, 16(12), 1940; https://doi.org/10.3390/v16121940 - 19 Dec 2024
Viewed by 1332
Abstract
Achieving the precise targeting of lentiviral vectors (LVs) to specific cell populations is crucial for effective gene therapy, particularly in cancer treatment where the modulation of the tumor microenvironment can enhance anti-tumor immunity. Programmed cell death protein 1 (PD-1) is overexpressed on activated [...] Read more.
Achieving the precise targeting of lentiviral vectors (LVs) to specific cell populations is crucial for effective gene therapy, particularly in cancer treatment where the modulation of the tumor microenvironment can enhance anti-tumor immunity. Programmed cell death protein 1 (PD-1) is overexpressed on activated tumor-infiltrating T lymphocytes, including regulatory T cells that suppress immune responses via FOXP3 expression. We developed PD1-targeted LVs by incorporating the anti-PD1 nanobody nb102c3 into receptor-blinded measles virus H and VSV-Gmut glycoproteins. We assessed the retargeting potential of nb102c3 and evaluated transduction efficiency in activated T lymphocytes. FOXP3 expression was suppressed using shRNA delivered by these LVs. Our results demonstrate that PD1-targeted LVs exerted pronounced tropism towards PD1+ cells, enabling the selective transduction of activated T lymphocytes while sparing naive T cells. The suppression of FOXP3 in Tregs reduced their suppressive activity. PD1-targeted glycoprotein H provided greater specificity, whereas the VSV-Gmut, together with the anti-PD1 pseudoreceptor, achieved higher viral titers but was less selective. Our study demonstrates that PD1-targeted LVs may offer a novel strategy to modulate immune responses within the tumor microenvironment with the potential for developing new therapeutic strategies aimed at enhancing anti-tumor immunity. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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6 pages, 610 KiB  
Case Report
Multiple Renal Infarctions in Spontaneous Double Renal Artery Dissection: A Case Report
by Gaetano Ferrara, Michelangelo Nasuto, Francesco Napolitano, Giovanni Ciccarese and Filippo Aucella
J. Clin. Med. 2024, 13(23), 7307; https://doi.org/10.3390/jcm13237307 - 1 Dec 2024
Cited by 1 | Viewed by 954
Abstract
Background: As spontaneous renal artery dissection (SRAD) is a rare cause of abdominal pain, bilateral dissection is an extremely rare event. Only approximately two hundred cases of SRAD have been reported in the literature. The diagnosis is often delayed due to the rarity [...] Read more.
Background: As spontaneous renal artery dissection (SRAD) is a rare cause of abdominal pain, bilateral dissection is an extremely rare event. Only approximately two hundred cases of SRAD have been reported in the literature. The diagnosis is often delayed due to the rarity of the disease and non-specific clinical presentations such as flank pain, hypertension, fever, nausea, vomiting, and hematuria, which can be often misdiagnosed as a genito-urinary infection or gastrointestinal or bowel disease. Before 1980, the diagnosis of SRAD was mostly confirmed via autopsy or, rarely, via angiography. At present, the diagnosis is made using advanced imaging approaches, including computed tomography angiography (CTA) and magnetic resonance angiography (MRA), with a higher number of incidentally diagnosed SRADs. Methods: we performed laboratory tests and radiological examinations (computed abdominal tomography and multiplanar reconstruction) that revealed multiple infarctions and ischemic areas with hypoperfusion in the upper middle third of the left kidney and in a large part of middle and lower areas of the right kidney; the left renal artery exhibited increased intimal thickening and arteritis. Results: The multiplanar reconstruction revealed bilateral renal artery dissection and multiple arterial infarctions disseminated throughout both kidneys. After a clinical follow-up and hypertension retargeting, the patient was discharged with dual antiplatelet therapy and ACE inhibitor drugs. No lipid-lowering therapy was needed. Conclusions: Spontaneous