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Oncogenic Ras mutations are widely considered to be locked in a permanent ‘On’ state and ‘constitutively active’. Yet, many healthy people have cells possessing mutant Ras without apparent harm, and in animal models mutant Ras causes transformation only after upregulation of Ras activity. Here, we demonstrate that oncogenic K-Ras is not constitutively active but can be readily activated by upstream stimulants to lead to prolonged strong Ras activity. These data indicate that in addition to targeting K-Ras downstream effectors, interventions to reduce K-Ras activation may have important cancer-preventive value, especially in patients with oncogenic Ras mutations. As other small G proteins are regulated in a similar manner, this concept is likely to apply broadly to the entire Ras family of molecules.

The maintenance of genome integrity is essential for the proper function and survival of all organisms. Human cells have evolved prompt and efficient DNA damage response to eliminate the detrimental effects of DNA lesions. The DNA damage response involves a complex network of processes that detect and repair DNA damage, in which long non-coding RNAs (lncRNAs), a new class of regulatory RNAs, may play important roles. Recent studies have identified a large number of lncRNAs in mammalian transcriptomes. However, little is known about the regulation and function of lncRNAs in the DNA damage response. In the present study, we demonstrate that one specific lncRNA, ANRIL, is transcriptionally up-regulated by the transcription factor E2F1 in an ATM-dependent manner following DNA damage, and elevated levels of ANRIL suppress the expression of INK4a, INK4b and ARF at the late-stage of DNA damage response, allowing the cell to return to normal at the completion of the DNA repair.

Accompanying the open door policy and economic reform, a dynamic population movement in China is occurring. International population movement of China is characterized mainly by the phenomenon of "brain drain" and illegal emigrants. Two-thirds of the overseas Chinese students stayed overseas, resulting in a severe shortage of middle aged professors and researchers in China. Illegal Chinese emigration into North America and Europe in recent years was considerable. Internal labour migration in China now is a big social and economic issue, numbering up to 60 million. Although instability accompanies mass internal migration, the possibility of turmoil or riots is very low. Further rural reform in China, there fore, is called for to solve the surplus labour problem.

To determine carboxyatractyloside and atractyloside in Xanthii Fructus by HPLC.By HPLC, Agilent ZORBAX SB-phenyl (4.6 mm x 250 mm, 5 microm) column was adopted, with acetonitrile-0.01 mol x L(-1) NaH2PO4 (pH 6) as the mobile phase for gradient elution at the flow rate of 1.0 mL x min(-1). The detection wavelength was 203 nm, and the temperature was set at 35 degrees C.Carboxyatractyloside showed a good linearity within the range of 0.0972-1.944 microg and atractyloside showed a good linearity within the range of 0.1030-2.060 microg. The recovery rate of carboxyatractyloside was 100. 3% and that of atractyloside was 102.5%. The RSD were 0.67% and 1.4% (n=6).This method is so simple, practical and highly repeatable that is can be used for quality control of Xanthii Fructus.

This work estimated the coseismic deformation field of the Yushu earthquake in 2010 using the C band ASAR data, and inverted the fault slip distributions and simulated the interferograms. The results demonstrated that the slip distributions were mainly presented in shallow depth above 15km.There were two slip-concentration areas, maximum slip was nearby the Jiegu town, and fault motion sense was left-lateral strike-slip, which were all reconciled with field observations.

TP53, a well-known tumour suppressor gene, is frequently inactivated by mutation or deletion in a majority of human tumours. A tremendous effort has been made to restore p53 activity in cancer therapies. However, no effective p53-based therapy has been successfully translated into clinical cancer treatment due to the complexity of p53 regulators and their poor drugability. Here, we demonstrate that genomic deletion of TP53 frequently encompasses neighbouring essential genes, rendering cancer cells with hemizygous TP53 deletion vulnerable to further suppression of such genes. POLR2A is identified as such an essential house-keeping gene that is virtually co-deleted with TP53 in many types of human cancer. It encodes the largest and catalytic subunit of RNA polymerase II complex, which is specifically inhibited by α-Amanitin. Our analysis of clinical samples and cancer cell lines in The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopaedia (CCLE) reveals that POLR2A expression levels are tightly correlated with its gene copy numbers in human colorectal tumours. Suppression of POLR2A with α-amanitin or short-hairpin RNAs, selectively inhibits proliferation, survival and tumorigenic potential of colorectal cancer cells with hemizygous TP53 loss in a p53-independent manner. Previous clinical applications of α-amanitin have been limited due to its liver toxicity. However, we found that α-amanitin-based antibody drug conjugates (ADCs) are highly effective therapeutic agents with dramatically reduced toxicity. Here, we show that low doses of α-amanitin-conjugated anti-EpCAM (Epithelial Cell Adhesion Molecule) antibody lead to complete tumour regression in murine models of human colorectal cancer with hemizygous deletion of POLR2A. We anticipate that inhibiting POLR2A will be a novel therapeutic approach for cancers harbouring such common genomic alterations. Citation Format: Yunhua Liu, Xiongbin Lu. TP53 loss creates therapeutic vulnerability in colorectal cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B156.

