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  1. Lynch Syndrome

    Science.gov (United States)

    ... colon cancer may include surgery, chemotherapy and radiation therapy. Cancer screening for people with Lynch syndrome If you ... et al. Milestones of Lynch syndrome: 1895-2015. Nature Reviews Cancer. http://www.nature.com/nrc/journal/vaop/ncurrent/ ...

  2. Diagnosing Lynch Syndrome

    LENUS (Irish Health Repository)

    Gleeson, J

    2016-11-01

    Lynch Syndrome, also known as Hereditary Non-Polyposis Colorectal Cancer (HNPCC), is a hereditary condition that increases an individual’s risk of developing a constellation of cancers. These most commonly arise in the colon, but also involve other solid organs such as the endometrium and ovaries in women, the stomach, brain and the skin. Ireland’s small population offers an opportunity to identify all those with Lynch Syndrome (LS) in the country, which would represent a powerful preventive opportunity to meaningfully impact on the incidence of cancer in Ireland.

  3. Lynch Syndrome revision.

    Directory of Open Access Journals (Sweden)

    Sila Castellón Mortera

    2013-07-01

    Full Text Available The literature regarding colon`s adenocarcinoma hereditary no poliposico or Lynch Syndrome is reviewed. The clinical characteristics, genetics and histologycal of colon´s adenocarcinoma hereditary, no poliposico are pointed out, so as the updated criteria approved in Amsterdam, for the diagnostic of patients with this Syndrome. The therapeutics is updated.

  4. Unusual presentation of Lynch Syndrome

    Directory of Open Access Journals (Sweden)

    Yu Veronica PCC

    2009-06-01

    Full Text Available Abstract Lynch Syndrome/HNPCC is a syndrome of cancer predisposition linked to inherited mutations of genes participating in post-replicative DNA mismatch repair (MMR. The spectrum of cancer associated with Lynch Syndrome includes tumours of the colorectum, endometrium, ovary, upper gastrointestinal tract and the urothelium although other cancers are rarely described. We describe a family of Lynch Syndrome with an hMLH1 mutation, that harbours an unusual tumour spectrum and its diagnostic and management challenges.

  5. Genetic testing for Lynch syndrome: family communication and motivation

    NARCIS (Netherlands)

    C.H.M. Leenen (Celine); M.D. Heijer (Mariska den); C.A. van der Meer (Conny); E.J. Kuipers (Ernst); M.E. van Leerdam (Monique); A. Wagner (Anja)

    2016-01-01

    textabstractCurrent genetic counselling practice for Lynch syndrome (LS) relies on diagnosed index patients to inform their biological family about LS, referred to as the family-mediated approach. The objective of this study was to evaluate this approach and to identify factors influencing the uptak

  6. Lynch syndrome-associated neoplasms

    DEFF Research Database (Denmark)

    Shia, Jinru; Holck, Susanne; Depetris, Giovanni;

    2013-01-01

    of interacting developments from the disciplines of clinical oncology, pathology, and molecular genetics, with each development serving to guide or enhance the next. The advancement of our understanding about the pathology of Lynch syndrome associated tumors exemplifies such intimate interplay among disciplines....... Today, accumulative knowledge has enabled surgical pathologists to detect tumors that are likely to be associated with Lynch syndrome, and the pathologist is playing an increasingly more important role in the care of these patients. The pathologist's ability is afforded primarily by information gained...... of such information. This article provides an overview of the development of histopathology and immunohistochemistry in Lynch syndrome-associated tumors, particularly in colorectal and endometrial cancers, and outlines the issues and current status of these specific pathologic aspects in not only the major tumors...

  7. Surveillance for urinary tract cancer in Lynch syndrome

    DEFF Research Database (Denmark)

    Bernstein, Inge Thomsen; Myrhøj, Torben

    2013-01-01

    Hereditary non-polyposis colorectal cancer (HNPCC) is an inherited multiorgan cancer syndrome, which when caused by a germline mutation in the mismatch repair (MMR) genes is known as Lynch syndrome (LS). Mutation carriers are at risk for developing cancers primarily in the colon, rectum and endom...

  8. [Founder mutation in Lynch syndrome].

    Science.gov (United States)

    Cajal, Andrea R; Piñero, Tamara A; Verzura, Alicia; Santino, Juan Pablo; Solano, Angela R; Kalfayan, Pablo G; Ferro, Alejandra; Vaccaro, Carlos

    2016-01-01

    Lynch syndrome is the most frequent syndrome in hereditary colorectal cancer, a family-specific deleterious mutations in genes encoding DNA reparation proteins: MLH1 (mutL homolog 1), MSH2, MSH6 (mutS homolog 2 y 6, respectively), PMS2 (PMS1 homolog 2, mismatch repair system component) y MUTYH (mutY DNA glycosylase). The c.2252_2253delAA, p.Lys751Serfs*3 mutation in MLH1 gene segregates with a haplotype reported in the northern region of Italy and whose origin was attributed to a founder effect. This mutation co-segregates with typical characteristics of Lynch syndrome, including early age at onset and multiple primary tumors in the same individual, a high frequency of pancreatic cancer, high microsatellite instability and lack of PMS2 expression. This report describes a mutation in an Argentinian patient with endometrioid adenocarcinoma of uterus. Her first-degree relatives had a history of colon cancer diagnosed before 50 years, fulfilling the Amsterdam Criteria I and Lynch syndrome II. The high pathogenicity associated to this mutation makes necessary the study of all members from families with hereditary cancer, allowing pre-symptomatic genetic diagnosis, early assessment and the instauration of preventive treatments.

  9. Quality of colonoscopy in Lynch syndrome.

    Science.gov (United States)

    Niv, Yaron; Moeslein, Gabriela; Vasen, Hans F A; Karner-Hanusch, Judith; Lubinsky, Jan; Gasche, Christoph

    2014-12-01

    Lynch syndrome (LS) accounts for 2 - 4 % of all colorectal cancers. Affected family members have a germline mutation in one of the DNA mismatch repair genes MLH1, PMS2, MSH2, or MSH6, and a lifetime risk for development of colorectal cancer of 25 - 75 %. Current guidelines recommend annual to biannual surveillance colonoscopy in mutation carriers. Several factors may predict failure to prevent interval cancer in LS: more lesions in the right colon; more flat ("non polypoid") and lateral growing polyps; small adenomas may already harbor high grade dysplasia or a high percentage of villous component and become advanced adenomas; there is a short duration of the adenoma - carcinoma sequence; synchronous lesions have high prevalence; patients are younger and less tolerant to colonoscopy (need more sedation); and repeated colonoscopies are needed for lifelong surveillance (patient experience is important for compliance). In order to prevent cancer in LS patients, surveillance colonoscopy should be performed in an endoscopic unit experienced with LS, every 1 - 2 years, starting at age 20 - 25 years, or 10 years younger than the age of first diagnosis in the family (whichever is first), and yearly after the age of 40 years. Colonoscopy in LS patients should be a very meticulous and precise procedure (i. e. taking sufficient withdrawal time, documentation of such warranted), with removal of all of the polyps, special attention to the right colon and alertness to flat lesions. Following quality indicators such as successful cleansing of the colon and removal of every polyp will probably improve prevention of interval cancers. At this moment, none of the new endoscopic techniques have shown convincing superiority over conventional high resolution white light colonoscopy.

  10. Is surveillance of the small bowel indicated for Lynch syndrome families?

    NARCIS (Netherlands)

    Kate, G.L. ten; Kleibeuker, J.H.; Nagengast, F.M.; Craanen, M.; Cats, A.; Menko, F.H.; Vasen, H.F.

    2007-01-01

    BACKGROUND: Small bowel cancer (SBC) is one of the tumours associated with Lynch syndrome (LS). To advise on screening for this tumour it is paramount to be informed about the lifetime risk. The aim of this study was to calculate the lifetime risk of SBC in LS and to identify possible risk factors.

  11. Is surveillance of the small bowel indicated for Lynch syndrome families?

    NARCIS (Netherlands)

    ten Kate, G. L.; Kleibeuker, J. H.; Nagengast, F. M.; Craanen, M.; Cats, A.; Menko, F. H.; Vasen, H. F. A.

    2007-01-01

    Background: Small bowel cancer (SBC) is one of the tumours associated with Lynch syndrome (LS). To advise on screening for this tumour it is paramount to be informed about the lifetime risk. The aim of this study was to calculate the lifetime risk of SBC in LS and to identify possible risk factors.

  12. Lynch syndrome: still not a familiar picture

    Directory of Open Access Journals (Sweden)

    Hes Frederik J

    2008-02-01

    Full Text Available Abstract Background Germ line mutations in mismatch repair genes underlie Lynch syndrome and predispose carriers for colorectal carcinoma and malignancies in many other organ systems. Case presentation A large Lynch syndrome family with 15 affected family members and involvement in 7 organs is reported. It illustrates a lack of awareness and knowledge about this hereditary tumor syndrome among doctors as well as patients. None of the described family members underwent presymptomatic screening on the basis of the family history. Conclusion Hereditary features, like young age at diagnosis, multiple tumors in multiple organs and a positive family history, should lead to timely referral of suspected cases for genetic counseling and diagnostics. For Lynch syndrome, these features can be found in the Amsterdam and Bethesda criteria. Subsequently, early identification of mutation carriers might have diminished, at least in part, the high and early morbidity and mortality observed in this family.

  13. The Lynch syndrome: a management dilemma.

    Science.gov (United States)

    Palumbo, Piergaspare; Amatucci, Chiara; Perotti, Bruno; Dezzi, Claudia; Girolami, Marco; Illuminati, Giulio; Angelici, Alberto M

    2013-05-01

    The case of a familial Lynch syndrome is reported. The criteria for early diagnosis, management and surveillance are briefly reviewed. A germline mutation of genes responsible for mismatch repair is at the basis of the Lynch syndrome. Carriers are predisposed to colorectal cancer and other tumors. Two members of the presently reported family developed colorectal cancer, whereas two others developed other neoplasms. The syndrome was confirmed in members of the same family with appropriate genetic workup. Clinical examination and endoscopy were consequently scheduled once-a-year. Given the high risk of neoplastic disease, such yearly controls can be proposed as the standard follow-up of this condition.

  14. Role for Genetic Anticipation in Lynch Syndrome

    DEFF Research Database (Denmark)

    Nilbert, Mef; Timshel, Susanne; Bernstein, Inge

    2009-01-01

    PURPOSE: Anticipation (ie, an earlier age at onset in successive generations) is linked to repeat expansion in neurodegenerative syndromes, whereas its role in hereditary cancer is unclear. We assessed anticipation in Lynch syndrome (hereditary nonpolyposis colorectal cancer [HNPCC]), in which DN...

  15. Novel Implications in Molecular Diagnosis of Lynch Syndrome

    Directory of Open Access Journals (Sweden)

    Raffaella Liccardo

    2017-01-01

    Full Text Available About 10% of total colorectal cancers are associated with known Mendelian inheritance, as Familial Adenomatous Polyposis (FAP and Lynch syndrome (LS. In these cancer types the clinical manifestations of disease are due to mutations in high-risk alleles, with a penetrance at least of 70%. The LS is associated with germline mutations in the DNA mismatch repair (MMR genes. However, the mutation detection analysis of these genes does not always provide informative results for genetic counseling of LS patients. Very often, the molecular analysis reveals the presence of variants of unknown significance (VUSs whose interpretation is not easy and requires the combination of different analytical strategies to get a proper assessment of their pathogenicity. In some cases, these VUSs may make a more substantial overall contribution to cancer risk than the well-assessed severe Mendelian variants. Moreover, it could also be possible that the simultaneous presence of these genetic variants in several MMR genes that behave as low risk alleles might contribute in a cooperative manner to increase the risk of hereditary cancer. In this paper, through a review of the recent literature, we have speculated a novel inheritance model in the Lynch syndrome; this could pave the way toward new diagnostic perspectives.

  16. Genetic testing for Lynch syndrome: family communication and motivation.

    Science.gov (United States)

    Leenen, Celine H M; Heijer, Mariska den; van der Meer, Conny; Kuipers, Ernst J; van Leerdam, Monique E; Wagner, Anja

    2016-01-01

    Current genetic counselling practice for Lynch syndrome (LS) relies on diagnosed index patients to inform their biological family about LS, referred to as the family-mediated approach. The objective of this study was to evaluate this approach and to identify factors influencing the uptake of genetic testing for LS. In 59 mutation carriers, 70 non carriers and 16 non-tested relatives socio-demographic characteristics, family communication regarding LS, experiences and attitudes towards the family-mediated approach and motivations for genetic testing, were assessed. The majority of all respondents (73 %) were satisfied with the family-mediated approach. Nevertheless, 59 % of the respondents experienced informing a family member and 57 % being informed by a family member as burdensome. Non-tested differed from tested respondents, in that they were younger, less closely related to the index patient and a lower proportion had children. The most important reasons for declining genetic testing were (1) anticipating problems with life insurance and mortgage, (2) being content with life as it is, and (3) not experiencing any physical complaints. In conclusion, the majority of respondents consider the current family-mediated information procedure acceptable, although the provision of information on LS by relatives may be burdensome. Special attention should be paid to communication of LS to more distant relatives.

  17. Dietary patterns and colorectal adenomas in Lynch syndrome: the GEOLynch cohort study

    NARCIS (Netherlands)

    Botma, A.; Vasen, H.F.; Duijnhoven, F.J.B. van; Kleibeuker, J.H.; Nagengast, F.M.; Kampman, E.

    2013-01-01

    BACKGROUND: Patients with Lynch syndrome (LS) have a high risk of developing colorectal cancer due to mutations in mismatch repair genes. Because dietary factors, alone and in combination, influence sporadic colorectal carcinogenesis, the association of dietary patterns with colorectal adenomas in L

  18. Dietary Patterns and Colorectal Adenomas in Lynch Syndrome The GEOLynch Cohort Study

    NARCIS (Netherlands)

    Botma, Akke; Vasen, Hans F. A.; van Duijnhoven, Franzel J. B.; Kleibeuker, Jan H.; Nagengast, Fokko M.; Kampman, Ellen

    2013-01-01

    BACKGROUND: Patients with Lynch syndrome (LS) have a high risk of developing colorectal cancer due to mutations in mismatch repair genes. Because dietary factors, alone and in combination, influence sporadic colorectal carcinogenesis, the association of dietary patterns with colorectal adenomas in L

  19. Mutation spectrum in South American Lynch syndrome families

    DEFF Research Database (Denmark)

    Dominguez-Valentin, Mev; Nilbert, Mef; Wernhoff, Patrik;

    2013-01-01

    Genetic counselling and testing for Lynch syndrome have recently been introduced in several South American countries, though yet not available in the public health care system.......Genetic counselling and testing for Lynch syndrome have recently been introduced in several South American countries, though yet not available in the public health care system....

  20. Management of extracolonic tumours in patients with Lynch syndrome

    NARCIS (Netherlands)

    Koornstra, Jan J; Mourits, Marian Je; Sijmons, Rolf H; Leliveld-Kors, Anna; Hollema, Harry; Kleibeuker, Jan H

    2009-01-01

    Hereditary nonpolyposis colorectal cancer, or Lynch syndrome, is responsible for 2-3% of all colorectal cancers. Lynch syndrome is also associated with a high risk of extracolonic cancers, including endometrial, stomach, small bowel, pancreas, biliary tract, ovary, urinary tract, brain, and skin can

  1. Role for Genetic Anticipation in Lynch Syndrome

    DEFF Research Database (Denmark)

    Nilbert, Mef; Timshel, Susanne; Bernstein, Inge

    2009-01-01

    parent-child pairs in which age at the first cancer diagnosis was assessed. A paired t-test and a specifically developed bivariate model were used to assess a possible role of anticipation. RESULTS: Both methods revealed anticipation with children developing cancer mean 9.8 years (P ... parents using the paired t-test and 5.5 years (P ... to initiate surveillance programs at young age. It should also stimulate research into the genetic mechanisms that determine age at onset and whether the genetic instability that characterizes Lynch syndrome can be linked to anticipation....

  2. Lynch syndrome-associated extracolonic tumors are rare in two extended families with the same EPCAM deletion

    NARCIS (Netherlands)

    Lynch, H.T.; Riegert-Johnson, D.L.; Snyder, C.; Lynch, J.F.; Hagenkord, J.; Boland, C.R.; Rhees, J.; Thibodeau, S.N.; Boardman, L.A.; Davies, J.; Kuiper, R.P.; Hoogerbrugge, N.; Ligtenberg, M.J.L.

    2011-01-01

    OBJECTIVES: The Lynch syndrome (LS) is an inherited cancer syndrome showing a preponderance of colorectal cancer (CRC) in context with endometrial cancer and several other extracolonic cancers, which is due to pathogenic mutations in the mismatch repair (MMR) genes, MLH1, MSH2, MSH6, and PMS2. Some

  3. Recurrence and Variability of Germline EPCAM Deletions in Lynch Syndrome

    NARCIS (Netherlands)

    Kuiper, Roland P.; Vissers, Lisenka E. L. M.; Venkatachalam, Ramprasath; Bodmer, Danielle; Hoenselaar, Eveline; Goossens, Monique; Haufe, Aline; Kamping, Eveline; Niessen, Renee C.; Hogervorst, Frans B. L.; Gille, Johan J. P.; Redeker, Bert; Tops, Carli M. J.; van Gijn, Marielle E.; van den Ouweland, Ans M. W.; Rahner, Nils; Steinke, Verena; Kahl, Philip; Holinski-Feder, Elke; Morak, Monika; Kloor, Matthias; Stemmler, Susanne; Betz, Beate; Hutter, Pierre; Bunyan, David J.; Syngal, Sapna; Culver, Julie O.; Graham, Tracy; Chan, Tsun L.; Nagtegaal, Iris D.; van Krieken, J. Han J. M.; Schackert, Hans K.; Hoogerbrugge, Nicoline; van Kessel, Ad Geurts; Ligtenberg, Marjolijn J. L.

    2011-01-01

    Recently, we identified 3' end deletions in the EPCAM gene as a novel cause of Lynch syndrome. These truncating EPCAM deletions cause allele-specific epigenetic silencing of the neighboring DNA mismatch repair gene MSH2 in tissues expressing EPCAM. Here we screened a cohort of unexplained Lynch-like

  4. Papillary thyroid carcinoma (PTC) in Lynch syndrome: Report of two cases and discussion on Lynch syndrome behaviour and genetics.

    Science.gov (United States)

    Pelizzo, M R; Pennelli, G; Zane, M; Galuppini, F; Colletti, P M; Merante Boschin, I; Rubello, D

    2015-08-01

    We present here two cases of papillary thyroid carcinoma (PTC) in patients affected by Lynch syndrome (LS). The first case is a 47-year-old woman with typical hereditary non-polyposis colorectal cancer (HNPCC) syndrome, reported with endometrial and ovarian carcinoma at age 43, and colon cancer at age 45. The patient underwent total thyroidectomy and central node dissection in 2007, at 47years old, with a histological diagnosis of PTC (T1aN1a). Molecular genetics showed a germ-line mutation of the MLH1 gene, 1858 G>T(E620X), with substitution of glycine with a stop codon at position 620. This mutation has pathogenetic significance and was considered responsible for the various tumours of the HNPCC spectrum. In particular, in the same kindred, spanning 5 generations, there were 5 members with colorectal cancer, 4 with endometrial cancer, 3 with gastric and 2 with breast cancer. The second case is a 34-year-old man with typical HNPCC syndrome with colonic resection for colon cancer at age 21. The patient underwent total thyroidectomy with central and lateral node dissection in 2010, at age 34, with a histological diagnosis of PTC with nodal metastases (pT4N1b). Molecular genetic analysis showed a germ-line mutation of the MSH2 gene (thymine insertion at position 907). This mutation had pathogenetic significance and was considered responsible for HNPCC development. Two similar cases have been reported: a 39-year-old woman, and a 44-year-old woman, affected by HNPCC syndrome, with anaplastic thyroid carcinoma and undifferentiated thyroid carcinoma, respectively. We reviewed the Lynch syndrome literature on the history, genetics and expanding tumour spectrum of this condition. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  5. Glioblastomas, astrocytomas and oligodendrogliomas linked to Lynch syndrome

    DEFF Research Database (Denmark)

    Therkildsen, C; Ladelund, S; Rambech, E

    2015-01-01

    BACKGROUND AND PURPOSE: Brain tumors represent a rare and relatively uncharacterized tumor type in Lynch syndrome. METHODS: The national Danish Hereditary Nonpolyposis Colorectal Cancer Register was utilized to estimate the cumulative life-time risk for brain tumors in Lynch syndrome...... staining suggestive of the IDH1 R132H mutation. CONCLUSION: In Lynch syndrome brain tumors occurred in 14% of the families with significantly higher risks for individuals with MSH2 gene mutations and development of childhood brain tumors in individuals with constitutional MMR defects....

  6. Body Mass Index Increases Risk of Colorectal Adenomas in Men With Lynch Syndrome : The GEOLynch Cohort Study

    NARCIS (Netherlands)

    Botma, Akke; Nagengast, Fokko M.; Braem, Marieke G. M.; Hendriks, Jan C. M.; Kleibeuker, Jan H.; Vasen, Hans F. A.; Kampman, Ellen

    2010-01-01

    Purpose High body mass index (BMI) is an established risk factor for sporadic colorectal cancer. Still, the influence of BMI on hereditary colorectal cancer (eg, Lynch syndrome [LS]), is unknown. The objective of this study was to assess whether BMI is associated with colorectal adenoma occurrence

  7. Revised guidelines for the clinical management of Lynch syndrome (HNPCC) : Recommendations by a group of European experts

    NARCIS (Netherlands)

    Vasen, Hans F. A.; Blanco, Ignacio; Aktan-Collan, Katja; Gopie, Jessica P.; Alonso, Angel; Aretz, Stefan; Bernstein, Inge; Bertario, Lucio; Burn, John; Capella, Gabriel; Colas, Chrystelle; Engel, Christoph; Frayling, Ian M.; Genuardi, Maurizio; Heinimann, Karl; Hes, Frederik J.; Hodgson, Shirley V.; Karagiannis, John A.; Lalloo, Fiona; Lindblom, Annika; Mecklin, Jukka-Pekka; Moller, Pal; Myrhoj, Torben; Nagengast, Fokko M.; Parc, Yann; de Leon, Maurizio Ponz; Renkonen-Sinisalo, Laura; Sampson, Julian R.; Stormorken, Astrid; Sijmons, Rolf H.; Tejpar, Sabine; Thomas, Huw J. W.; Rahner, Nils; Wijnen, Juul T.; Jaervinen, Heikki Juhani; Moeslein, Gabriela; Jarvinen, H.J.; Moslein, G.

    2013-01-01

    Lynch syndrome (LS) is characterised by the development of colorectal cancer, endometrial cancer and various other cancers, and is caused by a mutation in one of the mismatch repair genes: MLH1, MSH2, MSH6 or PMS2. In 2007, a group of European experts (the Mallorca group) published guidelines for th

  8. The Identification of Lynch Syndrome in British Columbia

    Directory of Open Access Journals (Sweden)

    Carol M Cremin

    2009-01-01

    Full Text Available OBJECTIVE: To determine the prevalence of Lynch syndrome mutations in a Canadian hereditary cancer clinic population, and to determine the effectiveness of the program’s referral criteria and testing algorithm.

  9. Whole Gene Capture Analysis of 15 CRC Susceptibility Genes in Suspected Lynch Syndrome Patients.

    Directory of Open Access Journals (Sweden)

    Anne M L Jansen

    Full Text Available Lynch Syndrome (LS is caused by pathogenic germline variants in one of the mismatch repair (MMR genes. However, up to 60% of MMR-deficient colorectal cancer cases are categorized as suspected Lynch Syndrome (sLS because no pathogenic MMR germline variant can be identified, which leads to difficulties in clinical management. We therefore analyzed the genomic regions of 15 CRC susceptibility genes in leukocyte DNA of 34 unrelated sLS patients and 11 patients with MLH1 hypermethylated tumors with a clear family history.Using targeted next-generation sequencing, we analyzed the entire non-repetitive genomic sequence, including intronic and regulatory sequences, of 15 CRC susceptibility genes. In addition, tumor DNA from 28 sLS patients was analyzed for somatic MMR variants.Of 1979 germline variants found in the leukocyte DNA of 34 sLS patients, one was a pathogenic variant (MLH1 c.1667+1delG. Leukocyte DNA of 11 patients with MLH1 hypermethylated tumors was negative for pathogenic germline variants in the tested CRC susceptibility genes and for germline MLH1 hypermethylation. Somatic DNA analysis of 28 sLS tumors identified eight (29% cases with two pathogenic somatic variants, one with a VUS predicted to pathogenic and LOH, and nine cases (32% with one pathogenic somatic variant (n = 8 or one VUS predicted to be pathogenic (n = 1.This is the first study in sLS patients to include the entire genomic sequence of CRC susceptibility genes. An underlying somatic or germline MMR gene defect was identified in ten of 34 sLS patients (29%. In the remaining sLS patients, the underlying genetic defect explaining the MMRdeficiency in their tumors might be found outside the genomic regions harboring the MMR and other known CRC susceptibility genes.

  10. Prevalence of somatic mutl homolog 1 promoter hypermethylation in Lynch syndrome colorectal cancer.

    Science.gov (United States)

    Moreira, Leticia; Muñoz, Jenifer; Cuatrecasas, Míriam; Quintanilla, Isabel; Leoz, Maria Liz; Carballal, Sabela; Ocaña, Teresa; López-Cerón, María; Pellise, Maria; Castellví-Bel, Sergi; Jover, Rodrigo; Andreu, Montserrat; Carracedo, Angel; Xicola, Rosa Maria; Llor, Xavier; Boland, Clement Richard; Goel, Ajay; Castells, Antoni; Balaguer, Francesc

    2015-05-01

    Colorectal cancers (CRCs) that have microsatellite instability (MSI) and mutL homolog 1 (MLH1) immunoloss are observed in 3 clinical scenarios: Lynch syndrome (LS), sporadic MSI CRC, and Lynch-like syndrome (LLS). v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutational analysis is used to differentiate LS from sporadic MSI CRC. The role of MLH1 promoter methylation status for the differential diagnosis of these clinical forms is not well established. The objectives of this study were: 1) to analyze MLH1 promoter methylation in MLH1-deficient CRCs by pyrosequencing, and 2) to assess its role in the differential diagnosis of MLH1-deficient CRCs. In total, 165 CRCs were analyzed, including LS (n = 19), MSI BRAF-mutated CRC (n = 37), MSI BRAF wild-type CRC (n = 60), and a control group of CRCs without MSI (microsatellite stable [MSS] CRC; n = 49). MLH1 promoter methylation status was analyzed by pyrosequencing, and the ability of different strategies to identify LS was assessed. The average ± standard deviation methylation in LS (9% ± 7%) was significantly lower than that in MSI BRAF-mutated CRC (42% ± 17%; P Cancer Society.

  11. A Systematic Review on the Existing Screening Pathways for Lynch Syndrome Identification

    Directory of Open Access Journals (Sweden)

    Alessia Tognetto

    2017-09-01

    Full Text Available BackgroundLynch syndrome (LS is the most common hereditary colon cancer syndrome, accounting for 3–5% of colorectal cancer (CRC cases, and it is associated with the development of other cancers. Early detection of individuals with LS is relevant, since they can take advantage of life-saving intensive care surveillance. The debate regarding the best screening policy, however, is far from being concluded. This prompted us to conduct a systematic review of the existing screening pathways for LS.MethodsWe performed a systematic search of MEDLINE, ISI Web of Science, and SCOPUS online databases for the existing screening pathways for LS. The eligibility criteria for inclusion in this review required that the studies evaluated a structured and permanent screening pathway for the identification of LS carriers. The effectiveness of the pathways was analyzed in terms of LS detection rate.ResultsWe identified five eligible studies. All the LS screening pathways started from CRC cases, of which three followed a universal screening approach. Concerning the laboratory procedures, the pathways used immunohistochemistry and/or microsatellite instability testing. If the responses of the tests indicated a risk for LS, the genetic counseling, performed by a geneticist or a genetic counselor, was mandatory to undergo DNA genetic testing. The overall LS detection rate ranged from 0 to 5.2%.ConclusionThis systematic review reported different existing pathways for the identification of LS patients. Although current clinical guidelines suggest to test all the CRC cases to identify LS cases, the actual implementation of pathways for LS identification has not been realized. Large-scale screening programs for LS have the potential to reduce morbidity and mortality for CRC, but coordinated efforts in educating all key stakeholders and addressing public needs are still required.

  12. The Use of Social Media to Recruit Participants With Rare Conditions: Lynch Syndrome as an Example.

    Science.gov (United States)

    Burton-Chase, Allison M; Parker, Wendy M; Hennig, Kelsey; Sisson, Faith; Bruzzone, Linda L

    2017-01-23

    Social media is increasingly being used as a means of recruiting participants, particularly for investigators whose areas of interest involve rare conditions or hard-to-reach populations. However, much of the literature to date has focused on paid advertisement recruitment. We used Lynch syndrome (LS), a rare hereditary cancer syndrome, as a model to demonstrate the successful partnership between researchers and a Web-based patient education and advocacy organization to facilitate participant recruitment. Recruitment was undertaken in partnership with Lynch Syndrome International (LSI), an advocacy organization with a strong social media presence. After LSI published our study information, participants followed up via email or phone call. Following prescreening and consent, interested and eligible participants were then sent a secure survey link. Within 36 hours of a single Facebook post by the site administrators for LSI, over 150 individuals responded via phone or email. Sixty-five individuals were sent the survey link and 57 individuals completed the survey (88% response rate). Of note, these 57 individuals were geographically diverse within the Unites States, representing LS patients from 26 different states. This approach has several advantages, including recruitment through a trusted source outside of a clinical setting, higher response rates, and cost-effectiveness with a small research team in a relatively short amount of time. Overall, social media recruitment with a trusted online partner can be highly effective in hard-to-reach clinical populations, such as patients with LS. However, this approach requires additional effort for eligibility screening.

  13. Decrease in mortality in Lynch syndrome families because of surveillance.

    NARCIS (Netherlands)

    Jong, A.E. de; Hendriks, Y.M.; Kleibeuker, J.H.; Boer, S.Y. de; Cats, A.; Griffioen, G.; Nagengast, F.M.; Nelis, F.G.; Rookus, M.A.; Vasen, H.F.

    2006-01-01

    BACKGROUND & AIMS: Lynch syndrome family members have a high risk of developing colorectal (CRC), endometrial (EC), and other cancers. A large-scale surveillance program was introduced in The Netherlands in the late 1980s. The aims of the study were to evaluate the effectiveness of this program by a

  14. Role of new endoscopic techniques in Lynch syndrome

    NARCIS (Netherlands)

    Haanstra, Jasmijn F.; Kleibeuker, Jan H.; Koornstra, Jan J.

    2013-01-01

    Lynch syndrome, or hereditary nonpolyposis colorectal cancer (HNPCC), is the most common hereditary condition predisposing for colorectal cancer. International guidelines recommend surveillance of the colorectum by colonoscopy every 1-2 years starting at the age of 20-25 years. This has been shown t

  15. Sense of coherence and self-concept in Lynch syndrome

    DEFF Research Database (Denmark)

    Petersen, Helle Vendel; Ladelund, Steen; Carlsson, Christina

    2013-01-01

    Most individuals who learn about hereditary cancer manage well, but identification of subgroups who find this knowledge burdening would allow psychosocial intervention. The objective of the study was to assess sense of coherence (SOC) in individuals with Lynch syndrome with comparison to a genera...... population and correlation to self-concept....

  16. Risks of lynch syndrome cancers for msh6 mutation carriers

    NARCIS (Netherlands)

    L. Baglietto (Laura); N.M. Lindor (Noralane); J.G. Dowty (James); D.M. White (Darren); A. Wagner (Anja); E.B. Gómez García (Encarna); A.H.J.T. Vriends (Anette); N.R. Cartwright (Nicola); R.A. Barnetson (Rebecca); S.M. Farrington (Susan); A. Tenesa (Albert); H. Hampel (Heather); D. Buchanan (Daniel); S. Arnold (Sven); J. Young (Joanne); M.D. Walsh (Michael); J. Jass (Jeremy); F.A. Macrae (Finlay); Y. Antill (Yoland); I.M. Winship (Ingrid); G.G. Giles (Graham); J. Goldblatt (Jack); S. Parry (Susan); G. Suthers (Graeme); B. Leggett (Barbara); M. Butz (Malinda); M. Aronson (Melyssa); J.N. Poynter (Jenny); J.A. Baron (John); L. Le Marchand (Loic); R. Haile (Robert); S. Gallinger (Steve); J.L. Hopper (John); J. Potter (John); A. de La Chapelle (Albert); H. Vasen (Hans); M.G. Dunlop (Malcolm); S.N. Thibodeau (Stephen); M.A. Jenkins (Mark)

    2010-01-01

    textabstractBackground: Germline mutations in MSH6 account for 10%-20% of Lynch syndrome colorectal cancers caused by hereditary DNA mismatch repair gene mutations. Because there have been only a few studies of mutation carriers, their cancer risks are uncertain. Methods: We identified 113 families

  17. Dietary B vitamin and methionine intake and MTHFR C677T genotype on risk of colorectal tumors in Lynch syndrome : the GEOLynch cohort study

    NARCIS (Netherlands)

    Jung, Audrey Y.; van Duijnhoven, Franzel J. B.; Nagengast, Fokko M.; Botma, Akke; Heine-Broring, Renate C.; Kleibeuker, Jan H.; Vasen, Hans F. A.; Harryvan, Jan L.; Winkels, Renate M.; Kampman, Ellen

    Dietary intake of B vitamins and methionine, essential components of DNA synthesis and methylation pathways, may influence colorectal tumor (CRT) development. The impact of B vitamins on colorectal carcinogenesis in individuals with Lynch syndrome (LS) is unknown but is important given their high

  18. Dietary B vitamin and methionine intake and MTHFR C677T genotype on risk of colorectal tumors in Lynch syndrome : the GEOLynch cohort study

    NARCIS (Netherlands)

    Jung, Audrey Y.; van Duijnhoven, Franzel J. B.; Nagengast, Fokko M.; Botma, Akke; Heine-Broring, Renate C.; Kleibeuker, Jan H.; Vasen, Hans F. A.; Harryvan, Jan L.; Winkels, Renate M.; Kampman, Ellen

    2014-01-01

    Dietary intake of B vitamins and methionine, essential components of DNA synthesis and methylation pathways, may influence colorectal tumor (CRT) development. The impact of B vitamins on colorectal carcinogenesis in individuals with Lynch syndrome (LS) is unknown but is important given their high li

  19. Recognition of Lynch Syndrome Amongst Newly Diagnosed Colorectal Cancers at St. Paul’s Hospital

    Directory of Open Access Journals (Sweden)

    Steven Pi

    2017-01-01

    Full Text Available Background. Lynch Syndrome (LS is the most common cause of inherited colorectal cancer (CRC. In British Columbia, most centres still use clinical criteria (Amsterdam II, Revised Bethesda, or the BC Cancer Agency’s criteria to determine who should undergo further first-line testing in the form of microsatellite instability or immunohistochemistry staining. Given the limitations with this strategy, LS is thought to be underrecognized. Objective. To investigate whether LS is truly underrecognized when compared to the reported prevalence. Methods. A retrospective chart review of all CRC cases diagnosed at St. Paul’s Hospital from 2010 to 2013 was conducted. Results. 246 patients met inclusion criteria. 76% (83/109 with a family history of malignancy were unable to recall the specific malignancy or age of diagnosis. 18% (43/235 were only asked about a history of gastrointestinal related malignancy and 26% (65/246 met at least one of the three criteria but only 21% (13/63 received further investigation. Only 1.6% (4/246 had LS compared to the reported prevalence of 2–5% of all CRC cases. Conclusion. This data supports our hypothesis that LS is underrecognized. Issues at the patient, physician, and systems level need to be evaluated to determine where the limitations preventing appropriate testing are occurring.

  20. Estimating successive cancer risks in Lynch Syndrome families using a progressive three-state model.

    Science.gov (United States)

    Choi, Yun-Hee; Briollais, Laurent; Green, Jane; Parfrey, Patrick; Kopciuk, Karen

    2014-02-20

    Lynch Syndrome (LS) families harbor mutated mismatch repair genes,which predispose them to specific types of cancer. Because individuals within LS families can experience multiple cancers over their lifetime, we developed a progressive three-state model to estimate the disease risk from a healthy (state 0) to a first cancer (state 1) and then to a second cancer (state 2). Ascertainment correction of the likelihood was made to adjust for complex sampling designs with carrier probabilities for family members with missing genotype information estimated using their family's observed genotype and phenotype information in a one-step expectation-maximization algorithm. A sandwich variance estimator was employed to overcome possible model misspecification. The main objective of this paper is to estimate the disease risk (penetrance) for age at a second cancer after someone has experienced a first cancer that is also associated with a mutated gene. Simulation study results indicate that our approach generally provides unbiased risk estimates and low root mean squared errors across different family study designs, proportions of missing genotypes, and risk heterogeneities. An application to 12 large LS families from Newfoundland demonstrates that the risk for a second cancer was substantial and that the age at a first colorectal cancer significantly impacted the age at any LS subsequent cancer. This study provides new insights for developing more effective management of mutation carriers in LS families by providing more accurate multiple cancer risk estimates.

  1. The genetic basis of Lynch syndrome and its implications for clinical practice and risk management.

    Science.gov (United States)

    Cohen, Stephanie A; Leininger, Anna

    2014-01-01

    Lynch syndrome is the most common cause of hereditary colon cancer, and accounts for as much as 3% of all colon and endometrial cancers. The identification and management of individuals with Lynch syndrome have evolved over the past 20 years, yet the syndrome remains vastly underdiagnosed. It is important for clinicians to recognize individuals and families who are at risk in order to be able to manage them appropriately and reduce their morbidity and mortality from this condition. This review will touch on the history of Lynch syndrome, the current knowledge of genotype-phenotype correlations, the cancers associated with Lynch syndrome, and management of individuals who are gene carriers.

  2. Management strategies in Lynch syndrome and familial adenomatous polyposis: a national healthcare survey in Japan.

    Science.gov (United States)

    Yamano, Tomoki; Hamanaka, Michiko; Babaya, Akihito; Kimura, Kei; Kobayashi, Masayoshi; Fukumoto, Miki; Tsukamoto, Kiyoshi; Noda, Masafumi; Matsubara, Nagahide; Tomita, Naohiro; Sugihara, Kenichi

    2017-02-01

    Lynch syndrome (LS) and familial adenomatous polyposis (FAP) are major sources of hereditary colorectal cancer (CRC) and are associated with other malignancies. There is some heterogeneity in management strategies in Japan. We undertook a survey of management of hereditary CRC in hospitals that are members of the Japan Society of Colorectal Cancer Research. One hundred and ninety departments responded, of which 127 were from designated cancer care hospitals (DCCHs) according to the Japanese government. There were 25 488 operations for CRC in these departments in 2015. The DCCHs performed better with regard to usage of Japan Society of Colorectal Cancer Research guidelines, referring new CRC patients for LS screening, and having in-house genetic counselors and knowledge of treatment for LS. There were 174 patients diagnosed with LS and 602 undergoing follow-up in 2011-2015, which is fewer than the number expected from CRC operations in 2015. These numbers were not affected by whether the institution was a DCCH. Universal screening for LS was carried out in 8% of the departments. In contrast, 541 patients were diagnosed with FAP and 273 received preventive proctocolectomy/colectomy in 2011-2015. The DCCH departments undertook more surgery than non-DCCH departments, although most of the management, including surgical procedures and use of non-steroidal anti-inflammatory drugs, was similar. Management of desmoid tumor in the abdominal cavity differed according to the number of patients treated. In conclusion, there was heterogeneity in management of LS but not FAP. Most patients with LS may be overlooked and universal screening for LS is not common in Japan.

  3. Surveillance colonoscopy practice in Lynch syndrome in the Netherlands: A nationwide survey

    Institute of Scientific and Technical Information of China (English)

    Jan J Koornstra; Hans FA Vasen

    2007-01-01

    Lynch syndrome, or hereditary nonpolyposis colorectal cancer (HNPCC), is the most common genetic disorder predisposing to colorectal cancer. As regular colonoscopic surveillance has been shown to reduce the incidence of colorectal cancer, this strategy is recommended worldwide. Recently, several advances in colonoscopic techniques have improved detection rates of neoplasia in Lynch syndrome. In this nationwide survey, we evaluated current surveillance colonoscopy practices for Lynch syndrome in the Netherlands and the extent to which advanced techniques have been adopted in routine clinical practice.

  4. Fertility and apparent genetic anticipation in Lynch syndrome.

    Science.gov (United States)

    Stupart, Douglas; Win, Aung Ko; Jenkins, Mark; Winship, Ingrid M; Goldberg, Paul; Ramesar, Rajkumar

    2014-09-01

    Genetic anticipation is the phenomenon in which age of onset of an inherited disorder decreases in successive generations. Inconsistent evidence suggests that this occurs in Lynch syndrome. A possible cause for apparent anticipation is fecundity bias, which occurs if the disease adversely affects fertility. The purpose of this study was to determine the effect of age of diagnosis of colorectal cancer (CRC) on lifetime fertility in Lynch syndrome, and whether this can falsely create the appearance of genetic anticipation. A computer model simulated age of diagnosis of CRC in hypothetical Lynch syndrome carriers and their offspring. The model assumed similar age distribution of CRC across generations (i.e. that there was no true anticipation). Age distribution of CRC diagnosis, and lifetime fertility rates (grouped by age of diagnosis of CRC) were determined from the Australasian Colorectal Cancer Family Registry (ACCFR). Apparent anticipation was calculated by comparing ages of diagnosis of CRC in affected parent-child pairs. A total of 1,088 patients with CRC were identified from the ACCFR. Total lifetime (cohort) fertility was related to age of diagnosis of CRC (correlation coefficient 0.13, P = 0.0001). In the simulation, apparent anticipation was 1.8 ± 0.54 years (P = 0.0044). Observed apparent anticipation in the ACCFR cohort was 4.8 ± 1.73 years (P = 0.0064). There was no difference in apparent anticipation between the simulate d and observed parent-child pairs (P = 0.89). The appearance of genetic anticipation in Lynch syndrome can be falsely created due to changes in fertility.

  5. The Use of Social Media to Recruit Participants With Rare Conditions: Lynch Syndrome as an Example

    Science.gov (United States)

    Parker, Wendy M; Hennig, Kelsey; Sisson, Faith; Bruzzone, Linda L

    2017-01-01

    Background Social media is increasingly being used as a means of recruiting participants, particularly for investigators whose areas of interest involve rare conditions or hard-to-reach populations. However, much of the literature to date has focused on paid advertisement recruitment. Objective We used Lynch syndrome (LS), a rare hereditary cancer syndrome, as a model to demonstrate the successful partnership between researchers and a Web-based patient education and advocacy organization to facilitate participant recruitment. Methods Recruitment was undertaken in partnership with Lynch Syndrome International (LSI), an advocacy organization with a strong social media presence. After LSI published our study information, participants followed up via email or phone call. Following prescreening and consent, interested and eligible participants were then sent a secure survey link. Results Within 36 hours of a single Facebook post by the site administrators for LSI, over 150 individuals responded via phone or email. Sixty-five individuals were sent the survey link and 57 individuals completed the survey (88% response rate). Of note, these 57 individuals were geographically diverse within the Unites States, representing LS patients from 26 different states. Conclusions This approach has several advantages, including recruitment through a trusted source outside of a clinical setting, higher response rates, and cost-effectiveness with a small research team in a relatively short amount of time. Overall, social media recruitment with a trusted online partner can be highly effective in hard-to-reach clinical populations, such as patients with LS. However, this approach requires additional effort for eligibility screening. PMID:28115298

  6. The mutational spectrum of Lynch syndrome in cyprus.

    Science.gov (United States)

    Loizidou, Maria A; Neophytou, Ioanna; Papamichael, Demetris; Kountourakis, Panteleimon; Vassiliou, Vassilios; Marcou, Yiola; Kakouri, Eleni; Ioannidis, Georgios; Philippou, Chrystalla; Spanou, Elena; Tanteles, George A; Anastasiadou, Violetta; Hadjisavvas, Andreas; Kyriacou, Kyriacos

    2014-01-01

    Lynch syndrome is the most common form of hereditary colorectal cancer and is caused by germline mutations in the mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2. Mutation carriers have an increased lifetime risk of developing colorectal cancer as well as other extracolonic tumours. The aim of the current study was to evaluate the frequency and distribution of mutations in the MLH1, MSH2 and MSH6 genes within a cohort of Cypriot families that fulfilled the revised Bethesda guidelines. The study cohort included 77 patients who fulfilled at least one of the revised Bethesda guidelines. Mutational analysis revealed the presence of 4 pathogenic mutations, 3 in the MLH1 gene and 1 in the MSH2 gene, in 5 unrelated individuals. It is noted that out of the 4 pathogenic mutations detected, one is novel (c.1610delG in exon 14 of the MLH1) and has been detected for the first time in the Cypriot population. Overall, the pathogenic mutation detection rate in our patient cohort was 7%. This percentage is relatively low but could be explained by the fact that the sole criterion for genetic screening was compliance to the revised Bethesda guidelines. Larger numbers of Lynch syndrome families and screening of the two additional predisposition genes, PMS2 and EPCAM, are needed in order to decipher the full spectrum of mutations associated with Lynch syndrome predisposition in Cyprus.

  7. Current Hypotheses on How Microsatellite Instability Leads to Enhanced Survival of Lynch Syndrome Patients

    Directory of Open Access Journals (Sweden)

    Kristen M. Drescher

    2010-01-01

    Full Text Available High levels of microsatellite instability (MSI-high are a cardinal feature of colorectal tumors from patients with Lynch Syndrome. Other key characteristics of Lynch Syndrome are that these patients experience fewer metastases and have enhanced survival when compared to patients diagnosed with microsatellite stable (MSS colorectal cancer. Many of the characteristics associated with Lynch Syndrome including enhanced survival are also observed in patients with sporadic MSI-high colorectal cancer. In this review we will present the current state of knowledge regarding the mechanisms that are utilized by the host to control colorectal cancer in Lynch Syndrome and why these same mechanisms fail in MSS colorectal cancers.

  8. 100 years lynch syndrome

    DEFF Research Database (Denmark)

    Bleiker, Eveline M A; Esplen, Mary Jane; Meiser, Bettina

    2013-01-01

    by an overview of important psychosocial issues identified in the past 20 years. The identification of mismatch repair genes in 1993-1994 made possible genetic counseling and testing for patients who had cancer and for potentially high-risk relatives without cancer. At that time, concerns were raised about......, reproductive technology utilization, and professional psychosocial support needs of members of families with LS. Finally, challenges for the future are discussed, including population screening and genomic testing....

  9. Lynch Syndrome Caused by Germline PMS2 Mutations

    DEFF Research Database (Denmark)

    Ten Broeke, Sanne W; Brohet, Richard M; Tops, Carli M

    2015-01-01

    . Standardized incidence ratios (SIRs) were calculated to estimate risks for other Lynch syndrome-associated cancers. RESULTS: The cumulative risk (CR) of CRC for male mutation carriers by age 70 years was 19%. The CR among female carriers was 11% for CRC and 12% for EC. The mean age of CRC development was 52......PURPOSE: The clinical consequences of PMS2 germline mutations are poorly understood compared with other Lynch-associated mismatch repair gene (MMR) mutations. The aim of this European cohort study was to define the cancer risk faced by PMS2 mutation carriers. METHODS: Data were collected from 98...... years, and there was a significant difference in mean age of CRC between the probands (mean, 47 years; range, 26 to 68 years) and other family members with a PMS2 mutation (mean, 58 years; range, 31 to 86 years; P

  10. Molecular testing for Lynch syndrome in people with colorectal cancer: systematic reviews and economic evaluation.

    Science.gov (United States)

    Snowsill, Tristan; Coelho, Helen; Huxley, Nicola; Jones-Hughes, Tracey; Briscoe, Simon; Frayling, Ian M; Hyde, Chris

    2017-09-01

    Inherited mutations in deoxyribonucleic acid (DNA) mismatch repair (MMR) genes lead to an increased risk of colorectal cancer (CRC), gynaecological cancers and other cancers, known as Lynch syndrome (LS). Risk-reducing interventions can be offered to individuals with known LS-causing mutations. The mutations can be identified by comprehensive testing of the MMR genes, but this would be prohibitively expensive in the general population. Tumour-based tests - microsatellite instability (MSI) and MMR immunohistochemistry (IHC) - are used in CRC patients to identify individuals at high risk of LS for genetic testing. MLH1 (MutL homologue 1) promoter methylation and BRAF V600E testing can be conducted on tumour material to rule out certain sporadic cancers. To investigate whether testing for LS in CRC patients using MSI or IHC (with or without MLH1 promoter methylation testing and BRAF V600E testing) is clinically effective (in terms of identifying Lynch syndrome and improving outcomes for patients) and represents a cost-effective use of NHS resources. Systematic reviews were conducted of the published literature on diagnostic test accuracy studies of MSI and/or IHC testing for LS, end-to-end studies of screening for LS in CRC patients and economic evaluations of screening for LS in CRC patients. A model-based economic evaluation was conducted to extrapolate long-term outcomes from the results of the diagnostic test accuracy review. The model was extended from a model previously developed by the authors. Ten studies were identified that evaluated the diagnostic test accuracy of MSI and/or IHC testing for identifying LS in CRC patients. For MSI testing, sensitivity ranged from 66.7% to 100.0% and specificity ranged from 61.1% to 92.5%. For IHC, sensitivity ranged from 80.8% to 100.0% and specificity ranged from 80.5% to 91.9%. When tumours showing low levels of MSI were treated as a positive result, the sensitivity of MSI testing increased but specificity fell. No end

  11. Development and validation of an instrument to measure the impact of genetic testing on self-concept in Lynch syndrome

    DEFF Research Database (Denmark)

    Esplen, M J; Stuckless, N; Gallinger, S

    2011-01-01

    with two dimensions identified through factor analysis: stigma/vulnerability and bowel symptom-related anxiety. The scale showed excellent reliability (Cronbach's α = 0.93), good convergent validity by a high correlation with impact of event scale (r(102) = 0.55, p self-esteem scale......Esplen MJ, Stuckless N, Gallinger S, Aronson M, Rothenmund H, Semotiuk K, Stokes J, Way C, Green J, Butler K, Petersen HV, Wong J. Development and validation of an instrument to measure the impact of genetic testing on self-concept in Lynch syndrome. A positive genetic test result may impact...... on a person's self-concept and affect quality of life. The purpose of the study was to develop a self-concept scale to measure such impact for individuals carrying mutations for a heritable colorectal cancer Lynch syndrome (LS). Two distinct phases were involved: Phase 1 generated specific colorectal self...

  12. Novel Mutations in MLH1 and MSH2 Genes in Mexican Patients with Lynch Syndrome

    Science.gov (United States)

    Moreno-Ortiz, Jose Miguel; Ayala-Madrigal, María de la Luz; Corona-Rivera, Jorge Román; Maciel-Gutiérrez, Víctor; Franco-Topete, Ramón Antonio; Armendáriz-Borunda, Juan; Pérez-Carbonell, Lucia; Rhees, Jennifer; Gutiérrez-Angulo, Melva

    2016-01-01

    Background. Lynch Syndrome (LS) is characterized by germline mutations in the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2. This syndrome is inherited in an autosomal dominant pattern and is characterized by early onset colorectal cancer (CRC) and extracolonic tumors. The aim of this study was to identify mutations in MMR genes in three Mexican patients with LS. Methods. Immunohistochemical analysis was performed as a prescreening method to identify absent protein expression. PCR, Denaturing High Performance Liquid Chromatography (dHPLC), and Sanger sequencing complemented the analysis. Results. Two samples showed the absence of nuclear staining for MLH1 and one sample showed loss of nuclear staining for MSH2. The mutations found in MLH1 gene were c.2103+1G>C in intron 18 and compound heterozygous mutants c.1852_1854delAAG (p.K618del) and c.1852_1853delinsGC (p.K618A) in exon 16. In the MSH2 gene, we identified mutation c.638dupT (p.L213fs) in exon 3. Conclusions. This is the first report of mutations in MMR genes in Mexican patients with LS and these appear to be novel. PMID:27247567

  13. Novel Mutations in MLH1 and MSH2 Genes in Mexican Patients with Lynch Syndrome

    Directory of Open Access Journals (Sweden)

    Jose Miguel Moreno-Ortiz

    2016-01-01

    Full Text Available Background. Lynch Syndrome (LS is characterized by germline mutations in the DNA mismatch repair (MMR genes MLH1, MSH2, MSH6, and PMS2. This syndrome is inherited in an autosomal dominant pattern and is characterized by early onset colorectal cancer (CRC and extracolonic tumors. The aim of this study was to identify mutations in MMR genes in three Mexican patients with LS. Methods. Immunohistochemical analysis was performed as a prescreening method to identify absent protein expression. PCR, Denaturing High Performance Liquid Chromatography (dHPLC, and Sanger sequencing complemented the analysis. Results. Two samples showed the absence of nuclear staining for MLH1 and one sample showed loss of nuclear staining for MSH2. The mutations found in MLH1 gene were c.2103+1G>C in intron 18 and compound heterozygous mutants c.1852_1854delAAG (p.K618del and c.1852_1853delinsGC (p.K618A in exon 16. In the MSH2 gene, we identified mutation c.638dupT (p.L213fs in exon 3. Conclusions. This is the first report of mutations in MMR genes in Mexican patients with LS and these appear to be novel.

  14. The genetic basis of Lynch syndrome and its implications for clinical practice and risk management

    Directory of Open Access Journals (Sweden)

    Cohen SA

    2014-07-01

    Full Text Available Stephanie A Cohen,1 Anna Leininger2 1Cancer Genetics Risk Assessment Program, St Vincent Health, Indianapolis, IN, USA; 2Minnesota Oncology, Woodbury, MN, USA Abstract: Lynch syndrome is the most common cause of hereditary colon cancer, and accounts for as much as 3% of all colon and endometrial cancers. The identification and management of individuals with Lynch syndrome have evolved over the past 20 years, yet the syndrome remains vastly underdiagnosed. It is important for clinicians to recognize individuals and families who are at risk in order to be able to manage them appropriately and reduce their morbidity and mortality from this condition. This review will touch on the history of Lynch syndrome, the current knowledge of genotype–phenotype correlations, the cancers associated with Lynch syndrome, and management of individuals who are gene carriers. Keywords: Lynch syndrome, hereditary cancer, hereditary nonpolyposis colorectal cancer, mismatch repair, mismatch repair genes, immunohistochemistry, microsatellite instability

  15. Lynch syndrome and exposure to aristolochic acid in upper-tract urothelial carcinoma: its clinical impact?

    Science.gov (United States)

    Colin, Pierre; Seisen, Thomas; Mathieu, Romain; Shariat, Sharohkh F.

    2016-01-01

    The purpose of the current review was to describe the clinical risk for Lynch syndrome (LS) after exposure to aristolochic acid (AA) in cases of upper urinary-tract urothelial carcinoma (UTUC). A systematic review of the scientific literature was performed using the Medline database (National Library of Medicine, PubMed) using the following keywords: epidemiology, risk factor, AA, Balkan nephropathy (BNe), LS, hereditary cancer, hereditary non-polyposis colorectal cancer (HNPCC), mismatch repair genes, urothelial carcinomas, upper urinary tract, renal pelvis, ureter, Amsterdam criteria, genetic counselling, mismatch repair genes, genetic instability, microsatellite, and Bethesda guidelines. LS is a specific risk for UTUC, which is the third most frequent cancer (in its tumor spectrum) after colon and uterine lesions. Mutation of the MSH2 gene is the most commonly described cause of UTUC in LS. Diagnosis is based on clinical suspicion and is guided by Bethesda and Amsterdam criteria. It is secondarily confirmed by immunohistochemical analyses of the tumor and a search for gene mutations. The presence of LS in patients with UTUC is a favorable prognosis factor for survival during follow-ups. AA is a specific environmental risk factor for UTUC and tubulo-interstitial nephropathy. It has been involved in the development of nephropathies in link with the Balkan disease and intake of Chinese herbal medicine. More broadly, the use of traditional plant medicines from the genus Aristolochia has created worldwide public-health concerns. UTUCs share common risk factors with other urothelial carcinomas such as tobacco or occupational exposure. However, these tumors have also specific risk factors such as AA exposure and LS that clinicians should be aware of because of their clinical implication in further management and follow-up.

  16. Bayesian Modeling for Genetic Anticipation in Presence of Mutational Heterogeneity: A Case Study in Lynch Syndrome

    DEFF Research Database (Denmark)

    Boonstra, Philip S; Mukherjee, Bhramar; Taylor, Jeremy M G;

    2011-01-01

    inferential conclusions. We compare the fit of four-candidate random effects distributions via Bayesian model fit diagnostics. A related statistical issue here is isolating the confounding effect of changes in secular trends, screening, and medical practices that may affect time to disease detection across...... to cause hereditary nonpolyposis colorectal cancer, also called Lynch syndrome (LS). We find evidence for a decrease in AOO between generations in this article. Our model predicts family-level anticipation effects that are potentially useful in genetic counseling clinics for high-risk families....... birth cohorts. Using historic cancer registry data, we borrow from relative survival analysis methods to adjust for changes in age-specific incidence across birth cohorts. Our motivating case study comes from a Danish cancer register of 124 families with mutations in mismatch repair (MMR) genes known...

  17. Molecular profile of the Lynch Syndrome in the Republic of Macedonia

    Directory of Open Access Journals (Sweden)

    Marija Hiljadnikova-Bajro

    2012-12-01

    Full Text Available The most frequent type of hereditary colorectal cancer, the one occurring in the setting of the Lynch syndrome (LS is considered a phenotypic manifestation of a germline defect in the mismatch repair mechanism i.e. in the MLH1, MSH2, MSH6 or PMS2 gene. Aiming towards establishment of a standardized protocol involving molecular analyses for diagnosis of this syndrome and developing a unique national register of families with hereditary colorectal cancer syndromes in the Republic of Macedonia, we began a prospective study to reveal the genetic defects among Macedonian patients with colorectal cancer (CRC and identifying families with hereditary CRC. A total of 53 patients fulfilling the revised Bethesda criteria for MSI-genetic testing were compared to 350 patients with sporadic CRC. The results reveal significant differences in age at diagnosis (p=0.03, involvement of microsatellite instability (pG nonsense mutation with a possible founder effect in the Macedonian population, the MLH1 ex.3-12 deletion, as well as the c.244A>G mutation, IVS14- 19A>G and IVS4+65A>C changes in MLH1 without confirmed pathological significance. The observed high frequency (87.5% of the Ile219Val (c.655A>G variant in MLH1 among the LS suspects prompts further analyses to evaluate its involvement in the development of hereditary CRC by itself or as a risk modifying factor among the patients from the Republic of Macedonia.

  18. Educational and Psychosocial Support Needs in Lynch Syndrome: Implementation and Assessment of an Educational Workshop and Support Group.

    Science.gov (United States)

    Corines, Marina J; Hamilton, Jada G; Glogowski, Emily; Anrig, Chris A; Goldberg, Rachael; Niehaus, Kate; Salo-Mullen, Erin; Harlan, Megan; Sheehan, Margaret R; Trottier, Magan; Ahsraf, Asad; Tran, Christina; Jacobs, Lauren; Rau-Murthy, Rohini; Lincoln, Anne G; Robson, Mark E; Guillem, Jose G; Markowitz, Arnold J; Offit, Kenneth; Stadler, Zsofia K

    2017-04-01

    Few reports of educational and counseling support resources exist for Lynch syndrome (LS), a disorder requiring multi-organ cancer screening and specialized medical care throughout adult life. Here we describe the development and efficacy of two resources designed to address this need, the Memorial Sloan Kettering Cancer Center Clinical Genetics Service annual Lynch Syndrome Educational Workshop (LSEW), and a quarterly Lynch Syndrome Patient Advocacy Network (LSPAN) support group. The LSEW and LSPAN were implemented beginning in 2012. Participant survey data evaluating satisfaction, clarity, and unmet needs for each event were retrospectively analyzed and summarized using descriptive statistics. Annual LSEW attendance ranged from 53 to 75 total participants. LSEW year 1 participants indicated a need for a support group, and preferred in-person meetings at a frequency of every 3-6 months. For LSEW year 2-5 participants, >96 % reported satisfaction with the LSEW, and >82 % expressed interest in secure online support. Common themes for improvement included increased time for question and answer sessions and additional introductory genetics education. Responding LSPAN participants (n = 57 total survey responses in 11 meetings) found the meetings helpful (100 %), information clear (91 %), and presence of a genetic counselor useful (67 %). Desired discussion topics included coping with stress and anxiety, development of a support network, family communication about LS, genetic testing decisions, and bereavement. Following genetic counseling, a need exists for ongoing educational and emotional support in LS. Implementation of resources such as the LSEW and LSPAN is feasible and perceived as helpful by participants.

  19. MLH1 promoter hypermethylation in the analytical algorithm of Lynch syndrome: a cost-effectiveness study

    Science.gov (United States)

    Gausachs, Mireia; Mur, Pilar; Corral, Julieta; Pineda, Marta; González, Sara; Benito, Llúcia; Menéndez, Mireia; Espinàs, Josep Alfons; Brunet, Joan; Iniesta, María Dolores; Gruber, Stephen B; Lázaro, Conxi; Blanco, Ignacio; Capellá, Gabriel

    2012-01-01

    The analytical algorithm of Lynch syndrome (LS) is increasingly complex. BRAF V600E mutation and MLH1 promoter hypermethylation have been proposed as a screening tool for the identification of LS. The aim of this study was to assess the clinical usefulness and cost-effectiveness of both somatic alterations to improve the yield of the diagnostic algorithm of LS. A total of 122 colorectal tumors from individuals with family history of colorectal cancer that showed microsatellite instability and/or loss of mismatch repair (MMR) protein expression were studied. MMR germline mutations were detected in 57 cases (40 MLH1, 15 MSH2 and 2 MSH6). BRAF V600E mutation was assessed by single-nucleotide primer extension. MLH1 promoter hypermethylation was assessed by methylation-specific multiplex ligation-dependent probe amplification in a subset of 71 cases with loss of MLH1 protein. A decision model was developed to estimate the incremental costs of alternative case-finding methods for detecting MLH1 mutation carriers. One-way sensitivity analysis was performed to assess robustness of estimations. Sensitivity of the absence of BRAF mutations for depiction of LS patients was 96% (23/24) and specificity was 28% (13/47). Specificity of MLH1 promoter hypermethylation for depiction of sporadic tumors was 66% (31/47) and sensitivity of 96% (23/24). The cost per additional mutation detected when using hypermethylation analysis was lower when compared with BRAF study and germinal MLH1 mutation study. Somatic hypermethylation of MLH1 is an accurate and cost-effective pre-screening method in the selection of patients that are candidates for MLH1 germline analysis when LS is suspected and MLH1 protein expression is absent. PMID:22274583

  20. Prevalence of Lynch syndrome and Lynch-like syndrome among patients with colorectal cancer in a Japanese hospital-based population.

