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Since it was observed that the structural class of a protein is related to its amino acid composition, various methods based on amino acid composition have been proposed to predict protein structural classes. Though those methods are effective to some degree, their predictive quality is confined because amino acid composition cannot sufficiently include the information of protein sequences. In this paper, a measure of information discrepancy is applied to the prediction of protein structural classes; different from the previous methods, this new approach is based on the comparisons of subsequence distributions; therefore, the effect of residue order on protein structure is taken into account. The predictive results of the new approach on the same data set are better than those of the previous methods. As to a data set of 1401 sequences with no more than 30% redundancy, the overall correctness rates of resubstitution test and Jackknife test are 99.4 and 75.02%, respectively, and to other data sets the similar results are also obtained. All tests demonstrate that the residue order along protein sequences plays an important role on recognition of protein structural classes, especially for α/β proteins and α+β proteins. In addition, the tests also show that the new method is simple and efficient. [Copyright &y& Elsevier]

In the globalization era, shrinking cities have emerged as a widespread phenomenon and become a new buzzword in regional and urban research discourse. The Pearl River Delta (PRD), one of the most representative areas of rapid urbanization in China, is characterized by export-oriented economy and " exo -urbanization." Induced by the financial crisis of 2008, new spatial symptoms related to urban shrinkage, such as factory collapses, job losses, and vacant dwellings, were observed in this area. To investigate spatial-temporal characteristics of the crisis-induced shrinkage in the PRD, this paper proposes a theoretical approach to interpret urban growth and shrinkage in combination with economic, population, and land dimensions. Moreover, through an analysis of statistical data and in-depth interviews in the case of Dongguan, three primary influences (i.e., global financial crisis, demographic dividend diminishment, and change in institutional arrangement) on urban shrinkage in town-level cities are evaluated. This study not only contributes to the literature by analyzing the short-term urban shrinkage influenced by sudden economic shock in globalization but also demonstrates the complexity and multiplicity of urban shrinkage that emerged in the rapidly urbanizing area of the Global South. • Shrinking cities in the exo-urbanization area represents a typical short-term pattern in the era of globalization. • Urban shrinkage tends to be more diverse and complex in the rapidly urbanizing area of the Global South. • Five typologies are classified in relation to both population and economic dimensions that intersect with the trajectories. • Growth and shrinkage is a nonlinear and non-homogeneous phenomenon closely related to multi-scale influences. [ABSTRACT FROM AUTHOR]

Abstract: This note points out that the comment article by , refer to ‘K-comment’ hereafter) was based on the code analysis with methodological and mathematical errors. The incorrect modification of the original code and FDOD method has resulted in the wrong conclusions in K-comment. [Copyright &y& Elsevier]

Abstract: The spatial distribution and source of polychlorinated biphenyls (PCBs) in 30 surface sediments of Yueqing Bay, Xiangshan Bay, and Sanmen Bay in Eastern China were analysed. Total concentrations of PCBs ranged from 9.33 to 19.60ngg−1 dry weight for all the sampling stations. The observed PCB levels were lower than those in areas of high urbanisation or contamination in the bay. Low-chlorinated PCBs, dominated by tri-PCB, were identified as the prevalent contaminate of surface sediments, and the top three PCB congeners were lighter chlorinated congeners (PCB 8, PCB 18 and PCB 28). These results were in agreement with the fact that tri-PCB compounds are the dominant contaminants in China. The result of the principal component analysis revealed that all samples were similar in composition to Aroclor 1242, suggesting they might originate from electrical capacitors and transformers. The levels of PCBs were significantly correlated with the total organic carbon in the sediments. [Copyright &y& Elsevier]

This study analyzed the direction and strength of the association between housing prices and their potential determinants in China, from a tripartite perspective that takes into account housing demand, housing supply, and the housing market. A data set made up of county-level housing prices and selected factors was constructed for the year 2014, and spatial regression and geographical detector technique were estimated. The results of the study indicate that the housing prices of Chinese counties are heavily influenced by the administrative level of the county in question. On the basis of results obtained using Moran's I , the study revealed the presence of significant spatial autocorrelation (or spatial agglomeration) in the data. Using spatial regression techniques, the study identifies the positive effect exerted by the proportion of renters, floating population, wage level, the cost of land, the housing market and city service level on housing prices, and the negative influence exerted by living space. The geographical detector technique revealed marked differences in the relative influence, as well as the strength of association, of the seven factors in relation to housing prices. The cost of land had a greater influence on housing prices than other factors. We argue that a better understanding of the determinants of housing prices in China at the county level will help Chinese policymakers to formulate more detailed and geographically specific housing policies. [ABSTRACT FROM AUTHOR]

Abstract: HIV-1 integrase catalyzes the insertion of viral DNA into the genome of the host cell. Integrase inhibitor N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide selectively inhibits the strand transfer process of integration. 4-Substituted pyrrolidinones possessing various groups on the pyrrolidinone nitrogen were introduced at the 5-position of the naphthyridine scaffold. These analogs exhibit excellent activity against viral replication in a cell-based assay. The preparation of these compounds was enabled by a three-step, two-pot reaction sequence from a common butenolide intermediate. [Copyright &y& Elsevier]

