PIK3CA activating mutation in colorectal carcinoma: associations with molecular features and survival.

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Christophe Rosty

Full Text Available Mutations in PIK3CA are present in 10 to 15% of colorectal carcinomas. We aimed to examine how PIK3CA mutations relate to other molecular alterations in colorectal carcinoma, to pathologic phenotype and survival. PIK3CA mutation testing was carried out using direct sequencing on 757 incident tumors from the Melbourne Collaborative Cohort Study. The status of O-6-methylguanine-DNA methyltransferase (MGMT was assessed using both immunohistochemistry and methyLight techniques. Microsatellite instability, CpG island phenotype (CIMP, KRAS and BRAF V600E mutation status, and pathology review features were derived from previous reports. PIK3CA mutation was observed in 105 of 757 (14% of carcinomas, characterized by location in the proximal colon (54% vs. 34%; P<0.001 and an increased frequency of KRAS mutation (48% vs. 25%; P<0.001. High-levels of CIMP were more frequently found in PIK3CA-mutated tumors compared with PIK3CA wild-type tumors (22% vs. 11%; P = 0.004. There was no difference in the prevalence of BRAF V600E mutation between these two tumor groups. PIK3CA-mutated tumors were associated with loss of MGMT expression (35% vs. 20%; P = 0.001 and the presence of tumor mucinous differentiation (54% vs. 32%; P<0.001. In patients with wild-type BRAF tumors, PIK3CA mutation was associated with poor survival (HR 1.51 95% CI 1.04-2.19, P = 0.03. In summary, PIK3CA-mutated colorectal carcinomas are more likely to develop in the proximal colon, to demonstrate high levels of CIMP, KRAS mutation and loss of MGMT expression. PIK3CA mutation also contributes to significantly decreased survival for patients with wild-type BRAF tumors.

Mutations in PIK3CA are infrequent in neuroblastoma

International Nuclear Information System (INIS)

Dam, Vincent; Morgan, Brian T; Mazanek, Pavel; Hogarty, Michael D

2006-01-01

Neuroblastoma is a frequently lethal pediatric cancer in which MYCN genomic amplification is highly correlated with aggressive disease. Deregulated MYC genes require co-operative lesions to foster tumourigenesis and both direct and indirect evidence support activated Ras signaling for this purpose in many cancers. Yet Ras genes and Braf, while often activated in cancer cells, are infrequent targets for activation in neuroblastoma. Recently, the Ras effector PIK3CA was shown to be activated in diverse human cancers. We therefore assessed PIK3CA for mutation in human neuroblastomas, as well as in neuroblastomas arising in transgenic mice with MYCN overexpressed in neural-crest tissues. In this murine model we additionally surveyed for Ras family and Braf mutations as these have not been previously reported. Sixty-nine human neuroblastomas (42 primary tumors and 27 cell lines) were sequenced for PIK3CA activating mutations within the C2, helical and kinase domain 'hot spots' where 80% of mutations cluster. Constitutional DNA was sequenced in cases with confirmed alterations to assess for germline or somatic acquisition. Additionally, Ras family members (Hras1, Kras2 and Nras) and the downstream effectors Pik3ca and Braf, were sequenced from twenty-five neuroblastomas arising in neuroblastoma-prone transgenic mice. We identified mutations in the PIK3CA gene in 2 of 69 human neuroblastomas (2.9%). Neither mutation (R524M and E982D) has been studied to date for effects on lipid kinase activity. Though both occurred in tumors with MYCN amplification the overall rate of PIK3CA mutations in MYCN amplified and single-copy tumors did not differ appreciably (2 of 31 versus 0 of 38, respectively). Further, no activating mutations were identified in a survey of Ras signal transduction genes (including Hras1, Kras2, Nras, Pik3ca, or Braf genes) in twenty-five neuroblastic tumors arising in the MYCN-initiated transgenic mouse model. These data suggest that activating

Gaasitoru loojad: olime Veneetsia biennaali ajaloo kõige ülbemad / Ingrid Ruudi, Maarja Kask, Ralf Lõoke

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Ruudi, Ingrid

2009-01-01

Maarja Kask, Neeme Külm, Ralf Lõoke ja Ingrid Ruudi pälvisid 11. Veneetsia arhitektuuribiennaalil eksponeeritud keskkonna- ja geopoliitilise ruumiinstallatsiooni "Gaasitoru" eest Eesti Kultuurkapitali peapreemia ja sihtkapitali preemia

NO99 Põhuteater = NO99 Straw Theatre / Ralf Lõoke, Maarja Kask ; intervjueerinud Margit Mutso

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Lõoke, Ralf, 1978-

2012-01-01

Põhuteatri arhitektid Maarja Kask, Karli Luik, Ralf Lõoke, Pelle-Sten Viiburg (Salto Arhitektid) ja Ene-Liis Semper pälvisid EK arhitektuuri sihtkapitali 2011. a. arhitektuuripreemia vormitähendustes edasi liikunud ning arhitektuurile kui sündmusele ja kohaloomele keskendunud aktsiooni eest. Konstruktor Tõnu Peipmann

p55PIK regulates alpha-fetoprotein expression through the NF-κB signaling pathway.

Science.gov (United States)

Ye, Guoguo; Sun, Ge; Cheng, Zhikui; Zhang, Lei; Hu, Kanghong; Xia, Xianmin; Zhou, Yin

2017-12-15

Alpha-fetoprotein (AFP) is regarded as a diagnostic and prognostic biomarker and a potential therapeutic target for hepatocellular carcinoma (HCC). However, the regulation of AFP expression in HCC remains poorly understood. This study aimed to investigate the mechanism by which AFP expression is regulated by p55PIK, an isoform of PI3K. Human HCC cell lines (HepG2 and Huh-7) were treated with p55PIK specific competitive inhibitor or shRNA, or p55PIK overexpression vector, in the absence or presence of NF-κB inhibitor PDTC. AFP expression was detected by quantitative real-time PCR and Western blotting. NF-κB responsive elements in AFP enhancer region were characterized by luciferase reporter assay. p55PIK significantly stimulated the expression of AFP by activating NF-κB signaling pathway in HCC cells. Furthermore, two NF-κB binding sites in AFP enhancer region were identified to be primarily responsible for p55PIK mediated upregulation of AFP expression. p55PIK/NF-κB signaling plays an important role in the upregulation of AFP expression in HCC. Copyright © 2017 Elsevier Inc. All rights reserved.

FGFR3, PIK3CA and RAS mutations in benign lichenoid keratosis.

Science.gov (United States)

Groesser, L; Herschberger, E; Landthaler, M; Hafner, C

2012-04-01

Benign lichenoid keratoses (BLKs) are solitary skin lesions which have been proposed to represent a regressive form of pre-existent epidermal tumours such as solar lentigo or seborrhoeic keratosis. However, the genetic basis of BLK is unknown. FGFR3, PIK3CA and RAS mutations have been shown to be involved in the pathogenesis of seborrhoeic keratosis and solar lentigo. We thus investigated whether these mutations are also present in BLK. After manual microdissection and DNA isolation, 52 BLKs were screened for FGFR3, PIK3CA and RAS hotspot mutations using SNaPshot(®) multiplex assays. We identified 6/52 (12%) FGFR3 mutations, 10/52 (19%) PIK3CA mutations, 6/52 (12%) HRAS mutations and 2/52 (4%) KRAS mutations. FGFR3 and RAS mutations were mutually exclusive. One BLK showed a simultaneous PIK3CA and HRAS mutation. In nine BLKs with a mutation, nonlesional control tissue from the epidermal margin and the dermal lymphocytic infiltrate were wild-type, indicating that these mutations are somatic. To demonstrate that these findings are specific, 10 samples of lichen planus were analysed without evidence for FGFR3, PIK3CA or RAS mutations. Our results indicate that FGFR3, PIK3CA and RAS mutations are present in approximately 50% of BLKs. These findings support the concept on the molecular genetic level that at least a proportion of BLKs represents regressive variants resulting from former benign epidermal tumours such as seborrhoeic keratosis and solar lentigo. © 2011 The Authors. BJD © 2011 British Association of Dermatologists 2011.

PIK reactor construction status

International Nuclear Information System (INIS)

Konoplev, K.A.; Smolsky, S.L.

2001-01-01

The 100MW reactor PIK for fundamental researches has a thermal neutron flux of more than 10 15 n/cm 2 sec. This presentation outlines the construction state as of 2001, its prospects and completion tactics in the conditions of unstable finance. Construction of the reactor started in 1976. In 1986 construction of the building was completed and significant part of the installation work fulfilled. Construction of cooling systems was finished, the control panel assembled, and adjustment of the pump and gate valve control circuits started. After Chernobyl catastrophe, the USSR nuclear reactor safety requirements were revised. The PIK design did not meet these requirements and underwent considerable revision. The reconstruction design resulted in double the initial cost. Creation of the containment was the bulkiest part of the reconstruction. It brought about the need to disassemble the roofing of the building, dismantle all the equipment of the two upper floors, and lay up the equipment of the lower floors. As of 2001, construction in accordance with the revised design is at the stage of assemblage of the most important units, i.e. reactor itself, cooling system, heavy water system, and a number of auxiliary systems, such as depleted fuel storage, emergency cooling system etc. (orig.)

PIK3CA mutations frequently coexist with RAS and BRAF mutations in patients with advanced cancers.

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Filip Janku

Full Text Available Oncogenic mutations of PIK3CA, RAS (KRAS, NRAS, and BRAF have been identified in various malignancies, and activate the PI3K/AKT/mTOR and RAS/RAF/MEK pathways, respectively. Both pathways are critical drivers of tumorigenesis.Tumor tissues from 504 patients with diverse cancers referred to the Clinical Center for Targeted Therapy at MD Anderson Cancer Center starting in October 2008 were analyzed for PIK3CA, RAS (KRAS, NRAS, and BRAF mutations using polymerase chain reaction-based DNA sequencing.PIK3CA mutations were found in 54 (11% of 504 patients tested; KRAS in 69 (19% of 367; NRAS in 19 (8% of 225; and BRAF in 31 (9% of 361 patients. PIK3CA mutations were most frequent in squamous cervical (5/14, 36%, uterine (7/28, 25%, breast (6/29, 21%, and colorectal cancers (18/105, 17%; KRAS in pancreatic (5/9, 56%, colorectal (49/97, 51%, and uterine cancers (3/20, 15%; NRAS in melanoma (12/40, 30%, and uterine cancer (2/11, 18%; BRAF in melanoma (23/52, 44%, and colorectal cancer (5/88, 6%. Regardless of histology, KRAS mutations were found in 38% of patients with PIK3CA mutations compared to 16% of patients with wild-type (wtPIK3CA (p = 0.001. In total, RAS (KRAS, NRAS or BRAF mutations were found in 47% of patients with PIK3CA mutations vs. 24% of patients wtPIK3CA (p = 0.001. PIK3CA mutations were found in 28% of patients with KRAS mutations compared to 10% with wtKRAS (p = 0.001 and in 20% of patients with RAS (KRAS, NRAS or BRAF mutations compared to 8% with wtRAS (KRAS, NRAS or wtBRAF (p = 0.001.PIK3CA, RAS (KRAS, NRAS, and BRAF mutations are frequent in diverse tumors. In a wide variety of tumors, PIK3CA mutations coexist with RAS (KRAS, NRAS and BRAF mutations.

MiR-124 suppresses cell proliferation in hepatocellular carcinoma by targeting PIK3CA

International Nuclear Information System (INIS)

Lang, Qingbo; Ling, Changquan

2012-01-01

Highlights: ► PIK3CA is a novel target of miR-124 in HepG2 cells. ► MiR-124 suppresses cell proliferation by downregulating PIK3CA expression. ► MiR-124 regulates the PI3K/Akt pathway in HepG2 cells. ► MiR-124 overexpression inhibits the tumorigenesis in nude mice. -- Abstract: MicroRNAs (miRNAs) have crucial roles in the development and progression of human cancers, including hepatocellular carcinoma (HCC). Recent studies have shown that microRNA-124 (miR-124) was downregulated in HCC; however, the underlying mechanisms by which miR-124 suppresses tumorigenesis in HCC are largely unknown. In this study, we report that phosphoinositide 3-kinase catalytic subunit alpha (PIK3CA) is a novel target of miR-124 in HepG2 cells. Overexpression of miR-124 resulted in decreased expression of PIK3CA at both mRNA and protein levels. We found that miR-124 overexpression markedly suppressed cell proliferation by inducing G1-phase cell-cycle arrest in vitro. Consistent with the restoring miR-124 expression, PIK3CA knockdown suppressed cell proliferation, whereas overexpression of PIK3CA abolished the suppressive effect of miR-124. Mechanistic studies showed that miR-124-mediated reduction of PIK3CA resulted in suppression of PI3K/Akt pathway. The expressions of Akt and mTOR, key components of the PI3K/Akt pathway, were all downregulated. Moreover, we found overexpressed miR-124 effectively repressed tumor growth in xenograft animal experiments. Taken together, our results demonstrate that miR-124 functions as a growth-suppressive miRNA and plays an important role in inhibiting the tumorigenesis through targeting PIK3CA.

MiR-124 suppresses cell proliferation in hepatocellular carcinoma by targeting PIK3CA

Energy Technology Data Exchange (ETDEWEB)

Lang, Qingbo [Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Ling, Changquan, E-mail: lingchangquan@hotmail.com [Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China)

2012-09-21

Highlights: Black-Right-Pointing-Pointer PIK3CA is a novel target of miR-124 in HepG2 cells. Black-Right-Pointing-Pointer MiR-124 suppresses cell proliferation by downregulating PIK3CA expression. Black-Right-Pointing-Pointer MiR-124 regulates the PI3K/Akt pathway in HepG2 cells. Black-Right-Pointing-Pointer MiR-124 overexpression inhibits the tumorigenesis in nude mice. -- Abstract: MicroRNAs (miRNAs) have crucial roles in the development and progression of human cancers, including hepatocellular carcinoma (HCC). Recent studies have shown that microRNA-124 (miR-124) was downregulated in HCC; however, the underlying mechanisms by which miR-124 suppresses tumorigenesis in HCC are largely unknown. In this study, we report that phosphoinositide 3-kinase catalytic subunit alpha (PIK3CA) is a novel target of miR-124 in HepG2 cells. Overexpression of miR-124 resulted in decreased expression of PIK3CA at both mRNA and protein levels. We found that miR-124 overexpression markedly suppressed cell proliferation by inducing G1-phase cell-cycle arrest in vitro. Consistent with the restoring miR-124 expression, PIK3CA knockdown suppressed cell proliferation, whereas overexpression of PIK3CA abolished the suppressive effect of miR-124. Mechanistic studies showed that miR-124-mediated reduction of PIK3CA resulted in suppression of PI3K/Akt pathway. The expressions of Akt and mTOR, key components of the PI3K/Akt pathway, were all downregulated. Moreover, we found overexpressed miR-124 effectively repressed tumor growth in xenograft animal experiments. Taken together, our results demonstrate that miR-124 functions as a growth-suppressive miRNA and plays an important role in inhibiting the tumorigenesis through targeting PIK3CA.

Mutation and genomic amplification of the PIK3CA proto-oncogene in pituitary adenomas

International Nuclear Information System (INIS)

Murat, C.B.; Braga, P.B.S.; Fortes, M.A.H.Z.; Bronstein, M.D.; Corrêa-Giannella, M.L.C.; Giorgi, R.R.

2012-01-01

The tumorigenesis of pituitary adenomas is poorly understood. Mutations of the PIK3CA proto-oncogene, which encodes the p110-α catalytic subunit of PI3K, have been reported in various types of human cancers regarding the role of the gene in cell proliferation and survival through activation of the PI3K/Akt signaling pathway. Only one Chinese study described somatic mutations and amplification of the PIK3CA gene in a large series of pituitary adenomas. The aim of the present study was to determine genetic alterations of PIK3CA in a second series that consisted of 33 pituitary adenomas of different subtypes diagnosed by immunohistochemistry: 6 adrenocorticotropic hormone-secreting microadenomas, 5 growth hormone-secreting macroadenomas, 7 prolactin-secreting macroadenomas, and 15 nonfunctioning macroadenomas. Direct sequencing of exons 9 and 20 assessed by qPCR was employed to investigate the presence of mutations and genomic amplification defined as a copy number ≥4. Previously identified PIK3CA mutations (exon 20) were detected in four cases (12.1%). Interestingly, the Chinese study reported mutations only in invasive tumors, while we found a PIK3CA mutation in one noninvasive corticotroph microadenoma. PIK3CA amplification was observed in 21.2% (7/33) of the cases. This study demonstrates the presence of somatic mutations and amplifications of the PIK3CA gene in a second series of pituitary adenomas, corroborating the previously described involvement of the PI3K/Akt signaling pathway in the tumorigenic process of this gland

Mutation and genomic amplification of the PIK3CA proto-oncogene in pituitary adenomas

Energy Technology Data Exchange (ETDEWEB)

Murat, C.B.; Braga, P.B.S.; Fortes, M.A.H.Z. [Laboratório de Endocrinologia Celular e Molecular (LIM-25), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Bronstein, M.D. [Unidade de Neuroendocrinologia, Serviço de Endocrinologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Corrêa-Giannella, M.L.C.; Giorgi, R.R. [Laboratório de Endocrinologia Celular e Molecular (LIM-25), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

2012-07-13

The tumorigenesis of pituitary adenomas is poorly understood. Mutations of the PIK3CA proto-oncogene, which encodes the p110-α catalytic subunit of PI3K, have been reported in various types of human cancers regarding the role of the gene in cell proliferation and survival through activation of the PI3K/Akt signaling pathway. Only one Chinese study described somatic mutations and amplification of the PIK3CA gene in a large series of pituitary adenomas. The aim of the present study was to determine genetic alterations of PIK3CA in a second series that consisted of 33 pituitary adenomas of different subtypes diagnosed by immunohistochemistry: 6 adrenocorticotropic hormone-secreting microadenomas, 5 growth hormone-secreting macroadenomas, 7 prolactin-secreting macroadenomas, and 15 nonfunctioning macroadenomas. Direct sequencing of exons 9 and 20 assessed by qPCR was employed to investigate the presence of mutations and genomic amplification defined as a copy number ≥4. Previously identified PIK3CA mutations (exon 20) were detected in four cases (12.1%). Interestingly, the Chinese study reported mutations only in invasive tumors, while we found a PIK3CA mutation in one noninvasive corticotroph microadenoma. PIK3CA amplification was observed in 21.2% (7/33) of the cases. This study demonstrates the presence of somatic mutations and amplifications of the PIK3CA gene in a second series of pituitary adenomas, corroborating the previously described involvement of the PI3K/Akt signaling pathway in the tumorigenic process of this gland.

Burnable absorber for the PIK reactor

International Nuclear Information System (INIS)

Gostev, V.V.; Smolskii, S.L.; Tchmshkyan, D.V.; Zakharov, A.S.; Zvezdkin, V.S.; Konoplev, K.A.

1998-01-01

In the reactor PIK design a burnable absorber is not used and the cycle duration is limited by the rods weight. Designed cycle time is two weeks and seams to be not enough for the 100 MW power research reactor equipped by many neutron beams and experimental facilities. Relatively frequent reloading reduces the reactor time on full power and in this way increases the maintenance expenses. In the reactor core fuel elements well mastered by practice are used and its modification was not approved. We try to find the possibilities of installation in the core separate burnable elements to avoid poison of the fuel. It is possible to replace a part of the fuel elements by absorbers, since the fuel elements are relatively small (diameter 5.15mm, uranium 235 content 7.14g) and there are more then 3800 elements in the core. Nevertheless, replacing decreases the fuel burnup and its consumption. In the PIK fuel assembles a little part of the volume is occupied by the dumb elements to create a complete package of the assembles shroud, that is necessary in the hydraulic reasons. In the presented report the assessment of such a replacement is done. As a burnable material Gadolinium was selected. The measurements or the beginning of cycle were performed on the critical facility PIK. The burning calculation was confirmed by measurements on the 18MW reactor WWR-M. The results give the opportunity to twice the cycle duration. The proposed modification of the fuel assembles does not lead to alteration in the other reactor systems, but it touch the burned fuel reprocessing technology. (author)

Expression of activated PIK3CA in ovarian surface epithelium results in hyperplasia but not tumor formation.

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Shun Liang

Full Text Available The Phosphatidylinositol 3'-kinase is a key regulator in various cancer-associated signal transduction pathways. Genetic alterations of its catalytic subunit alpha, PIK3CA, have been identified in ovarian cancer. Our in vivo data suggests that PIK3CA activation is one of the early genetic events in ovarian cancer. However, its role in malignant transformation of ovarian surface epithelium (OSE is largely unclear.Using the Müllerian inhibiting substance type II receptor (MISIIR promoter, we generated transgenic mice that expressed activated PIK3CA in the Müllerian epithelium. Overexpression of PIK3CA in OSE induced remarkable hyperplasia, but was not able to malignantly transform OSE in vivo. The consistent result was also observed in primary cultured OSEs. Although enforced expression of PIK3CA could not induce OSE anchorage-independent growth, it significantly increased anchorage-independent growth of OSE transformed by mutant K-ras.While PIK3CA activation may not be able to initiate OSE transformation, we conclude that activation of PIK3CA may be an important molecular event contributing to the maintenance of OSE transformation initiated by oncogenes such as K-ras.

Analysis of PIK3CA Mutations and Activation Pathways in Triple Negative Breast Cancer.

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Paolo Cossu-Rocca

Full Text Available Triple Negative Breast Cancer (TNBC accounts for 12-24% of all breast carcinomas, and shows worse prognosis compared to other breast cancer subtypes. Molecular studies demonstrated that TNBCs are a heterogeneous group of tumors with different clinical and pathologic features, prognosis, genetic-molecular alterations and treatment responsivity. The PI3K/AKT is a major pathway involved in the regulation of cell survival and proliferation, and is the most frequently altered pathway in breast cancer, apparently with different biologic impact on specific cancer subtypes. The most common genetic abnormality is represented by PIK3CA gene activating mutations, with an overall frequency of 20-40%. The aims of our study were to investigate PIK3CA gene mutations on a large series of TNBC, to perform a wider analysis on genetic alterations involving PI3K/AKT and BRAF/RAS/MAPK pathways and to correlate the results with clinical-pathologic data.PIK3CA mutation analysis was performed by using cobas® PIK3CA Mutation Test. EGFR, AKT1, BRAF, and KRAS genes were analyzed by sequencing. Immunohistochemistry was carried out to identify PTEN loss and to investigate for PI3K/AKT pathways components.PIK3CA mutations were detected in 23.7% of TNBC, whereas no mutations were identified in EGFR, AKT1, BRAF, and KRAS genes. Moreover, we observed PTEN loss in 11.3% of tumors. Deregulation of PI3K/AKT pathways was revealed by consistent activation of pAKT and p-p44/42 MAPK in all PIK3CA mutated TNBC.Our data shows that PIK3CA mutations and PI3K/AKT pathway activation are common events in TNBC. A deeper investigation on specific TNBC genomic abnormalities might be helpful in order to select patients who would benefit from current targeted therapy strategies.

Analysis of PIK3CA Mutations and Activation Pathways in Triple Negative Breast Cancer.

Science.gov (United States)

Cossu-Rocca, Paolo; Orrù, Sandra; Muroni, Maria Rosaria; Sanges, Francesca; Sotgiu, Giovanni; Ena, Sara; Pira, Giovanna; Murgia, Luciano; Manca, Alessandra; Uras, Maria Gabriela; Sarobba, Maria Giuseppina; Urru, Silvana; De Miglio, Maria Rosaria

2015-01-01

Triple Negative Breast Cancer (TNBC) accounts for 12-24% of all breast carcinomas, and shows worse prognosis compared to other breast cancer subtypes. Molecular studies demonstrated that TNBCs are a heterogeneous group of tumors with different clinical and pathologic features, prognosis, genetic-molecular alterations and treatment responsivity. The PI3K/AKT is a major pathway involved in the regulation of cell survival and proliferation, and is the most frequently altered pathway in breast cancer, apparently with different biologic impact on specific cancer subtypes. The most common genetic abnormality is represented by PIK3CA gene activating mutations, with an overall frequency of 20-40%. The aims of our study were to investigate PIK3CA gene mutations on a large series of TNBC, to perform a wider analysis on genetic alterations involving PI3K/AKT and BRAF/RAS/MAPK pathways and to correlate the results with clinical-pathologic data. PIK3CA mutation analysis was performed by using cobas® PIK3CA Mutation Test. EGFR, AKT1, BRAF, and KRAS genes were analyzed by sequencing. Immunohistochemistry was carried out to identify PTEN loss and to investigate for PI3K/AKT pathways components. PIK3CA mutations were detected in 23.7% of TNBC, whereas no mutations were identified in EGFR, AKT1, BRAF, and KRAS genes. Moreover, we observed PTEN loss in 11.3% of tumors. Deregulation of PI3K/AKT pathways was revealed by consistent activation of pAKT and p-p44/42 MAPK in all PIK3CA mutated TNBC. Our data shows that PIK3CA mutations and PI3K/AKT pathway activation are common events in TNBC. A deeper investigation on specific TNBC genomic abnormalities might be helpful in order to select patients who would benefit from current targeted therapy strategies.

Üks uks Eesti ja Jaapani vahel : köitekunst kohtub animatsiooniga / Maarja Undusk

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Undusk, Maarja

2003-01-01

Eestis viibiv jaapanlanna Maya Yonesho (sünd. 1965) hakkab tegema stipendiaadifilmi "Üks uks". Raamat-uksed teevad valmis eesti nahakunstnikud Külli Grünbach, Rene Haljasmäe, Pille Kivihall, Helen Maran-Poll, Lennart Mänd, Tiina Piisang, Jane Rannamets ja Maarja Undusk. Filmi muusika autor Sven Grünberg. M. Yonesho juhendas nahakunstnik Kadri Halliku diplomitööd

Õppetoetuste semantikast / Eleene Sammler ; kommenteerinud Siim Kanne, Kerstin Kruusmaa, Maarja Mälberg, Mihkel Tedremaa

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Sammler, Eleene

2009-01-01

Õppetoetuste jagamisest suuremates Eesti ülikoolides. Kommenteerivad Tartu Ülikooli füüsika 1. kursuse üliõpilane Siim Kanne, EMÜ maastikuarhitektuuri 1. kursuse üliõpilane Kerstin Kruusmaa, Tallinna Ülikooli riigiteaduste eriala 2. kursuse üliõpilane Maarja Mälberg ja TTÜ mehhatroonika 1. kursuse üliõpilane Mihkel Tedremaa

The state of the PIK reactor construction

International Nuclear Information System (INIS)

Konoplev, K.A.

1995-01-01

Principle concepts of the PIK reactor project were stated late in the 60's but its construction was started in 1976. By the year 1986 the initial project was realised by approximately 70% but then, after Chernobyl accident the construction was essentially frozen to adjust the project to the revised nuclear safety regulations. The revised project was approved only in 1990 when the country was on the threshold of serious economic problems. The PIK reactor is a source of neutrons placed in the heavy water reflector. The fuel is uranium-235 (90% enrichment) of total weight 27 kg. Light water is used as moderator and coolant. Design parameters: thermal power is 100 W; thermal neutron flux in the reflector is 1.2x10 15 n/cm 2 s; in the central vertical beam tube is 5x10 15 n/cm 2 s; number of horizontal beam tubes is 10; diameter of beam tubes is 10 cm, with the possibility of replacement with beam tubes up to 25 cm in diameter. The reactor will be equipped with sources of hot, cold, and ultracold neutrons to obtain beams in different intervals of energy spectrum. The low temperature circuit will enable to irradiate samples at helium temperatures. The reactor has three series cooling circuits. Emergency core cooling systems in LOCA are double and in emergency power supply system is triple. The PIK reactor has no single common containment but four separate systems: for pipelines and units of the first circuit, for heavy water reflector, for operating hall, and for experimental beam tubes hall

MicroRNA-375 inhibits colorectal cancer growth by targeting PIK3CA

Energy Technology Data Exchange (ETDEWEB)

Wang, Yihui [Department of Colorectal Surgery, The Third Affiliated Hospital of Harbin Medical University, 150 Haping Road, 150081 Harbin (China); Tang, Qingchao [Cancer Center, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, 150086 Harbin (China); Li, Mingqi; Jiang, Shixiong [Department of Colorectal Surgery, The Third Affiliated Hospital of Harbin Medical University, 150 Haping Road, 150081 Harbin (China); Wang, Xishan, E-mail: wxshan12081@163.com [Cancer Center, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, 150086 Harbin (China)

2014-02-07

Highlights: • miR-375 is downregulated in colorectal cancer cell lines and tissues. • miR-375 inhibits colorectal cancer cell growth by targeting PIK3CA. • miR-375 inhibits colorectal cancer cell growth in xenograft nude mice model. - Abstract: Colorectal cancer (CRC) is the second most common cause of death from cancer. MicroRNAs (miRNAs) represent a class of small non-coding RNAs that control gene expression by triggering RNA degradation or interfering with translation. Aberrant miRNA expression is involved in human disease including cancer. Herein, we showed that miR-375 was frequently down-regulated in human colorectal cancer cell lines and tissues when compared to normal human colon tissues. PIK3CA was identified as a potential miR-375 target by bioinformatics. Overexpression of miR-375 in SW480 and HCT15 cells reduced PIK3CA protein expression. Subsequently, using reporter constructs, we showed that the PIK3CA untranslated region (3′-UTR) carries the directly binding site of miR-375. Additionally, miR-375 suppressed CRC cell proliferation and colony formation and led to cell cycle arrest. Furthermore, miR-375 overexpression resulted in inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. SiRNA-mediated silencing of PIK3CA blocked the inhibitory effect of miR-375 on CRC cell growth. Lastly, we found overexpressed miR-375 effectively repressed tumor growth in xenograft animal experiments. Taken together, we propose that overexpression of miR-375 may provide a selective growth inhibition for CRC cells by targeting PI3K/Akt signaling pathway.

PIK3CA expression in diffuse large B cell lymphoma tissue and the effect of its knockdown in vitro

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Cui W

2017-04-01

Full Text Available Wenli Cui,1–4,* Shutao Zheng,5,6,* Zebing Liu,1–3 Weige Wang,1–3 Ying Cai,1–3 Rui Bi,1–3 Bing Cao,1–3 Xiaoyan Zhou1–3 1Department of Pathology, Shanghai Cancer Center, Fudan University, 2Department of Oncology, Shanghai Medical College, Fudan University, 3Institute of Pathology, Fudan University, Shanghai, 4Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, 5Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, 6State Key Lab Incubation Base of Xinjiang Major Diseases Research, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi, People’s Republic of China *These authors contributed equally to this work Abstract: PIK3CA has been extensively investigated from its molecular mechanism perspective and epidemiological association with its mutations in different types of cancers. However, little has been reported regarding the clinicopathological significance of PIK3CA expression in diffuse large B cell lymphoma (DLBCL. In the present study, we investigated the clinicopathological significance of PIK3CA in DLBCL by performing immunohistochemical evaluation of PIK3CA in tissue microarrays consisting of 199 cases of DLBCL. Kaplan–Meier survival analysis was performed to analyze the association between PIK3CA expression and overall prognosis. To further investigate the role of PIK3CA mediated in the proliferation, cell cycle and apoptosis of DLBCL cells, Cell Counting Kit-8 (CCK-8 and flow cytometry assays were carried out in DLBCL cell lines after successful, stable knockdown of PIK3CA using lentiviral short hairpin RNA inference. Our results indicated that although PIK3CA was shown to be extensively expressed in DLBCL, no significant association was observed between PIK3CA expression and clinical outcome or between PIK3CA expression and other clinicopathological parameters, except between performance state (PS

An integrative genomic and proteomic analysis of PIK3CA, PTEN and AKT mutations in breast cancer

Energy Technology Data Exchange (ETDEWEB)

Stemke-Hale, Katherine; Gonzalez-Angulo, Ana Maria; Lluch, Ana; Neve, Richard M.; Kuo, Wen-Lin; Davies, Michael; Carey, Mark; Hu, Zhi; Guan, Yinghui; Sahin, Aysegul; Symmans, W. Fraser; Pusztai, Lajos; Nolden, Laura K.; Horlings, Hugo; Berns, Katrien; Hung, Mien-Chie; van de Vijver, Marc J.; Valero, Vicente; Gray, Joe W.; Bernards, Rene; Mills, Gordon B.; Hennessy, Bryan T.

2008-05-06

Phosphatidylinositol-3-kinase (PI3K)/AKT pathway aberrations are common in cancer. By applying mass spectroscopy-based sequencing and reverse phase protein arrays to 547 human breast cancers and 41 cell lines, we determined the subtype specificity and signaling effects of PIK3CA, AKT and PTEN mutations, and the effects of PIK3CA mutations on responsiveness to PI3K inhibition in-vitro and on outcome after adjuvant tamoxifen. PIK3CA mutations were more common in hormone receptor positive (33.8%) and HER2-positive (24.6%) than in basal-like tumors (8.3%). AKT1 (1.4%) and PTEN (2.3%) mutations were restricted to hormone receptor-positive cancers with PTEN protein levels also being significantly lower in hormone receptor-positive cancers. Unlike AKT1 mutations, PIK3CA (39%) and PTEN (20%) mutations were more common in cell lines than tumors, suggesting a selection for these but not AKT1 mutations during adaptation to culture. PIK3CA mutations did not have a significant impact on outcome in 166 hormone receptor-positive breast cancer patients after adjuvant tamoxifen. PIK3CA mutations, in comparison with PTEN loss and AKT1 mutations, were associated with significantly less and indeed inconsistent activation of AKT and of downstream PI3K/AKT signaling in tumors and cell lines, and PTEN loss and PIK3CA mutation were frequently concordant, suggesting different contributions to pathophysiology. PTEN loss but not PIK3CA mutations rendered cells sensitive to growth inhibition by the PI3K inhibitor LY294002. Thus, PI3K pathway aberrations likely play a distinct role in the pathogenesis of different breast cancer subtypes. The specific aberration may have implications for the selection of PI3K-targeted therapies in hormone receptor-positive breast cancer.

Phosphatidyl inositol-3 kinase (PIK3CA) E545K mutation confers cisplatin resistance and a migratory phenotype in cervical cancer cells

Science.gov (United States)

Arjumand, Wani; Merry, Cole D.; Wang, Chen; Saba, Elias; McIntyre, John B.; Fang, Shujuan; Kornaga, Elizabeth; Ghatage, Prafull; Doll, Corinne M.; Lees, Susan P.

2016-01-01

The phosphatidylinositol-3 kinase (PI3K)/Akt/mTOR signaling pathway is activated in many human cancers. Previously, we reported that patients with early stage cervical cancer whose tumours harbour PIK3CA exon 9 or 20 mutations have worse overall survival in response to treatment with radiation and cisplatin than patients with wild-type PIK3CA. The purpose of this study was to determine whether PIK3CA-E545K mutation renders cervical cancer cells more resistant to cisplatin and/or radiation, and whether PI3K inhibition reverses the phenotype. We found that CaSki cells that are heterozygous for the PIK3CA-E545K mutation are more resistant to cisplatin or cisplatin plus radiation than either HeLa or SiHa cells that express only wild-type PIK3CA. Similarly, HeLa cells engineered to stably express PIK3CA-E545K were more resistant to cisplatin or cisplatin plus radiation than cells expressing only wild-type PIK3CA or with PIK3CA depleted. Cells expressing the PIK3CA-E545K mutation also had constitutive PI3K pathway activation and increased cellular migration and each of these phenotypes was reversed by treatment with the PI3K inhibitor GDC-0941/Pictilisib. Our results suggests that cervical cancer patients whose tumours are positive for the PIK3CA-E545K mutation may benefit from PI3K inhibitor therapy in concert with standard cisplatin and radiation therapy. PMID:27489350

Tumor PIK3CA genotype and prognosis in early-stage breast cancer

DEFF Research Database (Denmark)

Zardavas, Dimitrios; Te Marvelde, Luc; Milne, Roger L.

2018-01-01

% in the ER-negative/HER2-negative, HER2-positive, and ER-positive/HER2-negative subtypes, respectively. In univariable analysis, PIK3CA mutations were associated with better IDFS (HR, 0.77; 95% CI, 0.71 to 0.84; P, .001), with evidence for a stronger effect in the first years of follow-up (0 to 5 years: HR...... points. Conclusion In this large pooled analysis, PIK3CA mutations were significantly associated with a better IDFS, DDFS, and OS, but had a lesser prognostic effect after adjustment for other prognostic factors....

Mutant PIK3CA Induces EMT in a Cell Type Specific Manner.

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Divya Bhagirath

Full Text Available Breast cancer is characterized into different molecular subtypes, and each subtype is characterized by differential gene expression that are associated with distinct survival outcomes in patients. PIK3CA mutations are commonly associated with most breast cancer subtypes. More recently PIK3CA mutations have been shown to induce tumor heterogeneity and are associated with activation of EGFR-signaling and reduced relapse free survival in basal subtype of breast cancer. Thus, understanding what determines PIK3CA induced heterogeneity and oncogenesis, is an important area of investigation. In this study, we assessed the effect of mutant PIK3CA together with mutant Ras plus mutant p53 on oncogenic behavior of two distinct stem/progenitor breast cell lines, designated as K5+/K19- and K5+/K19+. Constructs were ectopically overexpressed in K5+/K19- and K5+/K19+ stem/progenitor cells, followed by various in-vitro and in-vivo analyses. Oncogene combination m-Ras/m-p53/m-PIK3CA efficiently transformed both K5+/K19- and K5+/K19+ cell lines in-vitro, as assessed by anchorage-independent soft agar colony formation assay. Significantly, while this oncogene combination induced a complete epithelial-to-mesenchymal transition (EMT in K5+/K19- cell line, mostly epithelial phenotype with minor EMT component was seen in K5+/K19+ cell line. However, both K5+/K19- and K5+/K19+ transformed cells exhibited increased invasion and migration abilities. Analyses of CD44 and CD24 expression showed both cell lines had tumor-initiating CD44+/CD24low cell population, however transformed K5+/K19- cells had more proportion of these cells. Significantly, both cell types exhibited in-vivo tumorigenesis, and maintained their EMT and epithelial nature in-vivo in mice tumors. Notably, while both cell types exhibited increase in tumor-initiating cell population, differential EMT phenotype was observed in these cell lines. These results suggest that EMT is a cell type dependent

Highly sensitive detection of the PIK3CAH1047R mutation in colorectal cancer using a novel PCR-RFLP method

International Nuclear Information System (INIS)

Li, Wan-Ming; Hu, Ting-Ting; Zhou, Lin-Lin; Feng, Yi-Ming; Wang, Yun-Yi; Fang, Jin

2016-01-01

The PIK3CA H1047R mutation is considered to be a potential predictive biomarker for EGFR-targeted therapies. In this study, we developed a novel PCR-PFLP approach to detect the PIK3CA H1047R mutation in high effectiveness. A 126-bp fragment of PIK3CA exon-20 was amplified by PCR, digested with FspI restriction endonuclease and separated by 3 % agarose gel electrophoresis for the PCR-RFLP analysis. The mutant sequence of the PIK3CA H1047R was spiked into the corresponding wild-type sequence in decreasing ratios for sensitivity analysis. Eight-six cases of formalin-fixed paraffin-embedded colorectal cancer (CRC) specimens were subjected to PCR-RFLP to evaluate the applicability of the method. The PCR-RFLP method had a capability to detect as litter as 0.4 % of mutation, and revealed 16.3 % of the PIK3CA H1047R mutation in 86 CRC tissues, which was significantly higher than that discovered by DNA sequencing (9.3 %). A positive association between the PIK3CA H1047R mutation and the patients’ age was first found, except for the negative relationship with the degree of tumor differentiation. In addition, the highly sensitive detection of a combinatorial mutation of PIK3CA, KRAS and BRAF was achieved using individual PCR-RFLP methods. We developed a sensitive, simple and rapid approach to detect the low-abundance PIK3CA H1047R mutation in real CRC specimens, providing an effective tool for guiding cancer targeted therapy

Assessing PIK3CA and PTEN in Early-Phase Trials with PI3K/AKT/mTOR Inhibitors

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Filip Janku

2014-01-01

Full Text Available Despite a wealth of preclinical studies, it is unclear whether PIK3CA or phosphatase and tensin homolog (PTEN gene aberrations are actionable in the clinical setting. Of 1,656 patients with advanced, refractory cancers tested for PIK3CA or PTEN abnormalities, PIK3CA mutations were found in 9% (146/1,589, and PTEN loss and/or mutation was found in 13% (149/1,157. In multicovariable analysis, treatment with a phosphatidylinositol 3-kinase (PI3K/AKT/mammalian target of rapamycin (mTOR inhibitor was the only independent factor predicting response to therapy in individuals harboring a PIK3CA or PTEN aberration. The rate of stable disease ≥6 months/partial response reached 45% in a subgroup of individuals with H1047R PIK3CA mutations. Aberrations in the PI3K/AKT/mTOR pathway are common and potentially actionable in patients with diverse advanced cancers. This work provides further important clinical validation for continued and accelerated use of biomarker-driven trials incorporating rational drug combinations.

Highly frequent promoter methylation and PIK3CA amplification in non-small cell lung cancer (NSCLC)

International Nuclear Information System (INIS)

Ji, Meiju; Guan, Haixia; Gao, Cuixia; Shi, Bingyin; Hou, Peng

2011-01-01

Lung cancer is the leading cause of cancer-related death worldwide. Genetic and epigenetic alterations have been identified frequently in lung cancer, such as promoter methylation, gene mutations and genomic amplification. However, the interaction between genetic and epigenetic events and their significance in lung tumorigenesis remains poorly understood. We determined the promoter methylation of 6 genes and PIK3CA amplification using quantitative methylation-specific PCR (Q-MSP) and real-time quantitative PCR, respectively, and explore the association of promoter methylation with PIK3CA amplification in a large cohort of clinically well-characterized non-small cell lung cancer (NSCLC). Highly frequent promoter methylation was observed in NSCLC. With 100% diagnostic specificity, excellent sensitivity, ranging from 45.8 to 84.1%, was found for each of the 6 genes. The promoter methylation was associated with histologic type. Methylation of CALCA, CDH1, DAPK1, and EVX2 was more common in squamous cell carcinomas (SCC) compared to adenocarcinomas (ADC). Conversely, there was a trend toward a higher frequency of RASSF1A methylation in ADC than SCC. In addition, PIK3CA amplification was frequently found in NSCLC, and was associated with certain clinicopathologic features, such as smoking history, histologic type and pleural indentation. Importantly, aberrant promoter methylation of certain genes was significantly associated with PIK3CA amplification. Our data showed highly frequent promoter methylation and PIK3CA amplification in Chinese NSCLC population, and first demonstrated the associations of gene methylation with PIK3CA amplification, suggesting that these epigenetic events may be a consequence of overactivation of PI3K/Akt pathway

SANA - project results and PIK contributions

Energy Technology Data Exchange (ETDEWEB)

Bellmann, K; Erhard, M; Flechsig, M; Grote, R; Suckow, F

1998-03-01

This report includes the final project results of the two groups at PIK, involved in the project: Firstly, the newly developed physiologically-based forest growth model FORSANA was applied for the first time to three pine stands, which differed largely in their air pollution and deposition history. (The evaluation of the model is presented in PIK Report 32). The model was able to explain the growth during the last decades of at least two of the three stands from the climatic and deposition conditions at the sites. The third site was shown to be exceptional with respect to its relation between dimension and age, and was supposed to be exposed to major disturbances in the past, which could not be accounted for by the model. To extrapolate from the stand level to the regional level, FORSANA was initialised with spatially explicit data from forestry inventory and soil maps. Simulations were executed with measured weather records and regional distributions of deposition and air pollution, which were estimated on the basis of emission inventories and wind directions. Different assumptions about the development of air pollution had been applied to investigate different pollution abatement strategies. The results showed that a positive effect can be expected from the actual emission reductions close the main centres of emission, but showed also that this effect is decreasing with increasing distance from the emission source. (orig./KW)

Kas postsovetlik kultuurikontekst on veel moes? / Hannaliisa Uusma, Terje Toomistu, Stephen Amico, Yngvar Steinholt ; intervjueerinud Maarja Merivoo-Parro

Index Scriptorium Estoniae

2017-01-01

Maarja Merivoo-Parroga vestlesid tänapäevastest muusikauuringutest sotsioloog ja muusikateadlane Hannaliisa Uusma, peagi esilinastuva Nõukogude hipiliikumist kaardistava dokumentaalfilmi režissöör ja etnoloogiadoktorant Terje Toomistu, ameeriklasest etnomusikoloogiadoktor Stephen Amico Bergeni ülikoolist ning norra pungiuurija, Tromsø ülikooli vene keele ja kirjanduse doktor Yngvar Steinholt. Neid kõiki paeluvad sooküsimused

Maailma arhitektuurifestival = World Architecture Festival / Ingrid Ruudi ; kommenteerinud Maarja Kask, Karli Luik, Ralf Lõoke, Indrek Allmann, Martin Aunin

Index Scriptorium Estoniae

Ruudi, Ingrid, 1978-

2011-01-01

Barcelonas 2.-4. nov. 2011 toimunud 4. Maailma arhitektuurifestivalist (WAF). Muljeid jagavad II vooru pääsenud eesti arhitektid Maarja Kask, Karli Luik ja Ralf Lõoke AB-st Salto (Põhuteater, Sõmeru keskus), Martin Aunin (Must maja Nõmmel), Indrek Allmann AB-st Pluss (poolautonoomne saun). Üldvõitja - Media-ICT Barcelonas (Cloud 9 / Enric Ruiz-Geli)

Uudised : Sumera VI sümfoonia Saksamaa esiettekanne. Mati Palm Peterburis. Globaliseerumine ja identiteet. Muusikapäevad Oleviste Maarja kabelis / Merike Utt

Index Scriptorium Estoniae

Utt, Merike

2001-01-01

5. ja 6. apr. toimus Frankfurdis L.Sumera 6. sümfoonia ettekanne. M.Palm andis soolokontserdi 15. mail Peterburis. Euroopa Koolimuusika Assotsiatsiooni konverentsist "Globaliseerumine ja identiteet" 10.-13. maini Riias. 22. mail alanud Oleviste Maarja kabeli muusikapäevadest

PIK3CA, HRAS and PTEN in human papillomavirus positive oropharyngeal squamous cell carcinoma

International Nuclear Information System (INIS)

Chiosea, Simion I; Nikiforova, Marina N; Grandis, Jennifer R; Lui, Vivian W Y; Diergaarde, Brenda; Maxwell, Jessica H; Ferris, Robert L; Kim, Seungwon W; Luvison, Alyssa; Miller, Megan

2013-01-01

Recent genomic evidence suggests frequent phosphatidylinositide 3-kinase (PI3K) pathway activation in human papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma. Mutations/amplification of the gene encoding p110α catalytic subunit of phosphoinositide 3-kinase (PIK3CA), loss of phosphatase and tensin homolog (PTEN) and HRAS mutations are known to activate PI3K pathway. PIK3CA mutations were identified by Sanger sequencing in 23 of 75 (31%) HPV-positive oropharyngeal carcinomas, including exon 9 (p.E545K [n = 10] and p.E542K [n = 5]) or exon 20 (p.H1047Y, n = 2) mutations. Five rare and one novel (p.R537Q) PIK3CA mutations were identified. HRAS mutation (p.Q61L) was detected in 1 of 62 tested cases. PIK3CA amplification by fluorescence in situ hybridization (FISH) was identified in 4 cases (4/21, 20%), while PTEN loss was seen in 7 (7/21, 33%) cases (chromosome 10 monosomy [n = 4], homozygous deletion [n = 3]). Overall, genetic alterations that likely lead to PI3K pathway activation were identified in 34 of 75 cases (45%) and did not correlate with disease specific survival. These findings offer a molecular rationale for therapeutic targeting of PI3K pathway in patients with HPV-positive oropharyngeal carcinoma

The sensitivity and efficacy method of PIK3CA exon 9 E545A as a high diagnostic accuracy in breast cancer

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Desriani

2018-06-01

Full Text Available The phosphatidylinositol 3-kinases (PIK3s are lipid kinases. Mutation in the exon 9 and exon 20 determined as a predictive factor in anti-HER-2 therapy. In some countries, such as Singapore, China, and Peru, PIK3CA exon 9 E545A was reported to produce the highest rate of mutation. In this research, we developed and optimized PIK3CA exon 9 E545A detection methods with intercalating dye SYBR Green I based on the Tm Shift approach by using prepared recombinant plasmid pGEMT-easy PIK3CA exon 9 and PIK3CA exon 9 E545A. Recombinant plasmid was used due to the limited number of samples. Methods: Recombinant plasmid was prepared based on manufactured procedures, and this process was then followed by Tm prediction with Poland software, Tm Shift SYBR Green I development, and its characterization (reproducibility, repeatability, sensitivity, qPCR efficiency, and qPCR amplification, respectively. Result: A method for PIK3CA E545A detection based on TM shift SYBR Green I has been successfully developed. The melting temperature for PIK3CA exon 9 was 78.1 ± 0.1 °C, while that for PIK3CA exon E545A was 80.20 °C. The Tm of mutant was the same as that predicted using Polland Software. The reproducibility of the methods was high, with the coefficient values for inter and intra assays were below 10% with a high sensitivity at 1%, while R2 0.99 and PCR efficiency was 97.75%. Conclusion: The results presented here demonstrate that the PIK3CA exon 9 E545A detection method has a good sensitivity and efficacy assay, which proves that the method has a high diagnostic accuracy in breast cancer. Keywords: SYBR Green I, PIK3CA E545A, Breast cancer, Real time PCR, Recombinant plasmid

Significance of PIK3CA Mutations in Patients with Early Breast Cancer Treated with Adjuvant Chemotherapy: A Hellenic Cooperative Oncology Group (HeCOG Study.

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George Papaxoinis

Full Text Available The PI3K-AKT pathway is frequently activated in breast cancer. PIK3CA mutations are most frequently found in the helical (exon 9 and kinase (exon 20 domains of this protein. The aim of the present study was to examine the role of different types of PIK3CA mutations in combination with molecular biomarkers related to PI3K-AKT signaling in patients with early breast cancer.Tumor tissue samples from 1008 early breast cancer patients treated with adjuvant chemotherapy in two similar randomized trials of HeCOG were examined. Tumors were subtyped with immunohistochemistry (IHC and FISH for ER, PgR, Ki67, HER2 and androgen receptor (AR. PIK3CA mutations were analyzed by Sanger sequencing (exon 20 and qPCR (exon 9 (Sanger/qPCR mutations. In 610 cases, next generation sequencing (NGS PIK3CA mutation data were also available. PIK3CA mutations and PTEN protein expression (IHC were analyzed in luminal tumors (ER and/or PgR positive, molecular apocrine carcinomas (MAC; ER/PgR negative / AR positive and hormone receptor (ER/PgR/AR negative tumors.PIK3CA mutations were detected in 235/1008 tumors (23% with Sanger/qPCR and in 149/610 tumors (24% with NGS. Concordance between the two methods was good with a Kappa coefficient of 0.76 (95% CI 0.69-0.82. Lobular histology, low tumor grade and luminal A tumors were associated with helical domain mutations (PIK3CAhel, while luminal B with kinase domain mutations (PIK3CAkin. The overall incidence of PIK3CA mutations was higher in luminal as compared to MAC and hormone receptor negative tumors (p = 0.004. Disease-free and overall survival did not significantly differ with respect to PIK3CA mutation presence and type. However, a statistically significant interaction between PIK3CA mutation status and PTEN low protein expression with regard to prognosis was identified.The present study did not show any prognostic significance of specific PIK3CA mutations in a large group of predominantly lymph-node positive breast cancer

CLOVES syndrome: review of a PIK3CA-related overgrowth spectrum (PROS).

Science.gov (United States)

Martinez-Lopez, A; Blasco-Morente, G; Perez-Lopez, I; Herrera-Garcia, J D; Luque-Valenzuela, M; Sanchez-Cano, D; Lopez-Gutierrez, J C; Ruiz-Villaverde, R; Tercedor-Sanchez, J

2017-01-01

Overgrowth syndromes are characterized by global or localized disproportionate growth associated with other anomalies, including vascular malformations and neurological and/or visceral disorders. CLOVES (Congenital Lipomatous asymmetric Overgrowth of the trunk with lymphatic, capillary, venous, and combined-type Vascular malformations, Epidermal naevi, Scoliosis/Skeletal and spinal anomalies) is an overgrowth syndrome caused by mosaic activating mutation in gene PIK3CA, which gives rise to abnormal PI3K-AKT-mTOR pathway activation. These mutations are responsible for the clinical manifestations of the syndrome, which include low- and high-flow vascular malformations, thoracic lipomatous hyperplasia, asymmetric growth, and visceral and neurological disorders. These common anomalies are illustrated with figures from two personal cases. Identification of the clinical and genetic characteristics of CLOVES syndrome is crucial for the differential diagnosis with other overgrowth syndromes, such as Proteus or Klippel-Trenaunay (K-T) syndromes, and for the therapeutic management of the different anomalies. In this context, a new entity comprising different syndromes with phenotypic mutations in PIK3CA has been proposed, designated PIK3CA-related overgrowth spectrum (PROS), with the aim of facilitating clinical management and establishing appropriate genetic study criteria. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Present status of PIK gadolinium control

International Nuclear Information System (INIS)

Petrov, Yu.V.; Garusov, E.A.; Shustov, V.A.

1994-01-01

A liquid control element (LCE) containing a water solution of gadolinium nitrate Gd(NO 3 ) 3 was originally planned for use at the PIK reactor for partial compensation of poisoning and fuel burnup [1-3]. However, a further analysis has shown that quick forcing-out, boiling up or flowing-out of the absorbing solution (though of low probability) can lead to the dangerous prompt overcriticality of the reactor. The results of the analysis are presented as well as the upper limit of the reactivity, quick insertion of which still is safe for the reactor (J.P.N.)

Physiological Levels of Pik3ca H1047R Mutation in the Mouse Mammary Gland Results in Ductal Hyperplasia and Formation of ERα-Positive Tumors

Science.gov (United States)

Tikoo, Anjali; Roh, Vincent; Montgomery, Karen G.; Ivetac, Ivan; Waring, Paul; Pelzer, Rebecca; Hare, Lauren; Shackleton, Mark; Humbert, Patrick; Phillips, Wayne A.

2012-01-01

PIK3CA, the gene coding for the p110α subunit of phosphoinositide 3-kinase, is frequently mutated in a variety of human tumors including breast cancers. To better understand the role of mutant PIK3CA in the initiation and/or progression of breast cancer, we have generated mice with a conditional knock-in of the common activating mutation, Pik3caH1047R, into one allele of the endogenous gene in the mammary gland. These mice developed a ductal anaplasia and hyperplasia by 6 weeks of age characterized by multi-layering of the epithelial lining of the mammary ducts and expansion of the luminal progenitor (Lin−; CD29lo; CD24+; CD61+) cell population. The Pik3caH1047R expressing mice eventually develop mammary tumors with 100% penetrance but with a long latency (>12 months). This is significantly longer than has been reported for transgenic models where expression of the mutant Pik3ca is driven by an exogenous promoter. Histological analysis of the tumors formed revealed predominantly ERα-positive fibroadenomas, carcinosarcomas and sarcomas. In vitro induction of Pik3caH1047R in immortalized mammary epithelial cells also resulted in tumor formation when injected into the mammary fat pad of immunodeficient recipient mice. This novel model, which reproduces the scenario of a heterozygous somatic mutation occurring in the endogenous PIK3CA gene, will thus be a valuable tool for investigating the role of Pik3caH1047R mutation in mammary tumorigenesis both in vivo and in vitro. PMID:22666336

Physiological levels of Pik3ca(H1047R mutation in the mouse mammary gland results in ductal hyperplasia and formation of ERα-positive tumors.

Directory of Open Access Journals (Sweden)

Anjali Tikoo

Full Text Available PIK3CA, the gene coding for the p110α subunit of phosphoinositide 3-kinase, is frequently mutated in a variety of human tumors including breast cancers. To better understand the role of mutant PIK3CA in the initiation and/or progression of breast cancer, we have generated mice with a conditional knock-in of the common activating mutation, Pik3ca(H1047R, into one allele of the endogenous gene in the mammary gland. These mice developed a ductal anaplasia and hyperplasia by 6 weeks of age characterized by multi-layering of the epithelial lining of the mammary ducts and expansion of the luminal progenitor (Lin(-; CD29(lo; CD24(+; CD61(+ cell population. The Pik3ca(H1047R expressing mice eventually develop mammary tumors with 100% penetrance but with a long latency (>12 months. This is significantly longer than has been reported for transgenic models where expression of the mutant Pik3ca is driven by an exogenous promoter. Histological analysis of the tumors formed revealed predominantly ERα-positive fibroadenomas, carcinosarcomas and sarcomas. In vitro induction of Pik3ca(H1047R in immortalized mammary epithelial cells also resulted in tumor formation when injected into the mammary fat pad of immunodeficient recipient mice. This novel model, which reproduces the scenario of a heterozygous somatic mutation occurring in the endogenous PIK3CA gene, will thus be a valuable tool for investigating the role of Pik3ca(H1047R mutation in mammary tumorigenesis both in vivo and in vitro.

KRASness and PIK3CAness in patients with advanced colorectal cancer: outcome after treatment with early-phase trials with targeted pathway inhibitors.

Directory of Open Access Journals (Sweden)

Ignacio Garrido-Laguna

Full Text Available To evaluate clinicopathologic and molecular features of patients with metastatic colorectal cancer (mCRC and their outcomes in early-phase trials using pathway-targeting agents.We analyzed characteristics of 238 patients with mCRC referred to the phase 1 trials unit at MD Anderson Cancer Center. KRAS, PIK3CA and BRAF status were tested using PCR-based DNA sequencing.Fifty-one percent of patients harbored KRAS mutations; 15% had PIK3CA mutations. In the multivariate regression model for clinical characteristics KRAS mutations were associated with an increased incidence of lung and bone metastases and decreased incidence of adrenal metastases; PIK3CA mutations were marginally correlated with mucinous tumors (p = 0.05. In the univariate analysis, KRAS and PIK3CA mutations were strongly associated. Advanced Duke's stage (p<0.0001 and KRAS mutations (p = 0.01 were the only significant independent predictors of poor survival (Cox proportional hazards model. Patients with PIK3CA mutations had a trend toward shorter progression-free survival when treated with anti-EGFR therapies (p = 0.07. Eighteen of 78 assessable patients (23% treated with PI3K/Akt/mTOR axis inhibitors achieved stable disease [SD] ≥6 months or complete response/partial response (CR/PR, only one of whom were in the subgroup (N = 15 with PIK3CA mutations, perhaps because 10 of these 15 patients (67% had coexisting KRAS mutations. No SD ≥6 months/CR/PR was observed in the 10 patients treated with mitogen-activating protein kinase (MAPK pathway targeting drugs.KRAS and PIK3CA mutations frequently coexist in patients with colorectal cancer, and are associated with clinical characteristics and outcome. Overcoming resistance may require targeting both pathways.

Genome Analysis of Latin American Cervical Cancer: Frequent Activation of the PIK3CA Pathway.

Science.gov (United States)

Lou, Hong; Villagran, Guillermo; Boland, Joseph F; Im, Kate M; Polo, Sarita; Zhou, Weiyin; Odey, Ushie; Juárez-Torres, Eligia; Medina-Martínez, Ingrid; Roman-Basaure, Edgar; Mitchell, Jason; Roberson, David; Sawitzke, Julie; Garland, Lisa; Rodríguez-Herrera, Maria; Wells, David; Troyer, Jennifer; Pinto, Francisco Castillo; Bass, Sara; Zhang, Xijun; Castillo, Miriam; Gold, Bert; Morales, Hesler; Yeager, Meredith; Berumen, Jaime; Alvirez, Enrique; Gharzouzi, Eduardo; Dean, Michael

2015-12-01

Cervical cancer is one of the most common causes of cancer mortality for women living in poverty, causing more than 28,000 deaths annually in Latin America and 266,000 worldwide. To better understand the molecular basis of the disease, we ascertained blood and tumor samples from Guatemala and Venezuela and performed genomic characterization. We performed human papillomavirus (HPV) typing and identified somatically mutated genes using exome and ultra-deep targeted sequencing with confirmation in samples from Mexico. Copy number changes were also assessed in the exome sequence. Cervical cancer cases in Guatemala and Venezuela have an average age of diagnosis of 50 years and 5.6 children. Analysis of 675 tumors revealed activation of PIK3CA and other PI3K/AKT pathway genes in 31% of squamous carcinomas and 24% of adeno- and adenosquamous tumors, predominantly at two sites (E542K, E545K) in the helical domain of the PIK3CA gene. This distribution of PIK3CA mutations is distinct from most other cancer types and does not result in the in vitro phosphorylation of AKT. Somatic mutations were more frequent in squamous carcinomas diagnosed after the age of 50 years. Frequent gain of chromosome 3q was found, and low PIK3CA mutation fractions in many tumors suggest that PI3K mutation can be a late event in tumor progression. PI3K pathway mutation is important to cervical carcinogenesis in Latin America. Therapeutic agents that directly target PI3K could play a role in the therapy of this common malignancy. ©2015 American Association for Cancer Research.

Dual HER2\\PIK3CA targeting overcomes single-agent acquired resistance in HER2 amplified uterine serous carcinoma cell lines in vitro and in vivo

Science.gov (United States)

Lopez, Salvatore; Cocco, Emiliano; Black, Jonathan; Bellone, Stefania; Bonazzoli, Elena; Predolini, Federica; Ferrari, Francesca; Schwab, Carlton L.; English, Diana P.; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E.; Terranova, Corrado; Angioli, Roberto; Santin, Alessandro D.

2015-01-01

HER2/neu gene amplification and PIK3CA driver mutations are common in uterine serous carcinoma (USC), and may represent ideal therapeutic targets against this aggressive variant of endometrial cancer. We examined the sensitivity to neratinib, taselisib and the combination of the two compounds in in vitro and in vivo experiments using PIK3CA mutated and PIK3CA-wild type HER2/neu amplified USC cell lines. Cell viability and cell cycle distribution were assessed using flow-cytometry assays. Downstream signaling was assessed by immunoblotting. Preclinical efficacy of single versus dual inhibition was evaluated in vivo using two USC-xenografts. We found both single agent neratinib and taselisib to be active but only transiently effective in controlling the in vivo growth of USC xenografts harboring HER2/neu gene amplification with or without oncogenic PIK3CA mutations. In contrast, the combination of the two inhibitors caused a stronger and long lasting growth inhibition in both USC xenografts when compared to single agent therapy. Combined targeting of HER2 and PIK3CA was associated with a significant and dose-dependent increase in the percentage of cells in the G0/G1 phase of the cell cycle and a dose-dependent decline in the phosphorylation of S6. Importantly, dual inhibition therapy initiated after tumor progression in single agent-treated mice was still remarkably effective at inducing tumor regression in both large PIK3CA or pan-ErbB inhibitor-resistant USC xenografts. Dual HER2/PIK3CA blockade may represent a novel therapeutic option for USC patients harboring tumors with HER2/neu gene amplification and mutated or wild type PIK3CA resistant to chemotherapy. PMID:26333383

Dual HER2/PIK3CA Targeting Overcomes Single-Agent Acquired Resistance in HER2-Amplified Uterine Serous Carcinoma Cell Lines In Vitro and In Vivo.

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Lopez, Salvatore; Cocco, Emiliano; Black, Jonathan; Bellone, Stefania; Bonazzoli, Elena; Predolini, Federica; Ferrari, Francesca; Schwab, Carlton L; English, Diana P; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Terranova, Corrado; Angioli, Roberto; Santin, Alessandro D

2015-11-01

HER2/neu gene amplification and PIK3CA driver mutations are common in uterine serous carcinoma (USC) and may represent ideal therapeutic targets against this aggressive variant of endometrial cancer. We examined the sensitivity to neratinib, taselisib, and the combination of the two compounds in in vitro and in vivo experiments using PIK3CA-mutated and PIK3CA wild-type HER2/neu-amplified USC cell lines. Cell viability and cell-cycle distribution were assessed using flow-cytometry assays. Downstream signaling was assessed by immunoblotting. Preclinical efficacy of single versus dual inhibition was evaluated in vivo using two USC xenografts. We found both single-agent neratinib and taselisib to be active but only transiently effective in controlling the in vivo growth of USC xenografts harboring HER2/neu gene amplification with or without oncogenic PIK3CA mutations. In contrast, the combination of the two inhibitors caused a stronger and long-lasting growth inhibition in both USC xenografts when compared with single-agent therapy. Combined targeting of HER2 and PIK3CA was associated with a significant and dose-dependent increase in the percentage of cells in the G0-G1 phase of the cell cycle and a dose-dependent decline in the phosphorylation of S6. Importantly, dual inhibition therapy initiated after tumor progression in single-agent-treated mice was still remarkably effective at inducing tumor regression in both large PIK3CA and pan-ErbB inhibitor-resistant USC xenografts. Dual HER2/PIK3CA blockade may represent a novel therapeutic option for USC patients harboring tumors with HER2/neu gene amplification and mutated or wild-type PIK3CA resistant to chemotherapy. ©2015 American Association for Cancer Research.

