9 research outputs found

    Memory Efficient Grasping Point Detection of Nontrivial Objects

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    Robotic manipulation with a nontrivial object providing various types of grasping points is of an industrial interest. Here, an efficient method of simultaneous detection of the grasping points is proposed. Specifically, two different 3 degree-of-freedom end effectors are considered for simultaneous grasping. The method utilizes an RGB data-driven perception system based on a specifically designed fully convolutional neural network called attention squeeze parallel U-Net (ASP U-Net). ASP U-Net detects grasping points based on a single RGB image. This image is transformed into a schematic grayscale frame, where the positions and poses of the grasping points are coded into gradient geometric shapes. In order to approve the ASP U-Net architecture, its performance was compared with nine competitive architectures using metrics based on generalized intersection over union and mean absolute error. The results indicate its outstanding accuracy and response time. ASP U-Net is also computationally efficient enough. With a more than acceptable memory size (77 MB), the architecture can be implemented using custom single-board computers. Here, its capabilities were tested and evaluated on the NVIDIA Jetson NANO platform

    Extremely rapid isotropic irradiation of nanoparticles with ions generated in situ by a nuclear reaction

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    Mass production of nanoparticles containing well-controlled structural defects is a challenge. Here the authors demonstrate the feasibility of homogeneous ion irradiation generated in a nuclear reactor, for the preparation of fluorescent nanodiamonds and silicon carbide nanoparticles

    Mitochondrially targeted tamoxifen as anticancer therapy: case series of patients with renal cell carcinoma treated in a phase I/Ib clinical trial

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    Mitochondrially targeted anticancer drugs (mitocans) that disrupt the energy-producing systems of cancer are emerging as new potential therapeutics. Mitochondrially targeted tamoxifen (MitoTam), an inhibitor of mitochondrial respiration respiratory complex I, is a first-in-class mitocan that was tested in the phase I/Ib MitoTam-01 trial of patients with metastatic cancer. MitoTam exhibited a manageable safety profile and efficacy; among 37% (14/38) of responders, the efficacy was greatest in patients with metastatic renal cell carcinoma (RCC) with a clinical benefit rate of 83% (5/6) of patients. This can be explained by the preferential accumulation of MitoTam in the kidney tissue in preclinical studies. Here we report the mechanism of action and safety profile of MitoTam in a case series of RCC patients. All six patients were males with a median age of 69 years, who had previously received at least three lines of palliative systemic therapy and suffered progressive disease before starting MitoTam. We recorded stable disease in four, partial response in one, and progressive disease (PD) in one patient. The histological subtype matched clear cell RCC (ccRCC) in the five responders and claro-cellular carcinoma with sarcomatoid features in the non-responder. The number of circulating tumor cells (CTCs) was evaluated longitudinally to monitor disease dynamics. Beside the decreased number of CTCs after MitoTam administration, we observed a significant decrease of the mitochondrial network mass in enriched CTCs. Two patients had long-term clinical responses to MitoTam, of 50 and 36 weeks. Both patients discontinued treatment due to adverse events, not PD. Two patients who completed the trial in November 2019 and May 2020 are still alive without subsequent anticancer therapy. The toxicity of MitoTam increased with the dosage but was manageable. The efficacy of MitoTam in pretreated ccRCC patients is linked to the novel mechanism of action of this first-in-class mitochondrially targeted drug

    Selective Disruption of Respiratory Supercomplexes as a New Strategy to Suppress Her2high Breast Cancer

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    Aims: Expression of the HER2 oncogene in breast cancer is associated with resistance to treatment, and Her2 may regulate bioenergetics. Therefore, we investigated whether disruption of the electron transport chain (ETC) is a viable strategy to eliminate Her2(high) disease.Results: We demonstrate that Her2(high) cells and tumors have increased assembly of respiratory supercomplexes (SCs) and increased complex I-driven respiration in vitro and in vivo. They are also highly sensitive to MitoTam, a novel mitochondrial-targeted derivative of tamoxifen. Unlike tamoxifen, MitoTam efficiently suppresses experimental Her2(high) tumors without systemic toxicity. Mechanistically, MitoTam inhibits complex I-driven respiration and disrupts respiratory SCs in Her2(high) background in vitro and in vivo, leading to elevated reactive oxygen species production and cell death. Intriguingly, higher sensitivity of Her2(high) cells to MitoTam is dependent on the mitochondrial fraction of Her2.Innovation: Oncogenes such as HER2 can restructure ETC, creating a previously unrecognized therapeutic vulnerability exploitable by SC-disrupting agents such as MitoTam.Conclusion: We propose that the ETC is a suitable therapeutic target in Her2(high) disease
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