renal artery dissection (SRAD) is a rare clinical event that typically presents with acute low-back or flank pain, hypertension, fever, hematuria, and acute renal failure. The condition could be misdiagnosed or receive a delayed diagnosis due to its relative rarity and non-specific presentation. The gold standard is enhanced computed tomography (CT) scans, and if the diagnosis is positive, vascular multiplanar reconstruction is generally suggested, as it can display lesions more clearly. Over 300 cases have been reported since the first characterization of SRAD; however, to date, a consensus has not been reached on the most appropriate treatment. Conservative therapy, open surgery, and intravascular intervention have been reported as treatments for SRAD. Full article
(This article belongs to the Special Issue Advanced Imaging Techniques for Nephrology and Urology)
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14 pages, 3424 KiB  
Article
Directorial Editing: A Hybrid Deep-Learning Approach to Content-Aware Image Retargeting and Resizing
by Elliot Dickman and Paul Diefenbach
Electronics 2024, 13(22), 4459; https://doi.org/10.3390/electronics13224459 - 14 Nov 2024
Viewed by 1134
Abstract
Image retargeting is a common computer graphics task which involves manipulating the size or aspect ratio of an image. This task often presents a challenge to the artist or user, because manipulating the size of an image necessitates some degree of data loss [...] Read more.
Image retargeting is a common computer graphics task which involves manipulating the size or aspect ratio of an image. This task often presents a challenge to the artist or user, because manipulating the size of an image necessitates some degree of data loss as pixels need to be removed to accommodate a different image size. We present an image retargeting framework which implements a confidence map generated by a segmentation model for content-aware resizing, allowing users to specify which subjects in an image to preserve using natural language prompts much like the role of an art director conversing with their artist. Using computer vision models to detect object positions also provides additional control over the composition of the retargeted image at various points in the image-processing pipeline. This object-based approach to energy map augmentation is incredibly flexible, because only minor adjustments to the processing of the energy maps can provide a significant degree of control over where seams—paths of pixels through the image—are removed, and how seam removal is prioritized in different sections of the image. It also provides additional control with techniques for object and background separation and recomposition. This research explores how several different types of deep-learning models can be integrated into this pipeline in order to easily make these decisions, and provide different retargeting results on the same image based on user input and compositional considerations. Because this is a framework based on existing machine-learning models, this approach will benefit from advancements in the rapidly developing fields of computer vision and large language models and can be extended for further natural language directorial controls over images. Full article
(This article belongs to the Special Issue Deep Learning in Image Processing and Computer Vision)
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17 pages, 2194 KiB  
Article
Long Terminal Repeats of Gammaretroviruses Retain Stable Expression after Integration Retargeting
by Dalibor Miklík, Martina Slavková, Dana Kučerová, Chahrazed Mekadim, Jakub Mrázek and Jiří Hejnar
Viruses 2024, 16(10), 1518; https://doi.org/10.3390/v16101518 - 25 Sep 2024
Cited by 1 | Viewed by 1257
Abstract
Retroviruses integrate into the genomes of infected host cells to form proviruses, a genetic platform for stable viral gene expression. Epigenetic silencing can, however, hamper proviral transcriptional activity. As gammaretroviruses (γRVs) preferentially integrate into active promoter and enhancer sites, the high transcriptional activity [...] Read more.