Abstract: A series of potent novel dihydroxypyridopyrazine-1,6-dione HIV-1 integrase inhibitors was identified. These compounds inhibited the strand transfer process of HIV-1 integrase and viral replication in cells. Compound 6 is active against replication of HIV with a CIC95 of 0.31μM and exhibits no shift in potency in the presence of 50% normal human serum. It displays a good pharmacokinetic profile when dosed in rats and no covalent binding with microsomal proteins in both in vitro and in vivo models. [Copyright &y& Elsevier]

Abstract: A series of β-site amyloid precursor protein cleaving enzyme (BACE-1) inhibitors containing a ψ(CH2NH) reduced amide bond were synthesized. Incorporation of this reduced amide isostere as a non-cleavable peptide surrogate afforded inhibitors possessing low nanomolar potencies in both an enzymatic and cell-based assay. [Copyright &y& Elsevier]

Abstract: A series of 5-amino derivatives of 8-hydroxy[1,6]-naphthyridine-7-carboxamide exhibiting sub-micromolar potency against replication of HIV-1 in cell culture was identified. One of these analogs, compound 12, displayed excellent pharmacokinetic properties when dosed orally in rats and in monkeys. This compound was demonstrated to be efficacious against replication of simian-human immunodeficiency virus (SHIV) 89.6P in infected rhesus macaques. [Copyright &y& Elsevier]

Abstract: Efforts directed to identifying potent HIV protease inhibitors (PI) have yielded a class of compounds that are not only very active against wild-type (NL4-3) HIV virus but also very potent against a panel of PI-resistant viral isolates. Chemistry and biology are described. [Copyright &y& Elsevier]

Abstract: Introduction of a 5,6-dihydrouracil functionality in the 5-position of N-(4-fluorobenzyl)-8-hydroxy-[1,6]naphthyridine-7-carboxamide 1 led to a series of highly active HIV-1 integrase inhibitors. These compounds displayed low nanomolar activity in inhibiting both the strand transfer process of HIV-1 integrase and viral replication in cells. Compound 11 is a 150-fold more potent antiviral agent than 1, with a CIC95 of 40nM in the presence of human serum. It displays good pharmacokinetics when dosed in rats and dogs. [Copyright &y& Elsevier]

HIV-1 protease inhibitors (PI) with an N-arylpyrrole moiety in the P3 position afforded excellent antiviral potency and substantially improved aqueous solubility over previously reported variants. The rapid in vitro clearance of these compounds in human liver microsomes prompted oral coadministration with indinavir to hinder their metabolism by the cyctochrome P450 3A4 isozyme and allow for in vivo PK assessment. [Copyright &y& Elsevier]

Transposition of the pyridyl nitrogen from the P3 substituent to the P1′ substituent in HIV-1 protease inhibitors (PI) affords compounds such as 3 with an improved inhibitory profile against multiple P450 isoforms. These compounds also displayed increased potency, with 3 inhibiting viral spread (CIC95) at <8 nM for every strain of PI-resistant HIV-1 tested. The poor to modest bioavailability of these compounds may correlate in part to their aqueous solubility. [Copyright &y& Elsevier]

Replacement of the pyridylmethyl moiety in indinavir with a pyridyl oxazole yielded HIV-1 protease inhibitors (PI) with greatly improved potency against PI-resistant HIV-1 strains. A meta-methoxy group on the pyridyl ring and a gem-dimethyl methyl linkage afforded compound 10 with notable in vitro antiviral activity against HIV-1 viral strains with reduced susceptibility to the clinically available PIs. Compound 10 also demonstrated favorable in vivo pharmacokinetics in animal models. [Copyright &y& Elsevier]

A series of highly potent HIV protease inhibitors have been designed and synthesized. These compounds are active against various clinical viral isolates as well as wild-type virus. The synthesis and biological activity of these HIV protease inhibitors are discussed. [Copyright &y& Elsevier]

Indinavir analogues with blocked metabolism sites show highly improved pharmacokinetic profiles in animals. The cis-aminochromanol substituted analogues exhibited excellent potency against both the wild-type (NL4-3) virus and protease inhibitor-resistant HIV strains. [Copyright &y& Elsevier]

Substitution of the t-butylcarboxamide substituent in analogues of the HIV protease inhibitor (PI) Indinavir with a trifluoroethylamide moiety confers greater potency against both the wild-type (NL4-3) virus and PI-resistant HIV. The trifluoroethyl substituent also affords a slower clearance rate in vivo (dogs); however, this may be due to more potent inhibition of at least two P450 isoforms. [Copyright &y& Elsevier]

A combinatorial library of 300HIV protease inhibitors has been synthesized. The library was screened against recombinant wild-type and mutant HIV-1 protease enzymes. The pharmacokinetics of the library was evaluated by dosing in dogs. Compounds that are notably more potent than indinavir and have favorable pharmacokinetic properties were identified. [Copyright &y& Elsevier]