We focus on rural capital formation, with particular attention to the direction of rural household saving toward housing versus “productive” investments or savings deposits in financial institutions. A two-period model of rural household behavior is developed, from which three equations for investment in housing, business-agricultural capital, and savings deposits are derived. These equations are estimated using data for 28 provinces over the period 1986–1989. The econometric results confirm that housing investment is sensitive to both the nominal deposit rate of interest (negatively) and to the rate of inflation (positively). Household agricultural and business investment is also negatively related to the real deposit interest rate, while savings deposits are positively, although weakly, related. These results suggest that if the expected real deposit rate of interest had been a positive one percent instead of an average of a negative three percent during the period studied (1986–1989), total expenditure on housing would have declined substantially; indeed, the decline in housing outlays would have been equal to three-fourths the amount spent by rural collectives on fixed capital. This finding leads us to recommend improvements in financial intermediation, possibly including a stock market, in order to increase the rate of rural economic development.

The test of distinctiveness, uniformity, and stability (DUS) is a necessary step for variety identification and new variety application. The objective of this study is to provide molecular marker-assisted approach combined with morphological trait-based testing for more convenient and fast DUS test and identification of varieties. Eighteen pairs of SRAP markers and 40 morphological traits for DUS test were applied for genetic diversity analysis of 50 lettuce (Lactuca sativa) varieties. Average polymorphism information content (PIC) of the SRAP markers was 0.80, ranging from 0.39 to 0.97. Cluster analysis using UPGMA of the band patterns amplified by SRAP marker and morphological trait-based clustering separated the varieties into three groups. The correlation coefficient of SRAP marker and morphological traits was 0.5455 reflecting that the two clustering results shared some similarity and consistence. It revealed that the combination of both SRAP marker and morphological trait analysis is more conducive to proper identification and classification of plant varieties, which will undoubtedly bring an alternative choice to DUS testing of plant new varieties and conservation of plant germplasm.

Kaposi's sarcoma-associated herpesvirus (KSHV) encodes 12 pre-microRNAs (pre-miRNAs). Current studies have shown that these miRNAs are involved in regulation of viral and host gene expression, implicating a role in the maintenance of viral latency and suppression of antiviral innate immunity. However, the functions of these miRNAs remain largely unknown. On the basis of the sequence homology between oncogenic miR-155 and KSHV-encoded miR-K12-11, we hypothesized that miR-K12-11 could attenuate transforming growth factor β (TGF-β) signaling, facilitating viral infection and tumorigenesis. In the present study, we demonstrated that ectopic expression of miR-K12-11 in Ramos, a TGF-β-sensitive cell line, downregulated TGF-β signaling and facilitated cell proliferation upon TGF-β treatment by directly targeting SMAD5, an important mediator in TGF-β signaling. In addition, the downregulation of SMAD5 by miR-K12-11 was further confirmed in a de novo KSHV infection system or latently infected KSHV-positive B-lymphoma cell lines. More importantly, repression of miR-K12-11 by a specific sponge inhibitor restored the expression of SMAD5 in both de novo -infected and latently infected cells. Finally, we found that restoration of SMAD5, in addition to the TGF-β type II receptor, which was epigenetically silenced by the latent viral protein latency-associated nuclear antigen, sensitized BC3 cells to the cytostatic effect of TGF-β signaling. Taken together, our findings highlight a novel mechanism in which miR-K12-11 downregulates TGF-β signaling and suggest that viral miRNAs and proteins may exert a dichotomy regulation in virus-induced oncogenesis by targeting the same signaling pathway.

In this work we employ the pixel offset tracking technique to capture large displacements in incoherent zone nearby the Yingxiu-Beichuan fault caused by 2008 Wenchuan Ms8.0 earthquake. The used data of 6 tracks is from ALOS/PASAR dataset of Japan. The result shows that the entire surface rupture belt is 238km long, extending almost linearly in a direction NE42°. It is offset left laterally by a NW-striking fault at Xiaoyudong and turns at Gaochuan, where the rupture belt shifts toward south by 5km largely keeping the original trend. In terms of features of rupture traces, the rupture belt can be divided into 5 sections and 3 types. North to rupture belt, surface displacements are 2.95m on average, mostly in 2.0∼3.5m with the maximum 7.0∼9.0m at individual places nearby Beichuan. South to the rupture belt, the average displacement is 1.75m, dominated by 1.0∼2.0m, with 3.0∼4.0m at a few sites. Along the Guanxian-Jiangyou fault, there is a uplift zone in the radar line of sight, which is 66km long, 1.5∼6.0km wide, with vertical displacements about 2m but no observable rupture traces.