Oligonucleotide PIK3CA/Chromosome 3 Dual in Situ Hybridization Automated Assay with Improved Signals, One-Hour Hybridization, and No Use of Blocking DNA.

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Zhang, Wenjun; Hubbard, Antony; Baca-Parkinson, Leslie; Stanislaw, Stacey; Vladich, Frank; Robida, Mark D; Grille, James G; Maxwell, Daniel; Tsao, Tsu-Shuen; Carroll, William; Gardner, Tracie; Clements, June; Singh, Shalini; Tang, Lei

2015-09-01

The PIK3CA gene at chromosome 3q26.32 was found to be amplified in up to 45% of patients with squamous cell carcinoma of the lung. The strong correlation between PIK3CA amplification and increased phosphatidylinositol 3-kinase (PI3K) pathway activities suggested that PIK3CA gene copy number is a potential predictive biomarker for PI3K inhibitors. Currently, all microscopic assessments of PIK3CA and chromosome 3 (CHR3) copy numbers use fluorescence in situ hybridization. PIK3CA probes are derived from bacterial artificial chromosomes whereas CHR3 probes are derived mainly from the plasmid pHS05. These manual fluorescence in situ hybridization assays mandate 12- to 18-hour hybridization and use of blocking DNA from human sources. Moreover, fluorescence in situ hybridization studies provide limited morphologic assessment and suffer from signal decay. We developed an oligonucleotide-based bright-field in situ hybridization assay that overcomes these shortcomings. This assay requires only a 1-hour hybridization with no need for blocking DNA followed by indirect chromogenic detection. Oligonucleotide probes produced discrete and uniform CHR3 stains superior to those from the pHS05 plasmid. This assay achieved successful staining in 100% of the 195 lung squamous cell carcinoma resections and in 94% of the 33 fine-needle aspirates. This robust automated bright-field dual in situ hybridization assay for the simultaneous detection of PIK3CA and CHR3 centromere provides a potential clinical diagnostic method to assess PIK3CA gene abnormality in lung tumors. Copyright © 2015 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Somatic mutations in PIK3CA and activation of AKT in intraductal tubulopapillary neoplasms of the pancreas.

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Yamaguchi, Hiroshi; Kuboki, Yuko; Hatori, Takashi; Yamamoto, Masakazu; Shiratori, Keiko; Kawamura, Shunji; Kobayashi, Makio; Shimizu, Michio; Ban, Shinichi; Koyama, Isamu; Higashi, Morihiro; Shin, Nobuhiro; Ishida, Kazuyuki; Morikawa, Takanori; Motoi, Fuyuhiko; Unno, Michiaki; Kanno, Atsushi; Satoh, Kennichi; Shimosegawa, Tooru; Orikasa, Hideki; Watanabe, Tomoo; Nishimura, Kazuhiko; Harada, Youji; Furukawa, Toru

2011-12-01

Intraductal tubulopapillary neoplasm (ITPN) is a recently recognized rare variant of intraductal neoplasms of the pancreas. Molecular aberrations underlying the neoplasm remain unknown. We investigated somatic mutations in PIK3CA, PTEN, AKT1, KRAS, and BRAF. We also investigated aberrant expressions of phosphorylated AKT, phosphatase and tensin homolog (PTEN), tumor protein 53 (TP53), SMAD4, and CTNNB1 in 11 cases of ITPNs and compared these data with those of 50 cases of intraductal papillary mucinous neoplasm (IPMN), another distinct variant of pancreatic intraductal neoplasms. Mutations in PIK3CA were found in 3 of 11 ITPNs but not in IPMNs (P = 0.005; Fisher exact test). In contrast, mutations in KRAS were found in none of the ITPNs but were found in 26 of the 50 IPMNs (P = 0.001; Fisher exact test). PIK3CA mutations were associated with strong expression of phosphorylated AKT (P AKT was apparent in most ITPNs but only in a few IPMNs (P SMAD4, and CTNNB1 were not statistically different between these neoplasms. Mutations in PIK3CA and the expression of phosphorylated AKT were not associated with age, sex, tissue invasion, and patients' prognosis in ITPNs. These results indicate that activation of the phosphatidylinositol 3-kinase pathway may play a crucial role in ITPNs but not in IPMNs. In contrast, the mutation in KRAS seems to play a major role in IPMNs but not in ITPNs. The activated phosphatidylinositol 3-kinase pathway may be a potential target for molecular diagnosis and therapy of ITPNs.

UCN sources at external beams of thermal neutrons. An example of PIK reactor

International Nuclear Information System (INIS)

Lychagin, E.V.; Mityukhlyaev, V.A.; Muzychka, A.Yu.; Nekhaev, G.V.; Nesvizhevsky, V.V.; Onegin, M.S.; Sharapov, E.I.; Strelkov, A.V.

2016-01-01

We consider ultracold neutron (UCN) sources based on a new method of UCN production in superfluid helium ("4He). The PIK reactor is chosen as a perspective example of application of this idea, which consists of installing "4He UCN source in the beam of thermal or cold neutrons and surrounding the source with moderator-reflector, which plays the role of cold neutron (CN) source feeding the UCN source. CN flux in the source can be several times larger than the incident flux, due to multiple neutron reflections from the moderator–reflector. We show that such a source at the PIK reactor would provide an order of magnitude larger density and production rate than an analogous source at the ILL reactor. We estimate parameters of "4He source with solid methane (CH_4) or/and liquid deuterium (D_2) moderator–reflector. We show that such a source with CH_4 moderator–reflector at the PIK reactor would provide the UCN density of ~1·10"5 cm"−"3, and the UCN production rate of ~2·10"7 s"−"1. These values are respectively 1000 and 20 times larger than those for the most intense UCN user source. The UCN density in a source with D_2 moderator-reflector would reach the value of ~2·10"5 cm"−"3, and the UCN production rate would be equal ~8·10"7 s"−"1. Installation of such a source in a beam of CNs would slightly increase the density and production rate.

BRAF, KRAS and PIK3CA mutations in colorectal serrated polyps and cancer: Primary or secondary genetic events in colorectal carcinogenesis?

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Schmitt Fernando

2008-09-01

Full Text Available Abstract Background BRAF, KRAS and PIK3CA mutations are frequently found in sporadic colorectal cancer (CRC. In contrast to KRAS and PIK3CA mutations, BRAF mutations are associated with tumours harbouring CpG Island methylation phenotype (CIMP, MLH1 methylation and microsatellite instability (MSI. We aimed at determine the frequency of KRAS, BRAF and PIK3CA mutations in the process of colorectal tumourigenesis using a series of colorectal polyps and carcinomas. In the series of polyps CIMP, MLH1 methylation and MSI were also studied. Methods Mutation analyses were performed by PCR/sequencing. Bisulfite treated DNA was used to study CIMP and MLH1 methylation. MSI was detected by pentaplex PCR and Genescan analysis of quasimonomorphic mononucleotide repeats. Chi Square test and Fisher's Exact test were used to perform association studies. Results KRAS, PIK3CA or BRAF occur in 71% of polyps and were mutually exclusive. KRAS mutations occur in 35% of polyps. PIK3CA was found in one of the polyps. V600E BRAF mutations occur in 29% of cases, all of them classified as serrated adenoma. CIMP phenotype occurred in 25% of the polyps and all were mutated for BRAF. MLH1 methylation was not detected and all the polyps were microsatellite stable. The comparison between the frequency of oncogenic mutations in polyps and CRC (MSI and MSS lead us to demonstrate that KRAS and PIK3CA are likely to precede both types of CRC. BRAF mutations are likely to precede MSI carcinomas since the frequency found in serrated polyps is similar to what is found in MSI CRC (P = 0.9112, but statistically different from what is found in microsatellite stable (MSS tumours (P = 0.0191. Conclusion Our results show that BRAF, KRAS and PIK3CA mutations occur prior to malignant transformation demonstrating that these oncogenic alterations are primary genetic events in colorectal carcinogenesis. Further, we show that BRAF mutations occur in association with CIMP phenotype in colorectal

BRAF, KRAS and PIK3CA mutations in colorectal serrated polyps and cancer: Primary or secondary genetic events in colorectal carcinogenesis?

International Nuclear Information System (INIS)

Velho, Sérgia; Moutinho, Cátia; Cirnes, Luís; Albuquerque, Cristina; Hamelin, Richard; Schmitt, Fernando; Carneiro, Fátima; Oliveira, Carla; Seruca, Raquel

2008-01-01

BRAF, KRAS and PIK3CA mutations are frequently found in sporadic colorectal cancer (CRC). In contrast to KRAS and PIK3CA mutations, BRAF mutations are associated with tumours harbouring CpG Island methylation phenotype (CIMP), MLH1 methylation and microsatellite instability (MSI). We aimed at determine the frequency of KRAS, BRAF and PIK3CA mutations in the process of colorectal tumourigenesis using a series of colorectal polyps and carcinomas. In the series of polyps CIMP, MLH1 methylation and MSI were also studied. Mutation analyses were performed by PCR/sequencing. Bisulfite treated DNA was used to study CIMP and MLH1 methylation. MSI was detected by pentaplex PCR and Genescan analysis of quasimonomorphic mononucleotide repeats. Chi Square test and Fisher's Exact test were used to perform association studies. KRAS, PIK3CA or BRAF occur in 71% of polyps and were mutually exclusive. KRAS mutations occur in 35% of polyps. PIK3CA was found in one of the polyps. V600E BRAF mutations occur in 29% of cases, all of them classified as serrated adenoma. CIMP phenotype occurred in 25% of the polyps and all were mutated for BRAF. MLH1 methylation was not detected and all the polyps were microsatellite stable. The comparison between the frequency of oncogenic mutations in polyps and CRC (MSI and MSS) lead us to demonstrate that KRAS and PIK3CA are likely to precede both types of CRC. BRAF mutations are likely to precede MSI carcinomas since the frequency found in serrated polyps is similar to what is found in MSI CRC (P = 0.9112), but statistically different from what is found in microsatellite stable (MSS) tumours (P = 0.0191). Our results show that BRAF, KRAS and PIK3CA mutations occur prior to malignant transformation demonstrating that these oncogenic alterations are primary genetic events in colorectal carcinogenesis. Further, we show that BRAF mutations occur in association with CIMP phenotype in colorectal serrated polyps and verified that colorectal serrated

SAR405, a PIK3C3/Vps34 inhibitor that prevents autophagy and synergizes with MTOR inhibition in tumor cells.

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Pasquier, Benoit

2015-04-03

Autophagy plays an important role in cancer and it has been suggested that it functions not only as a tumor suppressor pathway to prevent tumor initiation, but also as a prosurvival pathway that helps tumor cells endure metabolic stress and resist death triggered by chemotherapeutic agents. We recently described the discovery of inhibitors of PIK3C3/Vps34 (phosphatidylinositol 3-kinase, catalytic subunit type 3), the lipid kinase component of the class III phosphatidylinositol 3-kinase (PtdIns3K). This PtdIns3K isoform has attracted significant attention in recent years because of its role in autophagy. Following chemical optimization we identified SAR405, a low molecular mass kinase inhibitor of PIK3C3, highly potent and selective with regard to other lipid and protein kinases. We demonstrated that inhibiting the catalytic activity of PIK3C3 disrupts vesicle trafficking from late endosomes to lysosomes. SAR405 treatment also inhibits autophagy induced either by starvation or by MTOR (mechanistic target of rapamycin) inhibition. Finally our results show that combining SAR405 with everolimus, the FDA-approved MTOR inhibitor, results in a significant synergy on the reduction of cell proliferation using renal tumor cells. This result indicates a potential therapeutic application for PIK3C3 inhibitors in cancer.

Alterations in PTEN and PIK3CA in colorectal cancers in the EPIC Norfolk study: associations with clinicopathological and dietary factors

International Nuclear Information System (INIS)

Naguib, Adam; Arends, Mark J; Cooke, James C; Happerfield, Lisa; Kerr, Lucy; Gay, Laura J; Luben, Robert N; Ball, Richard Y; Mitrou, Panagiota N; McTaggart, Alison

2011-01-01

The PTEN tumour suppressor gene and PIK3CA proto-oncogene encode proteins which contribute to regulation and propagation of signal transduction through the PI3K/AKT signalling pathway. This study investigates the prevalence of loss of PTEN expression and mutations in both PTEN and PIK3CA in colorectal cancers (CRC) and their associations with tumour clinicopathological features, lifestyle factors and dietary consumptions. 186 adenocarcinomas and 16 adenomas from the EPIC Norfolk study were tested for PTEN and PIK3CA mutations by DNA sequencing and PTEN expression changes by immunohistochemistry. Dietary and lifestyle data were collected prospectively using seven day food diaries and lifestyle questionnaires. Mutations in exons 7 and 8 of PTEN were observed in 2.2% of CRC and PTEN loss of expression was identified in 34.9% CRC. Negative PTEN expression was associated with lower blood low-density lipoprotein concentrations (p = 0.05). PIK3CA mutations were observed in 7% of cancers and were more frequent in CRCs in females (p = 0.04). Analysis of dietary intakes demonstrated no link between PTEN expression status and any specific dietary factor. PTEN expression negative, proximal CRC were of more advanced Dukes' stage (p = 0.02) and poor differentiation (p < 0.01). Testing of the prevalence of PIK3CA mutations and loss of PTEN expression demonstrated that these two events were independent (p = 0.55). These data demonstrated the frequent occurrence (34.9%) of PTEN loss of expression in colorectal cancers, for which gene mutations do not appear to be the main cause. Furthermore, dietary factors are not associated with loss of PTEN expression. PTEN expression negative CRC were not homogenous, as proximal cancers were associated with a more advanced Dukes' stage and poor differentiation, whereas distal cancers were associated with earlier Dukes' stage

Relative quantification of PIK3CA gene expression level in fine-needle aspiration biopsy thyroid specimens collected from patients with papillary thyroid carcinoma and non-toxic goitre by real-time RT-PCR

Directory of Open Access Journals (Sweden)

Wojciechowska-Durczyńska Katarzyna

2010-08-01

Full Text Available Abstract Background Recent studies have shown that the phosphatidylinositol 3-kinase (PI3K signaling pathway is important regulator of many cellular events, including apoptosis, proliferation and motility. PI3K pathway alterations (PIK3CA gene mutations and/or amplification have been observed in various human tumours. In the majority of diagnosed cases, mutations are localized in one of the three "hot spots" in the gene, responsible for coding catalytic subunit α of class I PI3K (PIK3CA. Mutations and amplification of PIK3CA gene are characteristic for thyroid cancer, as well. Methods The aim of our study was to examine a gene expression level of PIK3CA in fine-needle aspiration biopsy (FNAB thyroid specimens in two types of thyroid lesions, papillary thyroid carcinoma (PTC and non-toxic goitre (NTG. Following conventional cytological examination, 42 thyroid FNAB specimens, received from patients with PTC (n = 20 and NTG (n = 22, were quantitatively evaluated regarding PIK3CA expression level by real-time PCR in the ABI PRISM® 7500 Sequence Detection System. Results Significantly higher expression level (RQ of PIK3CA in PTC group has been noted in comparison with NTG group (p Conclusion These observations may suggest role of PIK3CA alterations in PTC carcinogenesis.

Characterisation of mutations of the phosphoinositide-3-kinase regulatory subunit, PIK3R2, in perisylvian polymicrogyria: a next-generation sequencing study.

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Mirzaa, Ghayda M; Conti, Valerio; Timms, Andrew E; Smyser, Christopher D; Ahmed, Sarah; Carter, Melissa; Barnett, Sarah; Hufnagel, Robert B; Goldstein, Amy; Narumi-Kishimoto, Yoko; Olds, Carissa; Collins, Sarah; Johnston, Kathreen; Deleuze, Jean-François; Nitschké, Patrick; Friend, Kathryn; Harris, Catharine; Goetsch, Allison; Martin, Beth; Boyle, Evan August; Parrini, Elena; Mei, Davide; Tattini, Lorenzo; Slavotinek, Anne; Blair, Ed; Barnett, Christopher; Shendure, Jay; Chelly, Jamel; Dobyns, William B; Guerrini, Renzo

2015-12-01

Bilateral perisylvian polymicrogyria (BPP), the most common form of regional polymicrogyria, causes the congenital bilateral perisylvian syndrome, featuring oromotor dysfunction, cognitive impairment, and epilepsy. The causes of BPP are heterogeneous, but only a few genetic causes have been reported. The aim of this study was to identify additional genetic causes of BPP and characterise their frequency in this population. Children (aged ≤18 years) with polymicrogyria were enrolled into our research programme from July, 1980, to October, 2015, at two centres (Florence, Italy, and Seattle, WA, USA). We obtained samples (blood and saliva) throughout this period at both centres and did whole-exome sequencing on DNA from eight trios (two parents and one affected child) with BPP in 2014. After the identification of mosaic PIK3R2 mutations in two of these eight children, we performed targeted screening of PIK3R2 by two methods in a cohort of 118 children with BPP. First, we performed targeted sequencing of the entire PIK3R2 gene by single molecule molecular inversion probes (smMIPs) on 38 patients with BPP with normal to large head size. Second, we did amplicon sequencing of the recurrent PIK3R2 mutation (Gly373Arg) in 80 children with various types of polymicrogyria including BPP. One additional patient had clinical whole-exome sequencing done independently, and was included in this study because of the phenotypic similarity to our cohort. We identified a mosaic mutation (Gly373Arg) in a regulatory subunit of the PI3K-AKT-mTOR pathway, PIK3R2, in two children with BPP. Of the 38 patients with BPP and normal to large head size who underwent targeted next-generation sequencing by smMIPs, we identified constitutional and mosaic PIK3R2 mutations in 17 additional children. In parallel, one patient had the recurrent PIK3R2 mutation identified by clinical whole-exome sequencing. Seven of these 20 patients had BPP alone, and 13 had BPP in association with features of the

Breast Cancer Heterogeneity Examined by High-Sensitivity Quantification of PIK3CA, KRAS, HRAS, and BRAF Mutations in Normal Breast and Ductal Carcinomas

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Meagan B. Myers

2016-04-01

Full Text Available Mutant cancer subpopulations have the potential to derail durable patient responses to molecularly targeted cancer therapeutics, yet the prevalence and size of such subpopulations are largely unexplored. We employed the sensitive and quantitative Allele-specific Competitive Blocker PCR approach to characterize mutant cancer subpopulations in ductal carcinomas (DCs, examining five specific hotspot point mutations (PIK3CA H1047R, KRAS G12D, KRAS G12V, HRAS G12D, and BRAF V600E. As an approach to aid interpretation of the DC results, the mutations were also quantified in normal breast tissue. Overall, the mutations were prevalent in normal breast and DCs, with 9/9 DCs having measureable levels of at least three of the five mutations. HRAS G12D was significantly increased in DCs as compared to normal breast. The most frequent point mutation reported in DC by DNA sequencing, PIK3CA H1047R, was detected in all normal breast tissue and DC samples and was present at remarkably high levels (mutant fractions of 1.1 × 10−3 to 4.6 × 10−2 in 4/10 normal breast samples. In normal breast tissue samples, PIK3CA mutation levels were positively correlated with age. However, the PIK3CA H1047R mutant fraction distributions for normal breast tissues and DCs were similar. The results suggest PIK3CA H1047R mutant cells have a selective advantage in breast, contribute to breast cancer susceptibility, and drive tumor progression during breast carcinogenesis, even when present as only a subpopulation of tumor cells.

Characterization of mutations of the phosphoinositide-3-kinase regulatory subunit, PIK3R2, in perisylvian polymicrogyria: a next generation sequencing study

Science.gov (United States)

Mirzaa, Ghayda; Conti, Valerio; Timms, Andrew E.; Smyser, Christopher D.; Ahmed, Sarah; Carter, Melissa; Barnett, Sarah; Hufnagel, Robert B.; Goldstein, Amy; Narumi-Kishimoto, Yoko; Olds, Carissa; Collins, Sarah; Johnston, Kathreen; Deleuze, Jean-François; Nitschké, Patrick; Friend, Kathryn; Harris, Catharine; Goetsch, Allison; Martin, Beth; Boyle, Evan August; Parrini, Elena; Mei, Davide; Tattini, Lorenzo; Slavotinek, Anne; Blair, Ed; Barnett, Christopher; Shendure, Jay; Chelly, Jamel; Dobyns, William B.; Guerrini, Renzo

2015-01-01

SUMMARY Background Bilateral perisylvian polymicrogyria (BPP), the most common form of regional polymicrogyria, causes the congenital bilateral perisylvian syndrome, featuring oromotor dysfunction, cognitive impairment and epilepsy. BPP is etiologically heterogeneous, but only a few genetic causes have been reported. The aim of this study was to identify additional genetic etiologies of BPP and delineate their frequency in this patient population. Methods We performed child-parent (trio)-based whole exome sequencing (WES) on eight children with BPP. Following the identification of mosaic PIK3R2 mutations in two of these eight children, we performed targeted screening of PIK3R2 in a cohort of 118 children with BPP who were ascertained from 1980 until 2015 using two methods. First, we performed targeted sequencing of the entire PIK3R2 gene by single molecule molecular inversion probes (smMIPs) on 38 patients with BPP with normal-large head size. Second, we performed amplicon sequencing of the recurrent PIK3R2 mutation (p.Gly373Arg) on 80 children with various types of polymicrogyria including BPP. One additional patient underwent clinical WES independently, and was included in this study given the phenotypic similarity to our cohort. All patients included in this study were children (BPP. Of the 38 patients with BPP and normal-large head size who underwent targeted next generation sequencing by smMIPs, we identified constitutional and mosaic PIK3R2 mutations in 17 additional children. In parallel, one patient was found to have the recurrent PIK3R2 mutation by clinical WES. Seven patients had BPP alone, and 13 had BPP in association with features of the megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH). Nineteen patients had the same mutation (Gly373Arg), and one had a nearby missense mutation (p.Lys376Glu). Across the entire cohort, mutations were constitutional in 12 and mosaic in eight patients. Among mosaic patients, we observed substantial

The status of the PIK reactor

Energy Technology Data Exchange (ETDEWEB)

Petrov, Yu V [Academy of Sciences of Russia, Petersburg Nuclear Physics Institute, Gatchina, St. Petersburg (Russian Federation)

1992-07-01

This report describes the 100 MW research reactor PIK which is now under construction. The thermal neutron flux in the heavy water reflector exceeds 10{sup 15} cm{sup -2}s{sup -1}; in the light water trap, it is about 4{center_dot}10{sup 15} cm{sup -2}s{sup -1}. The replaceable core vessel allows to vary the parameters of the core over a wide range. The reactor provides sources of hot, cold and ultracold neutrons for 10 horizontal, 6 inclined neutron beams, and 8 neutron guides. At the ends of the beam tubes, the neutron flux is 10{sup 10} - 10{sup 11} cm{sup -2}s{sup -1}. The flux of the long wave neutrons exceeds 10{sup 9} cm{sup -2}s{sup -1}. To ensure precise measurements, the experimental hall is protected against vibrations. The project meets all modern safety requirements. The calculated parameters of the reactor were verified using a full-scale mock-up. Seventy percent of the reactor construction and installation were completed in the beginning of 1992. (author)

PRKCI negatively regulates autophagy via PIK3CA/AKT–MTOR signaling

Energy Technology Data Exchange (ETDEWEB)

Qu, Liujing; Li, Ge; Xia, Dan; Hongdu, Beiqi; Xu, Chentong; Lin, Xin [Key Laboratory of Medical Immunology, Ministry of Health, Peking University Health Sciences Center, Beijing (China); Peking University Center for Human Disease Genomics, Peking University, Beijing (China); Chen, Yingyu, E-mail: yingyu_chen@bjmu.edu.cn [Key Laboratory of Medical Immunology, Ministry of Health, Peking University Health Sciences Center, Beijing (China); Peking University Center for Human Disease Genomics, Peking University, Beijing (China)

2016-02-05

The atypical protein kinase C isoform PRKC iota (PRKCI) plays a key role in cell proliferation, differentiation, and carcinogenesis, and it has been shown to be a human oncogene. Here, we show that PRKCI overexpression in U2OS cells impaired functional autophagy in normal or cell stress conditions, as characterized by decreased levels of light chain 3B-II protein (LC3B-II) and weakened degradation of endogenous and exogenous autophagic substrates. Conversely, PRKCI knockdown by small interference RNA resulted in opposite effects. Additionally, we identified two novel PRKCI mutants, PRKCI{sup L485M} and PRKCI{sup P560R}, which induced autophagy and exhibited dominant negative effects. Further studies indicated that PRKCI knockdown–mediated autophagy was associated with the inactivation of phosphatidylinositol 3-kinase alpha/AKT–mammalian target of rapamycin (PIK3CA/AKT–MTOR) signaling. These data underscore the importance of PRKCI in the regulation of autophagy. Moreover, the finding may be useful in treating PRKCI-overexpressing carcinomas that are characterized by increased levels of autophagy. - Highlights: • The atypical protein kinase C iota isoform (PRKCI) is a human oncogene. • PRKCI overexpression impairs functional autophagy in U2OS cells. • It reduces LC3B-II levels and weakens SQSTM1 and polyQ80 aggregate degradation. • PRKCI knockdown has the opposite effect. • The effect of PRKCI knockdown is related to PIK3CA/AKT–MTOR signaling inactivation.

The Potsdam Parallel Ice Sheet Model (PISM-PIK) - Part 1: Model description

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Winkelmann, R.; Martin, M. A.; Haseloff, M.; Albrecht, T.; Bueler, E.; Khroulev, C.; Levermann, A.

2011-09-01

We present the Potsdam Parallel Ice Sheet Model (PISM-PIK), developed at the Potsdam Institute for Climate Impact Research to be used for simulations of large-scale ice sheet-shelf systems. It is derived from the Parallel Ice Sheet Model (Bueler and Brown, 2009). Velocities are calculated by superposition of two shallow stress balance approximations within the entire ice covered region: the shallow ice approximation (SIA) is dominant in grounded regions and accounts for shear deformation parallel to the geoid. The plug-flow type shallow shelf approximation (SSA) dominates the velocity field in ice shelf regions and serves as a basal sliding velocity in grounded regions. Ice streams can be identified diagnostically as regions with a significant contribution of membrane stresses to the local momentum balance. All lateral boundaries in PISM-PIK are free to evolve, including the grounding line and ice fronts. Ice shelf margins in particular are modeled using Neumann boundary conditions for the SSA equations, reflecting a hydrostatic stress imbalance along the vertical calving face. The ice front position is modeled using a subgrid-scale representation of calving front motion (Albrecht et al., 2011) and a physically-motivated calving law based on horizontal spreading rates. The model is tested in experiments from the Marine Ice Sheet Model Intercomparison Project (MISMIP). A dynamic equilibrium simulation of Antarctica under present-day conditions is presented in Martin et al. (2011).

Ernst Julius Öpik's (1916) note on the theory of explosion cratering on the Moon's surface—The complex case of a long-overlooked benchmark paper

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Racki, Grzegorz; Koeberl, Christian; Viik, Tõnu; Jagt-Yazykova, Elena A.; Jagt, John W. M.

2014-10-01

High-velocity impact as a common phenomenon in planetary evolution was ignored until well into the twentieth century, mostly because of inadequate understanding of cratering processes. An eight-page note, published in Russian by the young Ernst Julius Öpik, a great Estonian astronomer, was among the key selenological papers, but due to the language barrier, it was barely known and mostly incorrectly cited. This particular paper is here intended to serve as an explanatory supplement to an English translation of Öpik's article, but also to document an early stage in our understanding of cratering. First, we outline the historical-biographical background of this benchmark paper, and second, a comprehensive discussion of its merits is presented, from past and present perspectives alike. In his theoretical research, Öpik analyzed the explosive formation of craters numerically, albeit in a very simple way. For the first time, he approximated relationships among minimal meteorite size, impact energy, and crater diameter; this scaling focused solely on the gravitational energy of excavating the crater (a "useful" working approach). This initial physical model, with a rational mechanical basis, was developed in a series of papers up to 1961. Öpik should certainly be viewed as the founder of the numerical simulation approach in planetary sciences. In addition, the present note also briefly describes Nikolai A. Morozov as a remarkable man, a forgotten Russian scientist and, surprisingly, the true initiator of Öpik's explosive impact theory. In fact, already between 1909 and 1911, Morozov probably was the first to consider conclusively that explosion craters would be circular, bowl-shaped depressions even when formed under different impact angles.

PIK3CA-associated developmental disorders exhibit distinct classes of mutations with variable expression and tissue distribution

NARCIS (Netherlands)

Mirzaa, Ghayda; Timms, Andrew E.; Conti, Valerio; Boyle, Evan August; Girisha, Katta M.; Martin, Beth; Kircher, Martin; Olds, Carissa; Juusola, Jane; Collins, Sarah; Park, Kaylee; Carter, Melissa; Glass, Ian; Krägeloh-Mann, Inge; Chitayat, David; Parikh, Aditi Shah; Bradshaw, Rachael; Torti, Erin; Braddock, Stephen; Burke, Leah; Ghedia, Sondhya; Stephan, Mark; Stewart, Fiona; Prasad, Chitra; Napier, Melanie; Saitta, Sulagna; Straussberg, Rachel; Gabbett, Michael; O'Connor, Bridget C.; Keegan, Catherine E.; Yin, Lim Jiin; Lai, Angeline Hwei Meeng; Martin, Nicole; McKinnon, Margaret; Addor, Marie-Claude; Boccuto, Luigi; Schwartz, Charles E.; Lanoel, Agustina; Conway, Robert L.; Devriendt, Koenraad; Tatton-Brown, Katrina; Pierpont, Mary Ella; Painter, Michael; Worgan, Lisa; Reggin, James; Hennekam, Raoul; Tsuchiya, Karen; Pritchard, Colin C.; Aracena, Mariana; Gripp, Karen W.; Cordisco, Maria; Esch, Hilde Van; Garavelli, Livia; Curry, Cynthia; Goriely, Anne; Kayserilli, Hulya; Shendure, Jay; Graham, John; Guerrini, Renzo; Dobyns, William B.

2016-01-01

Mosaicism is increasingly recognized as a cause of developmental disorders with the advent of next-generation sequencing (NGS). Mosaic mutations of PIK3CA have been associated with the widest spectrum of phenotypes associated with overgrowth and vascular malformations. We performed targeted NGS

Mass-spectrometer of knock-on nuclei for reactor 'Pik'

International Nuclear Information System (INIS)

Begzhanov, P.B.; Nazarov, A.G.; Petrov, G.A.; Pikul', V.P.

1999-01-01

For reactor 'Pik' (that is being built in St. Petersburg Institute of Nuclear Physics) there was designed a universal two shoulder mass-spectrometer for non-decelerated fission products (FP) of nuclei. The spectrometer helps to obtain different values of linear magnification, dispersion, aberration coefficients and transmission without making structural changes in the device. To separate FP for one shoulder of spectrometer we chose ion-optical scheme (IOS) consisting of three electrostatic analyzers and three-sectional magnet 'JOSEF' that had high dispersion by masses at small deflection radius. IOS calculations of mass-spectrometer were performed with the help of program TRANSVOL (transfer of phase volume) designed basing on TRIO program. The program allows calculating of complete IOS transmission with taking into account elements aperture and beam officering

Two design aspects connected with the safety of the PIK reactor presently under construction

International Nuclear Information System (INIS)

Gostev, V.V.; Zakharov, A.S.; Konoplev, K.A.; Levandovskii, N.V.; Ploshchanskii, L.M.; Smolsky, S.L.

1993-01-01

The PIK reactor is designed for physical research with neutron beams and sample irradiation. In the central trap the thermal neutrons flux is 4x10 15 n/cm 2 s. The reactor power is 100 MW, the thermal neutron flux in the reflector at the maximum of distribution is 1x10 15 n/cm 2 s. The core with a high uranium concentration of 600 g/l is light water-cooled, heavy water being used in the reflector. The Chernobyl disaster happened at the time of equipment installation at the PIK. The code revision, a change of the authors ideas about the safety, and a change of public attitude towards nuclear installations resulted in a stopping of construction and project revision. Reconstruction project has led to a change of all safety systems and involved in various degrees all essential reactor systems. The construction is presently resumed in spite of economic difficulties in Russia. The reactor was inspected by experts from a number of European countries, USA, and European Commission delegated by their governments to prepare a report on whether supporting the construction to its completion would be reasonable. In the course of inspection the experts from USA and EU expressed doubts concerning two systems, namely, the containment and scram. These two points are discussed in the present paper. Three type of containments are proposed and an analysis of their efficiency is presented. The PIK reactor is controlled by eight rods in the heavy-water reflector -and an absorbing cylinder at the boundary between the core and the central light-water neutron trap. The rods are used for emergency protection and reactor start-up. The central control cylinder called here the shutter serves several functions, namely, as scram, automatic control, and burnup compensation. The delay time before the onset of negative reactivity is 1.05 sec for rods and 0.25 sec for the shutter

microRNA 126 inhibits the transition of endothelial progenitor cells to mesenchymal cells via the PIK3R2-PI3K/Akt signalling pathway.

Science.gov (United States)

Zhang, Junfeng; Zhang, Zongqi; Zhang, David Y; Zhu, Jianbing; Zhang, Tiantian; Wang, Changqian

2013-01-01

Endothelial progenitor cells (EPCs) are capable of proliferating and differentiating into mature endothelial cells, and they have been considered as potential candidates for coronary heart disease therapy. However, the transition of EPCs to mesenchymal cells is not fully understood. This study aimed to explore the role of microRNA 126 (miR-126) in the endothelial-to-mesenchymal transition (EndMT) induced by transforming growth factor beta 1 (TGFβ1). EndMT of rat bone marrow-derived EPCs was induced by TGFβ1 (5 ng/mL) for 7 days. miR-126 expression was depressed in the process of EPC EndMT. The luciferase reporter assay showed that the PI3K regulatory subunit p85 beta (PIK3R2) was a direct target of miR-126 in EPCs. Overexpression of miR-126 by a lentiviral vector (lenti-miR-126) was found to downregulate the mRNA expression of mesenchymal cell markers (α-SMA, sm22-a, and myocardin) and to maintain the mRNA expression of progenitor cell markers (CD34, CD133). In the cellular process of EndMT, there was an increase in the protein expression of PIK3R2 and the nuclear transcription factors FoxO3 and Smad4; PI3K and phosphor-Akt expression decreased, a change that was reversed markedly by overexpression of miR-126. Furthermore, knockdown of PIK3R2 gene expression level showed reversed morphological changes of the EPCs treated with TGFβ1, thereby giving the evidence that PIK3R2 is the target gene of miR-126 during EndMT process. These results show that miR-126 targets PIK3R2 to inhibit EPC EndMT and that this process involves regulation of the PI3K/Akt signalling pathway. miR-126 has the potential to be used as a biomarker for the early diagnosis of intimal hyperplasia in cardiovascular disease and can even be a therapeutic tool for treating cardiovascular diseases mediated by the EndMT process.

The Potsdam Parallel Ice Sheet Model (PISM-PIK – Part 1: Model description

Directory of Open Access Journals (Sweden)

R. Winkelmann

2011-09-01

Full Text Available We present the Potsdam Parallel Ice Sheet Model (PISM-PIK, developed at the Potsdam Institute for Climate Impact Research to be used for simulations of large-scale ice sheet-shelf systems. It is derived from the Parallel Ice Sheet Model (Bueler and Brown, 2009. Velocities are calculated by superposition of two shallow stress balance approximations within the entire ice covered region: the shallow ice approximation (SIA is dominant in grounded regions and accounts for shear deformation parallel to the geoid. The plug-flow type shallow shelf approximation (SSA dominates the velocity field in ice shelf regions and serves as a basal sliding velocity in grounded regions. Ice streams can be identified diagnostically as regions with a significant contribution of membrane stresses to the local momentum balance. All lateral boundaries in PISM-PIK are free to evolve, including the grounding line and ice fronts. Ice shelf margins in particular are modeled using Neumann boundary conditions for the SSA equations, reflecting a hydrostatic stress imbalance along the vertical calving face. The ice front position is modeled using a subgrid-scale representation of calving front motion (Albrecht et al., 2011 and a physically-motivated calving law based on horizontal spreading rates. The model is tested in experiments from the Marine Ice Sheet Model Intercomparison Project (MISMIP. A dynamic equilibrium simulation of Antarctica under present-day conditions is presented in Martin et al. (2011.

The dual PI3K/mTOR inhibitor NVP-BEZ235 induces tumor regression in a genetically engineered mouse model of PIK3CA wild-type colorectal cancer.

Directory of Open Access Journals (Sweden)

Jatin Roper

Full Text Available To examine the in vitro and in vivo efficacy of the dual PI3K/mTOR inhibitor NVP-BEZ235 in treatment of PIK3CA wild-type colorectal cancer (CRC.PIK3CA mutant and wild-type human CRC cell lines were treated in vitro with NVP-BEZ235, and the resulting effects on proliferation, apoptosis, and signaling were assessed. Colonic tumors from a genetically engineered mouse (GEM model for sporadic wild-type PIK3CA CRC were treated in vivo with NVP-BEZ235. The resulting effects on macroscopic tumor growth/regression, proliferation, apoptosis, angiogenesis, and signaling were examined.In vitro treatment of CRC cell lines with NVP-BEZ235 resulted in transient PI3K blockade, sustained decreases in mTORC1/mTORC2 signaling, and a corresponding decrease in cell viability (median IC(50 = 9.0-14.3 nM. Similar effects were seen in paired isogenic CRC cell lines that differed only in the presence or absence of an activating PIK3CA mutant allele. In vivo treatment of colonic tumor-bearing mice with NVP-BEZ235 resulted in transient PI3K inhibition and sustained blockade of mTORC1/mTORC2 signaling. Longitudinal tumor surveillance by optical colonoscopy demonstrated a 97% increase in tumor size in control mice (p = 0.01 vs. a 43% decrease (p = 0.008 in treated mice. Ex vivo analysis of the NVP-BEZ235-treated tumors demonstrated a 56% decrease in proliferation (p = 0.003, no effects on apoptosis, and a 75% reduction in angiogenesis (p = 0.013.These studies provide the preclinical rationale for studies examining the efficacy of the dual PI3K/mTOR inhibitor NVP-BEZ235 in treatment of PIK3CA wild-type CRC.

microRNA 126 inhibits the transition of endothelial progenitor cells to mesenchymal cells via the PIK3R2-PI3K/Akt signalling pathway.

Directory of Open Access Journals (Sweden)

Junfeng Zhang

Full Text Available AIMS: Endothelial progenitor cells (EPCs are capable of proliferating and differentiating into mature endothelial cells, and they have been considered as potential candidates for coronary heart disease therapy. However, the transition of EPCs to mesenchymal cells is not fully understood. This study aimed to explore the role of microRNA 126 (miR-126 in the endothelial-to-mesenchymal transition (EndMT induced by transforming growth factor beta 1 (TGFβ1. METHODS AND RESULTS: EndMT of rat bone marrow-derived EPCs was induced by TGFβ1 (5 ng/mL for 7 days. miR-126 expression was depressed in the process of EPC EndMT. The luciferase reporter assay showed that the PI3K regulatory subunit p85 beta (PIK3R2 was a direct target of miR-126 in EPCs. Overexpression of miR-126 by a lentiviral vector (lenti-miR-126 was found to downregulate the mRNA expression of mesenchymal cell markers (α-SMA, sm22-a, and myocardin and to maintain the mRNA expression of progenitor cell markers (CD34, CD133. In the cellular process of EndMT, there was an increase in the protein expression of PIK3R2 and the nuclear transcription factors FoxO3 and Smad4; PI3K and phosphor-Akt expression decreased, a change that was reversed markedly by overexpression of miR-126. Furthermore, knockdown of PIK3R2 gene expression level showed reversed morphological changes of the EPCs treated with TGFβ1, thereby giving the evidence that PIK3R2 is the target gene of miR-126 during EndMT process. CONCLUSIONS: These results show that miR-126 targets PIK3R2 to inhibit EPC EndMT and that this process involves regulation of the PI3K/Akt signalling pathway. miR-126 has the potential to be used as a biomarker for the early diagnosis of intimal hyperplasia in cardiovascular disease and can even be a therapeutic tool for treating cardiovascular diseases mediated by the EndMT process.

Predictive value of K-ras and PIK3CA in non-small cell lung cancer patients treated with EGFR-TKIs: a systemic review and meta-analysis

International Nuclear Information System (INIS)

Chen, Jie-Ying; Cheng, Ya-Nan; Han, Lei; Wei, Feng; Yu, Wen-Wen; Zhang, Xin-Wei; Cao, Shui; Yu, Jin-Pu

2015-01-01

A meta-analysis was performed to augment the insufficient data on the impact of mutative EGFR downstream phosphatidylinositol-3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways on the clinical efficiency of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment of non-small cell lung cancer (NSCLC) patients. Network databases were explored in April, 2015. Papers that investigated the clinical outcomes of NSCLC patients treated with EGFR-TKIs according to the status of K-ras and/or PIK3CA gene mutation were included. A quantitative meta-analysis was conducted using standard statistical methods. Odds ratios (ORs) for objective response rate (ORR) and hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS) were calculated. Mutation in K-ras significantly predicted poor ORR [OR =0.22; 95% confidence interval (CI), 0.13-0.35], shorter PFS (HR =1.56; 95% CI, 1.27-1.92), and shorter OS (HR =1.59; 95% CI, 1.33-1.91) in NSCLC patients treated with EGFR-TKIs. Mutant PIK3CA significantly predicted shorter OS (HR =1.83; 95% CI, 1.05-3.20), showed poor ORR (OR =0.70; 95% CI, 0.22-2.18), and shorter PFS (HR =1.79; 95% CI, 0.91-3.53) in NSCLC patients treated with EGFR-TKIs. K-ras mutation adversely affected the clinical response and survival of NSCLC patients treated with EGFR-TKIs. PIK3CA mutation showed similar trends. In addition to EGFR, adding K-ras and PIK3CA as routine gene biomarkers in clinical genetic analysis is valuable to optimize the effectiveness of EGFR-TKI regimens and identify optimal patients who will benefit from EGFR-TKI treatment

PIK3CA-associated developmental disorders exhibit distinct classes of mutations with variable expression and tissue distribution

OpenAIRE

Mirzaa, Ghayda; Timms, Andrew E.; Conti, Valerio; Boyle, Evan August; Girisha, Katta M.; Martin, Beth; Kircher, Martin; Olds, Carissa; Juusola, Jane; Collins, Sarah; Park, Kaylee; Carter, Melissa; Glass, Ian; Kr?geloh-Mann, Inge; Chitayat, David

2016-01-01

Mosaicism is increasingly recognized as a cause of developmental disorders with the advent of next-generation sequencing (NGS). Mosaic mutations of PIK3CA have been associated with the widest spectrum of phenotypes associated with overgrowth and vascular malformations. We performed targeted NGS using 2 independent deep-coverage methods that utilize molecular inversion probes and amplicon sequencing in a cohort of 241 samples from 181 individuals with brain and/or body overgrowth. We identifie...

Molecular spectrum of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC somatic gene mutations in Arab patients with colorectal cancer: determination of frequency and distribution pattern

Science.gov (United States)

Al-Shamsi, Humaid O.; Jones, Jeremy; Fahmawi, Yazan; Dahbour, Ibrahim; Tabash, Aziz; Abdel-Wahab, Reham; Abousamra, Ahmed O. S.; Shaw, Kenna R.; Xiao, Lianchun; Hassan, Manal M.; Kipp, Benjamin R.; Kopetz, Scott; Soliman, Amr S.; McWilliams, Robert R.; Wolff, Robert A.

2016-01-01

Background The frequency rates of mutations such as KRAS, NRAS, BRAF, and PIK3CA in colorectal cancer (CRC) differ among populations. The aim of this study was to assess mutation frequencies in the Arab population and determine their correlations with certain clinicopathological features. Methods Arab patients from the Arab Gulf region and a population of age- and sex-matched Western patients with CRC whose tumors were evaluated with next-generation sequencing (NGS) were identified and retrospectively reviewed. The mutation rates of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC were recorded, along with clinicopathological features. Other somatic mutation and their rates were also identified. Fisher’s exact test was used to determine the association between mutation status and clinical features. Results A total of 198 cases were identified; 99 Arab patients and 99 Western patients. Fifty-two point seven percent of Arab patients had stage IV disease at initial presentation, 74.2% had left-sided tumors. Eighty-nine point two percent had tubular adenocarcinoma and 10.8% had mucinous adenocarcinoma. The prevalence rates of KRAS, NRAS, BRAF, PIK3CA, TP53, APC, SMAD, FBXW7 mutations in Arab population were 44.4%, 4%, 4%, 13.1%, 52.5%, 27.3%, 2% and 3% respectively. Compared to 48.4%, 4%, 4%, 12.1%, 47.5%, 24.2%, 11.1% and 0% respectively in matched Western population. Associations between these mutations and patient clinicopathological features were not statistically significant. Conclusions This is the first study to report comprehensive hotspot mutations using NGS in Arab patients with CRC. The frequency of KRAS, NRAS, BRAF, TP53, APC and PIK3CA mutations were similar to reported frequencies in Western population except SMAD4 that had a lower frequency and higher frequency of FBXW7 mutation. PMID:28078112

Associations between primary tumor RAS, BRAF and PIK3CA mutation status and metastatic site in patients with chemo-resistant metastatic colorectal cancer

DEFF Research Database (Denmark)

Christensen, Troels Dreier; Palshof, Jesper Andreas; Larsen, Finn Ole

2018-01-01

investigated the association between RAS (KRAS or NRAS), BRAF, PIK3CA mutations and metastatic pattern in patients with metastatic (m) CRC. MATERIAL AND METHODS: This study reviewed Danish biobank and database of patients with mCRC who received cetuximab and irinotecan, independent of RAS mutation status...

PIK3CA mutations enable targeting of a breast tumor dependency through mTOR-mediated MCL-1 translation

OpenAIRE

Anderson, Grace R.; Wardell, Suzanne E.; Cakir, Merve; Crawford, Lorin; Leeds, Jim C.; Nussbaum, Daniel P.; Shankar, Pallavi S.; Soderquist, Ryan S.; Stein, Elizabeth M.; Tingley, Jennifer P.; Winter, Peter S.; Zieser-Misenheimer, Elizabeth K.; Alley, Holly M.; Yllanes, Alexander; Haney, Victoria

2016-01-01

Therapies that efficiently induce apoptosis are likely to be required for durable clinical responses in patients with solid tumors. Using a pharmacological screening approach, we discovered that the combined inhibition of BCL-XL and the mTOR/4E-BP axis results in selective and synergistic induction of apoptosis in cellular and animal models of PIK3CA mutant breast cancers, including triple negative tumors. Mechanistically, inhibition of mTOR/4E-BP suppresses MCL-1 protein translation only in ...

Promoter Variant of PIK3C3 Is Associated with Autoimmunity against Ro and Sm Epitopes in African-American Lupus Patients

Directory of Open Access Journals (Sweden)

Silvia N. Kariuki

2010-01-01

Full Text Available The PIK3C3 locus was implicated in case-case genome-wide association study of systemic lupus erythematosus (SLE which we had performed to detect genes associated with autoantibodies and serum interferon-alpha (IFN-α. Herein, we examine a PIK3C3 promoter variant (rs3813065/-442 C/T in an independent multiancestral cohort of 478 SLE cases and 522 controls. rs3813065 C was strongly associated with the simultaneous presence of both anti-Ro and anti-Sm antibodies in African-American patients [OR=2.24 (1.34–3.73, P=2.0×10−3]. This autoantibody profile was associated with higher serum IFN-α (P=7.6×10−6. In the HapMap Yoruba population, rs3813065 was associated with differential expression of ERAP2 (P=2.0×10−5, which encodes an enzyme involved in MHC class I peptide processing. Thus, rs3813065 C is associated with a particular autoantibody profile and altered expression of an MHC peptide processing enzyme, suggesting that this variant modulates serologic autoimmunity in African-American SLE patients.

Effective lifetime measurements in the $B_{s}^{0} \\rightarrow K^{+}K^{-}$, $B^{0} \\rightarrow K^{+}\\pi^{-}$ and $B_{s}^{0} \\rightarrow \\pi^{+}K^{-}$ decays

CERN Document Server

INSPIRE-00258707; Adeva, B.; Adinolfi, M.; Affolder, A.; Ajaltouni, Z.; Albrecht, J.; Alessio, F.; Alexander, M.; Ali, S.; Alkhazov, G.; Alvarez Cartelle, P.; Alves Jr, A.A.; Amato, S.; Amerio, S.; Amhis, Y.; An, L.; Anderlini, L.; Anderson, J.; Andreassen, R.; Andreotti, M.; Andrews, J.E.; Appleby, R.B.; Aquines Gutierrez, O.; Archilli, F.; Artamonov, A.; Artuso, M.; Aslanides, E.; Auriemma, G.; Baalouch, M.; Bachmann, S.; Back, J.J.; Badalov, A.; Balagura, V.; Baldini, W.; Barlow, R.J.; Barschel, C.; Barsuk, S.; Barter, W.; Batozskaya, V.; Bauer, Th.; Bay, A.; Beddow, J.; Bedeschi, F.; Bediaga, I.; Belogurov, S.; Belous, K.; Belyaev, I.; Ben-Haim, E.; Bencivenni, G.; Benson, S.; Benton, J.; Berezhnoy, A.; Bernet, R.; Bettler, M.O.; van Beuzekom, M.; Bien, A.; Bifani, S.; Bird, T.; Bizzeti, A.; Bjornstad, P.M.; Blake, T.; Blanc, F.; Blouw, J.; Blusk, S.; Bocci, V.; Bondar, A.; Bondar, N.; Bonivento, W.; Borghi, S.; Borgia, A.; Borsato, M.; Bowcock, T.J.V.; Bowen, E.; Bozzi, C.; Brambach, T.; van den Brand, J.; Bressieux, J.; Brett, D.; Britsch, M.; Britton, T.; Brook, N.H.; Brown, H.; Bursche, A.; Busetto, G.; Buytaert, J.; Cadeddu, S.; Calabrese, R.; Calvi, M.; Calvo Gomez, M.; Camboni, A.; Campana, P.; Campora Perez, D.; Carbone, A.; Carboni, G.; Cardinale, R.; Cardini, A.; Carranza-Mejia, H.; Carson, L.; Carvalho Akiba, K.; Casse, G.; Cassina, L.; Garcia, L.Castillo; Cattaneo, M.; Cauet, Ch.; Cenci, R.; Charles, M.; Charpentier, Ph.; Cheung, S.F.; Chiapolini, N.; Chrzaszcz, M.; Ciba, K.; Cid Vidal, X.; Ciezarek, G.; Clarke, P.E.L.; Clemencic, M.; Cliff, H.V.; Closier, J.; Coco, V.; Cogan, J.; Cogneras, E.; Collins, P.; Comerma-Montells, A.; Contu, A.; Cook, A.; Coombes, M.; Coquereau, S.; Corti, G.; Corvo, M.; Counts, I.; Couturier, B.; Cowan, G.A.; Craik, D.C.; Cruz Torres, M.; Cunliffe, S.; Currie, R.; D'Ambrosio, C.; Dalseno, J.; David, P.; David, P.N.Y.; Davis, A.; De Bruyn, K.; De Capua, S.; De Cian, M.; de Miranda, J.M.; De Paula, L.; De Silva, W.; De Simone, P.; Decamp, D.; Deckenhoff, M.; Del Buono, L.; Deleage, N.; Derkach, D.; Deschamps, O.; Dettori, F.; Di Canto, A.; Dijkstra, H.; Donleavy, S.; Dordei, F.; Dorigo, M.; Dosil Suarez, A.; Dossett, D.; Dovbnya, A.; Dupertuis, F.; Durante, P.; Dzhelyadin, R.; Dziurda, A.; Dzyuba, A.; Easo, S.; Egede, U.; Egorychev, V.; Eidelman, S.; Eisenhardt, S.; Eitschberger, U.; Ekelhof, R.; Eklund, L.; El Rifai, I.; Elsasser, Ch.; Esen, S.; Evans, T.; Falabella, A.; Farber, C.; Farinelli, C.; Farley, N.; Farry, S.; Ferguson, D.; Fernandez Albor, V.; Ferreira Rodrigues, F.; Ferro-Luzzi, M.; Filippov, S.; Fiore, M.; Fiorini, M.; Firlej, M.; Fitzpatrick, C.; Fiutowski, T.; Fontana, M.; Fontanelli, F.; Forty, R.; Francisco, O.; Frank, M.; Frei, C.; Frosini, M.; Fu, J.; Furfaro, E.; Gallas Torreira, A.; Galli, D.; Gallorini, S.; Gambetta, S.; Gandelman, M.; Gandini, P.; Gao, Y.; Garofoli, J.; Garra Tico, J.; Garrido, L.; Gaspar, C.; Gauld, R.; Gavardi, L.; Gersabeck, E.; Gersabeck, M.; Gershon, T.; Ghez, Ph.; Gianelle, A.; Giani', S.; Gibson, V.; Giubega, L.; Gligorov, V.V.; Gobel, C.; Golubkov, D.; Golutvin, A.; Gomes, A.; Gordon, H.; Gotti, C.; Grabalosa Gandara, M.; Graciani Diaz, R.; Granado Cardoso, L.A.; Grauges, E.; Graziani, G.; Grecu, A.; Greening, E.; Gregson, S.; Griffith, P.; Grillo, L.; Grunberg, O.; Gui, B.; Gushchin, E.; Guz, Yu.; Gys, T.; Hadjivasiliou, C.; Haefeli, G.; Haen, C.; Haines, S.C.; Hall, S.; Hamilton, B.; Hampson, T.; Han, X.; Hansmann-Menzemer, S.; Harnew, N.; Harnew, S.T.; Harrison, J.; Hartmann, T.; He, J.; Head, T.; Heijne, V.; Hennessy, K.; Henrard, P.; Henry, L.; Hernando Morata, J.A.; van Herwijnen, E.; Hess, M.; Hicheur, A.; Hill, D.; Hoballah, M.; Hombach, C.; Hulsbergen, W.; Hunt, P.; Hussain, N.; Hutchcroft, D.; Hynds, D.; Idzik, M.; Ilten, P.; Jacobsson, R.; Jaeger, A.; Jalocha, J.; Jans, E.; Jaton, P.; Jawahery, A.; Jezabek, M.; Jing, F.; John, M.; Johnson, D.; Jones, C.R.; Joram, C.; Jost, B.; Jurik, N.; Kaballo, M.; Kandybei, S.; Kanso, W.; Karacson, M.; Karbach, T.M.; Kelsey, M.; Kenyon, I.R.; Ketel, T.; Khanji, B.; Khurewathanakul, C.; Klaver, S.; Kochebina, O.; Kolpin, M.; Komarov, I.; Koopman, R.F.; Koppenburg, P.; Korolev, M.; Kozlinskiy, A.; Kravchuk, L.; Kreplin, K.; Kreps, M.; Krocker, G.; Krokovny, P.; Kruse, F.; Kucharczyk, M.; Kudryavtsev, V.; Kurek, K.; Kvaratskheliya, T.; La Thi, V.N.; Lacarrere, D.; Lafferty, G.; Lai, A.; Lambert, D.; Lambert, R.W.; Lanciotti, E.; Lanfranchi, G.; Langenbruch, C.; Langhans, B.; Latham, T.; Lazzeroni, C.; Le Gac, R.; van Leerdam, J.; Lees, J.P.; Lefevre, R.; Leflat, A.; Lefrancois, J.; Leo, S.; Leroy, O.; Lesiak, T.; Leverington, B.; Li, Y.; Liles, M.; Lindner, R.; Linn, C.; Lionetto, F.; Liu, B.; Liu, G.; Lohn, S.; Longstaff, I.; Lopes, J.H.; Lopez-March, N.; Lowdon, P.; Lu, H.; Lucchesi, D.; Luo, H.; Lupato, A.; Luppi, E.; Lupton, O.; Machefert, F.; Machikhiliyan, I.V.; Maciuc, F.; Maev, O.; Malde, S.; Manca, G.; Mancinelli, G.; Manzali, M.; Maratas, J.; Marchand, J.F.; Marconi, U.; Benito, C.Marin; Marino, P.; Marki, R.; Marks, J.; Martellotti, G.; Martens, A.; Martin Sanchez, A.; Martinelli, M.; Martinez Santos, D.; Martinez Vidal, F.; Martins Tostes, D.; Massafferri, A.; Matev, R.; Mathe, Z.; Matteuzzi, C.; Mazurov, A.; McCann, M.; McCarthy, J.; McNab, A.; McNulty, R.; McSkelly, B.; Meadows, B.; Meier, F.; Meissner, M.; Merk, M.; Milanes, D.A.; Minard, M.N.; Moggi, N.; Molina Rodriguez, J.; Monteil, S.; Moran, D.; Morandin, M.; Morawski, P.; Morda, A.; Morello, M.J.; Moron, J.; Mountain, R.; Muheim, F.; Muller, K.; Muresan, R.; Mussini, M.; Muster, B.; Naik, P.; Nakada, T.; Nandakumar, R.; Nasteva, I.; Needham, M.; Neri, N.; Neubert, S.; Neufeld, N.; Neuner, M.; Nguyen, A.D.; Nguyen, T.D.; Nguyen-Mau, C.; Nicol, M.; Niess, V.; Niet, R.; Nikitin, N.; Nikodem, T.; Novoselov, A.; Oblakowska-Mucha, A.; Obraztsov, V.; Oggero, S.; Ogilvy, S.; Okhrimenko, O.; Oldeman, R.; Onderwater, G.; Orlandea, M.; Otalora Goicochea, J.M.; Owen, P.; Oyanguren, A.; Pal, B.K.; Palano, A.; Palombo, F.; Palutan, M.; Panman, J.; Papanestis, A.; Pappagallo, M.; Parkes, C.; Parkinson, C.J.; Passaleva, G.; Patel, G.D.; Patel, M.; Patrignani, C.; Pazos Alvarez, A.; Pearce, A.; Pellegrino, A.; Pepe Altarelli, M.; Perazzini, S.; Perez Trigo, E.; Perret, P.; Perrin-Terrin, M.; Pescatore, L.; Pesen, E.; Petridis, K.; Petrolini, A.; Picatoste Olloqui, E.; Pietrzyk, B.; Pilar, T.; Pinci, D.; Pistone, A.; Playfer, S.; Plo Casasus, M.; Polci, F.; Poluektov, A.; Polycarpo, E.; Popov, A.; Popov, D.; Popovici, B.; Potterat, C.; Powell, A.; Prisciandaro, J.; Pritchard, A.; Prouve, C.; Pugatch, V.; Puig Navarro, A.; Punzi, G.; Qian, W.; Rachwal, B.; Rademacker, J.H.; Rakotomiaramanana, B.; Rama, M.; Rangel, M.S.; Raniuk, I.; Rauschmayr, N.; Raven, G.; Reichert, S.; Reid, M.M.; dos Reis, A.C.; Ricciardi, S.; Richards, A.; Rihl, M.; Rinnert, K.; Rives Molina, V.; Roa Romero, D.A.; Robbe, P.; Rodrigues, A.B.; Rodrigues, E.; Rodriguez Perez, P.; Roiser, S.; Romanovsky, V.; Vidal, A.Romero; Rotondo, M.; Rouvinet, J.; Ruf, T.; Ruffini, F.; Ruiz, H.; Valls, P.Ruiz; Sabatino, G.; Saborido Silva, J.J.; Sagidova, N.; Sail, P.; Saitta, B.; Salustino Guimaraes, V.; Sanchez Mayordomo, C.; Sanmartin Sedes, B.; Santacesaria, R.; Santamarina Rios, C.; Santovetti, E.; Sapunov, M.; Sarti, A.; Satriano, C.; Satta, A.; Savrie, M.; Savrina, D.; Schiller, M.; Schindler, H.; Schlupp, M.; Schmelling, M.; Schmidt, B.; Schneider, O.; Schopper, A.; Schune, M.H.; Schwemmer, R.; Sciascia, B.; Sciubba, A.; Seco, M.; Semennikov, A.; Senderowska, K.; Sepp, I.; Serra, N.; Serrano, J.; Sestini, L.; Seyfert, P.; Shapkin, M.; Shapoval, I.; Shcheglov, Y.; Shears, T.; Shekhtman, L.; Shevchenko, V.; Shires, A.; Coutinho, R.Silva; Simi, G.; Sirendi, M.; Skidmore, N.; Skwarnicki, T.; Smith, N.A.; Smith, E.; Smith, E.; Smith, J.; Smith, M.; Snoek, H.; Sokoloff, M.D.; Soler, F.J.P.; Soomro, F.; Souza, D.; Souza De Paula, B.; Spaan, B.; Sparkes, A.; Spinella, F.; Spradlin, P.; Stagni, F.; Stahl, S.; Steinkamp, O.; Stenyakin, O.; Stevenson, S.; Stoica, S.; Stone, S.; Storaci, B.; Stracka, S.; Straticiuc, M.; Straumann, U.; Stroili, R.; Subbiah, V.K.; Sun, L.; Sutcliffe, W.; Swientek, K.; Swientek, S.; Syropoulos, V.; Szczekowski, M.; Szczypka, P.; Szilard, D.; Szumlak, T.; T'Jampens, S.; Teklishyn, M.; Tellarini, G.; Teubert, F.; Thomas, C.; Thomas, E.; van Tilburg, J.; Tisserand, V.; Tobin, M.; Tolk, S.; Tomassetti, L.; Tonelli, D.; Topp-Joergensen, S.; Torr, N.; Tournefier, E.; Tourneur, S.; Tran, M.T.; Tresch, M.; Tsaregorodtsev, A.; Tsopelas, P.; Tuning, N.; Garcia, M.Ubeda; Ukleja, A.; Ustyuzhanin, A.; Uwer, U.; Vagnoni, V.; Valenti, G.; Vallier, A.; Vazquez Gomez, R.; Vazquez Regueiro, P.; Vazquez Sierra, C.; Vecchi, S.; Velthuis, J.J.; Veltri, M.; Veneziano, G.; Vesterinen, M.; Viaud, B.; Vieira, D.; Vieites Diaz, M.; Vilasis-Cardona, X.; Vollhardt, A.; Volyanskyy, D.; Voong, D.; Vorobyev, A.; Vorobyev, V.; Voss, C.; Voss, H.; de Vries, J.A.; Waldi, R.; Wallace, C.; Wallace, R.; Walsh, J.; Wandernoth, S.; Wang, J.; Ward, D.R.; Watson, N.K.; Websdale, D.; Whitehead, M.; Wicht, J.; Wiedner, D.; Wilkinson, G.; Williams, M.P.; Williams, M.; Wilson, F.F.; Wimberley, J.; Wishahi, J.; Wislicki, W.; Witek, M.; Wormser, G.; Wotton, S.A.; Wright, S.; Wu, S.; Wyllie, K.; Xie, Y.; Xing, Z.; Xu, Z.; Yang, Z.; Yuan, X.; Yushchenko, O.; Zangoli, M.; Zavertyaev, M.; Zhang, F.; Zhang, L.; Zhang, W.C.; Zhang, Y.; Zhelezov, A.; Zhokhov, A.; Zhong, L.; Zvyagin, A.

