Crowdsourced mapping of unexplored target space of kinase inhibitors

Despite decades of intensive search for compounds that modulate the activity of particular protein targets, a large proportion of the human kinome remains as yet undrugged. Effective approaches are therefore required to map the massive space of unexplored compound-kinase interactions for novel and potent activities. Here, we carry out a crowdsourced benchmarking of predictive algorithms for kinase inhibitor potencies across multiple kinase families tested on unpublished bioactivity data. We find the top-performing predictions are based on various models, including kernel learning, gradient boosting and deep learning, and their ensemble leads to a predictive accuracy exceeding that of single-dose kinase activity assays. We design experiments based on the model predictions and identify unexpected activities even for under-studied kinases, thereby accelerating experimental mapping efforts. The open-source prediction algorithms together with the bioactivities between 95 compounds and 295 kinases provide a resource for benchmarking prediction algorithms and for extending the druggable kinome. The IDG-DREAM Challenge carried out crowdsourced benchmarking of predictive algorithms for kinase inhibitor activities on unpublished data. This study provides a resource to compare emerging algorithms and prioritize new kinase activities to accelerate drug discovery and repurposing efforts

A Marketplace Price Anomaly Detection System at Scale

Online marketplaces execute large volume of price updates that are initiated by individual marketplace sellers each day on the platform. This price democratization comes with increasing challenges with data quality. Lack of centralized guardrails that are available for a traditional online retailer causes a higher likelihood for inaccurate prices to get published on the website, leading to poor customer experience and potential for revenue loss. We present MoatPlus (Masked Optimal Anchors using Trees, Proximity-based Labeling and Unsupervised Statistical-features), a scalable price anomaly detection framework for a growing marketplace platform. The goal is to leverage proximity and historical price trends from unsupervised statistical features to generate an upper price bound. We build an ensemble of models to detect irregularities in price-based features, exclude irregular features and use optimized weighting scheme to build a reliable price bound in real-time pricing pipeline. We observed that our approach improves precise anchor coverage by up to 46.6% in high-vulnerability item subsets

Glutaraldehyde Crosslinked High Content of Amylose/Polyvinyl Alcohol Blend Films with Potent Tensile Strength and Young’s Modulus

In recent years, with the development of green environmental protection, starch film has become of interest due to the wide availability of sources, low price, and biodegradability. Amylose/polyvinyl alcohol (PVA) blend films crosslinked with different amounts of glutaraldehyde (GLU) were prepared by a solution casting method. The cross-linking degree, water sorption, tensile property, crystallization and section morphology of the films were examined. With the increase in glutaraldehyde concentration, the cross-linking degree of the blend film was improved. The wide-angle X-ray scattering (WAXS) result indicated that cross-linking hindered the crystallization of film. The section morphology of films was examined by scanning electron microscope (SEM). The results showed that the cross-linking degree of amylose film improved while the crystallinity decreased with the increase in glutaraldehyde content. Cross-linking had no obvious effect on the water sorption property of the blend films. The cross-linking modification significantly enhanced the tensile strength and Young’s modulus, while it reduced the elongation at break of the blend films. It was found that the film with 0.5 wt % glutaraldehyde possessed the best performance: the tensile strength increased by 115%, while the elongation at break decreased by 18% even at high relative humidity (RH) of 90% compared to non-crosslinked films. The developed amylose/PVA blend films have promising application prospects as agricultural mulch films and packaging materials

Optical Control of the Localized Surface Plasmon Resonance in a Heterotype and Hollow Gold Nanosheet

The remote excitation and remote-controlling of the localized surface plasmon resonance (LSPR) in a heterotype and hollow gold nanosheet (HGNS) is studied using FDTD simulations. The heterotype HGNS contains an equilateral and hollow triangle in the center of a special hexagon, which forms a so-called hexagon–triangle (H–T) heterotype HGNS. If we focus the incident-exciting laser on one of the vertexes of the center triangle, the LSPR could be achieved among other remote vertexes of the outer hexagon. The LSPR wavelength and peak intensity depend sensitively on factors such as the polarization of the incident light, the size and symmetry of the H–T heterotype structure, etc. Several groups of the optimized parameters were screened out from numerous FDTD calculations, which help to further obtain some significant polar plots of the polarization-dependent LSPR peak intensity with two-petal, four-petal or six-petal patterns. Remarkably, based on these polar plots, the on-off switching of the LSPR coupled among four HGNS hotspots could be remote-controlled simply via only one polarized light, which shows promise for its potential application in remote-controllable surface-enhanced Raman scattering (SERS), optical interconnects and multi-channel waveguide switches