    Science.gov (United States)

    Chika, Noriyasu; Eguchi, Hidetaka; Kumamoto, Kensuke; Suzuki, Okihide; Ishibashi, Keiichiro; Tachikawa, Tetsuhiko; Akagi, Kiwamu; Tamaru, Jun-Ichi; Okazaki, Yasushi; Ishida, Hideyuki

    2017-02-09

    We investigated the prevalence of Lynch syndrome and Lynch-like syndrome among Japanese colorectal cancer patients, as there have been no credible data from Japan. Immunohistochemical analyses for mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2) were carried out in surgically resected, formalin-fixed paraffin-embedded specimens obtained from 1,234 newly diagnosed colorectal cancer patients between March 2005 and April 2014. The presence/absence of the BRAF V600E mutation and hypermethylation of the MLH1 promoter was analyzed where necessary. Genetic testing was finally undertaken in patients suspected as having Lynch syndrome. By the universal screening approach with immunohistochemical analysis for mismatch repair proteins followed by analyses for the BRAF V600E mutation and MLH1 promoter methylation status, 11 (0.9%) of the 1,234 patients were identified as candidates for genetic testing. Out of the 11 patients, 9 (0.7%) were finally diagnosed as having Lynch syndrome; the responsible genes included MLH1 (n = 1), MSH2 (n = 4), EPCAM (n = 1) and MSH6 (n = 3). The remaining two patients (0.2%) were regarded as having Lynch-like syndrome, since biallelic somatic deletion of the relevant mismatch repair genes was detected in the absence of germline mismatch repair alterations. None of the cases was identified as having germline MLH1 epimutation. The prevalence of Lynch syndrome among all newly diagnosed cases of colorectal cancer in Japan is in the same range as that recently reported by studies in Western population. The prevalence of Lynch-like syndrome seems to be extremely low.

  1. Prevalence of Lynch syndrome in a Middle Eastern population with colorectal cancer.

    Science.gov (United States)

    Siraj, Abdul K; Prabhakaran, Sarita; Bavi, Prashant; Bu, Rong; Beg, Shaham; Hazmi, Mohsen Al; Al-Rasheed, Maha; Al-Assiri, Mohammed; Sairafi, Rami; Al-Dayel, Fouad; Al-Sanea, Nasser; Uddin, Shahab; Al-Kuraya, Khawla S

    2015-06-01

    Lynch syndrome (LS; hereditary nonpolyposis colorectal cancer) is a common cause of hereditary colorectal cancer (CRC). CRC is the most common cancer diagnosed among males in Saudi Arabia but to the authors' knowledge there is a lack of data regarding the prevalence of LS in patients with CRC. There currently are no clear guidelines for the selection criteria for these patients to screen for LS. A comprehensive molecular characterization was performed in a cohort of 807 CRC cases by immunohistochemical and microsatellite analysis using polymerase chain reaction. BRAF mutation screening, high CpG island methylator phenotype, and analysis for germline mutations were performed in 425 CRC samples. These were all high microsatellite instability (MSI-H) samples (91 cases), all low MSI samples (143 cases), and selected cases from the microsatellite stable group (191 cases) that met revised Bethesda guidelines. Polymerase chain reaction identified 91 MSI-H cases (11.3%) and sequencing revealed mismatch repair germline mutations in 8 CRC cases only. Of the total of 807 CRC cases, these 8 cases (0.99%) were MSI-H, met the revised Bethesda guidelines, and did not harbor BRAF mutations. The results of the current study confirmed cases of LS in approximately 1.0% of CRC samples and reflects the efficacy of screening among MSI-H cases that lack BRAF mutations. This comprehensive study from Saudi Arabia will help in implementing a universal screening/reflex testing strategy in a clinical setting in Saudi Arabia and in conducting a national screening program that benefits both patients and their relatives. © 2015 American Cancer Society.

  2. Cost-Effectiveness Analysis of Different Genetic Testing Strategies for Lynch Syndrome in Taiwan.

    Science.gov (United States)

    Chen, Ying-Erh; Kao, Sung-Shuo; Chung, Ren-Hua

    2016-01-01

    Patients with Lynch syndrome (LS) have a significantly increased risk of developing colorectal cancer (CRC) and other cancers. Genetic screening for LS among patients with newly diagnosed CRC aims to identify mutations in the disease-causing genes (i.e., the DNA mismatch repair genes) in the patients, to offer genetic testing for relatives of the patients with the mutations, and then to provide early prevention for the relatives with the mutations. Several genetic tests are available for LS, such as DNA sequencing for MMR genes and tumor testing using microsatellite instability and immunohistochemical analyses. Cost-effectiveness analyses of different genetic testing strategies for LS have been performed in several studies from different countries such as the US and Germany. However, a cost-effectiveness analysis for the testing has not yet been performed in Taiwan. In this study, we evaluated the cost-effectiveness of four genetic testing strategies for LS described in previous studies, while population-specific parameters, such as the mutation rates of the DNA mismatch repair genes and treatment costs for CRC in Taiwan, were used. The incremental cost-effectiveness ratios based on discounted life years gained due to genetic screening were calculated for the strategies relative to no screening and to the previous strategy. Using the World Health Organization standard, which was defined based on Taiwan's Gross Domestic Product per capita, the strategy based on immunohistochemistry as a genetic test followed by BRAF mutation testing was considered to be highly cost-effective relative to no screening. Our probabilistic sensitivity analysis results also suggest that the strategy has a probability of 0.939 of being cost-effective relative to no screening based on the commonly used threshold of $50,000 to determine cost-effectiveness. To the best of our knowledge, this is the first cost-effectiveness analysis for evaluating different genetic testing strategies for LS in

  3. Distinct gene expression profiles in ovarian cancer linked to Lynch syndrome

    DEFF Research Database (Denmark)

    Jönsson, Jenny-Maria; Bartuma, Katarina; Dominguez-Valentin, Mev

    2014-01-01

    Ovarian cancer linked to Lynch syndrome represents a rare subset that typically presents at young age as early-stage tumors with an overrepresentation of endometrioid and clear cell histologies. We investigated the molecular profiles of Lynch syndrome-associated and sporadic ovarian cancer...... ovarian cancers. Lynch syndrome-associated and sporadic ovarian cancers differed by 349 significantly deregulated genes, including PTPRH, BIRC3, SHH and TNFRSF6B. The genes involved were predominantly linked to cell growth, proliferation, and cell-to-cell signaling and interaction. When stratified...... for histologic subtype, hierarchical clustering confirmed distinct differences related to heredity in the endometrioid and serous subtypes. Furthermore, separate clustering was achieved in an independent, publically available data set. The distinct genetic signatures in Lynch syndrome-associated and sporadic...

  4. Risk of Cancer in Cases of Suspected Lynch Syndrome Without Germline Mutation

    OpenAIRE

    Rodríguez-Soler, María; Pérez-Carbonell, Lucía; Guarinos, Carla; Zapater, Pedro; Castillejo, Adela; Barberá, Víctor Manuel; Juárez, Miriam; Bessa, Xavier; Xicola, Rosa M; Clofent, Juan; Bujanda, Luis; Balaguer, Francesc; Reñé, Josep-Maria; de Castro, Luisa; Marín-Gabriel, José C.

    2013-01-01

    Background & Aims: Colorectal cancers (CRCs) with microsatellite instability (MSI) and a mismatch repair (MMR) immunohistochemical deficit without hypermethylation of the MLH1 promoter are likely to be caused by Lynch syndrome. Some patients with these cancers have not been found to have pathogenic germline mutations and are considered to have Lynch-like syndrome (LLS). The aim of this study was to determine the risk of cancer in families of patients with LLS. Methods: We studied a population...

  5. Distinct Gene Expression Signatures in Lynch Syndrome and Familial Colorectal Cancer Type X

    DEFF Research Database (Denmark)

    Valentin, Mev; Therkildsen, Christina; Veerla, Srinivas;

    2013-01-01

    Heredity is estimated to cause at least 20% of colorectal cancer. The hereditary nonpolyposis colorectal cancer subset is divided into Lynch syndrome and familial colorectal cancer type X (FCCTX) based on presence of mismatch repair (MMR) gene defects.......Heredity is estimated to cause at least 20% of colorectal cancer. The hereditary nonpolyposis colorectal cancer subset is divided into Lynch syndrome and familial colorectal cancer type X (FCCTX) based on presence of mismatch repair (MMR) gene defects....

  6. Identification of patients at-risk for Lynch syndrome in a hospital-based colorectal surgery clinic

    Institute of Scientific and Technical Information of China (English)

    Patrícia Koehler-Santos; Mario Antonello Rosito; Patricia Ashton-Prolla; Jo(a)o Carlos Prolla; Patricia Izetti; Jamile Abud; Carlos Eduardo Pitroski; Silvia Liliana Cossio; Suzi Alves Camey; Cláudio Tarta; Daniel C Damin; Paulo Carvalho Contu

    2011-01-01

    AIM: To determine the prevalence of a family history suggestive of Lynch syndrome (LS) among patients with colorectal cancer (CRC) followed in a coloproctology outpatient clinic in Southern Brazil.METHODS: A consecutive sample of patients with CRC were interviewed regarding personal and family histories of cancer. Clinical data and pathology features of the tumor were obtained from chart review.RESULTS: Of the 212 CRC patients recruited, 61 (29%)reported a family history of CRC, 45 (21.2%) were diagnosed under age 50 years and 11 (5.2%) had more than one primary CRC. Family histories consistent with Amsterdam and revised Bethesda criteria for LS were identified in 22 (10.4%) and 100 (47.2%) patients,respectively. Twenty percent of the colorectal tumors had features of the high microsatellite instability phenotype,which was associated with younger age at CRC diagnosis and with Bethesda criteria (P < 0.001). Only 5.3% of the patients above age 50 years had been previously submitted for CRC screening and only 4% of patients with suspected LS were referred for genetic risk assessment.CONCLUSION: A significant proportion of patients with CRC were at high risk for LS. Education and training of health care professionals are essential to ensure proper management.

  7. How does genetic risk information for Lynch syndrome translate to risk management behaviours?

    Science.gov (United States)

    Steel, Emma; Robbins, Andrew; Jenkins, Mark; Flander, Louisa; Gaff, Clara; Keogh, Louise

    2017-01-01

    There is limited research on why some individuals who have undergone predictive genetic testing for Lynch syndrome do not adhere to screening recommendations. This study aimed to explore qualitatively how Lynch syndrome non-carriers and carriers translate genetic risk information and advice to decisions about risk managment behaviours in the Australian healthcare system. Participants of the Australasian Colorectal Cancer Family Registry who had undergone predictive genetic testing for Lynch syndrome were interviewed on their risk management behaviours. Transcripts were analysed thematically using a comparative coding analysis. Thirty-three people were interviewed. Of the non-carriers (n = 16), 2 reported having apparently unnecessary colonoscopies, and 6 were unsure about what population-based colorectal cancer screening entails. Of the carriers (n = 17), 2 reported they had not had regular colonoscopies, and spoke about their discomfort with the screening process and a lack of faith in the procedure's ability to reduce their risk of developing colorectal cancer. Of the female carriers (n = 9), 2 could not recall being informed about the associated risk of gynaecological cancers. Non-carriers and female carriers of Lynch syndrome could benefit from further clarity and advice about appropriate risk management options. For those carriers who did not adhere to colonoscopy screening, a lack of faith in both genetic test results and screening were evident. It is essential that consistent advice is offered to both carriers and non-carriers of Lynch syndrome.

  8. Bayesian modeling for genetic anticipation in presence of mutational heterogeneity: a case study in Lynch syndrome.

    Science.gov (United States)

    Boonstra, Philip S; Mukherjee, Bhramar; Taylor, Jeremy M G; Nilbert, Mef; Moreno, Victor; Gruber, Stephen B

    2011-12-01

    Genetic anticipation, described by earlier age of onset (AOO) and more aggressive symptoms in successive generations, is a phenomenon noted in certain hereditary diseases. Its extent may vary between families and/or between mutation subtypes known to be associated with the disease phenotype. In this article, we posit a Bayesian approach to infer genetic anticipation under flexible random effects models for censored data that capture the effect of successive generations on AOO. Primary interest lies in the random effects. Misspecifying the distribution of random effects may result in incorrect inferential conclusions. We compare the fit of four-candidate random effects distributions via Bayesian model fit diagnostics. A related statistical issue here is isolating the confounding effect of changes in secular trends, screening, and medical practices that may affect time to disease detection across birth cohorts. Using historic cancer registry data, we borrow from relative survival analysis methods to adjust for changes in age-specific incidence across birth cohorts. Our motivating case study comes from a Danish cancer register of 124 families with mutations in mismatch repair (MMR) genes known to cause hereditary nonpolyposis colorectal cancer, also called Lynch syndrome (LS). We find evidence for a decrease in AOO between generations in this article. Our model predicts family-level anticipation effects that are potentially useful in genetic counseling clinics for high-risk families.

  9. Lynch syndrome-associated colorectal carcinoma: frequent involvement of the left colon and rectum and late-onset presentation supports a universal screening approach.

    Science.gov (United States)

    Hartman, Douglas J; Brand, Randall E; Hu, Huankai; Bahary, Nathan; Dudley, Beth; Chiosea, Simon I; Nikiforova, Marina N; Pai, Reetesh K

    2013-11-01

    The optimal strategy for screening patients with colorectal carcinoma for Lynch syndrome (LS) is a subject of continued debate in the literature with some advocating universal screening while others arguing for selective screening. We evaluated 1292 colorectal carcinomas for DNA mismatch repair protein abnormalities and identified 150 (11.6%) tumors demonstrating high-levels of microsatellite instability (MSI-H). MSI-H colorectal carcinomas were divided into sporadic (112/1292, 8.7%) and LS/probable LS-associated (38/1292, 2.9%) groups based on BRAF V600E mutation, MLH1 promoter hypermethylation, cancer history, and germline mismatch repair gene mutation. All MSI-H colorectal carcinomas were analyzed for grade, location, and tumor histology. The utility of the revised Bethesda guidelines and published predictive pathology models for MSI-H colorectal carcinomas (PREDICT and MSPath) were evaluated. Left-sided MSI-H colorectal carcinomas were more frequently associated with LS compared with right-sided MSI-H colorectal carcinomas (12/21, 57% versus 26/129, 20%, P = .0008). There was no significant difference in histology between sporadic MSI-H and LS/probable LS-associated colorectal carcinomas except for a slightly higher proportion of sporadic MSI-H tumors demonstrating tumor-infiltrating lymphocytes (81% versus 61%, P = .015). Neither pathology predictive model identified all LS-associated colorectal carcinomas (PREDICT: 33/38, 87%; MSPath: 35/38, 92%). 12/117 (10%) MSI-H colorectal carcinomas identified in patients >60 years were LS/probable LS-associated. Our results demonstrate that models of predicting MSI-H fail to identify LS-associated colorectal carcinoma given their reliance on right-sided location. A significant proportion (32%) of LS-associated colorectal carcinoma is identified in patients >60 years. Finally, our results demonstrate similar morphologic features between LS-associated and sporadic MSI-H colorectal carcinomas.

  10. Truncation of the MSH2 C-terminal 60 amino acids disrupts effective DNA mismatch repair and is causative for Lynch syndrome.

    Science.gov (United States)

    Wielders, Eva; Delzenne-Goette, Elly; Dekker, Rob; van der Valk, Martin; Te Riele, Hein

    2017-04-01

    Missense variants of DNA mismatch repair (MMR) genes pose a problem in clinical genetics as long as they cannot unambiguously be assigned as the cause of Lynch syndrome (LS). To study such variants of uncertain clinical significance, we have developed a functional assay based on direct measurement of MMR activity in mouse embryonic stem cells expressing mutant protein from the endogenous alleles. We have applied this protocol to a specific truncation mutant of MSH2 that removes 60 C-terminal amino acids and has been found in suspected LS families. We show that the stability of the MSH2/MSH6 heterodimer is severely perturbed, causing attenuated MMR in in vitro assays and cancer predisposition in mice. This mutation can therefore unambiguously be considered as deleterious and causative for LS.

  11. Clinicopathological Features of Endometrial Carcino-ma Associated with Lynch Syndrome in China

    Institute of Scientific and Technical Information of China (English)

    Yingmei WANG; Fengxia XUE; Russell R. BROADDUS; Xia TAO; Susu XIE; Yanbin ZHU

    2009-01-01

    Background and objective To study the clinicopathoiogical characteristics of Lynch syn&ome-associated endometrial carcinoma in China.Methods Twenty-seven patients who fulfilled the Amsterdam Criteria Ⅱ were classified as having Lynch syndrome-associated endometrial carcinoma (Group A), and 331 patients without a family history of cancer were classified as having sporadic endometrial carcinoma (Group B).Results There were 81 malignancies in 27 Lynch syndrome-associated endometrial carcinoma families, including colorectal cancer (CRC, 24.7%), endometrial carcinoma (21.0%), liver (12.3%), stomach (9.9%), lung (6.2%), and breast (6.2%) cancers. Mean age at time of diagnosis was 49.7 years in Group A and 56.3 years in Group B (P=0.004). Second primary cancers occurred in 33.3% of patients in Group A and 5.1% in Group B (P<0.0001). "Ihe most common second primary cancers were colorectal cancer (44%) and ovarian cancer (22%). The percentage of obese patients was higher in Group A (P=0.013). There was no difference between the two groups in incidence of diabetes mellitns or hypertension or in histological type and FIGO stage. The 5-year survival rates for Group A and B were 96.2% and 79.6%, respectively. Prognosis for Group A was better than for Group B (P=0.045).Conclusion Some clinicopathologicai features of Lynch syndrome-associated endometrial carcinoma, such as early onset and multiple primary carcinomas, are similar in the Chinese and American/European populations. However, the Chinese population had a unique family cancer distribution that included lung and breast cancers. An increased number of grade 1 endometrioid tumors and a better prognosis imply better biobehavior in Chinese Lynch syndrome-associated endometrial carcinoma. Obesity may be a co-contributing factor for development of Lynch syndrome associated endometrial cancer in China.

  12. Isolated Loss of PMS2 Immunohistochemical Expression is Frequently Caused by Heterogenous MLH1 Promoter Hypermethylation in Lynch Syndrome Screening for Endometrial Cancer Patients.

    Science.gov (United States)

    Kato, Aya; Sato, Naoki; Sugawara, Tae; Takahashi, Kazue; Kito, Masahiko; Makino, Kenichi; Sato, Toshiharu; Shimizu, Dai; Shirasawa, Hiromistu; Miura, Hiroshi; Sato, Wataru; Kumazawa, Yukiyo; Sato, Akira; Kumagai, Jin; Terada, Yukihiro

    2016-06-01

    Lynch syndrome (LS) is an autosomal-dominant inherited disorder mainly caused by a germline mutation in the DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) and is associated with increased risk for various cancers, particularly colorectal cancer and endometrial cancer (EC). Women with LS account for 2% to 6% of EC patients; it is clinically important to identify LS in such individuals for predicting and/or preventing additional LS-associated cancers. PMS2 germline mutation (PMS2-LS) is the rarest contribution to LS etiology among the 4 LS-associated MMR germline mutations, and its detection is complicated. Therefore, prudent screening for PMS2-LS is important as it leads to an efficient LS identification strategy. Immunohistochemistry is recommended as a screening method for LS in EC. Isolated loss of PMS2 (IL-PMS2) expression is caused not only by PMS2-LS but also by MLH1 germline mutation or MLH1 promoter hypermethylation (MLH-PHM). This study aimed to determine the association between MLH1-PHM and IL-PMS2 to avoid inappropriate genetic analysis. We performed MLH1 methylation analysis and MLH1/PMS2 germline mutation testing on the IL-PMS2 cases. By performing MMR-immunohistochemistry on 360 unselected ECs, we could select 8 (2.2%) cases as IL-PMS2. Heterogenous MLH1 staining and MLH1-PHM were detected in 4 of 8 (50%) IL-PMS2 tumors. Of the 5 IL-PMS2 patients who underwent genetic analysis, 1 had PMS2 germline mutation with normal MLH1 expression (without MLH1-PHM), and no MLH1 germline mutation was detected. We suggest that MLH1 promoter methylation analysis for IL-PMS2 EC should be performed to exclude sporadic cases before further PMS2 genetic testing.

  13. A putative Lynch syndrome family carrying MSH2 and MSH6 variants of uncertain significance-functional analysis reveals the pathogenic one

    DEFF Research Database (Denmark)

    Kantelinen, Jukka; Hansen, Thomas V O; Kansikas, Minttu;

    2011-01-01

    Inherited pathogenic mutations in the mismatch repair (MMR) genes, MSH2, MLH1, MSH6, and PMS2 predispose to Lynch syndrome (LS). However, the finding of a variant or variants of uncertain significance (VUS) in affected family members complicates the risk assessment. Here, we describe a putative L...... identified VUS before predictive gene testing and genetic counseling are offered to a family.......Inherited pathogenic mutations in the mismatch repair (MMR) genes, MSH2, MLH1, MSH6, and PMS2 predispose to Lynch syndrome (LS). However, the finding of a variant or variants of uncertain significance (VUS) in affected family members complicates the risk assessment. Here, we describe a putative LS...... family carrying VUS in both MSH2 (c.2768T>A, p.Val923Glu) and MSH6 (c.3563G>A, p.Ser1188Asn). Two colorectal cancer (CRC) patients were studied for mutations and identified as carriers of both variants. In spite of a relatively high mean age of cancer onset (59.5 years) in the family, many CRC patients...

  14. Genetic screens to identify pathogenic gene variants in the common cancer predisposition Lynch syndrome

    DEFF Research Database (Denmark)

    Drost, Mark; Lützen, Anne; van Hees, Sandrine

    2013-01-01

    In many individuals suspected of the common cancer predisposition Lynch syndrome, variants of unclear significance (VUS), rather than an obviously pathogenic mutations, are identified in one of the DNA mismatch repair (MMR) genes. The uncertainty of whether such VUS inactivate MMR, and therefore...... for the translation of personalized genomics into targeted healthcare....

  15. Informing family members of individuals with Lynch syndrome : a guideline for clinical geneticists

    NARCIS (Netherlands)

    Menko, Fred H.; Aalfs, Cora M.; Henneman, Lidewij; Stol, Yrrah; Wijdenes, Miranda; Otten, Ellen; Ploegmakers, Marleen M. J.; Legemaate, Johan; Smets, Ellen M. A.; de Wert, Guido M. W. R.; Tibben, Aad

    2013-01-01

    The diagnosis of Lynch syndrome can lead to the prevention of colorectal cancer through periodic colonoscopies and removal of premalignant lesions in susceptible individuals. Therefore, predisposed individuals identified by mutation analysis are advised to inform their at-risk relatives about the op

  16. Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance

    DEFF Research Database (Denmark)

    Møller, Pål; Seppälä, Toni; Bernstein, Inge;

    2016-01-01

    OBJECTIVE: Estimates of cancer risk and the effects of surveillance in Lynch syndrome have been subject to bias, partly through reliance on retrospective studies. We sought to establish more robust estimates in patients undergoing prospective cancer surveillance. DESIGN: We undertook a multicentr...

  17. Gene variants of unknown clinical significance in Lynch syndrome. An introduction for clinicians

    NARCIS (Netherlands)

    Sijmons, Rolf H.; Greenblatt, Marc S.; Genuardi, Maurizio

    2013-01-01

    Clinicians referring patients for genetic testing for Lynch syndrome will sooner or later receive results for DNA Mismatch Repair (MMR) genes reporting DNA changes that are unclear from a clinical point of view. These changes are referred to as variants of unknown, or unclear, clinical significance

  18. Prediction of MLH1 and MSH2 mutations in lynch syndrome

    NARCIS (Netherlands)

    J. Balmana (Judith); D.H. Stockwell (David); E.W. Steyerberg (Ewout); E.M. Stoffel (Elena); A.M. Deffenbaugh (Amie); J.E. Reid (Julia); B. Ward (Brian); T. Scholl (Thomas); B. Hendrickson (Brant); J. Tazelaar (John); L.A. Burbidge (Lynn); S. Syngal (Sapna)

    2006-01-01

    textabstractContext: Lynch syndrome is caused primarily by mutations in the mismatch repair genes MLH1 and MSH2. Objectives: To analyze MLH1/MSH2 mutation prevalence in a large cohort of patients undergoing genetic testing and to develop a clinical model to predict the likelihood of finding a mutati

  19. Effect of aspirin or resistant starch on colorectal neoplasia in the Lynch syndrome

    NARCIS (Netherlands)

    J. Burn (John); D.T. Bishop (David Timothy); J.-P. Mecklin (Jukka-Pekka); F.A. Macrae (Finlay); G. Möslein (Gabriela); S. Olschwang (Sylviane); M.-L. Bisgaard (Marie-Luise); R.S. Ramesar (Rajkumar); D. Eccles (Diana); E.R. Maher (Eamonn); L. Bertario (Lucio); H.J. Jarvinen (Heikki); A. Lindblom (Annika); D.G. Evans (Gareth); J. Lubinski (Jan); P.J. Morrison (Patrick); J.W.C. Ho (Judy); H. Vasen (Hans); L. Side (Lucy); H.J.W. Thomas (Huw ); R.J. Scott (Rodney); M.G. Dunlop (Malcolm); G. Barker (Gail); F. Elliott (Faye); J.R. Jass (Jeremy ); R. Fodde (Riccardo); H. Lynch (Henry); J.C. Mathers (John )

    2008-01-01

    textabstractBACKGROUND: Observational and epidemiologic data indicate that the use of aspirin reduces the risk of colorectal neoplasia; however, the effects of aspirin in the Lynch syndrome (hereditary nonpolyposis colon cancer) are not known. Resistant starch has been associated with an antineoplas

  20. Smoking increases the risk for colorectal adenomas in patients with Lynch syndrome

    NARCIS (Netherlands)

    Winkels, R.M.; Botma, A.; Duijnhoven, van F.J.B.; Nagengast, F.M.; Kleibeuker, J.H.; Vasen, H.F.A.; Kampman, E.

    2012-01-01

    Background & Aims Individuals with Lynch syndrome have a high risk of developing colorectal carcinomas and adenomas at a young age, due to inherited mutations in mismatch repair genes. We investigated whether modifiable lifestyle factors, such as smoking and alcohol intake, increase this risk.

  1. Smoking Increases the Risk for Colorectal Adenomas in Patients With Lynch Syndrome

    NARCIS (Netherlands)

    Winkels, Renate M.; Botma, Akke; Van Duijnhoven, Franzel J. B.; Nagengast, Fokko M.; Kleibeuker, Jan H.; Vasen, Hans F. A.; Kampman, Ellen

    BACKGROUND & AIMS: Individuals with Lynch syndrome have a high risk of developing colorectal carcinomas and adenomas at a young age, due to inherited mutations in mismatch repair genes. We investigated whether modifiable lifestyle factors, such as smoking and alcohol intake, increase this risk.

  2. A frame-shift mutation of PMS2 is a widespread cause of Lynch syndrome

    DEFF Research Database (Denmark)

    Clendenning, Mark; Senter, Leigha; Hampel, Heather;

    2008-01-01

    on immunohistochemical analysis. RESULTS: We have identified a frequently occurring frame-shift mutation (c.736_741del6ins11) in 12 ostensibly unrelated Lynch syndrome patients (20% of patients we have identified with a deleterious mutation in PMS2, n=61). These individuals all display the rare allele (population...

  3. Smoking increases the risk for colorectal adenomas in patients with Lynch syndrome

    NARCIS (Netherlands)

    Winkels, R.M.; Botma, A.; Duijnhoven, van F.J.B.; Nagengast, F.M.; Kleibeuker, J.H.; Vasen, H.F.A.; Kampman, E.

    2012-01-01

    Background & Aims Individuals with Lynch syndrome have a high risk of developing colorectal carcinomas and adenomas at a young age, due to inherited mutations in mismatch repair genes. We investigated whether modifiable lifestyle factors, such as smoking and alcohol intake, increase this risk. M

  4. Smoking Increases the Risk for Colorectal Adenomas in Patients With Lynch Syndrome

    NARCIS (Netherlands)

    Winkels, Renate M.; Botma, Akke; Van Duijnhoven, Franzel J. B.; Nagengast, Fokko M.; Kleibeuker, Jan H.; Vasen, Hans F. A.; Kampman, Ellen

    2012-01-01

    BACKGROUND & AIMS: Individuals with Lynch syndrome have a high risk of developing colorectal carcinomas and adenomas at a young age, due to inherited mutations in mismatch repair genes. We investigated whether modifiable lifestyle factors, such as smoking and alcohol intake, increase this risk. METH

  5. Smoking increases the risk for colorectal adenomas in patients with Lynch syndrome.

    NARCIS (Netherlands)

    Winkels, R.M.; Botma, A.; Duijnhoven, F.J.B. van; Nagengast, F.M.; Kleibeuker, J.H.; Vasen, H.F.; Kampman, E.

    2012-01-01

    BACKGROUND & AIMS: Individuals with Lynch syndrome have a high risk of developing colorectal carcinomas and adenomas at a young age, due to inherited mutations in mismatch repair genes. We investigated whether modifiable lifestyle factors, such as smoking and alcohol intake, increase this risk. METH

  6. Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer).

    NARCIS (Netherlands)

    Vasen, H.F.; Moslein, G.; Alonso, A.; Bernstein, I.; Bertario, L.; Blanco, I.; Burn, J.; Capella, G.; Engel, C.; Frayling, I.; Friedl, W.; Hes, F.J.; Hodgson, S.; Mecklin, J.P.; Moller, P.; Nagengast, F.M.; Parc, Y.; Renkonen-Sinisalo, L.; Sampson, J.R.; Stormorken, A.; Wijnen, J.

    2007-01-01

    Lynch syndrome (hereditary non-polyposis colorectal cancer) is characterised by the development of colorectal cancer, endometrial cancer and various other cancers, and is caused by a mutation in one of the mismatch repair genes: MLH1, MSH2, MSH6 or PMS2. The discovery of these genes, 15 years ago,

  7. The InSiGHT database : utilizing 100 years of insights into Lynch Syndrome

    NARCIS (Netherlands)

    Plazzer, J. P.; Sijmons, R. H.; Woods, M. O.; Peltomaki, P.; Thompson, B.; Den Dunnen, J. T.; Macrae, F.

    2013-01-01

    This article provides a historical overview of the online database (www.insight-group.org/mutations) maintained by the International Society for Gastrointestinal Hereditary Tumours. The focus is on the mismatch repair genes which are mutated in Lynch Syndrome. APC, MUTYH and other genes are also an

  8. HEREDITARY NON-POLYPOSIS COLORECTAL CANCER (LYNCH SYNDROME PADA WANITA UMUR 16 TAHUN

    Directory of Open Access Journals (Sweden)

    Asril Zahari

    2011-09-01

    Full Text Available AbstrakKanker kolorektal menduduki peringkat ketiga jenis kanker yang paling sering terjadi di dunia. Sekitar 3% kasus kanker kolorektal merupakan jenis hereditary non polyposis colorectal cancer (HNPCC/Lynch syndrome, yang sering muncul pada usia muda. Dilaporkan satu kasus di rumah sakit Dr. M. Djamil Padang, wanita berumur 16 tahun dengan keluhan nyeri perut kanan bawah. Didapatkan riwayat penyakit serupa pada kakek, bibi pasien dan enam anggota keluarga yang lain. Pada pemeriksaan fisik abdomen teraba massa dengan konsistensi keras dan terfiksir. Pada kolonoskopi dan biopsi ditemukan tumor jenis adenocarcinoma colon moderatly differentiated di fleksura hepatika dan polip di kolon sigmoid. Berdasarkan kriteria Amsterdam pasien didiagnosa Lynch syndrome. Pada Pasien dilakukan subtotal kolektomi, anastomose ileorectal dan kemoterapi ajuvan. Identifikasi genetik sedang dikerjakan untuk melihat adanya kelainan genetik pada pasien. Pasien melakukan skrining berkala untuk mencegah kanker HNPCC jenis yang lain.Kata kunci : Hereditary non polyposis colorectal cancer, Lynch syndrome, Microsatellite instability, skrining.AbstractCarcinoma colorectal is the third most common type of cancer that occurs in the world. About 2% -3% of cases of colorectal cancer is hereditary non-polyposis colorectal cancer (HNPCC/Lynch syndrome, which often appear at a young age. Amsterdam and Bethesda criteria have been used to identify patients with Lynch syndrome.one case was reported at the Dr. M. Djamil Padang hospital, a 16-year-old girl with right lower abdominal pain. Obtained a history of similar disease in grandparents, aunts and six other family members. On physical examination found palpable fixed abdominal mass with hard consistency in the lower right abdomen. At colonoscopy and biopsy found a moderatly differentiated adenocarcinoma colon type at the hepatic flexure and the sigmoid colon polyp. Based on the Amsterdam criteria, patients diagnosed with HNPCC/Lynch

  9. Limited impact on self-concept in individuals with Lynch syndrome; results from a national cohort study

    DEFF Research Database (Denmark)

    Petersen, Helle Vendel; Esplen, Mary Jane; Ladelund, Steen;

    2011-01-01

    An increasing number of individuals seek genetic counseling and hereby learn about hereditary cancer in the family. Lynch syndrome is associated with an inherited high risk for colorectal and gynecological cancer, but knowledge about how family members at risk perceive their situation is limited....... We used the national Danish HNPCC register to collect data on self-concept from 413 individuals with Lynch syndrome. The recently developed Lynch syndrome self-concept scale contains 20 items within two subscales related to stigma-vulnerability and bowel symptom-related anxiety. Significantly higher...

  10. [Management and Nursing care for a patient with Lynch syndrome: A case report].

    Science.gov (United States)

    Pacheco-Pérez, Luis Arturo; Guevara Valtier, Milton Carlos

    2016-01-01

    Colorectal cancer is one of the leading causes of death from cancer worldwide. Main interventions to reduce the impact are aimed to enhance prevention and early detection. Results of several studies show that tests such as the fecal occult blood test and colonoscopy are effective for early diagnosis. There are hereditary syndromes such as Lynch Syndrome that can lead to certain types of cancers, including bowel neoplasms, therefore early detection needs to be included as part of the treatment. In these cases, family genetic testing is recommended if the bowel cancer is diagnosed before 50 years old. A care plan including the NANDA (North American Nursing Diagnosis Association), NOC (Nursing Outcomes Classification) and NIC (Nursing Interventions Classification) was developed for a patient with suspected Lynch Syndrome. Nurses should be qualified to identify potential cases of cancer associated with this syndrome, and thus, reduce the likelihood that family members develop the disease, through genetic counseling and education of environmental risk factors.

  11. Comprehensive population-wide analysis of Lynch syndrome in Iceland reveals founder mutations in MSH6 and PMS2

    DEFF Research Database (Denmark)

    Haraldsdottir, Sigurdis; Rafnar, Thorunn; Frankel, Wendy L

    2017-01-01

    Lynch syndrome, caused by germline mutations in the mismatch repair genes, is associated with increased cancer risk. Here using a large whole-genome sequencing data bank, cancer registry and colorectal tumour bank we determine the prevalence of Lynch syndrome, associated cancer risks...... hypermethylation or mutations in the mismatch repair genes. The population prevalence of Lynch syndrome is 0.442%. We discover a translocation disrupting MLH1 and three mutations in MSH6 and PMS2 that increase endometrial, colorectal, brain and ovarian cancer risk. We find thirteen mismatch repair variants...... and pathogenicity of several variants in the Icelandic population. We use colorectal cancer samples from 1,182 patients diagnosed between 2000-2009. One-hundred and thirty-two (11.2%) tumours are mismatch repair deficient per immunohistochemistry. Twenty-one (1.8%) have Lynch syndrome while 106 (9.0%) have somatic...

  12. Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-Society Task Force on colorectal cancer.

    Science.gov (United States)

    Giardiello, Francis M; Allen, John I; Axilbund, Jennifer E; Boland, C Richard; Burke, Carol A; Burt, Randall W; Church, James M; Dominitz, Jason A; Johnson, David A; Kaltenbach, Tonya; Levin, Theodore R; Lieberman, David A; Robertson, Douglas J; Syngal, Sapna; Rex, Douglas K

    2014-08-01

    The Multi-Society Task Force, in collaboration with invited experts, developed guidelines to assist health care providers with the appropriate provision of genetic testing and management of patients at risk for and affected with Lynch syndrome as follows: Figure 1 provides a colorectal cancer risk assessment tool to screen individuals in the office or endoscopy setting; Figure 2 illustrates a strategy for universal screening for Lynch syndrome by tumor testing of patients diagnosed with colorectal cancer; Figures 3-6 provide algorithms for genetic evaluation of affected and at-risk family members of pedigrees with Lynch syndrome; Table 10 provides guidelines for screening at-risk and affected persons with Lynch syndrome; and Table 12 lists the guidelines for the management of patients with Lynch syndrome. A detailed explanation of Lynch syndrome and the methodology utilized to derive these guidelines, as well as an explanation of, and supporting literature for, these guidelines are provided.

  13. Effect of aspirin or resistant starch on colorectal neoplasia in the Lynch syndrome

    DEFF Research Database (Denmark)

    Burn, John; Bishop, D Timothy; Mecklin, Jukka-Pekka

    2008-01-01

    .4%) (relative risk, 1.0; 95% CI, 0.7 to 1.4). Advanced adenomas and colorectal cancers were evenly distributed in the two groups. The prevalence of serious adverse events was low, and the events were evenly distributed. CONCLUSIONS: The use of aspirin, resistant starch, or both for up to 4 years has no effect......BACKGROUND: Observational and epidemiologic data indicate that the use of aspirin reduces the risk of colorectal neoplasia; however, the effects of aspirin in the Lynch syndrome (hereditary nonpolyposis colon cancer) are not known. Resistant starch has been associated with an antineoplastic effect...... on the incidence of colorectal adenoma or carcinoma among carriers of the Lynch syndrome. (Current Controlled Trials number, ISRCTN59521990.)...

  14. Urinary Tract Cancer in Lynch Syndrome; Increased Risk in Carriers of MSH2 Mutations

    DEFF Research Database (Denmark)

    Joost, Patrick; Therkildsen, Christina; Dominguez-Valentin, Mev

    2015-01-01

    nonpolyposis colorectal cancer registry was used to identify all 288 Lynch syndrome families in Denmark. Urothelial cancers that developed in mutation carriers and in their first-degree relatives were identified, mismatch-repair status was assessed, clinicopathologic variables were defined, and cumulative......OBJECTIVE: To evaluate the risk of urothelial cancer in the upper urinary tract and the bladder, determine the contribution from the different mismatch-repair genes, and define clinical characteristics of urothelial cancer in Lynch syndrome. MATERIALS AND METHODS: The national hereditary...... lifetime risks were determined. RESULTS: In total, 48 cancers of the ureter, 34 cancers of the renal pelvis, and 54 urinary bladder cancers developed at a mean age of 61 (24-89) years. The tumors were typically of high grade, showed loss of mismatch-repair protein expression in 90% of the tumors...

  15. Lynch syndrome: barriers to and facilitators of screening and disease management

    Directory of Open Access Journals (Sweden)

    Watkins Kathy E

    2011-09-01

    Full Text Available Abstract Background Lynch syndrome is a hereditary cancer with confirmed carriers at high risk for colorectal (CRC and extracolonic cancers. The purpose of the current study was to develop a greater understanding of the factors influencing decisions about disease management post-genetic testing. Methods The study used a grounded theory approach to data collection and analysis as part of a multiphase project examining the psychosocial and behavioral impact of predictive DNA testing for Lynch syndrome. Individual and small group interviews were conducted with individuals from 10 families with the MSH2 intron 5 splice site mutation or exon 8 deletion. The data from confirmed carriers (n = 23 were subjected to re-analysis to identify key barriers to and/or facilitators of screening and disease management. Results Thematic analysis identified personal, health care provider and health care system factors as dominant barriers to and/or facilitators of managing Lynch syndrome. Person-centered factors reflect risk perceptions and decision-making, and enduring screening/disease management. The perceived knowledge and clinical management skills of health care providers also influenced participation in recommended protocols. The health care system barriers/facilitators are defined in terms of continuity of care and coordination of services among providers. Conclusions Individuals with Lynch syndrome often encounter multiple barriers to and facilitators of disease management that go beyond the individual to the provider and health care system levels. The current organization and implementation of health care services are inadequate. A coordinated system of local services capable of providing integrated, efficient health care and follow-up, populated by providers with knowledge of hereditary cancer, is necessary to maintain optimal health.

  16. Lynch syndrome: barriers to and facilitators of screening and disease management.

    Science.gov (United States)

    Watkins, Kathy E; Way, Christine Y; Fiander, Jacqueline J; Meadus, Robert J; Esplen, Mary Jane; Green, Jane S; Ludlow, Valerie C; Etchegary, Holly A; Parfrey, Patrick S

    2011-09-07

    Lynch syndrome is a hereditary cancer with confirmed carriers at high risk for colorectal (CRC) and extracolonic cancers. The purpose of the current study was to develop a greater understanding of the factors influencing decisions about disease management post-genetic testing. The study used a grounded theory approach to data collection and analysis as part of a multiphase project examining the psychosocial and behavioral impact of predictive DNA testing for Lynch syndrome. Individual and small group interviews were conducted with individuals from 10 families with the MSH2 intron 5 splice site mutation or exon 8 deletion. The data from confirmed carriers (n = 23) were subjected to re-analysis to identify key barriers to and/or facilitators of screening and disease management. Thematic analysis identified personal, health care provider and health care system factors as dominant barriers to and/or facilitators of managing Lynch syndrome. Person-centered factors reflect risk perceptions and decision-making, and enduring screening/disease management. The perceived knowledge and clinical management skills of health care providers also influenced participation in recommended protocols. The health care system barriers/facilitators are defined in terms of continuity of care and coordination of services among providers. Individuals with Lynch syndrome often encounter multiple barriers to and facilitators of disease management that go beyond the individual to the provider and health care system levels. The current organization and implementation of health care services are inadequate. A coordinated system of local services capable of providing integrated, efficient health care and follow-up, populated by providers with knowledge of hereditary cancer, is necessary to maintain optimal health.

  17. Serum antibodies against frameshift peptides in microsatellite unstable colorectal cancer patients with Lynch syndrome.

    Science.gov (United States)

    Reuschenbach, Miriam; Kloor, Matthias; Morak, Monika; Wentzensen, Nicolas; Germann, Anja; Garbe, Yvette; Tariverdian, Mirjam; Findeisen, Peter; Neumaier, Michael; Holinski-Feder, Elke; von Knebel Doeberitz, Magnus

    2010-06-01

    High level microsatellite instability (MSI-H) occurs in about 15% of colorectal cancer (CRCs), either as sporadic cancers or in the context of hereditary non-polyposis cancer or Lynch syndrome. In MSI-H CRC, mismatch repair deficiency leads to insertion/deletion mutations at coding microsatellites and thus to the translation of frameshift peptides (FSPs). FSPs are potent inductors of T cell responses in vitro and in vivo. The present study aims at the identification of FSP-specific humoral immune responses in MSI-H CRC and Lynch syndrome. Sera from patients with history of MSI-H CRC (n = 69), healthy Lynch syndrome mutation carriers (n = 31) and healthy controls (n = 52) were analyzed for antibodies against FSPs using peptide ELISA. Reactivities were measured against FSPs derived from genes frequently mutated in MSI-H CRCs, AIM2, TGFBR2, CASP5, TAF1B, ZNF294, and MARCKS. Antibody reactivity against FSPs was significantly higher in MSI-H CRC patients than in healthy controls (P = 0.036, Mann-Whitney) and highest in patients with shortest interval between tumor resection and serum sampling. Humoral immune responses in patients were most frequently directed against FSPs derived from mutated TAF1B (11.6%, 8/69) and TGFBR2 (10.1%, 7/69). Low level FSP-specific antibodies were also detected in healthy mutation carriers. Our results show that antibody responses against FSPs are detectable in MSI-H CRC patients and healthy Lynch syndrome mutation carriers. Based on the high number of defined FSP antigens, measuring FSP-specific humoral immune responses is a highly promising tool for future diagnostic application in MSI-H cancer patients.

  18. Validation of a Self-Concept Scale for Lynch Syndrome in Different Nationalities

    DEFF Research Database (Denmark)

    Petersen, Helle Vendel; Domanska, Katarina; Bendahl, Pär-Ola;

    2011-01-01

    syndrome. We compared the performance of this scale in 591 mutation carriers from Denmark, Sweden and Canada. Principal component analysis identified two sets of linked statements-the first related to feeling different, isolated and labeled, and the second to concern and worry about bowel changes....... The scale performed consistently in the three countries. Minor differences were identified, with guilt about passing on a defective gene and feelings of losing one's privacy being more pronounced among Canadians, whereas Danes more often expressed worries about cancer. Validation of the Lynch syndrome self...

  19. Assessing Genetic Variants of Uncertain Significance: The Example of Lynch Syndrome

    DEFF Research Database (Denmark)

    Rasmussen, Lene Juel; Heinen, Christopher D.

    2014-01-01

    variants of uncertain significance (VUS). This leads to anxiety in carriers and noncarrying relatives alike, as well as to an unnecessary burden to preventive healthcare. The establishment of procedures that enable the diagnostic assessment of VUSs in individuals are discussed and hereditary colorectal...... cancer syndrome, Lynch syndrome, is used as an example. This challenge is addressed by illustrating the importance of combining genetic and functional data in future strategies to assess VUS. The proposed strategies combine clinical genetic, analytical, functional and in silico approaches....

  20. Subtotal Colectomy for Colon Cancer Reduces the Need for Subsequent Surgery in Lynch Syndrome.

    Science.gov (United States)

    Renkonen-Sinisalo, Laura; Seppälä, Toni T; Järvinen, Heikki J; Mecklin, Jukka-Pekka

    2017-08-01

    The risk of metachronous colorectal cancer is high after surgical resection for first colon cancer in Lynch syndrome. This study aimed to examine whether extended surgery decreases the risk of subsequent colorectal cancer and improves long-term survival. This was a retrospective study. Data were collected from a nationwide registry. Two hundred forty-two Lynch syndrome pathogenic variant carriers who underwent surgery for a first colon cancer from 1984 to 2009 were included. Patients underwent standard segmental colectomy (n = 144) or extended colectomy (n = 98) for colon cancer. Patients were followed a median of 14.6 up to 25 years. Risk of subsequent colorectal cancer in either group, overall and disease-specific survival, and operative mortality were the primary outcomes measured. Subtotal colectomy decreased the risk of subsequent colorectal cancer (HR, 0.20; 95% CI, 0.08-0.52; p = 0.001), compared with segmental resection. Subsequent colorectal cancer decreased in MLH1 carriers. The MSH2 carriers showed no statistical difference, possibly because of their small number. Disease-specific and overall survival within 25 years did not differ between the standard and extended surgeries (82.7% vs 87.2%, p = 0.76 and 47.2% vs 41.4%, p = 0.83). The cumulative risk of subsequent colorectal cancer was 20% in 10 years and 47% within 25 years after standard resection and 4% and 9% after extended surgery. The cumulative risk of metachronous colorectal cancer was 7% within 25 years after subtotal colectomy with ileosigmoidal anastomosis. One patient died of postoperative septicemia within 30 days after segmental colectomy. Data on surgical procedures were primarily collected retrospectively. Lynch syndrome pathogenic variant carriers may undergo subtotal colectomy to manage first colon cancer and avoid repetitive abdominal surgery and to reduce the remaining bowel to facilitate easier endoscopic surveillance. It provides no survival benefit, compared with segmental colon

  1. Role of the clinical pathology laboratory in the evaluation of endometrial carcinomas for Lynch syndrome.

    Science.gov (United States)

    Djordjevic, Bojana; Broaddus, Russell R

    2014-05-01

    Molecular diagnostic testing of endometrial carcinomas in the pathology laboratory has recently emerged as a key component of the clinical evaluation of Lynch syndrome in many centers. Testing modalities involve immunohistochemical and PCR-based analyses. This article outlines the routine application of these analyses, provides a practical guide for troubleshooting some of the common technical issues related to their performance, and reviews common pitfalls in their interpretation. Discrepancies between tissue testing and genetic testing results are discussed in the context of the current understanding of endometrial cancer biology. The merits of universal versus targeted tissue testing based on clinical patient history and histological tumor appearance are also addressed.

  2. Achieving behaviour change for detection of Lynch syndrome using the Theoretical Domains Framework Implementation (TDFI) approach: a study protocol.

    Science.gov (United States)

    Taylor, Natalie; Long, Janet C; Debono, Deborah; Williams, Rachel; Salisbury, Elizabeth; O'Neill, Sharron; Eykman, Elizabeth; Braithwaite, Jeffrey; Chin, Melvin

    2016-03-12

    Lynch syndrome is an inherited disorder associated with a range of cancers, and found in 2-5 % of colorectal cancers. Lynch syndrome is diagnosed through a combination of significant family and clinical history and pathology. The definitive diagnostic germline test requires formal patient consent after genetic counselling. If diagnosed early, carriers of Lynch syndrome can undergo increased surveillance for cancers, which in turn can prevent late stage cancers, optimise treatment and decrease mortality for themselves and their relatives. However, over the past decade, international studies have reported that only a small proportion of individuals with suspected Lynch syndrome were referred for genetic consultation and possible genetic testing. The aim of this project is to use behaviour change theory and implementation science approaches to increase the number and speed of healthcare professional referrals of colorectal cancer patients with a high-likelihood risk of Lynch syndrome to appropriate genetic counselling services. The six-step Theoretical Domains Framework Implementation (TDFI) approach will be used at two large, metropolitan hospitals treating colorectal cancer patients. Steps are: 1) form local multidisciplinary teams to map current referral processes; 2) identify target behaviours that may lead to increased referrals using discussion supported by a retrospective audit; 3) identify barriers to those behaviours using the validated Influences on Patient Safety Behaviours Questionnaire and TDFI guided focus groups; 4) co-design interventions to address barriers using focus groups; 5) co-implement interventions; and 6) evaluate intervention impact. Chi square analysis will be used to test the difference in the proportion of high-likelihood risk Lynch syndrome patients being referred for genetic testing before and after intervention implementation. A paired t-test will be used to assess the mean time from the pathology test results to referral for high

  3. A clinical scoring system to identify patients with sebaceous neoplasms at risk for the Muir-Torre variant of Lynch syndrome.

    Science.gov (United States)

    Roberts, Maegan E; Riegert-Johnson, Douglas L; Thomas, Brittany C; Rumilla, Kandelaria M; Thomas, Colleen S; Heckman, Michael G; Purcell, Jennifer U; Hanson, Nancy B; Leppig, Kathleen A; Lim, Justin; Cappel, Mark A

    2014-09-01

    The Muir-Torre syndrome variant of Lynch syndrome is characterized by the presence of sebaceous neoplasms (adenoma, epithelioma/sebaceoma, carcinoma) and Lynch syndrome-associated cancers (colon, endometrial, and others). Several clinical scoring systems have been developed to identify patients with colon cancer at high risk of Lynch syndrome. However, no such system has been described for patients presenting with sebaceous neoplasms. Based on logistic regression analysis, a scoring system was developed for patients with sebaceous neoplasm to identify those with the highest likelihood of having Muir-Torre syndrome. The final version of the scoring system included variables such as age at presentation of initial sebaceous neoplasm, total number of sebaceous neoplasms, personal history of a Lynch-related cancer, and family history of Lynch-related cancers. Patients with a score of 3 or more were more likely to have Muir-Torre syndrome (28 of 29 patients), those with a score of 2 had intermediate likelihood (12 of 20 patients), and no patient with a score of 0 or 1 was diagnosed with Muir-Torre syndrome. The Mayo Muir-Torre syndrome risk scoring system appears to identify whether patients who present with sebaceous neoplasms are in need of further Lynch syndrome evaluation using easily ascertained clinical information. Abnormal mismatch repair gene immunohistochemistry of a sebaceous neoplasm is a poor predictor in regard to diagnosing Lynch syndrome.

  4. Identification of individuals at risk for Lynch syndrome using targeted evaluations and genetic testing: National Society of Genetic Counselors and the Collaborative Group of the Americas on Inherited Colorectal Cancer joint practice guideline.

    Science.gov (United States)

    Weissman, Scott M; Burt, Randall; Church, James; Erdman, Steve; Hampel, Heather; Holter, Spring; Jasperson, Kory; Kalady, Matt F; Haidle, Joy Larsen; Lynch, Henry T; Palaniappan, Selvi; Wise, Paul E; Senter, Leigha

    2012-08-01

    Identifying individuals who have Lynch syndrome (LS) involves a complex diagnostic work up that includes taking a detailed family history and a combination of various genetic and immunohistochemical tests. The National Society of Genetic Counselors (NSGC) and the Collaborative Group of the Americas on Inherited Colorectal Cancer (CGA-ICC) have come together to publish this clinical practice testing guideline for the evaluation of LS. The purpose of this practice guideline is to provide guidance and a testing algorithm for LS as well as recommendations on when to offer testing. This guideline does not replace a consultation with a genetics professional. This guideline includes explanations in support of this and a summary of background data. While this guideline is not intended to serve as a review of LS, it includes a discussion of background information on LS, and cites a number of key publications which should be reviewed for a more in-depth understanding of LS. These guidelines are intended for genetic counselors, geneticists, gastroenterologists, surgeons, medical oncologists, obstetricians and gynecologists, nurses and other healthcare providers who evaluate patients for LS.

  5. Clinical problems of colorectal cancer and endometrial cancer cases with unknown cause of tumor mismatch repair deficiency (suspected Lynch syndrome

    Directory of Open Access Journals (Sweden)

    Buchanan DD

    2014-10-01

    Full Text Available Daniel D Buchanan,1,2 Christophe Rosty,1,3,4 Mark Clendenning,1 Amanda B Spurdle,5 Aung Ko Win2 1Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia; 2Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia; 3Envoi Specialist Pathologists, Herston, QLD, Australia; 4School of Medicine, University of Queensland, Herston, QLD, Australia; 5Molecular Cancer Epidemiology Laboratory, Genetics and Computational Biology Division, QIMR Berghofer Medical Research Institute, Herston, QLD, AustraliaAbstract: Carriers of a germline mutation in one of the DNA mismatch repair (MMR genes have a high risk of developing numerous different cancers, predominantly colorectal cancer and endometrial cancer (known as Lynch syndrome. MMR gene mutation carriers develop tumors with MMR deficiency identified by tumor microsatellite instability or immunohistochemical loss of MMR protein expression. Tumor MMR deficiency is used to identify individuals most likely to carry an MMR gene mutation. However, MMR deficiency can also result from somatic inactivation, most commonly methylation of the MLH1 gene promoter. As tumor MMR testing of all incident colorectal and endometrial cancers (universal screening is becoming increasingly adopted, a growing clinical problem is emerging for individuals who have tumors that show MMR deficiency who are subsequently found not to carry an MMR gene mutation after genetic testing using the current diagnostic approaches (Sanger sequencing and multiplex ligation-dependent probe amplification and who also show no evidence of MLH1 methylation. The inability to determine the underlying cause of tumor MMR deficiency in these "Lynch-like" or "suspected Lynch syndrome" cases has significant implications on the clinical management of these individuals and their relatives. When the

  6. Sessile serrated polyps of the colorectum are rare in patients with Lynch syndrome and in familial colorectal cancer families

    DEFF Research Database (Denmark)

    Andersen, S H; Lykke, E; Folker, M B

    2008-01-01

    Whereas the generally accepted carcinogenesis pathway of the microsatellite instabile high (MSI-H) colorectal carcinoma (CRC) involves the traditional adenoma in patients with Lynch syndrome, a serrate pathway involving serrate adenomas (SA) and sessile serrate polyps (SSP) characterize the spora......Whereas the generally accepted carcinogenesis pathway of the microsatellite instabile high (MSI-H) colorectal carcinoma (CRC) involves the traditional adenoma in patients with Lynch syndrome, a serrate pathway involving serrate adenomas (SA) and sessile serrate polyps (SSP) characterize...... the FCF, were considered examples of probable SSP. None of the 41 cases coded as adenoma possessed a morphology that qualified as SSP. The prevalence of SSP was not increased as compared to the background population and thus, this serrated lesion does not appear to play a tumorigenic role in Lynch...

  7. Evaluation of Lynch syndrome modifier genes in 748 MMR mutation carriers.

    Science.gov (United States)

    Houlle, Solene; Charbonnier, Françoise; Houivet, Estelle; Tinat, Julie; Buisine, Marie-Pierre; Caron, Olivier; Benichou, Jacques; Baert-Desurmont, Stéphanie; Frebourg, Thierry

    2011-08-01

    Several studies have reported that, in Lynch syndrome resulting from mutations of the mismatch repair (MMR) genes, a CA repeat ≤17 within the IGF1 promoter, SNPs within the xenobiotic metabolizing enzyme gene CYP1A1 and SNPs on 8q23.3 and 11q23.1 modify colorectal cancer (CRC) risk in MMR mutation carriers. We analysed the impact of these polymorphisms on CRC risk in 748 French MMR mutation carriers derived from 359 families. We also analysed the effect of the Novel 1 SNP (18q21), which has recently been shown to increase CRC risk in the general population. We observed a significant difference in the CRC-free survival time between males and females, between MSH2 and MSH6 mutation carriers and between MLH1 and MSH6, indicating that this series is representative of Lynch syndrome. In contrast, the univariate log-rank test, as well as multivariate Cox model analysis controlling for familial aggregation and mutated MMR gene, year of birth and gender showed that the polymorphic alleles tested were not associated with a significant CRC risk increase, neither on the entire sample nor among males and females. This discrepancy with previous reports might be explained both by the genetic heterogeneity between the different populations analysed and the allelic heterogeneity of the MMR mutations. We conclude that genotyping of these polymorphisms is not useful to evaluate CRC risk in MMR mutation carriers and to optimize their clinical follow-up.

  8. Limited impact on self-concept in individuals with Lynch syndrome; results from a national cohort study

    DEFF Research Database (Denmark)

    Petersen, Helle Vendel; Esplen, Mary Jane; Ladelund, Steen;

    2011-01-01

    An increasing number of individuals seek genetic counseling and hereby learn about hereditary cancer in the family. Lynch syndrome is associated with an inherited high risk for colorectal and gynecological cancer, but knowledge about how family members at risk perceive their situation is limited...

  9. Analysis of Families with Lynch Syndrome Complicated by Advanced Serrated Neoplasia: The Importance of Pathology Review and Pedigree Analysis

    Science.gov (United States)

    Walsh, Michael D; Buchanan, Daniel D; Walters, Rhiannon; Roberts, Aedan; Arnold, Sven; McKeone, Diane; Clendenning, Mark; Ruszkiewicz, Andrew R; Jenkins, Mark A; Hopper, John L; Goldblatt, Jack; George, Jillian; Suthers, Graeme K; Phillips, Kerry; Young, Graeme P; Macrae, Finlay; Drini, Musa; Woods, Michael O; Parry, Susan; Jass, Jeremy R; Young, Joanne P

    2009-01-01

    The identification of Lynch syndrome has been greatly assisted by the advent of tumour immunohistochemistry (IHC) for mismatch repair (MMR) proteins, and by the recognition of the role of acquired somatic BRAF mutation in sporadic MMR-deficient colorectal cancer (CRC). However, somatic BRAF mutation may also be present in the tumours in families with a predisposition to develop serrated polyps in the colorectum. In a subgroup of affected members in these families, CRCs emerge which demonstrate clear evidence of MMR deficiency with absent MLH1 staining and high-level microsatellite instability (MSI). This may result in these families being erroneously classified as Lynch syndrome or, conversely, an individual is considered “sporadic” due to the presence of a somatic BRAF mutation in a tumour. In this report, we describe two Lynch syndrome families who demonstrated several such inconsistencies. In one family, IHC deficiency of both MSH2 and MLH1 was demonstrated in tumours from different affected family members, presenting a confusing diagnostic picture. In the second family, MLH1 loss was observed in the lesions of both MLH1 mutation carriers and those who showed normal MLH1 germline sequence. Both families had Lynch syndrome complicated by an independently segregating serrated neoplasia phenotype, suggesting that in families such as these, tumour and germline studies of several key members, rather than of a single proband, are indicated to clarify the spectrum of risk. PMID:19241144

  10. Chromosome 8q23.3 and 11q23.1 Variants Modify Colorectal Cancer Risk in Lynch Syndrome

    NARCIS (Netherlands)

    Wijnen, Juul T.; Brohet, Richard M.; Van Eijk, Ronald; Jagmohan-Changur, Shanty; Middeldorp, Anneke; Tops, Carli M.; Van Puijenbroek, Mario; Ausems, Margreet G. E. M.; Garcia, Encarna Gomez; Hes, Frederik J.; Hoogerbrugge, Nicoline; Menko, Fred H.; Van Os, Theo A. M.; Sijmons, Rolf H.; Verhoef, Senno; Wagner, Anja; Nagengast, Fokko M.; Kleibeuker, Jan H.; Devilee, Peter; Morreau, Hans; Goldgar, David; Tomlinson, Ian P.; Houlston, Richard S.; Van Wezel, Tom; Vasen, Hans F. A.

    2009-01-01

    Background & Aims: Recent genome-wide association studies have identified common low-risk variants for colorectal cancer (CRC). To assess whether these influence CRC risk in the Lynch syndrome, we genotyped these variants in a large series of proven mutation carriers. Methods: We studied 675 individ

  11. Sessile serrated polyps of the colorectum are rare in patients with Lynch syndrome and in familial colorectal cancer families

    DEFF Research Database (Denmark)

    Andersen, S H; Lykke, E; Folker, M B;

    2008-01-01

    (FCF) is addressed. Polyps coded as hyperplastic polyps (HP) from subjects with Lynch syndrome and FCF enrolled in the HNPCC-register at the Hvidovre University Hospital as well as adenomas from this population were retrieved and reviewed for features of SSP. Ninety-eight polyps coded as HP and 41...