Retroviruses integrate into the genomes of infected host cells to form proviruses, a genetic platform for stable viral gene expression. Epigenetic silencing can, however, hamper proviral transcriptional activity. As gammaretroviruses (γRVs) preferentially integrate into active promoter and enhancer sites, the high transcriptional activity of γRVs can be attributed to this integration preference. In addition, long terminal repeats (LTRs) of some γRVs were shown to act as potent promoters by themselves. Here, we investigate the capacity of different γRV LTRs to drive stable expression within a non-preferred epigenomic environment in the context of diverse retroviral vectors. We demonstrate that different γRV LTRs are either rapidly silenced or remain active for long periods of time with a predominantly active proviral population under normal and retargeted integration. As an alternative to the established γRV systems, the feline leukemia virus and koala retrovirus LTRs are able to drive stable, albeit intensity-diverse, transgene expression. Overall, we show that despite the occurrence of rapid silencing events, most γRV LTRs can drive stable expression outside of their preferred chromatin landscape after retrovirus integrations. Full article
(This article belongs to the Section General Virology)
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29 pages, 1556 KiB  
Review
The Immunotherapy of Acute Myeloid Leukemia: A Clinical Point of View
by Federico Mosna
Cancers 2024, 16(13), 2359; https://doi.org/10.3390/cancers16132359 - 27 Jun 2024
Cited by 4 | Viewed by 4933
Abstract
The potential of the immune system to eradicate leukemic cells has been consistently demonstrated by the Graft vs. Leukemia effect occurring after allo-HSCT and in the context of donor leukocyte infusions. Various immunotherapeutic approaches, ranging from the use of antibodies, antibody–drug conjugates, bispecific [...] Read more.
The potential of the immune system to eradicate leukemic cells has been consistently demonstrated by the Graft vs. Leukemia effect occurring after allo-HSCT and in the context of donor leukocyte infusions. Various immunotherapeutic approaches, ranging from the use of antibodies, antibody–drug conjugates, bispecific T-cell engagers, chimeric antigen receptor (CAR) T-cells, and therapeutic infusions of NK cells, are thus currently being tested with promising, yet conflicting, results. This review will concentrate on various types of immunotherapies in preclinical and clinical development, from the point of view of a clinical hematologist. The most promising therapies for clinical translation are the use of bispecific T-cell engagers and CAR-T cells aimed at lineage-restricted antigens, where overall responses (ORR) ranging from 20 to 40% can be achieved in a small series of heavily pretreated patients affected by refractory or relapsing leukemia. Toxicity consists mainly in the occurrence of cytokine-release syndrome, which is mostly manageable with step-up dosing, the early use of cytokine-blocking agents and corticosteroids, and myelosuppression. Various cytokine-enhanced natural killer products are also being tested, mainly as allogeneic off-the-shelf therapies, with a good tolerability profile and promising results (ORR: 20–37.5% in small trials). The in vivo activation of T lymphocytes and NK cells via the inhibition of their immune checkpoints also yielded interesting, yet limited, results (ORR: 33–59%) but with an increased risk of severe Graft vs. Host disease in transplanted patients. Therefore, there are still several hurdles to overcome before the widespread clinical use of these novel compounds. Full article
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21 pages, 29279 KiB  
Article
Neutral Facial Rigging from Limited Spatiotemporal Meshes
by Jing Hou, Dongdong Weng, Zhihe Zhao, Ying Li and Jixiang Zhou
Electronics 2024, 13(13), 2445; https://doi.org/10.3390/electronics13132445 - 21 Jun 2024
Viewed by 1423
Abstract
Manual facial rigging is time-consuming. Traditional automatic rigging methods lack either 3D datasets or explainable semantic parameters, which makes it difficult to retarget a certain 3D expression to a new face. To address the problem, we automatically generate a large 3D dataset containing [...] Read more.
