Deliberately Losing Control of C−H Activation Processes in the Design of Small-Molecule-Fragment Arrays Targeting Peroxisomal Metabolism

Combined photochemical arylation, “nuisance effect” (S_NAr) reaction sequences have been employed in the design of small arrays for immediate deployment in medium-throughput X-ray protein–ligand structure determination. Reactions were deliberately allowed to run “out of control” in terms of selectivity; for example the ortho-arylation of 2-phenylpyridine gave five products resulting from mono- and bisarylations combined with S_NAr processes. As a result, a number of crystallographic hits against NUDT7, a key peroxisomal CoA ester hydrolase, have been identified.     

Tensile testing and fracture mechanism analysis of polyvinyl alcohol nanofibrous webs

A tensile properties testing study was conducted to understand the influence of thickness, cross-head speed (speed of testing), gauge length (GL; specimen test length), and sample shape on important tensile properties of polyvinyl alcohol (PVA) nanofiber webs. The effects of each testing parameter on load at break, extension at break, Young's modulus, and tensile stress–strain curve of PVA nanofiber webs are analyzed. The Welch two sample t-tests show the significant difference among tested data. Using interaction plots, two-way analysis of variance, and margin mean plots, the interaction effects among testing parameters have been analyzed. Of all the factors, cross-head speed, the interaction among GL, and sample thickness (GL: Thickness) and the interaction among GL, testing speed and sample thickness (GL: Speed: Thickness) have significant influence on the tensile properties of PVA nanofiber webs. Moreover, the hypothesized model of mechanism of tensile strain–stress curve of PVA nanofiber webs has been proposed. Based on the model, the tensile strain–stress curve can be split into three stages: linear elastic, partial break up, and complete breakage. This study will provide a better understanding of tensile testing parameters' effects and their interaction effects on the tensile properties of nanowebs.     

A Student's t-based density peaks clustering with superpixel segmentation (tDPCSS) method for image color clustering

Image color clustering is a basic technique in image processing and computer vision, which is often applied in image segmentation, color transfer, contrast enhancement, object detection, skin color capture, and so forth. Various clustering algorithms have been employed for image color clustering in recent years. However, most of the algorithms require a large amount of memory or a predetermined number of clusters. In addition, some of the existing algorithms are sensitive to the parameter configurations. In order to tackle the above problems, we propose an image color clustering method named Student's t-based density peaks clustering with superpixel segmentation (tDPCSS), which can automatically obtain clustering results, without requiring a large amount of memory, and is not dependent on the parameters of the algorithm or the number of clusters. In tDPCSS, superpixels are obtained based on automatic and constrained simple non-iterative clustering, to automatically decrease the image data volume. A Student's t kernel function and a cluster center selection method are adopted to eliminate the dependence of the density peak clustering on parameters and the number of clusters, respectively. The experiments undertaken in this study confirmed that the proposed approach outperforms k-means, fuzzy c-means, mean-shift clustering, and density peak clustering with superpixel segmentation in the accuracy of the cluster centers and the validity of the clustering results.     

Glibenclamide for the Treatment of Ischemic and Hemorrhagic Stroke

Ischemic and hemorrhagic strokes are associated with severe functional disability and high mortality. Except for recombinant tissue plasminogen activator, therapies targeting the underlying pathophysiology of central nervous system (CNS) ischemia and hemorrhage are strikingly lacking. Sur1-regulated channels play essential roles in necrotic cell death and cerebral edema following ischemic insults, and in neuroinflammation after hemorrhagic injuries. Inhibiting endothelial, neuronal, astrocytic and oligodendroglial sulfonylurea receptor 1–transient receptor potential melastatin 4 (Sur1–Trpm4) channels and, in some cases, microglial K_ATP (Sur1–Kir6.2) channels, with glibenclamide is protective in a variety of contexts. Robust preclinical studies have shown that glibenclamide and other sulfonylurea agents reduce infarct volumes, edema and hemorrhagic conversion, and improve outcomes in rodent models of ischemic stroke. Retrospective studies suggest that diabetic patients on sulfonylurea drugs at stroke presentation fare better if they continue on drug. Additional laboratory investigations have implicated Sur1 in the pathophysiology of hemorrhagic CNS insults. In clinically relevant models of subarachnoid hemorrhage, glibenclamide reduces adverse neuroinflammatory and behavioral outcomes. Here, we provide an overview of the preclinical studies of glibenclamide therapy for CNS ischemia and hemorrhage, discuss the available data from clinical investigations, and conclude with promising preclinical results that suggest glibenclamide may be an effective therapeutic option for ischemic and hemorrhagic stroke.     

Combined effects of wheat gluten and carboxymethylcellulose on dough rheological behaviours and gluten network of potato–wheat flour-based bread

Incorporating high level of potato flour into wheat flour enhances nutritional values of bread but induces a series of problems that lead to the decline of the bread quality. To overcome the barrier, wheat gluten and carboxymethylcellulose (CMC) were added into potato–wheat composite flour to improve dough machinability and bread quality. The rheological properties, thermo-mechanical properties and microstructures of dough were investigated. The results showed that the interaction between gluten and CMC mitigated the discontinuity of gluten matrix and gluten protein aggregation caused by the addition of potato flour, which yielded a more branched and compact gluten network. The compact three-dimensional viscoelastic structure induced improvements of gas retention capacity and dough stability, making it mimic the machinability properties of wheat flour dough. Bread qualities were apparently improved with the combined use of 4% gluten and 6% CMC, of which specific volume increased by 42.86%, and simultaneously, hardness reduced by 75.93%.     

On the local behavior of spaces of range image patches

We focus on the quantitative and local topological properties of range images. We consider the spaces M_m of m × m high-contrast patches of range images for m=?3, 5, 7, 9, 11. Using computational topological tools to analyze range image patches, we detect that M₃ (M₉, M₁₁) has core subsets with the topology of a circle, M₃, M₅, M₇, M₉ and that M₁₁ have some subspaces with the topology of a Klein bottle. We also discover that the largest subspace with the Klein bottle’s topology decreases as the measurements of patches increase, which generalizes the results in the paper of H. Adams and G. Carlsson, and demonstrates properties among optical images and range image patches, which are more similar than those established by Lee et al.

     

Behavior of 316L stainless steel containing corrosion pits under cyclic loading

The environmental performance of 316L grade stainless steel, in the form of tensile specimens containing a single corrosion pit with various aspect ratios, under cyclic loading in aerated chloride solutions is investigated in this study. Results from environmental tests were compared and contrasted with those obtained using finite element analysis (FEA). Fractography of the failed specimens obtained from experiments revealed that fatigue crack initiation took place at the base of the shallow pit. The crack initiation shifted towards the shoulder and the mouth of the pit for pits of increasing depth. This process is well predicted by FEA, as the strain contour maps show that strain is the highest around the centric strip of the pit. However, for shallow pits, local strain is uniformly distributed around that strip but begins to concentrate more towards the shoulder and the mouth region for increasingly deep pits.