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Site-specific chelator-antibody conjugation for PET and SPECT imaging with radiometals
摘要： Antibodies and their derivatives radiolabelled with positron- and gamma-emitting radiometals enable sensitive and quantitative molecular Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) imaging of antibody distribution in vivo. Chelators that are covalently attached to antibodies allow radiolabelling with metallic PET and SPECT radioisotopes. Conventional strategies for chelator-protein conjugation generate heterogeneous mixtures of bioconjugates that can exhibit reduced affinity for their targets, and undesirable biodistribution and pharmacokinetics. Recent advances in bioconjugation technology enable site-specific modification to generate well-defined constructs with superior properties. Herein we survey existing site-specific chelator-protein conjugation methods. These include chelator attachment to cysteines/disulfide bonds or the glycan region of the antibody, enzyme-mediated chelator conjugation, and incorporation of sequences of amino acids that chelate the radiometal. Such technology will allow better use of PET and SPECT imaging in the development of antibody-based therapies.
关键词： antibody,radiometals,PET,chelator,site-specific conjugation,SPECT,molecular imaging
更新于2025-09-23 15:21:21
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[IEEE 2019 IEEE Photonics Society Summer Topical Meeting Series (SUM) - Ft. Lauderdale, FL, USA (2019.7.8-2019.7.10)] 2019 IEEE Photonics Society Summer Topical Meeting Series (SUM) - Ultra-high Capacity Wireless Communication Enabled by Photonic Technologies
摘要： This letter presents a probabilistic omnidirectional millimeter-wave path loss model based on real-world 28 GHz and 73 GHz measurements collected in New York City. The probabilistic path loss approach uses a free space line-of-sight propagation model, and for non-line-of-sight conditions uses either a close-in free space reference distance path loss model or a floating-intercept path loss model. The probabilistic model employs a weighting function that specifies the line-of-sight probability for a given transmitter-receiver separation distance. Results show that the probabilistic path loss model offers virtually identical results whether one uses a non-line-of-sight close-in free space reference distance path loss model, with a reference distance of 1 meter, or a floating-intercept path loss model. This letter also shows that site-specific environmental information may be used to yield the probabilistic weighting function for choosing between line-of-sight and non-line-of-sight conditions.
关键词： mmWave,ray-tracing,probabilistic path loss,floating-intercept,close-in free space reference distance,site-specific
更新于2025-09-23 15:19:57
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[IEEE 2019 IEEE 8th Global Conference on Consumer Electronics (GCCE) - Osaka, Japan (2019.10.15-2019.10.18)] 2019 IEEE 8th Global Conference on Consumer Electronics (GCCE) - Bluetooth Based Wireless Control for iBeacon and VLC Enabled Lighting
摘要： This letter presents a probabilistic omnidirectional millimeter-wave path loss model based on real-world 28 GHz and 73 GHz measurements collected in New York City. The probabilistic path loss approach uses a free space line-of-sight propagation model, and for non-line-of-sight conditions uses either a close-in free space reference distance path loss model or a floating-intercept path loss model. The probabilistic model employs a weighting function that specifies the line-of-sight probability for a given transmitter-receiver separation distance. Results show that the probabilistic path loss model offers virtually identical results whether one uses a non-line-of-sight close-in free space reference distance path loss model, with a reference distance of 1 meter, or a floating-intercept path loss model. This letter also shows that site-specific environmental information may be used to yield the probabilistic weighting function for choosing between line-of-sight and non-line-of-sight conditions.
关键词： mmWave,ray-tracing,probabilistic path loss,floating-intercept,close-in free space reference distance,site-specific
更新于2025-09-23 15:19:57
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Development, optimization and structural characterization of an efficient peptide-based photoaffinity crosslinking reaction for generation of homogeneous conjugates from wild-type antibodies
摘要： Site-specific conjugation of small molecules to antibodies represents an attractive goal for the development of more homogeneous targeted therapies and diagnostics. Most site-specific conjugation strategies require modification or removal of antibody glycans or interchain disulfide bonds or engineering of an antibody mutant that bears a reactive handle. While such methods are effective, they complicate the process of preparing antibody conjugates and can negatively impact biological activity. Herein, we report the development and detailed characterization of a robust photoaffinity crosslinking method for site-specific conjugation to fully-glycosylated wild-type antibodies. The method employs a benzoylphenylalanine (Bpa) mutant of a previously-described 13-residue peptide derived from phage display to bind tightly to the Fc domain; upon UV irradiation, the Bpa residue forms a diradical that reacts with the bound antibody. First, we describe the initial discovery of an effective Bpa mutant peptide and optimization of reaction conditions to enable efficient conjugation without concomitant UV-induced photodamage of the antibody. Second, we assessed the scope of the photoconjugation reaction across different human and non-human antibodies and antibody mutants. Third, the specific site of conjugation on a human antibody was characterized in detail by mass spectrometry experiments and at atomic resolution by X-ray crystallography. Finally, we adapted the photoconjugation method to attach a cytotoxic payload site-specifically to a wild-type antibody and show that the resulting conjugate is both stable in plasma and as potent as a conventional antibody drug conjugate in cells, portending well for future biological applications.
