Labelled Triangle Indexing for Efficiency Gains in Distributed Interactive Subgraph Search
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A significant enhancement of detection capabilities of the room temperature MPQ is seen using optical lithography-defined, ferromagnetic iron-nickel alloy microdisks. Irreversible transitions between strongly non-collinear (vortex) and a collinear single domain states, driven by an ac magnetic field, translate into a nonlinear magnetic response that enables ultrasensitive detection of material at relatively small magnetic fields.
A system and method for tracking a plurality of objects. Unlabeled measurement data identifying a plurality of targets corresponding to the plurality of objects is received. A multi-target likelihood function is generated using a persistent target density, a birth target density, and a clutter density. The multi-target likelihood function is used to associate persistent targets with the unlabeled measurement data to update persistent tracks and to initiate a new track for each target in the plurality of targets in the measurement data that is not associated with a persistent target.
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Abstract not provided.
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Covalently cross-linked pilus polymers displayed on the cell surface of Gram-positive bacteria are assembled by class C sortase enzymes. These pilus-specific transpeptidases located on the bacterial membrane catalyze a two-step protein ligation reaction—first, cleaving the LPXTG motif of one pilin protomer to form an acyl-enzyme intermediate, and second, joining the terminal threonine to the nucleophilic lysine residue residing within the pilin motif of another pilin protomer. Informed by the high-resolution crystal structures of corynebacterial pilus-specific sortase (SrtA) and by developing structural variants of the sortase enzyme whose catalytic pocket has been unmasked by activating mutations, we have developed new reagents capable of forming isopeptide bonds in vitro. The reagents disclosed herein can catalyze ligation of isolated SpaA domains in vitro provide a facile and versatile new platform for protein engineering and bio-conjugation that has major implications for biotechnology.
A significant enhancement of detection capabilities of the room temperature MPQ is seen using optical lithography-defined, ferromagnetic iron-nickel alloy microdisks. Irreversible transitions between strongly non-collinear (vortex) and a collinear single domain states, driven by an ac magnetic field, translate into a nonlinear magnetic response that enables ultrasensitive detection of material at relatively small magnetic fields.
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This study aims to assess the impact of domain shift on chest X-ray classification accuracy and to analyze the influence of ground truth label quality and demographic factors such as age group, sex, and study year. We used a DenseNet121 model pre-trained MIMIC-CXR dataset for deep learning-based multi-label classification using ground truth labels from radiology reports extracted using the CheXpert and CheXbert Labeler. We compared the performance of the 14 chest X-ray labels on the MIMIC-CXR and Veterans Healthcare Administration chest X-ray dataset (VA-CXR). The validation of ground truth and the assessment of multi-label classification performance across various NLP extraction tools revealed that the VA-CXR dataset exhibited lower disagreement rates than the MIMIC-CXR datasets. Additionally, there were notable differences in AUC scores between models utilizing CheXpert and CheXbert. When evaluating multi-label classification performance across different datasets, minimal domain shift was observed in the unseen VA dataset, except for the label “Enlarged Cardiomediastinum.” The subgroup with the most significant variations in multi-label classification performance was study year. These findings underscore the importance of considering domain shift in chest X-ray classification tasks, paying particular attention to the temporality of the exam. Our study reveals the significant impact of domain shift and demographic factors on chest X-ray classification, emphasizing the need for improved transfer learning and robust model development. Addressing these challenges is crucial for advancing medical imaging research and improving patient care.
Hydroxyl radical protein footprinting (HRPF) using synchrotron radiation is a well-validated method to assess protein structure in the native solution state. In this method, X-ray radiolysis of water generates hydroxyl radicals that can react with solvent accessible side chains of proteins, with mass spectrometry used to detect the resulting labeled products. An ideal footprinting dose provides sufficient labeling to measure the structure but not so much as to influence the results. The optimization of hydroxyl radical dose is typically performed using an indirect Alexa488 fluorescence assay sensitive to hydroxyl radical concentration, but full evaluation of the experiment's outcome relies upon bottom-up liquid chromatography mass spectrometry (LC-MS) measurements to directly determine sites and extent of oxidative labeling at the peptide and protein level. A direct evaluation of the extent of labeling to provide direct and absolute measurements of dose and “safe” dose ranges in terms of, for example, average numbers of labels per protein, would provide immediate feedback on experimental outcomes prior to embarking on detailed LC-MS analyses. To this end, we describe an approach to integrate intact MS screening of labeled samples immediately following exposure, along with metrics to quantify the extent of observed labeling from the intact mass spectra. Intact MS results on the model protein lysozyme were evaluated in the context of Alexa488 assay results and a bottom-up LC-MS analysis of the same samples. In conclusion, this approach provides a basis for placing delivered hydroxyl radical dose metrics on firmer technical grounds for synchrotron X-ray footprinting of proteins, with explicit parameters to increase the likelihood of a productive experimental outcome. Further, the method directs approaches to provide absolute and direct dosimetry for all types of labeling for protein footprinting.
The Auger electron-emitting radionuclide 191 Pt is a promising candidate for radiopharmaceutical therapy. Herein, we explored novel labeling methods for 191 Pt using thiol-containing ligands to improve the in vivo stability and targeting ability of 191 Pt-labeled complexes. We synthesized dithiol-containing N 2 S 2 and NS 2 ligands, and a trithiol ligand, and then compared their radiochemical reactivity with 191 Pt. [ 191 Pt]Pt-trithiol was synthesized and its biodistribution was evaluated in mice and compared with free 191 Pt. Finally, a 191 Pt-trithiol complex targeting prostate-specific membrane antigen (PSMA): [ 191 Pt]Pt-trithiol-PSMA was developed and evaluated in mice bearing tumor xenografts and compared with a 191 Pt-complex labeled via monothiol-containing Cys ([ 191 Pt]Pt-Cys-PSMA). A comparison of N 2 S 2 , NS 2 , and trithiol showed that the trithiol ligand is the best for producing 191 Pt-labeled compounds in high yield and as a single peak in preparative HPLC. Notably, the trithiol ligand made 191 Pt-labeled compounds and precursors separatable, achieving 191 Pt-labeled products with a high molar activity: 200–400 mCi/μmol (7.4–14.8 GBq/μmol) at EOS. Additionally, [ 191 Pt]Pt-trithiol and [ 191 Pt]Pt-trithiol-PSMA were stable in vivo with rapid clearance compared with free 191 Pt and [ 191 Pt]Pt-Cys-PSMA. [ 191 Pt]Pt-trithiol-PSMA resulted in a low uptake in most normal organs and a high uptake in the kidneys and prostate cancer with PSMA expression. Furthermore, this study demonstrated that a labeling method with trithiol for Pt radionuclides achieves 191 Pt-labeled products with high molar activity. 191 Pt-trithiol-PSMA showed promising in vivo stability and tumor-targeting specificity, which should facilitate the pharmaceutical development of Pt radionuclides for radiopharmaceutical therapy, especially Auger electron cancer therapy.