Sustainable development of mountain areas and resource cities has been a significant issue worldwide. Transformation of mountain resource cities is facing tremendous difficulties. In the context of National Major Func...Sustainable development of mountain areas and resource cities has been a significant issue worldwide. Transformation of mountain resource cities is facing tremendous difficulties. In the context of National Major Function-oriented Zone Planning raised to a national strategic level in China, it is important to effectively implement the planning by studying geographical space development zone classification of prefecture- and county-level cities based on their major function orientation. This research is even more critical for the transformation of mountain resource cities. In this study, we evaluated geographical space development suitability, and classified geographical space development zones for Dongchuan Distric in Kunming City of Yunan Province, China, a typical mountain resource city. A quantitative grid-based evaluation was conducted using key-factor identification and restrictive-supportive comprehensive index determinati based on a geographic information system framework with different source data. The results included a classification of geographical space of Dongchuan into five types: the prohibited development zone, the inappropriate development zone, the controlled development zone, the moderate development zone and the preferential development zone. The distribution characteristics of geographical space development zones showed that the proportion of the prohibited development zone is the highest, while that of the other four development zones is comparatively lower and significantly fragmented. The geographical space development suitability is greatly controlled by the geomorphic pattern. Although Dongchuan is extremely restrained in terms of suitable geographical space for industrialization and urbanization, it still has the certain preferential and moderate development zones with an area of 207.81 km2 with large parts being concentrated and contiguous, which makes these areas the most favorable for development. Only by adapting to this reality and implementing centralized development strategy in the regions with higher suitability may Dongchuan achieve smooth transformation from expansion mode to compact mode and its sustainable development capacity may be improved. Suggestions with an angle of industrial and spatial development pattern were put forward for the transformation of the city in future.展开更多
To investigate the relation of two different mutations to the outcome of partial external biliary diversion (PEBD) in severe bile salt export pump (BSEP) deficiency. METHODSMutations in the gene encoding BSEP leading ...To investigate the relation of two different mutations to the outcome of partial external biliary diversion (PEBD) in severe bile salt export pump (BSEP) deficiency. METHODSMutations in the gene encoding BSEP leading to severe BSEP deficiency in two unrelated patients were identified by genomic sequencing. Native liver biopsies and transiently transfected human embryonic kidney (HEK) 293 cells expressing either wild-type or mutated BSEP were subjected to immunofluorescence analysis to assess BSEP transporter localization. Bile acid profiles of patient and control bile samples were generated by ultra-performance liquid chromatography-tandem mass spectrometry. Wild-type and mutant BSEP transport of [<sup>3</sup>H]-labeled taurocholate (TC) and taurochenodeoxycholate (TCDC) was assessed by vesicular transport assays. RESULTSA girl (at 2 mo) presented with pruritus, jaundice and elevated serum bile salts (BS). PEBD stabilized liver function and prevented liver transplantation. She was heterozygous for the BSEP deletion p.T919del and the nonsense mutation p.R1235X. At the age of 17 years relative amounts of conjugated BS in her bile were normal, while total BS were less than 3% as compared to controls. An unrelated boy (age 1.5 years) presenting with severe pruritus and elevated serum BS was heterozygous for the same nonsense and another missense mutation, p.G1032R. PEBD failed to alleviate pruritus, eventually necessitating liver transplantation. BS concentration in bile was about 5% of controls. BS were mainly unconjugated with an unusual low amount of chenodeoxycholate derivatives (< 5%). The patients’ native liver biopsies showed canalicular BSEP expression. Both BSEP p.T919del and p.G1032R were localized in the plasma membrane in HEK293 cells. In vitro transport assays showed drastic reduction of transport by both mutations. Using purified recombinant BSEP as quantifiable reference, per-molecule transport rates for TC and TCDC were determined to be 3 and 2 BS molecules per wild-type BSEP transporter per minute, respectively. CONCLUSIONIn summary, our findings suggest that residual function of BSEP as well as substrate specificity influence the therapeutic effectiveness of PEBD in progressive familial intrahepatic cholestasis type 2 (PFIC-2).展开更多
