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ABSTRACT:Zoning which is to divide the study area into different zones according to their geographical differences at the global, national or regional level, includes natural division, economic division, geographical zoning of departments, comprehensive zoning and so on. Zoning is of important practical significance, for example, knowing regional differences and characteristics, regional research and regional development planning, understanding the favorable and unfavorable conditions of the regional development etc. Geographical environment is arising from the geographical position linkages. Geographical environment unit division is also a type of zoning. The geographical environment indicators are deeply studied and summed up in the article, including the background, the associated and the potential. The background indicators are divided into four categories, such as the socio-economic, the political and military, the strategic resources and the ecological environment, which can be divided into more sub-indexes. While the sub-indexes can be integrated to comprehensive index system by weighted stacking method. The Jenks natural breaks classification method, also called the Jenks optimization method, is a data classification method designed to determine the best arrangement of values into different classes. This is done by seeking to minimize each class's average deviation from the class mean, while maximizing each class's deviation from the means of the other groups. In this paper, the experiment of Chinese surrounding geographical environment unit division has been done based on the natural breaks (jenks) method, the geographical environment index system and the weighted stacking method, taking South Asia as an example. The result indicates that natural breaks (jenks) method is of good adaptability and high accuracy on the geographical environment unit division.The geographical environment research was originated in the geopolitics and flourished in the geo-economics. The main representatives of the geopolitics are German geographer Friedrich Ratzel, British geographer Mackinder and American geographical politician Nicholas John Spykman etc. The main representative of the geo-economics is American geographical economist Edward Luttwak. China has the most neighboring countries in the world, and its geographical environment is extremely complex. With the continuous development of globalization, China's relations with neighboring countries have become more complex and more closely. So it is very meaningful to have depth research on geographical environment unit division of China.

We have discovered a novel class of nonsteroidal pyrazoline antagonists of the mineralocorticoid receptor (MR) that show excellent potency and selectivity against other nuclear receptors. Early analogues were poorly soluble and had a propensity to inhibit the hERG channel. Remarkably, both of these challenges were overcome by incorporation of a single carboxylate moiety. Structural modification of carboxylate-containing lead R-4g with a wide range of substituents at each position of the pyrazoline ring resulted in R-12o, which shows excellent activity against MR and reasonable pharmacokinetic profile. Introduction of conformational restriction led to a novel series characterized by exquisite potency and favorable steroid receptor selectivity and pharmacokinetic profile. Oral dosing of 3S,3aR-27d (PF-3882845) in the Dahl salt sensitive preclinical model of salt-induced hypertension and nephropathy showed blood pressure attenuation significantly greater than that with eplerenone, reduction in urinary albumin, and renal protection. As a result of these findings, 3S,3aR-27d was advanced to clinical studies.

The vast accumulation of environmental data and the rapid development of geospatial visualization and analytical techniques make it possible for scientists to solicit information from local citizens to map spatial variation of geographic phenomena. However, data provided by citizens (referred to as citizen data in this article) suffer two limitations for mapping: bias in spatial coverage and imprecision in spatial location. This article presents an approach to minimizing the impacts of these two limitations of citizen data using geospatial analysis techniques. The approach reduces location imprecision by adopting a frequency-sampling strategy to identify representative presence locations from areas over which citizens observed the geographic phenomenon. The approach compensates for the spatial bias by weighting presence locations with cumulative visibility (the frequency at which a given location can be seen by local citizens). As a case study to demonstrate the principle, this approach was applied to map the habitat suitability of the black-and-white snub-nosed monkey (Rhinopithecus bieti) in Yunnan, China. Sightings of R. bieti were elicited from local citizens using a geovisualization platform and then processed with the proposed approach to predict a habitat suitability map. Presence locations of R. bieti recorded by biologists through intensive field tracking were used to validate the predicted habitat suitability map. Validation showed that the continuous Boyce index (B cont (0.1)) calculated on the suitability map was 0.873 (95% CI: [0.810, 0.917]), indicating that the map was highly consistent with the fieldobserved distribution of R. bieti. B cont (0.1) was much lower (0.173) for the suitability map predicted based on citizen data when location imprecision was not reduced and even lower (−0.048) when there was no compensation for spatial bias. This indicates that the proposed approach effectively minimized the impacts of location imprecision and spatial bias in citizen data and therefore effectively improved the quality of mapped spatial variation using citizen data. It further implies that, with the application of geospatial analysis techniques to properly account for limitations in citizen data, valuable information embedded in such data can be extracted and used for scientific mapping.

We have studied a model compound for oxyhemoglobin and oxymyoglobin, the iron-dioxygen complex of "picket fence porphyrin" (5,10,15,a,a,porphyrinato)iron (II) ((1-Melm)02), as well as oxymyoglobin and oxyhemoglobin themselves, by using 170 solid-state nuclear magnetic resonance spectroscopy. For the model picket fence porphyrin, the principal components of the chemical shift tensors for both bridging and terminal oxygens in the Fe-02 unit have been determined, and the isotropic chemical shifts occur at 1200-1600 and 2000 ppm, respectively, somewhat deshielded from the -1750 and ~2500 ppm values found by Gerothanassis et al. in solution {J. Am. Chem. Soc. 1989, III, 7006-7012).The anisotropies of the shift tensors are very large for both oxygens ( = ~2200 ppm for the bridging oxygen and = 3350 ppm for the terminal oxygen, at 77 K). From partial averaging of the shift tensors at room temperature, due to fast axial rotation of the dioxygen ligand, an Fe-O-O bond angle of ~140°has been derived for the model system. Temperature dependence studies indicate essentially no change in the isotropic chemical shift of the terminal oxygen down to 4.2 K, while there is an apparent low-frequency shift of the bridging oxygen on cooling to 77 K, possibly due to the freezing in of one conformational substate. Spectra of oxymyoglobin and oxyhemoglobin, at 77 K, are very similar to those of the model compound at low temperature. Our results indicate that the 170 nuclear quadrupole coupling constants must be relatively small for both oxygens (55 MHz) in all systems, much smaller than the 8.5and 20-MHz values found for ozone, suggesting extensive ir-delocalization in the Fe-O-O fragment. Our results are also consistent with an overwhelmingly spin paired configuration, both in the model system, and in oxyhemoglobin and oxymyoglobin themselves.

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Nonimmunosuppressive cyclophilin inhibitors have demonstrated efficacy for the treatment of hepatitis C infection (HCV). However, alisporivir, cyclosporin A, and most other cyclosporins are potent inhibitors of OATP1B1, MRP2, MDR1, and other important drug transporters. Reduction of the side chain hydrophobicity of the P4 residue preserves cyclophilin binding and antiviral potency while decreasing transporter inhibition. Representative inhibitor 33 (NIM258) is a less potent transporter inhibitor relative to previously described cyclosporins, retains anti-HCV activity in cell culture, and has an acceptable pharmacokinetic profile in rats and dogs. An X-ray structure of 33 bound to rat cyclophilin D is reported.