  12. Barriers and Motivators for Referral of Patients with Suspected Lynch Syndrome to Cancer Genetic Services: A Qualitative Study

    Directory of Open Access Journals (Sweden)

    Yen Y. Tan

    2014-02-01

    Full Text Available This article explores the views of general practitioners and specialists on their referral of patients with suspected Lynch syndrome to cancer genetic services. Using a purposive maximum variation sampling strategy, we conducted semi-structured interviews face-to-face with 28 general practitioners and specialists in public or private hospitals and specialist clinics between March and August 2011. General practitioners and specialists were recruited in a major metropolitan area in Australia. Interview transcripts were reviewed by two independent researchers, and thematic analysis was performed using NVivo10 software. The main barriers and motivators identified were: (1 clinician-related (e.g., familiarity with Lynch syndrome and family history knowledge; (2 patient-related (e.g., patients’ interests and personal experience with cancer; and (3 organizational-related (e.g., access to services, guidelines and referral pathway. Referral of patients with suspected Lynch syndrome to cancer genetic services is motivated and hindered by a range of individual, interpersonal and organizational factors. In order to improve the care and quality of life of patients and family with suspected Lynch syndrome, further research is needed to develop supportive tools for clinicians.

  13. Rectal Cancer Diagnosed after Cesarean Section in Which High Microsatellite Instability Indicated the Presence of Lynch Syndrome

    Directory of Open Access Journals (Sweden)

    Tomohiro Okuda

    2015-01-01

    Full Text Available We report a case of rectal cancer with microsatellite instability (MSI that probably resulted from Lynch syndrome and that was diagnosed after Cesarean section. The patient was a 28-year-old woman (gravid 1, para 1 without a significant medical history. At 35 gestational weeks, vaginal ultrasonography revealed a 5 cm tumor behind the uterine cervix, which was diagnosed as a uterine myoma. The tumor gradually increased in size and blocked the birth canal, resulting in the patient undergoing an emergency Cesarean section. Postoperatively, the tumor was diagnosed as rectal cancer with MSI. After concurrent chemoradiation therapy, a lower anterior resection was performed. The patient’s family history revealed she met the criteria of the revised Bethesda guidelines for testing the colorectal tumor for MSI. Testing revealed that the tumor did indeed show high MSI and, combined with the family history, suggested this could be a case of Lynch syndrome. Our findings emphasize the importance of considering the possibility of Lynch syndrome in pregnant women with colorectal cancer, particularly those with a family history of this condition. We suggest that the presence of Lynch syndrome should also be considered for any young woman with endometrial, ovarian, or colorectal cancer.

  14. Evidence for classification of c.1852_1853AA>GC in MLH1 as a neutral variant for Lynch syndrome

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    Llor Xavier

    2011-01-01

    Full Text Available Abstract Background Lynch syndrome (LS is an autosomal dominant inherited cancer syndrome characterized by early onset cancers of the colorectum, endometrium and other tumours. A significant proportion of DNA variants in LS patients are unclassified. Reports on the pathogenicity of the c.1852_1853AA>GC (p.Lys618Ala variant of the MLH1 gene are conflicting. In this study, we provide new evidence indicating that this variant has no significant implications for LS. Methods The following approach was used to assess the clinical significance of the p.Lys618Ala variant: frequency in a control population, case-control comparison, co-occurrence of the p.Lys618Ala variant with a pathogenic mutation, co-segregation with the disease and microsatellite instability in tumours from carriers of the variant. We genotyped p.Lys618Ala in 1034 individuals (373 sporadic colorectal cancer [CRC] patients, 250 index subjects from families suspected of having LS [revised Bethesda guidelines] and 411 controls. Three well-characterized LS families that fulfilled the Amsterdam II Criteria and consisted of members with the p.Lys618Ala variant were included to assess co-occurrence and co-segregation. A subset of colorectal tumour DNA samples from 17 patients carrying the p.Lys618Ala variant was screened for microsatellite instability using five mononucleotide markers. Results Twenty-seven individuals were heterozygous for the p.Lys618Ala variant; nine had sporadic CRC (2.41%, seven were suspected of having hereditary CRC (2.8% and 11 were controls (2.68%. There were no significant associations in the case-control and case-case studies. The p.Lys618Ala variant was co-existent with pathogenic mutations in two unrelated LS families. In one family, the allele distribution of the pathogenic and unclassified variant was in trans, in the other family the pathogenic variant was detected in the MSH6 gene and only the deleterious variant co-segregated with the disease in both

  15. Ovarian cancer linked to lynch syndrome typically presents as early-onset, non-serous epithelial tumors

    DEFF Research Database (Denmark)

    Bartuma, Katarina; Bernstein, Inge; Malander, Susanne

    2011-01-01

    OBJECTIVE: Heredity is a major cause of ovarian cancer and during recent years the contribution from germline mismatch repair (MMR) gene mutations linked to Lynch syndrome has gradually been recognized. METHODS: We characterized clinical features, tumor morphology and mismatch repair defects in all....... The underlying MMR gene mutations in these families affected MSH2 in 49%, MSH6 in 33% and MLH1 in 17%. Immunohistochemical loss of the corresponding MMR protein was demonstrated in 33/36 (92%) tumors analyzed. CONCLUSION: The combined data from our cohorts demonstrate that ovarian cancer associated with Lynch...

  16. Structure of the human MLH1 N-terminus: implications for predisposition to Lynch syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Hong; Zeng, Hong; Lam, Robert; Tempel, Wolfram [University of Toronto, 101 College Street, Toronto, ON M5G 1L7 (Canada); Kerr, Iain D., E-mail: ikerr@myriad.com [Myriad Genetic Laboratories Inc., 320 Wakara Way, Salt Lake City, UT 84108 (United States); Min, Jinrong, E-mail: ikerr@myriad.com [University of Toronto, 101 College Street, Toronto, ON M5G 1L7 (Canada); University of Toronto, Toronto, ON M5G 1L7 (Canada)

    2015-07-28

    The crystal structure of the human MLH1 N-terminus is reported at 2.30 Å resolution. The overall structure is described along with an analysis of two clinically important mutations. Mismatch repair prevents the accumulation of erroneous insertions/deletions and non-Watson–Crick base pairs in the genome. Pathogenic mutations in the MLH1 gene are associated with a predisposition to Lynch and Turcot’s syndromes. Although genetic testing for these mutations is available, robust classification of variants requires strong clinical and functional support. Here, the first structure of the N-terminus of human MLH1, determined by X-ray crystallography, is described. The structure shares a high degree of similarity with previously determined prokaryotic MLH1 homologs; however, this structure affords a more accurate platform for the classification of MLH1 variants.

  17. Predicting the impact of Lynch syndrome-causing missense mutations from structural calculations

    DEFF Research Database (Denmark)

    Nielsen, Sofie V,; Stein, Amelie; Dinitzen, Alexander B.

    2017-01-01

    Accurate methods to assess the pathogenicity of mutations are needed to fully leverage the possibilities of genome sequencing in diagnosis. Current data-driven and bioinformatics approaches are, however, limited by the large number of new variations found in each newly sequenced genome, and often...... and for diagnosis of Lynch syndrome, and perhaps other hereditary diseases.......Accurate methods to assess the pathogenicity of mutations are needed to fully leverage the possibilities of genome sequencing in diagnosis. Current data-driven and bioinformatics approaches are, however, limited by the large number of new variations found in each newly sequenced genome, and often...... do not provide direct mechanistic insight. Here we demonstrate, for the first time, that saturation mutagenesis, biophysical modeling and co-variation analysis, performed in silico, can predict the abundance, metabolic stability, and function of proteins inside living cells. As a model system, we...

  18. Molecular testing in colorectal cancer: diagnosis of Lynch syndrome and personalized cancer medicine.

    Science.gov (United States)

    Shi, Chanjuan; Washington, Kay

    2012-06-01

    Currently, molecular testing in colorectal cancer (CRC) is aimed at detecting Lynch syndrome and predicting response to anti-epidermal growth factor receptor (EGFR) therapies. However, CRC is a complex disease, with at least 3 molecular pathways of carcinogenesis. The importance of the EGFR signaling pathway in colorectal carcinogenesis is underscored by the availability of anti-EGFR monoclonal antibodies for the treatment of some metastatic CRCs. Potentially, mutations in any of the genes in the EGFR signaling pathway may be associated with prognosis and may predict response to anti-EGFR or other targeted therapies. Although not currently the standard of care, molecular testing of CRCs is expanding to include mutational analysis of the genes in the EGFR pathway, in addition to more widely performed tests for identifying cancers with high microsatellite instability. Multiplex molecular prognostic panels for therapeutic decision making in stage II CRCs also represent expanding use of molecular testing for this common cancer.

  19. Germline mutation analysis of MLH1 and MSH2 in Malaysian Lynch syndrome patients

    Institute of Scientific and Technical Information of China (English)

    Mohd Nizam Zahary; Gurjeet Kaur; Muhammad Radzi Abu Hassan; Harjinder Singh; Venkatesh R Naik; Ravindran Ankathil

    2012-01-01

    AIM:To investigate the protein expression profile of mismatch repair (MMR) genes in suspected cases of Lynch syndrome and to characterize the associated germline mutations.METHODS:Immunohistochemical analysis of tumor samples was performed to determine the protein expression profile of MMR protein.Germline mutation screening was carried out on peripheral blood samples.The entire exon regions of MLH1 and MSH2 genes were amplified by polymerase chain reaction,screened by denaturing high performance liquid chromatography (dHPLC) and analyzed by DNA sequencing to characterize the germline mutations.RESULTS:Three out of 34 tissue samples (8.8%) and four out of 34 tissue samples (11.8%) showed loss of nuclear staining by immunohistochemistry,indicating the absence of MLH1 and MSH2 protein expression in carcinoma cells,respectively.dHPLC analysis followed by DNA sequencing showed these samples to have germline mutations of MSH2 gene.However,no deleterious mutations were identified in any of the 19 exons or coding regions of MLH1 gene,but we were able to identify MLH1 promoter polymorphism,-93G >A (rs1800734),in 21 out of 34 patients (61.8%).We identified one novel mutation,transversion mutation c.2005G > C,which resulted in a missense mutation (Gly669Arg),a transversion mutation in exon 1,c.142G > T,which resulted in a nonsense mutation (Glu48Stop)and splice-site mutation,c.2006-6T > C,which was adjacent to exon 13 of MSH2 gene.CONCLUSION:Germline mutations were identified in four Malaysian Lynch syndrome patients.Immunohistochemical analysis of tumor tissue proved to be a good pre-screening test before proceeding to germline mutation analysis of DNA MMR genes.

  20. Differential expression of CK20, β-catenin, and MUC2/5AC/6 in Lynch syndrome and familial colorectal cancer type X

    DEFF Research Database (Denmark)

    Haraldsson, Stefan; Klarskov, Louise; Nilbert, Mef

    2017-01-01

    BACKGROUND: Hereditary non-polyposis colorectal cancer comprises Lynch syndrome and familial colorectal cancer type X (FCCTX). Differences in genetics, demographics and histopathology have been extensively studied. The purpose of this study is to characterize their immunoprofile of markers other...... than MMR proteins. METHODS: We compared the expression patterns of cytokeratins (CK7 and CK20), mucins (MUC2/5 AC/6), CDX2 and β-catenin in Lynch syndrome and FCCTX. RESULTS: Differences were identified for CK20 and nuclear β-catenin, which were significantly more often expressed in FCCTX than in Lynch...

  1. Syndrome de Lynch: à propos d'un cas et revue de la litterature

    Science.gov (United States)

    Bouguenouch, Laila; Samri, Imane; Belhassan, Khadija; Sayel, Hanane; Abbassi, Meriame; Bennis, Sanae; Benajah, Dafr Allah; Ibrahimi, Adil; Amarti, Afaf; Ouldim, Karim

    2016-01-01

    Le syndrome de Lynch, ou cancer colorectal héréditaire sans polypose ou HNPCC (hereditary non-polyposis colorectal cancer), est la forme la plus fréquente de cancer colorectal héréditaire. Il conduit à une augmentation de la susceptibilité à développer des cancers, au premier rang le cancer colorectal, le cancer de l'endomètre chez les femmes, et dans une moindre mesure, d'autres cancers (ovaire, intestin grêle, estomac, voies excrétrices urinaires et hépatobiliaires). Ainsi, le risque cumulé de développer un cancer colorectal ou de l'endomètre à l’âge de 80 ans s’élève respectivement à 20 et 40%. Ces cancers sont caractérisés par leur contexte d'atteinte familiale, leur survenue à un âge précoce, ainsi que par le développement de cancers métachrones chez un même individu. Ce syndrome se transmet de manière autosomique dominante. Les gènes dont l'altération est associée à l'existence d'un syndrome HNPCC appartiennent à la famille des gènes de réparation des mésappariements de l'ADN (DNA mismatch repair ou MMR): MSH2, MLH1 et MSH6 sont impliqués, par ordre décroissant de fréquence, dans respectivement 35%, 25% et 2% des cas. Une surveillance coloscopique et gynécologique est proposée aux personnes porteuses d'une mutation constitutionnelle du gène MSH2, MLH1 ou MSH6. Nous rapportons une des premières observations marocaines d'un syndrome de Lynch dont la mutation constitutionnelle du gène MLH1 a été identifiée chez un des membres de la famille atteint d'un cancer du côlon. Suite à la demande d'autres sujets sains de la même famille, un diagnostic presymptomatique a été effectué conduisant à une stratégie de surveillance adaptée. A travers notre observation nous illustrons le rôle de l'oncogénétique dans la prise en charge des patients cancéreux et de leurs familles. PMID:27642480

  2. A de novo germline MLH1 mutation in a Lynch syndrome patient with discordant immunohistochemical and molecular biology test results

    Institute of Scientific and Technical Information of China (English)

    Fabrice Airaud; Sébastien Küry; Isabelle Valo; Ingrid Maury; Dominique Bonneau; Olivier Ingster; Stéphane Bezieau

    2012-01-01

    We describe a patient with a Homo sapiens mutL homolog 1 (MLH1)-associated Lynch syndrome with previous diagnoses of two distinct primary cancers:a sigmoid colon cancer at the age of 39 years,and a right colon cancer at the age of 50 years.The mutation identified in his blood and buccal cells,c.1771delG,p.Asp591Ilefs*25,appears to be a de novo event,as it was not transmitted by either of his parents.This type of de novo event is rare in MLH1 as only three cases have been reported in the literature so far.Furthermore,the discordant results observed between replication error phenotyping and immunohistochemistry highlight the importance of the systematic use of both pre-screening tests in the molecular diagnosis of Lynch syndrome.

  3. Population-Based Lynch Syndrome Screening by Microsatellite Instability in Patients ≤50: Prevalence, Testing Determinants, and Result Availability Prior to Colon Surgery.

    Science.gov (United States)

    Karlitz, Jordan J; Hsieh, Mei-Chin; Liu, Yong; Blanton, Christine; Schmidt, Beth; Jessup, J Milburn; Wu, Xiao-Cheng; Chen, Vivien W

    2015-07-01

    As there are no US population-based studies examining Lynch syndrome (LS) screening frequency by microsatellite instability (MSI) and immunohistochemistry (IHC), we seek to quantitate statewide rates in patients aged ≤50 years using data from a Centers for Disease Control and Prevention-funded Comparative Effectiveness Research (CER) project and identify factors associated with testing. Screening rates in this young, high-risk population may provide a best-case scenario as older patients, potentially deemed lower risk, may undergo testing less frequently. We also seek to determine how frequently MSI/IHC results are available preoperatively, as this may assist with decisions regarding colonic resection extent. Data from all Louisiana colorectal cancer (CRC) patients aged ≤50 years diagnosed in 2011 were obtained from the Louisiana Tumor Registry CER project. Registry researchers and physicians analyzed data, including pathology and MSI/IHC. Of the 2,427 statewide all-age CRC patients, there were 274 patients aged ≤50 years, representing health care at 61 distinct facilities. MSI and/or IHC were performed in 23.0% of patients. Testing-associated factors included CRC family history (Plocation (P<0.0370), and care at comprehensive cancer centers (P<0.0020) but not synchronous/metachronous CRC or MSI-like histology. Public hospital screening was disproportionately low (P<0.0217). Of those tested, MSI and/or IHC was abnormal in 21.7%. Of those with abnormal IHC, staining patterns were consistent with LS in 87.5%. MSI/IHC results were available preoperatively in 16.9% of cases. Despite frequently abnormal MSI/IHC results, LS screening in young, high-risk patients is low. Provider education and disparities in access to specialized services, particularly in underserved populations, are possible contributors. MSI/IHC results are infrequently available preoperatively.

  4. Mismatch repair-deficient crypt foci in Lynch syndrome--molecular alterations and association with clinical parameters.

    Directory of Open Access Journals (Sweden)

    Laura Staffa

    Full Text Available Lynch syndrome is caused by germline mutations of DNA mismatch repair (MMR genes, most frequently MLH1 and MSH2. Recently, MMR-deficient crypt foci (MMR-DCF have been identified as a novel lesion which occurs at high frequency in the intestinal mucosa from Lynch syndrome mutation carriers, but very rarely progress to cancer. To shed light on molecular alterations and clinical associations of MMR-DCF, we systematically searched the intestinal mucosa from Lynch syndrome patients for MMR-DCF by immunohistochemistry. The identified lesions were characterised for alterations in microsatellite-bearing genes with proven or suspected role in malignant transformation. We demonstrate that the prevalence of MMR-DCF (mean 0.84 MMR-DCF per 1 cm2 mucosa in the colorectum of Lynch syndrome patients was significantly associated with patients' age, but not with patients' gender. No MMR-DCF were detectable in the mucosa of patients with sporadic MSI-H colorectal cancer (n = 12. Microsatellite instability of at least one tested marker was detected in 89% of the MMR-DCF examined, indicating an immediate onset of microsatellite instability after MMR gene inactivation. Coding microsatellite mutations were most frequent in the genes HT001 (ASTE1 with 33%, followed by AIM2 (17% and BAX (10%. Though MMR deficiency alone appears to be insufficient for malignant transformation, it leads to measurable microsatellite instability even in single MMR-deficient crypts. Our data indicate for the first time that the frequency of MMR-DCF increases with patients' age. Similar patterns of coding microsatellite instability in MMR-DCF and MMR-deficient cancers suggest that certain combinations of coding microsatellite mutations, including mutations of the HT001, AIM2 and BAX gene, may contribute to the progression of MMR-deficient lesions into MMR-deficient cancers.

  5. Family perspectives in lynch syndrome becoming a family at risk, patterns of communication and influence on relations

    Directory of Open Access Journals (Sweden)

    Bartuma Katarina

    2012-05-01

    Full Text Available Abstract Background A growing number of individuals are diagnosed with hereditary cancer. Though increased levels of anxiety and depression have been demonstrated around the time of genetic counselling, most individuals handle life at increased risk well. Data have, however, been collected on individual basis, which led us to focus on family perspectives of hereditary cancer. Methods Lynch syndrome represents a major type of hereditary colorectal and gynaecological cancer. We preformed open-ended interviews with 27 informants from 9 Lynch syndrome families. Inductive content analysis revealed three major themes: transition to a risk family, patterns of communication and influence on family relations and individual roles. Results Family members described how learning about Lynch syndrome shifted focus from daily issues to concerns about cancer. Changes in communication related to difficulties in talking to children about heredity and informing new family members and distant relatives about an increased risk of cancer. Influence on relations was exemplified by family members taking on different roles, e.g. females often being responsible for coordinating information about heredity and providing support. Families in which members had experienced cancer at young age typically informed children soon after learning about heredity and at young age, whereas families with experience of cancer at higher age postponed information and thereby also genetic counselling. Conclusions Three major family perspectives are described in Lynch syndrome families; becoming a risk family, patterns of communication and influence on family relations. Since these issues are central, our findings suggests that such family perspectives should be considered during genetic counselling in order to contribute to information spread, help family members cope with the increased risk, and motivate family members at risk to undergo surveillance.

  6. Contribution of Large Genomic Rearrangements in Italian Lynch Syndrome Patients: Characterization of a Novel Alu-Mediated Deletion

    Directory of Open Access Journals (Sweden)

    Francesca Duraturo

    2013-01-01

    Full Text Available Lynch syndrome is associated with germ-line mutations in the DNA mismatch repair (MMR genes, mainly MLH1 and MSH2. Most of the mutations reported in these genes to date are point mutations, small deletions, and insertions. Large genomic rearrangements in the MMR genes predisposing to Lynch syndrome also occur, but the frequency varies depending on the population studied on average from 5 to 20%. The aim of this study was to examine the contribution of large rearrangements in the MLH1 and MSH2 genes in a well-characterised series of 63 unrelated Southern Italian Lynch syndrome patients who were negative for pathogenic point mutations in the MLH1, MSH2, and MSH6 genes. We identified a large novel deletion in the MSH2 gene, including exon 6 in one of the patients analysed (1.6% frequency. This deletion was confirmed and localised by long-range PCR. The breakpoints of this rearrangement were characterised by sequencing. Further analysis of the breakpoints revealed that this rearrangement was a product of Alu-mediated recombination. Our findings identified a novel Alu-mediated rearrangement within MSH2 gene and showed that large deletions or duplications in MLH1 and MSH2 genes are low-frequency mutational events in Southern Italian patients with an inherited predisposition to colon cancer.

  7. Interval colon cancer in a Lynch syndrome patient under annual colonoscopic surveillance: a case for advanced imaging techniques?

    Directory of Open Access Journals (Sweden)

    Oxentenko Amy S

    2012-05-01

    Full Text Available Abstract Background Lynch syndrome confers increased risk for various malignancies, including colorectal cancer. Colonoscopic surveillance programs have led to reduced incidence of colorectal cancer and reduced mortality from colorectal cancer. Colonoscopy every 1–2 years beginning at age 20–25, or 10 years earlier than the first diagnosis of colorectal cancer in a family, with annual colonoscopy after age 40, is the recommended management for mutation carriers. Screening programs have reduced colon cancer mortality, but interval cancers may occur. Case presentation We describe a 48-year-old woman with Lynch syndrome who was found to have an adenoma with invasive colorectal cancer within one year after a normal colonoscopy. Conclusion Our patient illustrates two current concepts about Lynch syndrome: 1 adenomas are the cancer precursor and 2 such adenomas may be “aggressive,” in the sense that the adenoma progresses more readily and more rapidly to carcinoma in this setting compared to usual colorectal adenomas. Our patient’s resected tumor invaded only into submucosa and all lymph nodes were negative; in that sense, she represents a success for annual colonoscopic surveillance. Still, this case does raise the question of whether advanced imaging techniques are advisable for surveillance colonoscopy in these high-risk patients.

  8. Characteristics of CdLS (Cornelia de Lange Syndrome)

    Science.gov (United States)

    ... Celebration and Memorial Gifts Planned Giving Monthly Giving Corporate Partnership Matching Gifts Stocks, Trusts and Other Gifts ... 25 percent of individuals with CdLS. Behavioral and communication issues and developmental delays often exist. Major Characteristics ...

  9. Prenatal Profile of Cornelia de Lange Syndrome (CdLS): A Review of 53 Pregnancies

    Science.gov (United States)

    Clark, Dinah M.; Sherer, Ilana; Deardorff, Matthew A.; Byrne, Janice L.B.; Loomes, Kathleen M.; Nowaczyk, Malgorzata J.M.; Jackson, Laird G.; Krantz, Ian D.

    2012-01-01

    Cornelia de Lange Syndrome (CdLS) is a multisystem developmental disorder characterized by growth retardation, cognitive impairment, external and internal structural malformations, and characteristic facial features. Currently, there are no definitive prenatal screening measures that lead to the diagnosis of CdLS. In this study, documented prenatal findings in CdLS syndrome were analyzed towards the development of a prenatal profile predictive of CdLS. We reviewed 53 cases of CdLS (29 previously reported and 24 unreported) in which prenatal observations/findings were available. The review of these cases revealed a pattern of sonographic findings, including obvious associated structural defects, growth restriction, as well as a more subtle, but strikingly characteristic, facial profile, suggestive of a recognizable prenatal ultrasonographic profile for CdLS. In addition the maternal serum marker, PAPP-A, may be reduced and fetal nuchal translucency may be increased in some pregnancies when measured at an appropriate gestational age. In conclusion, CdLS can be prenatally diagnosed or readily ruled out in a family with a known mutation in a CdLS gene. The characteristic ultrasonographic profile may allow for prenatal diagnosis of CdLS in 1) subsequent pregnancies to a couple with a prior child with CdLS in whom a mutation has not been identified or 2) when there are unexplained pregnancy signs of fetal abnormality such as oligo- or polyhydramnios, a low maternal serum PAPP-A level and/or increased nuchal translucency, fetal growth retardation, or structural anomalies consistent with CdLS. PMID:22740382

  10. Aspirin, Ibuprofen, and the Risk for Colorectal Cancer in Lynch Syndrome

    Science.gov (United States)

    Ait Ouakrim, Driss; Dashti, Seyedeh Ghazaleh; Chau, Rowena; Buchanan, Daniel D.; Clendenning, Mark; Rosty, Christophe; Winship, Ingrid M.; Young, Joanne P.; Giles, Graham G.; Leggett, Barbara; Macrae, Finlay A.; Ahnen, Dennis J.; Casey, Graham; Gallinger, Steven; Haile, Robert W.; Le Marchand, Loïc; Thibodeau, Stephen N.; Lindor, Noralane M.; Newcomb, Polly A.; Potter, John D.; Baron, John A.; Hopper, John L.; Jenkins, Mark A.

    2015-01-01

    Background: Inheritance of a germline mutation in one of the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2 causes a high risk of colorectal and other cancers (Lynch Syndrome). Use of aspirin has been shown to be associated with a reduced risk of colorectal cancer for the general population as well as for MMR gene mutation carriers. The aim of this study was to determine whether use of aspirin and ibuprofen in a nontrial setting is associated with the risk of colorectal cancer risk for MMR gene mutation carriers. Methods: We included 1858 participants in the Colon Cancer Family Registry who had been found to have a pathogenic germline mutation in a MMR gene (carriers). We used weighted Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided. Results: A total of 714 carriers (38%) were diagnosed with colorectal cancer at a mean age of 42.4 (standard deviation 10.6) years. A reduced risk of colorectal cancer was associated with aspirin use (for 1 month to 4.9 years: HR = 0.49, 95% CI = 0.27 to 0.90, P = .02; for ≥5 years: HR = 0.25, 95% CI = 0.10 to 0.62, P = .003) and ibuprofen use (for 1 month to 4.9 years: HR = 0.38, 95% CI = 0.18 to 0.79, P = .009; for ≥5 years: HR = 0.26, 95% CI = 0.10 to 0.69, P = .007), compared with less than one month of use. Conclusion: Our results provide additional evidence that, for MMR gene mutation carriers, use of aspirin and ibuprofen might be effective in reducing their high risk of colorectal cancer. PMID:26109217

  11. Is there evidence that we should screen the general population for Lynch syndrome with genetic testing? A systematic review

    Science.gov (United States)

    Prince, Anya E R; Cadigan, R Jean; Henderson, Gail E; Evans, James P; Adams, Michael; Coker-Schwimmer, Emmanuel; Penn, Dolly C; Van Riper, Marcia; Corbie-Smith, Giselle; Jonas, Daniel E

    2017-01-01

    Background The emerging dual imperatives of personalized medicine and technologic advances make population screening for preventable conditions resulting from genetic alterations a realistic possibility. Lynch syndrome is a potential screening target due to its prevalence, penetrance, and the availability of well-established, preventive interventions. However, while population screening may lower incidence of preventable conditions, implementation without evidence may lead to unintentional harms. We examined the literature to determine whether evidence exists that screening for Lynch-associated mismatch repair (MMR) gene mutations leads to improved overall survival, cancer-specific survival, or quality of life. Documenting evidence and gaps is critical to implementing genomic approaches in public health and guiding future research. Materials and methods Our 2014–2015 systematic review identified studies comparing screening with no screening in the general population, and controlled studies assessing analytic validity of targeted next-generation sequencing, and benefits or harms of interventions or screening. We conducted meta-analyses for the association between early or more frequent colonoscopies and health outcomes. Results Twelve studies met our eligibility criteria. No adequate evidence directly addressed the main question or the harms of screening in the general population. Meta-analyses found relative reductions of 68% for colorectal cancer incidence (relative risk: 0.32, 95% confidence interval: 0.23–0.43, three cohort studies, 590 participants) and 78% for all-cause mortality (relative risk: 0.22, 95% confidence interval: 0.09–0.56, three cohort studies, 590 participants) for early or more frequent colonoscopies among family members of people with cancer who also had an associated MMR gene mutation. Conclusion Inadequate evidence exists examining harms and benefits of population-based screening for Lynch syndrome. Lack of evidence highlights the need

  12. The role of religious and existential well-being in families with Lynch syndrome: prevention, family communication, and psychosocial adjustment.

    Science.gov (United States)

    Morris, Bronwyn A; Hadley, Donald W; Koehly, Laura M

    2013-08-01

    This study explored the role of religious (RWB) and existential well-being (EWB) on psychosocial factors, support network characteristics, and screening practices in families with Lynch syndrome, also referred to as hereditary nonpolyposis colon cancer (HNPCC). Participants were individuals with Lynch syndrome associated cancers and their first-degree relatives at risk of inheriting an identified deleterious mutation. Analyses considered both family RWB and EWB norms and individual deviations from that norm. Analyses controlled for age, gender, cancer diagnosis, number of respondents, and network size. Higher family RWB was associated with increased depressive symptoms (p family EWB was related to decreased depression symptoms (p family EWB was associated with fecal occult blood testing (p family communication about genetic counselling and testing (p family-level effects. Individuals with lower EWB than their family had lower perceived risk for colorectal cancer (p communicated disease risk information to less family members (p family also had higher cancer worry (p family network and being aware of family characteristics which may impact individual adjustment to disease risk. Interventions considering family-level factors may provide efficient pathways to improving psychosocial factors, screening practices, communication about disease risk and genetic testing, and cancer prevention.

  13. Ovarian metastasis from uveal melanoma with MLH1/PMS2 protein loss in a patient with germline MLH1 mutated Lynch syndrome: consequence or coincidence?

    Science.gov (United States)

    Lobo, João; Pinto, Carla; Freitas, Micaela; Pinheiro, Manuela; Vizcaino, Rámon; Oliva, Esther; Teixeira, Manuel R; Jerónimo, Carmen; Bartosch, Carla

    2017-03-01

    Currently, uveal melanoma is not considered within the Lynch syndrome tumor spectrum. However, there are studies suggesting a contribution of microsatellite instability in sporadic uveal melanoma tumorigenesis. We report a 45-year-old woman who was referred for genetic counseling due to a family history of Lynch syndrome caused by a MLH1 mutation. She originally underwent enucleation of the right eye secondary to a uveal spindle cell melanoma diagnosed at age 25. The tumor recurred 22 years later presenting as an ovarian metastasis and concurrently a microscopic endometrial endometrioid carcinoma, grade 1/3 was diagnosed. Subsequent studies highlighted that the uveal melanoma showed high microsatellite instability and loss of MLH1 and PMS2 protein expression, with no MLH1 promoter methylation or BRAF mutation. Additionally, a GNAQ mutation was found. We conclude that our patient's uveal melanoma is most likely related to MLH1 germline mutation and thus Lynch syndrome related. To the best of our knowledge, this is the first report of uveal melanoma showing MLH1/PMS2 protein loss in the context of Lynch syndrome.

  14. The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome

    DEFF Research Database (Denmark)

    Watson, Patrice; Vasen, Hans F A; Mecklin, Jukka-Pekka;

    2008-01-01

    strategies for these less common cancers require accurate, age-specific risk estimation. We pooled data from 4 LS research centers in a retrospective cohort study, to produce absolute incidence estimates for these cancer types, and to evaluate several potential risk modifiers. After elimination of 135...... after the median year of birth (p evaluate...

  15. Bayesian Modeling for Genetic Anticipation in Presence of Mutational Heterogeneity: A Case-Study in Lynch Syndrome

    Science.gov (United States)

    Boonstra, Philip S.; Mukherjee, Bhramar; Taylor, Jeremy M. G.; Nilbert, Mef; Moreno, Victor M.; Gruber, Stephen B.

    2011-01-01

    Summary Genetic anticipation, described by earlier age of onset (AOO) and more aggressive symptoms in successive generations, is a phenomenon noted in certain hereditary diseases. Its extent may vary between families and/or between mutation sub-types known to be associated with the disease phenotype. In this paper, we posit a Bayesian approach to infer genetic anticipation under flexible random effects models for censored data that capture the effect of successive generations on AOO. Primary interest lies in the random effects. Misspecifying the distribution of random effects may result in incorrect inferential conclusions. We compare the fit of four candidate random effects distributions via Bayesian model fit diagnostics. A related statistical issue here is isolating the confounding effect of changes in secular trends, screening and medical practices that may affect time to disease detection across birth cohorts. Using historic cancer registry data, we borrow from relative survival analysis methods to adjust for changes in age-specific incidence across birth cohorts. Our motivating case-study comes from a Danish cancer register of 124 families with mutations in mismatch repair genes known to cause hereditary non-polyposis colorectal cancer, also called Lynch syndrome. We find evidence for a decrease in AOO between generations in this study. Our model predicts family level anticipation effects which are potentially useful in genetic counseling clinics for high risk families. PMID:21627626

  16. The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome

    DEFF Research Database (Denmark)

    Watson, Patrice; Vasen, Hans F A; Mecklin, Jukka-Pekka

    2008-01-01

    persons missing crucial information, cohort included 6,041 members of 261 families with LS-associated MLH1 or MSH2 mutations. All were either mutation carriers by test, probable mutation carriers (endometrial/colorectal cancer-affected), or first-degree relatives of these. Among mutation carriers...... and probable carriers, urologic tract cancer (N = 98) had an overall lifetime risk (to age 70) of 8.4% (95% CI: 6.6-10.8); risks were higher in males (p families (p ... after the median year of birth (p families (p

  17. Phenotypic Heterogeneity by Germline Mismatch Repair Gene Defect in Lynch Syndrome Patients.

    Science.gov (United States)

    Hernâni-Eusébio, Jorge; Barbosa, Elisabete

    2016-10-01

    Introdução: A síndrome de Lynch é a forma hereditária mais comum de cancro colo-rectal, sendo também responsável por cancro do endométrio e de outros tipos. Associa-se a mutações germinativas nos genes de mismatch repair do ADN e a instabilidade de microssatélites. As mutações MLH1 e MSH2 têm um fenótipo de síndrome de Lynch ‘clássico’, sendo o MSH2 mais associado a cancro extra-cólico. Mutações do MSH6 e PMS2 têm um fenótipo atípico. A expressão clínica é heterogénea, existindo uma correlação entre o gene mismatch repair mutado e o padrão fenotípico. Material e Métodos: Análise retrospetiva dos dados clínicos de doentes que cumpriam os critérios de Amesterdão ou que tinha mutações nos genes mismatch repair, entre setembro de 2012 e outubro de 2015. Resultados: Identificámos 28 doentes. Dezassete tinham cancro colo-rectal sendo a localização no cólon direito predominante. Cinco tiveram cancro do endométrio (mediana da idade de diagnóstico – 53), sem qualquer mutação no MSH6. Cinco desenvolveram outros cancros. Todos os casos com mutações mismatch repair estudados tinham instabilidade de microssatélites. Discussão: Na maioria dos casos foi encontrada mutação no MSH2 apesar de o MLH1 ser descrito na literatura como o gene mais frequentemente mutado. Interessa dizer que os doentes com cancro colo-rectal não evidenciam uma tendência para ter muito infiltrado inflamatório. Na maioria dos casos foi realizada colectomia parcial apesar da incidência elevada de lesões síncronas e metácronas associadas. Histerectomia e anexectomia profilática foi realizada em doentes em menopausa/perimenopausa. Conclusão: O registo standardizado dos dados dos doentes poderá levar a um melhor acompanhamento e conhecimento desta síndrome. O uso das Guidelines de Bethesda poderá identificar novos casos que escapam aos critérios de Amesterdão. A pesquisa de instabilidade de microssatélites deve ser feita em muito maior n

  18. Hereditary diffuse gastric cancer and lynch syndromes in a BRCA1/2 negative breast cancer patient.

    Science.gov (United States)

    Njoroge, Scolastica W; Burgess, Kelly R; Cobleigh, Melody A; Alnajar, Hussein H; Gattuso, Paolo; Usha, Lydia

    2017-07-12

    Genetic counseling and testing is recommended for women with a personal and/or family history of breast and other cancers (ovarian, pancreatic, male breast and others). Mutations in the BRCA1 and BRCA2 genes (BRCA1/2) are the most common causes of hereditary breast and ovarian cancer. Additional genetic counseling and testing with a multi-gene panel may be considered in breast cancer patients who tested negative for mutations in these two genes. In about 11% of BRCA1/2-negative patients, further genetic testing reveals pathogenic mutations in other high or moderate cancer risk genes. In 0.2% of cases, an individual may carry pathogenic mutations in more than one high penetrance gene (a double heterozygote). Finding one or more pathogenic mutations is important for cancer prevention in patients and/or their families. Here we present a case of a breast cancer patient who did not have a pathogenic mutation in BRCA1/2 and had a family history of breast and stomach cancers. On an additional multi-gene panel testing, she was found to carry pathogenic mutations in the CDH1 and PMS2 genes, which cause Hereditary Diffuse Gastric Cancer and Lynch syndromes, respectively. To our knowledge, this is the first description of such a double heterozygote. Clinical manifestations, genetics, and management of both syndromes are reviewed, including prophylactic surgery and screening for unaffected family members. Management challenges for a mutation carrier with advanced breast cancer are discussed. Our case supports the clinical utility of additional multi-gene panel testing for breast cancer patients who do not have a pathogenic mutation in BRCA1/2 genes.

  19. Genetic heterogeneity in Cornelia de Lange syndrome (CdLS) and CdLS-like phenotypes with observed and predicted levels of mosaicism

    Science.gov (United States)

    Ansari, Morad; Poke, Gemma; Ferry, Quentin; Williamson, Kathleen; Aldridge, Roland; Meynert, Alison M; Bengani, Hemant; Chan, Cheng Yee; Kayserili, Hülya; Avci, Şahin; Hennekam, Raoul C M; Lampe, Anne K; Redeker, Egbert; Homfray, Tessa; Ross, Alison; Falkenberg Smeland, Marie; Mansour, Sahar; Parker, Michael J; Cook, Jacqueline A; Splitt, Miranda; Fisher, Richard B; Fryer, Alan; Magee, Alex C; Wilkie, Andrew; Barnicoat, Angela; Brady, Angela F; Cooper, Nicola S; Mercer, Catherine; Deshpande, Charu; Bennett, Christopher P; Pilz, Daniela T; Ruddy, Deborah; Cilliers, Deirdre; Johnson, Diana S; Josifova, Dragana; Rosser, Elisabeth; Thompson, Elizabeth M; Wakeling, Emma; Kinning, Esther; Stewart, Fiona; Flinter, Frances; Girisha, Katta M; Cox, Helen; Firth, Helen V; Kingston, Helen; Wee, Jamie S; Hurst, Jane A; Clayton-Smith, Jill; Tolmie, John; Vogt, Julie; Tatton–Brown, Katrina; Chandler, Kate; Prescott, Katrina; Wilson, Louise; Behnam, Mahdiyeh; McEntagart, Meriel; Davidson, Rosemarie; Lynch, Sally-Ann; Sisodiya, Sanjay; Mehta, Sarju G; McKee, Shane A; Mohammed, Shehla; Holden, Simon; Park, Soo-Mi; Holder, Susan E; Harrison, Victoria; McConnell, Vivienne; Lam, Wayne K; Green, Andrew J; Donnai, Dian; Bitner-Glindzicz, Maria; Donnelly, Deirdre E; Nellåker, Christoffer; Taylor, Martin S; FitzPatrick, David R

    2014-01-01

    Background Cornelia de Lange syndrome (CdLS) is a multisystem disorder with distinctive facial appearance, intellectual disability and growth failure as prominent features. Most individuals with typical CdLS have de novo heterozygous loss-of-function mutations in NIPBL with mosaic individuals representing a significant proportion. Mutations in other cohesin components, SMC1A, SMC3, HDAC8 and RAD21 cause less typical CdLS. Methods We screened 163 affected individuals for coding region mutations in the known genes, 90 for genomic rearrangements, 19 for deep intronic variants in NIPBL and 5 had whole-exome sequencing. Results Pathogenic mutations [including mosaic changes] were identified in: NIPBL 46 [3] (28.2%); SMC1A 5 [1] (3.1%); SMC3 5 [1] (3.1%); HDAC8 6 [0] (3.6%) and RAD21 1 [0] (0.6%). One individual had a de novo 1.3 Mb deletion of 1p36.3. Another had a 520 kb duplication of 12q13.13 encompassing ESPL1, encoding separase, an enzyme that cleaves the cohesin ring. Three de novo mutations were identified in ANKRD11 demonstrating a phenotypic overlap with KBG syndrome. To estimate the number of undetected mosaic cases we used recursive partitioning to identify discriminating features in the NIPBL-positive subgroup. Filtering of the mutation-negative group on these features classified at least 18% as ‘NIPBL-like’. A computer composition of the average face of this NIPBL-like subgroup was also more typical in appearance than that of all others in the mutation-negative group supporting the existence of undetected mosaic cases. Conclusions Future diagnostic testing in ‘mutation-negative’ CdLS thus merits deeper sequencing of multiple DNA samples derived from different tissues. PMID:25125236

  20. Phenotypic patterns of MELAS/LS overlap syndrome associated with m.13513G>A mutation, and neuropathological findings in one autopsy case.

    Science.gov (United States)

    Wang, Zhaoxia; Qi, Xiao Kun; Yao, Sheng; Chen, Bin; Luan, Xinghua; Zhang, Wei; Han, Manfu; Yuan, Yun

    2010-12-01

    The 13513G>A mutation in the ND5 gene of mitochondrial DNA (mtDNA) is usually associated with mitochondrial encephalomyopathy with lactate acidosis and stroke-like episodes (MELAS), or Leigh syndrome (LS). In this study, we describe three young Chinese patients with MELAS/LS overlap syndrome who carried the m.13513G>A mutation. Clinical and MRI features were characteristic of both MELAS and LS. Interestingly, the clinical presentation of this overlap syndrome could be variable depending on the degree of relative contribution of MELAS and LS, that is, MELAS as the initial presenting syndrome, LS as the predominant syndrome, or both MELAS and LS appearing at the same time. The final brain MRI showed findings characteristic of both MELAS and LS, with asymmetrical lesions in the cortex and subcortical white matter of the occipital, temporal, and frontal lobes (MELAS), and bilateral and symmetrical lesions in the basal ganglia and brainstem (LS). Brain autopsy in one case revealed infarct-like lesions in the cerebral cortex, basal ganglia and brainstem, providing further insight into the distribution of the pathological lesions in MELAS/LS overlap syndrome. This is the first report of the brain pathological changes in a patient with m.13513G>A mutation. The spatial distribution of infarct-like lesions in the brain could explain the symptoms in MELAS/LS overlap syndrome.

  1. Functional testing strategy for coding genetic variants of unclear significance in MLH1 in Lynch syndrome diagnosis.

    Science.gov (United States)

    Hinrichsen, Inga; Schäfer, Dieter; Langer, Deborah; Köger, Nicole; Wittmann, Margarethe; Aretz, Stefan; Steinke, Verena; Holzapfel, Stefanie; Trojan, Jörg; König, Rainer; Zeuzem, Stefan; Brieger, Angela; Plotz, Guido

    2015-02-01

    Lynch syndrome is caused by inactivating mutations in the MLH1 gene, but genetic variants of unclear significance frequently preclude diagnosis. Functional testing can reveal variant-conferred defects in gene or protein function. Based on functional defect frequencies and clinical applicability of test systems, we developed a functional testing strategy aimed at efficiently detecting pathogenic defects in coding MLH1 variants. In this strategy, tests of repair activity and expression are prioritized over analyses of subcellular protein localization and messenger RNA (mRNA) formation. This strategy was used for four unclear coding MLH1 variants (p.Asp41His, p.Leu507Phe, p.Gln689Arg, p.Glu605del + p.Val716Met). Expression was analyzed using a transfection system, mismatch repair (MMR) activity by complementation in vitro, mRNA formation by reverse transcriptase-PCR in carrier lymphocyte mRNA, and subcellular localization with dye-labeled fusion constructs. All tests included clinically meaningful controls. The strategy enabled efficient identification of defects in two unclear variants: the p.Asp41His variant showed loss of MMR activity, whereas the compound variant p.Glu605del + p.Val716Met had a defect of expression. This expression defect was significantly stronger than the pathogenic expression reference variant analyzed in parallel, therefore the defect of the compound variant is also pathogenic. Interestingly, the expression defect was caused additively by both of the compound variants, at least one of which is non-pathogenic when occurring by itself. Tests were neutral for p.Leu507Phe and p.Gln689Arg, and the results were consistent with available clinical data. We finally discuss the improved sensitivity and efficiency of the applied strategy and its limitations in analyzing unclear coding MLH1 variants.

  2. Psychological distress in newly diagnosed colorectal cancer patients following microsatellite instability testing for Lynch syndrome on the pathologist's initiative.

    Science.gov (United States)

    Landsbergen, K M; Prins, J B; Brunner, H G; van Duijvendijk, P; Nagengast, F M; van Krieken, J H; Ligtenberg, M; Hoogerbrugge, N

    2012-06-01

    According to the Dutch Guideline on Hereditary Colorectal Cancer published in 2008, patients with recently diagnosed colorectal cancer (CRC) should undergo microsatellite instability (MSI) testing by a pathologist immediately after tumour resection if they are younger than 50 years, or if a second CRC has been diagnosed before the age of 70 years, owing to the high risk of Lynch syndrome (MIPA). The aim of the present MIPAPS study was to investigate general distress and cancer-specific distress following MSI testing. From March 2007 to September 2009, 400 patients who had been tested for MSI after newly diagnosed CRC were recruited from 30 Dutch hospitals. Levels of general distress (SCL-90) and cancer-specific distress (IES) were assessed immediately after MSI result disclosure (T1) and 6 months later (T2). Response rates were 23/77 (30%) in the MSI-positive patients and 58/323 (18%) in the MSI-negative patients. Levels of general distress and cancer-specific distress were moderate. In the MSI-positive group, 27% of the patients had high general distress at T1 versus 18% at T2 (p = 0.5), whereas in the MSI-negative group, these percentage were 14 and 18% (p = 0.6), respectively. At T1 and T2, cancer-specific distress rates in the MSI-positive group and MSI-negative group were 39 versus 27% (p = 0.3) and 38 versus 36% (p = 1.0), respectively. High levels of general distress were correlated with female gender, low social support and high perceived cancer risk. Moderate levels of distress were observed after MSI testing, similar to those found in other patients diagnosed with CRC. Immediately after result disclosure, high cancer-specific distress was observed in 40% of the MSI-positive patients.

  3. Genetic testing for Lynch syndrome in the first year of colorectal cancer: a review of the psychological impact.

    Science.gov (United States)

    Landsbergen, Karin M; Prins, Judith B; Brunner, Han G; Kraaimaat, Floris W; Hoogerbrugge, Nicoline

    2009-01-01

    An increasing number of patients with colorectal cancer (CRC) receive genetic counselling within 1 year after diagnosis. Little is known whether specific subgroups are more vulnerable for genetic testing related distress. A literature review was conducted to identify the psychological impact of CRC in the first year, and the additional impact of genetic testing. The electronic databases of PubMed, PsychInfo, Embase and the Cochrane Library were searched to identify all reports published between January 1997 and October 2007 on the psychological impact of (1) CRC-diagnosis up to 1 year after treatment and of (2) genetic testing for Lynch syndrome in patients with CRC. Studies on the psychological impact of genetic testing in newly diagnosed patient with CRC were not available. Either CRC patients diagnosed several years ago were studied and the focus was also often on the psychological impact of genetic testing prior to DNA-test disclosure. They show that limitations in emotional and social functioning can persist up to 1 year after CRC treatment, especially in those with a stoma or diagnosed before age 60. Female patients and male patients diagnosed before age 50 appear to be more vulnerable to genetic test-related distress. It is well known that being treated for CRC has great impact on psychological functioning. Little is known about the psychological impact during the first year after diagnosis and very little is known about the additional psychological effect of genetic testing for hereditary cancer in this period. We found presumptive evidence that specific subgroups of patients with CRC are more vulnerable for genetic-testing-related distress.

  4. Tumour spectrum of non-polyposis colorectal cancer (Lynch syndrome) on the island of Tenerife and influence of insularity on the clinical manifestations.

    Science.gov (United States)

    Medina-Arana, V; Barrios, Y; Fernández-Peralta, A; Jiménez, A; Salido, E; González, F; González-Aguilera, J J

    2004-02-01

    Colorectal cancer is a complex disease from a genetic point of view because both genetic and environmental factors interact in its development. Only familial adenomatous polyposis (FAP) follows mendelian genetics, in that mutations of the APC gene lead to development of the tumours. Lynch syndrome is the most frequent form of hereditary colorectal cancer and appears to be associated with other types of extracolonic cancers. The genetic basis has been established as a defect in DNA mismatch repair genes, and there is genetic heterogeneity due to the involvement of several genes in this system. Germinal mutations in these genes predispose to appearance of the syndrome. The aim of this study is to describe the tumoral spectrum of 10 families, comprising a total of 488 individuals, from the island of Tenerife (Canary Islands) and to assess whether the geographical isolation of this population has changed any features of the tumoral spectrum of the syndrome in comparison with studies that cover larger geographical areas with more genetic exchange. From our results we can conclude that the genetic drift and consanguinity in this population with a demographic history of isolation did not significantly alter the tumoral spectrum of the syndrome. Our data confirm that families affected by Lynch syndrome are a high-risk population and should be closely monitored, since their careful supervision has been shown to be useful in preventing cancer. We also emphasize the importance of developing a complete family history that permits these families to be identified together with a mutational screening of DNA mismatch repair genes (mainly MLH1 and MSH2 genes) with the aim of a possible identification of members of a family that should be carefully monitored (the carriers of germline mutations in these genes), whereas the remaining members, originally, are no more at risk than the general population.

  5. David Lynch (Sammelrezension)

    OpenAIRE

    2002-01-01

    Ralfdieter Füller: Fiktion und Antifiktion. Die Filme David Lynchs und der Kulturprozeß im Amerika der 1980er und 90er Jahre.Stefan Höltgen: Spiegelbilder. Strategien der ästhetischen Verdoppelung in den Filmen von David Lynch

  6. Body mass index increases risk of colorectal adenomas in men with lunch syndrome: the GEOLynch cohort study

    NARCIS (Netherlands)

    Botma, A.; Nagengast, F.M.; Braem, M.G.M.; Hendriks, J.C.M.; Kleibeuker, J.H.; Vasen, H.F.A.; Kampman, E.

    2010-01-01

    Purpose: High body mass index (BMI) is an established risk factor for sporadic colorectal cancer. Still, the influence of BMI on hereditary colorectal cancer (eg, Lynch syndrome [LS]), is unknown. The objective of this study was to assess whether BMI is associated with colorectal adenoma occurrence

  7. Evaluating the performance of clinical criteria for predicting mismatch repair gene mutations in Lynch syndrome: a comprehensive analysis of 3,671 families.

    Science.gov (United States)

    Steinke, Verena; Holzapfel, Stefanie; Loeffler, Markus; Holinski-Feder, Elke; Morak, Monika; Schackert, Hans K; Görgens, Heike; Pox, Christian; Royer-Pokora, Brigitte; von Knebel-Doeberitz, Magnus; Büttner, Reinhard; Propping, Peter; Engel, Christoph

    2014-07-01

    Carriers of mismatch repair (MMR) gene mutations have a high lifetime risk for colorectal and endometrial cancers, as well as other malignancies. As mutation analysis to detect these patients is expensive and time-consuming, clinical criteria and tumor-tissue analysis are widely used as pre-screening methods. The aim of our study was to evaluate the performance of commonly applied clinical criteria (the Amsterdam I and II Criteria, and the original and revised Bethesda Guidelines) and the results of tumor-tissue analysis in predicting MMR gene mutations. We analyzed 3,671 families from the German HNPCC Registry and divided them into nine mutually exclusive groups with different clinical criteria. A total of 680 families (18.5%) were found to have a pathogenic MMR gene mutation. Among all 1,284 families with microsatellite instability-high (MSI-H) colorectal cancer, the overall mutation detection rate was 53.0%. Mutation frequencies and their distribution between the four MMR genes differed significantly between clinical groups (p small-bowel cancer (p small-bowel cancer were clinically relevant predictors for Lynch syndrome. © 2013 UICC.

  8. Chromosome Rearrangements in Cornelia de Lange Syndrome (CdLS): Report of a der(3)t(3;12)(p25.3;p13.3) in Two Half Sibs With Features of CdLS and Review of Reported CdLS Cases With Chromosome Rearrangements

    Science.gov (United States)

    DeScipio, Cheryl; Kaur, Maninder; Yaeger, Dinah; Innis, Jeffrey W.; Spinner, Nancy B.; Jackson, Laird G.; Krantz, Ian D.

    2016-01-01

    Cornelia de Lange syndrome (CdLS; OMIM 122470) is a dominantly inherited disorder characterized by multisystem involvement, cognitive delay, limb defects, and characteristic facial features. Recently, mutations in NIPBL have been found in ~50% of individuals with CdLS. Numerous chromosomal rearrangements have been reported in individuals with CdLS. These rearrangements may be causative of a CdLS phenotype, result in a phenocopy, or be unrelated to the observed phenotype. We describe two half siblings with a der(3)t(3;12)(p25.3;p13.3) chromosomal rearrangement, clinical features resembling CdLS, and phenotypic overlap with the del(3)(p25) phenotype. Region-specific BAC probes were used to fine-map the breakpoint region by fluorescence in situ hybridization (FISH). FISH analysis places the chromosome 3 breakpoint distal to RP11-115G3 on 3p25.3; the chromosome 12 breakpoint is distal to BAC RP11-88D16 on 12p13.3. A review of published cases of terminal 3p deletions and terminal 12p duplications indicates that the findings in these siblings are consistent with the del(3)(p25) phenotype. Given the phenotypic overlap with CdLS, we have reviewed the reported cases of chromosomal rearrangements involved in CdLS to better elucidate other potential loci that could harbor additional CdLS genes. Additionally, to identify chromosome rearrangements, genome-wide array comparative genomic hybridization (CGH) was performed on eight individuals with typical CdLS and without identifiable deletion or mutation of NIPBL. No pathologic rearrangements were identified. PMID:16075459

  9. Communication, cognitive development and behavior in children with Cornelia de Lange Syndrome (CdLS): preliminary results.

    Science.gov (United States)

    Ajmone, Paola Francesca; Rigamonti, Claudia; Dall'Ara, Francesca; Monti, Federico; Vizziello, Paola; Milani, Donatella; Cereda, Anna; Selicorni, Angelo; Costantino, Antonella

    2014-04-01

    In this study, we present preliminary data on cognitive, behavioral and communication domains of individuals with Cornelia de Lange Syndrome (CdLS), collected through a specific protocol combining direct and indirect tools. Seventeen subjects with CdLS were assessed, 2.5- to 13.4-year-old. Cognitive level of the subjects differed from what previously described in literature, showing more patients with normal or borderline cognitive abilities. We found a relation between severe autistic behavior and comprehension impairments: all children with high CARS score have severe receptive language disability. A correlation was also found between CARS score and ID: high CARS score occurred only in patients with profound levels of ID. Results of this study support the need for a specific assessment protocol tailored for the characteristics of subjects with multiple disabilities, to be able to identify their strengths avoiding the avalanche effect of weaknesses. Most tests on neuropsychological functions have been developed and standardized for typically developing children, and require the integrity of other functions aside the one that is evaluated, determining an underestimation of the level of functioning. This study could be a starting point to develop new models applicable to other genetic syndromes and complex situations; new and wider studies are needed in order to allow a more complete and accurate assessment, thereby ensuring more efficient and family-centered treatment plans. © 2014 Wiley Periodicals, Inc.

  10. Genetics Home Reference: Lynch syndrome

    Science.gov (United States)

    ... in preparation for cell division (a process called DNA replication ). Mutations in any of these genes prevent the proper repair of DNA replication mistakes. As the abnormal cells continue to divide, ...

  11. The intellectual capacity of patients with Laron syndrome (LS) differs with various molecular defects of the growth hormone receptor gene. Correlation with CNS abnormalities.

    Science.gov (United States)

    Shevah, O; Kornreich, L; Galatzer, A; Laron, Z

    2005-12-01

    The correlation between the molecular defects of the GH receptor (R), psychosocial development and brain abnormalities were evaluated in 10 patients with Laron syndrome (LS), in whom all data were available. The findings revealed that the intelligence quotient (IQ) and abnormalities in the brain of the patients with LS differ with various molecular defects of the GH-receptor. The most severe mental deficits and brain pathology occurred in patients with 3, 5, 6 exon deletion. Patients with point mutations in exons 2, 4 and 7 presented various degrees of medium to mild CNS abnormalities that correlated with the IQ. Notably, the patient with the E180 splice mutation in exon 6 had a normal IQ, which fits the report on normal IQ in a large Ecuadorian cohort with the same mutation. This is the first report to support a correlation between IQ, brain abnormalities and localization of the molecular defects in the GH-R gene. As all patients with LS are IGF-I-deficient, it must be assumed that other as yet unknown factors related to the molecular defects in the GH-R are the major cause of the differences in intellect and brain abnormalities.

  12. Do Surrealismo em David Lynch

    Directory of Open Access Journals (Sweden)

    Mirian Tavares

    2009-01-01

    Full Text Available O surrealismo, como a arte do seu tempo, propõe uma nova estética, capaz de extrair o belo do absurdo e de instaurar o desvio para que daí surja, de fato, o real. Através da análise de algumas obras de David Lynch e dos livros Les champs magnétiques de Breton e Philippe Soupault e Poisson soluble, de Breton, irei mostrar a pertinência da designação surrealista para a obra do cineasta norte-americano. Lynch, como os surrealistas, constrói uma operação dialética entre o racional/irracional. Ao mesmo tempo em que opera no campo artístico em direção à irracionalidade absoluta, Lynch não nega a sua inserção na sociedade. Acredito que o realizador, como os surrealistas, tenha conseguido encontrar um equilíbrio entre as duas formas de se estar no mundo, racional/irracional, jogando com suas antíteses. O prazer do jogo surrealista consiste em ir até as profundezas do inconsciente e retornar com matéria suficiente para fazer uma obra de arte.Surrealism, as the art of its time, proposes a new aesthetics, one that is able to extract the beautiful from the absurd and to establish the swerve from the standard, from which, in fact, the real comes through. Through the analysis of some works by David Lynch, of Breton and Soupault's Les champs magnétiques, and of Breton's Poisson soluble, I will attempt to show the relevance of the surrealist designation for the work of the American filmmaker. Lynch, like the surrealists, builds a dialectic operation between the rational and the irrational. While operating in the artistic field towards absolute irrationality, Lynch does not deny its role in society. It is my belief that the director, as the surrealists, has managed to find a balance between the two ways of being in the world: rational and irrational; by playing with their antitheses. The pleasure of the surrealist game is to go to the depths of the unconscious and return with sufficient material to make a work of art out of it.

  13. Modernization and Lynching in the New South

    Directory of Open Access Journals (Sweden)

    Mattias Smångs

    2016-09-01

    Full Text Available This article evaluates an emerging body of historical scholarship that challenges prevailing views of the primacy of rural conditions in southern lynching by positing that it was symbiotically associated with the processes of modernization underway in the region in the decades around 1900. Statistical analyses of lynching data that differentiate among events according to communal participation, support, and ceremony in Georgia and Louisiana from 1882 to 1930 and local-level indices of modernization (urbanization, rural depopulation, industrialization, agricultural commercialization, and dissolution of traditional family roles yield results that both support and contradict such a modernization thesis of lynching. The findings imply that the consequences of the social transformation in the South coinciding with the lynching era were not uniform throughout the region with regard to racial conflict and violence and that broad arguments proposing an intrinsic connection between modernization and lynchings therefore are overstated.

  14. Triple synchronous primary malignancies of the colon, endometrium and kidney in a patient with Lynch syndrome treated via minimally invasive techniques

    Directory of Open Access Journals (Sweden)

    Luis E. Mendez

    2016-08-01

    It is important to consider hereditary cancer syndromes in women with a strong family history presenting with synchronous multiple primary malignancies. A multidisciplinary surgical approach is key to best practices and optimal patient outcomes.

  15. Medical image of the week: Lynch syndrome

    Directory of Open Access Journals (Sweden)

    Athale A

    2016-11-01

    Full Text Available No abstract available. Article truncated at 150 words. A 43-year-old woman with a history of anemia, thrombocytopenia, and recent treatment for pyelonephritis was transferred to our hospital for increasing shortness of breath. Four months prior to admission, she developed unprovoked bilateral deep vein thrombosis (DVT and pulmonary emboli (PE and was started on rivaroxaban at that time. At presentation, she was complaining of worsening shortness of breath, heavy menstrual bleeding and pain in her calves. CT angiography of chest showed multiple pulmonary emboli to the lower lobes and left upper lobe (Figure 1 and lower extremity venous Doppler showed extensive, acute deep vein thrombosis involving the femoral, popliteal and calf veins bilaterally. Rivaroxaban was held due to anemia and thrombocytopenia and there was concern for respiratory failure since she developed new DVT and PE. She was transfused with 1 unit of packed red blood cells and started on a heparin drip. She continued to have significant menorrhagia, the ...

  16. Merrill Lynch kavandab äridelegatsiooni visiiti Eestisse

    Index Scriptorium Estoniae

    2000-01-01

    Investeerimispanga Merrill Lynch eestvedamisel kavandatakse mais ärimeeste visiiti Eestisse, ütles Jüri Mõis, kes viibis New Yorgis toimunud Maailmapanga seminaril "Omavalitsused rahvusvahelistel kapitaliturgudel"

  17. Pupazzi di neve. David Lynch fotografo e l’"Unheimliche"

    Directory of Open Access Journals (Sweden)

    Paolo Sebastiano Lanzi

    2013-02-01

    Full Text Available L’opera di David Lynch non si limita al cinema, come ha dimostrato l’esposizione del 2007 alla Fondation Cartier di Parigi, The Air is on Fire. Tuttavia gli studi teorici hanno trascurato ciò che gallerie e musei hanno evidenziato da tempo: il Lynch pittore, fotografo, musicista, artista poliedrico. L’articolo si focalizza su una serie fotografica, Snowmen, ed è tratto da una ricerca di Paolo Sebastiano Lanzi sulla figura di David Lynch fotografo. Alla luce del saggio di Freud sul Perturbante (Das Unheimliche, 1919 si interpretano gli Snowmen come immagini di morte. Si chiariscono alcuni aspetti della poetica dell’artista-regista, come l’inquietudine dell’Inland Empire o di certe idee care al Surrealismo. Lo studio della produzione fotografica di Lynch riempie un vuoto nell’analisi critica sul suo lavoro, che va necessariamente riconsiderato in una prospettiva più ampia.