2014-01-01

Measurements of the effective lifetimes in the $B_{s}^{0} \\rightarrow K^{+}K^{-}$, $B^{0} \\rightarrow K^{+}\\pi^{-}$ and $B_{s}^{0} \\rightarrow \\pi^{+}K^{-}$ decays are presented using $1.0~\\mathrm{fb^{-1}}$ of $pp$ collision data collected at a centre-of-mass energy of 7 TeV by the LHCb experiment. The analysis uses a data-driven approach to correct for the decay time acceptance. The measured effective lifetimes are $\\tau_{B_{s}^{0} \\rightarrow K^{+}K^{-}}$ = $1.407~\\pm~0.016~\\pm~0.007~\\mathrm{ps}$, $\\tau_{B^{0} \\rightarrow K^{+}\\pi^{-}}$ = $1.524~\\pm~0.011~\\pm~0.004~\\mathrm{ps}$, $\\tau_{B_{s}^{0} \\rightarrow \\pi^{+}K^{-}}$ = $1.60~\\pm~0.06~\\pm~0.01~\\mathrm{ps}$. This is the most precise determination to date of the effective lifetime in the $B_{s}^{0} \\rightarrow K^{+}K^{-}$ decay and provides constraints on contributions from physics beyond the Standard Model to the $B_{s}^{0}$ mixing phase and the width difference $\\Delta\\Gamma_{s}$.

Program for studying fundamental interactions at the PIK reactor facilities

International Nuclear Information System (INIS)

Serebrov, A. P.; Vassiljev, A. V.; Varlamov, V. E.; Geltenbort, P.; Gridnev, K. A.; Dmitriev, S. P.; Dovator, N. A.; Egorov, A. I.; Ezhov, V. F.; Zherebtsov, O. M.; Zinoviev, V. G.; Ivochkin, V. G.; Ivanov, S. N.; Ivanov, S. A.; Kolomensky, E. A.; Konoplev, K. A.; Krasnoschekova, I. A.; Lasakov, M. S.; Lyamkin, V. A.; Martemyanov, V. P.

2016-01-01

A research program aimed at studying fundamental interactions by means of ultracold and polarized cold neutrons at the GEK-4-4′ channel of the PIK reactor is presented. The apparatus to be used includes a source of cold neutrons in the heavy-water reflector of the reactor, a source of ultracold neutrons based on superfluid helium and installed in a cold-neutron beam extracted from the GEK-4 channel, and a number of experimental facilities in neutron beams. An experiment devoted to searches for the neutron electric dipole moment and an experiment aimed at a measurement the neutron lifetime with the aid of a large gravitational trap are planned to be performed in a beam of ultracold neutrons. An experiment devoted to measuring neutron-decay asymmetries with the aid of a superconducting solenoid is planned in a beam of cold polarized neutrons from the GEK-4′ channel. The second ultracold-neutron source and an experiment aimed at measuring the neutron lifetime with the aid of a magnetic trap are planned in the neutron-guide system of the GEK-3 channel. In the realms of neutrino physics, an experiment intended for sterile-neutrino searches is designed. The state of affairs around the preparation of the experimental equipment for this program is discussed.

Program for studying fundamental interactions at the PIK reactor facilities

Energy Technology Data Exchange (ETDEWEB)

Serebrov, A. P., E-mail: serebrov@pnpi.spb.ru; Vassiljev, A. V.; Varlamov, V. E. [National Research Center Kurchatov Institute, Petersburg Nuclear Physics Institute (Russian Federation); Geltenbort, P. [Institut Laue-Langevin (France); Gridnev, K. A. [St. Petersburg State University (Russian Federation); Dmitriev, S. P.; Dovator, N. A. [Russian Academy of Sciences, Ioffe Physical-Technical Institute (Russian Federation); Egorov, A. I.; Ezhov, V. F.; Zherebtsov, O. M.; Zinoviev, V. G.; Ivochkin, V. G.; Ivanov, S. N.; Ivanov, S. A.; Kolomensky, E. A.; Konoplev, K. A.; Krasnoschekova, I. A.; Lasakov, M. S.; Lyamkin, V. A. [National Research Center Kurchatov Institute, Petersburg Nuclear Physics Institute (Russian Federation); Martemyanov, V. P. [National Research Center Kurchatov Institute (Russian Federation); and others

2016-05-15

A research program aimed at studying fundamental interactions by means of ultracold and polarized cold neutrons at the GEK-4-4′ channel of the PIK reactor is presented. The apparatus to be used includes a source of cold neutrons in the heavy-water reflector of the reactor, a source of ultracold neutrons based on superfluid helium and installed in a cold-neutron beam extracted from the GEK-4 channel, and a number of experimental facilities in neutron beams. An experiment devoted to searches for the neutron electric dipole moment and an experiment aimed at a measurement the neutron lifetime with the aid of a large gravitational trap are planned to be performed in a beam of ultracold neutrons. An experiment devoted to measuring neutron-decay asymmetries with the aid of a superconducting solenoid is planned in a beam of cold polarized neutrons from the GEK-4′ channel. The second ultracold-neutron source and an experiment aimed at measuring the neutron lifetime with the aid of a magnetic trap are planned in the neutron-guide system of the GEK-3 channel. In the realms of neutrino physics, an experiment intended for sterile-neutrino searches is designed. The state of affairs around the preparation of the experimental equipment for this program is discussed.

Investigating the structure and dynamics of the PIK3CA wild-type and H1047R oncogenic mutant.

Directory of Open Access Journals (Sweden)

Paraskevi Gkeka

2014-10-01

Full Text Available The PIK3CA gene is one of the most frequently mutated oncogenes in human cancers. It encodes p110α, the catalytic subunit of phosphatidylinositol 3-kinase alpha (PI3Kα, which activates signaling cascades leading to cell proliferation, survival, and cell growth. The most frequent mutation in PIK3CA is H1047R, which results in enzymatic overactivation. Understanding how the H1047R mutation causes the enhanced activity of the protein in atomic detail is central to developing mutant-specific therapeutics for cancer. To this end, Surface Plasmon Resonance (SPR experiments and Molecular Dynamics (MD simulations were carried out for both wild-type (WT and H1047R mutant proteins. An expanded positive charge distribution on the membrane binding regions of the mutant with respect to the WT protein is observed through MD simulations, which justifies the increased ability of the mutated protein variant to bind to membranes rich in anionic lipids in our SPR experiments. Our results further support an auto-inhibitory role of the C-terminal tail in the WT protein, which is abolished in the mutant protein due to loss of crucial intermolecular interactions. Moreover, Functional Mode Analysis reveals that the H1047R mutation alters the twisting motion of the N-lobe of the kinase domain with respect to the C-lobe and shifts the position of the conserved P-loop residues in the vicinity of the active site. These findings demonstrate the dynamical and structural differences of the two proteins in atomic detail and propose a mechanism of overactivation for the mutant protein. The results may be further utilized for the design of mutant-specific PI3Kα inhibitors that exploit the altered mutant conformation.

Antitumor Efficacy of the Dual PI3K/mTOR Inhibitor PF-04691502 in a Human Xenograft Tumor Model Derived from Colorectal Cancer Stem Cells Harboring a PIK3CA Mutation.

Directory of Open Access Journals (Sweden)

Douglas D Fang

Full Text Available PIK3CA (phosphoinositide-3-kinase, catalytic, alpha polypeptide mutations can help predict the antitumor activity of phosphatidylinositol-3-kinase (PI3K/mammalian target of rapamycin (mTOR pathway inhibitors in both preclinical and clinical settings. In light of the recent discovery of tumor-initiating cancer stem cells (CSCs in various tumor types, we developed an in vitro CSC model from xenograft tumors established in mice from a colorectal cancer patient tumor in which the CD133+/EpCAM+ population represented tumor-initiating cells. CD133+/EpCAM+ CSCs were enriched under stem cell culture conditions and formed 3-dimensional tumor spheroids. Tumor spheroid cells exhibited CSC properties, including the capability for differentiation and self-renewal, higher tumorigenic potential and chemo-resistance. Genetic analysis using an OncoCarta™ panel revealed a PIK3CA (H1047R mutation in these cells. Using a dual PI3K/mTOR inhibitor, PF-04691502, we then showed that blockage of the PI3K/mTOR pathway inhibited the in vitro proliferation of CSCs and in vivo xenograft tumor growth with manageable toxicity. Tumor growth inhibition in mice was accompanied by a significant reduction of phosphorylated Akt (pAKT (S473, a well-established surrogate biomarker of PI3K/mTOR signaling pathway inhibition. Collectively, our data suggest that PF-04691502 exhibits potent anticancer activity in colorectal cancer by targeting both PIK3CA (H1047R mutant CSCs and their derivatives. These results may assist in the clinical development of PF-04691502 for the treatment of a subpopulation of colorectal cancer patients with poor outcomes.

Measurement of glacier velocity at Pik Lenin, Tajikistan, by feature tracking

Science.gov (United States)

Kumari, S.; Ghosh, S. K.; Buchroithner, M. F.

2014-11-01

Glaciers, especially in mountain area are sensitive indicators of climate fluctuations and also contribute to present rates of sea level rise. In Central Asia, these glaciers are the primary resource for fresh water. Understanding the seasonal behavior of these glaciers would help to make efficient use of the available water reservoir. Different methods have been employed to study glacier displacements in past. The conventional survey techniques are very cost-intensive and highly depend on accessibility to high mountain glaciers also directs us to look for new ways to study these areas. Here remote sensing comes in handy with freely available data and a good coverage with high spatial and temporal resolution. Optical satellite imagery, available free can be effectively used for research purpose. The glacier in this region fed lake Karakul (380 km2), the largest Lake in Tajikistan. The objective is to study the displacement tendency of the Glacier in Pik Lenin area using Landsat 7 dataset. Normalized cross correlation algorithm has been implemented via CIAS to estimate the motion of glacier surface. A number of combination of reference block and search area size were tested for 30 m resolution dataset. As a result the specifications: reference block size of 15 pixels and search area size of 10 pixels was found out as the best set of parameters and considered for further processing. The study derives a reliable set of data depicting the velocities in the glacier which after post processing shows peak velocity of 121 m/y of the glacier.

Tartu Jaani kiriku terrakotaskulptuurid

Index Scriptorium Estoniae

2004-01-01

10 fotot Kaur Alttoalt. Maarja võidukaare kohalt, Mooses, eestpalujad Maarja ja Ristija Johannes peaportaalilt, arvatav evangelist Johannes, portree peadefriisilt, daam tanuga, skulptuurid kesklöövi lõunaseinal, torni poolfiguur

Impact of KRAS, BRAF, PIK3CA mutations, PTEN, AREG, EREG expression and skin rash in ≥ 2 line cetuximab-based therapy of colorectal cancer patients.

Directory of Open Access Journals (Sweden)

Zacharenia Saridaki

2011-01-01

Full Text Available To investigate the predictive significance of KRAS, BRAF, PIK3CA mutational status, AREG- EREG mRNA expression, PTEN protein expression and skin rash in metastatic colorectal cancer (mCRC patients treated with cetuximab containing salvage chemotherapy.Primary tumors from 112 mCRC patients were analyzed. The worst skin toxicity during treatment was recorded.KRAS, BRAF and PIK3CA mutations were present in 37 (33%, 8 (7.2% and 11 (9.8% cases, respectively, PTEN was lost in 21 (19.8% cases, AREG and EREG were overexpressed in 48 (45% and 51 (49% cases. In the whole study population, time to tumor progression (TTP and overall survival (OS was significantly lower in patients with KRAS (p = 0.001 and p = 0.026, respectively or BRAF (p = 0.001 and p<0.0001, respectively mutant tumors, downregulation of AREG (p = 0.018 and p = 0.013, respectively or EREG (p = 0.002 and p = 0.004, respectively and grade 0-1 skin rash (p<0.0001 and p<0.0001, respectively. In KRAS wt patients TTP and OS was significantly lower in patients with BRAF (p = 0.0001 and p<0.0001, respectively mutant tumors, downregulation of AREG (p = 0.021 and p = 0.004, respectively or EREG (p = 0.0001 and p<0.0001, respectively and grade 0-1 skin rash (p<0.0001 and p<0.0001, respectively. TTP was significantly lower in patients with PIK3CA mutations (p = 0.01 or lost PTEN (p = 0.002. Multivariate analysis revealed KRAS (Hazard Ratio [HR] 4.3, p<0.0001, BRAF mutation (HR: 5.1, p<0.0001, EREG low expression (HR: 1.6, p = 0.021 and absence of severe/moderate skin rash (HR: 4.0, p<0.0001 as independent prognostic factors for decreased TTP. Similarly, KRAS (HR 2.9, p = 0.01, BRAF mutation (HR: 3.0, p = 0.001, EREG low expression (HR: 1.7, p = 0.021, absence of severe/moderate skin rash (HR: 3.7, p<0.0001 and the presence of undifferantited tumours (HR: 2.2, p = 0.001 were revealed as independent prognostic factors for decreased OS.These results underscore that KRAS-BRAF mutations and EREG

Lootuse festivalil osalesid lauljad Raplamaalt / Maire Kõrver

Index Scriptorium Estoniae

Kõrver, Maire, 1961-

2009-01-01

Tallinnas Saku Suurhallis 29.-31. maini toimunud evangeelsest üritusest - Lootuse festivalist, kus esinesid teiste seas lauljad Rapla Maarja- Magdaleena koguduse segakoorist, Hageri koguduse kammerkoorist Lambertus, Kohila babtistikoguduse segakoorist ja Märjamaa Maarja koguduse segakoorist Mariema

Raamat "Tööraamat" = "A life's work" book

Index Scriptorium Estoniae

2012-01-01

Eesti Sisearhitektide Liidu 2011. aasta publitsistika preemia: Pärtelpoeg, Leila. Tööraamat / koostaja Krista Roosi ; kujundaja Maarja Roosi. [Tartu] : Eesti Sisearhitektide Liit, [2011]. Loetletud Leila Pärtelpoja, Krista Roosi ja Maarja Roosi tehtud töid

Lack of Association between ABO, PPAP2B, ADAMST7, PIK3CG, and EDNRA and Carotid Intima-Media Thickness, Carotid Plaques, and Cardiovascular Disease in Patients with Rheumatoid Arthritis

Directory of Open Access Journals (Sweden)

Raquel López-Mejías

2014-01-01

Full Text Available Introduction. Rheumatoid arthritis (RA is a polygenic disease associated with accelerated atherosclerosis and increased cardiovascular (CV mortality. Recent studies have identified the ABO rs579459, PPAP2B rs17114036, and ADAMTS7 rs3825807 polymorphisms as genetic variants associated with coronary artery disease and the PIK3CG rs17398575 and EDNRA rs1878406 polymorphisms as the most significant signals related to the presence of carotid plaque in nonrheumatic Caucasian individuals. Accordingly, we evaluated the potential relationship between these 5 polymorphisms and subclinical atherosclerosis (assessed by carotid intima-media thickness (cIMT and presence/absence of carotid plaques and CV disease in RA. Material and Methods. 2140 Spanish RA patients were genotyped for the 5 polymorphisms by TaqMan assays. Subclinical atherosclerosis was evaluated in 620 of these patients by carotid ultrasonography technology. Results. No statistically significant differences were found when each polymorphism was assessed according to cIMT values and presence/absence of carotid plaques in RA, after adjusting the results for potential confounders. Moreover, no significant differences were obtained when RA patients were stratified according to the presence/absence of CV disease after adjusting for potential confounders. Conclusion. Our results do not confirm association between ABO rs579459, PPAP2B rs17114036, ADAMTS7 rs3825807, PIK3CG rs17398575, and EDNRA rs1878406 and subclinical atherosclerosis and CV disease in RA.

Short Communication

African Journals Online (AJOL)

protein whereas HB-1533 the least. High thousand kernel .... Kernel protein content was determined ... methods. The Additive main effects and multiplicative interaction (AMMI) analysis ... principal component analysis (Zobel et al., 1988).

Eestlased rajavad Veneetsiasse gaasitoru / Anneliis Aunapuu

Index Scriptorium Estoniae

Aunapuu, Anneliis

2008-01-01

Veneetsia arhitektuuribiennaalil Eestit esindav arhitektuuribüroo Salto töögrupp (Maarja Kask, Ralf Lõoke, Neeme Külm) rajab sinna gaasijuhtme NordStream sümboli. 63 meetri pikkune skulpturaalne vorm kulgeb näitusepaviljonide vahel, biennaaliala peamise käigutee kohal. Kommenteerivad Ingrid Ruudi, Maarja Kask, Ralf Lõoke

Moodsa luule maailmakeel / Märt Väljataga

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Väljataga, Märt, 1965-

2007-01-01

Magrelli, Valerio. Luule DNA = Il DNE della poesia / tõlkinudk Maarja Kangro ja Kalju Kruusa. Tallinn : Koma, 2006 ; Enzensberger, Hans. Tõmba sobimatu maha : [luuletused] / saksa keelest tõlkinud [ja järelsõna:] Maarja Kangro. Tallinn : Kultuurileht, 2006 ; Kronbergs, Juris. Maa-alune luule / läti keelest tõlkinud Guntars Godinsh, Livia Viitol. Tallinn : Kultuurileht, 2007

Mõtlik südasuvi / Andri Ksenofontov

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Ksenofontov, Andri, 1962-

2009-01-01

Näitused Tallinnas: Reti Saksa näitus Põlendruumis, Maarja Unduski ja Pille Kivihalli (külalisena) näitus "Maarja ilmutus" galeriis Hop 25. juunist 14. juulini, Jaan Elkeni näitus "Tagasi reaalsusesse" Draakoni galeriis 15. juunist 4. juulini, Sven Saagi ja Andres Koorti näitus "Kogu aeg" Tallinna Kunstihoone galeriis 27. juunist 12. juulini

Tallinn - Taani linn / Ago Vallas

Index Scriptorium Estoniae

Vallas, Ago

2002-01-01

rets. rmt.: Zobel, Rein. Tallinn (Reval) keskajal : linnaehitus 13. - 14. sajandil = Tallinn (Reval) in the middle ages : town building in the 13 th - 14 th centuries. Tallinn : Eesti Entsüklopeediakirjastus, 2001. 213 lk. : ill., kaart

The Potsdam Parallel Ice Sheet Model (PISM-PIK) - Part 2: Dynamic equilibrium simulation of the Antarctic ice sheet

Science.gov (United States)

Martin, M. A.; Winkelmann, R.; Haseloff, M.; Albrecht, T.; Bueler, E.; Khroulev, C.; Levermann, A.

2011-09-01

We present a dynamic equilibrium simulation of the ice sheet-shelf system on Antarctica with the Potsdam Parallel Ice Sheet Model (PISM-PIK). The simulation is initialized with present-day conditions for bed topography and ice thickness and then run to steady state with constant present-day surface mass balance. Surface temperature and sub-shelf basal melt distribution are parameterized. Grounding lines and calving fronts are free to evolve, and their modeled equilibrium state is compared to observational data. A physically-motivated calving law based on horizontal spreading rates allows for realistic calving fronts for various types of shelves. Steady-state dynamics including surface velocity and ice flux are analyzed for whole Antarctica and the Ronne-Filchner and Ross ice shelf areas in particular. The results show that the different flow regimes in sheet and shelves, and the transition zone between them, are captured reasonably well, supporting the approach of superposition of SIA and SSA for the representation of fast motion of grounded ice. This approach also leads to a natural emergence of sliding-dominated flow in stream-like features in this new 3-D marine ice sheet model.

Pärnu Keskkonnahariduskeskus = Pärnu Environmental Education Centre

Index Scriptorium Estoniae

2015-01-01

Pärnu Keskkonnahariduskeskus A.H. Tammsaare puiestee 57, valminud 2013. Arhitektuurivõistlus 2006, jagatud III koht. Võistlustöö autorid Maarja Kask, Karli Luik, Ralf Lõoke (Salto Arhitektuuribüroo). Arhitektid Maarja Kask, Karli Luik, Ralf Lõoke, Helin Kukk, Andro Mänd, Helen Rebane, Margus Tamm. Pärnumaa püsinäituse kujundus Malle Jürgenson, Krista Lepland (Laika, Belka & Strelka)

Kuni 3. X on Frankfurdi lennujaamas (terminal 2)...

Index Scriptorium Estoniae

2004-01-01

Kaasaegse ehtekunsti noorima põlvkonna ehtete väljapanek. Näitusele valiti kahe EKA ehtekunsti eriala lõpetaja tööd. Maarja Niinemäe käevõrud pälvisid III preemia, Anni Kagovere mokume gane tehnikas hõbevaagnad äramärkimise. Septembris sai Maarja Niinemägi Leipzigi Midora messil ajakirja "GZ (Goldschmiede Zeitung) preemia "Best Graduate"

PIK3CA mutations, PTEN, and pHER2 expression and impact on outcome in HER2-positive early-stage breast cancer patients treated with adjuvant chemotherapy and trastuzumab

DEFF Research Database (Denmark)

Jensen, J D; Knoop, Ann; Laenkholm, A V

2012-01-01

-stage breast cancer patients treated with adjuvant chemotherapy and trastuzumab. PATIENTS AND METHODS: Two hundred and forty HER2-positive early-stage breast cancer patients receiving adjuvant treatment (cyclophosphamide 600 mg/m(2), epirubicin 60 mg/m(2), and fluorouracil 600 mg/m(2)) before administration...... of 1 year trastuzumab were assessable. PTEN and pHER2 expression were assessed by immunohistochemistry. PIK3CA mutations (exons 9 and 20) were determined by pyrosequencing. RESULTS: Five-year overall survival (OS) and invasive disease-free survival were 87.8% and 81.0%, respectively. Twenty-six percent...... activity had a significantly poorer survival despite adequate treatment with adjuvant chemotherapy and trastuzumab....

The Potsdam Parallel Ice Sheet Model (PISM-PIK – Part 2: Dynamic equilibrium simulation of the Antarctic ice sheet

Directory of Open Access Journals (Sweden)

M. A. Martin

2011-09-01

Full Text Available We present a dynamic equilibrium simulation of the ice sheet-shelf system on Antarctica with the Potsdam Parallel Ice Sheet Model (PISM-PIK. The simulation is initialized with present-day conditions for bed topography and ice thickness and then run to steady state with constant present-day surface mass balance. Surface temperature and sub-shelf basal melt distribution are parameterized. Grounding lines and calving fronts are free to evolve, and their modeled equilibrium state is compared to observational data. A physically-motivated calving law based on horizontal spreading rates allows for realistic calving fronts for various types of shelves. Steady-state dynamics including surface velocity and ice flux are analyzed for whole Antarctica and the Ronne-Filchner and Ross ice shelf areas in particular. The results show that the different flow regimes in sheet and shelves, and the transition zone between them, are captured reasonably well, supporting the approach of superposition of SIA and SSA for the representation of fast motion of grounded ice. This approach also leads to a natural emergence of sliding-dominated flow in stream-like features in this new 3-D marine ice sheet model.

Žürii kommenteerib Kultuurkapitali arhitektuuripreemiaid 2008 / Marika Lõoke, Laila Põdra, Liina Jänes... [jt.

Index Scriptorium Estoniae

2009-01-01

Peapreemia: Markus Kaasik, Andres Ojari, Ilmar Valdur, Mihkel Tüür, Kalle Komissarov (Pärnu Keskraamatukogu hoone), tegevuspreemia: Maarja Kask, Ralf Lõoke, Neeme Külm, Ingrid Ruudi (projekt Gaasitoru 11. Veneetsia arhitektuuribiennaalil), aastapreemia: Maarja Kask, Ralf Lõoke, Karli Luik (Tartu Kesklinna Kooli juurdeehitus) ja Peep Jänes (Raudna Põhikooli spordihoone), sisearhitektuuri preemia: Tea Tammelaan, Malle Jürgenson, Krista Lepland, restaureerimispreemia: Mari Hammer, Tiiu Lõhmus, Helve Ilves, Villu Kadakas (Vanalinna Hariduskolleegiumi hoone)

Skoone bastion tekitas aukartust juba oma olemasoluga / Oliver Õunmaa

Index Scriptorium Estoniae

Õunmaa, Oliver

2011-01-01

Arhitektuuriajaloolane Rein Zobel Skoone bastioni minevikust ja peagi teatriks muunduva endise muldkindlustuse kasutusviisidest läbi aegade. 1948. a. avati ühel bastioni osal Nõukogude armeele kuuluv Madruste Klubi lõbustuspark ja puidust Suveteatri hoone, mis põles 10. juunil 1997. a. maha

Ministeeriumid toidavad parasiite / Madli Zobel, Kristina Traks

Index Scriptorium Estoniae

Zobel, Madli, 1976-

2000-01-01

Ministeeriumid peavad üleval kümneid erialaliitusid, mille mõttekus ja kasutegur on küsitav. Tabel: Raha, mis läheb sel aastal liitude toetuseks. Vastuseks vt. Äripäev Mar/29 lk. 26 P. Teppi art., A. Runge art. Äripäev Mar/31 lk. 27, J. Rausi art. Äripäev Apr/6 lk. 27

Linnaehitusest ja -kindlustustest Eestis uusajal / Rein Zobel

Index Scriptorium Estoniae

Zobel, Rein, 1928-2012

2005-01-01

Tallinna, Tartu, Narva, Pärnu, Kuressaare ja väikelinnade (Paide, Haapsalu, Rakvere, Viljandi) linnaehitusest ja -kindlustustest uusajal. 18. sajandil rajatud uuest kindluslinnast Paldiskist. Bibliograafia lk. 443-444

Marine Caulobacters. Isolation, Characterization and Assessing the Potential for Genetic Experimentation.

Science.gov (United States)

1987-01-01

grants from the Washington SeaGrant Program, the Office of Naval Research (N00014-81-C-0570) and the California Toxic Substances Research and Teaching ...negative bacteria. Biotechnology _, 269-275. 45.ZoBell, C.E. (1946) Marine microbiology: a monograph on hydrobacteriology. Chronica Botanica Co., Waltham

Pengembangan Sistem Pengelolaan Informasi Pusat Informasi dan Konseling Remaja Kota Padang

Directory of Open Access Journals (Sweden)

Isra Wilna

2017-04-01

Full Text Available Salah satu fungsi dari Pusat Informasi dan Konseling Remaja (PIK Remaja adalah memberikan pelayanan informasi dan konseling tentang perencanaan kehidupan berkeluarga bagi remaja. PIK Remaja ini terdapat di lembaga pendidikan sepert sekolah dan perguruan tinggi maupun lembaga non pendidikan. Lokasinya tersebar di 11 kecamatan yang ada di Kota Padang. Setiap PIK, diharuskan menyampaikan laporan-nya secara kolektif dan berkala ke Badan Pemberdayaan Masyarakat, Perempuan dan Keluarga Berencana (BPMPKB  Padang,. Keterbatasan ruang dan waktu, menjadi kendala bagi BPMPKB dalam menjalan perannya sebagai pengawas. Disamping itu, perubahan alamat kantor PIK Remaja  banyak tidak terkelola karena tidak terdokumentasi dengan baik. Oleh karena itu dibangun sebuah sistem yang mampu menyelesaikan masalah tersebut. Sistem infomasi geografis menjadi pilihan karena mampu menyajikan informasi dengan referensi geografis. Dukungan teknologi web terhadap visualisasi geografis akan memudahkan pemangku kebijakan dalam pengembangan PIK Remaja di Kota Padang. Metode pengembangan aplikasi mengadopsi model waterfall. Aplikasi ini dibangun dengan fungsional pencarian PIK Remaja berdasarkan kategori, berdasarkan wilayah, pencarian PIK Remaja yang terdekat dari posisi pengguna, melihat rute menuju PIK Remaja yang dipilih. Disamping itu BPMPKB dapat mengelola data dan laporan  kegiatan PIK remaja. Disamping itu, PIK Remaja dapat mengelola data PIK-nya dan menyampaikan laporan kegiatan. Semua data tesimpan dalam database terdiri dari 9 tabel dengan  17 rancangan user interface aplikasi. Pengujian dilakukan dengan validasi fungsional aplikasi yang dirancang dengan aplikasi secara Blackbox testing. Pengujian ini  melibatkan 5 orang pengguna dengan hasil rekomendasi fungsional dari sistem telah berjalan sesuai dengan rancangan.   Kata kunci: PIK Remaja, Sistem Informasi Geografis.

Miks liigid välja surevad? / Martin Zobel

Index Scriptorium Estoniae

Zobel, Martin, 1957-

2005-01-01

Euroopa bioloogilist mitmekesisust ohustavate tegurite väljaselgitamiseks ja nende mõju leevendamise strateegiate visandamiseks on loodud 27 riigi teadlastest ning 54 uurimisasutuse toel teadusprojekt ALARM. Projektis osalevatelt Eesti teadlastelt oodatakse panust eelkõige Euroopa maismaa ohutegurite üldistamisse

Lõbus linn ja kohalikud tondid / Triin Ojari

Index Scriptorium Estoniae

Ojari, Triin, 1974-

2008-01-01

Raamatutest: "Fun City" (Kopenhaagen : Danish Architectural Press, 2007, toimetajad: Gitte Marling, Martin Zerlang), Rein Zobel, Juhan Maiste, Mart Kalm "Toompea loss" (Tallinn : Riigikogu kantselei, 2008, eessõna: Harry Liivrand), "A10 : New European Architecture 07/08" (Amsterdam : A10 Media BV, 2007, toimetajad Hans Ibelings, Kirsten Hannema; ka kortermajast Tallinnas Koidula tänavas)

genotype by environment interaction and grain yield stability

African Journals Online (AJOL)

Preferred Customer

Farshadfar, 2008, on bread wheat; Abeya. Temesgen et al., 2008, on common bean; Girma. Mengistu et al., 2011, on Field pea). The most accurate model for AMMI can be predicted by using the first two PCAs (Gauch and. Zobel, 1996). This suggestion was later modified such that factors like type of crop, diversity of the.

Effects of the silvicultural intensity on the 4-years growth and leaf-level physiology of loblolly pine varieties

Science.gov (United States)

Marco Yanez; John Seiler; Thomas Fox

2015-01-01

The role that genetic improvement plays in the increase of productivity in loblolly pine (Pinus taeda L.) in the South has been recognized (McKeand and others 2003). Varietal forestry has the potential to improve the productivity and quality of loblolly pine stands, and higher genetic gains can be achieved in volume and stand uniformity (Zobel and Talbert 1984).

GLYCINE-RICH RNA-BINDING PROTEIN1 interacts with RECEPTOR-LIKE CYTOPLASMIC PROTEIN KINASE1 and suppresses cell death and defense responses in pepper (Capsicum annuum).

Science.gov (United States)

Kim, Dae Sung; Kim, Nak Hyun; Hwang, Byung Kook

2015-01-01

Plants use a variety of innate immune regulators to trigger cell death and defense responses against pathogen attack. We identified pepper (Capsicum annuum) GLYCINE-RICH RNA-BINDING PROTEIN1 (CaGRP1) as a RECEPTOR-LIKE CYTOPLASMIC PROTEIN KINASE1 (CaPIK1)-interacting partner, based on bimolecular fluorescence complementation and coimmunoprecipitation analyses as well as gene silencing and transient expression analysis. CaGRP1 contains an N-terminal RNA recognition motif and a glycine-rich region at the C-terminus. The CaGRP1 protein had DNA- and RNA-binding activity in vitro. CaGRP1 interacted with CaPIK1 in planta. CaGRP1 and CaGRP1-CaPIK1 complexes were localized to the nucleus in plant cells. CaPIK1 phosphorylated CaGRP1 in vitro and in planta. Transient coexpression of CaGRP1 with CaPIK1 suppressed the CaPIK1-triggered cell death response, accompanied by a reduced CaPIK1-triggered reactive oxygen species (ROS) burst. The RNA recognition motif region of CaGRP1 was responsible for the nuclear localization of CaGRP1 as well as the suppression of the CaPIK1-triggered cell death response. CaGRP1 silencing in pepper conferred enhanced resistance to Xanthomonas campestris pv vesicatoria (Xcv) infection; however, CaPIK1-silenced plants were more susceptible to Xcv. CaGRP1 interacts with CaPIK1 and negatively regulates CaPIK1-triggered cell death and defense responses by suppressing ROS accumulation. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

Decoupling of the PI3K Pathway via Mutation Necessitates Combinatorial Treatment in HER2+ Breast Cancer.

Directory of Open Access Journals (Sweden)

James E Korkola

Full Text Available We report here on experimental and theoretical efforts to determine how best to combine drugs that inhibit HER2 and AKT in HER2(+ breast cancers. We accomplished this by measuring cellular and molecular responses to lapatinib and the AKT inhibitors (AKTi GSK690693 and GSK2141795 in a panel of 22 HER2(+ breast cancer cell lines carrying wild type or mutant PIK3CA. We observed that combinations of lapatinib plus AKTi were synergistic in HER2(+/PIK3CA(mut cell lines but not in HER2(+/PIK3CA(wt cell lines. We measured changes in phospho-protein levels in 15 cell lines after treatment with lapatinib, AKTi or lapatinib + AKTi to shed light on the underlying signaling dynamics. This revealed that p-S6RP levels were less well attenuated by lapatinib in HER2(+/PIK3CA(mut cells compared to HER2(+/PIK3CAwt cells and that lapatinib + AKTi reduced p-S6RP levels to those achieved in HER2(+/PIK3CA(wt cells with lapatinib alone. We also found that that compensatory up-regulation of p-HER3 and p-HER2 is blunted in PIK3CA(mut cells following lapatinib + AKTi treatment. Responses of HER2(+ SKBR3 cells transfected with lentiviruses carrying control or PIK3CA(mut sequences were similar to those observed in HER2(+/PIK3CA(mut cell lines but not in HER2(+/PIK3CA(wt cell lines. We used a nonlinear ordinary differential equation model to support the idea that PIK3CA mutations act as downstream activators of AKT that blunt lapatinib inhibition of downstream AKT signaling and that the effects of PIK3CA mutations can be countered by combining lapatinib with an AKTi. This combination does not confer substantial benefit beyond lapatinib in HER2+/PIK3CA(wt cells.

Resistance to ketolide antibiotics by coordinated expression of rRNA methyltransferases in a bacterial producer of natural ketolides

DEFF Research Database (Denmark)

Almutairi, Mashal M; Park, Sung Ryeol; Rose, Simon

2015-01-01

venezuelae strain ATCC 15439. The producer avoids the inhibitory effects of its own antibiotics by expressing two paralogous rRNA methylase genes pikR1 and pikR2 with seemingly redundant functions. We show here that the PikR1 and PikR2 enzymes mono- and dimethylate, respectively, the N6 amino group in 23S r...

Role of Class III phosphoinositide 3-kinase in the brain development: possible involvement in specific learning disorders.

Science.gov (United States)

Inaguma, Yutaka; Matsumoto, Ayumi; Noda, Mariko; Tabata, Hidenori; Maeda, Akihiko; Goto, Masahide; Usui, Daisuke; Jimbo, Eriko F; Kikkawa, Kiyoshi; Ohtsuki, Mamitaro; Momoi, Mariko Y; Osaka, Hitoshi; Yamagata, Takanori; Nagata, Koh-Ichi

2016-10-01

Class III phosphoinositide 3-kinase (PIK3C3 or mammalian vacuolar protein sorting 34 homolog, Vps34) regulates vesicular trafficking, autophagy, and nutrient sensing. Recently, we reported that PIK3C3 is expressed in mouse cerebral cortex throughout the developmental process, especially at early embryonic stage. We thus examined the role of PIK3C3 in the development of the mouse cerebral cortex. Acute silencing of PIK3C3 with in utero electroporation method caused positional defects of excitatory neurons during corticogenesis. Time-lapse imaging revealed that the abnormal positioning was at least partially because of the reduced migration velocity. When PIK3C3 was silenced in cortical neurons in one hemisphere, axon extension to the contralateral hemisphere was also delayed. These aberrant phenotypes were rescued by RNAi-resistant PIK3C3. Notably, knockdown of PIK3C3 did not affect the cell cycle of neuronal progenitors and stem cells at the ventricular zone. Taken together, PIK3C3 was thought to play a crucial role in corticogenesis through the regulation of excitatory neuron migration and axon extension. Meanwhile, when we performed comparative genomic hybridization on a patient with specific learning disorders, a 107 Kb-deletion was identified on 18q12.3 (nt. 39554147-39661206) that encompasses exons 5-23 of PIK3C3. Notably, the above aberrant migration and axon growth phenotypes were not rescued by the disease-related truncation mutant (172 amino acids) lacking the C-terminal kinase domain. Thus, functional defects of PIK3C3 might impair corticogenesis and relate to the pathophysiology of specific learning disorders and other neurodevelopmental disorders. Acute knockdown of Class III phosphoinositide 3-kinase (PIK3C3) evokes migration defects of excitatory neurons during corticogenesis. PIK3C3-knockdown also disrupts axon outgrowth, but not progenitor proliferation in vivo. Involvement of PIK3C3 in neurodevelopmental disorders might be an interesting future

Vabaduse väljak = The first design stage of Freedom Square / Margit Mutso

Index Scriptorium Estoniae

Mutso, Margit, 1966-

2010-01-01

Tallinna Vabaduse väljakust, mis pälvis Eesti Kultuurkapitali 2009. aasta aastapreemia uue kvaliteedi eest Eesti linnaehituses ja avaliku ruumi loomisel. Arhitektid: Andres Alver, Veljo Kaasik, Tiit Trummal, kaasautorid Indrek Rünkla, Tarmo Laht, Sven Koppel, Ulla Saar, Toomas Tammis (Alver Arhitektid OÜ). Ajaloolane Rein Zobel. Žürii liikmete Kalle Komissarovi ja Mait Summataveti hinnang väljakule

Comparative Toxicity of Selected Aviation Fuels as Measured by Insect Bioassay

Science.gov (United States)

1982-07-01

Phillips and Stewart, 1974a, b; Atlas and Bartha , 1973; Zobell, 1969). General conclusions from these studies indicate that microorganisms contribute...R. BARTHA . 1973. Fate and effects of polluting petroleum in the marine environment. Residue Rev. 49:40-85. ATLAS , R. M., SCHOFIELD, E. A., MORELLI, F...BATTERTON. 1972. Ecological aspects of pesticide- microbial relationships. In: Environmental Toxicology of Pesticides. Matsumura, F., Boush, G. M., and T

Fort Dix Remedial Investigation/Feasibility Study for MAG-1 Area

Science.gov (United States)

1994-01-01

data produced for internal records and not reported as part of the analytical data include the following: laboratory worksheets , laboratory notebooks...Std. / Cond. Std. / __ Cond. Std. / Cond. Std. / Cond. Std. / Dissolved Oxygen Avg. Winkler Value __ ppm Meter Value __. ppm Redox Zobell Sol. Value...liquid limit less DRY STRENGTH DILATANCY (CONSISTENCY than half of than 50 (CRUSHING ( REACTION NEAR PLASTIC material is CHARACTERISTICS) TO SHAKING) UMIT

Noorarstid ei põruta välismaale / Madli Zobel

Index Scriptorium Estoniae

Zobel, Madli, 1976-

2005-01-01

Tänu residentuuris töötavate arstide palgatõusule 9000 kroonini on vähenenud arstieriala lõpetanute välismaale tööle asumine. Riigikontrolli auditi kohaselt on aastaks 2025 tööealisi arste üle kümnendiku vähem kui praegu, juhul kui tervishoiutöötajate koolitust jätkatakse samal tasemel

Isa Philippe Jourdan võttis vastu Tallinna Toomkiriku autasu / Tiiu Pikkur

Index Scriptorium Estoniae

Pikkur, Tiiu, 1947-

2008-01-01

5. oktoobril toimunud jumalateenistusel Tallinna Toomkirikus anti koguduse selle aasta kultuuripreemia laureaadile, Rooma-Katoliku Kririku Eesti apostellikule administraatorile piiskop Philippe Jourdanile üle Maarja medal

Frequent alterations of the PI3K/AKT/mTOR pathways in hereditary nonpolyposis colorectal cancer

DEFF Research Database (Denmark)

Ekstrand, Anna Isinger; Jönsson, Mats; Lindblom, Annika

2010-01-01

The phosphatidylinositol 3-kinases-AKT-mammalian target of rapamycin pathway (PI3K/AKT/mTOR) is central in colorectal tumors. Data on its role in hereditary cancers are, however, scarce and we therefore characterized mutations in PIK3CA and KRAS, and expression of PIK3CA, phosphorylated AKT......, and PTEN in colorectal cancers linked to hereditary nonpolyposis colorectal cancer (HNPCC). Sequencing was used to identify mutations in PIK3CA, a real-time PCR-based method to identify KRAS mutations, and immunohistochemical staining was used to evaluate the expression of PIK3CA, phosphorylated AKT...... and PTEN in 58 HNPCC-associated colorectal cancers. Derangements of at least one of the PI3K/AKT/mTOR components analyzed were found in 51/58 (88%) tumors. Mutations in PIK3CA and KRAS were identified in 14 and 31% of the tumors respectively. Overexpression of PIK3CA and phosphorylated AKT occurred in 59...

Tallinn - gorod kontrastov / Jelena Vassiljeva

Index Scriptorium Estoniae

Vassiljeva, Jelena

2006-01-01

Restauraatorite Maarja Tüüri ja Olari Kärmase alustatud Tallinna puitarhitektuuri kaitsmise aktsioonist, mille käigus inventariseeriti kesklinna puithooned. Linnaplaneerimise spetsialisti Aale Kase kommentaar

Korterelamu : Aleksandri 35, Tartu = Apartment building : Aleksandri 35, Tartu / Margit Mutso

Index Scriptorium Estoniae

Mutso, Margit, 1966-

2009-01-01

Karlova linnaosas asuva korterelamu arhitektuursest lahendusest, žürii hinnang kultuurkapitali aastapreemiale esitatud elamule. Arhitektid Maarja Kask, Ralf Lõoke, Karli Luik ja Kristiina Arusoo (Salto AB)

Baltijas birža - ēka, kas zaudējusi savu vietu / Carl-Dag Lige

Index Scriptorium Estoniae

Lige, Carl-Dag, 1982-

2016-01-01

Londonis asunud Balti börsihoone ajaloost. Kineetilisest ruumiinstallatsioonist "Face-to-face" (autorid Maarja Kask, Ralf Lõoke arhitektuuribüroost Salto Arhitektid, Neeme Külm) Eesti Arhitektuurimuuseumis

Ooper hetkest, mil inimene inimlikkuse kaotab / Timo Steiner ; intervjueerinud Anneli Sihvart

Index Scriptorium Estoniae

Steiner, Timo, 1976-

2011-01-01

Vestlus heliloojaga. Noblesseri valukojas Nargen Festivali raames 10. juunil esietenduvast uuest Eesti algupärasest ooperist "Kaks pead", libretist Maarja Kangro, lavastaja Mart Koldits, dirigent Tõnu Kaljuste

Intrigeeriv idee paneb mootori käima / Signe Sillasoo

Index Scriptorium Estoniae

Sillasoo, Signe

2011-01-01

Salto Arhitektuuribüroos (Maarja Kask, Ralf Lõoke, Karli Luik) projekteeritud hoonetest, koostööst klientidega, konkurssidel osalemisest, võidetud preemiatest. Pikemalt Tallinnasse püstitatud Põhuteatrist

B. B. ja järelpõlved / Ave Mattheus

Index Scriptorium Estoniae

Mattheus, Ave

2007-01-01

Arvustus: Enzensberger, Hans Magnus. Tõmba sobimatu maha / saksa keelest tlk. Maarja Kangro. Tallinn : Kultuurileht, 2006 (Loomingu Raamatukogu ; 33) ; Brecht, Bertolt. Luulet / koost. Märt Väljataga. Tallinn : Vagabund, 2007

BFM. Maja lava taga = BMF. The building behind the scenes / Triin Ojari

Index Scriptorium Estoniae

Ojari, Triin, 1974-

2012-01-01

Balti Filmi- ja Meediakooli uuest hoonest. Projekteerija: Salto Arhitektid. Autorid: Maarja Kask, Karli Luik, Ralf Lõoke, Pelle-Sten Viiburg. Sisekujundus: Ville Lausmäe. Projekt: 2009-2011, valmis: 2012

Phosphoinositide Kinase-3 Status Associated With Presence or Absence of Human Papillomavirus in Head and Neck Squamous Cell Carcinomas

International Nuclear Information System (INIS)

Yarbrough, Wendell G.; Whigham, Amy; Brown, Brandee; Roach, Michael; Slebos, Robbert

2007-01-01

Purpose: To investigate phosphoinositide kinase-3 (PI3K) activation in relation to human papillomavirus (HPV) status in head and neck squamous cell carcinoma (HNSCC). Methods and Materials: Gene expression microarray data were analyzed to determine differentially expressed genes between HPV(+) and HPV(-) HNSCC. PIK3CA gene expression was confirmed by quantitative reverse transcriptase-polymerase chain reaction in seven HPV(+) and seven HPV(-) primary HNSCCs. PIK3CA mutation status in three HPV(+) and nine HPV(-) cell lines was determined by polymerase chain reaction amplification of hot spot exons (1, 9, 20) followed by direct sequencing. Results: PIK3CA was overexpressed in HPV(+)-associated HNSCC compared with the expression in HPV(-) HNSCC. Activation of PIK3CA by mutation was found in 1 of the 12 tested HNSCC cell lines. Conclusion: Activation of PI3K by mutation of PIK3CA is rare in HNSCC cell lines and was not found in three HPV(+) cell lines. One mechanism by which HPV-associated HNSCC might activate PI3K is increased expression of PIK3CA

Torupäevik = Pipe diary / Ingrid Ruudi, Ralf Lõoke

Index Scriptorium Estoniae

Ruudi, Ingrid

2008-01-01

Eesti ekspositsioonist 11. Veneetsia arhitektuuribiennaalil. Autorid: Maarja Kask, Ralf Lõoke, Neeme Külm. Kuraator Ingrid Ruudi. Komissar Laila Põdra. Sündmustest päevikuna 14. märtsist 12. septembrini

Kuu plaat : Galaktlan "Constance". Plaadid kauplusest Lasering

Index Scriptorium Estoniae

2005-01-01

Heliplaatidest: Galaktlan "Constance", Bonnie "Prince" Billy & Matt Sweeney "Superwolf", Hinkus feat. Maarja "Look around", Noizmakaz "Valitud mõtted", Hedvig Hanson & Andre Maaker "You Bring Me Yoy", Nancy Sinatra "Nancy Sinatra"

Esitleti kakskeelset luulekogu "Luule DNA"

Index Scriptorium Estoniae

2007-01-01

Magrelli, Valerio. Luule DNA = Il DNA della poesia / tõlkinud [ja saatesõna:] Maarja Kangro ja Kalju Kruusa. Tallinn : Koma, 2006. Sisaldab autori teksti. Esitlus 24. jaan. Kirjanike majas Tallinnas

Development of Techniques for the Evaluation of Toxicant Impacts to Multispecies Systems

Science.gov (United States)

1994-06-28

bioremediation. In K.C. Marshall ed., Advances in Microbial Ecology , Volume 12. Plenum Press, New York, NY, pp. 287-338. Atlas , R.M. and R. Bartha . 1993... Atlas , 1981; Atlas and Bartha , 1993; Zobell, 1946, 1950). However, the importance and role of these microbial degradative processes have not been...high concentrations that may be inhibitory or toxic to the microbial communities ( Atlas and Bartha , 1973; Kappeler and Wuhrmann, 1978a). However, most

Paide linna ja gümnaasiumi spordihall = Paide city and upper secondary school sports building

Index Scriptorium Estoniae

2010-01-01

Paides Aedvilja 1 asuva spordihalli sisekujundusest. Sisearhitektid Ville Lausmäe ja Kadi Karmann (VL Sisearhitektuur). Akustik Linda Madalik. Hoone arhitektid: Karli Luik, Ralf Lõoke, Maarja Kask, Jaan Port (Salto AB)

Mitte ainult spordihoone = More than a Gym / Tuuli Köller

Index Scriptorium Estoniae

Köller, Tuuli

2009-01-01

Tartus 2009. a. valminud Eesti Maaülikooli spordihoonest, mille arhitektid on Maarja Kask, Karli Luik ja Ralf Lõoke, projekteerija AB Salto, sisekujundajad Katrin Kaevats ja Jaan Frank Port. Projekt 2007

Hollo kaasajastab Kangro-käsitust / Satu Grünthal ; soomekeelsest käsikirjast tõlkinud Johanna Ross

Index Scriptorium Estoniae

Grünthal, Satu

2016-01-01

Arvustus: Hollo, Maarja. Romantiline subjekt, mälu ja trauma Bernard Kangro sõjajärgses loomingus. Tartu : Tartu Ülikooli Kirjastus, 2016. (Dissertationes litterarum et contemplationis comparativae Universitatis Tartuensis ; 14)

Kirjanik soovitab / Triin Soomets

Index Scriptorium Estoniae

Soomets, Triin, 1969-

2010-01-01

Luuletaja Triin Soomets soovitab lugeda: Aravind Adiga "Valge tiiger", Sofi Oksase "Stalini lehmad", Doris Kareva "Deka", Leelo Tungla "Neitsi Maarja neli päeva", Berit Renseri ja Terje Toomistu "Seitse maailma"

Elamuslik arhitektuur : Salto AB Sõmeru keskusehoone = Salto AB experiential architecture and the Sõmeru Community Centre / Carl-Dag Lige

Index Scriptorium Estoniae

Lige, Carl-Dag

2011-01-01

Arhitektuuribüroo Salto loomingust, mille fookus on kasutaja teenimisel ning meeleheal. 2010. a. valminud Sõmeru keskusehoonest. Arhitektid Maarja Kask, Ralf Lõoke, Karli Luik, kaasautorid Kristiina Arusoo, Margit Argus. Projekt: 2004

Kirikukontserdid maestro mälestuseks / Ivi Kaarna

Index Scriptorium Estoniae

Kaarna, Ivi

2009-01-01

Võru Katariina kirikus 23. septembril ja Rõuge Maarja kirikus 24. septembril toimuvatest koorijuhi, organisti, pedagoogi, helilooja ja kunstniku Paul Elkeni sajandale sünnipäevale pühendatud kontserditest. Paul Elkenist

Nagu liivaterad kosmoses / Tõnu Kaalep

Index Scriptorium Estoniae

Kaalep, Tõnu, 1966-2018

2007-01-01

Stephen Hawkingi raamatu "A Brief History of Time" aineline lavastus "Õnne valem", helilooja Gavin Bryars, autor ja lavastaja Peeter Jalakas, kunstnik Kirke Kangro, libretist Maarja Kangro. Esietendus 9. apr. Tallinna tollilaos

Arhitektuuribürood pakkusid hipodroomi ala elamukvartaliks ümberehitamiseks julgeid projekte / Hille Tänavsuu

Index Scriptorium Estoniae

Tänavsuu, Hille, 1941-2014

2008-01-01

Tallinna Hipodroomi ala hoonestamise ideekonkursi võitsid QP Arhitektid (Tõnu Laigu, Koit Ojaliiv, Mari Rass, Asko Uukado) ja Salto Arhitektuuribüroo (Ralf Lõoke, Karli Luik, Maarja Kask). Kommenteerib Endrik Mänd

Põhuteater ehk Salto arhitektide must monoliit = Straw Theatre or the Black Monolith by the Salto Architects / Risto Kozer

Index Scriptorium Estoniae

Kozer, Risto

2011-01-01

Tallinnas 2011. a. valminud NO99 Põhuteatrist. Arhitektid: Maarja Kask, Karli Luik, Ralf Lõoke, Pelle-Sten Viiburg (Salto AB). Projekt: 2010. Loodud ajaperioodiks 30.04.-01.10.2011. Skoone bastionist enne Põhuteatrit

Trahv? Herned klassinurgas? Või hoopis ihunuhtlus? / Pilme, Lea; Kivistik, Ly; Sirgmets, Raili; Part, Aivar

Index Scriptorium Estoniae

2008-01-01

Suhtumisest koolijuhtidele trahvimisõiguse andmise ideesse vestlevad Rakvere Põhikooli direktor Lea Pilme, Uhtna Põhikooli direktor Ly Kivistik, Väike-Maarja Gümnaasiumi direktor Raili Sirgmets ja Rakvere Gümnaasiumi direktor Aivar Part

Балтийская школа кино и медиа (BFM), Таллин = Baltic Film and Media School (BFM), Tallinn / Михкель Кару

Index Scriptorium Estoniae

Кару, Михкель, 1983-

2013-01-01

Tallinna Ülikooli Balti Filmi- ja Meediakooli õppehoone "Nova". Arhitektid Maarja Kask, Karli Luik, Ralf Lõoke, Kristiina Arusoo, Pelle-Sten Viiburg (Salto Arhitektid), sisearhitektid Kadi Karmann, Ville Lausmäe, Tõnis Kalve

Новый корпус средней школы, Вильянди = Extension of Viljandi Secondary School / Михкель Кару

Index Scriptorium Estoniae

Кару, Михкель, 1983-

2013-01-01

Viljandi Riigigümnaasiumi uuest hoonest. Arhitektid Maarja Kask, Karli Luik, Ralf Lõoke, Andro Mänd, Margus Tamm (Salto Arhitektid), sisekujunduse autor Pille Lausmäe. Vana maja fassaadi renoveerimisprojekti autor Eva Laarmann

Rapla kihelkonna auhinna sai Ilse Rahkema / Margus Mikomägi

Index Scriptorium Estoniae

Mikomägi, Margus, 1956-

2009-01-01

Rapla kihelkonna päeval 22. juulil sai Rapla kihelkonna auhinna Raikküla teadjanaine, koduloolane Ilse Rahkema. Kihelkonna auhind kujutab endast pronksist valmistatud Maarja Magdaleena kuju, mille autor on skulptor Tauno Kangro

Isevärki kontorid / Liivi Tamm

Index Scriptorium Estoniae

Tamm, Liivi, 1978-

2009-01-01

Raivo Raidvee sisekujundusest MTV Eesti kontorile ja Maarja Mikkeni sisekujundusest brändingufirma Bränd Manual kontorile arhitektide Andrus Kõresaare ja Raivo Kotovi (KOKO Arhitektid) kavandatud tornidega majas Rotermanni kvartalis Roseni 7

Raamatututvustus

Index Scriptorium Estoniae

2008-01-01

2007. a. Tallinnas kirjastuselt Varrak ilmunud raamatust "1001 maali, mida elu jooksul peab nägema" (peatoimetaja Stephen Farthing, eessõna Geoff Dyer, tõlkinud Ann Kitsnik, Marika Liivamägi ja Maarja Merivoo)

Rotermanni laudsepatöökoja rekonstrueerimine Tallinnas / Raivo Kotov, Andrus Kõresaar, Marti Sein...[jt.

Index Scriptorium Estoniae

2009-01-01

Ill.: lõige, 4. korruse plaan, 2 välis- ja 2 sisevaadet; olemasoleva hoone kohale kavandati kolm eraldiseisvat majakat; arhitektuur: KOKO Arhitektid; konstruktsioonid: Neoprojekt; reklaamibüroo Brand Manuali kontori sisekujundaja: Maarja Mikkin

Keeletammik sai järjekordse nimipuu / Kristi Ehrlich

Index Scriptorium Estoniae

Ehrlich, Kristi, 1979-

2009-01-01

Väike-Maarjas peetud Wiedemanni keelepäevast, kus pidas ettekande ka tänavune keeleauhinna laureaat, Ohio ülikooli professor Ilse Lehiste. Keelekonverentsist võttis osa ka keeleteadlane ja TLÜ emeriitprofessor Mati Hint

[20. oktoobril esitleti Budapesti Kunstihallis ungari kirjandusajakirja "Prae" Eesti erinumbrit...

Index Scriptorium Estoniae

2010-01-01

Number sisaldab Tuglase preemiaga auhinnatud novellid Mehis Heinsaarelt, Jürgen Roostelt, Armin Kõomäelt, Ilmar Jaksilt, Jüri Tuulikult ja Andrei Hvostovilt ning Maarja Kangro, Kalju Kruusa, fs-i ja Hasso Krulli luuletusi

Muusika

Index Scriptorium Estoniae

2005-01-01

EMA kammersaalis avatakse Veljo Tormise regilaulukeskus ja esitatakse DVDd "Tegelik regilaulmine". Agentuuri Corelli Music kontserdisarja "Ajaloo ilu - J. S. Bach" kontsertidest. Pille Lille Muusikute Toetusfond korraldab sarjas "Hingemuusika" Otepää Maarja kirikus kontserdi

Sõmeru keskusehoone = Sõmeru community centre

Index Scriptorium Estoniae

2011-01-01

Sõmeru alevikus Kooli 2 asuva Sõmeru keskusehoone arhitektuursest lahendusest ja sisekujundusest. Autorid Kristiina Arusoo, Karli Luik, Ralf Lõoke, Maarja Kask (Salto AB), Margit Argus. Loetletud AB Salto ja Margit Arguse tehtud töid

Tartu Kesklinna Kooli juurdeehitus = Addition to Tartu Kesklinna (City Centre) School / Margit Mutso

Index Scriptorium Estoniae

Mutso, Margit, 1966-

2009-01-01

Juurdeehitise arhitektid Maarja Kask, Ralf Lõoke ja Karli Luik (Salto AB) pälvisid Eesti Kultuurkapitali arhitektuuri sihtkapitali aastapreemia 2008. Muinsuskaitse eritingimused koostas Maret Eimre. Juurdeehitise (Kroonuaia 7) arhitektuursest lahendusest, žürii hinnang

Genome-wide analysis of the phosphoinositide kinome from two ciliates reveals novel evolutionary links for phosphoinositide kinases in eukaryotic cells.

Directory of Open Access Journals (Sweden)

George Leondaritis

Full Text Available BACKGROUND: The complexity of phosphoinositide signaling in higher eukaryotes is partly due to expansion of specific families and types of phosphoinositide kinases (PIKs that can generate all phosphoinositides via multiple routes. This is particularly evident in the PI3Ks and PIPKs, and it is considered an evolutionary trait associated with metazoan diversification. Yet, there are limited comprehensive studies on the PIK repertoire of free living unicellular organisms. METHODOLOGY/PRINCIPAL FINDINGS: We undertook a genome-wide analysis of putative PIK genes in two free living ciliated cells, Tetrahymena and Paramecium. The Tetrahymena thermophila and Paramecium tetraurelia genomes were probed with representative kinases from all families and types. Putative homologs were verified by EST, microarray and deep RNA sequencing database searches and further characterized for domain structure, catalytic efficiency, expression patterns and phylogenetic relationships. In total, we identified and characterized 22 genes in the Tetrahymena thermophila genome and 62 highly homologues genes in Paramecium tetraurelia suggesting a tight evolutionary conservation in the ciliate lineage. Comparison to the kinome of fungi reveals a significant expansion of PIK genes in ciliates. CONCLUSIONS/SIGNIFICANCE: Our study highlights four important aspects concerning ciliate and other unicellular PIKs. First, ciliate-specific expansion of PI4KIII-like genes. Second, presence of class I PI3Ks which, at least in Tetrahymena, are associated with a metazoan-type machinery for PIP3 signaling. Third, expansion of divergent PIPK enzymes such as the recently described type IV transmembrane PIPKs. Fourth, presence of possible type II PIPKs and presumably inactive PIKs (hence, pseudo-PIKs not previously described. Taken together, our results provide a solid framework for future investigation of the roles of PIKs in ciliates and indicate that novel functions and novel regulatory

Küüditatuid mälestati kontserdiga Kohilas ja Raplas / Inge Põlma

Index Scriptorium Estoniae

Põlma, Inge

2009-01-01

1941. aastal küüditatute mälestuseks toimunud kontsertidest "Me ei näinud teda enam kunagi" 14. juunil Raplas Maarja-Magdaleena kirikus ja Kohilas EAÕ Angerja Issanda kirikus, esines ansambel Tallinn Baroque

Eesti Maaülikooli spordihoone = The Sports Hall of the Estonian University of Life Sciences / Margit Mutso

Index Scriptorium Estoniae

Mutso, Margit, 1966-

2010-01-01

Tartus Kreutzwaldi 3 asuva EMÜ spordihoone arhitektuursest lahendusest. Arhitektid: Maarja Kask, Karli Luik, Ralf Lõoke (Salto AB). Sisearhitektid: Katrin Kaevats, Jaan Port (Funk AB). Žürii liikme Kalle Komissarovi hinnang kultuurkapitali aastapreemiale esitatud hoonele

Akna varastamine : eesti Y-kirjandus / Berk Vaher

Index Scriptorium Estoniae

Vaher, Berk, 1975-

2014-01-01

Valdur Mikita, Erkki Luuk'i, Kiwa, Kaspari ja kirjanike rühmituse “14 NÜ” (Mait Laas, Paavo Matsin, Marko Mägi, Erkki Kadarik, Marianne Ravi, Maarja Vaino, Trip Jarvis, Johannes Üksi) loomingust

Plaadid / Mart Normet

Index Scriptorium Estoniae

Normet, Mart, 1979-

2006-01-01

Uutest heliplaatidest The Roots "Game Theory", Maarja ja Rannap "Läbi jäätunud klaasi", Natalie Walker " Urban Angel", Outkast "Idlewild", Peter Grant "New Vintage", Stone Sour "Come What May", Heather Greene "Five Dollar Dress"

Eesti ekspositsioon "Gaasitoru" Veneetsia XI arhitektuuribiennaalil = Estonia's entry at the 11th International Architecture Exhibition at La Biennale di Venezia: "Gas Pipe" / Margit Mutso

Index Scriptorium Estoniae

Mutso, Margit, 1966-

2009-01-01

Installatsiooni autorid on Maarja Kask, Ralf Lõoke (Salto AB) ja Neeme Külm, kuraator Ingrid Ruudi (pälvisid Eesti Kultuurkapitali peapreemia ja arhitektuuri sihtkapitali aastapreemia 2008) ning komissar Laila Põdra. Žürii hinnang "Gaasitorule"

Living with a parasite / Elo-Hanna Seljamaa

Index Scriptorium Estoniae

Seljamaa, Elo-Hanna, 1980-

2004-01-01

Ehtekunstnike Kärt Marani (s. 1980), Argo Männiku (s. 1977), Bruno Lillemetsa (s. 1979), Sven Tali, Ester Faimani (s. 1975), Maarja Niinemäe ja Katrin Veegeni näitus "Tallinna lennuväli : anti-venenos"

Paide Spordihall = Paide Sports Hall / Margit Mutso

Index Scriptorium Estoniae

Mutso, Margit, 1966-

2010-01-01

Paides Aiavilja 1 asuva spordihalli arhitektuursest lahendusest. Arhitektid: Maarja Kask, Karli Luik, Ralf Lõoke, kaasautor Jaan Port (Salto AB). Sisearhitekt Ville Lausmäe (VL Sisearhitektuur). Žürii liikme Kalle Komissarovi hinnang kultuurkapitali aastapreemiale esitatud hoonele

Kas president peaks Asso Kommerile armu andma? : kuueks ja pooleks aastaks vangi mõistetud endine jäägripealik Asso Kommer esitas veebruari lõpul armuandmispalve

Index Scriptorium Estoniae

1998-01-01

Eesti Päevalehe küsitlusele vastavad EELK Põlva Maarja koguduse kirikuõpetaja Üllar Kask, Medica Arstikeskuse perearst Ahti Virkus, AS Ius Dicere tegevdirektor Reigo Kala, Tallinna volikogu liige Arved Liivrand, Riigikogu majanduskomisjoni esimees Tiit Made

Passion House - kirega loodud valmismaja / Kersti Pikk

Index Scriptorium Estoniae

Pikk, Kersti

2013-01-01

Janar Toomesso ja Priit Vahe valmismajade projektist Passion Smart Design Houses. Valminud on moodulmaja mudel M1 (Architect 11 meeskond, peaarhitekt Eero Endjärv). Sisearhitektid Hannelore Kääramees, Kätlin Ölluk, Maarja Valk-Falk

Davaite budem nemnogo glupõmi / Luiza Mishina

Index Scriptorium Estoniae

Mishina, Luiza

1996-01-01

Nagibin, Juri. Tma v kontse tunnelja. Moja zolotaja teshtsha : Povesti. Moskva : PIK, 1994; Nagibin, Juri. Dafnis i Hloja epohhi kulta litshnosti, voljuntarisma i zastoja : Istorija odnoi ljubvi. Moskva : PIK, 1995

Modernizing the 5G 100/8 piston compressor by means of directly streaming valves

Energy Technology Data Exchange (ETDEWEB)

Tsvetanov, Ts.; Stoyanov, I.

1988-02-01

Deals with 5G 100/8 air compressors which, despite long service and lack of spare parts, are still widely used in Bulgarian underground coal mines. K-4-10 ring-type valves are in particularly short supply; maintenance engineers have been forced to modify the compresors. Initially, Bulgarian KP-3.1 valves with direct air streaming replaced the K-4-10; these were later replaced by PIK-220 and PIK-220A valves. Tests on overhauled compressors have shown that replacing the KP-3.1 with the PIK-220 or PIK-220A can result in a saving of up to 100,000 kWh of electricity per compressor. Details of reconstruction and testing of piston compressors are included. 10 refs.