Manual facial rigging is time-consuming. Traditional automatic rigging methods lack either 3D datasets or explainable semantic parameters, which makes it difficult to retarget a certain 3D expression to a new face. To address the problem, we automatically generate a large 3D dataset containing semantic parameters, joint positions, and vertex positions from a limited number of spatiotemporal meshes. We establish an expression generator based on a multilayer perceptron with vertex constraints from the semantic parameters to the joint positions and establish an expression recognizer based on a generative adversarial structure from the joint positions to the semantic parameters. To enhance the accuracy of key facial area recognition, we add local vertex constraints for the eyes and lips, which are determined by the 3D masks computed by the proposed projection-searching algorithm. We testthe generation and recognition effects on a limited number of publicly available Metahuman meshes and self-collected meshes. Compared with existing methods, our generator has the shortest generation time of 14.78 ms and the smallest vertex relative mean square error of 1.57 × 10−3, while our recognizer has the highest accuracy of 92.92%. The ablation experiment verifies that the local constraints can improve the recognition accuracy by 3.02%. Compared with other 3D mask selection methods, the recognition accuracy is improved by 1.03%. In addition, our method shows robust results for meshes of different levels of detail, and the rig has more dimensions of semantic space. The source code will be made available if this paper is accepted for publication. Full article
(This article belongs to the Special Issue Neural Networks and Deep Learning in Computer Vision)
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33 pages, 6045 KiB  
Article
A Display-Adaptive Pipeline for Dynamic Range Expansion of Standard Dynamic Range Video Content
by Gonzalo Luzardo, Asli Kumcu, Jan Aelterman, Hiep Luong, Daniel Ochoa and Wilfried Philips
Appl. Sci. 2024, 14(10), 4081; https://doi.org/10.3390/app14104081 - 11 May 2024
Cited by 1 | Viewed by 1696
Abstract
Recent advancements in high dynamic range (HDR) display technology have significantly enhanced the contrast ratios and peak brightness of modern displays. In the coming years, it is expected that HDR televisions capable of delivering significantly higher brightness and, therefore, contrast levels than today’s [...] Read more.
Recent advancements in high dynamic range (HDR) display technology have significantly enhanced the contrast ratios and peak brightness of modern displays. In the coming years, it is expected that HDR televisions capable of delivering significantly higher brightness and, therefore, contrast levels than today’s models will become increasingly accessible and affordable to consumers. While HDR technology has gained prominence over the past few years, low dynamic range (LDR) content is still consumed due to a substantial volume of historical multimedia content being recorded and preserved in LDR. Although the amount of HDR content will continue to increase as HDR becomes more prevalent, a large portion of multimedia content currently remains in LDR. In addition, it is worth noting that although the HDR standard supports multimedia content with luminance levels up to 10,000 cd/m2 (a standard measure of brightness), most HDR content is typically limited to a maximum brightness of around 1000 cd/m2. This limitation aligns with the current capabilities of consumer HDR TVs but is a factor approximately five times brighter than current LDR TVs. To accurately present LDR content on a HDR display, it is processed through a dynamic range expansion process known as inverse tone mapping (iTM). This LDR to HDR conversion faces many challenges, including the inducement of noise artifacts, false contours, loss of details, desaturated colors, and temporal inconsistencies. This paper introduces complete inverse tone mapping, artifact suppression, and a highlight enhancement pipeline for video sequences designed to address these challenges. Our LDR-to-HDR technique is capable of adapting to the peak brightness of different displays, creating HDR video sequences with a peak luminance of up to 6000 cd/m2. Furthermore, this paper presents the results of comprehensive objective and subjective experiments to evaluate the effectiveness of the proposed pipeline, focusing on two primary aspects: real-time operation capability and the quality of the HDR video output. Our findings indicate that our pipeline enables real-time processing of Full HD (FHD) video (1920 × 1080 pixels), even on hardware that has not been optimized for this task. Furthermore, we found that when applied to existing HDR content, typically capped at a brightness of 1000 cd/m2, our pipeline notably enhances its perceived quality when displayed on a screen that can reach higher peak luminances. Full article
(This article belongs to the Special Issue Intelligent Systems: Methods and Implementation)
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17 pages, 1614 KiB  
Article
Decrease in Heparan Sulphate Binding in Tropism-Retargeted Oncolytic Herpes Simplex Virus (ReHV) Delays Blood Clearance and Improves Systemic Anticancer Efficacy
by Andrea Vannini, Federico Parenti, Cristina Forghieri, Gaia Vannini, Catia Barboni, Anna Zaghini, Tatiana Gianni and Gabriella Campadelli-Fiume
Cancers 2024, 16(6), 1143; https://doi.org/10.3390/cancers16061143 - 13 Mar 2024
Cited by 1 | Viewed by 1658
Abstract
The role of the interaction with cell-surface glycosaminoglycans (GAGs) during in vivo HSV infection is currently unknown. The rationale of the current investigation was to improve the anticancer efficacy of systemically administered retargeted oHSVs (ReHVs) by decreasing their binding to GAGs, including those [...] Read more.