  18. Mars at Ls 357o

    Science.gov (United States)

    2006-01-01

    31 January 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 357o during a previous Mars year. This month, Mars looks similar, as Ls 357o occurred in mid-January 2006. The picture shows the south polar region of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Winter/Southern Summer

  19. Mars at Ls 324o

    Science.gov (United States)

    2005-01-01

    29 November 2005 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 324o during a previous Mars year. This month, Mars looks similar, as Ls 324o occurred in mid-November 2005. The picture shows the south polar region of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Winter/Southern Summer

  20. Mars at Ls 137o

    Science.gov (United States)

    2006-01-01

    13 November 2006 These images capture what Mars typically looks like in mid-afternoon at Ls 137o. In other words, with the exception of occasional differences in weather and polar frost patterns, this is what the red planet looks like this month (November 2006). Six views are shown, including the two polar regions. These are composites of 24-26 Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global mapping images acquired at red and blue wavelengths. The 'hole' over the south pole is an area where no images were obtained, because this polar region is enveloped in wintertime darkness. Presently, it is summer in the northern hemisphere and winter in the southern hemisphere. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Northern summer/southern winter begins at Ls 90o, northern autumn/southern spring start at Ls 180o, and northern winter/southern summer begin at Ls 270o. Ls 137o occurs in the middle of this month (November 2006). The pictures show how Mars appeared to the MOC wide angle cameras at a previous Ls 137o in March 2001. The six views are centered on the Tharsis region (upper left), Acidalia and Mare Eyrthraeum (upper right), Syrtis Major and Hellas (middle left), Elysium and Mare Cimmeria (middle right), the north pole (lower left), and the south pole (lower right).

  1. Mars at Ls 121o

    Science.gov (United States)

    2006-01-01

    1 October 2006 These images capture what Mars typically looks like in mid-afternoon at L s 121o. In other words, with the exception of occasional differences in weather and polar frost patterns, this is what the red planet looks like this month (October 2006). Six views are shown, including the two polar regions. These are composites of 24-26 Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global mapping images acquired at red and blue wavelengths. The 'hole' over the south pole is an area where no images were obtained, because this polar region is enveloped in wintertime darkness. Presently, it is summer in the northern hemisphere and winter in the southern hemisphere. Ls, solar longitude, a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Northern summer/southern winter begins at Ls 90o, northern autumn/southern spring start at Ls 180o, and northern winter/southern summer begin at Ls 270o. Ls 121o occurs in the middle of this month (October 2006). The pictures show how Mars appeared to the MOC wide angle cameras at a previous Ls 121o in February 2001. The six views are centered on the Tharsis region (upper left), Acidalia and Mare Eyrthraeum (upper right), Syrtis Major and Hellas (middle left), Elysium and Mare Cimmeria (middle right), the north pole (lower left), and the south pole (lower right).

  2. Main: LS5ATPR1 [PLACE

    Lifescience Database Archive (English)

    Full Text Available LS5ATPR1 S000323 04-January-2007 (last modified) kehi LS5; A negative regulatory el...e correction was made. TGA2; LS5; LS7; SA; NPR1; TGA6; auxin; salicylic acid; root; Arabidopsis thaliana; tobacco (Nicotiana tabacum); TCTACGTCAC ...

  3. Main: LS7ATPR1 [PLACE

    Lifescience Database Archive (English)

    Full Text Available transcriptional activator; TGA2.2 stabilizes TGA2.1 binding; NOTE: The motif sequence previously shown was that of LS5. The correcti...on was made. We are very sorry. TGA2; LS5; LS7; SA; NPR1; TGA6; auxin; salicylic acid; root; Arabidopsis thaliana; tobacco (Nicotiana tabacum); ACGTCATAGA ...

  4. LS1: exciting times ahead

    CERN Multimedia

    Caroline Duc

    2013-01-01

    As the first and last proton-lead run of 2013 draws to a close, the extensive upgrade and maintenance programme of the LHC's first long shutdown (LS1) is about to get under way.   The LHC has provided physicists with a huge quantity of data to analyse since the first physics run in 2009. Now it's time for the machine, along with CERN's other accelerators, to get a facelift. LS1 will start on 13 February 2013, but this doesn’t mean that life at the Laboratory will be any less rich and exciting. Although there will be no collisions for a period of almost two years, the whole CERN site will be a hive of activity, with large-scale work under way to modernise the infrastructure and prepare the LHC for operation at higher energy. "A whole series of renovation work will be carried out around the LHC during LS1,” explains Simon Baird, deputy head of the EN Department. "The key driver is of course the consolidation of the 10,170 high-curren...

  5. SPS completes LS1 activities

    CERN Multimedia

    Katarina Anthony

    2014-01-01

    On 27 June, the SPS closed its doors to the LS1 engineers, bringing to an end almost 17 months of activities. The machine now enters the hardware-testing phase in preparation for an October restart.   Photo 1: The SPS transfer tunnel, TT10, reinforced with steal beams. Having completed their LS1 activities right on schedule (to the day!), the SPS team is now preparing the machine for its restart. Over the next eight weeks, hardware tests of the SPS dipole and quadrupole power converters will be underway, led by the TE-EPC (Electrical Power Converters) team. "OP start-up test activities will also be running in parallel, utilising the off hours when EPC is not using the machine," says David McFarlane, the SPS technical coordinator from the Engineering Department. "The primary beam testing phase will start at the beginning of September, once hardware tests and DSO safety tests have been completed." It has been a long journey to this point, with several major...

  6. Facial Diagnosis of Mild and Variant CdLS: Insights From a Dysmorphologist Survey

    Science.gov (United States)

    Rohatgi, Sarika; Clark, Dinah; Kline, Antonie D.; Jackson, Laird G.; Pie, Juan; Siu, Victoria; Ramos, Feliciano J.; Krantz, Ian D.; Deardorff, Matthew A.

    2014-01-01

    Cornelia de Lange syndrome (CdLS) is a dominant disorder with classic severe forms and milder atypical variants. Central to making the diagnosis is identification of diagnostic facial features. With the recognition that patients with SMC1A and SMC3 mutations have milder, atypical features, we surveyed 65 dysmorphologists using facial photographs from 32 CdLS patients with the goals of (1) Illustrating examples of milder patients with SMC1A mutations and (2) Obtaining objective data to determine which facial features were useful and misleading in making a diagnosis of CdLS. Clinicians were surveyed whether the patient had CdLS or another diagnosis, the certainty of response and the clinical features used to support each response. Using only facial photographs, an average of 24 cases (75%) were accurately diagnosed per clinician. Correct diagnoses were made in 90% of classic CdLS and 87% of non-CdLS cases, however, only 54% of mild or variant CdLS were correctly diagnosed by respondents. We confirmed that CdLS is most accurately diagnosed in childhood and the diagnosis becomes increasingly difficult with age. This survey demonstrated that emphasis is placed on the eyebrows, nasal features, prominent upper lip and micrognathia. In addition, the presence of fuller, atypical eyebrows, a prominent nasal bridge and significant prognathism with age dissuaded survey takers from arriving at a diagnosis of CdLS in individuals with mild NIPBL and SMC1A mutations. This work underscores the difficulty in diagnosing patients with mild and variant CdLS and serves to objectively classify both useful and misleading features in the diagnosis of CdLS. PMID:20583156

  7. Ssk or Esw? -- the Bloor-Lynch Debate Revisited

    Science.gov (United States)

    Cheng, Kai-Yuan

    2014-03-01

    Philosophical discussions of rule-following in the later Wittgenstein (1953, 1967) are an important source of inspiration for the development of views on the social nature of scientific knowledge. Two major opposing views in this inquiry -- Bloor's sociology of scientific knowledge (SSK) (1983, 1991, 1992, 1997) and Lynch's (1992, 1993) ethnomethodological studies of work (ESW) -- represent two positions derived from two different readings of Wittgenstein's later writings on rule-following. The aim of this paper is two-fold. One is to re-examine the noted Bloor-Lynch debate by considering Kusch's (2004) recent discussion of this debate. Another is to show that a new semantic framework of rule-following ascriptions based on a cognitive approach to the study of generics can be provided such that SSK and ESW are compatible in it (Leslie, 2009; Cheng, 2011).

  8. Revised guidelines for the clinical management of Lynch syndrome (HNPCC)

    DEFF Research Database (Denmark)

    Vasen, Hans F A; Blanco, Ignacio; Aktan-Collan, Katja

    2013-01-01

    important clinical questions. Then a systematic literature search was performed using the Pubmed database and manual searches of relevant articles. During the workshops the outcome of the literature search was discussed in detail. The guidelines described in this paper may be helpful for the appropriate...

  9. Pathological assessment of mismatch repair gene variants in Lynch syndrome

    DEFF Research Database (Denmark)

    Rasmussen, Lene Juel; Heinen, Christopher D; Royer-Pokora, Brigitte;

    2012-01-01

    . Also, identifying family members that do not carry the variant is important so they can be released from the intensive surveillance. Determining which genetic variants are pathogenic and which are neutral is a major challenge in clinical genetics. The profound mechanistic knowledge on the genetics...

  10. Indsigter og udfordringer i danske Lynch-syndrom-familier

    DEFF Research Database (Denmark)

    Therkildsen, Christina; Timshel, Susanne; Nilbert, Mef

    2008-01-01

    The Danish Hereditary Nonpolyposis Colorectal Cancer (HNPCC) Register is a national resource that registers families with hereditary colorectal cancer. HNPCC is the most common type of hereditary colorectal cancer and carries an increased risk of other tumor types. Genetic diagnostics has identif...

  11. FROM FAMILIES SYNDROMES TO GENES… THE FIRST CLINICAL AND GENETIC CHARACTERIZATIONS OF HEREDITARY SYNDROMES PREDISPOSING TO CANCER: WHAT WAS THE BEGINNING?

    Directory of Open Access Journals (Sweden)

    Charité Ricker, MS, LCGC

    2017-07-01

    Full Text Available Assessment for hereditary susceptibility to cancer is considered standard of care, as it impacts not only a clinician's understanding of cancer causation but also options for prevention and treatment. The roots of our current knowledge about hereditary cancer syndromes can be traced to early reports of families with striking cancer histories. The purpose of this article is to review the historical timeline of the two most commonly assessed hereditary cancer syndromes, hereditary breast and ovarian cancer (HBOC and Lynch syndrome (LS. While many individuals identified with these syndromes today come from families similar to those seen in the early historical reports, our understanding of these syndromes, their expression and penetrance, has evolved over the years. In addition, the increased utilization of broad multi-gene panels continues to add to the complexity of defining associated phenotypes. These findings can lead to challenges with translating results to clinical management for patients and families, but also provide an opportunity to continue to gain understanding of the genetic underpinnings of cancer etiology.

  12. The Caring Business: Lynch Community Homes, Willow Grove, Pennsylvania. A Case Study.

    Science.gov (United States)

    Bogdan, Robert

    This paper, one of a series of reports describing innovative practices in integrating people with disabilities into community life, describes the Lynch Community Homes in Willow Grove, Pennsylvania. Lynch Homes is a for-profit organization that provides homes and supportive services for approximately 75 people with severe and profound…

  13. Advancing Scholarship and Intellectual Productivity: An Interview with Clifford A. Lynch

    Science.gov (United States)

    Hawkins, Brian L.

    2006-01-01

    In this second part of a two-part interview with Clifford A. Lynch, Executive Director of the Coalition for Networked Information, Lynch talks to Hawkins about the most provocative and exciting projects that are being developed in the field of networked information worldwide. He also talks on how institutional repositories are being currently…

  14. “Silencio”: hearing loss in David Lynch's Mulholland Drive

    Directory of Open Access Journals (Sweden)

    Allister Mactaggart

    2014-11-01

    Full Text Available In a filmmaking career replete with extraordinary images and sounds, David Lynch's Mulholland Drive (2001 stands out for attention as a striking and seemingly inexhaustible resource for analysis. In this article, this film is used to examine the specific ways in which Lynch uses pre-existing pop songs to wrap the spectator within the filmic soundscape. Nowhere is the complexity and uncanniness of pop music made more explicit than in Rebekah Del Rio's stunning performance of “Llorando (Crying” in the Club Silencio scene. The split between the singer's powerful performance and her subsequent collapse with the sound of the voice left hanging in the air marks a pivotal point in the film. This scene, coupled with other examples of feminine jouissance, is contrasted with the deadening roar of the master's voice, which solely demands obedience but is deaf to any reply. At the core of this article is an analysis of the status of the voice (and the gaze as examples of the Lacanian object a and its relationship to Marx's concept of surplus value. Mulholland Drive provides a powerful demonstration of how these concepts can be seen, heard, and felt in relation to film, and how sound can reverberate into the spaces and silences beyond the screen.

  15. Mars at Ls 93o: Syrtis Major

    Science.gov (United States)

    2006-01-01

    15 August 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 93o during a previous Mars year. This month, Mars looks similar, as Ls 93o occurs in mid-August 2006. The picture shows the Syrtis Major face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Summer/Southern Winter

  16. Mars at Ls 249o: Tharsis

    Science.gov (United States)

    2005-01-01

    5 July 2005 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 249o during a previous Mars year. This month, Mars looks similar, as Ls 249o occurs in mid-July 2005. The picture shows the Tharsis face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Autumn/Southern Spring

  17. Mars at Ls 53o: Tharsis

    Science.gov (United States)

    2006-01-01

    2 May 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 53o during a previous Mars year. This month, Mars looks similar, as Ls 53o occurs in mid-May 2006. The picture shows the Tharsis face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Spring/Southern Autumn

  18. Mars at Ls 79o: Syrtis Major

    Science.gov (United States)

    2006-01-01

    18 July 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 79o during a previous Mars year. This month, Mars looks similar, as Ls 79o occurs in mid-July 2006. The picture shows the Syrtis Major face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Spring/Southern Autumn

  19. Mars at Ls 269o: Tharsis

    Science.gov (United States)

    2005-01-01

    2 August 2005 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 269o during a previous Mars year. This month, Mars looks similar, as Ls 269o occurs in mid-August 2005. The picture shows the Tharsis face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: last days of Northern Autumn/Southern Spring

  20. Mars at Ls 12o: Tharsis

    Science.gov (United States)

    2006-01-01

    7 February 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 12o during a previous Mars year. This month, Mars looks similar, as Ls 12o occurs in mid-February 2006. The picture shows the Tharsis face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Winter/Southern Summer

  1. Mars at Ls 25o: Syrtis Major

    Science.gov (United States)

    2006-01-01

    21 March 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 25o during a previous Mars year. This month, Mars looks similar, as Ls 25o occurs in mid-March 2006. The picture shows the Syrtis Major face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Spring

  2. Mars at Ls 79o: Tharsis

    Science.gov (United States)

    2006-01-01

    4 July 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 79o during a previous Mars year. This month, Mars looks similar, as Ls 79o occurs in mid-July 2006. The picture shows the Tharsis face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Spring/Southern Autumn

  3. Mars at Ls 306o: Tharsis

    Science.gov (United States)

    2005-01-01

    4 October 2005 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 306o during a previous Mars year. This month, Mars looks similar, as Ls 306o occurs in mid-October 2005. The picture shows the Tharsis face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Winter/Southern Summer

  4. Mars at Ls 357o: Tharsis

    Science.gov (United States)

    2006-01-01

    4 January 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 357o during a previous Mars year. This month, Mars looks similar, as Ls 357o occurs in mid-January 2006. The picture shows the Tharsis face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. NASA/JPL/Malin Space Science SystemsSeason: Northern Winter/Southern Summer

  5. Mars at Ls 66o: Tharsis

    Science.gov (United States)

    2006-01-01

    6 June 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 66o during a previous Mars year. This month, Mars looks similar, as Ls 66o occurs in mid-June 2006. The picture shows the Tharsis face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Spring/Southern Autumn

  6. Mars at Ls 53o: Syrtis Major

    Science.gov (United States)

    2006-01-01

    16 May 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 53o during a previous Mars year. This month, Mars looks similar, as Ls 53o occurs in mid-May 2006. The picture shows the Syrtis Major face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Spring/Southern Autumn

  7. Mars at Ls 341o: Tharsis

    Science.gov (United States)

    2005-01-01

    6 December 2005 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 341o during a previous Mars year. This month, Mars looks similar, as Ls 341o occurs in mid-December 2005. The picture shows the Tharsis face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Winter/Southern Summer

  8. Mars at Ls 25o: Tharsis

    Science.gov (United States)

    2006-01-01

    7 March 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 25o during a previous Mars year. This month, Mars looks similar, as Ls 25o occurs in mid-March 2006. The picture shows the Tharsis face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Spring/Southern Autumn

  9. Mars at Ls 93o: Tharsis

    Science.gov (United States)

    2006-01-01

    1 August 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 93o during a previous Mars year. This month, Mars looks similar, as Ls 93o occurs in mid-August 2006. The picture shows the Tharsis face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Summer/Southern Winter

  10. Mars at Ls 12o: Syrtis Major

    Science.gov (United States)

    2006-01-01

    21 February 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 12o during a previous Mars year. This month, Mars looks similar, as Ls 12o occurs in mid-February 2006. The picture shows the Syrtis Major face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Winter/Southern Summer

  11. Mars at Ls 39o: Syrtis Major

    Science.gov (United States)

    2006-01-01

    18 April 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 39o during a previous Mars year. This month, Mars looks similar, as Ls 39o occurs in mid-April 2006. The picture shows the Syrtis Major face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Spring/Southern Autumn

  12. Mars at Ls 39o: Tharsis

    Science.gov (United States)

    2006-01-01

    4 April 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 39o during a previous Mars year. This month, Mars looks similar, as Ls 39o occurs in mid-April 2006. The picture shows the Tharsis face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Spring/Southern Autumn

  13. Mars at Ls 324o: Tharsis

    Science.gov (United States)

    2005-01-01

    1 November 2005 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 324o during a previous Mars year. This month, Mars looks similar, as Ls 324o occurs in mid-November 2005. The picture shows the Tharsis face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Winter/Southern Summer

  14. Mars at Ls 288o: Tharsis

    Science.gov (United States)

    2005-01-01

    6 September 2005 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 288o during a previous Mars year. This month, Mars looks similar, as Ls 288o occurs in mid-September 2005. The picture shows the Tharsis face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Winter/Southern Summer

  15. Mars at Ls 66o: Syrtis Major

    Science.gov (United States)

    2006-01-01

    20 June 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 66o during a previous Mars year This month, Mars looks similar, as Ls 66o occurs in mid-June 2006. The picture shows the Syrtis Major face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Spring/Southern Autumn

  16. A generic procedure for determining atomic LS spectral terms and their LS eigenfunctions

    Institute of Scientific and Technical Information of China (English)

    Xiong Zhuang; Bacalis N C

    2009-01-01

    This paper develops a Fortran code which is capable to construct the simplest LS eigcnfunctions for desired symmetry and determine all permitted atomic LS spectral terms under a given orbital occupancy by implementing and extending the Schaefer and Harris method. Examples (in some cases the most complete set to date) of multiple spectroscopic terms of LS coupling of atomic states for both non-equlvalent and equivalent electronic configurations arc given. It also corrects a few observed errors from the recent literature.

  17. Cornelia de Lange Syndrome Foundation

    Science.gov (United States)

    ... org Outside Links Privacy & Terms Site Map The Cornelia de Lange Syndrome (CdLS) Foundation is a family support organization that exists to ensure early and accurate diagnosis of CdLS, promote ... a diagnosis of CdLS make informed decisions throughout their lives.

  18. Strong association between respiratory viral infection early after hematopoietic stem cell transplantation and the development of life-threatening acute and chronic alloimmune lung syndromes

    NARCIS (Netherlands)

    Versluys, A. Birgitta; Rossen, John W. A.; van Ewijk, Bart; Schuurman, Rob; Bierings, Marc B.; Boelens, Jaap J.

    2010-01-01

    Alloimmune lung syndromes (allo-LS), including idiopathic pneumonia syndrome, bronchiolitis obliterans syndrome, and bronchiolitis obliterans organizing pneumonia, are severe complications after hematopoietic stem cell transplantation (HSCT). In our cohort of 110 pediatric patients, 30 had allo-LS (

  19. Media lynching in Romanian mass media and politics. Definition and short explanations

    OpenAIRE

    Ion Novăcescu

    2013-01-01

    The Monitoring Report of justice in Romania, published by the European Commission in late January of this year, has sparked an intense controversy in Romanian politics between the president of Romania and the prime minister of the country, which has focused on the mediatic lynching who was practiced against the judges and the anti-corruption prosecutors. This article defines and analyzes the mediatic lynching and its specific features that distinguish it from a press campaign.

  20. Media lynching in Romanian mass media and politics. Definition and short explanations

    Directory of Open Access Journals (Sweden)

    Ion Novăcescu

    2013-04-01

    Full Text Available The Monitoring Report of justice in Romania, published by the European Commission in late January of this year, has sparked an intense controversy in Romanian politics between the president of Romania and the prime minister of the country, which has focused on the mediatic lynching who was practiced against the judges and the anti-corruption prosecutors. This article defines and analyzes the mediatic lynching and its specific features that distinguish it from a press campaign.

  1. Hereditary colorectal cancer syndromes: Epidemiological studies on Peutz-Jeghers syndrome & Lynch syndrome

    NARCIS (Netherlands)

    M.G.F. van Lier (Margot)

    2011-01-01

    textabstractColorectal cancer (CRC) is the second most common malignancy among women after breast cancer, and the third most common malignancy among men after lung and prostate cancer in the European Union. In the Netherlands, approximately 10000 cases are diagnosed each year. CRC is moreover associ

  2. LS1: electrical engineering upgrades and consolidation

    CERN Document Server

    Duval, F

    2012-01-01

    Compared to past shutdowns, the Engineering Department Electrical Engineering (EN-EL) Group's activity volume will be multiplied by about four during LS1. The Group is experienced in handling such situations and will cope with this by transferring manpower from studies to worksite supervision and thanks to its subcontractors who know how to increase their manpower in such a manner as to maintain a good level of professionalism. EN-EL is substantially increasing its resources to cope with this workload. This increase in resources is, however, limited by the management capacity of EN-EL's core staff. As a consequence, not all of the requested activities will be possible and prioritization will be necessary. This paper details the upgrades and the consolidation to be carried out during LS1 and the measures taken by EN-EL to cope with this heavy workload.

  3. Syndromic Gastric Polyps : At the Crossroads of Genetic and Environmental Cancer Predisposition

    NARCIS (Netherlands)

    Brosens, Lodewijk A A; Giardiello, Francis M; Offerhaus, G Johan; Montgomery, Elizabeth A

    2016-01-01

    Gastric polyps occur in 1-4 % of patients undergoing gastroscopy. Although most are sporadic, some gastric polyps are part of an underlying hereditary syndrome. Gastric polyps can be seen in each of the well-known gastrointestinal polyposis syndromes, but also in Lynch syndrome and in several rare n

  4. TAOS/LS1 development final report

    Energy Technology Data Exchange (ETDEWEB)

    Phipps, G.S.; Gentry, S.M.; Falls, J.M.; Claassen, P.J.; Alder, G.J.

    1997-12-01

    The Laser Sensor No. 1 (LS1) is a system designed and built by Sandia to detect and report laser illumination of an orbiting satellite. It was launched March 1994 as part of the U.S. Air Force Phillips Laboratory, Technology for Autonomous Operational Survivability (TAOS) satellite program. The engineering details of the system are described in this report. Operation characteristics and results have been reserved for inclusion in a classified Air Force report prepared by the TAOS Program Office of Phillips Laboratory.

  5. Isogeometric Analysis with LS-DYNA

    Science.gov (United States)

    Hartmann, S.; Benson, D.; Nagy, A.

    2016-08-01

    In the last decade numerous research has been done in the area of Isogeometric Analysis (IGA). The intention of this rather new technology is the wish to have a stronger integration of Computer Aided Design (CAD) and Finite Element Analysis (FEA). Its basic idea is to use the same mathematical description for the geometry as well in the design process (CAD) as in the later analysis (FEA). One of the wide spread geometry description methodology in CAD-systems is the usage of Non-Uniform Rational B-Splines (NURBS) as basis functions. NURBS-based finite elements have been proven to be very well suited for computational analysis leading to qualitatively more accurate results in comparison with standard finite elements based on Lagrange polynomials. Therefore continuous development of Isogeometric Analysis has been added to LS-DYNA in the last years. The present contribution will give an overview about the current possibilities in LS-DYNA to use NURBS-based CAD-geometry description for numerical simulation and outline future plans for their enhancements.

  6. LS1 Report: nearing the finish line

    CERN Multimedia

    Katarina Anthony

    2014-01-01

    The LS1 team will be popping the champagne next week, on Tuesday 27 May, celebrating the completion of the consolidation of the splices in the framework of the SMACC project.   A technician works on one of the final shunts during LS1. "It has been a long journey into the heart of the LHC, tackling over 27,000 shunts*," says Luca Bottura, TE-MSC Group leader. "We are happy that the final train has, at last, reached its rest station, and look forward to sending it on many new adventures," confirm Frédéric Savary, TE-MSC Large Magnet Facility Section leader, and Jean-Philippe Tock, SMACC Project leader. Also in the LHC, pressure tests in Sector 1-2 - the third sector to be tackled - are almost complete. The temperature in Sector 6-7 is around 100K and it will be accessible again from next week. As for the SPS, all the LSS1 beam elements excluding one monitor are back in position. Vacuum teams are now ...

  7. Non-stop training during LS1!

    CERN Multimedia

    HSE Unit

    2013-01-01

    The year 2013 is a busy year for the Safety Training team, who are seeing a dramatic increase in their activities during LS1. The Safety Training Service within the HSE Unit offers training courses all year round to people working on the CERN site who are exposed to a variety of potential hazards (e.g. chemical hazards, fire hazards, etc.) either because of the activities they perform (e.g. work in confined spaces or on machines) and/or their place of work (e.g. workshops, laboratories, underground areas, etc.).   LS1 has triggered an increase in the number of requests for training, mainly from people requiring to carry out work on the LHC. Indeed, in order to access the underground areas, it is obligatory to have taken certain safety courses such as the self-rescue mask or radiation protection training courses. Consequently, the number of training sessions and the number of people trained is currently twice what it was during the same period in 2012, with almost 4,600 people trained in 530 s...

  8. The Kids Are (Mostly) Alright: Second-Generation Assimilation--Comments on Haller, Portes and Lynch

    Science.gov (United States)

    Alba, Richard; Kasinitz, Philip; Waters, Mary C.

    2011-01-01

    This paper presents the authors' comments on "Dreams Fulfilled, Dreams Shattered: Determinants of Segmented Assimilation in the Second Generation" by William Haller, Alejandro Portes and Scott M. Lynch. The overall well-being and integration of second-generation immigrant youth constitute an important topic for researchers and policy makers, one…

  9. Lynch, Urry and city marketing: Taking advantage of the city as a built and graphic image

    NARCIS (Netherlands)

    Hospers, G-J.

    2009-01-01

    City marketing is usually addressed from the perspective of marketing theory. This article follows an alternative approach by exploring city marketing from the viewpoint of urban planning and the sociology of tourism. In his classic ‘The Image of the City’ (1960), planner Kevin Lynch found that peop

  10. Lemierre's syndrome

    DEFF Research Database (Denmark)

    Johannesen, Katrine M; Bodtger, Uffe

    2016-01-01

    This is a systematic review of cases with Lemierre's syndrome (LS) in the past 5 years. LS is characterized by sepsis often evolving after a sore throat or tonsillitis and then complicated by various septic emboli and thrombosis of the internal jugular vein. Symptoms include sepsis, pain, and...... necrophorum. We found a total of 137 cases of LS, of which 47 were infected with F. necrophorum and others with Staphylococcus and Streptococcus. Complications of this rare but severe disease included osteomyelitis, meningitis, and acute respiratory distress syndrome. Mortality was extremely high in the pre......-antibiotic era but has diminished with the advent of antibiotics. This review showed a mortality rate of only 2% of which none of the cases involved fusobacteria. Duration of treatment varied; a 4-6-week course of carbapenem or piperacillin/tazobactam in combination with metronidazole was optimum. Other...

  11. The post-perspectival: screens and time in David Lynch's Inland Empire

    Directory of Open Access Journals (Sweden)

    Anne Jerslev

    2012-03-01

    Full Text Available Taking Anne Friedberg's notion of the post-perspectival as the point of departure for her analysis of David Lynch's digitally shot and edited Inland Empire from 2006, Anne Jerslev argues that the film deconstructs continuous time and coherent space by constructing multiple planes of representation, multiple layerings of screens and, hence, multiple and fractured modes of perception. The article further suggests that the film's enigmatic structure might best be understood with reference to a new media genre like the website with its hyperlink structure. Finally, the article discusses how a sense of ubiquitous surveillance coalesces with the screen logic.Author Biography Anne Jerslev (PhD is Professor of Film and Media Studies at the Department of Media, Cognition and Communication, University of Copenhagen. Anne Jerslev has published and edited books in Danish and English and published dozens of articles in journals and anthologies in Danish, Scandinavian languages, German and English. Her first book was titled David Lynch i vore øjne (David Lynch in our eyes (1991; it was published in German in 1995 under the title David Lynch—mentale Landschaften. After the Lynch book she published books about cult movies, youth and media and media and intimacy. She has edited two volumes in English, Realism and Reality in Film and Media (2002, where she contributed a piece about Lars von Trier's The Idiots, and Performative Realism (co-edited with Rune Gade (2005. Her latest edited volume (co-edited with Christa Lykke Christensen is Hvor går grænsen? Brudflader i den moderne mediekultur [Are there no limits? The crossing of boundaries in contemporary media culture] (Copenhagen 2010. She is currently editing a volume about “Impure Cinema” together with professor Lúcia Nagib from the University of Leeds, which will appear in 2013. Her own contribution to the book is an article about David Lynch's Interview Project.

  12. A PREPROCESSING LS-CMA IN HIGHLY CORRUPTIVE ENVIRONMENT

    Institute of Scientific and Technical Information of China (English)

    Guo Yan; Fang Dagang; Thomas N.C.Wang; Liang Changhong

    2002-01-01

    A fast preprocessing Least Square-Constant Modulus Algorithm (LS-CMA) is proposed for blind adaptive beamforming. This new preprocessing method precludes noise capture caused by the original LS-CMA with the preprocessing procedure controlled by the static Constant Modulus Algorithm (CMA). The simulation results have shown that the proposed fast preprocessing LS-CMA can effectively reject the co-channel interference, and quickly lock onto the constant modulus desired signal with only one snapshot in a highly corruptive environment.

  13. UFOs in the LHC after LS1

    CERN Document Server

    Baer, T; Carlier, E; Cerutti, F; Dehning, B; Ducimetière, L; Ferrari, A; Garrel, N; Gérardin, A; Goddard, B; Holzer, E B; Jackson, S; Jimenez, J M; Kain, V; Lechner, A; Mertens, V; Misiowiec, M; Morón Ballester, R; Nebot del Busto, E; Norderhaug Drosdal, L; Nordt, A; Uythoven, J; Velghe, B; Vlachoudis, V; Wenninger, J; Zamantzas, C; Zimmermann, F; Fuster Martinez, N

    2012-01-01

    UFOs (Unidentified Falling Objects) are potentially a major luminosity limitation for nominal LHC operation. With large-scale increases of the BLM thresholds, their impact on LHC availability was mitigated in the second half of 2011. For higher beam energy and lower magnet quench limits, the problem is expected to be considerably worse, though. Therefore, in 2011, the diagnostics for UFO events were significantly improved, dedicated experiments and measurements in the LHC and in the laboratory were made and complemented by FLUKA simulations and theoretical studies. In this paper, the state of knowledge is summarized and extrapolations for LHC operation after LS1 are presented. Mitigation strategies are proposed and related tests and measures for 2012 are specified.

  14. Gibraltar Experiment CTD data report, USNS Lynch, 1986-03-26 to 1986-04-19 (NODC Accession 8800167)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Temperature profile, ocean circulation, and chemical data were collected using CTD casts from the USNS LYNCH in the Gulf of Cadiz, Alboran Sea, and Strait of...

  15. Some remarks on photons statistics in the LS-counter

    Energy Technology Data Exchange (ETDEWEB)

    Broda, R. [Institute of Atomic Energy, Radioisotope Centre POLATOM, 05-400 Otwock-Swierk (Poland)], E-mail: r.broda@polatom.pl

    2008-06-15

    The available experimental data relating to processes in the liquid scintillation (LS) detector that lead to fluorescence have been analysed and the evaluated number of photons created are given. The evaluated global distribution of photons emitted from the LS-vial in the case of low-energy emitters is presented. The global distribution of photons is well fitted by the Polya distribution.

  16. Doing Violence, Making Race: Southern Lynching and White Racial Group Formation.

    Science.gov (United States)

    Smångs, Mattias

    2016-03-01

    This article presents a theoretical framework of how intergroup violence may figure into the activation and maintenance of group categories, boundaries, and identities, as well as the mediating role played by organizations in such processes. The framework's analytical advantages are demonstrated in an application to southern lynchings. Findings from event- and community-level analyses suggest that "public" lynchings, carried out by larger mobs with ceremonial violence, but not "private" ones, perpetrated by smaller bands without public or ceremonial violence, fed off and into the racial group boundaries, categories, and identities promoted by the southern Democratic Party at the turn of the 20th century and on which the emerging Jim Crow system rested. Highlighting that racialized inequalities cannot be properly understood apart from collective processes of racial group boundary and identity making, the article offers clues to the mechanisms by which past racial domination influences contemporary race relations.

  17. LS1 Report: Thank you magnetic horn!

    CERN Multimedia

    Antonella Del Rosso & Katarina Anthony

    2014-01-01

    Experiments at the Antimatter Decelerator (AD) have been receiving beams since the beginning of this week. There is a crucial element at the heart of the chain that prepares the antiproton beam: the so-called magnetic horn, a delicate piece of equipment that had to be refurbished during LS1 and that is now showing just how well it can perform.   View from the top of the target and horn trolley, along the direction of the beam. Antiprotons for the AD are produced by smashing a beam of protons from the PS onto an iridium target. However, the particles produced by the nuclear interactions are emitted at very wide angles; without a focussing element, all these precious particles would be lost. “A magnetic horn is placed at the exit of the target to focus back a large fraction of the negative particles, including antiprotons, parallel to the beam line and with the right momentum,” explains Marco Calviani, physicist in the EN Department and the expert in charge of the AD targe...

  18. LS1 Report: LHCb's early Christmas

    CERN Multimedia

    Katarina Anthony

    2014-01-01

    Accelerator chain up and running... CCC Operators back at their desks... all telltale signs of the start of Run 2! For the experiments, that means there are just a few short weeks left for them to prepare for beams. Over at LHCb, teams have kept ahead of the curve by focusing on new installations and improvements.   A delicate task: re-connecting the beam pipe in LHCb. From the primary detector services to the DAQ system to the high level trigger, November's injector test beams saw their way through a well-prepared LHCb experiment. “We set the transfer line tests as our deadline for the restart - the entire experiment had to be at nominal position and conditions,” says Eric Thomas, LHCb deputy Technical Coordinator and LHCb LS1 Project Coordinator. “Achieving this was a major milestone for the collaboration. If beam were to come tomorrow, we would be ready.” The injector tests gave the LHCb team a chance to synchronise their detectors, and to al...

  19. LS1 Report: ALICE ups the ante

    CERN Multimedia

    Katarina Anthony

    2014-01-01

    SPS up and running... LHC almost cold... CCC Operators back at their desks... all telltale signs of the start of Run 2! For the experiments, that means there are just a few short months left for them to prepare for beams. The CERN Bulletin will be checking in with each of the Big Four to see how they are getting on during these closing months...   It has been a long road for the ALICE LS1 team. From major improvements to the 19 sub-detectors to a full re-cabling and replacement of LEP-era electrical infrastructure, no part of the ALICE cavern has gone untouched.* With the experiment set to close in early December, the teams are making finishing touches before turning their focus towards re-commissioning and calibration. "Earlier this week, we installed the last two modules of the di-jet calorimeter," explains Werner Riegler, ALICE technical coordinator. "These are the final parts of a 60 degree calorimeter extension that is installed opposite the present calorimeter, c...

  20. LS1 Report: the clouds are lifting

    CERN Multimedia

    Anaïs Schaeffer

    2014-01-01

    To combat the problem of electron clouds, which perturbate the environment of the particle beams in our accelerators, the Vacuum team have turned to amorphous carbon. This material is being applied to the interior of 16 magnets in the SPS during LS1 and will help prevent the formation of the secondary particles which are responsible for these clouds.   This photo shows the familiar coils of an SPS dipole magnet in brown. The vacuum chamber is the metallic rectangular part in the centre. The small wheeled device you can see in the vacuum chamber carries the hollow cathodes  along the length of the chamber. When a particle beam circulates at high energy in a vacuum chamber, it unavoidably generates secondary particles. These include electrons produced by the ionisation of residual molecules in the vacuum or indirectly generated by synchrotron radiation. When these electrons hit the surface of the vacuum chamber, they produce other electrons which, through an avalanche-like process, re...

  1. CMS outreach event to close LS1

    CERN Multimedia

    Achintya Rao

    2015-01-01

    CMS opened its doors to about 700 students from schools near CERN, who visited the detector on 16 and 17 February during the last major CMS outreach event of LS1.   Pellentesque sapien mi, pharetra vitae, auctor eu, congue sed, turpis. Enthusiastic CMS guides spent a day and a half showing the equally enthusiastic visitors, aged 10 to 18, the beauty of CMS and particle physics. The recently installed wheelchair lift was called into action and enabled a visitor who arrived on crutches to access the detector cavern unimpeded.  The CMS collaboration had previously devoted a day to school visits after the successful “Neighbourhood Days” in May 2014 and, encouraged by the turnout, decided to extend an invitation to local schools once again. The complement of nearly 40 guides and crowd marshals was aided by a support team that coordinated the transportation of the young guests and received them at Point 5, where a dedicated safety team including first-aiders, security...

  2. LS1 Report: achieving the unachievable

    CERN Multimedia

    Anaïs Schaeffer

    2013-01-01

    The dismantling and extraction of a defective DFBA module from LHC Point 6, announced a few weeks ago, has been completed without a hitch. The DFBAs in the LHC are unique and irreplaceable components that must be handled with care.   The Transport team extract the defective module in one of the two DFBAs at Point 6. This module was brought to the surface, where it is currently being repared. Dismantling and extracting part of an electrical feed box (DFBA) had not been planned and could not have been foreseen. Nonetheless, that is what had to be done. When the LS1 teams discovered that the bellows of one of the DFBAs in Sector 5-6 were damaged - and completely inaccessible - they were not exactly overwhelmed with solutions. In fact, they had only one option: to dismantle them and take them up to the surface. Step 1: measure the alignment of the module to be taken out in relation to the beam lines to ensure that when the DFBA is put back in, it is in the right position for the beam to pass thr...

  3. LS1 Report: Summer cool down

    CERN Multimedia

    Katarina Anthony

    2014-01-01

    As the final LS1 activities are carried out in the machine, teams have been cooling down the accelerator sector by sector in preparation for beams.   The third sector of the LHC to be cooled down - sector 1-2 - has seen the process begin this week. During the cool-down phase, survey teams are measuring and smoothing (or realigning) the magnets at cold. By the end of August, five sectors of the machine will be in the process of cooling down, with one (sector 6-7) at cold. The LHC Access Safety System (LASS) is now being commissioned, and will be validated during the DSO tests at the beginning of October. As teams consolidate the modifications made to LASS during the shutdown, many points were closed for testing purposes. The CSCM (copper stabiliser continuity measurement) tests have been completed in the first sector (6-7) and no defect has been found. These results will be presented to the LHC Machine Committee next week. CSCM tests will start in the second sector in mid-August. Following many...

  4. LS1 Report: onwards and upwards

    CERN Multimedia

    Katarina Anthony

    2013-01-01

    For the first time since 2008, engineers have taken most of the LHC’s electromagnetic circuits up to the current needed for magnets to guide beams around the machine at the design energy of 7 TeV. This first phase of intensive tests has been instrumental for the planning of upcoming machine interventions.   All of the circuits in Sector 67 were powered to a 7 TeV equivalent current, with the main circuits (to be consolidated during LS1) powered at 4 TeV. Around 1700 magnet circuits are needed to circulate beams in the LHC. Come 2015, each and every one of these circuits will have to be able to accept their 7 TeV equivalent current. For the LHC’s 24 main dipole and quadrupole circuits, this will mean the consolidation of all their interconnections. But what about the rest of the LHC’s circuits that had been mostly operating at around 60% of the nominal value? How will they handle the ramp-up to design energy? Those questions were asked and answered during the rec...

  5. Fermi LAT Observations of LS 5039

    Energy Technology Data Exchange (ETDEWEB)

    Abdo, A.A.; /Naval Research Lab, Wash., D.C. /Federal City Coll.; Ackermann, M.; /Stanford U., HEPL /KIPAC, Menlo Park /Stanford U., Phys. Dept.; Ajello, M.; /Stanford U., HEPL /KIPAC, Menlo Park /Stanford U., Phys. Dept.; Atwood, W.B.; /UC, Santa Cruz; Axelsson, M.; /Stockholm U. /Stockholm U., OKC; Baldini, L.; /INFN, Pisa; Ballet, J.; /DAPNIA, Saclay; Barbiellini, G.; /INFN, Trieste /Trieste U.; Bastieri, D.; /INFN, Padua /Padua U.; Baughman, B.M.; /Ohio State U.; Bechtol, K.; /Stanford U., HEPL /KIPAC, Menlo Park /Stanford U., Phys. Dept.; Bellazzini, R.; /INFN, Pisa; Berenji, B.; /Stanford U., HEPL /KIPAC, Menlo Park /Stanford U., Phys. Dept.; Blandford, R.D.; /Stanford U., HEPL /KIPAC, Menlo Park /Stanford U., Phys. Dept.; Bloom, E.D.; /Stanford U., HEPL /KIPAC, Menlo Park /Stanford U., Phys. Dept.; Bonamente, E.; /INFN, Perugia /Perugia U.; Borgland, A.W.; /Stanford U., HEPL /KIPAC, Menlo Park /Stanford U., Phys. Dept.; Bregeon, J.; /INFN, Pisa; Brez, A.; /INFN, Pisa; Brigida, M.; /Bari U. /INFN, Bari; Bruel, P.; /Ecole Polytechnique /Washington U., Seattle /Padua U. /Bari U. /INFN, Bari /Stanford U., HEPL /KIPAC, Menlo Park /Stanford U., Phys. Dept. /IASF, Milan /Milan Polytechnic /DAPNIA, Saclay /ASDC, Frascati /INFN, Perugia /Perugia U. /NASA, Goddard /NASA, Goddard /CSST, Baltimore /DAPNIA, Saclay /Naval Research Lab, Wash., D.C. /George Mason U. /NASA, Goddard /Stanford U., HEPL /KIPAC, Menlo Park /Stanford U., Phys. Dept. /INFN, Perugia /Perugia U. /Stanford U., HEPL /KIPAC, Menlo Park /Stanford U., Phys. Dept. /Montpellier U. /Sonoma State U. /Stockholm U. /Stockholm U., OKC /DAPNIA, Saclay /NASA, Goddard /CSST, Baltimore /SLAC /ASDC, Frascati /Naval Research Lab, Wash., D.C. /INFN, Trieste /Bari U. /INFN, Bari /Stanford U., HEPL /KIPAC, Menlo Park /Stanford U., Phys. Dept. /Stanford U., HEPL /KIPAC, Menlo Park /Stanford U., Phys. Dept. /Stanford U., HEPL /KIPAC, Menlo Park /Stanford U., Phys. Dept. /Stanford U., HEPL /KIPAC, Menlo Park /Stanford U., Phys. Dept. /SLAC /Grenoble Observ. /CENBG, Gradignan /CENBG, Gradignan /Montpellier U.; /more authors..

    2012-03-29

    The first results from observations of the high-mass X-ray binary LS 5039 using the Fermi Gamma-ray Space Telescope data between 2008 August and 2009 June are presented. Our results indicate variability that is consistent with the binary period, with the emission being modulated with a period of 3.903 {+-} 0.005 days; the first detection of this modulation at GeV energies. The light curve is characterized by a broad peak around superior conjunction in agreement with inverse Compton scattering models. The spectrum is represented by a power law with an exponential cutoff, yielding an overall flux (100 MeV-300 GeV) of 4.9 {+-} 0.5(stat) {+-} 1.8(syst) x 10{sup -7} photon cm{sup -2} s{sup -1}, with a cutoff at 2.1 {+-} 0.3(stat) {+-} 1.1(syst) GeV and photon index {Gamma} = 1.9 {+-} 0.1(stat) {+-} 0.3(syst). The spectrum is observed to vary with orbital phase, specifically between inferior and superior conjunction. We suggest that the presence of a cutoff in the spectrum may be indicative of magnetospheric emission similar to the emission seen in many pulsars by Fermi.

  6. LS1 Report: short-circuit tests

    CERN Multimedia

    Katarina Anthony

    2014-01-01

    As the LS1 draws to an end, teams move from installation projects to a phase of intense testing. Among these are the so-called 'short-circuit tests'. Currently under way at Point 7, these tests verify the cables, the interlocks, the energy extraction systems, the power converters that provide current to the superconducting magnets and the cooling system.   Thermal camera images taken during tests at point 4 (IP4). Before putting beam into the LHC, all of the machine's hardware components need to be put to the test. Out of these, the most complicated are the superconducting circuits, which have a myriad of different failure modes with interlock and control systems. While these will be tested at cold - during powering tests to be done in August - work can still be done beforehand. "While the circuits in the magnets themselves cannot be tested at warm, what we can do is verify the power converter and the circuits right up to the place the cables go into the magn...

  7. LS1 Report: Setting the bar high

    CERN Multimedia

    Anaïs Schaeffer

    2014-01-01

    This week LS1 successfully passed an important milestone: the first pressure test of a complete sector, sector 6-7.  The objective of this test was to check the mechanical integrity and overall leak-tightness of this section of the LHC by injecting it with pressurised helium.   The team in charge of the preparation and of the realisation of the pressure tests in sector 6-7. “Given the scale of the work and of the operations carried out during 2013, particularly in the framework of the SMACC project and of the repair of the compensators of the cryogenic distribution line (QRL), we need to revalidate the integrity of the systems before the accelerator starts up again,” explains Olivier Pirotte, who is in charge of the pressure tests (TE-CRG). The pressure tests are performed over a single day after two weeks of intensive activity to prepare and specially configure the cryogenic instrumentation in the tunnel, and the pressure within a sector is increased in stages,...

  8. Temperature Drift Modeling of FOG Based on LS-WSVM

    Institute of Scientific and Technical Information of China (English)

    WANG Li-ping; KONG Xiao-mei; FU Meng-yin; WANG Mei-ling; ZHANG Jia-wen; JIANG Ming

    2008-01-01

    Large temperature drift is an important factor for improving the performance of FOG. A trend term of temperature drift of FOG is obtained using stationary wavelets transform, and an FOG drift algorithm with least squares wavelet support vector machine (LS-WSVM) is developed. The algorithm used Maxihat wavelet as a kernel function of LSWSVM to establish an FOG drift model. It has better modeling precise than LS-WSVM model with Gauss kernel. Results indicate the efficiency of this algorithm of LS-WSVM.

  9. Online LS-SVM for function estimation and classification

    Institute of Scientific and Technical Information of China (English)

    Jianghua Liu; Jia-pin Chen; Shan Jiang; Junshi Cheng

    2003-01-01

    An online algorithm for training LS-SVM (Least Square Support Vector Machines) was proposed for the application of function estimation and classification. Online LS-SVM means that LS-SVM can be trained in an incremental way, and can be pruned to get sparse approximation in a decremental way. When a SV (Support Vector) is added or removed, the online algorithm avoids computing large-scale matrix inverse. Thus the computation cost is reduced. Online algorithm is especially useful to realistic function estimation problem such as system identification. The experiments with benchmark function estimation problem and classification problem show the validity of this online algorithm.

  10. Leopard syndrome

    Directory of Open Access Journals (Sweden)

    Dallapiccola Bruno

    2008-05-01

    Full Text Available Abstract LEOPARD syndrome (LS, OMIM 151100 is a rare multiple congenital anomalies condition, mainly characterized by skin, facial and cardiac anomalies. LEOPARD is an acronym for the major features of this disorder, including multiple Lentigines, ECG conduction abnormalities, Ocular hypertelorism, Pulmonic stenosis, Abnormal genitalia, Retardation of growth, and sensorineural Deafness. About 200 patients have been reported worldwide but the real incidence of LS has not been assessed. Facial dysmorphism includes ocular hypertelorism, palpebral ptosis and low-set ears. Stature is usually below the 25th centile. Cardiac defects, in particular hypertrophic cardiomyopathy mostly involving the left ventricle, and ECG anomalies are common. The lentigines may be congenital, although more frequently manifest by the age of 4–5 years and increase throughout puberty. Additional common features are café-au-lait spots (CLS, chest anomalies, cryptorchidism, delayed puberty, hypotonia, mild developmental delay, sensorineural deafness and learning difficulties. In about 85% of the cases, a heterozygous missense mutation is detected in exons 7, 12 or 13 of the PTPN11 gene. Recently, missense mutations in the RAF1 gene have been found in two out of six PTPN11-negative LS patients. Mutation analysis can be carried out on blood, chorionic villi and amniotic fluid samples. LS is largely overlapping Noonan syndrome and, during childhood, Neurofibromatosis type 1-Noonan syndrome. Diagnostic clues of LS are multiple lentigines and CLS, hypertrophic cardiomyopathy and deafness. Mutation-based differential diagnosis in patients with borderline clinical manifestations is warranted. LS is an autosomal dominant condition, with full penetrance and variable expressivity. If one parent is affected, a 50% recurrence risk is appropriate. LS should be suspected in foetuses with severe cardiac hypertrophy and prenatal DNA test may be performed. Clinical management should

  11. Diagnosis of Constitutional Mismatch Repair-Deficiency Syndrome Based on Microsatellite Instability and Lymphocyte Tolerance to Methylating Agents

    DEFF Research Database (Denmark)

    Bodo, Sahra; Colas, Chrystelle; Buhard, Olivier

    2015-01-01

    BACKGROUND & AIMS: Patients with bi-allelic germline mutations in mismatch repair (MMR) genes (MLH1, MSH2, MSH6, or PMS2) develop a rare but severe variant of Lynch syndrome called constitutional MMR deficiency (CMMRD). This syndrome is characterized by early-onset colorectal cancers, lymphomas o...

  12. LS-SVM的组合优化算法研究%Research on LS-SVM combination optimization algorithm

    Institute of Scientific and Technical Information of China (English)

    曾绍华

    2007-01-01

    根据LS-SVM不具稀疏解的特性,提出了LS-SVM的组合优化算法及其改进算法,并利用整数规划优化了LS-SVM的组合优化算法中划分的样本子集包含的样本个数p.最后,对算法复杂性做了分析,仿真验证了算法的收敛性和有效性.

  13. Mars at Ls 306o: Acidalia/Mare Erythraeum

    Science.gov (United States)

    2005-01-01

    11 October 2005 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 306o during a previous Mars year. This month, Mars looks similar, as Ls 306o occurs in mid-October 2005. The picture shows the Acidalia/Mare Erythraeum face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Winter/Southern Summer

  14. Mars at Ls 79o: Elysium/Mare Cimmerium

    Science.gov (United States)

    2006-01-01

    25 July 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 79o during a previous Mars year. This month, Mars looks similar, as Ls 79o occurred in mid-July 2006. The picture shows the Elysium/Mare Cimmerium face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Spring/Southern Autumn

  15. Mars at Ls 53o: North Polar Region

    Science.gov (United States)

    2006-01-01

    30 May 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 53o during a previous Mars year. This month, Mars looks similar, as Ls 53o occurred in mid-May 2006. The picture shows the north polar region of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Winter/Southern Summer

  16. Mars at Ls 324o: Acidalia/Mare Erythraeum

    Science.gov (United States)

    2005-01-01

    8 November 2005 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 324o during a previous Mars year. This month, Mars looks similar, as Ls 324o occurs in mid-November 2005. The picture shows the Acidalia/Mare Erythraeum face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Winter/Southern Summer

  17. Mars at Ls 12o: Elysium/Mare Cimmerium

    Science.gov (United States)

    2006-01-01

    28 February 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 12o during a previous Mars year. This month, Mars looks similar, as Ls 12o occurred in mid-February 2006. The picture shows the Elysium/Mare Cimmerium face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Spring/Southern Autumn

  18. Mars at Ls 269o: South Polar Region

    Science.gov (United States)

    2005-01-01

    30 August 2005 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 269o during a previous Mars year. This month, Mars looks similar, as Ls 269o occurred in mid-August 2005. The picture shows the south polar region of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: last days of Northern Autumn/Southern Spring

  19. Mars at Ls 39o: Elysium/Mare Cimmerium

    Science.gov (United States)

    2006-01-01

    25 April 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 39o during a previous Mars year. This month, Mars looks similar, as Ls 39o occurred in mid-April 2006. The picture shows the Elysium/Mare Cimmerium face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Spring/Southern Autumn

  20. Mars at Ls 53o: Acidalia/Mare Erythraeum

    Science.gov (United States)

    2006-01-01

    9 May 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 53o during a previous Mars year. This month, Mars looks similar, as Ls 53o occurs in mid-May 2006. The picture shows the Acidalia/Mare Erythraeum face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Spring/Southern Autumn

  1. Mars at Ls 306o: Elysium/Mare Cimmerium

    Science.gov (United States)

    2005-01-01

    25 October 2005 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 306o during a previous Mars year. This month, Mars looks similar, as Ls 306o occurred in mid-October 2005. The picture shows the Elysium/Mare Cimmerium face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Winter/Southern Summer

  2. Mars at Ls 269o: Acidalia/Mare Erythraeum

    Science.gov (United States)

    2005-01-01

    9 August 2005 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 269o during a previous Mars year. This month, Mars looks similar, as Ls 269o occurs in mid-August 2005. The picture shows the Acidalia/Mare Erythraeum face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: last days of Northern Autumn/Southern Spring

  3. Mars at Ls 288o: Elysium/Mare Cimmerium

    Science.gov (United States)

    2005-01-01

    27 September 2005 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 288o during a previous Mars year. This month, Mars looks similar, as Ls 288o occurred in mid-September 2005. The picture shows the Elysium/Mare Cimmerium face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Winter/Southern Summer

  4. Mars at Ls 107o: Acidalia/Mare Erythraeum

    Science.gov (United States)

    2006-01-01

    13 September 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 107o during a previous Mars year. This month, Mars looks similar, as Ls 107o occurs in mid-September 2006. The picture shows the Acidalia/Mare Erythraeum face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Summer/Southern Winter

  5. Mars at Ls 357o: Acidalia/Mare Erythraeum

    Science.gov (United States)

    2006-01-01

    10 January 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 357o during a previous Mars year. This month, Mars looks similar, as Ls 357o occurs in mid-January 2006. The picture shows the Acidalia/Mare Erythraeum face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Winter/Southern Summer

  6. Mars at Ls 25o: Acidalia/Mare Erythraeum

    Science.gov (United States)

    2006-01-01

    14 March 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 25o during a previous Mars year. This month, Mars looks similar, as Ls 25o occurs in mid-March 2006. The picture shows the Acidalia/Mare Erythraeum face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Spring/Southern Autumn

  7. Mars at Ls 93o: Elysium/Mare Cimmerium

    Science.gov (United States)

    2006-01-01

    22 August 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 93o during a previous Mars year. This month, Mars looks similar, as Ls 93o occurred in mid-August 2006. The picture shows the Elysium/Mare Cimmerium face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Location near: 86.1oN, 208.5oW Image width: 3 km (1.9 mi) Illumination from: lower left Season: Northern Summer/Southern Winter

  8. Mars at Ls 230o: Elysium/Mare Cimmerium

    Science.gov (United States)

    2005-01-01

    28 June 2005 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 230o during a previous Mars year. This month, Mars looks similar, as Ls 230o occurred in mid-June 2005. The picture shows the Elysium/Mare Cimmerium face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season Northern Autumn/Southern Spring

  9. Mars at Ls 324o: Elysium/Mare Cimmerium

    Science.gov (United States)

    2005-01-01

    22 November 2005 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 324o during a previous Mars year. This month, Mars looks similar, as Ls 324o occurred in mid-November 2005. The picture shows the Elysium/Mare Cimmerium face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Winter/Southern Summer

  10. A new TDCR-LS counter using Channel photomultiplier tubes.

    Science.gov (United States)

    Ivan, C; Cassette, P; Sahagia, Maria

    2008-01-01

    A new Triple to Double Coincidence Ratio (TDCR) liquid scintillation (LS) counter using recently available photodetectors, the Channel photomultiplier (CPM) tubes, was constructed and tested in the framework of a scientific cooperation between IFIN-HH and LNHB. The prototype LS counter uses 3CPM tubes arranged symmetrically in an optical chamber around a standard LS vial. The behavior of the prototype was first evaluated with a light emitting diode (LED) light pulser. The counter was then compared against a TDCR counter using conventional photomultiplier tubes, by measuring (55)Fe, (3)H, (63)Ni and (90)Sr/(90)Y LS sources prepared in commercial liquid scintillation cocktails. Although the observed detection efficiency was significantly lower than the one achieved with the traditional counter, we found a remarkable agreement on the activity determination using the two counters. Details on the prototype and the measurement results obtained are discussed in this paper.

  11. Mars at Ls 12o: Acidalia/Mare Erythraeum

    Science.gov (United States)

    2006-01-01

    15 February 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 12o during a previous Mars year. This month, Mars looks similar, as Ls 12o occurs in mid-February 2006. The picture shows the Acidalia/Mare Erythraeum face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Winter/Southern Summer

  12. Mars at Ls 39o: Acidalia/Mare Erythraeum

    Science.gov (United States)

    2006-01-01

    11 April 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 39o during a previous Mars year. This month, Mars looks similar, as Ls 39o occurs in mid-April 2006. The picture shows the Acidalia/Mare Erythraeum face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Spring/Southern Autumn

  13. Mars at Ls 107o: Elysium/Mare Cimmerium

    Science.gov (United States)

    2006-01-01

    26 September 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 107o during a previous Mars year. This month, Mars looks similar, as Ls 107o occurred in mid-September 2006. The picture shows the Elysium/Mare Cimmerium face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Summer/Southern Winter

  14. Mars at Ls 249o: Acidalia/Mare Erythraeum

    Science.gov (United States)

    2005-01-01

    12 July 2005 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 249o during a previous Mars year. This month, Mars looks similar, as Ls 249o occurs in mid-July 2005. The picture shows the Acidalia/Mare Erythraeum face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Autumn/Southern Spring

  15. Mars at Ls 288o: Acidalia/Mare Erythraeum

    Science.gov (United States)

    2005-01-01

    13 September 2005 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 288o during a previous Mars year. This month, Mars looks similar, as Ls 288o occurs in mid-September 2005. The picture shows the Acidalia/Mare Erythraeum face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Winter/Southern Summer

  16. Mars at Ls 25o: Elysium/Mare Cimmerium

    Science.gov (United States)

    2006-01-01

    28 March 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 25o during a previous Mars year. This month, Mars looks similar, as Ls 25o occurred in mid-March 2006. The picture shows the Elysium/Mare Cimmerium face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Spring/Southern Autumn

  17. Mars at Ls 79o: Acidalia/Mare Erythraeum

    Science.gov (United States)

    2006-01-01

    11 July 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 79o during a previous Mars year. This month, Mars looks similar, as Ls 79o occurs in mid-July 2006. The picture shows the Acidalia/Mare Erythraeum face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Spring/Southern Autumn

  18. Mars at Ls 341o: Elysium/Mare Cimmerium

    Science.gov (United States)

    2005-01-01

    27 December 2005 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 341o during a previous Mars year. This month, Mars looks similar, as Ls 341o occurred in mid-December 2005. The picture shows the Elysium/Mare Cimmerium face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Winter/Southern Summer

  19. Mars at Ls 66o: Acidalia/Mare Erythraeum

    Science.gov (United States)

    2006-01-01

    13 June 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 66o during a previous Mars year. This month, Mars looks similar, as Ls 66o occurs in mid-June 2006. The picture shows the Acidalia/Mare Erythraeum face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Spring/Southern Autumn

  20. Mars at Ls 357o: Elysium/Mare Cimmerium

    Science.gov (United States)

    2006-01-01

    25 January 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 357o during a previous Mars year. This month, Mars looks similar, as Ls 357o occurred in mid-January 2006. The picture shows the Elysium/Mare Cimmerium face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Winter/Southern Summer

  1. Mars at Ls 66o: Elysium/Mare Cimmerium

    Science.gov (United States)

    2006-01-01

    27 June 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 66o during a previous Mars year. This month, Mars looks similar, as Ls 66o occurred in mid-June 2006. The picture shows the Elysium/Mare Cimmerium face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Northern Spring/Southern Autumn

  2. Mars at Ls 93o: Acidalia/Mare Erythraeum

    Science.gov (United States)

    2006-01-01

    8 August 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 93o during a previous Mars year. This month, Mars looks similar, as Ls 93o occurs in mid-August 2006. The picture shows the Acidalia/Mare Erythraeum face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Summer/Southern Winter

  3. Mars at Ls 53o: Elysium/Mare Cimmerium

    Science.gov (United States)

    2006-01-01

    23 May 2006 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 53o during a previous Mars year. This month, Mars looks similar, as Ls 53o occurred in mid-May 2006. The picture shows the Elysium/Mare Cimmerium face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Spring/Southern Autumn

  4. Mars at Ls 249o: Elysium/Mare Cimmerium

    Science.gov (United States)

    2005-01-01

    26 July 2005 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 249o during a previous Mars year. This month, Mars looks similar, as Ls 249o occurred in mid-July 2005. The picture shows the Elysium/Mare Cimmerium face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: Northern Autumn/Southern Spring

  5. Mars at Ls 269o: Elysium/Mare Cimmerium

    Science.gov (United States)

    2005-01-01

    23 August 2005 This picture is a composite of Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) daily global images acquired at Ls 269o during a previous Mars year. This month, Mars looks similar, as Ls 269o occurred in mid-August 2005. The picture shows the Elysium/Mare Cimmerium face of Mars. Over the course of the month, additional faces of Mars as it appears at this time of year are being posted for MOC Picture of the Day. Ls, solar longitude, is a measure of the time of year on Mars. Mars travels 360o around the Sun in 1 Mars year. The year begins at Ls 0o, the start of northern spring and southern autumn. Season: last days of Northern Autumn/Southern Spring

  6. VIDEOGIOCHI E ITALIANO L2/LS

    Directory of Open Access Journals (Sweden)

    Filippo Zanoli

    2010-09-01

    Full Text Available L'articolo prende in considerazione alcune ipotesi sull'uso del videogioco nell'insegnamento/apprendimento della lingua straniera supportate dall'analisi di alcuni videogames per uso didattico. Pur non nascondendo le difficoltà che l'insegnante può incontrare nell'integrare il videogioco nel percorso di insegnamento/apprendimento di una lingua straniera in classe, diversi sono i motivi per i quali il videogioco può essere considerato un efficace strumento di apprendimento linguistico. Innanzitutto perché gli input linguistici possono essere numerosi e vari, in secondo luogo perché è vettore di lingua che coinvolge i diversi sensi e diverse operazioni cognitive e, in terzo luogo perché trasforma il processo dell'apprendimento da simbolico a esperienziale. Infine perché si tratta di un mezzo divertente capace di creare interesse ad apprendere offrendo opportunità straordinarie in quanto attiva negli apprendenti, soprattutto più giovani, due fattori chiave per un apprendimento solido e duraturo: l'esperienza e la motivazione, elementi che spesso le metodologie tradizionali trascurano. A conclusione dell'articolo viene proposta di attività didattica di italiano LS con una serie di suggerimenti per l'insegnante.   This article discusses the use of videogames in teaching/learning a foreign language and analyzes a few didactic videogames. While not underestimating the difficulties that teachers may have in integrating videogames in the teaching/learning process in a classroom, there are different reasons why videogames can be considered effective tools for language learning. First of all, the linguistic input is varied and rich, and secondly it is a way of engaging different senses and cognitive processes, and in the third place it transforms learning from something symbolic to something experiential. Finally, it is an amusing way to generate interest in learning by offering an extraordinary opportunity, since it activates two key aspects

  7. A cohesin-independent role for NIPBL at promoters provides insights in CdLS.

    Directory of Open Access Journals (Sweden)

    Jessica Zuin

    2014-02-01

    Full Text Available The cohesin complex is crucial for chromosome segregation during mitosis and has recently also been implicated in transcriptional regulation and chromatin architecture. The NIPBL protein is required for the loading of cohesin onto chromatin, but how and where cohesin is loaded in vertebrate cells is unclear. Heterozygous mutations of NIPBL were found in 50% of the cases of Cornelia de Lange Syndrome (CdLS, a human developmental syndrome with a complex phenotype. However, no defects in the mitotic function of cohesin have been observed so far and the links between NIPBL mutations and the observed developmental defects are unclear. We show that NIPBL binds to chromatin in somatic cells with a different timing than cohesin. Further, we observe that high-affinity NIPBL binding sites localize to different regions than cohesin and almost exclusively to the promoters of active genes. NIPBL or cohesin knockdown reduce transcription of these genes differently, suggesting a cohesin-independent role of NIPBL for transcription. Motif analysis and comparison to published data show that NIPBL co-localizes with a specific set of other transcription factors. In cells derived from CdLS patients NIPBL binding levels are reduced and several of the NIPBL-bound genes have previously been observed to be mis-expressed in CdLS. In summary, our observations indicate that NIPBL mutations might cause developmental defects in different ways. First, defects of NIPBL might lead to cohesin-loading defects and thereby alter gene expression and second, NIPBL deficiency might affect genes directly via its role at the respective promoters.