Tallinna ülikool jagas auhindu

Index Scriptorium Estoniae

2009-01-01

Tallinna Ülikooli vilistlaste, tudengite ja töötajate vahel jagatavad kirjandusauhinnad läksid tänavu Maarja Kangrole luulekogu "Heureka" eest ja Mari Tarvasele Sigmund Freudi teose "Nali ja selle seos teadvustamatusega" tõlkimise eest

Eesti oopereid Nargen-festivalil / Evi Arujärv

Index Scriptorium Estoniae

Arujärv, Evi, 1953-

2011-01-01

Timo Steineri ooperist "Kask pead", libretist Maarja Kangro, lavastaja Mart Koldits, dirigent Tõnu Kaljuste ja Anti Marguste mini mono-ooperite A. H. Tammsaare, August Kitzbergi ja Oskar Lutsu tekstidele "Andreses monoloogid", "Tiina monoloogid", "Arno monoloogid", dirigent Tõnu Kaljuste,

IDH2 Mutations Define a Unique Subtype of Breast Cancer with Altered Nuclear Polarity

Science.gov (United States)

Chiang, Sarah; Weigelt, Britta; Wen, Huei-Chi; Pareja, Fresia; Raghavendra, Ashwini; Martelotto, Luciano G.; Burke, Kathleen A.; Basili, Thais; Li, Anqi; Geyer, Felipe C.; Piscuoglio, Salvatore; Ng, Charlotte K.Y.; Jungbluth, Achim A.; Balss, Jörg; Pusch, Stefan; Baker, Gabrielle M.; Cole, Kimberly S.; von Deimling, Andreas; Batten, Julie M.; Marotti, Jonathan D.; Soh, Hwei-Choo; McCalip, Benjamin L.; Serrano, Jonathan; Lim, Raymond S.; Siziopikou, Kalliopi P.; Lu, Song; Liu, Xiaolong; Hammour, Tarek; Brogi, Edi; Snuderl, Matija; Iafrate, A. John; Reis-Filho, Jorge S.; Schnitt, Stuart J.

2017-01-01

Solid papillary carcinoma with reverse polarity (SPCRP) is a rare breast cancer subtype with an obscure etiology. In this study, we sought to describe its unique histopathologic features and to identify the genetic alterations that underpin SPCRP using massively parallel whole-exome and targeted sequencing. The morphologic and immunohistochemical features of SPCRP support the invasive nature of this subtype. Ten of 13 (77%) SPCRPs harbored hotspot mutations at R172 of the isocitrate dehydrogenase IDH2, of which 8 of 10 displayed concurrent pathogenic mutations affecting PIK3CA or PIK3R1. One of the IDH2 wild-type SPCRPs harbored a TET2 Q548* truncating mutation coupled with a PIK3CA H1047R mutation. Functional studies demonstrated that IDH2 and PIK3CA hotspot mutations are likely drivers of SPCRP, resulting in its reversed nuclear polarization phenotype. Our results offer a molecular definition of SPCRP as a distinct breast cancer subtype. Concurrent IDH2 and PIK3CA mutations may help diagnose SPCRP and possibly direct effective treatment. PMID:27913435

Mai kinos linastub uus Eesti film "Kõrini!"

Index Scriptorium Estoniae

2006-01-01

Täna linastub Pärnus Eesti-Saksa koostööfilm "Kõrini" : režissöör Peeter Simm : osades Maarja Jakobson, Rasmus Kaljujärv, Heio von Stetten, Thomas Schmauser : Ruut Pictures (Eesti) - Saxonia Film (Saksa) 2005

Plaadiesitlus

Index Scriptorium Estoniae

2005-01-01

Heliplaatidest: Erdman/Sooäär" Peer Gynt & Other Stories" (esitlus 29. apr. Sakala keskuses), "Mi tango en Buenos Aires" (esitlus 24. apr. Sakala keskuses), Hinkus ja Maarja "Look Around" (esitlus 28. Rock Cafés grupiga Reel People)

Kolleegide tunnustus

Index Scriptorium Estoniae

2010-01-01

Teatri Vanemuine draamatrupp valis kolleegipreemiate laureaadid 2010. a. tööde põhjal. Naispeaosa auhinna sai Külliki Saldre, meespeaosa auhinna Aivar Tommingas, naiskõrvalosa auhinna Maarja Mitt, meeskõrvalosa auhinna Margus Jaanovits. Parim lavastus - Ingo Normeti "Huntluts"

Tuntud ja tundmatud meistrid 4 / Helena Risthein

Index Scriptorium Estoniae

Risthein, Helena, 1954-

2003-01-01

Kadrioru lossis eksponeeritud teos "Madonna puuviljapärja keskel" koosneb kahest maalitahvlist, kuna tolleaegsed kunstnikud spetsialiseerusid kitsale erialale. Pieter Franzs. de Grebber (1600-1653) maalis Maarja Kristus-lapsega ja Frans Ykens (1601-1693) Maarjat ümbritseva puuviljapärja

Multiple metabolic alterations exist in mutant PI3K cancers, but only glucose is essential as a nutrient source.

Directory of Open Access Journals (Sweden)

Rebecca Foster

Full Text Available Targeting tumour metabolism is becoming a major new area of pharmaceutical endeavour. Consequently, a systematic search to define whether there are specific energy source dependencies in tumours, and how these might be dictated by upstream driving genetic mutations, is required. The PI3K-AKT-mTOR signalling pathway has a seminal role in regulating diverse cellular processes including cell proliferation and survival, but has also been associated with metabolic dysregulation. In this study, we sought to define how mutations within PI3KCA may affect the metabolic dependency of a cancer cell, using precisely engineered isogenic cell lines. Studies revealed gene expression signatures in PIK3CA mutant cells indicative of a consistent up-regulation of glycolysis. Interestingly, the genes up- and down-regulated varied between isogenic models suggesting that the primary node of regulation is not the same between models. Additional gene expression changes were also observed, suggesting that metabolic pathways other than glycolysis, such as glutaminolysis, were also affected. Nutrient dependency studies revealed that growth of PIK3CA mutant cells is highly dependent on glucose, whereas glutamine dependency is independent of PIK3CA status. In addition, the glucose dependency exhibited by PIK3CA mutant cells could not be overridden by supplementation with other nutrients. This specific dependence on glucose for growth was further illustrated by studies evaluating the effects of targeted disruption of the glycolytic pathway using siRNA and was also found to be present across a wider panel of cancer cell lines harbouring endogenous PIK3CA mutations. In conclusion, we have found that PIK3CA mutations lead to a shift towards a highly glycolytic phenotype, and that despite suggestions that cancer cells are adept at utilising alternative nutrient sources, PIK3CA mutant cells are not able to compensate for glucose withdrawal. Understanding the metabolic

Impact of KRAS, BRAF and PI3KCA mutations in rectal carcinomas treated with neoadjuvant radiochemotherapy and surgery

International Nuclear Information System (INIS)

Derbel, Olfa; La Fouchardière, Christelle de; Wang, Qing; Desseigne, Françoise; Rivoire, Michel; Meeus, Pierre; Peyrat, Patrice; Stella, Mattia; Martel-Lafay, Isabelle; Lemaistre, Anne-Isabelle

2013-01-01

Conventional treatment for locally advanced rectal cancer usually combines neoadjuvant radiochemotherapy and surgery. Until recently, there have been limited predictive factors (clinical or biological) for rectal tumor response to conventional treatment. KRAS, BRAF and PIK3CA mutations are commonly found in colon cancers. In this study, we aimed to determine the mutation frequencies of KRAS, BRAF and PIK3CA and to establish whether such mutations may be used as prognostic and/or predictive factors in rectal cancer patients. We retrospectively reviewed the clinical and biological data of 98 consecutive operated patients between May 2006 and September 2009. We focused in patients who received surgery in our center after radiochemotherapy and in which tumor samples were available. In the 98 patients with a rectal cancer, the median follow-up time was 28.3 months (4–74). Eight out of ninety-eight patients experienced a local recurrence (8%) and 17/98 developed distant metastasis (17%). KRAS, BRAF and PIK3CA were identified respectively in 23 (23.5%), 2 (2%) and 4 (4%) patients. As described in previous studies, mutations in KRAS and BRAF were mutually exclusive. No patient with local recurrence exhibited KRAS or PIK3CA mutation and one harbored BRAF mutation (12.5%). Of the seventeen patients with distant metastasis (17%), 5 were presenting KRAS mutation (29%), one BRAF (5%) and one PIK3CA mutation (5%). No relationship was seen between PIK3CA, KRAS or BRAF mutation and local or distant recurrences. The frequencies of KRAS, BRAF and PIK3CA mutations in our study were lower than the average frequencies reported in colorectal cancers and no significant correlation was found between local/distant recurrences and KRAS, BRAF or PIK3CA mutations. Future studies with greater number of patients, longer follow-up time and greater power to predict associations are necessary to fully understand this relationship

FACE-TO-FACE: Balti börsihoone lugu

Index Scriptorium Estoniae

2016-01-01

Raamat käib käsikäes Ralf Lõokese, Maarja Kase ja Neeme Külma samanimelise kineetilise installatsiooniga ning tutvustab Londoni Balti börsihoone ebatavalist käekäiku ja selle jõudmist merekonteineritesse pakitult Eestisse

Kaitstud tööd 2013 : [doktori- ja magistriväitekirjad

Index Scriptorium Estoniae

2014-01-01

Doktoritööd kaitses Anu Sarv; magistritööd Anto Alasepp, Ott Puumeister, Marili Pärtel, Maarja Yano, Eva Väljaots, Ana Koncul, Derek Clayton Jenkins, Mark Richard Lemon, Matthew Campanella, Montana Jean Salvoni, Muzayin Arifin Nazaruddin, Oleg Sobchuk

On tegu ja nägu / Ralf Lõoke ; interv. Karin Paulus

Index Scriptorium Estoniae

Lõoke, Ralf, 1978-

2008-01-01

Tartu Kesklinna kool valmis 1912. aastal arhitekt Arved Eichhorni projekti järgi. 1965. aastal valmis Udo Tiirmaa projekti järgi juurdeehitis. 2007. aastal avati kooli laiendus, autoriteks arhitektuuribüroo Salto arhitektid Maarja Kask, Karli Luik ja Ralf Lõoke

Kivist kirjanik / Jaanus Rohumaa

Index Scriptorium Estoniae

Rohumaa, Jaanus, 1969-

2007-01-01

Jaanus Rohumaa räägib 2006. aastal lavastatud "Vargamäe kuningriigist" : "Tõe ja õiguse" I köite esmailmumise 80. aastapäevale pühendatud konverentsi ettekanded 8. XII 2006 / koost. Maarja Vaino. - [Tallinn] : Anton Hansen Tammsaare Muuseum

Vanuajalehti sirvides : 1984 : 25 aastat tagasi / Raigo Kollom, Heldur Peterson, Helle Rätsep

Index Scriptorium Estoniae

Kollom, Raigo, 1936-

2009-01-01

Kolm ratsaspordi artiklit aastast 1984: Krasnodaris toimunud üleliidulisest kolhooside, sohvooside ja põllumajandusasutuste ratsavõistlusest; Luunjas ja Vooremäel hooajalõpu üritusena taaselustatud Balti liiduvabariikide kohtumisest kolmevõistluses; Väike-Maarja kolhoosi VII ratsaspordi päevast.

Noored kunstnikud Põlvas

Index Scriptorium Estoniae

1998-01-01

Aapo Ilvese maalide ja Silver Kommusaare graafika näitus 16. novembrist Põlvas Maarja galeriis. Boris Lukatsi ja soome graafiku Esa Riipa juures õppinud kunstnikud on esinenud ühisnäitustega 1993. aastast, tavaliselt A. Ilves graafika ja S. Kommusaar maalidega

Antifouling potential of some marine organisms from India against species of Bacillus and Pseudomonas

Digital Repository Service at National Institute of Oceanography (India)

Bhosale, S.H; Nagle, V.L.; Jagtap, T.G.

Potential of Some Marine Organisms from India Against Species of Bacillus and Pseudomonas S.H. Bhosale, V.L. Nagle, and T.G. Jagtap* National Institute of Oceanography, Dona Paula, Goa-403004, India Abstract: Crude methanolic extracts of 37 marine organisms.... The discs were placed in Zobell marine agar (pH 7.3) plates seeded with different strains of bacteria selected for studies. The cultures were incubated for 24 to 48 hours at room temperature, to obtain maximum growth in the culture media. The zones of inhi...

Zagadki Klemensa Pale / Vladimir Lesment

Index Scriptorium Estoniae

Lesment, Vladimir, 1931-

2004-01-01

Ehitusmeister ja kujur Clemens Pale'st (16. saj.) ja tema loodust Tallinnas. Osales Oleviste kiriku Maarja kabeli ehitamises ja raius osa Hans Pawelsi kenotaafi reljeefe. Kõrge mütsi ja habemega mehe figuuri kabeli konsoolil ja ühel reljeefidest peetakse tema autoportreedeks

Peeter Simmi uus film jõuab kinno

Index Scriptorium Estoniae

2006-01-01

Tallinna, Tartu ja Pärnu kinodes linastub homsest Eesti-Saksa koostööfilm "Kõrini" : režissöör Peeter Simm : osades Maarja Jakobson, Rasmus Kaljujärv, Heio von Stetten, Thomas Schmauser : Ruut Pictures (Eesti) - Saxonia Film (Saksa) 2005

Tule tagasi, Peeter! / Jaan Ruus

Index Scriptorium Estoniae

Ruus, Jaan, 1938-2017

2006-01-01

Eesti-Saksa koostööfilm "Kõrini" : režissöör Peeter Simm : operaator Rein Kotov : helilooja Sven Grünberg : osades Maarja Jakobson, Rasmus Kaljujärv, Heio von Stetten, Thomas Schmauser : Ruut Pictures (Eesti) - Saxonia Film (Saksa) 2005

"Dostali!" - s segodnjashnego dnja / Peeter Simm, Artur Talvik ; interv. Boris Tuch

Index Scriptorium Estoniae

Simm, Peeter, 1953-

2006-01-01

Tallinnas ning Tartu ja Pärnu kinodes esilinastub Eesti-Saksa koostööfilm "Kõrini" : režissöör Peeter Simm : osades Maarja Jakobson, Rasmus Kaljujärv, Heio von Stetten, Thomas Schmauser : Ruut Pictures (Eesti) - Saxonia Film (Saksa) 2005

PÖFFi žürii : Euraasia parim naisnäitleja on eestlane

Index Scriptorium Estoniae

2007-01-01

Lõppes 11. Pimedate Ööde Filmifestival. EurAsia programmi parima naisnäitleja auhinna sai Maarja Jakobson, elutööpreemia nukufilmi Heino Pars. Lisaks "Võistlusprogrammi EurAsia žürii auhinnad", "Scottish Leaderi Eesti filmi žürii auhinnad", "Teised auhinnad"

Evidence for $\\pi K$ -atoms with DIRAC-II

CERN Document Server

Allkofer, Yves

2008-01-01

DIRAC-II is a fixed-target experiment at the CERN Proton Synchroton (PS) which has been designed to search for piK atoms, a bound state of a pi±K± pair, and measure their lifetime. These atoms are observed through an excess of low energetic piK pairs over the background, detected in the two spectrometer arms. This excess comes from the ionization of piK atoms in the target and can be related to their mean life. The piK S-wave scattering length combination |a1/2 - a3/2| (for isospin 1/2 and 3/2) can be related to the latter. The aim of the upgraded DIRAC-II experiment is a measurement of the scattering length combination |a1/2 - a3/2| with a precision of 5%. piK atoms have not been observed so far. The original DIRAC experiment was designed to measure the scattering lengths of pipi atoms. So far, close to 15 000 atoms have been detected, leading to a precision on |a0 - a2| which is better than 10%. In chiral perturbation theories (ChPT) the pipi scattering lengths have been calculated with 2% precision a...

Eesti luule 2008 / Maarja Kangro

Index Scriptorium Estoniae

Kangro, Maarja, 1973-

2009-01-01

Ülevaade 2008. aasta eesti luulest. Pikemalt käsitletakse järgmisi autoreid ja nende luulekogusid: Kalju Kruusa "Pilvedgi mindgi liigutavadgi", Andrus Kasemaa "Poeedirahu", Jürgen Rooste "Tavaline eesti idioot" ja "21. sajandi armastusluule", fs "Alasti ja elus", Asko Künnap "Su ööd on loetud", Mats Traat "Soe õhtu", Paavo Piik "Lakoonia", Mathura "Inimene on rohi" ja "Luuletused Atitlani järvelt", Lauri Sommer "K. L. ja N.", Jaan Kaplinski "Teiselpool järve", Andres Langemets "Vooder", Jüri Talvet "Silmad peksavad une seinu", Kätlin Kätlin "Üks pole ühtegi", Bibi-Mai Suumann "Imelik võõramaa puu", Andres Ehin "Udusulistaja", Meelis Oidsalu "Koertepõud", Marko Kompus "Surnud kuldnokkade märjad esmaspäevad", Kaupo Meiel "Eesti elulood", (:)kivisildnik "Joosepi kahtlused", Leonhard Lapin ja Albert Trapeež "Isiklik. Üleüledine", Hando Runnel "Armukahi", Contra "Tahaksin olla autobuss", Gregor Elm "Varastatud jalajälg", Mart Juur "Pane Eesti peale tagasi", Esa Tarik "Kompuutertomograafilise madaltiheda mana kõrgtehnoloogilise taaskasutusteraapia tautoloogika", Liisi Ojamaa "Jõgi asfaldi all", Jana Lepik "Tuhahelbed", Krista Ojasaar "Unemuusika", Marje Ingel "Sulg", Elo-Mall Toomet "Nagu ei kusagil mujal", Joanna Ellmann "Liivaterade lend", Ingel Tael "Aja elu"

Figaro ja Taska / Maarja Undusk

Index Scriptorium Estoniae

Undusk, Maarja, 1959-

2010-01-01

Eduard Taska 120. sünniaastapäevale pühendatud Eduard Taska ja 1982. aastast Rootsis elava Marje Taska näitus "Vanaisa ja mina" Eesti Tarbekunsti- ja Disainimuuseumis 30. maini 2010, kuraator Anne Tiivel. Näitus "Eesti köited Prantsusmaal III" Eesti Rahvusraamatukogus 17. aprillini 2010. Väljas on tööd, mis osalesid 2009. a. X rahvusvahelisel köitekunstibiennaalil St. Rémy-lès Chevreuse'is, kus Euroopa Liidu poolt välja pandud peapreemia võitis Kristiina Nurk

Eesti mood Berliinis / Maarja Tali

Index Scriptorium Estoniae

Tali, Maarja

1998-01-01

Rahvusvahelise konkursi 'Smirnoff Fashion Awards' finaalvõistlus teemal 'Metamorphosis' 21. juulil Berliinis. Eesti eelvooru võitnud Aldo Järvsoo tööst 'Est', esinemisest. I koht - Elena Zarubina (Venemaa), II - Manija Ismat (Inglismaa), III - Desmond Yang (Hok¡Cai, Singapur). Kommentaar A. Järvsoolt

Kellele kuulub keel? / Maarja Siiner

Index Scriptorium Estoniae

Siiner, Maarja

2012-01-01

Arvustus: Kadri Koreinik. Language ideologies in the contemporary Estonian public: with a focus on South Estonian. Tartu : Tartu University Press, 2011.(Dissertationes sociologicae Universitatis Tartuensis ; 5)

Vilistlasküsimus: Kes endistest õpetajatest on olnud sulle elus eeskujuks? / Aino Arro, Kersti Luha, Evar Ojasaar ...[jt.

Index Scriptorium Estoniae

2008-01-01

Küsimusele vastavad Väike-Maarja Gümnaasiumi vilistlased: 41. lennu lõpetanu Aino Arro, 73. lennu lõpetanu Kersti Luha, 73. lennu lõpetanu Evar Ojasaar, 76. lennu lõpetanu Nele Münter-Trušin ja 80. lennu lõpetanu Arnis Alt

Mälestusmärk iseendale / Rein Veidemann

Index Scriptorium Estoniae

Veidemann, Rein, 1946-

2009-01-01

Lembit Petersonist ja tema lavastusest "Maarja kuulutamine", mille eest ta pälvis aastapreemia ja osatäitmiste eest samas lavastuses said aasta naisnäitlejapreemiad tema tütred Maria ja Laura Peterson. Poeg Marius Peterson sai preemia osatäitmise eest lavastuses "Linn"

Impeeriumikollane madu globaalsete võimusuhete paradiisis : kontseptualism / Maria-Kristiina Soomre

Index Scriptorium Estoniae

Soomre, Maria-Kristiina, 1978-

2008-01-01

12. IX 2008. a. avati Veneetsia XI rahvusvahelisel arhitektuuribiennaalil Eesti ekspositsioon "Gaasitoru" (autorid Maarja Kask, Ralf Lõoke, Neeme Külm, kuraator Ingrid Ruudi) Giardini pargis (ja videosillana Arsenale Artiglieries). Biennaali üldkuraatori Aaron Betsky kõnest Eesti ekspositsiooni ametlikul avamisel, lühidalt projekti kataloogist

Täna esilinastub uus Eesti mängufilm

Index Scriptorium Estoniae

2006-01-01

Täna Tallinnas, homsest ka Tartu ja Pärnu kinodes linastub Eesti-Saksa koostööfilm "Kõrini" : režissöör Peeter Simm : osades Maarja Jakobson, Rasmus Kaljujärv, Heio von Stetten, Thomas Schmauser : Ruut Pictures (Eesti) - Saxonia Film (Saksa) 2005

Rotermanni laudsepatöökoda = Rotermann cabinetmarker's workshop / Raivo Kotov, Andrus Kõresaar

Index Scriptorium Estoniae

Kotov, Raivo, 1976-

2009-01-01

Tallinna endise Rotermanni tööstuskvartali arhitektuuri kaasajastamine. Olemasoleva laudsepatöökoja kohale kavandati kolm eraldiseisvat majakat. Arhitektid Andrus Kõresaar ja Raivo Kotov (KOKO Arhitektid), konstruktorid Marti Sein ja Matis Teeäär, reklaamibüroo Brand Manuali kontori sisekujundaja Maarja Mikkin

Praostkondade uudised : Viljandi. Põltsamaa

Index Scriptorium Estoniae

2006-01-01

10.-11. aug. Helme kogudust külastanud norra koori Lillebergkvartetten kontserdist Taageperas Helme valla hooldekodus. 15. aug. Helme Maarja koguduses peetud maarjapäeval saatis koguduse laule Tõrva puhkpilliorkester. Põltsamaa kogudus külastas 14.-18. aug. sõpruskogudusi Soomes, andes barokkmuusika kontserdi

Ars longa vita brevis est : kunst on pikk, elu lühike / Margit Bunder

Index Scriptorium Estoniae

Bunder, Margit, 1970-

2004-01-01

Fotokonkursist "Noored on tõelised võitjad". Loetletud preemiad saanud autorid ja tööd. Plakatinäitusest "Meil pole ükskõik". Maarja Galeriis avatud näitusest "Põhjamaine tunnetus". Riho Lahi eksliibriste ja Edgar Valteri raamatuillustratsioonide näitusest Põlva Keskraamatukogus

Neutron response matrix for unfolding NE-213 measurements to 21 MeV

International Nuclear Information System (INIS)

Ingersoll, D.T.; Wehring, B.W.; Johnson, R.H.

1976-01-01

A neutron response matrix from measured neutron responses of NE-213 in the energy range of 0.2 to 22 MeV is presented. An interpolation scheme was used to construct an 81-column matrix from the data of Verbinski, Burrus, Love, Zobel, and Hill. As a test of the new response matrix, the Cf-252 neutron spectrum was measured and unfolded using the new response matrix and the FORIST unfolding code. The spectrum agrees well with previous measurements at lower energies, while providing new information above 8 MeV

Pi3kcb links Hippo-YAP and PI3K-AKT signaling pathways to promote cardiomyocyte proliferation and survival.

Science.gov (United States)

Lin, Zhiqiang; Zhou, Pingzhu; von Gise, Alexander; Gu, Fei; Ma, Qing; Chen, Jinghai; Guo, Haidong; van Gorp, Pim R R; Wang, Da-Zhi; Pu, William T

2015-01-02

Yes-associated protein (YAP), the nuclear effector of Hippo signaling, regulates cellular growth and survival in multiple organs, including the heart, by interacting with TEA (transcriptional enhancer activator)-domain sequence-specific DNA-binding proteins. Recent studies showed that YAP stimulates cardiomyocyte proliferation and survival. However, the direct transcriptional targets through which YAP exerts its effects are poorly defined. To identify direct YAP targets that mediate its mitogenic and antiapoptotic effects in the heart. We identified direct YAP targets by combining differential gene expression analysis in YAP gain- and loss-of-function with genome-wide identification of YAP-bound loci using chromatin immunoprecipitation and high throughput sequencing. This screen identified Pik3cb, encoding p110β, a catalytic subunit of phosphoinositol-3-kinase, as a candidate YAP effector that promotes cardiomyocyte proliferation and survival. YAP and TEA-domain occupied a conserved enhancer within the first intron of Pik3cb, and this enhancer drove YAP-dependent reporter gene expression. Yap gain- and loss-of-function studies indicated that YAP is necessary and sufficient to activate the phosphoinositol-3-kinase-Akt pathway. Like Yap, Pik3cb gain-of-function stimulated cardiomyocyte proliferation, and Pik3cb knockdown dampened YAP mitogenic activity. Reciprocally, impaired heart function in Yap loss-of-function was significantly rescued by adeno-associated virus-mediated Pik3cb expression. Pik3cb is a crucial direct target of YAP, through which the YAP activates phosphoinositol-3-kinase-AKT pathway and regulates cardiomyocyte proliferation and survival. © 2014 American Heart Association, Inc.

Eesti ehted Firenzes

Index Scriptorium Estoniae

2005-01-01

Galeriis Le Arti Orafe on avatud kuue nimeka Euroopa ehtekoolkonna näitus "Chroma". Eestist on töödega esindatud Andrus Rumm, Eve Margus-Villems, Julia-Maria Pihlak, Kertu Tuberg, Kristiina Laurits, Kärt Maran, Maarja Niinemägi, Merle Kasonen, Piret Hirv, Tanel Veenre

Världsligt och andligt äktenskap - Marie trolovning i flandriska altarskåp = Profane and sacred marriage: the betrothal of the Virgin in the Netherlandish carved altarpieces / Mia Åkestam

Index Scriptorium Estoniae

Åkestam, Mia

2006-01-01

Neitsi Maarja ja Joosepi abielu sõlmimist kujutavatest, Brüsselis valminud altaritest kolmes Rootsi kirikus - Skepptunas, Jäderis ja Strängnäsis. Seda motiivi hakati kasutama alles 16. sajandi algusest, kui tunnistati kiriklik abielu sakramendiks ja abielu sai sõlmida ainult kirikliku laulatusega

Monopol suretab kohaliku loomakasvataja / Oleg Gross ; interv . Illar Mõttus

Index Scriptorium Estoniae

Gross, Oleg, 1952-

2005-01-01

Väike-Maarja jäätmetehase monopoolse seisundi vastu sõna võtnud OG Elektra omanik Oleg Gross on kindel, et jäätmetehasega suretatakse kohalikud väiksemad lihatootjad välja. Kommenteerivad talupidaja Jüri Järvet ja Rakvere Lihakombinaadi direktor Olle Horm

Iharus iseenda järele / Vaapo Vaher

Index Scriptorium Estoniae

Vaher, Vaapo, 1945-

2006-01-01

Tutvustus: Gide, André. Surra, et elada / tlk. Leena Tomasberg. Tallinn : Varrak, 2006 ; Soosaar, Martti. Lase vareseid! Tallinn : Tänapäev, 2006 ; Otsides : Juhan Peegel. Meenutusi pikalt teelt / koost. Maarja Lõhmus. Tallinn : Tänapäev, 2006 ; Steffenson, Jakob. Meie, ruhnlased. Tartu : A. Tuulberg, 2006

Elon levyraati eli kuinka suomalaiset musiikki-ihmiset kokevat virolaisten rakkaimmat laulut / Jartse Tuominen, Tommi Liuhala, Mikko Alatalo, Heikki, Salo ; intervjueerinud Harri Rinne

Index Scriptorium Estoniae

2013-01-01

Soome muusikud hindavad eestlaste lemmiklaule: Tõnis Mägi "Koit", Maarja "Suudlus läbi jäätunud klaasi", Siiri Sisaski "Mis maa see on" Liisi Koiksoni ja Marko Matvere "Tuulevaiksel ööl", Rihol Sibula "Videvik", Chalice´i "Minu inimesed" ja Ivo Linna "Julge laul"

Frequent alterations of the PI3K/AKT/mTOR pathways in hereditary nonpolyposis colorectal cancer

DEFF Research Database (Denmark)

Ekstrand, Anna Isinger; Jönsson, Mats; Lindblom, Annika

2010-01-01

The phosphatidylinositol 3-kinases-AKT-mammalian target of rapamycin pathway (PI3K/AKT/mTOR) is central in colorectal tumors. Data on its role in hereditary cancers are, however, scarce and we therefore characterized mutations in PIK3CA and KRAS, and expression of PIK3CA, phosphorylated AKT...... and PTEN in 58 HNPCC-associated colorectal cancers. Derangements of at least one of the PI3K/AKT/mTOR components analyzed were found in 51/58 (88%) tumors. Mutations in PIK3CA and KRAS were identified in 14 and 31% of the tumors respectively. Overexpression of PIK3CA and phosphorylated AKT occurred in 59...... and 75% and were strongly associated (P = 0.005). Reduced/lost PTEN expression was found in 63% of the tumors. Though HNPCC-associated colorectal cancers show simple genetic profiles with few chromosomal alterations, we demonstrate frequent and repeated targeting of the PI3K/AKT/mTOR pathway, which...

Sõmeru keskushoone = Sõmeru centre building / Ralf Lõoke ; intervjueerinud Margit Mutso

Index Scriptorium Estoniae

Lõoke, Ralf, 1978-

2011-01-01

Sõmeru keskushoone (Kooli 2, Sõmeru alevik) arhitektuursest lahendusest. Arhitektid Maarja Kask, Karli Luik ja Ralf Lõoke pälvisid Eesti Kultuurkapitali aastapreemia (2010) kõrgetasemelise panuse eest Eesti maa-arhitektuuri: Sõmeru keskushoone (kaasautorid Kristiina Arusoo ja Margit Argus) ja Eesti Maanteemuuseumi välialad (kaasautor Pelle-Sten Viiburg)

Teateid Eestist Läänemere läänekaldal / Anu Saluäär

Index Scriptorium Estoniae

Saluäär, Anu, 1948-

2008-01-01

Hans Dahlbergi raamatust "Läänemeri. Võitlus ühe mere pärast 862-1990" (Östersjön. Kampen om ett hav 862-1990), Mats Miljandi teosest "Maaletulek" (Landstigning) ning Maarja Talgre raamatust "Leo - vastupanu surmani" (Leo - ett estniskt öde). - Varem ilmunud: Looming 1991, nr. 1

Bruno võidujooksus eelistas žürii tarbijate südameid võitnud tooteid / Tanel Veenre

Index Scriptorium Estoniae

Veenre, Tanel, 1977-

2010-01-01

2010. aastal pälvis tootedisaini kategoorias disainiauhinna Bruno Veiko Liisi kujundatud kilepiima voldik-kann. Parimaks disainiprojektiks valiti Maarja Mõtuse jalatsiprojekt "Võru'82". Eeskujuliku design management'i tiitliga pärjati Kadarbiku talu. Bruno nominentide tööde näitus Arhitektuuri- ja Disainigaleriis 8. oktoobrini 2010

A mutant crp allele that differentially activates the operons of the fuc regulon in Escherichia coli.

Science.gov (United States)

Zhu, Y; Lin, E C

1988-05-01

L-Fucose is used by Escherichia coli through an inducible pathway mediated by a fucP-encoded permease, a fucI-encoded isomerase, a fucK-encoded kinase, and a fucA-encoded aldolase. The adolase catalyzes the formation of dihydroxyacetone phosphate and L-lactaldehyde. Anaerobically, lactaldehyde is converted by a fucO-encoded oxidoreductase to L-1,2-propanediol, which is excreted. The fuc genes belong to a regulon comprising four linked operons: fucO, fucA, fucPIK, and fucR. The positive regulator encoded by fucR responds to fuculose 1-phosphate as the effector. Mutants serially selected for aerobic growth on propanediol became constitutive in fucO and fucA [fucO(Con) fucA(Con)], but noninducible in fucPIK [fucPIK(Non)]. An external suppressor mutation that restored growth on fucose caused constitutive expression of fucPIK. Results from this study indicate that this suppressor mutation occurred in crp, which encodes the cyclic AMP-binding (or receptor) protein. When the suppressor allele (crp-201) was transduced into wild-type strains, the recipient became fucose negative and fucose sensitive (with glycerol as the carbon and energy source) because of impaired expression of fucA. The fucPIK operon became hyperinducible. The growth rate on maltose was significantly reduced, but growth on L-rhamnose, D-galactose, L-arabinose, glycerol, or glycerol 3-phosphate was close to normal. Lysogenization of fuc+ crp-201 cells by a lambda bacteriophage bearing crp+ restored normal growth ability on fucose. In contrast, lysogenization of [fucO(Con)fucA(Con)fucPIK(Non)crp-201] cells by the same phage retarded their growth on fucose.

"Kõrini" filmist ei saa poolteise tunni jooksul kõrini / Piret Linnamägi

Index Scriptorium Estoniae

Linnamägi, Piret

2006-01-01

Esilinastus Eesti-Saksa koostööfilm "Kõrini" : režissöör Peeter Simm : osades Maarja Jakobson, Rasmus Kaljujärv, Heio von Stetten, Thomas Schmauser : Ruut Pictures (Eesti) - Saxonia Film (Saksa) 2005. Filmist rääkisid režissöör, produtsent Artur Talvik. Filmi sisust

LIFT11 linnas

Index Scriptorium Estoniae

2010-01-01

Tallinn 2011 programmi kuuluva installatsioonide festivali "Lift11" avalikule ideekonkursile esitati 129 tööd, välja valiti 17. Tutvustatakse Maarja Kase ja Ralf Lõokese tööd "L", Tomomi Hayashi tööd "Merele!", Toomas Paaveri, Teele Pehki ja Triin Talki tööd "Kalarand"

Kodust kehakinnitust Amanda Puhvetist / Vivika Veski

Index Scriptorium Estoniae

Veski, Vivika

2007-01-01

Psühhiaater Tiina Keldrimale kuuluvast Amanda Puhvetist Üdruma külas Läänemaal. Endisele kauplusehoonele ehitati juurde torn, mille I korrusel on ehtekunstnik Maarja Jõevee Käsitöökuur. Ruumid sisustati vana mööbli ja vanavaraga. Sisearhitekt Martti Ruus. 6 värv. vaadet

Eesti Maaülikooli uus üliõpilasesindus astus ametisse / Silver Kuusik

Index Scriptorium Estoniae

Kuusik, Silver

2008-01-01

Maaülikooli üliõpilasesinduse üldistest ja konkreetsetest eesmärkidest. Küsimusele, mida vast valitud esinduse liikmed kooli heaks teha saavad, vastasid Kersti Pärtelpoeg, Veikko Kiis, Anni Haavakats, Julia Koltsova, Maarja Sõrmus, Rainer Zirnask, Gerlin Järvela, Iiris Rausk, Marili Köster, Christina Birnbaum ja Siim Lokko

Viljandi Riigigümnaasium = Viljandi Upper Secondary School

Index Scriptorium Estoniae

2015-01-01

Viljandi Riigigümnaasiumi uus hoone Hariduse tänav 2, valminud 2013. Arhitektuuri sihtkapitali arhitektuuripreemia 2013 ja Arhitektuuri sihtkapitali renoveerimispreemia 2013. Arhitektid Maarja Kask, Karli Luik, Ralf Lõoke, Andro Mänd, Margus Tamm (Salto Arhitektid), Eva Laarmann. Sisearhitektid Pille Lausmäe, Kristina Roots, Kerli Lepp. Muinsuskaitse eritingimused Mart Siilivask

Molecular Scree ning of Blast Resistance Genes in Rice Germplasms Resistant to Magnaporthe oryzae

Directory of Open Access Journals (Sweden)

Liang Yan

2017-01-01

Full Text Available Molecular screening of major rice blast resistance genes was determined with molecular markers, which showed close-set linkage to 11 major rice blast resistance genes (Pi-d2, Pi-z, Piz-t, Pi-9, Pi-36, Pi-37, Pi5, Pi-b, Pik-p, Pik-h and Pi-ta2, in a collection of 32 accessions resistant to Magnaporthe oryzae. Out of the 32 accessions, the Pi-d2 and Pi-z appeared to be omnipresent and gave positive express. As the second dominant, Pi-b and Piz-t gene frequencies were 96.9% and 87.5%. And Pik-h and Pik-p gene frequencies were 43.8% and 28.1%, respectively. The molecular marker linkage to Pi-ta2 produced positive bands in eleven accessions, while the molecular marker linkage to Pi-36 and Pi-37 in only three and four accessions, respectively. The natural field evaluation analysis showed that 30 of the 32 accessions were resistant, one was moderately resistant and one was susceptible. Infection types were negatively correlated with the genotype scores of Pi-9, Pi5, Pi-b, Pi-ta2 and Pik-p, although the correlation coefficients were very little. These results are useful in identification and incorporation of functional resistance genes from these germplasms into elite cultivars through marker-assisted selection for improved blast resistance in China and worldwide.

miR-203 inhibits cell proliferation and promotes cisplatin induced cell death in tongue squamous cancer

Energy Technology Data Exchange (ETDEWEB)

Lin, Jiong; Lin, Yao [Guangdong Provincial Key Laboratory of Stomatology, Department of Orthodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, 510055 (China); Fan, Li [Department of Pharmaceutical Analysis, School of Pharmacy, The Fourth Military Medical University, Xi' an, Shaanxi, 710032 (China); Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055 (China); Kuang, Wei [Department of Stomatology, Guangzhou General Hospital of Guangzhou Military Command, 111 Liuhua Road, Guangzhou, 510010 (China); Zheng, Liwei [State Key Laboratory of Oral Diseases, Sichuan University, Wuhou District, Chengdu, 610041 (China); Wu, Jiahua [Guangdong Provincial Key Laboratory of Stomatology, Department of Orthodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, 510055 (China); Shang, Peng [Patient-specific Orthopedic Technology Research Center in GuangDong Research Centre for Neural Engineering, 1068 Xueyuan Boulevard, University Town of Shenzhen, Xili, Nanshan, Shenzhen, 518055 (China); Wang, Qiaofeng [Department of Pharmaceutical Chemistry, School of Pharmacy, The Fourth Military Medical University, Xi' an, Shanxi, 710032 (China); Tan, Jiali, E-mail: jasminenov@163.com [Guangdong Provincial Key Laboratory of Stomatology, Department of Orthodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, 510055 (China)

2016-04-29

Oral squamous cell carcinoma (OSCC) is one of the most common types of the head and neck cancer. Chemo resistance of OSCC has been identified as a substantial therapeutic hurdle. In this study, we analyzed the role of miR-203 in the OSCC and its effects on cisplatin-induced cell death in an OSCC cell line, Tca8113. There was a significant decrease of miR-203 expression in OSCC samples, compared with the adjacent normal, non-cancerous tissue. After 3 days cisplatin treatment, the survived Tca8113 cells had a lower expression of miR-203 than that in the untreated control group. In contrast, PIK3CA showed an inverse expression in cancer and cisplatin survived Tca8113 cells. Transfection of Tca8113 cells with miR-203 mimics greatly reduced PIK3CA expression and Akt activation. Furthermore, miR-203 repressed PIK3CA expression through targeting the 3′UTR. Restoration of miR-203 not only suppressed cell proliferation, but also sensitized cells to cisplatin induced cell apoptosis. This effect was absent in cells that were simultaneously treated with PIK3CA RNAi. In summary, these findings suggest miR-203 plays an important role in cisplatin resistance in OSCC, and furthermore delivery of miR-203 analogs may serve as an adjuvant therapy for OSCC. - Highlights: • Much lower miR-203 expression in cisplatin resistant Tca8113 cells is discovered. • Delivery of miR-203 can sensitize the Tca8113 cells to cisplatin induced cell death. • MiR-203 can downregulate PIK3CA through the 3′UTR. • The effects of miR-203 on cisplatin sensitivity is mainly through PIK3CA pathway.

Biohuumus - looduslik, kuid tõhus lahendus mullaviljakuse tõstmiseks / Nadezda Knjazeva

Index Scriptorium Estoniae

Knjazeva, Nadezda

2010-01-01

Biohuumus "Green-PIK" on orgaaniliste jääkide tehnoloogiliste vihmaussidega "Staratel" ümbertöötlemise produkt. See kontsentreeritud väetis sisaldab tasakaalustatud kombinatsioonis tervet kompleksi vajalikke toitaineid ja mikroelemente, fermente, pinnasantibiootikume, vitamiine, taimede kasvu ja arengu hormoone. Väetamine muutub efektiivsemaks biohuumuse ja vedela kontsentraadi Gumistar "Grin-PIK" kompleksse kasutamise korral

Vanemuislased jagasid oma majja tunnustust

Index Scriptorium Estoniae

2010-01-01

Vanemuise loomenõukogu jagas aastaauhindu. Autospiriti-nimeline draamaauhind läks Maarja Mittile, Torrese-nimelise balletiauhinna sai Colin Thomas Maggs, Kinema-nimelise tehnilise töötaja auhinna sai Jaan Koiduaru, loomenõukogu eripreemia sai trupijuht Eda Hinno ning haldustöötaja müügiassistendi preemia Sanna Pindma. Samuti jagati kolleegipreemiaid

Jukebox'i ja tšello kohtumine / Donald Tomberg

Index Scriptorium Estoniae

Tomberg, Donald, 1972-

2006-01-01

Eesti-Saksa koostööfilm "Kõrini" : stsenaristid Hans-Werner Honert, Thomas Steinke, Valentin Kuik, Peeter Simm : režissöör Peeter Simm : operaator Rein Kotov : helilooja Sven Grünberg : osades Maarja Jakobson, Rasmus Kaljujärv, Heio von Stetten, Thomas Schmauser : Ruut Pictures (Eesti) - Saxonia Film (Saksa) 2005

Ülikooli kirjandusauhinna said Kangro ja Valton

Index Scriptorium Estoniae

2008-01-01

Tallinna Ülikooli kirjandusauhinna pälvisid noor luuletaja ja tõlkija Maarja Kangro luulekogu "Tule mu koopasse mateeria" eest ja Arvo Valton tõlkesarjade "Väikeste rahvaste suur kirjandus" ja "Noorte luule" väljaandmise eest. Vt. ka Keel ja Kirjandus, nr. 4, 2008, lk. 317; Looming, nr. 4, 2008, lk. 634

Georgi söögituba Kotli majas / Helju Koger

Index Scriptorium Estoniae

Koger, Helju, 1943-

2006-01-01

Georg Lurichi järgi nime saanud söögitoast arhitekt Alar Kotli vanaisale kuulunud hoones Väike-Maarjas. Enne renoveerimist koliti hoone teise kohta. Söögitoa kujunduse tegi Kai Tort, mööbli valmistasid kohalikud puusepad, plekist lambid - Ilmar Aasumets. Omanik Avo Part. 7 värv. ill

Eesti Maaülikooli spordihoone = Estonian University of Life Sciences' Athletics Centre

Index Scriptorium Estoniae

2010-01-01

Eesti Sisearhitektide Liidu 2009. a. ühiskondliku interjööri preemia pälvinud Eesti Maaülikooli spordihoonest Tartus Kreutzwaldi t. 3. Sisekujunduse autorid Katrin Kaevats ja Jaan Port (Funk AB), nende tähtsamate tööde loetelu. Hoone arhitekt Salto AB (Karli Luik, Ralf Lõoke, Maarja Kask)

Ablation of phosphoinositide-3-kinase class II alpha suppresses hepatoma cell proliferation

Energy Technology Data Exchange (ETDEWEB)

Ng, Stanley K.L. [Singapore Immunology Network A-STAR (Singapore); Neo, Soek-Ying, E-mail: neo_soek_ying@sics.a-star.edu.sg [Singapore Immunology Network A-STAR (Singapore); Yap, Yann-Wan [Singapore Immunology Network A-STAR (Singapore); Karuturi, R. Krishna Murthy; Loh, Evelyn S.L. [Genome Institute of Singapore A-STAR (Singapore); Liau, Kui-Hin [Department of General Surgery, Tan Tock Seng Hospital (Singapore); Ren, Ee-Chee, E-mail: ren_ee_chee@immunol.a-star.edu.sg [Singapore Immunology Network A-STAR (Singapore); Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore (Singapore)

2009-09-18

Cancer such as hepatocellular carcinoma (HCC) is characterized by complex perturbations in multiple signaling pathways, including the phosphoinositide-3-kinase (PI3K/AKT) pathways. Herein we investigated the role of PI3K catalytic isoforms, particularly class II isoforms in HCC proliferation. Among the siRNAs tested against the eight known catalytic PI3K isoforms, specific ablation of class II PI3K alpha (PIK3C2{alpha}) was the most effective in impairing cell growth and this was accompanied by concomitant decrease in PIK3C2{alpha} mRNA and protein levels. Colony formation ability of cells deficient for PIK3C2{alpha} was markedly reduced and growth arrest was associated with increased caspase 3 levels. A small but significant difference in gene dosage and expression levels was detected between tumor and non-tumor tissues in a cohort of 19 HCC patients. Taken together, these data suggest for the first time that in addition to class I PI3Ks in cancer, class II PIK3C2{alpha} can modulate HCC cell growth.

Kulka aastapreemiate žürii hinnang = Comments from the panel of judges / Laila Põdra, Eva Hirvesoo, Tiit Sild, Epp Lankots ; intervjueerinud Margit Mutso

Index Scriptorium Estoniae

2011-01-01

Arhitektuuriaastast 2010. Eesti Kultuurkapitali aastapreemia - Maarja Kask, Karli Luik, Ralf Lõoke, Kristiina Arusoo, Margit Argus, Pelle-Sten Viiburg (Sõmeru keskusehoone, maanteemuuseumi välialad). Arhitektuuri sihtkapitali arhitektuuripreemia - Hannes Koppel (Kuressaare rannahoone), Raul Vaiksoo (eramu), restaureerimispreemia - Jaan Jõgi (Laupa mõis), sisearhitektuuri preemia - Leila Pärtelpoeg (Röa mõis), tegevuspreemia - Karin Hallas-Murula, Eesti Arhitektuurikeskus

Õigeusu kiriku arhitektuur Eestis 16.-18. sajandil / Aleksandr Pantelejev

Index Scriptorium Estoniae

Pantelejev, Aleksandr

2005-01-01

Tallinna Püha Nikolai kirik. Tallinnas Rootsi Mihkli, Narvas saksa Maarja (ikonostaasi teostas Jacob Leu, u. 1708) ja rootsi Jaani kiriku ümberehitamine õigeusu kirikuteks. Ikonostaaside kavandamisel osalesid Ivan Zarudnõi Tallinnas ja arvatavasti Dominico Trezzini (1670-1734) Narvas. Polgukirikud. Pärnu Püha Jekaterina õigeusu kirik (arhitekt Pjotr Jegorov, 1765-1768). Bibliograafia lk. 460

Short outlines of books by Estonian authors / Janika Kronberg and Rutt Hinrikus

Index Scriptorium Estoniae

Kronberg, Janika, 1963-

2010-01-01

Arvustus: Käsper, Kalle. Buridanid. I-V. Tallinn : Eesti Keele Sihtasutus, 2005-2010 ; Kivastik, Mart. Eesti asjad. Tartu : Kaks Musketäri, 2010 ; Kangro, Maarja. Ahvid ja solidaarsus. Tallinn : Eesti keele Sihtasutus, 2010 ; Põder, Rein. Unustatud. Tallinn : Eesti Raamat, 2010 ; Kesküla, Kalev. Elu sumedusest. Tallinn : Tuum, 2009 ; Pilv, Aare. Ramadaan. Tallinn : Tuum, 2010

Tammsaare ja piltlugu

Index Scriptorium Estoniae

2006-01-01

Anton Hansen Tammsaare muuseumi korraldatud koomiksivõistlusest "Teistmoodi Tammsaare", žürii koosseis. Esimese koha pälvis Joonas Sildre koomiks "Kuningal on külm", teise koha Elina Sildre töö "Koolis", kolmanda koha soomlase Jyrki Heikkineni töö "Soo peal". Kommenteerivad Tõnu Kaalep, Maarja Lõhmus, Ivar Laus, Meelik Mallene, Mari Laaniste

Lavakad, 23. lend / Eva Kübar

Index Scriptorium Estoniae

Kübar, Eva

2008-01-01

Eesti Muusika- ja Teatriakadeemia lavakunstikooli XXIII lennu lõpetajatest - näitlejad Marek Tammets, Ago Soots, Agnes Aaliste, Martin Mill, Andres Oja, Juss Haasma, Maarja Mitt, Meelis Põdersoo, Jekaterina Novosjolova, Elina Pähklimägi ja Kristo Viiding, dramaturgid Marion Jõepera, Mart Kase ja Maria Lee Liivak ning lavastajad Robert Annus ja Uku Uusberg

Dave Bentoni jõulud lauluga / Ille Grün-Ots

Index Scriptorium Estoniae

Grün-Ots, Ille, 1960-2016

2004-01-01

Poplaulja Dave Bentoni arvamusi jõulutraditsioonidest. Jõulutuurist Tallinnas Viimsi kultuurimajas 10. dets.ja Kaarli kirikus 11. dets., Pärnu Eliisabeti kirikus 15. dets., Kuressaare Laurentiuse kirikus 16. dets, Rapla Maarja-Magdaleena kirikus 19. dets., Tartu Peetri kirikus 20. dets., Oleviste kirikus Tallinnas 21. dets., Haapsalu Toomkirikus 22. dets., Jõelähtme kirikus 23. detsembril

Margus Laanet - erakust mässaja / Erle Selling

Index Scriptorium Estoniae

Selling, Erle

2001-01-01

Eesti päritolu kunstnikust Margus Laanetist (s. 16. juulil 1965 Väike-Maarjas), kes peab oma kodumaaks Hondurast, elab peamiselt Guatemalas, korraldab näitusi ka teistes Ladina-Ameerika maades. Tema üheksast isiknäitusest (1989-2000), retseptsioonist. Mehhiko kunstiteadlase Karen Reiman Cordero, argentiina kunstiteadlase Laura Malosetti-Costa ja M. Laaneti kommentaarid.

Gaasitoru tõstatab olulisi küsimusi / Laila Põdra

Index Scriptorium Estoniae

Põdra, Laila, 1967-

2008-01-01

XI Veneetsia arhitektuuribiennaalil esindas Eestit Maarja Kase, Ralf Lõokese ja Neeme Külma (Salto arhitektuuribüroo) gaasitoruinstallatsioon "Gaasitoru / Gas Pipe". Gaasijuhtme Nord Stream toruelementidest erkkollane 63 meetri pikkune skulpturaalne vorm kulges Giardini pargis näitusepaviljonide vahel. Projekti kuraator Ingrid Ruudi. Installatsiooniga kaasnes ajalehevormis kataloog. Eesti ekspositsiooni avamisel viibis biennaali üldkuraator Aaron Betsky

Saku Suurhall Rocca al Mares = Saku Suurhall in Rocca al Mare / Inga Raukas

Index Scriptorium Estoniae

Raukas, Inga, 1967-

2001-01-01

Peaprojekteerija, detailplaneering: Nord Projekt AS. Arhitektid Esa Viitanen (Soome), Andres Kariste, kaastöö: Meeli Truu, Loomet Raudsepp. Sisekujundus: Eero Jürgenson, Maarja Valk-Falk, Tambet Pedak, ARS Interjöörprojekt. Konstruktsioonid: Kaido Kuusiku, Tiit Arumäe, Aive Sau, Jaan Port. Projekteerimise projektijuht Andres Mikker. Projekt 1999-2001, valmis 2001. 9 ill

Kosmosest maa peale / Alina Kurvits

Index Scriptorium Estoniae

Kurvits, Alina

2004-01-01

Eesti noorte moeloojate võistlusest "Supernoova 2004". Üksikute finalistide kollektsioonide iseloomustus - Heleliis Hõim, Kati Ilves, Lemmiki Ehatamm, Triin Kaiv, Kaisa Reimand, Marin Sild, Maria Ossadtsaja, Kris Lemsalu, Ingel Undusk, Mari Hiietamm, Kaspar Paas, Maarja Metspalu, Kätlin Kaljuvee, Marje Mõttus, Julia Korovina, Külli-Kerttu Siplane,Piret Paal, Raili Nõlvak, Oksana Tandit, Vassilissa Shehovtsova

Sõpruslinnad toovad kultuuri / Arja Korhonen

Index Scriptorium Estoniae

Korhonen, Arja

2005-01-01

Teiste Soome päevade kultuuriürituste seas soome jazzviiuldaja ja laulja Heidi Piirala ja Jukka Lumme kvarteti ning akordionist Kaisa Kujanpää kontserdist Art Cafes 19. mail ja Soome simmanil Virma pubis 20. mail, Kaisa Kujanpää ja laulja Timo Kaitalahti kontserdist Väike-Maarja rahvamajas. Lappeenranna tsirkusekooli Tuikko etendustest

Veneetsia arhitektuuribiennaal

Index Scriptorium Estoniae

2008-01-01

Veneetsia XI arhitektuuribiennaalist. Biennaali üldkuraator Aaron Betsky. Giardini parki rajatud eestlaste installatsioonist "Gaasitoru" (autorid: Maarja Kask, Ralf Lõoke ja Neeme Külm, kuraator Ingrid Ruudi), rahvusekspositsioonide peapreemia saanud Poola paviljonist "Hotel Polonia", Austraalia, Tšehhi ja Slovakkia ekspositsioonidest, objektipreemia pälvinud Greg Lynn'i vanadest mänguasjadest valmistatud mööblist

Mina ja Mina Kunstihoones / Maarja Undusk

Index Scriptorium Estoniae

Undusk, Maarja

2004-01-01

Tallinna Kunstihoone nõukogu liige M. Undusk Tallinna Kunstihoones eksponeeritud Eesti Kunstnike Liidu aastanäitusest "Mina ja Teine", selle arutelust 16. I. Tallinna Kunstihoone näitusekorraldusest, kuraatoritest, suhetest EKL-ga

Vana arm ei roosteta / Maarja Vaino

Index Scriptorium Estoniae

Vaino, Maarja

2005-01-01

A. H. Tammsaare romaani "Ma armastasin sakslast" ilmumisest möödub 70 aastat. Tammsaare muuseum korraldab selle tähistamiseks 7. novembril koos Tallinna Ülikooli eesti kirjanduse õppetooliga konverentsi. Vt. ka sõnum lk. 19

Kogunenud kunst Tuglase majas / Maarja Undusk

Index Scriptorium Estoniae

Undusk, Maarja, 1959-

2011-01-01

Underi ja Tuglase Kirjanduskeskuse muuseumiosakonna kunstikogust ning selle põhjal korraldatud näitustest, millest viimane, "Hingede ränd. Ado Vabbe ja Friedebert Tuglas" toimus 2011. a. sügisel Vabaduse galeriis. Ka näitustega kaasnenud kataloogidest

Prediction of Response to Therapy and Clinical Outcome through a Pilot Study of Complete Genetic Assessment of Ovarian Cancer

Science.gov (United States)

2015-12-01

B, PIK3CA, BRCA2, ATM, SETD2, ATRX, MTOR, PIK3R1 Mucinous KRAS, TP53, CDKN2A, SMAD4 , TERT Carcinosarcoma TP53, RB1, APC Granulasa cell ATM...alterations in the PTEN- PI3K- AKT -mTOR pathway in a cohort of 379 ovarian cancer patients. Submitted to American Society of Clinical Oncology Annual meeting

Ernst Enno etluskonkursil kõlas saja aasta tagune luule / Krista Kumberg

Index Scriptorium Estoniae

Kumberg, Krista, 1959-

2007-01-01

Läänemaal toimus maakondlik Ernst Ennole pühendatud etluskonkurss. E. Enno nimelise etluskonkursi 2007 "Saja aasta tagused luuletused" parimad etlejad olid Mike Richard Koch, Janno Allika, Hanna Ring, Karl Poll, Britta Sool, Antero Rea, Jennifer Cohen, Brita Kaljuvee, Eva-Maria Brock, Kaupo Engel, Liisi Räli, Laivi Kovalenko, Merje Viigand, Carmen Freimann, Rauno Punk, Maarja Palmiste

Eesti Maanteemuuseumi välialad : avalik maastikuarhitektuuri ideekonkurss = Public Landscape Architectural Idea Competition "Outdoor Spaces of the Estonian Highway Museum" / Toomas Muru

Index Scriptorium Estoniae

Muru, Toomas, 1970-

2004-01-01

Põlvamaal, endises Varbuse hobupostijaamas avatava Eesti Maanteemuuseumi välialade konkursi eesmärgist, tingimustest, žürii koosseisust, premeeritud töödest. Preemiad: I - Margit Kärner, II - Karli Luik, Ralf Lõoke ja Maarja Kask, III - Taavi Kuningas, Andrus Padu ja Martin Prommik, ergutuspreemiad - Piret Looveer ja Remi Kübar ning Maria Pukk ja Ivar Lubjak

Tiskre-Hansu elamud = Tiskre-Hansu Homes / Tiit Sild

Index Scriptorium Estoniae

Sild, Tiit, 1977-

2005-01-01

Projekteerija: KPME Engineering & Design. Planeeringu eskiisi autorid Maarja Kask, Tiit Sild, kaasa töötas Kalle Rannula. Detailplaneering: Andres Volens, Kalle Rannula. I etapi kortermajade autor Tiit Sild, kaasa töötasid Maret Volens, Andres Volens, Kristo Tihvand. Valmis 2004-2005. Ill.: I, II ja III korruse plaan, 4 värv. välisvaadet

Crème de la crème / Joel Sang

Index Scriptorium Estoniae

Sang, Joel, 1950-

2011-01-01

Auhinnažürii esimees iseloomustab Eesti Kultuurkapitali kirjandusauhindade laureaate: Indrek Koff (luule), Maarja Kangro (proosa), Urmas Vadi (näitekirjandus), Toomas Haug (esseistika), Lauri Sommer (vabaauhind), Amar Annus (ilukirjanduslik tõlge võõrkeelest eesti keelde), Ilmar Lehtpere (ilukirjanduslik tõlge eesti keelest võõrkeelde), Kristiina Kass (lastekirjandus), Sergei Issakov (venekeelse autori kirjandusauhind) ja Mart Velsker (artikliauhind)

Von Krahli teater kolib mõneks ajaks Saksamaale / Rain Tolk

Index Scriptorium Estoniae

Tolk, Rain, 1977-

2006-01-01

Von Krahli Teatri selle hooaja eelviimane esietendus "Europiraadid" on 17. mail Düsseldorfis, koostöös Saksamaa teatrirühmaga Showcase Beat Le Mot. Eesti poole pealt teevad kaasa Juhan Ulfsak, Taavi Eelmaa, Maarja Jakobson ja üllatusmängijana filmimees Rain Tolk, kes räägib oma suhtumisest teatrisse ja suhetest Von Krahli Teatriga

Eilne, tänane ja homne ehtekunst Marzees / Eilve Manglus

Index Scriptorium Estoniae

Manglus, Eilve, 1977-

2004-01-01

Euroopa ehtekunstikoolide lõputööde väljapanek Marzee galeriis kuni 6. X. Kuraator Manuel Vilhena. Eestit esindanud Kertu Tubergi, Maarja Niinemäe ja Epp Perteli ning Bas Boumani, Jantine Bindelsi (Holland) ja Andrew Lambi (London) töödest. Marzee kollektsiooni kuuluvad EKA lõpetanud ehtekunstnike Villu Plingi, Piret Hirve ja Kristiina Lauritsa ehted

Lõpp annab tähenduse / Olev Remsu

Index Scriptorium Estoniae

Remsu, Olev, 1947-

2006-01-01

Eesti-Saksa koostööfilm "Kõrini" : stsenaristid Hans-Werner Honert, Thomas Steinke, Valentin Kuik, Peeter Simm : režissöör Peeter Simm : operaator Rein Kotov : helilooja Sven Grünberg : osades Maarja Jakobson, Rasmus Kaljujärv, Heio von Stetten, Thomas Schmauser : Ruut Pictures (Eesti) - Saxonia Film (Saksa) 2005. Lisatud P. Simmi filmograafia lk. 106

Gruzinski gambit / Nikolai Hrustaljov

Index Scriptorium Estoniae

Hrustaljov, Nikolai

2005-01-01

Anapas lõppes SRÜ ja Baltimaade XIV avatud filmifestival "Kinoshokk 2005". Žürii andis parima näitlejanna preemia Maarja Jakobsonile tema rolli eest P. Urbla filmis "Stiilipidu". Parima filmi auhinna sai grusiin Levan Tutberidze "Jalutuskäik Mägi-Karabahhis" ja parima režii auhinna samuti grusiin Levan Zakareishvili filmi eest "Thbilisi-Thbilisi"

Nargen Opera toob vaataja ette uue eesti kammerooperi / Priit Pruul

Index Scriptorium Estoniae

Pruul, Priit

2006-01-01

20. apr. esietendub Von Krahli Teatris Peeter Jalaka lavastuses Tõnu Kõrvitsa kammerooper "Mu luiged, mu mõtted", mille aluseks on luuletaja Marie Heibergi saatus. Libreto autor on Maarja Kangro. Kammerooper tuleb lavale Von Krahli Teatri ja Nargen Opera koostöös. Esitavad Kädy Plaas, Helen Lokuta, Nargen Opera koor ja Tallinna Kammerorkester, dirigent Tõnu Kaljuste

Nargen Opera lummas Kõrvitsa muusikaga / Ruth Alaküla, Andres Laasik

Index Scriptorium Estoniae

Alaküla, Ruth, 1957-

2006-01-01

Von Krahli Teatris Peeter Jalaka lavastuses esietendunud Tõnu Kõrvitsa uued kammerooperid "Tuleaed" ja "Mu luiged, mu mõtted", mille aluseks on luuletaja Marie Heibergi saatus. Libretode autor on Maarja Kangro. Kammerooperid tulevad lavale Von Krahli Teatri ja Nargen Opera koostöös. Esitavad Kädy Plaas, Helen Lokuta, Nargen Opera koor ja Tallinna Kammerorkester, dirigent Tõnu Kaljuste

["Lääne Elu" väljakuulutatud jõululuuletuste konkursil osalejad

Index Scriptorium Estoniae

2003-01-01

Taive Kesseli "Toa nurgas jõulupuu ehete säras..." ; Ülle Ehala "Advent" ; Heldi Leidsalu "Laul jõuluvanale" ; Silja Paulus "Olen olnud paha laps" ; Erika Raudsepp "Jõuluvanal "Kopp on ees"..." ; Kelvin Vaske "Jõulususs ootab" ; Allar Lillenurm "Öö sinine, helge..." ; Maarja-Liis Mäeste "Jõululuuletus" ; Merilin Serg "Lumi tuli" ; Silvi-Astrid Mickelin "Sajandite reel", "Hing ihkab"

Kultuurkapital nimetas aasta parimad

Index Scriptorium Estoniae

2011-01-01

Eesti Kultuurkapitali aastapreemia 2010 laureaadid: arhitektid Maarja Kask, Ralf Lõoke, Karli Luik (Sõmeru keskusehoone), animaator Mati Kütt (Taevalaul), helilooja Urmas Sisask, kirjanik Mats Traat (Minge üles mägedele), sporditreener Anna Levandi, kunstnik Denes Kalev Farkas (Let's Play, the Game Is Over), teatriühendus R.A.A.A.M., folklorist Anu Korb (Eesti asundused)

Triumf gruzinskogo kino / Irina Ivanova

Index Scriptorium Estoniae

Ivanova, Irina

2005-01-01

Anapas lõppes SRÜ ja Baltimaade XIV avatud filmifestival "Kinoshokk 2005". Žürii andis parima näitlejanna preemia Maarja Jakobsonile tema rolli eest P. Urbla filmis "Stiilipidu". Parima filmi auhinna sai grusiin Levan Tutberidze "Jalutuskäik Mägi-Karabahhis" ja parima režii auhinna samuti grusiin Levan Zakareishvili filmi eest "Thbilisi-Thbilisi"

Tallinna Ülikooli Balti Filmi- ja Meediakooli õppehoone Nova = Tallinn University Baltic Film and Media School "Nova"

Index Scriptorium Estoniae

2015-01-01

Tallinna Ülikooli Balti Filmi- ja Meediakooli õppehoone "Nova" Narva maantee 27, valminud 2012. Arhitektuuri sihtkapitali arhitektuuripreemia 2012 ja Arhitektuuri sihtkapitali sisearhitektuuripreemia 2013. Arhitektid Maarja Kask, Karli Luik, Ralf Lõoke, Pelle-Sten Viiburg (Salto Arhitektid). Sisearhitektid Ville Lausmäe, Kadi Karmann (VLS). Mööbel Ville Lausmäe, Tõnis Kalve. Konstruktor Jaanus Natka (EA Reng)

Tühirand ja maailma äär / Donald Tomberg

Index Scriptorium Estoniae

Tomberg, Donald

2006-01-01

Mati Undi jutustuse "Tühirand" (1972) ainetel valminud samanimeline lühimängufilm (2006). Filmi režissöör on Veiko Õunpuu, peaosades Rain Tolk, Maarja Jakobson, Mirtel Pohla ja Taavi Eelmaa. Paralleel samuti M. Undi novelli ainetel 1966.a. aastal valminud telefilmiga "Võlg" (režissöör Valdur Himbek, operaator Anton Mutt)

[Literaturwerkstatt Berlin`i loodud ja koordineeritud rahvusvaheline kaasaegse luule portaal

Index Scriptorium Estoniae

2014-01-01

42 riigi kirjandusorganisatsioonide ühistöö varal täienevas kaasaegse luule portaalis http://www.lyrikline.org saab kuulata ja lugeda 1000 luuletaja loomingut ja neist 11 on eesti autorid: Elo Viiding, Maarja Kangro, Jürgen Rooste, Birk Rohelend, Kaur Riismaa, Indrek Mesikepp, Maria Lee, Asko Künnap, Hasso Krull, Veronika Kivisilla ja Igor Kotjuh

Arhitektuurivõistlus 21. sajandi kodu Lahemaal

Index Scriptorium Estoniae

2012-01-01

Hinnang peapreemia pälvinud töödele "Ranna-Niidu" (Mikk Mutso), "Sirmik" (Maarja Elm, Sten Ader), "Akupunktuur" (Lidia Zarudnaja, Martin Noorväli, Urmas Paul) ja "Adaptsioon" (Kristjan Tõlk, Olavi Kukk, Heleriin Vaher) ning eripreemia pälvinud töödele "Greg" (Eve Komp, Artur Staškevitš) ja "Potjomkin" (Johan Tali)

Predictive role of multiple gene alterations in response to cetuximab in metastatic colorectal cancer: A single center study

Directory of Open Access Journals (Sweden)

Ulivi Paola

2012-05-01

Full Text Available Abstract Background KRAS mutations negatively affect outcome after treatment with cetuximab in metastatic colorectal cancer (mCRC patients. As only 20% of KRAS wild type (WT patients respond to cetuximab it is possible that other mutations, constitutively activating the EGFR pathway, are present in the non-responding KRAS WT patients. We retrospectively analyzed objective tumor response rate, (ORR progression-free (PFS and overall survival (OS with respect to the mutational status of KRAS, BRAF, PIK3CA and PTEN expression in mCRC patients treated with a cetuximab-based regimen. Methods 67 mCRC patients were enrolled onto the study. DNA was extracted from paraffin-embedded sections derived from primary or metastatic lesions. Exon 2 of KRAS and exon 15 of BRAF were analyzed by direct sequencing, PIK3CA was evaluated by pyrosequencing and PTEN expression by immunohistochemistry. Results BRAF and PIK3CA mutations were independently associated with worse PFS (p = 0.006 and p = 0.028, respectively and OS (p = 0.008 and p = 0.029, respectively. No differences in clinical outcome were found between patients who were positive or negative for PTEN expression. Conversely, patients negative for KRAS, BRAF and PIK3CA mutations were characterized by significantly better ORR, PFS and OS than patients with at least one of these mutations. Conclusions BRAF and PIK3CA mutations would seem to be independent predictors of anti-EGFR therapy effectiveness and could be taken into consideration during treatment decision making.