Tumor metastasis is one of the most serious challenges for human cancers as the majority of deaths caused by cancer are associated with metastasis,rather than the primary tumor.Recent studies have demonstrated that tu...Tumor metastasis is one of the most serious challenges for human cancers as the majority of deaths caused by cancer are associated with metastasis,rather than the primary tumor.Recent studies have demonstrated that tumor cell plasticity plays a critical role in tumor metastasis by giving rise to various cell types which is necessary for tumor to invade adjacent tissues and form distant metastasis.These include differentiation of cancer stem cells(CSCs),or epithelial-mesenchymal transition(EMT)and its reverse process,mesenchymal-epithelial transition(MET).A growing body of evidence has demonstrated that the biology of tumor cell plasticity is tightly linked to functions of non-coding RNAs(ncRNAs),especially microRNAs(miRNAs)and long non-coding RNAs(lncRNAs).Therefore,understanding the mechanisms how non-coding RNAs regulate tumor cell plasticity is essential for discovery of new diagnostic markers and therapeutic targets to overcome metastasis.展开更多
The authors compute the(rational) Betti number of real toric varieties associated to Weyl chambers of type B, and furthermore show that their integral cohomology is p-torsion free for all odd primes p.
Toward the problem of judgement of enterprise crisis degree, the paper adopts fuzzy classification and fuzzy recognition method, forms enterprise character objective function in fuzzy condition, and brings forward to ...Toward the problem of judgement of enterprise crisis degree, the paper adopts fuzzy classification and fuzzy recognition method, forms enterprise character objective function in fuzzy condition, and brings forward to solve approach of optimal fuzzy classification center matrix, optimal fuzzy recognition matrix and optimal index weight under different crisis degree. By using the method in enterprise crisis early-warning example, it can distinguish enterprise crisis degree effectively.展开更多
基金Under the auspices of National Basic Research Program of China(No.2015CB452706)National Natural Science Foundation of China(No.41301193)Knowledge Innovation Program of Chinese Academy of Sciences(No.KZCX2-YW-333)
文摘Sustainable development of mountain areas and resource cities has been a significant issue worldwide. Transformation of mountain resource cities is facing tremendous difficulties. In the context of National Major Function-oriented Zone Planning raised to a national strategic level in China, it is important to effectively implement the planning by studying geographical space development zone classification of prefecture- and county-level cities based on their major function orientation. This research is even more critical for the transformation of mountain resource cities. In this study, we evaluated geographical space development suitability, and classified geographical space development zones for Dongchuan Distric in Kunming City of Yunan Province, China, a typical mountain resource city. A quantitative grid-based evaluation was conducted using key-factor identification and restrictive-supportive comprehensive index determinati based on a geographic information system framework with different source data. The results included a classification of geographical space of Dongchuan into five types: the prohibited development zone, the inappropriate development zone, the controlled development zone, the moderate development zone and the preferential development zone. The distribution characteristics of geographical space development zones showed that the proportion of the prohibited development zone is the highest, while that of the other four development zones is comparatively lower and significantly fragmented. The geographical space development suitability is greatly controlled by the geomorphic pattern. Although Dongchuan is extremely restrained in terms of suitable geographical space for industrialization and urbanization, it still has the certain preferential and moderate development zones with an area of 207.81 km2 with large parts being concentrated and contiguous, which makes these areas the most favorable for development. Only by adapting to this reality and implementing centralized development strategy in the regions with higher suitability may Dongchuan achieve smooth transformation from expansion mode to compact mode and its sustainable development capacity may be improved. Suggestions with an angle of industrial and spatial development pattern were put forward for the transformation of the city in future.