  8. Self-Injurious Behaviour in Cornelia De Lange Syndrome: 1. Prevalence and Phenomenology

    Science.gov (United States)

    Oliver, C.; Sloneem, J.; Hall, S.; Arron, K.

    2009-01-01

    Background: Self-injurious behaviour is frequently identified as part of the behavioural phenotype of Cornelia de Lange syndrome (CdLS). We conducted a case-control study of the prevalence and phenomenology of self-injurious behaviour (SIB) in CdLS. Methods: A total of 54 participants with CdLS were compared with 46 individuals who were comparable…

  9. Cornelia De Lange Syndrome: A Case Report

    Directory of Open Access Journals (Sweden)

    Hojatollah Mortezaian

    2009-12-01

    Full Text Available Cornelia de Lange syndrome (CdLS is a rare syndrome characterized by multiple congenital anomalies, mental retardation, characteristic facial appearance, developmental delay, skeletal malformation, hirsutism, and various cardiac and ophthalmological problems. The diagnosis of this syndrome is clinical. The patient of the present case report was the second case of CdLS from Iran; only a few cases of CdLS have thus far been reported from countries outside Europe and North America. Reporting CdLS cases of different ethnic backgrounds can add nuances to the phenotypic description of the syndrome and be helpful in diagnosis. Furthermore, an increased awareness of this syndrome may result in an early diagnosis and a decrease in morbidity.

  10. The effectiveness of b-lynch sutures in management of atonic postpartum haemorrhage during caesarean section

    Directory of Open Access Journals (Sweden)

    Nidhi Kalkal

    2016-09-01

    Conclusions: This procedure proves to be a valuable addition for surgical treatment of atonic PPH and great advantage in young patients with restoration of future fertility with the added advantage of lesser time of application, lesser blood loss, lesser blood transfusion, lesser skill required. Thus, B-Lynch suturing can be adopted as a mid-step before resorting to uterine devascularisation or hysterectomy when medical line of management fails. [Int J Reprod Contracept Obstet Gynecol 2016; 5(9.000: 2915-2920

  11. The Importance of Older Family Members in Providing Social Resources and Promoting Cancer Screening in Families with a Hereditary Cancer Syndrome

    Science.gov (United States)

    Ashida, Sato; Hadley, Donald W.; Goergen, Andrea F.; Skapinsky, Kaley F.; Devlin, Hillary C.; Koehly, Laura M.

    2011-01-01

    Purpose: This study evaluates the role of older family members as providers of social resources within familial network systems affected by an inherited cancer susceptibility syndrome. Design and Methods: Respondents who previously participated in a study that involved genetic counseling and testing for Lynch syndrome and their family network…

  12. Self-Injurious Behaviour in Cornelia De Lange Syndrome: 2. Association with Environmental Events

    Science.gov (United States)

    Sloneem, J.; Arron, K.; Hall, S. S.; Oliver, C.

    2009-01-01

    Background: Self-injurious behaviour is commonly seen in Cornelia de Lange syndrome (CdLS). However, there has been limited research into the aetiology of self-injury in CdLS and whether environmental factors influence the behaviour. Methods: We observed the self-injury of 27 individuals with CdLS and 17 participants who did not have CdLS matched…

  13. Cervical spine malformation in cornelia de lange syndrome: a report of three patients.

    Science.gov (United States)

    Bettini, Laura Rachele; Locatelli, Laura; Mariani, Milena; Cianci, Paola; Giussani, Carlo; Canonico, Francesco; Cereda, Anna; Russo, Silvia; Gervasini, Cristina; Biondi, Andrea; Selicorni, Angelo

    2014-06-01

    Cornelia de Lange syndrome (CdLS) is a complex genetic disease with skeletal involvement mostly related to upper limb malformations. We report on three males with clinical and molecular diagnoses of CdLS. Besides typical CdLS features, all showed different cervical spine malformations. To the best of our knowledge, this is an unusual malformation in the CdLS phenotypic spectrum. © 2014 Wiley Periodicals, Inc.

  14. The PD-1/PD-Ls pathway and autoimmune diseases.

    Science.gov (United States)

    Dai, Suya; Jia, Ru; Zhang, Xiao; Fang, Qiwen; Huang, Lijuan

    2014-07-01

    The programmed death (PD)-1/PD-1 ligands (PD-Ls) pathway, is a new member of the B7/CD28 family, and consists of the PD-1 receptor and its ligands PD-L1 (B7-H1, CD274) and PD-L2 (B7-DC, CD273). Recently, it is reported that PD-1, PD-L1 and PD-L2 also have soluble forms aside from their membrane bound forms. The soluble forms increase the diversity and complexity of PD-1/PD-Ls pathway in both composition and function. The PD-1/PD-Ls pathway is broadly expressed and exerts a wider range of immunoregulatory roles in T-cell activation and tolerance compared with other B7/CD28 family members. Studies show that the PD-1/PD-Ls pathway regulates the induction and maintenance of peripheral tolerance and protects tissues from autoimmune attack in physiological conditions. In addition, it is also involved in various diseases mediated by T cells, such as autoimmunity, tumor immunity, chronic viral infections, and transplantation immunity. In this review, we will summarize the relevance of the soluble forms and the latest researches on the role of PD-1/PD-Ls pathway in autoimmune diseases.

  15. Behavioral and psychiatric manifestations in Cornelia de Lange syndrome.

    Science.gov (United States)

    Grados, Marco A; Alvi, Mustafa H; Srivastava, Siddharth

    2017-03-01

    Cornelia de Lange syndrome (CdLS) is a rare genetic syndrome with clinical manifestations due to multiple affected organ systems including limbs, gastrointestinal, skin, and central nervous systems. Although the genetic basis of CdLS is now uncovered, how behavioral manifestations are associated with genetic and brain differences are less well understood. The current focused review systematically describes the main behavioral observations to date in individuals with CdLS, which have a significant impact on quality of life and adaptive functioning. The CdLS behavioral phenotype includes autistic traits as a prominent feature; however, brain imaging studies, required to understand gene-brain-behavior connections in CdLS, are scarce. Moreover, autistic features in CdLS have a greater emphasis on repetitive behaviors, including self-injurious behaviors (SIB) and expressive communication deficits, different that the core social deficit seen in idiopathic autism. Current data strongly support the use of CdLS as a model disease for repetitive behaviors and associated developmental delay manifestations. Behavioral phenotype characteristics in CdLS point to a preponderance of repetitive clinical phenomena as well as expressive verbal deficits that ought to inform specific treatment approaches in CdLS. In particular, repetitive behaviors associated with self-injury are of high negative impact on the quality of life for individuals with CdLS and their families. Treatment approaches geared to manage repetitive behaviors and self-injurious behaviors in CdLS are required in this developmental condition.

  16. Semisupervised learning using Bayesian interpretation: application to LS-SVM.

    Science.gov (United States)

    Adankon, Mathias M; Cheriet, Mohamed; Biem, Alain

    2011-04-01

    Bayesian reasoning provides an ideal basis for representing and manipulating uncertain knowledge, with the result that many interesting algorithms in machine learning are based on Bayesian inference. In this paper, we use the Bayesian approach with one and two levels of inference to model the semisupervised learning problem and give its application to the successful kernel classifier support vector machine (SVM) and its variant least-squares SVM (LS-SVM). Taking advantage of Bayesian interpretation of LS-SVM, we develop a semisupervised learning algorithm for Bayesian LS-SVM using our approach based on two levels of inference. Experimental results on both artificial and real pattern recognition problems show the utility of our method.

  17. Exclusion mapping of a third HNPCC locus in a large Lynch I kindred

    Energy Technology Data Exchange (ETDEWEB)

    Morasse, J.; Khandjian, E.W.; Rousseau, F. [Hopital St-Francois d`Assise, Quebec (Canada)] [and others

    1994-09-01

    Hereditary Non-Polyposis Colorectal Cancer (HNPCC) accounts for 5-10% of all the cases of colorectal cancers. HNPCC can be classified in two clinical forms: (1) Hereditary Site-Specific Colorectal Cancer (HSSCC or Lynch I) and (2) colon cancer associated with extracolonic cancers (Lynch II). Segregation analyses show an autosomal dominant mode of inheritance. In order to identify the HNPCC gene involved in a large Canadian kindred, we performed linkage analysis using microsatellites spanning 9 candidate regions. For all loci tested, the lod score data obtained were negative. Our results demonstrate that the genes hMSH1 and hMLH1 recently reported in HNPCC are not linked in this family. Five loci frequently altered in colorectal tumor cells, APC, MCC, K-ras, p53 and DCC and the DRA gene whose expression is confined to the colon mucosa cells and deregulated in colonic adenomas, are also unlinked to HNPCC susceptibility in this family. We have also excluded chromosomes 4, 5, 8, 11 and 17 as containing the cancer predisposition gene in this family.

  18. An {sup 57}Fe Mössbauer study of the ordinary chondrite meteorite Lynch 001

    Energy Technology Data Exchange (ETDEWEB)

    Elewa, Nancy N., E-mail: nancy.elewa@student.unsw.edu.au; Cadogan, J. M. [The University of New South Wales at the Australian Defence Force Academy, School of Physical, Environmental and Mathematical Sciences (Australia)

    2017-11-15

    The Lynch 001 meteorite was found in the Nullarbor Plain region of Western Australia in 1977. This meteorite is classified as an ordinary chondrite of the petrologic group L5/6 that has undergone ‘minor to moderate’ terrestrial weathering. Here, we characterize the Fe-bearing phases in this chondrite using {sup 57}Fe Mössbauer spectroscopy carried out over the temperature range 13 K to room temperature (295 K). The paramagnetic doublets of olivine, pyroxene and a superparamagnetic ferric phase dominate the room temperature Mössbauer spectrum. On the basis of the room temperature quadrupole splitting of the olivine component, we estimate its composition to be Fa {sub 30(5)}. Besides the paramagnetic ferric component, accounting for ∼15 % of the spectral area at room temperature, magnetically ordered ferric phases were also detected. The total relative proportion of the Fe {sup 3+} components allows us to estimate the terrestrial age of Lynch 001 to be 6,500 ± 1,500 yr, consistent with the value of 6,700 ± 1,300 yr determined by {sup 14}C dating.

  19. A Longitudinal Follow-Up Study of Affect in Children and Adults with Cornelia de Lange Syndrome

    Science.gov (United States)

    Nelson, Lisa; Moss, Jo; Oliver, Chris

    2014-01-01

    Studies of individuals with Cornelia de Lange syndrome (CdLS) have described changes in mood and behavior with age, although no empirical or longitudinal studies have been conducted. Caregivers of individuals with CdLS (N = 67), cri du chat syndrome (CdCS; N = 42), and Fragile X syndrome (FXS; N = 142) completed the Mood, Interest and Pleasure…

  20. Anticancer activity of the iron facilitator LS081

    Directory of Open Access Journals (Sweden)

    Glass Jonathan

    2011-03-01

    Full Text Available Abstract Background Cancer cells have increased levels of transferrin receptor and lower levels of ferritin, an iron deficient phenotype that has led to the use of iron chelators to further deplete cells of iron and limit cancer cell growth. As cancer cells also have increased reactive oxygen species (ROS we hypothesized that a contrarian approach of enhancing iron entry would allow for further increased generation of ROS causing oxidative damage and cell death. Methods A small molecule library consisting of ~11,000 compounds was screened to identify compounds that stimulated iron-induced quenching of intracellular calcein fluorescence. We verified the iron facilitating properties of the lead compound, LS081, through 55Fe uptake and the expression of the iron storage protein, ferritin. LS081-induced iron facilitation was correlated with rates of cancer cell growth inhibition, ROS production, clonogenicity, and hypoxia induced factor (HIF levels. Results Compound LS081 increased 55Fe uptake in various cancer cell lines and Caco2 cells, a model system for studying intestinal iron uptake. LS081 also increased the uptake of Fe from transferrin (Tf. LS081 decreased proliferation of the PC-3 prostate cancer cell line in the presence of iron with a lesser effect on normal prostate 267B1 cells. In addition, LS081 markedly decreased HIF-1α and -2α levels in DU-145 prostate cancer cell line and the MDA-MB-231 breast cancer cell lines, stimulated ROS production, and decreased clonogenicity. Conclusions We have developed a high through-put screening technique and identified small molecules that stimulate iron uptake both from ferriTf and non-Tf bound iron. These iron facilitator compounds displayed properties suggesting that they may serve as anti-cancer agents.

  1. Improvement of endometrial biopsy over transvaginal ultrasound alone for endometrial surveillance in women with Lynch syndrome.

    NARCIS (Netherlands)

    Gerritzen, L.H.; Hoogerbrugge-van der Linden, N.; Oei, A.L.M.; Nagengast, F.M.; Ham, M.A.P.C. van; Massuger, L.F.A.G.; Hullu, J.A. de

    2009-01-01

    In women with hereditary non polyposis colorectal carcinoma (HNPCC) an annual gynaecological surveillance has been recommended because of an increased lifetime risk of developing endometrial and ovarian carcinoma. The aim of this study was to assess the efficacy of gynaecological surveillance with r

  2. DNA mismatch repair deficiency in sporadic colorectal cancer and Lynch Syndrome

    OpenAIRE

    Poulogiannis, George; Frayling, Ian; Arends, Mark

    2009-01-01

    Abstract DNA mismatch repair (MMR) deficiency is one of the best understood forms of genetic instability in colorectal cancer (CRC), and is characterised by the loss of function of the MMR pathway. Failure to repair replication-associated errors due to a defective MMR system allows persistence of mismatch mutations all over the genome, but especially in regions of repetitive DNA known as microsatellites, giving rise to the phenomenon of microsatellite instability (MSI). A high freq...

  3. A review of statistical methods for testing genetic anticipation: looking for an answer in Lynch syndrome

    DEFF Research Database (Denmark)

    Boonstra, Philip S; Gruber, Stephen B; Raymond, Victoria M

    2010-01-01

    , and this right truncation effect is more pronounced in children than in parents. In this study, we first review different statistical methods for testing genetic anticipation in affected parent-child pairs that address the issue of bias due to right truncation. Using affected parent-child pair data, we compare......Anticipation, manifested through decreasing age of onset or increased severity in successive generations, has been noted in several genetic diseases. Statistical methods for genetic anticipation range from a simple use of the paired t-test for age of onset restricted to affected parent-child pairs...... to a recently proposed random effects model which includes extended pedigree data and unaffected family members [Larsen et al., 2009]. A naive use of the paired t-test is biased for the simple reason that age of onset has to be less than the age at ascertainment (interview) for both affected parent and child...

  4. Frequent mismatch-repair defects link prostate cancer to Lynch syndrome

    DEFF Research Database (Denmark)

    Dominguez-Valentin, Mev; Joost, Patrick; Therkildsen, Christina;

    2016-01-01

    were high-grade tumors with Gleason scores 8-10. Prostate cancer was associated with mutations in MSH2, MLH1 and MSH6 with loss of the respective mismatch repair protein in 69 % of the tumors, though a MSI-high phenotype was restricted to 13 % of the tumors. The cumulative risk of prostate cancer...

  5. Bayesian Modeling for Genetic Anticipation in Presence of Mutational Heterogeneity: A Case Study in Lynch Syndrome

    DEFF Research Database (Denmark)

    Boonstra, Philip S; Mukherjee, Bhramar; Taylor, Jeremy M G

    2011-01-01

    Summary Genetic anticipation, described by earlier age of onset (AOO) and more aggressive symptoms in successive generations, is a phenomenon noted in certain hereditary diseases. Its extent may vary between families and/or between mutation subtypes known to be associated with the disease phenoty...

  6. A review of statistical methods for testing genetic anticipation: looking for an answer in Lynch syndrome

    DEFF Research Database (Denmark)

    Boonstra, Philip S; Gruber, Stephen B; Raymond, Victoria M

    2010-01-01

    Anticipation, manifested through decreasing age of onset or increased severity in successive generations, has been noted in several genetic diseases. Statistical methods for genetic anticipation range from a simple use of the paired t-test for age of onset restricted to affected parent-child pairs......, and this right truncation effect is more pronounced in children than in parents. In this study, we first review different statistical methods for testing genetic anticipation in affected parent-child pairs that address the issue of bias due to right truncation. Using affected parent-child pair data, we compare...... to a recently proposed random effects model which includes extended pedigree data and unaffected family members [Larsen et al., 2009]. A naive use of the paired t-test is biased for the simple reason that age of onset has to be less than the age at ascertainment (interview) for both affected parent and child...

  7. Screening for urinary tract cancer with urine cytology in Lynch syndrome and familial colorectal cancer

    DEFF Research Database (Denmark)

    Myrhøj, T; Andersen, M-B; Bernstein, I

    2008-01-01

    AIM: The aim of this study was to evaluate if Urine Cytology (UC) is an appropriate screening procedure for detecting urinary tract neoplasia at an early stage in persons at risk in Hereditary Non-Polyposis Colorectal Cancer families. METHOD: In the National Danish HNPCC-register persons at risk...

  8. Diagnosis of Lynch Syndrome: Genetic Testing Identifies a Potentially Deadly Hereditary Disease

    Science.gov (United States)

    ... the sequencing can identify variants in a person’s genes—places where their genetic sequence differs from an expected sequence,” says Katie Lewis, a research coordinator at NIH’s National Human Genome ...

  9. Functional characterization of MLH1 missense variants identified in Lynch Syndrome patients

    DEFF Research Database (Denmark)

    Andersen, Sofie Dabros; Liberti, Sascha Emilie; Lützen, Anne;

    2012-01-01

    localization and protein-protein interaction with the dimer partner PMS2 and the MMR-associated exonuclease 1. We show that a significant proportion of examined variant proteins have functional defects in either subcellular localization or protein-protein interactions, which is suspected to lead to the cancer...

  10. Forecasting Models for Hydropower Unit Stability Using LS-SVM

    Directory of Open Access Journals (Sweden)

    Liangliang Qiao

    2015-01-01

    Full Text Available This paper discusses a least square support vector machine (LS-SVM approach for forecasting stability parameters of Francis turbine unit. To achieve training and testing data for the models, four field tests were presented, especially for the vibration in Y-direction of lower generator bearing (LGB and pressure in draft tube (DT. A heuristic method such as a neural network using Backpropagation (NNBP is introduced as a comparison model to examine the feasibility of forecasting performance. In the experimental results, LS-SVM showed superior forecasting accuracies and performances to the NNBP, which is of significant importance to better monitor the unit safety and potential faults diagnosis.

  11. Out of Amazonia: the unexpected trans-Andean distribution of Cochranella resplendens (Lynch and Duellman, 1978) (Anura: Centrolenidae).

    Science.gov (United States)

    Molina-Zuluaga, Claudia; Cano, Estefany; Restrepo, Adriana; Rada, Marco; Daza, Juan M

    2017-03-02

    The glassfrog genus Cochranella, with nine recognized species, is distributed in the lowlands and mid elevation of the Neotropical forests, from Nicaragua to Bolivia (Guayasamin et al. 2009; Twomey et al. 2014). Four species are trans-Andean-C. granulosa (Taylor 1949) occurs in the lowlands and mountains, at mid elevation, of Central America, C. litoralis (Ruiz-Carranza & Lynch 1996) and C. mache Guayasamin & Bonaccorso 2004 occur in the Pacific lowlands and the western cloud forests of Colombia and Ecuador, and C. euknemos (Savage & Starrett 1967) occurs both in Central America and South America (northwestern Colombia).-The other five species have cis-Andean distributions in the Amazonian slopes and lowlands, from Colombia to Bolivia: C. nola Harvey 1996, C. guayasamini Twomey, Delia & Castroviejo-Fisher 2014, C. resplendens (Lynch & Duellman 1973), C. erminea Torres-Gastello, Suárez-Segovia & Cisneros-Heredia 2007, and C. phryxa Aguayo-Vedia & Harvey 2006. In Colombia, C. resplendens is known from the foothills of the Amazon versant in Caquetá (Malambo et al. 2013) and Putumayo (Lynch & Duellman 1973; Ruiz-Carranza et al. 1996). The species is also known from Ecuador (Lynch & Duellman 1973) and Peru (Twomey et al. 2014). Here, we report two new records of Cochranella resplendens, extending the species distribution beyond the Amazonian lowlands into the northern Cordillera Central in Colombia.

  12. Social Anxiety in Cornelia de Lange Syndrome

    Science.gov (United States)

    Richards, Caroline; Moss, Jo; O'Farrell, Laura; Kaur, Gurmeash; Oliver, Chris

    2009-01-01

    In this study we assessed the behavioral presentation of social anxiety in Cornelia de Lange syndrome (CdLS) using a contrast group of Cri du Chat syndrome (CdCS). Behaviors indicative of social anxiety were recorded in twelve children with CdLS (mean age = 11.00; SD = 5.15) and twelve children with CdCS (8.20; SD = 2.86) during social…

  13. Safety, Quality, Schedule: the motto of LS1

    CERN Multimedia

    2013-01-01

    The LHC’s first long shutdown, LS1, is a marathon that began on 16 February and will take us through to the beginning of 2015. Just as Olympic marathon runners have a motto, Citius, Altius, Fortius, so the athletes of LS1 work to the mantra of Safety, Quality, Schedule. Four months into LS1, they have settled into their rhythm, and things are going to plan.   The first task of LS1 was to bring the LHC up to room temperature - this was achieved in just 10 weeks. In parallel, preliminary tests for electrical quality assurance and leaks revealed essentially the level of wear and tear we’d expect after three years of running. One slightly anxious moment came when we looked at the RF fingers – the devices that ensure electrical contact in the beam pipes as they pass from one magnet to the next. Those of you with long memories will recall that before start-up, some of these got damaged at warm-up. The good news today is that with all eight sectors test...

  14. CONSISTENCY OF LS ESTIMATOR IN SIMPLE LINEAR EV REGRESSION MODELS

    Institute of Scientific and Technical Information of China (English)

    Liu Jixue; Chen Xiru

    2005-01-01

    Consistency of LS estimate of simple linear EV model is studied. It is shown that under some common assumptions of the model, both weak and strong consistency of the estimate are equivalent but it is not so for quadratic-mean consistency.

  15. LS/2000--The Integrated Library System from OCLC.

    Science.gov (United States)

    Olson, Susan

    1984-01-01

    Discusses design features of the Online Catalog of LS/2000, OCLC's enhanced version of Integrated Library System. This minicomputer-based system provides bibliographic file maintenance, circulation control, and online catalog searching. Examples of available displays--holdings, full MARC, work forms, keyword entry, index selection, brief citation,…

  16. A mid-term report for LS1

    CERN Multimedia

    2014-01-01

    As the LHC’s first long shutdown, LS1, enters its second calendar year, it’s a good time for a mid-term report on how things are progressing.    Towards the end of last year, I had the pleasure to go down to the LHC tunnel to witness the closure of the first of the machine’s sectors to be completed. As I write, three sectors are now closed up, with a fourth not far behind. These are important milestones, and you can follow progress in detail in the regular LS1 reports in the Bulletin. They show that we’re on schedule for physics to resume in about a year from now, but more than that, they are an important reminder of the LS1 motto: safety, quality, schedule. It is fantastic news that we are on schedule, and testimony to the rigour that went into the detailed and complex planning of all the work that had to be undertaken in LS1. But more important than the schedule is the fact that we’ve carried out the work safely and that the qualit...

  17. Immunologic features of Cornelia de Lange syndrome.

    Science.gov (United States)

    Jyonouchi, Soma; Orange, Jordan; Sullivan, Kathleen E; Krantz, Ian; Deardorff, Matthew

    2013-08-01

    Cornelia de Lange syndrome (CdLS) is a genetic syndrome with multisystem abnormalities. Infections are a significant cause of morbidity and mortality. The goals of our study were to identify the frequency and types of infections in CdLS and to determine if underlying immunodeficiency contributes to the clinical spectrum of this syndrome. We assessed infectious histories in 45 patients with CdLS and evaluated conventional immunologic screening tests in 27 patients. Among these 27 subjects, additional phenotypic enumeration of T-cell subsets, expression of activation markers in T cells, and production of cytokines in response to T-cell stimulants were studied in 12 CdLS subjects compared with 12 normal case control subjects. Recurrent infections were reported at high frequency in CdLS patients and included chronic ear infections (53%), chronic viral respiratory infections (46%), pneumonia (42%), sinus infections (33%), oral candidiasis (13%), sepsis (6%), and bacterial skin infections (4%). Full immune evaluation in 27 subjects led to identification of 9 cases of antibody deficiency syndrome in patients with severe forms of CdLS. Subjects with CdLS had decreased percentages of T regulatory cells and T follicular helper cells compared with normal control subjects (P < .05). This study identified for the first time a high frequency of antibody deficiency in CdLS subjects, indicating a critical need for screening and management of immunodeficiency in CdLS patients with a history of well-documented severe or recurrent infections. Furthermore, our results indicate that impaired T-cell populations may be associated with antibody deficiency in CdLS.

  18. Lynching Luther

    DEFF Research Database (Denmark)

    Backe, Hans-Joachim

    2016-01-01

    police procedurals. The character of DCI John Luther is indicative of the series’ general approach: he is unmistakably constructed from stereotypes of US television, yet not in a straightforward way, as he combines elements of both the impulsive, physical maverick cop and the psychologically adept......, cerebral detective – two character-types traditionally rather juxtaposed as irreconcilable opposites. In this fashion, the overall story arc meshes together elements from Thomas Harris-style serial killer fiction and intuitive detection in the tradition of George Simenon’s Maigret. Similarly...... as the id to his superior Rose Teller’s super-ego and his former partner Ian Reed’s ego, a configuration his subconscious tries to overwrite by juxtaposing those two characters to sociopath Alice Morgan and sophomore detective Justin Ripley. The second season finds Luther at odds with several mother figures...

  19. A Radio Pulsar Search of the Gamma-ray Binaries LS I +61 303 and LS 5039

    CERN Document Server

    McSwain, M Virginia; Ransom, Scott M; Roberts, Mallory S E; Dougherty, Sean M; Pooley, Guy G

    2011-01-01

    LS I +61 303 and LS 5039 are exceptionally rare examples of HMXBs with MeV-TeV emission, making them two of only five known or proposed "gamma-ray binaries". There has been disagreement within the literature over whether these systems are microquasars, with stellar winds accreting onto a compact object to produce high energy emission and relativistic jets, or whether their emission properties might be better explained by a relativistic pulsar wind colliding with the stellar wind. Here we present an attempt to detect radio pulsars in both systems with the Green Bank Telescope. The upper limits of flux density are between 4.1-14.5 uJy, and we discuss the null results of the search. Our spherically symmetric model of the wind of LS 5039 demonstrates that any pulsar emission will be strongly absorbed by the dense wind unless there is an evacuated region formed by a relativistic colliding wind shock. LS I +61 303 contains a rapidly rotating Be star whose wind is concentrated near the stellar equator. As long as th...

  20. Delineation of Behavioral Phenotypes in Genetic Syndromes: Characteristics of Autism Spectrum Disorder, Affect and Hyperactivity

    Science.gov (United States)

    Oliver, Chris; Berg, Katy; Moss, Jo; Arron, Kate; Burbidge, Cheryl

    2011-01-01

    We investigated autism spectrum disorder (ASD) symptomatology, hyperactivity and affect in seven genetic syndromes; Angelman (AS; n = 104), Cri du Chat (CdCS; 58), Cornelia de Lange (CdLS; 101), Fragile X (FXS; 191), Prader-Willi (PWS; 189), Smith-Magenis (SMS; 42) and Lowe (LS; 56) syndromes (age range 4-51). ASD symptomatology was heightened in…

  1. Delineation of Behavioral Phenotypes in Genetic Syndromes: Characteristics of Autism Spectrum Disorder, Affect and Hyperactivity

    Science.gov (United States)

    Oliver, Chris; Berg, Katy; Moss, Jo; Arron, Kate; Burbidge, Cheryl

    2011-01-01

    We investigated autism spectrum disorder (ASD) symptomatology, hyperactivity and affect in seven genetic syndromes; Angelman (AS; n = 104), Cri du Chat (CdCS; 58), Cornelia de Lange (CdLS; 101), Fragile X (FXS; 191), Prader-Willi (PWS; 189), Smith-Magenis (SMS; 42) and Lowe (LS; 56) syndromes (age range 4-51). ASD symptomatology was heightened in…

  2. Facial Expression of Affect in Children with Cornelia de Lange Syndrome

    Science.gov (United States)

    Collis, L.; Moss, J.; Jutley, J.; Cornish, K.; Oliver, C.

    2008-01-01

    Background: Individuals with Cornelia de Lange syndrome (CdLS) have been reported to show comparatively high levels of flat and negative affect but there have been no empirical evaluations. In this study, we use an objective measure of facial expression to compare affect in CdLS with that seen in Cri du Chat syndrome (CDC) and a group of…

  3. Spin Crossover in Dinuclear N4S2 Iron(II) Thioether-Triazole Complexes: Access to [HS-HS], [HS-LS], and [LS-LS] States.

    Science.gov (United States)

    Hogue, Ross W; Feltham, Humphrey L C; Miller, Reece G; Brooker, Sally

    2016-05-01

    Access to a new family of thioether-linked PSRT ligands, 4-substituted-3,5-bis{[(2-pyridylmethyl)sulfanyl]methyl}-4H-1,2,4-triazoles (analogues of the previously studied amino-linked PMRT ligands), has been established. Four such ligands have been prepared, PSPhT, PS(i)BuT, PS(t-Bu)PhT, and PS(Me)PhT, with R = Ph, (i)Bu, (t-Bu)Ph, and (Me)Ph, respectively. Three dinuclear colorless to pale green iron(II) complexes, [Fe(II)2(PSRT)2](BF4)4·solvent, featuring N4S2 donor sets, were prepared. Single-crystal structure determinations on [Fe(II)2(PSPhT)2](BF4)4·2MeCN·H2O, [Fe(II)2(PSPhT)2](BF4)4·2(1)/2MeCN·(1)/2H2O·THF, [Fe(II)2(PS(Me)PhT)2](BF4)4·2MeCN, and [Fe(II)2(PS(i)BuT)2](BF4)4·4MeCN reveal that all four are stabilized in the [HS-HS] state to 100 K and that both possible binding modes of the bis-terdentate ligands, cis- and trans-axial, are observed. Variable-temperature magnetic susceptibility studies of air-dried crystals (solvatomorphs of the single crystal samples) reveal the first examples of spin crossover (SCO) for a dinuclear iron(II) complex with N4S2 coordination. Specifically, [Fe(II)2(PSPhT)2](BF4)4·2(1)/2H2O undergoes a multistep but complete SCO from [HS-HS] to [LS-LS], whereas [Fe(II)2(PS(Me)PhT)2](BF4)4·1(1)/2MeCN·2H2O exhibits a half-SCO from [HS-HS] to [HS-LS]. In contrast, [Fe(II)2(PS(i)BuT)2](BF4)4·MeCN·H2O remains [HS-HS] down to 50 K. The reflectance spectrum of pale green [Fe(II)2(PSPhT)2](BF4)4·(1)/2CHCl3·2(1)/2H2O (solvatomorph A) reveals a trace of LS character (572 nm band (1)A1g → (1)T1g). Evans' (1)H NMR method and UV-vis spectroscopy studies revealed that on cooling dark green acetonitrile solutions of these complexes from 313 to 233 K, all three undergo SCO centered at or near room temperature. The tendency of the complexes to go LS in solution reflects the electronic impact of R on the σ-donor strength of the PSRT ligand, whereas the opposite trend in stabilization of the LS state is seen in the solid state, where

  4. Relations Between Helicity Coupling Amplitude and L-S Coupling Amplitude

    Institute of Scientific and Technical Information of China (English)

    WU Ning; RUAN Tu-Nan

    2001-01-01

    Relations between helicity coupling amplitude and L-S coupling amplitude are discussed. The equivalence condition for these two kinematic analysis methods and the limitations of the L-S coupling amplitude are also studied in this paper.``

  5. Measurable versions of the LS category on laminations

    CERN Document Server

    Meniño, Carlos

    2011-01-01

    We give two new versions of the LS category for the set-up of measurable laminations defined by Berm\\'udez. Both of these versions must be considered as "tangential categories". The first one, simply called (LS) category, is the direct analogue for measurable laminations of the tangential category of (topological) laminations introduced by Colman Vale and Mac\\'ias Virg\\'os. For the measurable lamination that underlies any lamination, our measurable tangential category is a lower bound of the tangential category. The second version, called the measured category, depends on the choice of a transverse invariant measure. We show that both of these "tangential categories" satisfy appropriate versions of some well known properties of the classical category: the homotopy invariance, a dimensional upper bound, a cohomological lower bound (cup length), and an upper bound given by the critical points of a smooth function.

  6. LS 5039 and HD 259440: A Multiwavelength Approach

    Science.gov (United States)

    Aragona, Christina

    2012-07-01

    A handful of Galactic High Mass X-ray Binaries have been observed to emit radiation at very high energies (MeV-TeV), dubbed gamma-ray binaries. This poster will review the importance of multiwavelength observations for understanding two of these systems, HD 259440 and LS 5039. For HD 259440, detection of a nearby high-energy source instigated optical observations to search for evidence the system's binarity. For LS 5039, optically determined orbital and stellar parameters combined with constraints on the system inclination angle from X-ray, UV, and radio observations are bringing us closer to identifying the nature of the interaction region and the compact object. I am grateful for support from NSF grant AST-1109247 and Lehigh University.

  7. Effectiveness of the Biology PTechLS Module in a Felda Science Centre

    Science.gov (United States)

    Alias, Norlidah; DeWitt, Dorothy; Rahman, Mohd Nazri Abdul; Gelamdin, Rashidah Begum; Rauf, Rose Amnah Abd; Siraj, Saedah

    2014-01-01

    The PTechLS module combines learning styles with the use of technology to increase students' learning experience, especially in learning abstract concepts. The PTechLS module prototype was developed by Norlidah Alias (2010). The aim of this study is to evaluate the implementation effectiveness of the Biology PTechLS module in a Felda Learning…

  8. Revitalising Mathematics Classroom Teaching through Lesson Study (LS): A Malaysian Case Study

    Science.gov (United States)

    Lim, Chap Sam; Kor, Liew Kee; Chia, Hui Min

    2016-01-01

    This paper discusses how implementation of Lesson Study (LS) has brought about evolving changes in the quality of mathematics classroom teaching in one Chinese primary school. The Japanese model of LS was adapted as a teacher professional development to improve mathematics teachers' teaching practices. The LS group consisted of five mathematics…

  9. Characteristics of Autism Spectrum Disorder in Cornelia de Lange Syndrome

    Science.gov (United States)

    Moss, Jo; Howlin, Patricia; Magiati, Iliana; Oliver, Chris

    2012-01-01

    Background: The prevalence of autism spectrum disorder (ASD) symptomatology is comparatively high in Cornelia de Lange syndrome (CdLS). However, the profile and developmental trajectories of these ASD characteristics are potentially different to those observed in individuals with idiopathic ASD. In this study we examine the ASD profile in CdLS in…

  10. ls - Ponomarev - Systems and 1 - sequence - covering Images%ls-Ponomarev-systems与1-序列覆盖映像

    Institute of Scientific and Technical Information of China (English)

    孙秀华; 吕诚

    2012-01-01

    In order to characterize images of locally separable metric spaces, the concept of double point - star sn - covers was introduced in this paper. By using " ls - Ponomarev - system" which is a generalization of "Ponomarev - system". The new characterizations of 1 - sequence - covering compact images of locally separable metric spaces were given.%为了寻求局部可分度量空间的映像,引入双点星sn覆盖这一概念,并借用近年来由传统的Ponomarev-system推广而得的ls-Ponomarev-system,给出了局部可分度量空间1-序列覆盖映像的一个新刻画,并且这一新刻画较以往所得相关刻画更为简洁.

  11. A Subgeneric Classification of the Genus Uranotaenia Lynch Arribalzaga, with a Historical Review and Notes on Other Categories

    Science.gov (United States)

    1972-01-01

    first applied by Lynch Arribalzaga in 1891. It was derived from the Greek and Latin combinations of urano (heaven) and taenia (band or stripe) in...have been seen in the subgenus Urano taenia d Other secondary characters seen in Pseudoficalbia only are conspicuous setae at or near the apical...o o e ANNULATA SERIES Although a few of these characters are found in other Urano- taenia species, the peculiar larval head seta 1-C in the annulata

  12. People typically experience extended periods of relative happiness or unhappiness due to positive feedback loops between LS and variables which are both causes and consequences of LS

    NARCIS (Netherlands)

    Headey, Bruce; Muffels, R.J.A.

    2015-01-01

    Long term panel data enable researchers to construct trajectories of LS for individuals over time. Bar charts of trajectories, and subsequent statistical analysis, show that respondents typically spend multiple consecutive years above and below their own long-term mean level of LS. We attempt to exp

  13. LS1 Report: Handing in the ATLAS keys

    CERN Multimedia

    Antonella Del Rosso, Katarina Anthony

    2014-01-01

    After completing more than 250 work packages concerning the whole detector and experimental site, the ATLAS and CERN teams involved with LS1 operations are now wrapping things up before starting the commissioning phase in preparation for the LHC restart. The giant detector is now more efficient, safer and even greener than ever thanks to the huge amount of work carried out over the past two years.   Cleaning up the ATLAS cavern and detector in preparation for Run 2. Hundreds of people, more than 3000 certified interventions, huge and delicate parts of the detector completely refurbished: the ATLAS detector that will take data during Run 2 is a brand new machine, which will soon be back in the hands of the thousands of scientists who are preparing for the high-energy run of the LHC accelerator. “During LS1, we have upgraded the detector’s basic infrastructure and a few of its sub-detectors,” explains Beniamino Di Girolamo, ATLAS Technical Coordinator. &...

  14. Edge Detector Design Based on LS-SVR

    Directory of Open Access Journals (Sweden)

    Zhongdang Yu

    2014-01-01

    Full Text Available For locating inaccurate problem of the discrete localization criterion proposed by Demigny, a new criterion expression of “good localization” is proposed. Firstly, a discrete expression of good detection and good localization criterion of two dimension edge detection operator is employed, and then an experiment to measure optimal parameters of two dimension Canny's edge detection operator is introduced after. Moreover, a detailed performance comparison and analysis of two dimension optimal filter obtained via utilizing tensor product for one dimension optimal filter are provided which can prove that least square support vector regression (LS-SVR is a smoothness filter and give the construct method of the derivate operator. This paper uses LS-SVR as the object function constructor and then realizes the approximation of two dimension optimal edge detection operator. This paper proposes the utility method of using singleness operator to realize multiscale edge detection by referencing the multiscale analysis technology of the wavelets theory. Experiment shows that the method has utility and efficiency.

  15. 3-Ls: A MODEL FOR TEACHING YOUNG LEARNERS

    Directory of Open Access Journals (Sweden)

    Chuzaimah Dahlan Diem

    2011-07-01

    Full Text Available The fact that EFL literacy in Indonesia is still low led me to conduct this study to cultivate reading habits and increase literacy skills of young learners. Using the 3-Ls—libraries, literature, and literacy—as an instructional model, the study involved five methods: Informational Text Structures; Online Resources; Partnership with Librarians; Big6; and Literature Circles. The sample consisted of 200 fifth graders divided equally into five groups, each of which was also divided into experimental and control groups. Each of tThe experimental groups was taught for three months using one method. All the students in both groups were given English tests and a questionnaire before and after the experiment. The results showed that the experimental groups outperformed the control groups with a significant mean difference of 21.73 on literacy skills and 10.15 on reading habits. Using regression analysis, it was also found that 3-Ls as a whole had given a significant contribution to both students’ reading habits (R2 0,793 and literacy skills (R 0,943 with the highest percentage contributed by every method was reading skill. However, in spite of demonstrating significant effects on students’ literacy, these methods still did not bring the students’ literacy to an acceptable level. A factor that might contribute to the low achievement of their English literacy was that the 3-Ls model requires optimal facilities.

  16. LS1 Report: The cryogenic line goes through the scanner

    CERN Multimedia

    CERN Bulletin

    2013-01-01

    In spite of the complexity of LS1, with many different activities taking place in parallel and sometimes overlapping, the dashboard shows that work is progressing on schedule. This week, teams have started X-raying the cryogenic line to examine its condition in minute detail.   The LS1 schedule is pretty unfathomable for those who don't work in the tunnels or installations, but if you look down all the columns and stop at the line indicating today’s date, you can see that all of the priority and critical items are bang on time, like a Swiss watch. More specifically: the SMACC project in the LHC is on schedule, with a new testing phase for the interconnections which have already been consolidated; preparations are under way for the cable replacement campaign at Point 1 of the SPS (about 20% of the cables will not be replaced as they are completely unused); and the demineralised water distribution line is back in service, as are the electrical substations for the 400 and 66 kV line...

  17. LS-SVR and AGO Based Time Series Prediction Method

    Institute of Scientific and Technical Information of China (English)

    ZHANG Shou-peng; LIU Shan; CHAI Wang-xu; ZHANG Jia-qi; GUO Yang-ming

    2016-01-01

    Recently , fault or health condition prediction of complex systems becomes an interesting research topic.However, it is difficult to establish precise physical model for complex systems , and the time series properties are often necessary to be incorporated for the prediction in practice .Currently ,the LS -SVR is widely adopted for prediction of systems with time series data .In this paper , in order to improve the prediction accuracy, accumulated generating operation (AGO) is carried out to improve the data quality and regularity of raw time series data based on grey system theory;then, the inverse accumulated generating operation ( IAGO) is performed to obtain the prediction results .In addition , due to the reason that appropriate kernel function plays an important role in improving the accuracy of prediction through LS-SVR, a modified Gaussian radial basis function (RBF) is proposed.The requirements of distance functions-based kernel functions are satisfied , which ensure fast damping at the place adjacent to the test point and a moderate damping at infinity .The presented model is applied to the analysis of benchmarks .As indicated by the results , the proposed method is an effective prediction one with good precision .

  18. Cornelia de Lange syndrome: What every otolaryngologist should know.

    Science.gov (United States)

    Eliason, Michael J; Melzer, Jonathan M; Gallagher, Thomas Q

    2017-08-01

    Cornelia de Lange Syndrome (CdLS) can be expressed in multiple organ systems requiring a variety of specialists, including pediatric otolaryngology. We present the case of a 20-month-old boy with CdLS actively managed by an aerodigestive team consisting of pediatric otolaryngology, pediatric pulmonology, pediatric gastroenterology, with support staff from audiology, speech, and nutrition. His presentation included mixed hearing loss, dysphagia, microaspiration, gastroesophageal reflux, and failure to thrive. We submit this challenging case of CdLS with a review of the literature to focus specific attention on the otolaryngic manifestations of the syndrome and to discuss the benefits of a multidisciplinary approach to these unique patients.

  19. High Prevalence of Hereditary Cancer Syndromes in Adolescents and Young Adults With Colorectal Cancer.

    Science.gov (United States)

    Mork, Maureen E; You, Y Nancy; Ying, Jun; Bannon, Sarah A; Lynch, Patrick M; Rodriguez-Bigas, Miguel A; Vilar, Eduardo

    2015-11-01

    Established guidelines recommend evaluation for hereditary cancer syndromes in patients younger than 50 years diagnosed with colorectal cancer (CRC). This group has been well described in the literature; however, patients diagnosed as adolescents and young adults are not well represented in CRC studies. Here, we define the clinical profile, including the extent of hereditary cancer syndromes and family history of cancer, in patients diagnosed with CRC at age 35 or younger. We reviewed patients who underwent genetic counseling at our institution during 5 years (2009 to 2013). Data were collected regarding demographics, clinicopathologic information, tumor and genetic testing, and family history. Patients with an identified hereditary cancer syndrome were compared with those without a syndrome. Of the 193 patients with evaluable data, 35% had an identifiable hereditary cancer syndrome, including 23 with Lynch syndrome, 22 with mutation-negative Lynch syndrome, 16 with familial adenomatous polyposis, two with constitutional mismatch repair deficiency, two with biallelic MUTYH mutations, and one with Li-Fraumeni syndrome. Patients without a hereditary syndrome more frequently presented with metastatic disease, whereas patients with a syndrome were more likely to present at earlier stages and to have a family history of cancer. Nevertheless, a substantial proportion of the hereditary syndromes (19%) were diagnosed in individuals with no family history of the disease. We conclude that patients diagnosed with CRC at age 35 years or younger should receive genetic counseling regardless of their family history and phenotype. © 2015 by American Society of Clinical Oncology.

  20. A Data Communication Optimization Algorithm for LS SIMD C Compiler%LS SIMD C编译器的数据通信优化算法

    Institute of Scientific and Technical Information of China (English)

    王晖; 何华灿; 陈丹; 胡麒; 张宝稳

    2001-01-01

    LS SIMD is an embedded memory-shared massively parallel machine. In this paper,we present a deep study of data communication optimizations techniques of LS SIMD parallel compiler. First,some conceptions of data layout and data communication are given,and the data communication principle of LS SIMD is analyzed. Second,we propose an optimization algorithm of data communication,and discuss some aspects in detail ,such as the representation of register state space ,decision and generation of inner data communication and batch data communication in PE array.

  1. Leigh-Like Syndrome Due to Homoplasmic m.8993T>G Variant with Hypocitrullinemia and Unusual Biochemical Features Suggestive of Multiple Carboxylase Deficiency (MCD)

    NARCIS (Netherlands)

    Balasubramaniam, S.; Lewis, B.; Mock, D.M.; Said, H.M.; Tarailo-Graovac, M.; Mattman, A.; Karnebeek, C.D; Thorburn, D.R.; Rodenburg, R.J.T.; Christodoulou, J.

    2017-01-01

    Leigh syndrome (LS), or subacute necrotizing encephalomyelopathy, is a genetically heterogeneous, relentlessly progressive, devastating neurodegenerative disorder that usually presents in infancy or early childhood. A diagnosis of Leigh-like syndrome may be considered in individuals who do not

  2. ATLAS TDAQ application gateway upgrade during LS1

    CERN Document Server

    KOROL, A; The ATLAS collaboration; BOGDANCHIKOV, A; BRASOLIN, F; CONTESCU, A C; DUBROV, S; HAFEEZ, M; LEE, C J; SCANNICCHIO, D A; TWOMEY, M; VORONKOV, A; ZAYTSEV, A

    2014-01-01

    The ATLAS Gateway service is implemented with a set of dedicated computer nodes to provide a fine-grained access control between CERN General Public Network (GPN) and ATLAS Technical Control Network (ATCN). ATCN connects the ATLAS online farm used for ATLAS Operations and data taking, including the ATLAS TDAQ (Trigger and Data Aquisition) and DCS (Detector Control System) nodes. In particular, it provides restricted access to the web services (proxy), general login sessions (via SSH and RDP protocols), NAT and mail relay from ATCN. At the Operating System level the implementation is based on virtualization technologies. Here we report on the Gateway upgrade during Long Shutdown 1 (LS1) period: it includes the transition to the last production release of the CERN Linux distribution (SLC6), the migration to the centralized configuration management system (based on Puppet) and the redesign of the internal system architecture.

  3. Sulphate Geoengineering in the UT/LS: Some Relevant Processes

    Science.gov (United States)

    Tuck, A. F.; Donaldson, D. J.; Hitchman, M. H.; Richard, E. C.; Tervahattu, H.; Vaida, V.; Wilson, J. C.

    2008-12-01

    We consider the potential effects of meteorological dynamics, the physics and chemistry of aerosols and the photodissociation of sulphuric acid upon the posited maintenance of a 'parasol' of geoengineered sulphate aerosol in the lower stratosphere. Specific observational and experimental results include the spread of tungsten-185 from the Hardtack series of nuclear weapon tests in 1958, satellite observations of the spread of volcanic eruptions, tracer and water profiles in the tropical UT/LS, the organic coating of surfactants on aerosols, the observed distributions of aerosols and the overtone driven photodissociation of sulphuric acid in the stratosphere. A few implications for the logistics of any possible future geoengineering injection are considered briefly. The uncertainties arising from the analysis subtract significantly from the predictability of any supposed amelioration of the effects of global warming from continued increases in carbon dioxide from fossil fuel combustion.

  4. Iconografía, música y narración en Wild at Heart, de David Lynch

    OpenAIRE

    García Escrivá, Vicente

    2011-01-01

    El análisis del texto fílmico Corazón Salvaje (Wild at Heart, David Lynch, EEUU, 1990) permite localizar toda una serie de rasgos característicos de la narrativa y la estética cinematográfica posmoderna. Por un lado, el film presenta una notable descomposición narrativa, lo que se traduce en una sucesión de escenas un tanto inconexas, a modo de cuadros intensos pero poco trabados. Asimismo, en la película se produce una suerte de hibridación de géneros, aglutinados por un tono general de paro...

  5. Behavioral Phenotype and Autism Spectrum Disorders in Cornelia de Lange Syndrome.

    Science.gov (United States)

    Parisi, Lucia; Di Filippo, Teresa; Roccella, Michele

    2015-09-30

    Cornelia de Lange syndrome (CdLS) is a congenital disorder characterized by distinctive facial features, growth retardation, limb abnormalities, intellectual disability, and behavioral problems. Cornelia de Lange syndrome is associated with abnormalities on chromosomes 5, 10 and X. Heterozygous point mutations in three genes (NIPBL, SMC3 and SMC1A), are responsible for approximately 50-60% of CdLS cases. CdLS is characterized by autistic features, notably excessive repetitive behaviors and expressive language deficits. The prevalence of autism spectrum disorder (ASD) symptomatology is comparatively high in CdLS. However, the profile and developmental trajectories of these ASD characteristics are potentially different to those observed in individuals with idiopathic ASD. A significantly higher prevalence of self-injury are evident in CdLS. Self-injury was associated with repetitive and impulsive behavior. This study describes the behavioral phenotype of four children with Cornelia de Lange syndrome and ASDs and rehabilitative intervention that must be implemented.

  6. The Behavioural Phenotype of Cornelia de Lange Syndrome: A Study of 56 Individuals

    Science.gov (United States)

    Basile, Emanuele; Villa, L.; Selicorni, A.; Molteni, M.

    2007-01-01

    Background: Few studies have investigated functional and behavioural variables of Cornelia de Lange Syndrome (CdLS) in a large sample of individuals. The aim of this study is to provide greater insight into the clinical, behavioural and cognitive characteristics that are associated with CdLS. Methods: In total, 56 individuals with CdLS…

  7. Health and Sleep Problems in Cornelia de Lange Syndrome: A Case Control Study

    Science.gov (United States)

    Hall, S. S.; Arron, K.; Sloneem, J.; Oliver, C.

    2008-01-01

    Background: Self-injury, sleep problems and health problems are commonly reported in Cornelia de Lange Syndrome (CdLS) but there are no comparisons with appropriately matched participants. The relationship between these areas and comparison to a control group is warranted. Method: 54 individuals with CdLS were compared with 46 participants with…

  8. Extending JPEG-LS for low-complexity scalable video coding

    DEFF Research Database (Denmark)

    Ukhanova, Anna; Sergeev, Anton; Forchhammer, Søren

    2011-01-01

    JPEG-LS, the well-known international standard for lossless and near-lossless image compression, was originally designed for non-scalable applications. In this paper we propose a scalable modification of JPEG-LS and compare it with the leading image and video coding standards JPEG2000 and H.264/SVC...

  9. Los actos tienen consecuencias. Lógicas del mind-game film en la trilogía de Los Ángeles de David Lynch

    NARCIS (Netherlands)

    Elsaesser, T.

    2013-01-01

    Actions Do Have Consequences. Logics of the Mind-Game Film in David Lynch’s Los Angeles-Trilogy. David Lynch is a director, along with other auteurs, notably Michael Haneke and Lars von Trier, whose authorial identity and creative authority —and the challenges these encounter in the 21st century— ar

  10. Los actos tienen consecuencias. Lógicas del mind-game film en la trilogía de Los Ángeles de David Lynch

    NARCIS (Netherlands)

    Elsaesser, T.

    2013-01-01

    Actions Do Have Consequences. Logics of the Mind-Game Film in David Lynch’s Los Angeles-Trilogy. David Lynch is a director, along with other auteurs, notably Michael Haneke and Lars von Trier, whose authorial identity and creative authority —and the challenges these encounter in the 21st century—

  11. Range and railgun development results at LS and PA ``Soyuz``

    Energy Technology Data Exchange (ETDEWEB)

    Babakov, Y.P.; Plekhanov, A.V.; Zheleznyi, V.B. [Lyubertsy Scientific and Production Association Soyuz, Dzerzhinskiy (Russian Federation). Energophyzika Dept.

    1995-01-01

    A rail electromagnetic accelerator is one of the most reliable and simple devices for accelerating macroparticles up to high velocity. These accelerators allow scientists to carry out fundamental and applied investigations to study both equation-of-state of materials at high pressure due to high velocity encounters, and creation of conditions for shock thermonuclear fusion. In the department ``Energophyzika`` LS and PA ``Soyuz`` range was created. It was equipped with an inductor with storage capacity up to 12.5 MJ energized by a solid propellant MHD generator and a capacitor bank (energy capacity up to 6 MJ). These systems deliver currents of 1 MA and 2 MA, respectively. Diagnostic, recording, and autocalculation systems allow use of as many as 120 data channels with acquisition frequency up to 10 MHz. Recent technical successes in railgun construction, using special methods to compact plasma armature and produce high velocity trailing contact, creation of hybrid armatures, and optimizing acceleration made possible to gain velocities in the range of 6.2 to 6.8 km/s (masses of 3.8 to 10 g) and velocities 2.7 to 3.8 km/s (masses of 50 to 100 g) on railguns with length 2 to 4 m.

  12. LS1 Report: antimatter research on the starting blocks

    CERN Multimedia

    Antonella Del Rosso

    2014-01-01

    The consolidation work at the Antiproton Decelerator (AD) has been very intensive and the operators now have a basically new machine to “drive”. Thanks to the accurate preparation work still ongoing, the machine will soon deliver its first beam of antiprotons to the experiments. The renewed efficiency of the whole complex will ensure the best performance of the whole of CERN’s antimatter research programme in the long term.   The test bench for the new Magnetic Horn stripline. On the left, high voltage cables are connected to the stripline, which then feeds a 6 kV 400 kA pulse to the Horn. The Horn itself (the cylindrical object on the right) can be seen mounted on its chariot. The consolidation programme at the AD planned during LS1 has involved some of the most vital parts of the decelerator such as the target area, the ring magnets, the stochastic cooling system, vacuum system, control system and various aspects of the instrumentation. In addit...

  13. New Representation of Bearings in LS-DYNA

    Science.gov (United States)

    Carney, Kelly S.; Howard, Samuel A.; Miller, Brad A.; Benson, David J.

    2014-01-01

    Non-linear, dynamic, finite element analysis is used in various engineering disciplines to evaluate high-speed, dynamic impact and vibration events. Some of these applications require connecting rotating to stationary components. For example, bird impacts on rotating aircraft engine fan blades are a common analysis performed using this type of analysis tool. Traditionally, rotating machines utilize some type of bearing to allow rotation in one degree of freedom while offering constraints in the other degrees of freedom. Most times, bearings are modeled simply as linear springs with rotation. This is a simplification that is not necessarily accurate under the conditions of high-velocity, high-energy, dynamic events such as impact problems. For this reason, it is desirable to utilize a more realistic non-linear force-deflection characteristic of real bearings to model the interaction between rotating and non-rotating components during dynamic events. The present work describes a rolling element bearing model developed for use in non-linear, dynamic finite element analysis. This rolling element bearing model has been implemented in LS-DYNA as a new element, *ELEMENT_BEARING.

  14. LS1 Report: on the home straight in 2014

    CERN Multimedia

    Anaïs Schaeffer

    2013-01-01

    At 7.24 a.m. on 14 February 2013 the last beams for physics were absorbed into the LHC, marking the end of Run 1. The achievements since then over the first ten months of LS1 have been remarkable. The excellent progress of the maintenance work on CERN's accelerators, which is overwhelmingly on schedule – and even ahead of schedule in some cases! – was praised by the CERN Council last week.   That being said, there is still a long way to go before the LHC re-start, with many challenges and potential pitfalls to be overcome. An overview of what still lies ahead: For the injectors (Linac 2, PS booster, LEIR, PS and AD), 2014 will begin with the recommissioning of all the access systems (scheduled for mid-February). The first power tests (to check the magnets and the power converters) will follow hot on its heels, starting in early April in the case of the PS booster. The final power tests of the injectors will be carried out at the Antiproton Decelerator in June. Th...

  15. LS1 Report: PS Booster prepares for beam

    CERN Multimedia

    Katarina Anthony

    2014-01-01

    With Linac2 already up and running, the countdown to beam in the LHC has begun! The next in line is the PS Booster, which will close up shop to engineers early next week. The injector will be handed over to the Operations Group who are tasked with getting it ready for active duty.   Taken as we approach the end of LS1 activities, this image shows where protons will soon be injected from Linac2 into the four PS Booster rings. Over the coming two months, the Operations Group will be putting the Booster's new elements through their paces. "Because of the wide range of upgrades and repairs carried out in the Booster, we have a very full schedule of tests planned for the machine," says Bettina Mikulec, PS Booster Engineer in Charge. "We will begin with cold checks; these are a wide range of tests carried out without beam, including system tests with power on/off and with varying settings, as well as verification of the controls system and timings." Amon...

  16. LS1 Report: the electric atmosphere of the LHC

    CERN Multimedia

    Simon Baird

    2013-01-01

    In the LHC, testing of the main magnet (dipole and quadrupole) circuits has been completed. At the same time, the extensive tests of all the other circuits up to current levels corresponding to 7 TeV beam operation have been performed, and now the final ElQA (Electrical Quality Assurance) tests of the electrical circuits are proceeding.   In Sectors 4-5 and 5-6, where the ElQA checks have been finished, the process of removing and storing the helium has started (see the article Heatwave warning for the LHC, in this issue). This is the first step in warming up the whole machine to room temperature so that the main LS1 activities, SMACC (Super Conducting Magnet and Circuit Consolidation) and the R2E (Radiation Two Electronics) programmes, which are scheduled to start on 19 April and 22 March respectively, can get under way. As far as the LHC injectors are concerned, LINAC2 and the PS Booster are in shutdown mode, having completed their preparatory hardware test programmes, and shutdown work has alr...

  17. A rapid screening with direct sequencing from blood samples for the diagnosis of Leigh syndrome

    Directory of Open Access Journals (Sweden)

    Hiroko Shimbo

    2014-01-01

    Full Text Available Large numbers of genes are responsible for Leigh syndrome (LS, making genetic confirmation of LS difficult. We screened our patients with LS using a limited set of 21 primers encompassing the frequently reported gene for the respiratory chain complexes I (ND1–ND6, and ND4L, IV(SURF1, and V(ATP6 and the pyruvate dehydrogenase E1α-subunit. Of 18 LS patients, we identified mutations in 11 patients, including 7 in mDNA (two with ATP6, 4 in nuclear (three with SURF1. Overall, we identified mutations in 61% of LS patients (11/18 individuals in this cohort. Sanger sequencing with our limited set of primers allowed us a rapid genetic confirmation of more than half of the LS patients and it appears to be efficient as a primary genetic screening in this cohort.

