Open-Source Data Analysis Tool for Spectral Small-Angle X-ray Scattering Using Spectroscopic Photon-Counting Detector.

Spectral small-angle X-ray scattering (sSAXS) is a powerful technique for material characterization from thicker samples by capturing elastic X-ray scattering data in angle- and energy-dispersive modes at small angles. This approach is enabled by the use of a 2D spectroscopic photon-counting detector that provides energy and position information of scattered photons when a sample is irradiated by a polychromatic X-ray beam. Here, we describe an open-source tool with a graphical interface for analyzing sSAXS data obtained from a 2D spectroscopic photon-counting detector with a large number of energy bins.

Synthetic β-sheets mimicking fibrillar and oligomeric structures for evaluation of spectral X-ray scattering technique for biomarker quantification.

Background: Archetypical cross-β spines sharpen the boundary between functional and pathological proteins including β-amyloid, tau, α-synuclein and transthyretin are linked to many debilitating human neurodegenerative and non-neurodegenerative amyloidoses. An increased focus on development of pathogenic β-sheet specific fluid and imaging structural biomarkers and conformation-specific monoclonal antibodies in targeted therapies has been recently observed. Identification and quantification of pathogenic oligomers remain challenging for existing neuroimaging modalities.

Feasibility of imaging amyloid in the brain using small-angle x-ray scattering.

Small-angle x-ray scattering (SAXS) imaging may have the potential to image-amyloid plaquesin the brain without tracers for assessment of Alzheimer's disease (AD). We use a laboratory SAXS system for planar imaging of AD model and control mouse brains slices to detect regions with high density of amyloid plaques. These regions were validated with histology methods.

Label-free X-ray estimation of brain amyloid burden.

Amyloid plaque deposits in the brain are indicative of Alzheimer's and other diseases. Measurements of brain amyloid burden in small animals require laborious post-mortem histological analysis or resource-intensive, contrast-enhanced imaging techniques. We describe a label-free method based on spectral small-angle X-ray scattering with a polychromatic beam for in vivo estimation of brain amyloid burden.

Feasibility of a label-free X-ray method to estimate brain amyloid load in small animals.

Background: Amyloid plaque in the brain is associated with a wide range of neurodegenerative diseases such as Alzheimer's and Parkinson's and defined as aggregates of amyloid fibrils rich in β-sheet structures.

New Method: We report a label-free method based on small-angle X-ray scattering (SAXS) to estimate amyloid load in an intact mouse head with skull. The method is based on recording and analyzing the X rays elastically scattered from the β-sheets of amyloid plaques in a mouse head at angles smaller than 10° and energies between 30 and 45 keV.

Small-angle X-ray scattering characterization of a [Formula: see text]-amyloid model in phantoms.

Objective: We present a method to prepare an amyloid model at scalable quantities for phantom studies to evaluate small-angle x-ray scattering systems for amyloid detection. Two amyloid models were made from a plasma protein with and without heating. Both models mimic the [Formula: see text]-sheet structure of the [Formula: see text]-amyloid ([Formula: see text]) plaques in Alzheimer's disease.

Enhanced Loading of Functional miRNA Cargo via pH Gradient Modification of Extracellular Vesicles.

Based on their identification as physiological nucleic acid carriers in humans and other organisms, extracellular vesicles (EVs) have been explored as therapeutic delivery vehicles for DNA, RNA, and other cargo. However, efficient loading and functional delivery of nucleic acids remain a challenge, largely because of potential sources of degradation and aggregation. Here, we report that protonation of EVs to generate a pH gradient across EV membranes can be utilized to enhance vesicle loading of nucleic acid cargo, specifically microRNA (miRNA), small interfering RNA (siRNA), and single-stranded DNA (ssDNA).

Technical Note: In silico imaging tools from the VICTRE clinical trial.

Purpose: In silico imaging clinical trials are emerging alternative sources of evidence for regulatory evaluation and are typically cheaper and faster than human trials. In this Note, we describe the set of in silico imaging software tools used in the VICTRE (Virtual Clinical Trial for Regulatory Evaluation) which replicated a traditional trial using a computational pipeline.

Materials And Methods: We describe a complete imaging clinical trial software package for comparing two breast imaging modalities (digital mammography and digital breast tomosynthesis).

Stable gelatin-based phantom materials with tunable x-ray attenuation properties and 3D printability for x-ray imaging.

We report a novel method for developing gelatin-based phantom materials for transmission x-ray imaging with high stability at room temperature and tunable x-ray attenuation properties. This is achieved by efficiently cross-linking gelatin in a glycerin solution with only 10% water by volume and systematically decreasing their x-ray attenuation coefficients by doping with microbubbles that are originally designed to be used as lightweight additives for paints and crack fillers. For demonstration, we mimic breast glandular and adipose tissues by using such gelatin materials and also study the feasibility of 3D printing them based on the extrusion-based technique.

Structural evaluation of an amyloid fibril model using small-angle x-ray scattering.

Amyloid fibrils are highly structured protein aggregates associated with a wide range of diseases including Alzheimer's and Parkinson's. We report a structural investigation of an amyloid fibril model prepared from a commonly used plasma protein (bovine serum albumin (BSA)) using small-angle x-ray scattering (SAXS) technique. As a reference, the size estimates from SAXS are compared to dynamic light scattering (DLS) data and the presence of amyloid-like fibrils is confirmed using Congo red absorbance assay.

Evaluation of the catalytic activity and cytotoxicity of palladium nanocubes: the role of oxygen.

Recently, it has been reported that palladium nanocubes (PdNC) are capable of generating singlet oxygen without photoexcitation simply via chemisorption of molecular oxygen on its surface. Such a trait would make PdNC a highly versatile catalyst suitable in organic synthesis and a Reactive Oxygen Species (ROS) inducing cancer treatment reagent. Here we thoroughly investigated the catalytic activity of PdNC with respect to their ability to produce singlet oxygen and to oxidize 3,3',5,5'-tetramethylbenzidine (TMB), and analyzed the cytotoxic properties of PdNC on HeLa cells.