Hepatitis E as a self-limiting disease and is generally not chronic, although in a small number of cases it appears to be so. Complete data were collected from 1104 cases of hepatitis E out of which 28 did not heal after liver treatment. These 28 cases were followed-up for 6-10 years. It was found that hepatitis can be chronic. Chronic hepatitis cases are more common in males, but a high degree of inflammatory activity and fibrosis were not evident. After 6-10 years of follow-up observation, cirrhosis or liver cancer did not appear. This is significantly different from the hepatitis B and hepatitis C viruses. Further, most cases of chronic hepatitis E occurred in older patients, in which the ability to remove the virus may decline, contributing to the more than six months duration, along with other important reasons. In addition, we also observed that several cases were unhealed or chronic because of a combination with other viruses. Chronic disease or the long-term use of immune agents may be one of the causes for chronic hepatitis E.

To establish the HPLC fingerprint and determine six kinds of ester-type alkaloids of Radix Aconiti lateralis praeparata slice.HPLC analysis was performed on a Phenomenex Gemini C18 (4.6 mm x 250 mm, 5 microm) with 0.04 mol x L(-1) ammonium acetate (adjusted to pH 10.0 with ammonia water)and acetonitrile as mobile phase. Similarity evaluation system for chromatographic fingerprint of traditional Chinese medicine (2004 AB)was used in data analysis.Baifupian, Heifupian from different samples were of high similarity in fingerprint, and the separation of six kinds of ester-type alkaloids was good. Huangfupian and crude aconite root showed significant difference in fingerprint, comparing with Baifupian and Heifupian.This method is simple and reliable. The HPLC fingerprint and contents of six kinds of ester-type alkaloids of Radix Aconiti lateralis praeparata slice can be used for their quality control.

The Haiyuan fault is a major active left-lateral fault in the northeast edge of Tibet-Qinghai Plateau. Studying this fault is important to understanding current deformation of the plateau and the mechanism of continental deformation. IPTA (Interferometric Point Target Analysis) can be summarized as an iterative improvement of the model parameters to achieve an optimal match to observe interferometric phases. The analysis is done for a selected set of points which correspond to point target candidates, and is a collection of tools to exploit the temporal and spatial characteristics of interferometric signatures collected from point targets to accurately map surface deformation histories, terrain heights, and relative atmospheric path delays. Surface deformation in the Haiyuan fault is about 4-6mm/y.

Due to the adverse weather condition such as raining after the Wenchuan earthquake, the applicability of optical imagery in decision making for mitigating earthquake disasters had been highly restricted. As a synthetic aperture radar (SAR) sensor possesses all-weather imaging capability, SAR imagery emerges as a very important data source for earthquake rescue operation at the earlier stage. This paper utilizes 4 pairs of ENVISAT ASAR images (3 pre-earthquake, 1 postearthquake) to perform ratio coherence change detection by comparing pre-seismic between post-seismic images over Dujiangyan City and its neighboring areas. The testing results indicate that the interferometric coherence map is sensitive to physical surface changes and show that there were significant changes within the urban area and the main shock had caused substantial damage. This study demonstrates that it is feasible to use SAR images to conduct damage assessment. With the polarization radar technology becoming more sophisticated, radar satellites in decision making for disaster rescue will play more and more important role.

TP53, a well-known tumor suppressor gene, is frequently inactivated by mutation or deletion in a majority of human tumors. Theoretically, targeting the p53 pathway would lead to successful anti-cancer treatments. However, no effective p53-based anti-cancer therapy has been developed due to the complexity of the p53 regulators and their poor drugability. Here we demonstrate that focal deletion of TP53 often encompasses neighboring essential genes, rendering cancer cells with hemizygous p53 deletion highly vulnerable to further suppression of such genes. One such gene, POLR2A, encodes the largest subunit of RNA polymerase II complex. We found that its expression correlates with copy number changes and suppression of POLR2A with its inhibitors, alpha-amanitin or short-hairpin RNA, selectively inhibits growth, survival and tumorigenic potential in colon cancer cells with hemizygous TP53 loss, suggesting an novel and effective strategy for cancers with such genomic alternations. Note: This abstract was not presented at the meeting. Citation Format: Yunhua Liu, Xiongbin Lu. TP53 loss creates therapeutic vulnerability in cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2633. doi:10.1158/1538-7445.AM2014-2633

We use a panel data set of seven East Asian countries for the time period 2000–2010 to evaluate the importance of four determinants for manufacturing competitiveness by estimation the proxy export equation. The four main determinants examined are demander's national income, real effective exchange rate (REER), unit labor cost and provision of infrastructure. The results show the importance is changing with country's characteristics. Raising labor productivity and improving infrastructure are two universal requirements for long-term competitiveness in manufacturing.

