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An appropriate therapeutic index is crucial for drug discovery and development since narrow therapeutic index (NTI) drugs with slight dosage variation may induce severe adverse drug reactions or potential treatment failure. To date, the shared characteristics underlying the targets of NTI drugs have been explored by several studies, which have been applied to identify potential drug targets. However, the association between the drug therapeutic index and the related disease has not been dissected, which is important for revealing the NTI drug mechanism and optimizing drug design. Therefore, in this study, two classes of disease (cancers and cardiovascular disorders) with the largest number of NTI drugs were selected, and the target property of the corresponding NTI drugs was analyzed. By calculating the biological system profiles and human protein-protein interaction (PPI) network properties of drug targets and adopting an AI-based algorithm, differentiated features between two diseases were discovered to reveal the distinct underlying mechanisms of NTI drugs in different diseases. Consequently, ten shared features and four unique features were identified for both diseases to distinguish NTI from NNTI drug targets. These computational discoveries, as well as the newly found features, suggest that in the clinical study of avoiding narrow therapeutic index in those diseases, the ability of target to be a hub and the efficiency of target signaling in the human PPI network should be considered, and it could thus provide novel guidance in the drug discovery and clinical research process and help to estimate the drug safety of cancer and cardiovascular disease.

Ephemeral gully erosion is an important process in the black soil region, Northeast China and can be responsible for severe damage to agricultural lands. However, little research on gully formation in this area has been published. The study described in this paper attempted to quantify soil losses, the spatial distribution and morphology of the gullies, and the factors that control their development. Ephemeral gullies were measured in spring and summer of 2005 in two small catchments. The critical periods for ephemeralgullyformationwerelatespringandsummerinthestudyarea.Meansoil lossesduetoephemeralgullyerosionwere0.40 and 0.43 kg m � 2 year � 1 for only croplands despite low slope gradients, and this loss is above the tolerable erosion rates of 0.20 kg m � 2 year � 1 . The erosion rates were greater in spring because the topsoil thawed before deeper layers, reducing infiltration into the soil, and the bare vegetation cover provided no barriers to surface flow. In contrast, summer erosion occurred primarily in response to intense rain events. Development of the gullies was promoted by freeze-thaw cycles in spring and was affected by the type of agricultural operations and crops in summer. A linear regression model for the prediction of ephemeral gully length at the catchment level was established using field data, and although it did not successfully predict the length of individual gullies, it explained 55% of the variation in ephemeral gully length. # 2007 Published by Elsevier B.V.