Poisson Noise Reduction with Non-local PCA

Photon-limited imaging arises when the number of photons collected by a sensor array is small relative to the number of detector elements. Photon limitations are an important concern for many applications such as spectral imaging, night vision, nuclear medicine, and astronomy. Typically a Poisson distribution is used to model these observations, and the inherent heteroscedasticity of the data combined with standard noise removal methods yields significant artifacts. This paper introduces a novel denoising algorithm for photon-limited images which combines elements of dictionary learning and sparse patch-based representations of images. The method employs both an adaptation of Principal Component Analysis (PCA) for Poisson noise and recently developed sparsity-regularized convex optimization algorithms for photon-limited images. A comprehensive empirical evaluation of the proposed method helps characterize the performance of this approach relative to other state-of-the-art denoising methods. The results reveal that, despite its conceptual simplicity, Poisson PCA-based denoising appears to be highly competitive in very low light regimes.     

Software mutational robustness

Neutral landscapes and mutational robustness are believed to be important enablers of evolvability in biology. We apply these concepts to software, defining mutational robustness to be the fraction of random mutations to program code that leave a program’s behavior unchanged. Test cases are used to measure program behavior and mutation operators are taken from earlier work on genetic programming. Although software is often viewed as brittle, with small changes leading to catastrophic changes in behavior, our results show surprising robustness in the face of random software mutations. The paper describes empirical studies of the mutational robustness of 22 programs, including 14 production software projects, the Siemens benchmarks, and four specially constructed programs. We find that over 30 % of random mutations are neutral with respect to their test suite. The results hold across all classes of programs, for mutations at both the source code and assembly instruction levels, across various programming languages, and bear only a limited relation to test suite coverage. We conclude that mutational robustness is an inherent property of software, and that neutral variants (i.e., those that pass the test suite) often fulfill the program’s original purpose or specification. Based on these results, we conjecture that neutral mutations can be leveraged as a mechanism for generating software diversity. We demonstrate this idea by generating a population of neutral program variants and showing that the variants automatically repair latent bugs. Neutral landscapes also provide a partial explanation for recent results that use evolutionary computation to automatically repair software bugs.     

Grain Boundary Sliding in Aluminum Nano‐Bi‐Crystals Deformed at Room Temperature

Room‐temperature uniaxial compressions of 900‐nm‐diameter aluminum bi‐crystals, each containing a high‐angle grain boundary with a plane normal inclined at 24° to the loading direction, revealed frictional sliding along the boundary plane to be the dominant deformation mechanism. The top crystallite sheared off as a single unit in the course of compression instead of crystallographic slip and extensive dislocation activity, as would be expected. Compressive stress strain data of deforming nano bicrystals was continuous, in contrast to single crystalline nano structures that show a stochastic stress strain signature, and displayed a peak in stress at the elastic limit of ～176 MPa followed by gradual softening and a plateau centered around ～125 MPa. An energetics‐based physical model, which may explain observed room‐temperature grain boundary sliding, in presented, and observations are discussed within the framework of crystalline nano‐plasticity and defect microstructure evolution.     

Identification of the FDA-Approved Drug Pyrvinium as a Small-Molecule Inhibitor of the PD-1/PD-L1 Interaction

Immune checkpoint blockade involving inhibition of the PD-1/PD-L1 interaction has provided unprecedented clinical benefits in treating a variety of tumors. To date, a total of six antibodies that bind to either PD-1 or PD-L1 protein and in turn inhibit the PD-1/PD-L1 interaction have received clinical approvals. Despite being highly effective, these expensive large biotherapeutics possess several inherent pharmacokinetic limitations that can be successfully overcome through the use of low-molecular-weight inhibitors. One such promising approach involves small-molecule induced dimerization and sequestration of PD-L1, leading to effective PD-1/PD-L1 inhibition. Herein, we present the discovery of such potential bioactive PD-L1 dimerizers through a structure- and ligand-based screening of a focused library of approved and investigational drugs worldwide. Pyrvinium, an FDA-approved anthelmintic drug, showed the highest activity in our study with IC₅₀ value of ∼29.66 μM. It is noteworthy that Pyrvinium, being an approved drug, may prove especially suitable as a good starting point for further medicinal chemistry efforts, leading to design and development of even more potent structural analogs as selective PD-1/PD-L1 inhibitors. Furthermore, the adopted integrated virtual screening protocol may prove useful in screening other larger databases of lead- and drug-like molecules for hit identification in the domain of small-molecule PD-1/PD-L1 inhibitors.     

Flexural creep of zirconium diboride–silicon carbide up to 2200 °C in minutes with non-contact electromagnetic testing

Flexural creep of ZrB₂–30 vol% SiC ultra high temperature ceramic composite was studied at 1700–2200 °C and 20–50 MPa using the novel method of electromagnetic Lorentz force loading of electrically heated specimens. Experiments were conducted in air and in non-oxidizing atmospheres. The apparent activation energy for creep was 344 ± 35 kJ/mol for non-oxidizing conditions. The stress exponent was 1.4 ± 0.4. The creep rate was slightly higher in air due to a decrease in the size of the load bearing substrate because of oxidation. There was no evidence of electric field effects. Creep experiments could be performed up to 2200 °C very quickly, with experiments conducted in a few minutes.     