Prospective Biomarker Analysis of the Randomized CHER-LOB Study Evaluating the Dual Anti-HER2 Treatment With Trastuzumab and Lapatinib Plus Chemotherapy as Neoadjuvant Therapy for HER2-Positive Breast Cancer.

Science.gov (United States)

Guarneri, Valentina; Dieci, Maria Vittoria; Frassoldati, Antonio; Maiorana, Antonino; Ficarra, Guido; Bettelli, Stefania; Tagliafico, Enrico; Bicciato, Silvio; Generali, Daniele Giulio; Cagossi, Katia; Bisagni, Giancarlo; Sarti, Samanta; Musolino, Antonino; Ellis, Catherine; Crescenzo, Rocco; Conte, PierFranco

2015-09-01

The CHER-LOB randomized phase II study showed that the combination of lapatinib and trastuzumab plus chemotherapy increases the pathologic complete remission (pCR) rate compared with chemotherapy plus either trastuzumab or lapatinib. A biomarker program was prospectively planned to identify potential predictors of sensitivity to different treatments and to evaluate treatment effect on tumor biomarkers. Overall, 121 breast cancer patients positive for human epidermal growth factor 2 (HER2) were randomly assigned to neoadjuvant chemotherapy plus trastuzumab, lapatinib, or both trastuzumab and lapatinib. Pre- and post-treatment samples were centrally evaluated for HER2, p95-HER2, phosphorylated AKT (pAKT), phosphatase and tensin homolog, Ki67, apoptosis, and PIK3CA mutations. Fresh-frozen tissue samples were collected for genomic analyses. A mutation in PIK3CA exon 20 or 9 was documented in 20% of cases. Overall, the pCR rates were similar in PIK3CA wild-type and PIK3CA-mutated patients (33.3% vs. 22.7%; p = .323). For patients receiving trastuzumab plus lapatinib, the probability of pCR was higher in PIK3CA wild-type tumors (48.4% vs. 12.5%; p = .06). Ki67, pAKT, and apoptosis measured on the residual disease were significantly reduced from baseline. The degree of Ki67 inhibition was significantly higher in patients receiving the dual anti-HER2 blockade. The integrated analysis of gene expression and copy number data demonstrated that a 50-gene signature specifically predicted the lapatinib-induced pCR. PIK3CA mutations seem to identify patients who are less likely to benefit from dual anti-HER2 inhibition. p95-HER2 and markers of phosphoinositide 3-kinase pathway deregulation are not confirmed as markers of different sensitivity to trastuzumab or lapatinib. HER2 is currently the only validated marker to select breast cancer patients for anti-HER2 treatment; however, it is becoming evident that HER2-positive breast cancer is a heterogeneous disease. In addition, more

Comparison of Akt/mTOR/4E-BP1 pathway signal activation and mutations of PIK3CA in Merkel cell polyomavirus-positive and Merkel cell polyomavirus-negative carcinomas.

Science.gov (United States)

Iwasaki, Takeshi; Matsushita, Michiko; Nonaka, Daisuke; Kuwamoto, Satoshi; Kato, Masako; Murakami, Ichiro; Nagata, Keiko; Nakajima, Hideki; Sano, Shigetoshi; Hayashi, Kazuhiko

2015-02-01

Merkel cell polyomavirus (MCPyV) integrates monoclonally into the genomes of approximately 80% of Merkel cell carcinomas (MCCs), affecting their clinicopathological features. The molecular mechanisms underlying MCC development after MCPyV infection remain unclear. We investigated the association of MCPyV infection with activation of the Akt/mammalian target of rapamycin (mTOR)/4E-binding protein 1 (4E-BP1) signaling pathway in MCCs to elucidate the role of these signal transductions and to identify molecular targets for treatment. We analyzed the molecular and pathological characteristics of 41 MCPyV-positive and 27 MCPyV-negative MCCs. Expression of mTOR, TSC1, and TSC2 messenger RNA was significantly higher in MCPyV-negative MCCs, and Akt (T308) phosphorylation also was significantly higher (92% vs 66%; P = .019), whereas 4E-BP1 (S65 and T70) phosphorylation was common in both MCC types (92%-100%). The expression rates of most other tested signals were high (60%-100%) and not significantly correlated with MCPyV large T antigen expression. PIK3CA mutations were observed more frequently in MCPyV-positive MCCs (6/36 [17%] vs 2/20 [10%]). These results suggest that protein expression (activation) of most Akt/mTOR/4E-BP1 pathway signals was not significantly different in MCPyV-positive and MCPyV-negative MCCs, although these 2 types may differ in tumorigenesis, and MCPyV-negative MCCs showed significantly more frequent p-Akt (T308) activation. Therefore, certain Akt/mTOR/4E-BP1 pathway signals could be novel therapeutic targets for MCC regardless of MCPyV infection status. Copyright © 2015 Elsevier Inc. All rights reserved.

Gaasitoru, ujuv saun ning helisevad tuutud / Karin Paulus

Index Scriptorium Estoniae

Paulus, Karin, 1975-

2008-01-01

Veneetsia XI arhitektuuribiennaalile kandideerinud tööde tutvustus. Biennaali teemaks on "Majade taga. Arhitektuur väljaspool ehitisi". Eestit esindab projekt "Gaasitoru", autorid Maarja Kask ja Ralf Lõoke arhitektuuribüroost Salto ning skulptor Neeme Külm. Teise koha said Eve Kask, Signe Kivi ja Andrus Kõresaar tööga "Peatus". Kolmas koht läks Villem Tomiste projektile "Veealune Veneetsia"

5 küsimust Leila Pärtelpojale / Leila Pärtelpoeg ; interv. Ell-Maaja Randküla

Index Scriptorium Estoniae

Pärtelpoeg, Leila, 1927-

2006-01-01

Leila Pärtelpojast, talle omistatud aastapreemiad, tema tuntumad tööd ja autorile kõige rohkem huvi pakkunud tööd. Leila Pärtelpoeg pälvis ESL-i 2005. a. publitsistika preemia raamatu "Pööningul. Auf dem Dachboden" eest. Autor raamatust, mille toimetaja on Krista Roosi, kujundaja ja fotograaf Maarja Roosi, ning kollektsionäär Leonhard Venest

Loeme veel! / Kristi Pärn-Valdoja, Katrin Pauts

Index Scriptorium Estoniae

Pärn-Valdoja, Kristi, 1970-

2006-01-01

TNS Emor väärtushinnangute uuringu RISC 2006 andmetel on igapäevane lugemisharjumus 29 protsendil Eesti naistest ja 20 protsendil meestest. Tallinna abilinnapea Kaia Jäppinen, investeerimistoodete turundusjuht Piret Reinson, KUMU direktor Sirje Helme, laulja Maarja-Liis Ilus ning näitleja Riina Maide kõige enam nende elu ja tegevust mõjutanud raamatutest. Lisa: Millised on Hollywoodi naiste lemmikraamatud?

Noort moodi / Kätlin Karik

Index Scriptorium Estoniae

Karik, Kätlin

2011-01-01

ERKI Moeshow Volta tehases 4. juunil 2011. Loetletud lavale pääsenud kollektsioonid. Pikemalt kollektsioonidest "All that money" (Madis Luik, Karen Milistver, Nele Aunap), "Satellite orchids" (Olga Jazepova), "Vaktsiin" (Triinu Jõhve, Diana Tombak, Katrina Kaubi, Maarja Siim, Piret Mägi, Elina Peippo), "I love you...me neither" (Olga Rattik), "Haute sport couture" (Kristina Tatarinova). Kollektsioonide autorid vastavad kolmele küsimusele

The Effectiveness of Cognitive Reflection and Re-structurization on Career Decision Making of High School Students

Directory of Open Access Journals (Sweden)

Wagimin Wagimin

2015-03-01

Key Words: career decision making, CIP model, reflection, cognitive restructuring Abstrak: Penelitian ini bertujuan untuk menguji keefektifan  refleksi dan penstrukturan ulang kognitif guna meningkatkan pengambilan keputusan karier siswa SMA berdasarkan model PIK. Penelitian eksperimen ini menggunakan rancangan RCTs, dan subjek 40 orang siswa sebagai kelompok eksperi-men dan 40 sebagai kelompok kontrol. Sub-kemampuan pengambilan keputusan karier model PIK yang dikembangkan meliputi: memahami diri, memahami pilihan pekerjaan, komunikasi, analisis, sinte-sis, penilaian, pelaksanaan, dan proses pelaksanaan. Hasil penelitian menunjukkan bahwa ada perbeda-an kemampuan pengambilan keputusan karier antara siswa kelompok eksperimen dan kelompok kon-trol di mana kelompok eksperimen memiliki nilai rata-rata yang lebih tinggi. Informasi controlled trials menguatkan juga bahwa refleksi dan penstrukturan ulang kognitif  efektif untuk  meningkatkan kemampuan pengambilan keputusan karier siswa SMA. Kata kunci: pengambilan keputusan karier, model PIK, refleksi, penstrukturan ulang kognitif

Kuldne Salto: Ralf Lõoke, Maarja Kask ja Karli Luik / Ralf Lõoke, Maarja Kask, Karli Luik ; intervjueerinud Tanel Veenre

Index Scriptorium Estoniae

Lõoke, Ralf, 1978-

2010-01-01

Arhitektuurivõistlustel edukalt esinenud büroo Salto arhitektid buumiajast, kui tööd oli meeletult palju, tööde skaalast, reisimisest, oma tööst ja meeskonnatööst, konkurssidel osalemisest, projektist "Gaasitoru", Tallinnast, unistuste kodust. Konkursivõite 2004-2009

Petersonide dünastia teatriaasta mõjukaim

Index Scriptorium Estoniae

2009-01-01

27. märtsil jagas žürii Rakvere Teatris välja teatripreemiad 2008. aasta töö eest. Lavastaja auhinna pälvis Lembit Peterson lavastuste eest "Maarja kuulutamine" ja "Linn" Theatrumis ning Priit Põldroosi preemia oma pedagoogilise tegevuse eest, naisnäitleja auhinnad said Maria Peterson ja Laura Peterson ning meesnäitleja auhinna pälvis Marius Peterson. Lisatud kõikide auhinnasaajate nimekiri

Mõtteid Eesti Kultuurkapitali arhitektuuripreemiatest = Thoughts about the Cultural Endowment of Estonia's prizes for architecture / Epp Lankots

Index Scriptorium Estoniae

Lankots, Epp, 1976-

2012-01-01

Arhitektuuriaastast 2011. Eesti Kultuurkapitali aastapreemia - Juta Lember (Peterburi Jaani kirik). Arhitektuuri sihtkapitali maastikuarhitektuuri preemia - Kersti Lootus, Kiur Lootus, Siim Lootus, Katri Soonberg, Heidi Viilop (Pärnu Vallikääru park), restaureerimispreemia - Nele Rohtla (Kiltsi mõis), arhitektuuripreemia - Maarja Kask, Ralf Lõoke, Karli Luik, Ene-Liis Semper, Pelle-Sten Viiburg (NO99 Põhuteater), tegevuspreemia - Margit Argus, Margit Aule, Maarin Ektermann, Ingrid Ruudi (festivali "LIFT11" kuraatorid)

Kiikuv maja / Anu Arm

Index Scriptorium Estoniae

Arm, Anu

2006-01-01

Eesti Kunstiakadeemia esimese kursuse arhitektuuriüliõpilaste II semestri töö. Juhendaja arhitekt Andres Alver, ehitamise Pedaspeale organiseeris suvepraktika juhendaja arhitekt Jaan Tiidemann. Autor Anu Arm, kaasa töötasid ja valmis ehitasid: Ott Alver, Maarja Elm, Mari Hunt, Alvin Järving, Marten Kaevats, Riho Kerge, Reedik Poopuu, Anu Põime, Helen Rebane, Kaisa Saarva, Martin Tago, Reet Volt. Valmis: 19. VIII 2006

Hullud päevad von Krahlis

Index Scriptorium Estoniae

2006-01-01

Von Krahli Teatris mängitakse neil päevi neli korda Peeter Jalaka lavastuses Tõnu Kõrvitsa kammeroopereid "Tuliaed" ja "Mu luiged, mu mõtted", mille aluseks on luuletaja Marie Heibergi saatus. Libreto autor on Maarja Kangro. Kammerooperid tulevad lavale Von Krahli Teatri ja Nargen Opera koostöös. Esitavad Kädy Plaas, Helen Lokuta, Nargen Opera koor ja Tallinna Kammerorkester, dirigent Tõnu Kaljuste

Tallinna ülikooli uueks südameks saab avar loovainete hoovimaja / Mari Kodres

Index Scriptorium Estoniae

Kodres, Mari

2009-01-01

Tallinna Ülikooli linnaku arhitektuurivõistluse võitsid Salto AB OÜ arhitektid Ralf Lõoke, Karli Luik ja Maarja Kask. Ülikoolil on soov kujundada peamiselt Balti Filmi- ja Meediakoolile koduks saavast hoonest ning hoovialast ülikooli uus süda. Uute õppekavadena pakub Tallinna Ülikool tuleva aasta sügisest magistritasemel infotehnoloogia ettevõtluse ja haridustehnoloogia õpet, doktoriõppe tasemel infoühiskonna tehnoloogia õpet

Seitse luuleraamatut, seitse debüüti / Veiko Märka

Index Scriptorium Estoniae

Märka, Veiko, 1964-

2006-01-01

Arvustus: Teede, Andra. Takso Tallinna taevas. Luige : Verb, 2006 ; Vabat, Martin. Mina olengi kirjandusklassik. Tartu : Eesti Kirjanduse Selts, 2006 ; Kangro, Maarja. Kurat õrnal lumel. Luige : Verb, 2006 ; Ojasaar, Krista. Hommikused unenäod. Tartu : Ilmamaa, 2006 ; Korts, Eliina. Lööklaused murravad metsi. Tartu : Eesti Kirjanduse Selts, 2006 ; Piik, Paavo. Kummuli linnad. Tallinn : Tuum, 2006 ; Oidsalu, Meelis. Jumala kihvt luulekogu. Tallinn : Sirp ja Vaseliin, 2006

Ballywood ehk Balti Küpsis = Ballywood aka Baltic Cookie / Kalle Komissarov

Index Scriptorium Estoniae

Komissarov, Kalle, 1976-

2010-01-01

Žürii liige Tallinna Ülikooli Loomemaja ja ülikoolilinnaku sisehoovi kavandamiseks korraldatud avalikust arhitektuurivõistlusest, võidutööst. 1. auhinna sai võistlustöö "Küpsis", mille autoriteks on Maarja Kask, Karli Luik ja Ralf Lõoke (Salto). 2. auhind läks võistlustööle "Camera Obscura" (Luhse ja Tuhal), 3. auhind võistlustööle "2. oktoober" (Arhitektuuriagentuur)

Kui sõnadest enam ei piisa, siis - muusika / Kadri Mälk

Index Scriptorium Estoniae

Mälk, Kadri, 1958-

2008-01-01

Rahvusvahelisest ehtekunstisündmusest "Schmuckszene" (peakorraldaja Wolfgang Lösche) Münchenis, peanäitusest (kuraator Ralph Turner) Müncheni messikeskuses, satelliitnäitustest. Eestist pääses peanäitusele Maarja Niinemägi, peapreemia sai Jantje Fleischhut. Kaasaegse ehtekunsti toetajate ühenduse (Die Fördergesellschaft Neuer Schmuck) aastapreemia sai Peter Chang. Võrdluseks Tanel Veenre näitusest "Kui sõnadest ei piisa" Hop-galeriis

Tartu Ülikooli Narva Kolledž = Narva College of the University of Tartu

Index Scriptorium Estoniae

2015-01-01

Tartu Ülikooli Narva Kolledž Raekoja plats 2, valminud 2012. Eesti kultuurkapitali aastapreemia 2013. Arhitektid Siiri Vallner, Katrin Koov, Indrek Peil (Kavakava), kaasautorid Heidi Urb, Andro Mänd, Sten-Mark Mändmaa, Maarja Tüür, sisearhitekt Hannes Praks. Kaasa töötasid Kadri Tamme, Kristjan Holm, Liisi Murula, Toomas Pääsuke, Ahti Grünberg, Daniel Marius Reisser, Helen Sarapuu

Kuldmunast žürii liikme pilguga / Lylian Meister

Index Scriptorium Estoniae

Meister, Lylian, 1966-

2010-01-01

2010. a. disainiauhinna Bruno žürii liikme kommentaarid kandidaatidele ja jagatud auhindadele. Tootedisaini kategoorias pälvis auhinna Veiko Liisi kilepiima voldik-kann, parimaks disainiprojektiks valiti Maarja Mõtuse jalatsiprojekt "Võru'82", design management'i auhind läks Kadarbiku tallu. Disainiauhinna kandidaatide tööde näitus Arhitektuuri- ja Disainigaleriis 8. okt.-ni, Rotermanni kvartali vanas elevaatorihoones 3. okt.-ni ("100 meetrit disaini")

PI3K pathway activation results in low efficacy of both trastuzumab and lapatinib

International Nuclear Information System (INIS)

Wang, Leiping; Hu, Xichun; Zhang, Qunling; Zhang, Jian; Sun, Si; Guo, Haiyi; Jia, Zhen; Wang, Biyun; Shao, Zhimin; Wang, Zhonghua

2011-01-01

Human epidermal growth factor receptor 2 (HER2) is the most crucial ErbB receptor tyrosine kinase (RTK) family member in HER2-positive (refered to HER2-overexpressing) breast cancer which are dependent on or 'addictive' to the Phosphatidylinositol-3-kinase (PI3K) pathway. HER2-related target drugs trastuzumab and lapatinib have been the foundation of treatment of HER2--positive breast cancer. This study was designed to explore the relationship between PI3K pathway activation and the sensitivity to lapatinib in HER2--positive metastatic breast cancer patients pretreated with anthracyclins, taxanes and trastuzumab. Sixty-seven HER2-positive metastatic breast cancer patients were recruited into a global lapatinib Expanded Access Program and 57 patients have primary tumor specimens available for determination of PI3K pathway status. PTEN status was determined by immunohistochemical staining and PIK3CA mutations were detected via PCR sequencing. All patients were treated with lapatinib 1250 mg/day continuously and capecitabine 1000 mg/m 2 twice daily on a 2-week-on and 1-week-off schedule until disease progression, death, withdrawal of informed consent, or intolerable toxicity. PIK3CA mutations and PTEN loss were detected in 12.3% (7/57) and 31.6% (18/57) of the patients, respectively. Twenty-two patients with PI3K pathway activation (defined as PIK3CA mutation and/or PTEN expression loss) had a lower clinical benefit rate (36.4% versus 68.6%, P = 0.017) and a lower overall response rate (9.1% versus 31.4%, P = 0.05), when compared with the 35 patients with no activation. A retrospective analysis of first trastuzumab-containing regimen treatment data showed that PI3K pathway activation correlated with a shorter median progression-free survival (4.5 versus 9.0 months, P = 0.013). PIK3CA mutations occur more frequently in elder patients for HER2-positive breast cancer. PIK3CA mutations and PTEN loss are not mutually exclusive. PI3K pathway activation resulting

LHCb: Observation of CP violation in $B^{\\pm} \\to DK^{\\pm}$ decays at LHCb

CERN Multimedia

Gandini, Paolo

2012-01-01

An analysis of $B^+ \\to DK^+$ and $B^+ \\to D\\pi^+$ decays is presented where the D meson is reconstructed in the two-body final states: $K^+\\pi-, K^+K^-, \\pi^+\\pi^-$ and $\\pi^+K^-$. Using 1.0 fb$^{-1}$ of LHCb data, measurements of several observables are made including the first observation of the suppressed mode $B^+ \\to DK^+, D \\to \\pi^+K^-$. CP violation in $B^+ \\to DK^+$ decays is observed with 5.8 $\\sigma$ significance.

Molecular characterization of apocrine salivary duct carcinoma.

Science.gov (United States)

Chiosea, Simion I; Williams, Lindsay; Griffith, Christopher C; Thompson, Lester D R; Weinreb, Ilan; Bauman, Julie E; Luvison, Alyssa; Roy, Somak; Seethala, Raja R; Nikiforova, Marina N

2015-06-01

Contemporary classification and treatment of salivary duct carcinoma (SDC) require its thorough molecular characterization. Thirty apocrine SDCs were analyzed by the Ion Ampliseq Cancer HotSpot panel v2 for mutations in 50 cancer-related genes. Mutational findings were corroborated by immunohistochemistry (eg, TP53, BRAF, β-catenin, estrogen, and androgen receptors) or Sanger sequencing/SNaPshot polymerase chain reaction. ERBB2 (HER2), PTEN, FGFR1, CDKN2A/P16, CMET, EGFR, MDM2, and PIK3CA copy number changes were studied by fluorescence in situ hybridization. TP53 mutations (15/27, 56%), PTEN loss (11/29, 38%, including 2 cases with PTEN mutation), PIK3CA hotspot mutations (10/30, 33%), HRAS hotspot mutations (10/29; 34%), and ERBB2 amplification (9/29, 31%, including 1 case with mutation) represented the 5 most common abnormalities. There was no correlation between genetic changes and clinicopathologic parameters. There was substantial overlap between genetic changes: 8 of 9 cases with ERBB2 amplification also harbored a PIK3CA, HRAS, and TP53 mutation and/or PTEN loss. Six of 10 cases with PIK3CA mutation also had an HRAS mutation. These findings provide a molecular rationale for dual targeting of mitogen-activated protein kinase and phosphoinositide 3-kinase pathways in SDC. FGFR1 amplification (3/29, 10%) represents a new potential target. On the basis of studies of breast carcinomas, the efficacy of anti-ERBB2 therapy will likely be decreased in SDC with ERBB2 amplification co-occurring with PIK3CA mutation or PTEN loss. Therefore, isolated ERBB2 testing is insufficient for theranostic stratification of apocrine SDC. On the basis of the prevalence and type of genetic changes, apocrine SDC appears to resemble one subtype of breast carcinoma-"luminal androgen receptor positive/molecular apocrine."

Kirjanduspärand ja vuntsid / Maarja Vaino

Index Scriptorium Estoniae

Vaino, Maarja, 1976-

2014-01-01

Projektist "Comparing Learning Opportunities in the Field of Literary Heritage", mille eesmärgiks oli osalejate võimalus võrrelda ja arutleda teistest riikidest pärit sama valkonna ekspertidega täiskasvanute õpivõimaluste üle kirjanduspärandi vallas

Köitekunstist pärikarva / Maarja Undusk

Index Scriptorium Estoniae

Undusk, Maarja

2000-01-01

Rahvusvahelisest köitekunsti ja kalligraafianäirusest "Scripta manent II" Tallinna Kunstihoones. Miks valiti tekstiautoreiks J. Kaplinski ja D. Kareva. Peeter Brambati ja Peep Laansalu videofilmis näidatakse köiteid ka seestpoolt. Filmi muusika - Peeter Vähi

Nahk on ruumis. Otsides disaini / Maarja Undusk

Index Scriptorium Estoniae

Undusk, Maarja

2004-01-01

Eesti Nahakunstnike Liidu aastanäitus "Nahk on ruumis" Tartu Kunstimajas kuni 21. III. Näituse korraldaja Pille Kivihall, kujundaja Tea Tammelaan. Jaapani animatsioonikunstniku Maya Yonesho ja eesti köitekunstnike koostööna sündinud film "Üks uks". Muusika - Sven Grünberg

Vastuseks Kajar Lemberi artiklile / Anne-Maarja Olei

Index Scriptorium Estoniae

Olei, Anne-Maarja

2009-01-01

Vastukaja art. Lember, Kajar. Mis kuradi riigis me küll elame!? // Hiiu Leht 10. märts 2009, lk. 2. Siseministeeriumi kommentaarid Rahvaliidu 5. märtsi pressiteatele. Haldusterritoriaalse korralduse reformi seaduse eelnõust

Teadlased usuvad Pekingis dopingutarbimist / Maarja Värv

Index Scriptorium Estoniae

Värv, Maarja

2008-01-01

Vt. ka Postimees : na russkom jazõke 22. juuli, lk. 12. BBC uurimuse tulemusel selgus, et dopingutestis on tegelikult mitmeid puudujääke, mistõttu paljud EPOt tarvitanud sportlaste positiivsed proovid võidakse negatiivseks tunnistada

EGFR related mutational status and association to clinical outcome of third-line cetuximab-irinotecan in metastatic colorectal cancer

Directory of Open Access Journals (Sweden)

Frifeldt Sanne K

2011-03-01

Full Text Available Abstract Background As supplement to KRAS mutational analysis, BRAF and PIK3CA mutations as well as expression of PTEN may account for additional non-responders to anti-EGFR-MoAbs treatment. The aim of the present study was to investigate the utility as biomarkers of these mutations in a uniform cohort of patients with metastatic colorectal cancer treated with third-line cetuximab/irinotecan. Methods One-hundred-and-seven patients were prospectively included in the study. Mutational analyses of KRAS, BRAF and PIK3CA were performed on DNA from confirmed malignant tissue using commercially available kits. Loss of PTEN and EGFR was assessed by immunohistochemistry. Results DNA was available in 94 patients. The frequency of KRAS, BRAF and PIK3CA mutations were 44%, 3% and 14%, respectively. All were non-responders. EGF receptor status by IHC and loss of PTEN failed to show any clinical importance. KRAS and BRAF were mutually exclusive. Supplementing KRAS analysis with BRAF and PIK3CA indentified additional 11% of non-responders. Patient with any mutation had a high risk of early progression, whereas triple-negative status implied a response rate (RR of 41% (p Conclusion Triple-negative status implied a clear benefit from treatment, and we suggest that patient selection for third-line combination therapy with cetuximab/irinotecan could be based on triple mutational testing.

Mõtestatud käsitöölised / Tõnu Kaalep

Index Scriptorium Estoniae

Kaalep, Tõnu, 1966-2018

1999-01-01

Tartu Kunstikoolist väljakasvanud mööblikujundajate ئ Priit Verlin, Rain Pluutus, Priit Videvik, Maarja Inno, Dan Lukas ئ rühmitusest Class X Furniture. Nende loomingu vastandumisest trendiga, praegusest tegevusest jm. Toimetaja Ingo Maurer on valinud P. Verlini tooli 'Allegro' järgmisse Disaini Aastaraamatusse. Jaak Roosi oma põhimõtetest mööblikujundajate õpetamisel Tartu Kunstikoolis. Harry Liivranna arvamus. Kommentaarid: P. Verlin, R. Pluutus

80 aastat tagasi : Detsember 1926 / Mati Märtin

Index Scriptorium Estoniae

Märtin, Mati

2006-01-01

Muusikasündmustest 80 aastat tagasi: Enrico Bossi oratooriumi "Kaotatud paradiis" esitusest Estonia Muusika Osakonna segakoori poolt Juhan Aaviku juhatusel 28. märtsil Tallinna Kaarli kirikus. Vaimuliku muusika õhtutest prof. August Topmani eestvõttel Tallinna Jaani kirikus. J. S. Bachi muusikale pühendatud õhtust 5. dets. Tartu ülikooli kirikus. David Otto Wirkhausi mälestuskontserdist Maarja Kiriku Lauluseltsi eestvõttel Pauluse kirikus 12. dets.Tartus

Haṭhapradīpikā

DEFF Research Database (Denmark)

Olesen, Bjarne Wernicke; Einarsen, Silje Lyngar; , .

), prāṇāyāma (åndedrætsteknikker), mudrā (yogiske teknikker) og samādhi (meditative indsigter). Dertil er HYP et encyklopædisk værk (formodentligt sammensat af mere end 20 forskellige yogaskrifter) fra haṭhayogaens klassisk-formative fase, hvorfor værket tillige udgør en forståelsesnøgle til yoga, tantra og...

Bringing Climate Into the Classroom: Inside a Teaching Retreat Around Naomi Klein’s This Changes Everything

Directory of Open Access Journals (Sweden)

Bill Bigelow

2015-06-01

Full Text Available Jill Howdyshell lives and teaches 5th grade in Togiak, a small Yu’pik fishing village in southwestern Alaska. In Togiak, harvesting berries is a practice that goes back countless generations. The berries are the key ingredient in akutaq, called eskimo ice cream. In her classes, Howdyshell’s students write identity poems with lines proclaiming “I am from akutaq,” and describing cherished excursions with parents and grandparents. In 2014, residents discovered that there would be no berries that year: the tundra had not frozen for a sufficient length of time for the berries to regenerate. With a dramatic rise in temperatures, Yu’pik people can no longer rely on digging deep into the permafrost to store food in makeshift freezers. And most distressing: as a result of rising seas, during the next few years, Yu’pik people will be forced to relocate large parts of their community.

The Prognostic Influence of BRAF Mutation and other Molecular, Clinical and Laboratory Parameters in Stage IV Colorectal Cancer.

Science.gov (United States)

Karadima, Maria L; Saetta, Angelica A; Chatziandreou, Ilenia; Lazaris, Andreas C; Patsouris, Efstratios; Tsavaris, Nikolaos

2016-10-01

Our aim was to evaluate the predictive and prognostic influence of BRAF mutation and other molecular, clinical and laboratory parameters in stage IV colorectal cancer (CRC). 60 patients were included in this retrospective analysis, and 17 variables were examined for their relation with treatment response and survival. KRAS mutation was identified in 40.3 % of cases, BRAF and PIK3CA in 8.8 % and 10.5 % respectively. 29.8 % of patients responded to treatment. Median survival time was 14.3 months. Weight loss, fever, abdominal metastases, blood transfusion, hypoalbuminaimia, BRAF and PIK3CA mutations, CRP and DNA Index were associated with survival. In multivariate analysis, male patients had 3.8 times higher probability of response, increased DNA Index was inversely correlated with response and one unit raise of DNA Index augmented 6 times the probability of death. Our findings potentiate the prognostic role of BRAF, PIK3CA mutations and ploidy in advanced CRC.

Arhitektuuribiennaalil arhitektuurile mõeldes / Karin Hallas-Murula

Index Scriptorium Estoniae

Hallas-Murula, Karin, 1957-

2008-01-01

Veneetsia arhitektuuribiennaalist teemal "Out there : Architecture Beyond Buildings". Biennaali üldkuraator Aaron Betsky. Eestlaste gaasitoruinstallatsioonist (autorid Maarja Kask, Ralf Lõoke, Neeme Külm). Lühidalt Hispaania, Inglismaa, Prantsusmaa, Hollandi, Taani, Saksamaa, Hiina ja Poola ekspositsioonidest, pikemalt Venemaa paviljonist. Nigel Coatsi, Zaha Hadidi, Frank Gehry, Herzog & de Meuroni ja Ai Weiwei töödest biennaalil, filmist Rem Koolhaasi Bordeaux' villast. Vt. repliik: Ruudi, Ingrid. Hea Sirbi toimetus! (Sirp, 2009, 30. jaan., lk. 8)

Installation complete / Aet Ader, Kadri Klementi

Index Scriptorium Estoniae

Ader, Aet

2015-01-01

Linnainstallatsioonidest avalikus ruumis. "Gas Pipe" Venezia Arhitektuuribiennaalil (Maarja Kask, Ralf Lõoke, Neeme Külm, Ingrid Ruudi, 2008). "Artificial Queue" (Andra Aaloe, Aet Ader, Flo Kasearu, Grete Soosalu, 2010). "To the Sea" (autorid Tomomi Hayashi, Mihkel Sagar, 2011). "Chimney" (tundmatu autor, 2011). "Straw Theatre" (Salto Arhitektid, 2011). "A Path in the Forest" (Tetsuo Kondo, Mitsuru Maekita, Mutsuro Sasaki, Yoshiyuki Hiraiwa, 2011). "O" (Aet Ader, Andra Aaloe, Kaarel Künnap, Grete Soosalu, Flo Kasearu, 2011)

Von Krahl klaarib piraadina asju euroliidus / Andres Laasik

Index Scriptorium Estoniae

Laasik, Andres, 1960-2016

2006-01-01

Von Krahli Teatri selle hooaja eelviimane esietendus "Europiraadid" on 17. mail Düsseldorfis, koostöös Saksamaa teatrirühmaga Showcase Beat Le Mot. (Varem on tehtud sama teatrirühmaga koostöös "Piraadid", mida mängiti nii Eestis kui Saksamaal). Eesti poole pealt teevad kaasa Juhan Ulfsak, Taavi Eelmaa, Maarja Jakobson ja Rain Tolk. Sakslaste poole pealt on tegijad Nikola Duric, Thorsten Eibler, Dariusz Kostyra ja Veit Spengler

Prof. dr. Felix Oinase mälestusõhtu külalisesinejad

Index Scriptorium Estoniae

2005-01-01

on Jaan Undusk, kirjandusteadlane, kirjanik, Felix Oinase elutöö tundja Eestis. Tema ettekande teemaks on "Mõnda Felix Oinase teaduslikust mõtteviisist". New Yorki tuleb ka Jaani abikaasa Maarja Undusk, kes on kirjanik, kunstnik ja raamatuillustraator, tema toob külakostiks kaasa näituse oma töödest. Muusikaliseks esinejaks on kandlemängija Tiit Kao Kanadast. Ettekannete õhtu korraldab Eesti Kultuurifond Ameerika Ühendriikides 12. novembril 2005 New Yorgi Eesti Majas

Paide gümnaasiumi spordihoone konkurss = Paide Gymnasium Sports Hall Competition / Tiit Trummal

Index Scriptorium Estoniae

Trummal, Tiit, 1954-

2006-01-01

Žürii liige konkursist, võidutöödest. Žürii koosseis. Konkursi tulemused: I preemia - Karli Luik, Ralf Lõoke, Maarja Kask, töö "Täheke"; II - Ott Kadarik, Villem Tomiste, Mihkel Tüür, töö "Unioon"; III - Koit Ojaliiv, Juhan Rohtla, kaasautor Tõnu Laigu, töö "Kivi"; ostupreemia - Lauri Saar, Tõnu Laanemäe, Indrek Järve, Jaak-Adam Looveer (PAIK Arhitektid), töö "Sensei"

Îles et continents

OpenAIRE

Resztak, Karolina; Sanson, Hervé

2017-01-01

Ce numéro huit de la revue Continents manuscrits, à l’enseigne des « Iles et continents », se veut un numéro de varias, une fois n’est pas coutume. Iles et continents car : du Congo aux Antilles, en passant par l’Amérique du Nord, le numéro assume sa géographie plurielle, polycentrée. Le panorama d’auteurs représentés dans la revue est riche et varié : de Joseph Zobel à Sony Labou Tansi, d’Aimé Césaire à Nathanaël, ou René Maran, c’est bien des cartographies mises en relation que ce numéro té...

Blockade of PI3Kgamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis.

Science.gov (United States)

Camps, Montserrat; Rückle, Thomas; Ji, Hong; Ardissone, Vittoria; Rintelen, Felix; Shaw, Jeffrey; Ferrandi, Chiara; Chabert, Christian; Gillieron, Corine; Françon, Bernard; Martin, Thierry; Gretener, Denise; Perrin, Dominique; Leroy, Didier; Vitte, Pierre-Alain; Hirsch, Emilio; Wymann, Matthias P; Cirillo, Rocco; Schwarz, Matthias K; Rommel, Christian

2005-09-01

Phosphoinositide 3-kinases (PI3K) have long been considered promising drug targets for the treatment of inflammatory and autoimmune disorders as well as cancer and cardiovascular diseases. But the lack of specificity, isoform selectivity and poor biopharmaceutical profile of PI3K inhibitors have so far hampered rigorous disease-relevant target validation. Here we describe the identification and development of specific, selective and orally active small-molecule inhibitors of PI3Kgamma (encoded by Pik3cg). We show that Pik3cg(-/-) mice are largely protected in mouse models of rheumatoid arthritis; this protection correlates with defective neutrophil migration, further validating PI3Kgamma as a therapeutic target. We also describe that oral treatment with a PI3Kgamma inhibitor suppresses the progression of joint inflammation and damage in two distinct mouse models of rheumatoid arthritis, reproducing the protective effects shown by Pik3cg(-/-) mice. Our results identify selective PI3Kgamma inhibitors as potential therapeutic molecules for the treatment of chronic inflammatory disorders such as rheumatoid arthritis.

Kiviõli linnaväljaku avalik arhitektuurivõistlus = Kiviõli town square open architecture competition / Tiit Sild

Index Scriptorium Estoniae

Sild, Tiit, 1977-

2006-01-01

Arhitektuurivõistluse eesmärgist, premeeritud töödest. Tulemused: I preemia - Tiina Skolimowski, Kai Süda, Risto Parve, töö "Figuur", II - Karli Luik, Ralf Lõoke, Maarja Kask (AB Salto), töö "Saarestik", III - Jaak-Adam Looveer, Toomas Paaver, Lauri Saar, Indrek Järve, Tõnu Laanemäe (AB Paik Arhitektid), töö "Mult", ergutuspreemia - Ott Kadarik, Villem Tomiste, Mihkel Tüür, Kaiko Kivi, Krista Saluveer (AB Kosmos), töö "Sammal"

Glavnõi priz PÖFF ujehhal v Turtsiju / Tiit Tuumalu

Index Scriptorium Estoniae

Tuumalu, Tiit, 1971-

2007-01-01

Lõppes 11. Pimedate Ööde Filmifestival. EurAsia programmi grand prix läks Türgi filmile "Takva", parim režissöör on Aleksandr Sokurov ("Aleksandra"), parima naisnäitleja auhinna sai Maarja Jakobson ("Sügisball"), parima meesnäitleja auhinna sai Zdenek Sverak ("Tühjad pudelid"). Parim Eesti film on "Sügisball", mis üldse sai festivalil kuus auhinda. Lisaks auhinnasaajate nimekiri ja lühiintervjuu "3 voprossa" Veiko Õunpuult

Pöffi lõppedes asume ootama järgmist Pöffi / Kristiina Davidjants

Index Scriptorium Estoniae

Davidjants, Kristiina, 1974-

2007-01-01

Lõppes 11. Pimedate Ööde Filmifestival. EurAsia programmi grand prix läks Türgi filmile "Takva", parim režissöör on Aleksandr Sokurov ("Aleksandra"), parima naisnäitleja auhinna sai Maarja Jakobson ("Sügisball"), parima meesnäitleja auhinna sai Zdenek Sverak ("Tühjad pudelid"), elutööpreemia nukufilmi lavastaja Heino Pars. Parim Eesti film on "Sügisball". Lisaks nimekiri "Pöffi auhinnad" ja Jaak Kilmi kommentaar "Minu lemmik oli "La France"

Kolmene ülikool esitles professoreid ja kirjanduspreemia laureaate

Index Scriptorium Estoniae

2008-01-01

Tallinna Ülikool esitles 3. aastapäeva aktusel aasta jooksul professoreiks valituid: Lorenzo Cañás Bottos, Jyrki Käkönen, Aaro Toomela, Airi Värnik, Marika Mägi, Priit Reiska, Eve Kikas ja Karsten Brüggemann. Selgusid ka tänavused Tallinna Ülikooli kirjanduspreemia laureaadid. Algupärase ilukirjanduse vallas pälvis auhinna romanist, luuletaja ja tõlkija, doktorant Maarja Kangro, tõlkepreemia sai kirjanik ja tõlkija Arvo Valton

Tarbekunsti- ja Disainimuuseum taas avatud

Index Scriptorium Estoniae

2005-01-01

2. VI avati rekonstrueeritud muuseumihoone. Rekonstrueerimisprojekti autorid: Arhitektuuriagentuuri arhitekt Inga Raukas, sisearhitekt Monika Löve. Ehitustööd: Rihti Projekt. Avatud nahakunstinäitus "Järjehoidja" (kuraator Airi Ligi, kujundaja Siiri Nõva, näha saab ka nahakunsti üliõpilaste töid; filmiprogramm: Maya Yonesho "Üks uks", "Ecce libri" Pille Kivihallist, Tiina Piisangust ja Maarja Unduskist) ja rahvusvaheline köitekunstinäitus "Scripta manent III. Maailma parim asi", kujundaja Lennart Mänd

80 aastat tagasi : November 1926 / Mati Märtin

Index Scriptorium Estoniae

Märtin, Mati

2006-01-01

Muusikasündmustest 80 aastat tagasi: balti-saksa luuletaja ja muusikaarvustaja Carl Hunniuse 70. sünnipäeva tähistamisest 6. nov. Tartus, vaimulikest muusikaõhtutest 10. ja 14 nov.Tallinna Jaani kirikus, Tartu Jaani kiriku lauluseltsi koori kontserdist 7. nov. Tallinna Niguliste kirikus, Narva Meestelaulu Seltsi segakoori kontserdist 7. nov. Narva Aleksandri kirikus, Johannes Jürgensoni (Juhan Jürme) autorikontserdist 9. nov. Tallinna Tütarlastegümnaasiumis, kontserdist 21. nov. Tartu Maarja kirikus

Eraldiste arvestusest ettevõttes / Maarja Valler, Inga Lõokene

Index Scriptorium Estoniae

Valler, Maarja

2002-01-01

Tagamaks võimalikult objektiivset ülevaadet ettevõtte tegelikest kohustustest, tuleb analüüsida, kas tegemist on potentsiaalse kohustuse või eraldisega sellest sõltub, kas vastavat kohustust kirjeldatakse üksnes finantsaruandluse lisades või võetakse arvele ka bilansis

Materjalide jagamisest võidavad kõik / Maarja Soone

Index Scriptorium Estoniae

Soone, Maarja

2011-01-01

Koolitusest Colchesteris - Content and Language Integrated Learning, mis tähendab võõrkeelset aineõpet, kus vajadusel võetakse kasutusele ka emakeel, mistõttu viidatakse sellele tihti kui kakskeelsele õppele

Short outlines of books by Estonian authors / Brita Melts, Rutt Hinrikus, Maret Vaher and Arno Oja

Index Scriptorium Estoniae

Melts, Brita

2014-01-01

Arvustus: Kronberg, Janika. Rännud kuue teejuhiga. Tallinn : Go Group, 2013 ; Kallaste, Helen. Kogutud hetked. Tallinn : Verb, 2012 ; Ahi, Eda. Gravitatsioon. Tallinn : Verb, 2013 ; Heinsaar, Mehis. Ülikond. Tallinn : Menu Kirjastus, 2013 ; Kann, Kaja. Eratee. Tallinn : Hea Lugu, 2013 ; Kivirähk, Andrus. Maailma otsas. Tallinn : Eesti Keele Sihtasutus, 2013 ; Kurvitz, Robert. Püha ja õudne lõhn. Tallinn : ZA/UM, 2013 ; Mattheus, Ülo. Tema salajane palve. Tallinn : Tuum, 2013 ; Kangro, Maarja. Dantelik auk. Tallinn : Eesti Keele Sihtasutus, 2012

Targeted capture massively parallel sequencing analysis of LCIS and invasive lobular cancer: Repertoire of somatic genetic alterations and clonal relationships.

Science.gov (United States)

Sakr, Rita A; Schizas, Michail; Carniello, Jose V Scarpa; Ng, Charlotte K Y; Piscuoglio, Salvatore; Giri, Dilip; Andrade, Victor P; De Brot, Marina; Lim, Raymond S; Towers, Russell; Weigelt, Britta; Reis-Filho, Jorge S; King, Tari A

2016-02-01

Lobular carcinoma in situ (LCIS) has been proposed as a non-obligate precursor of invasive lobular carcinoma (ILC). Here we sought to define the repertoire of somatic genetic alterations in pure LCIS and in synchronous LCIS and ILC using targeted massively parallel sequencing. DNA samples extracted from microdissected LCIS, ILC and matched normal breast tissue or peripheral blood from 30 patients were subjected to massively parallel sequencing targeting all exons of 273 genes, including the genes most frequently mutated in breast cancer and DNA repair-related genes. Single nucleotide variants and insertions and deletions were identified using state-of-the-art bioinformatics approaches. The constellation of somatic mutations found in LCIS (n = 34) and ILC (n = 21) were similar, with the most frequently mutated genes being CDH1 (56% and 66%, respectively), PIK3CA (41% and 52%, respectively) and CBFB (12% and 19%, respectively). Among 19 LCIS and ILC synchronous pairs, 14 (74%) had at least one identical mutation in common, including identical PIK3CA and CDH1 mutations. Paired analysis of independent foci of LCIS from 3 breasts revealed at least one common mutation in each of the 3 pairs (CDH1, PIK3CA, CBFB and PKHD1L1). LCIS and ILC have a similar repertoire of somatic mutations, with PIK3CA and CDH1 being the most frequently mutated genes. The presence of identical mutations between LCIS-LCIS and LCIS-ILC pairs demonstrates that LCIS is a clonal neoplastic lesion, and provides additional evidence that at least some LCIS are non-obligate precursors of ILC. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Molecular Subgroup Analysis of Clinical Outcomes in a Phase 3 Study of Gemcitabine and Oxaliplatin with or without Erlotinib in Advanced Biliary Tract Cancer

Directory of Open Access Journals (Sweden)

Seung Tae Kim

2015-02-01

Full Text Available BACKGROUND: We previously reported that the addition of erlotinib to gemcitabine and oxaliplatin (GEMOX resulted in greater antitumor activity and might be a treatment option for patients with biliary tract cancers (BTCs. Molecular subgroup analysis of treatment outcomes in patients who had specimens available for analysis was undertaken. METHODS: Epidermal growth factor receptor (EGFR, KRAS, and PIK3CA mutations were evaluated using peptide nucleic acid–locked nucleic acid polymerase chain reaction clamp reactions. Survival and response rates (RRs were analyzed according to the mutational status. Sixty-four patients (48.1% were available for mutational analysis in the chemotherapy alone group and 61 (45.1% in the chemotherapy plus erlotinib group. RESULTS: 1.6% (2/116 harbored an EGFR mutation (2 patients; exon 20, 9.6% (12/121 harbored a KRAS mutation (12 patients; exon 2, and 9.6% (12/118 harbored a PIK3CA mutation (10 patients, exon 9 and 2 patients, exon 20. The addition of erlotinib to GEMOX in patients with KRAS wild-type disease (n = 109 resulted in significant improvements in overall response compared with GEMOX alone (30.2% vs 12.5%, P = .024. In 95 patients with both wild-type KRAS and PIK3CA, there was evidence of a benefit associated with the addition of erlotinib to GEMOX with respect to RR as compared with GEMOX alone (P = .04. CONCLUSION: This study demonstrates that KRAS mutational status might be considered a predictive biomarker for the response to erlotinib in BTCs. Additionally, the mutation status of PIK3CA may be a determinant for adding erlotinib to chemotherapy in KRAS wild-type BTCs.

Coordinated Expression of Phosphoinositide Metabolic Genes during Development and Aging of Human Dorsolateral Prefrontal Cortex.

Directory of Open Access Journals (Sweden)

Stanley I Rapoport

Full Text Available Phosphoinositides, lipid-signaling molecules, participate in diverse brain processes within a wide metabolic cascade.Gene transcriptional networks coordinately regulate the phosphoinositide cascade during human brain Development and Aging.We used the public BrainCloud database for human dorsolateral prefrontal cortex to examine age-related expression levels of 49 phosphoinositide metabolic genes during Development (0 to 20+ years and Aging (21+ years.We identified three groups of partially overlapping genes in each of the two intervals, with similar intergroup correlations despite marked phenotypic differences between Aging and Development. In each interval, ITPKB, PLCD1, PIK3R3, ISYNA1, IMPA2, INPPL1, PI4KB, and AKT1 are in Group 1, PIK3CB, PTEN, PIK3CA, and IMPA1 in Group 2, and SACM1L, PI3KR4, INPP5A, SYNJ1, and PLCB1 in Group 3. Ten of the genes change expression nonlinearly during Development, suggesting involvement in rapidly changing neuronal, glial and myelination events. Correlated transcription for some gene pairs likely is facilitated by colocalization on the same chromosome band.Stable coordinated gene transcriptional networks regulate brain phosphoinositide metabolic pathways during human Development and Aging.

Structure, design and statistical programme library of the meteorological database of Potsdam-Institut fuer Klimaforschung; Struktur, Aufbau und statistische Programmbibliothek der meteorologischen Datenbank am Potsdam-Institut fuer Klimaforschung

Energy Technology Data Exchange (ETDEWEB)

Oesterle, H.; Glauer, J. [Potsdam-Institut fuer Klimafolgenforschung (PIK), Potsdam (Germany); Denhard, M. [Frankfurt Univ. (Germany). Inst. fuer Meteorologie und Geophysik

1999-01-01

The relational database management system (ORACLE) using different client interfaces (browser, SQL, precompiler) is the most important basis for data organization and storage. The creation of a data bank system at PIK includes: Acquisition of meteorological data series for the projects executed at PIK; development of a database structure on the basis of daily values; control, analysis and classification of data into given storage formats; development and application of statistical software. There are currently 20 different types of data sets with daily, monthly and annual data which are functionally interconnected and updated. All data sets are continuously updated. (orig.) [Deutsch] Wesentliche Grundlage der Datenorganisation und -speicherung bildet das relationale Datenbanksystem ORACLE mit den dazugehoerigen Werkzeugen (Browser, SQL- und Precompiler). Die Entwicklung des Datenbanksystems am PIK umfasst folgende Etappen: - Erwerb von meteorologischen Datensaetzen fuer die am Institut laufenden Forschungsvorhaben; - Entwicklung einer Speicherstruktur auf der Basis von Tageswerten; - Kontrolle, Analyse und Einordnung der Daten in die vorgegebenen Speicherformate; - Entwicklung der zur Datennutzung notwendigen statistischen Programmbibliothek. Zur Zeit gibt es 20 verschiedene Typen von Datensaetzen. Sie enthalten taegliche, monatliche und jaehrliche Daten und sind funktional miteinander verbunden. Alle Datensaetze werden kontinuierlich erweitert. (orig.)

Uus vaatus : EKA uue õppehoone arhitektuurivõistlus / Andres Ojari

Index Scriptorium Estoniae

Ojari, Andres, 1970-

2014-01-01

EKA uue õppehoone arhitektuurivõistlusel konkureeris 10 tööd. Kolmanda koha pälvis Salto Arhitektide töö märgusõnaga "Akadeemia" (autorid Maarja Kask, Ralf Lõoke, Margus Tamm, Helin Kukk ja Martin McLean). Teine koht kuulus tööle märgusõnaga "Aletheia" (autorid Jaan Kuusemets, Üllar Ambos, Pille Noole, Kaisa Lasner ja Jiannis Lykouras). Konkursi võitis töö märgusõnaga "Linea" (autorid Joel Kopli, Koit Ojaliiv, Juhan Rohtla ja Eik Hermann KUU Arhitektidest

Mõned sammud 2007. aasta eesti luule platool / Jan Kaus

Index Scriptorium Estoniae

Kaus, Jan, 1971-

2008-01-01

Ülevaade 2007. aasta eesti luulest. Käsitlemist leiavad järgmised autorid ja nende teosed: Eeva Park "Tulearm", Maarja Kangro "Tule mu koopasse, mateeria", Katrin Väli "Neli", Andra Teede "Saage üle", Merca "Narrivile", Doris Kareva "Lõige", Martin Oja "Pärastlõuna platoo", Kivisildnik "Torti ja aborti", Kivisildnik "Sumo", Timo Maran "Metsa pööramine", Lemming Nagel "Tahtetuse triumf", Aare Pilv "Näoline", Igor Kotjuh "Teises keeles", Urmo Mets "Toimumata tulvade toimik", Neeme Põder "Kaktuste puiestee", Maria Lee "Äramõte"

PÖFFi võit läks Türki, "Sügisballil" läks hästi / Tiit Tuumalu

Index Scriptorium Estoniae

Tuumalu, Tiit, 1971-

2007-01-01

Lõppes 11. Pimedate Ööde Filmifestival. EurAsia programmi grand prix läks Türgi filmile "Takva", parim režissöör on Aleksandr Sokurov ("Aleksandra"), parima naisnäitleja auhinna sai Maarja Jakobson ("Sügisball"), parima meesnäitleja auhinna sai Zdenek Sverak ("Tühjad pudelid"). Parim Eesti film on "Sügisball", mis üldse sai festivalil kuus auhinda. Lisaks nimekiri "Pimedate Ööde filmifestival jagas auhindu" ja lühiintervjuu "3 küsimust" Veiko Õunpuult

δ-Tocopherol inhibits receptor tyrosine kinase-induced AKT activation in prostate cancer cells.

Science.gov (United States)

Wang, Hong; Hong, Jungil; Yang, Chung S

2016-11-01

The cancer preventive activity of vitamin E is suggested by epidemiological studies and supported by animal studies with vitamin E forms, γ-tocopherol and δ-tocopherol (δ-T). Several recent large-scale cancer prevention trials with high dose of α-tocopherol, however, yielded disappointing results. Whether vitamin E prevents or promotes cancer is a serious concern. A better understanding of the molecular mechanisms of action of the different forms of tocopherols would enhance our understanding of this topic. In this study, we demonstrated that δ-T was the most effective tocopherol form in inhibiting prostate cancer cell growth, by inducing cell cycle arrest and apoptosis. By profiling the effects of δ-T on the cell signaling using the phospho-kinase array, we found that the most inhibited target was the phosphorylation of AKT on T308. Further study on the activation of AKT by EGFR and IGFR revealed that δ-T attenuated the EGF/IGF-induced activation of AKT (via the phosphorylation of AKT on T308 induced by the activation of PIK3). Expression of dominant active PIK3 and AKT in prostate cancer cell line DU145 in which PIK3, AKT, and PTEN are wild type caused the cells to be reflectory to the inhibition of δ-T, supporting that δ-T inhibits the PIK3-mediated activation of AKT. Our data also suggest that δ-T interferes with the EGF-induced EGFR internalization, which leads to the inhibition of the receptor tyrosine kinase-dependent activation of AKT. In summary, our results revealed a novel mechanism of δ-T in inhibiting prostate cancer cell growth, supporting the cancer preventive activity δ-T. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Revealing the Effects of the Herbal Pair of Euphorbia kansui and Glycyrrhiza on Hepatocellular Carcinoma Ascites with Integrating Network Target Analysis and Experimental Validation.

Science.gov (United States)

Zhang, Yanqiong; Lin, Ya; Zhao, Haiyu; Guo, Qiuyan; Yan, Chen; Lin, Na

2016-01-01

Although the herbal pair of Euphorbia kansui (GS) and Glycyrrhiza (GC) is one of the so-called "eighteen antagonistic medicaments" in Chinese medicinal literature, it is prescribed in a classic Traditional Chinese Medicine (TCM) formula Gansui-Banxia-Tang for cancerous ascites, suggesting that GS and GC may exhibit synergistic or antagonistic effects in different combination designs. Here, we modeled the effects of GS/GC combination with a target interaction network and clarified the associations between the network topologies involving the drug targets and the drug combination effects. Moreover, the "edge-betweenness" values, which is defined as the frequency with which edges are placed on the shortest paths between all pairs of modules in network, were calculated, and the ADRB1-PIK3CG interaction exhibited the greatest edge-betweenness value, suggesting its crucial role in connecting the other edges in the network. Because ADRB1 and PIK3CG were putative targets of GS and GC, respectively, and both had functional interactions with AVPR2 approved as known therapeutic target for ascites, we proposed that the ADRB1-PIK3CG-AVPR2 signal axis might be involved in the effects of the GS-GC combination on ascites. This proposal was further experimentally validated in a H22 hepatocellular carcinoma (HCC) ascites model. Collectively, this systems-level investigation integrated drug target prediction and network analysis to reveal the combination principles of the herbal pair of GS and GC. Experimental validation in an in vivo system provided convincing evidence that different combination designs of GS and GC might result in synergistic or antagonistic effects on HCC ascites that might be partially related to their regulation of the ADRB1-PIK3CG-AVPR2 signal axis.

Short outlines of books by Estonian authors / Janika Kronberg, Rutt Hinrikus

Index Scriptorium Estoniae

Kronberg, Janika, 1963-

2008-01-01

Arvustus: Kareva, Doris. Lõige. Tallinn : Verb, 2007 ; Õnnepalu, Tõnu. Flandria päevik. Tallinn : Varrak, 2007 ; Mihkelson, Ene. Katkuhaud. Tallinn : Varrak, 2007 ; Vint, Toomas. Mäluauguga naine. Tallinn : Eesti Keele Sihtasutus, 2007 ; Pervik, Aino. Suleline, Puhuja ja must munk. Tallinn : Tänapäev, 2007 ; Mutt, Mihkel. Siseemigrant. Novellid Rui taevalike kommentaaridega. Tallinn : Fabian, 2007 ; Nõlvak, Valentine. Ellujääja mälestused. Tallinn : Varrak, 2007 ; Tungal, Leelo. Täisminevik. Tallinn : Tänapäev, 2007 ; Kangro, Maarja. Tule mu koopasse, mateeria. Tallinn : Eesti Keele Sihtasutus, 2007

Euroopa Liidu IT-agentuur / Katrin Koov

Index Scriptorium Estoniae

Koov, Katrin, 1973-

2015-01-01

Arhitektuurivõistluse eesmärk oli leida Euroopa Liidu IT-agentuuri peahoone rajamiseks Vesilennuki tänavale Tallinnas parim arhitektuuriline lahendus. Esitati 15 ideekavandit, millest kvalfitseerusid 14. Esimese koha sai töö märgusõnaga "Turing" (autorid: Jaan Kuusemets, Üllar Ambos, Pille Noole, Ioannis Lykouras, Erko Luhaaru, DAGOpen ja LÜNK Arhitektid). Teisele kohale tuli töö märgusõnaga "Platoo" (autor Karli Luik, AB Kontekst). Kolmandale kohale tuli töö märgusõnaga "Bastion" (autorid: Ralf Lõoke, Maarja Kask, Martin McLean, Salto AB).

Mõned ülestähendused disainiaasta puhul : disainist Tartus ja ka Dartu tisainist / Raimu Hanson

Index Scriptorium Estoniae

Hanson, Raimu, 1957-

2006-01-01

Hollandi disaineri Kees Dorsti raamatust "Kuidas mõista disaini? 150 mõtisklust disaineri elukutse üle", Tartus tegutsevast Disainijaamast. Leila Pärtelpoja raamatust "Pööningul. Auf dem Dachboden" (kujundaja Maarja Roosi). Leo Leola kujundatud Kellukese karastusjoogi pudelisildist, mille redisainis reklaamiagentuur Taevas Ogivly. Tüüne-Kristin Vaikla ja Urmo Vaikla disainitud pinkidest Tartu kaubamajas. Disainerite kujundatud Tartu südalinnast. Rahvusvahelisest seminarist "Disain ja säästev mõtteviis" Viinistu Kunstimuuseumis. "Tartu Postimehe" võidetud auhindadest maailma ajalehtede kujunduskonkursil. Disainiaasta üritustest Tartus, disainihariduse andmisest Eestis

Short outlines of books by Estonian authors / Brita Melts, Rutt Hinrikus and Janika Kronberg

Index Scriptorium Estoniae

Melts, Brita

2015-01-01

Arvustus: Viitol, Livia. Jutte ja novelle. Tallinn : Libri Livoniae, 2014 ; Talvet, Jüri. Ten Letters to Montaigne : "Self" and "other". Tartu : Tartu Ülikooli Kirjastus, 2014 ; Rooste, Jürgen. Suur sume, suur tume. [Luige (Kiili vald)] : Verb, 2014 ; Kross, Märten. Hullumäng. [Tallinn] : Tammerraamat, 2014 ; Kaus, Jan. Ma olen elus. Tallinn : Tuum, 2014 ; Kangro, Maarja. Hüppa tulle. Tallinn : Nähtamatu Ahv, 2014 ; Kasemaa, Andrus. Minu viimane raamat. Tallinn : Varrak, 2014 ; Raik, Katri. Minu Narva : kahe maailma vahel. [Tartu] : Petrone Print, 2013 ; Kareva, Doris. Maailma asemel. [Kordustr. Tallinn] : Verb, 2014

Viinistu suvi - kultuurikolhoos laieneb veelgi / Tiiu Laks, Tõnu Kaljuste, Sirje Eelma...[jt.

