Immune-based mutation classification enables neoantigen prioritization and immune feature discovery in cancer immunotherapy.

Genetic mutations lead to the production of mutated proteins from which peptides are presented to T cells as cancer neoantigens. Evidence suggests that T cells that target neoantigens are the main mediators of effective cancer immunotherapies. Although algorithms have been used to predict neoantigens, only a minority are immunogenic. The factors that influence neoantigen immunogenicity are not completely understood. Here, we classified human neoantigen/neopeptide data into three categories based on their TCR-pMHC binding events. We observed a conservative mutant orientation of the anchor residue from immunogenic neoantigens which we termed the NP rule. By integrating this rule with an existing prediction algorithm, we found improved performance in neoantigen prioritization. To better understand this rule, we solved several neoantigen/MHC structures. These structures showed that neoantigens that follow this rule not only increase peptide-MHC binding affinity but also create new TCR-binding features. These molecular insights highlight the value of immune-based classification in neoantigen studies and may enable the design of more effective cancer immunotherapies

Principles and methods of scaling geospatial Earth science data

The properties of geographical phenomena vary with changes in the scale of measurement. The information observed at one scale often cannot be directly used as information at another scale. Scaling addresses these changes in properties in relation to the scale of measurement, and plays an important role in Earth sciences by providing information at the scale of interest, which may be required for a range of applications, and may be useful for inferring geographical patterns and processes. This paper presents a review of geospatial scaling methods for Earth science data. Based on spatial properties, we propose a methodological framework for scaling addressing upscaling, downscaling and side-scaling. This framework combines scale-independent and scale-dependent properties of geographical variables. It allows treatment of the varying spatial heterogeneity of geographical phenomena, combines spatial autocorrelation and heterogeneity, addresses scale-independent and scale-dependent factors, explores changes in information, incorporates geospatial Earth surface processes and uncertainties, and identifies the optimal scale(s) of models. This study shows that the classification of scaling methods according to various heterogeneities has great potential utility as an underpinning conceptual basis for advances in many Earth science research domains. © 2019 Elsevier B.V

Preparation of Ir0.4Ru0.6MoxOy for oxygen evolution by modified Adams' fusion method

A novel anodic electrocatalyst Ir0.4Ru0.6MoxOy for solid polymer electrolyte (SPE) water electrolysis is prepared by the modified Adams' fusion method. The XRD, ICP, and BET are employed to determine the physical characteristics of Ir0.4Ru0.6MoxOy and Ir0.4Ru0.6O2, and the electrochemical properties of the electrocatalysts are examined by cyclic voltammetry (CV) in 0.5 M H2SO4. The results show that Ir0.4Ru0.6MoxOy has much smaller particle size, larger specific surface areas and active surface area compared with Ir0.4Ru0.6O2. The results of single cell performance and the electrochemical impedance spectroscopy (EIS) tests also prove that Ir0.4Ru0.6MoxOy has higher performance than Ir0.4Ru0.6O2. (C) 2009 International Association for Hydrogen Energy. Published by Elsevier Ltd. All rights reserved

MRI Findings of Early Myositis Ossificans without Calcification or Ossification

Purpose. To characterize and evaluate the MR imaging features of early myositis ossificans (MO) without calcification or ossification. Methods. The MRI manifestations of seven patients with pathologically proven early MO were retrospectively analyzed with regard to tumor location, size, margins, signal intensity, and enhancement appearance in MR images. Additionally, the surrounding soft-tissue edema and adjacent bone change were assessed. Results. All cases (n=7) had intramuscular tumor-like masses without calcifications. The lesions appeared as isointense in T1-weighted images (T1-WI) and inhomogeneous hyperintense in T2-weighted MR images (T2-WI). On T2-WI and postcontrast T1-WI, the heterogeneously high signal intensity in the expanded muscle interspersed with a few hypointense linear structures consistent with intact muscle fibers showed “striate pattern” in the plane parallel with muscle fibers. The relatively hypointense areas with geometrical pattern consistent with the bundles of intact muscle fibers are found within the lesion with diffuse high signal intensity, displaying the “checkerboard-like pattern” in the plane vertical to muscle fibers. A “striate pattern” (n = 7) and “checkerboard-like pattern” (n = 3) in the lesion appeared in T2-WI. In contrast-enhanced MRI images, all cases showed diffuse “striate pattern” enhancement. Among them, one case demonstrated “checkerboard-like pattern” enhancement. All cases had diffuse and prominent muscle edema that preserved the muscle fascicles. For two lesions located in the deep muscle group, the adjacent bone showed bone marrow edema. Conclusion. MR imaging has unique advantages for diagnosis of early MO without calcification or ossification: the “striate pattern” and “checkerboard-like pattern” appearance shown in T2-WI and contrast-enhanced MRI images can be helpful for differential diagnosis. MRI can delineate the extent of the tumor and provides accurate anatomical information, which is important in diagnosis, treatment, and follow-up