The role of the interaction with cell-surface glycosaminoglycans (GAGs) during in vivo HSV infection is currently unknown. The rationale of the current investigation was to improve the anticancer efficacy of systemically administered retargeted oHSVs (ReHVs) by decreasing their binding to GAGs, including those of endothelial cells, blood cells, and off-tumor tissues. As a proof-of-principle approach, we deleted seven amino acids critical for interacting with GAGs from the glycoprotein C (gC) of R-337 ReHV. The modification in the resulting R-399 recombinant prolonged the half-life in the blood of systemically administered R-399 and enhanced its biodistribution to tumor-positive lungs and to the tumor-negative liver. Ultimately, it greatly increased the R-399 efficacy against metastatic-like lung tumors upon IV administration but not against subcutaneous tumors upon IT administration. These results provide evidence that the increased efficacy seen upon R-399 systemic administration correlated with the slower clearance from the circulation. To our knowledge, this is the first in vivo evidence that the partial impairment of the gC interaction with GAGs resulted in a prolonged half-life of circulating ReHV, an increase in the amount of ReHV taken up by tissues and tumors, and, ultimately, an enhanced anticancer efficacy of systemically administered ReHV. Full article
(This article belongs to the Collection Advances and Future Prospects in Oncolytic Virus Immunotherapy)
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16 pages, 4179 KiB  
Article
Elevated Levels of Mislocalised, Constitutive Ras Signalling Can Drive Quiescence by Uncoupling Cell-Cycle Regulation from Metabolic Homeostasis
by Elliot Piper-Brown, Fiona Dresel, Eman Badr and Campbell W. Gourlay
Biomolecules 2023, 13(11), 1619; https://doi.org/10.3390/biom13111619 - 6 Nov 2023
Cited by 1 | Viewed by 2006
Abstract
The small GTPase Ras plays an important role in connecting external and internal signalling cues to cell fate in eukaryotic cells. As such, the loss of RAS regulation, localisation, or expression level can drive changes in cell behaviour and fate. Post-translational modifications and [...] Read more.
The small GTPase Ras plays an important role in connecting external and internal signalling cues to cell fate in eukaryotic cells. As such, the loss of RAS regulation, localisation, or expression level can drive changes in cell behaviour and fate. Post-translational modifications and expression levels are crucial to ensure Ras localisation, regulation, function, and cell fate, exemplified by RAS mutations and gene duplications that are common in many cancers. Here, we reveal that excessive production of yeast Ras2, in which the phosphorylation-regulated serine at position 225 is replaced with alanine or glutamate, leads to its mislocalisation and constitutive activation. Rather than inducing cell death, as has been widely reported to be a consequence of constitutive Ras2 signalling in yeast, the overexpression of RAS2S225A or RAS2S225E alleles leads to slow growth, a loss of respiration, reduced stress response, and a state of quiescence. These effects are mediated via cAMP/PKA signalling and transcriptional changes, suggesting that quiescence is promoted by an uncoupling of cell-cycle regulation from metabolic homeostasis. The quiescent cell fate induced by the overexpression of RAS2S225A or RAS2S225E could be rescued by the deletion of CUP9, a suppressor of the dipeptide transporter Ptr2, or the addition of peptone, implying that a loss of metabolic control, or a failure to pass a metabolic checkpoint, is central to this altered cell fate. Our data suggest that the combination of an increased RAS2 copy number and a dominant active mutation that leads to its mislocalisation can result in growth arrest and add weight to the possibility that approaches to retarget RAS signalling could be employed to develop new therapies. Full article
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