Index Scriptorium Estoniae

2008-01-01

Viinistu ajaloost, kultuurist ja hümnidest. 2008. a. suvekontserte tutvustab Tõnu Kaljuste - esinevad Maarja-Liis Ilus, Koit Toome, ansambel Jäääär, Nargen festivalil esitatakse Joseph Haydni ooper "Elu kuu peal"; katlamaja teatrietendusi tutvustab Hendrik Toompere juunior - etendub tema lavastatud Boguslaw Schaefferi "Loojang", Ingomar Vihmari lavastatud Andrus Kivirähki "Keiserlik kokk" ja välilaval Mart Kivastiku "Eesti asi"; kuraator Sirje Eelma toob välja Maarit Murka, August Künnapu, Pusa ja Toomas Kuusingu teosed. Üritusi ootab Emil Urbeli ja Toivo Raidmetsa endisest külmmahutist ümberehitatud kabel

Prognostic and predictive value of p-Akt, EGFR, and p-mTOR in early breast cancer

International Nuclear Information System (INIS)

Lazaridis, Georgios; Lambaki, Sofia; Karayannopoulou, Georgia; Eleftheraki, Anastasia G.; Papaspirou, Irene; Bobos, Mattheos; Efstratiou, Ioannis; Pentheroudakis, George; Zamboglou, Nikolaos; Fountzilas, George; Aristotle Univ. of Thessaloniki School of Medicine, Thessaloniki

2014-01-01

There are scarce data available on the prognostic/predictive value of p-Akt and p-mTOR protein expression in patients with high-risk early breast cancer. Formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from 997 patients participating in two adjuvant phase III trials were assessed for EGFR, PTEN, p-Akt, p-mTOR protein expression, and PIK3CA mutational status. These markers were evaluated for associations with each other and with selected patient and tumor characteristics, immunohistochemical subtypes, disease-free survival (DFS), and overall survival (OS). p-mTOR protein expression was negatively associated with EGFR and positively associated with PTEN, with p-Akt473, and with the presence of PIK3CA mutations. EGFR expression was positively associated with p-Akt473, p-Akt308, and PIK3CA wild-type tumors. Finally, p-Akt308 was positively associated with p-Akt473 expression. In univariate analysis, EGFR (p = 0.016) and the coexpression of EGFR and p-mTOR (p = 0.015) were associated with poor OS. Among patients with p-Akt308-negative or low-expressing tumors, those treated with hormonal therapy were associated with decreased risk for both relapse and death (p = 0.013 and p [de

Role of p38 MAPK in enhanced human cancer cells killing by the combination of aspirin and ABT-737

Science.gov (United States)

Zhang, Chong; Shi, Jing; Mao, Shi-ying; Xu, Ya-si; Zhang, Dan; Feng, Lin-yi; Zhang, Bo; Yan, You-you; Wang, Si-cong; Pan, Jian-ping; Yang, You-ping; Lin, Neng-ming

2015-01-01

Regular use of aspirin after diagnosis is associated with longer survival among patients with mutated-PIK3CA colorectal cancer, but not among patients with wild-type PIK3CA cancer. In this study, we showed that clinically achievable concentrations of aspirin and ABT-737 in combination could induce a synergistic growth arrest in several human PIK3CA wild-type cancer cells. In addition, our results also demonstrated that long-term combination treatment with aspirin and ABT-737 could synergistically induce apoptosis both in A549 and H1299 cells. In the meanwhile, short-term aspirin plus ABT-737 combination treatment induced a greater autophagic response than did either drug alone and the combination-induced autophagy switched from a cytoprotective signal to a death-promoting signal. Furthermore, we showed that p38 acted as a switch between two different types of cell death (autophagy and apoptosis) induced by aspirin plus ABT-737. Moreover, the increased anti-cancer efficacy of aspirin combined with ABT-737 was further validated in a human lung cancer A549 xenograft model. We hope that this synergy may contribute to failure of aspirin cancer therapy and ultimately lead to efficacious regimens for cancer therapy. PMID:25388762

Gene Expression Correlation for Cancer Diagnosis: A Pilot Study

Directory of Open Access Journals (Sweden)

Binbing Ling

2014-01-01

Full Text Available Poor prognosis for late-stage, high-grade, and recurrent cancers has been motivating cancer researchers to search for more efficient biomarkers to identify the onset of cancer. Recent advances in constructing and dynamically analyzing biomolecular networks for different types of cancer have provided a promising novel strategy to detect tumorigenesis and metastasis. The observation of different biomolecular networks associated with normal and cancerous states led us to hypothesize that correlations for gene expressions could serve as valid indicators of early cancer development. In this pilot study, we tested our hypothesis by examining whether the mRNA expressions of three randomly selected cancer-related genes PIK3C3, PIM3, and PTEN were correlated during cancer progression and the correlation coefficients could be used for cancer diagnosis. Strong correlations (0.68≤r≤1.0 were observed between PIK3C3 and PIM3 in breast cancer, between PIK3C3 and PTEN in breast and ovary cancers, and between PIM3 and PTEN in breast, kidney, liver, and thyroid cancers during disease progression, implicating that the correlations for cancer network gene expressions could serve as a supplement to current clinical biomarkers, such as cancer antigens, for early cancer diagnosis.

First observation of $\\pi^{-}K^+$ and $\\pi^{+}K^-$ atoms, their lifetime measurement and $\\pi K$ scattering lengths evaluation

CERN Document Server

Afanasyev, Leonid

2016-01-01

The Low Energy QCD allows to calculate the ππ and π K scattering lengths with high precision. There are accurate relations between these scattering lengths and π + π − , π − K + , π + K − atoms lifetimes. The experiment on the first observation of π − K + and π + K − atoms is described. The atoms were generated in Nickel and Platinum targets hit by the PS CERN proton beam with momentum of 24 GeV/ c . Moving in the target, part of atoms break up producing characteristic π K pairs (atomic pairs) with small relative momentum Q in their c.m.s. In the experiment, we detected n A = 349 ± 62 (5.6 standard deviations) π − K + and π + K − atomic pairs. The main part of π K pairs are produced in free state. The majority of such particles are generated directly or from short-lived sources as ρ , ω and similar resonances. The electromagnetic interactions in the final state create Coulomb pairs with a known sharp dependence on Q . This effect allows to evaluate the number of these Coulomb pai...

Veski - Peegli liinilt / Ellen Uuspõld ; vestelnud Maarja Lõhmus

Index Scriptorium Estoniae

Uuspõld, Ellen, 1927-

2014-01-01

Juhan Peegel eesti keele kateedri aspirandi ja õppejõuna ning ajaloo-keeleteaduskonna dekaanina. Ka Ellen Uuspõllu õpingutest Tartu Riikliku Ülikooli kaugõppes alates 1945 ning tööst eesti keele kateedris

Eesti koondis sõidab Bulgaariasse Kanepita / Maarja Värv

Index Scriptorium Estoniae

Värv, Maarja

2007-01-01

Vt. ka Postimees : na russkom jazõke 17. apr., lk. 13. Järgmisel nädalal alustab Eesti tennisenaiskond Bulgaarias karikavõistluste (Fed Cup) Euroopa-Aafrika tsooni esimeses liigas ilma Kaia Kanepita. Lisa: Fed Cup

José Bernardo : kas nahakunst on olemas? / Maarja Undusk

Index Scriptorium Estoniae

Undusk, Maarja

1998-01-01

Augustis Eestis viibinud mehhiko nahakunstnikust José Maria Bernardo Sappiast, tema loomingust. Nahakunstist maailmas. Eesti nahakunstnike rahvusvahelisse naha-ellu lülitumise võimalustest. Nahaeriala entusiastidest maailmas: portugaallasest Franklin Pereirast, kes alustas ajakirja "The Leather Times" väljaandmist ja Hamburgis tegutsevast Rene Berendsist, Karu galerii omanikust, kes andis välja kataloogi "Leder Gilde"

Üliõpilasteater teeb nalja armastusega / Maarja Mänd

Index Scriptorium Estoniae

Mänd, Maarja

2008-01-01

Minski lavastaja Sergei Turbani lavastusest "Naljad armastusest" Anton Tshehhovi lühinäidendite "Juubel" ja "Abieluettepanek" ainetel Tartu Üliõpilasteatri näitlejate esituses. Esietendus 7. dets. Athena pööningusaalis

Eestlased jutustasid meediast / Maarja Lõhmus, Aive Villota, Kadri Klettenberg

Index Scriptorium Estoniae

Lõhmus, Maarja, 1960-

2004-01-01

Autorid teevad ülevaate Tartu Ülikooli meedia ja kommunikatsiooni õppetooli ja Eesti Kirjandusmuuseumi poolt 2003. aasta 20. novembril läbi viidud meediatarbimisele keskendunud uuringu "Üks meediapäev" tulemustest. Vt. samas: Kiitus kirjutajatele

Identification of Epigenetic Changes in Prostate Cancer using Induced Pluripotent Stem Cells

Science.gov (United States)

2013-04-01

NDUFA12,CYC1,DHODH,NDUFA2,COX7C Melanoma Signaling 8.10E-01 6.52E-02 PIK3C3,CDK4,MDM2 Maturity Onset Diabetes of Young ( MODY ) Signaling 7.99E-01 6.45E...ACTG1,CACNA1A Inhibition of Angiogenesis by TSP1 1.63E+00 1.03E-01 CD47,SDC1,GUCY1A3,MAPK10 Type I Diabetes Mellitus Signaling 1.61E+00 6.67E-02...Pathway 5.02E-01 5.71E-02 CCNH,POLR2K Type II Diabetes Mellitus Signaling 4.89E-01 3.11E-02 MAP3K7,PIK3C3,MAPK10,SOCS5,PRKCB Hereditary Breast Cancer

An improved $\\pi$K atom lifetime measurement

CERN Document Server

Yazkov, V

2016-01-01

This note describes details of analysis of data samples collected by DIRAC experiment on a Pt target in 2007 and Ni targets in 2008–2010 in order to estimate the lifetime of πK atoms. Experimental results consist of eight distinct data samples: both charge combinations ( π + K − and K + π − atoms) obtained in different experimental conditions corresponding to each year of data taking. Estimations of systematic errors are presented. Taking into account both statistical and systematic uncertainties, the lifetime of πK atoms is estimated by the maximum likelihood method. The above sample comprises the total statistics, available for the analysis, thus the improvement over the previous estimation [1,3] of the πK atom lifetime is achieved.

Tõendid praktikasse / Ere Uibu, Ester Öpik

Index Scriptorium Estoniae

Uibu, Ere

2016-01-01

Eesti Õdede Liidu konverentsil tunnustati meditsiiniõdesid Sirje Kõvermäge, Kadri Piiri, Evelyn Evertit, Ere Uibut, Jane Freimani, Reet Tohvret, Teija Toivarit, Jane Remmerit, Ülle Tammsaart, Lily Parmu ja Kätlin Lünekundu

High-incidence of PTEN mutations in Chinese patients with primary small cell carcinoma of the esophagus

International Nuclear Information System (INIS)

Zhang, Zhimin; Wang, Ge; Xiao, Hualiang; Xie, Fei; Zhang, Hui; Chen, Chuan; Xiao, He; Yang, Zhenzhou; Wang, Dong; Li, Zengpeng

2014-01-01

Primary small cell carcinoma of the esophagus (PSCCE) is a rare and aggressive tumor with poor prognosis. The aim of this study was to investigate the existence of EGFR, KRAS, PIK3CA and PTEN mutations in PSCCE. Clinical–pathological data and paraffin-embedded specimens were collected from 38 patients. Exons 18 to 21 of EGFR, KRAS and PIK3CA status were analyzed by real-time PCR based on ARMS and Scorpion technology in all patients, and the PTEN gene was also screened using real-time PCR and high-resolution melting curve analysis (HRMA). Only 1 (2.63%) out of 38 patients had EGFR mutations in L858R missense, and KRAS and PIK3CA were not found in the mutational spot in all patients. However, PTEN mutations presented in 14 (36.84%) out of 38 patients, including exon 5 coding for PTEN missense mutation (n =4, 10.53%), exon 6 (n =7, 18.42%), concurrent exon 5 and exon 6 (n =2, 5.26%), and exon 8 (n =1, 2.63%). Concurrent mutations of these genes were not detected in all samples. No statistically significant associations were found between the clinicopathological features and the mutation status of PTEN. The incidence of PTEN mutations in Chinese patients with PSCCE was higher than that of previous reports in other histological subtypes of esophageal cancer

Exploratory biomarker analysis for treatment response in KRAS wild type metastatic colorectal cancer patients who received cetuximab plus irinotecan

International Nuclear Information System (INIS)

Kim, Seung Tae; Ahn, Tae Jin; Lee, Eunjin; Do, In-Gu; Lee, Su Jin; Park, Se Hoon; Park, Joon Oh; Park, Young Suk; Lim, Ho Yeong; Kang, Won Ki; Kim, Suk Hyeong; Lee, Jeeyun; Kim, Hee Cheol

2015-01-01

More than half of the patients selected based on KRAS mutation status fail to respond to the treatment with cetuximab in metastatic colorectal cancer (mCRC). We designed a study to identify additional biomarkers that could act as indicators for cetuximab treatment in mCRC. We investigated 58 tumor samples from wild type KRAS CRC patients treated with cetuximab plus irinotecan (CI). We conducted the genotyping for mutations in either BRAF or PIK3CA and profiled comprehensively the expression of 522 kinase genes. BRAF mutation was detected in 5.1 % (3/58) of patients. All 50 patients showed wild type PIK3CA. Gene expression patterns that categorized patients with or without the disease control to CI were compared by supervised classification analysis. PSKH1, TLK2 and PHKG2 were overexpressed significantly in patients with the disease control to IC. The higher expression value of PSKH1 (r = 0.462, p < 0.001) and TLK2 (r = 0.361, p = 0.005) had the significant correlation to prolonged PFS. The result of this work demonstrated that expression nature of kinase genes such as PSKH1, TLK2 and PHKG2 may be informative to predict the efficacy of CI in wild type KRAS CRC. Mutations in either BRAF or PIK3CA were rare subsets in wild type KRAS CRC

Romaanirindel muutustega / Tarmo Teder

Index Scriptorium Estoniae

Teder, Tarmo, 1958-

2001-01-01

Romaanivõistluse võitjatest: I koht - Aarne Rubeni ""Volta" annab kaeblikku vilet"; II koht - Leo Kunnase "Sõdurjumala teener"; III koht - Maimu Veske "Continental" ja Lehte Hainsalu "Kellakuuljad"; Ulmekirjanduse eripreemia Varrakult - Indrek Hargla "Baiita needus". Esiletõstetud tööd: Lembit Uustulndi "Süvameri"; Wimbergi [Jaak Urmet] "Lipamäe"; Maarja Oderi "Inglinägu"; Aarne Biini "Kuningavesi"; Reet Kudu "Täiskuu ja tänavalatern"; Erik Tohvri [Hans-Erik Laansalu] "Majad jõe ääres"; Tambet Tamme "Suur tühemik"; Erik Tohvri [Hans-Erik Laansalu] "Kollaste lehtede aegu"; Maniakkide tänav, pseud. "Mu aknad on puust..."

Arhitektuurikonkursid 2004

Index Scriptorium Estoniae

2004-01-01

Tulemused: Pärnu kergejõustikumaneezh: I preemia - Ralf Lõoke ja Karli Luik; Tartus Raatuse, Pika, Fortuuna ja Põigu tänava vahelise ala hoonestuskava: I - Kai Kuusik ja Taavi Kuri; Aasta betoonehitis 2003: peapreemia - Emil Urbel; Veneetsia IX rahvusvahelise arhitektuuribiennaali "Metamorfoosid" raames eksponeeritava eesti kaasaegse arhitektuuri näituse ideekonkurss: I - Kristjan Holm; äri- ja elumaja Pärnus Aida t. 5: I - Andres Lember; Eesti parim puitehitis 2003-2004: I - Aivo Schults; Eesti parim tellishoone 2003-2004: I- Tiit Trummal; Sõmeru keskusehoone: I - Ralf Lõoke ja Maarja Kask; Eesti Maanteemuuseumi välialade maastikuarhitektuurne ideekonkurss: I - Margit Kärner

Short outlines of books by Estonian authors / Brita Melts, Rutt Hinrikus and Janika Kronberg

Index Scriptorium Estoniae

Melts, Brita

2013-01-01

Arvustus: Baturin, Nikolai. Lendav hollandlanna. Tallinn : Eesti Raamat, 2012 ; Friedenthal, Meelis. Mesilased. Tallinn : Varrak, 2012 ; Kaus, Jan. Koju. Tallinn : Tuum, 2012 ; Kaldmaa, Kätlin. Armastuse tähestik. Tallinn : NyNorden, 2012 ; Kivastik, Mart. Vietnami retsept. Tartu : Väike Öömuusika, 2012 ; Õnnepalu, Tõnu. Kuidas on elada. Tallinn : Varrak, 2012 ; Õnnepalu, Tõnu. Mandala. Tallinn : Varrak, 2012 ; Riismaa, Kaur. Rebase matmine. Tallinn : Näo Kirik, 2012 ; Vadi, Urmas. Tagasi Eestisse. Saarde-Pärnu : Jumalikud Ilmutused, 2012 ; Vint, Toomas. Avalikult abielust. Tallinn : Tulikiri, 2012 ; Kangro, Maarja. Dantelik auk. Tallinn : Eesti Keele Sihtasutus, 2012 ; Kaevats, Mihkel. Ungari kirsid & teisi luuletusi. Tallinn : Pegasus, 2012.

Siivsalt lahendatud Skoone bastion / Karin Paulus

Index Scriptorium Estoniae

Paulus, Karin, 1975-

2005-01-01

Tallinna vanalinnas asuva Skoone bastioni ja sellega külgneva staadioni arendamiseks väljakuulutatud ideekonkursi võidutöödest. Peapreemia sai töö "Glassii" (autorid Maarja Kask, Ralf Lõoke, Karli Luik arhitektuuribüroost Salto). Teise preemia pälvis töö "SK-one" (autorid Timo Subbi, Mihkel Urmet, Taavi Kaldaru arhitektuuribüroost Suburb OÜ). Kolmanda preemia sai töö "Karl XI" (autorid Ott Kadarik, Villem Tomiste, Mihkel Tüür, Paco-Ernest Ulman arhitektuuribüroost Kosmos). Võistlustöödega saab tutvuda Arhitektuuri- ja Disainigaleriis. Harry Liivranna lühike ülevaade Skone bastioni ajaloost

78 FR 37782 - Proposed Information Collection; Comment Request; Collection of State Level Data on Nutrition...

Science.gov (United States)

2013-06-24

... Food and Nutrition Service (FNS) of the United States Department of Agriculture (USDA) would like to... assign a PIK to each person record involves matching based on name, address, sex, date of birth, and...

Energy fluxes and spectra for turbulent and laminar flows

KAUST Repository

Verma, Mahendra K.

2017-05-14

Two well-known turbulence models to describe the inertial and dissipative ranges simultaneously are by Pao~[Phys. Fluids {\\\\bf 8}, 1063 (1965)] and Pope~[{\\\\em Turbulent Flows.} Cambridge University Press, 2000]. In this paper, we compute energy spectrum $E(k)$ and energy flux $\\\\Pi(k)$ using spectral simulations on grids up to $4096^3$, and show consistency between the numerical results and predictions by the aforementioned models. We also construct a model for laminar flows that predicts $E(k)$ and $\\\\Pi(k)$ to be of the form $\\\\exp(-k)$, and verify the model predictions using numerical simulations. The shell-to-shell energy transfers for the turbulent flows are {\\\\em forward and local} for both inertial and dissipative range, but those for the laminar flows are {\\\\em forward and nonlocal}.

"Kohtume Eestis!" algtaseme keelefunktsioonidest lähtudes / Elle Sõrmus

Index Scriptorium Estoniae

Sõrmus, Elle

2002-01-01

Rets. rmt.: Sander, Klarika. Kohtume Eestis! : eestin kielen alkeisoppikirja = Estonian for beginners. Helsinki : Finn Lectura, 1999. 202 lk. + 1 helikassett. Õpik on mõeldud täiskasvanud õppijale, kes alustab eesti keele õppimist algtasemel

Genetic diversity of the causative agent of ice-ice disease of the seaweed Kappaphycus alvarezii from Karimunjawa island, Indonesia

Science.gov (United States)

Syafitri, E.; Prayitno, S. B.; Ma'ruf, W. F.; Radjasa, O. K.

2017-02-01

An essential step in investigating the bacterial role in the occurrence of diseases in Kappaphycus alvarezii is the characterization of bacteria associated with this seaweed. A molecular characterization was conducted on the genetic diversity of the causative agents of ice-ice disease associated with K. alvarezii widely known as the main source of kappa carrageenan. K. alvrezii infected with ice-ice were collected from the Karimunjawa island, North Java Sea, Indonesia. Using Zobell 2216E marine agar medium, nine bacterial species were isolated from the infected seaweed. The molecular characterizations revealed that the isolated bacteria causing ice-ice disease were closely related to the genera of Alteromonas, Bacillus, Pseudomonas, Pseudoalteromonas, Glaciecola, Aurantimonas, and Rhodococcus. In order to identify the symptoms causative organisms, the isolated bacterial species were cultured and were evaluated for their pathogenity. Out of 9 species, only 3 isolates were able to cause the ice-ice symptoms and consisted of Alteromonas macleodii, Pseudoalteromonas issachenkonii and Aurantimonas coralicida. A. macleodii showed the highest pathogenity.

Complete genome sequence of Kytococcus sedentarius type strain (strain 541T)

Energy Technology Data Exchange (ETDEWEB)

Sims, David; Brettin, Thomas; Detter, John C.; Han, Cliff; Lapidus, Alla; Copeland, Alex; Glavina Del Rio, Tijana; Nolan, Matt; Chen, Feng; Lucas, Susan; Tice, Hope; Cheng, Jan-Fang; Bruce, David; Goodwin, Lynne; Pitluck, Sam; Ovchinnikova, Galina; Pati, Amrita; Ivanova, Natalia; Mavrommatis, Konstantinos; Chen, Amy; Palaniappan, Krishna; D' haeseleer, Patrick; Chain, Patrick; Bristow, James; Eisen, Jonathan A.; Markowitz, Victor; Hugenholtz, Philip; Schneider, Susanne; Goker, Markus; Pukall, Rudiger; Kyrpides, Nikos C.; Klenk, Hans-Peter

2009-05-20

Kytococcus sedentarius (ZoBell and Upham 1944) Stackebrandt et al. 1995 is the type strain of the species, and is of phylogenetic interest because of its location in the Dermacoccaceae, a poorly studied family within the actinobacterial suborder Micrococcineae. K. sedentarius is known for the production of oligoketide antibiotics as well as for its role as an opportunistic pathogen causing valve endocarditis, hemorrhagic pneumonia, and pitted keratolysis. It is strictly aerobic and can only grow when several amino acids are provided in the medium. The strain described in this report is a free-living, nonmotile, Gram-positive bacterium, originally isolated from a marine environment. Here we describe the features of this organism, together with the complete genome sequence, and annotation. This is the first complete genome sequence of a member of the family Dermacoccaceae and the 2,785,024 bp long single replicon genome with its 2639 protein-coding and 64 RNA genes is part of the Genomic Encyclopedia of Bacteria and Archaea project.

Systematic Functional Characterization of Resistance to PI3K Inhibition in Breast Cancer.

Science.gov (United States)

Le, Xiuning; Antony, Rajee; Razavi, Pedram; Treacy, Daniel J; Luo, Flora; Ghandi, Mahmoud; Castel, Pau; Scaltriti, Maurizio; Baselga, Jose; Garraway, Levi A

2016-10-01

PIK3CA (which encodes the PI3K alpha isoform) is the most frequently mutated oncogene in breast cancer. Small-molecule PI3K inhibitors have shown promise in clinical trials; however, intrinsic and acquired resistance limits their utility. We used a systematic gain-of-function approach to identify genes whose upregulation confers resistance to the PI3K inhibitor BYL719 in breast cancer cells. Among the validated resistance genes, Proviral Insertion site in Murine leukemia virus (PIM) kinases conferred resistance by maintaining downstream PI3K effector activation in an AKT-independent manner. Concurrent pharmacologic inhibition of PIM and PI3K overcame this resistance mechanism. We also observed increased PIM expression and activity in a subset of breast cancer biopsies with clinical resistance to PI3K inhibitors. PIM1 overexpression was mutually exclusive with PIK3CA mutation in treatment-naïve breast cancers, suggesting downstream functional redundancy. Together, these results offer new insights into resistance to PI3K inhibitors and support clinical studies of combined PIM/PI3K inhibition in a subset of PIK3CA-mutant cancers. PIM kinase overexpression confers resistance to small-molecule PI3K inhibitors. Combined inhibition of PIM and PI3K may therefore be warranted in a subset of breast cancers. Cancer Discov; 6(10); 1134-47. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 1069. ©2016 American Association for Cancer Research.

Four MicroRNAs Promote Prostate Cell Proliferation with Regulation of PTEN and Its Downstream Signals In Vitro

Science.gov (United States)

Xue, Jing-lun; Chen, Jin-zhong

2013-01-01

Background Phosphatase and tensin homologue (PTEN), as a tumor suppressor, plays vital roles in tumorigenesis and progression of prostate cancer. However, the mechanisms of PTEN regulation still need further investigation. We here report that a combination of four microRNAs (miR-19b, miR-23b, miR-26a and miR-92a) promotes prostate cell proliferation by regulating PTEN and its downstream signals in vitro. Methodology/Principal Findings We found that the four microRNAs (miRNAs) could effectively suppress PTEN expression by directly interacting with its 3’ UTR in prostate epithelial and cancer cells. Under-expression of the four miRNAs by antisense neutralization up-regulates PTEN expression, while overexpression of the four miRNAs accelerates epithelial and prostate cancer cell proliferation. Furthermore, the expression of the four miRNAs could, singly or jointly, alter the expression of the key components in the phosphoinositide 3-kinase (PI3K)/Akt pathway, including PIK3CA, PIK3CD, PIK3R1 and Akt, along with their downstream signal, cyclin D1. Conclusions These results suggested that the four miRNAs could promote prostate cancer cell proliferation by co-regulating the expression of PTEN, PI3K/Akt pathway and cyclin D1 in vitro. These findings increase understanding of the molecular mechanisms of prostate carcinogenesis and progression, even provide valuable insights into the diagnosis, prognosis, and rational design of novel therapeutics for prostate cancer. PMID:24098737

Substantiation of the TVR-M reactor parameter selection and specific features of the research program

International Nuclear Information System (INIS)

Abov, Yu.G.; Kiselev, G.V.; Shvedov, O.V.

1986-01-01

Comparative analysis of characteristics of the T-VR-M(ITEP, USSR), GRHF(France) and PIK(LNPI USSR) high-flux heavy water cooled and moderated research reactors is given. The TVR-M reactor design concepts are mainly based on a 35-year experience in operating of the first Soviet heavy water research TVR reactor. As a result of the reactor reconstruction its thermal power will increase up to 25 MW neutron flux in experimental channels will increase 10 fold and reach 5.6x10 14 neutron/cm 2 xc. The TVR-M reactor has the quality value the ratio of maximum thermal neutron flux value the reflector to reactor power in practically the same as for the GRHF reactor (2.24x10 13 (neutron/cm 2 xc)/MW) which allows one to place it among the best research reactors in the world. Maximum fuel burnup of the order of 50% and minimum fuel loading are forseen for the TVR-M reactor which provides for operation cost minimum as compared to the GRHF and PIK reactors. The TVR-M reactor practically does not yield to the PIK and GRMF reactors in experimental channel quantity and exceeds the in the number of vertical channels. The TVR-M reactor experimental capabilities allow one to reduce measuring time and provide for conducting the experiments at a qualitatively new level. At the same time capabilities of radioactive nuclide production in qualitative and quantitative senses are increased

Belgia rahvuspüha puhul kuuleb Eestis kammermuusikat / Maarja Pehk

Index Scriptorium Estoniae

Pehk, Maarja

2007-01-01

21. juulil on Belgia Kuningriigil rahvuspüha. Suursaadik Pierre Clement Dubuisson tutvustab sel puhul belgia kultuuri kolme kontserdi kaudu. Sel aastal tutvustab saatkond Belgia kultuuri ka koostöös Pimedate Ööde filmifestivaliga

Diplomaatiline kaitse rahvusvahelises õiguses : olemus, teostamine ja piirangud / Maarja Teder

Index Scriptorium Estoniae

Teder, Maarja, 1983-

2007-01-01

Rahvusvahelises õiguses juurdunud diplomaatilisest instituudist, selle olemusest ja teostamise põhimõtetest ning erireeglitest mitme kodakondsusega isikute rahvusvahelise kaitse puhul. Vatteli fiktsioonist

Päevad : [luuletused] / Philip Larkin ; inglise keelest tlk. Maarja Kangro

Index Scriptorium Estoniae

Larkin, Philip

2007-01-01

Sisu: Päevad ; Mitte midagi öelda ; See olgu värss ; Uurimus lugemisharjumustest ; Hommage valitsusele ; Vesi ; Vajakud ; Viige üks koju lastele ; Jutt voodis ; Kõrged aknad ; Sa jätkad elu ; Kui. Orig.: Days ; Nothing to be said ; This be the verse ; A study of reading habits ; Homage to a government ; Water ; Wants ; Take one home for the kiddies ; Talking in bed ; High windows ; Continuing to live ; If

Sotsiaaltöö professioon tänases Eestis / Maarja Seppel

Index Scriptorium Estoniae

Seppel, Maarja

2006-01-01

Autori magistritööst, mis käsitleb sotsiaaltöötaja elukutse positsiooni ja prestiizhi ühiskonnas selle liikmete hinnangute alusel. Lisa: Vabavastuste näiteid sotsiaaltöötajate ülesannetest ühiskonnas

Tervishoiuteenuse osutaja tsiviilõiguslik ja karistusõiguslik vastutus / Maarja Lillsaar

Index Scriptorium Estoniae

Lillsaar, Maarja, 1983-

2012-01-01

Tervishoiuteenuse osutamise lepingu olemusest, lepingu pooltest ja kohustustest. Tsiviilõigusliku vastutuse alustest, lepingulisest vastutusest, hüvitatava kahju liigist ja suurusest, deliktilisest vastutusest. Tsiviilõigusliku vastutuse piiramisest ning karistusõiguslikust vastutusest

Salto! / Karli Luik, Maarja Kask, Ralf Lõoke ; intervjueerinud Margit Mutso

Index Scriptorium Estoniae

Luik, Karli, 1977-

2011-01-01

Eesti Kultuurkapitali 2010. a. arhitektuuri peapreemia pälvis AB Salto Eesti Maanteemuuseumi väliala ja Sõmeru keskusehoone lahenduse eest. Büroo arhitektid oma büroost, osalemiset arhitektuurivõistlustel, valminud ja käsilolevatest töödest. Valik AB Salto arhitektuurikonkursil pälvitud jt. preemiatest

Estonian energy forest project

International Nuclear Information System (INIS)

Koppel, A.; Kirt, E.; Kull, K.; Lasn, R.; Noormets, A.; Roostalu, H.; Ross, J.; Ross, V.; Sulev, M.

1994-04-01

In February 1993 an agreement of Swedish-Estonian scientific co-operation on energy forest was signed. In may five energy forest plantations (altogether 2 ha) were established in Estonia with Swedish selected clones of Salix viminalis and Salix dasyclados. The research within this project is carried out within three main directions. The studies of basic ecophysiological processes and radiation regime of willow canopy will be carried out in Toravere. The production ecology studies, comparison of the productivity of multiple clones on different soil types is based on the plantations as vegetation filter for wastewater purification is studied on the basis of plantations in Vaeike-Maarja and Valga (author)

Molecular alterations and clinical prognostic factors for cholangiocarcinoma in Thai population

Directory of Open Access Journals (Sweden)

Trachu N

2017-10-01

Full Text Available N Trachu,1,2 E Sirachainan,3 N Larbcharoensub,4 W Rattanadech,3 S Detarkom,3 N Monnamo,1 K Kamprerasart,4 D MunTham,5 C Sukasem,6,7 T Reungwetwattana3 1Research Center, Faculty of Medicine Ramathibodi Hospital, 2Molecular Medicine Program, Multidisciplinary Unit, Faculty of Science, 3Division of Medical Oncology, Department of Medicine, 4Division of Anatomical Pathology, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 5Section for Mathematic, Faculty of Science and Technology, Rajamangala University of Technology Suvarnabhumi, 6Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, 7Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand Abstract: This study explores genomic alterations in cholangiocarcinoma (CCC tissues in Thai patients. We identified and reviewed the records of patients who had been diagnosed with CCC and for whom sufficient tumor samples for DNA and RNA extraction were available in our database. The specimens were explored for EGFR, KRAS, BRAF, and PIK3CA mutations and ROS1 translocation in 81 samples. Immunohistochemistry staining for HER2, ALK, and Ki-67 expression was tested in 74 samples. Prevalence of EGFR, KRAS, and PIK3CA mutations in this study was 21%, 12%, and 16%, respectively. No BRAF V600 mutation or ROS1 translocation was found. Patients with T790M mutation had a significantly longer overall survival (18.84 months than those with the other types of EGFR mutations (4.08  months; hazard ratio [HR]: 0.26, P=0.038 and also had a significantly lower median Ki-67 (22.5% vs 80%, P=0.025. Furthermore, patients with PIK3CA mutations had a significantly longer median progression-free survival (15.87 vs 7.01 months; HR: 0.46, P=0.043. Strongly positive HER2 expression was found in only 1 patient, whereas ALK expression was not found. The presence of EGFR

Trastuzumab anti-tumor efficacy in patient-derived esophageal squamous cell carcinoma xenograft (PDECX mouse models

Directory of Open Access Journals (Sweden)

Wu Xianhua

2012-08-01

Full Text Available Abstract Background Trastuzumab is currently approved for the clinical treatment of breast and gastric cancer patients with HER-2 positive tumors, but not yet for the treatment of esophageal carcinoma patients, whose tumors typically show 5 ~ 35% HER-2 gene amplification and 0 ~ 56% HER-2 protein expression. This study aimed to investigate the therapeutic efficacy of Trastuzumab in patient-derived esophageal squamous cell carcinoma xenograft (PDECX mouse models. Methods PDECX models were established by implanting patient esophageal squamous cell carcinoma (ESCC tissues into immunodeficient (SCID/nude mice. HER-2 gene copy number (GCN and protein expression were determined in xenograft tissues and corresponding patient EC samples by FISH and IHC analysis. Trastuzumab anti-tumor efficacy was evaluated within these PDECX models (n = 8 animals/group. Furthermore, hotspot mutations of EGFR, K-ras, B-raf and PIK3CA genes were screened for in the PDECX models and their corresponding patient’s ESCC tissues. Similarity between the PDECX models and their corresponding patient’s ESCC tissue was confirmed by histology, morphology, HER-2 GCN and mutation. Results None of the PDECX models (or their corresponding patient’s ESCC tissues harbored HER-2 gene amplification. IHC staining showed HER-2 positivity (IHC 2+ in 2 PDECX models and negativity in 3 PDECX models. Significant tumor regression was observed in the Trastuzumab-treated EC044 HER-2 positive model (IHC 2+. A second HER-2 positive (IHC 2+ model, EC039, harbored a known PIK3CA mutation and showed strong activation of the AKT signaling pathway and was insensitive to Trastuzumab treatment, but could be resensitised using a combination of Trastuzumab and AKT inhibitor AZD5363. In summary, we established 5 PDECX mouse models and demonstrated tumor regression in response to Trastuzumab treatment in a HER-2 IHC 2+ model, but resistance in a HER-2 IHC 2+/PIK3CA mutated model. Conclusions

Energy fluxes and spectra for turbulent and laminar flows

KAUST Repository

Verma, Mahendra K.; Kumar, Abhishek; Kumar, Praveen; Barman, Satyajit; Chatterjee, Anando G.; Samtaney, Ravi

2017-01-01

spectrum $E(k)$ and energy flux $\\Pi(k)$ using spectral simulations on grids up to $4096^3$, and show consistency between the numerical results and predictions by the aforementioned models. We also construct a model for laminar flows that predicts $E(k

Molecular Profiles for Lung Cancer Pathogenesis and Detection in U.S. Veterans

Science.gov (United States)

2013-10-01

independent survival and growth of cancer cells, including a catalytic subunit of phosphatidylinositol 3- kinase (PIK3CA) (33) and the SH2 -containg...comparative genomic hybridization: implications of the phosphatidylinositol 3- kinase pathway. Cancer Res. 2002;62:3636-40. 28. Massion PP, Zou Y, Uner

Kingiks kaunimale soole / Christel Karits

Index Scriptorium Estoniae

Karits, Christel, 1966-

2007-01-01

Naistepäeva tähistamise kontsertidest: Francis Goya 06. 03 Pärnu kontserdimajas, 08. 03 Estonia kontserdisaalis ja 10. 03 Vanemuise kontserdimajas; Naistepäevagala (Maarja & Koit, Tallinna Kammerorkester, Meelis Tauk, Mihkel Mälgand, Petteri Hasa, Andrus Rannaääre, dirigent Jüri-Ruut Kangur) 05. 03 Vanemuise kontserdimajas, 06. 03 Estonia kontserdisaalis ja 07. 03 Pärnu kontserdimajas; "Meestelt naistele" (Alen & Repriis, Vello Orumets, Jassi Zahharov, Andres Dvinjaninov 06. 03 Vanemuise kontserdimajas, 07. 03 Estonia kontserdisaalis, 09. 03 Jõhvi kontserdimajas; "Diplomaatilise noodid" raames "Sulle üks laul" (Daniel Bonilla-Torres, Kristo Käo, Jüri Aarma 08. 03 KuMu auditooriumis; Mõisaromantika kaunitele daamidele (Ooper-kvartett, Jüri Aarma) 10. 03 Vihterpalu mõisas

Tammsaare segase saatusega tähtis teenetemärk / Maarja Vaino

Index Scriptorium Estoniae

Vaino, Maarja, 1976-

2009-01-01

Anton Hansen Tammsaarele 1938. aastal antud Eesti Punase Risti II klassi teenetemärgist. Samas ka tsitaadid Anton Hanseni kirjutisest iseenesele romaani "Tõde ja Õigus" asjus "Avalik kiri kirjanik A. H. Tammsaarele", mis ilmus ajalehes Vaba Maa 11. märtsil 1927

Kala töötlemine : [andmeid aastatest 1995-2004] / Maarja Purik

Index Scriptorium Estoniae

Purik, Maarja

2005-01-01

Ilmunud ka: Agriculture and the development of rural life : overview 2004/2005. - Tallinn, 2005, lk. 49-52. Kalatöötlemise osatähtsus toiduainetööstuses moodustas 2004. a. 11,9% ja ekspordis 24,9%. Tabelid. Diagrammid

Somatic mutations in breast and serous ovarian cancer young patients: a systematic review and meta-analysis

Directory of Open Access Journals (Sweden)

Giselly Encinas

2015-10-01

Full Text Available Summary Objective: our aim was to evaluate whether somatic mutations in five genes were associated with an early age at presentation of breast cancer (BC or serous ovarian cancer (SOC. Methods: COSMIC database was searched for the five most frequent somatic mutations in BC and SOC. A systematic review of PubMed was performed. Young age for BC and SOC patients was set at ≤35 and ≤40 years, respectively. Age groups were also classified in <30years and every 10 years thereafter. Results: twenty six (1,980 patients, 111 younger and 16 studies (598, 41 younger, were analyzed for BC and SOC, respectively. In BC, PIK3CA wild type tumor was associated with early onset, not confirmed in binary regression with estrogen receptor (ER status. In HER2-negative tumors, there was increased frequency of PIK3CA somatic mutation in older age groups; in ER-positive tumors, there was a trend towards an increased frequency of PIK3CA somatic mutation in older age groups. TP53 somatic mutation was described in 20% of tumors from both younger and older patients; PTEN, CDH1 and GATA3 somatic mutation was investigated only in 16 patients and PTEN mutation was detected in one of them. In SOC, TP53 somatic mutation was rather common, detected in more than 50% of tumors, however, more frequently in older patients. Conclusion: frequency of somatic mutations in specific genes was not associated with early-onset breast cancer. Although very common in patients with serous ovarian cancer diagnosed at all ages, TP53 mutation was more frequently detected in older women.

Preoperative chemoradiation with capecitabine, irinotecan and cetuximab in rectal cancer: significance of pre-treatment and post-resection RAS mutations.

Science.gov (United States)

Gollins, Simon; West, Nick; Sebag-Montefiore, David; Myint, Arthur Sun; Saunders, Mark; Susnerwala, Shabbir; Quirke, Phil; Essapen, Sharadah; Samuel, Leslie; Sizer, Bruce; Worlding, Jane; Southward, Katie; Hemmings, Gemma; Tinkler-Hundal, Emma; Taylor, Morag; Bottomley, Daniel; Chambers, Philip; Lawrie, Emma; Lopes, Andre; Beare, Sandy

2017-10-24

The influence of EGFR pathway mutations on cetuximab-containing rectal cancer preoperative chemoradiation (CRT) is uncertain. In a prospective phase II trial (EXCITE), patients with magnetic resonance imaging (MRI)-defined non-metastatic rectal adenocarinoma threatening/involving the surgical resection plane received pelvic radiotherapy with concurrent capecitabine, irinotecan and cetuximab. Resection was recommended 8 weeks later. The primary endpoint was histopathologically clear (R0) resection margin. Pre-planned retrospective DNA pyrosequencing (PS) and next generation sequencing (NGS) of KRAS, NRAS, PIK3CA and BRAF was performed on the pre-treatment biopsy and resected specimen. Eighty-two patients were recruited and 76 underwent surgery, with R0 resection in 67 (82%, 90%CI: 73-88%) (four patients with clinical complete response declined surgery). Twenty-four patients (30%) had an excellent clinical or pathological response (ECPR). Using NGS 24 (46%) of 52 matched biopsies/resections were discrepant: ten patients (19%) gained 13 new resection mutations compared to biopsy (12 KRAS, one PIK3CA) and 18 (35%) lost 22 mutations (15 KRAS, 7 PIK3CA). Tumours only ever testing RAS wild-type had significantly greater ECPR than tumours with either biopsy or resection RAS mutations (14/29 [48%] vs 10/51 [20%], P=0.008), with a trend towards increased overall survival (HR 0.23, 95% CI 0.05-1.03, P=0.055). This regimen was feasible and the primary study endpoint was met. For the first time using pre-operative rectal CRT, emergence of clinically important new resection mutations is described, likely reflecting intratumoural heterogeneity manifesting either as treatment-driven selective clonal expansion or a geographical biopsy sampling miss.

Dynamic changes to survivin subcellular localization are initiated by DNA damage

Directory of Open Access Journals (Sweden)

Maritess Gay Asumen

2010-07-01

Full Text Available Maritess Gay Asumen1, Tochukwu V Ifeacho2, Luke Cockerham3, Christina Pfandl4, Nathan R Wall31Touro University’s College of Osteopathic Medicine, Vallejo, CA, USA; 2University of Southern California, Los Angeles, CA, USA; 3Center for Health Disparities Research and Molecular Medicine, Loma Linda University, CA, USA; 4Green Mountain Antibodies, Burlington, VT, USAAbstract: Subcellular distribution of the apoptosis inhibitor survivin and its ability to relocalize as a result of cell cycle phase or therapeutic insult has led to the hypothesis that these subcellular pools may coincide with different survivin functions. The PIK kinases (ATM, ATR and DNA-PK phosphorylate a variety of effector substrates that propagate DNA damage signals, resulting in various biological outputs. Here we demonstrate that subcellular repartitioning of survivin in MCF-7 cells as a result of UV light-mediated DNA damage is dependent upon DNA damage-sensing proteins as treatment with the pan PIK kinase inhibitor wortmannin repartitioned survivin in the mitochondria and diminished it from the cytosol and nucleus. Mitochondrial redistribution of survivin, such as was recorded after wortmannin treatment, occurred in cells lacking any one of the three DNA damage sensing protein kinases: DNA-PK, ATM or ATR. However, failed survivin redistribution from the mitochondria in response to low-dose UV occurred only in the cells lacking ATM, implying that ATM may be the primary kinase involved in this process. Taken together, this data implicates survivian’s subcellular distribution is a dynamic physiological process that appears responsive to UV light- initiated DNA damage and that its distribution may be responsible for its multifunctionality.Keywords: survivin, PIK kinases, ATM, ATR, DNA-PK

Synergistic effects of targeted PI3K signaling inhibition and chemotherapy in liposarcoma.

Directory of Open Access Journals (Sweden)

Shang Guo

Full Text Available While liposarcoma is the second most common soft tissue malignant tumor, the molecular pathogenesis in this malignancy is poorly understood. Our goal was therefore to expand the understanding of molecular mechanisms that drive liposarcoma and identify therapeutically-susceptible genetic alterations. We studied a cohort of high-grade liposarcomas and benign lipomas across multiple disease sites, as well as two liposarcoma cell lines, using multiplexed mutational analysis. Nucleic acids extracted from diagnostic patient tissue were simultaneously interrogated for 150 common mutations across 15 essential cancer genes using a clinically-validated platform for cancer genotyping. Western blot analysis was implemented to detect activation of downstream pathways. Liposarcoma cell lines were used to determine the effects of PI3K targeted drug treatment with or without chemotherapy. We identified mutations in the PIK3CA gene in 4 of 18 human liposarcoma patients (22%. No PIK3CA mutations were identified in benign lipomas. Western blot analysis confirmed downstream activation of AKT in both PIK3CA mutant and non-mutant liposarcoma samples. PI-103, a dual PI3K/mTOR inhibitor, effectively inhibited the activation of the PI3K/AKT in liposarcoma cell lines and induced apoptosis. Importantly, combination with PI-103 treatment strongly synergized the growth-inhibitory effects of the chemotherapy drugs doxorubicin and cisplatin in liposarcoma cells. Taken together, these findings suggest that activation of the PI3K/AKT pathway is an important cancer mechanism in liposarcoma. Targeting the PI3K/AKT/pathway with small molecule inhibitors in combination with chemotherapy could be exploited as a novel strategy in the treatment of liposarcoma.

Studies on Culture Technological Conditions of Vibrio harveyi Y91301%哈维氏弧菌Y91301菌株培养工艺的研究

Institute of Scientific and Technical Information of China (English)

毛芝娟; 楼丹; 吴建军

2004-01-01

用大黄鱼分离的哈维氏弧菌Y91301进行试验,研究接种浓度、培养瓶装液量、起始pH值、培养时间、培养温度和培养液配方等因素对菌株生长的影响,确定静置培养时最适条件为:接种母液浓度1×108～1×109cfu/ml,接种量6%～8%(相对培养瓶装液量),装液量40～50 ml/250 ml,培养液初始pH值为6.0～6.5,培养温度28℃;使用Zobell 2216E培养配方更适合大量培养和生产的需要;旋转培养能够获得更高的生物量.

Tartu Ülikooli kümme geeniust / Alo Lõhmus

Index Scriptorium Estoniae

Lõhmus, Alo

2007-01-01

Valik Tartu Ülikoolis 375 aasta jooksul kõige rohkem maailmateadust mõjutanud teadlasi: Friedrich Georg Wilhelm Stuve, Martin Heinrich Rathke, Karl Ernst von Baer, Karl Wilhelm von Kupffer, Juri Lotman, Ludvig Puusepp Nikolai Pirogov, Ernst Öpik, Ivan Kondakov, Karl Bücher, Karl Friedrich Burdach ja Gustav Teichmüller

7 CFR 1435.504 - Timing of distribution of CCC-owned sugar.

Science.gov (United States)

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Timing of distribution of CCC-owned sugar. 1435.504... CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS SUGAR PROGRAM Processor Sugar Payment-In-Kind (PIK) Program § 1435.504 Timing of distribution of CCC-owned sugar. Distribution of sugar...

ATM/Wip1 activities at chromatin control Plk1 re-activation to determine G2 checkpoint duration

Czech Academy of Sciences Publication Activity Database

Jaiswal, H.; Benada, Jan; Müllers, E.; Akopyan, K.; Burdová, Kamila; Koolmeister, T.; Helleday, T.; Medema, R.H.; Macůrek, Libor; Lindqvist, A.

2017-01-01

Roč. 36, č. 14 (2017), s. 2161-2176 ISSN 0261-4189 R&D Projects: GA ČR GA13-18392S Institutional support: RVO:68378050 Keywords : ATM * ATR * checkpoint recovery * G2 * Pik1 Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Cell biology Impact factor: 9.792, year: 2016

Molecular Markers Increase Precision of the European Association of Urology Non-Muscle-Invasive Bladder Cancer Progression Risk Groups

DEFF Research Database (Denmark)

van Kessel, Kim E M; van der Keur, Kirstin A; Dyrskjøt, Lars

2018-01-01

prospectively included 1,239 patients in follow-up for NMIBC in six European countries. Fresh-frozen tumor samples were analyzed for GATA2, TBX2, TBX3, and ZIC4 methylation and FGFR3, TERT, PIK3CA, and RAS mutation status. Cox regression analyses identified markers that were significantly associated...

Arstidel on keeruline võõrsilt naasta / Hanneli Rudi

Index Scriptorium Estoniae

Rudi, Hanneli

2011-01-01

Aastaid välismaal töötanud arstidel on raske Eestis tööd leida, sest vastavaid töökuulutusi Eesti Arstide Liidu ja haiglate kodulehed ei avalda. Eestisse tagasi tulla sooviv neuroloog Merle Ööpik ja lastepsühholoog Airiin Demir oma tööotsimiskogemustest

Врачам сложно возвращаться в родную страну / Ханнели Руди

Index Scriptorium Estoniae

Руди, Ханнели

2011-01-01

Aastaid välismaal töötanud arstidel on raske Eestis tööd leida, sest vastavaid töökuulutusi Eesti Arstide Liidu ja haiglate kodulehed ei avalda. Eestisse tagasi tulla sooviv neuroloog Merle Ööpik ja lastepsühholoog Airiin Demir oma tööotsimiskogemustest

Prognostic and predictive value of p-Akt, EGFR, and p-mTOR in early breast cancer

Energy Technology Data Exchange (ETDEWEB)

Lazaridis, Georgios; Lambaki, Sofia [Hospital, Department of Pathology, Thessaloniki (Greece); Karayannopoulou, Georgia [Aristotle Univ. of Thessaloniki School of Medicine, Thessaloniki (Greece). Dept. of Pathology; Eleftheraki, Anastasia G. [Data Office, Athens (Greece). Section of Biostatistics; Papaspirou, Irene [Alexandra Hospital, Athens (Greece). Dept. of Pathology; Bobos, Mattheos [Aristotle Univ. of Thessaloniki School of Medicine, Thessaloniki (Greece). Lab. of Molecular Oncology; Efstratiou, Ioannis [Papageorgiou Hospital, Thessaloniki (Greece). Dept. of Pathology; Pentheroudakis, George [Ioannina Univ. Hospital, Ioannina (Greece). Dept. of Medical Oncology; Zamboglou, Nikolaos [Klinikum Offenbach (Germany). Dept. of Radiation Oncology; Fountzilas, George [Hospital, Department of Pathology, Thessaloniki (Greece); Aristotle Univ. of Thessaloniki School of Medicine, Thessaloniki (Greece). Lab. of Molecular Oncology

2014-07-15

There are scarce data available on the prognostic/predictive value of p-Akt and p-mTOR protein expression in patients with high-risk early breast cancer. Formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from 997 patients participating in two adjuvant phase III trials were assessed for EGFR, PTEN, p-Akt, p-mTOR protein expression, and PIK3CA mutational status. These markers were evaluated for associations with each other and with selected patient and tumor characteristics, immunohistochemical subtypes, disease-free survival (DFS), and overall survival (OS). p-mTOR protein expression was negatively associated with EGFR and positively associated with PTEN, with p-Akt473, and with the presence of PIK3CA mutations. EGFR expression was positively associated with p-Akt473, p-Akt308, and PIK3CA wild-type tumors. Finally, p-Akt308 was positively associated with p-Akt473 expression. In univariate analysis, EGFR (p = 0.016) and the coexpression of EGFR and p-mTOR (p = 0.015) were associated with poor OS. Among patients with p-Akt308-negative or low-expressing tumors, those treated with hormonal therapy were associated with decreased risk for both relapse and death (p = 0.013 and p < 0.001, respectively). In the subgroup of patients with locoregional relapse, positive EGFR and mTOR protein expression was found to be associated with increased (p = 0.034) and decreased (p < 0.001) risk for earlier relapse, respectively. In multivariate analysis, low levels of p-Akt308 and the coexpression of EGFR and p-mTOR retained their prognostic value. Low protein expression of p-Akt308 was associated with improved DFS and OS among patients treated with hormonal therapy following adjuvant chemotherapy. Coexpression of EGFR and p-mTOR was associated with worse OS. (orig.) [German] Geringe Daten existieren ueber den prognostischen/praediktiven Wert der p-Akt- und p-mTOR-Proteinexpression bei Patienten mit ''High-risk''-Mammakarzinom im Fruehstadium

Genetics Home Reference: ovarian cancer

Science.gov (United States)

... is most often associated with mutations in the MLH1 or MSH2 gene and accounts for between 10 ... AKT1 BARD1 BRCA1 BRCA2 BRIP1 CDH1 CHEK2 CTNNB1 MLH1 MRE11 MSH2 MSH6 NBN OPCML PALB2 PIK3CA PMS2 ...

Alternative splicing in colon, bladder, and prostate cancer identified by exon-array analysis

DEFF Research Database (Denmark)

Thorsen, Kasper; Sørensen, Karina D.; Brems-Eskildsen, Anne Sofie

2008-01-01

, PIK4CB, TPM1, and VCL). The validated tumor-specific splicing alterations were highly consistent, enabling clear separation of normal and cancer samples and in some cases even of different tumor stages. A subset of the tumor-specific splicing alterations (ACTN1, CALD1, and VCL) was found in all three...

Kuressaarest kaks laureaaditiitlit / Riina Mägi

Index Scriptorium Estoniae

Mägi, Riina, 1957-

2008-01-01

Maakondlikust etlejate konkursist. Žüriisse kuulusid Maret Oomer, Asta Leiten ja Kalle Piiskoppel. 5.-7. klasside arvestuses I koht: Marleen Petersell. Äramärkimist leidsid: Kristian Käresk, Maarja-Liis Mölder ja Anita Tuula. 7.-9. klasside arvestuses I koht: Oliver Taul. Esile tõsteti: Rauno Reinas, Riko Osila, Linda Maisväli ja Piia Puuraid. 10.-12. klasside arvestuses I koht: Karl Sakrits. Ära märgiti: Elin Küti, Virgo Ernits, Maria Orb. Kommenteerisid Asta Leiten, Liann Saage-Vahur. Ka Kuressaares toimunud vabariiklikust etlejate konkursist, kommentaare jagasid Merle Rekaya, Rita Ilves. Zhürisse kuulusid Aare Toikka, Tiina Rebane, Hans Kaldoja, Kristiina Omer ja Keete Viira. Peapreemia nooremas vanuseastmes Markkus Pulgale, keskmises vanuseastmes Anna Talvile ja vanemas vanuseastmes Doris Täkkerile.

"Kuis sa nii võimsalt tuled minu üle..." : [luuletused] / Marie Under

Index Scriptorium Estoniae

Under, Marie, 1883-1980

1998-01-01

Sisu: "Kuis sa nii võimsalt tuled minu üle..." ; Sügesemaru ; Talvel ; Sinine terrass ; Õnne ootel ; Ekstaas ; Unistus ; Üllatus ; Ehtides ; Ma armastan su armastust ; Valge värav ; Meeletus ; On siiski kurb ; Verivalla ; Surnute rongkäik ; A rebours ; Luukambris ; Kiusaja ; Hingetund ; Inimene ; Koduotsimine ; Surelik ; Saladus ; Memento mori ; Kontvõõras ; Ahastaja ; Ummikus ; Hommikupalve ; Suudlus ; Kutse ; Raismik. Mets ; Valge lind ; Rändav järv ; Porkuni preili ; Lapsehukkaja ; Maarja leid ; Surmamõrsjad ; Taevaminek ; Laul eimillestki ; Õnnevaras ; Puhastus ; Soolaul ; Lõikuspühaks ; "Üksteisest pimesi me mööda käime..." ; Loomine ; Muutus ; Selgus ; Haige unistus ; Jõulutervitus 1941 ; Mõrane hommik ; Pärast ema surma ; Kutse ; Kes? ; Hääl tuulde ; Mine! ; Nägemus ; Veel mitte ; Visioon ; Langes üks täht

Ovarian carcinomas with genetic and epigenetic BRCA1 loss have distinct molecular abnormalities

International Nuclear Information System (INIS)

Press, Joshua Z; Smith, Margaret; Spellman, Paul T; Wang, Yuker; Miller, Dianne M; Horsman, Doug; Faham, Malek; Gilks, C Blake; Gray, Joe; Huntsman, David G; De Luca, Alessandro; Boyd, Niki; Young, Sean; Troussard, Armelle; Ridge, Yolanda; Kaurah, Pardeep; Kalloger, Steve E; Blood, Katherine A

2008-01-01

Subclassification of ovarian carcinomas can be used to guide treatment and determine prognosis. Germline and somatic mutations, loss of heterozygosity (LOH), and epigenetic events such as promoter hypermethylation can lead to decreased expression of BRCA1/2 in ovarian cancers. The mechanism of BRCA1/2 loss is a potential method of subclassifying high grade serous carcinomas. A consecutive series of 49 ovarian cancers was assessed for mutations status of BRCA1 and BRCA2, LOH at the BRCA1 and BRCA2 loci, methylation of the BRCA1 promoter, BRCA1, BRCA2, PTEN, and PIK3CA transcript levels, PIK3CA gene copy number, and BRCA1, p21, p53, and WT-1 immunohistochemistry. Eighteen (37%) of the ovarian carcinomas had germline or somatic BRCA1 mutations, or epigenetic loss of BRCA1. All of these tumours were high-grade serous or undifferentiated type. None of the endometrioid (n = 5), clear cell (n = 4), or low grade serous (n = 2) carcinomas showed loss of BRCA1, whereas 47% of the 38 high-grade serous or undifferentiated carcinomas had loss of BRCA1. It was possible to distinguish high grade serous carcinomas with BRCA1 mutations from those with epigenetic BRCA1 loss: tumours with BRCA1 mutations typically had decreased PTEN mRNA levels while those with epigenetic loss of BRCA1 had copy number gain of PIK3CA. Overexpression of p53 with loss of p21 expression occurred significantly more frequently in high grade serous carcinomas with epigenetic loss of BRCA1, compared to high grade serous tumors without loss of BRCA1. High grade serous carcinomas can be subclassified into three groups: BRCA1 loss (genetic), BRCA1 loss (epigenetic), and no BRCA1 loss. Tumors in these groups show distinct molecular alterations involving the PI3K/AKT and p53 pathways

Use of molecular markers in identification and characterization of resistance to rice blast in India.

Directory of Open Access Journals (Sweden)

Manoj Kumar Yadav

Full Text Available Rice blast disease caused by Magnaporthe oryzae is one of the most destructive disease causing huge losses to rice yield in different parts of the world. Therefore, an attempt has been made to find out the resistance by screening and studying the genetic diversity of eighty released rice varieties by National Rice Research Institute, Cuttack (NRVs using molecular markers linked to twelve major blast resistance (R genes viz Pib, Piz, Piz-t, Pik, Pik-p, Pikm Pik-h, Pita/Pita-2, Pi2, Pi9, Pi1 and Pi5. Out of which, nineteen varieties (23.75% showed resistance, twenty one were moderately resistant (26.25% while remaining forty varieties (50% showed susceptible in uniform blast nursery. Rice varieties possessing blast resistance genes varied from four to twelve and the frequencies of the resistance genes ranged from 0 to 100%. The cluster analysis grouped the eighty NRVs into two major clusters at 63% level of genetic similarity coefficient. The PIC value for seventeen markers varied from 0 to 0.37 at an average of 0.20. Out of seventeen markers, only five markers, 195R-1, Pi9-i, Pita3, YL155/YL87 and 40N23r corresponded to three broad spectrum R genes viz. Pi9, Pita/Pita2 and Pi5 were found to be significantly associated with the blast disease with explaining phenotypic variance from 3.5% to 7.7%. The population structure analysis and PCoA divided the entire 80 NRVs into two sub-groups. The outcome of this study would help to formulate strategies for improving rice blast resistance through genetic studies, plant-pathogen interaction, identification of novel R genes, development of new resistant varieties through marker-assisted breeding for improving rice blast resistance in India and worldwide.

Use of molecular markers in identification and characterization of resistance to rice blast in India.

Science.gov (United States)

Yadav, Manoj Kumar; S, Aravindan; Ngangkham, Umakanta; Shubudhi, H N; Bag, Manas Kumar; Adak, Totan; Munda, Sushmita; Samantaray, Sanghamitra; Jena, Mayabini

2017-01-01

Rice blast disease caused by Magnaporthe oryzae is one of the most destructive disease causing huge losses to rice yield in different parts of the world. Therefore, an attempt has been made to find out the resistance by screening and studying the genetic diversity of eighty released rice varieties by National Rice Research Institute, Cuttack (NRVs) using molecular markers linked to twelve major blast resistance (R) genes viz Pib, Piz, Piz-t, Pik, Pik-p, Pikm Pik-h, Pita/Pita-2, Pi2, Pi9, Pi1 and Pi5. Out of which, nineteen varieties (23.75%) showed resistance, twenty one were moderately resistant (26.25%) while remaining forty varieties (50%) showed susceptible in uniform blast nursery. Rice varieties possessing blast resistance genes varied from four to twelve and the frequencies of the resistance genes ranged from 0 to 100%. The cluster analysis grouped the eighty NRVs into two major clusters at 63% level of genetic similarity coefficient. The PIC value for seventeen markers varied from 0 to 0.37 at an average of 0.20. Out of seventeen markers, only five markers, 195R-1, Pi9-i, Pita3, YL155/YL87 and 40N23r corresponded to three broad spectrum R genes viz. Pi9, Pita/Pita2 and Pi5 were found to be significantly associated with the blast disease with explaining phenotypic variance from 3.5% to 7.7%. The population structure analysis and PCoA divided the entire 80 NRVs into two sub-groups. The outcome of this study would help to formulate strategies for improving rice blast resistance through genetic studies, plant-pathogen interaction, identification of novel R genes, development of new resistant varieties through marker-assisted breeding for improving rice blast resistance in India and worldwide.

The Genetic Landscape of Breast Carcinomas with Neuroendocrine Differentiation

Science.gov (United States)

Marchiò, Caterina; Geyer, Felipe C; Ng, Charlotte KY; Piscuoglio, Salvatore; De Filippo, Maria R; Cupo, Marco; Schultheis, Anne M; Lim, Raymond S; Burke, Kathleen A; Guerini-Rocco, Elena; Papotti, Mauro; Norton, Larry; Sapino, Anna; Weigelt, Britta; Reis-Filho, Jorge S

2016-01-01

Neuroendocrine breast carcinomas (NBCs) account for 2–5% of all invasive breast cancers and are histologically similar to neuroendocrine tumours from other sites. They typically express oestrogen receptor (ER), are HER2-negative and of luminal 'intrinsic' subtype. Here we sought to define the mutational profile of NBCs, and to investigate whether NBCs and common forms of luminal (ER+/HER2-) breast cancer display distinct repertoires of somatic mutations. Eighteen ER+/HER2- NBCs, defined as harbouring >50% of tumour cells expressing chromogranin A and/or synaptophysin, and matched normal tissue were microdissected and subjected to massively parallel sequencing targeting all exons of 254 genes most frequently mutated in breast cancer and/or related to DNA repair. Their mutational repertoire was compared to that of ER+/HER2- (n=240), PAM50-defined luminal breast cancers (n=209 luminal A; n=111 luminal B) and invasive lobular carcinomas (n=127) from The Cancer Genome Atlas. NBCs were found to harbour a median of 4.5 (range 1-11) somatic mutations, similar to that of luminal B breast cancers (median=3, range 0-17) but significantly higher than that of luminal A breast cancers (median=3, range 0-18, p=0.02). The most frequently mutated genes were GATA3, FOXA1, TBX3, ARID1A (3/18, 17%), and PIK3CA, AKT1, CDH1 (2/18, 11%). NBCs less frequently harboured PIK3CA mutations than common forms of ER+/HER2, luminal A and invasive lobular carcinomas (pcancers. No TP53 somatic mutations were detected in NBCs. Compared to common forms of luminal breast cancers, NBCs display a distinctive repertoire of somatic mutations featuring lower frequency of TP53 and PIK3CA mutations, and enrichment for FOXA1, TBX3 mutations, and akin to neuroendocrine tumours from other sites, ARID1A mutations. PMID:27925203

Colorectal cancer cell-derived exosomes containing miR-10b regulate fibroblast cells via the PI3K/Akt pathway.