  18. Global transcriptional disturbances underlie Cornelia de Lange syndrome and related phenotypes

    National Research Council Canada - National Science Library

    Yuan, Bo; Pehlivan, Davut; Karaca, Ender; Patel, Nisha; Charng, Wu-Lin; Gambin, Tomasz; Gonzaga-Jauregui, Claudia; Sutton, V Reid; Yesil, Gozde; Bozdogan, Sevcan Tug; Tos, Tulay; Koparir, Asuman; Koparir, Erkan; Beck, Christine R; Gu, Shen; Aslan, Huseyin; Yuregir, Ozge Ozalp; Al Rubeaan, Khalid; Alnaqeb, Dhekra; Alshammari, Muneera J; Bayram, Yavuz; Atik, Mehmed M; Aydin, Hatip; Geckinli, B Bilge; Seven, Mehmet; Ulucan, Hakan; Fenercioglu, Elif; Ozen, Mustafa; Jhangiani, Shalini; Muzny, Donna M; Boerwinkle, Eric; Tuysuz, Beyhan; Alkuraya, Fowzan S; Gibbs, Richard A; Lupski, James R

    2015-01-01

    Cornelia de Lange syndrome (CdLS) is a genetically heterogeneous disorder that presents with extensive phenotypic variability, including facial dysmorphism, developmental delay/intellectual disability (DD/ID...

  19. What factors affect life satisfaction (LS) among the oldest-old?

    Science.gov (United States)

    Enkvist, Asa; Ekström, Henrik; Elmståhl, Sölve

    2012-01-01

    Few studies have examined the association between LS in the oldest-old and not only health-related, but also psychological and socio-economical factors. The aim of this study was to examine LS in relation to functional capacity, locus of control (LoC) health status and other factors previously known to influence LS in the oldest-old. The study population consisted of 681 individuals aged 78-98 years, drawn from the longitudinal population study "Good Aging in Skåne" (GÅS), part of a national survey (SNAC) who fulfilled a questionnaire. In a regression model was shown that the number of symptoms, marital status, LoC, especially internal and powerful others, depressive mood and age significantly could predict life satisfaction three years later. Specific diagnoses like stroke, dementia and cardiac disease were not related to LS. Independence in physical functioning was related to unchanged LS, stratified for age and gender during a 3-year follow-up. The clinical implications of this study are that attention should be paid to recognizing and treating factors that affect LS and are reachable for medical intervention. Relieving symptoms and paying attention to personality factors that modify LS seem to be key-factors in the care of elderly.

  20. A role of RnlA in the RNase LS activity from Escherichia coli.

    Science.gov (United States)

    Otsuka, Yuichi; Koga, Mitsunori; Iwamoto, Akira; Yonesaki, Tetsuro

    2007-08-01

    Escherichia coli ribonuclease LS is a potential antagonist of bacteriophage T4. When the T4 dmd gene is defective, RNase LS cleaves T4 mRNAs and antagonizes T4 reproduction. Our previous work demonstrated that E. coli rnlA is essential for RNase LS activity. Here we show that His-tagged RnlA cleaves T4 soc RNA at one of the sites also cleaved by RNase LS in a cell extract. The cleavage activities of His-tagged RnlA and the RNase LS activity in a cell extract were inhibited by Dmd encoded by T4 phage. Fractionation of the RNase LS activity in a cell extract showed that it sedimented through a sucrose density gradient as a 1000-kDa complex that included RnlA. Pull-down experiments revealed more than 10 proteins associated with His-tagged RnlA. Among these, triose phosphate isomerase exhibited a remarkable affinity to RnlA. These results suggest that RnlA plays a central role in RNase LS activity and that its activity is regulated by multiple components.

  1. Merits of online electrochemistry liquid sample desorption electrospray ionization mass spectrometry (EC/LS DESI MS).

    Science.gov (United States)

    Looi, Wen Donq; Brown, Blake; Chamand, Laura; Brajter-Toth, Anna

    2016-03-01

    A new online electrochemistry/liquid sample desorption electrospray ionization mass spectrometry (EC/LS DESI MS) system with a simple electrochemical thin-layer flow-through cell was developed and tested using N,N-dimethyl-p-phenylenediamine (DMPA) as a model probe. Although oxidation of DMPA is observed as a result of ionization of LS in positive ion mode LS DESI, application of voltage to the online electrochemical (EC) cell in EC/LS DESI MS increases yields of oxidation products. An advantage of LS DESI MS is its sensitivity in aqueous electrolyte solutions, which improves efficiency of electrochemical reactions in EC/LS DESI MS. In highly conductive low pH aqueous buffer solutions, oxidation efficiency is close to 100%. EC/ESI MS typically requires mixed aqueous/organic solvents and low electrolyte concentrations for efficient ionization in MS, limiting efficiency of electrochemistry online with MS. Independently, the results verify higher electrochemical oxidation efficiency during positive mode ESI than during LS DESI.

  2. Time-series gas prediction model using LS-SVR within a Bayesian framework

    Institute of Scientific and Technical Information of China (English)

    Qiao Meiying; Ma Xiaoping; Lan Jianyi; Wang Ying

    2011-01-01

    The traditional least squares support vector regression (LS-SVR) model, using cross validation to determine the regularization parameter and kernel parameter, is time-consuming. We propose a Bayesian evidence framework to infer the LS-SVR model parameters. Three levels Bayesian inferences are used to determine the model parameters, regularization hyper-parameters and tune the nuclear parameters by model comparison. On this basis, we established Bayesian LS-SVR time-series gas forecasting models and provide steps for the algorithm. The gas outburst data of a Hebi 10th mine working face is used to validate the model. The optimal embedding dimension and delay time of the time series were obtained by the smallest differential entropy method. Finally, within a MATLAB7.1 environment, we used actual coal gas data to compare the traditional LS-SVR and the Bayesian LS-SVR with LS-SVMlab1.5 Toolbox simulation. The results show that the Bayesian framework of an LS-SVR significantly improves the speed and accuracy of the forecast

  3. Biodegradation test of SPS-LS blends as polymer electrolyte membrane fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Putri, Zufira, E-mail: zufira.putri@gmail.com, E-mail: arcana@chem.itb.ac.id; Arcana, I Made, E-mail: zufira.putri@gmail.com, E-mail: arcana@chem.itb.ac.id [Inorganic and Physical Chemistry Research Groups, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Bandung (Indonesia)

    2014-03-24

    Sulfonated polystyrene (SPS) can be applied as a proton exchange membrane fuel cell due to its fairly good chemical stability. In order to be applied as polymer electrolyte membrane fuel cells (PEMFCs), membrane polymer should have a good ionic conductivity, high proton conductivity, and high mechanical strength. Lignosulfonate (LS) is a complex biopolymer which has crosslinks and sulfonate groups. SPS-LS blends with addition of SiO{sub 2} are used to increase the proton conductivity and to improve the mechanical properties and thermal stability. However, the biodegradation test of SPS-LS blends is required to determine whether the application of these membranes to be applied as an environmentally friendly membrane. In this study, had been done the synthesis of SPS, biodegradability test of SPS-LS blends with variations of LS and SiO{sub 2} compositions. The biodegradation test was carried out in solid medium of Luria Bertani (LB) with an activated sludge used as a source of microorganism at incubation temperature of 37°C. Based on the results obtained indicated that SPS-LS-SiO{sub 2} blends are more decomposed by microorganism than SPS-LS blends. This result is supported by analysis of weight reduction percentage, functional groups with Fourier Transform Infrared (FTIR) Spectroscopy, and morphological surface with Scanning Electron Microscopy (SEM)

  4. Biodegradation test of SPS-LS blends as polymer electrolyte membrane fuel cells

    Science.gov (United States)

    Putri, Zufira; Arcana, I. Made

    2014-03-01

    Sulfonated polystyrene (SPS) can be applied as a proton exchange membrane fuel cell due to its fairly good chemical stability. In order to be applied as polymer electrolyte membrane fuel cells (PEMFCs), membrane polymer should have a good ionic conductivity, high proton conductivity, and high mechanical strength. Lignosulfonate (LS) is a complex biopolymer which has crosslinks and sulfonate groups. SPS-LS blends with addition of SiO2 are used to increase the proton conductivity and to improve the mechanical properties and thermal stability. However, the biodegradation test of SPS-LS blends is required to determine whether the application of these membranes to be applied as an environmentally friendly membrane. In this study, had been done the synthesis of SPS, biodegradability test of SPS-LS blends with variations of LS and SiO2 compositions. The biodegradation test was carried out in solid medium of Luria Bertani (LB) with an activated sludge used as a source of microorganism at incubation temperature of 37°C. Based on the results obtained indicated that SPS-LS-SiO2 blends are more decomposed by microorganism than SPS-LS blends. This result is supported by analysis of weight reduction percentage, functional groups with Fourier Transform Infrared (FTIR) Spectroscopy, and morphological surface with Scanning Electron Microscopy (SEM).

  5. [Systemic and ophthalmological findings in Cornelia de Lange syndrome].

    Science.gov (United States)

    Mrugacz, Małgorzata; Sielicka, Danuta

    2012-01-01

    Cornelia de Lange Syndrome (CdLS, de Lange syndrome, Brachmann-de Lange syndrome), is a relatively rare genetic disorder, characterized by set of clinical abnormalities concerning different organs and systems. Phenotypic diagnosis is based on a specific dysmorphic features seen after the birth. We described a genetic basis, hereditary patterns, characteristic dysmorphic features and the most common clinical findings of patients Cornelia de Lange Syndrome concerning eye and vision, hearing, cardiovascular, respiratory, gastrointestinal, genitourinary, skeletal and psychomotor development.

  6. Steady Modeling for an Ammonia Synthesis Reactor Based on a Novel CDEAS-LS-SVM Model

    Directory of Open Access Journals (Sweden)

    Zhuoqian Liu

    2014-01-01

    Full Text Available A steady-state mathematical model is built in order to represent plant behavior under stationary operating conditions. A novel modeling using LS-SVR based on Cultural Differential Evolution with Ant Search is proposed. LS-SVM is adopted to establish the model of the net value of ammonia. The modeling method has fast convergence speed and good global adaptability for identification of the ammonia synthesis process. The LS-SVR model was established using the above-mentioned method. Simulation results verify the validity of the method.

  7. Clinical management of hereditary colorectal cancer syndromes.

    Science.gov (United States)

    Vasen, Hans F A; Tomlinson, Ian; Castells, Antoni

    2015-02-01

    Hereditary factors are involved in the development of a substantial proportion of all cases of colorectal cancer. Inherited forms of colorectal cancer are usually subdivided into polyposis syndromes characterized by the development of multiple colorectal polyps and nonpolyposis syndromes characterized by the development of few or no polyps. Timely identification of hereditary colorectal cancer syndromes is vital because patient participation in early detection programmes prevents premature death due to cancer. Polyposis syndromes are fairly easy to recognize, but some patients might have characteristics that overlap with other clinically defined syndromes. Comprehensive analysis of the genes known to be associated with polyposis syndromes helps to establish the final diagnosis in these patients. Recognizing Lynch syndrome is more difficult than other polyposis syndromes owing to the absence of pathognomonic features. Most investigators therefore recommend performing systematic molecular analysis of all newly diagnosed colorectal cancer using immunohistochemical methods. The implementation in clinical practice of new high-throughput methods for molecular analysis might further increase the identification of individuals at risk of hereditary colorectal cancer. This Review describes the clinical management of the various hereditary colorectal cancer syndromes and demonstrates the advantage of using a classification based on the underlying gene defects.

  8. Thrombocytopenia and Cornelia de Lange syndrome: Still an enigma?

    Science.gov (United States)

    Cavalleri, Valeria; Bettini, Laura R; Barboni, Chiara; Cereda, Anna; Mariani, Milena; Spinelli, Marco; Gervasini, Cristina; Russo, Silvia; Biondi, Andrea; Jankovic, Momcilo; Selicorni, Angelo

    2016-01-01

    Cornelia de Lange Syndrome (CdLS) is a rare genetic disorder caused by mutations in the cohesion complex and its regulators. The syndrome is characterized by multiple organ system abnormalities, pre- and post-natal growth retardation and typical facial features. Thrombocytopenia is a reduction in platelet count to <150 × 10(9)  L. It can be caused by congenital or acquired decreased production, increased destruction, or sequestration of platelets. In recent years, several papers reported thrombocytopenia and immune thrombocytopenia in patients affected by CdLS. In 2011, Lambert et al. estimated the risk of idiopathic thrombocytopenia purpura in CdLS patients to be 31-633 times greater than in the general population. We describe the incidence of thrombocytopenia in 127 Italian CdLS patients, identifying patients with transient or persistent thrombocytopenia, but a lower incidence of true idiopathic thrombocytopenic purpura (ITP). © 2015 Wiley Periodicals, Inc.

  9. 米根霉RhizopusoryzaeLS-1对糠醛抑制物的耐受性%Tolerance of Rhizopus oryzae LS-1 on Furfural Inhibitor

    Institute of Scientific and Technical Information of China (English)

    李志忠; 张曼芳; 任海伟; 王永刚; 张轶

    2015-01-01

    通过考察不同糠醛浓度对米根霉 (Rhizopus oryzae LS-1) 发酵产乳酸过程中糖酸转化率和糖利用率的影响, 探索了解Rhizopus oryzae LS-1对木质纤维水解副产物糠醛抑制物的耐受性, 寻找Rhizopus oryzae LS-1对糠醛抑制物的耐受浓度. 结果表明: Rhizopus oryzae LS-1对糠醛的耐受浓度为12.5g/L, 在0~12.5g/L可提高糖酸转化率和糖利用率. 当糠醛浓度大于12.5g/L时, 菌株生长完全受到抑制. 研究结果对乳酸生产用木质纤维素水解液的脱毒处理工艺具有指导作用.%Through studying effects of glucose acid conversion rate and glucose utilization rate on different furfural concen-tration, tolerance of Rhizopus oryzae LS-1 on furfural inhibitor in lignocelluloses hydrolysates were explored, and tolerance con-centration was searched. Results showed that tolerance threshold for Rhizopus oryzae LS-1was 12.5g/L, when furfural was indi-vidually added. Yield of lactic acid increased when furfural concentration was lower than 12.5g/L. quantitative view to the lactic acid production under the inhibition of lignocellulose degradation products were gave, and it has some guiding significances for overcome the difficulties of the lignocellulosic hydrolysates fermentation.

  10. 大卫·林奇的生平和作品%David Lynch's Biography and Filmmography

    Institute of Scientific and Technical Information of China (English)

    游飞

    2003-01-01

    @@ 生平 大卫·林奇(David Lynch)是现代美国电影创作的伟大复兴者,一个受到广泛赞誉的编剧兼导演,他还是电视制片人、摄影家、动画专家、作曲家和电脑影像艺术家.运用惊人的平衡感和技巧游走于主流电影和先锋电影的边缘,林奇为电影银幕带来一种怪诞、黑暗和诡异不安的真实感,一种由极端的暴力、怪异的喜剧和奇妙的美丽为特征的噩梦世界.

  11. Temperature profiles from expendable bathythermograph (XBT) casts from the LYNCH in the North Atlantic Ocean in support of the Integrated Global Ocean Services System (IGOSS) project from 26 June 1973 to 14 July 1973 (NODC Accession 7301081)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — XBT data were collected from the LYNCH in support of the Integrated Global Ocean Services System (IGOSS) project. Data were collected US Navy; Naval Oceanographic...

  12. Family perspectives in lynch syndrome becoming a family at risk, patterns of communication and influence on relations

    DEFF Research Database (Denmark)

    Bartuma, Katarina; Nilbert, Mef; Carlsson, Christina

    2012-01-01

    A growing number of individuals are diagnosed with hereditary cancer. Though increased levels of anxiety and depression have been demonstrated around the time of genetic counselling, most individuals handle life at increased risk well. Data have, however, been collected on individual basis, which...... led us to focus on family perspectives of hereditary cancer....

  13. Interdisciplinary therapy in Cornelia de Lange syndrome - review of the literature.

    Science.gov (United States)

    Mikołajewska, Emilia

    2013-01-01

    Cornelia de Lange syndrome (CdLS, also called Brachmann-de Lange syndrome - BdLS) is a multisystem developmental disorder characterized by distinctive facial features, growth and mental retardation, microcephaly, and various malformations. According to their clinical status, patients with CdLS require individual interdisciplinary therapy. The therapy is difficult and mainly symptomatic. To optimize the therapy results, early diagnosis programs and appropriate developmental and therapeutic intervention are recommended. The interdisciplinary approach described in the article needs further clinical research and detailed guidelines.

  14. Speech and regulation of behavior: the works of LS Vygosty and AR Luria

    National Research Council Canada - National Science Library

    Derouesné, Christian

    2011-01-01

    The role of speech in the regulation of behavior was described in child psychology by LS Vygotsky and AR Luria in the Soviet Union during the twenties, and extended to neuropsychology by Luria after the World War II...

  15. 76 FR 253 - Airworthiness Directives; ROLLADEN-SCHNEIDER Flugzeugbau GmbH Model LS6 Gliders

    Science.gov (United States)

    2011-01-04

    ... rescinds AD 86-25-07. Applicability (c) This AD rescission applies to Model LS6 gliders, all serial numbers... Association (ATA) of America Code 27, Flight Controls. ] Issued in Kansas City, Missouri, on December 21, 2010...

  16. Diagnosis of Elevator Faults with LS-SVM Based on Optimization by K-CV

    Directory of Open Access Journals (Sweden)

    Zhou Wan

    2015-01-01

    Full Text Available Several common elevator malfunctions were diagnosed with a least square support vector machine (LS-SVM. After acquiring vibration signals of various elevator functions, their energy characteristics and time domain indicators were extracted by theoretically analyzing the optimal wavelet packet, in order to construct a feature vector of malfunctions for identifying causes of the malfunctions as input of LS-SVM. Meanwhile, parameters about LS-SVM were optimized by K-fold cross validation (K-CV. After diagnosing deviated elevator guide rail, deviated shape of guide shoe, abnormal running of tractor, erroneous rope groove of traction sheave, deviated guide wheel, and tension of wire rope, the results suggested that the LS-SVM based on K-CV optimization was one of effective methods for diagnosing elevator malfunctions.

  17. IMPARARE L’ITALIANO L2/LS CON TESTI TEATRALI

    Directory of Open Access Journals (Sweden)

    Erminia Ardissino

    2010-09-01

    Full Text Available Il saggio tratta dell'impiego di testi teatrali come fonti di esercizi per l'apprendimento dell'italiano L2/LS. Dopo alcune riflessioni teoriche, si presentano sei proposte di lavoro, con relative soluzioni, adatte a studenti del livello B2-C2 del quadro di riferimento. Si tratta di esercizi ricavati da drammi in un unico atto di Pirandello (La morsa e Lumìe di Sicilia, da Verga (un confronto fra Cavalleria rusticana nella forma drammatica e novellistica, e da Tommaso Landolfi (Ombre. Ogni proposta sfrutta una peculiarità del testo teatrale che si costituisce nell'incontro di dialoghi con didascalie. Anzitutto si tratta di comprendere come si costruiscono i personaggi, quindi di vedere la funzione delle didascalie in relazione al testo, infine di riflettere sulle diverse modalità in cui avvengono i dialoghi, includendo le forme di silenzio. Il testo teatrale appare così molto adatto ad esercizi di lingua, perché mette in gioco le capacità interpretative e immaginative degli studenti, li fa discutere e parlare sulla base delle loro intuizioni.   This paper investigates the use of play scripts as inspiration for Italian L2/FL exercises. After a brief discussion on theory, six project proposals and their solutions, suitable for B2-C2 level students, are presented.  These exercises are based on one-act plays by Pirandello (La Morsa and Lumìe di Sicilia, Verga (a comparison between Cavalleria Rusticana in drama and narrative forms and Tommaso Landolfi (Ombre.  Each project focuses on a specific aspect of the script  and is made up of dialogues with captions. After the way the characters are constructed is investigated, then the function of the captions in relation to the texts is considered, and finally students reflect on the different ways the dialogues are presented, including the pauses. Play scripts lend themselves to language exercises, because they encourage students to use their interpretation skills and imaginations to talk about

  18. 基于LS-SVM的电子电路故障预测措施

    Institute of Scientific and Technical Information of China (English)

    许瑾

    2015-01-01

    对电力电子电路进行故障预测,选择基于LS-SVM的电子电路故障预测技术,可以降低故障预测误差,有效实现对于电子电路故障的预测。以下主要探究基于LS-SVM的电子电路故障预测措施。

  19. Nonlinear Time Series Prediction Using LS-SVM with Chaotic Mutation Evolutionary Programming for Parameter Optimization

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Nonlinear time series prediction is studied by using an improved least squares support vector machine (LSSVM) regression based on chaotic mutation evolutionary programming (CMEP) approach for parameter optimization.We analyze how the prediction error varies with different parameters (σ, γ) in LS-SVM. In order to select appropriate parameters for the prediction model, we employ CMEP algorithm. Finally, Nasdaq stock data are predicted by using this LS-SVM regression based on CMEP, and satisfactory results are obtained.

  20. Comparison of central corneal thickness measured by Lenstar LS900, OrbscanⅡ and ultrasonic pachmetry

    Directory of Open Access Journals (Sweden)

    Hong-Tao Zhang

    2013-09-01

    Full Text Available AIM: To investigate the difference of central corneal thickness(CCTmeasured by Lenstar LS900, OrbscahⅡ system and ultrasonic pachmetry, and to evaluate the correlation and consistency of the results for providing a theoretical basis for clinical application.METHODS: The mean value of CCT in 70 eyes of 35 patients measured three times by Lenstar LS900, OrbscahⅡ system and ultrasonic pachmetry underwent statistical analysis. The difference of CCT was compared, and the correlation and consistency of three measurements were analyzed to provide theoretical basis for clinical application. CCT values measured by different methods were analyzed with randomized block variance analysis. LSD-t test was used for pairwise comparison between groups. The correlation of three measurement methods were analyzed by linear correlation analysis, and Bland-Altman was used to analyze the consistency.RESULTS: The mean CCT values measured by Lenstar LS900, OrbscanⅡ and ultrasonic pachmetry were 542.75±40.06, 528.74±39.59, 538.54±40.93μm, respectively. The mean difference of CCT measurement was 4.21±8.78μm between Lenstar LS900 and ultrasonic pachmetry, 14.01±13.39μm between Lenstar LS900 and Orbscan Ⅱ, 9.8±10.57μm between ultrasonic pachmetry and Orbscan Ⅱ. The difference was statistically significant(PP>0.05: There was positive correlation between CCT with Lenstar LS900 and ultrasonic pachmetry(r=0.977, 0.944; PCONCLUSION: There are excellent correlation among Lenstar LS900, Orbscan Ⅱ and ultrasonic pachmetry. Lenstar LS900 can be used as CCT non-contact measurement tool.

  1. Genetics Home Reference: Peutz-Jeghers syndrome

    Science.gov (United States)

    ... Genetic and Rare Diseases Information Center Frequency The prevalence of this condition is uncertain; estimates range from ... A, Lynch HT, Lynch JF, Howe JR. Hereditary colorectal cancer-part II. Curr Probl Surg. 2005 May;42( ...

  2. Dynamic contact analysis of cam mechanism based on ANSYS/LS-DYNA%基于ANSYS/LS-DYNA凸轮机构的动态接触分析

    Institute of Scientific and Technical Information of China (English)

    董龙治; 王保民

    2013-01-01

    Accurate modeling of cam mechanism is built using PRO/E ,and it is introduced into ANSYS/LS-DYNA using the seamless connection between PRO/E and ANSYS . The stress , strain distribution of cam mechanism at every moment and the trajectory of push-rod can obtained using finite element dynamic analysis software ANSYS/LS-DYNA ,to verify whether the cam mechanism could meet the design requirements .%利用PRO/E对凸轮机构进行精确建模,采用PRO/E和ANSYS的无缝连接,将模型导入ANSYS/LS-DYNA中。利用有限元动力分析软件ANSYS/LS-DYNA 得到凸轮机构在每一时刻的应力、应变等分布情况和推杆的位移变化规律,从而验证凸轮机构是否满足设计要求。

  3. Long-Term Monitoring of the High-Energy Gamma-Ray Emission from LS I +61 deg 303 and LS 5039

    Science.gov (United States)

    Hadasch, D.; Torres, D. F.; Tanaka, T.; Corbet, R. H. D.; Hill, A. B.; Dubois, R.; Dubus, G.; Glanzman, T.; Corbel, S.; Li, J.; Chen, Y. P.; Zhang, S.; Caliandro, G. A.; Kerr, M.; Richards, J. L.; Max-Moerbeck, W.; Readhead, A.; Pooley, G.

    2012-01-01

    The Fermi Large Area Telescope (LAT) reported the first definitive gigaelectron volts detections of the binaries LS I +61 deg 303 and LS 5039 in the first year after its launch in 2008 June. These detections were unambiguous as a consequence of the reduced positional uncertainty and the detection of modulated gamma-ray emission on the corresponding orbital periods. An analysis of new data from the LAT, comprising 30 months of observations, identifies a change in the gamma-ray behavior of LS I +61 deg 303. An increase in flux is detected in 2009 March and a steady decline in the orbital flux modulation is observed. Significant emission up to 30 gigaelectron volts is detected by the LAT; prior data sets led to upper limits only. Contemporaneous terraelectron volt observations no longer detected the source, or found it-in one orbit-close to periastron, far from the phases at which the source previously appeared at terraelectron volt energies. The detailed numerical simulations and models that exist within the literature do not predict or explain many of these features now observed at gigaelectron volt and terraelectron volt energies. New ideas and models are needed to fully explain and understand this behavior. A detailed phase-resolved analysis of the spectral characterization of LS I +61 deg 303 in the gigaelectron volt regime ascribes a power law with an exponential cutoff spectrum along each analyzed portion of the system's orbit. The on-source exposure of LS 5039 is also substantially increased with respect to our prior publication. In this case, whereas the general gamma-ray properties remain consistent, the increased statistics of the current data set allows for a deeper investigation of its orbital and spectral evolution.

  4. Loss-of-function mutations of SURF-1 are specifically associated with Leigh syndrome with cytochrome c oxidase deficiency.

    Science.gov (United States)

    Tiranti, V; Jaksch, M; Hofmann, S; Galimberti, C; Hoertnagel, K; Lulli, L; Freisinger, P; Bindoff, L; Gerbitz, K D; Comi, G P; Uziel, G; Zeviani, M; Meitinger, T

    1999-08-01

    Mutations of SURF-1, a gene located on chromosome 9q34, have recently been identified in patients affected by Leigh syndrome (LS), associated with deficiency of cytochrome c oxidase (COX), the terminal component of the mitochondrial respiratory chain. To investigate to what extent SURF-1 is responsible for human disorders because of COX deficiency, we undertook sequence analysis of the SURF-1 gene in 46 unrelated patients. We analyzed 24 COX-defective patients classified as having typical Leigh syndrome (LS(COX)), 6 patients classified as Leigh-like (LL(COX)) cases, and 16 patients classified as non-LS(COX) cases. Frameshift, stop, and splice mutations of SURF-1 were detected in 18 of 24 (75%) of the LS(COX) cases. No mutations were found in the LL(COX) and non-LS(COX) group of patients. Rescue of the COX phenotype was observed in transfected cells from patients harboring SURF-1 mutations, but not in transfected cell lines from 2 patients in whom no mutations were detected by sequence analysis. Loss of function of SURF-1 protein is specifically associated with LS(COX), although a proportion of LS(COX) cases must be the result of abnormalities in genes other than SURF-1. SURF-1 is the first nuclear gene to be consistently mutated in a major category of respiratory chain defects. DNA analysis can now be used to accurately diagnose LS(COX), a common subtype of Leigh syndrome.

  5. The Uterine Sandwich Method for Placenta Previa Accreta in Mullerian Anomaly: Combining the B-Lynch Compression Suture and an Intrauterine Gauze Tampon

    Directory of Open Access Journals (Sweden)

    Mustafa Kaplanoğlu

    2013-01-01

    Full Text Available Mullerian duct anomalies may cause obstetric complications, such as postpartum hemorrhage (PPH and placental adhesion anomalies. Uterine compression suture may be useful for controlling PPH (especially atony. In recent studies, uterine compression sutures have been used in placenta accreta. We report a case of PPH, a placenta accreta accompanying a large septae, treated with B-Lynch suture and intrauterine gauze tampon.

  6. Ambiguity and the Ethics of Reading Race and Lynching in James W. Johnson’s The Autobiography of an Ex-Colored Man (1912

    Directory of Open Access Journals (Sweden)

    Dexl, Carmen

    2009-01-01

    Full Text Available James Weldon Johnson’s novel The Autobiography of an Ex-Colored Man (1912 discusses the causes, conditions, and implications of passing in a segregated society. The essay argues that the novel’s aesthetics of ambiguity conveys and reflects an ambivalence towards the concept of race. Using theories of Geoffrey Galt Harpham and John Guillory, it elaborates an ethics of reading race and lynching in The Autobiography of an Ex-Colored Man.

  7. Effect of low B-Lynch suture on menstrual cycle recovery and sex hormone levels in patients after cesarean section for placenta previa

    Institute of Scientific and Technical Information of China (English)

    Su-Lan Zhang; Wan-Cheng Feng; Yan Mi

    2016-01-01

    Objective:To explore the effect of low B-Lynch suture on the menstrual cycle recovery and sex hormone levels in patients after cesarean section for placenta previa.Methods:A total of 40 patients who were admitted in our hospital from August, 2013 to August, 2015 for cesarean section due to placenta previa were included in the study and randomized into the observation group and the control group. The patients in the observation group were given low B-lynch suture, while in the control group, yarns were plugged in the uterus. The bleeding during operation and 24 h after operation, the postpartum lochia duration, and menstrual cycle recovery in the two groups were observed. The postpartum FSH, E2, and LH levels in the two groups were determined.Results:The amount of bleeding during operation and 24 h after operation in the observation group was significantly less than that in the control group (P0.05). The comparison of FSH, E2, and LH levels between the two groups was not statistically significant (P>0.05).Conclusions:Low B-Lynch suture can effectively reduce the amount of bleeding after cesarean section for placenta previa, and has no effect on the menstrual recovery and ovarian function with a simple operation and less postoperative complications; therefore, it deserves to be widely recommended in the clinic.

  8. LINCHAMENTO: O CRESCIMENTO DA (INJUSTIÇA COLETIVA DIANTE DA OMISSÃO DO ESTADO / LYNCHING: GROWTH OF PUBLIC (INJUSTICE FRONT THE FAILURE OF THE STATE

    Directory of Open Access Journals (Sweden)

    Sarah Ludmilla do Nascimento Félix

    2015-12-01

    Full Text Available This article presents the relationship between the increase in the number of lynching in Brazil and the omission of state to comply with its duty to punish and reintegrate of offenders into community. It is explained the origins and causes of the phenomenon and its use as a form of exhibitionism punishment. Additionally, it is showed how the state inaction in combating crime allows the occurrence of private punishment and encourages its practice. It is exposed the relationship between this lethargy and the growth in crime rates which creates a cycle of violence. It is used literature review as a research methodology and it is analyzed fundamental rights and constitutional guarantees and the intolerable disrespect in relation to the case of lynched people. It is indicated that these offenses are the main reason to start an effective combat against the practice of lynching. It is justified why government needs to work together with civil society in pursuing an effective security policies and investments to combat factors that cause violence in Brazil and the mechanisms to avoid these criminal offenses.

  9. Executive functioning in Cornelia de Lange syndrome: domain asynchrony and age-related performance.

    Science.gov (United States)

    Reid, Donna; Moss, Jo; Nelson, Lisa; Groves, Laura; Oliver, Chris

    2017-01-01

    The aim of this study was to examine executive functioning in adolescents and adults with Cornelia de Lange syndrome (CdLS) to identify a syndrome and age-related profile of cognitive impairment. Participants were 24 individuals with CdLS aged 13-42 years (M = 22; SD = 8.98), and a comparable contrast group of 21 individuals with Down syndrome (DS) aged 15-33 years (M = 24; SD = 5.82). Measures were selected to test verbal and visual fluency, inhibition, perseverance/flexibility, and working memory and comprised both questionnaire and performance tests. Individuals with CdLS showed significantly greater impairment on tasks requiring flexibility and inhibition (rule switch) and on forwards span capacity. These impairments were also reported in the parent/carer-rated questionnaire measures. Backwards Digit Span was significantly negatively correlated with chronological age in CdLS, indicating increased deficits with age. This was not identified in individuals with DS. The relative deficits in executive functioning task performance are important in understanding the behavioural phenotype of CdLS. Prospective longitudinal follow-up is required to examine further the changes in executive functioning with age and if these map onto observed changes in behaviour in CdLS. Links with recent research indicating heightened responses to oxidative stress in CdLS may also be important.

  10. Geochemical and geophysical examination of submarine groundwater discharge and associated nutrient loading estimates into Lynch Cove, Hood Canal, WA

    Science.gov (United States)

    Swarzenski, P.W.; Simonds, F.W.; Paulson, A.J.; Kruse, S.; Reich, C.

    2007-01-01

    Geochemical tracer data (i.e., 222Rn and four naturally occurring Ra isotopes), electromagnetic (EM) seepage meter results, and high-resolution, stationary electrical resistivity images were used to examine the bi-directional (i.e., submarine groundwater discharge and recharge) exchange of a coastal aquifer with seawater. Our study site for these experiments was Lynch Cove, the terminus of Hood Canal, WA, where fjord-like conditions dramatically limit water column circulation that can lead to recurring summer-time hypoxic events. In such a system a precise nutrient budget may be particularly sensitive to groundwater-derived nutrient loading. Shore-perpendicular time-series subsurface resistivity profiles show clear, decimeter-scale tidal modulation of the coastal aquifer in response to large, regional hydraulic gradients, hydrologically transmissive glacial terrain, and large (4-5 m) tidal amplitudes. A 5-day 222Rn time-series shows a strong inverse covariance between 222Rn activities (0.5−29 dpm L-1) and water level fluctuations, and provides compelling evidence for tidally modulated exchange of groundwater across the sediment/water interface. Mean Rn-derived submarine groundwater discharge (SGD) rates of 85 ± 84 cm d-1 agree closely in the timing and magnitude with EM seepage meter results that showed discharge during low tide and recharge during high tide events. To evaluate the importance of fresh versus saline SGD, Rn-derived SGD rates (as a proxy of total SGD) were compared to excess 226Ra-derived SGD rates (as a proxy for the saline contribution of SGD). The calculated SGD rates, which include a significant (>80%) component of recycled seawater, are used to estimate associated nutrient (NH4+, Si, PO43-, NO3 + NO2, TDN) loads to Lynch Cove. The dissolved inorganic nitrogen (DIN = NH4 + NO2 + NO3) SGD loading estimate of 5.9 × 104 mol d-1 is 1−2 orders of magnitude larger than similar estimates derived from atmospheric deposition and surface water runoff

  11. Geochemical and geophysical examination of submarine groundwater discharge and associated nutrient loading estimates into Lynch Cove, Hood Canal, WA.

    Science.gov (United States)

    Swarzenski, Peter W; Simonds, F William; Paulson, Anthony J; Kruse, Sarah; Reich, Chris

    2007-10-15

    Geochemical tracer data (i.e., 222Rn and four naturally occurring Ra isotopes), electromagnetic (EM) seepage meter results, and high-resolution, stationary electrical resistivity images were used to examine the bi-directional (i.e., submarine groundwater discharge and recharge) exchange of a coastal aquifer with seawater. Our study site for these experiments was Lynch Cove, the terminus of Hood Canal, WA, where fjord-like conditions dramatically limit water column circulation that can lead to recurring summer-time hypoxic events. In such a system a precise nutrient budget may be particularly sensitive to groundwater-derived nutrient loading. Shore-perpendicular time-series subsurface resistivity profiles show clear, decimeter-scale tidal modulation of the coastal aquifer in response to large, regional hydraulic gradients, hydrologically transmissive glacial terrain, and large (4-5 m) tidal amplitudes. A 5-day 222Rn time-series shows a strong inverse covariance between 222Rn activities (0.5-29 dpm L(-1)) and water level fluctuations, and provides compelling evidence for tidally modulated exchange of groundwater across the sediment/water interface. Mean Rn-derived submarine groundwater discharge (SGD) rates of 85 +/- 84 cm d(-1) agree closely in the timing and magnitude with EM seepage meter results that showed discharge during low tide and recharge during high tide events. To evaluate the importance of fresh versus saline SGD, Rn-derived SGD rates (as a proxy of total SGD) were compared to excess 226Ra-derived SGD rates (as a proxy for the saline contribution of SGD). The calculated SGD rates, which include a significant (>80%) component of recycled seawater, are used to estimate associated nutrient (NH4+, Si, PO4(3-), NO3 + NO2, TDN) loads to Lynch Cove. The dissolved inorganic nitrogen (DIN = NH4 + NO2 + NO3) SGD loading estimate of 5.9 x 10(4) mol d(-1) is 1-2 orders of magnitude larger than similar estimates derived from atmospheric deposition and surface water

  12. Linchamientos y conflicto político en Los Andes Lynchings and Political conflict in The Andes

    Directory of Open Access Journals (Sweden)

    Carlos M. Vilas

    2007-06-01

    Full Text Available En 2004, los alcaldes de dos municipalidades de la región aimara de los Andes fueron linchados en la aparente culminación de agudos conflictos políticos internos y entre las respectivas comunidades y el Estado central. En este artículo se discuten ambos casos con el fin de ilustrar las transformaciones experimentadas en años recientes en la organización y la dinámica interna de las comunidades andinas, y de la articulación conflictiva de la política local en los procesos e instituciones de más amplio alcance. Precariedad social e incapacidad o renuencia del Estado para responder con eficacia a demandas básicas de determinados grupos de población configuran enmarcamientos socioeconómicos e institucionales de los linchamientos. En contraste con enfoques que enfatizan en factores culturales tradicionales o en un supuesto nacionalismo indígena, en el artículo se destaca la gravitación de fenómenos y procesos político- institucionales recientes en la transformación cultural y política de las comunidades, en el modo en que éstas procesan sus conflictos internos y con el Estado central.In 2004, two municipalitys mayors form the aimara Andes of Peru and Bolivia were subjected to mass lynchings as a result of the apparent culmination of violent political confrontations. This paper deals with these events as dramatic illustrations of the transformations the Andean communities experienced during recent decades in their internal dynamics, as well as in the articulation of local politics to processes and institutions beyond the communal limits. Structural precariousness combined with the state's inability or reluctance to come to terms with social or political demands from relevant segments of the people in the communities set the socioeconomic and institutional stage for lynchings. In contrast with approaches relating these events to an alleged indigenous cultural identity, the analysis points to the impact of the communities' political

  13. LS14: a novel human adipocyte cell line that produces prolactin.

    Science.gov (United States)

    Hugo, Eric R; Brandebourg, Terry D; Comstock, Clay E S; Gersin, Keith S; Sussman, Jeffrey J; Ben-Jonathan, Nira

    2006-01-01

    Adipose tissue is an integral component within the endocrine system. Adipocytes produce numerous bioactive substances, and their dysregulation has serious pathophysiological consequences. We previously reported that human adipose tissue from several depots produces significant amounts of prolactin (PRL). To study locally produced PRL, we sought an acceptable in vitro model. Consequently, we developed an adipocyte cell line derived from a metastatic liposarcoma. The cell line, designated LS14, has been in continuous culture for 2 yr. These cells exhibit many properties of primary preadipocytes, including the ability to undergo terminal differentiation, as judged by morphological alterations, lipid accumulation, and increase in glycerol-3-phosphate dehydrogenase. LS14 cells express many adipose-associated genes, such as adipocyte fatty acid-binding protein (aP(2)), hormone-sensitive lipase, lipoprotein lipase, preadipocyte factor 1, adiponectin, leptin, and IL-6. Similar to primary adipocytes, LS14 cells also produce and respond to PRL, thus making them an attractive model to study adipose PRL production and function. The expression of PRL was confirmed at the transcriptional level by RT-PCR, and PRL secretion was determined by the Nb2 bioassay. Addition of exogenous PRL to LS14 cells resulted in a dose-dependent inhibition of IL-6 release. In summary, we have established a novel human adipocyte cell line with many characteristics of primary adipocytes. The LS14 cells open up new avenues for research on human adipocyte biology and add to the repertoire of nonpituitary, PRL-producing cell lines.

  14. [Measurement of soil organic matter and available K based on SPA-LS-SVM].

    Science.gov (United States)

    Zhang, Hai-Liang; Liu, Xue-Mei; He, Yong

    2014-05-01

    Visible and short wave infrared spectroscopy (Vis/SW-NIRS) was investigated in the present study for measurement of soil organic matter (OM) and available potassium (K). Four types of pretreatments including smoothing, SNV, MSC and SG smoothing+first derivative were adopted to eliminate the system noises and external disturbances. Then partial least squares regression (PLSR) and least squares-support vector machine (LS-SVM) models were implemented for calibration models. The LS-SVM model was built by using characteristic wavelength based on successive projections algorithm (SPA). Simultaneously, the performance of LSSVM models was compared with PLSR models. The results indicated that LS-SVM models using characteristic wavelength as inputs based on SPA outperformed PLSR models. The optimal SPA-LS-SVM models were achieved, and the correlation coefficient (r), and RMSEP were 0. 860 2 and 2. 98 for OM and 0. 730 5 and 15. 78 for K, respectively. The results indicated that visible and short wave near infrared spectroscopy (Vis/SW-NIRS) (325 approximately 1 075 nm) combined with LS-SVM based on SPA could be utilized as a precision method for the determination of soil properties.

  15. IscR regulates RNase LS activity by repressing rnlA transcription.

    Science.gov (United States)

    Otsuka, Yuichi; Miki, Kumiko; Koga, Mitsunori; Katayama, Natsu; Morimoto, Wakako; Takahashi, Yasuhiro; Yonesaki, Tetsuro

    2010-07-01

    The Escherichia coli endoribonuclease LS was originally identified as a potential antagonist of bacteriophage T4. When the T4 dmd gene is defective, RNase LS cleaves T4 mRNAs and antagonizes T4 reproduction. This RNase also plays an important role in RNA metabolisms in E. coli. rnlA is an essential gene for RNase LS activity, but the transcriptional regulation of this gene remains to be elucidated. An Fe-S cluster protein, IscR, acts as a transcription factor and controls the expression of genes that are necessary for Fe-S cluster biogenesis. Here, we report that overexpression of IscR suppressed RNase LS activity, causing the loss of antagonist activity against phage T4. This suppressive effect did not require the ligation of Fe-S cluster into IscR. beta-Galactosidase reporter assays showed that transcription from an rnlA promoter increased in iscR-deleted cells compared to wild-type cells, and gel-mobility shift assays revealed specific binding of IscR to the rnlA promoter region. RT-PCR analysis demonstrated that endogenous rnlA mRNA was reduced by overexpression of IscR and increased by deletion of iscR. From these results, we conclude that IscR negatively regulates transcription of rnlA and represses RNase LS activity.

  16. A new expert system for diagnosis of lung cancer: GDA-LS_SVM.

    Science.gov (United States)

    Avci, Engin

    2012-06-01

    In nowadays, there are many various diseases, whose diagnosis is very hardly. Lung cancer is one of this type diseases. It begins in the lungs and spreads to other organs of human body. In this paper, an expert diagnostic system based on General Discriminant Analysis (GDA) and Least Square Support Vector Machine (LS-SVM) Classifier for diagnosis of lung cancer. This expert diagnosis system is called as GDA-LS-SVM in rest of this paper. The GDA-LS-SVM expert diagnosis system has two stages. These are 1. Feature extraction and feature reduction stage and 2. Classification stage. In feature extraction and feature reduction stage, lung cancer dataset is obtained and dimension of this lung cancer dataset, which has 57 features, is reduced to eight features using Generalized Discriminant Analysis (GDA) method. Then, in classification stage, these reduced features are given to Least Squares Support Vector Machine (LS-SVM) classifier. The lung cancer dataset used in this study was taken from the UCI machine learning database. The classification accuracy of this GDA-LS-SVM expert system was obtained about 96.875% from results of these experimental studies.

  17. Experimental and Analytical Studies on Improved Feedforward ML Estimation Based on LS-SVR

    Directory of Open Access Journals (Sweden)

    Xueqian Liu

    2013-01-01

    Full Text Available Maximum likelihood (ML algorithm is the most common and effective parameter estimation method. However, when dealing with small sample and low signal-to-noise ratio (SNR, threshold effects are resulted and estimation performance degrades greatly. It is proved that support vector machine (SVM is suitable for small sample. Consequently, we employ the linear relationship between least squares support vector regression (LS-SVR’s inputs and outputs and regard LS-SVR process as a time-varying linear filter to increase input SNR of received signals and decrease the threshold value of mean square error (MSE curve. Furthermore, it is verified that by taking single-tone sinusoidal frequency estimation, for example, and integrating data analysis and experimental validation, if LS-SVR’s parameters are set appropriately, not only can the LS-SVR process ensure the single-tone sinusoid and additive white Gaussian noise (AWGN channel characteristics of original signals well, but it can also improves the frequency estimation performance. During experimental simulations, LS-SVR process is applied to two common and representative single-tone sinusoidal ML frequency estimation algorithms, the DFT-based frequency-domain periodogram (FDP and phase-based Kay ones. And the threshold values of their MSE curves are decreased by 0.3 dB and 1.2 dB, respectively, which obviously exhibit the advantage of the proposed algorithm.

  18. Identification of a novel mutation in the human growth hormone receptor gene (GHR) in a patient with Laron syndrome.

    Science.gov (United States)

    Gennero, Isabelle; Edouard, Thomas; Rashad, Mona; Bieth, Eric; Conte-Aurio, Françoise; Marin, Françoise; Tauber, Maithé; Salles, Jean Pierre; El Kholy, Mohamed

    2007-07-01

    Deletions and mutations in the growth hormone receptor (GHR) gene are the underlying etiology of Laron syndrome (LS) or growth hormone (GH) insensitivity syndrome (GHIS), an autosomal recessive disease. Most patients are distributed in or originate from Mediterranean and Middle-Eastern countries. Sixty mutations have been described so far. We report a novel mutation in the GHR gene in a patient with LS. Genomic DNA sequencing of exon 5 revealed a TT insertion at nucleotide 422 after codon 122. The insertion resulted in a frameshift introducing a premature termination codon that led to a truncated receptor. We present clinical, biochemical and molecular evidence of LS as the result of this homozygous insertion.

  19. The Dynamics Simulation of the Deep Groove Ball Bearing Based on LS-DYNA%基于LS-DYNA深沟球轴承的动力学仿真

    Institute of Scientific and Technical Information of China (English)

    康晓晨; 乔长帅; 吴楠

    2013-01-01

    基于ANSYS/LS-DYNA建立了深沟球轴承的有限元模型,有效处理了考虑摩擦条件的接触问题,实现了深沟球轴承显式动力学的运动过程仿真。并以6203深沟球轴承为例,进行了动力学仿真与分析。%The finite element model of deep groove ball bearing was established based on ANSYS/LS-DYNA, effectively deal with the contact problem with friction condition,the explicit dynamic simulation of deep groove ball bearing was realized. Taking the 6203 deep groove ball bearing as an example,the dynamics simulation and analysis is carried out.

  20. Brachman de lange syndrome

    Directory of Open Access Journals (Sweden)

    Leena Verma

    2010-01-01

    Full Text Available Brachman de Lange syndrome or Cornelia de Lange syndrome (CdLS is a genetic disorder which can lead to severe developmental anomalies. It affects both the physical and intellectual development of a child. It is characterized by skeletal, craniofacial deformities, gastrointestinal and cardiac malformations. This syndrome is of rare occurrence and affects between 1/10,000 and 1/60,000 neonates. Diagnosis is based on the characteristic phenotype, in particular, a striking facial appearance, prenatal and postnatal growth retardation, various skeletal abnormalities, hypertrichosis, and developmental delay. Here, we present the case of a 13-year-old patient, with micrognathia, delayed eruption, multiple carious teeth, missing teeth and periodontal problems together, which had never been reported before. The father was also found to have the same missing teeth as the girl child.

  1. Engraving Simulation Based on ANSYS/LS-DYNA%基于ANSYS/LS-DYNA的弹带挤进过程仿真

    Institute of Scientific and Technical Information of China (English)

    马帅; 张相炎; 游修东

    2014-01-01

    The finite element model of one large-caliber artil ery’ s engraving process is established based on the ANSYS/LS-DY-NA software, and the engraving resistance with engraving displacement changes is particularly studied in the engraving process. By exporting some graphics at critical, the whole belt deformation pattern of the engraving process is revealed and by the curves of some analytic model elements, the personal view on the erosion of rifling is put forward. Based on D'Alembert principle, the curves of accelerate and velocity and matlab are used to get the engraving resistance curve. By comparison with theoretical curve, the correctness of the calculation result is verified and ANSYS / LS-DYNA is showed to be a good tool for the study of engraving process.%基于ANSYS/LS-DYNA瞬态动力学分析软件,建立了某火炮挤进过程的有限元模型,重点研究挤进过程中挤进阻力随挤进行程的变化。通过输出关键时刻的图形,展示了整个挤进过程中弹带的变形规律,然后通过分析模型中某些单元的应力曲线,对膛线起始部的磨损提出了看法。利用仿真获得的加速度曲线和速度曲线,基于达朗贝尔原理,利用matlab对数据进行处理,得到了挤进阻力曲线,并与理论所得阻力曲线进行了对比,表明ANSYS/LS-DYNA是研究挤进过程的一个很好的工具。

  2. Photofragmentation of CF{sub 3}Cl following photoabsorption in the Cl-ls threshold region

    Energy Technology Data Exchange (ETDEWEB)

    Lindle, D.W.; Manner, W.L.; Steinbeck, L. [and others

    1993-05-01

    Measurements of photofragmentation of CF{sub 3}Cl near the Cl-ls threshold (hv=2.8 keV) are reported. Because of the dominant decay mode of a Cl-ls hole state, Auger-electron emission, usually occurs sequentially in a vacancy cascade, high degrees of ionization of the parent molecule are induced. As a result, the observed photofragment-ion spectra of CF{sub 3}Cl contain primarily singly and multiply charged atomic fragments. Based on modelling of the spectral peak shapes, these fragments have a wide range of kinetic energies due to the dissociation process. Changes in peak shapes are observed following resonant excitation, as oppossed to ionization, of the Cl-ls electron, and may be due to either sequential fragmentation of CF{sub 3}Cl{sup n+} or to angular-distribution effects due to alignment of the initially excited resonant state.

  3. Water Quantity Prediction Using Least Squares Support Vector Machines (LS-SVM Method

    Directory of Open Access Journals (Sweden)

    Nian Zhang

    2014-08-01

    Full Text Available The impact of reliable estimation of stream flows at highly urbanized areas and the associated receiving waters is very important for water resources analysis and design. We used the least squares support vector machine (LS-SVM based algorithm to forecast the future streamflow discharge. A Gaussian Radial Basis Function (RBF kernel framework was built on the data set to optimize the tuning parameters and to obtain the moderated output. The training process of LS-SVM was designed to select both kernel parameters and regularization constants. The USGS real-time water data were used as time series input. 50% of the data were used for training, and 50% were used for testing. The experimental results showed that the LS-SVM algorithm is a reliable and efficient method for streamflow prediction, which has an important impact to the water resource management field.

  4. Weighted LS-SVM for function estimation applied to artifact removal in bio-signal processing.

    Science.gov (United States)

    Caicedo, Alexander; Van Huffel, Sabine

    2010-01-01

    Weighted LS-SVM is normally used for function estimation from highly corrupted data in order to decrease the impact of outliers. However, this method is limited in size and big time series should be segmented in smaller groups. Therefore, border discontinuities represent a problem in the final estimated function. Several methods such as committee networks or multilayer networks of LS-SVMs are used to address this problem, but these methods require extra training and hence the computational cost is increased. In this paper a technique that includes an extra weight vector in the formulation of the cost function for the LS-SVM problem is proposed as an alternative solution. The method is then applied to the removal of some artifacts in biomedical signals.

  5. Preventive use of Lactobacillus plantarum LS/07 and inulin to relieve symptoms of acute colitis.

    Science.gov (United States)

    Hijová, Emília; Šoltésová, Alena; Salaj, Rastislav; Kuzma, Jozef; Strojný, Ladislav; Bomba, Alojz; Gregová, Kristína

    2015-01-01

    The aim of presented study was to investigate the influence of Lactobacillus plantarum LS/07 and inulin on the activity of β-glucuronidase enzyme, and counts of coliform and lactobacilli in fresh caecal digesta, cytokine levels (IL-6, IL-8), and trancription nuclear factor kappa beta (NFκB) activities in colon tissue and blood samples of rats with dextran sulphate sodium (DSS) induced acute colitis. The rats were randomly divided into four groups - CG, AC, AC+PRE and AC+PRO. Colitis was induced using of 5% DSS in drinking water for 7d. DSS application increased activity of β-glucuronidase (P LS/07 decreased β-glucuronidase activity (P LS/07 and inulin suppressed expression observed markers, which play an important role in the inflammatory process, which predisposes their use in prevention or treatment of acute colitis.

  6. [Classification technique for hyperspectral image based on subspace of bands feature extraction and LS-SVM].

    Science.gov (United States)

    Gao, Heng-zhen; Wan, Jian-wei; Zhu, Zhen-zhen; Wang, Li-bao; Nian, Yong-jian

    2011-05-01

    The present paper proposes a novel hyperspectral image classification algorithm based on LS-SVM (least squares support vector machine). The LS-SVM uses the features extracted from subspace of bands (SOB). The maximum noise fraction (MNF) method is adopted as the feature extraction method. The spectral correlations of the hyperspectral image are used in order to divide the feature space into several SOBs. Then the MNF is used to extract characteristic features of the SOBs. The extracted features are combined into the feature vector for classification. So the strong bands correlation is avoided and the spectral redundancies are reduced. The LS-SVM classifier is adopted, which replaces inequality constraints in SVM by equality constraints. So the computation consumption is reduced and the learning performance is improved. The proposed method optimizes spectral information by feature extraction and reduces the spectral noise. The classifier performance is improved. Experimental results show the superiorities of the proposed algorithm.

  7. Structural and electrical properties of microwave processed Ag modified KNN-LS ceramics.

    Science.gov (United States)

    Palei, Prakash; Kumar, Pawan; Agrawal, Dinesh K

    2012-01-01

    Microwave processing steps of 0.95[(K0.5Na0.5)0.94Ag0.06NbO3]-0.05[LiSbO3]/(KNAN-LS) lead free ferroelectric ceramics were optimized for better densification and electrical properties. Calcination temperature and time for single perovskite phase formation were optimized and found to be 850 degrees C for 60 min., respectively. Crystal structural study revealed the presence of mixed structure in the microwave processed (MWP) KNAN-LS ceramics. The sintering of the KNAN-LS ceramics was carried out at 1080 degrees C for 10 min, 20 min and 30 min, respectively, and the sample sintered for 20 min exhibited best properties.

  8. 试用柯达LS 633数码相机

    Institute of Scientific and Technical Information of China (English)

    阿俊

    2003-01-01

    今年2月底,在美国拉斯维加斯的PMA(PHOTO MARKETlNG ASSOCIATI0N)展会上,柯达公司又推出一款民用级数码相机——LS 633。此前柯达曾经推出了两款LS系列数码相机,它们是:LS 420和LS 443。柯达的LS系列数码相机面向喜欢尝试新鲜事物的时尚人士,所以前面两款相机推出时,引起了许多年轻人的极大关注。

  9. One hybrid model combining singular spectrum analysis and LS + ARMA for polar motion prediction

    Science.gov (United States)

    Shen, Yi; Guo, Jinyun; Liu, Xin; Wei, Xiaobei; Li, Wudong

    2017-01-01

    Accurate real-time polar motion parameters play an important role in satellite navigation and positioning and spacecraft tracking. To meet the needs for real-time and high-accuracy polar motion prediction, a hybrid model that integrated singular spectrum analysis (SSA), least-squares (LS) extrapolation and an autoregressive moving average (ARMA) model was proposed. SSA was applied to separate the trend, the annual and the Chandler components from a given polar motion time series. LS extrapolation models were constructed for the separated trend, annual and Chandler components. An ARMA model was established for a synthetic sequence that contained the remaining SSA component and the residual series of LS fitting. In applying this hybrid model, multiple sets of polar motion predictions with lead times of 360 days were made based on an IERS 08 C04 series. The results showed that the proposed method could effectively predict the polar motion parameters.

  10. 可编程数字延迟定时器LS7213

    Institute of Scientific and Technical Information of China (English)

    卢玲军

    2003-01-01

    @@ LS721 3是一种可编程数字延迟定时器CMOS单片IC,该芯片在3~5.5V的.电压下工作,静态电流不超过150 μ A.LS721 3输出(OUT1)源电流I oH≥3mA,输出陷电流lOL≥15mA,可以驱动继电器等开关元件.LS7213有8个定时范围,定时时间从0.1s到10小时.

  11. Proteoglycan synthesis in normal and Lowe syndrome fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Harper, G.S.; Hascall, V.C.; Yanagishita, M.; Gahl, W.A.

    1987-04-25

    Lowe (oculocerebrorenal) syndrome (LS) is an X-linked disorder characterized by congenital cataracts, generalized hypotonia, mental retardation, and renal Fanconi syndrome. The basic defect remains unknown, but the possibility that fibroblasts express reduced sulfation of glycosaminoglycans has been studied in several laboratories. A mechanism involving overproduction of an enzyme (nucleotide pyrophosphatase) active against adenosine 3'-phosphate, 5'-phosphosulfate (PAPS) has been postulated. Decreased synthesis of normally sulfated glycosaminoglycans was also reported. We measured the synthesis of proteoglycans and glycosaminoglycans by incorporation of (/sup 3/H)glucosamine and Na/sub 2/(/sup 35/)SO/sub 4/ into cultured fibroblasts from four LS patients and related it directly to the synthesis in six normal fibroblast cultures. We found that the rate of synthesis varied greatly among the normal cultures (cv, 30%), but not significantly between LS and the normal. The LS fibroblasts' ability to sulfate glycosaminoglycans was assayed as the amount of /sup 3/H-glycosaminoglycan eluting at low ionic strength on anion exchange chromatography, the amount of non-sulfated disaccharide present in chondroitinase digests of labeled proteoglycans, and the ratio of /sup 35/S to 3H incorporation into proteoglycans. Each parameter suggested that the LS cells were synthesizing normally sulfated glycosaminoglycans (e.g. % delta Di-0S, 21 +/- 6 in normal; 27 +/- 6 in LS). The cells' ability to sulfate glycosaminoglycans was tested under conditions of markedly stimulated glycosaminoglycan synthesis, by treating the cultures with a beta-D-xyloside.

  12. Molecular cloning and characterization of high mobility group box1 (Ls-HMGB1) from humphead snapper, Lutjanus sanguineus.

    Science.gov (United States)

    Cai, Jia; Xia, Hongli; Huang, Yucong; Lu, Yishan; Wu, Zaohe; Jian, Jichang

    2014-10-01

    High mobility group box1 (HMGB1) is a kind of chromatin-associated nonhistone protein important for nucleosome formation, transcriptional regulation and inflammation. However, the reports about HMGB1 of marine fish were still limited. Here, we cloned and characterized a HMGB1 gene from humphead snapper, Lutjanus sanguineus (Ls-HMGB1). The Ls-HMGB1 cDNA composed of 1199 bp with a 70 bp of 5'-UTR, 630 bp open reading frame (ORF) and 499 bp 3'-UTR, encoded a polypeptide of 210 amino acids (GenBank Accession No: KJ783442). Sequence alignment of Ls-HMGB1 showed the highest similarity of 91% with Sciaenops ocellatus HMGB1 protein. Quantitative real-time PCR (qRT-PCR) analysis revealed that Ls-HMGB1 had relatively high expression level in skin, kidney and heart. After Vibrio harveyi and poly I:C stimulation, transcripts of Ls-HMGB1 were significantly increased and reached to peak at 18 h p.i. The L. sanguineus interleukin-6 (Ls-IL6) transcription in HK leukocytes was significantly induced by recombinant LsHMGB1 (rLsHMGB1). These results indicated that Ls-HMGB1 may play an important role in immune response of L. sanguineus during pathogen challenge.

  13. LS-SVM: uma nova ferramenta quimiométrica para regressão multivariada. Comparação de modelos de regressão LS-SVM e PLS na quantificação de adulterantes em leite em pó empregando NIR LS-SVM: a new chemometric tool for multivariate regression. Comparison of LS-SVM and pls regression for determination of common adulterants in powdered milk by nir spectroscopy

    Directory of Open Access Journals (Sweden)

    Marco F. Ferrão

    2007-08-01

    Full Text Available Least-squares support vector machines (LS-SVM were used as an alternative multivariate calibration method for the simultaneous quantification of some common adulterants found in powdered milk samples, using near-infrared spectroscopy. Excellent models were built using LS-SVM for determining R², RMSECV and RMSEP values. LS-SVMs show superior performance for quantifying starch, whey and sucrose in powdered milk samples in relation to PLSR. This study shows that it is possible to determine precisely the amount of one and two common adulterants simultaneously in powdered milk samples using LS-SVM and NIR spectra.

  14. Asymptotic Normality of LS Estimate in Simple Linear EV Regression Model

    Institute of Scientific and Technical Information of China (English)

    Jixue LIU

    2006-01-01

    Though EV model is theoretically more appropriate for applications in which measurement errors exist, people are still more inclined to use the ordinary regression models and the traditional LS method owing to the difficulties of statistical inference and computation. So it is meaningful to study the performance of LS estimate in EV model.In this article we obtain general conditions guaranteeing the asymptotic normality of the estimates of regression coefficients in the linear EV model. It is noticeable that the result is in some way different from the corresponding result in the ordinary regression model.

  15. On the Molecular Etiology of Cornelia de Lange Syndrome

    Science.gov (United States)

    Dorsett, Dale; Krantz, Ian D.