Effect of crosslink density on fracture behavior of model epoxies containing block copolymer nanoparticles

Model diglycidyl ether of bisphenol-A based epoxy resins containing well-dispersed 15 nm block copolymer (BCP) nanoparticles were prepared to study the effect of matrix crosslink density on their fracture behavior. The crosslink density of the model epoxies was varied via the controlled epoxy thermoset technology and estimated experimentally. As expected, it was found that the fracture toughness of the BCP-toughened epoxy is strongly influenced by the crosslink density of the epoxy matrix, with higher toughenability for lower crosslink density epoxies. Key operative toughening mechanisms of the above model BCP-toughened epoxies were found to be nanoparticle cavitation-induced matrix shear banding for the low crosslink density epoxies. The toughening effect from BCP nanoparticles was also compared with core-shell rubber-toughened epoxies having different levels of crosslink density. The usefulness of the present findings for designing toughened thermosetting materials with desirable properties is discussed.     

Non-contact mechanical property measurements at ultrahigh temperatures

The “Electro-Magnetic Mechanical Apparatus”, a novel non-contact method of mechanical testing of ultrahigh temperature ceramics at high temperatures, was developed where a mechanical stress is applied using Lorenz forces on a sample heated to high temperatures with an electric current. The design of the apparatus and an analysis relating stress to magnetic flux density, electrical current, and specimen dimensions are presented here. Significant creep deformations were observed in ZrB₂–SiC samples deformed under 20 MPa of flexural stress resulting in 0.08% strain after 240 s at 1600 °C and 0.21% strain after 150 s at 1750 °C. A fatigue load of 6 MPa at 60 Hz frequency at 1700 °C in air increased the oxidation rate. This mechanical apparatus has potential application not only for high temperature creep and fatigue experiments but also fracture and elasticity. Though developed for ceramics, this technique can be used to study high temperature mechanical properties of any conducting material.     

Hierarchical Polymer Blend Fibers of High Structural Regularity Prepared by Facile Solvent Vapor Annealing Treatment

In this study, a facile solvent vapor annealing (SVA) method is utilized to inscribe hierarchical secondary nanostructures onto electrospun poly(ε‐caprolactone)(PCL)/poly(ethylene oxide) (PEO) blend fibers. By carefully understanding the phase separation and crystallization behavior of PCL/PEO blends during the electrospinning process, one can tune the spatial distribution of the PCL phase, the growth of the PCL crystalline regions, and therefore the amount and even the sensitivity of free amorphous PCL chains in response to acetone vapor. Here, the PEO domains serve as mini‐dividers to restrict the growth of the semicrystalline PCL phase. During acetone vapor annealing, the PEO phase remains largely unchanged while swollen‐free amorphous PCL chains are deposited on pre‐existing PCL or even PEO crystalline lamellae, giving rise to hierarchical structures of high regularity. The morphologies of PCL/PEO hierarchical structures reported in this study are of striking uniformity, further demonstrating the reliability of the facile SVA method, not only for a few layers of thin fiber mats but also for thicker fiber mats.     

Phospholipid monolayer coated microfabricated electrodes to model the interaction of molecules with biomembranes

The hanging mercury (Hg) drop electrode (HMDE) has a classical application as a tool to study adsorption and desorption processes of surface organic films due to its: (a) atomically smooth surface and, (b) hydrophobicity at its potential of zero charge. In this study we report on a replacement of the HMDE for studying supported organic layers in the form of platinum (Pt) working electrodes fabricated using lithography techniques on which a thin film of Hg is electrodeposited. These wafer-based Pt/Hg electrodes are characterised and compared to the HMDE using rapid cyclic voltammetry (RCV) and show similar capacitance-potential profiles while being far more mechanically stable and consuming considerably less Hg over their lifetime of several months. The electrodes have been used to support self-assembled phospholipid monolayers which are dynamic surface coatings with unique dielectric properties. The issue of surface contamination has been solved by regenerating the electrode surface prior to phospholipid coating by application of extreme cathodic potentials more negative than −2.6 V (vs. Ag/AgCl). The phospholipid coated electrodes presented in this paper mimic one half of a phospholipid bilayer and exhibit interactions with the biomembrane active drug molecules chlorpromazine, and quinidine. The magnitudes of these interactions have been assessed by recording changes in the capacitance-potential profiles in real time using RCV at 40 V s⁻¹ over potential ranges >1 V. A method for electrode coating with phospholipids with the electrodes fitted in a flow cell device has been developed. This has enabled sequential rapid cleaning/coating/interaction cycles for the purposes of drug screening and/or on-line monitoring for molecules of interest.