Paul Ricœur is a scholar-type philosopher with a lot of thoughts. Domestic research on his thoughts is still in its infancy, and many researches have not yet followed an unified train of thought. This research tries to take the philosophical anthropological category of the basic human ability in Ricœur’s thought as a brand new context to investigate the important role of imagination in human innovation. We discuss a kind of “I can” poetics around the four basic abilities according to Ricœur, namely, the ability to speak, the ability to narrate, the ability to act, and the ability to be responsible. This kind of poetics directly focuses on the poetic dimensions of language, narrative, action and ethics as well as the role of imagination in them., En ce moment, l’étude de la pensée de Paul Ricœur en Chine n’en est qu’à ses balbutiements. Il manque souvent d’un fil pour illustrer la recherche. Notre travail essaie de tenir à une catégorie essentielle de la philosophie anthropologique chez Ricœur, à savoir la capacité humaine, de manière à comprendre le rôle de l’imagination dans la créativité humaine. Autour des quatre capacités fondamentales d’après Ricœur, c’est-à-dire capacité de parler, de raconter, d’agir et de se tenir responsable de ses actions, nous envisageons de démontrer une poétique du « Je peux », qui prête attention directement à la dimension poétique ainsi que le rôle de l’imagination dans les champs du langage, du récit, de l’action, et de l’éthique.

In Paul Claudel’s drama, the Catholic spirit and the Buddhist exoticism intersect in a very distinctive way. The Soteriology remains the central proposition, but it is never limited to traditional redemptive dogma, but enriches it with that of Buddhist deliverance which combines with the philosophy and aesthetics of India, China and Japan. This syncretism created a very singular literary atmosphere in his drama. Claudel’s acceptance and transformation of Buddhist ideas on deliverance is a long personal and cultural history. We combined the external philological studies with the intensive analysis of the texts in order to show how the dialogue between Catholic theology and Buddhism exerts influence on French literature from the nineteenth to the twentieth century. This study takes into account the characteristics of the Oriental experience of Claudel, as well as the development of his literary thought and his Buddhist source. We have extracted three stereotyped Buddhist systems: primitive Buddhism in the Indian region, which preaches suffering, emptiness and nihilism; the “degraded" Chinese Buddhism awaiting the salvation of Christ; Japanese Buddhism, with the beauty of pleasant melancholy, serves as a spiritual healing of the West in crisis. We choose three representative works: Tête d'Or, Le Repos du Septième Jour, Le Soulier de Satin. By combining external historical study with text analysis, we have re-established a three-step process, in keeping with the diachronic development of Claudel’s Buddhi-Catholic ideology., Dans le drame de Paul Claudel, l’esprit catholique et l’exotisme bouddhiste se croisent d’une façon bien distinctive. La sotériologie y reste la proposition centrale, mais il ne se limite jamais au dogme traditionnel rédempteur, mais l’enrichit avec celui de la délivrance bouddhiste qui combine avec la philosophie et l'esthétique indienne, chinoise et japonaise. Ce synchrétisme a créé une ambiance littéraire très singulier dans son drame.L’acceptation et la transformation claudéliennes des idées bouddhistes sur la délivrance est une longue histoire personnelle et culturelle. Nous avons combiné les études philologiques externes avec l'analyse intensive des textes, en vue de montrer comment le dialogue entre la théologie catholique et le bouddhisme exerce des influences sur la littérature française du XIXe au XXe siècle. Cette étude tient compte des caractéristiques de l'expérience orientale de Claudel, ainsi que le développement de sa pensée littéraire et sa source bouddhiste. Nous en avons extrait trois système bouddhistes stéréotypés: le Bouddhisme primitif en région indienne, qui prêche la souffrance, le vide et le nihilisme; le Bouddhisme chinois “dégénéré” qui attend le salut du Christ; Le bouddhisme japonais, avec la beauté de la mélancolie agréable, sert d’une guérison spirituelle de l'Occident en crise. Nous choisissons trois ouvrages représentatifs: Tête d'Or, Le Repos du Septième Jour, Le Soulier de Satin. En combinant l'étude historique externe avec l'analyse de texte, nous avons rétabli un processus en trois étapes, qui conforme bien au développement diachronique de l’idéologie buddho-catholique claudélienne.