Notes

Deep learning-assisted (automatic) diagnosis of glaucoma using a mobile phone.
According to the World Health Organization (WHO), 422 million people are suffering from diabetes worldwide. Current diabetes therapies are focused on optimizing blood glucose control to prevent long-term diabetes complications. Unfortunately, current therapies have failed to achieve glycemic targets in the majority of people with diabetes. In this context, regeneration of functional insulin-producing human β-cells in people with diabetes through the use of DYRK1A inhibitor drugs has recently received special attention. Several small molecule DYRK1A inhibitors have been identified that induce human β-cell proliferation in vitro and in vivo. Furthermore, DYRK1A inhibitors have also been shown to synergize β-cell proliferation with other classes of drugs, such as TGFβ inhibitors and GLP-1 receptor agonists. In this perspective, we review the status of DYRK1A as a therapeutic target for β-cell proliferation and provide perspectives on technical and scientific challenges for future translational development.Post-translational modifications of proteins play an important role in the regulation of cellular processes. The mass spectrometry analysis of proteome modifications offers huge potential for the study of how protein inhibitors affect the phosphosignaling mechanisms inside the cells. We have recently proposed PHONEMeS, a method that uses high-content shotgun phosphoproteomic data to build logical network models of signal perturbation flow. However, in its original implementation, PHONEMeS was computationally demanding and was only used to model signaling in a perturbation context. We have reformulated PHONEMeS as an Integer Linear Program (ILP) that is orders of magnitude more efficient than the original one. We have also expanded the scenarios that can be analyzed. PHONEMeS can model data upon perturbation on not only a known target but also deregulated pathways upstream and downstream of any set of deregulated kinases. Finally, PHONEMeS can now analyze data sets with multiple time points, which helps us to obtain better insight into the dynamics of the propagation of signals. We illustrate the value of the new approach on various data sets of medical relevance, where we shed light on signaling mechanisms and drug modes of action.The larger size of graphene sheets should intuitively generate higher overall properties of their macroscopic materials. However, this intuitive notion still remains ambiguous. Here, we uncover that the wrinkle formation causes the counterintuitive size predicament of graphene sheets in their macroscopic materials. selleck inhibitor In the model of graphene oxide assembled papers, we reveal that the giant size of graphene oxide sheets aggravates the formation of larger wrinkles and more microvoids, causing the negative size effect in mechanical strength. A major microscopic origin of the size predicament is the skin wrinkling in the drying process, and the wrinkling behavior follows a general rule of deformation of an elastic thin plate. We use a wrinkle-engineering strategy to depress the spontaneously formed large wrinkles and succeed in the resolution of the size predicament. After wrinkle modulation, an authentically positive size effect reversely appears in which giant graphene sheets generate ultrahigh mechanical strength and superior functionalities of graphene papers. The origin of the size predicament reminds us of the hidden importance of modulating wrinkles for graphene macroscopic materials and provides a guidance of wrinkle engineering for graphene materials with advanced performances.Benzophenone is a mutagen, carcinogen, and endocrine disruptor. Its presence in food products or food packaging is banned in the United States. Under California Proposition 65, there is no safe harbor for benzophenone in any personal care products, including sunscreens, anti-aging creams, and moisturizers. The purpose of this study was to determine (1) if benzophenone was present in a wide variety of commercial sun protection factor (SPF)/sunscreen products, (2) whether benzophenone concentration in the product increased over time, and (3) if the degradation of octocrylene was the likely source for benzophenone contamination. Benzophenone concentration was assayed in nine commercial sunscreen products from the European Union and eight from the United States (in triplicate), including two single ingredient sources of octocrylene. These same SPF items were subjected to the United States Food and Drug Administration (U.S. FDA)-accelerated stability aging protocol for 6 weeks. Benzophenone was measured in the accconsumer products should be expeditiously reviewed by regulatory agencies.An irregular porous structure plays a major role in bone tissue engineering, and it is more suitable for bone tissue growth than a regular porous structure. The response surface method was used to establish a relationship between the average pore size and the design parameters. The technology of selective laser melting was utilized to fabricate the porous Ti-6Al-4V scaffolds with an irregularity of (0.4) and porosities of (70, 80, and 90%) designed using the Voronoi-tessellation method. Compression tests of porous scaffolds showed an elastic modulus range of 0.84-1.97 GPa and an ultimate strength ranging within 21.0-99.1 MPa. The elastic modulus was mainly influenced by the porosity and heat-treatment process. Furthermore, the fatigue test results suggested that the number of cycles (9 × 104 to 1.8 × 106) was greatly influenced by the porosity and heat-treatment process. The heat treatment of annealing greatly improved the fatigue performance of porous scaffolds. The irregular porous scaffolds with lower porosity and after full annealing exhibited the best fatigue behavior.Estimates of ground-level ozone concentrations are necessary to determine the human health burden of ozone. To support the Global Burden of Disease Study, we produce yearly fine resolution global surface ozone estimates from 1990 to 2017 through a data fusion of observations and models. As ozone observations are sparse in many populated regions, we use a novel combination of the M3Fusion and Bayesian Maximum Entropy (BME) methods. With M3Fusion, we create a multimodel composite by bias-correcting and weighting nine global atmospheric chemistry models based on their ability to predict observations (8834 sites globally) in each region and year. BME is then used to integrate observations, such that estimates match observations at each monitoring site with the observational influence decreasing smoothly across space and time until the output matches the multimodel composite. After estimating at 0.5° resolution using BME, we add fine spatial detail from an additional model, yielding estimates at 0.1° resolution. Observed ozone is predicted more accurately (R2 = 0.
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