Science.gov (United States)

Dai, Guangyao; Yao, Xiaoguang; Zhang, Yubin; Gu, Jianbin; Geng, Yunfeng; Xue, Fei; Zhang, Jingcheng

2018-04-01

Cancer-associated fibroblasts (CAFs) contribute to the proliferation of colorectal cancer(CRC) cells. However, the mechanism by which CAFs develop in the tumor microenvironment remains unknown. Exosomes may be involved in activating CAFs. Using a miRNA expression profiling array, we determined the miRNA expression profile of secretory exosomes in CRC cells and then identified potential miRNAs with significant differential expression compared to normal cells via enrichment analysis. Predicted targets of candidate miRNAs were then assessed via bioinformatics analysis. Realtime qPCR, western blot, and cell cycle analyses were performed to evaluate the role of candidate exosomal miRNAs. Luciferase reporter assays were applied to confirm whether candidate exosomal miRNAs control target pathway expression. A CRC xenograft mouse model was constructed to evaluate tumor growth in vivo. Exosomes from CRC cells contained significantly higher levels of miR-10b than did exosomes from normal colorectal epithelial cells. Moreover, exosomes containing miR-10b were transferred to fibroblasts. Bioinformatics analysis identified PIK3CA, as a potential target of miR-10b. Luciferase reporter assays confirmed that miR-10b directly inhibited PIK3CA expression. Co-culturing fibroblasts with exosomes containing miR-10b significantly suppressed PIK3CA expression and decreased PI3K/Akt/mTOR pathway activity. Finally, exosomes containing miR-10b reduced fibroblast proliferation but promoted expression of TGF-β and SM α-actin, suggesting that exosomal miR-10b may activate fibroblasts to become CAFs that express myofibroblast markers. These activated fibroblasts were able to promote CRC growth in vitro and in vivo. CRC-derived exosomes actively promote disease progression by modulating surrounding stromal cells, which subsequently acquire features of CAFs. Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

TRIM24 promotes glioma progression and enhances chemoresistance through activation of the PI3K/Akt signaling pathway.

Science.gov (United States)

Zhang, L-H; Yin, A-A; Cheng, J-X; Huang, H-Y; Li, X-M; Zhang, Y-Q; Han, N; Zhang, X

2015-01-29

The tripartite motif protein TRIM24 (tripartite motif-containing 24) has been found to play distinct roles in tumor development and progression, according to different tumor contexts. However, it remains elusive whether TRIM24 plays a role in malignant gliomas that are the most common and deadly primary brain tumors in adults. We report here that TRIM24 expression is positively correlated with glioma malignancy and is negatively associated with prognosis of patients with newly diagnosed glioblastoma, which is the most malignant form of gliomas but displays highly heterogeneous clinical outcome. The multivariate Cox regression analysis demonstrates the independent predictive value of TRIM24 expression level for overall and progression-free survival. Knockdown of TRIM24 suppresses cell proliferation, cell cycle progression, clone formation and in vivo tumor development, whereas overexpression of TRIM24 promotes cell growth. Chromatin immunoprecipitation, real-time reverse transcription-PCR and mutation analyses demonstrate that TRIM24 binds to the PIK3CA promoter via its PHD-Bromo domain to activate the transcription of PIK3CA gene, thus enhancing phosphatidylinositide 3-kinase (PI3K)/Akt signaling. The pan-PI3K inhibitor LY294002 and small interfering RNA targeting PIK3CA both abrogate the growth-promoting effect of TRIM24. Moreover, TRIM24 regulates the expression of DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT) through PI3K/Akt/nuclear factor-κB signaling transduction and enhances resistance to temozolomide, the standard chemotherapeutic agent for glioblastoma. Finally, glioblastoma patients with low TRIM24 expression benefit from chemotherapy, whereas those with high TRIM24 expression do not have such benefit. Our results suggest that TRIM24 might serve as a potential prognostic marker and therapeutic target for the management of malignant gliomas.

Hot spot mutations in Finnish non-small cell lung cancers.

Science.gov (United States)

Mäki-Nevala, Satu; Sarhadi, Virinder Kaur; Rönty, Mikko; Kettunen, Eeva; Husgafvel-Pursiainen, Kirsti; Wolff, Henrik; Knuuttila, Aija; Knuutila, Sakari

2016-09-01

Non-small cell lung cancer (NSCLC) is a common cancer with a poor prognosis. The aim of this study was to screen Finnish NSCLC tumor samples for common cancer-related mutations by targeted next generation sequencing and to determine their concurrences and associations with clinical features. Sequencing libraries were prepared from DNA isolated from formalin-fixed, paraffin-embedded tumor material of 425 patients using the AmpliSeq Colon and Lung panel covering mutational hot spot regions of 22 cancer genes. Sequencing was performed with the Ion Torrent Personal Genome Machine (PGM). Data analysis of the hot spot mutations revealed mutations in 77% of the patients, with 7% having 3 or more mutations reported in the Catalogue of Somatic Mutations in Cancer (COSMIC) database. Two of the most frequently mutated genes were TP53 (46%) and KRAS (25%). KRAS codon 12 mutations were the most recurrently occurring mutations. EGFR mutations were significantly associated with adenocarcinoma, female gender and never/light-smoking history; CTNNB1 mutations with light ex-smokers, PIK3CA and TP53 mutations with squamous cell carcinoma, and KRAS with adenocarcinoma. TP53 mutations were most prevalent in current smokers and ERBB2, ERBB4, PIK3CA, NRAS, NOTCH1, FBWX7, PTEN and STK11 mutations occurred exclusively in a group of ever-smokers, however the association was not statistically significant. No mutation was found that associated with asbestos exposure. Finnish NSCLC patients have a similar mutation profile as other Western patients, however with a higher frequency of BRAF mutations but a lower frequency of STK11 and ERBB2 mutations. Moreover, TP53 mutations occurred frequently with other gene mutations, most commonly with KRAS, MET, EGFR and PIK3CA mutations. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Frequency of Somatic TP53 Mutations in Combination with Known Pathogenic Mutations in Colon Adenocarcinoma, Non–Small Cell Lung Carcinoma, and Gliomas as Identified by Next-Generation Sequencing

Directory of Open Access Journals (Sweden)

Zahra Shajani-Yi

2018-03-01

Full Text Available The tumor suppressor gene TP53 is the most frequently mutated gene in human cancer. It encodes p53, a DNA-binding transcription factor that regulates multiple genes involved in DNA repair, metabolism, cell cycle arrest, apoptosis, and senescence. TP53 is associated with human cancer by mutations that lead to a loss of wild-type p53 function as well as mutations that confer alternate oncogenic functions that enable them to promote invasion, metastasis, proliferation, and cell survival. Identifying the discrete TP53 mutations in tumor cells may help direct therapies that are more effective. In this study, we identified the frequency of individual TP53 mutations in patients with colon adenocarcinoma (48%, non–small cell lung carcinoma (NSCLC (36%, and glioma/glioblastoma (28% at our institution using next-generation sequencing. We also identified the occurrence of somatic mutations in numerous actionable genes including BRAF, EGFR, KRAS, IDH1, and PIK3CA that occurred concurrently with these TP53 mutations. Of the 480 tumors examined that contained one or more mutations in the TP53 gene, 219 were colon adenocarcinomas, 215 were NSCLCs, and 46 were gliomas/glioblastomas. Among the patients positive for TP53 mutations diagnosed with colon adenocarcinoma, 50% also showed at least one mutation in pathogenic genes of which 14% were BRAF, 33% were KRAS, and 3% were NRAS. Forty-seven percent of NSCLC patients harboring TP53 mutations also had a mutation in at least one actionable pathogenic variant with the following frequencies: BRAF: 4%, EGFR: 10%, KRAS: 28%, and PIK3CA: 4%. Fifty-two percent of patients diagnosed with glioma/glioblastoma with a positive TP53 mutation had at least one concurrent mutation in a known pathogenic gene of which 9% were CDKN2A, 41% were IDH1, and 11% were PIK3CA.

Ovarian carcinomas with genetic and epigenetic BRCA1 loss have distinct molecular abnormalities

Energy Technology Data Exchange (ETDEWEB)

Gilks, C. Blake; Press, Joshua Z.; De Luca, Alessandro; Boyd, Niki; Young, Sean; Troussard, Armelle; Ridge, Yolanda; Kaurah, Pardeep; Kalloger, Steve E.; Blood, Katherine A.; Smith, Margaret; Spellman, Paul T.; Wang, Yuker; Miller, Dianne M.; Horsman, Doug; Faham, Malek; Gilks, C. Blake; Gray, Joe; Huntsman, David G.

2008-05-02

Subclassification of ovarian carcinomas can be used to guide treatment and determine prognosis. Germline and somatic mutations, loss of heterozygosity (LOH), and epigenetic events such as promoter hypermethylation can lead to decreased expression of BRCA1/2 in ovarian cancers. The mechanism of BRCA1/2 loss is a potential method of subclassifying high grade serous carcinomas. A consecutive series of 49 ovarian cancers was assessed for mutations status of BRCA1 and BRCA2, LOH at the BRCA1 and BRCA2 loci, methylation of the BRCA1 promoter, BRCA1, BRCA2, PTEN, and PIK3CA transcript levels, PIK3CA gene copy number, and BRCA1, p21, p53, and WT-1 immunohistochemistry. Eighteen (37%) of the ovarian carcinomas had germline or somatic BRCA1 mutations, or epigenetic loss of BRCA1. All of these tumors were high-grade serous or undifferentiated type. None of the endometrioid (n=5), clear cell (n=4), or low grade serous (n=2) carcinomas showed loss of BRCA1, whereas 47% of the 38 high-grade serous or undifferentiated carcinomas had loss of BRCA1. It was possible to distinguish high grade serous carcinomas with BRCA1 mutations from those with epigenetic BRCA1 loss: tumors with BRCA1 mutations typically had decreased PTEN mRNA levels while those with epigenetic loss of BRCA1 had copy number gain of PIK3CA. Overexpression of p53 with loss of p21 expression occurred significantly more frequently in high grade serous carcinomas with epigenetic loss of BRCA1, compared to high grade serous tumors without loss of BRCA1. High grade serous carcinomas can be subclassified into three groups: BRCA1 loss (genetic), BRCA1 loss (epigenetic), and no BRCA1 loss. Tumors in these groups show distinct molecular alterations involving the PI3K/AKT and p53 pathways.

Ovarian carcinomas with genetic and epigenetic BRCA1 loss havedistinct molecular abnormalities

Energy Technology Data Exchange (ETDEWEB)

Press, Joshua Z.; De Luca, Alessandro; Boyd, Niki; Young, Sean; Troussard, Armelle; Ridge, Yolanda; Kaurah, Pardeep; Kalloger, Steve E.; Blood, Katherine A.; Smith, Margaret; Spellman, Paul T.; Wang, Yuker; Miller, Dianne M.; Horsman, Doug; Faham, Malek; Gilks, C. Blake; Gray,Joe; Huntsman, David G.

2007-07-23

Subclassification of ovarian carcinomas can be used to guide treatment and determine prognosis. Germline and somatic mutations, loss of heterozygosity (LOH), and epigenetic events such as promoter hypermethylation can lead to decreased expression of BRCA1/2 in ovarian cancers. The mechanism of BRCA1/2 loss is a potential method of subclassifying high grade serous carcinomas. A consecutive series of 49 ovarian cancers was assessed for mutations status of BRCA1 and BRCA2, LOH at the BRCA1 and BRCA2 loci, methylation of the BRCA1 promoter, BRCA1, BRCA2, PTEN, and PIK3CA transcript levels, PIK3CA gene copy number, and BRCA1, p21, p53, and WT-1 immunohistochemistry. Eighteen (37%) of the ovarian carcinomas had germline or somatic BRCA1 mutations, or epigenetic loss of BRCA1. All of these tumors were high-grade serous or undifferentiated type. None of the endometrioid (n = 5), clear cell (n = 4), or low grade serous (n = 2) carcinomas showed loss of BRCA1, whereas 47% of the 38 high-grade serous or undifferentiated carcinomas had loss of BRCA1. It was possible to distinguish high grade serous carcinomas with BRCA1 mutations from those with epigenetic BRCA1 loss: tumors with BRCA1 mutations typically had decreased PTEN mRNA levels while those with epigenetic loss of BRCA1 had copy number gain of PIK3CA. Overexpression of p53 with loss of p21 expression occurred significantly more frequently in high grade serous carcinomas with epigenetic loss of BRCA1, compared to high grade serous tumors without loss of BRCA1. High grade serous carcinomas can be subclassified into three groups: BRCA1 loss (genetic), BRCA1 loss (epigenetic), and no BRCA1 loss. Tumors in these groups show distinct molecular alterations involving the PI3K/AKT and p53 pathways.

The estimation of production rates of $\\pi^+K^-, \\pi^-K^+$ and $\\pi^+\\pi^-$ atoms in proton-nucleus interactions at 450 GeV/c

CERN Document Server

Gorchakov, O

2015-01-01

Short-lived (τ ∼ 3 × 10 − 15 s) π+ K− , K+ π− and π+ π− atoms as well as long- lived (τ ≥ 1 × 10 − 11 s) π+ π− atoms produced in proton-nucleus interactions at 24 GeV/c are observed and studied in the DIRAC experiment at the CERN PS. The purpose of this paper is to show that the yields of the short-lived π+ K−, K+ π− and π+ π− atoms in proton-nucleus interactions at 450 GeV/c and θ lab = 4◦ are estimated to be, respectively, 17, 38 and 16 times higher per time unit. This may allow significantly improving the precision of their lifetime measurement and ππ and πK scattering length combinations |a0 − a2| and |a 1/2 − a3/2| . The yields of the long-lived π+ K− , K+ π− and π+ π− atoms at 450 GeV/c are estimated to be 370, 1600 and 750 times higher than at 24 GeV/c. This may allow the resonance method to be used for measuring the Lamb shift in the ππ atom and a new ππ scattering length combination 2 a0 + a2 to be obtained.

Screening for circulating RAS/RAF mutations by multiplex digital PCR

DEFF Research Database (Denmark)

Andersen, Rikke Fredslund; Jakobsen, Anders

2016-01-01

by technical challenges primarily due to the low levels of ctDNA in patients with localized disease and in patients responding to therapy. The approach presented here is a multiplex digital PCR method of screening for 31 mutations in the KRAS, NRAS, BRAF, and PIK3CA genes in the plasma. The upper level...

MAQUETTE ORL Décembre 2004

African Journals Online (AJOL)

35- Mtasiwa DM, Imamura N, Inda T et al. Immunophenotype, histology and cli- nical stage: their predictive value in the prognosis of non Hodgkin's lymphomas. Hiroshima J Med Sci 1990; 39(4): 95-102. 36- Hutchison RE, Berard CW, Shuster JJ, Link MP, Pik TE, Murphy SB; B-cell lineage confers a favorable outcome ...

JPRS Report: Environmental Issues

Science.gov (United States)

1993-05-28

Enhanced Safety come in contact with its discharges. Lung diseases, 93WN0407A St. Petersburg CHAS PIK in Russian diseases of the larynx and asthma are...The contraband goods produced in the Far East consist of system of payments for pollution and the use of natural pelts and other parts of bears, tigers

Whole genomes redefine the mutational landscape of pancreatic cancer.

Science.gov (United States)

Waddell, Nicola; Pajic, Marina; Patch, Ann-Marie; Chang, David K; Kassahn, Karin S; Bailey, Peter; Johns, Amber L; Miller, David; Nones, Katia; Quek, Kelly; Quinn, Michael C J; Robertson, Alan J; Fadlullah, Muhammad Z H; Bruxner, Tim J C; Christ, Angelika N; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Wani, Shivangi; Wilson, Peter J; Markham, Emma; Cloonan, Nicole; Anderson, Matthew J; Fink, J Lynn; Holmes, Oliver; Kazakoff, Stephen H; Leonard, Conrad; Newell, Felicity; Poudel, Barsha; Song, Sarah; Taylor, Darrin; Waddell, Nick; Wood, Scott; Xu, Qinying; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Lee, Hong C; Jones, Marc D; Nagrial, Adnan M; Humphris, Jeremy; Chantrill, Lorraine A; Chin, Venessa; Steinmann, Angela M; Mawson, Amanda; Humphrey, Emily S; Colvin, Emily K; Chou, Angela; Scarlett, Christopher J; Pinho, Andreia V; Giry-Laterriere, Marc; Rooman, Ilse; Samra, Jaswinder S; Kench, James G; Pettitt, Jessica A; Merrett, Neil D; Toon, Christopher; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Jamieson, Nigel B; Graham, Janet S; Niclou, Simone P; Bjerkvig, Rolf; Grützmann, Robert; Aust, Daniela; Hruban, Ralph H; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Corbo, Vincenzo; Bassi, Claudio; Falconi, Massimo; Zamboni, Giuseppe; Tortora, Giampaolo; Tempero, Margaret A; Gill, Anthony J; Eshleman, James R; Pilarsky, Christian; Scarpa, Aldo; Musgrove, Elizabeth A; Pearson, John V; Biankin, Andrew V; Grimmond, Sean M

2015-02-26

Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded.

Unique molecular signatures as a hallmark of patients with metastatic breast cancer: implications for current treatment paradigms.

Science.gov (United States)

Wheler, Jennifer J; Parker, Barbara A; Lee, Jack J; Atkins, Johnique T; Janku, Filip; Tsimberidou, Apostolia M; Zinner, Ralph; Subbiah, Vivek; Fu, Siqing; Schwab, Richard; Moulder, Stacy; Valero, Vicente; Schwaederle, Maria; Yelensky, Roman; Miller, Vincent A; Stephens, M Philip J; Meric-Bernstam, Funda; Kurzrock, Razelle

2014-05-15

Our analysis of the tumors of 57 women with metastatic breast cancer with next generation sequencing (NGS) demonstrates that each patient's tumor is unique in its molecular fingerprint. We observed 216 somatic aberrations in 70 different genes, including 131 distinct aberrations. The most common gene alterations (in order of decreasing frequency) included: TP53, PIK3CA, CCND1, MYC, HER2 (ERBB2), MCL1, PTEN, FGFR1, GATA3, NF1, PIK3R1, BRCA2, EGFR, IRS2, CDH1, CDKN2A, FGF19, FGF3 and FGF4. Aberrations included mutations (46%), amplifications (45%), deletions (5%), splices (2%), truncations (1%), fusions (0.5%) and rearrangements (0.5%), with multiple distinct variants within the same gene. Many of these aberrations represent druggable targets, either through direct pathway inhibition or through an associated pathway (via 'crosstalk'). The 'molecular individuality' of these tumors suggests that a customized strategy, using an "N-of-One" model of precision medicine, may represent an optimal approach for the treatment of patients with advanced tumors.

Off-diagonal long-range order, cycle probabilities, and condensate fraction in the ideal Bose gas.

Science.gov (United States)

Chevallier, Maguelonne; Krauth, Werner

2007-11-01

We discuss the relationship between the cycle probabilities in the path-integral representation of the ideal Bose gas, off-diagonal long-range order, and Bose-Einstein condensation. Starting from the Landsberg recursion relation for the canonic partition function, we use elementary considerations to show that in a box of size L3 the sum of the cycle probabilities of length k>L2 equals the off-diagonal long-range order parameter in the thermodynamic limit. For arbitrary systems of ideal bosons, the integer derivative of the cycle probabilities is related to the probability of condensing k bosons. We use this relation to derive the precise form of the pik in the thermodynamic limit. We also determine the function pik for arbitrary systems. Furthermore, we use the cycle probabilities to compute the probability distribution of the maximum-length cycles both at T=0, where the ideal Bose gas reduces to the study of random permutations, and at finite temperature. We close with comments on the cycle probabilities in interacting Bose gases.

Whole genomes redefine the mutational landscape of pancreatic cancer

Science.gov (United States)

Waddell, Nicola; Pajic, Marina; Patch, Ann-Marie; Chang, David K.; Kassahn, Karin S.; Bailey, Peter; Johns, Amber L.; Miller, David; Nones, Katia; Quek, Kelly; Quinn, Michael C. J.; Robertson, Alan J.; Fadlullah, Muhammad Z. H.; Bruxner, Tim J. C.; Christ, Angelika N.; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Wani, Shivangi; Wilson, Peter J; Markham, Emma; Cloonan, Nicole; Anderson, Matthew J.; Fink, J. Lynn; Holmes, Oliver; Kazakoff, Stephen H.; Leonard, Conrad; Newell, Felicity; Poudel, Barsha; Song, Sarah; Taylor, Darrin; Waddell, Nick; Wood, Scott; Xu, Qinying; Wu, Jianmin; Pinese, Mark; Cowley, Mark J.; Lee, Hong C.; Jones, Marc D.; Nagrial, Adnan M.; Humphris, Jeremy; Chantrill, Lorraine A.; Chin, Venessa; Steinmann, Angela M.; Mawson, Amanda; Humphrey, Emily S.; Colvin, Emily K.; Chou, Angela; Scarlett, Christopher J.; Pinho, Andreia V.; Giry-Laterriere, Marc; Rooman, Ilse; Samra, Jaswinder S.; Kench, James G.; Pettitt, Jessica A.; Merrett, Neil D.; Toon, Christopher; Epari, Krishna; Nguyen, Nam Q.; Barbour, Andrew; Zeps, Nikolajs; Jamieson, Nigel B.; Graham, Janet S.; Niclou, Simone P.; Bjerkvig, Rolf; Grützmann, Robert; Aust, Daniela; Hruban, Ralph H.; Maitra, Anirban; Iacobuzio-Donahue, Christine A.; Wolfgang, Christopher L.; Morgan, Richard A.; Lawlor, Rita T.; Corbo, Vincenzo; Bassi, Claudio; Falconi, Massimo; Zamboni, Giuseppe; Tortora, Giampaolo; Tempero, Margaret A.; Gill, Anthony J.; Eshleman, James R.; Pilarsky, Christian; Scarpa, Aldo; Musgrove, Elizabeth A.; Pearson, John V.; Biankin, Andrew V.; Grimmond, Sean M.

2015-01-01

Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded. PMID:25719666

Kas Roger Federer suudab Rafael Nadali alistada ka Pariisis? / Maarja Värv

Index Scriptorium Estoniae

Värv, Maarja

2007-01-01

Prantsusmaa lahtiste tennisemeistrivõistluste eel on paljude jaoks suurim küsimus, kas maailma esinumber Roger Federer suudab lõpuks võita ka Roland Garros' esikoha ning astuda sammu suure slämmi suunas. Vt. samas: Maret Ani põhiturniirile ei pääsenud

Varemed ja aiad : barokk-kirjanduse esteetika Bernard Kangro Tartu-romaanides / Maarja Hollo

Index Scriptorium Estoniae

Hollo, Maarja

2014-01-01

Tuuakse välja barokk-kirjanduse ja Bernard Kangro romaanide olulisemad ühisjooned ning peatutakse Walter Benjamini allegooriakäsitlustel, mille valguses analüüsitakse Tartu-romaanides esinevaid allegoorilisi stseene

Kohalduva õiguse ja selle sisu kindlakstegemine rahvusvahelistes eraõiguslikes vaidlustes / Maarja Torga

Index Scriptorium Estoniae

Torga, Maarja, 1984-

2014-01-01

Ülevaate sellest, kuidas peaks Eesti kohtutes toimuma kohalduva õiguse ning kohalduva välisriigi õiguse sisu kindlakstegemine. Kohalduva õiguse määramist reguleerivate õigusaktide (rahvusvaheliste lepingute, Euroopa Liidu määruste ning riigisiseste õigusaktide) omavahelisest vahekorrast

"mina usun sõna..." : [luuletused] / Maarja Kangro, Mart Kangur, Lauri Kitsnik jt

Index Scriptorium Estoniae

2007-01-01

Sisu: "mina usun sõna..." ; Tüdruk heitis mulle silma (Silmapartii) ; "Helista siis mulle. Hoolimata sellest, mis kell ma täna magama..." ; Tärkab ; Toad ; "Tee sees on augud. Maa sees on augud..." ; "Puuk on perses. Ai-ai, valus on..." ; Päärätik ; Pliidikütt ; "Ukrainlannast põetaja..." ; Stereonurr ; "Luuletused..."

Rein Pill võitis Venemaal kõrgetasemelise võistluse / Maarja Värv

Index Scriptorium Estoniae

Värv, Maarja

2008-01-01

Ratsutaja Rein Pill tegi Venemaal Tsherjahovskis CS14* taseme rahvusvahelistel ratsutamise takistussõiduvõistlustel ajalugu, võites hobusel A Big Boy võistluste Grand Prix' 160 cm kõrgusel parkuuril ja täites seega Euroopa meistrivõistluste kvalifikatsiooninormi

Know-how : loomeinkubaator / Katriin Fisch-Uibopuu, Raul Oreshkin ; interv. Maarja Mänd

Index Scriptorium Estoniae

Fisch-Uibopuu, Katriin

2008-01-01

Tartu linnavalitsuse kultuuriosakonna juhataja R. Oreshkin ja loomemajanduse koordinaator K. Fisch-Uibopuu Tartu loomemajanduskeskuse ning loomeinkubaatori võimalustest, mis hakkavad pakkuma tuge alustavatele loome-ettevõtjatele

Rein Pilli hobusel on hüppamine sisse kodeeritud / Maarja Värv

Index Scriptorium Estoniae

Värv, Maarja

2008-01-01

Tänavusest aastast A Big Boyga ratsutav takistussõitja Rein Pill võitis septembri alguses Venemaal kõrgetasemelise maailmakarikaetapi ning püüab saavutust korrata ka Tallinn International Horse Show'l. Lisa: Takistussõidu grand prix' rajaskeem

Georgi söögituba Väike-Maarjas / Kai Tort, Ilmar Aasumets

Index Scriptorium Estoniae

Tort, Kai

2006-01-01

7 ill.; Georg Lurichi järgi nime saanud söögituba asub arhitekt Alar Kotli vanaisale kuulunud hoones; söögitoa kujunduse tegi Kai Tort, mööbli valmistasid kohalikud puusepad, plekist lambid - Ilmar Aasumets, omanik Avo Part

Kanepi kohtub 17 000 vastasega - publiku ja selle lemmikuga / Maarja Värv

Index Scriptorium Estoniae

Värv, Maarja

2008-01-01

Vt. ka Postimees : na russkom jazõke 13. aug., lk. 9. Kaia Kanepi eelseisvast mängust hiinlanna Na Liga, kes paikneb maailma edetabelis Kanepist viis rida kõrgemal ehk 42. postisioonil. Vt. samas: Tandem Ani - Kanepi langesid juba avaringis

Interaktiivne õpe eeldab kõva tahet / Sonja Merisalo ; intervjueerinud Pirgita-Maarja Hallas

Index Scriptorium Estoniae

Merisalo, Sonja

2009-01-01

Intervjuu soomlanna Sonja Merisaloga, kes lõpetab kevadel Tallinna Ülikooli interaktiivse meedia magistriprogrammi. Tallinna Ülikooli IMKE (interaktiivne meedia ja teadmuskeskkonnad) rahvusvahelisest magistriõppekavast, mille juht on uusmeedia professor Mauri Kaipainen

Kolmepoolne koostöölepe Tehnikaülikooli, OÜ TTÜ Sport ja SEB Ühispanga vahel

Index Scriptorium Estoniae

2006-01-01

Tallinna Tehnikaülikool rektor Peep Sürje, Osaühing TTÜ Sport juhatuse esimees Andres Öpik ja AS SEB Eesti Ühispank juhatuse esimees Mart Altvee allkirjastasid kolmepoolse koostöölepingu, milles nähakse ette ühistegevused TTÜ üliõpilastele õppekavadega seotud äriplaanikonkursi korraldamisel, üliõpilaste sporditegevuse edasiarendamisel ning üliõpilastele osutatud pangateenuste parandamisel

On the Maximum Separation of Visual Binaries M. I. Nouh1,∗ & M. A. ...

Indian Academy of Sciences (India)

Stars, http://www.ad.usno.navy.mil/wds/orb6/orb6.html. Kuiper, G. P. 1935, Publ. Astron. Soc. Pacific., 47(15), 12. Öpik, E. 1924, Publ. Obs. Astro. Univ. Tartu., 25, 6. Press, W. H., Teukolsky, S. A., Vetterling, W. H., Flannery, B.P. 1992, Numerical Recipes. (Cambridge Univ. Press). Reed, B. C. 1984, J. R. Astron. Soc. Can.

Short outlines of books by Estonian authors / Brita Melts, Rutt Hinrikus, Maire Iro and Maret Vaher

Index Scriptorium Estoniae

2013-01-01

Arvustus: Pärtna, Maarja. Läved ja tüved. Tallinn : Eesti Keele Sihtasutus, 2013 ; Sauter, Peeter. Ära jäta mind rahule. Tallinn : P. Sauter, 2012 ; Viiding, Elo. Teised. Tallinn : Tuum, 2012 ; Mathura. Kumalasepäev. Lelle : Allikaäärne, 2012 ; Kadastik, Mart. Kevad saabub sügisel. Tallinn : Varrak, 2013 ; Mutt, Mihkel. Kooparahvas läheb ajalukku. Tallinn : Fabian, 2012 ; Hargla, Indrek. Apteeker Melchior ja Pirita kägistaja. Tallinn : Varrak, 2013 ; Raud, Rein. Rekonstruktsioon. Tallinn : Mustvalge Kirjastus, 2012 ; Toona, Elin. Into exile : a life story of war and peace. Woodsville (N.H.) : Lakeshore Press, 2013 ; Berg, Maimu. Moemaja. Tartu : Petrone Print, 2012 ; Kareva, Doris, Rooste, Jürgen. Elutants. Tallinn : Verb, 2013 ; Ehin, Kristiina. Paleontoloogi päevaraamat. Tartu : Petrone Print, 2013 ; Maria Lee. Stereomeetria. Tallinn : Verb, 2012

The PRIMAP-hist national historical emissions time series

Science.gov (United States)

Gütschow, Johannes; Jeffery, M. Louise; Gieseke, Robert; Gebel, Ronja; Stevens, David; Krapp, Mario; Rocha, Marcia

2016-11-01

To assess the history of greenhouse gas emissions and individual countries' contributions to emissions and climate change, detailed historical data are needed. We combine several published datasets to create a comprehensive set of emissions pathways for each country and Kyoto gas, covering the years 1850 to 2014 with yearly values, for all UNFCCC member states and most non-UNFCCC territories. The sectoral resolution is that of the main IPCC 1996 categories. Additional time series of CO2 are available for energy and industry subsectors. Country-resolved data are combined from different sources and supplemented using year-to-year growth rates from regionally resolved sources and numerical extrapolations to complete the dataset. Regional deforestation emissions are downscaled to country level using estimates of the deforested area obtained from potential vegetation and simulations of agricultural land. In this paper, we discuss the data sources and methods used and present the resulting dataset, including its limitations and uncertainties. The dataset is available from doi:10.5880/PIK.2016.003 and can be viewed on the website accompanying this paper (de/primap-live/primap-hist/" target="_blank">http://www.pik-potsdam.de/primap-live/primap-hist/).

Active PI3K pathway causes an invasive phenotype which can be reversed or promoted by blocking the pathway at divergent nodes.

Directory of Open Access Journals (Sweden)

Jeffrey J Wallin

Full Text Available The PTEN/PI3K pathway is commonly mutated in cancer and therefore represents an attractive target for therapeutic intervention. To investigate the primary phenotypes mediated by increased pathway signaling in a clean, patient-relevant context, an activating PIK3CA mutation (H1047R was knocked-in to an endogenous allele of the MCF10A non-tumorigenic human breast epithelial cell line. Introduction of an endogenously mutated PIK3CA allele resulted in a marked epithelial-mesenchymal transition (EMT and invasive phenotype, compared to isogenic wild-type cells. The invasive phenotype was linked to enhanced PIP(3 production via a S6K-IRS positive feedback mechanism. Moreover, potent and selective inhibitors of PI3K were highly effective in reversing this phenotype, which is optimally revealed in 3-dimensional cell culture. In contrast, inhibition of Akt or mTOR exacerbated the invasive phenotype. Our results suggest that invasion is a core phenotype mediated by increased PTEN/PI3K pathway activity and that therapeutic agents targeting different nodes of the PI3K pathway may have dramatic differences in their ability to reverse or promote cancer metastasis.

Q-balls of quasi-particles in a (2,0)-theory model of the fractional quantum Hall effect

NARCIS (Netherlands)

Ganor, O.J.; Hong, Y.P.; Moore, N.; Sun, H.Y.; Tan, H.S.; Torres-Chicon, N.R.

2015-01-01

A toy model of the fractional quantum Hall effect appears as part of the low-energy description of the Coulomb branch of the A(1) (2, 0)-theory formulated on (S-1 x R-2)/Z(k), where the generator of Z(k) acts as a combination of translation on S-1 and rotation by 2 pi/k on R-2. At low energy the

Composite Biomarkers For Non-invasive Screening, Diagnosis And Prognosis Of Colorectal Cancer

KAUST Repository

Mansour, Hicham; Incitti, Roberto; Bajic, Vladimir B.

2014-01-01

The present invention concerns particular biomarkers for diagnosing and/or prognosticating colorectal cancer, in particular in a non-invasive manner. The methods and compositions concern analysis of methylation patterns of one or more genes from a set of 29 genes identified as described herein. In certain embodiments, the gene set includes at least P15.INK4b, SST, GAS7, CNRIP1, and PIK3CG.

Liigapörssi-pelin verkkopelaamisen työkalu

OpenAIRE

Finning, J. (Jaakko)

2015-01-01

Tiivistelmä Liigapörssin, ja saman valmistajan muiden vastaavien pelien, pelaaminen on suosittu harrastus penkkiurheilijoiden keskuudessa. Pelaaminen sisältää paljon haasteita. Ongelmia aiheuttavat jakson pelilistan läpikäynti, joukkueiden kokoaminen sekä vaihtojen tekeminen. Näitä haasteita kohdataan pelissä päivittäin. Monet yksittäiset pelaajat ovatkin laatineet itselleen alkeellisia tilastoja ja taulukoita, joiden avull...

Composite Biomarkers For Non-invasive Screening, Diagnosis And Prognosis Of Colorectal Cancer

KAUST Repository

Mansour, Hicham

2014-09-11

The present invention concerns particular biomarkers for diagnosing and/or prognosticating colorectal cancer, in particular in a non-invasive manner. The methods and compositions concern analysis of methylation patterns of one or more genes from a set of 29 genes identified as described herein. In certain embodiments, the gene set includes at least P15.INK4b, SST, GAS7, CNRIP1, and PIK3CG.

Distinct molecular features of different macroscopic subtypes of colorectal neoplasms.

Directory of Open Access Journals (Sweden)

Kenichi Konda

Full Text Available Colorectal adenoma develops into cancer with the accumulation of genetic and epigenetic changes. We studied the underlying molecular and clinicopathological features to better understand the heterogeneity of colorectal neoplasms (CRNs.We evaluated both genetic (mutations of KRAS, BRAF, TP53, and PIK3CA, and microsatellite instability [MSI] and epigenetic (methylation status of nine genes or sequences, including the CpG island methylator phenotype [CIMP] markers alterations in 158 CRNs including 56 polypoid neoplasms (PNs, 25 granular type laterally spreading tumors (LST-Gs, 48 non-granular type LSTs (LST-NGs, 19 depressed neoplasms (DNs and 10 small flat-elevated neoplasms (S-FNs on the basis of macroscopic appearance.S-FNs showed few molecular changes except SFRP1 methylation. Significant differences in the frequency of KRAS mutations were observed among subtypes (68% for LST-Gs, 36% for PNs, 16% for DNs and 6% for LST-NGs (P<0.001. By contrast, the frequency of TP53 mutation was higher in DNs than PNs or LST-Gs (32% vs. 5% or 0%, respectively (P<0.007. We also observed significant differences in the frequency of CIMP between LST-Gs and LST-NGs or PNs (32% vs. 6% or 5%, respectively (P<0.005. Moreover, the methylation level of LINE-1 was significantly lower in DNs or LST-Gs than in PNs (58.3% or 60.5% vs. 63.2%, P<0.05. PIK3CA mutations were detected only in LSTs. Finally, multivariate analyses showed that macroscopic morphologies were significantly associated with an increased risk of molecular changes (PN or LST-G for KRAS mutation, odds ratio [OR] 9.11; LST-NG or DN for TP53 mutation, OR 5.30; LST-G for PIK3CA mutation, OR 26.53; LST-G or DN for LINE-1 hypomethylation, OR 3.41.We demonstrated that CRNs could be classified into five macroscopic subtypes according to clinicopathological and molecular differences, suggesting that different mechanisms are involved in the pathogenesis of colorectal tumorigenesis.

Value of preoperative enhanced multi-slice spiral CT scan for judging TNM staging of gastric cancer as well as its relationship with tumor marker and proliferation molecule expression

Directory of Open Access Journals (Sweden)

Ai-Jun Wu

2016-12-01

Full Text Available Objective: To study the value of preoperative enhanced multi-slice spiral CT scan for judging TNM staging of gastric cancer as well as its relationship with tumor marker and proliferation molecule expression. Methods: A total of 135 patients with gastric cancer who received surgical resection in our hospital between May 2012 and October 2015 were selected as the research subjects, preoperative enhanced multi-slice spiral CT scan was conducted to judge TNM staging, and serum was collected to determine the content of tumor markers; tumor tissue was collected after operation to determine the content of cytokines and pro-proliferation molecules. Results: CEA, CA199, CA153, CA125 and CA724 content in serum as well as TGFβ1, TGFβ2, VEGF, FGF2, PTP1B, PIK3CD, Survivin, Ezrin and YAP content in gastric cancer tissue of patients with TNM II, III and IV stage gastric cancer were significantly higher than those of patients with TNM I stage; CEA, CA199, CA153, CA125 and CA724 content in serum as well as TGFβ1, TGFβ2, VEGF, FGF2, PTP1B, PIK3CD, Survivin, Ezrin and YAP content in gastric cancer tissue of patients with TNM III and IV stage gastric cancer were significantly higher than those of patients with TNM II stage; CEA, CA199, CA153, CA125 and CA724 content in serum as well as TGFβ1, TGFβ2, VEGF, FGF2, PTP1B, PIK3CD, Survivin, Ezrin and YAP content in gastric cancer tissue of patients with TNM IV stage gastric cancer were significantly higher than those of patients with TNM III stage. Conclusions: TNM staging of gastric cancer decided by preoperative enhanced multi-slice spiral CT scan has good consistency with the content of tumor markers in serum and proliferation molecules in tumor lesion.

Analysis of molecular markers as predictive factors of lymph node involvement in breast carcinoma.

Science.gov (United States)

Paula, Luciana Marques; De Moraes, Luis Henrique Ferreira; Do Canto, Abaeté Leite; Dos Santos, Laurita; Martin, Airton Abrahão; Rogatto, Silvia Regina; De Azevedo Canevari, Renata

2017-01-01

Nodal status is the most significant independent prognostic factor in breast cancer. Identification of molecular markers would allow stratification of patients who require surgical assessment of lymph nodes from the large numbers of patients for whom this surgical procedure is unnecessary, thus leading to a more accurate prognosis. However, up to now, the reported studies are preliminary and controversial, and although hundreds of markers have been assessed, few of them have been used in clinical practice for treatment or prognosis in breast cancer. The purpose of the present study was to determine whether protein phosphatase Mg2+/Mn2+ dependent 1D, β-1,3-N-acetylglucosaminyltransferase, neural precursor cell expressed, developmentally down-regulated 9, prohibitin, phosphoinositide-3-kinase regulatory subunit 5 (PIK3R5), phosphatidylinositol-5-phosphate 4-kinase type IIα, TRF1-interacting ankyrin-related ADP-ribose polymerase 2, BCL2 associated agonist of cell death, G2 and S-phase expressed 1 and PAX interacting protein 1 genes, described as prognostic markers in breast cancer in a previous microarray study, are also predictors of lymph node involvement in breast carcinoma Reverse transcription-quantitative polymerase chain reaction analysis was performed on primary breast tumor tissues from women with negative lymph node involvement (n=27) compared with primary tumor tissues from women with positive lymph node involvement (n=23), and was also performed on primary tumors and paired lymph node metastases (n=11). For all genes analyzed, only the PIK3R5 gene exhibited differential expression in samples of primary tumors with positive lymph node involvement compared with primary tumors with negative lymph node involvement (P=0.0347). These results demonstrate that the PIK3R5 gene may be considered predictive of lymph node involvement in breast carcinoma. Although the other genes evaluated in the present study have been previously characterized to be involved with

Genomic alterations in neuroendocrine cancers of the ovary.

Science.gov (United States)

Yaghmour, George; Prouet, Philippe; Wiedower, Eric; Jamy, Omer Hassan; Feldman, Rebecca; Chandler, Jason C; Pandey, Manjari; Martin, Mike G

2016-08-26

As we have previously reported, small cell carcinoma of the ovary (SCCO) is a rare, aggressive form of ovarian cancer associated with poor outcomes. In an effort to identify new treatment options, we utilized comprehensive genomic profiling to assess the potential for novel therapies in SCCO. Patients with SCCO, SCCO-HT (hypercalcemic type), neuroendocrine tumors of the ovary (NET-O), and small cell carcinoma of the lung (SCLC) profiled by Caris Life Sciences between 2007-2015 were identified. Tumors were assessed with up to 21 IHC stains, in situ hybridization of cMET, EGFR, HER2 and PIK3CA, and next-generation sequencing (NGS) as well as Sanger sequencing of selected genes. Forty-six patients with SCCO (10 SCCO, 18 SCCO-HT, 18 NET-O) were identified as well as 58 patients with SCLC for comparison. Patients with SCCO and SCCO-HT were younger (median 42 years [range 12-75] and 26 years [range 8-40], respectively) than patients with NET-O 62 [range 13-76] or SCLC 66 [range 36-86]. SCCO patients were more likely to be metastatic (70 %) than SCCO-HT (50 %) or NET-O (33 %) patients, but at a similar rate to SCLC patients (65 %). PD1 expression varied across tumor type with SCCO (100 %), SCCO-HT (60 %), NET-O (33 %) vs SCLC (42 %). PDL1 expression also varied with SCCO (50 %), SCCO-HT (20 %), NET-O (33 %) and SCLC (0 %). No amplifications were identified in cMET, EGFR, or HER2 and only 1 was found in PIK3CA (NET-O). Actionable mutations were rare with 1 patient with SCCO having a BRCA2 mutation and 1 patient with NET-O having a PIK3CA mutation. No other actionable mutations were identified. No recurrent actionable mutations or rearrangements were identified using this platform in SCCO. IHC patterns may help guide the use of chemotherapy in these rare tumors.

Integrated genomic and immunophenotypic classification of pancreatic cancer reveals three distinct subtypes with prognostic/predictive significance.

Science.gov (United States)

Wartenberg, Martin; Cibin, Silvia; Zlobec, Inti; Vassella, Erik; Eppenberger-Castori, Serenella M M; Terracciano, Luigi; Eichmann, Micha; Worni, Mathias; Gloor, Beat; Perren, Aurel; Karamitopoulou, Eva

2018-04-16

Current clinical classification of pancreatic ductal adenocarcinoma (PDAC) is unable to predict prognosis or response to chemo- or immunotherapy and does not take into account the host reaction to PDAC-cells. Our aim is to classify PDAC according to host- and tumor-related factors into clinically/biologically relevant subtypes by integrating molecular and microenvironmental findings. A well-characterized PDAC-cohort (n=110) underwent next-generation sequencing with a hotspot cancer panel, while Next-generation Tissue-Microarrays were immunostained for CD3, CD4, CD8, CD20, PD-L1, p63, hyaluronan-mediated motility receptor (RHAMM) and DNA mismatch-repair proteins. Previous data on FOXP3 were integrated. Immune-cell counts and protein expression were correlated with tumor-derived driver mutations, clinicopathologic features (TNM 8. 2017), survival and epithelial-mesenchymal-transition (EMT)-like tumor budding.  Results: Three PDAC-subtypes were identified: the "immune-escape" (54%), poor in T- and B-cells and enriched in FOXP3+Tregs, with high-grade budding, frequent CDKN2A- , SMAD4- and PIK3CA-mutations and poor outcome; the "immune-rich" (35%), rich in T- and B-cells and poorer in FOXP3+Tregs, with infrequent budding, lower CDKN2A- and PIK3CA-mutation rate and better outcome and a subpopulation with tertiary lymphoid tissue (TLT), mutations in DNA damage response genes (STK11, ATM) and the best outcome; and the "immune-exhausted" (11%) with immunogenic microenvironment and two subpopulations: one with PD-L1-expression and high PIK3CA-mutation rate and a microsatellite-unstable subpopulation with high prevalence of JAK3-mutations. The combination of low budding, low stromal FOXP3-counts, presence of TLTs and absence of CDKN2A-mutations confers significant survival advantage in PDAC-patients. Immune host responses correlate with tumor characteristics leading to morphologically recognizable PDAC-subtypes with prognostic/predictive significance. Copyright ©2018

Indrek Kasela, Hamlet ärimaailmas / Indrek Kasela ; intervjueerinud Priit Pullerits ; kommenteerinud Maarja Neilvelt

Index Scriptorium Estoniae

Kasela, Indrek, 1971-

2010-01-01

Ettevõtja, kino Sõprus taasavaja ning Premia börsile viija Indrek Kasela oma tegevusest fondihaldurina, New Yorgi ülikoolis saadud kogemustest, Eesti ühiskonnakorralduses vaja minevatest muutustest

Võlaõiguslike õiguskaitsevahendite kohaldamine au teotamisel sotsiaalmeedias Facebooki näide / Maarja Pild

Index Scriptorium Estoniae

Pild, Maarja, 1991-

2016-01-01

Uue meedia mõistest ja sotsiaalmeediast. Erisustest võlaõiguslike õiguskaitsevahendite kohaldamisel sotsiaalvõrgustiku au teotamise vaidlustes. Sotsiaalvõrgustiku kasutaja faktiväite või väärtushinnangu avaldamise teost, selle õigusvastasuse määramisest. Sisaldab asjakohast kohtupraktikat

Radioisotope dust pollution monitor

International Nuclear Information System (INIS)

Szepke, R.; Harasimczuk, J.; Dobrowiecki, J.

1990-01-01

Measuring principles and specification of two dust monitors: station-type AMIZ and portable-type PIK-10 for ambient air pollution are presented. The first one, a fully automatic instrument is destined for permanent monitoring of air pollution in preset sampling time from .25 to 24 hours. The second one was developed as a portable working model. Both instruments display their results in digital form in dust concentration units. (author)

Paneeldiskussioon (fonogrammilt lühendatult) / Ain Heinaru, Rein Vaikmäe, Rein Raud, Hardi Tullus, Urve Lippus, Andres Tali, Martin Zobel

Index Scriptorium Estoniae

2006-01-01

Projekti "Eesti doktoriõppe kvaliteedi, tulemuslikkuse ja jätkusuutlikkuse tagamise süsteem" (2005-2008) II konverentsi "Doktorid Eesti tuleviku arengumootoriks" paneeldiskussioonist, millel arutleti doktoriõppe rahastamise ning doktoriõppe korralduse ja doktorandi juhendamise teemadel

The estimation of production rates of $\\pi^+K^-, \\pi^-K^+$ and $\\pi^+\\pi^-$ atoms in proton-Ni interactions at proton momentum of 450 GeV/c

CERN Document Server

Gorchakov, O

2015-01-01

In the DIRAC experiment at CERN the π+ K− , K+ π− and π+ π− atoms generated in proton-nucleus interaction at proton momentum Pp = 24 GeV/c were investigated. This work shows that the yields of π+ K− , K+ π− and π+ π− atoms in the p-nucleus interactions at Pp = 450 GeV/c and θ lab = 4◦ are 17, 38 and 16 times more than the one in the DIRAC experiment. The increased yields of the short-lived ππ ( πK ) atoms with minimum lifetime τ th = 2.9 . 10 − 15 s ( τ th = 3.5 . 10 − 15 s ) allows to improve the precisions of their lifetime measurement and ππ ( πK ) scattering length combinations | a 0 − a 2 | ( | a 1 / 2 − a 3/2 | ). In the DIRAC experiment the long-lived ππ atoms( τ th ≥ 1.2 . 10 − 11 s) were observed also. It was detected n A = 436 ± 61 π + π − pairs(atomic pairs) originating in the breakup of long-lived ππ atoms in the Pt foil with probability more than 90%. After the change of experiment scheme the number of produced long-lived π+ π− , π+ K− a...

INFLUENCE OF EUROPEAN CORN BORER (Ostrinia nubilalis Hübner ON CORN HYBRIDS IN NORTH-WEST AND EASTERN CROATIA

Directory of Open Access Journals (Sweden)

Zvjezdana Augustinović

2005-12-01

Full Text Available European corn borer (Ostrinia nubilalis Hubner is one of the major corn pest in the world and in Croatia. Former investigations of corn borer in Croatia covered mostly its Eastern region. In trials conducted in 1998 and 1999 the research was extended to the North Western part of Croatia too. Macro trials were carried out with corn hybrids of FAO groups 200-600 at three localities: Križevci, Agricultural institute Osijek and at «Belje» PIK Karanac. In 1998 the intensity of the corn borer attack at the locality of «Belje» PIK Karanac was about 37.92% and in Agricultural institute Osijek 80.83%. In 1999 it varied between 37.08% at the locality of Agricultural Institute Osijek and 71.20% at the locality in Križevci. The estimated number of holes per plant in all three localities in both years was higher than the number of caterpillars. Length of damage per plant was between 0.38 and 18.80 cm. The data showed significant differences in the intensity of damaging effects on different localities while no significant differences concerning various hybrids were found. The statistical data concerning yield in both years showed significant differences among hybrids, localities and their interactions.

MOLEKÜLER CIMBIZLAMAYA DAYALI YENİ BİR BISFENOL-BIPHENANTHROLINE SENTEZİ

Directory of Open Access Journals (Sweden)

Said nadeem

2015-11-01

Full Text Available 1,10-fenantrolin’den elde edilen "dugdugi" 8 molekülü sentezlendi ve NMR, EIMS ve UV kullanılarak yapısı aydınlatıldı. Bisfenol 8’I elde etmek için 1,3dibrompropan kullanılarak alkillendi ve 4-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-ylphenol ile reaksiyona sokuldu. Molekül 8’in 30 molL-1 çözeltisi %10 DMF içeren etanolde hazırlandı, ve etanol ile hazırlanmış 30 m L-1 Co2+, Cr3+, Cu2+, Fe3+, Mn2+, Ni2+, Ag+, and Zn2+ çözeltisi ile 30 dakika karıştırıldı.Kemosensör 8, Fe3+ varlığında pembe renk vererek çalışırken, diğer metallerin varlığında ayırt edici bir renk gözlenmedi. "Dugdugi" nin moleküler UV spektrumunda 279 nm’de bulunan pik Fe3+ ile etkileştirilince 290 nm’ye kaydı. Ayrıca, 524 nm’de yeni bir pik oluştuğu görüldü

Targeting the PI3K signaling pathway in KRAS mutant colon cancer

International Nuclear Information System (INIS)

Hong, Suntaek; Kim, SoYoung; Kim, Hye Youn; Kang, Myunghee; Jang, Ho Hee; Lee, Won-Suk

2015-01-01

Metastatic colorectal cancer (CRC) patients with v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations are resistant to monoclonal antibody that targets the epidermal growth factor receptor such as cetuximab. BKM120 targets phosphatidylinositide-3-kinase (PIK3CA), but it is unknown whether BKM120 can reverse cetuximab resistance in KRAS mutant CRC. Human CRC cell lines with KRAS mutations (DLD-1, HCT116, and LoVo) were used to test the effect of cetuximab, BKM120, and cetuximab plus BKM120 on cell proliferation in vitro and in vivo. BKM120 reduced cell proliferation in a concentration-dependent manner in the LoVo (PI3KCA wild type) as well as the HCT116 and DLD1 cells (that carry a PI3KCA mutation). BKM120 only inhibited ERK phosphorylation in LoVo cells (PIK3CA wild type), but not in DLD1 or HCT116 cells at a concentration of 1 μmol/L. Treatment with cetuximab and BKM120 significantly reduced the growth of xenograft tumors originating from KRAS mutant cells compared with cetuximab alone (P = 0.034). BKM120 may overcome cetuximab resistance in colon cancer cells with KRAS mutation

MDM2 Amplification and PI3KCA Mutation in a Case of Sclerosing Rhabdomyosarcoma

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Ken Kikuchi

2013-01-01

Full Text Available A rare sclerosing variant of rhabdomyosarcoma characterized by prominent hyalinization and pseudovascular pattern has recently been described as a subtype biologically distinct from embryonal, alveolar, and pleomorphic forms. We present cytogenetic and molecular findings as well as experimental studies of an unusual case of sclerosing rhabdomyosarcoma. The primary lesion arose within the plantar subcutaneous tissue of the left foot of an otherwise healthy 23-year-old male who eventually developed pulmonary nodules despite systemic chemotherapy. Two genetic abnormalities identified in surgical and/or autopsy samples of the tumor were introduced into 10T1/2 murine fibroblasts to determine whether these genetic changes cooperatively facilitated transformation and growth. Cytogenetic analysis revealed a complex abnormal hyperdiploid clone, and MDM2 gene amplification was confirmed by fluorescence in situ hybridization. Cancer gene mutation screening using a combination of multiplexed PCR and mass spectroscopy revealed a PIK3CA exon 20 H1047R mutation in the primary tumor, lung metastasis, and liver metastasis. However, this mutation was not cooperative with MDM2 overexpression in experimental assays for transformation or growth. Nevertheless, MDM2 and PIK3CA are genes worthy of further investigation in patients with sclerosing rhabdomyosarcoma and might be considered in the enrollment of these patients into clinical trials of targeted therapeutics.

Activation of the PI3K/AKT pathway in Merkel cell carcinoma.

Directory of Open Access Journals (Sweden)

Christian Hafner

Full Text Available Merkel cell carcinoma (MCC is a highly aggressive skin cancer with an increasing incidence. The understanding of the molecular carcinogenesis of MCC is limited. Here, we scrutinized the PI3K/AKT pathway, one of the major pathways activated in human cancer, in MCC. Immunohistochemical analysis of 41 tumor tissues and 9 MCC cell lines revealed high levels of AKT phosphorylation at threonine 308 in 88% of samples. Notably, the AKT phosphorylation was not correlated with the presence or absence of the Merkel cell polyoma virus (MCV. Accordingly, knock-down of the large and small T antigen by shRNA in MCV positive MCC cells did not affect phosphorylation of AKT. We also analyzed 46 MCC samples for activating PIK3CA and AKT1 mutations. Oncogenic PIK3CA mutations were found in 2/46 (4% MCCs whereas mutations in exon 4 of AKT1 were absent. MCC cell lines demonstrated a high sensitivity towards the PI3K inhibitor LY-294002. This finding together with our observation that the PI3K/AKT pathway is activated in the majority of human MCCs identifies PI3K/AKT as a potential new therapeutic target for MCC patients.

Cell of Origin and Cancer Stem Cell Phenotype in Medulloblastomas

Science.gov (United States)

2015-07-01

medulloblastoma by activating N1ICD and PIK3CA in cerebellar NSCs and NPCs in the developing mouse brain. N1ICD models : We previously published...Aims: 1. Validate general applicability and clinical potential of SP66 as a theragnostic agent by measuring tumor uptake in PDX GBM models and a...spontaneous mouse medulloblastoma model ; 2. Evaluate the therapeutic potential of SP66 in vitro and in vivo. Overlap: None Contracting/ Grants

Recolonization of laser-ablated bacterial biofilm.

Science.gov (United States)

Nandakumar, Kanavillil; Obika, Hideki; Utsumi, Akihiro; Toshihiko, Ooie; Yano, Tetsuo

2004-01-20

The recolonization of laser-ablated bacterial monoculture biofilm was studied in the laboratory by using a flow-cytometer system. The marine biofilm-forming bacterium Pseudoalteromonas carrageenovora was used to develop biofilms on titanium coupons. Upon exposure to a low-power pulsed irradiation from an Nd:YAG laser, the coupons with biofilm were significantly reduced both in terms of total viable count (TVC) and area cover. The energy density used for a pulse of 5 ns was 0.1 J/cm(2) and the durations of irradiation exposure were 5 and 10 min. When placed in a flow of dilute ZoBell marine broth medium (10%) the laser-destructed bacterial film in a flow-cytometer showed significant recovery over a period of time. The flow of medium was regulated at 3.2 ml/min. The increase in area cover and TVC, however, was significantly less than that observed for nonirradiated control (t-test, Precolonization compared to control was thought be due to the lethal and sublethal impacts of laser irradiation on bacteria. This observation thus provided data on the online recolonization speed of biofilm, which is important when considering pulsed laser irradiation as an ablating technique of biofilm formation and removal in natural systems. Copyright 2003 Wiley Periodicals, Inc.

"Tere! Head teatripäeva!" : Rakveres jagati auhindu mulluste teatriteenete eest / Verni Leivak

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Leivak, Verni, 1966-

2009-01-01

Rakvere Teatris toimunud teatriauhindade jagamisest. Lisatud aastaauhindade laureaadid - Tiit Ojasoo ja Ene-Liis Semper parim lavastus ("Ruja"), Lembit Peterson - lavastaja auhind ("Maarja kuulutamine" ja "Linn"), Maria Peterson ja Laura Peterson - naisnäitleja auhind, Marius Peterson - meesnäitleja auhind, Piret Laurimaa - naiskõrvalosa auhind, Rain Simmul - meeskõrvalosa auhind, Liisi Eelmaa - kunstniku auhind, Ain Saviauk - žürii eriauhind, Valle-Sten Maiste - Reet Neimari kriitikaauhind, Arvo Volmer - muusikalavastuse auhind, Eve Andre - balletilavastuse auhind, Jaan Undusk - algupärase dramaturgia auhind, Marius Peterson - sõnalavastuse muusikalise kujunduse auhind, Tiina Tauraite ja Margus Prangel - Ants Lauteri auhind, Lembit Peterson - Priit Põldroosi auhind, Mart Madiste - Georg Otsa auhind, Sigrid Orusaar - Otto Hermanni auhind, Tiit Härm - Rahel Olbrei auhind, Ene-Liis Semper - Natalie Mei auhind, Jevgeni Ibragimov - Salme Reegi auhind, Margus Alver - Aleksander Kurtna auhind, Toomas Suuman - Karl Adra auhind, Sten Karpov ja Uku Uusberg - Kristallkingakese auhind

Mitmekülgne eesti lastekirjandus [2006. a.] / Jaanika Palm

Index Scriptorium Estoniae

Palm, Jaanika, 1973-

2008-01-01

Arvustus: Tungal, Leelo. Lätikeelne jäätis ja teisi luuletusi. Tallinn : Tuum, 2006 ; Trull, Ilmar. Musta kassi mumba. Tallinn : Eesti Ekspressi Kirjastus, 2006 ; Wimberg. Põngerjate laulud. Tallinn : Varrak, 2006 ; Muidugi, Eino. Lõbus pere ütleb tere! Tallinn : Koolibri, 2006 ; Nemvalts, Urmas. Väikeste meeste jutud. [Tallinn] : Grenader, 2006 ; Kangro, Maarja, Kangro, Kirke. Puuviljadraakon. Tallinn : Koolibri, 2006 ; Kilkson, Tiina. Pisikese Peetri pikk pühapäev. Tallinn : Koolibri, 2006 ; Pelmas, Elsa. Sussipäkapikk Siisi seiklused. Tallinn : TEA Kirjastus, 2006 ; Sauter, Peeter. Laiskade laste raamat. Tallinn : Huma, 2006 ; Kivirähk, Andrus. Leiutajateküla Lotte. Tallinn : Eesti Joonisfilm, 2006 ; Ulman, Mihkel. Nukkude teater. Tartu : Elmatar, 2006 ; Rannap, Jaan. Roheline kindlus. Tallinn : Tiritamm, 2006 ; Vallik, Aidi. Narkohollo ehk Florose vabastamine. Haapsalu : Lugu-Loo, 2006 ; Leesalu, Diana. Mängult on päriselt. Tallinn : Tänapäev, 2006 ; Laidla, Siiri. Pärnaõietee. Tallinn : Canopus, 2006

Mitmekülgne eesti lastekirjandus [2006. a.] / Jaanika Palm

Index Scriptorium Estoniae

Palm, Jaanika, 1973-

2007-01-01

Arvustus: Tungal, Leelo. Lätikeelne jäätis ja teisi luuletusi. Tallinn : Tuum, 2006 ; Trull, Ilmar. Musta kassi mumba. Tallinn : Eesti Ekspressi Kirjastus, 2006 ; Wimberg. Põngerjate laulud. Tallinn : Varrak, 2006 ; Muidugi, Eino. Lõbus pere ütleb tere! Tallinn : Koolibri, 2006 ; Nemvalts, Urmas. Väikeste meeste jutud. [Tallinn] : Grenader, 2006 ; Kangro, Maarja, Kangro, Kirke. Puuviljadraakon. Tallinn : Koolibri, 2006 ; Kilkson, Tiina. Pisikese Peetri pikk pühapäev. Tallinn : Koolibri, 2006 ; Pelmas, Elsa. Sussipäkapikk Siisi seiklused. Tallinn : TEA Kirjastus, 2006 ; Sauter, Peeter. Laiskade laste raamat. Tallinn : Huma, 2006 ; Kivirähk, Andrus. Leiutajateküla Lotte. Tallinn : Eesti Joonisfilm, 2006 ; Ulman, Mihkel. Nukkude teater. Tartu : Elmatar, 2006 ; Rannap, Jaan. Roheline kindlus. Tallinn : Tiritamm, 2006 ; Vallik, Aidi. Narkohollo ehk Florose vabastamine. Haapsalu : Lugu-Loo, 2006 ; Leesalu, Diana. Mängult on päriselt. Tallinn : Tänapäev, 2006 ; Laidla, Siiri. Pärnaõietee. Tallinn : Canopus, 2006

Tunnustame tõenduspõhise õendusabi edendajaid / Ester Öpik, Ilme Aro

Index Scriptorium Estoniae

Öpik, Ester

2014-01-01

Tunnustati meditsiiniõdesid Tiina Freimanni, Reet Urbanit, Marika Asbergi, Tiina Tõemetsa, Kersti Viitkarit ja Ireen Bruusi Eesti Õdede Liidu poolt 2011. aastani kaitstud õendusteaduslike uurimistööde eest

TU-CD-BRB-07: Identification of Associations Between Radiologist-Annotated Imaging Features and Genomic Alterations in Breast Invasive Carcinoma, a TCGA Phenotype Research Group Study

Energy Technology Data Exchange (ETDEWEB)

Rao, A; Net, J [University of Miami, Miami, Florida (United States); Brandt, K [Mayo Clinic, Rochester, Minnesota (United States); Huang, E [National Cancer Institute, NIH, Bethesda, MD (United States); Freymann, J; Kirby, J [Leidos Biomedical Research Inc., Frederick, MD (United States); Burnside, E [University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin (United States); Morris, E; Sutton, E [Memorial Sloan Kettering Cancer Center, New York, NY (United States); Bonaccio, E [Roswell Park Cancer Institute, Buffalo, NY (United States); Giger, M; Jaffe, C [Univ Chicago, Chicago, IL (United States); Ganott, M; Zuley, M [University of Pittsburgh Medical Center - Magee Womens Hospital, Pittsburgh, Pennsylvania (United States); Le-Petross, H [MD Anderson Cancer Center, Houston, TX (United States); Dogan, B [UT MDACC, Houston, TX (United States); Whitman, G [UTMDACC, Houston, TX (United States)

2015-06-15

Purpose: To determine associations between radiologist-annotated MRI features and genomic measurements in breast invasive carcinoma (BRCA) from the Cancer Genome Atlas (TCGA). Methods: 98 TCGA patients with BRCA were assessed by a panel of radiologists (TCGA Breast Phenotype Research Group) based on a variety of mass and non-mass features according to the Breast Imaging Reporting and Data System (BI-RADS). Batch corrected gene expression data was obtained from the TCGA Data Portal. The Kruskal-Wallis test was used to assess correlations between categorical image features and tumor-derived genomic features (such as gene pathway activity, copy number and mutation characteristics). Image-derived features were also correlated with estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/neu) status. Multiple hypothesis correction was done using Benjamini-Hochberg FDR. Associations at an FDR of 0.1 were selected for interpretation. Results: ER status was associated with rim enhancement and peritumoral edema. PR status was associated with internal enhancement. Several components of the PI3K/Akt pathway were associated with rim enhancement as well as heterogeneity. In addition, several components of cell cycle regulation and cell division were associated with imaging characteristics.TP53 and GATA3 mutations were associated with lesion size. MRI features associated with TP53 mutation status were rim enhancement and peritumoral edema. Rim enhancement was associated with activity of RB1, PIK3R1, MAP3K1, AKT1,PI3K, and PIK3CA. Margin status was associated with HIF1A/ARNT, Ras/ GTP/PI3K, KRAS, and GADD45A. Axillary lymphadenopathy was associated with RB1 and BCL2L1. Peritumoral edema was associated with Aurora A/GADD45A, BCL2L1, CCNE1, and FOXA1. Heterogeneous internal nonmass enhancement was associated with EGFR, PI3K, AKT1, HF/MET, and EGFR/Erbb4/neuregulin 1. Diffuse nonmass enhancement was associated with HGF/MET/MUC20/SHIP

Stream Lifetimes Against Planetary Encounters

Science.gov (United States)

Valsecchi, G. B.; Lega, E.; Froeschle, Cl.