关键词： wild-type antibodies,Fc domain,photoaffinity crosslinking,site-specific conjugation,antibody-drug conjugates
更新于2025-09-23 15:19:57
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Beyond the Toolpath: Site-Specific Melt Pool Size Control Enables Printing of Extra-Toolpath Geometry in Laser Wire-Based Directed Energy Deposition
摘要： A variety of techniques have been utilized in metal additive manufacturing (AM) for melt pool size management, including modeling and feed-forward approaches. In a few cases, closed-loop control has been demonstrated. In this research, closed-loop melt pool size control for large-scale, laser wire-based directed energy deposition is demonstrated with a novel modification, i.e., site-specific changes to the controller setpoint were commanded at trigger points, the locations of which were generated by the projection of a secondary geometry onto the primary three-dimensional (3D) printed component geometry. The present work shows that, through this technique, it is possible to print a specific geometry that occurs beyond the actual toolpath of the print head. This is denoted as extra-toolpath geometry and is fundamentally different from other methods of generating component features in metal AM. A proof-of-principle experiment is presented in which a complex oak leaf geometry was embossed on an otherwise ordinary double-bead wall made from Ti-6Al-4V. The process is introduced and characterized primarily from a controls perspective with reports on the performance of the control system, the melt pool size response, and the resulting geometry. The implications of this capability, which extend beyond localized control of bead geometry to the potential mitigations of defects and functional grading of component properties, are discussed.
关键词： closed-loop control,lasers,metal,directed energy deposition,additive manufacturing,3D printing,titanium,site-specific,melt pool size
更新于2025-09-19 17:13:59
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[American Society of Agricultural and Biological Engineers 2018 Detroit, Michigan July 29 - August 1, 2018 - ()] 2018 Detroit, Michigan July 29 - August 1, 2018 - <i>The Assessment of Accuracy and Stability for a UAS Sensor Platform as a Precision Agriculture Management Tool in Detecting and Mapping Geospatial Field Variability</i>
摘要： The unmanned aerial system (UAS), that is used as a precision agricultural management tool for detecting and mapping geospatial variability in the crop health of the agricultural row field, is dependent on global positioning system (GPS) receivers and remote sensor (RS) systems. Unlike a ground platform, the UAS is subject to additional platform factors such as autonomous flight system, inertial navigational system (INS), aerodynamics, and aerial climate conditions which can affect flight path accuracy and stability. Such factors can result in diminished quality of trajectory accuracy or aerial Nadir stability that is needed for the precision mapping of geospatial variability zones that are used in the management decisions for geospatial input of treatments. The diminished quality of the UAS flight path can in turn cause RS image-stitching distortions that will render a precision treatment zone map geospatially insufficient. Using the scientific method, this project proposes bringing geospatial assessment tools to the agricultural field that serve to independently verify the flight path accuracy and stability aspects of any UAS sensor platform apart from sole reliance on ortho-stitching processing or sole reliance on on-board platform systems. In a field, a set pattern of elevation posts with global navigational satellite system (GNSS) obtained coordinates will be erected to be viewed from the Nadir orientation of any UAS. With any UAS autonomous platform equipped for optically tracking geospatial flight path metrics, the UAS flight path will follow the posted field pattern at various altitudes. The expected result will be a repeatable testing regimen that will be suitable in standardizing the assessment of any UAS sensor platform for flight path stability and accuracy where precision mapping and true global accuracy are needed such as in the management decisions for the geospatial input of treatments.
关键词： sensor platform,timeliness,unmanned aerial system (UAS),Accuracy,Nadir view stability,testing regimen,geospatial variability (GSV),site specific management (SSM)
更新于2025-09-09 09:28:46
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Quantifying the Initial Unfolding of Bacteriorhodopsin Reveals Retinal Stabilization
摘要： The forces that stabilize membrane proteins remain elusive to precise quantification. Particularly important but poorly resolved are the forces present during a membrane protein’s initial unfolding, where the most native set of interactions are present. We developed a high-precision, atomic force microscopy assay to study the initial unfolding of bacteriorhodopsin. We discovered rapid near-equilibrium folding between the first three unfolding states that corresponded to the unfolding of 5 and 8 amino-acids respectively when using a cantilever optimized for 2-μs resolution. Interestingly, the third of these states was retinal stabilized and previously undetected despite being the most mechanically stable state in the whole unfolding pathway, supporting 150 pN for >1 min. We expect that this ability to measure the rapid and reversible dynamics in the initial unfolding of bacteriorhodopsin provides a platform for quantifying the energetics of membrane proteins under native-like conditions.
关键词： protein folding,single molecule force spectroscopy,site-specific bioconjugation,membrane proteins,atomic force microscopy
更新于2025-09-04 15:30:14
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Element- and Site-Specific Many-Body Interactions in Few-Layer MoS <sub/>2</sub> During X-Ray Absorption Processes
摘要： Few-layer MoS2 is a promising 2D material for nano-electronic device applications. However, the performance of these devices is often deteriorated. One of the reasons is that the electronic properties are influential to the many-body effects such as excitonic effects and Anderson orthogonality catastrophe (AOC) which could renormalize the band-dispersion and density-of-states(DOS). Hence, the authors investigate the effect of many-body interactions on MoS2 device performance by using X-ray absorption spectro-microscopy (m-XAS) on a few-layer MoS2 transistor in operation, through the application of gate-bias or contact with a metal. The results show a significant peak shift in m-XAS spectra while varying the gate-bias. The applied negative gate-bias induces more holes which attracts excited electrons resulting strong many-body interactions followed by Fermi level shift. This effect is discussed with the aid of XAS-Auger electron phenomena. However, the AOC contribution in XAS peak-intensity is ignored since the bands around the energy-gap in MoS2 are relatively flat and the DOS is empty above Fermi level (unlike graphene). The authors observe a redshift in photon energy near the MoS2/metal-electrode interface due to charge transfer ensuring carrier-doping induced through metal-contact. These observations provide significant insight into element- and site-specific many-body interactions in MoS2 tunable by gate-bias or contact with a metal.
关键词： many-body interactions,element- and site-specific,MoS2,X-ray absorption spectromicroscopy
更新于2025-09-04 15:30:14