Interleukin-9 Deletion Relieves Vascular Dysfunction and Decreases Blood Pressure via the STAT3 Pathway in Angiotensin II-Treated Mice

Background. Multiple interleukin (IL) family members were reported to be closely related to hypertension. We aimed to investigate whether IL-9 affects angiotensin II- (Ang II-) induced hypertension in mice. Methods. Mice were treated with Ang II, and IL-9 expression was determined. In addition, effects of IL-9 knockout (KO) on blood pressure were observed in Ang II-infused mice. To determine whether the effects of IL-9 on blood pressure was mediated by the signal transducer and activator of the transcription 3 (STAT3) pathway, Ang II-treated mice were given S31-201. Furthermore, circulating IL-9 levels in patients with hypertension were measured. Results. Ang II treatment increased serum and aortic IL-9 expression in a dose-dependent manner; IL-9 levels were the highest in the second week and continued to remain high into the fourth week after the treatment. IL-9 KO downregulated proinflammatory cytokine expression, whereas it upregulated anti-inflammatory cytokine levels, relieved vascular dysfunction, and decreased blood pressure in Ang II-infused mice. IL-9 also reduced smooth muscle 22α (SM22α) expression and increased osteopontin (OPN) levels both in mice and in vitro. The effects of IL-9 KO on blood pressure and inflammatory response were significantly reduced by S31-201 treatment. Circulating IL-9 levels were significantly increased in patients with the hypertension group than in the control group, and elevated IL-9 levels positively correlated with both systolic blood pressure and diastolic blood pressure in patients with hypertension. Conclusions. IL-9 KO alleviates inflammatory response, prevents phenotypic transformation of smooth muscle, reduces vascular dysfunction, and lowers blood pressure via the STAT3 pathway in Ang II-infused mice. IL-9 might be a novel target for the treatment and prevention of clinical hypertension

CT and MRI Findings of Soft Tissue Adult Fibrosarcoma in Extremities

Objective. To characterize and evaluate CT and MRI features of extremity soft tissue adult fibrosarcoma. Methods. CT and MRI images from 10 adult patients with pathologically proven fibrosarcomas were retrospectively analyzed with regard to tumor location, size, number, shape, margins, attenuation, signal intensity, and enhancement patterns on MR images. Additionally, the relationships between lesions, deep fascia, and change in adjacent bones were also assessed. Results. Nineteen tumor lesions in 10 patients were selected for this study. Eighteen lesions were lobulated and one was oval in shape. Most cases were located under the deep fascia, including seven cases that had a nodular lump adjacent to the deep fascia and one case that had broken lesion through the deep fascia. On CT, the adult fibrosarcomas mostly showed iso-attenuated soft tissue masses (n=6). On MRI, all the cases (n=9) displayed low signal on T1-weighted imaging (T1WI) and heterogeneous low and high intensity signals on T2-weighted imaging (T2WI), with band-like areas of low signal on both T1WI and T2WI. On contrast-enhanced MRI images, three cases showed heterogeneous peripheral enhancement and one case demonstrated a spoke-wheel-like enhancement. Eight cases showed muscle edema signals in the peritumoral muscle and one case involved adjacent bone. Conclusion. CT and MR imaging have respective advantages in diagnosing adult fibrosarcoma. Combined application of CT and MR is recommended for patients with suspected adult fibrosarcoma