基金Supported by the German -Research Foun-dation-through the Clin-ical Research Group KFO217“Hepatobiliary tran-sport an-d liver diseases”the Collaborative Research Cen-tre 974“Commun-ication-an-d Systemic Relevan-ce in-Liver Damage an-d Regen-eration-”
文摘To investigate the relation of two different mutations to the outcome of partial external biliary diversion (PEBD) in severe bile salt export pump (BSEP) deficiency. METHODSMutations in the gene encoding BSEP leading to severe BSEP deficiency in two unrelated patients were identified by genomic sequencing. Native liver biopsies and transiently transfected human embryonic kidney (HEK) 293 cells expressing either wild-type or mutated BSEP were subjected to immunofluorescence analysis to assess BSEP transporter localization. Bile acid profiles of patient and control bile samples were generated by ultra-performance liquid chromatography-tandem mass spectrometry. Wild-type and mutant BSEP transport of [<sup>3</sup>H]-labeled taurocholate (TC) and taurochenodeoxycholate (TCDC) was assessed by vesicular transport assays. RESULTSA girl (at 2 mo) presented with pruritus, jaundice and elevated serum bile salts (BS). PEBD stabilized liver function and prevented liver transplantation. She was heterozygous for the BSEP deletion p.T919del and the nonsense mutation p.R1235X. At the age of 17 years relative amounts of conjugated BS in her bile were normal, while total BS were less than 3% as compared to controls. An unrelated boy (age 1.5 years) presenting with severe pruritus and elevated serum BS was heterozygous for the same nonsense and another missense mutation, p.G1032R. PEBD failed to alleviate pruritus, eventually necessitating liver transplantation. BS concentration in bile was about 5% of controls. BS were mainly unconjugated with an unusual low amount of chenodeoxycholate derivatives (< 5%). The patients’ native liver biopsies showed canalicular BSEP expression. Both BSEP p.T919del and p.G1032R were localized in the plasma membrane in HEK293 cells. In vitro transport assays showed drastic reduction of transport by both mutations. Using purified recombinant BSEP as quantifiable reference, per-molecule transport rates for TC and TCDC were determined to be 3 and 2 BS molecules per wild-type BSEP transporter per minute, respectively. CONCLUSIONIn summary, our findings suggest that residual function of BSEP as well as substrate specificity influence the therapeutic effectiveness of PEBD in progressive familial intrahepatic cholestasis type 2 (PFIC-2).
基金supported by the National Basic Research Program of China(2010CB912800,2011CB504203)National Natural Science Foundation of China(81230060,81261140373)+2 种基金National Science and Technology Major Special Project on New Drug Innovation of China(2011ZX09102010-02)Science Foundation of Guangdong Province(S2012030006287)Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes,Sun Yat-sen University(KLB09001)
文摘Tumor metastasis is one of the most serious challenges for human cancers as the majority of deaths caused by cancer are associated with metastasis,rather than the primary tumor.Recent studies have demonstrated that tumor cell plasticity plays a critical role in tumor metastasis by giving rise to various cell types which is necessary for tumor to invade adjacent tissues and form distant metastasis.These include differentiation of cancer stem cells(CSCs),or epithelial-mesenchymal transition(EMT)and its reverse process,mesenchymal-epithelial transition(MET).A growing body of evidence has demonstrated that the biology of tumor cell plasticity is tightly linked to functions of non-coding RNAs(ncRNAs),especially microRNAs(miRNAs)and long non-coding RNAs(lncRNAs).Therefore,understanding the mechanisms how non-coding RNAs regulate tumor cell plasticity is essential for discovery of new diagnostic markers and therapeutic targets to overcome metastasis.
基金supported by the Basic Science Research Program through the National Research Foundation of Korea(Nos.NRF-2016R1D1A1A09917654,NRF-2015R1C1A1A01053495)
文摘The authors compute the(rational) Betti number of real toric varieties associated to Weyl chambers of type B, and furthermore show that their integral cohomology is p-torsion free for all odd primes p.
基金The work is supported by National Natural Science Foundation of China （70372011） and Higher Education PH.D Discipline-spot Special Fund（20030006009）
文摘Toward the problem of judgement of enterprise crisis degree, the paper adopts fuzzy classification and fuzzy recognition method, forms enterprise character objective function in fuzzy condition, and brings forward to solve approach of optimal fuzzy classification center matrix, optimal fuzzy recognition matrix and optimal index weight under different crisis degree. By using the method in enterprise crisis early-warning example, it can distinguish enterprise crisis degree effectively.