    2009-01-01

    Cornelia de Lange syndrome (CdLS) is genetically heterogeneous and is usually sporadic, occurring approximately once per ten thousand births. CdLS individuals display diverse and variable deficits in growth, mental development, limbs and organs. In the past few years it has been shown that CdLS is caused by gene mutations affecting proteins involved in sister chromatid cohesion. Studies in model organisms, and more recently in human cells have revealed, somewhat unexpectedly, that the developmental deficits in CdLS likely arise from changes in gene expression. The mechanisms by which cohesion factors regulate gene expression remain to be elucidated, but current data suggest that they likely regulate transcription in multiple ways. PMID:19154515

  16. Cornelia de Lange syndrome.

    Science.gov (United States)

    Boyle, M I; Jespersgaard, C; Brøndum-Nielsen, K; Bisgaard, A-M; Tümer, Z

    2015-07-01

    Cornelia de Lange syndrome (CdLS; MIM #122470, 300590, 610759, 614701, 300882) is a rare and clinically variable disorder that affects multiple organs. It is characterized by intellectual disability (mild to severe), distinctive facial features, prenatal and postnatal growth retardation, and hirsutism. Congenital anomalies include malformations of the upper limbs, gastrointestinal malformation/rotation, pyloric stenosis, diaphragmatic hernia, heart defects and genitourinary malformations. Gastroesophageal reflux disease is present in almost all patients. In addition to classic forms, milder phenotypes have been reported. To date five genes [NIPBL (Nipped-B-like protein), SMC1A (structural maintenance of chromosomes 1A), SMC3 (structural maintenance of chromosomes 3), RAD21 (human homolog of Schizosaccharomyces pombe radiation sensitive mutant 21) and HDAC8 (histone deacetylase 8)] have been associated with CdLS and mutations of these genes comprise the underlying defect in 70% of the patients. Here, we will provide a brief review of the clinical features of CdLS, summarize the known underlying genetic defects, prenatal and postnatal diagnosis possibilities, and genetic counseling. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Lemierre’s syndrome: current perspectives on diagnosis and management

    Directory of Open Access Journals (Sweden)

    Johannesen KM

    2016-09-01

    Full Text Available Katrine M Johannesen,1 Uffe Bodtger1–3 1Department of Lung Medicine, Naestved Hospital, Naestved, 2Institute for Regional Health Research, University of Southern Denmark, Odense, 3Department of Pulmonology, Zealand University Hospital, Roskilde, Denmark Abstract: This is a systematic review of cases with Lemierre’s syndrome (LS in the past 5 years. LS is characterized by sepsis often evolving after a sore throat or tonsillitis and then complicated by various septic emboli and thrombosis of the internal jugular vein. Symptoms include sepsis, pain, and/or swelling in the throat or neck, as well as respiratory symptoms. Laboratory findings show elevated infectious parameters and radiological findings show thrombosis of the internal jugular vein and emboli in the lungs or other organs. The syndrome is often associated with an infection with Fusobacterium necrophorum. We found a total of 137 cases of LS, of which 47 were infected with F. necrophorum and others with Staphylococcus and Streptococcus. Complications of this rare but severe disease included osteomyelitis, meningitis, and acute respiratory distress syndrome. Mortality was extremely high in the pre-antibiotic era but has diminished with the advent of antibiotics. This review showed a mortality rate of only 2% of which none of the cases involved fusobacteria. Duration of treatment varied; a 4–6-week course of carbapenem or piperacillin/tazobactam in combination with metronidazole was optimum. Other treatment options included anticoagulants in 46% of cases, which is unwarrantedly high, as to date, no evidence of the positive effects of anticoagulants in LS exists. Only two cases had ligation of the internal jugular vein performed. This review confirms the rare, but severe aspects of LS. Mortality from LS in this day and age appears to be low, however the syndrome is difficult to recognize, and still requires the full attention of the clinician. Keywords: Lemierre’s syndrome

  18. Regional-scale calculation of the LS factor using parallel processing

    Science.gov (United States)

    Liu, Kai; Tang, Guoan; Jiang, Ling; Zhu, A.-Xing; Yang, Jianyi; Song, Xiaodong

    2015-05-01

    With the increase of data resolution and the increasing application of USLE over large areas, the existing serial implementation of algorithms for computing the LS factor is becoming a bottleneck. In this paper, a parallel processing model based on message passing interface (MPI) is presented for the calculation of the LS factor, so that massive datasets at a regional scale can be processed efficiently. The parallel model contains algorithms for calculating flow direction, flow accumulation, drainage network, slope, slope length and the LS factor. According to the existence of data dependence, the algorithms are divided into local algorithms and global algorithms. Parallel strategy are designed according to the algorithm characters including the decomposition method for maintaining the integrity of the results, optimized workflow for reducing the time taken for exporting the unnecessary intermediate data and a buffer-communication-computation strategy for improving the communication efficiency. Experiments on a multi-node system show that the proposed parallel model allows efficient calculation of the LS factor at a regional scale with a massive dataset.

  19. Pressure Model of Control Valve Based on LS-SVM with the Fruit Fly Algorithm

    Directory of Open Access Journals (Sweden)

    Huang Aiqin

    2014-07-01

    Full Text Available Control valve is a kind of essential terminal control component which is hard to model by traditional methodologies because of its complexity and nonlinearity. This paper proposes a new modeling method for the upstream pressure of control valve using the least squares support vector machine (LS-SVM, which has been successfully used to identify nonlinear system. In order to improve the modeling performance, the fruit fly optimization algorithm (FOA is used to optimize two critical parameters of LS-SVM. As an example, a set of actual production data from a controlling system of chlorine in a salt chemistry industry is applied. The validity of LS-SVM modeling method using FOA is verified by comparing the predicted results with the actual data with a value of MSE 2.474 × 10−3. Moreover, it is demonstrated that the initial position of FOA does not affect its optimal ability. By comparison, simulation experiments based on PSO algorithm and the grid search method are also carried out. The results show that LS-SVM based on FOA has equal performance in prediction accuracy. However, from the respect of calculation time, FOA has a significant advantage and is more suitable for the online prediction.

  20. A lossless compression method for medical image sequences using JPEG-LS and interframe coding.

    Science.gov (United States)

    Miaou, Shaou-Gang; Ke, Fu-Sheng; Chen, Shu-Ching

    2009-09-01

    Hospitals and medical centers produce an enormous amount of digital medical images every day, especially in the form of image sequences, which requires considerable storage space. One solution could be the application of lossless compression. Among available methods, JPEG-LS has excellent coding performance. However, it only compresses a single picture with intracoding and does not utilize the interframe correlation among pictures. Therefore, this paper proposes a method that combines the JPEG-LS and an interframe coding with motion vectors to enhance the compression performance of using JPEG-LS alone. Since the interframe correlation between two adjacent images in a medical image sequence is usually not as high as that in a general video image sequence, the interframe coding is activated only when the interframe correlation is high enough. With six capsule endoscope image sequences under test, the proposed method achieves average compression gains of 13.3% and 26.3% over the methods of using JPEG-LS and JPEG2000 alone, respectively. Similarly, for an MRI image sequence, coding gains of 77.5% and 86.5% are correspondingly obtained.

  1. Low rank updated LS-SVM classifiers for fast variable selection.

    Science.gov (United States)

    Ojeda, Fabian; Suykens, Johan A K; De Moor, Bart

    2008-01-01

    Least squares support vector machine (LS-SVM) classifiers are a class of kernel methods whose solution follows from a set of linear equations. In this work we present low rank modifications to the LS-SVM classifiers that are useful for fast and efficient variable selection. The inclusion or removal of a candidate variable can be represented as a low rank modification to the kernel matrix (linear kernel) of the LS-SVM classifier. In this way, the LS-SVM solution can be updated rather than being recomputed, which improves the efficiency of the overall variable selection process. Relevant variables are selected according to a closed form of the leave-one-out (LOO) error estimator, which is obtained as a by-product of the low rank modifications. The proposed approach is applied to several benchmark data sets as well as two microarray data sets. When compared to other related algorithms used for variable selection, simulations applying our approach clearly show a lower computational complexity together with good stability on the generalization error.

  2. Atomic electronic states: the L-S and j-j coupling schemes and their correlation

    CERN Document Server

    Li, Wai-Kee

    2014-01-01

    In the first part of this paper, we review the assumption of the L-S coupling scheme, with which we derive the electronic states arising from a given atomic configuration. Then, with the aid of the spectral data of Group 15 elements, it becomes clear that the assumption of the L-S coupling scheme is no longer valid as we go farther and farther down the Periodic Table. In the second part, we introduce the j-j coupling scheme, which is seldom covered in standard inorganic chemistry texts, and contrast the assumptions of the two schemes. Next, we use two worked examples to demonstrate the derivation of electronic states with the j-j coupling scheme. Finally, the correlation between the states derived by L-S and j-j schemes is pictorially shown. It is believed a student, by also studying j-j coupling schemes (by no means a difficult task) along with the L-S scheme, will gain a better understanding of the concept of atomic electronic states.

  3. Effect of L.S. Vygotsky's Ideas on the Development of Russian Didactics (Primary School)

    Science.gov (United States)

    Vinogradova, N. F.

    2016-01-01

    This article characterizes the changes that occurred and are occurring in the didactics of primary school as an effect of L.S. Vygotsky's psychological ideas. It underscores the characteristic features of the step-by-step convergence of psychology and pedagogy and discloses the reasons psychological knowledge is not used sufficiently to organize…

  4. Candidate counterparts to the soft gamma-ray flare in the direction of LS I +61303

    CERN Document Server

    Munoz-Arjonilla, A J; Combi, J A; Luque-Escamilla, P; Sanchez-Sutil, J R; Zabalza, V; Paredes, J M

    2009-01-01

    Context. A short duration burst reminiscent of a soft gamma-ray repeater/anomalous X-ray pulsar behaviour was detected in the direction of LS I +61 303 by the Swift satellite. While the association with this well known gamma-ray binary is likely, a different origin cannot be excluded. Aims. We explore the error box of this unexpected flaring event and establish the radio, near-infrared and X-ray sources in our search for any peculiar alternative counterpart. Methods. We carried out a combined analysis of archive Very Large Array radio data of LS I +61 303 sensitive to both compact and extended emission. We also reanalysed previous near infrared observations with the 3.5 m telescope of the Centro Astronomico Hispano Aleman and X-ray observations with the Chandra satellite. Results. Our deep radio maps of the LS I +61 303 environment represent a significant advancement on previous work and 16 compact radio sources in the LS I +61 303 vicinity are detected. For some detections, we also identify near infrared and...

  5. Sleep disorders in Cornelia de Lange syndrome.

    Science.gov (United States)

    Zambrelli, Elena; Fossati, Chiara; Turner, Katherine; Taiana, Matteo; Vignoli, Aglaia; Gervasini, Cristina; Russo, Silvia; Furia, Francesca; Masciadri, Maura; Ajmone, Paola; Kullman, Gaia; Canevini, Maria Paola; Selicorni, Angelo

    2016-06-01

    Cornelia de Lange syndrome (CdLS) is a rare genetic disorder characterized by growth retardation, intellectual disability, limb defects, typical facial dysmorphism, and other systemic involvement. Sleep disturbances have been frequently reported in CdLS, but these have not been completely characterized, and prevalence data are conflicting. The aim of this paper is to characterize and determine the prevalence of sleep disorders in CdLS patients by means of a validated questionnaire. From November 2012 to November 2013, we asked 46 consecutive parents/caregivers of CdLS patients aged more than 3 years old to fill out the sleep disturbances scale for children (SDSC). The subjects were also characterized by the presence of epilepsy, intellectual disability (ID), behavioral problems, CdLS severity score, gastroesophageal reflux disease (GERD), and genetic test results. An abnormal total sleep score was found in 7 patients (15.2%), 26 (56.5%) showed a borderline total score, and 18 (39.1%) had an abnormal score for at least one SDSC factor. In our study sleep disorders were found to be positively associated to presence of epilepsy, GERD, ID, and behavioral disturbances. No correlation was evident with specific mutations of the different genes, BMI, and severity score. Our results confirm that sleep disorders represent a common problem in CdLS, with higher incidence than in the normal population. In these patients sleep disorders seem to be more prevalent in comorbid settings, representing a clinical indicator for different medical and neuropsychiatric disorders. Better knowledge and characterization of typology of sleep disorders in CdLS patients could permit a more specific therapeutic approach. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. A Case Report of Cornelia De Lange Syndrome in Northern Iran; A Clinical and Diagnostic Study.

    Science.gov (United States)

    Hosseininejad, Seyyed-Mohsen; Bazrafshan, Behnaz; Alaee, Ehsan

    2016-02-01

    As a rare multisystem congenital anomaly disorder, Cornelia de Lange syndrome (CdLS) is featured by delayed growth and development, distinct facial dimorphism, limb malformations and multiple organ defects. CdLS is a genetic syndrome affecting 1/10000-1/60000 neonates with unknown genetic basis. Delayed growth and development, hirsute, structural anomalies of the limbs and distinct facial dimorphism are considered as its main clinical characteristics. Introducing CdLS cases of different ethnic backgrounds could add distinctions to the phenotypic picture of the syndrome and be useful in diagnosis. Early diagnosis and decreased death rates are achievable through enhanced awareness on this syndrome. We present here a 45-day-old girl, as the first case of Cornelia in Golestan (Northern Iran), referred to our hospital with the symptoms as mentioned above.

  7. The Relationship between Locomotive Syndrome and Depression in Community-Dwelling Elderly People

    Directory of Open Access Journals (Sweden)

    Misa Nakamura

    2017-01-01

    Full Text Available Locomotive syndrome (LS is a concept that refers to the condition of people requiring healthcare services because of problems associated with locomotion. Depression is a major psychiatric disease among the elderly, in addition to dementia. The purpose of this study was to determine the association between LS and depression. The study participants were 224 healthy elderly volunteers living in a rural area in Japan. LS was defined as scores ≥ 16 on the 25-question Geriatric Locomotive Function Scale (GLFS-25. Depression was defined as scores ≥ 5 on the 15-item Geriatric Depression Scale (GDS-15. Height and body weight were measured. The prevalence of LS and depression was 13.9% and 24.2%, respectively. Compared with the non-LS group, the LS group was older, was shorter, had a higher BMI, and had higher GDS-15 scores. Logistic regression analysis showed that participants with GDS-15 scores ≥ 6 had higher odds for LS than those with GDS-15 scores < 6 (odds ratio [OR] = 4.22. Conversely, the depression group had higher GLFS-25 scores than the nondepression group. Participants with GLFS-25 scores ≥ 5 had higher odds for depression than those with GLFS-25 scores < 5 (OR = 4.53. These findings suggest that there is a close relationship between LS and depression.

  8. PD-1/PD-Ls pathways between CD4(+) T cells and pleural mesothelial cells in human tuberculous pleurisy.

    Science.gov (United States)

    Yin, Wen; Tong, Zhao-Hui; Cui, Ai; Zhang, Jian-Chu; Ye, Zhi-Jian; Yuan, Ming-Li; Zhou, Qiong; Shi, Huan-Zhong

    2014-03-01

    Programmed death 1 (PD-1), PD-ligand 1 (PD-L1), and PD-L2 have been demonstrated to be involved in tuberculosis immunity, however, the expression and regulation of PD-1/PD-Ls pathways in pleural mesothelial cells (PMCs) and CD4(+) T cells in tuberculous pleural effusion (TPE) have not been investigated. Expression of PD-1 on CD4(+) T cells and expressions of PD-L1 and PD-L2 on PMCs in TPE were determined. The impacts of PD-1/PD-Ls pathways on proliferation, apoptosis, adhesion, and migration of CD4(+) T cells were explored. Concentrations of soluble PD-l, but not of soluble PD-Ls, were much higher in TPE than in serum. Expressions of PD-1 on CD4(+) T cells in TPE were significantly higher than those in blood. Expressions of PD-Ls were much higher on PMCs from TPE when compared with those from transudative effusion. Interferon-γ not only upregulated the expression of PD-1 on CD4(+) T cells, but also upregulated the expressions of PD-Ls on PMCs. Blockage PD-1/PD-Ls pathways abolished the inhibitory effects on proliferation and adhesion activity of CD4(+) T cells induced by PMCs. PD-1/PD-Ls pathways on PMCs inhibited proliferation and adhesion activity of CD4(+) T cells, suggesting that Mycobacterium tuberculosis might exploit PD-1/PD-Ls pathways to evade host cell immune response in human.

  9. 利用端部效应改正的LS+AR模型进行日长变化预报%Prediction of LOD Change Based on the LS and AR Model with Edge Effect Corrected

    Institute of Scientific and Technical Information of China (English)

    刘建; 王琪洁; 张昊

    2013-01-01

    Aiming to resolve the edge effect in the process of predicting length of day (LOD) by the least squares and autoregressive (LS+AR) model,we employed a time series analysis model to extrapolate LOD series and produce a new series.Then,we used the new series to solve the coefficients for the LS model.At last,we used the LS+AR model to predict the LOD series again.By comparing the accuracy of LOD prediction by edge-effect corrected LS +AR and that by LS+AR,we conclude that edge-effect corrected LS+AR can improve the prediction accuracy,especially for medium-term and long-term predictions.%针对LS+AR模型在日长变化预报过程中存在的端部效应现象,采用时间序列分析方法对日长变化的序列进行外推,形成一个新的序列,用这个新序列求得LS模型的系数,然后再用LS+ AR模型对日长变化原始序列进行预报.实验结果表明,利用端部效应改正的LS+ AR模型与LS+ AR模型相比,在日长变化的预报精度上有一定的改善,尤其在跨度为中长期时改善更为明显.

  10. Exome-first approach identified a novel gloss deletion associated with Lowe syndrome.

    Science.gov (United States)

    Watanabe, Miki; Nakagawa, Ryuji; Kohmoto, Tomohiro; Naruto, Takuya; Suga, Ken-Ichi; Goji, Aya; Horikawa, Hideaki; Masuda, Kiyoshi; Kagami, Shoji; Imoto, Issei

    2016-01-01

    Lowe syndrome (LS) is an X-linked disorder affecting the eyes, nervous system and kidneys, typically caused by missense or nonsense/frameshift OCRL mutations. We report a 6-month-old male clinically suspected to have LS, but without the Fanconi-type renal dysfunction. Using a targeted-exome sequencing-first approach, LS was diagnosed by the identification of a deletion involving 1.7 Mb at Xq25-q26.1, encompassing the entire OCRL gene and neighboring loci.

  11. Discrimination of Rice Varieties using LS-SVM Classification Algorithms and Hyperspectral Data

    Directory of Open Access Journals (Sweden)

    Jin Xiaming

    2015-03-01

    Full Text Available Fast discrimination of rice varieties plays a key role in the rice processing industry and benefits the management of rice in the supermarket. In order to discriminate rice varieties in a fast and nondestructive way, hyperspectral technology and several classification algorithms were used in this study. The hyperspectral data of 250 rice samples of 5 varieties were obtained using FieldSpec®3 spectrometer. Multiplication Scatter Correction (MSC was used to preprocess the raw spectra. Principal Component Analysis (PCA was used to reduce the dimension of raw spectra. To investigate the influence of different linear and non-linear classification algorithms on the discrimination results, K-Nearest Neighbors (KNN, Support Vector Machine (SVM and Least Square Support Vector Machine (LS-SVM were used to develop the discrimination models respectively. Then the performances of these three multivariate classification methods were compared according to the discrimination accuracy. The number of Principal Components (PCs and K parameter of KNN, kernel function of SVM or LS-SVM, were optimized by cross-validation in corresponding models. One hundred and twenty five rice samples (25 of each variety were chosen as calibration set and the remaining 125 rice samples were prediction set. The experiment results showed that, the optimal PCs was 8 and the cross-validation accuracy of KNN (K = 2, SVM, LS-SVM were 94.4, 96.8 and 100%, respectively, while the prediction accuracy of KNN (K = 2, SVM, LS-SVM were 89.6, 93.6 and 100%, respectively. The results indicated that LS-SVM performed the best in the discrimination of rice varieties.

  12. Thermal Decomposition Characteristics of LS-Based Propellant%LS基推进剂的热解特性

    Institute of Scientific and Technical Information of China (English)

    胡松启; 陈静; 吴素丽; 邓哲

    2013-01-01

    用差示扫描(DSC)和热重分析(TG)研究了斯蒂芬酸铅(LS)/硝化棉(NC)/双铅2(SQ-2)推进剂热稳定性.用热力计算方法分析了四种推进剂(高氯酸铵(AP)/端羟基聚丁二烯(HTPB),AP/NC,LS/NC和LS/SQ-2)的能量特性.研究了配比为5∶5,6∶4,7∶3三种LS/NC推进剂和配比为4∶6,5∶5,6∶4,7∶3四种LS/SQ-2推进剂的热分解特性.结果表明:添加NC或SQ-2能降低LS的热稳定性,提高推进剂的能量,其中NC的效果更显著,认为LS和NC可选作微型发动机用推进剂的组分.%Thermal stabilities of lead styphnate(LS) / nitrocellulose(NC)/ dibasic lead stearate(SQ-2) were studied by Different Scanning Calorimetry(DSC) and Thermogravimetry (TG).The energetic properties of four propellants(ammonium perchlorate (AP) / hydroxy-terminated polybutadiene(HTPB),AP/NC,LS/ NC and LS /SQ-2) were analyzed with thermodynamic calculation method.Thermal decomposition characteristics of three LS/NC propellants with ratio of LS to NC as 5 ∶ 5,6 ∶ 4 and 7 ∶ 3 and four LS/SQ-2 propellants with ratio of LS to SQ-2 as 4 ∶ 6,5 ∶ 5,6 ∶ 4 and 7 ∶ 3 were researched.Results show that the thermostability of LS decreases by adding NC or SQ-2,and its energy enhances,in which the effect of NC is more obvious,considering that LS and NC can be chosen as the components of propellant used in micro solid rocket motor.

  13. Serum leptin in obese patients with Laron syndrome before and during IGF-I treatment.

    Science.gov (United States)

    Laron, Z; Silbergeld, A; Lilos, P; Blum, F W

    1998-01-01

    Fifteen patients with primary GH resistance (Laron syndrome, LS) were studied before and during 6 months of daily replacement treatment with IGF-I. The main findings were that patients with LS and normal or high serum GH binding protein (GHBP) were less obese than those with a negative GHBP, and that serum leptin levels varied with body mass as in other types of obesity.

  14. Stock price forecast based on LS-SVM phase space reconstruction%基于相空间重构的LS-SVM股票价格预测

    Institute of Scientific and Technical Information of China (English)

    林琦; 吴少雄

    2010-01-01

    提出一种基于相空间重构的最小二乘支持向量机(LS-SVM)的股票价格预测方法.采用混沌时间序列对股票价格数据进行相空间重构,应用贝叶斯框架对最小二乘支持向量机的参数选优.预测结果表明,该模型具有误差小、拟合程度高等优点,可适用于股票价格预测.

  15. Supplement Analysis for the Transmission System Vegetation Management Program FEIS (DOE/EIS-0285/SA-104–Lynch Creek Tap to LaGrande-Cowlitz No. 1

    Energy Technology Data Exchange (ETDEWEB)

    Martin, Mark A. [Bonneville Power Administration (BPA), Portland, OR (United States)

    2002-08-21

    Vegetation Management for the Lynch Creek to LaGrande-Cowlitz No. 1. BPA proposes to remove unwanted vegetation along the right-of-way, access roads and around tower structures along the subject transmission line corridor. The right-of-way will be treated using selective and non-selective methods that include hand cutting, mowing and herbicide treatments. Approximately 29 miles of access roads and corridor will be treated. Vegetation management is required for unimpeded operation and maintenance of the subject transmission line. See Section 1 of the attached checklist for a complete description of the proposal.

  16. De onde se vê? Duplicação e dissolução do olhar em Alfred Hitchcock e David Lynch

    Directory of Open Access Journals (Sweden)

    Ulysses Pinheiro

    2015-07-01

    Full Text Available Este artigo compara dois filmes, Janela indiscreta, de Alfred Hitchcock, e Estrada perdida, de David Lynch, com o objetivo de mostrar que eles ilustram duas maneiras distintas de caracterizar o olhar inumano da percepção cinematográfica, tal como ele foi descrito por Gilles Deleuze. Essas duas maneiras distintas não foram discriminadas pelo próprio Deleuze, mas convergem em direção a sua crítica à hermenêutica.

  17. 55,000 yrs of Environmental Change in the Southern Hemisphere: Peat Stratigraphy and Inorganic Geochemistry of Lynch's Crater, NE Queensland, Australia.

    Science.gov (United States)

    Muller, J.; Kylander, M. E.; Wust, R. A.; Weiss, D. J.

    2005-12-01

    This study presents one of the first applications of geochemical proxies to define changes in vegetation, hydrology and atmospheric dust recorded in a peat deposit in the Southern Hemisphere. The Lynch's Crater archive has captured local, regional and global environmental changes and reveals dynamic ecosystem changes as a result of climate shifts over the past 55,000 yrs BP. The 13 m peat record consists of 1.5 m of ombrotrophic peat underlain by a minerotrophic peat. The ombrotrophic section consists of low inorganic content ("ash") and low pH, as expected in of an ombrotrophic environment. The minerotrophic section contains several layers, up to a few cm thick, where abundant sponge spicules, diatom fragments and detrital quartz are indicative of high algal and protista productivity. These layers are characterised by high (up to 50%) ash, indicating persistent flooding of the peat deposits of Lynch's Crater and signalling periods of change in precipitation in North Queensland, Australia. Geochemical data are used to differentiate between climatic episodes associated with flooding events and internal and external atmospheric dust fluxes. Lead isotopes with lithogenic and chalcophile elements tell us that two distinctive sources are prevalent in the Lynch's Crater record. Most of the inorganic fractions of the deposits have the same geochemical signatures as the rocks and sediments of the crater wall, with low As concentrations, high Al, Ti and Sc concentrations and a more radiogenic Pb isotope signature. Influence from long-range dust is distinguished in the lower sections of the core (~35,000-55,000 cal yrs BP) where increases in As concentrations and less radiogenic Pb isotopes are found. Leading up to the Holocene (~35,000-10,000) the influence of increased dust influx becomes more significant (increasing lithogenics, chalcophiles and ash content) and where possible long-range sources are still active, but diluted by a prevailing dominance of the local sources

  18. Scheie syndrome

    Science.gov (United States)

    ... Hurler syndrome) MPS II (Hunter syndrome) MPS IV (Morquio syndrome) MPS III (Sanfilippo syndrome) Causes Scheie syndrome ... Autosomal recessive Cloudy cornea Hearing loss Hurler syndrome Morquio syndrome Review Date 4/20/2015 Updated by: ...

  19. LS-DYNA带单元在绳索体仿真中的应用研究%The Application of LS-DYNA Seatbelt Element in Net Simulation

    Institute of Scientific and Technical Information of China (English)

    赵国伟; 朱鸥宁; 徐云飞; 郑正路

    2013-01-01

    复杂绳索体动力学过程的数值模拟在产品设计中有着越来越多的需求.本文讨论了绳索单元特征及其动力学模型,并基于有限元法,研究了在LS-DYNA中采用安全带单元实现复杂绳索体动力学仿真建模的方法,包括绳索体材料与单元定义、载荷设置、初始状态设置和接触问题的处理等;对柔性网体展开过程进行了数值仿真,结果表明:采用LS-DYNA安全带单元,可有效地实现复杂绳索体动力学过程的模拟;采用“节点-表面”的接触类型,可有效地实现柔性网体与其它对象的接触模拟.

  20. Study on damping effect of damping ditch by using LS-DYNA%基于LS-DYNA的减震沟减震效应研究

    Institute of Scientific and Technical Information of China (English)

    张袁娟; 王公忠

    2015-01-01

    为了研究减震沟的减震作用,运用大型动力分析软件LS-DYNA,基于具体工况分别对有减震沟和无减震沟的露天矿台阶爆破进行数值模拟。结果表明,减震沟距离爆源越近,减震效果越好,减震率最高可达77%,为减震沟的减震效应研究和类似工况提供了理论支持。%In order to study the damping effect of damping ditch,the explicit nonlinear dynamic analysis finite element program LS-DYNA is used based on the specific conditions. The two different numerical models with damping ditch and without damping ditch are made respectively to study the damping effect of open-pit blasting. Numerical simulation results show that the nearer the damping ditch from the explosion source is,the better the damping effect will be,and the biggest decreasing amplitude ratio can reach to about 77%,it provides the theoretical support for the research of damping effect of damping ditch and similar conditions.

  1. Short-term Load Forecasting Based on ARIMA-LS-SVM Model%基于ARIMA和LS-SVM组合模型的短期负荷预测

    Institute of Scientific and Technical Information of China (English)

    刘国徽; 刘小满; 余雪芳; 王勇

    2010-01-01

    经实例预测分析发现,利用累积式自回归动平均法(autoregressive integrated moving average,ARIMA)进行电力短期负荷预测时所得误差序列有较明显的周期规律性,针对此现象及其原因,为提高预测精度,提出采用最小二乘支持向量机(least squares support vector machine,LS-SVM)对ARIMA预测误差进行修正的ARIMA-LS-SVM组合模型;利用该改进模型对哈尔滨电网负荷进行实例预测,结果表明:该方法能够提高短期负荷的预测精度,并且具有较强的推广性和应用能力.

  2. Clinical Report: Germline Mosaicism in Cornelia de Lange Syndrome

    Science.gov (United States)

    Slavin, Thomas P.; Lazebnik, Noam; Clark, Dinah M.; Vengoechea, Jaime; Cohen, Leslie; Kaur, Maninder; Konczal, Laura; Crowe, Carol A.; Corteville, Jane E.; Nowaczyk, Malgorzata J.; Byrne, Janice L.; Jackson, Laird G.; Krantz, Ian D.

    2012-01-01

    Cornelia de Lange syndrome (CdLS) is a genetic disorder associated with delayed growth, intellectual disability, limb reduction defects and characteristic facial features. Germline mosaicism has been a described mechanism for CdLS when there are several affected offspring of apparently unaffected parents. Presently, the recurrence risk for CdLS has been estimated to be as high as 1.5%; however, this figure may be an underrepresentation. We report on the molecularly defined germline mosaicism cases from a large CdLS database, representing the first large case series on germline mosaicism in CdLS. Of the 12 families, eight have been previously described; however, four have not. No one specific gene mutation, either in the NIPBL or the SMC1A gene, was associated with an increased risk for germline mosaicism. Suspected or confirmed cases of germline mosaicism in our database range from a conservative 3.4% up to 5.4% of our total cohort. In conclusion, the potential reproductive recurrence risk due to germline mosiacism should be addressed in prenatal counseling for all families who have had a previously affected pregnancy or child with CdLS. PMID:22581668

  3. Nonlinear Channel Estimation for OFDM System by Complex LS-SVM under High Mobility Conditions

    CERN Document Server

    Charrada, Anis; 10.5121/ijwmn.2011.3412

    2011-01-01

    A nonlinear channel estimator using complex Least Square Support Vector Machines (LS-SVM) is proposed for pilot-aided OFDM system and applied to Long Term Evolution (LTE) downlink under high mobility conditions. The estimation algorithm makes use of the reference signals to estimate the total frequency response of the highly selective multipath channel in the presence of non-Gaussian impulse noise interfering with pilot signals. Thus, the algorithm maps trained data into a high dimensional feature space and uses the structural risk minimization (SRM) principle to carry out the regression estimation for the frequency response function of the highly selective channel. The simulations show the effectiveness of the proposed method which has good performance and high precision to track the variations of the fading channels compared to the conventional LS method and it is robust at high speed mobility.

  4. Segmentation of Magnetic Resonance Imaging MRI using LS-SVM and Wavelet Multiresolution Analysis

    Directory of Open Access Journals (Sweden)

    Luis A. Muñoz-Bedoya

    2013-11-01

    Full Text Available Currently, support vector machines (SVM have become a powerful tool to solve nonlinear classification problems. For the optimization of the tool, has developed a reformulation known as LS-SVM (Support Vector Machine least squares, which works with a model based on function minimization and Lagrange polynomials. Therefore, this paper presents a method for segmentation of magnetic resonance images specifically to study the morphology of the lungs and reach the quantification of relevant features in these images using SVM and LS-SVM. In addition to sorting technique in this work using techniques such as wavelet analysis to eliminate irrelevant information (compression and Splines algorithms to interpolate the information found and quantify the characteristics, which in this work were based on the recognition area, shape and abnormal structures present in the lung of these images.

  5. Design of a multiple kernel learning algorithm for LS-SVM by convex programming.

    Science.gov (United States)

    Jian, Ling; Xia, Zhonghang; Liang, Xijun; Gao, Chuanhou

    2011-06-01

    As a kernel based method, the performance of least squares support vector machine (LS-SVM) depends on the selection of the kernel as well as the regularization parameter (Duan, Keerthi, & Poo, 2003). Cross-validation is efficient in selecting a single kernel and the regularization parameter; however, it suffers from heavy computational cost and is not flexible to deal with multiple kernels. In this paper, we address the issue of multiple kernel learning for LS-SVM by formulating it as semidefinite programming (SDP). Furthermore, we show that the regularization parameter can be optimized in a unified framework with the kernel, which leads to an automatic process for model selection. Extensive experimental validations are performed and analyzed.

  6. LS1 “First Long Shutdown of LHC and its Injector Chains”

    CERN Multimedia

    Foraz, K; Barberan, M; Bernardini, M; Coupard, J; Gilbert, N; Hay, D; Mataguez, S; McFarlane, D

    2014-01-01

    The LHC and its Injectors were stopped in February 2013, in order to maintain, consolidate and upgrade the different equipment of the accelerator chain, with the goal of achieving LHC operation at the design energy of 14 TeV in the centre-of-mass. Prior to the start of this First Long Shutdown (LS1), a major effort of preparation was performed in order to optimize the schedule and the use of resources across the different machines, with the aim of resuming LHC physics in early 2015. The rest of the CERN complex will restart beam operation in the second half of 2014. This paper presents the schedule of the LS1, describes the organizational set-up for the coordination of the works, the main activities, the different main milestones, which have been achieved so far, and the decisions taken in order to mitigate the issues encountered.

  7. Semantic Web applications and tools for the life sciences: SWAT4LS 2010.

    Science.gov (United States)

    Burger, Albert; Paschke, Adrian; Romano, Paolo; Marshall, M Scott; Splendiani, Andrea

    2012-01-25

    As Semantic Web technologies mature and new releases of key elements, such as SPARQL 1.1 and OWL 2.0, become available, the Life Sciences continue to push the boundaries of these technologies with ever more sophisticated tools and applications. Unsurprisingly, therefore, interest in the SWAT4LS (Semantic Web Applications and Tools for the Life Sciences) activities have remained high, as was evident during the third international SWAT4LS workshop held in Berlin in December 2010. Contributors to this workshop were invited to submit extended versions of their papers, the best of which are now made available in the special supplement of BMC Bioinformatics. The papers reflect the wide range of work in this area, covering the storage and querying of Life Sciences data in RDF triple stores, tools for the development of biomedical ontologies and the semantics-based integration of Life Sciences as well as clinicial data.

  8. ls1 mardyn: The massively parallel molecular dynamics code for large systems

    CERN Document Server

    Niethammer, Christoph; Bernreuther, Martin; Buchholz, Martin; Eckhardt, Wolfgang; Heinecke, Alexander; Werth, Stephan; Bungartz, Hans-Joachim; Glass, Colin W; Hasse, Hans; Vrabec, Jadran; Horsch, Martin

    2014-01-01

    The molecular dynamics simulation code ls1 mardyn is presented. It is a highly scalable code, optimized for massively parallel execution on supercomputing architectures, and currently holds the world record for the largest molecular simulation with over four trillion particles. It enables the application of pair potentials to length and time scales which were previously out of scope for molecular dynamics simulation. With an efficient dynamic load balancing scheme, it delivers high scalability even for challenging heterogeneous configurations. Presently, multi-center rigid potential models based on Lennard-Jones sites, point charges and higher-order polarities are supported. Due to its modular design, ls1 mardyn can be extended to new physical models, methods, and algorithms, allowing future users to tailor it to suit their respective needs. Possible applications include scenarios with complex geometries, e.g. for fluids at interfaces, as well as non-equilibrium molecular dynamics simulation of heat and mass ...

  9. Deep Chandra observations of TeV binaries I : LS I+61 303

    NARCIS (Netherlands)

    Rea, N.; Torres, D.F.; Klis, M. van der; Mendez, M.; Sierpowska-Bartosik, A.; Jonker, P.G.

    2010-01-01

    We report on a 95 ks Chandra observation of the TeV emitting High Mass X– ray Binary LS I+61303, using the ACIS-S camera in Continuos Clocking mode to search for a possible X-ray pulsar in this system. The observation was performed while the compact object was passing from phase 0.94 to 0.98 in its

  10. Deep Chandra observations of TeV binaries - I. LS I +61°303

    NARCIS (Netherlands)

    Rea, N.; Torres, D.F.; van der Klis, M.; Jonker, P.G.; Méndez, M.; Sierpowska-Bartosik, A.

    2010-01-01

    We report on a 95 ks Chandra observation of the TeV emitting high-mass X-ray binary LS I +61°303, using the ACIS-S camera in continuous clocking mode to search for a possible X-ray pulsar in this system. The observation was performed while the compact object was passing from phase 0.94 to 0.98 in it

  11. Hydraulic Press with LS System for Modelling of Plastic Working Operations

    Directory of Open Access Journals (Sweden)

    Janusz Pluta

    2008-03-01

    Full Text Available At first, the paper describes destination of the presented hydraulic press. Next, the substance of load sensing (LS systems’ operation was introduced, and electro-hydraulic system of this type, installed in laboratory hydraulic press, was described. The control and measurement circuit of the device was also described, and exemplary test results obtained during plastic working operations on soft non-ferrous alloys were presented.

  12. Determination of the catalytic activity of LEOPARD syndrome-associated SHP2 mutants toward parafibromin, a bona fide SHP2 substrate involved in Wnt signaling

    Energy Technology Data Exchange (ETDEWEB)

    Noda, Saori [Division of Microbiology, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan); Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba (Japan); Takahashi, Atsushi; Hayashi, Takeru [Division of Microbiology, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan); Tanuma, Sei-ichi [Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba (Japan); Hatakeyama, Masanori, E-mail: mhata@m.u-tokyo.ac.jp [Division of Microbiology, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan)

    2016-01-22

    SHP2, encoded by the PTPN11 gene, is a protein tyrosine phosphatase that plays a key role in the proliferation of cells via RAS-ERK activation. SHP2 also promotes Wnt signaling by dephosphorylating parafibromin. Germline missense mutations of PTPN11 are found in more than half of patients with Noonan syndrome (NS) and LEOPARD syndrome (LS), both of which are congenital developmental disorders with multiple common symptoms. However, whereas NS-associated PTPN11 mutations give rise to gain-of-function SHP2 mutants, LS-associated SHP2 mutants are reportedly loss-of-function mutants. To determine the phosphatase activity of LS-associated SHP2 more appropriately, we performed an in vitro phosphatase assay using tyrosine-phosphorylated parafibromin, a biologically relevant substrate of SHP2 and the positive regulator of Wnt signaling that is activated through SHP2-mediated dephosphorylation. We found that LS-associated SHP2 mutants (Y279C, T468M, Q506P, and Q510E) exhibited a substantially reduced phosphatase activity toward parafibromin when compared with wild-type SHP2. Furthermore, each of the LS-associated mutants displayed a differential degree of decrease in phosphatase activity. Deviation of the SHP2 catalytic activity from a certain range, either too strong or too weak, may therefore lead to similar clinical outcomes in NS and LS, possibly through an imbalanced Wnt signal caused by inadequate dephosphorylation of parafibromin. - Highlights: • LS-associated SHP2 mutants dephosphorylate parafibromin on Y290, Y293, and Y315. • LS-associated SHP2 mutants display a reduced tyrosine phosphatase activity. • LS-specific SHP2-Y279C is catalytically less active than LS-specific SHP2-T468M. • NS/LS-associated SHP2-Q506P has both hyper- and hypomorphic enzymatic properties.

  13. [Fe(II)LSCo(III)LS]2 ⇔ [Fe(III)LSCo(II)HS]2 photoinduced conversion in a cyanide-bridged heterobimetallic molecular square.

    Science.gov (United States)

    Mercurol, Julie; Li, Yanling; Pardo, Emilio; Risset, Olivia; Seuleiman, Mannan; Rousselière, Hélène; Lescouëzec, Rodrigue; Julve, Miguel

    2010-12-21

    The self-assembly of [Fe(III){B(pz)(4)}(CN)(3)](-) and [Co(II)(bik)(2)(S)(2)](2+) affords the diamagnetic cyanide-bridged [Fe(II)(LS)Co(III)(LS)](2) molecular square which is converted into the corresponding magnetic [Fe(III)(LS)Co(II)(HS)](2) species under light irradiation at relatively low temperatures.

  14. Successful Growth Hormone Therapy in Cornelia de Lange Syndrome.

    Science.gov (United States)

    de Graaf, Michael; Kant, Sarina G; Wit, Jan Maarten; Willem Redeker, Egbert Johan; Eduard Santen, Gijs Willem; Henriëtta Verkerk, Annemieke Johanna Maria; Uitterlinden, André Gerardus; Losekoot, Monique; Oostdijk, Wilma

    2017-06-07

    Cornelia de Lange Syndrome (CdLS) is a heterogeneous syndrome, both clinically and genetically, in its classical form characterised by distinctive facial features, intra-uterine growth retardation, short stature, developmental delay and anomalies in multiple organ systems. NIPBL, SMC1A, SMC3, RAD21 and HDAC8, all involved in the Cohesin pathway, have been identified to cause CdLS. Growth hormone (GH) secretion has been reported as normal, and to our knowledge there are no reports on the effect of recombinant human GH (r-hGH) treatment in CdLS patients. We present a patient born small for gestational age (SGA) with persistent severe growth retardation (height -3.4 SDS) and mild dysmorphic features, who was treated with GH from 4.3 years of age onward, and diagnosed 6 years later with CdLS using whole exome sequencing. Treatment led to a height gain of 1.6 standard deviation score (SDS) over 8 years. Treatment was interrupted shortly due to high serum IGF-1 serum values. We conclude that GH therapy appears effective and safe for short children with CdLS.

  15. [Research of adaptive notch filter based on QRD-LS algorithm for power line interference in ECG].

    Science.gov (United States)

    Wang, Shuyan; Dong, Jian; Guan, Xin

    2008-10-01

    In this paper, an adaptive notch filter based on QRD-LS algorithm for power line interference in ECG is researched. It can automatically eliminate the power line interference in order to improve the signal-to-interference ratio. Furthermore, QLD-LS algorithm, which is recursive least-squares minimization using systolic arrays, is employed to adjust the weight vector. Compared with the adaptive notch filter based on LMS (least mean square) algorithm, it has good robustness. Simulation examples confirm the results. QRD-LS adaptive notch filter has better performance in comparison with LMS method.

  16. Simple Detection of Large InDeLS by DHPLC: The ACE Gene as a Model

    Directory of Open Access Journals (Sweden)

    Renata Guedes Koyama

    2008-01-01

    Full Text Available Insertion-deletion polymorphism (InDeL is the second most frequent type of genetic variation in the human genome. For the detection of large InDeLs, researchers usually resort to either PCR gel analysis or RFLP, but these are time consuming and dependent on human interpretation. Therefore, a more efficient method for genotyping this kind of genetic variation is needed. In this report, we describe a method that can detect large InDeLs by DHPLC (denaturating high-performance liquid chromatography using the angiotensin-converting enzyme (ACE gene I/D polymorphism as a model. The InDeL targeted in this study is characterized by a 288 bp Alu element insertion (I. We used DHPLC at nondenaturating conditions to analyze the PCR product with a flow through the chromatographic column under two different gradients based on the differences between D and I sequences. The analysis described is quick and easy, making this technique a suitable and efficient means for DHPLC users to screen InDeLs in genetic epidemiological studies.

  17. Launch of new e-learning course “Safety during LS1”

    CERN Multimedia

    HSE Unit

    2013-01-01

    After 3 years of activity, the LHC and the rest of the accelerator chain have been shut down for about 2 years (from February 2013 to December 2014) due to maintenance and upgrade work, on the surface as well as underground.   CERN has developed a new e-learning course related to this Long Shutdown period (LS1) so as to provide all the collaborators working in the LS1 area with accurate security-oriented information. The objectives of this new course are to: Present LS1 and its context, Identify CERN facilities’ major risks, Identify the main risks associated with our co-activities, Explain how safety issues are being handled at CERN, Present all the basic safety measures to be respected, Present all emergency and rescue instructions. The course is available via the e-learning SIR application. It is compulsory for all newcomers at CERN, along with the “CERN Safety Introduction” training. It is also highly recommended that people who were already w...

  18. Exceptionally Bright TeV Flares from the Binary LS I +61 303

    Science.gov (United States)

    Archambault, S.; Archer, A.; Aune, T.; Barnacka, A.; Benbow, W.; Bird, R.; Buchovecky, M.; Buckley, J. H.; Bugaev, V.; Byrum, K.; Cardenzana, J. V.; Cerruti, M.; Chen, X.; Ciupik, L.; Collins-Hughes, E.; Connolly, M. P.; Cui, W.; Dickinson, H. J.; Dumm, J.; Eisch, J. D.; Falcone, A.; Feng, Q.; Finley, J. P.; Fleischhack, H.; Flinders, A.; Fortin, P.; Fortson, L.; Furniss, A.; Gillanders, G. H.; Griffin, S.; Grube, J.; Gyuk, G.; Hütten, M.; Håkansson, N.; Hanna, D.; Holder, J.; Humensky, T. B.; Johnson, C. A.; Kaaret, P.; Kar, P.; Kelley-Hoskins, N.; Kertzman, M.; Khassen, Y.; Kieda, D.; Krause, M.; Krennrich, F.; Kumar, S.; Lang, M. J.; Maier, G.; McArthur, S.; McCann, A.; Meagher, K.; Millis, J.; Moriarty, P.; Mukherjee, R.; Nieto, D.; O'Brien, S.; O'Faoláin de Bhróithe, A.; Ong, R. A.; Otte, A. N.; Pandel, D.; Park, N.; Pelassa, V.; Pohl, M.; Popkow, A.; Pueschel, E.; Quinn, J.; Ragan, K.; Reynolds, P. T.; Richards, G. T.; Roache, E.; Rousselle, J.; Rulten, C.; Santander, M.; Sembroski, G. H.; Shahinyan, K.; Smith, A. W.; Staszak, D.; Telezhinsky, I.; Tucci, J. V.; Tyler, J.; Vincent, S.; Wakely, S. P.; Weiner, O. M.; Weinstein, A.; Wilhelm, A.; Williams, D. A.; Zitzer, B.

    2016-01-01

    The TeV binary system LS I +61° 303 is known for its regular, non-thermal emission pattern that traces the orbital period of the compact object in its 26.5 day orbit around its B0 Ve star companion. The system typically presents elevated TeV emission around apastron passage with flux levels between 5% and 15% of the steady flux from the Crab Nebula (>300 GeV). In this article, VERITAS observations of LS I +61° 303 taken in late 2014 are presented, during which bright TeV flares around apastron at flux levels peaking above 30% of the Crab Nebula flux were detected. This is the brightest such activity from this source ever seen in the TeV regime. The strong outbursts have rise and fall times of less than a day. The short timescale of the flares, in conjunction with the observation of 10 TeV photons from LS I +61° 303 during the flares, provides constraints on the properties of the accelerator in the source.

  19. A Computational Approach for Probabilistic Analysis of LS-DYNA Water Impact Simulations

    Science.gov (United States)

    Horta, Lucas G.; Mason, Brian H.; Lyle, Karen H.

    2010-01-01

    NASA s development of new concepts for the Crew Exploration Vehicle Orion presents many similar challenges to those worked in the sixties during the Apollo program. However, with improved modeling capabilities, new challenges arise. For example, the use of the commercial code LS-DYNA, although widely used and accepted in the technical community, often involves high-dimensional, time consuming, and computationally intensive simulations. Because of the computational cost, these tools are often used to evaluate specific conditions and rarely used for statistical analysis. The challenge is to capture what is learned from a limited number of LS-DYNA simulations to develop models that allow users to conduct interpolation of solutions at a fraction of the computational time. For this problem, response surface models are used to predict the system time responses to a water landing as a function of capsule speed, direction, attitude, water speed, and water direction. Furthermore, these models can also be used to ascertain the adequacy of the design in terms of probability measures. This paper presents a description of the LS-DYNA model, a brief summary of the response surface techniques, the analysis of variance approach used in the sensitivity studies, equations used to estimate impact parameters, results showing conditions that might cause injuries, and concluding remarks.

  20. A Computational Approach for Model Update of an LS-DYNA Energy Absorbing Cell

    Science.gov (United States)

    Horta, Lucas G.; Jackson, Karen E.; Kellas, Sotiris

    2008-01-01

    NASA and its contractors are working on structural concepts for absorbing impact energy of aerospace vehicles. Recently, concepts in the form of multi-cell honeycomb-like structures designed to crush under load have been investigated for both space and aeronautics applications. Efforts to understand these concepts are progressing from tests of individual cells to tests of systems with hundreds of cells. Because of fabrication irregularities, geometry irregularities, and material properties uncertainties, the problem of reconciling analytical models, in particular LS-DYNA models, with experimental data is a challenge. A first look at the correlation results between single cell load/deflection data with LS-DYNA predictions showed problems which prompted additional work in this area. This paper describes a computational approach that uses analysis of variance, deterministic sampling techniques, response surface modeling, and genetic optimization to reconcile test with analysis results. Analysis of variance provides a screening technique for selection of critical parameters used when reconciling test with analysis. In this study, complete ignorance of the parameter distribution is assumed and, therefore, the value of any parameter within the range that is computed using the optimization procedure is considered to be equally likely. Mean values from tests are matched against LS-DYNA solutions by minimizing the square error using a genetic optimization. The paper presents the computational methodology along with results obtained using this approach.

  1. Parallel design of JPEG-LS encoder on graphics processing units

    Science.gov (United States)

    Duan, Hao; Fang, Yong; Huang, Bormin

    2012-01-01

    With recent technical advances in graphic processing units (GPUs), GPUs have outperformed CPUs in terms of compute capability and memory bandwidth. Many successful GPU applications to high performance computing have been reported. JPEG-LS is an ISO/IEC standard for lossless image compression which utilizes adaptive context modeling and run-length coding to improve compression ratio. However, adaptive context modeling causes data dependency among adjacent pixels and the run-length coding has to be performed in a sequential way. Hence, using JPEG-LS to compress large-volume hyperspectral image data is quite time-consuming. We implement an efficient parallel JPEG-LS encoder for lossless hyperspectral compression on a NVIDIA GPU using the computer unified device architecture (CUDA) programming technology. We use the block parallel strategy, as well as such CUDA techniques as coalesced global memory access, parallel prefix sum, and asynchronous data transfer. We also show the relation between GPU speedup and AVIRIS block size, as well as the relation between compression ratio and AVIRIS block size. When AVIRIS images are divided into blocks, each with 64×64 pixels, we gain the best GPU performance with 26.3x speedup over its original CPU code.

  2. VSOP and Stellar Sources - The Case of LS I +61°303

    Science.gov (United States)

    Dougherty, S. M.

    2009-08-01

    Space-VLBI observations of stellar sources represent a challenge since there are few sources with sufficiently high brightness temperature for detection on space-ground baselines. X-ray binaries (XRB) are among the few types of stellar radio sources that can be detected. Observations of the unusual X-ray and γ-ray binary system LS I +61°303 obtained with the HALCA satellite and a 20-element ground array are described. The data in this 48-hour experiment represent some of the best quality VLBI observations of LS I +61°303. No fringes were detected on HALCA baselines. 10-minute snapshot images were produced from the global ground array data and reveal an expansion velocity of 800 km s-1. Some of these image data reveal hints of more extended emission but high-SNR closure phase data do not support relativistic outflow in the plane-of-the-sky in LS I +61°303. The largest closure phase rates are consistent with an outflow of ˜1000 km s-1 as deduced from the image data. The closure phases also show no evidence of structure variation on size scales greater than ˜10 mas. A number of issues related to VSOP2 observations of stellar radio sources are raised.

  3. Hybrid LS-LMMSE Channel Estimation Technique for LTE Downlink Systems

    CERN Document Server

    Khlifi, Abdelhakim; 10.5121/ijngn.2011.3401

    2012-01-01

    In this paper, we propose to improve the performance of the channel estimation for LTE Downlink systems under the effect of the channel length. As LTE Downlink system is a MIMO-OFDMA based system, a cyclic prefix (CP) is inserted at the beginning of each transmitted OFDM symbol in order to mitigate both inter-carrier interference (ICI) and inter-symbol interference (ISI). The inserted CP is usually equal to or longer than the channel length. However, the cyclic prefix can be shorter because of some unforeseen channel behaviour. Previous works have shown that in the case where the cyclic prefix is equal to or longer than the channel length, LMMSE performs better than LSE but at the cost of computational complexity .In the other case, LMMSE performs also better than LS only for low SNR values. However, LS shows better performance for LTE Downlink systems for high SNR values. Therefore, we propose a hybrid LS-LMMSE channel estimation technique robust to the channel length effect. MATLAB Monte-Carlo simulations a...

  4. Exceptionally bright TeV flares from the binary LS I +61$^\\circ$ 303

    CERN Document Server

    Archambault, S; Aune, T; Barnacka, A; Benbow, W; Bird, R; Buchovecky, M; Buckley, J H; Bugaev, V; Byrum, K; Cardenzana, J V; Cerruti, M; Chen, X; Ciupik, L; Collins-Hughes, E; Connolly, M P; Cui, W; Dickinson, H J; Dumm, J; Eisch, J D; Falcone, A; Feng, Q; Finley, J P; Fleischhack, H; Flinders, A; Fortin, P; Fortson, L; Furniss, A; Gillanders, G H; Griffin, S; Grube, J; Gyuk, G; Huetten, M; Hakansson, N; Hanna, D; Holder, J; Humensky, T B; Johnson, C A; Kaaret, P; Kar, P; Kelley-Hoskins, N; Kertzman, M; Khassen, Y; Kieda, D; Krause, M; Krennrich, F; Kumar, S; Lang, M J; Maier, G; McArthur, S; McCann, A; Meagher, K; Millis, J; Moriarty, P; Mukherjee, R; Nieto, D; O'Brien, S; de Bhroithe, A O'Faolain; Ong, R A; Otte, A N; Pandel, D; Park, N; Pelassa, V; Pohl, M; Popkow, A; Pueschel, E; Quinn, J; Ragan, K; Reynolds, P T; Richards, G T; Roache, E; Rousselle, J; Rulten, C; Santander, M; Sembroski, G H; Shahinyan, K; Smith, A W; Staszak, D; Telezhinsky, I; Tucci, J V; Tyler, J; Vincent, S; Wakely, S P; Weiner, O M; Weinstein, A; Wilhelm, A; Williams, D A; Zitzer, B

    2016-01-01

    The TeV binary system LS I +61$^\\circ$ 303 is known for its regular, non-thermal emission pattern which traces the orbital period of the compact object in its 26.5 day orbit around its B0 Ve star companion. The system typically presents elevated TeV emission around apastron passage with flux levels between 5% and 15% of the steady flux from the Crab Nebula (> 300 GeV). In this article, VERITAS observations of LS I +61$^\\circ$ 303 taken in late 2014 are presented, during which bright TeV flares around apastron at flux levels peaking above 30% of the Crab Nebula flux were detected. This is the brightest such activity from this source ever seen in the TeV regime. The strong outbursts have rise and fall times of less than a day. The short timescale of the flares, in conjunction with the observation of 10 TeV photons from LS I +61$^\\circ$ 303 during the flares, provides constraints on the properties of the accelerator in the source.

  5. High-energy emissions from the gamma-ray binary LS 5039

    CERN Document Server

    Takata, J; Tam, P H T; Kong, A K H; Hui, C Y; Cheng, K S

    2014-01-01

    We study mechanisms of multi-wavelength emissions (X-ray, GeV and TeV gamma-rays) from the gamma-ray binary LS~5039. This paper is composed of two parts. In the first part, we report on results of observational analysis using four year data of \\fermi\\ Large Area Telescope. Due to the improvement of instrumental response function and increase of the statistics, the observational uncertainties of the spectrum in $\\sim$100-300 MeV bands and $>10$GeV bands are significantly improved. The present data analysis suggests that the 0.1-100GeV emissions from LS~5039 contain three different components; (i) the first component contributes to $<$1GeV emissions around superior conjunction, (ii) the second component dominates in 1-10GeV energy bands and (iii) the third component is compatible to lower energy tail of the TeV emissions. In the second part, we develop an emission model to explain the properties of the phase-resolved emissions in multi-wavelength observations. Assuming that LS~5039 includes a pulsar, we argu...

  6. Lamb Wave Damage Quantification Using GA-Based LS-SVM

    Directory of Open Access Journals (Sweden)

    Fuqiang Sun

    2017-06-01

    Full Text Available Lamb waves have been reported to be an efficient tool for non-destructive evaluations (NDE for various application scenarios. However, accurate and reliable damage quantification using the Lamb wave method is still a practical challenge, due to the complex underlying mechanism of Lamb wave propagation and damage detection. This paper presents a Lamb wave damage quantification method using a least square support vector machine (LS-SVM and a genetic algorithm (GA. Three damage sensitive features, namely, normalized amplitude, phase change, and correlation coefficient, were proposed to describe changes of Lamb wave characteristics caused by damage. In view of commonly used data-driven methods, the GA-based LS-SVM model using the proposed three damage sensitive features was implemented to evaluate the crack size. The GA method was adopted to optimize the model parameters. The results of GA-based LS-SVM were validated using coupon test data and lap joint component test data with naturally developed fatigue cracks. Cases of different loading and manufacturer were also included to further verify the robustness of the proposed method for crack quantification.

  7. Clinical and Molecular Features of Laron Syndrome, A Genetic Disorder Protecting from Cancer.

    Science.gov (United States)

    Janecka, Anna; Kołodziej-Rzepa, Marta; Biesaga, Beata

    2016-01-01

    Laron syndrome (LS) is a rare, genetic disorder inherited in an autosomal recessive manner. The disease is caused by mutations of the growth hormone (GH) gene, leading to GH/insulin-like growth factor type 1 (IGF1) signalling pathway defect. Patients with LS have characteristic biochemical features, such as a high serum level of GH and low IGF1 concentration. Laron syndrome was first described by the Israeli physician Zvi Laron in 1966. Globally, around 350 people are affected by this syndrome and there are two large groups living in separate geographic regions: Israel (69 individuals) and Ecuador (90 individuals). They are all characterized by typical appearance such as dwarfism, facial phenotype, obesity and hypogenitalism. Additionally, they suffer from hypoglycemia, hypercholesterolemia and sleep disorders, but surprisingly have a very low cancer risk. Therefore, studies on LS offer a unique opportunity to better understand carcinogenesis and develop new strategies of cancer treatment.

  8. [Multiple dependent variables LS-SVM regression algorithm and its application in NIR spectral quantitative analysis].

    Science.gov (United States)

    An, Xin; Xu, Shuo; Zhang, Lu-Da; Su, Shi-Guang

    2009-01-01

    In the present paper, on the basis of LS-SVM algorithm, we built a multiple dependent variables LS-SVM (MLS-SVM) regression model whose weights can be optimized, and gave the corresponding algorithm. Furthermore, we theoretically explained the relationship between MLS-SVM and LS-SVM. Sixty four broomcorn samples were taken as experimental material, and the sample ratio of modeling set to predicting set was 51 : 13. We first selected randomly and uniformly five weight groups in the interval [0, 1], and then in the way of leave-one-out (LOO) rule determined one appropriate weight group and parameters including penalizing parameters and kernel parameters in the model according to the criterion of the minimum of average relative error. Then a multiple dependent variables quantitative analysis model was built with NIR spectrum and simultaneously analyzed three chemical constituents containing protein, lysine and starch. Finally, the average relative errors between actual values and predicted ones by the model of three components for the predicting set were 1.65%, 6.47% and 1.37%, respectively, and the correlation coefficients were 0.9940, 0.8392 and 0.8825, respectively. For comparison, LS-SVM was also utilized, for which the average relative errors were 1.68%, 6.25% and 1.47%, respectively, and the correlation coefficients were 0.9941, 0.8310 and 0.8800, respectively. It is obvious that MLS-SVM algorithm is comparable to LS-SVM algorithm in modeling analysis performance, and both of them can give satisfying results. The result shows that the model with MLS-SVM algorithm is capable of doing multi-components NIR quantitative analysis synchronously. Thus MLS-SVM algorithm offers a new multiple dependent variables quantitative analysis approach for chemometrics. In addition, the weights have certain effect on the prediction performance of the model with MLS-SVM, which is consistent with our intuition and is validated in this study. Therefore, it is necessary to optimize

  9. Development and Application of LS2000 Bagged Urea Train Loader%LS2000型尿素装车机的开发与应用

    Institute of Scientific and Technical Information of China (English)

    刘陶

    2001-01-01

    回顾了国内大化肥装置铁路站台装车机的使用概况,对国产化ZD1型装车机,从性能、结构、参数和使用等方面,作了详细的剖析和深入的探讨.在国内长期来缺少可靠合用的装车机的不利情况下,针对ZD1型装车机所暴露的缺点,对新开发的LS2000型装车机作了介绍,并对其基本性能、结构特点、工作原理等,作了系统的说明.

  10. Simultaneous Analysis of the Behavioural Phenotype, Physical Factors, and Parenting Stress in People with Cornelia De Lange Syndrome

    Science.gov (United States)

    Wulffaert, J.; van Berckelaer-Onnes, I.; Kroonenberg, P.; Scholte, E.; Bhuiyan, Z.; Hennekam, R.

    2009-01-01

    Background: Studies into the phenotype of rare genetic syndromes largely rely on bivariate analysis. The aim of this study was to describe the phenotype of Cornelia de Lange syndrome (CdLS) in depth by examining a large number of variables with varying measurement levels. Virtually the only suitable multivariate technique for this is categorical…

  11. Social Behavior and Characteristics of Autism Spectrum Disorder in Angelman, Cornelia de Lange, and Cri du Chat Syndromes

    Science.gov (United States)

    Moss, Joanna; Howlin, Patricia; Hastings, Richard Patrick; Beaumont, Sarah; Griffith, Gemma M.; Petty, Jane; Tunnicliffe, Penny; Yates, Rachel; Villa, Darrelle; Oliver, Chris

    2013-01-01

    We evaluated autism spectrum disorder (ASD) characteristics and social behavior in Angelman (AS; "n" ?=? 19; mean age ?=?10.35 years), Cornelia de Lange (CdLS; "n" ?=? 15; mean age ?=?12.40 years), and Cri du Chat (CdCS, also known as 5 p-syndrome; "n" ?=? 19; mean age ?=? 8.80 years) syndromes. The proportion of…

  12. Dynamic Simulation Analysis of Fruiter Trimmer Based on ANSYS/LS-DYNA%基于ANSYS/LS-DYNA的果树剪枝动力学仿真分析

    Institute of Scientific and Technical Information of China (English)

    周波; 樊啟洲; 陈宝龙

    2012-01-01

    为了更好地研究果树剪枝机理,应用Pro/E软件对剪枝剪进行建模,利用接口将建立的模型导入ANSYS进行网络划分.在ANSYS/LS-DYNA环境下,建立了果树剪技有限元模型,对果树剪枝进行了动力学仿真.通过动力学仿真研究果树剪枝过程中的受力分析表明,当树枝直径为30mm时,刀片组最大应力为218.67 MPa,发生在定刀片刀刃附近.所得结论为改进果树剪枝剪结构、改善其受力状况和工作性能、延长使用寿命提供了依据.%In order to study the mechanism of fruiter trimmer, pruning shears were modeled by Pro/E, and the model established was guided into ANSYS for dividing of network, the three dimension model of fruiter trimmer was built for dynanmics simulation in the ANSYS/LS-DYNA environment. Stress analysis in the dynamics simulation of fruit tree's pruning process showed that when the tree branch' diameter was 30 nun, the maximum stress of the blade group was 218.67 Mpa in the vicinity of the fixed-blade cutting edge. It provides a basis for the improvement of fruit tree pruning shear's structure and the status and performance of its force, and also it extends the service life.

