A Multisite Study of a Breast Density Deep Learning Model for Full-Field Digital Mammography and Synthetic Mammography.

Purpose: To develop a Breast Imaging Reporting and Data System (BI-RADS) breast density deep learning (DL) model in a multisite setting for synthetic two-dimensional mammographic (SM) images derived from digital breast tomosynthesis examinations by using full-field digital mammographic (FFDM) images and limited SM data.

Materials And Methods: A DL model was trained to predict BI-RADS breast density by using FFDM images acquired from 2008 to 2017 (site 1: 57 492 patients, 187 627 examinations, 750 752 images) for this retrospective study. The FFDM model was evaluated by using SM datasets from two institutions (site 1: 3842 patients, 3866 examinations, 14 472 images, acquired from 2016 to 2017; site 2: 7557 patients, 16 283 examinations, 63 973 images, 2015 to 2019).

Effect of proline mutations on the monomer conformations of amylin.

The formation of human islet amyloid polypeptide (hIAPP) is implicated in the loss of pancreatic β-cells in type II diabetes. Rat amylin, which differs from human amylin at six residues, does not lead to formation of amyloid fibrils. Pramlintide is a synthetic analog of human amylin that shares three proline substitutions with rat amylin.

α-helix to β-hairpin transition of human amylin monomer.

The human islet amylin polypeptide is produced along with insulin by pancreatic islets. Under some circumstances, amylin can aggregate to form amyloid fibrils, whose presence in pancreatic cells is a common pathological feature of Type II diabetes. A growing body of evidence indicates that small, early stage aggregates of amylin are cytotoxic.

Ultrastable glasses from in silico vapour deposition.

Glasses are generally prepared by cooling from the liquid phase, and their properties depend on their thermal history. Recent experiments indicate that glasses prepared by vapour deposition onto a substrate can exhibit remarkable stability, and might correspond to equilibrium states that could hitherto be reached only by glasses aged for thousands of years. Here we create ultrastable glasses by means of a computer-simulation process that mimics physical vapour deposition.

Efficient Free Energy Calculation of Biomolecules from Diffusion-Biased Molecular Dynamics.

Recently proposed metadynamics techniques offer an effective means for improving sampling in simulations of complex systems, including polymers and biological macromolecules. One of the drawbacks of such methods has been the absence of well-defined or effective convergence criteria. A solution to this problem is considered here in which an optimal ensemble is introduced to minimize the travel time across the entire order parameter range of interest.

Two-dimensional infrared spectroscopy reveals the complex behaviour of an amyloid fibril inhibitor.

Amyloid formation has been implicated in the pathology of over 20 human diseases, but the rational design of amyloid inhibitors is hampered by a lack of structural information about amyloid-inhibitor complexes. We use isotope labelling and two-dimensional infrared spectroscopy to obtain a residue-specific structure for the complex of human amylin (the peptide responsible for islet amyloid formation in type 2 diabetes) with a known inhibitor (rat amylin). Based on its sequence, rat amylin should block formation of the C-terminal β-sheet, but at 8 h after mixing, rat amylin blocks the N-terminal β-sheet instead.

Density of states-based molecular simulations.

One of the central problems in statistical mechanics is that of finding the density of states of a system. Knowledge of the density of states of a system is equivalent to knowledge of its fundamental equation, from which all thermodynamic quantities can be obtained. Over the past several years molecular simulations have made considerable strides in their ability to determine the density of states of complex fluids and materials.

2DIR spectroscopy of human amylin fibrils reflects stable β-sheet structure.

The aggregation of human amylin to form amyloid contributes to islet β-cell dysfunction in type 2 diabetes. Studies of amyloid formation have been hindered by the low structural resolution or relatively modest time resolution of standard methods. Two-dimensional infrared (2DIR) spectroscopy, with its sensitivity to protein secondary structures and its intrinsic fast time resolution, is capable of capturing structural changes during the aggregation process.

A molecular view of vapor deposited glasses.

Recently, novel organic glassy materials that exhibit remarkable stability have been prepared by vapor deposition. The thermophysical properties of these new "stable" glasses are equivalent to those that common glasses would exhibit after aging over periods lasting thousands of years. The origin of such enhanced stability has been elusive; in the absence of detailed models, past studies have discussed the formation of new polyamorphs or that of nanocrystals to explain the observed behavior.

Stable and metastable states of human amylin in solution.

Patients with type II diabetes exhibit fibrillar deposits of human amylin protein in the pancreas. It has been proposed that amylin oligomers arising along the aggregation or fibril-formation pathways are important in the genesis of the disease. In a step toward understanding these aggregation pathways, in this work we report the conformational preferences of human amylin monomer in solution using molecular simulations and infrared experiments.