2011-01-01

We study, both analytically and numerically, the perturbation induced by an encounter with a planet on a meteoroid stream. Our analytical tool is the extension of pik s theory of close encounters, that we apply to streams described by geocentric variables. The resulting formulae are used to compute the rate at which a stream is dispersed by planetary encounters into the sporadic background. We have verified the accuracy of the analytical model using a numerical test.

Streso problema įvairiose ugdymo įstaigose

OpenAIRE

Charašauskienė, Vaiva

2006-01-01

Place of writing the study: Lithuanian university of agriculture. Institute of rural culture. Academy. 2006 years. Volume of work:57 pages There are:3 tables, 14 pictures, 5 appendices Bibliography:39 publications Object of research: Stress experienced by the the people at work in educational institutions Methods of research: 1. The analysis of bibliography. 2. The questionnaire about stress at work taken from J.Pikūnas, A.Palujanskienė‘s book „Stresas“ (2005), page...

Eesti ekspositsioon "Gaasitoru" Veneetsia XI arhitektuuribiennaalil / Maarja Kask, Ralf Lõoke, Neeme Külm...[jt.

Index Scriptorium Estoniae

2009-01-01

Ill.: situatsiooniplaan, 3 vaadet; fotod: Reio Avaste; autorid: M. Kask, R. Lõoke (Salto), N. Külm, kuraator: I. Ruudi, komissar: L. Põdra. Eesti Kultuurkapitali peapreemia ja arhitektuuri sihtkapitali aastapreemia 2008 pälvisid M. Kask, R. Lõoke, N. Külm ja I. Ruudi

Hagi tagamine ja esialgne õiguskaitse tsiviilasjades: rahvusvaheline mõõde / Gea Lepik, Maarja Torga

Index Scriptorium Estoniae

Lepik, Gea, 1989-

2013-01-01

Kaitsemeetmete kohaldamine Eesti kohtute poolt välisriigis asuva vara või isikute suhtes. Kaitsemeetmed seoses välisriigis toimuva kohtumenetlusega. Välisriigi kohtute kohaldatud kaitsemeetmete Eestis tunnustamine ja täidetavaks tunnistamine

Äri- ja ettevõtluskeeldude piiriülene mõju / Maarja Torga, Juhan Sarv

Index Scriptorium Estoniae

Torga, Maarja, 1984-

2017-01-01

Eestis kohaldatud äri- ja ettevõtluskeeldude piiriülesest mõjust ning välisriigis kohaldatud äri- ja ettevõtluskeelu mõjust Eestis. Äri- ja ettevõtluskeeldude piiriülesest tsiviilõiguslikust ja karistusõiguslikust mõjust. Sisaldab asjakohast kohtupraktikat

Kuhu kadus antropoloogia? : ehk vajadus "inimloomuse" järele / Maurice Bloch ; tlk. Maarja Kaaristo

Index Scriptorium Estoniae

Bloch, Maurice

2007-01-01

Antropoloogia kui distsipliini akadeemilisest ajaloost, sotsiaal- ja kultuuriantropoloogia hariduse puudujääkidest. Antropoloogia põhilistest uurimisteemadest ja uurimisteooriatest: difusionismist, evolutsionismist ning funktsionalismist

mTOR inhibition elicits a dramatic response in PI3K-dependent colon cancers.

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Dustin A Deming

Full Text Available The phosphatidylinositide-3-kinase (PI3K signaling pathway is critical for multiple cellular functions including metabolism, proliferation, angiogenesis, and apoptosis, and is the most commonly altered pathway in human cancers. Recently, we developed a novel mouse model of colon cancer in which tumors are initiated by a dominant active PI3K (FC PIK3ca. The cancers in these mice are moderately differentiated invasive mucinous adenocarcinomas of the proximal colon that develop by 50 days of age. Interestingly, these cancers form without a benign intermediary or aberrant WNT signaling, indicating a non-canonical mechanism of tumorigenesis. Since these tumors are dependent upon the PI3K pathway, we investigated the potential for tumor response by the targeting of this pathway with rapamycin, an mTOR inhibitor. A cohort of FC PIK3ca mice were treated with rapamycin at a dose of 6 mg/kg/day or placebo for 14 days. FDG dual hybrid PET/CT imaging demonstrated a dramatic tumor response in the rapamycin arm and this was confirmed on necropsy. The tumor tissue remaining after treatment with rapamycin demonstrated increased pERK1/2 or persistent phosphorylated ribosomal protein S6 (pS6, indicating potential resistance mechanisms. This unique model will further our understanding of human disease and facilitate the development of therapeutics through pharmacologic screening and biomarker identification.

Combined targeting of BRAF and CRAF or BRAF and PI3K effector pathways is required for efficacy in NRAS mutant tumors.

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Bijay S Jaiswal

Full Text Available BACKGROUND: Oncogenic RAS is a highly validated cancer target. Attempts at targeting RAS directly have so far not succeeded in the clinic. Understanding downstream RAS-effectors that mediate oncogenesis in a RAS mutant setting will help tailor treatments that use RAS-effector inhibitors either alone or in combination to target RAS-driven tumors. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we have investigated the sufficiency of targeting RAS-effectors, RAF, MEK and PI3-Kinase either alone or in combination in RAS mutant lines, using an inducible shRNA in vivo mouse model system. We find that in colon cancer cells harboring a KRAS(G13D mutant allele, knocking down KRAS alone or the RAFs in combination or the RAF effectors, MEK1 and MEK2, together is effective in delaying tumor growth in vivo. In melanoma cells harboring an NRAS(Q61L or NRAS(Q61K mutant allele, we find that targeting NRAS alone or both BRAF and CRAF in combination or both BRAF and PIK3CA together showed efficacy. CONCLUSION/SIGNIFICANCE: Our data indicates that targeting oncogenic NRAS-driven melanomas require decrease in both pERK and pAKT downstream of RAS-effectors for efficacy. This can be achieved by either targeting both BRAF and CRAF or BRAF and PIK3CA simultaneously in NRAS mutant tumor cells.

Maternal and fetal genomes interplay through phosphoinositol 3-kinase(PI3K)-p110α signaling to modify placental resource allocation

Science.gov (United States)

Sferruzzi-Perri, Amanda N.; López-Tello, Jorge; Fowden, Abigail L.; Constancia, Miguel

2016-01-01

Pregnancy success and life-long health depend on a cooperative interaction between the mother and the fetus in the allocation of resources. As the site of materno-fetal nutrient transfer, the placenta is central to this interplay; however, the relative importance of the maternal versus fetal genotypes in modifying the allocation of resources to the fetus is unknown. Using genetic inactivation of the growth and metabolism regulator, Pik3ca (encoding PIK3CA also known as p110α, α/+), we examined the interplay between the maternal genome and the fetal genome on placental phenotype in litters of mixed genotype generated through reciprocal crosses of WT and α/+ mice. We demonstrate that placental growth and structure were impaired and associated with reduced growth of α/+ fetuses. Despite its defective development, the α/+ placenta adapted functionally to increase the supply of maternal glucose and amino acid to the fetus. The specific nature of these changes, however, depended on whether the mother was α/+ or WT and related to alterations in endocrine and metabolic profile induced by maternal p110α deficiency. Our findings thus show that the maternal genotype and environment programs placental growth and function and identify the placenta as critical in integrating both intrinsic and extrinsic signals governing materno-fetal resource allocation. PMID:27621448

Modeling of transports of water and matter in landscape. Proceedings; Modellierung des Wasser- und Stofftransportes in grossen Einzugsgebieten. Beitraege

Energy Technology Data Exchange (ETDEWEB)

Bronstert, A.; Krysanova, V.; Schroeder, A.; Becker, A.; Bork, H.R. [eds.

1998-04-01

During recent years, the quantitative description of the water fluxes and the coupled transport of physical and chemical matter in the landscape has become steadily more and more important. The reasons for this are an increasing public awareness about the possible impacts of changes of land use, land cover, and of changes in regional and global climatic conditions together with a need for sound, multi-objective management of large river basins. The investigation areas of concern a usually much larger in extent than a typically sized hydrological investigation catchment. The tools primarily used in the quantification of the hydrological fluxes at the large scale are the so-called large-scale hydrological models. These models are comparatively new and still at the stage of development and improvement. The mentioned need for advanced large-scale hydrological models provided the reason for inviting scientists from German-speaking countries with experience in large-scale hydrological and hydro-meteorological models to exchange and discuss their modelling concepts and to identify research needs. The workshop was held at the Potsdam Institute for Climate Impact Research (PIK) on 15 and 16 December 1997, and was jointly organised by PIK, the University of Potsdam and the Centre for Agriculture and Land Use Research (ZALF). The workshop was attended by over 40 scientists, of whom 19 gave a presentation. (orig.)

Vikergallup : Eesti kirjandus 2006

Index Scriptorium Estoniae

2007-01-01

19 arvustaja vastus küsimusele, milline oli 2006. aasta parim uudisraamat ja debüütteos. Ära nimetati Hasso Krulli luulekogu "Talv", Jan Kausi romaan "Tema", Madis Kõivu "Näidendid I", Jaan Pehki luulekogu "Tuigu kui tuled", Tarmo Tedre romaan "Onanistid", Kristiina Ehini romaan "Pillipuhujanaine ja pommipanijanaine", Marko Kompuse luulekogu "Vallaliste jõgede tõkkejooksja", Mathura luulekogu "Kohalolu", Rein Põdra romaan "Eike", Indrek Ryytle luulekogu "Inglid rokijaamas", Triin Soometsa "Väljas" ja Ervin Õunapuu romaan "Meie igapäevane jää". Debüütteostest mainiti Kaupo Meieli luulekogu "Polügrafisti käsiraamat", Anti Saare romaani "Kuidas sa ära läksid ja mina maha jäin", Andra Teede luulekogu "Takso Tallinna taevas", Maarja Kangro luulekogu "Kurat õrnal lumel", Andrus Elbingu luulekogu "Siin Beebilõust, tere!", Tiina Ilvese juturaamat "Augustihambad", Indrek Koffi luulekogu "Vana laul", Eliina Kortsu luulekogu "Lööklaused murravad metsi", Carolina Pihelga luulekogu "Sõrmemuster" ja Paavo Piigi luulekogu "Kummuli linnad"

Vikergallup : eesti kirjandus 2008 / Peeter Helme, Ott Kilusk, Igor Kotjuh... [jt.

Index Scriptorium Estoniae

2009-01-01

21 arvustaja vastus küsimusele, milline oli 2008. aasta parim uudisteos ja debüüt. Ära nimetati fs-i luulekogu "Alasti ja elus", Andrei Hvostovi proosaraamatut "Võõrad lood", Maarja Kangro luulekogu "Heureka", Kalju Kruusa luulekogu "Pilvedgi mindgi liigutavadgi", Asko Künnapi luulekogu "Su ööd on loetud", Elo Viidingu proosaraamatut "Püha Maama", Mart Juure luulekogu "Pane Eesti peale tagasi", Jaan Kaplisnki luulekogu "Teiselpool järve", Mart Kivastiku proosaraamatut "Kurb raamat", Leo Kunnase romaani "Gort Ashryn I", Andres Langemetsa luulekogu "Vooder", Erkki Luugi "Valitud luuletusi", Rein Põdra romaani "Juba olnud", Rein Raua lühiromaani "Vend" ja Jaan Tangsoo romaani "Méduse'i parv". Parima debüüdina mainiti Andrus Kasemaa luulekogu "Poeedirahu", Barthol Lo Mejori proosaraamatut "Popdada" ja Chaneldiori proosaraamatut "Kontrolli alt väljas", Lauri Saatpalu laulutekstiraamatut "Nähtused ja tehtused", Tamur Kusnetsi romaani "Hundipäikese aeg" ja Jaanika Merilo luulekogu "Rütmist väljas"

Cytotoxicity and Phytochemical Profiling of Sargassum Sp. Extract As Anti-Mdr Bacteria

Science.gov (United States)

Setyati, Wilis A.; Pramesti, Rini; Zainuddin, Muhamad; Puspita, Maya; Renta, Person P.

2018-02-01

Sargassum sp. contains bioactive compounds having the potential as an antibacterial agent. Sargassum sp. was collected from five different locations, i.e., Teluk Awur, Panjang Island, Bandengan, Ujung Piring, and Bondo. There were several different species of Sargassum sp. identified from each sampling locations. The collected seaweeds were washed, naturally dried, and ground to the powder-sized dry material. Dry seaweed was extracted gradually using n-hexane, ethyl acetate, and methanol (1:3 w/v). The antibacterial analysis was conducted based on Agar Diffusion method using Zobell as media. Resistance analysis was performed to evaluate the resistance of pathogen against commercial antibiotics, namely, chloramphenicol, ampicillin, erythromycin, amoxycillin, and tetracycline. Each Sargassum sp. extract was tested against three candidates of MDR bacteria, i.e., Staphylococcus aureus, Escherichia coli, and S. epidermidis. Results showed that S. aureus was resistant towards four out of five commercial antibiotics. E. coli and S. epidermidis were not susceptible to two and three out of five commercial antibiotics, respectively. N-hexane, ethyl acetate and methanol yielded 0.1-0.3%, 0.3-0.7 % and 0.8-4.7% of dry extract. Ethyl acetate extract of Sargassum from Teluk Awur performed the best antibacterial activity and contained an alkaloid, flavonoid, and phenolic compounds. Toxicity analysis showed that this ethyl acetate extract had LC50 at 463 ppm and categorized as chronic toxicity.

Synkkä turismi : Kärsimyksen aakkoset

OpenAIRE

Tahvanainen, Tuukka-Pekka

2014-01-01

Tiivistelmä Opinnäytetyössä tutustuttiin synkän turismin luonteeseen, teoriaan ja kohteisiin. Synkkä turismi ei ole laajuudestaan huolimatta kovin tiedostettu ilmiö, joten sen esitteleminen luo hyvän pohjan jatkotutkimuksille. Työhön kuului seuraavat osa-alueet: synkän turismin teorian esitteleminen ja perustavien termien läpikäyminen, valikoitujen kolmen synkän turismin kohteiden luokitteleminen synkän turismin kentälle ja synkän turismin kohteissa vierailevien matkailijoiden kertomu...

Particle identification aerogel counter with n=1.13 for {pi}/K separation

Energy Technology Data Exchange (ETDEWEB)

Barnyakov, A.Yu.; Barnyakov, M.Yu. [Budker Institute of Nuclear Physics, 11, akademika Lavrentieva prospect, Novosobirsk 630090 (Russian Federation); Beloborodov, K.I., E-mail: K.I.Beloborodov@inp.nsk.s [Budker Institute of Nuclear Physics, 11, akademika Lavrentieva prospect, Novosobirsk 630090 (Russian Federation); Novosibirsk State University, 2, Pirogova Street, Novosibirsk 630090 (Russian Federation); Bobrovnikov, V.S.; Buzykaev, A.R. [Budker Institute of Nuclear Physics, 11, akademika Lavrentieva prospect, Novosobirsk 630090 (Russian Federation); Danilyuk, A.F. [Boreskov Institute of Catalysis, 5, akademika Lavrentieva prospect, Novosibirsk 630090 (Russian Federation); Golubev, V.B. [Budker Institute of Nuclear Physics, 11, akademika Lavrentieva prospect, Novosobirsk 630090 (Russian Federation); Novosibirsk State University, 2, Pirogova Street, Novosibirsk 630090 (Russian Federation); Kirillov, V.L. [Boreskov Institute of Catalysis, 5, akademika Lavrentieva prospect, Novosibirsk 630090 (Russian Federation); Kononov, S.A. [Budker Institute of Nuclear Physics, 11, akademika Lavrentieva prospect, Novosobirsk 630090 (Russian Federation); Kravchenko, E.A. [Budker Institute of Nuclear Physics, 11, akademika Lavrentieva prospect, Novosobirsk 630090 (Russian Federation); Novosibirsk State University, 2, Pirogova Street, Novosibirsk 630090 (Russian Federation); Onuchin, A.P. [Budker Institute of Nuclear Physics, 11, akademika Lavrentieva prospect, Novosobirsk 630090 (Russian Federation); Martin, K.A. [Budker Institute of Nuclear Physics, 11, akademika Lavrentieva prospect, Novosobirsk 630090 (Russian Federation); Novosibirsk State Technical University, 20, Karl Marx prospect, Novosibirsk 630092 (Russian Federation); Serednyakov, S.I. [Budker Institute of Nuclear Physics, 11, akademika Lavrentieva prospect, Novosobirsk 630090 (Russian Federation); Novosibirsk State University, 2, Pirogova Street, Novosibirsk 630090 (Russian Federation)

2010-11-01

The paper is devoted to the cosmic muon tests of particle identification system for the SND detector at the new VEPP-2000 e{sup +}e{sup -} collider. The goal of the tests is to measure average signal for the relativistic particles. The measurements of the average signal were done at five different points of the counter. Obtained values of the signal are close to 10 photoelectrons. Preliminary results for misidentification probability for {pi} and K mesons with the energy of 1000 MeV are presented.

The relationship of serum HE4, CP2 and HCgp-39 levels with tumor malignancy in patients with endometrial carcinoma

Directory of Open Access Journals (Sweden)

Yun-Xia Rao

2017-04-01

Full Text Available Objective: To study the relationship of serum human epididymis protein (HE4, cancer protein-2 (CP2 and human cartilage glycoprotein-39 (HCgp-39 levels with tumor malignancy in patients with endometrial carcinoma. Methods: A total of 90 patients with endometrial carcinoma treated in our hospital between May 2012 and August 2015 were collected and divided into early-to-mid (Ⅰ-Ⅲ stage endometrial carcinoma group (n=59 and advanced (Ⅳ stage endometrial carcinoma group (n=31 according to the pathological staging, and 34 patients with endometrial thickening who received uterine curettage in our hospital during the same period were selected as control group. The levels of HE4, CP2, HCgp-39 and tumor markers in serum as well as the mRNA expression of proliferation genes and invasion genes in tumor tissue were determined. Results: HE4, CP2, HCgp-39, CA125, CA19-9 and CEA levels in serum as well as Bcl2, Chk1, PIK1, HER2 and GDF-15 mRNA expression in tumor tissues of early-to-mid endometrial carcinoma group and advanced endometrial carcinoma group were significantly higher than those of control group while the miRNA-199a-3p, Bax, caspase3, BRCA1, Kiss-1 and KAI1 mRNA expression were lower than those of control group; HE4, CP2, HCgp-39, CA125, CA19-9 and CEA levels in serum as well as Bcl2, Chk1, PIK1, HER2 and GDF-15 mRNA expression in tumor tissues of advanced endometrial carcinoma group were significantly higher than those of early-to-mid endometrial carcinoma group while the miRNA-199a-3p, Bax, caspase3, BRCA1, Kiss-1 and KAI1 mRNA expression were lower than those of early-to-mid endometrial carcinoma group; serum HE4, CP2 and HCgp-39 levels were positively correlated with CA125, CA19-9, CEA, Bcl2, Chk1, PIK1, HER2 and GDF- 15, and negatively correlated with miRNA-199a-3p, Bax, caspase3, BRCA1, Kiss-1 and KAI1. Conclusion: Serum HE4, CP2 and HCgp-39 levels can directly reflect the tumor malignancy in patients with endometrial carcinoma, and are

Targeted next generation sequencing of parotid gland cancer uncovers genetic heterogeneity.

Science.gov (United States)

Grünewald, Inga; Vollbrecht, Claudia; Meinrath, Jeannine; Meyer, Moritz F; Heukamp, Lukas C; Drebber, Uta; Quaas, Alexander; Beutner, Dirk; Hüttenbrink, Karl-Bernd; Wardelmann, Eva; Hartmann, Wolfgang; Büttner, Reinhard; Odenthal, Margarete; Stenner, Markus

2015-07-20

Salivary gland cancer represents a heterogeneous group of malignant tumors. Due to their low incidence and the existence of multiple morphologically defined subtypes, these tumors are still poorly understood with regard to their molecular pathogenesis and therapeutically relevant genetic alterations.Performing a systematic and comprehensive study covering 13 subtypes of salivary gland cancer, next generation sequencing was done on 84 tissue samples of parotid gland cancer using multiplex PCR for enrichment of cancer related gene loci covering hotspots of 46 cancer genes.Mutations were identified in 22 different genes. The most frequent alterations affected TP53, followed by RAS genes, PIK3CA, SMAD4 and members of the ERB family. HRAS mutations accounted for more than 90% of RAS mutations, occurring especially in epithelial-myoepithelial carcinomas and salivary duct carcinomas. Additional mutations in PIK3CA also affected particularly epithelial-myoepithelial carcinomas and salivary duct carcinomas, occurring simultaneously with HRAS mutations in almost all cases, pointing to an unknown and therapeutically relevant molecular constellation. Interestingly, 14% of tumors revealed mutations in surface growth factor receptor genes including ALK, HER2, ERBB4, FGFR, cMET and RET, which might prove to be targetable by new therapeutic agents. 6% of tumors revealed mutations in SMAD4.In summary, our data provide novel insight into the fundamental molecular heterogeneity of salivary gland cancer, relevant in terms of tumor classification and the establishment of targeted therapeutic concepts.

[Aspirin and colorectal cancer].

Science.gov (United States)

Grancher, Adrien; Michel, Pierre; Di Fiore, Frédéric; Sefrioui, David

2018-02-01

Colorectal cancer is a worldwide public health problem. Aspirin has been identified as a protective factor against the apparition of colorectal cancer. There are several mechanisms about the actions by aspirin on colorectal tumorogenesis. These are not perfectly known nowadays. On one hand, there are direct mechanisms on colorectal mucosa, on the other hand there are indirect mechanisms through platelet functions. Aspirin also plays a role by its anti-inflammatory action and the stimulation of antitumor immunity. Several studies show that long-term treatment with low-doses of aspirin decreases the incidence of adenomas and colorectal cancers. In the United States, aspirin is currently recommended for primary prevention of the risk of colorectal cancer in all patients aged 50 to 59, with a 10-year risk of cardiovascular event greater than 10 %. However, primary prevention with aspirin should not be a substitute for screening in colorectal cancer. Furthermore, aspirin seems to be beneficial when used in post-diagnosis of colorectal cancer. It could actually decrease the risk of metastasis in case of a localized colorectal cancer, and increase the survival in particular, concerning PIK3CA mutated tumors. The association of aspirin with neoadjuvant treatment of colorectal cancer by radiochimiotherapy seems to have beneficial effects. French prospective randomized study is currently being conducted to investigate postoperative aspirin in colorectal cancers with a PIK3CA mutation. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Inhibitors of EGFR and PI3K/Akt/mtor pathways for the treatment of head and neck cancer

Energy Technology Data Exchange (ETDEWEB)

Navarro Palomares, E. M.

2015-07-01

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and although new therapeutic approaches have been recently evaluated, improvement in overall patient survival is still poor. For this reason, new effective and selective clinical treatments are urgently needed. Genomic analysis allowing the identification of differences between normal and tumor cells provides new therapeutic options identifying novel targets or drugs that have shown efficacy in other tumor types. In this sense, EGFR amplification and/or overexpression are frequent events in HNSCC; in fact, the only targeted therapy approved to treat HNSCC is the anti-EFGR antibody Cetuximab. Based on cell line drug screening studies we identified Bosutinib (SKI-606), a Src/Abl inhibitor, as a candidate drug to treat HNSCC. Using a panel of HNSCC cell lines we found that the treatment with Bosutinib was able to reduce cell proliferation and to induce apoptosis at higher doses. We verified that the drug rapidly inhibited EGFR phosphorylation, and sensitivity to Bosutinib correlated with the activation of EGFR in tumor-derived cell lines. Moreover, Bosutinib showed a synergistic effect on cell viability with the PI3K? inhibitor BYL719 only in those cell lines with mutations in PIK3CA. These results suggest that Bosutinib could be a new effective drug in the treatment of HNSCC cancer, especially in tumors with high activity of EGFR, and its combination with BYL719 could especially benefit those patients bearing activating mutations of PIK3CA. (Author)

Genomic portfolio of Merkel cell carcinoma as determined by comprehensive genomic profiling: implications for targeted therapeutics.

Science.gov (United States)

Cohen, Philip R; Tomson, Brett N; Elkin, Sheryl K; Marchlik, Erica; Carter, Jennifer L; Kurzrock, Razelle

2016-04-26

Merkel cell carcinoma is an ultra-rare cutaneous neuroendocrine cancer for which approved treatment options are lacking. To better understand potential actionability, the genomic landscape of Merkel cell cancers was assessed. The molecular aberrations in 17 patients with Merkel cell carcinoma were, on physician request, tested in a Clinical Laboratory Improvement Amendments (CLIA) laboratory (Foundation Medicine, Cambridge, MA) using next-generation sequencing (182 or 236 genes) and analyzed by N-of-One, Inc. (Lexington, MA). There were 30 genes harboring aberrations and 60 distinct molecular alterations identified in this patient population. The most common abnormalities involved the TP53 gene (12/17 [71% of patients]) and the cell cycle pathway (CDKN2A/B, CDKN2C or RB1) (12/17 [71%]). Abnormalities also were observed in the PI3K/AKT/mTOR pathway (AKT2, FBXW7, NF1, PIK3CA, PIK3R1, PTEN or RICTOR) (9/17 [53%]) and DNA repair genes (ATM, BAP1, BRCA1/2, CHEK2, FANCA or MLH1) (5/17 [29%]). Possible cognate targeted therapies, including FDA-approved drugs, could be identified in most of the patients (16/17 [94%]). In summary, Merkel cell carcinomas were characterized by multiple distinct aberrations that were unique in the majority of analyzed cases. Most patients had theoretically actionable alterations. These results provide a framework for investigating tailored combinations of matched therapies in Merkel cell carcinoma patients.

Four o`clock lecture never starts at four / Kristina Lukk ; interviewed by Pirgita-Maarja Hallas

Index Scriptorium Estoniae

Lukk, Kristina

2009-01-01

Vestlus Tallinna Ülikoolis psühholoogia magistrantuuri lõpetanud Kristina Lukkiga, kes jätkab õpinguid doktoriõppeprogrammis Lõuna- Hispaanias Huelva ülikoolis, uurides sealseid integreerumisprotsesse. Muljeid Hispaania ülikooliõppest

Kella neljane loeng ei hakka mitte kunagi kella neljast / Kristina Lukk ; intervjueerinud Pirgita-Maarja Hallas

Index Scriptorium Estoniae

Lukk, Kristina

2009-01-01

Vestlus Tallinna Ülikoolis psühholoogia magistrantuuri lõpetanud Kristina Lukkiga, kes jätkab õpinguid doktoriõppeprogrammis Lõuna-Hispaanias Huelva ülikoolis, uurides sealseid integreerumisprotsesse. Muljeid Hispaania ülikooliõppest

Välisriigis sõlmitud samasooliste abielu ja kooselu tunnustamine Eestis / Kätlin Jaadla, Maarja Torga

Index Scriptorium Estoniae

Jaadla, Kätlin, 1988-

2013-01-01

Kas kehtivat Eesti rahvusvahelise eraõiguse regulatsiooni arvestades oleks Eestis võimalik anda õiguskaitset välisriigis sõlmitud samasooliste ühendustele ning millised oleksid võimalikud lahendusvariandid sellistest ühendustest tulenevate nõuete kvalifitseerimisel

Systematic Functional Interrogation of Rare Cancer Variants Identifies Oncogenic Alleles | Office of Cancer Genomics

Science.gov (United States)

Cancer genome characterization efforts now provide an initial view of the somatic alterations in primary tumors. However, most point mutations occur at low frequency, and the function of these alleles remains undefined. We have developed a scalable systematic approach to interrogate the function of cancer-associated gene variants. We subjected 474 mutant alleles curated from 5,338 tumors to pooled in vivo tumor formation assays and gene expression profiling. We identified 12 transforming alleles, including two in genes (PIK3CB, POT1) that have not been shown to be tumorigenic.

Potency of sponge-associated bacteria producing bioactive compounds as biological control of vibriosis on shrimp

Directory of Open Access Journals (Sweden)

Adityawati Fajar Rini

2017-07-01

Full Text Available ABSTRACT The aims of this study were to obtain sponge-associated bacteria as biocontrol to inhibit vibriosis in vitro and in vivo, to identify the bacterial isolates based on 16S-rRNA gene, and to detect the presence of nonribosomal peptide synthetase (NRPS, and polyketide synthase (PKS genes to prove its ability of bioactive compounds synthesis. Aaptos sp. and Hyrtios sp. sponges were collected from Pramuka Island, Jakarta. The isolation using sea water complete (SWC and  zobel marine agar (ZMA medium obtained 174 isolates. A total 69 isolates were screened successfully based on their antibacterial activity. 47 isolates showed negative haemolysis through hemolytic assays. The pathogenicity test used twelve selected isolates that have a broad spectrum of antibacterial activity and haemolysis negative. The result of pathogenicity test showed  that 12 isolates were not pathogenic to the shrimp post larvae with no significantly different (P>0.05 between treatment and negative control. Results of challenge test with Vibrio harveyi have a significant difference survival (70±5.0–90±0.0% (P<0.05 compared with positive control (38.3±2.9%. Genetic analysis based on 16S-rRNA revealed the groups of three genera belonged to Pseudomonas, Staphylococcus, and Alcaligenes. Based on amplification of NRPS and PKS genes, four bacterial isolates have been detected to have only NRPS gene, one isolate has only PKS, and one isolate has both genes. The results indicate that the potency of six sponge-associated bacteria as bioactive compounds producers. Keywords: NRPS, PKS, anti-vibriosis, Pacific white shrimp  ABSTRAK Penelitian ini bertujuan untuk memperoleh isolat bakteri asosiasi spons yang mempunyai kemampuan dalam menghambat vibriosis secara in vitro, in vivo dan mendeteksi gen 16S-rRNA, nonribosomal peptide synthase (NRPS serta polyketide synthase (PKS untuk memastikan kemampuan mensintesis senyawa bioaktif. Spons Aaptos sp. dan Hyrtios sp. berhasil

Identification of Top-ranked Proteins within a Directional Protein Interaction Network using the PageRank Algorithm: Applications in Humans and Plants.

Science.gov (United States)

Li, Xiu-Qing; Xing, Tim; Du, Donglei

2016-01-01

Somatic mutation of signal transduction genes or key nodes of the cellular protein network can cause severe diseases in humans but can sometimes genetically improve plants, likely because growth is determinate in animals but indeterminate in plants. This article reviews protein networks; human protein ranking; the mitogen-activated protein kinase (MAPK) and insulin (phospho- inositide 3kinase [PI3K]/phosphatase and tensin homolog [PTEN]/protein kinase B [AKT]) signaling pathways; human diseases caused by somatic mutations to the PI3K/PTEN/ AKT pathway; use of the MAPK pathway in plant molecular breeding; and protein domain evolution. Casitas B-lineage lymphoma (CBL), PTEN, MAPK1 and PIK3CA are among PIK3CA the top-ranked proteins in directional rankings. Eight proteins (ACVR1, CDC42, RAC1, RAF1, RHOA, TGFBR1, TRAF2, and TRAF6) are ranked in the top 50 key players in both signal emission and signal reception and in interaction with many other proteins. Top-ranked proteins likely have major impacts on the network function. Such proteins are targets for drug discovery, because their mutations are implicated in various cancers and overgrowth syndromes. Appropriately managing food intake may help reduce the growth of tumors or malformation of tissues. The role of the protein kinase C/ fatty acid synthase pathway in fat deposition in PTEN/PI3K patients should be investigated. Both the MAPK and insulin signaling pathways exist in plants, and MAPK pathway engineering can improve plant tolerance to biotic and abiotic stresses such as salinity.

Primary tumor location predicts poor clinical outcome with cetuximab in RAS wild-type metastatic colorectal cancer.

Science.gov (United States)

Kim, Dalyong; Kim, Sun Young; Lee, Ji Sung; Hong, Yong Sang; Kim, Jeong Eun; Kim, Kyu-Pyo; Kim, Jihun; Jang, Se Jin; Yoon, Young-Kwang; Kim, Tae Won

2017-11-23

In metastatic colorectal cancer, the location of the primary tumor has been suggested to have biological significance. In this study, we investigated whether primary tumor location affects cetuximab efficacy in patients with RAS wild-type metastatic colorectal cancer. Genotyping by the SequenomMassARRAY technology platform (OncoMap) targeting KRAS, NRAS, PIK3CA, and BRAF was performed in tumors from 307 patients who had been given cetuximab as salvage treatment. Tumors with mutated RAS (KRAS or NRAS; n = 127) and those with multiple primary location (n = 10) were excluded. Right colon cancer was defined as a tumor located in the proximal part to splenic flexure. A total of 170 patients were included in the study (right versus left, 23 and 147, respectively). Patients with right colon cancer showed more mutated BRAF (39.1% vs. 5.4%), mutated PIK3CA (13% vs. 1.4%), poorly differentiated tumor (17.4% vs. 3.4%), and peritoneal involvement (26.1% vs. 8.8%) than those with left colon and rectal cancer. Right colon cancer showed poorer progression-free survival (2.0 vs.5.0 months, P = 0.002) and overall survival (4.1 months and 13.0 months, P < 0.001) than the left colon and rectal cancer. By multivariable analysis, BRAF mutation, right colon primary, poorly differentiated histology, and peritoneal involvement were associated with risk of death. In RAS wild-type colon cancer treated with cetuximab as salvage treatment, right colon primary was associated with poorer survival outcomes than left colon and rectal cancer.

Stage III & IV colon and rectal cancers share a similar genetic profile: a review of the Oregon Colorectal Cancer Registry.

Science.gov (United States)

Gawlick, Ute; Lu, Kim C; Douthit, Miriam A; Diggs, Brian S; Schuff, Kathryn G; Herzig, Daniel O; Tsikitis, Vassiliki L

2013-05-01

Determining the molecular profile of colon and rectal cancers offers the possibility of personalized cancer treatment. The purpose of this study was to determine whether known genetic mutations associated with colorectal carcinogenesis differ between colon and rectal cancers and whether they are associated with survival. The Oregon Colorectal Cancer Registry is a prospectively maintained, institutional review board-approved tissue repository with associated demographic and clinical information. The registry was queried for any patient with molecular analysis paired with clinical data. Patient demographics, tumor characteristics, microsatellite instability status, and mutational analysis for p53, AKT, BRAF, KRAS, MET, NRAS, and PIK3CA were analyzed. Categorical variables were compared using chi-square tests. Continuous variables between groups were analyzed using Mann-Whitney U tests. Kaplan-Meier analysis was used for survival studies. Comparisons of survival were made using log-rank tests. The registry included 370 patients: 69% with colon cancer and 31% with rectal cancer. Eighty percent of colon cancers and 68% of rectal cancers were stages III and IV. Mutational analysis found no significant differences in detected mutations between colon and rectal cancers, except that there were significantly more BRAF mutations in colon cancers compared with rectal cancers (10% vs 0%, P colon versus rectal cancers when stratified by the presence of KRAS, PIK3CA, and BRAF mutations. Stage III and IV colon and rectal cancers share similar molecular profiles, except that there were significantly more BRAF mutations in colon cancers compared with rectal cancers. Copyright © 2013 Elsevier Inc. All rights reserved.

Territorial Indicative Budget Ceilings (PIK as Instrument of Technocracy of Regional Development Planning

Directory of Open Access Journals (Sweden)

Sarjiyanto Sarjiyanto

2017-03-01

Full Text Available This research aims at analyzing the local government policy related to the local budget posture in the each territorial. There are uncertainty methods in dividing and formulating the local budget posture in each territorial in Indonesia. It is not depend on the actual economic variables of each territorial. This study uses the literature studies to collect the data of planning and budgeting. The content analysis of this local government economic policy is based on of the planning and budgeting process itself. The detailed information is found by observations and in-depth interview with the informants about the planning and budgeting process in Rembang. The result shows the variables that can determine the fair instrument in formulating the local budget posture some of which are: the number of population, the number of drop out (DO, the illiteracy (IR, the infant mortality rate (IMR, the malnutrition data, the number of poor (HCI, the economic growth, the damaged road infrastructure, the damaged irrigation system, the damaged schools, the land building tax, and the amount of retribution.

Endometriosis and Type I Interferon & Characterization of a Mammalian Flippase

DEFF Research Database (Denmark)

Vestergaard, Anna Lindeløv

2010-01-01

endometriosis lesion. Human papillomavirus (HPV) is the causative agent of cervix cancer, and DNA viruses might play a role in endometriosis. DNA purified from tissue samples were subjected to highly sensitive PCR tests detecting HPV types, the herpes family viruses HSV-1 and -2, CMV, and EBV......, and ERa, when analyzed by bisulfate PCR and melting curve analysis. Also, no mutations of BRAF, HRAS, NRAS, CTNNB1, CDK4, FGFR3, PIK3CA, P53, and PTEN were detected by PCR denaturing gradient gel electrophoresis analysis. A well-known cancer-associated mutation in KRAS was detected in a single...

IGORR 2: Proceedings of the 2. meeting of the International Group On Research Reactors

Energy Technology Data Exchange (ETDEWEB)

NONE

1992-07-01

The International group on Research Reactors was formed to facilitate the sharing of knowledge and experience among those institutions and individuals who are actively working to design, build, and promote new research reactors or to make significant upgrades to existing facilities. Sessions during this second meeting were devoted to research reactor reports (GRENOBLE reactor, FRM-II, HIFAR, PIK, reactors at JAERI, MAPLE, ANS, NIST, MURR, TRIGA, BR-2, SIRIUS 2); other neutron sources; and two workshops were dealing with research and development results and needs and reports on progress in needed of R and D areas identified at IGORR 1.

Mõned erilised hetked EPIKoja võrgustiku tegemistest aastal 2016

Index Scriptorium Estoniae

2016-01-01

Fotosid Eesti Puuetega Inimeste Koja liikmesorganisatsioonide üritustest 2016. aastal: Eesti Reumaliidu 17. käimispäev Tartus, puuetega noortele tervisepäev Pannjärve terviserajal, Eesti Autismiühingu korraldatud rahvusvahelisest autismipäevast Tallinna Tondi Põhikoolis, Eesti Tsöliaakia Seltsi suvelaager Tartumaal 8.-10. juulil, Vahtra Tantsud Tähtedega 2016 finaal, Tartu PIK-i projektis “Ajaga kaasa” osalejad Stenbocki maja, Eesti Pimedate Liit andis valge kepi päeva tänuseminaril üle tunnustused “Aasta tegu 2016”, Eesti Psoriaasiliit tähistas 26. märtsil oma 25. aastapäeva konverentsiga Tallinnas

IGORR 2: Proceedings of the 2. meeting of the International Group On Research Reactors

International Nuclear Information System (INIS)

1992-01-01

The International group on Research Reactors was formed to facilitate the sharing of knowledge and experience among those institutions and individuals who are actively working to design, build, and promote new research reactors or to make significant upgrades to existing facilities. Sessions during this second meeting were devoted to research reactor reports (GRENOBLE reactor, FRM-II, HIFAR, PIK, reactors at JAERI, MAPLE, ANS, NIST, MURR, TRIGA, BR-2, SIRIUS 2); other neutron sources; and two workshops were dealing with research and development results and needs and reports on progress in needed of R and D areas identified at IGORR 1

Mutational analysis of cutaneous squamous cell carcinomas and verrucal keratosis in patients taking BRAF inhibitors.

Science.gov (United States)

Anforth, Rachael; Tembe, Varsha; Blumetti, Tatiana; Fernandez-Peñas, Pablo

2012-09-01

B-RAF inhibitors (BRAFi) have been shown to improve rates of overall and progression-free survival in patients with stage IV metastatic melanoma positive for the BRAF V600E mutation. However, the main drawback is the development of verrucal keratosis (hyperkeratotic papules with verruca-like characteristics with benign histological findings) and cutaneous squamous cell carcinomas (cuSCC). We have found upstream mutations in RAS as well as PIK3CA in both verrucal keratosis and cuSCC. This suggests that verrucal keratosis is an early clinical presentation of cuSCC in patients on BRAFi. © 2012 John Wiley & Sons A/S.

Carpal Tunnel Syndrome in Aberrant Muscle Syndrome: A Case Report and Review of the Literature.

Science.gov (United States)

Steele, Jessica; Coombs, Christopher

2018-06-01

Aberrant Muscle Syndrome (AMS) is a rare congenital hand difference that is characterised by unilateral non-progressive muscular hyperplasia. The aetiology of aberrant muscle syndrome is not known, but a recently published case has shown a somatic PIK3CA activating mutation in a patient with AMS. Carpal tunnel syndrome (CTS) in children is rare. The most common causes are the mucopolysaccaridoses but space-occupying lesions have also been reported to cause CTS in children. We report the first case of CTS in a child with AMS successfully treated with open carpal tunnel release and excision of aberrant muscles.

Interdependency of EGF and GLP-2 Signaling in Attenuating Mucosal Atrophy in a Mouse Model of Parenteral Nutrition

DEFF Research Database (Denmark)

Feng, Yongjia; Demehri, Farok R; Xiao, Weidong

2017-01-01

BACKGROUND & AIMS: Total parenteral nutrition (TPN), a crucial treatment for patients who cannot receive enteral nutrition, is associated with mucosal atrophy, barrier dysfunction, and infectious complications. Glucagon-like peptide-2 (GLP-2) and epidermal growth factor (EGF) improve intestinal...... deprived of enteral nutrition. METHODS: Adult C57BL/6J, IEC-Egfr(knock out (KO)) and IEC-pik3r1(KO) mice receiving TPN or enteral nutrition were treated with EGF or GLP-2 alone or in combination with reciprocal receptor inhibitors, GLP-2(3-33) or gefitinib. Jejunum was collected and mucosal atrophy and IEC...

Elujõuline Eesti etnoloogia / Terje Anepaio, Aivar Jürgenson, Timothy King, Art Leete ; interv. Maarja Kaaristo

Index Scriptorium Estoniae

2006-01-01

Etnoloogia hetkeseisu ja tuleviku üle arutlevad Eesti Rahva Muuseumi teadusdirektor Terje Anepaio, Ajaloo Instituudi etnoloogia osakonna juhataja vanemteadur Aivar Jürgenson, Tallinna Ülikooli antropoloogia õppekava juht Timothy King ja Tartu Ülikooli etnoloogia õppetooli professor Art Leete

Jaanus Rohumaa: "Every person should be a creator" / Jaanus Rohumaa ; intervjueerinud Maarja-Liis Arujärv

Index Scriptorium Estoniae

Rohumaa, Jaanus, 1969-

2010-01-01

SA Tallinn 2011 programmiosakonna juhataja Jaanus Rohumaa kultuuripealinna aasta mõttest, eesmärkidest ja programmist, ürituste kvaliteedist, eesti kultuurist ja rahvakultuurist, juurdepääsust kultuurile, loomekeskkonna parandamise võimalusest, Tallinna mitmetahulisusest ja rikkusest, koostööst jm.

Disease Evolution and Response to Rapamycin in Activated Phosphoinositide 3-Kinase δ Syndrome: The European Society for Immunodeficiencies-Activated Phosphoinositide 3-Kinase δ Syndrome Registry

Directory of Open Access Journals (Sweden)

Maria Elena Maccari

2018-03-01

Full Text Available Activated phosphoinositide 3-kinase (PI3K δ Syndrome (APDS, caused by autosomal dominant mutations in PIK3CD (APDS1 or PIK3R1 (APDS2, is a heterogeneous primary immunodeficiency. While initial cohort-descriptions summarized the spectrum of clinical and immunological manifestations, questions about long-term disease evolution and response to therapy remain. The prospective European Society for Immunodeficiencies (ESID-APDS registry aims to characterize the disease course, identify outcome predictors, and evaluate treatment responses. So far, 77 patients have been recruited (51 APDS1, 26 APDS2. Analysis of disease evolution in the first 68 patients pinpoints the early occurrence of recurrent respiratory infections followed by chronic lymphoproliferation, gastrointestinal manifestations, and cytopenias. Although most manifestations occur by age 15, adult-onset and asymptomatic courses were documented. Bronchiectasis was observed in 24/40 APDS1 patients who received a CT-scan compared with 4/15 APDS2 patients. By age 20, half of the patients had received at least one immunosuppressant, but 2–3 lines of immunosuppressive therapy were not unusual before age 10. Response to rapamycin was rated by physician visual analog scale as good in 10, moderate in 9, and poor in 7. Lymphoproliferation showed the best response (8 complete, 11 partial, 6 no remission, while bowel inflammation (3 complete, 3 partial, 9 no remission and cytopenia (3 complete, 2 partial, 9 no remission responded less well. Hence, non-lymphoproliferative manifestations should be a key target for novel therapies. This report from the ESID-APDS registry provides comprehensive baseline documentation for a growing cohort that will be followed prospectively to establish prognostic factors and identify patients for treatment studies.

LPJmL4 - a dynamic global vegetation model with managed land - Part 2: Model evaluation

Science.gov (United States)

Schaphoff, Sibyll; Forkel, Matthias; Müller, Christoph; Knauer, Jürgen; von Bloh, Werner; Gerten, Dieter; Jägermeyr, Jonas; Lucht, Wolfgang; Rammig, Anja; Thonicke, Kirsten; Waha, Katharina

2018-04-01

The dynamic global vegetation model LPJmL4 is a process-based model that simulates climate and land use change impacts on the terrestrial biosphere, agricultural production, and the water and carbon cycle. Different versions of the model have been developed and applied to evaluate the role of natural and managed ecosystems in the Earth system and the potential impacts of global environmental change. A comprehensive model description of the new model version, LPJmL4, is provided in a companion paper (Schaphoff et al., 2018c). Here, we provide a full picture of the model performance, going beyond standard benchmark procedures and give hints on the strengths and shortcomings of the model to identify the need for further model improvement. Specifically, we evaluate LPJmL4 against various datasets from in situ measurement sites, satellite observations, and agricultural yield statistics. We apply a range of metrics to evaluate the quality of the model to simulate stocks and flows of carbon and water in natural and managed ecosystems at different temporal and spatial scales. We show that an advanced phenology scheme improves the simulation of seasonal fluctuations in the atmospheric CO2 concentration, while the permafrost scheme improves estimates of carbon stocks. The full LPJmL4 code including the new developments will be supplied open source through https://gitlab.pik-potsdam.de/lpjml/LPJmL" target="_blank">https://gitlab.pik-potsdam.de/lpjml/LPJmL. We hope that this will lead to new model developments and applications that improve the model performance and possibly build up a new understanding of the terrestrial biosphere.

LPJmL4 - a dynamic global vegetation model with managed land - Part 1: Model description

Science.gov (United States)

Schaphoff, Sibyll; von Bloh, Werner; Rammig, Anja; Thonicke, Kirsten; Biemans, Hester; Forkel, Matthias; Gerten, Dieter; Heinke, Jens; Jägermeyr, Jonas; Knauer, Jürgen; Langerwisch, Fanny; Lucht, Wolfgang; Müller, Christoph; Rolinski, Susanne; Waha, Katharina

2018-04-01

This paper provides a comprehensive description of the newest version of the Dynamic Global Vegetation Model with managed Land, LPJmL4. This model simulates - internally consistently - the growth and productivity of both natural and agricultural vegetation as coherently linked through their water, carbon, and energy fluxes. These features render LPJmL4 suitable for assessing a broad range of feedbacks within and impacts upon the terrestrial biosphere as increasingly shaped by human activities such as climate change and land use change. Here we describe the core model structure, including recently developed modules now unified in LPJmL4. Thereby, we also review LPJmL model developments and evaluations in the field of permafrost, human and ecological water demand, and improved representation of crop types. We summarize and discuss LPJmL model applications dealing with the impacts of historical and future environmental change on the terrestrial biosphere at regional and global scale and provide a comprehensive overview of LPJmL publications since the first model description in 2007. To demonstrate the main features of the LPJmL4 model, we display reference simulation results for key processes such as the current global distribution of natural and managed ecosystems, their productivities, and associated water fluxes. A thorough evaluation of the model is provided in a companion paper. By making the model source code freely available at https://gitlab.pik-potsdam.de/lpjml/LPJmL" target="_blank">https://gitlab.pik-potsdam.de/lpjml/LPJmL, we hope to stimulate the application and further development of LPJmL4 across scientific communities in support of major activities such as the IPCC and SDG process.

Synergistic Interactions with PI3K Inhibition that Induce Apoptosis. | Office of Cancer Genomics

Science.gov (United States)

Activating mutations involving the PI3K pathway occur frequently in human cancers. However, PI3K inhibitors primarily induce cell cycle arrest, leaving a significant reservoir of tumor cells that may acquire or exhibit resistance. We searched for genes that are required for the survival of PI3K mutant cancer cells in the presence of PI3K inhibition by conducting a genome scale shRNA-based apoptosis screen in a PIK3CA mutant human breast cancer cell. We identified 5 genes (PIM2, ZAK, TACC1, ZFR, ZNF565) whose suppression induced cell death upon PI3K inhibition.

Potsdam Institute for Climate Impact Research. Biennial report 1996 and 1997; Potsdam-Institut fuer Klimafolgenforschung. Zweijahresbericht 1996 und 1997

Energy Technology Data Exchange (ETDEWEB)

Andre, G; Bruch, S vom [comps.

1999-12-31

The Potsdam Institute for Climate Impact Research was founded in 1992, the year that the Rio Conference was expected to grind out the blue-print for global sustainable development. The Institute`s general philosophy and methodology have been described before (e.g., in the introduction to the first biennal report 1994/95). Here, it is emphasized that the heterogeneity of the scientific tasks to be solved by PIK (ranging from empirical time series analysis to paradigms for ecosphere management) and the complexity of the environmental systems to be investigated call for a specific research strategy, which generally compromises between high-precision analysis and educated guesswork. (orig./KWE)

Potsdam Institute for Climate Impact Research. Biennial report 1996 and 1997; Potsdam-Institut fuer Klimafolgenforschung. Zweijahresbericht 1996 und 1997

Energy Technology Data Exchange (ETDEWEB)

Andre, G.; Bruch, S. vom [comps.

1998-12-31

The Potsdam Institute for Climate Impact Research was founded in 1992, the year that the Rio Conference was expected to grind out the blue-print for global sustainable development. The Institute`s general philosophy and methodology have been described before (e.g., in the introduction to the first biennal report 1994/95). Here, it is emphasized that the heterogeneity of the scientific tasks to be solved by PIK (ranging from empirical time series analysis to paradigms for ecosphere management) and the complexity of the environmental systems to be investigated call for a specific research strategy, which generally compromises between high-precision analysis and educated guesswork. (orig./KWE)

Impact of rs361072 in the phosphoinositide 3-kinase p110beta gene on whole-body glucose metabolism and subunit protein expression in skeletal muscle

DEFF Research Database (Denmark)

Ribel-Madsen, Rasmus; Poulsen, Pernille; Holmkvist, Johan

2010-01-01

OBJECTIVE: Phosphoinositide 3-kinase (PI3K) is a major effector in insulin signaling. rs361072, located in the promoter of the gene (PIK3CB) for the p110beta subunit, has previously been found to be associated with homeostasis model assessment for insulin resistance (HOMA-IR) in obese subjects...... infusion. rs361072 did not associate with insulin-stimulated peripheral glucose disposal despite a decreased muscle p85alpha:p110beta protein ratio (P(add) = 0.03) in G allele carriers. No association with HOMA-IR or type 2 diabetes (odds ratio 1.07, P = 0.5) was identified, and obesity did not interact...

New POLDI - project of reincarnation of a polarized neutron diffractometer at the reactor PIK

Science.gov (United States)

Zobkalo, I.; Gavrilov, S.; Matveev, V.; Fenske, J.

2017-06-01

The project of a considerable modernization of the polarized neutron diffractometer POLDI is discussed. It assumes the adoption of POLDI to a broader range of magnetic investigations such as determination of magnetic structures, detailed investigation of complex magnetic structures, studies of magnetic domains, study of the magnetization density maps, magnetic form-factor particularities, local susceptibility, etc. The flexible construction should permit to use either spherical neutron polarimetry technique or flipping ratio technique. Different types of polarization system were analyzed. Original focusing fan-like bender is proposed as polarizer unit. Our simulations give evidence that for the wavelength range 1.3 - 3 Å and with suitable size, such a device can give much better efficiency than 3He cells, which are often in use. The higher flux at the sample position of a factor of at least 3.3, with lower divergence and good polarization degree from 98% (1.3 Å) to above 94% (3 Å) makes the bender set-up favorable over the layout with a 3He-cell.

Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial.

Science.gov (United States)

Cristofanilli, Massimo; Turner, Nicholas C; Bondarenko, Igor; Ro, Jungsil; Im, Seock-Ah; Masuda, Norikazu; Colleoni, Marco; DeMichele, Angela; Loi, Sherene; Verma, Sunil; Iwata, Hiroji; Harbeck, Nadia; Zhang, Ke; Theall, Kathy Puyana; Jiang, Yuqiu; Bartlett, Cynthia Huang; Koehler, Maria; Slamon, Dennis

2016-04-01

In the PALOMA-3 study, the combination of the CDK4 and CDK6 inhibitor palbociclib and fulvestrant was associated with significant improvements in progression-free survival compared with fulvestrant plus placebo in patients with metastatic breast cancer. Identification of patients most suitable for the addition of palbociclib to endocrine therapy after tumour recurrence is crucial for treatment optimisation in metastatic breast cancer. We aimed to confirm our earlier findings with this extended follow-up and show our results for subgroup and biomarker analyses. In this multicentre, double-blind, randomised phase 3 study, women aged 18 years or older with hormone-receptor-positive, HER2-negative metastatic breast cancer that had progressed on previous endocrine therapy were stratified by sensitivity to previous hormonal therapy, menopausal status, and presence of visceral metastasis at 144 centres in 17 countries. Eligible patients-ie, any menopausal status, Eastern Cooperative Oncology Group performance status 0-1, measurable disease or bone disease only, and disease relapse or progression after previous endocrine therapy for advanced disease during treatment or within 12 months of completion of adjuvant therapy-were randomly assigned (2:1) via a centralised interactive web-based and voice-based randomisation system to receive oral palbociclib (125 mg daily for 3 weeks followed by a week off over 28-day cycles) plus 500 mg fulvestrant (intramuscular injection on days 1 and 15 of cycle 1; then on day 1 of subsequent 28-day cycles) or placebo plus fulvestrant. The primary endpoint was investigator-assessed progression-free survival. Analysis was by intention to treat. We also assessed endocrine therapy resistance by clinical parameters, quantitative hormone-receptor expression, and tumour PIK3CA mutational status in circulating DNA at baseline. This study is registered with ClinicalTrials.gov, NCT01942135. Between Oct 7, 2013, and Aug 26, 2014, 521 patients were

Lähme, naised / Tiina Kuuler

Index Scriptorium Estoniae

Kuuler, Tiina, 1969-

2008-01-01

Muusikasündmustest: ansambli Metsatöll heliplaadi "Iivakivi" esitluskontsertidest 7. märtsil Tallinnas klubis Hollywood ja 8. märtsil Tartu Sadamateatris, Ultima Thule sünnipäevakontserdist 7. märtsil Tallinnas Rock Cafés, Jäääär 8. märtsil Rock Cafés, Koit Toome ja Uku Suviste 12. märtsil Pärnu kontserdimajas, Kuninglik kvintett 8. märtsil Kiviõli rahvamajas, "Naerata nüüd jälle sa" (Maarja-Liis Ilus, Alen Veziko, Margus Vaher, Andre Hein, Raimondo Laikre) 9. märtsil Vanemuise kontserdimajas, "Kaunimad... su elus" (ansambel Kaunimate Aastate Vennaskond) 7. märtsil Jõhvi kontserdimajas, 8. märtsil Vanemuise kontserdimajas ja 9. märtsil Pärnu kontserdimajas, Tarmo ja Toomas Urb 8. märtsil Viljandi kultuurimajas, Koit Toome 7. märtsil Tartu Jaani kirikus, Noorkuu naistepäevakontsert 8. märtsil Rakvere spordihallis, Eesti heliloojate armastuslaulud ETV tütarlastekoori esituses 8. märtsil Jõhvi kontserdimajas, Brides in Bloom + DJ Kahurid 8. märtsil Tallinnas klubis Woodstock, Richard Clayderman 11. märtsil Estonia kontserdisaalis

Nissi Maarja kiriku kooriruumi kahe vitraažakna restaureerimine / H. Beyermann, Illar Kannelmäe, Dolores Hoffmann

Index Scriptorium Estoniae

Beyermann, H.

2005-01-01

4 ill.; aknad valmistas Riia meister H. Beyermann, ühel aknal on kujutatud evangelist Johannest, teisel apostel Peetrust; töid teostasid Dolores Hoffmanni juhendamisel OÜ Domini Canes meistrid B. Morejev, S. Ganin ja A. Bruk, kaitseklaaside projekti tegi Illar Kannelmäe

Introduction of Eucalyptus spp. into the United States with Special Emphasis on the Southern United States

Directory of Open Access Journals (Sweden)

R. C. Kellison

2013-01-01

Full Text Available Introduction of Eucalyptus spp. into the United States from Australia on a significant scale resulted from the gold rush into California in 1849. Numerous species were evaluated for fuel, wood products, and amenity purposes. The first recorded entry of eucalyptus into the southern United Stated was in 1878. Subsequent performance of selected species for ornamental purposes caused forest industry to visualize plantations for fiber production. That interest led the Florida Forestry Foundation to initiate species-introduction trials in 1959. The results were sufficiently promising that a contingent of forest products companies formed a cooperative to work with the USDA Forest Service, Lehigh Acres, FL, USA, on genetic improvement of selected species for fiber production. The Florida initiative caused other industrial forestry companies in the upper South to establish plantations regardless of the species or seed source. The result was invariably the same: failure. Bruce Zobel, Professor of Forestry, North Carolina State University, initiated a concerted effort to assess the potential worth of eucalyptus for plantation use. The joint industrial effort evaluated 569 sources representing 103 species over a 14-year period. The three levels of testing, screening, in-depth, and semioperational trials led to identification of some species and sources that offered promise for adaptation, but severe winter temperatures in late 1983 and early 1984 and 1985 terminated the project. Despite the failed attempt valuable silvicultural practices were ascertained that will be beneficial to other researchers and practitioners when attempts are again made to introduce the species complex into the US South.

Oncogene mutational profile in nasopharyngeal carcinoma

Directory of Open Access Journals (Sweden)

Zhang ZC

2014-03-01

Full Text Available Zi-Chen Zhang,1,* Sha Fu,1,* Fang Wang,1 Hai-Yun Wang,1 Yi-Xin Zeng,2 Jian-Yong Shao11Department of Molecular Diagnostics, 2Department of Experimental Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, People's Republic of China *These authors contributed equally to this work Abstract: Nasopharyngeal carcinoma (NPC is a common tumor in Southern China, but the oncogene mutational status of NPC patients has not been clarified. Using time-of-flight mass spectrometry, 238 mutation hotspots in 19 oncogenes were examined in 123 NPC patients. The relationships between mutational status and clinical data were assessed with a χ2 or Fisher's exact test. Survival analysis was performed using the Kaplan–Meier method with the log-rank test. In 123 patients, 21 (17.1% NPC tumors were positive for mutations in eight oncogenes: six patients had PIK3CA mutations (4.9%, five NRAS mutations (4.1%, four KIT mutations (3.3%, two PDGFRA mutations (1.6%, two ABL mutations (1.6%, and one with simultaneous mutations in HRAS, EGFR, and BRAF (1%. Patients with mutations were more likely to relapse or develop metastasis than those with wild-type alleles (P=0.019. No differences or correlations were found in other clinical characteristics or in patient survival. No mutations were detected in oncogenes AKT1, AKT2, CDK, ERBB2, FGFR1, FGFR3, FLT3, JAK2, KRAS, MET, and RET. These results demonstrate an association between NPC and mutations in NRAS, KIT, PIK3CA, PDGFRA, and ABL, which are associated with patient relapse and metastasis. Keywords: NPC, oncogene, mutation

Interleukin 21 Controls mRNA and MicroRNA Expression in CD40-Activated Chronic Lymphocytic Leukemia Cells.

Directory of Open Access Journals (Sweden)

Loris De Cecco

Full Text Available Several factors support CLL cell survival in the microenvironment. Under different experimental conditions, IL21 can either induce apoptosis or promote CLL cell survival. To investigate mechanisms involved in the effects of IL21, we studied the ability of IL21 to modulate gene and miRNA expressions in CD40-activated CLL cells. IL21 was a major regulator of chemokine production in CLL cells and it modulated the expression of genes involved in cell movement, metabolism, survival and apoptosis. In particular, IL21 down-regulated the expression of the chemokine genes CCL4, CCL3, CCL3L1, CCL17, and CCL2, while it up-regulated the Th1-related CXCL9 and CXCL10. In addition, IL21 down-regulated the expression of genes encoding signaling molecules, such as CD40, DDR1 and PIK3CD. IL21 modulated a similar set of genes in CLL and normal B-cells (e.g. chemokine genes, whereas other genes, including MYC, TNF, E2F1, EGR2 and GAS-6, were regulated only in CLL cells. An integrated analysis of the miRNome and gene expression indicated that several miRNAs were under IL21 control and these could, in turn, influence the expression of potential target genes. We focused on hsa-miR-663b predicted to down-regulate several relevant genes. Transfection of hsa-miR-663b or its specific antagonist showed that this miRNA regulated CCL17, DDR1, PIK3CD and CD40 gene expression. Our data indicated that IL21 modulates the expression of genes mediating the crosstalk between CLL cells and their microenvironment and miRNAs may take part in this process.

Biomarker-driven trial in metastatic pancreas cancer: feasibility in a multicenter study of saracatinib, an oral Src inhibitor, in previously treated pancreatic cancer

International Nuclear Information System (INIS)

Arcaroli, John; Quackenbush, Kevin; Dasari, Arvind; Powell, Rebecca; McManus, Martine; Tan, Aik-Choon; Foster, Nathan R; Picus, Joel; Wright, John; Nallapareddy, Sujatha; Erlichman, Charles; Hidalgo, Manuel; Messersmith, Wells A

2012-01-01

Src tyrosine kinases are overexpressed in pancreatic cancers, and the oral Src inhibitor saracatinib has shown antitumor activity in preclinical models of pancreas cancer. We performed a CTEP-sponsored Phase II clinical trial of saracatinib in previously treated pancreas cancer patients, with a primary endpoint of 6-month survival. A Simon MinMax two-stage phase II design was used. Saracatinib (175 mg/day) was administered orally continuously in 28-day cycles. In the unselected portion of the study, 18 patients were evaluable. Only two (11%) patients survived for at least 6 months, and three 6-month survivors were required to move to second stage of study as originally designed. The study was amended as a biomarker-driven trial (leucine rich repeat containing protein 19 [LRRC19] > insulin-like growth factor-binding protein 2 [IGFBP2] “top scoring pairs” polymerase chain reaction [PCR] assay, and PIK3CA mutant) based on preclinical data in a human pancreas tumor explant model. In the biomarker study, archival tumor tissue or fresh tumor biopsies were tested. Biomarker-positive patients were eligible for the study. Only one patient was PIK3CA mutant in a 3′ untranslated region (UTR) portion of the gene. This patient was enrolled in the study and failed to meet the 6-month survival endpoint. As the frequency of biomarker-positive patients was very low (<3%), the study was closed. Although we were unable to conclude whether enriching for a subset of second/third line pancreatic cancer patients treated with a Src inhibitor based on a biomarker would improve 6-month survival, we demonstrate that testing pancreatic tumor samples for a biomarker-driven, multicenter study in metastatic pancreas cancer is feasible