  13. Effects of Doxycycline on Invasion and Metastasis of Colorectal Cancer Cell Line LS174T%Doxycycline抑制大肠癌LS174T细胞侵袭的体外实验研究

    Institute of Scientific and Technical Information of China (English)

    徐海涛; 杜杰; 董新舒

    2007-01-01

    目的:观察多西环素(Doxycycline)在体外对LS174T侵袭能力的抑制作用,并尝试探讨该抑制作用的分子机制.方法:1)MTT法观察Doxycycline对LS174T细胞粘附力的影响;Transwell小室法检测不同浓度Doxycycline对细胞侵袭和运动能力的抑制作用;2)RT-PCR法检测不同浓度Doxycycline作用48h后,MMP2的mRNA表达情况,同时明胶酶谱法检测MMP2分泌.结果:1)Doxycycline能够以剂量依赖方式抑制大肠癌LS174T细胞的体外运动和侵袭能力,但不影响其粘附能力;2)Doxycycline能够抑制LS174T细胞MMP2的mRNA表达.结论:Doxycycline在体外能够有效地抑制大肠癌LS174T细胞的侵袭、转移,其中MMP2是抑制大肠癌细胞LS174T的一个有效靶点.

  14. Rare form of autosomal dominant familial Cornelia de Lange syndrome due to a novel duplication in SMC3.

    Science.gov (United States)

    Infante, Elena; Alkorta-Aranburu, Gorka; El-Gharbawy, Areeg

    2017-08-01

    Clinical features are variable in patients with Cornelia de Lange syndrome (CdLS). Milder forms exist with structural maintenance of chromosomes 3 (SMC3) mutations. Inherited milder forms of CdLS are uncommon and may be missed if genetic testing is limited to Nipped-B-like protein (NIPBL) and SMC1A. Parental studies should be pursued if there is a history of learning disabilities and/or dysmorphic features.

  15. Study on the performance of the Particle Identification Detectors at LHCb after the LHC First Long Shutdown (LS1)

    CERN Document Server

    Fontana, Marianna

    2016-01-01

    During the First Long Shutdown (LS1), the LHCb experiment has introduced major modification in the data-processing procedure and modified part of the detector to deal with the increased energy and the increased heavy-hadron production cross-section. In this contribution we review the performance of the particle identification detectors at LHCb, Rich, Calorimeters, and Muon system, after the LS1

  16. NIPBL rearrangements in Cornelia de Lange syndrome: evidence for replicative mechanism and genotype–phenotype correlation

    Science.gov (United States)

    Pehlivan, Davut; Hullings, Melanie; Carvalho, Claudia M.B.; Gonzaga-Jauregui, Claudia G.; Loy, Elizabeth; Jackson, Laird G.; Krantz, Ian D.; Deardorff, Matthew A.; Lupski, James R.

    2013-01-01

    Purpose Cornelia de Lange syndrome (CdLS) is a multisystem congenital anomaly disorder characterized by mental retardation, limb abnormalities, distinctive facial features, and hirsutism. Mutations in three genes involved in sister chromatid cohesion, NIPBL, SMC1A, and SMC3, account for ~55% of CdLS cases. The molecular etiology of a significant fraction of CdLS cases remains unknown. We hypothesized that large genomic rearrangements of cohesin complex subunit genes may play a role in the molecular etiology of this disorder. Methods Custom high-resolution oligonucleotide array comparative genomic hybridization analyses interrogating candidate cohesin genes and breakpoint junction sequencing of identified genomic variants were performed. Results Of the 162 patients with CdLS, for whom mutations in known CdLS genes were previously negative by sequencing, deletions containing NIPBL exons were observed in 7 subjects (~5%). Breakpoint sequences in five patients implicated microhomology-mediated replicative mechanisms—such as serial replication slippage and fork stalling and template switching/microhomology-mediated break-induced replication—as a potential predominant contributor to these copy number variations. Most deletions are predicted to result in haploinsuflciency due to heterozygous loss-of-function mutations; such mutations may result in a more severe CdLS phenotype. Conclusion Our findings suggest a potential clinical utility to testing for copy number variations involving NIPBL when clinically diagnosed CdLS cases are mutation-negative by DNA-sequencing studies. PMID:22241092

  17. Autism traits in children and adolescents with Cornelia de Lange syndrome.

    Science.gov (United States)

    Srivastava, Siddharth; Landy-Schmitt, Colleen; Clark, Bennett; Kline, Antonie D; Specht, Matt; Grados, Marco A

    2014-06-01

    Cornelia de Lange syndrome (CdLS) is a cohesinopathy causing delayed growth and limb deficits. Individuals with CdLS have mild to profound intellectual disability and autistic features. This study characterizes the behavioral phenotype of children with CdLS, focusing on autistic features, maladaptive behaviors, and impact of age. Children with CdLS (5-18 years) were administered normed instruments to characterize autism features (Childhood Autism Rating Scale, CARS), maladaptive behaviors (Aberrant Behavior Checklist), and adaptive skills (Vineland Adaptive Behaviors Scales). CdLS features and severity were rated with Diagnostic Criteria for CdLS. Forty-one children with CdLS (23 females, 18 males) were classified as having "no autism" (n = 7; 17.1%), "mild autism" (n = 17; 41.4%), and "severe autism" (n = 17; 41.4%), using CARS scores. Characteristic items were abnormal emotional response, stereotypies, odd object use, rigidity, lack of verbal communication, and low intellectual functioning. Verbal communication deficits and repetitive behaviors were higher compared to sensory, social cognition, and behavior abnormalities (P ≤ 0.0001). Maladaptive behaviors associated with autism traits were stereotypies (P = 0.003), hyperactivity (P = 0.01), and lethargy (P = 0.03). Activities of daily living were significantly affected; socialization adaptive skills were a relative strength. However, with advancing age, both socialization (P socialization adaptive skills are less affected. Advancing age can worsen communication and socialization deficits relative to neurotypical peers.

  18. 改良 B-Lynch 缝合术在剖宫产术中宫缩乏力性出血的应用%Application of improved B-Lynch sutura in hemorrhage caused by uterine inertia during the ce-sarean section

    Institute of Scientific and Technical Information of China (English)

    白琳

    2014-01-01

    Objective To investigate the application methods and clinical effect of improved B-Lynch sutura on hemorrhage caused by uterine inertia during the cesarean section. Methods A retro-spective analysis was performed on the clinical data of 72 patients with hemorrhage caused by uterine in-ertia during the cesarean section,who were treated by improved B-Lynch sutura in the first people’s hos-pital of Shangqiu from April 2008 to June 2013. Results The hemorrhage dosage during operation of the 72 patients was 600 - 2300 ml,all of the patients were stanched effectively,the effective rate was 100%and there was no hemorrhagic shock occured during the operation,7 cases were taken transfusion for 400 - 800 ml,no one was cut the uterus because of hemorrhage out-of-control. The uterus wounds of the patients healed well and there was no complication of rehaemorrhagia,infection,intrauterine adhesion or endometriosis occur. Follow-up visited for 7 - 14 months after the patients left the hospital,found their lochia was regular,when reviewed the patients by B ultrasound 42 days after the operation showed that, their involution of uterus was good. Conclusions The B-Lynch sutura is easy to handle,dispense with special instrument and high technical requirements,it has the characteristics of rapid,valid and definite when salvaging the patients with massive haemorrhage caused by uterine inertia during the cesarean sec-tion,besides,it is also beneficial to uterus recovery and suitable for primary hospital to use.%目的:探讨改良 B-Lynch 缝扎术治疗剖宫产术中宫缩乏力性产后出血的应用方法及临床效果。方法回顾性分析2008年4月至2013年6月间商丘市第一人民医院采用改良式 B-Lynch 缝合术治疗的72例剖宫产术中宫缩乏力性产后出血患者的临床资料。结果72例患者术中出血600~2300 ml,均有效止血,有效率100%,无术中失血性休克发生,7例患者输血400~800 ml,无因出血无法控制行子宫

  19. A magnetar-like event from LS I +61 303 and its nature as a gamma-ray binary

    CERN Document Server

    Torres, Diego F; Esposito, Paolo; Li, Jian; Chen, Yupeng; Zhang, Shu

    2011-01-01

    We report on the Swift-BAT detection of a short burst from the direction of the TeV binary LS I +61 303, resembling those generally labelled as magnetar-like. We show that it is likely that the short burst was indeed originating from LS I +61 303 (although we cannot totally exclude the improbable presence of a far-away line-of-sight magnetar) and that it is a different phenomena with respect to the previously-observed ks-long flares from this system. Accepting as a hypothesis that LS I +61 303 is the first magnetar detected in a binary system, we study which are the implications. We find that a magnetar-composed LS I +61 303-system would most likely be (i.e., for usual magnetar parameters and mass-loss rate) subject to a flip-flop behavior, from a rotational powered regime (in apastron) to a propeller regime (in periastron) along each of the LS I +61 303, eccentric orbital motion. We prove that whereas near apastron an inter-wind shock can lead to the normally observed LS I +61 303behavior, with TeV emission,...

  20. Cloning and expression analysis of nonspecific cytotoxic cell receptor 1 (Ls-NCCRP1) from red snapper (Lutjanus sanguineus).

    Science.gov (United States)

    Cai, Jia; Wei, Shina; Wang, Bei; Huang, Yucong; Tang, Jufen; Lu, Yishan; Wu, Zaohe; Jian, Jichang

    2013-09-01

    It is well known that nonspecific cytotoxic cells (NCCs) are kinds of natural killer cell mediated innate immune responses in teleosts. The nonspecific cytotoxic cell receptor protein 1 (NCCRP-1) is an important cell surface protein on NCC, which serves crucial functions in target cell recognition and cytotoxicity activation. In the present study, a nonspecific cytotoxic cell receptor protein NCCRP-1 (Ls-NCCRP1) was cloned from red snapper, Lutjanus sanguineus. The Ls-NCCRP1 cDNA is composed of 986bp with a 43bp of 5'-UTR, 702bp open reading frame (ORF) and 241bp 3'-UTR, encoding a polypeptide of 233 amino acids (GenBank accession no: ADK32635). Phylogenetic analysis revealed that Ls-NCCRP1 showed highest similarity to sea bream NCCRP-1. Quantitative real-time PCR (qRT-PCR) analysis showed that Ls-NCCRP1 had relatively high expression level in the head kidney, spleen and liver. After Vibrio alginolyticus infection, transcripts of Ls-NCCRP1 increased and reached its peak at 4h p.i. These results indicated that Ls-NCCRP1 may play an important role in innate immune response to bacteria.

  1. Global transcriptional disturbances underlie Cornelia de Lange syndrome and related phenotypes.

    Science.gov (United States)

    Yuan, Bo; Pehlivan, Davut; Karaca, Ender; Patel, Nisha; Charng, Wu-Lin; Gambin, Tomasz; Gonzaga-Jauregui, Claudia; Sutton, V Reid; Yesil, Gozde; Bozdogan, Sevcan Tug; Tos, Tulay; Koparir, Asuman; Koparir, Erkan; Beck, Christine R; Gu, Shen; Aslan, Huseyin; Yuregir, Ozge Ozalp; Al Rubeaan, Khalid; Alnaqeb, Dhekra; Alshammari, Muneera J; Bayram, Yavuz; Atik, Mehmed M; Aydin, Hatip; Geckinli, B Bilge; Seven, Mehmet; Ulucan, Hakan; Fenercioglu, Elif; Ozen, Mustafa; Jhangiani, Shalini; Muzny, Donna M; Boerwinkle, Eric; Tuysuz, Beyhan; Alkuraya, Fowzan S; Gibbs, Richard A; Lupski, James R

    2015-02-01

    Cornelia de Lange syndrome (CdLS) is a genetically heterogeneous disorder that presents with extensive phenotypic variability, including facial dysmorphism, developmental delay/intellectual disability (DD/ID), abnormal extremities, and hirsutism. About 65% of patients harbor mutations in genes that encode subunits or regulators of the cohesin complex, including NIPBL, SMC1A, SMC3, RAD21, and HDAC8. Wiedemann-Steiner syndrome (WDSTS), which shares CdLS phenotypic features, is caused by mutations in lysine-specific methyltransferase 2A (KMT2A). Here, we performed whole-exome sequencing (WES) of 2 male siblings clinically diagnosed with WDSTS; this revealed a hemizygous, missense mutation in SMC1A that was predicted to be deleterious. Extensive clinical evaluation and WES of 32 Turkish patients clinically diagnosed with CdLS revealed the presence of a de novo heterozygous nonsense KMT2A mutation in 1 patient without characteristic WDSTS features. We also identified de novo heterozygous mutations in SMC3 or SMC1A that affected RNA splicing in 2 independent patients with combined CdLS and WDSTS features. Furthermore, in families from 2 separate world populations segregating an autosomal-recessive disorder with CdLS-like features, we identified homozygous mutations in TAF6, which encodes a core transcriptional regulatory pathway component. Together, our data, along with recent transcriptome studies, suggest that CdLS and related phenotypes may be "transcriptomopathies" rather than cohesinopathies.

  2. The mitochondrial DNA 10197 G > A mutation causes MELAS/Leigh overlap syndrome presenting with acute auditory agnosia.

    Science.gov (United States)

    Leng, Yinglin; Liu, Yuhe; Fang, Xiaojing; Li, Yao; Yu, Lei; Yuan, Yun; Wang, Zhaoxia

    2015-04-01

    Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes/Leigh (MELAS/LS) overlap syndrome is a mitochondrial disorder subtype with clinical and magnetic resonance imaging (MRI) features that are characteristic of both MELAS and Leigh syndrome (LS). Here, we report an MELAS/LS case presenting with cortical deafness and seizures. Cranial MRI revealed multiple lesions involving bilateral temporal lobes, the basal ganglia and the brainstem, which conformed to neuroimaging features of both MELAS and LS. Whole mitochondrial DNA (mtDNA) sequencing and PCR-RFLP revealed a de novo heteroplasmic m.10197 G > A mutation in the NADH dehydrogenase subunit 3 gene (ND3), which was predicted to cause an alanine to threonine substitution at amino acid 47. Although the mtDNA m.10197 G > A mutation has been reported in association with LS, Leber hereditary optic neuropathy and dystonia, it has never been linked with MELAS/LS overlap syndrome. Our patient therefore expands the phenotypic spectrum of the mtDNA m.10197 G > A mutation.

  3. Spectral and Temporal Characteristics of LS PEG and TW PIC Using XMM-NEWTON Data

    Science.gov (United States)

    Talebpour Sheshvan, Nasrin; Balman, Solen

    2016-07-01

    We report the analysis of archival XMM-Newton X-ray observations of LS Peg and TW Pic. These are Cataclysmic Variables (CVs) suggested as Intermediate Polars (IPs), but unconfirmed in the X-rays. Identification of several periodic oscillations in the optical band hint them as IPs. Unlike the previous spectral analysis on the EPIC-MOS data by fitting a hot optically thin plasma emission model with a single temperature for LS Peg, we simultaneously fitted all EPIC spectrum (pn+MOS) using a composite model of absorption for interstellar medium (tbabs) with two different partial covering absorbers (pcfabs) including a multitemperature plasma emission component (cevmkl) and a Gaussian emission line at 6.4 keV. TW Pic is best modeled in a similar manner with only one partial covering absorber and an extra Gaussian emission line at 6.7 keV. LS Peg has a maximum plasma temperature of ˜14.8 keV with an X-ray luminosity of ˜5×10^{32}ergs ^{-1} translating to an accretion rate of ˜1.27×10^{-10}M _{⊙}yr ^{-1}. TW Pic shows kT _{max} ˜38.7 keV with an X-ray luminosity around 1.6×10^{33}ergs ^{-1} at an accretion rate of ˜4×10^{-10}M _{⊙}yr ^{-1}. In addition, we discuss orbital modulations in the X-rays and power spectral analysis, and derive the EPIC pn spectra for orbital minimum and orbital maximum phases for both sources. We elaborate on the geometry of accretion and absorption in the X-ray emitting regions of both sources with articulation on the magnetic nature.

  4. MORFOLOGIA DERIVAZIONALE: RISVOLTI APPLICATIVI PER L’INSEGNAMENTO DELL’ITALIANO L2/LS

    Directory of Open Access Journals (Sweden)

    Laura Mantovani

    2014-07-01

    Full Text Available Questo articolo si presenta come un piccolo saggio relativo all’analisi e all’utilizzo della morfologia derivazionale con i possibili risvolti applicativi per l’insegnamento dell’italiano come L2/LS. Dopo una breve introduzione alla morfologia derivazionale, vengono presi in esame tre testi, uno di ambito scientifico, uno di ambito letterario e uno di ambito giornalistico, allo scopo di mettere in evidenza aspetti della morfologia derivazionale specifici del linguaggio della medicina, della chimica, dei giornali, della letteratura e, là dove possibile, le differenze di utilizzo e di realizzazione della derivazione. La riflessione condotta sui testi analizzati consente di sottolineare come la pratica dell’‘insegnamento derivazionale’ possa consentire all’apprendente di accrescere il suo vocabolario e di conseguenza aumentare anche la sua capacità di fare inferenze e di riflettere sulla lingua.  Derivational morphology: application implications on teaching italian L2/LS   Laura Mantovani    This article focuses on the analysis and use of derivational morphology and the resulting possible application implications on teaching Italian as a L2/LS. After a brief introduction on derivational morphology, we examine three texts, one scientific, one literary and one journalistic, in order to highlight specific aspects of derivational morphology in the languages of medicine, chemistry, newspapers, literature and, where possible, the differences in the use and implementation of  derivations. Discussions of the texts analyzed underscore how the practice of "derivational" teaching allows learners to increase their vocabulary and consequently also increase their ability to make inferences and reflect on the language. 

  5. Mass and orbit constraints of the gamma-ray binary LS 5039

    CERN Document Server

    Szalai, T; Kiss, L L; Matthews, J M; Vinkó, J; Kiss, Cs

    2011-01-01

    We present the results of space-based photometric and ground-based spectroscopic observing campaigns on the gamma-ray binary LS 5039. The new orbital and physical parameters of the system are similar to former results, except we found a lower eccentricity. Our MOST-data show that any broad-band optical photometric variability at the orbital period is below the 2 mmag level. Light curve simulations support the lower value of eccentricity and imply that the mass of the compact object is higher than 1.8 solar masses.

  6. Longitudinal Maps of Mars’ O2 (singlet Delta) Emission for Ls=72.5° and Ls=88.0°

    Science.gov (United States)

    Novak, Robert E.; Mumma, Michael J.; Villanueva, Geronimo L.

    2015-11-01

    We report longitudinal maps of the O2 (singlet Delta) emission rate (a tracer for high-altitude ozone) taken at two seasonal points, Ls=72.5° (03 April 2010) and Ls=88.0° (10 February 2014) using CSHELL at NASA’s IRTF. On these dates, the entrance slit of the spectrometer was positioned E-W on Mars centered at the sub-Earth point, but, on 10 Feb 2014 additional spectra were taken with the slit positioned 3 arc seconds North of the sub-Earth point. On both dates, spectral/spatial images (near 1.27 microns) were repeatedly taken over a four-hour period. Spectral extracts from these images were taken at 0.6 arcsec intervals along the slit. A model consisting of solar continuum with Fraunhofer lines, two-way transmission through Mars’ atmosphere, and a one-way transmission through the Earth’s atmosphere was used to isolate and analyze individual spectral lines. Boltzmann analysis of these lines yielded the rotational temperature (~175 K) that was used to determine the total emission rate from the measured lines.The slit on 03 Apr 2010 crossed the morning terminator, yielding measurements between 06:00-14:00 Local Time; on 10 Feb 2014, the slit went through the evening terminator (10:00-18:00 LT). For both dates, data were taken over a four-hour interval in UT. When displayed versus local time, the extracted emission rates reveal similar patterns of growth before mid-day and of decline before sunset, regardless of surface topography. The measured emission rates, that peak after noon local time, depend on the angles to both Sun and Earth. The post-noon emission rates (10 Feb 2014), vary with latitude, because they depend on the location of the hygropause.This work was partially funded by grants from NASA's Planetary Astronomy Program (344-32-51-96), NASA’s Astrobiology Program (344-53-51), and the NSF-RUI Program (AST-805540). We thank the administration and staff of the NASA-IRTF for awarding observing times and coordinating our observations.

  7. Cornelia de Lange syndrome, cohesin, and beyond

    Science.gov (United States)

    Liu, J; Krantz, ID

    2010-01-01

    Cornelia de Lange syndrome (CdLS) (OMIM #122470, #300590 and #610759) is a dominant genetic disorder with multiple organ system abnormalities which is classically characterized by typical facial features, growth and mental retardation, upper limb defects, hirsutism, gastrointestinal and other visceral system involvement. Mutations in three cohesin proteins, a key regulator of cohesin, NIPBL, and two structural components of the cohesin ring SMC1A and SMC3, etiologically account for about 65% of individuals with CdLS. Cohesin controls faithful chromosome segregation during the mitotic and meiotic cell cycles. Multiple proteins in the cohesin pathway are also involved in additional fundamental biological events such as double-strand DNA break repair and long-range regulation of transcription. Moreover, chromosome instability was recently associated with defective sister chromatid cohesion in several cancer studies, and an increasing number of human developmental disorders is being reported to result from disruption of this pathway. Here, we will discuss the human disorders caused by alterations of cohesin function (termed ‘cohesinopathies’), with an emphasis on the clinical manifestations of CdLS and mechanistic studies of the CdLS-related proteins. PMID:19793304

  8. Mutational Screening and Prenatal Diagnosis in Cornelia de Lange syndrome.

    Science.gov (United States)

    Dave, Usha; Shetty, Dhanlaxmi

    2014-02-01

    Phenotypic variability and the lack of a diagnostic marker have complicated the rapid diagnosis and genetic counseling for Cornelia de Lange syndrome (CdLS). The clinical features of CdLS are striking and easily recognizable by characteristic facial dysmorphism, upper-extremity malformations, hirsutism, cardiac defects, growth and cognitive retardation, and gastrointestinal abnormalities with severe mental retardation. The molecular diagnosis is essential for predicting prognosis and genetic counseling in the affected family, especially while planning the next pregnancy. We report here from India six cases of CdLS and how precise mutational screening in two cases helped in prenatal diagnosis and proved significant in prevention of recurrence in the affected family.

  9. Behavioral phenotype and autism spectrum disorders in Cornelia de Lange syndrome

    Directory of Open Access Journals (Sweden)

    Lucia Parisi

    2015-09-01

    Full Text Available Cornelia de Lange syndrome (CdLS is a congenital disorder characterized by distinctive facial features, growth retardation, limb abnormalities, intellectual disability, and behavioral problems. Cornelia de Lange syndrome is associated with abnormalities on chromosomes 5, 10 and X. Heterozygous point mutations in three genes (NIPBL, SMC3 and SMC1A, are responsible for approximately 50-60% of CdLS cases. CdLS is characterized by autistic features, notably excessive repetitive behaviors and expressive language deficits. The prevalence of autism spectrum disorder (ASD symptomatology is comparatively high in CdLS. However, the profile and developmental trajectories of these ASD characteristics are potentially different to those observed in individuals with idiopathic ASD. A significantly higher prevalence of self-injury are evident in CdLS. Self-injury was associated with repetitive and impulsive behavior. This study describes the behavioral phenotype of four children with Cornelia de Lange syndrome and ASDs and rehabilitative intervention that must be implemented.

  10. The successful completion of LS1, consolidation and preparations for the future

    CERN Multimedia

    Antonella Del Rosso

    2014-01-01

    For CERN’s Technology (TE) Department, success in LS1 is more important than finishing. In other words, the aim is to reach the finish line having maintained the highest standards of safety, quality and performance. Other challenges need to be faced too, before, during and after LS1, and the Department always approaches them with optimism. The new Department Head tells us how his 750 colleagues work to keep the Laboratory at the cutting edge of high-energy physics technology.   José Miguel Jiménez. “We can only grow once we’ve stabilised our base.” The message presented by José Miguel Jiménez, who stepped into the role of TE Department Head in January 2014, is clear, as are his priorities going forward: “The Technology Department needs to be consolidated in terms of both its personnel and its assembly and test infrastructures, some of which are unique.” The TE Department is tasked with pr...

  11. IMPROVED LS-SVM USING ACO TO ESTIMATE FLASHOVER VOLTAGE OF POLLUTED INSULATORS

    Directory of Open Access Journals (Sweden)

    SID AHMED BESSEDIK

    2017-01-01

    Full Text Available The reliability of insulators under polluted environment is one of the guiding factors in the insulation coordination of high voltage transmission lines. In order to improve understanding of the flashover phenomenon in polluted insulators, several experimental studies and mathematical approaches have been made‎ in‎ last‎ year’s.‎ In‎ this‎ paper,‎ the‎ critical flashover voltage behavior of polluted insulators has been calculated and a hybrid model between machine Learning (ML and optimization technique has been proposed. For this purpose, firstly the ant colony optimization (ACO technique is utilized to optimize the hyper-parameters needed in least squares support vector machines (LS-SVM. Then, a LS-SVM-ACO model is designed to establish a nonlinear model between the characteristics of the insulator and the critical flashover voltage. The data used to train the model and test its performance is derived from experimental measurements and a mathematical model. The results obtained from the proposed model are in good accord with other mathematical and experimental results of previous researchers.

  12. Docosahexaenoic acid suppresses arachidonic acid-induced proliferation of LS-174T human colon carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Piet Habbel; Karsten H Weylandt; Katja Lichopoj; Johannes Nowak; Martin Purschke; Jing-Dong Wang; Cheng-Wei He; Daniel C Baumgart; Jing X Kang

    2009-01-01

    AIM: To investigate the impact of arachidonic acid (AA) and docosahexaenoic acid (DHA) and their combination on colon cancer cell growth.METHODS: The LS-174T colon cancer cell line was used to study the role of the prostaglandin precursor AA and the omega-3 polyunsaturated fatty acid DHA on cell growth. Cell viability was assessed in XTT assays. For analysis of cell cycle and cell death, flow cytometry and DAPI staining were applied. Expression of cyclooxygenase-2 (COX-2), p21 and bcl-2 in cells incubated with AA or DHA was examined by real-time RT-PCR. Prostaglandin E2 (PGE2) generation in the presence of AA and DHA was measured using a PGE2ELISA.RESULTS: AA increased cell growth, whereas DHA reduced viability of LS 174T cells in a time- and dosedependent manner. Furthermore, DHA down- regulated mRNA of bcl-2 and up-regulated p21. Interestingly,DHA was able to suppress AA-induced cell proliferation and significantly lowered AA-derived PGE2 formation.DHA also down-regulated COX-2 expression. In addition to the effect on PGE2 formation, DHA directly reduced PGE2-induced cell proliferation in a dosedependent manner.CONCLUSION: These results suggest that DHA can inhibit the pro-proliferative effect of abundant AA or PGE2.

  13. VERITAS Observations of the TeV Binary LS I +61 303 During 2008-2010

    CERN Document Server

    Acciari, V A; Arlen, T; Aune, T; Beilicke, M; Benbow, W; Bradbury, S M; Buckley, J H; Bugaev, V; Byrum, K; Cannon, A; Cesarini, A; Ciupik, L; Collins-Hughes, E; Connolly, M P; Cui, W; Dickherber, R; Duke, C; Errando, M; Falcone, A; Finley, J P; Finnegan, G; Fortson, L; Furniss, A; Galante, N; Gall, D; Gillanders, G H; Godambe, S; Griffin, S; Grube, J; Guenette, R; Gyuk, G; Hanna, D; Holder, J; Hughes, G; Hui, C M; Humensky, T B; Kaaret, P; Karlsson, N; Kertzman, M; Kieda, D; Krawczynski, H; Krennrich, F; Lang, M J; LeBohec, S; Maier, G; Majumdar, P; McArthur, S; McCann, A; Moriarty, P; Mukherjee, R; Ong, R A; Orr, M; Otte, A N; Park, N; Perkins, J S; Pohl, M; Prokoph, H; Quinn, J; Ragan, K; Reyes, L C; Reynolds, P T; Roache, E; Rose, H J; Ruppel, J; Saxon, D B; Schroedter, M; Sembroski, G H; Senturk, G Demet; Smith, A W; Staszak, D; Tesic, G; Theiling, M; Thibadeau, S; Tsurusaki, K; Varlotta, A; Vassiliev, V V; Vincent, S; Vivier, M; Wakely, S P; Ward, J E; Weekes, T C; Weinstein, A; Weisgarber, T; Williams, D A; Zitzer, B

    2011-01-01

    We present the results of observations of the TeV binary LS I +61 303 with the VERITAS telescope array between 2008 and 2010, at energies above 300 GeV. In the past, both ground-based gamma-ray telescopes VERITAS and MAGIC have reported detections of TeV emission near the apastron phases of the binary orbit. The observations presented here show no strong evidence for TeV emission during these orbital phases; however, during observations taken in late 2010, significant emission was detected from the source close to the phase of superior conjunction (much closer to periastron passage) at a 5.6 standard deviation (5.6 sigma) post-trials significance. In total, between October 2008 and December 2010 a total exposure of 64.5 hours was accumulated with VERITAS on LS I +61 303, resulting in an excess at the 3.3 sigma significance level for constant emission over the entire integrated dataset. The flux upper limits derived for emission during the previously reliably active TeV phases (i.e. close to apastron) are less...

  14. LS1 to LHC Report: LHC key handed back to Operations

    CERN Multimedia

    CERN Bulletin

    2015-01-01

    This week, after 23 months of hard work involving about 1000 people every day, the key to the LHC was symbolically handed back to the Operations team. The first long shutdown is over and the machine is getting ready for a restart that will bring its beam to full energy in early spring.   Katy Foraz, LS1 activities coordinator, symbolically hands the LHC key to the operations team, represented, left to right, by Jorg Wenninger, Mike Lamont and Mirko Pojer. All the departments, all the machines and all the experimental areas were involved in the first long shutdown of the LHC that began in February 2013. Over the last two years, the Bulletin has closely followed  all the work and achievements that had been carefully included in the complex general schedule drawn up and managed by the team led by Katy Foraz from the Engineering Department. “The work on the schedule began two years before the start of LS1 and one of the first things we realised was that there was no commercial...

  15. VERITAS observations of exceptionally bright TeV flares from LS I +61$^\\circ$ 303

    CERN Document Server

    de Bhroithe, Anna O'Faolain

    2015-01-01

    The very-high-energy (VHE; E > 100 GeV) gamma-ray experiment, VERITAS, detected exceptionally bright flares from the high-mass X-ray binary LS I +61$^\\circ$ 303 during the period October-December 2014. LS I +61$^\\circ$ 303 is a known VHE gamma-ray source, the flux from which varies strongly with the orbital period of ~26.5 days. The maximum VHE flux is found around apastron (orbital phase ~0.6) at a level typically corresponding to 10-15% of the Crab Nebula flux (>300 GeV). During these most recent observations, relatively short (day scale), bright TeV flares were observed from the source around apastron in two orbital cycles (October and November). Both cases exhibited peak fluxes above 25% of the Crab Nebula flux (>300 GeV), making these the brightest VHE flares ever detected from this source. In the last orbital cycle observed (December), the source had returned to its historical level of activity. The results of these VERITAS observations from 2014 will be presented.

  16. Signal Simulation and Experimental Research on Acoustic Emission using LS-DYNA

    Directory of Open Access Journals (Sweden)

    Zhang Jianchao

    2015-09-01

    Full Text Available To calculate sound wave velocity, we performed the Hsu-Nielsen lead break experiment using the ANSYS/LS-DYNA finite element software. First, we identified the key problems in the finite element analysis, such as selecting the exciting force, dividing the grid density, and setting the calculation steps. Second, we established the finite element model of the sound wave transmission in a plate under the lead break simulation. Results revealed not only the transmission characteristics of the sound wave but also the simulation and calculation of the transmission velocity of the longitudinal and transverse waves through the time travel curve of the vibration velocity of the sound wave at various nodes. Finally, the Hsu-Nielsen lead break experiment was implemented. The results of the theoretical calculation and simulation analysis were consistent with the experimental results, thus demonstrating that the research method using the ANSYS/LS-DYNA software to simulate sound wave transmissions in acoustic emission experiments is feasible and effective.

  17. Dynamic Impact Tolerance of Shuttle RCC Leading Edge Panels using LS-DYNA

    Science.gov (United States)

    Fasanella, Edwin; Jackson, Karen E.; Lyle, Karen H.; Jones, Lisa E.; Hardy, Robin C.; Spellman, Regina L.; Carney, Kelly S.; Melis, Matthew E.; Stockwell, Alan E.

    2008-01-01

    This paper describes a research program conducted to enable accurate prediction of the impact tolerance of the shuttle Orbiter leading-edge wing panels using 'physics-based- codes such as LS-DYNA, a nonlinear, explicit transient dynamic finite element code. The shuttle leading-edge panels are constructed of Reinforced-Carbon-Carbon (RCC) composite material, which issued because of its thermal properties to protect the shuttle during re-entry into the Earth's atmosphere. Accurate predictions of impact damage from insulating foam and other debris strikes that occur during launch required materials characterization of expected debris, including strain-rate effects. First, analytical models of individual foam and RCC materials were validated. Next, analytical models of individual foam cylinders impacting 6-in. x 6-in. RCC flat plates were developed and validated. LS-DYNA pre-test models of the RCC flat plate specimens established the impact velocity of the test for three damage levels: no-detectable damage, non-destructive evaluation (NDE) detectable damage, or visible damage such as a through crack or hole. Finally, the threshold of impact damage for RCC on representative Orbiter wing panels was predicted for both a small through crack and for NDE-detectable damage.

  18. Gamma-ray binaries beyond one-zone models: an application to LS 5039

    CERN Document Server

    del Palacio, Santiago; Romero, Gustavo E

    2014-01-01

    Context. Several binary systems hosting massive stars present gamma-ray emission. In most of these systems, despite detailed observational information is available, the nature and the structure of the emitter are still poorly known. Aims. We investigate the validity of the so-called one-zone approximation for the high-energy emitter in binary systems hosting a massive star. In particular, the case of LS 5039 is considered. Methods. Assuming a point-like emitter at rest, the presence of a nearby massive star, and taking as a reference the observed MeV and GeV fluxes, a non-thermal leptonic model is systematically applied for di?erent locations, magnetic fields, and non-radiative losses. This allows the identification of both the emitter configurations most compatible with observations and inconsistencies between model predictions and the available data. Results. In the case of LS 5039, the best parameter combination is fast non-radiative cooling and a low magnetic field. However, discrepancies appear when comp...

  19. PC-LabView Based Control System in SAGA-LS

    CERN Document Server

    Ohgaki, Hideaki; Koda, Shigeru; Takabayashi, Yuichi; Tomimasu, Takio; Toyokawa, Hiroyuki; Yoshida, Katuhide

    2005-01-01

    A control system for SAGA Synchrotron Light Source (SAGA-LS) has been constructed. SAGA-LS is a small-medium size light source and is run by local government, which means there are a few number of staff in the laboratory. Thus the control system must be simple and robust, while inexpensive, easy to develop and maintain. The basic ideas of the system are 1) using PCs to build a low cost control system, 2) using off-shelf devices, FieldPoint (National Instrument) and PLCs, (FA-M3, Yokogawa), for robust and replaceable system, 3) using LabView for a quick in-house system development, 4) using channel access protocol between server and client to transparent from regular EPICS utilities, 5) using ActiveX CA to emulate the CA protocol. About 1,000 PVs are employed to control the magnet power supplies, the RF control sub-system, vacuum monitors, BPM data and several LCW data. The system has been operated and tuned at the beginning of the commissioning, spring 2004. MySQL database system also archives data to assist ...

  20. The nature of LS 5039 under the scrutiny of gamma-rays

    CERN Document Server

    Torres, Diego F

    2008-01-01

    Several gamma-ray binaries have been recently detected by the High-Energy Stereoscopy Array (H.E.S.S.) and the Major Atmospheric Imaging Cerenkov (MAGIC) telescope. In two cases, their nature is unknown, since a final observational feature for a black hole or a pulsar compact object companion is still missing. One such system is LS 5039. Here we present results from a model (it includes a detailed account of the system geometry, the angular dependence of processes such as Klein-Nishina inverse Compton and gamma-gamma absorption, and a Monte Carlo simulation of cascading) of the high energy phenomenology of LS 5039 in which it is assumed that the companion object is a pulsar rotating around an O6.5V star in the 3.9 days orbit. We show that the H.E.S.S. phenomenology at all scales (spectra along the orbit in both broad and short phase-bins and lightcurve) is described within this model. We focus on presenting predictions for photons with lower energies (for E>1 GeV), subject to test in the forthcoming months wi...

  1. Exploring the connection between the stellar wind and the non-thermal emission in LS 5039

    CERN Document Server

    Bosch-Ramon, V; Ribó, M; De Oliveira, R L; Janot-Pacheco, E; Negueruela, I; Paredes, J M; Martocchia, A

    2007-01-01

    New xmm observations have been performed around periastron and apastron passages in September 2005, during an epoch of presumably enhanced O star wind. Also, 2005 Chandra observations on LS 5039 are revisited. Moreover, a compilation of the Halpha EW and rxte/ASM X-ray count rate obtained since the 1990s is carried out, being both quantities compared with each other and also with historical radio data. xmm observations show higher and harder emission around apastron than around periastron. No signatures of thermal emission or a reflection iron line indicating the presence of an accretion disk are found in the spectrum, and the hydrogen column density (N_H) is compatible with a constant and with the interstellar value in both observations. The hardness ratio and the count rate seem uncorrelated at periastron and may be correlated at apastron. We find that LS 5039 was bright and hard in 2005 chandra observations. The ASM count rate shows changes by a ~80% on year timescales, and the Halpha EW shows yearly varia...

  2. Forging of Naval Brass (ASTM B16) - Finite Element Analysis using Ls Dyna

    Science.gov (United States)

    Subha Sankari, T.; Sangavi, S.; Paneerselvam, T.; Venkatraman, R.; Venkatesan, M.

    2016-09-01

    Forging is one of the important manufacturing process in which products like connecting rod, transmission shaft, clutch hubs and gears are produced. Finite element analysis (FEA) in forming techniques is of recent interest for the optimal design and determination of right manufacturing forming process. The data from the numerical results can help in providing the information for selecting the ideal process conditions. Thus aside from experimental values, simulation by the finite element analysis software's such as LS DYNA can be used for the analysis of strain distribution in forging processes. In the present work, Finite element simulation of open die forging of naval brass (ASTM B16) is done at an optimal temperature. An advanced multi physics simulation software package by the Livermore software technology cooperation LSTC - LS DYNA is utilized for the simulation of forging process. For the forging validation, experiment is conducted with a cylindrical billet having height 45 mm and diameter of 40mm. The numerical results are compared with that of experimental results carried out at the same temperature and dimensions for validation. The distribution of strain is analyzed. Energy analysis due to impact load is detailed. The simulation results are found to be in good agreement with the experimental results.

  3. Non-local potentials with LS terms in algebraic scattering theory

    Energy Technology Data Exchange (ETDEWEB)

    Levay, Peter [Department of Theoretical Physics, Institute of Physics, Technical University of Budapest, Budapest (Hungary)

    1997-10-21

    The group theoretical analysis of Coulomb scattering based on the SO(3,1) group is revisited. Using matrix-valued differential operators, modifying the angular momentum and the Runge-Lenz vector used hitherto for the realization of the so(3,1) (Lorentz) algebra, we obtain a three-dimensional solvable two-channel scattering problem. The interaction term besides the Coulomb potential contains a non-local potential of LS-type. Using the momentum representation the S-matrix can be calculated analytically. By employing a canonical transformation, another solvable three-dimensional scattering problem is found, in agreement with the expectations of algebraic scattering theory. The potential in this case is of Poeschl-Teller type with an LS term. It is also pointed out that our matrix-valued realization of the so(3,1) algebra can be cast to an instructive form with the help of su(2) gauge fields. An interesting connection between gauge transformations and supersymmetry transformations of supersymmetric quantum mechanics is also observed. These results enable us to construct other solvable scattering problems by using su(2) gauge transformations. (author)

  4. Understanding the periodicities in radio and GeV emission from LS I+61303

    CERN Document Server

    Jaron, F; Massi, M

    2016-01-01

    Accretion models predict two ejections along the eccentric orbit of LS I +61 303: one major ejection at periastron and a second, lower ejection towards apastron. We develop a physical model for LS I +61 303 in which relativistic electrons are ejected twice along the orbit. The ejecta form a conical jet that is precessing with P2. The jet radiates in the radio band by the synchrotron process and the jet radiates in the GeV energy band by the external inverse Compton and synchrotron self-Compton processes. We compare the output fluxes of our physical model with two available large archives: OVRO radio and Fermi Large Area Telescope (LAT) GeV observations, the two databases overlapping for five years. The larger ejection around periastron passage results in a slower jet, and severe inverse Compton losses result in the jet also being short. While large gamma-ray emission is produced, there is only negligible radio emission. Our results are that the periastron jet has a length of 3.0 10^6 rs and a velocity beta ~ ...

  5. Dumping Syndrome

    Science.gov (United States)

    ... System & How it Works Digestive Diseases A-Z Dumping Syndrome What is dumping syndrome? Dumping syndrome occurs when food, especially sugar, ... the colon and rectum—and anus. What causes dumping syndrome? Dumping syndrome is caused by problems with ...

  6. Cornelia de Lange syndrome with NIPBL mutation and mosaic Turner syndrome in the same individual

    Directory of Open Access Journals (Sweden)

    Wierzba Jolanta

    2012-06-01

    Full Text Available Abstract Background Cornelia de Lange syndrome (CdLS is a dominantly inherited disorder characterized by facial dysmorphism, growth and cognitive impairment, limb malformations and multiple organ involvement. Mutations in NIPBL gene account for about 60% of patients with CdLS. This gene encodes a key regulator of the Cohesin complex, which controls sister chromatid segregation during both mitosis and meiosis. Turner syndrome (TS results from the partial or complete absence of one of the X chromosomes, usually associated with congenital lymphedema, short stature, and gonadal dysgenesis. Case presentation Here we report a four-year-old female with CdLS due to a frameshift mutation in the NIPBL gene (c.1445_1448delGAGA, who also had a tissue-specific mosaic 45,X/46,XX karyotype. The patient showed a severe form of CdLS with craniofacial dysmorphism, pre- and post-natal growth delay, cardiovascular abnormalities, hirsutism and severe psychomotor retardation with behavioural problems. She also presented with minor clinical features consistent with TS, including peripheral lymphedema and webbed neck. The NIPBL mutation was present in the two tissues analysed from different embryonic origins (peripheral blood lymphocytes and oral mucosa epithelial cells. However, the percentage of cells with monosomy X was low and variable in tissues. These findings indicate that, ontogenically, the NIPBL mutation may have appeared before the mosaic monosomy X. Conclusions The coexistence in several patients of these two rare disorders raises the issue of whether there is indeed a cause-effect association. The detailed clinical descriptions indicate predominant CdLS phenotype, although additional TS manifestations may appear in adolescence.

  7. Decon2LS: An open-source software package for automated processing and visualization of high resolution mass spectrometry data

    Directory of Open Access Journals (Sweden)

    Anderson Gordon A

    2009-03-01

    Full Text Available Abstract Background Data generated from liquid chromatography coupled to high-resolution mass spectrometry (LC-MS-based studies of a biological sample can contain large amounts of biologically significant information in the form of proteins, peptides, and metabolites. Interpreting this data involves inferring the masses and abundances of biomolecules injected into the instrument. Because of the inherent complexity of mass spectral patterns produced by these biomolecules, the analysis is significantly enhanced by using visualization capabilities to inspect and confirm results. In this paper we describe Decon2LS, an open-source software package for automated processing and visualization of high-resolution MS data. Drawing extensively on algorithms developed over the last ten years for ICR2LS, Decon2LS packages the algorithms as a rich set of modular, reusable processing classes for performing diverse functions such as reading raw data, routine peak finding, theoretical isotope distribution modelling, and deisotoping. Because the source code is openly available, these functionalities can now be used to build derivative applications in relatively fast manner. In addition, Decon2LS provides an extensive set of visualization tools, such as high performance chart controls. Results With a variety of options that include peak processing, deisotoping, isotope composition, etc, Decon2LS supports processing of multiple raw data formats. Deisotoping can be performed on an individual scan, an individual dataset, or on multiple datasets using batch processing. Other processing options include creating a two dimensional view of mass and liquid chromatography (LC elution time features, generating spectrum files for tandem MS data, creating total intensity chromatograms, and visualizing theoretical peptide profiles. Application of Decon2LS to deisotope different datasets obtained across different instruments yielded a high number of features that can be used to

  8. New founding mutation in MSH2 associated with hereditary nonpolyposis colorectal cancer syndrome on the Island of Tenerife.

    Science.gov (United States)

    Medina-Arana, Vicente; Barrios, Ysamar; Fernández-Peralta, Antonia; Herrera, Mercedes; Chinea, Nancy; Lorenzo, Nieves; Jiménez, Alejandro; Martín-López, Juana Victoria; González-Hermoso, Fernando; Salido, Eduardo; González-Aguilera, Juan J

    2006-12-01

    Lynch syndrome or hereditary nonpolyposis colorectal cancer (HNPCC) is a hereditary syndrome with genetic heterogeneity. The disease is caused by mutations or epigenetic silencing in DNA mismatch repair genes, MLH1, MSH2, MSH6, PMS2 and MLH3, although the vast majority of cases correspond to mutations of MLH1 and MSH2. We herein describe a nucleotide change, c.2063T>G in exon 13 of the MSH2 gene, present in families that fulfill the Amsterdam criteria for Lynch syndrome and originate from northern Tenerife (Canary Islands-Spain). This mutation is expected to result in a nonconservative amino acid change, M688R, at the ATPase domain of the MSH2 protein. We found five large families with this mutation, and about half the individuals heterozygous for M688R developed malignancies by the sixth decade of life. In many cases analyzed, their tumors revealed loss of the normal allele, being homozygous for M688R. There is an evidence of historical isolation for the population studied, which could have favored a considerable genetic drift. The presence of the same mutation and the disease associated-haplotype conservation in families not directly related can be probably the consequence of a bottleneck in the founding of this population (rather than a relatively recent founding of the mutation).

  9. A forecasting and forewarning model for methane hazard in working face of coal mine based on LS-SVM

    Institute of Scientific and Technical Information of China (English)

    CAO Shu-gang; LIU Yan-bao; WANG Yan-ping

    2008-01-01

    To improve the precision and reliability in predicting methane hazard in working face of coal mine, we have proposed a forecasting and forewarning model for methane hazard based on the least square support vector (LS-SVM) multi-classifier and regression machine. For the forecasting model, the methane concentration can be considered as a nonlinear time series and the time series analysis method is adopted to predict the change in methane concentration using LS-SVM regression. For the forewarning model, which is based on the forecasting results, by the multi-classification method of LS-SVM, the methane hazard was identified to four grades: normal, attention, warning and danger. According to the forewarning results, corresponding measures are taken. The model was used to forecast and forewarn the K9 working face. The results obtained by LS-SVM regression show that the forecast- ing have a high precision and forewarning results based on a LS-SVM multi-classifier are credible. Therefore, it is an effective model building method for continuous prediction of methane concentration and hazard forewarning in working face.

  10. Refractive outcomes comparison between the Lenstar LS 900® optical biometry and immersion A-scan ultrasound.

    Science.gov (United States)

    Naicker, Palanyraj; Sundralingam, Siva; Peyman, Mohammadreza; Juana, Azida; Mohamad, Nor Fadhilah; Win, Maung Maung; Loo, Angela; Subrayan, Visvaraja

    2015-08-01

    To determine the accuracy of intraocular lens (IOL) calculations in eyes undergoing phacoemulsification cataract surgery with IOL implantation using immersion A-scan ultrasound (US) and Lenstar LS 900(®) biometry. In this prospective study, 200 eyes of 200 patients were randomized to undergo either Lenstar LS 900(®) or immersion A-scan US biometry to determine the IOL dioptric power prior to phacoemulsification cataract surgery. Post-operative refractive outcomes of these two groups of patients were compared. The result showed no significant difference between the target spherical equivalent (SE) and the post-operative SE value by the Lenstar LS 900(®) (p value = 0.632) or immersion A-scan US biometry (p value = 0.438) devices. The magnitude of difference between the two biometric devices were not significantly different (p value = 0.868). There was no significant difference in the predicted post-operative refractive outcome between immersion A-scan US biometry and Lenstar LS 900(®). Based on the results, the immersion A-scan US technique is as accurate as Lenstar LS 900(®) in the hands of an experienced operator.

  11. A new ganglioside in human meconium detected by antiserum against the human milk sialyloligosaccharide, LS-tetrasaccharide b.

    Science.gov (United States)

    Prieto, P A; Smith, D F

    1985-08-15

    Antibodies directed against human milk sialyloligosaccharides [D. F. Smith and V. Ginsburg (1980) J. Biol. Chem. 255, 55-59] are used to identify human meconium gangliosides by radioimmuneoverlay-thin-layer chromatography or by direct binding on nitrocellulose filters of sialyl[3H]oligosaccharide alditols obtained from gangliosides after ozonolysis and alkali-fragmentation. Thin-layer chromatograms of meconium monosialylgangliosides immunostained with rabbit antisera specific for LS-tetrasaccharide c (NeuAc alpha 2-6Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc) or LS-tetrasaccharide b (Gal beta 1-3[NeuAc alpha 2-6]GlcNAc beta 1-3Gal beta 1-4Glc) reveal their corresponding gangliosides, 6'-LM1 and a previously undescribed ceramide derivative of LS-tetrasaccharide b, respectively. The sialyl[3H]oligosaccharides derived from the monosialylganglioside fraction of meconium are separated by paper chromatography and assayed for binding to specific anti-sialyloligosaccharide sera. Antisera specific for LS-tetrasaccharide c and 3'-sialyllactose (NeuAc alpha 2-3Gal beta 1-4Glc) identify their corresponding 3H-labeled haptens released from the major meconium gangliosides 6'-LM1 and GM3, respectively. Binding of a ganglioside-derived sialyl[3H]oligosaccharide by anti-LS-tetrasaccharide b serum is consistent with the presence in meconium of a monosialylganglioside with the following proposed structure: (formula; see text)

  12. 基于小波变换和LS-SVM的短期风速预测方法%SHORT TERM WIND SPEED PREDICTION BASED ON WAVELET TRANSFORM AND LS-SVM

    Institute of Scientific and Technical Information of China (English)

    韩晓娟; 曹慧; 李勇; 肖运启; 唐晓

    2011-01-01

    Aiming at the periodicity and non-stability of the wind speed change, a wind speed prediction model for wind farm based on wavelet and LS-SVM was proposed in this paper, in which wind speed sequence was decomposed by multi-resolution analysis method of wavelet transform and was reflected to different spaces. Combining with the characteristic of the strong learning ability and computation ability of LS-SVM' s for small sample, the sub-sequences after wavelet decomposing were trained and tested by LS-SVM and the final wind speed prediction values could be yielded by the linearity superposition for each prediction result. Compared with LS-SVM, the method proposed in this paper can obviously improve the prediction accuracy of short term wind speed and has strong adaptability as well as quite bright prospect for engineering applications.%针对风速序列的周期性和非平稳性,提出了基于小波变换和LS-SVM相结合的风电场风速预测模型,利用小波变换的多分辩分析法对风速序列进行分解,将风速序列投影到不同尺度上.结合LS-SVM的小样本学习能力强和计算简单等特点,将小波分解后的各风速子序列分别采用LS-SVM进行训练和预测,最后将各预测结果进行叠加得到最终的风速预测值.与LS-SVM风速预测方法进行比较,采用该文提出的方法可明显提高短期风速预测的精度,并具有较强的适应性,具有一定的工程应用前景.最后通过具体实例验证了该模型的有效性.

  13. De novo heterozygous mutations in SMC3 cause a range of Cornelia de Lange syndrome-overlapping phenotypes.

    Science.gov (United States)

    Gil-Rodríguez, María Concepción; Deardorff, Matthew A; Ansari, Morad; Tan, Christopher A; Parenti, Ilaria; Baquero-Montoya, Carolina; Ousager, Lilian B; Puisac, Beatriz; Hernández-Marcos, María; Teresa-Rodrigo, María Esperanza; Marcos-Alcalde, Iñigo; Wesselink, Jan-Jaap; Lusa-Bernal, Silvia; Bijlsma, Emilia K; Braunholz, Diana; Bueno-Martinez, Inés; Clark, Dinah; Cooper, Nicola S; Curry, Cynthia J; Fisher, Richard; Fryer, Alan; Ganesh, Jaya; Gervasini, Cristina; Gillessen-Kaesbach, Gabriele; Guo, Yiran; Hakonarson, Hakon; Hopkin, Robert J; Kaur, Maninder; Keating, Brendan J; Kibaek, María; Kinning, Esther; Kleefstra, Tjitske; Kline, Antonie D; Kuchinskaya, Ekaterina; Larizza, Lidia; Li, Yun R; Liu, Xuanzhu; Mariani, Milena; Picker, Jonathan D; Pié, Ángeles; Pozojevic, Jelena; Queralt, Ethel; Richer, Julie; Roeder, Elizabeth; Sinha, Anubha; Scott, Richard H; So, Joyce; Wusik, Katherine A; Wilson, Louise; Zhang, Jianguo; Gómez-Puertas, Paulino; Casale, César H; Ström, Lena; Selicorni, Angelo; Ramos, Feliciano J; Jackson, Laird G; Krantz, Ian D; Das, Soma; Hennekam, Raoul C M; Kaiser, Frank J; FitzPatrick, David R; Pié, Juan

    2015-04-01

    Cornelia de Lange syndrome (CdLS) is characterized by facial dysmorphism, growth failure, intellectual disability, limb malformations, and multiple organ involvement. Mutations in five genes, encoding subunits of the cohesin complex (SMC1A, SMC3, RAD21) and its regulators (NIPBL, HDAC8), account for at least 70% of patients with CdLS or CdLS-like phenotypes. To date, only the clinical features from a single CdLS patient with SMC3 mutation has been published. Here, we report the efforts of an international research and clinical collaboration to provide clinical comparison of 16 patients with CdLS-like features caused by mutations in SMC3. Modeling of the mutation effects on protein structure suggests a dominant-negative effect on the multimeric cohesin complex. When compared with typical CdLS, many SMC3-associated phenotypes are also characterized by postnatal microcephaly but with a less distinctive craniofacial appearance, a milder prenatal growth retardation that worsens in childhood, few congenital heart defects, and an absence of limb deficiencies. While most mutations are unique, two unrelated affected individuals shared the same mutation but presented with different phenotypes. This work confirms that de novo SMC3 mutations account for ∼ 1%-2% of CdLS-like phenotypes. © 2015 WILEY PERIODICALS, INC.

  14. Characterisation of the Angelman syndrome critical region

    Energy Technology Data Exchange (ETDEWEB)

    Gilbert, H.L.; Buxton, J.; Chan, C.T.J. [Univ. of London (United Kingdom)] [and others

    1994-09-01

    Angelman syndrome (AS) and Prader-Willi syndrome (PWS) are distinct neurogenetic disorders associated with a deletion of 15q11-13, a region subject to genomic imprinting. The chromosomal deletions are either maternal (AS) or paternal (PWS) in origin. The AS critical region was previously defined by an inherited deletion of approximately 1.5 Mb, encompassing TD3-21, LS6-1 and GABRB3. An individual with classical AS has been identified whose deletion includes LS6-1 but not TD3-21 or GABRB3. Both maternal and paternal methylation patterns at ZNF127, PW71B and SNRPN are present, suggesting that the AS gene itself is a disrupted, rather than imprinting sequences, as proposed recently for some familial cases. Initially, the deletion was detected by (CA)n repeat analysis. Cosmids derived from a 260 kb LS6-1 YAC were then used to confirm the deletion by fluorescence in-situ hybridization (FISH). Neither end cosmid from the YAC is deleted, suggesting that the AS critical region is less than 200 kb. Fragments isolated from the cosmids which span the deletion were used to further delineate the AS critical region by Southern blot analysis. Single copy genomic fragments within this region were then used to search for differential parental methylation patterns and potential coding sequences. We have used cosmids from the region in exon-trapping experiments. Using this combination of approaches, we aim to identify candidate genes for AS.

  15. David Lynch - Dark Splendor. Raum Bilder Klang, hrg. von Werner Spies, Ostfildern 2009; See this Sound. Versprechungen von Bild und Ton, hrg. von Cosima Rainer u.a., Köln 2009

    Directory of Open Access Journals (Sweden)

    Sarah Mauksch

    2010-09-01

    Full Text Available Das Max Ernst Museum in Brühl und das Lentos Kunstmuseum in Linz haben jüngst zwei Ausstellungskataloge herausgebracht, denen eine jeweils bemerkenswerte Ausstellung vorausging.Der Regisseur David Lynch wurde vor allem durch seine beeindruckenden Spielfilme wie Lost Highway, Mulholland Drive, Blue Velvet oder durch die Serie Twin Peaks aus den 90er Jahren bekannt. Die Ausstellung David Lynch – Dark Splendor. Raum Bilder Klang enthüllt eine Seite des Kultregisseurs, die vielen Filmliebhabern noch unentdeckt geblieben sein könnte. Brühl zeigt hier erstmals in Deutschland eine Sammlung, die sich nur mit dem bildnerischen Schaffen des Künstlers befasst.

  16. 回归系数LS估计的改进%Improvement of LS Estimation in Regression Coefficients

    Institute of Scientific and Technical Information of China (English)

    赵丽棉; 黄基廷

    2011-01-01

    This paper discusses the influence of multicollinearity on the LS estimate.When multicollinearity exists,comparing the LS estimate with the principal component estimate,there is a smaller mean square error.And then some examples are given to demonstrate the methods and steps by which the principal component estimate is used to improve the LS estimation.%论述了复共线性对LS估计的影响,复共线性存在时主成分估计比LS估计有较小均方误差.通过实例说明利用主成分估计对LS估计改进的方法与步骤.

  17. Application of PC-ANN and PC-LS-SVM in QSAR of CCR1 antagonist compounds: a comparative study.

    Science.gov (United States)

    Shahlaei, Mohsen; Fassihi, Afshin; Saghaie, Lotfollah

    2010-04-01

    Principal component regression (PCR), principal component-artificial neural network (PC-ANN), and principal component-least squares-support vector machine (PC-LS-SVM) as regression methods were investigated for building quantitative structure-activity relationships for the prediction of inhibitory activity of some CCR1 antagonists. Nonlinear methods (PC-ANN and PC-LS-SVM) were better than the PCR method considerably in the goodness of fit and predictivity parameters and other criteria for evaluation of the proposed model. These results reflect a nonlinear relationship between the principal components obtained from molecular descriptors and the inhibitory activity of this set of molecules. The maximum variance in activity of the molecules, in PCR method was 45.5%, whereas nonlinear methods, PC-ANN and PC-LS-SVM, could explain more than 93.7% and 95.6% variance in activity data respectively.

  18. Performance demonstration of 4πβ(LS)-γ coincidence counting system for standardization of radionuclides with complex decay scheme.

    Science.gov (United States)

    Kulkarni, D B; Anuradha, R; Joseph, Leena; Kulkarni, M S; Tomar, B S

    2016-02-01

    A standardization of (134)Cs and (131)I was carried out in order to demonstrate the performance and applicability of the 4πβ(LS)-γ coincidence counting system for standardization of radionuclides with complex decay scheme. The coincidence analyzer, capable of analyzing coincidence between beta and two gamma windows simultaneously, was developed and used for the standardization. The use of this dual coincidence analyzer has reduced the total experimental time by half. The activity concentrations obtained using the 4πβ(LS)-γ coincidence counting system, a 4πβ(PC)-γ coincidence counting system, and the CIEMAT/NIST method are in excellent agreement with each other within uncertainty limits and hence demonstrates its performance for standardization of radionuclides decaying with complex decay scheme. Hence use of this 4πβ(LS)-γ coincidence counting system can be an alternative method suitable to standardize radionuclides with complex decay scheme with acceptable precision.

  19. Latvijas Studentu apvienības tēls nacionālajos drukātajos medijos

    OpenAIRE

    Upleja, Aija

    2012-01-01

    Bakalaura darba „Latvijas Studentu apvienības tēls nacionālajos drukātajos medijos” mērķis ir noteikt, kāds ir Latvijas Studentu apvienības (LSA) tēls nacionālajos drukātajos medijos „Diena”, „Latvijas Avīze”, „Neatkarīgā Rīta Avīze”. Pētnieciskais jautājums ir noskaidrot, kāds ir LSA tēls nacionālajos drukātajos medijos un Latvijas Universitātes studentu vidū. Darbā aplūkota organizāciju ārējā komunikācija un komunikācijas modeļi kopumā, Hunta un Gruninga Ekselences teorija, Latvijas...

  20. Comparison of different multiple flow algorithms for topographic RUSLE factor (LS) calculation in Switzerland

    Science.gov (United States)

    Bircher, Pascal; Liniger, Hanspeter; Prasuhn, Volker

    2016-04-01

    Soil erosion is a well-known challenge both from a global perspective and in Switzerland, and it is assessed and discussed in many projects (e.g. national or European erosion risk maps). Meaningful assessment of soil erosion requires models that adequately reflect surface water flows. Various studies have attempted to achieve better modelling results by including multiple flow algorithms in the topographic length and slope factor (LS-factor) of the Revised Universal Soil Loss Equation (RUSLE). The choice of multiple flow algorithms is wide, and many of them have been implemented in programs or tools like Saga-Gis, GrassGis, ArcGIS, ArcView, Taudem, and others. This study compares six different multiple flow algorithms with the aim of identifying a suitable approach to calculating the LS factor for a new soil erosion risk map of Switzerland. The comparison of multiple flow algorithms is part of a broader project to model soil erosion for the entire agriculturally used area in Switzerland and to renew and optimize the current erosion risk map of Switzerland (ERM2). The ERM2 was calculated in 2009, using a high resolution digital elevation model (2 m) and a multiple flow algorithm in ArcView. This map has provided the basis for enforcing soil protection regulations since 2010 and has proved its worth in practice, but it has become outdated (new basic data are now available, e.g. data on land use change, a new rainfall erosivity map, a new digital elevation model, etc.) and is no longer user friendly (ArcView). In a first step towards its renewal, a new data set from the Swiss Federal Office of Topography (Swisstopo) was used to generate the agricultural area based on the existing field block map. A field block is an area consisting of farmland, pastures, and meadows which is bounded by hydrological borders such as streets, forests, villages, surface waters, etc. In our study, we compared the six multiple flow algorithms with the LS factor calculation approach used in