Study on the ratchetting behavior of glass fiber-reinforced epoxy composites: Experiment and theory

To discuss the ratchetting behavior of short glass fiber-reinforced epoxy polymer composites, experimental and theoretical studies were carried out. The effects of the fiber content and peak stress on the ratchetting behavior of the composite materials were discussed. The results show that the ratchetting strain decreases with increasing fiber content and decreasing peak stress. It was also found that the residual strain after unloading partly recovers with time, which indicates that the ratchetting strain consists of viscoelastic strain and plastic strain. Based on the experimental results, a viscoelastic-viscoplastic constitutive model is proposed, which can well simulate the ratchetting behavior and strain recovery of composites with different fiber contents

Design and Experimental Study of Potato-Soil Separation Device for Sticky Soils Condition

The potato-soil separation device comprising five function areas (i.e., shearing, bending, throwing, cleaning, and conveying) was developed to address the mentioned problems (e.g., soil with high moisture content, large viscosity, and poor separation efficacy) in the harvesting process for winter idle paddy fields of Southern China. Given the kinetic analyses for the potato-soil mixture of five function areas, the crucial factors of the effect of potato-soil separation were determined. Subsequently, the orthogonal test of 4 factors and 3 levels was performed, and the percentage of small soil λ, the percentage of soil adhering to potato tuber γ, and damage rate of potato tuber K were adopted as assessment indexes. Regression analyses and programming for the orthogonal test result were conducted to optimize the device run parameters, and the optimal run parameters included the rotational speed of the soil-crushing mechanism of 84.18 r/min, linear velocity of second-stage lifting chain of 0.75 m/s, and inclination angle of lifting chain of 15.87°. The field experiments were performed with the modified potato harvester. As indicated from the result, the visible potato rate was 94.31% and damage rate of potato was 0.89%, and the requirement of the national standard was satisfied. This study presented technical feasibility data and equipment for potato-soil separation under sticky soils condition

Changing Treatment May Affect the Predictive Ability of European Treatment Outcome Study Scoring for the Prognosis of Patients with Chronic Myeloid Leukemia

Objective: Previous studies compared the predictive ability of the European Treatment Outcome Study (EUTOS), Sokal, and Hasford scoring systems and demonstrated inconsistent findings with unknown reasons. This study was conducted to determine a useful scoring system to predict the prognosis of patients with chronic myeloid leukemia (CML) and identify the probable factors that affect the scoring. Materials and Methods: This is a retrospective cohort study. The predictive ability of EUTOS and the factors that affect scoring were analyzed in 234 Chinese chronic-phase CML patients treated with frontline imatinib, including a few patients temporarily administered hydroxyurea for cytoreduction before imatinib. Patients were stratified into different risk groups according to each scoring system to assess the treatment outcomes and the predictive ability of EUTOS scores between patients who received imatinib during the entire followup period and patients who received altered treatment because of intolerance, progression, and treatment failure. Results: Sixty-one (26.0%) patients received altered treatments during the follow-up. In the EUTOS low- and high-risk groups, the 5-year overall survival was 94.6% and 84.7% (p=0.011), 5-year eventfree survival was 92.6% and 77.6% (p=0.001), and 5-year progressionfree survival (PFS) was 95.3% and 82.4% (p=0.001), respectively. The predictive ability of EUTOS was better than that of the Sokal and Hasford scores (p=0.256, p=0.062, p=0.073) without statistical significance. All three scoring systems were valid in predicting early optimal response. Kaplan-Meier analysis showed a high association between overall PFS and the EUTOS scores in the standard-dose imatinib group (p<0.001). Conclusion: This study suggests that the EUTOS scoring system could predict the outcome of chronic-phase CML patients treated with standard-dose imatinib. Altered treatment is a crucial factor that affects the prognostic impact of EUTOS scoring. Achieving complete cytogenetic response at 18 months is an essential factor in predicting the prognosis of patients with CML